Nicht alles, was in der Natur wächst, kann der Mensch essen. Gifte in Pflanzen und Tieren und Pilzen gehören zu den natürlichen Abwehrstoffen, mit denen sich diese Lebewesen gegen ihre Freßfeinde und Nahrungskonkurrenten durchsetzen.
Algen gehören zu den verbreitetsten Lebewesen auf der Erde. Einige sind für den Menschen sehr giftig, entweder sie selbst direkt oder indirekt durch die von ihnen produzierten Stoffwechselprodukte.
Eine weitere Quelle für Gifte können aber auch aufgenommene Stoffe aus der Umwelt sein (vor allem Schwermetalle) und andere Lebewesen, die in, an oder mit den Algen leben.
Algen lassen sich sehr leicht züchten bzw ernten. Mit den entsprechenden Werbelügen angepriesen, werden sie vor allem an Kranke in anderen Ländern verkauft.
Zu den bekanntesten Algen im Gesundheitsmarkt gehören die "chlorella pyrenoidosa" und die "Blau-grün-Algen aus dem Lake Klamath" ("blue-green algae (BGA)") in den USA.
Obwohl die chlorella pyrenoidosa angeblich die am schnellsten wachsende Pflanze der Erde ist, wird sie verkauft zum Preis von 500 DM pro Kilogramm, das heißt zum 500-fachen des Preises von Getreidemehl.
Helfen sollen die Algen gegen Schwermetallvergiftungen, ADS (Hyperaktivität, ADHD), und alles mögliche und unmögliche andere. Den Beweis für die Wirksamkeit der Algen bleiben die Verkäufer schuldig. Oder sie lügen das Blaue vom Himmel herunter.
In der amerikanischen "PubMed" sind über Algen und Gifte brauchbare Fundstellen aufgelistet. Ich habe 171 abstracts bzw Hinweise gefunden als weitere Quellen zu dem hier als Nr. 1 genannten Beitrag.
Item 1 displayed (out of 171 found).
Assessing potential health risks from microcystin toxins in blue-green algae dietary supplements.
Gilroy DJ, Kauffman KW, Hall RA, Huang X, Chu FS.Environ Health Perspect. 2000 May;108(5):435-9.
Environmental Services and Consultation Section, Oregon Health Division, Portland, Oregon 97232, USA. firstname.lastname@example.org
The presence of blue-green algae (BGA) toxins in surface waters used for drinking water sources and recreation is receiving increasing attention around the world as a public health concern. However, potential risks from exposure to these toxins in contaminated health food products that contain BGA have been largely ignored. BGA products are commonly consumed in the United States, Canada, and Europe for their putative beneficial effects, including increased energy and elevated mood. Many of these products contain Aphanizomenon flos-aquae, a BGA that is harvested from Upper Klamath Lake (UKL) in southern Oregon, where the growth of a toxic BGA, Microcystis aeruginosa, is a regular occurrence. M. aeruginosa produces compounds called microcystins, which are potent hepatotoxins and probable tumor promoters. Because M. aeruginosa coexists with A. flos-aquae, it can be collected inadvertently during the harvesting process, resulting in microcystin contamination of BGA products. In fall 1996, the Oregon Health Division learned that UKL was experiencing an extensive M. aeruginosa bloom, and an advisory was issued recommending against water contact. The advisory prompted calls from consumers of BGA products, who expressed concern about possible contamination of these products with microcystins. In response, the Oregon Health Division and the Oregon Department of Agriculture established a regulatory limit of 1 microg/g for microcystins in BGA-containing products and tested BGA products for the presence of microcystins. Microcystins were detected in 85 of 87 samples tested, with 63 samples (72%) containing concentrations > 1 microg/g. HPLC and ELISA tentatively identified microcystin-LR, the most toxic microcystin variant, as the predominant congener.
Risk assessment of microcystin in dietary Aphanizomenon flos-aquae.
Schaeffer DJ, Malpas PB, Barton LL.Ecotoxicol Environ Saf. 1999 Sep;44(1):73-80.
Department of Veterinary Biosciences, University of Illinois, 2001 South Lincoln Avenue, Urbana, Illinois 61802, USA.
Aphanizomenon flos-aquae, a cyanobacterium that is marketed as a health food supplement, is harvested from natural blooms in Klamath Lake (Oregon) that are occasionally contaminated by Microcystis spp. Regulatory agencies in several countries are developing regulations to control the amount of microcystin in drinking water and other products, including products produced from A. flos-aquae. Regulation of microcystin (MC), a toxin produced by Microcystis spp. that is potentially present in natural culture of A. flos-aquae, should be based on studies in which a test species is exposed to the natural mixture of these cyanobacteria. A 1984 feeding trial to determine the effects of high dietary levels of A. flos-aquae on reproduction and development of mice is reanalyzed in light of recent analyses for microcystin-LR (MCLR) in the diets of those mice. Young adult mice consuming up to 333 microg MCLR/kg body weight (bw)/day exhibited no adverse effects on growth and reproduction, fetal development, and survival and organ weights of neonates. Based on a NOAEL of 333 microg MCLR/kg bw/day, a safety factor of 1000, consumption of 2 g/day of A. flos-aquae by a 60-kg adult, the safe level of MCLR as a contaminant of A. flos-aquae products is calculated to be 10.0 microg MCLR/g.Copyright 1999 Academic Press.
Detection of cyanobacterial toxins (microcystins) in waters of northeastern Wisconsin by a new immunoassay technique.
McDermott CM, Feola R, Plude J.Toxicon. 1995 Nov;33(11):1433-42.
Department of Biology and Microbiology, University of Wisconsin, Oshkosh 54901, USA.
The development of reliable, sensitive immunoassay techniques for detection of microcystins in water is becoming increasingly important. We have developed an enzyme-linked immunosorbent assay (ELISA) potentially able to detect microcystins at concentrations as low as 95 pg microcystin/ml water. The procedure uses antibodies extracted from the eggs of immunized chickens, eliminating the need to collect blood from laboratory rabbits. The antibody is able to recognize microcystin-LR, and -RR, and may recognize other forms of microcystin. The newly developed ELISA technique was utilized to measure the amount of microcystin in waters of northeastern Wisconsin. Of the water samples analyzed, 87% contained measurable amounts of microcystin (0.2-200 ng/ml). Organisms of the genus Microcystis were identified most frequently from microcystin-containing waters. The distribution of microcystin-producing cyanobacterial strains was apparently random throughout the sampling area.
Silent but widespread use of dietary supplements.
Naylor S, Gleich GJ.Mayo Clin Proc. 1999 Aug;74(8):845-6.
Release of heptapeptide toxin (microcystin) during the decomposition process of Microcystis aeruginosa.
Watanabe MF, Tsuji K, Watanabe Y, Harada K, Suzuki M.Nat Toxins. 1992;1(1):48-53.
Tokyo Metropolitan Research Laboratory of Public Health, Japan.
The decomposition process of toxic blue-green alga (cyanobacteria), Microcystis aeruginosa, under dark and aerobic condition was investigated in relation to the change of the amounts of heptapeptide toxins (microcystins YR and LR) by two experiments: one with Microcystis cells and the other with two purified microcystins. In the experiment with Microcystis cells, an increase of heterotrophic bacteria observed from the beginning of the experiment, was followed by decomposition of the algal cells and the subsequent release of microcystins into the filtrate fraction. The amounts of the toxins initially present in the cells were quantitatively detected in the filtrate fraction on the 35th day. The decomposition of microcystin YR began on the 42nd day. The decomposition rate of the two toxins was different. The decomposition rate of purified microcystins YR and LR, compared in distilled water and culture medium, respectively, indicated clearly that microcystin YR was more labile to decomposition than microcystin LR in the culture medium. At the end of the experiment (45th day) microcystin YR decreased to 58.6%, while 86.2% of microcystin LR remained.
Survey of microcystins in water between 1995 and 1996 in Parana, Brazil using ELISA.
Hirooka EY, Pinotti MH, Tsutsumi T, Yoshida F, Ueno Y.Nat Toxins. 1999;7(3):103-9.
Department of Food and Drug Technology, Center of Agricultural Sciences, State University of Londrina, Parana, Brazil. email@example.com
An enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody was used to determine microcystin (MC) concentrations in water supplies and water plant samples collected between November 1995 and October 1996, from five regions of Parana, Brazil. In addition, the presence of Microcystis sp. was monitored. Of the 50 samples obtained, 12 were from an urban lake, 8 from human water supplies, 10 from recreational lakes, 13 from farm waters used for animal pasture and 7 from aquaculture facilities. M. aeruginosa was positive in all locations. MCs were positive (>50 pg ml(-1)) in 9 samples (2 samples from human water supplies, 5 from recreational lakes and 2 from animal pasture). Heavy contamination with MCs was observed in water samples collected in May 1996 from 2 recreation (swimming-fishing sites at Itaipu dam, 6380 and 10,000 pg ml(-1)) and human supplies (6627 pg ml(-1)) samples. At these sites, a large bloom of Microcystis sp. was detected. Treatment with 1 ppm Cl- reduced MCs levels, although 267 pg ml(-1) remained in the water plant samples. Our data showed frequent occurrence of Microcystis sp., which may be a hazard to humans and animals in the state of Parana. More detailed investigations are required to evaluate the risk of natural MC contamination in the water supplied in this region.
Isolation and preparative purification of microcystin variants.
Ramanan S, Tang J, Velayudhan A.J Chromatogr A. 2000 Jun 23;883(1-2):103-12.
Department of Bioresource Engineering, Oregon State University, Corvallis 97331-3906, USA.
Preparative reversed-phase liquid chromatography was successfully used to purify two microcystins (microcystin LR and microcystin LA) from a cyanobacterial process waste. The separation protocol involved extraction of lyophilized cells by methanol, isolation and concentration by solid-phase extraction, and purification by reversed-phase HPLC. Milligram-level loading of microcystins was obtained on a solid-phase extraction cartridge packed with 0.5 g of C18 stationary phase. The separations were first carried out on an analytical column and then scaled-up to a preparative column. The microcystins were quantified by HPLC and enzyme-linked immunosorbent assay. A method to remove microcystins rapidly and economically from the cyanobacterial process waste is also described.
Use of protein phosphatase inhibition assay to detect microcystins in Donghu Lake and a fish pond in China.
Xu LH, Lam PK, Chen JP, Xu JM, Wong BS, Zhang YY, Wu RS, Harada KI.Chemosphere. 2000 Jul;41(1-2):53-8.
Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan, People's Republic of China.
Seasonal variations in the level of total microcystins in water samples collected from Donghu Lake and a fish pond in Wuhan, China, were studied between March 1995 and February 1996 using a protein phosphatase inhibition assay involving a radioactive 32P-labelled substrate. The assay is highly reliable and repeatable, and is probably the most sensitive assay for microcystin detection to date. Results of the survey indicated the presence of microcystins in the water samples, and the concentration of microcystins appeared to be related to the degree of eutrophication and water temperature. There is also a correlative relationship between the quantity of microcystins and the abundance of microcystin-producing cyanobacteria (Anabaena and Oscillatoria) in the water bodies over a year cycle. In the present study, the positive detection of microcystins in water bodies having no signs of algal bloom warns of considerable potential threat of these waters to public health.
[Detection of microcystins in source and tap water from a lake].
Dong C, Yu S, Chen G, Chen C.Wei Sheng Yan Jiu. 1998 Mar;27(2):100-2.
[Article in Chinese]
Department of Epidemiology, Shanghai Medical University, China.
The microcystins in source and tap water collected from seven waterworks around a lake in summer, 1996 were detected by enzyme-linked immunosorbent assay (ELISA). Microcystins were determined in the source water from all the seven waterworks, and the concentrations ranged from 280 to 35,300 ng/L. Low concentrations of microcystins were also detected in the tap water of three waterworks. The results suggest that microcystins in source water could not be removed completely by conventional adding bleaching powder treatment.
Use of a colorimetric protein phosphatase inhibition assay and enzyme linked immunosorbent assay for the study of microcystins and nodularins.
An J, Carmichael WW.Toxicon. 1994 Dec;32(12):1495-507.
Department of Biological Sciences, Wright State University, Dayton, OH 45435.
Microcystins and nodularins are cyclic peptide hepatotoxins and tumor promoters produced by several genera of cyanobacteria. Using a rabbit anti-microcystin-LR polyclonal antibody preparation, the cross-reactivity with 18 microcystin and nodularin variants was tested. A hydrophobic amino acid, 3-amino-9-methoxy-10-phenyl-2,6,8-trimethyl-deca-4(E),6(E)-dienoic acid (Adda), which has the (E) form at the C-6 double bond in both microcystin and nodularin, was found essential for these toxins to express antibody specificity. Modification of -COOH in glutamic acid of microcystin and nodularin did not alter their antigenicity. Antibody cross-reactivity of these toxins was compared with their ability to inhibit protein phosphatase type 1 (PP1). Detection of PP1 inhibition was done by measuring the inhibition effect of the toxins on p-nitrophenol phosphate activity toward PP1. PP1 was obtained as recombinant PP1 expressed in E. coli. The inhibition effect of five microcystins and two nodularins on recombinant PP1 activity toward p-nitrophenol phospate was measured in a microwell plate reader. The concentration of microcystin-LR causing 50% inhibition of recombinant PP1 activity (IC50) was about 0.3 nM, while that of two modified microcystins had a significantly higher IC50. Microcystin-LR and nodularin with the (z) form of Adda at the C-6 double bond or having the monoester of glutamic acid did not inhibit PP1. These three toxins were also nontoxic in the mouse bioassay. These results show the importance of Adda and glutamic acid in toxicity of these cyclic peptides and that PP1 inhibition is related to the toxins' mechanism of action.
[The occurrence, distribution and toxicity of cyanobacteria in the estuary of Lagoa dos Patos, Rio Grande do Sul].
Matthiensen A, Yunes JS, Codd GA.Rev Bras Biol. 1999 Aug;59(3):361-76.
[Article in Portuguese]
Departamento de Quimica, FURG, C.P. 474, Rio Grande, RS.
Several blooms of Microcystis aeruginosa have been observed in the Patos Lagoon estuary during the last fifteen years without a proper investigation of their ecological importance or possible toxicity. The present study has identified and quantified the presence of cyanobacteria in the Patos Lagoon estuary, particularly of M. aeruginosa. During this survey, identification and quantification of the main phytoplankton groups were done in relation to geographical distribution in the estuary. The presence of M. aeruginosa colonies in the estuarine region confirmed their superficial distribution throughout the estuarine waters during twelve months with a maximum of 1, 3.10(6) cells. L-1 in December, 1994 and a minimum of 1, 5.10(5) cells. L-1 in August, 1995 and also confirmed that M. aeruginosa originated from waters in the north of the estuary. The period of the highest cell and colonies densities was coincident with high chlorophyll-a levels in surface waters. Toxicity of M. aeruginosa bloom material was determined by bioassay and concentrations of hepatotoxins microcystins were identified by HPLC-DAD. M. aeruginosa blooms were considered highly toxic, presenting a 24 h-LD50 lower than 100 mg.Kg-1 b.w. and a toxin content higher than 1 microgram.mg-1 d.w. Several microcystin variants were found in the extracts with microcystin-LR predominating.
Role of microcystins in poisoning and food ingestion inhibition of Daphnia galeata caused by the cyanobacterium Microcystis aeruginosa.
Rohrlack T, Dittmann E, Henning M, Borner T, Kohl JG.Appl Environ Microbiol. 1999 Feb;65(2):737-9.
Research Group Ecology, Department of Biology, Humboldt University, D-10099 Berlin, Germany. ThRohrlack@compuserve.com
The effects of microcystins on Daphnia galeata, a typical filter-feeding grazer in eutrophic lakes, were investigated. To do this, the microcystin-producing wild-type strain Microcystis aeruginosa PCC7806 was compared with a mcy- PCC7806 mutant, which could not synthesize any variant of microcystin due to mutation of a microcystin synthetase gene. The wild-type strain was found to be poisonous to D. galeata, whereas the mcy- mutant did not have any lethal effect on the animals. Both variants of PCC7806 were able to reduce the Daphnia ingestion rate. Our results suggest that microcystins are the most likely cause of the daphnid poisoning observed when wild-type strain PCC7806 is fed to the animals, but these toxins are not responsible for inhibition of the ingestion process.
The toxicology of microcystins.
Dawson RM.Toxicon. 1998 Jul;36(7):953-62.
Defence Science and Technology Organisation, Aeronautical and Maritime Research Laboratory, Melbourne VIC, Australia.
Microcystins are a family of more than 50 structurally similar hepatotoxins produced by species of freshwater cyanobacteria, primarily Microcystis aeruginosa. They are monocyclic heptapeptides, characterised by some invariant amino acids, including one of unusual structure which is essential for expression of toxicity. Microcystins are chemically stable, but suffer biodegradation in reservoir waters. The most common member of the family, microcystin-LR (L and R identifying the 2 variable amino acids, in this case leucine and arginine respectively) has an LD50 in mice and rats of 36-122 microg/kg by various routes, including aerosol inhalation. Although human illnesses attributed to microcystins include gastroenteritis and allergic/irritation reactions, the primary target of the toxin is the liver, where disruption of the cytoskeleton, consequent on inhibition of protein phosphatases 1 and 2A, causes massive hepatic haemorrhage. Microcystins are tight-binding inhibitors of these protein phosphatases, with inhibition constants in the nanomolar range or lower. Uptake of microcystins into the liver occurs via a carrier-mediated transport system, and several inhibitors of uptake can antagonise the toxic effects of microcystins. The most effective of these is the antibiotic rifampin (a drug approved for clinical use), which protects mice and rats against microcystin-induced lethality when given prophylactically and, in some cases, therapeutically.
Immuno-crossreactivity and toxicity assessment of conjugation products of the cyanobacterial toxin, microcystin-LR.
Metcalf JS, Beattie KA, Pflugmacher S, Codd GA.FEMS Microbiol Lett. 2000 Aug 15;189(2):155-8.
Department of Biological Sciences, University of Dundee, Dundee DD1 4HN, UK.
Immunoassays are increasingly used to investigate the production, properties and fates of the cyanobacterial hepatotoxic microcystins in vitro and in vivo. Responses of an ELISA immunoassay to microcystins have been determined using the authentic toxin antigen, microcystin-LR, and conjugation products between the toxin and glutathione, cysteine-glycine and cysteine. The antibodies against microcystin-LR crossreacted with the toxin conjugation products with similar affinities (96-112%) to that of microcystin-LR, when assayed at a concentration of 1 microg l(-1). Toxicity assessment of the conjugates, in comparison to microcystin-LR, indicated a reduction according to mouse bioassay. In vitro protein phosphatase inhibition assay indicated that the conjugates possessed approximately 3-9-fold lower toxicity than microcystin-LR.
Biliary excretion of biochemically active cyanobacteria (blue-green algae) hepatotoxins in fish.
Sahin A, Tencalla FG, Dietrich DR, Naegeli H.Toxicology. 1996 Jan 8;106(1-3):123-30.
Institute of Pharmacology and Toxicology, University of Zurich-Tierspital, Switzerland.
Previous reports demonstrated that microcystin and related cyanobacteria polypeptides are rapidly cleared from plasma and accumulate in liver tissue. In the present study, we have used their ability to inhibit protein phosphatases to show that these cyanobacteria hepatotoxins are excreted into the bile of experimentally poisoned rainbow trout. At various times after oral administration of hepatotoxic Microcystis aeruginosa, bile samples were analysed for microcystin content by methanol extraction and protein phosphatase assays. An inhibitory principle that specifically suppressed protein phosphatase activity was detected in all bile samples removed between 1 and 72 h after oral exposure to toxic algae. These results indicate that biochemically active microcystin molecules are excreted into the biliary tract of poisoned fish.
Hazardous freshwater cyanobacteria (blue-green algae).
Elder GH, Hunter PR, Codd GA.Lancet. 1993 Jun 12;341(8859):1519-20.
Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, UK.
Immunoaffinity column as clean-up tool for determination of trace amounts of microcystins in tap water.
Tsutsumi T, Nagata S, Hasegawa A, Ueno Y.Food Chem Toxicol. 2000 Jul;38(7):593-7.
Research Institute for Biosciences and Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Ichigaya, Japan. firstname.lastname@example.org
Trace amounts of microcystins (MCs) in drinking water should be monitored because of their potential hazard for human health as an environmental tumor promoter. We describe here a new clean-up tool with immunoaffinity column (IAC) for determination of trace amounts of MCs (from pg to microg/litre) in tap water. The water samples were concentrated with IAC clean-up and MCs levels were determined by HPLC with UV detection or enzyme-linked immunosorbent assay (ELISA). In the combination with HPLC analysis, mean recovery of microcystin-LR (MCLR),-RR and-YR spiked to tap water were 91.8%, 77.3% and 86.4%, respectively, in the range 2.5-100 microg/litre. The chromatogram of MCs-spiked tap water sample cleaned up with IAC showed effective elimination of the impurities compared to that with octadecyl silanized cartridge, which had been cleaned up with a conventional method. Also, in the combination with highly sensitive ELISA, mean recovery of MCLR spiked to tap water was 80% in the range 0.1-1000 ng/litre. The combined methods developed here can detect pg to microg/litre of MCs in tap water. The overall results indicated that IAC will be suitable as a clean-up tool for trace amounts of MCs in tap water.
Dynamics of microcystins in the mussel Mytilus galloprovincialis.
Amorim A, Vasconcelos V.Toxicon. 1999 Jul;37(7):1041-52.
Departamento de Zoologia e Antropologia, Faculdade de Ciencias, Praca Gomes Teixeira, Porto, Portugal.
The accumulation and depuration of hepatotoxins produced by the freshwater cyanobacterium Microcystis aeruginosa in the mussel Mytilus galloprovincialis was studied. Mussels were fed daily 10(5) cells/ml of the toxic cyanobacterium that produces microcystin-LR (MCYST-LR), for four days. After that period animals were placed in toxin free water and were fed the diatom Nitzschia sp. During two weeks the concentration of the toxin in the mussels, as also in their feces and in the water where animals were placed individually during 24 h, were monitored using an ELISA assay. No mussel mortality was registered during the whole experiment. Mussels showed a maximum detectable level of MCYST of 10.7 microg/g mussels dry weight (DW) during the accumulation period, rising to 16.0 microg MCYST/g mussel DW by day two of the depuration period. Then there was a decrease trend with peaks of toxin at days 6, 8, 11 and 14. The rise of the toxin level on day two of the depuration period seems to have been due to the reingestion of contaminated feces. In fact, feces showed high amounts of MCYST during the first days of depuration with a maximum of 140 microg/d DW on day 3. This coincided with a 50% decrease on the detectable toxin in the mussels reflecting the emptiness of their digestive tract. In the water the highest level of the toxin was 2.5 microg MCYST/liter and some toxin peaks were also observed during the depuration period. This fluctuation of the toxin levels in the mussels, feces and water may be related to the renewal of protein phosphatases and subsequent release of unbound toxins. Results show that depuration of MCYST by mussels is not a very rapid process and contamination by feces containing MCYST is likely to occur and increase the persistence of these toxins in the mussels after the bloom disappearance. Monitoring programs for harmful algal blooms usually include only toxic dinoflagellates and diatoms and their toxins in bivalves. Taken into account the present work they should also include hepatotoxins from cyanobacteria, namely in brackish waters such as estuaries of eutrophic rivers in order to avoid human health hazard.
Microcystin toxicosis in cattle due to overgrowth of blue-green algae.
Frazier K, Colvin B, Styer E, Hullinger G, Garcia R.Vet Hum Toxicol. 1998 Feb;40(1):23-4.
Veterinary Diagnostic and Investigational Laboratory, College of Veterinary Medicine, University of Georgia, Tifton 37193, USA.
Toxicosis due to microcystin-containing blue-green algae has been sporadically reported in a variety of animal species. Most reports of intoxication involve algal blooms during periods of warm temperatures and abundant sunshine in the spring or early summer. A case of blue-green algae toxicosis with lesions attributable to toxins from Microcystis aeruginosa is described in 4 cattle from southern Georgia during November. The case was unusual in that characteristic hepatic necrosis was accompanied by severe mesenteric edema and peritoneal effusion. In addition, weather conditions and location were not expected to be conducive to algal blooms. Rapid diagnosis and identification of the probable source of intoxication allowed the owner to move the herd away from the affected pond. This action limited losses to only the 4 cattle.
Detection of cyanobacterial toxins (microcystins) in cell extracts by micellar electrokinetic chromatography.
Bouaicha N, Rivasseau C, Hennion MC, Sandra P.J Chromatogr B Biomed Appl. 1996 Oct 11;685(1):53-7.
CEMATMA, Laboratoire de Chimie Analytique, ESPCI, Paris, France.
A micellar electrokinetic chromatography (MEKC) method with UV detection is described for the rapid and efficient separation of three microcystins: microcystin-YR (MCYST-YR), microcystin-LR (MCYST-LR) and microcystin-RR (MCYST-RR). A detection limit of 7.5 pg for each toxin was achieved. The UV intensities of these toxins measured at 200 nm showed good linearity in the range 7.5-150 pg. The production of MCYST-LR in three cultured strains of cyanobacteria, namely Microcystis aeruginosa strain IP7806, Microcystis aeruginosa strain IP7813 and Oscillatoria agardhii strain IP7805, was evaluated.
Structural modifications imparting reduced toxicity in microcystins from Microcystis spp.
Stotts RR, Namikoshi M, Haschek WM, Rinehart KL, Carmichael WW, Dahlem AM, Beasley VR.Toxicon. 1993 Jun;31(6):783-9.
A cyanobacterial (blue-green algal) bloom containing Microcystis aeruginosa (dominant), M. viridis, and M. wesenbergii, was collected from Homer Lake (Illinois, U.S.A.) in the summer of 1988 and microcystins were isolated. One microcystin of substantially reduced toxicity was isolated, together with ten hepatotoxic microcystins. The compound with reduced toxicity was nonlethal at 1 mg/kg (i.p. mouse) and was determined to have a (C3H7O2) mono-ester of the alpha-carboxyl on the Glu unit of microcystin-LR. The other nine microcystins apart from MCLR had approximate LD50S ranging from 97 micrograms/kg to 750 micrograms/kg.
Isolation and detection of microcystins and nodularins, cyanobacterial peptide hepatotoxins.
Meriluoto J, Lawton L, Harada K.Methods Mol Biol. 2000;145:65-87.
Department of Biochemistry and Pharmacy, Abo Akademi University, Turku, Finland.
Photocatalytic degradation of cyanobacterial microcystin toxins in water.
Shephard GS, Stockenstrom S, De Villiers D, Engelbrecht WJ, Sydenham EW, Wessels GF.Toxicon. 1998 Dec;36(12):1895-901.
Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council, Tygerberg, South Africa.
The microcystins are hepatotoxins produced by a number of cyanobacterial species (blue green algae) in fresh water systems. The increasing eutrophication of natural waters has led to an increase in the incidence of algal blooms and the consequent increased risk of microcystin contamination of water resources. The removal of microcystins LR, YR and YA from contaminated water was investigated using an experimental laboratory-scale photocatalytic 'falling film' reactor in which an oxygen purge, UV radiation and semiconductor titanium dioxide (TiO2) catalyst were used to oxidatively decompose the microcystin pollutants. Preliminary studies, using algal extracts spiked into distilled water, indicated that the microcystins were rapidly decomposed in this reactor. The decomposition followed first order reaction kinetics with half-lives of less than 5 min with the reactor operating in a closed-loop mode. Reaction rates were strongly dependent on the amount of TiO2 catalyst (O-5 g/l), but only marginally influenced by a change in gas purge from oxygen to compressed air. The use of lake water, rather than distilled water, showed that this process is feasible in natural waters, although increased levels of catalyst (up to 5 g/l) were required to achieve comparable decomposition rates.
First report of microcystins in Taiwan.
Lee TH, Chen YM, Chou HN.Toxicon. 1998 Feb;36(2):247-55.
Department of Zoology, National Taiwan University, Taipei, ROC.
This is the first report on microcystins from Microcystis aeruginosa Kutzing in Taiwan. A total of nine strains of cyanobacteria have been isolated from eutrophic aquaculture ponds and water reservoirs. By mouse toxicity assay, six of the nine strains had LD100 in the range of 25-100 mg per kg mouse for dried bacterial mass. Microcystin-LR and -RR were found in all toxic strains and their contents ranged from 0.11-10.06 microg and 0.08 2.21 microg per mg of dried bacteria, respectively. Microcystin-RA, a minor component found only in M. TN-2 and M. CY-1 strains, was identified as a new microcystin. All three toxins were isolated by a serial separation on an LH-20 column, Si-flash column chromatography and reverse phase HPLC. Toxins were further identified by comparing their FABMS, 1H and 1H-1H COSY NMR spectra with the authentic microcystin-LR. Several other microcystin-like compounds were also found in the cultured strains and their structures are being determined.
Should nature be standardized?
Grant KL, Benda W.Am J Health Syst Pharm. 1999 Oct 1;56(19):1927.
Hepatotoxin (microcystin) and neurotoxin (anatoxin-a) contained in natural blooms and strains of cyanobacteria from Japanese freshwaters.
Park HD, Watanabe MF, Harda K, Nagai H, Suzuki M, Watanabe M, Hayashi H.Nat Toxins. 1993;1(6):353-60.
Department of Hygiene, School of Medicine, Shinshu University, Matsumoto, Japan.
Amounts of hepatotoxic microcystin and neurotoxic anatoxin-a were estimated in natural blooms and strains of cyanobacteria from freshwaters in Japan. A simultaneous analysis method of anatoxin-a and microcystin was applied to natural bloom samples, which has been dominated by several species and the strains of cyanobacteria which produced simultaneously both toxins. The natural blooms examined in the present study were mainly composed of Anabaena and Oscillatoria, but most also contained Microcystis and other cyanobacteria. Only one sample was almost unialgal, Anabaena spiroides, collected from Lake Sagami. The toxins in 14 samples collected from nine different natural blooms during 1988-1992 were identified as microcystins-RR, -YR, and -LR; desmethyl-7-microcystin-LR (7-DMLR); and anatoxin-a. Microcystins were the main toxins contained in these natural blooms, with anatoxin-a not being detected or of very little quantity. 7-DMLR was detected in samples only from Lake Kasumigaura. Five strains of Anabaena isolated from waters in Japan produced a small amount of anatoxin-a, but no microcystins. One half of the strains of Microcystis produced microcystins and/or anatoxin-a. This is the first study showing Microcystis producing both anatoxin-a and microcystins.
Simple and efficient method for isolation and measurement of cyanobacterial hepatotoxins by plant tests (Sinapis alba L.).
Kos P, Gorzo G, Suranyi G, Borbely G.Anal Biochem. 1995 Feb 10;225(1):49-53.
Institute of Plant Biology, Biological Research Center, Szeged, Hungary.
A simple and cost-effective method for isolating and assaying microcystins, cyanobacterial toxins, by C-18 cartridges, DEAE-cellulose (DE-52) chromatography, and a mustard (Sinapis alba L.) plant seedling test is described. The procedure results in a purity of up to 95-97% microcystin without the need for an HPLC system and justifies the use of the S. alba L. seedling test in the quantitative assessment of the toxin with an IC50 of 3 micrograms ml-1 instead of the mouse intraperitoneal test.
Microwave oven and boiling waterbath extraction of hepatotoxins from cyanobacterial cells.
Metcalf JS, Codd GA.FEMS Microbiol Lett. 2000 Mar 15;184(2):241-6.
Department of Biological Sciences, University of Dundee, Dundee, UK.
Low-cost, straightforward methods for the extraction of microcystins and nodularins from cyanobacterial cells were developed using a microwave oven and boiling waterbath. The use of organic solvents, such as methanol, which can interfere with sensitive analytical procedures, e.g. immunoassays, can thus be avoided. Analysis by protein phosphatase inhibition assay and high performance liquid chromatography indicated that purified microcystin-LR was unaffected by the microwave oven and boiling waterbath treatments. Four microcystins of differing hydrophobicities were successfully extracted from Microcystis PCC 7813 by both treatments at yields equivalent to those obtained by longer protocols using methanol. Assessment of the microwave oven and boiling waterbath extraction methods with laboratory strains and environmental samples of cyanobacteria showed good correlation with results from lyophilisation and methanol extraction, when extracts were analysed by high performance liquid chromatography with diode array detection (R(2)>/=0.92). The microwave and boiling waterbath extraction methods also sterilised the environmental bloom samples, as evidenced by the abolition of heterotrophic bacterial growth.
Generation of antibodies directed against the low-immunogenic peptide-toxins microcystin-LR/RR and nodularin.
Baier W, Loleit M, Fischer B, Jung G, Neumann U, Weiss M, Weckesser J, Hoffmann P, Bessler WG, Mittenbuhler K.Int J Immunopharmacol. 2000 May;22(5):339-53.
Institut fur Immunbiologie der Universitat, Stefan-Meier-Str. 8, D-79104, Freiburg, Germany.
The preparation of antibodies against the liver toxin microcystin, as described here, is of major importance for its detection and purification in food and water, and for a therapeutic approach to neutralize the toxin by passive immunization. Microcystin-LR (MLR) and microcystin-RR (MRR) were purified from cyanobacterial cell materials by extraction, Sephadex LH-20-, ODS silica gel-, ionic exchange and RP-HPLC-chromatography. In order to reduce the toxicity for parenteral administration, microcystins were coupled by the carbodiimide method to poly-L-lysine (PLL(50.000)). Mice and rabbits were immunized with the conjugates in the presence of two lipopeptide immunoadjuvants (P(3)CSK(4) and P(3)CS-T(h)). High MLR-specific antibody levels were observed after parenteral coadministration of antigen and lipopeptides, whereas no anti-MLR antibodies were obtained with free microcystin or the microcystin-PLL(50.000)-conjugate in the absence of lipopeptide. In oral immunization, coadministration of antigen and adjuvants resulted in an accelerated development of anti MLR-specific antibodies and high antibody levels. Using the antisera, we could detect different microcystins and nodularin down to a concentration range of 10-50 ng/ml by a competitive inhibition ELISA; detection of microcystins in crude cell preparations was also possible. Furthermore, microcystins from different sources could be detected and discriminated from cyclic cyanopeptolines.
Betz JM.J AOAC Int. 1999 May-Jun;82(3):781-4.
U.S. Food and Drug Administration, Division of Natural Products, Washington, DC 20204, USA.
Insertional mutagenesis of a peptide synthetase gene that is responsible for hepatotoxin production in the cyanobacterium Microcystis aeruginosa PCC 7806.
Dittmann E, Neilan BA, Erhard M, von Dohren H, Borner T.Mol Microbiol. 1997 Nov;26(4):779-87.
Institute for Biology (Genetics), Humboldt University, Berlin, Germany.
Several bloom-forming cyanobacterial genera produce potent inhibitors of eukaryotic protein phosphatases called microcystins. Microcystins are hepatotoxic cyclic heptapeptides and are presumed to be synthesized non-ribosomally by peptide synthetases. We identified putative peptide synthetase genes in the microcystin-producing strain Microcystis aeruginosa PCC 7806. Non-hepatotoxic strains of M. aeruginosa lack these genes. Strain PCC 7806 was transformed to chloramphenicol resistance. The antibiotic resistance cassette insertionally inactivated a peptide synthetase gene of strain PCC 7806 as revealed by Southern hybridization and DNA amplification. This is the first report of genetic transformation and mutation, by homologous recombination, of a bloom-forming cyanobacterium. Chemical and enzymatic analyses, including high-performance liquid chromatography (HPLC), mass spectrometry, amino acid activation, and protein phosphatase inhibition, revealed the inability of derived mutant cells to produce any variant of microcystin while maintaining their ability to synthesize other small peptides. The disrupted gene therefore encodes a peptide synthetase (microcystin synthetase) that is specifically involved in the biosynthesis of microcystins. Our results confirm that microcystins are synthesized non-ribosomally and that a basic difference between toxic and non-toxic strains of M. aeruginosa is the presence of one or more genes coding for microcystin synthetases.
Cytotoxicity of cyanobacterium Microcystis aeruginosa.
Henning K, Cremer J, Meyer H.Zentralbl Veterinarmed [B]. 1992 Jun;39(4):307-10.
Institute of Microbiology, Federal Armed Forces, Medical Academy, Munich.
Cytotoxic effects of crude extracts and fractions of the purification steps towards Microcystin-LR (MCYST-LR) were investigated in vitro. Cytotoxicity was evaluated by measure of lactate dehydrogenase liberation of Chang liver cells and by hemolysis. Crude extracts of strain PCC 7806 damaged the cells within a few minutes. In contrast, MCYST-LR did not show any detectable cytotoxic effects. The cytotoxic activity could be related to a heat-labile substance with a molecular weight of about 30,000 Da.
Microcystin-LR toxicodynamics, induced pathology, and immunohistochemical localization in livers of blue-green algae exposed rainbow trout (oncorhynchus mykiss).
Fischer WJ, Hitzfeld BC, Tencalla F, Eriksson JE, Mikhailov A, Dietrich DR.Toxicol Sci. 2000 Apr;54(2):365-73.
Environmental Toxicology, University of Konstanz, Germany.
With this retrospective study, we investigated the temporal pattern of toxin exposure and pathology, as well as the topical relationship between hepatotoxic injury and localization of microcystin-LR, a potent hepatotoxin, tumor promoter, and inhibitor of protein phosphatases-1 and -2A (PP), in livers of MC-gavaged rainbow trout (Oncorhynchus mykiss) yearlings, using an immunohistochemical detection method and MC-specific antibodies. H&E stains of liver sections were used to determine pathological changes. Nuclear morphology of hepatocytes and ISEL analysis were employed as endpoints to detect the advent of apoptotic cell death in hepatocytes. Trout had been gavaged with lyophilized cyanobacteria (Microcystis aeruginosa, strain PCC 7806) at acutely toxic doses of 5700 microg microcystin (MC) per kg of body weight (bw), as described previously (Tencalla and Dietrich, 1997). Briefly, 3 control and 3 test animal were killed 1, 3, 12, 24, 48, and 72 h after bolus dosing, and livers were fixed and paraffin embedded for histological analysis and later retrospective histochemical analyses. The results of the immunohistochemistry reported here revealed a time dependent, discernible increase in MC-positive staining intensity throughout the liver, clearly not concurring with the kinetics of hepatic PP inhibition observed in the same fish and reported in an earlier publication by Tencalla and Dietrich (1997). After 3 h, marked and increasing MC-immunopositivity was observed in the cytoplasm, as well as the nuclei of hepatocytes. Apoptotic cell death could be detected after 48 h, at the very earliest. These data suggest that accumulation of MC and subsequent changes in cellular morphology, PP inhibition, and hepatocyte necrosis represent the primary events in microcystin induced hepatotoxicity and appear to be associated with the reversible interaction of MC with the PP. In contrast, apoptotic cell death, as demonstrated here, seems to be of only secondary nature and presumably results from the covalent interaction of MC with cellular and nuclear PP as well as other thiol containing cellular proteins.
Hepatic necrosis in sheep associated with ingestion of blue-green algae.
Done SH, Bain M.Vet Rec. 1993 Dec 11;133(24):600.
Central Veterinary Laboratory, New Haw, Addlestone, Surrey.
Immuno-gold localization of hepatotoxins in cyanobacterial cells.
Shi L, Carmichael WW, Miller I.Arch Microbiol. 1995 Jan;163(1):7-15.
Department of Biological Sciences, Wright State University, Dayton, OH 45435.
A polyclonal antibody against the potent hepatotoxic cyclic peptide microcystins and nodularins was used in conjunction with immuno-gold labelling to localize the toxins in three strains of cyanobacteria. Ultrastructurally, there were no major differences between unicellular Microcystis aeruginosa strain PCC 7820 (toxin-producing strain) and M. aeruginosa strain UTEX 2063 (non-toxin-producing strain), except that M. aeruginosa PCC 7820 cells had a sheath. The thickness of the sheath was about 12 nm and was distinguishable from the cell wall at the ultrastructural level only when the specimen was stained en bloc with uranyl acetate. Microcystins and nodularin were found in M. aeruginosa PCC 7820 and Nodularia spumigena strain L-575 respectively, but not in nontoxic M. aeroginosa UTEX 2063. In M. aeruginosa PCC 7820 cells, microcystin was found primarily in the thylakoid area and nucleoid, with smaller amounts in the cell wall and sheath. Only nonspecific labelling was found in other cellular inclusions, such as polyhedral bodies, cyanophycin granules and membrane-limited inclusions. In strain N. spumigena L-575, nodularin was found in both vegetative cells and heterocysts with a distribution similar to that in M. aeruginosa PCC 7820.
First report on the identification of microcystin in a water bloom collected in Belgium.
Wirsing B, Hoffmann L, Heinze R, Klein D, Daloze D, Braekman JC, Weckesser J.Syst Appl Microbiol. 1998 Mar;21(1):23-7.
Institut fur Biologie II, Mikrobiologie, Albert-Ludwigs-Universitat, Freiburg, Germany. email@example.com
A toxic cyanobacterial bloom dominated by Microcystis aeruginosa occurred in 1995 in three adjacent ponds near Liege (Belgium) where at the same time conspicuous bird deaths were observed. The toxicity assay using primary rat hepatocytes indicated a high hepatoxicity. A 4 h incubation yielded a LD50 of 0.23 mg bloom material (dry weight)/ml cell culture medium. Toxicity was due to hepatotoxins of the microcystin class, microcystin-LR and-RR being the major microcystins present as determined by RP-HPLC absorption spectra, 1H NMR, and ESMS spectra. Additionally, the bloom sample contained small amounts of microcystin-YR. The microcystin content of the dry bloom biomass was 870 micrograms/g (on the basis of the hepatotoxicity assay) and 556 micrograms/g (on the basis of the RP-HPLC peak area). A higher yield of microcystins was obtained by acetic acid extraction instead of methanol extraction, whereas different extraction temperatures (20 degrees C, 40 degrees C) had no effect on the yield.
Toxicosis due to microcystin hepatotoxins in three Holstein heifers.
Fitzgerald SD, Poppenga RH.J Vet Diagn Invest. 1993 Oct;5(4):651-3.
Department of Pathology, College of Veterinary Medicine, Michigan State University, East Lansing 48824.
The identification and toxicity of the microcystin in the waterbloom obtained from an eutrophied lake.
Xu JK, Liu YF, Zhu HG, Ding WX.Biomed Environ Sci. 2000 Jun;13(2):97-104.
Department of Environment Health, Shanghai Medical University, China.
The water of "J" lake has been seriously eutrophied; concentration of total nitrogen (TN), total phosphorus (TP) and chlorophyll a were all far above the 3rd level of the National Standard of Ground Water of China. The concentration of microcystin (MCYST) of the water at one site (M) was 1865 micrograms/l. There were 2.36 micrograms MCYST-LR per mg dry waterbloom powder.
Raw animal tissues and dietary supplements.
Norton SA.N Engl J Med. 2000 Jul 27;343(4):304-5.
Monitoring of microcystin-protein phosphatase adduct formation with immunochemical methods.
Liu BH, Yu FY, Huang X, Chu FS.Toxicon. 2000 May;38(5):619-32.
Department of Food Microbiology & Toxicology, University of Wisconsin-Madison 53706, USA.
Using anti-microcystin-LR monoclonal antibodies, an immunoblotting procedure was developed to monitor the formation of microcystin-protein phosphatase adducts in vitro and in vivo. The detection limits for the covalent binding of MCYST-LR with the recombinant protein phosphatase 1 (PP1) and rabbit liver cytosol proteins were found to be 0.1 ng and 0.3 ng per assay, respectively. MCYST-PP1 adducts were detected 30 s after the addition of MCYST-LR into the reaction mixture. Reduction of the methyldehydroalanine (Mdha) residue of MCYST-LR with ethanethiol totally abolished the covalent binding of the toxin to PP1, but retained its inhibitory toxicity on PP1. Immunoblotting analyses and enzyme-linked immunosorbant assay showed that between 5 min to 16 h after i.p. injection of single dose (35 microg/kg) of MCYST-LR into mice, approximately 0-27% of the injected toxin was found covalently bound while 0.2-9.2% existed as free form in liver cytosol.
Detection of microcystins, a blue-green algal hepatotoxin, in drinking water sampled in Haimen and Fusui, endemic areas of primary liver cancer in China, by highly sensitive immunoassay.
Ueno Y, Nagata S, Tsutsumi T, Hasegawa A, Watanabe MF, Park HD, Chen GC, Chen G, Yu SZ.Carcinogenesis. 1996 Jun;17(6):1317-21.
Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
An epidemiological survey for the causes of a high incidence of primary liver cancer (PLC) in Haimen city, Jian-Su province and Fusui county, Guangxi province in China, found a close correlation between the incidence of PLC and the drinking of pond and ditch water. With an aim to clarify whether microcystins (MC), a hepatotoxic peptide produced by water bloom algae, contaminate the drinking water in the endemic areas of PLC in China, a highly sensitive enzyme-linked immunosorbent assay with a detection limit of 50 pg/ml, was introduced to monitor the MC. Three trials to survey the drinking water were carried out in 1993-1994. Samples, 1135 in total, were collected from different sources such as: ponds, ditches, rivers, shallow wells and deep wells in Haimen city. The first survey in September 1993 found that three out of 14 ditch water specimens were positive for MC, with a range of 90-460 pg/ml. Several toxic algae such as Oscillatoria agardhii were present in some of the ditches. In the second trial, samples were collected from five ponds/ditches, two rivers, two shallow wells and two deep wells monthly for the whole year of 1994. These data showed that MC was highest in June to September, with a range of 62-296 pg/ml. A third trial on the 989 different water samples collected from the different types of water sources in July 1994 revealed that 17% of the pond/ditch water, 32% of the river water, and 4% of the shallow-well water were positive for MC, with averages of 101, 160 and 68 pg/ml respectively. No MC was detected in deep well water. A similar survey on 26 drinking water samples in Fusui, Guangxi province, demonstrated a high contamination frequency of MC in the water of ponds/ditches and rivers but no MC in shallow and deep wells. These data support a hypothesis that the blue-green algal toxin MC in the drinking water of ponds/ditches and rivers, or both, is one of the risk factors for the high incidence of PLC in China. Based on previous findings on the epidemiology of PLC and the present results from the mass screening of MC in the drinking water, an advisory level of MC in drinking water was proposed to below 0.01 microg/l. The combined effect of a potent hepatocarcinogen AFB1 and an intermittent intake of MC in drinking water in the summer season was discussed as an etiology of PLC.
Isolation and identification of eight microcystins from thirteen Oscillatoria agardhii strains and structure of a new microcystin.
Luukkainen R, Sivonen K, Namikoshi M, Fardig M, Rinehart KL, Niemela SI.Appl Environ Microbiol. 1993 Jul;59(7):2204-9.
Department of Applied Chemistry and Microbiology, University of Helsinki, Finland.
Microcystins (cyclic heptapeptide hepatotoxins), isolated from 13 freshwater Oscillatoria agardhii strains from eight different Finnish lakes by high-performance liquid chromatography, were characterized by amino acid analysis, fast atom bombardment mass spectrometry (FABMS), and tandem FABMS (FABMS/collisionary-induced dissociation/MS). All strains produced two to five different microcystins. In total, eight different compounds, of which five were known microcystins, were isolated. The known compounds identified were [D-Asp3]MCYST (microcystin)-LR, [Dha7]MCYST-LR, [D-Asp3]MCYST-RR, [Dha7]MCYST-RR, and [D-Asp3,Dha7]MCYST-RR. This is the first time that isolation of these toxins from Oscillatoria spp., with the exception of [D-Asp3]MCYST-RR, has been reported. Three of the strains produced a new microcystin, and the structure was assigned as [D-Asp3,Mser7]MCYST-RR. The structures of two new microcystins, produced as minor components by one Oscillatoria strain, could not be determined because of the small amounts isolated from the cells. Four strains produced [Dha7]MCYST-RR as the main toxin, but [D-Asp3]MCYST-RR was clearly the most abundant and most frequently occurring toxin among these isolates of O. agardhii.
Possible cause of unnatural mass death of wild birds in a pond in Nishinomiya, Japan: sudden appearance of toxic cyanobacteria.
Matsunaga H, Harada KI, Senma M, Ito Y, Yasuda N, Ushida S, Kimura Y.Nat Toxins. 1999;7(2):81-4.
School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
During the summer of 1995, about 20 spot-billed ducks died unnaturally in a pond (Shin-ike) in Nishinomiya, Hyogo Prefecture, Japan. The suspected cause was the sudden appearance of toxic freshwater bloom of cyanobacteria. However, no birds died in a nearby pond (Oo-ike) in which the cyanobacteria was also present. Morphological observation of these cyanobacteria by microscope revealed that they were almost unialgal and were both Microcystis aeruginosa. The lyophilized algal cell powder from Shin-ike contained large amounts of microcystins which showed acute toxicity for mouse, while that from Oo-ike had only a very small amount of microcystin-RR which did not show acute toxicity. Autopsy of one of the birds revealed that the liver was necrotic and severely jaundiced with a dark green color, suggesting the toxicity of the microcystins. These results point to the cause of the unnatural death of spot-billed ducks in Shin-ike as being the sudden appearance of toxic Microcystis aeruginosa. This was due to eutrophication of the pond, following the influx of untreated sewage related to damage from the Great Hanshinn Earthquake of January 1995. This is the first experimental report of toxic cyanobacteria being implicated in the mass death of wild birds in Japan.Copyright 1999 John Wiley & Sons, Ltd.
Characterization of heptapeptide toxins extracted from Microcystis aeruginosa (Egyptian isolate). Comparison with some synthesized analogs.
Abdel-Rahman S, el-Ayouty YM, Kamael HA.Int J Pept Protein Res. 1993 Jan;41(1):1-7.
Chemistry Department, Faculty of Science, Zagazig University, Egypt.
Four toxic peptides from local fresh water cyanobacterium Microcystis aeruginosa were purified and identified by high performance liquid chromatography (HPLC) and ion spray mass spectroscopic studies as: RR; YR; LR and LA with molecular weights of 1006.8, 1073, 984.8 and 910.6 respectively. Amino acid analysis indicated the presence of equimolar amounts of aspartic acid, glutamic acid, arginine, leucine and tyrosine, in addition to both alanine and dehydroalanine. Mouse assay toxicity indicated that the first two peptides, at the peak area of RR, YR, were highly toxic with LD50 20, 18.2 micrograms/kg body weight; however, the latter two, at the peak areas LR and LA, have a lesser toxicity with LD50 36 and 40 micrograms/kg body weight respectively. Three linear peptide analogs to those naturally found devoid of Adda were synthesized using the continuous flow technique. HPLC pure synthesized analog products were tested for toxicity using male mice (i.p. injection). None of them induced toxic activity.
[Natural poisons: (1) Algae toxins].
Ueno Y, Nagata S.J Toxicol Sci. 1994 Aug;19(3):App75-84.
[Article in Japanese]
An ultrasensitive competitive binding assay for the detection of toxins affecting protein phosphatases.
Serres MH, Fladmark KE, Doskeland SO.Toxicon. 2000 Mar;38(3):347-60.
Department of Anatomy and Cell Biology, University of Bergen, Norway.
An ultrasensitive assay is described for microcystin-LR and other substances (microcystins, nodularin, okadaic acid, calyculin A, tautomycin) which block the active site of protein phosphatases (PP) 1 and 2A. The assay is based on competition between the unknown sample and [125I]microcystin-YR for binding to the catalytic subunit of PP2A. The PP2A-bound [125I]microcystin-YR was stable (half-time of dissociation = 1.8 h), allowing non-bound [125I]microcystin-YR to be removed by Sephadex G-50 size-exclusion chromatography. Compared to current assays based on inhibition of protein phosphatase activity the present assay was more robust against interference (from fluoride, ATP, histone, and casein), and had an even better sensitivity. The detection limit was below 50 pM (2.5 fmol) for nodularin and microcystin-LR, and below 200 pM (10 fmol) for okadaic acid. The method was used successfully to detect extremely low concentrations of either microcystin or nodularin in drinking water or seawater, and okadaic acid in shellfish extract.
The toxicity of cyanobacterial toxins in the mouse: I microcystin-LR.
Fawell JK, Mitchell RE, Everett DJ, Hill RE.Hum Exp Toxicol. 1999 Mar;18(3):162-7.
WRc National Centre for Environmental Toxicology, Medmenham, Bucks, England.
Blooms of cyanobacteria or blue-green algae are known to have caused poisoning in fish, waterfowl, animals and man. One of the toxins responsible for this is the hepatotoxin microcystin-LR which has been found to occur in blooms present intermittently in sources used for domestic water supplies. Three sets of experiments were undertaken to investigate the acute toxicity of microcystin-LR in mice and rats by the oral and intraperitoneal routes, the potential for effects on foetal development in the mouse, and the effects of repeated oral dosing over 13 weeks in the mouse. The results of this work were as follows: (1) Microcystin-LR is 30-100 times less toxic via oral ingestion than via intraperitoneal injection; (2) Microcystin-LR is not a selective developmental toxicant in the mouse. There was a No Observed Adverse Effect Level (NOAEL) of 600 microg kg(-1) bodyweight per day given on days 6-15 of pregnancy for any form of developmental toxicity; (3) There was a clear NOAEL for tissue damage in the liver of 40 microg kg(-1) bodyweight per day of microcystin-LR. Using this data, a value of 1 microg l(-1) microcystin-LR would be an appropriate guideline value for drinking water.
Seven new microcystins possessing two L-glutamic acid units, isolated from Anabaena sp. strain 186.
Namikoshi M, Yuan M, Sivonen K, Carmichael WW, Rinehart KL, Rouhiainen L, Sun F, Brittain S, Otsuki A.Chem Res Toxicol. 1998 Feb;11(2):143-9.
Department of Ocean Sciences, Tokyo University of Fisheries, Japan. firstname.lastname@example.org
Electrospray ionization mass spectrometry has been applied to the structure assignment of seven new microcystins (1-7), obtained from cultured Anabaena sp. strain 186. The seven new microcystins contain the dehydroalanine (Dha) or L-Ser unit instead of the N-methyldehydroalanine unit and the L-Glu and/or its delta-methyl ester [E(OMe)] units at the two variable L-amino acid units, and the structures were assigned as [Dha7]microcystin-E(OMe)E(OMe) (1), [D-Asp3,Dha7]microcystin-E(OMe)E(OMe) (2), [L-Ser7]microcystin-E(OMe)E(OMe) (3), [D-Asp3,L-Ser7]microcystin-E(OMe)E(OMe) (4), [Dha7]microcystin-EE(OMe) (5), [D-Asp3,Dha7]microcystin-EE(OMe) (6), and [L-Ser7]microcystin-EE(OMe) (7). These microcystins are the first examples containing dicarboxylic amino acids at the two variable L-amino acid units in microcystins.
[Effect of the toxigenic strains of cyanobacterium Microcystis aeruginosa on the larvae of the common frog].
Gromov BV, Mamkaeva KA, Filatova EV.Dokl Akad Nauk. 1997 Sep;356(3):422-3.
[Article in Russian]
[Cyanobacteria, their toxins and health risks].
Thebault l, Lesne J, Boutin JP.Med Trop (Mars). 1995;55(4):375-80.
[Article in French]
Service de Medecine des Collectivites, l'Hopital d'Instruction des Armees Clermont-Tonnerre, Brest, France.
Cyanobacteria (blue-green algae) commonly occur in fresh and brackish water where they produce blooms under certain environmental and climatic conditions. Since some species produce neurotoxins, hepatotoxins, cytotoxins, and endotoxins, blooms can be hazardous for animal and human health. Several cases of human cyanobacterial poisoning have been documented, but accurate assessment of the risk is difficult for lack of knowledge concerning exposure levels and the incidence of this kind of poisoning. Most human cases have been reported after oral consumption of contaminated drinking water or swimming in recreation waters where blooms have occurred. Further study is needed to evaluate and manage this risk, especially in regions dependent on surface water for drinking and recreational water areas. This is especially true in tropical and intertropical areas where climatic conditions promote occurrence of cyanobacteria blooms and nothing is known of the impact on public health.
Toxins and genetically modified food.
Trewavas A.Lancet. 2000 Mar 11;355(9207):931.
The adsorption of microcystin-LR by natural clay particles.
Morri RJ, Williams DE, Luu HA, Holmes CF, Andersen RJ, Calvert SE.Toxicon. 2000 Feb;38(2):303-8.
Department of Chemistry, University of British Columbia, Vancouver, Canada.
The microcystin cyanobacterial hepatotoxins represent an increasingly severe global health hazard. Since microcystins are found world wide in drinking water reservoirs concern about the impact on human health has prompted investigations into remedial water treatment methods. This preliminary study investigates the scavenging from water of microcystin-LR by fine-grained particles known to have a high concentration of the clay minerals kaolinite and montmorillonite. The results show that more than 81% of microcystin-LR can be removed from water by clay material. Thus, microcystin-LR is indeed scavenged from water bodies by fine-grained particles and that this property may offer an effective method of stripping these toxins from drinking water supplies.
Fatal microcystin intoxication in haemodialysis unit in Caruaru, Brazil.
Pouria S, de Andrade A, Barbosa J, Cavalcanti RL, Barreto VT, Ward CJ, Preiser W, Poon GK, Neild GH, Codd GA.Lancet. 1998 Jul 4;352(9121):21-6.
Institute of Urology and Nephrology, University College London Medical School, UK.
BACKGROUND: After a drought in February, 1996, all 126 patients in a haemodialysis unit in Caruaru, north-east Brazil, developed signs and symptoms of acute neurotoxicity and subacute hepatotoxicity following the use of water from a lake with massive growth of cyanobacteria (blue-green algae). 60 patients died. METHODS: Besides recording clinical details and outcome at follow-up, we arranged laboratory, radiological, and histological investigations on the patients and toxicological studies of serum and haemodialysis water filters. FINDINGS: The acute presentation was with malaise, myalgia and weakness, nausea and vomiting, and tender hepatomegaly, with a range of neurological symptoms from tinnitus, vertigo, headaches, and deafness to blindness and convulsions. Liver injury ranged from abnormal liver-function test results to rapidly progressive and fatal hepatic failure. Biochemical investigations revealed gross hyperbilirubinaemia, abnormal liver enzyme activities, and hypertriglyceridaemia, but there was no evidence of haemolysis or microangiopathy. Histology revealed a novel acute toxic hepatitis with diffuse panlobular hepatocyte necrosis, neutrophil infiltration, canalicular cholestasis, and regenerative multinucleate hepatocytes. Samples of serum, dialysis filters, and water-treatment columns contained microcystins, the highly toxic low-molecular-weight hepatotoxins produced by cyanobacteria. INTERPRETATION: Cyanobacteria present water-borne hazards to health via drinking water and recreational water. Haemodialysis presents an additional high-risk exposure route: when they enter directly into the circulation, microcystins can lead to fatal clinical syndromes ranging from acute neurotoxic illness to subacute liver failure.
Enzymatic pathway for the bacterial degradation of the cyanobacterial cyclic peptide toxin microcystin LR.
Bourne DG, Jones GJ, Blakeley RL, Jones A, Negri AP, Riddles P.Appl Environ Microbiol. 1996 Nov;62(11):4086-94.
Department of Biochemistry, University of Queensland, St. Lucia, Australia.
An isolated bacterium, identified as a new Sphingomonas species, was demonstrated to contain a novel enzymatic pathway which acted on microcystin LR, the most common cyanobacterial cyclic peptide toxin. Degradation of microcystin LR was mediated by at least three intracellular hydrolytic enzymes. The use of classic protease inhibitors allowed (i) the classification of these enzymes into general protease families and (ii) the in vitro accumulation of otherwise transient microcystin LR degradation products. The initial site of hydrolytic cleavage of the parent cyclic peptide by an enzyme that we designate microcystinase is at the 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid (Adda)-Arg peptide bond. Two intermediates of microcystin LR enzymatic degradation have been identified; one is linearized (acyclo-) microcystin LR, NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-Leu-beta-methylas partate-Arg-OH, and the other is the tetrapeptide NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-OH. The intermediate degradation products were less active than the parent cyclic peptide; the observed 50% inhibitory concentrations for crude chicken brain protein phosphatase were 0.6 nM for microcystin LR, 95 nM for linear LR, and 12 nM for the tetrapeptide. These linear peptides were nontoxic to mice at doses up to 250 micrograms/kg. Ring opening of the potent hepatotoxin microcystin LR by bacterial microcystinase effectively renders the compound nontoxic by dramatically reducing the interaction with the target protein phosphatase.
Katan MB.Lancet. 1999 Sep 4;354(9181):794.
Wageningen Centre for Food Sciences and Division of Human Nutrition and Epidemiology, Wageningen Agricultural University, The Netherlands.
A biochemical profile for predicting the chronic exposure of sheep to Microcystis aeruginosa, an hepatotoxic species of blue-green alga.
Carbis CR, Simons JA, Mitchell GF, Anderson JW, McCauley I.Res Vet Sci. 1994 Nov;57(3):310-6.
La Trobe University, Department of Botany, Victoria, Australia.
Sheep which grazed on the shoreline of a fresh-water lake which had a toxic bloom of Microcystis aeruginosa were studied for evidence of chronic poisoning, and a serum biochemical profile was developed to indicate sub-lethal, chronic poisoning in the sheep which had been exposed to microcystins. The profile included measurements of glutamate dehydrogenase (GLDH), gamma-glutamyl transferase (gamma GT), bile acids, bilirubin and albumin. Of 18 sheep which were exposed to M aeruginosa for more than three months, 100 per cent had high serum concentrations of bile acids, 94 per cent had high activities of GLDH and gamma GT, 83 per cent had high bilirubin and 72 per cent had low albumin concentrations compared with the median values of unexposed animals. Other sheep which were exposed for shorter periods, showed evidence of hepatic injury after one week of exposure. The majority of the sheep showed no preference for an alternative, uncontaminated source of water.
Toxicology and risk assessment of freshwater cyanobacterial (blue-green algal) toxins in water.
Duy TN, Lam PK, Shaw GR, Connell DW.Rev Environ Contam Toxicol. 2000;163:113-85.
Faculty of Environmental Sciences, Griffith University, Nathan, Queensland, Australia.
The occurrence of cyanobacterial toxins affects aquatic organisms, terrestrial animals (both wild and domestic), and humans. Detrimental effects have been documented in the scientific literature during the past 50 years. Possible guideline values of some cyanobacterial toxins (microcystins, cylindrospermopsin, and anatoxin-a) are estimated, and they show that children and infants are more susceptible to cyanobacterial toxins than adults. Therefore, particular attention should be paid when cyanobacterial blooms occur, even at relatively low cell counts, to protect children and infants from possible risks. Based on these guideline values and the occurrence of the toxins, it can be concluded that chronic and subchronic exposure to cyanobacterial toxins does occur in some populations, particularly in developing countries where high proportions of the population consume untreated surface water directly, such as pond, ditch, river, or reservoir water. Because wildlife and domestic animals consume a large amount of untreated water daily, they are at higher risk than humans from cyanobacterial toxins. Calculated guideline values in Section X show that a relatively high risk posed by the toxins to these animals is likely to occur, even at low cell densities.
Cyanobacterial toxins: removal during drinking water treatment, and human risk assessment.
Hitzfeld BC, Hoger SJ, Dietrich DR.Environ Health Perspect. 2000 Mar;108 Suppl 1:113-22.
Environmental Toxicology, University of Konstanz, Konstanz, Germany. email@example.com
Cyanobacteria (blue-green algae) produce toxins that may present a hazard for drinking water safety. These toxins (microcystins, nodularins, saxitoxins, anatoxin-a, anatoxin-a(s), cylindrospermopsin) are structurally diverse and their effects range from liver damage, including liver cancer, to neurotoxicity. The occurrence of cyanobacteria and their toxins in water bodies used for the production of drinking water poses a technical challenge for water utility managers. With respect to their removal in water treatment procedures, of the more than 60 microcystin congeners, microcystin-LR (L, L-leucine; R, L-arginine) is the best studied cyanobacterial toxin, whereas information for the other toxins is largely lacking. In response to the growing concern about nonlethal acute and chronic effects of microcystins, the World Health Organization has recently set a new provisional guideline value for microcystin-LR of 1.0 microg/L drinking water. This will lead to further efforts by water suppliers to develop effective treatment procedures to remove these toxins. Of the water treatment procedures discussed in this review, chlorination, possibly micro-/ultrafiltration, but especially ozonation are the most effective in destroying cyanobacteria and in removing microcystins. However, these treatments may not be sufficient during bloom situations or when a high organic load is present, and toxin levels should therefore be monitored during the water treatment process. In order to perform an adequate human risk assessment of microcystin exposure via drinking water, the issue of water treatment byproducts will have to be addressed in the future.
Detection of an anatoxin-a(s)-like anticholinesterase in natural blooms and cultures of cyanobacteria/blue-green algae from Danish lakes and in the stomach contents of poisoned birds.
Henriksen P, Carmichael WW, An J, Moestrup O.Toxicon. 1997 Jun;35(6):901-13.
Department of Phycology, University of Copenhagen, Denmark.
Ten natural bloom samples of cyanobacteria from the Danish lakes Knud so (5), Ravn so (4), and Salten Langso (1) collected during 1993-1995 were assayed for toxicity by mouse bioassay, for acetylcholinesterase inhibiting activity by a colorimetric method, and for microcystins by enzyme-linked immunosorbent assay. In the mouse bioassay, seven samples were neurotoxic, two were non-toxic and one gave a protracted toxic response. One of the non-toxic and the single protracted toxic sample both contained anticholinesterase activity equivalent to 4 micrograms anatoxin-a(s) g-1. The neurotoxic samples contained equivalents to 20-3300 micrograms anatoxin-a(s) g-1. The highest anticholinesterase activities (equivalent to 2300 and 3300 micrograms anatoxin-a(s) g-1, respectively) were found in samples collected from Lake Knud so in connection with bird-kills in 1993 and 1994. Small amounts of microcystins (0.1-0.9 microgram g-1) were detected in all samples but one. All Lake Knud so and Lake Ravn so samples were dominated by Anabaena lemmermannii, and the Lake Salten Langso sample by several species of Anabaena. Gel filtration profiles indicated similarity between the toxic component from the Lake Knud so 1994 bloom with registered bird-kills and anatoxin-a(s) isolated from Anabaena flos-aquae NRC-525-17. Anticholinesterase-producing cultures of A. lemmermannii were isolated from the Lake Knud so 1993 bloom. These laboratory cultures produced anatoxin-a(s) equivalents of 29-743 micrograms g-1. Other cultures of A. lemmermannii isolated from Lake Knud so and Lake Ravn so were hepatotoxic or non-toxic. Dead birds collected from Lake Knud so during the neurotoxic 1993 Anabaena bloom possibly died from cyanobacterial toxicosis. The stomach contents contained colonies and single trichomes of Anabaena, and anticholinesterase activities equivalent to 2.1-89.7 micrograms anatoxin-a(s) kg-1 body weight and microcystins (53-95 ng kg-1) were also detected.
Microcystin uptake inhibits growth and protein phosphatase activity in mustard (Sinapis alba L.) seedlings.
Kurki-Helasmo K, Meriluoto J.Toxicon. 1998 Dec;36(12):1921-6.
Department of Biochemistry and Pharmacy, Abo Akademi University, Turku, Finland.
Mustard (Sinapis alba L.) seeds were cultivated for seven days on a solid nutrient medium supplemented with 040 microg microcystin-RR per ml. Microcystin-RR affected seedling growth (IC50 0.8 microg/ml) and microcystin concentrations > or =5.0 microg/ml produced malformed plants. The inhibition of protein phosphatase 1 and 2A activity correlated with the growth inhibition. The seedlings were also shown to take up 3H-dihydromicrocystin-LR derived radioactivity up to a level corresponding to ca. 80 ng toxin per mg plant protein.
Natural health products get own directorate at Health Canada.
Gray C.CMAJ. 2000 Jul 11;163(1):77.
SAMe: a dietary remedy for mind and body?
Cerrato PL, Rowell N.RN. 1999 Dec;62(12):61-2, 64.
Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, Westchester Medical Center, City University of New York, USA.
14C-labeled microcystin-LR administered to Atlantic salmon via intraperitoneal injection provides in vivo evidence for covalent binding of microcystin-LR in salmon livers.
Williams DE, Craig M, Dawe SC, Kent ML, Andersen RJ, Holmes CF.Toxicon. 1997 Jun;35(6):985-9.
Department of Chemistry, University of British Columbia, Vancouver, Canada.
The tissue distribution and clearance of radiolabeled microcystin-LR administered to Atlantic salmon via i.p. injection has been re-examined using uniformly 14C-labeled toxin. Significant differences were found to exist between these results and those obtained when fish received an i.p. injection of tritium-labeled dihydromicrocystin-LR. In addition, MeOH liver extracts were assayed by both phosphatase assay and 14C counts and the results compared with the total levels of incorporation determined by digestion and subsequent 14C counting of the same live tissues. An attempt to investigate the metabolism and to document the putative products was also undertaken. It was found that microcystin-LR was extensively metabolized to compounds that are more polar than the parent compound.
Variation of microcystin content of microcystis aeruginosa relative to medium N:P ratio and growth stage.
Lee SJ, Jang MH, Kim HS, Yoon BD, Oh HM.J Appl Microbiol. 2000 Aug;89(2):323-9.
Environmental Bioresources Laboratory, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea.
Changes in the microcystin content of Microcystis aeruginosa UTEX 2388 were investigated at several N:P ratios of the medium and various growth stages. Under the P-fixed condition, the microcystin content of the cells changed with different medium N:P ratios, with the highest at 2748 microg g-1 at a N:P ratio of 16 after incubation for 7 d. The microcystin content of M. aeruginosa exhibited a high correlation with the total N content regardless of an N-fixed or P-fixed culture. When the N:P ratio of the medium was fixed to 16 : 1, the microcystin content of M. aeruginosa at various growth stages was highest at 2191 &mgr;g g-1 after an incubation of 4 d and the chlorophyll-a content showed a similar tendency. There was a highly significant relationship between the microcystin content of M. aeruginosa and the chlorophyll-a concentration in the culture during the incubation. Accordingly, the microcystin content of M. aeruginosa during incubation can be easily estimated and monitored by measuring the in vivo fluorescence changes in the culture.
Cyanobacterial toxins in Portugal: effects on aquatic animals and risk for human health.
Vasconcelos VM.Braz J Med Biol Res. 1999 Mar;32(3):249-54.
Departamento de Zoologia e Antropologia, Faculdade de Ciencias do Porto, Universidade do Porto, Portugal.
Toxic cyanobacteria are common in Portuguese freshwaters and the most common toxins are microcystins. The occurrence of microcystin-LR (MCYST-LR) has been reported since 1990 and a significant number of water reservoirs that are used for drinking water attain high levels of this toxin. Aquatic animals that live in eutrophic freshwater ecosystems may be killed by microcystins but in many cases the toxicity is sublethal and so the animals can survive long enough to accumulate the toxins and transfer them along the food chain. Among these, edible mollusks, fish and crayfish are especially important because they are harvested and sold for human consumption. Mussels that live in estuarine waters and rivers where toxic blooms occur may accumulate toxins without many significant acute toxic effects. In this study data are presented in order to understand the dynamics of the accumulation and depuration of MCYST-LR in mussels. The toxin is readily accumulated and persists in the shellfish for several days after contact. In the crayfish the toxin is accumulated mainly in the gut but is also cleared very slowly. In carps, although the levels of the toxins found in naturally caught specimens were not very high, some toxin was found in the muscle and not only in the viscera. This raises the problem of the toxin accumulation by fish and possible transfer through the food chain. The data gathered from these experiments and from naturally caught specimens are analyzed in terms of risk for human consumption. The occurrence of microcystins in tap water and the incidence of toxic cyanobacteria in fresh water beaches in Portugal are reported. The Portuguese National Monitoring Program of cyanobacteria is mentioned and its implications are discussed.
Variation of microcystins, cyanobacterial hepatotoxins, in Anabaena spp. as a function of growth stimuli.
Rapala J, Sivonen K, Lyra C, Niemela SI.Appl Environ Microbiol. 1997 Jun;63(6):2206-12.
Department of Applied Chemistry and Microbiology, University of Helsinki, Finland.
Cyanobacterial hepatotoxins, microcystins, are specific inhibitors of serine/threonine protein phosphatases and potent tumor promoters. They have caused several poisonings of animals and also pose a health hazard for humans through the use of water for drinking and recreation. Different strains of the same cyanobacterial species may variously be nontoxic, be neurotoxic, or produce several microcystin variants. It is poorly understood how the amount of toxins varies in a single strain. This laboratory study shows the importance of external growth stimuli in regulating the levels and relative proportions of different microcystin variants in two strains of filamentous, nitrogen-fixing Anabaena spp. The concentration of the toxins in the cells increased with phosphorus. High temperatures (25 to 30 degrees C), together with the highest levels of light studied (test range, 2 to 100 mumol m-2 s-1), decreased their amount. Different structural variants of microcystins responded differently to growth stimuli. Variants of microcystin (MCYST)-LR correlated with temperatures below 25 degrees C, and those of MCYST-RR correlated with higher temperatures. Nitrogen added into the growth medium and increasing temperatures increased the proportion of microcystin variants demethylated in amino acid 3. All variants remained mostly intracellular. Time was the most important factor causing the release of the toxins into the growth medium. Time, nitrogen added into the growth medium, and light fluxes above 25 mumol m-2 s-1 significantly increased the concentrations of the dissolved toxins. According to the results, it thus seems that the reduction of phosphorus loads in bodies of water might play a role in preventing the health hazards that toxic cyanobacterial water blooms pose, not only by decreasing the cyanobacteria but also by decreasing their toxin content.
Larvicidal microcystin toxins of cyanobacteria affect midgut epithelial cells of Aedes aegypti mosquitoes.
Saario E, Abdel-Hameed A, Kiviranta J.Med Vet Entomol. 1994 Oct;8(4):398-400.
Department of Pathology, College of Veterinary Medicine, University of Helsinki, Finland.
Microcystins (cyanobacterial toxins) in drinking water enhance the growth of aberrant crypt foci in the mouse colon.
Humpage AR, Hardy SJ, Moore EJ, Froscio SM, Falconer IR.J Toxicol Environ Health A. 2000 Oct 13;61(3):155-65.
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
Microcystis aeruginosa produces toxic cyclic peptides called microcystins, potent hepatotoxins that have been implicated in tumor promotion in skin and liver. The model used in this investigation was the azoxymethane (AOM)-induced aberrant crypt focus (ACF) in the male C57Bl/6J mouse colon. Three intraperitoneal (i.p.) injections of 5 mg/kg AOM were administered at 7-d intervals to mice; 19 d after the last AOM injection, drinking water containing Microcystis extract was commenced and continued for a further 212 d. The content of microcystins in the drinking water was determined by mouse bioassay, high-performance liquid chromatography (HPLC), capillary eletrophoresis, and protein phosphatase inhibition. The doses employed were 0, 382, and 693 micrograms/kg bodyweight/d at the midpoint of the trial. Following postmortem examination blood cells, serum enzymes and organ pathology were investigated. A significant microcystin dose-dependent increase in the area of aberrant crypt foci was observed. There was no marked increase in the number of crypts/colon. Two overt colonic tumors (approximately 30 mm3) were seen in microcystin-treated mice, and one microscopic colonic tumor in an AOM-alone-treated mouse. This investigation provides the first evidence for the stimulation of preneoplastic colon tumor growth by microcystin.
Preference of mice to consume Microcystis aeruginosa (toxin-producing cyanobacteria): a possible explanation for numerous fatalities of livestock and wildlife.
Lopez Rodas V, Costas E.Res Vet Sci. 1999 Aug;67(1):107-10.
Genetica, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, 28040, Spain.
Cyanobacteria often produce severe illness and in some cases spectacular fatality on livestock and wildlife world-wide. Heavy cyanobacterial waterblooms usually form patches of dense surface scum, and terrestrial animals drinking such concentrated dirty froth can consume a fatal dose. Surprisingly, animals do not avoid swallowing concentrated microbial scum. Different experiments of drink selection were performed with laboratory mice to determine why animals drink these concentrated scum. These experiments showed that animals elected to consume dense cultures of the toxic cyanobacteria Microcystis aeruginosa in preference to limpid water. When M. aeruginosa cells were supplied ad libitum, mice avidly swallowed these toxic cyanobacteria until this led to their death. Mice were unable to detect the phycotoxin (microcystin). In contrast, mice did not select cultures containing other non-toxic phytoplanktonic organisms. Observations in nature suggest that this preference in the consumption of toxic cyanobacteria is common among other animal species.Copyright 1999 Harcourt Publishers Ltd.
Production of an emetic toxin, cereulide, is associated with a specific class of Bacillus cereus.
Agata N, Ohta M, Mori M.Curr Microbiol. 1996 Jul;33(1):67-9.
Nagoya City Public Health Research Institute, Japan.
The emetic toxin (cereulide) of Bacillus cereus was quantified in several isolates of B. cereus and in various food sources. When the emetic toxin was produced, vomiting-type food poisoning was observed in humans. We also found that the H-1 serovar phenotype was strongly associated with the production of cereulide and that none of the isolates that hydrolyzed starch or expressed diarrheal enterotoxin activity produced cereulide.
Hepatic ultrastructural changes induced by the toxin microcystin-LR (MCLR) in mice.
Hermansky SJ, Markin RS, Fowler EH, Stohs SJ.J Environ Pathol Toxicol Oncol. 1993 Apr-Jun;12(2):101-6.
Creighton University Health Sciences Center, Omaha, NE 68178.
Microcystin-LR (MCLR) is a cyclic heptapeptide produced by the blue-green algae Microcystis aeruginosa. It is highly toxic and causes death in rodents due to hypovolemic shock with associated intrahepatic hemorrhage. The molecular mechanism of toxicity is unknown. In order to provide additional information regarding the toxicity of MCLR, the ultrastructural changes present in livers of mice following the administration of 100 micrograms MCLR/kg intraperitoneally, (i.p.) were examined. Time-dependent changes were observed. Disruption of cell to cell contact occurred with infiltration of erythrocytes 60 min after MCLR treatment. Hepatocyte distortion, mitochondrial aggregation, and the prominent accumulation of large areas of endoplasmic reticulum were observed. No detectable hepatic changes in sinusoidal endothelial cells were present. The results suggest that MCLR preferentially affects hepatocytes, although the observations do not preclude the involvement of hepatic vasculature in the toxicity of MCLR.
Detection and quantification of microcystins (cyanobacterial hepatotoxins) with recombinant antibody fragments isolated from a naive human phage display library.
McElhiney J, Lawton LA, Porter AJ.FEMS Microbiol Lett. 2000 Dec 1;193(1):83-8.
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, UK.
Single-chain antibody fragments against the cyanobacterial hepatotoxin microcystin-LR were isolated from a naive human phage display library and expressed in Escherichia coli. In competition enzyme-linked immunosorbent assay (ELISA), the most sensitive antibody clone selected from the library detected free microcystin-LR with an IC(50) value of 4 microM. It was found to cross react with three other microcystin variants - microcystin-RR, microcystin-LW and microcystin-LF - and detected microcystins in extracts of the cyanobacterium Microcystis aeruginosa, found to contain the toxins by high-performance liquid chromatography (HPLC). The quantification of microcystins in these extracts by ELISA and HPLC showed good correlation. Although the antibody isolated in this study was considerably less sensitive than the polyclonal and monoclonal antibodies already available for microcystin detection, phage display technology represents a cheaper, more rapid alternative for the production of anti-microcystin antibodies than the methods currently in use.
Joint FAO/WHO Geneva consultation--acute dietary intake methodology.
Crossley SJ.Food Addit Contam. 2000 Jul;17(7):557-62.
Australia New Zealand Food Authority, Barton ACT, Australia. firstname.lastname@example.org
Significant developments have been made at the international level in the methodology for conducting dietary risk assessments. The existing chronic exposure assessment methodology has been updated so that it takes account of the level of residues to which consumers are most likely to be exposed. In addition, short-term exposure assessment methodology has also been developed. This uses portion size data and takes account of the variability in residue levels between individual units where this is appropriate to the way the commodity is consumed. Other refinements to the assessment can also be made. Although the short-term methodology has been used successfully by a number of regulatory authorities, there is a need for data on portion sizes and typical unit weights before it can be fully implemented internationally.
Oral dietary supplements before and after surgery.
Hessov I.Nutrition. 2000 Sep;16(9):776.
Department of Surgery, Aarhus University Hospital, Denmark.
Lead in calcium supplements.
Scelfo GM, Flegal AR.Environ Health Perspect. 2000 Apr;108(4):309-19.
Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA. email@example.com
Intercalibrated measurements of lead in calcium supplements indicate the importance of rigorous analytical techniques to accurately quantify contaminant exposures in complex matrices. Without such techniques, measurements of lead concentrations in calcium supplements may be either erroneously low, by as much as 50%, or below the detection limit needed for new public health criteria. In this study, we determined the lead content of 136 brands of supplements that were purchased in 1996. The calcium in the products was derived from natural sources (bonemeal, dolomite, or oyster shell) or was synthesized and/or refined (chelated and nonchelated calcium). The dried products were acid digested and analyzed for lead by high resolution-inductively coupled plasma-mass spectrometry. The method's limit of quantitation averaged 0.06 microg/g, with a coefficient of variation of 1.7% and a 90-100% lead recovery of a bonemeal standard reference material. Two-thirds of those calcium supplements failed to meet the 1999 California criteria for acceptable lead levels (1.5 microg/daily dose of calcium) in consumer products. The nonchelated synthesized and/or refined calcium products, specifically antacids and infant formulas, had the lowest lead concentrations, ranging from nondetectable to 2.9 microg Pb/g calcium, and had the largest proportion of brands meeting the new criteria (85% of the antacids and 100% of the infant formulas).
Health effects of exposure to cyanobacteria (blue-green algae) during recreational water-related activities.
Pilotto LS, Douglas RM, Burch MD, Cameron S, Beers M, Rouch GJ, Robinson P, Kirk M, Cowie CT, Hardiman S, Moore C, Attewell RG.Aust N Z J Public Health. 1997 Oct;21(6):562-6.
National Centre for Epidemiology and Population Health, Australian National University, Canberra. firstname.lastname@example.org
The aim of this study was to investigate effects on health of exposure to cyanobacteria as a result of recreational water activities. Participants, who were aged six years and over, were interviewed at water recreation sites in South Australia, New South Wales and Victoria on selected Sundays during January and February 1995. Telephone follow-up was conducted two and seven days later to record any subsequent diarrhoea, vomiting, flu-like symptoms, skin rashes, mouth ulcers, fevers and eye or ear irritations. On the Sundays of interview, water samples from the sites were collected for cyanobacterial cell counts and toxin analysis. There were 852 participants, of whom 75 did not have water contact on the day of interview and were considered unexposed. The 777 who had water contact were considered exposed. No significant differences in overall symptoms were found between the unexposed and exposed after two days. At seven days, there was a significant trend to increasing symptom occurrence with duration of exposure (P = 0.03). There was a significant trend to increasing symptom occurrence with increase in cell count (P = 0.04). Participants exposed to more than 5000 cells per mL for more than one hour had a significantly higher symptom occurrence rate than the unexposed. Symptoms were not correlated with the presence of hepatotoxins. These results suggest symptom occurrence was associated with duration of contact with water containing cyanobacteria, and with cyanobacterial cell density. The findings suggest that the current safety threshold for exposure of 20,000 cells per mL may be too high.
Bioaccumulation and clearance of microcystins from salt water mussels, Mytilus edulis, and in vivo evidence for covalently bound microcystins in mussel tissues.
Williams DE, Dawe SC, Kent ML, Andersen RJ, Craig M, Holmes CF.Toxicon. 1997 Nov;35(11):1617-25.
Department of Chemistry and Oceanography, University of British Columbia, Vancouver, Canada.
Over a period of 3 days saltwater mussels, Mytilus edulis, were fed a cyanobacteria, Microcystis aeruginosa, that contained a high concentration of microcystins. The mussels were killed on a periodic basis over the course of 2 months. Mussels were also collected at two sites were high levels of microcystins in tissues had been noted. A strategy based on the chemically unique nature of the C20 beta-amino acid, (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6- dienoic acid (Adda), portion of the microcystins was used in conjunction with a protein phosphatase (PPase) assay to analyse for both covalently bound microcystins and free microcystins in the mussel tissues. The mussel PPase assay results were compared with the Lemieux oxidation gas chromatography-mass spectrometry (GCMS) analysis. Less than 0.1% of the total microcystin burden in the mussel tissue was found to be extractable with MeOH. Thus, direct evidence was provided for the existence of covalently bound microcystins in mussel tissues in vivo. The mussels rapidly cleared the covalently bound microcystins when transferred to untreated seawater. Within 4 days the total microcystin burden dropped from a high of 336.9 (+/- 45.8) micrograms/g wet tissue to 11.3 (+/- 2.6) micrograms/g. After 4 days postexposure until completion of the experiment the total levels remained below the detection limits of the GCMS method. The levels of free microcystins, extracted with MeOH and detected by the PPase assay, fell from 204 ng/g wet tissue to a residual 14 ng/g over a 53 day postexposure period. Presumably the bound microcystin present in the mussel tissue exists as a covalent complex with the PP-1 and PP-2A enzymes. We conclude that in any shellfish monitoring program it is the total tissue microcystin burden that needs to be considered.
Neoplastic nodular formation in mouse liver induced by repeated intraperitoneal injections of microcystin-LR.
Ito E, Kondo F, Terao K, Harada K.Toxicon. 1997 Sep;35(9):1453-7.
Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan.
Neoplastic nodules were observed in mice liver treated with microcystin-LR (MCLR) by the intraperitoneal (i.p.) route over 28 weeks. After 100 i.p. injections of a sublethal dose (20 micrograms/kg) of MCLR, neoplastic nodules were observed without the use of an initiator. Multiple neoplastic nodules up to 5 mm in diameter were observed in the liver of mice in both groups, i.e. those injected 100 times i.p. and those injected 100 times with a 2 month withdrawal. The cysteine conjugate of MCLR was detected mainly in the affected livers. In contrast, when 80 micrograms/kg was orally administered 100 times, characteristic chronic injuries such as fibrous changes and nodule formation were not observed.
[Blue-green algae as a cause of human disease].
Martin PR.Tidsskr Nor Laegeforen. 1994 May 20;114(13):1531-3.
[Article in Norwegian]
Fylkeslegen i Buskerud, Drammen.
Blue-green algae can cause significant public health problems. There is an abundance of scientific literature on their effects, but much of it either reports laboratory studies of toxicological effects or discusses practical problems affecting water supply. There are many reports of poisonings of farm animals and wildlife, and a number of reports of adverse health effects in humans, but the effects of blue-green algae on human health do not seem to have attracted serious attention amongst practising physicians. It is probable that the occurrence of blue-green algae in algal blooms in the aquatic environment, often with production of toxins, will continue to increase as a result of human activity. It thus seems important that clinicians should become more aware of their effects. On this background the author briefly summarizes proven and potential adverse effects on health.
From herbal Prozac to Mark McGwire's tonic: how the Dietary Supplement Health and Education Act changed the regulatory landscape for health products.
Kaczka KA.J Contemp Health Law Policy. 2000 Summer;16(2):463-99.
First report on the distribution of orally administered microcystin-LR in mouse tissue using an immunostaining method.
Ito E, Kondo F, Harada K.Toxicon. 2000 Jan;38(1):37-48.
Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan.
The purpose of this study was to investigate the distribution of microcystin-LR (MCLR) orally administered to mice using an immunostaining method. MCLR was orally dosed at 500 microg/kg to aged Balb/C and ICR mice and their lethality was 23.9%. The former was more sensitive to MCLR than the latter, suggesting that oral toxicity by MCLR is related to the animal strains tested, although the pathological and immunostaining changes were essentially the same in both strains. According to this method the distribution of MCLR and related compounds were indicated as the red staining. Particularly, livers of dead aged mice were intensively stained. The main route of absorption was considered to be the small intestine because the villi contained a large amount of MCLR in both surface epithelial cells and lamina propria, resulting in erosion. The absorbed MCLR was contained in blood plasma and moved to the liver, lung, and heart, and finally to capillaries of the whole body. Excretion of MCLR was shown in the mucous from goblet cells in both the small intestine and large intestine.
Microcystin production by Microcystis aeruginosa in a phosphorus-limited chemostat.
Oh HM, Lee SJ, Jang MH, Yoon BD.Appl Environ Microbiol. 2000 Jan;66(1):176-9.
Environmental Microbiology Research Unit, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon 305-600, Korea. email@example.com
The production of microcystins (MC) from Microcystis aeruginosa UTEX 2388 was investigated in a P-limited continuous culture. MC (MC-LR, MC-RR, and MC-YR) from lyophilized M. aeruginosa were extracted with 5% acetic acid, purified by a Sep-Pak C(18) cartridge, and then analyzed by high-performance liquid chromatography with a UV detector and Nucleosil C(18) reverse-phase column. The specific growth rate (mu) of M. aeruginosa was within the range of 0.1 to 0.8/day and was a function of the cellular P content under a P limitation. The N/P atomic ratio of steady-state cells in a P-limited medium varied from 24 to 15 with an increasing mu. The MC-LR and MC-RR contents on a dry weight basis were highest at mu of 0.1/day at 339 and 774 microg g(-1), respectively, while MC-YR was not detected. The MC content of M. aeruginosa was higher at a lower mu, whereas the MC-producing rate was linearly proportional to mu. The C fixation rate at an ambient irradiance (160 microeinsteins m(-2) s(-1)) increased with mu. The ratios of the MC-producing rate to the C fixation rate were higher at a lower mu. Accordingly, the growth of M. aeruginosa was reduced under a P limitation due to a low C fixation rate, whereas the MC content was higher. Consequently, increases in the MC content per dry weight along with the production of the more toxic form, MC-LR, were observed under more P-limited conditions.
Effect of microcystin on growth of single species and on mixed natural populations of heterotrophic nanoflagellates.
Christoffersen K.Nat Toxins. 1996;4(5):215-20.
Freshwater Biological Laboratory, University of Copenhagen, Hillerod, Denmark.
Natural populations of heterotrophic nanoflagellates were reduced in numbers and in situ growth rates during a toxic Microcystis bloom in a eutrophic lake. Microcystin was found in the particulate phase (algae) and in the dissolved phase (water) with maximum concentrations of 414 micrograms g freeze-dried algal material-1 and 141 micrograms l-1 lake water, respectively. An average reduction in growth rates of 49% was found when comparing the growth estimates before and after the toxic bloom had peaked. Similar reductions were found in laboratory experiments when growing mixed flagellate populations from two different systems with microcystin, but without predators. Concentrations of 10 micrograms toxin 1-1 reduced the growth rates by 36-41% (significantly different from the controls) and 1 microgram toxin 1-1 reduced the growth rates by 24-28% (not significant). Thus, natural populations of heterotrophic nanoflagellates seem very sensitive to microcystin. The growth characteristic of two cultured species was also tested in the presence of microcystin. Both the cultured species, Heteromita globosa and Spumella sp., grew well at 1-10 micrograms microcystin 1-1 and Spumella sp. was able to grow at 50 micrograms microcystin 1-1. However, the growth curves indicate that the decline in numbers during the stationary phase occurred faster in the presence of microcystin. The ecological consequences of a highly sensitive protozoan community may be that larger zooplankton species (copepods and cladocerans) are affected by reduced availability of food.
Viability changes in human neutrophils and monocytes following exposure to toxin extracted from Aphanizomenon flos-aquae.
Barton LL, Foster EW, Johnson GV.Can J Microbiol. 1980 Feb;26(2):272-4.
An in vitro method for detecting toxin produced by Aphanizomenon flos-aquae is described. This procedure is more sensitive than the mouse toxicity test and is based on viability changes in human leukocytes.
NIH studying dietary supplements for arthritis.
[No authors listed].Mayo Clin Health Lett. 2000 Aug;18(8):4.
The frustrations of fighting foodborne disease.
Tamblyn SE.CMAJ. 2000 May 16;162(10):1429-30.
Department of Epidemiology and Biostatistics, University of Western Ontario, London. firstname.lastname@example.org
Development and evaluation of a PCR-microplate capture hybridization method for direct detection of verotoxigenic Escherichia coli strains in artificially contaminated food samples.
Cocolin L, Astori G, Manzano M, Cantoni C, Comi G.Int J Food Microbiol. 2000 Mar 10;54(1-2):1-8.
Dipartimento di Scienze degli Alimenti, Facolta' di Agraria, Universita' di Udine, Italy.
For the purpose of detecting, directly in food, verotoxigenic Escherichia coli, a microplate hybridization method for the detection of PCR products from the SLT I and SLT II genes, was developed and evaluated. Two pairs of primers and two probes, specific for the SLT I gene and for the SLT II gene, were designed and tested. For the strains containing both genes, two PCR products of different molecular weights were obtained, whereas when only one gene was present only one fragment resulted from PCR. The use of the biotin-labeled probes allowed the immobilization of the PCR products in the microtiter plate wells and by this means their detection was possible using an ELISA-based technique. Forty artificially contaminated and fifty naturally contaminated food samples were analyzed by using the PCR-microplate hybridization technique developed in this study. All the artificially contaminated food samples were positive, independently of the number of cells inoculated before the enrichment step, whereas the naturally contaminated food samples were all negative.
The Mayo Clinic doctor. Pass the Vitameatavegamin.
Hensrud DD.Fortune. 2000 Jul 10;142(2):310.
Adsorption of the cyanobacterial hepatotoxin microcystin-LR by a low-cost activated carbon from the seed husks of the pan-tropical tree, Moringa oleifera.
Warhurst AM, Raggett SL, McConnachie GL, Pollard SJ, Chipofya V, Codd GA.Sci Total Environ. 1997 Nov 27;207(2-3):207-11.
Department of Civil and Environmental Engineering, University of Edinburgh, UK.
A low-cost activated carbon from the pan-tropical multipurpose tree Moringa oleifera removes the cyanobacterial hepatotoxin microcystin-LR in quantitative amounts from water in batch adsorption trials. The potential of M. oleifera seed husk carbon for cyanobacterial toxin removal in drinking water treatment in tropical countries is discussed.
Degradation of the cyanobacterial hepatotoxin, nodularin, under light and dark conditions.
Twist H, Codd GA.FEMS Microbiol Lett. 1997 Jun 1;151(1):83-8.
Department of Biological Sciences, University of Dundee, Scotland, UK.
The stability of the cyanobacterial hepatotoxin, nodularin, was determined during the incubation of purified toxin, and in nodularin-containing cell-free extracts and whole filaments of the nodularin-producer, Nodularia spumigena in sunlight and darkness. Levels of purified nodularin in aqueous solution remained approximately constant throughout the 9-day trials under all conditions, but decreased in cell-free extracts and whole filaments when incubated under all conditions, with losses being greatest in full sunlight, intermediate in sunlight minus ultraviolet wavelengths and lowest in continuous darkness. Photodegradation and detoxification in Artemia salina bioassays occurred when purified nodularin was irradiated with ultraviolet wavelengths using a laboratory lamp.
Evidence for a covalently bound form of microcystin-LR in salmon liver and Dungeness crab larvae.
Williams DE, Craig M, McCready TL, Dawe SC, Kent ML, Holmes CF, Andersen RJ.Chem Res Toxicol. 1997 Apr;10(4):463-9.
Department of Chemistry, University of British Columbia, Vancouver, Canada.
The chemically unique nature of the C20 beta-amino acid (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6- dienoic acid (Adda) portion of the microcystins has been exploited to develop a strategy to analyze for the total microcystin-LR (1; see Figure 1) burden in salmon liver and crab larvae tissues. Lemieux oxidation of microcystin-LR (1) gives 2-methyl-3-methoxy-4-phenylbutanoic acid (2), a unique marker for the presence of microcystins. The butanoic acid 2 can be isolated and detected by GC/MS from the livers of Atlantic salmon that received an ip injection of microcystin-LR (1) and from tissues of wild-caught crab larvae. The Lemieux oxidation-GC/MS results are compared with those from MeOH extraction-PPase analysis. Only approximately 24% of the total microcystin-LR (1) burden in salmon liver tissue is found to be extractable with MeOH. Similarly, the Lemieux oxidation-GC/MS method detected 10,000-fold greater microcystin concentrations in Cypress Island Dungeness crab larvae than did the MeOH extraction-PPase method. The disparity in microcystin concentrations measured by the two methods is taken as direct evidence for the existence of covalently bound microcystins in vivo.
Hemagglutination method for detection of freshwater cyanobacteria (blue-green algae) toxins.
Carmichael WW, Bent PE.Appl Environ Microbiol. 1981 Jun;41(6):1383-8.
Strains of the freshwater cyanobacteria (blue-green algae) Anabaena flosaquae and Microcystis aeruginosa produced toxins that caused intermittent but repeated cases of livestock, waterfowl, and other animal deaths. They also caused illness, especially gastrointestinal, in humans. The most common group of toxins produced by these two species were peptide toxins termed microcystin, M. Aeruginosa type c, and anatoxin-c. A method was found to detect the toxins which utilizes their ability to cause agglutination of isolated blood cells from mice, rats, and humans. The method could detect the toxin in samples from natural algal blooms, laboratory cultures, and toxin extracts. The method consists of: (i) washing lyophilized cyanobacteria cells with physiological saline (0.9% NaCl), (ii) centrifuging the suspension and then mixing portions of the cell-free supernatant with equal volumes of saline-washed erythrocytes in V-shaped microtiter plates, (iii) allowing the mixture to stand for 3 to 4 h, and (iv) scoring the presence of the toxin as indicated by blood cell agglutination. Nontoxic strains, as determined by intraperitoneal mouse bioassay of cyanobacteria or green algae, did not produce an agglutination response.
Functional foods and health claims: a public health policy perspective.
Lawrence M, Rayner M.Public Health Nutr. 1998 Jun;1(2):75-82.
Division of Public Health and Primary Health Care, University of Oxford, UK. email@example.com
OBJECTIVE: To propose a policy framework for the regulation of functional foods and health claims within a public health context. DESIGN: This article reviews the empirical evidence and public health principles associated with functional foods and health claims to analyse the issues, challenge the assumptions that have emerged and explore options for moving forward. SETTING: Functional foods and health claims are among the more controversial and complex issues being debated by food regulators internationally. Proponents of functional foods and health claims state that functional foods may reduce health care expenditure and health claims are a legitimate nutrition education tool that will help them inform consumers of the health benefits of certain food products. Conversely, opponents of these developments respond that it is the total diet that is important for health, not so-called 'magic bullets'. Moreover, they argue that health claims will enable manufacturers to indulge in marketing hyperbole and essentially blur the distinction between food and drugs. This topic provides a valuable case study of public policy in relation to food and health. CONCLUSION: The need to maintain a general prohibition on health claims while accommodating specific exemptions supported by scientific substantiation is recommended. Nutrition education and monitoring and evaluation are integral to the proposed regulatory framework. The intention of this policy position is to encourage research and development of innovative food products while avoiding an inappropriate medicalization of the general food supply.
Teratology society: presentation to the FDA public meeting on safety issues associated with the use of dietary supplements during pregnancy.
Friedman JM.Teratology. 2000 Aug;62(2):134-7.
Department of Medical Genetics, University of British Columbia, Vancouver, Canada V6T 1Z2.
Uncertain quality of dietary supplements: history repeated.
Hasegawa GR.Am J Health Syst Pharm. 2000 May 15;57(10):951.
National standards for organic foods proposed.
[No authors listed].J Am Vet Med Assoc. 2000 May 1;216(9):1381.
Occurrence of aflatoxin M1 in Korean dairy products determined by ELISA and HPLC.
Kim EK, Shon DH, Ryu D, Park JW, Hwang HJ, Kim YB.Food Addit Contam. 2000 Jan;17(1):59-64.
Graduate School of Biotechnology, Korea University, Seoul, Korea.
The occurrence of aflatoxin M1 (AFM1) in pasteurized milk and dairy products was investigated by using direct competitive enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). The recoveries of AFM1 from the samples spiked at levels between 5 and 500 pg/ml were 88.0-106.5% for pasteurized milk and 84.0-94.0% for yoghurt by ELISA. By HPLC, the recoveries were 103-120% for pasteurized milk and 87.0-93.0% for yoghurt. The limits of detection were found to be 2 pg/ml by ELISA and 10 pg/ml by HPLC. Among a total of 180 samples collected in Seoul, Korea, the incidence of AFM1 in pasteurized milk, infant formula, powdered milk and yoghurt was 76, 85, 75, and 83%, respectively, with a mean concentration of 18, 46, 200, and 29 pg/g, respectively, when determined by ELISA. These results obtained by ELISA were closely related to those by HPLC for AFM1 (r2 = 0.9783).
Keeping up with the increasing popularity of nonvitamin, nonmineral supplements.
Hankin J.J Am Diet Assoc. 2000 Apr;100(4):419-20.
University of Hawaii at Manoa, Cancer Research Center of Hawaii, Honolulu 96813, USA.
National Public Health Week.
Ziskin LZ.N J Med. 2000 Mar;97(3):12.
Comparative toxicity of four microcystins of different hydrophobicities to the protozoan, Tetrahymena pyriformis.
Ward CJ, Codd GA.J Appl Microbiol. 1999 May;86(5):874-82.
Department of Biological Sciences, University of Dundee, UK.
Microcystins (MC) are a group of over 60 cyclic heptapeptide hepatotoxins produced by cyanobacteria. The 1-octanol/water partition coefficients (log P) of MC-LR, -LY, -LW and -LF have been estimated by HPLC to be 2.16, 2.92, 3.46 and 3.56, respectively. Their in vivo toxicities to Tetrahymena pyriformis was also investigated. Twenty-four hour LC50 values followed the order MC-LR > -LY > -LW approximately -LF. The LC50 values of MC-LR and -LY were significantly reduced in the presence of 1% (v/v) dimethylsulphoxide, although no significant effect occurred with MC-LW or -LF. Tetrahymena pyriformis respiration rates were inhibited by MC-LR in both a time- and dose-dependent manner. Increasing log P of the MC used caused a significantly greater inhibition of respiration. Population growth rate and maximum culture density were inhibited by all MC variants in proportion to log P. Positive correlations between all toxicological endpoints and log P occurred, with the most hydrophobic toxin, MC-LF, being 1.4 to 3.5 times more toxic than MC-LR. MC-LW had a similar toxicity to MC-LF, while MC-LY toxicity was intermediate between that of MC-LR and -LF. Implications of this positive relationship between in vivo toxicity and hydrophobicity for the toxicity of MC to aquatic organisms, and the potential for using log P as a descriptor in a quantitative structure-activity relationship for MC, are discussed.
A fluorescent microplate assay for microcystin-LR.
Fontal OI, Vieytes MR, Baptista de Sousa JM, Louzao MC, Botana LM.Anal Biochem. 1999 May 1;269(2):289-96.
Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, 27002, Spain.
A fluorescent enzyme inhibition assay for microcystin-LR was developed using a new fluorescent substrate of protein phosphatases 1 (PP1) and 2A (PP2A), 6,8-difluoro-4-methylumbelliferyl phosphate. The PP1 and PP2A inhibition assay for microcystin-LR was performed in a microtiter plate and the fluorescence yielded by the enzymatic hydrolysis of the substrate was quantified in a fluorescence plate reader. The concentration of microcystin-LR causing 50% inhibition of PP1 and PP2A activity (IC50) was 0.01 nM for PP1 and 0.08 nM for PP2A. The measurable range of microcystin-LR was 800 to 0.08 pg/well for both enzymes. The described assay is fast and very sensitive for the detection of microcystin-LR. Furthermore, this assay can be successfully applied to the study of toxins that inhibit PP1 or PP2A.Copyright 1999 Academic Press.
Formation of 3-amino-2,6,8-trimethyl-10-phenyldeca-4E,6E-dienoic acid from microcystin LR by the treatment with various proteases, and its detection in mouce liver.
Takenaka S.Chemosphere. 1998 Apr;36(10):2277-82.
Fukuoka Institute of Health & Environmental Sciences, Japan.
Microcystin LR metabolism in mammals was examined. The degradation of microcystin LR by the enzymes, pepsin, trypsin and chymotrypsin, from porcine or human gastrointestinal tract was examined. Microcystin LR was digested by these proteases, but 3-amino-2, 6, 8-trimethyl-10-phenyldeca-4E, 6E-dienoic acid (DmADDA) was not formed from microcystin LR treated with pepsin and chymotrypsin. The formation of DmADDA was detected from microcystin LR treated with trypsin. Furthermore, DmADDA was detected from the male ddY mice liver orally administered microcystin LR.
Assessment of rapid bioassays for detecting cyanobacterial toxicity.
Lahti K, Ahtiainen J, Rapala J, Sivonen K, Niemela SI.Lett Appl Microbiol. 1995 Aug;21(2):109-14.
National Board of Waters and the Environment, Helsinki, Finland.
Simple and easy-to-use bioassays with Artemia salina (brine shrimp) larvae, luminescent bacteria and Pseudomonas putida were evaluated for the detection of toxicity due to cyanobacterial hepato- and neurotoxins. The hepatotoxins and a neurotoxin, anatoxin-a, were extracted from laboratory-grown cultures and natural bloom samples by the solid phase fractionation method and dissolved in diluent for different bioassays. The toxin concentration of cyanobacterial extracts was determined with HPLC. The Artemia biotest appeared to be quite sensitive to cyanobacterial hepatotoxins, with LC 50 values of 3-17 mg l-1. The Artemia test was also shown to be of value for the detection of toxicity caused by anatoxin-a. The fractionated extract of anatoxin-a was not lethal to Artemia but it disturbed the ability of the larvae to move forwards. Filtered cyanobacterial cultures with anatoxin-a, on the other hand, caused mortality of Artemia larvae at concentrations of 2-14 mg l-1. With the solid phase fractionation of cyanobacterial samples, no non-specific toxicity due to compounds other than hepato- and neurotoxins was observed. In the luminescent bacteria test, the inhibition of luminescence did not correlate with the abundance of hepatotoxins or anatoxin-a. The growth of Ps. putida was enhanced, rather than inhibited by cyanobacterial toxin fractions.
Microcystic cyanobacteria extract induces cytoskeletal disruption and intracellular glutathione alteration in hepatocytes.
Ding WX, Shen HM, Ong CN.Environ Health Perspect. 2000 Jul;108(7):605-9.
Center for Environmental and Occupational Health, Department of Community, Occupational and Family Medicine, National University of Singapore.
Microcystins are a group of highly liver-specific toxins, although their exact mechanisms of action remain unclear. We examined the effects of microcystic cyanobacteria extract (MCE) collected from a contaminated water source on the organization of cellular microtubules (MTs) and microfilaments (MFs) in hepatocytes. We also investigated the effects on lactate dehydrogenase (LDH) leakage and intracellular glutathione (GSH). Primary cultured rat hepatocytes exposed to MCE (equivalent to 125 &mgr;g/mL lyophilized algae cells) showed a characteristic disruption of MTs and MFs in a time-dependent manner. Under these conditions, MCE caused aggregation of MTs and MFs and a severe loss of MTs in some cells. Moreover, MCE-induced cytoskeletal alterations preceded the LDH leakage. On the other hand, the treatment of cells with MCE led to a dose-dependent increase of intracellular GSH. However, time-course study showed a biphasic change of intracellular GSH levels with a significant increase in the initial stage followed by a decrease after prolonged treatment. Furthermore, pretreatment with N-acetylcystein (NAC), a GSH precursor, significantly enhanced the intracellular GSH level and decreased the MCE-induced cytotoxicity as well as cytoskeleton changes. In contrast, buthionine-(S, R)-sulfoximine, a specific GSH synthesis inhibitor, increased the cell susceptibility to MCE-induced cytotoxicity by depleting the intracellular GSH level. These findings suggest that intracellular GSH plays an important role in MCE-induced cytotoxicity and cytoskeleton changes in primary cultured rat hepatocytes. Increasing intracellular GSH levels protect cells from MCE-induced cytotoxicity and cytoskeleton changes.
FDA backs away from elements of plan to regulate ephedrine supplements.
[No authors listed].Am J Health Syst Pharm. 2000 May 15;57(10):922.
Study on the cytotoxicity of microcystin-LR on cultured cells.
Chong MW, Gu KD, Lam PK, Yang M, Fong WF.Chemosphere. 2000 Jul;41(1-2):143-7.
Department of Biology and Chemistry, Centre for Environmental Science, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, People's Republic of China.
The toxicity of purified blue-green algal toxin, microcystin-LR, on permanent cell lines KB, NIH/3T3, H-4-II-E, HeLa, Vero, Hep G2, Caco-2 and HL-60 was studied. Assessment of cell viability using colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays indicated that purified microcystin-LR induced toxic effect on KB and H-4-II-E cell lines after 96 h incubation at toxin concentrations greater than 18.75 microg/ml. KB cell line was selected for further study when reproducibility, consistency and sensitivity were considered. Significant amounts of lactate dehydrogenase (LDH) were released from KB cells when incubation durations were 72 and 96 h with toxin concentrations of 18.75 microg/ml and higher. Although previous studies suggested that microcystin-LR had no cytotoxic effect on permanent cell lines, LDH release assay performed on KB cells indicated that exposure to microcystin-LR could result in damage to the cell membrane.
Quail spleen is enlarged by microcystin RR as a blue-green algal hepatotoxin.
Takahashi S, Kaya K.Nat Toxins. 1993;1(5):283-5.
Division of Environmental Chemistry, National Institute for Environmental Studies, Tsukuba, Japan.
Toxic effects of microcystin RR as a blue-green algal hepatotoxin in laboratory quails were examined. In order to determine the microcystin RR LD50, purified microcystin RR was injected into the peritoneum of the quails. The value obtained was 256 micrograms/kg quail. Usually the quails died between 14 and 18 hr after the injection. After administration of the toxin, the quail spleens were enlarged to a doubling of the control spleens, whereas the lives did not change. These effects are quite different from those in mice and rats, indicating the toxic mechanism of the toxin in quails is different.
Lead in calcium supplements: cause for alarm or celebration?
Heaney RP.JAMA. 2000 Sep 20;284(11):1432-3.
Fein ER.RDH. 1999 Jul;19(7):42, 62.
[Challenges and updating in public health].
Hernandez Avila M.Salud Publica Mex. 2000 Jan-Feb;42(1):4-5.
[Article in Spanish]
National Institutes of Health Workshop on the Role of Dietary Supplements for Physically Active People. Bethesda, Maryland, USA. June 3-4, 1996. Proceedings.
[No authors listed].Am J Clin Nutr. 2000 Aug;72(2 Suppl):503S-674S.
Is there a difference between soy foods and soy supplements?
[No authors listed].Johns Hopkins Med Lett Health After 50. 2000 Sep;12(7):8.
Detection of microcystins using electrospray ionization high-field asymmetric waveform ion mobility mass spectrometry/mass spectrometry.
Ells B, Froese K, Hrudey SE, Purves RW, Guevremont R, Barnett DA.Rapid Commun Mass Spectrom. 2000;14(16):1538-42.
Department of Public Health Sciences, University of Alberta, Edmonton, AB, Canada T6G 2G3.
A combination of electrospray ionization, high-field asymmetric waveform ion mobility spectrometry, and mass spectrometry (ESI-FAIMS/MS) was used to analyze standard solutions of microcystins-LR, -RR, and -YR. The ability of FAIMS to separate ions in the gas phase reduced the amount of background in the mass spectrum without compromising the absolute signal for these microcystins. This reduction in background resulted in a ten-fold improvement in the signal-to-background ratio over conventional ESI-MS. Detection limits, using direct infusion, were determined to be 4, 2, and 1 nM for microcystins-LR, -RR, and -YR, respectively.Copyright 2000 John Wiley & Sons, Ltd.
Public health implications or urban agriculture.
Brown KH, Jameton AL.J Public Health Policy. 2000;21(1):20-39.
Department of Occupational Therapy, Creighton University, Omaha, Nebraska 68178, USA.
The article presents the case for stronger public policies in support of urban gardening as a means to improve public health. It considers several beneficial aspects of gardening, such as food security, economic development, exercise, psychological and community well-being, and environmental stewardship. It also considers some of the public health problems associated with urban agriculture and suggests policies to ameliorate them. In the balance, urban gardening has potential as an important element of urban public health.
The use and limitations of current 'standard' toxicological data packages in the setting of acute reference doses.
Dewhurst IC.Food Addit Contam. 2000 Jul;17(7):611-5.
To perform risk assessments for short term dietary intakes of pesticides it is necessary to determine an acceptable level of exposure from the available toxicity studies. This type of assessment is a relatively new development in regulatory toxicology and often the studies currently available are not optimal for such uses. The strengths and weaknesses of currently performed study types are presented. Consideration of the entire toxicity data base is essential.
Medicines availability--the millennium muddle.
Choraine P.Vet J. 2000 Jul;160(1):1-2.
Federation of Veterinarians of Europe, Brussels.
[Health-toxicologic aspects of some fungi].
Ochmanski W, Barabasz W.Przegl Lek. 2000;57(1):32-5.
[Article in Polish]
I Katedra i Klinika Chorob Wewnetrznych Collegium Medicum UJ w Krakowie.
Recent findings of fungi in food products of such renomed companies as Coca-Cola and Danone resulted in society-wide alert in Poland. Humans have contact with fungi everywhere. Every food product covered with mould or having marks of it should be discarded. We should mention that cutting of or skimming the mould is totally ineffective and dangerous, because of the fact that rest of the product will contain products of fungal metabolism such as mikotoxins, which are, of course, invisible. Modern food producing technologies effected in microorganism-free products, but sporadically we can find dead fungi debris due to improper washing procedures of multi-use bottles, like it was observed in Coca-Cola products. As for mould-covered cottage cheese type products of Danone, most probably reason was improper handling of ready, sealed products during transport and storage. Even minimal physical injuries to air-tight containers resulted in sporae penetration to milk products and finally contamination with mikotoxins.
Whittle K, Gallacher S.Br Med Bull. 2000;56(1):236-53.
Torry Research Ltd, Aberdeenshire, UK.
Seafood products are important both nutritionally and economically. Within Europe, some 12 billion Pounds of fishery products are consumed annually and an enormous variety of species are available. Although seafood is rarely implicated in food poisoning, compared to other food sources, it does provide some specific human health hazards unique to this particular resource. Generally, these are toxins from toxic microscopic algae which accumulate through the food-chain. The toxins can cause various neurological and gastrointestinal illnesses and, potentially, consumers are exposed from seafood produced within Europe, from imported products, or from seafood eaten while travelling abroad. The symptoms of illness which may be encountered, the source and mode of action of the toxins, and some emerging problems are described. European legislation aims to ensure the quality and safety of seafood products by prohibiting sale of some toxic species, setting toxin limits, requiring monitoring and controlling imports.
Herbal supplements and prescription drugs. A risky combination?
Stein K.J Am Diet Assoc. 2000 Apr;100(4):412.
Meat hygiene controls: new rules on enforcement.
[No authors listed].Vet Rec. 2000 Mar 11;146(11):298-9.
Blue-green alga Microcystis aeruginosa Kutz. in natural medium.
Kim BH, Choi MK, Chung YT, Lee JB, Wui IS.Bull Environ Contam Toxicol. 1997 Jul;59(1):35-43.
Institute for Environmental Science, Wonkwang University, Iksan 570-749, Korea.
Regulations on statements made for dietary supplements concerning the effect of the product on the structure or function of the body. Food and Drug Administration, HHS. Final rule.
[No authors listed].Fed Regist. 2000 Jan 6;65(4):1000-50.
The Food and Drug Administration (FDA) is issuing final regulations defining the types of statements that can be made concerning the effect of a dietary supplement on the structure or function of the body. The regulations also establish criteria for determining when a statement about a dietary supplement is a claim to diagnose, cure, mitigate, treat, or prevent disease. This action is intended to clarify the types of claims that may be made for dietary supplements without prior review by FDA and the types of claims that require prior authorization as health claims or prior approval as drug claims.
Aluminium levels in spices and aromatic herbs.
Lopez FF, Cabrera C, Lorenzo ML, Lopez MC.Sci Total Environ. 2000 Aug 10;257(2-3):191-7.
Department of Nutrition and Bromatology, School of Pharmacy, University of Granada, Spain.
We evaluated the levels of aluminium in a total of 72 samples of 17 different spices and aromatic herbs that are widely consumed in Spain, and in the Mediterranean diet, in general. Aluminium was determined in the samples mineralized with HNO3 and V2O5, using electrothermal atomization atomic absorption spectroscopy as the analytical technique. The accuracy and precision of the proposed method was verified against an NBS-certified reference material. Precision, expressed as relative standard deviation, ranged from 1.10 to 4.07%. The results obtained from recovery studies were of 97.90 +/- 1.20. Aluminium concentrations ranged from 3.74 to 56.50 microg/g (dry wt.). The presence of this metal was detected in all the samples we analysed.
Binding of aflatoxin B1 to bifidobacteria in vitro.
Oatley JT, Rarick MD, Ji GE, Linz JE.J Food Prot. 2000 Aug;63(8):1133-6.
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824, USA.
Aflatoxins are mycotoxins that cause health and economic problems when they contaminate food and feed. One potential method for reducing human health effects due to aflatoxin ingestion is to block uptake via binding by bacteria that either make up the normal gut flora or are present in fermented foods in our diet. These bacteria would bind aflatoxin and make it unavailable for absorption in the intestinal tract. Bifidobacteria comprise a large fraction of the normal gut flora, are thought to provide many probiotic effects and are increasingly used in fermented dairy products. These qualities targeted bifidobacteria for studies to determine if various strains of heat-killed bifidobacteria can bind aflatoxin B1 (AFB1) in vitro. The AFB1 binding affinities of various strains of bifidobacteria, Staphylococcus aureus, and Escherichia coli were quantitated utilizing enzyme-linked immunosorbent and [3H]AFB1 binding assays. The bacteria analyzed were found to bind significant quantities of AFB1 ranging from 25% to nearly 60% of the added toxin. The data also suggest that there are reproducible strain differences in AFB1 binding capacity.
Health food store recommendations for breast cancer patients.
Gotay CC, Dumitriu D.Arch Fam Med. 2000 Aug;9(8):692-9.
Cancer Research Center of Hawaii, Honolulu 96813, USA. firstname.lastname@example.org
CONTEXT: Despite cancer patients' widespread and growing use of complementary and alternative medicine, minimal attention has been paid to the role of health food stores in the "supply side" of this phenomenon. OBJECTIVE: To gain a better understanding of health food store personnel's recommendations for breast cancer patient care. DESIGN: Researcher posing as the daughter of a breast cancer patient and surveying health food store personnel on their product recommendations for cancer care. SETTING: Oahu, Hawaii, summer 1998. PARTICIPANTS: All health food stores (N = 40) offering products for cancer patients. MAIN OUTCOME MEASURES: Recommended products and services, proposed mechanism of action, and costs. RESULTS: Store personnel readily provided information and product recommendations, with shark cartilage being the most frequent. Suggested mechanisms of action drew on traditional healing, scientific, and pseudoscientific rationales. Costs for recommended dosages varied multifold across stores and brands. CONCLUSIONS: Retailers supplying supplements can play an important role in the network of "authorities" for patients with breast and other cancers, as they readily provide advice and recommend products. The reasons why patients seek health food store remedies are useful in developing approaches to patient education. Physicians and other providers are in a key position to assist cancer patients in making informed choices when considering health store products.
Elemental and radioactive analysis of commercially available seaweed.
van Netten C, Hoption Cann SA, Morley DR, van Netten JP.Sci Total Environ. 2000 Jun 8;255(1-3):169-75.
Department of Health Care and Epidemiology, University of British Columbia, Vancouver, Canada. email@example.com
Edible seaweed products have been used in many countries, specifically Japan, as a food item. Recently these products have become popular in the food industry because of a number of interesting medicinal properties that have been associated with certain edible marine algae. Very little control exists over the composition of these products, which could be contaminated with a number of agents including heavy metals and certain radioactive isotopes. Fifteen seaweed samples (six local samples from the coast of British Columbia, seven from Japan, one from Norway and one undisclosed) were obtained. All samples were analyzed for multiple elements, using ICP mass spectrometry and for radioactive constituents. It was found that six of eight imported seaweed products had concentrations of mercury orders of magnitude higher than the local products. Lead was found at somewhat higher concentrations in only one local product. Laminaria japonica had the highest level of iodine content followed by Laminaria setchellii from local sources. Only traces of cesium-137 were found in a product from Norway and radium-226 was found in a product from Japan. Arsenic levels were found to be elevated. In order to estimate the effect of these levels on health, one needs to address the bioavailability and the speciation of arsenic in these samples.
Getting political: racism and urban health.
Cohen HW, Northridge ME.Am J Public Health. 2000 Jun;90(6):841-2.
Health impairments arising from drinking water polluted with domestic sewage and excreta in China.
Ling B.Schriftenr Ver Wasser Boden Lufthyg. 2000;105:43-6.
Institute of Environmental Health & Engineering, Chinese Academy of Preventive Medicine, Beijing, China.
Raw water of poor quality still causes many drinking-water associated health problems all over China, largely because of poor sanitation, inadequate disposal of sewage and excreta. Eutrophication due to excess of total nitrogen and phosphorous in some sources for drinking-water has led to massive proliferation of cyanobacteria. The dominant species of cyanophyta can produce microcystins, a potent liver cancer promotor. As in previous studies, high incidence of liver cancer coincided with high microcystin concentration in the source water, especially in pond water. A frequent consequence of heavy pollution of source water is further the high incidence of infectious intestinal diseases, which are more than 10-100 times as frequent in China than in developed countries.
Once again, 140/90 is the goal.
Marwick C.JAMA. 2000 Jun 7;283(21):2778.
Content versus label claims in ephedra-containing dietary supplements.
Gurley BJ, Gardner SF, Hubbard MA.Am J Health Syst Pharm. 2000 May 15;57(10):963-9.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock 72205, USA. firstname.lastname@example.org
The content of ephedra alkaloids in herbal dietary supplements containing ephedra (ma huang) was studied. The ephedra alkaloid content of 20 ephedra-containing supplements was determined by high-performance liquid chromatography. Contents of (-)-ephedrine, (+)-pseudoephedrine, (-)-methylephedrine, (-)-norephedrine, and (+)-norpseudoephedrine were measured. Ephedra alkaloid content varied considerably among products. Total alkaloid content ranged from 0.0 to 18.5 mg per dosage unit. Ranges for (-)-ephedrine and (+)-pseudoephedrine were 1.1-15.3 mg and 0.2-9.5 mg, respectively. (+)-Norpseudoephedrine, a Schedule IV controlled substance, was often present. Significant lot-to-lot variations in alkaloid content were observed for four products. For one product, lot-to-lot variations in the content of (-)-ephedrine, (+)-pseudoephedrine, and (-)-methylephedrine exceeded 180%, 250%, and 1000%, respectively. Half of the products exhibited discrepancies between the label claim for ephedra alkaloid content and actual alkaloid content in excess of 20%. One product was devoid of ephedra alkaloids. Assay of 20 ephedra-containing dietary supplements showed that alkaloid content often differed markedly from label claims and was inconsistent between two lots of some products.
Influence of microcystine-YR and nodularin on the activity of some glucosidases in mouse liver.
Lankoff A, Kolataj A.Toxicology. 2000 May 5;146(2-3):177-85.
Division of Cell Biology, Institute of Biology, Pedagogical University, 25-406, Kielce, Poland.
Microcystine-YR (20 ug/kg bodyweight) and 8 ug/kg bodyweight of nodularin were intraperitoneally injected to 90 female Swiss mice. After 15, 30, 60 min and 24 h the changes were observed in the activity of some glucosidases in the complete cell homogenate and in the lysosomal, microsomal and cytosol fraction. Significant differences were connected with the time after administration of poison and with the cellular fraction. Nodularin induces the activity of beta-D-glucuronidase, alpha-glucosidase, lysosomal esterase and N-acetyl-glucosaminidase and influenced on the labilization of endoplasmatic reticulum membranes. Microcystine-YR inhibited the biosynthesis of glucosidases and revealed a destructive effect on membranes of lysosomes and endoplasmatic reticulum.
The food quality protection act: a public health perspective.
Sumner D.Neurotoxicology. 2000 Feb-Apr;21(1-2):183-8.
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA. email@example.com
The Food Quality Protection Act (FQPA) includes provisions to consider the combined risks of chemicals that have similar toxicological effects from all sources of exposure. The organophosphate (OP) insecticides are drawing a great deal of attention under this provision. Significant challenges for the regulatory activities at the EPA may develop. Environmentalists will apply political pressure to ban most of these products. Farmers may fear they will be unable to control pests and may exercise their own political muscle. The regulatory decisions in the dilemma may prove to be complex and difficult. Three areas of concern about potential adverse impacts of FQPA on public health are discussed; these include: diseases caused or carried by pests, increased natural toxins because of poor pest control, and increases in food costs because of regulatory action. It is important that the EPA consider not only the risks arising from the use of chemicals, but also the risks of not having those same chemicals.
Nonvitamin, nonmineral dietary supplements: issues and findings from NHANES III.
Radimer KL, Subar AF, Thompson FE.J Am Diet Assoc. 2000 Apr;100(4):447-54.
Applied Research Program, National Cancer Institute, Bethesda, MD 20892-7344, USA.
The Commission on Dietary Supplement Labels encourages nutrition professionals to become knowledgeable about all dietary supplements. The Dietary Supplement Health and Education Act of 1995 (DSHEA) expanded the definition of dietary supplements beyond essential nutrients while distinguishing them from drugs or food additives. In order to give practical advice to consumers and policymakers, dietetics professionals need to understand the implications resulting from this less-restrictive regulatory environment for supplements. Dietetics professionals must also become familiar with claims made by manufacturers, retailers, and others regarding popular nonvitamin, nonmineral (NVNM) supplements, as well as usage prevalence and trends. However, NVNM supplements currently are classified inconsistently, and information on the prevalence of use is limited. Sales data suggest that total intake is increasing, and garlic and ginseng are consistently among the most popular supplements. Reported use of NVNM supplements in the third National Health and Nutrition Examination Survey was highest for garlic and lecithin. The data suggest associations of NVNM supplement use with age and more healthful lifestyles; however, there is also a reported link with higher alcohol consumption and obesity. Associations with education, income, region, and urbanization are not evident from the sales data. Standardized survey procedures regarding question phraseology, referent time period, and supplement categorization--along with use of representative samples--will improve our ability to assess supplement use, prevalence, and trends.
Lead content of calcium supplements.
Ross EA, Szabo NJ, Tebbett IR.JAMA. 2000 Sep 20;284(11):1425-9.
End-Stage Renal Disease Program, Division of Nephrology, Hypertension, and Transplantation, University of Florida, Box 100224, Gainesville, FL 32610-0224, USA. Rossea@medicine.ufl.edu
CONTEXT: Substantial quantities of lead have been reported in some over-the-counter calcium supplement preparations, including not only bone-meal and dolomite, but also over-the-counter natural and refined calcium carbonate formulations. Examination of this issue is warranted given recent increases in physician recommendations for calcium supplements for prevention and treatment of osteoporosis. OBJECTIVES: To determine the lead content of calcium supplements and to quantify the lead exposure from popular brands of calcium in dosages used for childhood recommended daily allowance, osteoporosis, and phosphate binding in dialysis patients. DESIGN AND SETTING: Analysis of lead content in 21 formulations of nonprescription calcium carbonate (including 7 natural [ie, oyster shell] and 14 refined), 1 brand of prescription-only calcium acetate, and 1 noncalcium synthetic phosphate binder conducted in March 2000. MAIN OUTCOME MEASURES: Lead content, assayed using electrothermal atomic absorption, expressed as micrograms of lead per 800 mg/d of elemental calcium, per 1500 mg/d of calcium, and for a range of dosages for patients with renal failure. Six microg/d of lead was considered the absolute dietary limit, with no more than 1 microg/d being the goal for supplements. RESULTS: Four of 7 natural products had measurable lead content, amounting to approximately 1 microg/d for 800 mg/d of calcium, between 1 and 2 microg/d for 1500 mg/d of calcium, and up to 10 microg/d for renal dosages. Four of the 14 refined products had similar lead content, including up to 3 microg/d of lead in osteoporosis calcium dosages and up to 20 microg/d in high renal dosages. No lead was detected in the calcium acetate or polymer products. Lead was present even in some brand name products from major pharmaceutical companies not of natural oyster shell derivation. CONCLUSIONS: Despite increasingly stringent limits of lead exposure, many calcium supplement formulations contain lead and thereby may pose an easily avoidable public health concern. JAMA. 2000;284:1425-1429.
Competitive ELISA for bovine brucellosis suitable for testing poor quality samples.
Stack JA, Perrett LL, Brew SD, MacMillan AP.Vet Rec. 1999 Dec 18-25;145(25):735-6.
Veterinary Laboratories Agency, Weybridge, Surrey.
[The Alpbach Public Health Conference 1997. Proceedings].
[No authors listed].Gesundheitswesen. 2000 Apr;62(1 Suppl):S1-81.
[Article in German]
Kern A.Int J Sport Nutr Exerc Metab. 2000 Jun;10(2):vi-vii.
[Report on the use of radiation as intervention action in public health].
Atrian Salazar ML.Salud Publica Mex. 2000 Mar-Apr;42(2):162-4.
[Article in Spanish]
A call for glossaries in public health
Munoz-Baell I I, Alvarez-Dardet C.J Epidemiol Community Health. 2000 Aug;54(8):561.
Department of Linguistics and Literature, University of Alicante.
[Record as supplied by publisher]PMID: 10890863
Alternative medicine. Herbal product linked to cancer.
Greensfelder L.Science. 2000 Jun 16;288(5473):1946.
Bacterial protein toxins. An overview.
Alouf JE.Methods Mol Biol. 2000;145:1-26.
Institut Pasteur de Lille, France.
Proceedings of the workshop on possible health implications of the dioxin crisis.
Vanpoucke I, Willems J.Verh K Acad Geneeskd Belg. 2000;62(2):81-102.
[Cholesterol reducing health food products].
Rasmussen LB.Tidsskr Nor Laegeforen. 2000 Feb 28;120(6):736.
[Article in Norwegian]
Polyketide synthase gene coupled to the peptide synthetase module involved in the biosynthesis of the cyclic heptapeptide microcystin.
Nishizawa T, Ueda A, Asayama M, Fujii K, Harada K, Ochi K, Shirai M.J Biochem (Tokyo). 2000 May;127(5):779-89.
Division of Biotechnology, School of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan.
The peptide synthetase gene operon, which consists of mcyA, mcyB, and mcyC, for the activation and incorporation of the five amino acid constituents of microcystin has been identified [T. Nishizawa et al. (1999) J. Biochem. 126, 520-529]. By sequencing an additional 34 kb of DNA from microcystin-producing Microcystis aeruginosa K-139, we identified the residual microcystin synthetase gene operon, which consists of mcyD, mcyE, mcyF, and mcyG, in the opposite orientation to the mcyABC operon. McyD consisted of two polyketide synthase modules, and McyE contained a polyketide synthase module at the N-terminus and a peptide synthetase module at the C-terminus. McyF was found to exhibit similarity to amino acid racemase. McyG consisted of a peptide synthetase module at the N-terminus and a polyketide synthase at the C-terminus. The microcystin synthetase gene cluster was conserved in another microcystin-producing strain, Microcystis sp. S-70, which produces Microcystin-LR, -RR, and -YR. Insertional mutagenesis of mcyA, mcyD, or mcyE in Microcystis sp. S-70 abolished microcystin production. In conclusion, the mcyDEFG operon is presumed to be responsible for 3-amino-9-methoxy-2,6, 8-trimethyl-10-phenyldeca-4,6-dienoic acid (Adda) biosynthesis, and the incorporation of Adda and glutamic acid into the microcystin molecule.
Antibiotic use in food animals: controlling the human health impact.
Tollefson L, Miller MA.J AOAC Int. 2000 Mar-Apr;83(2):245-54.
U.S. Food and Drug Administration, Center for Veterinary Medicine, Office of Surveillance and Compliance, Rockville, MD 20855, USA.
Resistance to antimicrobial drugs has compromised control of many bacterial pathogens. For foodborne pathogens, the most likely source of resistance is use of antimicrobials in food-producing animals. To control the human health impact from use of antimicrobials in animals, the U.S. Food and Drug Administration (FDA) recently announced plans to assess the microbial safety of all antimicrobials intended for use in food-producing animals. This paper describes the history of antimicrobial use and regulation in animals, the public health concern, the current animal drug approval process in the United States, the international perspective, and FDA's proposed procedures to evaluate the human health impact of the antimicrobial effects associated with animal drugs intended for use in food-producing animals. The primary public health goal of the improved regulatory paradigm is to ensure that significant human antimicrobial therapies are not lost due to use of antimicrobials in food animals.
Ethics and schools of public health.
Hyder AA.Am J Public Health. 2000 Apr;90(4):639-40.
Insect (Locusta migratoria migratorioides) test monitoring the toxicity of cyanobacteria.
Hiripi L, Nagy L, Kalmar T, Kovacs A, Voros L.Neurotoxicology. 1998 Aug-Oct;19(4-5):605-8.
Balaton Limnological Research Institute of the Hungarian Academy of Sciences, Tihany.
An insect test was developed to investigate the toxicity of cyanobacteria. The African locust, Locusta migratoria migratorioides R.F. was used as a test animal instead of mouse. The cyanobacteria tested were Aphanizomenon flos-aque, Anabaena aphanizomenoides, Cylindrospermopsis raciborskii, Microcystis aeruginosa. The toxicity of authentic microcystin-LR was also tested. Cyanobacteria producing toxins killed the animals when the homogenized cell suspension was injected into the animals. The locust test proved to be more sensitive than the mouse test. The LD50 values of the different cyanobacteria for locusts and for mice, respectively were the following: 90 microg/animal (60 mg/kg) and 8000 microg/animal (320 mg/kg), for Aphanizomenon flos-aquae; 255 microg/animal (170.2 mg/kg) and 3750 microg/animal (150 mg/kg), for Anabaena aphanizomenoides; 195 microg/animal (131.4 mg/kg) and 5750 microg/animal (230 mg/kg), for Cylindrospermopsis raciborskii; 22.5 microg/animal (15 mg/kg) and 6000 microg/ animal (240 mg/kg), for Microcystis aeruginosa. In locusts the LD50 value for authentic microcystin-LR was 0.2 microg/animal (130 mg/kg). Since the weight of the mice is 15 to 20 times larger than that of the locusts, hence less toxic cells are needed to kill the locusts. The locust test is cheaper than the mouse test, large number of animals can be used in the experiments and the LD50 values can be estimated more precisely. The toxicity of C. raciborskii was significantly lower when the lyophilized cells were extracted in methanol (LD50 = 767 mg/kg), instead of NaCl solution (LD50 = 131.4 mg/kg).
Scientific concepts of functional foods in Europe. Consensus document.
[No authors listed].Br J Nutr. 1999;81 Suppl 1:S1-27.
Serine proteases inhibiting cyanopeptides.
Radau G.Pharmazie. 2000 Aug;55(8):555-60.
Department of Pharmaceutical/Medicinal Chemistry, Ernst-Moritz-Arndt-University, Greifswald, Germany. firstname.lastname@example.org
There are many compounds inhibiting serine proteases which play an important role in the human organism. This article reviews publications on the low-molecular weight, serine protease inhibitory cyanopeptides and reports on new developments in establishing structure-activity relationships.
[Directions for detection procedure of bacterial toxins].
Tanaka M.Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi. 1999 Dec;10(2):141-6.
[Article in Japanese]
Kobe National Hospital, Clinical Laboratory, Nishiochiai, Japan.
Functional foods: the Food and Drug Administration perspective.
Ross S.Am J Clin Nutr. 2000 Jun;71(6 Suppl):1735S-8S; discussion 1739S-42S.
Office of Special Nutritionals, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC 20204, USA. email@example.com
Because the Federal Food, Drug, and Cosmetic Act (FFDCA) does not provide a statutory definition of functional foods, the Food and Drug Administration has no authority to establish a formal regulatory category for such foods. The primary determinant of the regulatory status of a food is its intended use, which is determined largely by the label and labeling information accompanying the product. This information includes nutrient information, nutrient content claims, and various types of health claims. In marketing these foods, manufacturers may come under one of several existing regulatory options. The first decision manufacturers will make that will help determine their product's regulatory status is whether the product is a food or a drug. Thus, manufacturers and retailers have a range of legal and regulatory categories in which their products may be classified. This article describes the definitions provided in the FFDCA for a drug and a food, the safety and labeling requirements of various food categories, and types of possible claims for dietary supplements.
Functional foods: an ecologic perspective.
Marriott BM.Am J Clin Nutr. 2000 Jun;71(6 Suppl):1728S-34S.
Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86001-4087, USA. firstname.lastname@example.org
A functional food is defined as any food or food ingredient that may provide a health benefit beyond that conferred by the nutrients the food contains. As nutrition scientists move into this arena, they must build on the wealth of information that already exists in plant biology. In particular, the evolutionary and physiologic bases for the production of secondary plant chemicals in plants must be considered in order to plan meaningful experiments for testing the functionality of these chemical compounds for humans. One problem that may arise is that in using the term functional food, the meaning may be lost in the continued proliferation of related terms used in product marketing. The new National Institutes of Health Office of Dietary Supplements addressed some of these issues as it developed the operating definitions described in this report.
Bacterial toxins in pediatric infectious diseases.
Balkundi DR, Kumar A.Indian J Pediatr. 1995 May-Jun;62(3):281-91.
Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing 48824-1317, USA.
Public health concerns about caliciviruses as waterborne contaminants.
Schaub SA, Oshiro RK.J Infect Dis. 2000 May;181 Suppl 2:S374-80.
US Environmental Protection Agency, Office of Water, Washington, DC 20460, USA. email@example.com.
Caliciviruses are disseminated by the fecal-oral route and are found in contaminated surface and ground waters. The US Environmental Protection Agency (EPA) is interested in preventing calicivirus contamination in treated waters used for consumption, and these viruses are on the EPA's "contaminant candidate list" for regulatory consideration in drinking waters. These viruses also present a health threat for recreation and shellfish-growing waters. However, before EPA can make regulatory decisions regarding caliciviruses, significant information and technology needs must be established, including analytical methods for sampling, identifying, and quantifying the viruses; applicability of surrogates to determine their presence; efficacy of water and wastewater treatment or disinfection; waterborne occurrence levels and distribution; dose response; and the viruses' effect(s) on health. Future drinking-water regulations may need to ensure that treatments are adequate to remove caliciviruses from source waters. For recreation and shellfish-growing waters, surrogate indicators and health criteria may need to be based upon establishing risks of exposure to caliciviruses.
[Bacterial toxins and their use].
Zdanovskii AG, Zdanovskaia MV, Iankovskii NK.Mol Biol (Mosk). 2000 Mar-Apr;34(2):193-200.
[Article in Russian]
Affinity and potency of proinhibitory antipeptide antibodies against CYP2D6 is enhanced using cyclic peptides as immunogens.
Schulz-Utermoehl T, Edwards RJ, Boobis AR.Drug Metab Dispos. 2000 May;28(5):544-51.
Section on Clinical Pharmacology, Division of Medicine, Imperial College School of Medicine, Hammersmith Campus, London, United Kingdom.
A series of antipeptide antibodies directed against CYP2D6 were produced by immunizing rabbits with peptides that were sterically unrestrained (linear) or conformationally restricted by cyclization. A variety of sites within the region comprising residues 254 to 290 of CYP2D6 were targeted. In immunoblotting studies, each of the antibodies against the linear and cyclic peptides recognized only a single immunoreactive band of 54 kDa in human liver microsomal fraction and bound to recombinant CYP2D6, but not recombinant CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2E1, or CYP3A4. However, the relative intensity of immunoreactive bands was considerably stronger for those antibodies raised against cyclic peptides. Similarly, in an enzyme-linked immunosorbent assay, antibodies raised against cyclic peptides bound 10 to 100 times more strongly to recombinant CYP2D6 than antibodies raised against the corresponding linear peptides. None of the antibodies raised against linear peptides had any effect on debrisoquine 4-hydroxylase activity of human hepatic microsomal fraction; however, anticyclic peptide antibodies targeted against residues 254 to 273, 261 to 272, and 257 to 268 of CYP2D6 inhibited enzyme activity by a maximum of 60, 75, and 91%, respectively. In contrast, despite binding strongly to CYP2D6, an anticyclic peptide antibody directed against residues 278 to 290 did not inhibit enzyme activity. The epitope of the proinhibitory anticyclic peptide antibody directed against residues 257 to 268 of CYP2D6 included Thr-261 and Trp-262, and indicates a role for these residues in enzyme inhibition. In conclusion, immunization with peptides conformationally restricted by cyclization to mimic loop regions of CYP2D6 resulted in strongly binding antibodies that when targeted appropriately were able to inhibit CYP2D6-catalyzed activity.
The question of herbal supplements: are they here to stay?
Monsen ER.J Am Diet Assoc. 2000 Apr;100(4):409.
Crazy for creatine. Everyone from Mark McGwire to kiddie jocks is using this muscle builder. But is it safe?
Smith IK.Time. 2000 Jun 12;155(24):93.
Micronutrient intakes in a group of UK vegans and the contribution of self-selected dietary supplements.
Lightowler HJ, Davies GJ.J R Soc Health. 2000 Jun;120(2):117-24.
Nutrition Research Centre, School of Applied Science, South Bank University, London. firstname.lastname@example.org
Micronutrient intakes and the contribution of self-selected dietary supplements were investigated in 26 vegans, comprising 17 non-supplement users (NSU) and nine supplement users (SU), consuming their habitual diet. Micronutrient intakes were estimated using a four-day weighed record and the contribution of self-selected dietary supplements was assessed according to the manufacturers' declarations on the packaging. Mean daily intakes from food sources were similar in NSU and SU. Dietary supplements significantly increased intakes of riboflavin (p < 0.05), niacin (p < 0.05), folate (p < 0.01), vitamin A (p < 0.05) and vitamin D (p < 0.05). The mean daily contribution of dietary supplements ranged from 7-1640% of the reference nutrient intake (RNI). Intakes of vitamin B12 and selenium (Se) were below the appropriate lower reference nutrient intake (LRNI) in 80% and 65% of NSU respectively. After supplements, 33% of SU remained below the LRNI for vitamin B12 and 33% below the LRNI for Se. Some vegans who took supplements were not taking certain micronutrients in amounts sufficient to meet the RNIs but were taking a mix of micronutrients, some of which they needed and others which they did not need. Some vegans who did not take supplements had a potential need for the addition of supplements to their diets. Advice on the appropriate usage of dietary supplements for those on a vegan diet is needed.
Autoantibodies to complement components.
Davies KA, Norsworthy P.Methods Mol Biol. 2000;150:173-92.
Rheumatology Section, Imperial College School of Medicine, London, UK.
A rapid interferent-free assay for the determination of LD-1 in biological samples.
Cronin CP, Kelly S, O'Sullivan CK, Guilbault GG.Artif Cells Blood Substit Immobil Biotechnol. 2000 May;28(3):203-14.
Department of Chemistry, University College Cork, Ireland.
A highly specific enzyme linked immunosorbent assay (ELISA) for the detection of lactate dehydrogenase-1 (LD-1) has been developed. A competition assay is described with polyclonal antibody to LD-1 passively adsorbed on an ELISA 96-well plate, with non-labelled and labelled LD-1 antigen competing. The LD-1 antigen is conjugated to alkaline phosphatase (ALP) using the one step glutaraldehyde method. A linear range of 10-4000 U/L was obtained, and cross-reactivity was only observed with LD-2. It was possible to eliminate this cross-reactivity by carrying out the final incubation step at 65 degrees C. The developed assay was applied to the analysis of spiked serum and plasma samples and the recoveries obtained were acceptable.
Zinc and Health: Current Status and Future Directions. Proceedings of a workshop. Bethesda, Maryland, USA. November 4-5, 1998.
[No authors listed].J Nutr. 2000 May;130(5S Suppl):1341S-1519S.
Functional foods: the US perspective.
Milner JA.Am J Clin Nutr. 2000 Jun;71(6 Suppl):1654S-9S; discussion 1674S-5S.
Department of Nutrition, The Pennsylvania State University, University Park 16802, USA. email@example.com
Widespread interest in the possibility that selected foods might promote health has resulted in the coining of the term functional food, although agreement about what is and what is not a functional food is lacking. Public interest in functional foods is increasing because of higher health care costs; the passage of federal legislation affecting many food categories, including the expanded category of dietary supplements; and recent scientific discoveries linking dietary habits with the development of many diseases, including coronary heart disease and some cancers. A variety of foods have been proposed as providing health benefits by altering one or more physiologic processes. Biomarkers are needed to assess the ability of functional foods or their bioactive components to modify disease and to evaluate the ability of these foods to promote health, growth, and well-being. Evidence suggests that several biomarkers may be useful for distinguishing between diseased and nondiseased states and even for predicting future susceptibility to disease. A variety of biomarkers will probably be needed to develop a profile for an individual that reflects the impact of diet on performance and health. Another area of interest is the interaction of nutrients and their association with genetics. These interactions may account for the inconsistent interrelations observed between specific dietary constituents and the incidence of disease. Greater understanding of how diet influences a person's genetic potential, overall performance, and susceptibility to disease can have enormous implications for society. As new discoveries are made in this area, consumers will need access to this information so that they can make informed decisions.
cis,cis- and trans,trans-ceratospongamide, new bioactive cyclic heptapeptides from the Indonesian red alga Ceratodictyon spongiosum and symbiotic sponge Sigmadocia symbiotica.
Tan LT, Williamson RT, Gerwick WH, Watts KS, McGough K, Jacobs R.J Org Chem. 2000 Jan 28;65(2):419-25.
Department of Pharmacology, University of California at Santa Barbara, California 93106, USA.
Chemical investigation of the marine red alga (Rhodophyta) Ceratodictyon spongiosum containing the symbiotic sponge Sigmadocia symbiotica collected from Biaro Island, Indonesia, yielded two isomers of a new and bioactive thiazole-containing cyclic heptapeptide, cis,cis-ceratospongamide (1) and trans, trans-ceratospongamide (2). Isolation of these peptides was assisted by bioassay-guided fractionation using a brine shrimp toxicity assay (Artemia salina). The structures of the ceratospongamides, which each consist of two L-phenylalanine residues, one (L-isoleucine)-L-methyloxazoline residue, one L-proline residue, and one (L-proline)thiazole residue, were established through extensive NMR spectroscopy, including (1)H-(13)C HMQC-TOCSY, and (1)H-(15)N HMBC experiments, as well as chemical degradation and chiral analysis. cis,cis- and trans,trans-ceratospongamide are stable conformational isomers of the two proline amide bonds. Molecular modeling of these two ceratospongamide isomers showed the trans, trans isomer to be quite planar, whereas the cis,cis isomer has a more puckered overall conformation. trans,trans-Ceratospongamide exhibits potent inhibition of sPLA(2) expression in a cell-based model for antiinflammation (ED(50) 32 nM), whereas the cis,cis isomer is inactive. trans,trans-Ceratospongamide was also shown to inhibit the expression of a human-sPLA(2) promoter-based reporter by 90%.
Development of a novel ELISA for 1,25-dihydroxyvitamin D.
Armbruster FP, Friedl S, Karmatschek M, Heckl-Ostreicher B, Reichel H, Woloszczuk.Clin Lab. 2000;46(3-4):165-6.
Immundiagnostik GmbH, Bensheim, Germany.
[DEA research summaries on Epidemiology and Public Health].
[No authors listed].Rev Epidemiol Sante Publique. 2000 Jan;48(1):109-15.
[Article in French]
Blood mercury levels and fish consumption in Louisiana.
Bellanger TM, Caesar EM, Trachtman L.J La State Med Soc. 2000 Feb;152(2):64-73.
Louisiana State University Health Sciences Center, New Orleans, USA.
The primary source of non-occupational exposure to mercury is through the consumption of contaminated fish. Since 1994, the Louisiana Department of Environmental Quality has reported mercury contamination in fish obtained from bodies of water throughout the state and has issued fish consumption advisories accordingly. To determine the extent of mercury intoxication in Louisiana, screening for blood mercury levels was offered to volunteers residing near selected advisory areas. A total of 313 residents participated in the screening; 6 were found to have elevated levels. No level was detected in 48 of the participants, while the remaining participants had normal levels. Significantly higher levels were found in those associated with commercial fishing and those reporting increased fish consumption. For most people, ordinary consumption of fish contaminated with mercury does not currently appear to pose a public health hazard in Louisiana; however, educational efforts regarding the risks of fish consumption in great quantities should be continued.
Toward a better educated public health workforce.
Sommer A.Am J Public Health. 2000 Aug;90(8):1194-5.
Derivation of shellfish harvest reopening criteria following the New Carissa oil spill in Coos Bay, Oregon.
Gilroy DJ.J Toxicol Environ Health A. 2000 Jul 14;60(5):317-29.
Oregon Health Division, Portland 97232, USA. firstname.lastname@example.org
Oil spills in Alaska, California, Maine, and other states have raised concerns regarding potential contamination of fish and shellfish, and have led to temporary closures of seafood harvests while health risks are assessed. Lacking standardized protocols, these assessments are generally ad hoc, site-specific efforts, with significant differences in risk evaluation criteria. This article describes the response of a state health agency to shellfish contamination following an oil spill on the Oregon coast, and discusses some of the factors that can complicate the evaluation of potential health risks from consumption of oil-contaminated shellfish. On 4 February 1999, the Japanese-owned cargo ship M/V New Carissa, carrying an estimated 400,000 gallons of light diesel and heavy fuel oil, ran aground 2 miles north of Coos Bay, Oregon. Damage to the ship's hull from the grounding and pounding surf caused the release of an estimated 25,000 to 70,000 gallons of oil. Concern for potential contamination of local recreational shellfish and commercial oyster beds prompted the Oregon Department of Agriculture (ODA) to close shellfish harvesting in Coos and Douglas counties. ODA requested assistance from the Oregon Health Division in the derivation of risk-based criteria for reopening the shellfish harvest. Criteria were developed for the primary contaminants of concern, polycyclic aromatic hydrocarbons (PAHs) expressed as total benzo[a]-pyrene (BaP) equivalents. "Safe" (<10 microg/kg) and "unsafe" (>45 microg/kg) BaP equivalent levels were derived based on upper end (32.5 g/d) and average (7.5 g/d) estimates of shellfish consumption, respectively. Composite samples of oysters, clams, and mussels (15-20 per composite) were collected from target areas and analyzed for PAHs by gas chromatography/mass spectroscopy (GC/MS). Carcinogenic PAHs were converted to total BaP equivalents (wet weight) and compared with criteria. Two oyster samples, collected from a slough off of Coos Bay, contained 33.9 and 34.5 microg/kg BaP equivalents; all other samples had less than 10 microg/kg BaP equivalents. An evaluation of the PAH profiles in the two higher oyster samples indicated a primary source other than the New Carissa oil. Because shellfish sample BaP equivalents attributable to the New Carissa oil spill did not exceed 10 microg/kg, shellfish harvesting was reopened on 4 March 1999. This study revealed some of the inherent difficulties in attempting to quantify health risks from contaminated shellfish following an oil spill and demonstrated the clear need for standardized protocols for responding to such events.
Mueggelone, a novel inhibitor of fish development from the fresh water cyanobacterium Aphanizomenon flos-aquae.
Papendorf O, Konig GM, Wright AD, Chorus I, Oberemm A.J Nat Prod. 1997 Dec;60(12):1298-300.
Institute for Pharmaceutical Biology, Technical University of Braunschweig, Germany.
A novel C18 lipid, containing a 10-membered lactone, mueggelone (1), was isolated from a field-collected sample of Aphanizomenon flos-aquae, together with the known compound lupenyl acetate (3). Both structures were secured using extensive spectroscopic analysis (1D and 2D NMR, MS, IR). Biological activity assessment of both compounds indicated them to have significant inhibitory effects on fish embryo larval development.
Plasticizers in total diet samples, baby food and infant formulae.
Petersen JH, Breindahl T.Food Addit Contam. 2000 Feb;17(2):133-41.
Institute of Food Research and Nutrition, Danish Veterinary and Food Administration, Soborg, Denmark. email@example.com
The plasticizers di-n-butylphthalate (DBP), butylbenzylphthalate (BBP), di-2-(ethylhexyl)phthalate (DEHP) and di-2-(ethylhexyl)adipate (DEHA) were analysed in 29 total diet samples, in 11 samples of baby food and in 11 samples of infant formulae. In all of the total diet samples the presence of one or more of the plasticizers was demonstrated. Maximum and minimum mean concentrations in the total diet samples were: 0.09-0.19 mg DBP/kg, 0.017-0.019 mg BBP/kg, 0.11-0.18 mg DEHP/kg and 0.13-0.14 mg DEHA/kg. One or more of the phthalates was also found in about 50% of the samples of baby food as well as in infant formulae. The calculated mean maximum intakes of the individual compounds from the total diet samples were below 10% of the restrictions proposed by the EU Scientific Committee for Food (SCF), and the spread in individual intakes was considerable. DEHP was the plasticizer determined most frequently and contributed the highest fraction of its tolerable daily intake (TDI). Hence, the maximum calculated intake of DEHP from single samples of the foodstuffs analysed could be up to one-third of the TDI. The calculated mean intake of DEHA was about 1% of the TDI with a maximum value of 13% of the TDI. Violations of the restrictions proposed by the EU Scientific Committee for Food (SCF) in the form of TDI values or specific migration limits were not found in this investigation.
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