THE MYCOTOXINS

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****** DATA-MÉDICOS *********

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LAS MICOTOXINAS / THE MYCOTOXINS 

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***** DERMAGIC-EXPRESS No 4 ******

****** 18 OCTUBRE DE 1.998 ******* 

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EDITORIAL ESPAÑOL

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Hola amigos Dermágicos, a propósito del simposio VIRTUAL sobre MICOTOXINAS, que la Dra. Gioconda San Blas invita entre el 19 y 23 de Octubre (esta semana) ENCONTRÉ, en las BASES DE DATOS algunas referencias interesantes al respecto, de modo que el tema sobre el FINASTERIDE irá después.

La idea de esta LISTA BIBLIOGRÁFICA, es cubrir en lo posible TODOS los capítulos ligados a la dermatología, y la MICOLOGIA forma parte integral de ella, es por ello que la edición de hoy va dedicada a este tema, sobre LAS MICOTOXINAS. Espero que les guste.

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DERMAGIC/EXPRESS(4)

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L A S M I C O T O X I N A S / THE MYCOTOXINS

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REFERENCIA: 1: Ochratoxin A

REFERENCIA: 2: T-2 toxin

REFERENCIA: 3: aflatoxin B1, zearalenone and deoxynivalenol

REFERENCIA: 4: Stachybotrys chartarum

REFERENCIA: 5: ochratoxin A

REFERENCIA: 6: Fumonisin B1 (FB1)

REFERENCIA: 7: aflatoxin B1, aflatoxin B1-8,9-epoxide

REFERENCIA: 8: micotoxinas y quesos

REFERENCIA: 9: rubratoxin-B biosynthesis

REFERENCIA: 10: Ochratoxin A y nefropatia

REFERENCIA: 11: fumonisin, Fusarium moniliforme 

REFERENCIA: 12: trichothecene toxin T-2 

REFERENCIA: 13: Ochratoxin A y nefropatia

REFERENCIA: 14: nivalenol.

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1.) Ochratoxin A-induced stimulation of extracellular signal-regulated kinases 1/2 is associated with Madin-Darby canine kidney-C7 cell dedifferentiation.

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AU: Schramek-H; Wilflingseder-D; Pollack-V; Freudinger-R; Mildenberger-S; Gekle-M

AD: Department of Physiology, University of Innsbruck, Innsbruck, Austria.

SO: J-Pharmacol-Exp-Ther. 1997 Dec; 283(3): 1460-8

ISSN: 0022-3565

PY: 1997

LA: ENGLISH

CP: UNITED-STATES

AB: The kidneys represent one of the main targets of ochratoxin A (OTA), a secondary fungal metabolite that is produced by certain species of Aspergillus and Penicillium. OTA has the ability to disturb Madin-Darby canine kidney (MDCK) cell pH homeostasis, leading to intracellular alkalinization and morphological alterations resembling those that occur when MDCK cells are exposed to transient alkaline stress. Because alkali-induced epithelial dedifferentiation of MDCK-C7 cells is associated with an increase in the activity of extracellular signal-regulated kinases (ERK), we performed experiments that investigated a possible role for ERK1 and ERK2 as intracellular signaling molecules mediating some of the mycotoxin's effects on renal epithelia. We studied the effects of OTA on ERK1/2 phosphorylation and activation, as well as on cell morphology by using cloned MDCK-C7 and MDCK-C11 cells. In MDCK-C7 cells, but not in MDCK-C11 cells, OTA led to a time-dependent and concentration-dependent increase in ERK1/2 phosphorylation. OTA-induced ERK1/2 phosphorylation in MDCK-C7 cells occurred at concentrations of 500 nM, started after 2 hr and was maximal after 8 hr. Furthermore, after 8 hr of incubation, 500 nM and 1 &mgr;M OTA significantly increased ERK1/2 activity in MDCK-C7 but not in MDCK-C11 cells. This OTA-stimulated ERK1/2 phosphorylation and ERK1/2 activation in MDCK-C7 cells was partially inhibited by the synthetic mitogen-activated protein kinase kinase (MKK or MEK) inhibitor PD098059. Transepithelial resistance and lactate dehydrogenase release remained unaltered after incubation in the presence of 1 microM OTA for 8 hr or of 100 nM OTA for 24 hr, so it is unlikely that these OTA effects on ERK1/2 are due to secondary toxic effects of the mycotoxin. Interestingly, OTA-induced long-term activation of ERK1/2 in MDCK-C7 cells was associated with epithelial dedifferentiation, as assessed by analysis of vectorial solute and water transport as well as cell morphology. In contrast, MDCK-C11 cells, which do not show significant increases in ERK1/2 phosphorylation and ERK1/2 activity in response to OTA, retained their epithelial phenotype under identical experimental conditions. Taken together, our data demonstrate an epithelial dedifferentiation of MDCK-C7 cells, but not of MDCK-C11 cells, after long-term incubation in the presence of OTA, a result associated with the ability of this mycotoxin to stimulate ERK1/2 in MDCK-C7 cells but not in MDCK-C11 cells. We conclude that OTA-induced activation of ERK1/2 could be an important intracellular signaling pathway that mediates some of the mycotoxin's effects on renal epithelia.

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2.) TI: Apoptotic cellular damage in mice after T-2 toxin-induced acute toxicosis.

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AU: Ihara-T; Sugamata-M; Sekijima-M; Okumura-H; Yoshino-N; Ueno-Y

AD: Department of Pathology, Institute of Tochigi Clinical Pathology, Tochigi, Japan.

SO: Nat-Toxins. 1997; 5(4): 141-5

ISSN: 1056-9014

PY: 1997

LA: ENGLISH

CP: UNITED-STATES

AB: By histopathologic, electron microscopic, and immunochemical observation, the mechanism of cellular death was investigated in thymus, spleen, and liver of mice given intraperitoneally sublethal doses of T-2 toxin, a trichothecene mycotoxin. In the thymus and spleen of mice given 5.0 mg/kg body weight of T-2 toxin and killed 12 hours later, a massive cellular destruction characterized by chromatin condensation was evident, and electron microscopy analysis revealed the presence of apoptotic bodies. In the liver of mice given 2.5 mg/kg of T-2 toxin and killed 2 hours later, the induction of apoptotic cellular lesions was observed by electron microscopy, and Kupffer cells phagocytosed the apoptotic bodies. Such lesions were not observed in the mice killed 12 hours after receiving the toxin. In situ nick translation analysis (Tunel method) revealed DNA fragmentation in thymus, spleen, and liver shortly after administration of T-2 toxin. As previously observed in vitro, these findings indicated that T-2 toxin is a potent inducer of apoptotic cell death in thymus, spleen, and liver in vivo; especially in liver, apoptosis is induced rapidly as compared with the other tissues observed, and Kupffer cells play an important role for clearance of apoptosis.

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3.) TI: Mycoflora and incidence of aflatoxin B1, zearalenone and deoxynivalenol in poultry feeds in Argentina.

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AU: Dalcero-A; Magnoli-C; Chiacchiera-S; Palacios-G; Reynoso-M

AD: Dpto. de Microbiologia e Inmunologia, Facultad de Ciencias, Exactas Fisico-Quimicas y Naturales, Universidad Nacional de Rio Cuarto.

SO: Mycopathologia. 1997; 137(3): 179-84

ISSN: 0301-486X

PY: 1997

LA: ENGLISH

CP: NETHERLANDS

AB: In Argentina, there is rather little information about the natural occurrence of mycotoxins in feedstuffs. The aim of this work was to determine the fungal flora and natural incidence of aflatoxin B1 (AFB1), zearalenone (ZEA) and deoxynivalenol (DON) in poultry feeds from 5 factories of Rio Cuarto, Cordoba. Three hundred samples were taken from May 1995 to May 1996. Fungal counts of poultry feeds ranged 10(4) to 10(6) CFU g-1. The lowest counts were obtained on the first months from the sampling (May to September 1995) with mean values significantly different from those found at the last of the sampling (October 1995 to April 1996). The most prevalent species isolated of poultry feed samples belonged to the genera Penicillium that was present in 98% of the samples, Fusarium (87%) and Aspergillus (52%). Fusarium species isolated were: F moniliforme in 73% of the samples, F subglutinans (35%), F graminearum (20%) and within Aspergillus species: A. parasiticus (33%) and A. flavus (8%) were identified. In poultry feeds aflatoxin B1 (AFB1) was the most significant mycotoxin with levels ranging from 17 to 197 ng/g. For deoxynivalenol (DON) the levels ranged from 240 to 410 ng/g. Only three out of 300 samples were contaminated with zearalenone (ZEA) in concentrations of 30, 120 and 280 ng/g. These are preliminary data on this subject in our region.

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4.) TI: [Mass development of Stachybotrys chartarum on compostable plant pots made from recycled paper]

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TO: Massenentwicklung von Stachybotrys chartarum auf kompostierbaren Pflanztopfen aus Altpapier.

AU: Dill-I; Trautmann-C; Szewzyk-R

AD: Fachgebiet Okologie der Mikroorganismen, Technische Universitat Berlin, BR Deutschland.

SO: Mycoses. 1997; 40 Suppl 1: 110-4

ISSN: 0933-7407

PY: 1997

LA: GERMAN; NON-ENGLISH

CP: GERMANY

AB: After handling plants grown in decomposable pots made of recycling paper, three women working in a big horticulture developed very painful inflammated efflorescences at the finger-tips, followed by scaling off the skin. The pots appeared to be very mouldy. Black masses of conidia of Stachybotrys chartarum and perithecia of Chaetomium globosum were identified on almost every pot. Apart from various other fungal genera, Trichoderma und Acremonium were frequently detected. Considering the observed symptoms, special attention was payed to the mycotoxin producing species St. chartarum. To evaluate the inhalative spore load, air sampling was performed. The detection of St. chartarum in the air was only possible with the spore trap (sampling of particles) but not with the Andersen sampler (detection of colony forming units). Without moving the pots, measurements yielded values of 30-100 St. chartarum conidia per m3 of air. The concentration of air-borne conidia increased drastically by handling the pots, thus attaining up to 7,500 conidia per m3 of air for St. chartarum only. The occurrence of St. chartarum in such amounts is alarming because of possible toxin production. In addition, the allergenic stress by fungal spores has to be emphasized. The results are discussed with regard to general medical-mycological aspects related to the degradation of environmentally-friendly decomposable materials.

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5.) TI: Effects of ochratoxin A on DNA repair in cultures of rat hepatocytes and porcine urinary bladder epithelial cells.

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AU: Dorrenhaus-A; Follmann-W

AD: Institut fur Arbeitsphysiologie an der Universitat Dortmund, Germany.

SO: Arch-Toxicol. 1997; 71(11): 709-13

ISSN: 0340-5761

PY: 1997

LA: ENGLISH

CP: GERMANY

AB: In cultured rat hepatocytes the mycotoxin ochratoxin A (OTA) induced unscheduled DNA synthesis (UDS) only in a narrow concentration range. Using a culture medium supplemented with 1% fetal calf serum, at 750 nM OTA a weak induction and at 1 microM OTA a marked induction of DNA repair was observed (15 +/- 11 and 38 +/- 24% cells in repair, respectively). Concentrations > 1 microM OTA were cytotoxic, and <750 nM no induction occurred. In cultures of cells from the urinary bladder (porcine urinary bladder epithelial cells; PUBEC), a target organ of the mycotoxin, OTA induced UDS in a concentration-dependent manner. To inhibit the proliferation of the cultured epithelial cells, which would counteract the detection of DNA repair, epidermal growth factor was omitted and an arginine-deficient medium (ADM) was used. Under these serum-free culture conditions the amount of cells undergoing DNA repair in PUBEC control cultures was approximately 7 +/- 4%, a value also comparable to those of control cultures of rat hepatocytes. At concentrations between 250 nM and 1 microM OTA a concentration-dependent increase of cells in repair was observed. Above 1 microM OTA was cytotoxic. At this concentration a maximum of approximately 61 +/- 9% of the cells undergo DNA repair. This amount is comparable to control cultures incubated with 5 or 10 mM ethylmethane-sulphonate (EMS) (49 +/- 9 and 69 +/- 10% cells in repair, respectively), used as a positive control. These results show that in cultured rat hepatocytes induction of UDS is relatively weak whereas in urothelial cells this effect was significant. Whether this effect is due to OTA metabolites formed locally in the urothelium cannot be excluded since PUBEC have been shown to be able to metabolize xenobiotics independently from the liver.

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6.) TI: Mycotoxin-induced elevation of free sphingoid bases in precision-cut rat liver slices: specificity of the response and structure-activity relationships.

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AU: Norred-WP; Plattner-RD; Dombrink-Kurtzman-MA; Meredith-FI; Riley-RT

AD: Richard B. Russell Agricultural Research Center, ARS/USDA, Athens, Georgia 30604-5677, USA.

SO: Toxicol-Appl-Pharmacol. 1997 Nov; 147(1): 63-70

ISSN: 0041-008X

PY: 1997

LA: ENGLISH

CP: UNITED-STATES

AB: Fumonisin B1 (FB1) is the predominant member of a family of toxic metabolites produced by several species of Fusarium and is commonly found on corn. FB1 is a potent competitive inhibitor of ceramide synthase, which catalyzes the conversion of sphinganine and sphingosine to ceramide. The resultant accumulation of free sphingoid bases and the disruption of sphingolipid metabolism is believed to be the mechanism of toxicity of the fumonisins. The objectives of this study were to determine the relative potency of analogs of FB1 to inhibit ceramide synthase and to determine whether the inhibition is specific to mycotoxins with fumonisin-like structures. Fumonisins B1, B2, B3, B4, C4, and TA toxin (a structurally similar mycotoxin produced by the tomato pathogen, Alternaria alternata f. sp. lycopersici) were approximately equipotent inhibitors. Hydrolyzed fumonisins B1, B2, and B3, which lack the tricarballylic side chains, were only 30-40% as potent as the parent toxins. N-acetylated FB1 (FA1) did not block ceramide synthase, suggesting that FA1 is nontoxic. Inhibition of ceramide synthase by fumonisin analogs did not appear to be related to the lipophilicity of the compounds, as determined by computer estimation of log P values. The ability of relatively high (10 and 100 &mgr;m) doses of other mycotoxins that bear no structural similarity to fumonisins, including aflatoxin B1, cyclopiazonic acid, beauvericin, T-2 toxin, sterigmatocystin, luteoskyrin, verrucarin A, scirpentriol, and zearalenone, to block ceramide synthase was also determined. All of the toxins tested were negative in the bioassay with the exception of fumonisins, indicating that disruption of sphingolipid metabolism is a specific cytotoxic response. Copyright 1997 Academic Press.

MESH: Acetylation-; Alternaria-; Liver-metabolism; Rats-; Rats,-Sprague-Dawley; Sphingosine-analogs-and-derivatives; Sphingosine-analysis; Structure-Activity-Relationship; Tomatoes-metabolism; Tomatoes-microbiology

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7.) TI: Metabolic activation of aflatoxin B1 to aflatoxin B1-8,9-epoxide in woodchucks undergoing chronic active hepatitis.

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AU: Gemechu-Hatewu-M; Platt-KL; Oesch-F; Hacker-HJ; Bannasch-P; Steinberg-P

AD: Institute of Toxicology, University of Mainz, Germany.

SO: Int-J-Cancer. 1997 Nov 14; 73(4): 587-91

ISSN: 0020-7136

PY: 1997

LA: ENGLISH

CP: UNITED-STATES

AB: Chronic hepatitis B virus infection as well as consumption of food contaminated with the mycotoxin aflatoxin B1 are considered to be 2 major risk factors for the development of primary liver cancer in humans. Furthermore, epidemiological surveys indicate that hepatitis B virus and aflatoxin B1 might act synergistically to induce primary liver cancer. In the present study, we have tested the hypothesis that the metabolic activation of aflatoxin B1 to aflatoxin B1-8,9-epoxide, the ultimate mutagenic and carcinogenic mycotoxin metabolite, is enhanced in an experimental model of chronic hepatitis using woodchucks, chronically infected with the woodchuck hepatitis virus. Woodchuck liver microsomes were incubated with radiolabeled aflatoxin B1, the resulting aflatoxin B1-8,9-epoxide was trapped as a glutathione conjugate and its formation rate was determined by a reversed-phase HPLC analysis. In woodchuck hepatitis virus-positive woodchucks, activation of aflatoxin B1 to aflatoxin B1-8,9-epoxide was reduced when compared to woodchuck hepatitis virus-free animals, and the extent of the reduction was dependent on the severity of the hepatitis. Hence, at least in woodchucks, a chronic hepadnaviral infection does not lead to an enhanced activation of aflatoxin B1.

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8.) Development of a semisynthetic cheese medium for fungi using chemometric methods.

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Hansen BV; Nielsen PV

Department of Biotechnology, Technical University of Denmark, Lyngby, Denmark.

J Dairy Sci (UNITED STATES) Jul 1997 80 (7) p1237-45 ISSN: 0022-0302

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9711

Subfile: INDEX MEDICUS

The growth, color formation, and mycotoxin production of six cheese-related fungi 

were studied on nine types of natural cheeses and 24 semisynthetic cheese media and 

compared using principal component analysis. The semisynthetic cheese media 

contained various amounts of Ca, K, Mg, Na, P, Fe, Cu, Zn, lactate, lactose, and 

casein. A robust well-defined and easily prepared semisynthetic cheese medium was 

developed for Penicillium commune, the most frequently occurring contaminant on 

semihard cheese. Growth experiments on the medium were repeatable and reproducible. 

The medium was also suitable for Penicillium camemberti. The medium had the 

following composition: 100 g of casein, 8.3 g of 90% lactate, 7.9 g of lactose, 7.3 g 

of CaCl2.2H2O, 2.6 g of MgSO4.7H2O, 26.0 g of NaCl, 20 g of agar, 0.025 g of 

FeSO4.7H2O, 0.004 g of CuSO4.5H2O, and water to a total weight of 1 kg. The 

semisynthetic cheese medium was less suitable for Penicillium roqueforti, Penicillium 

discolor, Penicillium verrucosum, and Aspergillus versicolor. However, another 

semisynthetic cheese medium could be recommended for P. roqueforti and P. discolor. 

That medium had higher contents of P (5000 ppm, wt/wt), K (5000 ppm), and Zn (50 ppm) 

and lower contents of Na (2700 ppm), Fe (1 ppm), Cu (0.1 ppm), and casein (1%).

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9.) Regulation of rubratoxin-B biosynthesis: assessment of role of gamma-irradiation, 

pH and carbohydrates.

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Aziz NH; Abdel-Aal SS

National Centre for Radiation Research and Technology, Cairo, Egypt.

Microbios (ENGLAND) 1997 89 (358) p47-54 ISSN: 0026-2633

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9710

Subfile: INDEX MEDICUS

The maximum rubratoxin-B yield was obtained at pH 5.5,, and by increasing the 

initial pH to near neutrality the yield decreased for both yeast extract sucrose 

(YES) and Sabouraud dextrose yeast extract (SDYE) media, but the concentration of 

mycotoxin was higher in YES medium. The rubratoxin-B yield from Penicillium 

purpurogenium decreased with increasing gamma-irradiation, and at 1.0 kGy no 

mycotoxin was detected at any pH values. In both the unirradiated and irradiated P. 

purpurogeniium cultures, as the rubratoxin-B synthesis increased from 46 to 72 h, the 

lipid content decreased. The concentration (mmoles/g dry wt mycelium) of puridine 

nucleotides in the mycelium of P. purpurogenium during growth in YES and SDYE media 

may be a factor in rubratoxin-B synthesis. An elevated NADPH/ NADP ratio favours 

fatty acid synthesis whereas a depressed NADPH/NADP ratio favours mycotoxin formation. 

The gamma-irradiation played a role in the regulation of rubratoxin-B biosynthesis.

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10.) Molecular and epidemiological approaches to the etiology of urinary tract tumors in an area with Balkan endemic nephropathy.

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Nikolov IG; Petkova-Bocharova D; Castegnaro M; Pfohl-Leskowicz A; Gill C; Day N; 

Chernozemsky IN

National Oncological Centre, Sofia, Bulgaria.

J Environ Pathol Toxicol Oncol (UNITED STATES) 1996 15 (2-4) p201-7 ISSN: 0731-

8898

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9710

Subfile: INDEX MEDICUS

Recently, we completed a second biostatistical study of urinary tract tumors (UTT) 

in areas with Balkan endemic nephropathy (BEN) in the Vratza district, Bulgaria, 

during the period 1975 to 1991. We confirmed the positive correlation between the 

incidence of urinary tract tumors (UTT) and BEN demonstrated in our first population-

based case control 1977 study. A UTT incidence of 98.9 per 100,000 men and 74.7 per 

100,000 women was found in villages most affected by BEN when compared with 11.0 and 

6.7 for men and women, respectively, in nonendemic villages. The relative risk (RR) 

of UTT in BEN villages showed tumors of kidney pelvis and ureters-29 in men and 35 in 

women and urinary bladder tumors-4 in men and 11 in women. The percentage of food 

and blood samples containing nephrotoxic and carcinogenic mycotoxin Ochratoxin A 

(OTA) correlated with the origin of the samples. The most contaminated samples were 

found in BEN villages and households, and the urinary excretion of OTA was higher in 

the group of BEN/UTT patients. The UTT DNA's were studied by the 32P-postlabeling 

method for the presence of OTA-DNA adducts. Some OTA-DNA adducts characteristic for 

endemic UTT and absent in control nonendemic UTT and nontumorous tissues were 

described for the first time.

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11.) Dietary Fusarium moniliforme culture material induces in vitro tumor necrosis 

factor-alpha like activity in the sera of swine.

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Guzman RE; Bailey K; Casteel SW; Turk J; Rottinghaus G

Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, 

University of Missouri-Columbia, USA.

Immunopharmacol Immunotoxicol (UNITED STATES) May 1997 19 (2) p279-89 ISSN: 

0892-3973

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9710

Subfile: INDEX MEDICUS

Sera obtained from a group of pigs (n = 5) fed a diet amended with fumonisin 

containing Fusarium moniliforme culture material was used to determine the levels of 

Tumor Necrosis Factor-Alpha (TNF) activity by a functional bioassay utilizing the TNF 

sensitive WEHI 140 mouse fibrosarcoma cell line. Two pigs developed signs consistent 

with pulmonary edema which was confirmed by pathologic examination in only one pig. 

Significant, time dependent increases in TNF-like activity were observed in all pigs 

during the five days of the trial. Another group of pigs (n = 5) was given a defined 

daily dose of the same culture material by gastric intubation. Two pigs developed 

fulminant pulmonary edema and sharp increases in TNF activity were observed during 

the 3 days of the trial in all pigs. In both cases the activity was not abrogated by 

addition of a neutralizing anti-human TNF monoclonal antibody suggesting that other 

factors may have been responsible for these effects, possibly the increased levels of 

sphingoid bases in the serum. Since the pig has become an important model in the 

study of TNF mediated endotoxic shock, these studies illustrate the relevance of 

certifying the absence of this important mycotoxin from corn based animal diets, 

specially if functional assays are used to monitor the activity of TNF in serum.

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12.) [Studies on relationship between toxicity of trichothecene toxin T-2 and its 

structure]

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Peng S; Dong J; Yang J

Institute of Toxicology and Pharmacology Academy of Military Medical Sciences, 

Beijing.

Chung Hua Yu Fang I Hsueh Tsa Chih (CHINA) May 1996 30 (3) p141-3 ISSN: 0253-

9624

Language: CHINESE Summary Language: ENGLISH

Document Type: 

JOURNAL ARTICLE English Abstract

Journal Announcement: 9709

Subfile: INDEX MEDICUS

Toxic action of mycotoxin T-2 and its metabolite T-2 tetraol and deepoxy T-2; 

tetraol was studied by cytotoxicity and animal toxicity tests to explore the 

relationship between toxin T-2 and its structure. Restults showed that proliferation 

of LLC-PK1 cells and synthesis of DNA could be inhibited by both toxin T-2 and T-2 

tetraol. Toxicity of toxin T-2 was 100 times greater than that of T-2 tetraol. 

There was no obvious toxicity to the proliferation of LLC-PK1 cells and synthesis of 

DNA in a dose of 10 mg/L deepoxy T-2 tetraol. But, toxin T-2 caused obvious damage 

in heart muscle and articular cartilage of chicken embryos, and T-2 tetraol and 

deepoxy T-2 tetraol in heart muscle, but not in articular cartilage. T-2 tetraol 

produced by hydrolysis of toxin T-2 had toxicity to certain extent, but its strength 

was significantly less than that of the latter. It suggests that the epoxide group 

in toxin T-2 played a determinant role for its toxicity. If epoxy cycle of the basic 

nucleus of the molecule is open, its toxicity will change significantly.

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13.) Ochratoxin A in human sera in the area with endemic nephropathy in Croatia.

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Radic B; Fuchs R; Peraica M; Lucic A

Department of Toxicology, Institute for Medical Research and Occupational Health, 

Zagreb, Croatia.

Toxicol Lett (NETHERLANDS) Apr 28 1997 91 (2) p105-9 ISSN: 0378-4274

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9709

Subfile: INDEX MEDICUS

Ochratoxin A (OA) is nephrotoxic fungal metabolite (mycotoxin) occurring in 

foodstuffs. The compound is causally associated with mycotoxin porcine nephropathy, 

a disease comparable with a human kidney disease called endemic nephropathy (EN). In 

this paper we presented results obtained over a 10-year period in the hyperendemic 

village Kaniza, and in control villages where no clinical cases of nephropathy had 

been found. In the hyperendemic village Kaniza and non-endemic villages the 

incidence of OA in human blood was up to 4.5% (range 2-50 ng/ml) and up to 2.4% 

(range 2-10 ng/ml), respectively. Almost all samples of food and feed, collected 

randomly in the hyperendemic village were found to contain OA. Considering marked 

exposure to OA in Kaniza, it was assumed that incidence of EN in this population 

could be related to OA contamination of food and feed.

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14 Experimental IgA nephropathy induced by a low-dose environmental mycotoxin, 

nivalenol.

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Hinoshita F; Suzuki Y; Yokoyama K; Hara S; Yamada A; Ogura Y; Hashimoto H; Tomura S; 

Marumo F; Ueno Y

Kidney Center, Toranomon Hospital, Tokyo, Japan.

Nephron (SWITZERLAND) 1997 75 (4) p469-78 ISSN: 0028-2766

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9708

Subfile: INDEX MEDICUS

Based on the hypothesis that IgA nephropathy (IgAN) is triggered by some exogenous 

antigen(s) which induces dysregulation of the mucosal immune system, we developed an 

experimental model of orally induced IgAN by an environmental mycotoxin, nivalenol 

(NIV), which often contaminates agricultural products in Southeast Asia and Japan. 

In the present study, low doses of oral NIV reproducibly induced significant IgA 

deposits in the glomerular mesangium and elevated serum IgA levels in mice 

irrespective of the strain; the degree of immunopathological changes analogous to 

human IgAN was associated with the dose and duration of NIV treatment. Furthermore, 

a competitive enzyme-linked immunosorbent assay with an NIV analogue-protein 

conjugate disclosed that the IgA antibody in the sera from the NIV model mice had a 

higher affinity to the mycotoxin. Conclusively, these findings suggest that NIV 

induces some pathological changes in mice which resemble those in human IgAN, and 

that this mycotoxin is associated with pathogenesis in some types of 

glomerulonephritis.

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DATA-MEDICOS/DERMAGIC-EXPRESS No (4) 18/10/98 DR. JOSE LAPENTA R. DERMATOLOGO

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Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.0024

Tlf: 0414-2976087 - 04127766810