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Biomedical subjects

B Yagen

Publications and source records attributed to B Yagen.

At least 73 records · Page 4Linked to original sources
PubMed1983

T-2 toxin-induced pathology in the hearts of rats.

T-2 toxin is the major lethal component of several Fusarium fungi implicated in diseases of man and animals. We report here on the histological and ultrastructural changes in hearts of rats given i.p. single large or repeated small doses of T-2 toxin. One, 2 and 3 days after a single large dose, there were lesions in most hearts. They consisted of interstitial oedema, focal cellularity and damage to single or groups of myocytes. The small intramural coronaries were constricted, swollen and sometimes disrupted. After 7 days, most of the changes subsided. In rats killed 1 or 2 months after the last of 10 daily injections of T-2 toxin, cardiomyopathy-like changes were seen with hypertrophy, focal fibrosis and abundant cellularity especially in the subendocardial regions of the left ventricle. The findings, although non-specific, indicate that T-2 toxin is cardiotoxic.

Animals↗
PubMed1982

Mutagenicity of (R) and (S) styrene 7,8-oxide and the intermediary mercapturic acid metabolites formed from styrene 7,8-oxide.

We have tested the two enantiomers of styrene 7,8-oxide and various thioether metabolites of racemic styrene 7,8-oxide for their direct mutagenicity in Salmonella typhimurium TA100. The mutagenicity data suggests that the (R) enantiomer is more mutagenic than the (S) enantiomer, with the racemic mixture intermediate between the two. The thioether metabolites were not mutagenic. The difference in the mutagenicities of enantiomers probably resulted from a stereoselective process in the Salmonella tester strain. At the present time it is not clear whether the rate-limiting reaction is the interaction of the enantiomers with DNA or some other cellular component.

DNA, Bacterial↗
PubMed1981

Antiparasitic structure-activity relationships of congocidine derivatives.

Several congocidine analogs were synthesized and tested for in vivo activity against Trypanosoma congolense and in vitro activity against amastigotes of Leishmania tropica. The tripyrrole derivative, beta-([N-methyl-4-[N-methyl-4-(guanidinoacetamido)pyrrole-2-carboxamido]pyrrole -2-carboxamido]pyrrole-2-carboxamido)butyroamidine dihydrochloride, was less toxic and more active than congocidine. The guanidinoacetyl moiety appears to be a structural requirement for antiparasitic activity in the congocidine series.

Animals↗
PubMed1981

Synthesis and relative stereochemistry of the four mercapturic acids derived from styrene oxide and N-acetylcysteine.

The chemical reaction between (+/-)-styrene oxide and N-acetylcysteine produces both positional isomers (1 and 2) as a mixture of diastereoisomers with a preference for the benzylic thioether isomer 1 (2 : 1). Synthesis of the mercapturic acid conjugates from either (+)- or (-)-styrene oxide produces only two of the four possible stereoisomers. The single diastereoisomers of 1 and 2 were separated by high pressure liquid chromatography (HPLC) and identified by 1H- and 13C-nuclear magnetic resonance (NMR). The relative stereochemistry at the benzylic carbon center of the mercapturic acid conjugates was assigned on the basis of the established chemical correlation between optically pure styrene oxide and its precursor mandelic acid, and considerations on the mechanism of ring opening of epoxides by sulfur nucleophiles. The stereochemical definition of the isomers 3-6 should prove useful in investigations of the biotransformation of the glutathione (GSH) conjugates of styrene oxide.

Acetylcysteine↗
PubMed1981

Mycotoxicosis caused by a single dose of T-2 toxin or diacetoxyscirpenol in broiler chickens.

T-2 toxin (3-hydroxy-4,15-diacetoxy-8-[3-methyl-butyrloxy]-12,13-epoxy-delta 9-trichothecene) and diacetoxyscirpenol, structurally similar trichothecene mycotoxins, in dimethylsulfoxide:saline (1:9 v/v) solvent, were given by crop gavage to 7-day-old male broiler chickens. Selected birds were killed at 1, 6, 12, 18, 24, 72, and 168 hours post-treatment. The lesions induced by the two toxins were similar, but were more severe in chicks given T-2 toxin. Necrosis of lymphoid tissue and bone marrow began one hour after treatment with T-2 toxin, and was followed by rapid cell depletion. Cell repletion also was rapid, occurring by hour 24 in mildly injured tissues from birds given diacetoxyscirpenol and by hours 72 and 168 in more severely injured tissues from chickens given T-2 toxin. Hepatic lesions were multiple foci of cell necrosis resolved rapidly and the inflammatory cell reaction was minimal. Necrosis of gall bladder epithelium and secondary cholecystitis followed hepatic cell necrosis. In the alimentary tract, necrosis of the epithelium on the tips of villi in the duodenum was followed by necrosis of the epithelium of villi and crypts in the small and large intestine, and of mucosal epithelium of the proventriculus and ventriculus. Atrophy of intestinal villi and fewer mitotic figures were seen by 18 hours after treatment. The alimentary tract epithelium, however, looked normal by hour 72. Lesions in the integument, including necrosis of feather epidermis and of the follicular epidermis at the neck of the feather follicle, occurred at 12 to 24 hours after treatment.

Animals↗
PubMed1981

The metabolism and excretion of styrene oxide-glutathione conjugates in the rat and by isolated perfused liver, lung and kidney preparations.

The metabolism and excretion of styrene oxide-glutathione conjugates were studied in the intact rat and by isolated perfusion techniques in rat lung, liver and kidney. The intact animals converted the styrene oxide-glutathione conjugates almost entirely to styrene oxide-n-acetylcysteine derivatives mercapturic acids), with much smaller amounts of cysteine, cysteinylglycine and (unchanged) glutathione conjugates. Only small amounts of biliary excretion (approximately 5%) and less than 1% of fecal excretion of radioactivity were found. The isolated perfused kidney retains the capacity to transform virtually all of the glutathione conjugates at the dose level studied (25-30 mumol/kidney) and the principal component in urine from the isolated kidney was the cysteine conjugate. Isolated perfused lung experiments demonstrated that this organ has a minor role in styrene oxide-thioether conjugate. Isolated perfused lung experiments demonstrated that this organ has a minor role in styrene oxide-thioether conjugate metabolism. The isolated perfused liver experiments showed that phenobarbital pretreatment has little effect on biliary excretion but barbital pretreatment has little effect on biliary excretion but that it causes profound qualitative and quantitative effects on metabolism of styrene oxide-glutathione conjugates in the perfusion medium. The high level of styrene oxide-cysteine conjugates in the perfusion medium of an isolated perfused liver, especially after phenobarbital treatment, is consistent with the theory that gamma-glutamyltransferase activity is extracellular. The high-pressure liquid chromatography system of analysis described offers the ability to simultaneously separate and quantitate the major thioether conjugates of styrene oxide and other electrophilic epoxides.

Animals↗
PubMed1980

Structure-activity relationships of pyrrole amidine antiviral antibiotics III: preparation of distamycin and congocidine derivatives based on 2,5-disubstituted pyrroles.

Isomers of distamycin A and tripyrrole congocidine containing 2,5-disubstituted pyrroles were synthesized along with distamycin and congocidine homologs containing a single pyrrole ring. Selected compounds were evaluated for their cytotoxicity and antiviral activity. All of the tripyrrole derivatives tested in this series were nontoxic but were less active than distamycin A. The monopyrrole derivative, N-methyl-5-nitropyrrole-2-carboxamido-beta-propionamidine hydrochloride, was nontoxic and was almost as active antivirally as distamycin A.

Antiviral Agents↗
PubMed1980

Structure-activity relationships of pyrrole amidine antiviral antibiotics. 2. Preparation of mono- and tripyrrole derivatives of congocidine.

Representatives of three types of congocidine (1) analogues were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, and effects on the synthesis of HS DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polymerase. All synthesized tripyrrole derivatives of congocidine were less cytotoxic and more active than the parent drug in all the three ant iviral tests.

Antiviral Agents↗
PubMed1979

Structure--activity relationships of pyrrole amidine antiviral antibiotics. 1. Modifications of the alkylamidine side chain.

Representatives of three types of side-chain analogues of distamycin A (1) were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, effects on the synthesis of HSV DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polymerase. Distamycin A was the most active compound in all three antiviral tests, as well as the most toxic. However, several compounds, in particular the aromatic analogues 15 and 16, showed no toxicity under the experimental conditions used but were still very active in the three antiviral tests.

Animals↗
PubMed1979

Determination of lipopolysaccharide by a bioluminescence technique.

The determination of the lipid A content of bacterial lipopolysaccharide by using a dim mutant of the luminous bacterium Beneckea harveyi is described. The luminous bacteria emitted light upon the addition of an acid hydrolysate of lipopolysaccharide which contained myristic acid, thus making it possible to detect as little as 1 ng of lipopolysaccharide. By converting the 3-OH-myristic acid to myristic acid, it was possible to further increase the detection sensitivity and to establish a basis for a specific and highly sensitive bioassay for the detection of lipopolysaccharide.

Biological Assay↗
PubMed1979

Cardiovascular lesions and various tumors found in rats given T-2 toxin, a trichothecene metabolite of Fusarium.

White rats given intragastrically 3alpha-hydroxy-4beta,15-diacetoxy-8alpha-(3-methylbutyryloxy)-12,13-epoxy-tricholthec-9-en (T-2 toxin), a trichothecene metabolite of several Fusarium species, developed various acute and chronic, topical and systemic lesions. The rats that survived 12 to 27.5 months after the first of three to eight doses of T-2 toxin (0.2 to 4 mg/kg body weight) alone or in conjunction with nicotinamide given i.p. (200 to 250 mg/kg body weight) developed cardiovascular lesions of various degrees of severity and/or tumors, benign and malignant, of the digestive tract and of the brain. T-2 toxin is known occasionally to contaminate cereals and other agricultural products, harvested or stored under damp and cold conditions. T-2 toxin was responsible for an often fatal disease in humans, known in the U.S.S.R. as "alimentary toxic aleukia," and also for outbreaks of hemorrhagic mycotoxicoses in livestock in various countries. T-2 toxin and other Fusarium mycotoxins may be involved in the etiology of cardiovascular lesions and of certain tumors considered as "spontaneous" in animals and humans.

Animals↗
PubMed1978

Progesterone biotransformation by plant cell suspension cultures.

Progesterone was converted to 5alpha-pregnane-3alpha-ol-20-one, delta4-pregnene-20alpha-ol-3-one, delta4-pregnene-14alpha-ol-3,20-dione, delta4-pregnene-7beta,14alpha-diol-3,20-dione, and delta4-pregnene-6beta,11alpha-diol-3,20-dione by cell cultures of Lycopersicon esculentum. Cell cultures of Capsicum frutescens (green) metabolized progesterone to delta4-pregnene-20alpha-ol-3-one in very high yield, and Vinca rosea yielded delta4-pregnene-20beta-ol-3-one and delta4-pregnene-14alpha-ol-3,20-dione. A stereospecific reduction of the keto groups and a double bond and stereospecific introduction of hydroxyl groups at the 6, 11, and 14 positions have been observed. The mono- and dihydroxylated progesterones have not previously been reported as metabolic products of progesterone by plant cell systems and represent de novo hydroxylation of a nonglycosylated steroid.

Chemical Phenomena↗