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Biomedical subjects

B Kowalski

Publications and source records attributed to B Kowalski.

At least 19 recordsLinked to original sources

Relationships among ecology, demography and diseases of European bison (Bison bonasus).

The bison population in the Bialowieza Forest in Poland has now grown to approximately 300, while the herds in the Belarusian part of the forest total about 240 bison. The first signs of a health problem in these herds appeared in 1980, when two cases of balanoposthitis were detected in two bulls (2 and 5 years of age). Since 1980 research has been conducted to explain the cause of diseases, particularly balanoposthitis, and to monitor the health of bison in Bialowieza Forest. A total number of 614 bison (294 male and 320 female) of different ages was eliminated between 1980 and 2000. Not all the culled bison were examined (postmortem analysis, histopathological, bacteriological, virological and toxicological examinations, serological tests, molecular research). Based on the increase in numbers, reproduction in this population for the past 21 years is generally considered successful. Among 182 male bison eliminated during 1990-2000, only 85, or 47%, of the animals had balanoposthitis. Thus, the percentage of balanoposthitis cases went from 100% during the 1980s down to 47% in the past decade. It appears that the culling process has been a major factor leading to this decrease. It can be assumed that a set of factors is involved in the appearance of the disease (Corynebacterium spp., Bacillus sp., Pseudomonas aeruginosa, Escherichia coli, Ureoplasma spp, Fusobacterium necrophorum, Streptoccocus spp., Staphyloccocus spp.) while opportunistic infections including nematodes (Onchocerca spp.) are responsible for the occurrence of secondary lesions.

Animals↗

Epithelial binding of 1,2-dichloroethane in mice.

The metabolism and binding of 14C-labelled 1,2-dichloroethane (DCE) in female C57BL-mice were studied. As shown by whole-body autoradiography with heated and organic solvent-extracted tissue sections of i.v. injected mice, a selective localization of non-volatile and bound DCE-metabolites occurred in the nasal olfactory mucosa and the tracheo-bronchial epithelium. Low levels of metabolites were also present in the epithelia of the upper alimentary tract, vagina and eyelid, and in the liver and kidney. A decreased mucosal and epithelial binding was observed after pretreatment with metyrapone, indicating that the binding might be due to an oxidative metabolism of DCE. The quantitated levels of in vivo binding were considerably lower in mice injected i.p. with DCE, as compared to mice given equimolar doses of 14C-labelled 1,2-dibromoethane. In vitro experiments with 1000 g supernatants from various tissues showed that the nasal mucosa has a marked ability to activate DCE into products that become irreversibly bound to the tissue. It is proposed that the nasal olfactory mucosa is a target tissue for toxicity of DCE.

Animals↗

Tissue localization of the carcinogenic glutamic acid pyrolysis product Glu-P-1 in control and beta-naphthoflavone-treated mice and rats.

Autoradiograms obtained after i.v. injection of the 14C-labelled carcinogenic glutamic acid pyrolysis product Glu-P-1 to mice and rats showed a pronounced uptake of radioactivity in the liver, kidney, thyroid and nasal mucosa. High concentrations of radioactivity were present in the bile and intestinal contents at short post-injection times. In the male rat, the Zymbal's gland and the preputial gland were identified as sites of high and specific binding at all post-injection times examined. The liver and nasal mucosa were identified as sites of retention of non-extractable radioactivity. In the pigmented mouse, Glu-P-1 and/or its metabolites were accumulated in melanin. Glu-P-1 is known to be activated by cytochrome P-448. Pretreatment with beta-naphthoflavone (a cytochrome P-448 inducer) did not change the tissue localization of radioactivity in either species except for the liver where the overall labelling was decreased. Neither did pretreatment of mice with the glutathione-depleting agent phorone change the distribution pattern significantly. However, combined pretreatments of mice with either phorone or beta-naphthoflavone and the cytochrome P-448 inhibitor 9-hydroxyellipticine resulted in an increased overall retention of radioactivity in the body.

Animals↗

Cytologic characteristics of neoplastic and of regenerating hepatocytes in fine needle aspirates of rat liver.

L-azaserine (l-aza)-induced hepatocellular carcinoma (HCA) and hyperplastic liver lesions were studied in livers from 86 l-aza treated animals and 16 saline controls. Eight additional rats studied 24 or 48 hr after partial hepatectomy and 8 young rats studied after no experimental manipulation served as additional controls for determination of cytologic effects of increased cell turnover. Fine needle aspirates (FNA) were made of all gross liver lesions and of grossly normal liver; H&E stained sections of liver surrounding each needle track were made. The FNA were fixed in 95% ethanol, stained with a routine Papanicolaou stain, randomized, and evaluated using 18 cytologic features. They were diagnosed without knowledge of the histologic diagnosis or treatment group. Features were analyzed with discriminant function analysis to determine their relative importance in making the diagnosis. FNA proved to be an accurate method for diagnosis of hepatocellular lesions in laboratory animals. The cytologic features of greatest usefulness in establishing the diagnosis were cord pattern, chromatin pattern, nucleolar size and nuclear membrane irregularity. FNA could provide a useful experimental technique for following evolving lesions serially and for identifying subgroups within hyperplastic nodules.

Animals↗

Tissue binding of 1,2-dibromoethane in the cynomolgus monkey (Macaca fascicularis).

Autoradiography at different levels of resolution was used to study the tissue-binding of 1,2-dibromo[14C]ethane (DBE) in the cynomolgus monkey (Macaca fascicularis) in vivo (i.p. injection) and in vitro. The results show that DBE is metabolized to products which become bound to the tissues, preferentially in the liver and the kidney tubules. A distinct binding of radioactivity was also found in the adrenal zona reticularis. The binding of radioactivity in the surface epithelia of the respiratory and upper alimentary tract was not as high and striking as that previously observed in rodents. The results show that the sites of tissue-binding of DBE in the cynomolgus monkey correspond to the sites of tissue lesion observed in humans poisoned with DBE.

Animals↗

Binding of the aliphatic halides 1,2-dibromoethane and chloroform in the rodent vaginal epithelium.

Whole-body and light microscopic autoradiography were used to study the binding of 1,2-dibromo(14C)ethane (14C-DBE) and 14C-chloroform (14C-CF) in the mouse and rat vaginal epithelium in vitro and in vivo. In pregnant mice, mice pretreated with pregnant mare's serum gonadotropin (PMSG) or ovariectomized mice primed with medroxyprogesterone, a high level of bound 14C-DBE metabolites were present in the epithelium, while in ovariectomized oestradiol-primed mice or intact oestradiol-primed mice, the binding was low. Similar results were obtained with 14C-CF, although the level of binding generally was lower than that observed after 14C-DBE-exposure. No binding of 14C-DBE-metabolites was observed in the juvenile rat vaginal epithelium, whereas a high binding was present in the PMSG-primed adult rat vaginal epithelium. Collectively, these data show that 14C-DBE and 14C-CF are transformed in situ to metabolites that are irreversibly bound to the vaginal epithelium. The results also suggest that the activating enzyme is under endocrine control and has a low activity in the juvenile and oestradiol-primed adult animal.

Animals↗

Metabolism of 2,3,4',6-tetrachlorobiphenyl: formation and tissue localization of mercapturic acid pathway metabolites in mice.

2,3,4',6-Tetrachlorobiphenyl (tetraCB) and the corresponding 14C-labelled compound (14C-tetraCB) were synthesized. Two reference compounds, 4-methylthio- and 4-methylsulphonyl-2,3,4',6-tetrachlorobiphenyl were also prepared and characterized. TetraCB and 35S-cysteine were given to groups of female mice. Formation of methyl[35S]sulphonyl-tetraCB was indicated by the presence of extractable sulphuric acid-soluble radioactivity in lung, liver, kidney and fat of the tetraCB-treated mice. As demonstrated by gel permeation chromatography followed by gas chromatography-mass spectrometry, the tissues of the tetraCB-treated mice contained mainly methylsulphonyl-tetraCB, minor amounts of tetraCB and traces of methylthiotetraCB. The major compound present in lung was 4-methylsulphonyl-tetraCB, indicating the presence of specific binding sites for this metabolite in lung tissue. According to autoradiography of mice injected with 14C-tetraCB, these binding sites were present mainly in the tracheo-bronchial mucosa.

Acetylcysteine↗

Fetal epithelial binding of 1,2-dibromoethane in mice.

Whole-body autoradiography and computer-assisted image analysis were used to study the tissue binding of the volatile carcinogenic pesticide 1,2-dibromo[14C]ethane (DBE) in C57BL mouse fetuses. Autoradiograms obtained from pregnant mice in late gestation (day 16-17), showed a high level of non-volatile metabolites in the epithelia of the fetal upper alimentary tract and respiratory tract. As determined by image analysis, the concentration of non-extractable (presumably covalently bound) metabolites in the oral epithelium was three times higher than in the maternal liver (day 17). The concentrations in the junction region of the forestomach and the mucosa of the nasal cavity were equal to that in the maternal liver, whereas the bronchi contained lower levels of non-extractable metabolites than the maternal liver. Autoradiography of excised fetal tissues incubated with DBE showed that high levels of non-extractable metabolites were present in the epithelia of the oral cavity, oesophagus and forestomach also in vitro. The results indicate that the fetal epithelia can activate DBE to products that bind to the tissue; they also raise the possibility that DBE is a transplacental carcinogen in mice.

Animals↗

Epithelial binding of 1,2-dibromoethane in the respiratory and upper alimentary tracts of mice and rats.

The metabolism and binding of the volatile carcinogen 1,2-dibromo[14C]ethane (DBE) were studied in C57BL mice, Sprague-Dawley rats, and Fischer rats. As shown by the whole-body and light microscopic autoradiography with heated and/or extracted sections, a selective accumulation of metabolites occurred in a number of tissues, preferentially in the reported target tissues for DBE-induced lesions [i.e., in the nasal cavity, lung, forestomach, and liver (tumors) and the adrenal, testicle, liver, and kidney (nonneoplastic lesions)]. High levels of nonextractable metabolites were registered in the epithelia of the entire respiratory tract, the upper alimentary tract, the vagina, and the subepithelial glands of the olfactory mucosa. Lower levels of metabolites were observed in the liver, adrenal cortex, testicular interstitium, and kidney. Autoradiography of slices from various extrahepatic tissues incubated in vitro with DBE showed that most epithelia of the respiratory tract, upper alimentary tract, vagina, and the testicular interstitium have a marked ability to activate DBE to metabolites that become bound to the tissue. Further in vitro experiments, performed with S-1 fractions prepared from various tissues, indicated that the nasal mucosa was most active in transforming DBE to products which could not be extracted from the protein precipitate. It is proposed that tissue-selective metabolism and activation of DBE in the epithelia of the respiratory and upper alimentary tract are responsible for the observed DBE-induced lesions in these organ systems.

Animals↗

Mutagenicity of quindoxin, its metabolites, and two substituted quinoxaline-di-N-oxides.

The quinoxaline-di-N-oxides carbadox, olaquindox, and quindoxin, which are potent antibacterial agents, were tested for mutagenicity in the Salmonella microsomal system. They all induced base pair substitutions and frameshift mutations in Salmonella, and occurred independently of the presence of a rat liver microsomal fraction in the test system. Mutagenicity was dependent on the presence of their N-oxide groups, since quinoxaline, a completely reduced derivative of quindoxin, was not mutagenic, whereas the partially reduced quinoxaline-N-oxide exhibited a lower mutagenic activity than quindoxin. recA and uvrB Salmonella were found to be more susceptible to mutagenic quinoxaline derivatives than wild-type strains. The mutagenicity of quinoxaline-di-N-oxides was enhanced under anaerobic incubation as was the antibacterial activity. These results suggest that both the antibacterial and mutagenic activity of quinoxaline-di-N-oxides depend upon the same bacterial activation mechanism.

Anaerobiosis↗

Occurrence and formation of nitrosamines in animal feeds.

A total of 465 samples of ingredients of animal feeds (fish meal, antarctic krill meal, experimental silage containing 40% dried animal wastes) and complete mixed feeds and protein concentrates were analysed for nitrate and nitrite content in the period 1973-78. Over 62% of the samples contained nitrates in concentrations ranging from 1 to 1020 mg/kg, and 6% contained 1-15 mg/kg of nitrites. After a preliminary survey, the samples having the highest levels of nitrate, nitrite and amines were selected and analysed for volatile N-nitrosamines. Of 171 selected samples, 40% were found to contain N-nitrosodimethylamine in the range of 0.003 to 0.417 mg/kg. No statistically confirmed correlation between concentrations of nitrates or nitrites and nitrosamines could be demonstrated. Large amounts of dimethylamine, ranging from 110 to 1765 mg/kg, were found in all samples of krill meal. Incubation of krill meal and fish meal with nitrite, under conditions similar to those existing in the animal stomach, resulted in the formation of substantial amounts of NDMA. The occurrence of N-nitrosamines in feeds and their possible formation in vivo from precursors present in feeds seems to be an important problem from the hygienic standpoint, because of possible "carry-over" to tissues, milk and eggs.

Animal Feed↗

Intake of volatile nitrosamines from consumption of alcohols.

Volatile nitrosamines were determined in alcoholic drinks during epidemiologic studies on the relationship between esophageal cancer incidence and alcohol consumption in Normandy, France. Nitrosodimethylamine (NDMA) was found commonly in most alcoholic drinks tested, with the exception of wine. The average level, about 2 micrograms/liter in beers, was higher than that for other drinks; the range was 0.2--8.6 micrograms/liter. Traces of nitrosodiethylamine (NDEA) were also detected in spirits and ciders. No significant increases in levels were found after nitrosation. Calculation of daily intake in the study region showed that the main intake of volatile nitrosamine is from NDMA in beer. The intake of NDEA through consumption of cider is about one-third that of NDMA from all sources.

Alcoholic Beverages↗