[Experimental research on the toxicity of pharmapentoxifylline (II)]. / Eksperimentalni prouchvaniia vurkhu toksichnostta na farmapentoksifilin (II suobshtenie).

The results from morphological studies on liver, lung, heart, spleen, intestine, brain, skin, testes (ovaries), obtained in the end of the first and third month of animals, treated with pharmapentoxiphyline (PP), are described. The experiments were carried out on 312 white rats (male and female), divided into 2 series: I series--oral usage of the preparation in doses of 100, 300 and 6 mg/kg, II series--intraperitoneal administration in doses of 30, 75 and 150 mg/kg. It was established that PP, administered for a period of 3 months orally in a dose of 100 mg/kg and intraperitoneally in a dose of 30 mg/kg did not induced changes in the structure of all examined organs. Slight dystrophic changes in liver, lung and spleen occurred in the end of the third month under the influence of an oral dose of 300 mg/kg and an intraperitoneal dose of 75 mg/kg. The obtained results are discussed in connection with the pharmacological action of drug-peripheral vasodilatator.

[Effects of preliminary fasting on the development of D-galactosamine-induced acute lesion of the liver in rats]. / Vliianie predvaritel'nogo golodaniia na razvitie ostrogo povrezhdeniiapecheni D-galaktozaminom u krys.

The effect of 48-hour preliminary fasting on the development of acute hepatitis in 24 h after the use of 1,855 mmol D-galactosamine per 1 kg bw has been studied on rats. Both intensification of dystrophic and necrotic processes in the liver and aggravation of ultrastructural changes and disorders have been observed. Concentrations of reduced glutathione in the liver and D-glucaric acid in the urine are not changed under the effect of intoxication.

[Effect of prior starvation on the development of acute thioacetamide-induced liver damage in rats]. / Vliianie predvaritel'nogo golodaniia na razvitie ostrogo pechenochnogo povrezhdeniia tioatsetamidom u krys.

The effect of previous fasting on the liver morphological changes and microsomal cytochrome P-450 and b5 content was studied in thioacetamide-induced (100 mg/kg) rat liver necrosis. Starvation for 48 hours immediately before thioacetamide administration aggravates the dystrophic and necrotic processes, as revealed by histology, electron microscopic investigations and serum aminotransferase activity. The liver microsomal cytochrome P-450 concentration tended to decrease after thioacetamide challenge, with fasting resulting in a more significant loss of cytochrome P-450. Cytochrome b5 content, however, was found to increase in acute liver necrosis induced by thioacetamide.

Immunological and radioimmunological studies in food allergy.

Experiments in order to induce food allergy were carried out in guinea pigs. The sensitization with egg albumin, pasteurized cow milk and bovine serum albumin provoked anaphylactic shock. The passive cutaneous anaphylaxis, serum antibodies, liver cytochrome P-450 concentration and the anaphylactic shock were determined. Some correlation between the mortality, anaphylactic antibodies and cytochrome P-450 monooxygenase system was established. The morphology of the jejunal mucosa, the activities of the 5 disaccharidases, the number of immunoglobulin secreting cells (Ig SC) and the mastocytes were investigated in 35 patients with food allergy. Normal mucosa was found in 28 cases as well as a significant decrease of the lactase, sucrase and trehalase activities. An increase of IgM and IgG secreting cells and of mastocytes, different electron microscopic changes in the enterocytes (an increased number of lysosomes, appearance of vesicles in cytoplasma, shortening, enlargement and uneven distribution of microvilli) as well as symptoms of functional activity in the plasmocytes and some others were also revealed. The experimental model obtained is similar to that one in humans according to the enteral way of sensitization the high selectivity of the allergic reaction which is of reagin type as the immunoglobulin changes are involved.

[Ultrastructure of fat cells of obese patients with diabetes mellitus before and after treatment with a reducing diet]. / Ultrastrukturelle Untersuchungen der Fettzellen Adipöser mit Diabetes mellitus vor und nach Behandlung mit Reduktionskost.

Ultrastructural investigation of lipocytes of obese diabetics (Diabetes mellitus) before and after treatment with a reducing diet 21 diabetics not depending on insulin with obesity of the second or third degree were given for 3 months a reducing diet containing 5110 kJ/day (86 g protein, 41 g fat, 119 g carbohydrates). After treatment the test persons had a loss of weight of 7.60 kg on average. Before and after treatment subcutaneous adipose tissue was taken by puncture biopsy and investigated by electron microscopy. After treatment extended intercellular spaces are evident in which collagenic and elastic fibres appear quantitatively enlarged. A certain plication and inequality of the cell membranes, a penetration of the fat droplet by cytoplasmatic outgrowths as well as a diminution of the lipocytes and the big fat droplet were found. The investigations show that even the relatively short treatment of 3 months exercises an influence on the structure of the lipocytes. That shows new possibilities of therapy and prophylaxis of obesity.

[Morphologic and morphometric studies of the liver of the white rat during inadequate feeding and aflatoxin poisoning]. / Morfologicheskie i morfometricheskie issledoavniia pecheni belykh krys pri nedostatochnom pitanii i khronicheskoi aflatoksinovoi intoksikatsii.

The authors carried out morphological and morphometric studies of the liver of rats under malnutrition and chronic aflatoxin intoxication for 2 and 7 months. Malnourished animals demonstrated atrophic alterations. Animals exposed to aflatoxin B1 manifested severe dystrophic and necrobiotic alterations which did not depend on the nutrition regimen. In rats administered aflatoxin, blastomic processes were identified only at the 7th month. Whatever the diet.

Ultrastructural changes in the liver of rats treated with aflatoxin B1 and undernutrition.

White male Wistar rats were treated with Aflatoxin B1 for 2 months while on standard pellet food ad libitum or 80% undernutrition. Although each animal received 400 micrograms of AFB1 no cancer in the liver or elsewhere developed. Histologically the findings in the groups treated with the mycotoxin were the well known until now. Undernutrition led to atrophic and degenerative changes in the liver. Electronmicroscopically there were found marked changes in the nucleus, with microsegregation of the nucleolus; diminution and disorganization of endoplasmic reticulum and mitochondria; changes in the lysosomes, abundance of microbodies etc. with difference according to the intoxication, nutrition, or both of them. However, the combination of the 2 etiologic factors did not lead to a simple summation of the deleterious effect. At the same time, we do not have the right to claim a real "anticarcinogenic" action of undernutrition.

[Morphological changes in the organs of rats subjected to limited feeding and physical loading]. / Morfologichni promeni v niakoi organi na plukhove, podlozheni na ogranichno khranene i fizichesko natovarvane.

Changes in the liver, stomach, small intestine, kidneys, lungs, myocardium, aorta, spleen and mesenterial lymph nodes are studied histologically in 120 male white rats from the Wistar line, subjected to a deficient alimentation regime, with and without physical exertion. The observed slight degree of adiposogenital dystrophy of the liver during free feeding regime indicates that the latter is equivalent to overfeeding. Variations from the normal histological picture in some organs (liver, myocardium, stomach and small intestine) are detected in the groups undergoing rather prolonged, moderate undernourishment--a sign of the sensitivity of these organs to the limited supply of nutritive ingredients. Physical loading, combined with free alimentary regimen, exert a beneficial effect on the organism which is suggested by the morphological data disclosing a slightly enhanced function of the myocardium and kidneys in these animals.

Histochemical, biochemical and ultrastructural studies on the liver of fasted rats.

The subjection of rats with body weight 150 +/- 10 g to complete starvation for a period of four days leads to a diminution of total protein, total lipids, blood sugar, body weight and liver weight. Lipid dystrophy develops in the liver, as well as deposition of lipofuscin-like pigment and atrophy. Lipid dystrophy and desposition of pigment increase during the first three days and abruptly decrease during the fourth. Atrophy is a progressive process. The delineation of three phases in the atrophic - dystrophic process is possible with the application of histological, enzyme-histochemical, morphometric, biochemical and electron microscopic methods: Phase I (first 24 hours) - a common adaptive phase. It engages both the liver, which must utilize the increased nutrients from the organism depots and the homeostatic mechanisms of the organism as a whole. Phase II - (second and third 24 hours) - alterative-restorative, manifested markedly at the liver parenchimal level and especially by autophagic lysosome function. Phase III - (fourth 24 hours) - alterative. Exhaustion of adaptive-restorative liver process (and the hepatocyte in particular), and the organism as a whole as well.