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Biomedical subjects

V M Dil'man

Publications and source records attributed to V M Dil'man.

At least 55 records · Page 3Linked to original sources

[Effect of miskleron (clofibrate) on dimethylhydrazine induction of intestinal tumors in rats].

Intestinal tumors were induced in male rats by dimethylhydrazine (14 mg/kg body weight subcutaneously once a week during 20 weeks). Part of animals received clofibrat per os in a dose of 25 mg a day 5 times a week. Clofibrat did not influence the frequency of the development of intestinal tumors but significantly decreased the number of medium-size and large tumors. The possible mechanisms of clofibrat action as well as the use of clofibrat and some related agents in oncology are discussed.

Animals↗

[Supression of the lymphocyte blast transformation reaction evoked in human subjects by a fat load].

It has been shown that "Intralipid"--triglycerides emulsion, used for parenteral feeding, administered intravenously in the amount of 200 ml would induce within 2 hours in human subjects a metabolic immunosuppression, estimated by a drop in the labelled thymidine and uridine incorporation into phytohemagglutinin stimulated lymphocytes. The dosage blood loss (25 ml of blood) would prevent the inhibition of lymphocytic blasttransformation reaction, that seems to prove the functional nature of metabolic immunosuppression, induced by the increased concentration of fatty acids in blood due to hydrolysis of administered triglycerides. The relationship between metabolic immunosuppression and the standard methods of treatment used in oncology is briefly discussed.

Bloodletting↗

[Increase in the sensitivity threshold of the hypothalamo-hypophyseal complex to the inhibiting action of dexamethasone in the process of aging and in cervical cancer].

The basal level of the androgenic and glucocorticoid hormones excretion and the level of blood glucocorticoids were studied in 237 females (52--control group, 185--cervical cancer patients) depending on the age and the ovarian function state. Also, the threshold of sensitivity of the hypothalamo-hypophyseal function complex was estimated by a dexametazone test. Healthy females were shown with progressive ageing to have a relative preponderance of glucocorticoid hormones over androgenous ones, which is also observed in cervical cancer irrespective of age group. With ageing in healthy females the threshold of the hypothalamo-hypophyseal complex sensitivity is raised, whereas in cervical cancer patients an increased threshold of the sensitivity is observed in younger age groups and is more manifest. The increased threshold of the hypothalamo-hypophyseal complex sensitivity seems to be one of the mechanisms responsible for the occurrence of such unfavourable hormonal shift (a relative predominance of glucocorticoid hormones over androgenic ones), which in its turn play a significant part in tumors origination and development.

11-Hydroxycorticosteroids↗

[Age and increase in the sensitivity threshold of the tonic region of the hypothalamic sex center to inhibition by estradiol in female rats].

Estradiol-17 beta was injected into the 3rd ventricle of hemiovariectomized rats to study the sensitivity of the hypothalamic sexual centre. In aged (14--16-month-old) rats the dose of estradiol required for suppression of the compensatory ovarian hypertrophy by 50 and 100 per cent was 4--5 times greater than in young (3-month-old) rats. The results obtained suggest the age-associated increase of the threshold sensitivity of the tonic region of the hypothalamic sexual centre to estrogen suppression. These data can be used for the interpretation of the mechanism of both the age-associated elevation of gonadotropin secretion, and of the reproductive function.

Age Factors↗

[Improvement of the indicators of cellular immunity under the effect of polypeptide epiphyseal extract (epithalamine)].

The data obtained previously at our laboratory have evidenced that pineal polypeptide factors enhance the sensitivity of the hypothalamo-hypophyseal complex to the inhibiting action of glucocorticoids and estrogens and show an antistressor effect and the capacity to decrease the level of insulin and triglycerides in the experiment, and also suppress the growth of transplantable mammary gland cancer. In view of this, the pineal polypeptide extract was employed in a patient with reduced indices of cellular immunity. A restoration of indices of blasttransformation reaction induced by phytohemagglutinin, an increased number of rosette-forming cells and an improved response to dinitrochlorobenzene skin test were noted.

Adult↗

[Antibodies to thyroglobulin in patients with cancer].

Investigations of over 300 oncological patients and 120 healthy individuals have evidenced a considerable increase in the frequency of detecting antibodies to thyreoglobulin (in the titre 1/80 and higher) in patients with cancer of the breast, sigmoid and stomach in females and a tendency to such increase in cancer of the uterine body, and a number of other localizations.

Adult↗

[Phenformin elimination of the immunodepression caused by 1,2-dimethylhydrazine in rats].

Treatment of rats with 1,2-dimethylhydrazine (SDMH) with the doze of 21 mg/kg per body weight once a week during four weeks caused the decrease of biogenic amine level, particularly, of dopamine in the hypothalamus, the decrease of glucose tolerance, the increase of the blood level of insulin and triglycerides. According to the previously achieved data SDMH causes the elevation of the hypothalamic threshold of sensitivity to the inhibitory action of estrogens. At the same time SDMH provides considerable suppression of lymphocyte blastogenic response to phytohemagglutinin and lipopolisaccharide, the decrease of the level of antibody produced against sheep erythrocytes, and the decrease of phagocytic activity of macrophages. Thus SDMH provides the syndrome of intensified aging. Recently our laboratory achieved the data, that antidiabetic drug-phenformin-improves cell-mediated immunity indices and the activity of phagocytosis in middle-aged subjects, as well as in patients with atherosclerosis and cancer (Vopr. Oncol., 1976, N 2, p. 13). On the basis of these findings phenformin (2 mg/day per os) was administered in rats in combination with SDMH. This resulted in restoration of all the abovementioned immunologic indices. It may be suggested that SDMH causes metabolic immunodepression, similar to the immunodepression, inherent to normal aging, pregnancy, stress and specific age-associated pathology--diseases of compensation (Vopr. Oncol., 1976, N 8, p. 3). If immunodepression is one of the components of cancerogenesis, then the elimination of metabolic immunodepression, which arises in course of normal aging or under the influence of cehmical cancerogens, can provide an anticancerogenic prophylactic effect.

Administration, Oral↗

[Decrease in the excretion of antigonadotropic factor in patients with cancer of the uterine cervix and prostate gland. Experimental antitumor effect of an epiphyseal extract].

Kaolin-acetone extracts from the urine of patients with cancer of the prostatic gland and uterine neck were found to contain much less quantity of antigonadotropic factor than corresponding substances from the urine of control groups of males and females. This evidences a decreased function of the epiphysis in these groups of tumor patients. Acetic acid extract from cattle epiphyses inhibits the growth of transplantable tumor of mice strain RSM.

Animals↗

[Correlation between immunological reactivity and the fat-carbohydrate metabolism. Influence of phenformin].

Based on the conceptions of the relationship between energy and adaptation-immunological systems a number of hormone-metabolic indices were compared with immune reactivity as evidenced by skin tests and rosette-formation reaction. It is shown that lowering of immunological indices in oncological patients is associated with a decreased sensitivity of dexametasone suppression of cortisol, an increased concentration of 11-oxycorticosteroids in blood, a higher level of triglycerides, cholestrol, beta-lipoproteins and less glucose tolerance. The use of phenformin during 3 months in patients with atherosclerosis resulted in a considerable increase of the index of phytohemagglutinin stimulated blasttransformation of lymphocytes and rosette-formation reaction. This effect was associated with normalization of lipid metabolism indices.

17-Hydroxycorticosteroids↗

[Mutational-metabolic model of carcinogenesis and the progression of the neoplastic process].

The given data indicate the presence of a negative correlation between metabolic indices (a decrease of the tolerance to glucose, increase of the blood level of free fatty acids, insulin, cholesterol triglycerides, cortisol, stc) and the indices of cellular immunity, which is determined by the number of rosette-forming cells and blasttransformation reaction to PHA and skin tests. Accordingly, the administration of an antidiabetic drug-phenformin (phenetylbiguanide)--apart from the improvement of metabolic pattern, results in the restoration of the cell-mediated immunity indices. These findings provide a basis for stating the phenomenon of metabolic immunodepression. The metabolic immunodepression may be supposed to prevent immunological surveillance activation, which normally is realized through the signals, provided by cells subjected to somatic mutation. It is noteworthy that the given metabolic conditions (hypercholesterinemia, hyperinsulinemia, the enhanced utilization of free fatty acids) promote the division of somatic cells. Thus, the same metabolic shifts which increase the pull of proliferating cells and, accordingly, increase the possibility of mutation development, also cause the metabolic immunodepression at the same time. These opposite metabolic influences on somatic cells and T-dependent lymphocytes cause the development of the syndrome of cancrophilia. The syndrome of cancrophilia normally arises at pregnancy, in intensive growth of the organism in childhood, accelerated development, stress and during normal ageing. Many carcinogens cause the decrease of tolerance to glucose, the increase in blood-insulin level and elevation of the threshold of sensitivity of the hypothalamus to feedback suppression. This phenomenon is based on the decrease of catecholamine level in thehypothalamus in ageing, stress and the action of some carcinogens. Thus, the syndrome of cacrophilia provides the conditions for cancer development and tumor progression, besides, the tumor itself produces the metabolic shifts typical of cancrophilia. In the light of mutation-metabolic model of cancer development, it is possible to consider the fundamental factors which increase of hinder carcinogenesis.

Aging↗

[Correction of endocrine-metabolic disorders in oncologic patients. The effect of biguanides (phenformin and adebita), miskleron and diphenin].

The study was conducted on 40 patients previously operated upon radically for cancer of the mammary gland, uterine body, lung and colon. All patients were explored and treated during 2-14 months. As evidenced by the data obtained, biguanides proved to be mostly effective with regard to normalization of an excessive weight in oncological patients and an impared tolerance to glucose, whereas myscleron-in cases of hyperlipemia with marked hypercholesterinemia, diphenin - in a concomitant excessive production of corticosteroids. Moreover, the pharmacological drugs concerned were shown to influence also the production of gonadotropic, steroid and thyroid hormones.

Adrenal Cortex Hormones↗

[An increase in hypothalamic sensitivity to the inhibiting effects of estrogens caused by use of L-DOPA, diphenine, epithalamin and phenformin in old rats].

Daily treatment of hemicastrated young rats with 0.57 mug of stilbestrol inhibited compensatory ovarian hypertrophy (COH) by 48% in the 3-month animals and by 3% only in the 18-month animals. Administration of L-DOPA, dilantin, epithalamin or phenoformin with the same dose of estrogen to old rats suppressed the COH by 65-98%. L-DOPA and epithalamin were effective when administered into the 3rd cerebral ventricle. A functional nature of the age changes in the hypothalamic sensitivity to the estrogen action is suggested.

Animals↗