Vol 39, No 1 (1993)

Clinical endocrinology
Cellular and humoral immunity of diabetics at the early stages of the disease development: experience gained in the treatment with azathioprin, an immunosuppressant
Dedov I.I., Abugova I.A., Shishko P.I., Shamkhalova M.S.
Abstract

A total of 40 patients with type 1 diabetes mellitus, in whom the disease was diagnosed 1 to 12 months previously, were examined. An imbalance between the T and В cellular components of the immunity was found in the patients with the early stages of the disease, as was an elevated titer of the complement Cl component as against the reference group. The degree of the immunologic shifts was in direct correlation with the HLA A9 antigen expression, this relationship being the most marked in cases with the HLA DR3 and DR4. The incidence of these antigens expression was significantly higher in the patients with marked immunity shifts, than in those with negligible immunity changes. Therapy with an immunosuppressant azathioprin was associated with a noticeable reduction of the initially elevated cellular immunity parameters (total T and В lymphocyte counts, T helpers-inductors, DR carriers) and a trend towards a reduction of all the components and total activity of the classical route of the complement activation predominantly at the expense of the Cl and C5 components. The efficacy of this drug in therapy of new cases of insulin-dependent diabetes mellitus was confirmed, and the undisputable relationship between the efficacy of immunity suppression, that helped achieve a clinical remission, and the disease duration, was demonstrated. Monitoring of the cellular and humoral immunity parameters, of the activity of the classical route of the complement activation permitted an indirect judgement on the usefulness of immunity suppression for the correction of immunity disorders as factors contributing to the development of microvascular disturbances in insulin-dependent diabetes mellitus.

Problems of Endocrinology. 1993;39(1):3-7
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Immune characteristics of patients with insulin-dependent diabetes mellitus with various duration of the disease
Shishko P.I., Dreval A.V., Sadykova R.E., Efuni S.S., Matyukov A.E., Abugova I.A., Polyanskaya I.S., Skuibin B.G., Filatov A.B.
Abstract

The paper presents data on the cellular and humoral immunity in different periods of insulindependent diabetes mellitus (with the disease standing of 0.5±0.4 years, group A; 3±1.8 years, group B; and 15±4 years, group C). Group A patients presented with the immunity system activation: increased counts of T cells, В lymphocytes, T helpers and T inductors, increased share of active T cells (that is, DR positive ones), elevated content of IgM, IgG, IgA (214±51 mg%, 1200±124 mg%, 250±34 mg%, respectively) as against the reference group (156±74, 914±387, 189±49 mg%, respectively) (p<0.01). In group В patients, who suffered a longer disease, the immunity parameters were within the normal range, and in group C patients, in whom the disease standing was the longest, these shifts were contrarywise as against those in group A, that is, T and В cell counts were lowered, as were the counts of T-helpers-inductors, lg levels, and the phagocytosis index was 65±5 vs. 85±10 % in the controls (p<0.05), the phagocytosis level being 4±2 vs. 10±2 in the controls (p<0.05). The authors analyze the association of the HLA system characteristics with the immunity shifts. Patients with the HLA A9, B8, B15, B18, DR3, DR4 presented with significant shifts in the immunity status as against those with the HLA Al, A10, B5, B12, B16, B27, DR5, DR7. These data confirm a high informative value of the HLA markers for predicting the degree of alterations in the immunological homeostasis.

Problems of Endocrinology. 1993;39(1):8-11
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Activities of membranebound proteinkinase c and red cell ATPases in diabetic angiopathy
Yefimov A.S., Serghiyenko A.A., Vorobets Z.D., Serghiyenko L.M.
Abstract

The activities of proteinkinase C, total, Mg2 and Na+, K+-dependent ATPases in red cell membranes were compared in 46 patients with insulin independent, 30 ones with insulin dependent diabetes mellitus with various degrees of vascular disorders, and in 17 patients with atherosclerosis with the predominant involvement of the main vessels of the lower limbs. Diabetes mellitus and the progress of vascular disorders were associated with a more marked depression of proteinkinase C, total and Na+, K+-dependent ATPase activities, this being particularly characteristic of the patients with insulin-independent diabetes and macrovascular disorders, inhibited activities of proteinkinase C and ATPases in red cell membranes in the course of diabetic vascular disorders progress evidence their contribution to the pathogenesis of diabetic angiopathy.

Problems of Endocrinology. 1993;39(1):11-14
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Blood serum atherogenicity in children with type 1 diabetes mellitus
Shagayeva M.M., Slavina L.S., Sobenin I.A., Orekhov A.N.
Abstract

Blood serum atherogenicity was studied in children suffering from type 1 diabetes mellitus, as was the relationship between the serum atherogenicity and a number of clinical biochemical parameters. Of the 34 serum samples from children with diabetes 16 did not influence the intracellular cholesterol levels, the rest 18 were found atherogenic, that is, they increased the total cholesterol levels in the cells by 50-70%. Blood serum atherogenicity in all the examinees and in groups A and В separately was. unrelated to the patients’ age, insulin dose, fructosamine levels, or the disease standing. A positive correlation was detected between the patients’ ages and the insulin dose.

Problems of Endocrinology. 1993;39(1):14-15
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Automated calculation of the RD parameter in euglycemic insulinmic clamp
Dreval A.V., Suzdalnitsky R.S., Dreval T.P., Vladimirov P.V., Bairamkulov K.D., Titova G.V., Grebenev D.E., Anykina N.V.
Abstract

The authors proposed a new analytical approach to a search for the RD parameter in euglycemic insulinemic clamp which imparts a rate to glucose infusion. Two diabetic patients were investigated (RD parameter in the first case was determined by intuition, and in the second case — on the basis of mathematical iterative formulas). The analytical approach permitted a two-fold reduction of the time of clamp investigation improving its quality.

Problems of Endocrinology. 1993;39(1):15-20
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Diabetes mellitus epidemiology in Daghestan
Abusuyev S.A., Khachirov J.G., Akhmedkhanov A.A.
Abstract

The authors analyze the prevalence of diabetes mellitus in Daghestan, a republic with various climatic and geographic zones, whose population belongs to a great variety of ethnic groups, over 1987-1991. The findings evidence a lower prevalence of this condition in Daghestan than in other regions, but there is a trend to an annual increment in the morbidity, mostly at the expense of Type II diabetes. The urban residents of Daghestan more often develop the disease, may be due to the fact that wine-making industry is concentrated mainly in town. In the country diabetes mellitus in more incident on the planes, less incident in the foothills, and still less incident in the mountains. The highlanders, when they come to the planes, develop diabetes mellitus as frequently as the residents of the planes. Of the ethnic groups the Russians suffer from the disease most frequently, then come the Kumyks, Lakts, Darghines, Lezghines, Aguls, Tabasaranes; the Avares and Rutules are the least frequent among the diabetics. Preventive measures should be concentrated mostly in towns and on the planes. These specific features of diabetes mellitus epidemiology should be taken into consideration when organizing a net of endocrine service.

Problems of Endocrinology. 1993;39(1):21-24
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Differentiated approach to the treatment of autoimmune ophthalmopathy
Mazurov V.I., Svyatova L.Y., Danilichev V.F., Cheremisin V.M., Gurevich K.Y., Paskhina M.N., Mikhaltsov A.N.
Abstract

The results of comprehensive examinations and therapy of 67 patients with autoimmune ophthalmopathy are presented. In 80 % of the patients the disease coursed along with thyrotoxicosis, in 10 % thyroid function was reduced because of autoimmune thyroiditis, and in the rest autoimmune ophthalmopathy was an individual entity. A staged therapeutic complex for the treatment of this condition is suggested, aimed at correction of thyroid function (stage 1), followed by pathogenetic therapy including antiinflammatory measures, glucocorticoids and nonsteroid antiinflammatory drugs to arrest aseptic inflammation in the orbit, and immunosuppressive therapy to correct the immunity shifts. After clinical and immunologic remission was achieved, courses of maintenance therapy (nonsteroid antiinflammatory drugs) were carried out for 3-5 months monitored by blood analyses and ophthalmologic examinations, immunity status tests, CT clinical data. Choice of the treatment strategy was governed by the morphologic variant of ophthalmopathy, immunologic activity of the process, disease severity and pattern. Such an approach helped achieve positive results and clinico-immunologic remission, as well as timely prevent the progress of the disease.

Problems of Endocrinology. 1993;39(1):24-27
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HLA antigens in nodular formations of the thyroid
Rasovsky В.L., Dimova M.N., Kiselyova T.P., Akhmedyanova L.G., Minina V.M.
Abstract

Distribution of the HLA system Class 1 specificities was studied in 97 patients with thyroid carcinoma, 101 ones with nodular goiter and 500 donors in the Central Urals. B15, B18 antigens were very frequent and All antigens quite rare in the patients with thyroid carcinoma; in patients with nodular goiter the incidence of Awl9, A28, B18 antigens was the highest, whereas the incidence of All antigen and the A2-B35 haplotype was low. The groups of patients with thyroid carcinoma and nodular goiter differed only by the incidence of A28 antigen and A2-B35 haplotype, this fact indicating the immunogenetic similarity of the diseases in question. Similar pathogenetic mechanisms of the formation of mammary carcinoma and of nodular goiter in the thyroid may be supposed, this giving grounds for the radical approach to the treatment of nodular formations of the thyroid.

Problems of Endocrinology. 1993;39(1):28-30
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Some cardohydrate metabolism parameters in the patients prior to and after removal of insulinoma
Trofimov V.M., Mazurov V.I., Arkhipov V.F., Klimko N.N.
Abstract

Measurements of the daily fluctuations in the sugar blood levels, fasting test, the double glucose tolerance test, and measurements of the blood insulin and C peptide levels were carried out in 13 patients with organic hyperinsulinism prior to insulinoma removal and in the immediate and late periods after it. The double glucose tolerance test was for the first time used to study carbohydrate metabolism in patients with organic hyperinsulinism. The curve of this test in insulinoma patients was found to resemble that in health, though with lower levels and a more abrupt lowering of its end section. This feature may be used to define the origin of hyper insulinism. No correlation between the blood glucose, insulin, and C peptide levels was detectable before surgery in this patient population. After surgery the imbalance in these three parameters relationships is eliminated. Carbohydrate metabolism parameters normalized after the operation; the lowest blood sugar level was increased twofold in the fasting test. Transitory hyperglycemia persisted for two weeks after elimination of hyperinsulinism. Daily fluctuations in the blood sugar levels normalize during the third week after surgery.

Problems of Endocrinology. 1993;39(1):30-33
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Diagnosis and surgical treatment of microcorticotropinomas
Serpukhovitin S.Y., Trunin Y.K., Arapova S.D.
Abstract

Microsurgical selective removal of hypophyseal adenomas is more and more frequently used in the treatment of Icenko-Cushing”s disease of late. This permits complete cure of approximately 90 % of the patients. Ten patients with this disease, induced by corticotropinoma, were observed. The hormonal methods, as well as computer-aided tomography and NMR tomography, were used to diagnose the condition. A high resolving power of these methods for the diagnosis of this disease is noteworthy. The authors describe the method for microadenoma detection during the operation and present the data of hormonal studies after selective adenomectomy. They emphasize that in cases when clinical data are supported by the hormonal and x-ray findings that confirm the presence of a microcorticotropinoma in Icenko-Cushing’s disease transsphenoidal adenomectomy must be the method of choice for the treatment of such patients.

Problems of Endocrinology. 1993;39(1):33-36
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Isotopic composition of blood plasma carbon in patients with endocrine diseases
Ivlev A.A., Goncharov N.P.
Abstract

Forty-eight patients suffering from diabetes mellitus, obesity, hyper- and hypothyrosis, Icenko-Cushing’s disease were examined to elucidate the relationship between blood plasma carbon isotopic composition and the type of the endocrine disease. This value varied within the range of 19.7  to 24.7 ‰, the mean value being 5 ‰. Blood plasma carbon in the diabetics is enriched for 12C light isotope (delta-13C from 23.0 to 24.5 ‰) as against a similar characteristic in obese patients (delta-13C from 20.5 to 21.99 ‰). Patients with hypo- and hyperthyrosis and the Icenko- Cushing’s disease have a wider range of delta-13C values that seems to be explained by the Icenko-Cushing’s disease heterogeneity and the presence of biorhythms. Clear-cut isotopic differences in the blood sera of adults and children were revealed whatever the disease type, these differences indicating the changes in cellular metabolism energy in the ontogenesis. These data can be satisfactorily explained within the frames of the model of cellular division of carbon isotopes, suggested previously.

Problems of Endocrinology. 1993;39(1):36-40
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Short Messages
School for training of children and adolescents suffering from diabetes mellitus: The first experience and prospects
Maximova V.P., Andrianova Y.A., Lebedev N.B., Dedov I.I.
Abstract

Around the world, the problem of maintaining sustained compensation for diabetes on an outpatient basis is currently receiving much attention. Given the current therapeutic possibilities, we can say with confidence that the introduction of a patient education system in clinical diabetology is a real way to increase the effectiveness of medical and preventive care. Due to the importance of this problem, the introduction of a properly organized system of training patients and their families in self-control methods, which leads to the achievement of stable compensation for the disease, a decrease in the frequency of acute complications, reducing the time of hospitalization, and better social adaptation of patients.

Problems of Endocrinology. 1993;39(1):40-41
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Experimental endocrinology
The hypophyseogonadal system of male rats with diabetes: an experimental study
Babichev V.N., Peryshkova T.A., Adamskaya Y.I.
Abstract

The hypophyseogonadal system of male rats with streptozotocin-induced diabetes was studied. The hypophyseal sensitivity to LH releasing hormone was analyzed in vitro and concentrations of sex hormone nuclear receptors in the adenohypophysis, participating in gonadotropin secretion regulation according to a negative feedback mechanism, measured. Streptozotocin injection reduced blood testosterone concentration and levels of androgen nuclear receptors in the rat hypophysis. Blood LH and FSH levels in the rats with diabetes were virtually the same as in intact animals. In vitro experiments have demonstrated that diabetes development in rats did not influence the level of LH basal secretion by the hypophysis. The maximal response to LH releasing hormone was recorded in the control males in 3h incubation, whereas the rate of LH secretion in the experimental animals did not differ from the normal one. The authors suggest that changed mechanism of the hypothalamo-hypophyseo-gonadal system regulation in experimental diabetes is related to the hypophyseal disorders, involving reduction of the LH-RH-stimulated gonadotropin release and of the testosterone receptor levels, this resulting in poor reproductive function control according to the negative feedback principle.

Problems of Endocrinology. 1993;39(1):42-45
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Vasopressin, oxitocin, and corticoliberin-synthesizing hypothalamic structures in rats of both sexes with induced diabetes mellitus
Kolesnik Y.M., Orestenko Y.N., Abramov A.V.
Abstract

The endocrine status of the pancreas and the hypothalamic neurosecretory nuclei were studied by radioimmunoassay, immunocytochemical, morphometric and histochemical methods in Wistar rats of both sexes with experimental diabetes mellitus. The development of diabetes mellitus was characterized by beta-cell destruction and insulin concentrations reduction in these cells and the blood, by increase of glucagon and somatostatin levels in the alfa- and delta-cells, respectively, as well as by the growth of these substances concentrations in the peripheral blood. These changes were parallelled by activation of the vasopressin-, oxitocin and corticoliberin-synthesizing neurones of the paraventricular and supraoptic nuclei of the hypothalamus, as evidenced by morphometric findings and by increase of the blood vasopressin and corticoliberin concentrations and oxitocin level in the hypothalamus. Experimental diabetes mellitus was found to be characterized by activation of the hypothalamo-hypophyseo-adrenal system. Functional differences in the contribution of vasopressin- and oxitocin-synthesizing neurones of the hypothalamic nuclei in the pathogenesis of the disease is shown, as are their sex-specific reactions.

Problems of Endocrinology. 1993;39(1):45-48
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Active avoidance training of rats with experimental diabetes mellitus
Zaraiskaya Y.I., Alexandrova Y.A., Lukashev A.O., Shvyrkova N.A.
Abstract

Specific features of training the rats in a new form of defense behavior in insulin deficiency in animal body were under study. Experiments were carried out with 51 male Wistar rats, 24 of these with streptozotocin-induced diabetes. The method of bilateral active avoidance with acoustic signal stimulation, followed by electric stimulation of the skin, was employed. The curves of training, reflecting the time course of the number of effective behavioral acts, were analyzed, and the parameters of the shape of the individual curves of training estimated to classify the animals, making use of analysis of factors. A significant variability of the examined individual parameters of training was associated with the absence of noticeable differences in the approximated results of examinations of intact and streptozotocin-treated rats. Analysis of factors helped single out a group of rats with streptozotocin induced diabetes among the groups of animals that were characterized by similar training parameters, that could sooner learn a new habit after a longer latent period as against intact animals.

Problems of Endocrinology. 1993;39(1):48-50
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Hormonal function of the adrenal cortex in «medical castration» induced by prolonged infusion of LH releasing factor agonists
Goncharova N.D., Mkhitarova L.A.
Abstract

Time course of the major corticosteroid hormones and the precursors in the biosynthesis chain was studied, as was the type of corticosteroid complex formation with transcortin in the peripheral blood plasma in male papua hamadryas exposed to a 4-16 week infusions of LH releasing factor agonists (busereline, Hoechst A. G., Germany, and surfagon, Cardiology Research Center of the Russian Academy of Medical Sciences) with the use of osmotic mini-pumps (Alza Corp., Palo Alto, USA). Suppression of the gonadal function resultant from prolonged infusion of LH releasing factor agonists was not associated with essential shifts in the adrenal steroidogenesis and in the specific corticosteroid transport. Such exposure induced a somewhat more marked activation of glucocorticoid and adrenal androgen secretion in response to acute stressor exposure (a single injection of insulin in'a dose of 0.2 U/kg b. m.). One should bear in mind this fact when prescribing therapy with LH releasing factor agonists to patients with prostatic carcinoma, for the adrenal androgens are transformed into active androgens in the prostatic tissue.

Problems of Endocrinology. 1993;39(1):51-54
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Relationship between chorionic gonadotropin immunomodulating effects and the initial functional activity of the splenocytes mediating the adoptive immune response
Shirshev S.V., Kevorkov N.N.
Abstract

CBA and (СВАхC57BL/6) F1 male mice were used in experiments. One hour incubation of splenocytes with chorionic gonadotropin in doses 10 or 50 MU/ml statistically significantly reduced the count of antibody-producing cells detectable in the syngeneic transfer system. Addition of conA or recombinant human interleukin 2 to the splenocyte culture did not alter the processes of the formation of antibodyproducing cells. Addition of chorionic gonadotropin simultaneously with conA resulted in discontinuation of the immunosuppression induced by a low hormone dose, whereas 50 MU/ml of chorionic gonadotropin in the presence of conA had a marked immunodepressant effect. Combination of interleukin 2 with chorionic gonadotropin lead either to immunosuppression cessation (10 MU/ml) or to more than twofold stimulation of the adoptive immune response (50 MU/ml). Voltaren a cycloxygenase inhibitor, was used in some experiments to elucidate the degree of endogenic prostaglandin relationships with the mechanisms of chorionic gonadotropin immunomodulating effects. Cycloxygenase activity was found to be related to the immunosuppressive effect of chorionic gonadotropin low dose, whereas the costimulating effect of a high dose of the hormone in the presence of interleukin 2 was unrelated to endogenic prostaglandin synthesis.

Problems of Endocrinology. 1993;39(1):54-57
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Reviews
Lipid peroxidation system-antioxidant protection and the role of its disorders in the pathogenesis of diabetes mellitus and angiopathies
Lyajfer A.I., Solun M.N.
Abstract

The urgency of the problem of diabetic angiopathies is highlighted by the fact that among patients with insulin-dependent diabetes mellitus under the age of 20 years mortality rate is 7 times higher than the average mortality among the General population, and after reaching 20 years, the average annual risk of mortality is 20 times higher than the total population. Recently, in the study of many pathological conditions, considerable attention has been paid to structurally functional changes in cell membranes. The severity and duration of membrane-damaging processes in the body determine the clinical severity and features of the course of many diseases. Membrane destruction as a pathological phenomenon is primarily due to the involvement of cell membrane lipids in lipid peroxidation processes, which leads to a change in lipid-protein bonds, the strength of the complex of enzymes and other membrane macromolecules, damage to nucleic acids, and impaired cellular metabolism.

Problems of Endocrinology. 1993;39(1):57-60
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