The process of antibody production against thyroid peroxidase and their relation to the complement-mediated cytotoxicity have the most pronounced cytotoxic effect on thyrocytes in Graves’ disease.

Aim.

To study the clinical and immunological indices and their interaction with thyroid status in patients with Graves’ disease depending on thyrocytes peroxidase autoantibodies level.

Material and methods.

The study included 35 women aged 18 to 55 years, mean age of 39.1±7.2, with verified diagnosis of Graves’ disease for the first time, before antithyroid therapy. The clinical and immunological parameters and their relationship with thyroid status studied depending on the level of AT-TPO. The definition of thyroid hormones content was measured using immunoradiometricassay analysis with standard test kits. AT-TPO was assessed by ELISA. Population and subpopulation composition of blood lymphocytes was evaluated using the method of indirect immunofluorescence using monoclonal antibodies to CD3, CD4, CD8, CD16, CD19 and HLA-DR. The humoral subset pattern characterized by the relative synthesis of IgA/CD19+, Ig M/CD19+, IgG/CD19+.

Results.

The most significant changes in population and subpopulation composition of lymphocytes was found in patients with more than 100 IU/L AT-TPO level and characterized by an increase in absolute lymphocyte, relative and absolute number of CD19+ and HLA-DR+cells, and CD3+ and CD8+cells, as compared to the control range and the values identified in group with AT-TPO less than 100 IU/L. A strong negative relationship AT-TPO with the number of T-lymphocytes (r=–0.75; p<0.001) and moderate with the relative synthesis level of IgM (r=–0,53; p=0.017) have been revealed. In Graves’ disease patients with AT-TPO more than 100 IU/l levels the statistically significant relationships were not found.

Conclusion.

The immunopathogenesis of Graves’ disease is characterized by positive correlation in AT-TPO and indicators of b-cell immunity, and negative — with the parameters of T-cell immunity, regardless of thyrocytes peroxidase autoantibodies concentration.

The article is devoted to the analysis of clinical and anthropometric indicators of 38 children and adolescents with pituitary dwarfism in the Stavropol region, receiving replacement therapy with recombinant growth hormone (rGH). The authors demonstrated a high growth stimulating efficacy of the rGR, as well as a positive impact on the level of blood cholesterol in children with somatotropic deficiency. Prognostic factors influencing the effectiveness of treatment were found (chronological age of initiation of therapy, baseline SDS of growth). In particular, it is shown that therapy with preparations of GH in children aged 8 to 10 years allows you to achieve a higher growth-stimulating effect in comparison with patients whose treatment is carried out at a later age. The study of the relationship between the initial deviation of the length of the body and the results of therapy in patients with growth hormone deficiency illustrates that a pronounced lag in growth is a predictive factor provides a more significant effect drugs rGR.

Aim.

To study the association of chronic inflammation, oxidative stress with telomere biology in people with type 2 diabetes mellitus (T2DM).

Material and Methods.

A total 50 patients with T2D and without cardiovascular disease (CVD) and 139 people from control group were included in the study. All subjects were measured for carbohydrate metabolism; oxidative stress (malondialdehyde (MDA)); inflammation (C-reactive protein — CRP, fibrinogen, interleukin-6); lymphocyte telomere length, telomerase activity.

Results.

In diabetic patients telomeres were shorter than in controls (9.59±0.54 and 9.76±0.47; p=0.031), telomerase activity was lower (0.47±0.40 and 0.62±0.36; p=0.039), inflammation (CRP, elevated fibrinogen) was higher. All patients were divided by telomere length. In T2DM group CRP was higher in patients with «short» telomeres (7.39±1.47 and 3.59±0.58 mg/L; p=0.02). There were no significant differences in the level of chronic inflammation and oxidative stress in ‘long’ telomeres group: CRP 3.59±0.58 and 3.66±0.50 mg/L (p=0.93), MDA 2.81±0.78 and 3.24±0.78 mmol/l (p=0.08). Diabetic patients in «short» telomeres group had greater chronic inflammation: CRP 7.39±1.47 and 4.03±0.62 mg/L (p=0.046), increased fibrinogen, 0.371 and 0.159 (p=0.022). All patients were divided by telomerase activity. Severity of chronic inflammation was greatest in T2DM and the «low» activity of telomerase. There were relationship between telomere length and CRP in T2DM patients (r=–0.40; p=0.004).

Conclusions. 

Chronic inflammation and cell aging were more pronounced in patients with T2DM. However, despite diabetes, signs of chronic inflammation were minimal in patients with «long» telomeres compared to healthy people. Perhaps long telomeres protect diabetic patients from the damaging effect of chronic inflammation.

Treatment management strategy for patients with type 2 diabetes mellitus (2DM) includes glycaemic control, blood pressure and lipid metabolism parameters. Pharmacoepidemiological monitoring allows evaluating the compliance of the treatment really provided for 2DM with the present guidelines.

Aim.

To study the actual implementation of pharmaceuticals control for patientswith type 2 diabetes, residents of the city of Omsk, in 2013—2014.

Material and methods. 

It was a retrospective open cohort study based on the fragment data of the Regional Diabetes Register including 33 187 cases with prescription of oral antidiabetic drugs (OAD), 285 patient cases and OAD consumption and expenses data in 2014. The prescribed daily dose (PDD) was determined. It was assessed the efficiency and effectiveness of antihypertensive and lipid-lowering therapy.

Results.

In Omsk metformin prevails in OAD take-in that corresponds to the modern Clinical Guidelines. Prescribed daily doses of metformin (PDD) are significantly lower (by 34.71%) than the doses fixed by the WHO Centre. The second frequently prescribed drugs are sulfonylureas with gliclazide MB at the top. PDD of glimepiride and glibenclamide are considerably higher than DDD. DPP-4 medicines are quite often prescribed (up to 10.2% as a part of the combined therapy, including fixed combinations).

Conclusion.

The efficacy of antihyperglycemic therapy assessed upon achievement of HbA1c individual target in Omsk is 40.5%. Most patients with type 2 diabetes in the studied cohort have had the adequate antihypertensive therapy with reaching a target blood pressure in 75.8% of patients. Statin drugs are prescribed only in 39.3% of cases of dyslipidemia in type 2 diabetes, and only in 32.3% of them the targets of lipid metabolism parameters are achieved.

Aim.

In the real research test with an antiestrogen clomifene is offered for differential diagnostics of potential reversibility of a hypogonadism.

Material and methods.

After initial determination of levels of testosterone and LH, to 55 men with a hypogonadism clomifene citrate of 50 mg orally daily in the morning for 10 days was administrated. Levels of testosterone and LH repeatedly were defined on the 11th day.

Results.

The carried-out test with clomifene eliminated a hypogonadism at 85,5% of patients, thus the effect remained at 40%. The test was safe, at one of men of side effects it wasn’t noted. For patients with negative result of test (preservation of a hypogonadism) administration of preparations of testosterone was recommended. 

Conclusions. 

Test allows not only to differentiate reversibility of a hypogonadism, but also in some cases completely to eliminate it.

Hypoglycemic drugs affecting the incretin system increasingly becoming popular because of its high safety and efficacy. The regulation of the secretion of endogenous incretin involves a number of receptors on the enteroendocrine cells, among which the most promising is GPR119. After activation it increases the incretins secretion and glucose-dependent insulin secretion, that is important from the point of view of effective control of postprandial glucose levels with minimal risk of hypoglycemia.

Aims.

To conduct a comparative study of hypoglycemic activity of DPP-4 inhibitors (sitagliptin) and novel GPR119 agonist receptor — compound ZB-16 in streptozotocin-nicotinamide-induced rat model of type 2 diabetes mellitus (T2DM).

Material and methods.

The hypoglycemic effect of ZB-16 (0.1 and 1 mg/kg per os) and sitagliptin (10 mg/kg per os) was studied during 4-week administration in 50 adult female rats (6 months, 240—260 g) with streptozotocin-nicotinamide-induced T2DM. The oral glucose tolerance test (OGTT) was performed on the 14th and 28th day after the start of treatment.

Results.

Animals receiving compound ZB-16 at a dose of 1 mg/kg by the end of treatment there have a significant reduction in fasting glucose as compared with the control group (7.9±0.43 and 0.54±9,6 mmol/l, respectively). During the OGTT on day 28 of treatment compound ZB-16 improves the rate of glucose utilization, reducing «peak» of growth glycemia (15,7±0,88 versus 21,6±1,06 mmol/L) and area under the curve «glucose concentration-time» (to 25%) compared with the control group during the OGTT.

Conclusions.

Novel GPR119 agonist — ZB-16 (1 mg/kg) has a clear hypoglycemic effect comparable to that of sitagliptin in rats with streptozotocin-nicotinamide-induced T2DM.

The search for new drugs for the treatment of type 2 diabetes mellitus (T2DM) and obesity remains an urgent problem. Drugs with influence on incretin system are widely used in the treatment of T2DM and obesity, since in addition to the hypoglycemic action of their inherent hypophagic effects. With the discovery of GPR119 receptor, there is the opportunity to pharmacological stimulation of endogenous secretion of incretins. Compound ZB-16 is active GPR119 agonist with IC50=7 nM. Its activation leads to increased secretion of the major incretins (GLP-1 and GIP), which are able to influence glucose metabolism and feeding behavior.

Aims — to study the effect of GPR 119 receptor agonist compounds ZB-16 on blood glucose, body weight and food intake in rats with obesity.

Material and methods.

Male rats with initial weight 390—400 g were fed with high-carbohydrate and high-fat diet. During the next four weeks the animals orally received ZB-16 (1 mg/kg) and metformin (400 mg/kg) and then we assessed the level of water and food consumption, blood glucose levels, and performed oral glucose tolerance test (OGTT).

Results.

Compound ZB-16 and metformin reduced fasting blood glucose levels and weight of experimental animals, while the control rats gained weight. GPR119 agonist is more pronounced than metformin reduced the area under the curve «glucose of concentration—time» during the OGTT.

Conclusions.

Novel GPR119 agonist — ZB-16 is comparable to metformin in hypoglycemic and anorexigenic effect in animals with obesity caused high-carbohydrate and high-fat diet.

We report the case of a 61 year old woman with a typical clinical picture of ACTH dependent Cushing’s syndrome. Diagnostic tests confirmed ACTH dependent Cushing’s syndrome, which is caused by corticomedullary mixed tumor. ACTH-secreting pheochromocytoma are rarely described in accessible literature, there is no one case report about ACTH-secreting corticomedullary mixed tumor. Due to the rarity of the disease, we believe it appropriate to share our experience and consider all variants of interaction in hypothalamic-pituitary-adrenal axis, which could lead to morphology and clinical changes uncovered in this case.

Steroidogenic factor 1 (SF1/AdBP4/FTZF1, NR5A1) is a nuclear receptor transcription factor that plays a critical role in different processes of sex development. Homozygous mutations in SF1 result in adrenal failure and complete testicular disgenesis in 46,XY individuals. According to recent studies heterozygous mutations in SF1 are associated with milder phenotype: they are found in children with 46,XY disorders of sex development (DSD) but with apparently normal adrenal structure and function. Here we present for the first time in Russian literature a case of SF1 deficiency. Molecular genetic analysis of NR5A1 gene revealed a novel heterozygous mutation c.951delC p.H317QfsX17. This clinical case demonstrates the importance of molecular genetic studies in DSD 46,XY, especially severe forms.

A review of the reports of the Institute of Pediatric Endocrinology Endocrinology Research Centre (Russia) at the 54th Annual Conference of the European Society for Pediatric Endocrinology.