[The features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves' disease in dynamics after radioactive iodine therapy].

BACKGROUND: The content of regulatory T cells (Treg) at different stages in formation of effector subpopulations and the level of CD25 expression on the membrane of their various fractions in Graves' disease can determine the long-term autoimmune process persistence and be the target of immunotropic therapy of the disease. AIM: To study the features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves' disease in dynamics after radioactive iodine therapy (RIT) to identify the specific Treg subpopulations for potential immunotropic therapy targets of the disease. MATERIALS AND METHODS: A single-center, prospective, cohort, open, controlled study was conducted with the participation of women with laboratory-confirmed Graves' disease. The features of regulatory T-blood cells subpopulation and the level of expression (MFI) CD25 surface receptor were studied by flow cytometry using direct immunofluorescence using monoclonal antibodies. RESULTS: The study included 36 women with recurrent Graves' disease, middle age 46.34±14.32 years. In patients with Graves' disease before and during the entire period after RIT a low percentage of naive (CD45R0-CD62L+) and terminally differentiated (CD45R0-CD62L-) Treg was established relative to the control, and on 3 and 6 months after RIT a significant decrease of cells with this phenotype was revealed relative to the values detected in patients before and 1 month after RIT (p<0.001). Against the background of compensated hypothyroidism the most significant changes of expression CD25 receptor in patients with Graves' disease were found on 3 and 6 months after RIT: reduced levels of MFI CD25 on surface of naive and terminally differentiated Treg. CONCLUSION: A decrease in the level of naive Treg was found (apparently due to a violation of differentiation processes in thymus) and terminally differentiated Tregs (due to maturation and survival processes), which are supplemented by a reduced expression of the CD25 receptor on the surface of these cells and do not depend on hyperthyroidism compensation, the titer of TSH receptor antibodies, previous conservative therapy with thiamazole and RIT. The obtained new data reveal the role of naive and terminally differentiated Treg subpopulations in immunopathogenesis and help to outline further ways to develop approaches for immunotropic therapy.

[T-lymphocytes phenotypic composition of peripheral blood in patients with Graves' disease undergoing conservative therapy with thiamazole].

BACKGROUND: Effective control of autoimmune inflammation in Graves' disease determines necessity to study the T helper (Th) and cytotoxic T-lymphocytes dysfunction, as well as the level of regulatory T-cells (Treg) activation in patients with Graves' disease on thyrostatic medication, which will clarify the immunomodulatory effects of long-term thiamazole treatment serve as targets for more specific therapies. AIM: To study the phenotypic composition of T-lymphocytes in the peripheral blood of patients with Graves' disease to assess the direction of immune response depending on thimazole-induced euthyroidism duration. MATERIALS AND METHODS: A single-center, cohort, continuous, open-label, controlled trial was conducted to assess the phenotypic composition of T-lymphocytes in peripheral blood in women with Graves' disease on long-term thiamazole treatment. The phenotypic composition of T-lymphocytes was determined by flow cytometry using direct immunofluorescence with conjugated FITC monoclonal antibodies depending on the duration of thimazole-induced euthyroidism of long-term thiamazole treatment. RESULTS: The study included 135 women with Graves' disease, mean age 43.09±12.81 years, 120 (88.91%) with a relapse of the disease and 15 (11.09%) with newly diagnosed hyperthyroidism. An increase of activated CD3+CD4+CD25+ was found in patients with Graves' disease with a duration of thimazole-induced euthyroidism 5-8 months and 9-12 months, respectively, Me=0.94 (0.48-1.45), p=0.020) and Me=0.95 (0.41-1.80), p=0.025), in control group - Me=0.12 (0.03-0.68). Compared to the control an increase of CD4+CD25+CD127Low (Treg) was found in patients with a duration of thimazole-induced euthyroidism 5-8 and 9-12 months. The content of Treg in peripheral blood in Graves' disease patients with a duration of thimazole-induced euthyroidism more than 12 months decreases, but remains elevated relative to the control. CONCLUSION: In patients with Graves' disease with a duration of thimazole-induced euthyroidism 5-8 months and 9-12 months the level of Treg has been increased. The increase of activated Th (CD3+CD4+CD25+) persists independently of thimazole-induced euthyroidism. In patients with Graves' disease with a duration of thimazole-induced euthyroidism for more than 12 months, there is a compensatory increase in regulatory T-lymphocyte, and the total number of T-helpers is restored to the control.

[Impaired visual pathway functions in patients with type 1 diabetes].

The study was undertaken to examine visual pathway function by psycho- and electrophysiological studies in patients with type 1 diabetes. Sixty-three patients (age 25±2.3 years) with moderate type 1 diabetes in a subcompensated state (mean HbA1c 7.4±0.2%), including 32 patients without diabetic retinopathy (DR) and 31 patients with nonproliferative diabetic retinopathy were examined. A control group consisted of 30 healthy individuals. The complex of diagnosis included critical flicker frequency test, retinal light and contrast sensitivity threshold tests, electroretmography (ERG), and studies of optic nerve lability and visual evoked potentials (VEP). A comprehensive study established functional visual pathway abnormalities that were undetectable on routine ophthalmologlcal examination. Lower ERG "a" wave amplitudes, higher latency, and reductions in the amplitude of VEP P100 peak and in spatial contrast sensitivity for low frequencies were of the greatest value in the diagnosis of diabetic abnormalities of the visual pathway. Visual pathway lesions are detectable in patients with type 1 diabetes without DR. In the latter, these lesions are more pronounced.

[Clinical and biochemical characteristics of biliferous tract diseases in patients with diabetes mellitus].

The aim of the study was to investigate manifestations of biliferous tract diseases in patients with diabetes mellitus (DM) and to measure concentrations and the ratio of lipids in gall-bladder and liver bile in these patients. 125patients with DM and biliferous tract diseases were examined. Patients with chronic cholecystitis (CC), cholelithiasis, and biliary dyskinesia underwent clinical examination as well as biochemical and instrumental tests. The control group included 87 healthy individuals of comparable age and gender. CC was diagnosed in 35.2% of DM patients, cholelithiasis - in 17.6% patients. In liver and gall-bladder bile samples taken from patients with CC and cholelithiasis, fatty acids concentrations was not significantly different, cholesterol level was significantly higher, and phospholipids level was lower than in the control group. Thus, indices of cholesterol saturation in liver and gall-bladder bile portions were higher in patients with cholelithiasis than in the control group. The study revealed high biliferous tract diseases morbidity in patients with DM. Thomas-Hofmann index, which characterizes bile saturation with cholesterol, is significantly higher in patients with cholelithiasis and DM, then in healthy individuals.

[Lipid composition of blood serum and bile in biliary diseases in patients with diabetes mellitus].

AIM: To study content and correlation of lipids in the serum and bile from diabetic patients with biliary diseases (BD). MATERIAL AND METHODS: Serum and bile lipids were studied biochemically in 125 patients with BD and diabetes mellitus and 87 healthy control subjects aged 20-59 years. Serum lipids were studied biochemically as well as content and correlation of duodenal bile lipids. Correlation was investigated between blood and bile lipids. RESULTS: Compared to healthy controls, diabetic patients with chronic cholecystitis and cholelithiasis had higher serum total cholesterol, triglycerides (by 28-34% and 63%, respectively) and a 18-22% decrease in HDLP cholesterol. Bile of such patients is oversaturated with cholesterol. Patients with diabetes type 2 had a close direct correlation between levels of total cholesterol, LDLP in the serum and Thomas-Hofmann index. CONCLUSION: BD patients with diabetes mellitus had high levels of serum lipids and high bile concentrations of cholesterol. Serum and bile lipids concentrations direcly correlate.

Prevalence of type 2 diabetes in northern populations of Siberia.

In the first part of the study the prevalence and incidence of diagnosed Type 2 diabetes among adult rural populations of southern, central and northern areas of the Krasnoyarsk region of Siberia is compared. The six-year mean incidence of diabetes in the southern area was 0.86 per 1000 (95% CI: 0.66-1.06), in the central area this incidence was 0.79 (0.57-1.01). In contrast, in the northern area the mean Type 2 incidence among indigenous population was 0.16 per 1000 (0-0.43) and among aliens it was 0.38 (0.22-0.54). The age-standardised Type 2 diabetes prevalence in the population of southern and central areas were 10.23 (9.55-10.-92) and 10.77 (9.99-11.55), respectively. In the northern area among aliens it was 8.98 (8.18-9.78) and among indigenous peoples only 2.54 per 1000 (1.46-3.62). The second part of this study consists of a population based survey to determine the prevalence rate of Type 2 diabetes among 596 Evenks and 306 alien inhabitants in Evenkia (82% eligible participants of Baikit district). No cases of glucose intolerance were found among Evenks in this study and one case of Type 2 diabetes was confirmed among aliens (prevalence rate 3.27 per 1000). These data indicate that Type 2 diabetes is still rare among northern indigenous populations of Siberia and that diabetes in northern alien populations is less prevalent than among peoples of central and southern areas of Siberia.

[Neural network modeling of triiodothyronine concentrations by the levels of lymphocytic NADP-dependent dehydrogenases in patients with thyroid hypo- and hyperfunction]. / Neirosetevoe modelirovanie kontsentratsii triiodtironina po urovniam NAD(P)-zavisimykh degidrogenaz limfotsitov krovi u lits s gipo- i giperfunktsiei shchitovidnoi zhelezy.

Whether a computer model which calculates serum triiodothyronine concentrations (T3) can be constructed by the levels of metabolic enzymes in the immunocompetent cells by means of a neural network predictor of real numbers. For this, the concentration of serum T3 and the activity lymphocytic NADP-dependent dehydrogenases were determined by radioimmune assay and bioluminescence technique, respectively. It was found that the neural network prediction might be only in each examined group alone. Conceivably, this is associated with the presence of compensatory processes of intracellular metabolism at high and low concentrations of thyroid hormones. The involvement of the examined enzymes in the metabolic mechanisms of immuno-endocrine interaction both in health and in disease, as well as in the thyroid hypo- and hyperfunction can be judged from the value of the input parameters of the neural network model.

[Activity of lymphocyte NAD(P)-dependent dehydrogenase and level of hormones in the blood of healthy people and patients with recurrent acute respiratory diseases]. / Aktivnost' NAD(F)-zavisimykh degidrogenaz limfotsitov i soderzhanie gormonov v krovi zdorovykh liudei i lits, chasto boleiushchikh ORZ.

The activity of NAD(P)-dependent lymphocyte dehydrogenases and their correlation with the blood levels of hormones was studied in healthy individuals and patients with frequently recurrent acute respiratory diseases. There were decreases in the activity of glucose-6-phosphate-, malate-, NAD-dependent glutamate dehydrogenases and direct and reverse reactions catalyzed by lactate dehydrogenase. In the blood of the examinees, the content of the hormones was similar to the physiological values; however, a decrease in content of thyroglobulin and somatotropin was found in the patients with acute respiratory disease. A model of multiple linear regression was applied to study the interrelationships between the content of hormones and the activity of the NAD(P)-dependent lymphocyte dehydrogenases. Dissimilar alterations in the activity of these enzymes and in their correlation with the content of hormones as compared with those in healthy persons suggest that decreased rates of immunoreactivity in the patients with acute respiratory disease determined by impairments in immunocompetent cell metabolism and in relationships between the immune and the endocrine systems.

Goitre prevalence in indigenous population of Evenkia.

Representatives of indigenous northern peoples (the Evenks and the Kets) living in a large Siberian territory named Evenkia were studied. There were children 6-14 years of age and adults aged 18-45 years. Thyroid volumes were determined by ultrasound. Iodine excretion was estimated. Normal thyroid volumes were found in 27.5% of the children. A high prevalence of goitre was detected in the adults. 55.4% of the women and 29.1% of the men had thyroid volumes above normal upper limits. Nodular goitres were found in 10.8% of the adults. 58.8% of the subjects had urinary iodine excretion below 10 micrograms/dl. Data show that the territory of Evenkia, settled by northern aborigines, is iodine deficient. The usage of the iodinated salt is ineffective. The preservation of the iodine content in salt remains the main problem in this area. In addition, some other goitrogenic agents may contribute to the high goitre prevalence in the indigenous population in Evenkia.