Role of B cells in presentation of autoantigens to CD4(+) T cells in patients with autoimmune thyroiditis.

The antigen-presenting activity of B cells and expression of molecules involved in antigen presentation by B cells have been studied in patients with autoimmune thyroiditis (AIT). The disease is characterized by enhanced expression of the costimulatory molecule CD80 in naive B cells (CD19(+)CD27(-) cells) both ex vivo and under the conditions of polyclonal cell activation in a culture. Under in vitro conditions, antigen-loaded B cells have been shown to be capable of inducing proliferation of autologous CD4(+) cells, in particular, proliferation of autospecific T cells in patients with AIT. Given that an intense infiltration of thyroid tissue by B cells is a typical sign of AIT, the antigen-presenting activity of B cells appears to contribute to this pathology.

[Effects of tanakan on blood lipid peroxidation and platelet aggregation properties in patients with insulin-dependent diabetes mellitus]. / Vliianie tanakana na perekisnoe okislenie lipidov krovi i agregatsionnye svoistva trombotsitov u bol'nykh insulinzavisimym sakharnym diabetom.

AIM: To elucidate tanakan effects on lipid peroxidation (LPO) products in blood serum, red cell and platelet membranes of patients with insulin-dependent diabetes mellitus (IDDM) with and without vascular complications. MATERIALS AND METHODS: Twenty-seven diabetics and 15 donors were examined. Platelet aggregation, malonic dialdehyde (MDA), hemoglobin (including glycosylated), blood total cholesterol and lipoproteins were measured routinely. RESULTS: Elevated levels of malonic dialdehyde (MDA) in the serum and red cell membrane in IDDM patients diminished in response to 6-week treatment with tanakan. Basal and induced MDA in platelets reduced, more noticeably in patients without angiopathy. Platelets resumed sensitivity to low-dose ristomycin. A 6-week course of tanakan failed to normalize platelet function completely. Moreover, platelets sensitivity to some inductors (ADP, adrenalin) enhanced, more noticeable in patients without angiopathy. CONCLUSION: Tanakan in IDDM shows properties of an effective antioxidant and return to normal LPO products level both in blood serum and red cell membrane. This eradicates a damaging action of free radical products in blood cells and endothelium. It is suggested that for normalization of platelet aggregation in IDDM a longer tanakan course is required or combined use of tanakan with other antithrombotic medicines of different mechanism of action may be effective.

[Possibility of regulating platelet aggregation ability with the S2-receptor blocker, naftidrofuril, in patients with insulin-dependent diabetes mellitus]. / O vozmozhnosti reguliatsii blokatorom S2-retseptorov naftidrofurilom agregatsionnoi sposobnostii trombotsitov bol'nykh insulinzavisimym sakharnym diabetom.

The actions of S2-receptor antagonist naftidrofuril (Duzodril-retard, Byk Gulden, FRG) on both basal and thrombin-induced levels of malondialdehyde in platelets as well as platelet aggregability in patients with insulin-dependent diabetes mellitus with or without angiopathies were studied. Significant decrease in the basal level of MDA was observed after treatment and the effect was more profound in patients without vascular complications. The treatment with Duzodril-retard at daily dose of 200 mg during 40 days was not shown to decrease in platelet hyperfunction in response to the inductors: ADP, 1 and 5 microM; adrenaline, 1 microM; collagen, 4 mu/ml; ristomycin, 0.9 and 1.2 mg/ml; and thrombin 0.5 U/ml). The reduction of hyperreactivity of platelets in response to adrenaline in patients without angiopathies was found out during treatment with Duzodril-retard. This could be referred as positive sign for prognosis because of decrease in sensitivity of platelets to adrenaline may lead to corresponding decrease in reactivity to ADP during long-term usage of naftidrofuril. Platelets of the patients were shown to be hypersensitive to ADP at maximal extent. The decrease in the sensitivity of platelets to large concentrations of ristomycin was found, the fact which may serve as an evident for some normalization of functional activity of platelets as well endothelin-platelet interactions in patients without vasal complications. Thus, Duzodril-retard has an activity as angio-protector in most degree at the cases when vasal disturbances are not clinically significant yet.

[Disordered Na+/H+ metabolism in the erythrocytes of patients with insulin-dependent diabetes mellitus]. / Narushenie Na+/H(+)-obmena v éritrotsitakh bol'nykh insulinzavisimym sakharnym diabetom.

Na+/H+ countertransport speed in red cells of insulin-dependent diabetes (IDDM) patients was studied. The rate of Na+/H+ exchange in diabetic erythrocytes did not differ statistically from the rate of such exchange in control erythrocytes. Statistically significant differences in the rates of Na+/H+ exchange in red cells of patients with and without angiopathies were not found either, though the above rate was higher in nephropathy patients compared to those with retinopathy. Statistically significant acceleration of the Na+/H+ exchange rate was found in red cells of patients with family history of IDDM compared to patients without hereditary predisposition. There was no correlation between the rate of Na+/H+ exchange and duration of diabetes mellitus. It is suggested that acceleration of Na+/H+ countertransport in red cells of different diabetic groups may be polyetiological.

[Hemolytic uremic syndrome as a clinical manifestation of oxidative stress]. / Gemolitiko-uremicheskii sindrom kak klinicheskoe proiavlenie oksidatnogo stressa.

An examination was made of seventeen children having various stages of the hemolytic uremic syndrome: Stage 1 is the period of an expanded clinical picture of the disease, the patients' condition is grave (anuria, azotemia, severe hemolytic anemia and thrombocytopenia); Stage 2 is the period of recovery. The plasma levels of malonic dialdehyde, dienic conjugates, alpha-tocopherol at the first stage of the disease were considerably higher than the control ones, on recovery there were their reductions though their levels remained higher than the normal levels. The levels of malonic dialdehyde in the red blood cell membranes in ill children were also much higher than those in healthy donors, but at the second stage they decreased, but remained high. The activity of superoxide dismutase in the red blood cells of ill children in the acute period of the disease did not significantly differ from that of donors. At the second stage of the disease there was a significant fall in the activity of red blood cell superoxide dismutase. The activity of catalase in the red blood cells of ill children was thrice higher than in the controls; however, this index decreased during treatment and at the second stage it did not differ from that in the controls. There were no significant differences in the activity of red blood cell superoxide dismutase in donors and ill children. Mechanisms responsible for abnormal plasma and red blood cell peroxidation are considered in the hemolytic uremic syndrome. It is concluded that free radical reactions play a substantial role in the pathogenesis of this abnormality.

[The erythrocyte pro-oxidant and antioxidant systems of patients with chronic kidney failure]. / Sostoianie prooksidantnoi i antioksidantnoi sistem éritrotsita u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu.

Lipid peroxidation as shown by malonic dialdehyde (MDA) levels and enzymic antioxidant defense systems were evaluated in red cells from patients with renal affections free of chronic renal failure (group 1), in conservative curable stage of chronic renal failure (group 2a), in terminal stage nondialysis patients (group 2b) and in healthy donors. MDA was higher in patients, in group 2b in particular. MDA levels correlated with concentrations of endogenic creatinine in the serum. Catalase and glutathione peroxidase were at control levels. SOD was not changed in group 1 but appeared reduced in other groups. Its activity was not related to serum creatinine. An inverse relationship existed between MDA content and SOD activity in red cells. It is believed that progression of chronic renal insufficiency leads to activation of lipid peroxidation and deterioration of antioxidant defense in red cells contributing to more active red cell destruction causing anemia in uremia.

[Effect of biosynthetic insulin on lipid peroxidation in erythrocyte membranes in patients with type I diabetes mellitus]. / Vliianie biosinteticheskogo insulina na perekisnoe okislenie lipidov membran éritrotsitov u bol'nykh sakharnym diabetom I tipa.

The aim of our research was elucidation of a relationship between red cell membrane lipid peroxidation (LPO) and antioxidant defense enzymes, on the one hand, and the age, disease duration, and presence of vascular complications in patients with type I diabetes mellitus, on the other. The possibility of correcting red cell peroxide status with human insulin preparations was investigated. Red cell membrane LPO was found increased more than twofold and antioxidant defense enzymes activities virtually unchanged vs. controls in 16 patients with diabetes aged 20 to 43. These characteristics of red cell peroxidation status do not depend on patients' age, disease standing, or presence of vascular complications. A twelve-week therapy with biosynthetic insulin resulted in complete normalization of LPO processes in patients with angiopathies aged under 35 and with disease standing of less than 10 years. In diabetics with angiopathies aged over 35 and disease standing of more than 10 years red cell MDA level reduced under the effect of therapy with human insulin preparations but was still increased vs. that in healthy donors by 1.5 times. Red cell GP and SOD activities reduced in the course of insulin therapy in all the examined groups of diabetics. Catalase activity increased by approximately 50% in patients with angiopathies, those aged over 35, and a disease standing of more than 10 years under the effect of insulin. In the rest groups of patients catalase activity did not differ from its initial level. Our results permit us recommending besides human insulin preparations antioxidant therapy for patients with vascular complications, those aged over 35, and a disease standing of more than 10 years.

[The effect of recombinant human erythropoietin during hemodialysis on the thrombocyte and erythrocyte functions of patients with chronic kidney failure]. / Vliianie rekombinantnogo chelovecheskogo éritropoétina v usloviiakh gemodializa na funktsiiu trombotsitov i éritrotsitov bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu.

To elucidate causes of thrombotic complications early in the course of RHE treatment, the authors studied platelet function (by aggregation of washed platelets), cAMP and cGMP as well as TxB2 levels in blood plasma, red cell function (by MDA content) in 16 patients suffering from chronic renal failure (CRF) on hemodialysis. 8 of them had been on RHE for 1.5 months. It appeared that plasma levels of TxB2 and cGMP increased, thrombin-induced platelet aggregation slightly decreased, MDA in red cells on treatment month 1.5 rose. The authors made the conclusion that early in the course of RHE treatment the conditions promoting active thrombogenesis may arise as a result of red cell induced platelet activation due to increased number of red cells with poor resistance to oxidant damage and hemolysis. Application of RHE in CRF patients should be combined with antioxidant therapy, especially in patients at high thrombogenesis risk.

[The results of a comparative study of the lipid peroxidation processes and of the malondialdehyde level of the blood cells in patients with diabetic angiopathies and during insulin therapy]. / Rezul'taty sravnitel'nogo izucheniia protsessov perekisnogo okisleniia lipidov i urovnia malonovogo dial'degida v kletkakh krovi bol'nykh diabeticheskimi angiopatiiami i v protsesse insulinoterapii.

Lipid peroxidation was studied by the levels of malonic dialdehyde (MDA) in the platelets and red cells of patients with diabetes mellitus (DM) type 1 as to relationships to vascular complications and insulin therapy. MDA appeared elevated both in red cells and platelets of DM patients, but was high in red cells only in DM patients with retinopathy. Insulin therapy contributed to gradual recovery of MDA levels both in platelets and red cells of all the DM patients except those with angiopathy who retained high red cell MDA on insulin treatment week 12. This suggests the necessity of adjuvant antioxidants in insulin treatment given to DM patients with vascular complications to arrest progression of angiopathy.

[Antioxidant enzymatic activity in the limbic-reticular structures of the rat brain after short-term immobilization]. / Aktivnost' antioksidantnykh fermentov v limbiko-retikuliarnykh strukturakh golovnogo mozga krys posle kratkovremennoi immobilizatsii.

Superoxide dismutase, glutathione peroxidase, and glutathione reductase activities were measured in 15-to 30-mg specimens of the cerebral cortex, amygdala, hypothalamus, and midbrain of adult male August rats subjected to 1-h immobilization stress. Of all these brain regions, the hypothalamus and amygdala had the strongest baseline total antioxidant defenses. However, immobilization inhibited the antioxidant enzymes in hypothalamus to much greater extent (an average of 30%) than in any other brain region (10% to 18%). After immobilization, the activities of glutathione reductase in the four brain regions were strongly and positively correlated. These data are consistent with our earlier findings of rapid accumulation of thiobarbituric acid-reactive material in the rat hypothalamus after a brief immobilization and suggest that hypothalamus is subject to strong pro-oxidant impacts arising at the early stages of immobilization stress.

[The effect of human recombinant erythropoietin on the lipid peroxidation processes and antioxidant protection of the erythrocytes in patients with chronic kidney failure on hemodialysis]. / Vliianie rekombinantnogo chelovecheskogo éritropoétina na protsessy perekisnogo okisleniia lipidov i antioksidantnuiu zashchitu éritrotsitov bol'nykh khronicheskoi pochechnoi nedostatochnost'iu v usloviiakh gemodializa.

Twenty patients with terminal-stage chronic renal failure (CRF) underwent long-term hemodialysis. Ten of them (group 1) did not receive human erythropoietin (HEP), four patients (group 2) received HEP for 1 month, six patients (group 3) for 12 months. Group 3 patients exhibited a marked increase in Hb, hematocrit, red cell number, while serum Fe was reduced. MDA rose in group 1 by 34% (p < 0.05), in group 2 by 199% (p < 0.05), was normal in group 3. Red cell catalase and glutathione peroxidase activities were normal. The results evidence that 1-month HEP treatment enhances oxidant degradation of erythrocytic membrane lipids. Lipid peroxidation becomes normal to the end of 1-year HEP treatment despite low SOD activity. Application of HEP in CRF patients is advisable to combine with antioxidant modalities to intensify red cell resistance to hemodialysis.

[Lipid peroxidation and the antioxidant protection of the erythrocytes in diabetes mellitus patients]. / Perekisnoe okislenie lipidov i antioksidantnaia zashchita éritrotsitov u bol'nykh sakharnym diabetom.

The study included 16 patients with diabetes mellitus (DM) type 1 and 15 healthy controls. By the moment of examination the patients had achieved subcompensation. 10 patients developed diabetic vascular complications. The patients received biosynthetic insulins Humulin S, Humulin I, Humulin M3. Pretreatment glycemia in the patients surpassed that in the controls, MDA red cell levels per ml of hemolysate were higher by 121% and 130% per protein 1 mg. MDA measured equal both in angiopathy patients and those without it. The activity of the antioxidant enzymes in DM patients was similar to control indices. Human insulin administration reduced red cell MDA levels both in angiopathy and free of it patients, though in the former MDA remained higher than normal, while in the latter normal levels are obtained. The parameters of the antioxidant defense enzymes changed on the treatment week 12: catalase activity rose by 41%, that of superoxide dismutase and glutathione peroxidase lowered by 35 and 65%, respectively. Variations in these enzymes activity showed no dependence on vascular complications.

[Lipid peroxidation as a possible mechanism of erythrocyte damage in patients with chronic kidney failure on hemodialysis]. / Perekisnoe okislenie lipidov kak vozmozhnyi mekhanizm povrezhdeniia éritrotsitov u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu v usloviiakh gemodializa.

Ten patients with chronic renal failure (CRF) treated by hemodialysis (HD) were examined. All the patients demonstrated remarkable anemia. The red blood cell count was (2.7 +/- 0.2) x 10(12)/I the concentration of hemoglobin 79.5 +/- 5.6 g/l, on the average, hematocrit 23.2 +/- 1.8%. The content of malonic dialdehyde in the patients' red blood cells was far greater than in controls, amounting to 132% (per 1 ml of hemolysate), 134% (per 1 mg of protein) (p < 0.05). Catalase and glutathione peroxidase activity in the patients' red blood cells did not differ from that in controls. Superoxide dismutase activity reduced by 43% as compared to that in donors (p < 0.001). The authors review possible mechanisms of lipid peroxidation (LPO) and a decrease of antioxidant defense in red blood cells of CRF patients on hemodialysis. It is concluded that activation of LPO processes and the decrease of antioxidant defense produce a noticeable destructive effect on the integrity of the red blood cell membrane. They also influence the development of hemolysis.

[The role of antioxidants in the action of thyroxine on myocardial functional properties in rats]. / Rol' antioksidantov v deistvii tiroksina na funktsional'nye svoistva miokarda u krys.

In conditions of excessive hormones in the blood, alpha-tocopherol increases the cardiomyocytes antioxidant defence, partially prevents the enhancement of the heart tissue sensitivity to induced peroxide oxidation of lipids, and considerably diminishes disorders in the heart contractile function. Under the same conditions, reduced glutathione no only does not exert its defensive action, but even decreases the heart resistance against hypoxia.