Serum interleukin-6 levels and bone mineral density at the femoral neck in post-menopausal women with Type 1 diabetes.

BACKGROUND: Although osteopenia is often reported in Type 1 diabetes mellitus, the pathogenic mechanisms are not fully understood. Oestrogen deficiency also leads to decreased bone mineral density (BMD). Enhanced interleukin-6 (IL-6) production among Type 1 diabetic patients could be involved in the pathogenesis of diabetic bone loss since it is a potent bone resorbing cytokine. AIMS: To evaluate the relationship between serum bioactive IL-6 levels and BMD at the femoral neck of post-menopausal women with Type 1 diabetes. METHODS: We studied BMD, urine excretion of deoxypirydynoline crosslinks, serum bioactive IL-6 and soluble IL-6 receptor (sIL-6R) levels in 20 post-menopausal women with Type 1 diabetes mellitus, and compared these results with 20 matched healthy post-menopausal controls. RESULTS: Post-menopausal women with Type 1 diabetes had significantly lower BMD at the femoral neck and increased serum bioactive IL-6 levels compared with the control group, but no relationship was observed between these variables in a multiple regression analysis. Using BMD at the femoral neck of diabetic women as the dependent variable in the multiple step regression analysis model, we found that independent variables that were strongly associated with bone mass at the femoral neck in this group were: time since menopause and duration of diabetes. CONCLUSIONS: Although our study had a small sample size, we found that post-menopausal women with Type 1 diabetes mellitus present lower bone mass and higher serum bioactive IL-6 levels than matched healthy controls, but we were unable to find a correlation between these two parameters.

Effects of oestrogen deprivation on interleukin-6 production by peripheral blood mononuclear cells of postmenopausal women.

Various hormones can influence the expression of interleukin-6 (IL-6) and oestrogens are the most extensively studied. There is, however, controversy about the nature of the IL-6 secreted by human cells and its regulation by 17beta-oestradiol. The aim of this work was to clarify whether oestrogen deprivation after menopause may contribute to an enhanced IL-6 production by peripheral blood mononuclear cells (PBMC) in postmenopausal women. Twenty-two healthy postmenopausal women, age range 45-63 years, with clinical symptoms of oestrogen deficiency were enrolled in the study. The control group consisted of 16 healthy young women, age range 22-31 years, with regular menses and who were not taking oral contraceptives. Levels of IL-6 in the sera and PBMC culture supernatants were measured by the biological B9 cell-proliferation assay and expression of the IL-6 gene in non-stimulated PBMC was detected by RT-PCR. The effect of 17beta-oestradiol on spontaneous IL-6 production by the PBMC of postmenopausal women was also studied in vitro and in vivo. Seventeen out of the twenty-two postmenopausal women were given hormonal replacement therapy of 50 microg 17beta-oestradiol/day transdermally and the spontaneous production of IL-6 by the PBMC was analysed after 6 and 12 months of treatment. The postmenopausal women had significantly higher serum levels of IL-6 than the young controls. The spontaneous production of IL-6 by non-stimulated PBMC into the culture supernatants was also significantly higher in the postmenopausal women compared with the young. We also found that IL-6 gene expression was present in the non-stimulated PBMC isolated directly from the venous blood of the majority of the postmenopausal women. Women with IL-6 gene expression in the non-stimulated PBMC had significantly lower serum levels of 17beta-oestradiol compared with those where the IL-6 gene was not expressed in the PBMC. Our in vitro experiments showed that 17beta-oestradiol at concentrations of 10(-9) M and 10(-10) M decreased spontaneous IL-6 production by the PBMC of postmenopausal women. In vivo treatment with 17beta-oestradiol transdermally also significantly decreased spontaneous IL-6 production by the PBMC of postmenopausal women after 12 months of the therapy. Our results indicate that oestrogen deprivation after menopause may enhance IL-6 production by the PBMC of postmenopausal women. We suspect that the late complications of oestrogen deficiency, such as osteoporosis, coronary heart disease and Alzheimer's disease, may be mediated by an exaggerated production of IL-6 - a cytokine which seems to play a pivotal role in the pathogenesis of these age-related diseases.

[Evaluation of hemodynamic changes in patients with primary arterial hypertension after treatment with a combination of pindolol and clopamide (Viskaldix)]. / Ocena zmian w dynamice krazenia u chorych z pierwotnym nadcisnieniem tetniczym po leczeniu trwalym polaczeniem pindololu z klopamidem (Viskaldix).

In 35 patients with mild essential hypertension the influence of 9 week Viskaldix therapy on hemodynamics was evaluated. Twelve of them underwent repeated hemodynamic examinations after mean 13 months treatment. Viskaldix therapy lowered total peripheral resistance --TPR and there was no significant influence on the heart rate, stroke volume, and cardiac output. It was demonstrated that decrease of total peripheral resistance after treatment with Viskaldix was directly proportional to the initial values of TPR.

Hypotension and renal impairment during infusion of atrial natriuretic factor in liver cirrhosis with ascites.

Plasma immunoreactive atrial natriuretic factor (irANF) levels and the effects of alpha-human ANF (alpha-hANF) infusion were investigated in 7 patients with liver cirrhosis and ascites. Under basal conditions, supine blood pressure (BP) averaged 136/76 +/- 9/4 mm Hg (mean +/- SEM). Plasma irANF concentrations (124 +/- 33 pg/ml) were higher (p less than 0.01) than those in age-matched normal subjects (47 +/- 5 pg/ml). Plasma renin activity (PRA 5.9 +/- 2.2 ng/ml/h), aldosterone (18 +/- 7 ng/dl) and norepinephrine (NE, 66 +/- 5 ng/dl) levels were also elevated compared to the age-related normal range. Alpha-hANF infusion for 60 min at 0.036 micrograms/kg/min decreased the mean BP (-14%; p less than 0.05), increased PRA (+179%; p less than 0.05) and plasma NE (+24%; p less than 0.05). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), diuresis and natriuresis were not modified. A subsequent 60-min infusion of alpha-hANF at 0.067 micrograms/kg/min produced a marked fall in mean BP (-26%; p less than 0.001), hemoconcentration (hematocrit +6%; p less than 0.001) despite stable body fluid balance and a further increase in PRA (+350%, p less than 0.005). GFR and ERPF were severely reduced (-55 and -56%, respectively; p less than 0.001), while diuresis and natriuresis were not modified. Plasma aldosterone was unaltered during, but rose (+72%; p less than 0.01) after the cessation of alpha-hANF infusion. Variations in natriuresis during alpha-hANF infusion correlated positively with BP (r = 0.47; p less than 0.01), ERPF (r = 0.53; p less than 0.01) or GFR (r = 0.51; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)