Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys

Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.     

Clinico-immunological characteristics of patients with rheumatoid arthritis and symptoms of cutaneous vasculitis (cooperative Soviet-Polish study)

The paper presents the results of a comparative study performed in the USSR and Poland of rheumatoid arthritis (RA) patients with extra-articular manifestations of the disease (with skin vasculitis and free of it). The comparison included clinical, biochemical and immunological parameters. The results confirm the role of immune complexes in the onset of vascular affections in RA. High incidence of sensitive polyneuropathy in patients with skin vasculitis allows one to define it as a sign of systemic vasculitis. Rheumatoid nodes occur with similar frequency in both groups. It is shown that the problem of vascular pathology in RA remains complex and that further studies are needed to specify mechanisms of vasculopathy development in RA.     

Clinical, hemodynamic and neurohumoral effects of long-term therapy of patients with severe chronic heart failure with beta-adrenoblocker bisoprolol

The use of beta-adrenoblockers in conjunction with angiotensin converting enzyme inhibitors improves quality of life and prognosis of patients with chronic heart failure. However basic mechanisms of these positive effects in severe heart failure remain to be elucidated. METHODS: Patients (n=54) with NYHA class III-IV heart failure and left ventricular ejection fraction < or =35% were randomized either to treatment with bisoprolol (1.25-10 mg/day) (n=30) or in control group (n=24) and were followed up for 12 months. RESULTS: The use of bisoprolol was associated with significant improvement of heart failure functional class, lowering of heart rate (by 14%, p<0.01), elevation of systolic blood pressure (by 7.2+/-12.3 mm Hg, p<0.01) and increase of walking distance (by 30.1+/-29.0 m, p<0.01). No significant changes of these parameters occurred in control group. After 12 months increases of left ventricular end diastolic and end systolic volumes (by 85+/-69.2 and 71+/-51.5 ml, respectively, p<0.001) and of ejection fraction (by 5.7+/-7.3%, p<0.01) took place in bisoprolol treated patients. These changes were significantly (p<0.001) higher than those in control group. After 6 months of treatment with bisoprolol noradrenaline concentration fell from 533 to 402 pg/ml (p<0.05) while in controls it rose from 369 to 474 pg/ml, p<0.01). Decreases of plasma renin activity (from 1.2 to 0.42 ng/ml/h), plasma concentrations of angiotensin II (from 17.1 to 13.1 pg/ml) and aldosterone (from 173 to 148 pg/ml, p<0.05) were also observed in bisoprolol group. No substantial dynamics of activity of main components of renin angiotensin system took place in controls. There were no significant changes of atrial natriuretic peptide in both groups. Significant positive dynamics of parameters of heart rate variability was registered only in bisoprolol group: SDNN increased by 25% (p<0.05), high frequency spectrum by 106% (p=0.03), LF/HF ratio from 2.18+/-1.41 to 1.82+/-0.7. CONCLUSION: Long term use of bisoprolol was associated with improved clinical and hemodynamic status, increased systolic BP, blocked processes of pathological left ventricular remodeling, lowered activity of not only sympathetic-adrenal but also of main components of renin-angiotensin system and improved heart rate variability.