The etiology of osteoporosis associated with rheumatoid arthritis (RA) is unknown. We studied the calcium and vitamin D metabolism in 143 women with RA (mean age 50.7 years). Albumin corrected serum calcium was normal. Serum alkaline phosphatase was increased in 29 percent of cases. Serum vitamin D levels were frequently very low. In 16 percent of the RA patients serum 25(OH)D concentration was below 12.5 nmol/L, which is arbitrarily considered as the limit of vitamin D deficiency osteomalacia. In the winter season 73 percent of the patients had serum 1,25(OH)2D levels below the seasonally adjusted normal range. The lowest values were found in patients with high disease activity. We suggest that there is a disturbance in vitamin D metabolism in RA. This might play a role in osteoporosis associated with RA.
Inhibins are gonadal glycoproteins with endocrine effects on pituitary FSH secretion and para/autocrine effects on ovarian and testicular function. The purpose of this study was to investigate the endocrine and para/autocrine regulation of inhibin A and inhibin B secretion in human ovarian granulosa-luteal cells. The cells were obtained from women undergoing in vitro fertilization, and the primary cultures were treated with FSH, LH, human chorionic gonadotropin (hCG), activin A, 8-bromo cyclic AMP (8-BrcAMP), staurosporine (a protein kinase C inhibitor) and an antagonist of IGF action (type-1 IGF receptor antibody IR3). The secretion of inhibins was measured by ELISA assays capable of reliably distinguishing between inhibin A and B.FSH, LH, hCG and 8-BrcAMP increased inhibin A secretion on average up to 180% (P<0·01), 192% (P<0·05), 210% (P<0·01) and 243% (P<0·01) respectively of the control level, while their stimulatory effect on inhibin B secretion was less pronounced (up to 167%, P<0·01; 139%, P<0·05; 127%, P>0·05; 133%, P>0·05 of the controls respectively). IR3 decreased inhibin A and B secretion down to 70% (P<0·01) and 50% (P<0·01) respectively of the control. Staurosporine decreased inhibin B secretion down to 49% (P<0·01) of the control; its effect on inhibin A secretion was not significant. Activin A increased inhibin B secretion up to fourfold of the control (P<0·05) while its effect on inhibin A secretion was insignificant.We conclude that gonadotropins via the protein kinase A signal transduction pathway are the main positive regulators of inhibin A and B secretion in human granulosa-luteal cells. The protein kinase C signal transduction pathway seems to be important especially for inhibin B secretion. Locally produced IGFs are probably important inducers of the production of both forms of inhibin in human ovaries while activins seem to upregulate inhibin B secretion.
SummaryWe analyzed plasma fibrinogen level in relation to genetic polymorphisms in the a- and β-fibrinogen gene loci. Furthermore, the association of other CVD risk markers with fibrinogen was studied twice, with a time interval of one year in 50 to 60 year old men (n = 183). DNA polymorphisms were detected by PCR and digestion with TaqI (α-fibrinogen), Hind III and Bcl I (β-fibrinogen) restriction enzymes. The correlation coefficient between fibrinogen measurements was 0.48 (p <0.001). Blood leucocytes and waist-to-hip circumference ratio were the strongest correlates of fibrinogen level in both examinations, and the changes in leucocyte count and plasma fibrinogen correlated positively (r = 0.40, p <0.001). In Eastern Finnish men, the Taq I, Hind III or Bcl I restriction fragment length polymorphisms of the a- or β-fibrinogen gene loci did not associate with fibrinogen level, either cross- sectionally or longitudinally.
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