Muscle relaxation training and quality of life in rheumatoid arthritis. A randomized controlled clinical trial.

The purpose of the study was to investigate the effects of supervised muscle relaxation training in individuals with rheumatoid arthritis (RA). Sixty-eight participants were allocated at random either to a muscle relaxation training group or to a control group. Every participant was evaluated for health-related quality of life, muscle function, pain, and disease activity. The training group exercised 30 minutes, twice a week for 10 weeks, while no intervention was made in the control group. The results indicated improvements in the training group regarding self-care according to the Arthritis Impact Measurement Scales 2, and in recreation and pastimes according to the Sickness Impact Profile-RA (p < 0.05) directly after the intervention. Mobility and arm function (p < 0.01) according to the Arthritis Impact Measurement Scales 2, and muscle function of the lower limbs (p < 0.05) were improved after six months. No improvements remained after twelve months. It thus seems that 10 weeks' relaxation training might have some short-term influence in individuals with RA.

Sex and depot-specific stimulation of creatine kinase B in rat adipose tissues by gonadal steroids.

We report a sex- and depot-specific response of rat adipose tissues to gonadal steroids. The epididymal fat pad in male rats responded to androgens (testosterone and dihydrotestosterone; DHT), but not to 17beta-estradiol (E2), by increased specific activity of the brain type isozyme of creatine kinase (CK). In female rats, the parametrial fat as well as the fat surrounding the spleen responded to E2 but not to dihydrotestosterone. In both sexes, subcutaneous fat from the inguinal, abdominal or thigh region did not respond to any sex steroid. The parametrial fat showed increasing responsiveness to E2 during postnatal development, in parallel to the response of the uterus. In cycling female rats, parametrial fat showed the highest basal activity of CK at estrus; stimulation by E2 was achieved on all the other days of the cycle. Both phytoestrogens and diethylstilbestrol stimulated CK activity in both parametrial and spleen fat, in parallel to their estrogenic potencies; parametrial fat also responded to progesterone. The stimulation of CK activity in parametrial fat by E2 was completely blocked by actinomycin D or cycloheximide. Treatment with the antiestrogen, tamoxifen, caused moderate stimulation of CK activity in parametrial fat as well as partial inhibition of E2 stimulation of CK activity; the "pure" antiestrogen ICI 164,384 had no agonistic effect and completely blocked the E2 effect. Ovariectomy caused an increased response to E2 without changes in the basal CK activity, but did not lead to any response to DHT. As well as being a reliable response marker, the differential modulation of CK activity can thus serve to distinguish adipose cells from different sources.

Tissue distribution of human gp330/megalin, a putative Ca(2+)-sensing protein.

We used riboprobes and monoclonal antibodies to characterize tissue distribution of the human 550-kD homologue to gp330/megalin, primarily identified in the rat kidney. Human gp330/megalin mRNA and protein are readily identified in human parathyroid cells, placental cytotrophoblasts, kidney proximal tubule cells, and epididymal epithelial cells. The immunoreactivity is found on the surface of the cells and is heterogeneously downregulated in parathyroid hyperplasia and adenomas. Cells of the proximal kidney tubule and epididymis express the protein on their luminal aspect. Moreover, the protein is expressed in Type II pneumocytes, mammary epithelial and thyroid follicular cells, and the ciliary body of the eye. Sequence analysis of cDNA fragments, obtained by RT-PCR, revealed identical nucleotide sequences in parathyroid, kidney, placenta, epididymis, and lung. Immunohistochemistry for parathyroid hormone-related protein (PTHrP) revealed partial co-expression with human gp330/megalin in parathyroid, placenta, and mammary gland. The findings substantiate human gp330/megalin expression in a variety of human tissues expected to possess calcium-sensing functions. It may constitute a protein of utmost importance to adult and fetal calcium homeostasis, although other important functions may also be coupled to this exceptionally large protein with highly restricted tissue distribution.

Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties.

We present here the complete primary structure of human gp330, the human variant of the principal kidney autoantigen causing Heymann membranous glomerulonephritis in rats. The deduced 4655 amino acid residues give a calculated molecular mass of 519636 Da for the mature protein and consists of a probable 25-amino-acid N-terminal signal peptide sequence, an extracellular region of 4398 amino acids, a single transmembrane-spanning domain of 23 amino acids, and an intracellular C-terminal region of 209 amino acid residues. Three types of cysteine-rich repeats characteristic of the low density lipoprotein receptor (LDLR) superfamily are present in human gp330. In the extracellular region, there are a total of 36 LDLR ligand-binding repeats, comprising four distinct domains, 16 growth factor repeats separated by eight YWTD spacer regions, and one epidermal growth factor-like repeat. No consensus cleavage sequence for the processing endoprotease furin is detected in human gp330. The intracellular tail contains not only two copies of the F(X)NPXY coated-pit mediated internalization signal characteristic of LDLR superfamily members, but also intriguing and potentially functional motifs including several Src-homology 3 recognition motifs, one Src-homology 2 recognition motif for the p85 regulatory subunit of phosphatidylinositol 3-kinase, and additional sites for protein kinase C, casein kinase II and cAMP-/cGMP-dependent protein kinase. There is approximately 77% amino acid identity between human and rat gp330 with minor differences between the extracellular and intracellular regions. Recently gp330 has been implicated in Ca2+ regulation in the parathyroid, the placenta, and the renal tubule, but its overall physiological and pathological role still remains uncertain.

Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer--I. General findings.

The influence of oral high dose progestin (medroxyprogesterone acetate, MPA and megestrol acetate, MA) treatment on serum hormone levels was studied in ten postmenopausal women with advanced breast cancer. The gonadotropins and ACTH were significantly reduced by greater than 50 and 23%, respectively. Serum cortisol, DHEAS, androstenedione and testosterone were all significantly reduced (mean reduction between 64 and 76%), while serum estrone, estradiol and estrone sulfate were significantly reduced by 20-30%. Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CGB) were reduced by 68 and 25%, respectively. Although the dose of MA used (160 mg/day) was only 1/6 of the MPA dose (1000 mg/day), the mean serum level of MA was 2-fold higher than the mean serum level of MPA. MPA treatment gave a more pronounced suppression of SHBG than MA treatment, while estrone sulfate levels were more suppressed by MA. These findings suggest a differential effect of MPA and MA on certain plasma hormones, possibly of importance for understanding the mechanism of action of the two drugs. The reduction of estrone sulfate may be beneficial for the action of MA against breast cancer.

The actual dose delivery from a diazepam enema differs depending on the patients position during administration.

In a randomized single-blind cross-over study on 14 volunteers the relation between dose, effect and serum concentration was studied when diazepam in solution was administered in a dose of 0.5 mg/kg bodyweight rectally with the volunteer placed either laterally or prone. When lying prone the delivered diazepam dose was on average 24% higher compared to in the lateral position. The difference in delivered dose affected sedation as well as serum concentration but did not prolong recovery time. At the time of clinical recovery, the serum concentration was still at a very high level. Oxygen (p02) and carbon dioxide (pCO2) tensions were monitored transcutaneously in 9 subjects and were unaffected by the sedative level. The study suggests that when diazepam enemas similar to the ones used here, they should be administered with the patient in a prone position.

Effect of oral high-dose progestins on the disposition of antipyrine, digitoxin, and warfarin in patients with advanced breast cancer.

The influence of two progestins, medroxyprogesterone acetate (MPA) and megestrol acetate (MA), given orally in high doses, on the pharmacokinetics of antipyrine, digitoxin, and warfarin were studied in patients with advanced breast cancer. Antipyrine and warfarin were given as a single test dose before and after 5 weeks of progestin treatment. The pharmacokinetics of digitoxin was investigated at steady state in patients receiving this drug therapeutically before and during treatment with progestins. Small changes in clearance rates for antipyrine, warfarin, and digitoxin were found. A minor decrease observed in warfarin clearance however may be of clinical importance. Half-lives decreased by 13% for antipyrine and increased by 71% for warfarin. High-dose progestins given orally do not seem to have a major influence on drug metabolism, probably reflecting a minor effect on drug and steroid-metabolizing microsomal mono-oxygenases in the liver.