Alfacalcidol (alpha D3) and calcium in osteoporosis.

In a prospective, randomized study, 66 osteoporotic postmenopausal women (mean age, 67 years) were scheduled to receive either alfacalcidol 0.25 microgram twice daily together with calcium 500 mg twice daily (treatment group, n = 24) or placebo twice daily with calcium 500 mg twice daily (control group, n = 42) for three years. In the treatment group, bone mineral content at the distal radius may have increased by 2% compared to a significant decrease of 7.8% in the control group. The difference between the two groups was also significant. Since the dose of alfacalcidol and calcium remained unadjusted, frequent hypercalciuria, as well as occasional mild, transient elevations of serum calcium, were observed in the treatment group. No changes in serum creatinine levels or creatinine clearance throughout the study were observed. The two groups did not differ with respect to the frequency of clinical side effects, which were mainly gastrointestinal and probably related to the calcium supplementation. Alfacalcidol and calcium may prevent further bone loss in women suffering from postmenopausal osteoporosis.

Effect of 1 alpha-hydroxyvitamin D3 treatment on production of tumor necrosis factor-alpha by peripheral blood mononuclear cells and on serum concentrations of soluble tumor necrosis factor receptors in hemodialysis patients.

The effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] deficiency, as well as of replacement therapy with 1 alpha-hydroxyvitamin D3[1 alpha-(OH)D3], on the production of tumor necrosis factor-alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMC) and on the serum levels of soluble TNF receptors (sTNFRs) in hemodialysis (HD) patients was investigated. PBMC from HD patients without prior therapy with hydroxylated vitamin D3 analogs and from normal controls produced similar amounts of TNF-alpha, either spontaneously or after stimulation with lipopolysaccharide (LPS). After oral administration of 1 alpha-(OH)D3, a precursor of 1,25-(OH)2D3, LPS-induced TNF-alpha production by PBMC of HD patients was significantly higher than that of HD patients prior to the treatment or of healthy controls. Such treatment did not, however, affect spontaneous TNF-alpha production by PBMC. Serum concentrations of both soluble TNF receptors [sTNFR-A(p75) and sTNFR-B(p55)] were significantly higher in HD patients than in controls. The ratio of sTNFR-A/sTNFR-B decreased significantly in HD patients following 1 alpha-(OH)D3 therapy. These results suggest that therapy with 1 alpha-hydroxylated vitamin D3 analogs normally given to HD patients for the management of renal osteodystrophy may also regulate the in vivo activity of TNF-alpha.

The involvement of gonads and gonadal steroids in the regulation of food intake, body weight and adiposity in the white Leghorn cock.

The effects of long-term injections of testosterone propionate (TP), diethylstilbestrol (DES) and TP+DES simultaneously to castrated and sham-operated White Leghorn cocks on feeding, weight gain, obesity, blood lipids and weight of various glands were studied. DES induced marked adiposity while TP reduced carcass fat content. Injections of TP+DES induced only moderate obesity. The responses of the castrated cocks to TP or DES were not always parallel to those of the sham-operated ones. In sham-operated cocks, TP induced permanent hypophagia and emaciation while in castrated cocks, although alleviating adiposity, it did not reduce the rate of weight gain and induced only a transient hypophagia. DES induced permanent hyperphagia and accelerated weight gain in sham-operated cocks while in those castrated, it induced only transient hyperphagia which later on changed into hypophagia. Although the latter cocks did not gain more weight than those castrated with no steroids supplementation, they were much more obese and had a fat content similar to that of the sham-operated ones treated with DES. The castration was found to alleviate the depressing effect of TP on adenohypophyseal and thyroidal weights. The results may suggest: (1) In the White Leghorn cocks, DES increases lipogenesis and food intake while TP results in the contrary. (2) Castration should not be considered as a lack of gonadal steroids only.

Effect of N,N-dimethyl-p-methoxyphenylethylamine on blood pressure and brain catecholamines in DOCA-saline hypertensive rats.

Intraperitoneal and intraventricular injections of N,N-dimethyl-p-methoxyphenyl ethylamine (PMPEA) decreased blood pressure in conscious DOCA-saline hypertensive rats. Bilateral injection of this agent into the nucleus tractus solitarii (NTS) of anaesthetized normotensive rats also caused a decrease in blood pressure. The increased turnover of noradrenaline in the dorsal part of the caudal medulla oblongata in DOCA-saline hypertensive rats was found to be restored to normal following treatment with N,N-dimethyl PMPEA. The data indicate a central site of action for the antihypertensive effect of N,N-dimethyl PMPEA.

The Pharmacology of the hypotensive action of N,N-dimethyl para-methoxyphenylethylamine in rats.

N,N-dimethyl para-methoxyphenylethylamine prevents hypertension and reverses existing high blood pressure in DOCA-saline treated rats. Indomethacin prevents its hypotensive effect, therefore the suggested mechanism is increase in prostaglandin(s) synthesis. The effect of the usual receptor antagonists on the hypotensive effect of the title compound can also be fitted into the framework of this hypothesis.

d-Tyrosine prevents hypertension in DOCA-saline treated uninephrectomised rats.

High blood pressure in DOCA-saline treated uninephrectomised rats is prevented or even reversed by tyrosine, tyramine or by treatments which - based on circumstantial evidence - might increase local brain tyramine concentration.

Central tyramine prevents hypertension in uninephrectomized DOCA-saline treated rats.

Prevention of high blood pressure in uninephrectomized, DOCA-saline treated rats was observed after treatment with central tyramine precursors. We suggest that the high blood pressure is either due to relative lack of tyrosine, which might be caused by the hyperactivity of tyrosine hydroxylase, or to hypoactivity of the decarboxylase: in both cases the result is diminished tyramine synthesis.

Sodium chloride preference in hypertensive (H) and normotensive (N) rats.

Salt consumption was compared in two strains of rats, selected for their disparate proneness (strain "H") or resistance (strain "N") to Doca-salt hypertension. NaCl intake was similar in "H" and "N" rats prior to an following administration of Doca, while their respective blood pressures at the end of this experiment was 178 +/- 5mm Hg vs. 134 +/- 3 mm Hg. Thus, disparate responses of the blood pressure to Doca in the two strains cannot be ascribed to differences in salt intake. In another study, salt preference was tested in "H" and "N" rats by two-bottle self-selecting technique. Before Doca, saline preference in "H" rats averaged 60.3 +/- 5.8% of total daily fluid consumption, vs 18 +/- 4.2% in "N" rats. Following Doca treatment for 3 weeks the respective values were 96 +/- 1.7% vs 67 +/- 6.6%. Thus Doca treatment enhanced salt appetite in both strains, but salt preference remained significantly higher in the "H" rats. The increased susceptibility to hypertension and enhanced salt appetite in the "H" rat, corroborates similar reports in the Okamoto "SH" rat. In the Brookhaven "S" rat, however, susceptibility to hypertension is associated with salt avoidance. The conflicting data do not support a unified concept of a genetically determined link between salt appetite and proneness to hypertension.