Increased isoprostane content in coronary plaques obtained from vulnerable patients.

8-Iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), a representative isoprostane, is a reliable biomarker for enhanced oxidant stress in vivo. Its urinary excretion has been proposed as a risk marker in patients with coronary heart disease. Isoprostane content has not yet been well elucidated so far in human coronary plaques. The aim of this study was to evaluate content of immunoreactive 8-iso-PGF(2)(alpha) in directional coronary atherectomy (DCA) specimens from patients with coronary heart diseases. Twenty-seven patients with stable angina pectoris (SAP) and 8 vulnerable patients (5 patients with unstable angina pectoris and 3 with recent myocardial infarction) were subjected to DCA. The specimens from SAP consisted of 14 de novo and 13 restenotic lesions, whereas those from the vulnerable patients were all de novo lesions. Total 8-iso-PGF(2)(alpha) content in the DCA specimens from the vulnerable patients was significantly greater than that from patients with SAP (5.48 (2.70-10.43) versus 2.38 (1.19-4.32)ng/g tissue, median (interquartile range), P<0.05). There was no significant difference in total 8-iso-PGF(2)(alpha) content between de novo and restenotic lesions from patients with SAP (3.25 (1.48-5.05) versus 1.57 (0.62-2.47)ng/g tissue, respectively, P=0.895). Total 8-iso-PGF(2)(alpha) content in apparently normal peripheral artery specimens was only 0.34 (0.26-0.46)ng/g tissue. In conclusion, 8-iso-PGF(2)(alpha) was enriched in the DCA specimens from vulnerable patients, suggesting a crucial role of free radicals in formation of vulnerable plaques and a putative benefit of anti-oxidant therapy on these patients.

Exogenous ouabain is accumulated in the adrenals and mimics the kinetics of endogenous digitalis-like factor in rats.

Ouabain has been isolated as an endogenous pathogenetic factor in salt-induced hypertension and has been shown to be rich in the adrenals. In this study, organ accumulation of orally administered [3H]ouabain was examined in rats. Exogenous [3H]ouabain was accumulated in high levels in the adrenals, especially in the zona intermedia, and was not metabolized in the rat. Accumulated [3H]ouabain mimicked the movement of "endogenous" digitalis-like factor, since 1) the plasma [3H]ouabain level decreased in bilaterally adrenalectomized rats, 2) the plasma [3H]ouabain level increased accompanied by a decrease in [3H]ouabain content in the adrenals in reduced renal mass hypertensive rats, and 3) [3H]ouabain levels in plasma and in the adrenals increased in spontaneously hypertensive rats, as compared with those in respective control animals. Moreover, the rat diet contained a relatively high amount of ouabain-like immunoreactivity (OLI), and the ratio of the [3H]ouabain content to OLI in each organ was comparable to that of the daily intake of dietary [3H]ouabain to OLI. Furthermore, high 3H-radioactivities were also observed in the adrenals of rats that ingested [3H]digoxin and [3H]digitoxin. These data suggest that exogenous ouabain, related cardiotonic glycosides of plant origin, or both accumulate in the adrenals and, at least in part, act as "endogenous" digitalis-like factor(s).

[Feminizing syndrome and gynecomastia in males].

Gynecomastia is one of the common symptoms of feminizing syndrome in males. Causes of feminizing syndrome are considered the increase of serum level of estrogen, prolactin, LH and hCG and testosterone deficiency. The condition of gynecomastia was commonly silent. Gynecomastia is classified three groups those are physiological, pathological and ideopathic gynecomastia. Physiological gynecomastia was reported to break out healthy males. Ideopathic gynecomastia is the main cause in medicine. Characterization of pathological gynecomastia are known side effect of drugs, testosterone deficiency and increased estrogen production. Gynecomastia is making satisfactory progress by treatment of the causes, but long term of the history merely have need resection.

Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells.

Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the increase in intracellular Ca2+ ([Ca2+]i) induced by angiotensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+]i level or the maximal response of [Ca2+]i increase induced by AII. Furthermore, IL-2-induced enhancement was not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimulation of DNA synthesis induced by AII, although IL-2 alone did not stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases, significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-2-induced enhancement of DNA synthesis induced by AII. These findings suggest that autocrine HB-EGF is partially involved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play important roles in the pathogenesis of atherosclerosis and vascular disease by modulating the responsiveness to AII in VSMC.

[Effect of estriol and bone mineral density of lumbar vertebrae in elderly and postmenopausal women].

To compare the efficacy of estriol (E3) in postmenopausal and senile osteoporosis, we administered orally 1 g/day calcium lactate either alone (control groups) or with 2 mg/day estriol (estrogen groups) for 10 months to 20 postmenopausal women aged 50-65 years and to 29 elderly women aged 70-84 years, and measured their bone mineral density of the lumbar vertebrae by dual energy X-ray absorptiometry. Out of 41 subjects who completed 10 months of treatment, 8 postmenopausal women and 12 elderly women in the estrogen groups had significant (p < 0.05) increases in bone mineral density (5.59 +/- 4.79% of the respective basal values). Ten postmenopausal women and 11 elderly women in the control groups had decreases bone mineral density (-4.02 +/- 7.00% and -3.26 +/- 4.60% of the respective basal values) at the 10th month. Genital bleeding as a side effect of estriol was seen in 6 out 29 elderly subjects at this dose. Moreover, decreases in the levels of calcium, total cholesterol, and triglycerides in serum, and an increase in the level of high-density lipoprotein-cholesterol were seen only in the elderly women receiving estriol. Although a lower dosage of estriol may be recommended for elderly subjects, these observations suggest that hormone replacement therapy with estriol is effective against degenerative osteoporosis, and that low-turnover bones in elderly women are also responsive to estriol.

Parathyroid hormone-related protein inhibits indothelin-1 production.

The effect of human parathyroid hormone-related protein, a powerful vasodilator, on endothelin-1 production in cultured bovine pulmonary arterial endothelial cells was studied. Treatment with parathyroid hormone-related protein(1-34) at concentrations of 10(-9) to 10(-6) mol/L for 24 hours caused dose-dependent suppression of the secretion of endothelin-1, with maximal suppression at 10(-7) mol/L to 74% of the control value. This inhibitory effect was completely abolished by coincubation with 100 ng/mL pertussis toxin, an inhibitor of GTP binding protein. Furthermore, addition of Ng-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, at 10(-3) mol/L significantly blocked the suppressive effect of parathyroid hormone-related protein (1-34) on endothelin-1 secretion, and further addition of 5x10(-3) mol/L L-arginine significantly attenuated the blocking effect of N(G)-monomethyl-L-arginine. Parathyroid hormone-related protein (1-34) at 10(-7) mol/L resulted in an approximately fivefold increase in intracellular cGMP level. Northern blot analysis revealed that parathyroid hormone-related protein (1-34) inhibited both basal and thrombin-induced endothelin-1 gene expression. These findings suggest that the vasodilating property of parathyroid hormone-related protein may be mediated in part through its inhibitory effect on endothelin-1 production, which is probably mediated through nitric oxide and cGMP in endothelial cells. Thus, a feedback regulatory mechanism may exist between parathyroid hormone-related protein and endothelin-1 in the vascular wall.

Calcitonin prevents CCl4-induced hydroperoxide generation and cytotoxicity possibly through C1b receptor in rat hepatocytes.

The effects of calcitonin (CT) on oxyradical generation and cellular damage induced by carbon tetrachloride (CCl4) were investigated in rat hepatocytes. Addition of CCl4 to the cells concentration dependently increased intracellular production of hydroperoxides and release of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The hepatocytes expressed mRNA for a CT receptor, C1b. Coaddition of CT to the cells concentration dependently suppressed the CCl4-induced increase in hydroperoxide production and also decreased the release of AST and ALT. The suppressive effect of CT on hydroperoxide production was reversed by further addition of H7 or by pretreatment with phorbol 12-myristate 13-acetate for 24 h. These results suggest that CT prevents CCl4-induced oxyradical production and cellular damage through activation of protein kinase C in hepatocytes.