Relaxant effect and possible mechanism of 17-nor-subincanadine E in rabbit corpora cavernosa

Compounds with dual action on cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) may be a treatment option for erectile dysfunction, as they not only promote penile erection but also prevent the upregulation of phosphodiesterase-5. In this study, we examined the possible relaxant effect and mechanism of 17-nor-subincanadine E (SEC, 0.2–200 µmol l⁻¹), a plant-derived alkaloid, in rabbit corpus cavernosum (RbCC) strips that had been precontracted by exposure to phenylephrine (10 µmol l⁻¹) or a high concentration of K⁺ (60 mmol l⁻¹) in vitro. In addition to SEC''s effect on cAMP and cGMP levels, electrical field stimulation (EFS) in phenylephrine-precontracted RbCC and calcium chloride (1–100 mmol l⁻¹) evoked responses in depolarized RbCC were analysed. SEC relaxed the phenylephrine-precontracted RbCCs in a concentration-dependent manner. Atropine, guanethidine and N-ω-nitro-ℓ-arginine methyl ester (L-NAME) did not have any effect on the relaxation of RBCCs. When 1H-^{1, 2, 4}oxadiazole[4,3-a] quinoxalin-1-one (ODQ) was added, it effectively blocked the relaxant response of SEC. Although SEC enhanced the maximal relaxation produced by sodium nitroprusside (SNP) and forskolin in phenylephrine-precontracted cavernosal smooth muscle, it caused a decrease in the maximal contractile response induced by calcium chloride in depolarized RbCCs. The relaxant effect of SEC was paralleled by an increase in the tissue levels of the cyclic nucleotides cAMP and cGMP. We conclude that SEC promotes the relaxation of RbCC, possibly favouring cAMP and cGMP accumulation and calcium blockade. This novel mechanism could be useful for patients who do not benefit from phosphodiesterase inhibitors and for those with endothelial and nitrergic dysfunction, such as patients with diabetes, hypertension and dyslipidaemias.     

Mean platelet volume/platelet count ratio as a predictor of long-term mortality after non-ST-elevation myocardial infarction

Previous studies reported an association between elevated mean platelet volume (MPV) and post-myocardial infarction mortality. This study explores the association between long-term mortality after non-ST-segment elevation myocardial infarction (NSTEMI) and the peripheral blood platelet indices (i.e., the mean platelet volume (MPV), platelet count, and the MPV/platelet (MPV/P) ratio). Two physicians independently reviewed the data of 619 NSTEMI patients. The blood samples were drawn and analyzed within 1?h of admission, the second, and the last hospital days. Patients were stratified into equal tertiles according to the platelet count, MPV, and MPV/platelet ratio. The primary outcome, 4-year all-cause mortality, was compared among the platelet indices tertile models. According to MPV, platelet count, and MPV/platelet ratio tertile models, there was a trend of higher 4-year mortality for the lower and upper tertiles in comparison to the middle tertiles. However, only the admission MPV/platelet ratio tercile model was statistically significant for predicting the 4-year mortality. The mortality rate of the highest MPV/platelet (48/207 (23%)) and the lowest (41/206 (20%)) tertiles were significantly higher than the middle tertile (19/206 (9%)), p?=?0.0004 by the chi-squared test. After adjusting for Global Registry of Acute Coronary Events, the patients in the combined first and third MPV/P tertiles had higher mortality in reference to those in the middle MPV/P tercile (hazard ratio 1.951, confidence interval 1.032-3.687, and p?相似文献   

中国成人硒需要量研究

目的 探讨使人体血浆硒蛋白P(SEPPI)达到饱和的硒摄入量,以评估硒需要量,为膳食硒参考摄入量DRIB的修订提供参考.方法 时98名低硒健康受试者(体重平均58kg)进行为期40w的双盲补硒实验.随机分为七组,补硒(以硒蛋氨酸形式)剂量分别为0、21、35、55、79、102和125 μg/d.定期检测血浆中谷胱甘肽...     

Promises of apoptosis-inducing peptides in cancer therapeutics

Until recently, most research efforts aimed at developing anti-cancer tools were focusing on small molecules. Alternative compounds are now being increasingly assessed for their potential anti-cancer properties, including peptides and their derivatives. One earlier limitation to the use of peptides was their limited capacity to cross membranes but this limitation was alleviated with the characterization of cell-permeable sequences. Additionally, means are designed to target peptides to their malignant targets. Most anti-cancer peptidic compounds induce apoptosis of tumor cells by modulating the activity of Bcl-2 family members that control the release of death factors from the mitochondria or by inhibiting negative regulators of caspases, the proteases that mediate the apoptotic response in cells. Some of these peptides have been shown to inhibit the growth of tumors in mouse models. Hopefully, pro-apoptotic anti-tumor peptides will soon be tested for their efficacy in patients with cancers.