It is well documented that vascular tone is the key determinant of blood vessel resistance and blood flow. But vascular tone could be regulated by modulating the activity of potassium channel directly. Potassium channel openers promote vasodilation by inhibiting the activity of voltage dependent calcium channels and reducing Ca 2+ influx. In this case, inhibition results from membrane hyperpolarisation, which arises due to the stimulation of K + efflux through smooth muscle K + channels. While K + channels are blocked, vasoconstriction could be observed as a result of membrane depolarization, which opens voltage dependent calcium channels. The influx of Ca 2+ can promote smooth muscle contraction by making myosin light chain phosphorylation and arising thick myofilament and thin myofilament relative movements. In this article, the gene structure, current character, Pharmacological and physiological effects of the four subtypes potassium channels are reviewed.

A kind of magnesium potassium phosphate cement developed for bone repair was cleared by FDA in 2009 and has been presently in clinical use in America.The biomaterial has the powerful adhesive capability to bind bone,ligament,and tendon to bone,as well as possessing good biocompatiblity,appropriate biodegradability and osteogenicity; to data,it is the only material which possesses the combination of adhesivity and osteogenicity among bone repair biomaterials.The clinical application of the innovative biomaterial will unprecedentedly alter the treatment in orthopedic surgery and related disciplines.To provide a comprehensive appreciation of the innovative biomaterial,this article summaries its development,characteristics of composition and preparation,formation mechanism,application study and superiority.

China ; epidemiology ; Humans ; Pneumoconiosis ; epidemiology ; Retrospective Studies

OBJECTIVETo investigate the effects of total flavonoids of propolis (TFP) on apoptosis of myocardial cells of chronic heart failure and its possible mechanism in rats.

METHODSSix male SD rats were randomly selected as normal control group, the remaining rats were made as chronic heart failure (CHF) model by intraperitoneal injection of adriamycin. The rats in the successful model were randomly divided into five groups (n = 6): CHF group, total flavonoids of propolis low dose group (LD group), total flavonoids of propolis middle dose group (MD group), total flavonoids of propolis high dose group (HD group), digoxin group (DIG group). After six week treatment, cardiac function indexes of rats were recorded by signal acquisition system; brain natriuretic peptide (BNP), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) content in plasma were detected; Myocardial morphological changes and collagen fiber hyperplasia by HE and Masson staining were observed; Myocardial apoptosis was detected with TUNEL method and protein connexin 43(P-Cx43) expression was detected by Western blot method.

RESULTSCompared with NC group, left ventricular systolic pressure(LVSP) and maximal rise/fall velocity of left ventriculad pressure (± dP/dt(max)) absolute value in CHF group were significantly lowered (P < 0.01) while left ventricular end diastolic pressure (LVEDP) was increased significantly (P < 0.01); Contents of plasma BNP, cTnI, TNF-α and IL-6 in the CHF group were significantly improved (P < 0.01). Compared with CHF group, LVSP, ± dP/dt(max) absolute value in MD and HD groups were increased (P < 0.05), and LVEDP was significantly lowered (P < 0.01); LVEDP in LD group was significantly lowered (P < 0.01), changes in LVSP and ± dp/dt(max) absolue value were not obvious (P > 0.05). BNP, cTnI, TNF-α and IL-6 contents in MD and HD groups were significantly reduced (P < 0.01), but those plasma indicator changes were not obvious in LD group (P > 0.05). Western blot showed that P-Cx43 expression in CHF group was significantly higher than that in NC group (P < 0.01) and that in all TFP treatment groups it was decreased compared with CHF group (P < 0.05, P < 0.01), among which pairwise comparisons also showed differences (P < 0.05), myocardial apoptosis index (%)(22.62 ± 3.39) in CHF group was higher than that in NC group( 1.12 ± 0.24) (P < 0.01); compared with CHF group, the apoptosis index of myocardial cells (%) in LD,MD and HD groups, (15.79 + 2.8), (9.28 + 2.1) and (4.73 + 1.14) respectively, were significantly lower than those in the CHF group( P < 0.01). The expression level of P-Cx43 positively correlated with the apoptotic index (r = 0. 861, P < 0.01).

CONCLUSIONTotal flavonaids of propolis have inhibitory effect on apoptosis of myocardial cells of chronic heart failure induced by adriamycin in rats, and the mechanism may be closely related to the regulation of Cx43 expression, especially the regulatory phosphorylation status.

Animals ; Apoptosis ; Chronic Disease ; Connexin 43 ; metabolism ; Disease Models, Animal ; Doxorubicin ; adverse effects ; Flavonoids ; pharmacology ; Heart Failure ; drug therapy ; Interleukin-6 ; blood ; Male ; Myocardium ; pathology ; Myocytes, Cardiac ; drug effects ; Natriuretic Peptide, Brain ; blood ; Phosphorylation ; Propolis ; chemistry ; Rats ; Rats, Sprague-Dawley ; Troponin I ; blood ; Tumor Necrosis Factor-alpha ; blood

Animals ; Arterioles ; cytology ; growth & development ; Cell Culture Techniques ; methods ; Cell Proliferation ; Cells, Cultured ; Lung ; anatomy & histology ; Myocytes, Smooth Muscle ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley

Aged ; Coronary Artery Bypass, Off-Pump ; methods ; Coronary Artery Disease ; surgery ; Female ; Humans ; Male ; Retrospective Studies ; Treatment Outcome

Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.
Binding Sites ; Cytochrome P-450 Enzyme System ; metabolism ; Drug Design ; Drug Discovery ; methods ; Drug Recalls ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Humans ; Structure-Activity Relationship

Objective To evaluate the efficacy of different doses of glucocorticoid for prevention of postoperative complications in patients undergoing coronary artery bypass grafting (CABG).Methods We searched PubMed,EMBASE,Highwire,CENTREN and its affiliated clinical trial registration data center,Chinese Biomedical Database,and CNKI from 2000 to 2010 for randomized controlled trials involving the efficacy of different doses of glucocorticoid for prevention of postoperative complications in patients undergoing CABG.The quality of the studies was evaluated by the method recommended by Cochrane Collaboration.Evaluation indexes included development of fibrillation,requirement for insulin treatment because of hyperglycosemia,infection,and death (during stay in hospital or within 30 days after discharge from hospital) after operation and mechanical ventilation time.Meta-analysis was conducted using the RevMan 5.1 software.Results Twenty-one randomized controlled trials involving 1737 patients were included in our meta-analysis.Different doses of glucocorticoid decreased the risk of fibrillation,and did not increase the risk of various causes-induced infection and death.Moderate and large doses of glucocorticoid increased the risk of requirement for insulin treatment because of hyperglucosemia.Large dose of glucocorticoid resulted in prolongation of ventilation time.Conclusion Different doses of glucocorticoid can decrease the development of postoperative fibrillation without increasing the risk of infection and death,moderate and large doses of glucocorticoid increase the risk of requirement for insulin treatment because of hyperglucosemia and large dose of glucocorticoid increases the risk of prolonged ventilation time in patients undergoing CABG.

AIM To investigate the effects of the novel antihypertensive drug iptakalim hydrochloride on potassium currents in artery smooth muscle cells. METHODS The effects of iptakalim hydrochloride on potassium currents in smooth muscle cells derived from rat pulmonary arteries were observed by using patch clamp technique(whole cell recording) after application of the drug in the bath. RESULTS The potassium current-voltage curves ( I-U curves) of smooth muscle cells derived from normotensive rat pulmonary arteries were up-ward shifted by iptakalim hydrochloride(0.1,1,10 and 100 ?mol?L -1 ). Within 5 minutes after application of the drug, the current amplitude could increase to[(118.6?15.9)%, P

The microbial populations and community structure characterization technologies of the enhanced biological phosphate removal system were reviewed comprehensively in this paper, and their future research directions were outlined.