The effects of genistein (GST) on intracellular calcium concentration ([Ca(2+)](i)) were investigated in guinea pig ventricular myocytes. [Ca(2+)](i) was detected by confocal microscopy and represented by relative fluorescent intensity (FI-F(0)) /FI(0), %). The results showed that GST (10-40 micromol/L) reduced [Ca(2+)](i) in normal Tyrode's solution, Ca(2+)-free Tyrode's solution and normal Tyrode's solution containing 3 mmol/L EGTA in a concentration-dependent manner. The effects of GST on [Ca(2+)](i) in normal Tyrode's solution were partially inhibited by pretreatment with sodium orthovanadate, a potent inhibitor of protein tyrosine phosphatase, or L-type Ca(2+) channel agonist Bay K8644. GST also markedly inhibited the ryanodine-induced [Ca(2+)](i) responses in Ca(2+)-free Tyrode's solution. When Ca(2+) waves were produced by increasing extracellular Ca(2+) concentration from 1 to 10 mmol/L, GST (40 micromol/L) could block the propagating waves of elevated [Ca(2+)](i), and reduce the velocity and duration of propagating waves. These results suggest that GST may reduce the [Ca(2+)](i) in isolated guinea pig ventricular myocytes. The inhibition of voltage-dependent Ca(2+) channel, tyrosine kinase inhibition, and alleviation of Ca(2+) release from SR are possibly involved in the GST effect.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Animals ; Calcium ; metabolism ; Calcium Channel Blockers ; pharmacology ; Calcium Channels, L-Type ; Genistein ; pharmacology ; Guinea Pigs ; Heart Ventricles ; Male ; Microscopy, Confocal ; Myocytes, Cardiac ; cytology ; metabolism ; ultrastructure ; Protein Tyrosine Phosphatases ; antagonists & inhibitors ; Sarcoplasmic Reticulum ; metabolism ; Vanadates ; pharmacology

Aim The effect of tetrandrine on TGF-?1 mRNA expression in glomerulosclerosis rat was observed. Methods The rats were randomly divided into four groups, such as the normal control group (sham operative rat), glomerulosclerosis model group,tetrandrine group and amlodipine group. The expression of TGF-?1 mRNA was analyzed by Northern blot hybridization. Results The expressions of TGF-?1 mRNA in two treating groups were much lower than untreated model group. There were no difference between these two treating groups. Conclusion Tetrandrine can decrease the expression of TGF-?1 mRNA in glomerulosclerosis rat induced by unilateral renctomy plus adriamycin.

The effects of adrenomedullin (ADM) on intracellular calcium concentration ([Ca(2+)](i)) were investigated in cultured hippocampal neurons. Changes in [Ca(2+)](i) were detected by laser scanning confocal microscopy using Fluo 3-AM as the calcium fluorescent probe. [Ca(2+)](i) was represented by relative fluorescent intensity. The results showed that: (1) ADM (0.01-1.0 micromol/L) decreased the resting [Ca(2+)](i) in a concentration-dependent manner. (2) Calcitonin gene-related peptide receptor antagonist CGRP(8-37) significantly inhibited the effects of ADM. (3) ADM significantly reduced the increase in [Ca(2+)](i) induced by high K(+). (4) ADM markedly inhibited the inositol 1,4,5-trisphosphate (IP(3))-induced increase in [Ca(2+)](i), while did not influence ryanodine-evoked increase in [Ca(2+)](i). These results suggest that ADM reduces [Ca(2+)](i) in cultured hippocampal neurons through suppressing Ca(2+) release from IP(3)-sensitive stores. Although ADM does not alter resting Ca(2+) influx, it significantly suppresses Ca(2+) influx activated by high K(+). These effects may be partly mediated by CGRP receptors. ADM in the CNS may act as a cytoprotective factor in ischemic/hypoxic conditions.
Adrenomedullin ; Animals ; Animals, Newborn ; Calcitonin Gene-Related Peptide ; metabolism ; Calcium ; metabolism ; Cells, Cultured ; Embryo, Mammalian ; Hippocampus ; cytology ; metabolism ; Inositol 1,4,5-Trisphosphate ; antagonists & inhibitors ; Neurons ; cytology ; metabolism ; Peptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitonin Gene-Related Peptide ; antagonists & inhibitors ; metabolism

OBJECTIVETo explore the clinical effects of diaplastic external fixator on the treatment of unstable fractures of distal radius.

METHODSA clinical data of 60 patients with unstable fractures of distal radius admitted to Wangjing Hospital from August 2005 to September 2009 were retrospectively analyzed with the paired design. According to the paired design, 60 patients were equally divided into two groups (internal fixation group and external fixation group), which were respectively treated with open reduction and steel plate internal fixation (internal fixation group) or closed reduction and external fixation (external fixation group), including 8 males and 52 females, with an average age of 60.27 years ranging from 34 to 85 years. Left side was in 33 cases and right side was in 27 cases. All fractures were closed and caused by hand supporting when falling down. According to AO classification, type A3 was in 22 cases, type B2 was in 4 cases, type B3 was in 2 cases, type C1 was in 20 cases, type C2 was in 8 cases, type C3 was in 4 cases. Palmar flexion, dorsiflexion, radial deviation, ulnar deviation, pronation, supination, grip strength, radial angle, radial length, volar tilt were observed before and after operation.

RESULTSAll the patients were followed up from 12 to 18 months with an average of 15.4 months. The radial length was (4.85 +/- 2.75) mm,volar tilt (14.66 +/- 10.77) degrees, radial angle (7.90 +/- 4.70) degrees in the external fixation group,while those were (4.29 +/- 1.53) mm, (14.39 +/- 5.01) degrees, (6.19 +/- 3.15) degrees in the internal fixation group, but with no statistical significance (P>0.05). Function comparison of internal and external fixation group, P-value of every function is more than 0.05 or equal to 0.05, with no statistical significance except for supination and radial deviation. The functions of wrist joints were evaluated according to Batra scoring system at 1 year after operation. The average radiological scores of external fixation group was 86.27,in which 15 cases were excellent, 11 good, 1 fair,3 poor,while the average functional scores was 94.93, and all the cases were excellent. The average radiological scores of internal fixation group was 91.27, 16 cases were excellent, 12 good, 2 fair, while the average functional scores was 94.23, in which all the cases were excellent.

CONCLUSIONCompared with the open reduction and steel plate fixation, the unstable fractures of distal radius treating by diaplastic external fixator can be achieved a similar result, with no statistical significance.

Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; External Fixators ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged ; Radius Fractures ; surgery ; Retrospective Studies

Adult ; Aged ; China ; ethnology ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; genetics ; Polymorphism, Genetic ; Thrombospondin 1 ; genetics

OBJECTIVETo explore the mechanism of continuous traction in treating unstable distal radius fracture.

METHODSThirty patients with unstable distal radius fractures were treated by diaplastic external fixator including 4 males and 26 females with an average age of 61 years ranging from 18 to 85 years. According to AO classification, 12 cases were type A3, 3 were type B2, 8 were type C1, 4 were type C2, 3 were type C3. The distance of the processus radial malleolus and ulnar articularis were measured through X-ray examination.

RESULTSThirty patients were followed-up for 6 to 15 months with an average of 11.2 months. The results of distance before treatment measuring in X-ray was (0.55+/-0.22) cm, and the distance after treatment was (1.07+/-0.23) cm. The distance after treatment was higher than the distance before treatment, there were significant difference between them (P<0.01).

CONCLUSIONContinuous traction by diaplastic external fixator can explain by the theory of tendon reinforced bone and ligament restoration, or distraction osteogenesis.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; External Fixators ; utilization ; Female ; Fracture Fixation, Internal ; Fracture Healing ; physiology ; Humans ; Male ; Middle Aged ; Radiography ; Radius Fractures ; diagnostic imaging ; surgery ; Range of Motion, Articular ; physiology ; Recovery of Function ; Traction ; methods ; Treatment Outcome ; X-Rays ; Young Adult

OBJECTIVETo evaluate the effect of a 10-day course of triptolide (TP) on rat cytochrome (CY) P3A4 activity, and on the pharmacokinetics of cyclophosphamide (CPA).

METHODSIn the pharmacokinetics experiment, rats were orally given 0.9% NaCl solution (n=5) and TP [1.2 (mg/kg·d)] for 10 days and a single dose of CPA was administered intravenously (100 mg/kg) to rats on day 11. Blood samples were collected up to 4 h at predetermined time intervals, the plasma concentration of CPA was determined by high performance liquid chromatography (HPLC) and pharmacokinetic parameters were determined. In the in vitro CYP3A4 activity inhibition research, rat blank liver microsomes were divided into 3 groups: a control group, a TS (5 μL, 200 μmol/L) with TP (5 μL, 12.5 μmol/L) group, a TS with ketoconazole (5 μL, 1 μmol/L) group. Concentration of 6β-hydroxylated testosterone (6β-OHT) in liver microsomes was measured by HPLC and the activity of CYP 3A4 was calculated through the following formula: Einhibitor/Econtrol × 100%=Cinhibitor/Ccontrol × 100%.

RESULTSCompared with the control group, the area under the plasma concentration-time curve (AUC0-∞) of CPA was significantly increased by 229.05% pretreated with TP (P<0.01). Peak plasma concentrations (Cmax) of CPA was significantly increased and plasma half-life was correspondingly extended. The CYP3A4 activity was significantly inhibited by ketoconazole 93.5%±0.2% and TP 84.6%±0.3% compared with the control group (P<0.01 and P<0.05, respectively).

CONCLUSIONOur results strongly suggested that long-term oral intake of TP can distinctly inhibit the CYP3A4 activity and this inhibition evidently decrease the formation of toxic metabolites of CPA.

Animals ; Cyclophosphamide ; pharmacokinetics ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; pharmacology ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Herb-Drug Interactions ; Hydroxytestosterones ; metabolism ; Immunosuppressive Agents ; pharmacokinetics ; Injections, Intravenous ; Ketoconazole ; pharmacology ; Male ; Microsomes, Liver ; drug effects ; metabolism ; Phenanthrenes ; pharmacology ; Rats, Sprague-Dawley

Objective On July 6, 2010, the parents of a patient with confirmed measles reported several suspected measles patients with fever and rash in their village. An investigation was carried out to verify and understand the cause of the outbreak. Methods Several suspected cases had an onset of fever and rash in this and other neighboring villages during June 1 to August 3,2010. A confirmed case was a suspected case with measles-specific IgM identified in the serum. We conducted door-to-door visits and searched the Chinese Center for Disease Control and Prevention Information System to identify cases, also conducted a retrospective cohort study among migrant children aged 8 months-14 years to identify risk factors related to measles. Results We identified 19 measles cases (17 confirmed case, 2 suspected cases)in the village, and all of them were migrants. Children aged 1-2 years had the highest attack rate(13%). The primary case-patient had onset on the day she arrived in this village(June 4,2010). Caretakers from an unlicensed private clinic were providing service in the village but did not report the outbreak to the public health authority. The outbreak was identified only after receiving a report from the parents of one of the patients, by that time the outbreak had lasted for one month. The measles vaccine coverage rate was 81% among the 315 migrant children aged 8 months-14 years. Among the 61 unvaccinated children, those who reportedly being contacted a measles patient had a higher attack rate(14/16, 88%)than those who did not(2/45, 4.4%)(Relative risk=20, Fisher' s exact 95% confidence interval: 5.7-94). Conclusion The low measles vaccine coverage among migrant children and lack of measures taken on the incident, timely isolation diagnosis/reporting by the caretakers from the unlicensed private clinic etc. had contributed to this prolonged outbreak. Measures need to be taken to improve the immunization services for migrant populations and to enhance measles surveillance programs in the area.

Objective In order to shorten the transparency time of clear,unobstructed brain imaging cocktails and computational analysis(CUBIC),improve the transparency efficiency,and explore the possibility of applying hydrophilic tissue transparency technique,this study was conducted to optimize the perfusion of CUBIC technique and compare it with four hydrophilic tissue clearing method in terms of tissue transparency effect,transparency time,area change,volume change and adeno-associated virus(AAV)fluorescence retention.Methods Brain,liver,spleen and kidney of 6 adult Institute of Cancer Research(ICR)mice were subjected to clearing treatment by SeeDB,FRUIT,ScaleS and CUBIC method,respectively.The area and gray value of the samples were measured by Image J 1.8.0,and the volume before and after transparency was measured by drainage method to compare the transparency effect,time and size deformation of each group.Perfusion optimization of the CUBIC was performed by improving the perfusion rate with the optimal perfusion dose,each group of the experimental sample size was 6.Fluorescence preservation by different techniques was evaluated by injecting AAV in the motor cortex of 16 adult mice and taking the cervical spinal segments for transparency treatment after four weeks,and the fluorescence photographs were measured by Image J 1.8.0 to measure the mean fluorescent intensity.Results The optimal perfusion rate and dose of CUBIC was 15 ml/min and 200 ml respectively.For transparency ability and speed,the perfusion CUBIC had the lowest mean gray value and took the shortest time,while CUBIC consumed the longest time,and SeeDB,FRUIT,and ScaleS did not show good transparency ability.In terms of area and volume changes,several techniques showed different degrees of expansion after transparency of tissues or organs.In terms of fluorescence retention,perfusion CUBIC showed the best retention of green fluorescent protein(GFP)fluorescence signal,followed by CUBIC,ScaleS,FRUIT,and SeeDB.Conclusion Perfusion CUBIC technique shows the best tissue transparency,the shortest transparency time,and the most AAV fluorescence retention compared with other techniques.

OBJECTIVETo evaluate the efficacy and safety of aildenafil citrate, an oral phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction.

METHODSIntegrated analyses were made of 8-week, randomized, double-blind, placebo-controlled phase 2 clinical trials involving 250 men with mild-to-severe erectile dysfunction of various etiologies who received aildenafil citrate 30 or 60 mg (n = 167) or placebo (n = 83).

RESULTSThe statistic results of International Index of Erectile Function, Patient Sexual Encounter Profile (SEP) diaries and Global Assessment Question (GAQ) were significantly higher in the aildenafil citrate patients than in the placebo controls. The main drug-related adverse events were flushing, headache, dizziness and naupathia, which were mild and could be self-relieved.

CONCLUSIONThe aildenafil citrate therapy significantly ameliorated erectile function and was well tolerated by a wide range of patients with erectile dysfunction.

Administration, Oral ; Double-Blind Method ; Drug Administration Schedule ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Phosphodiesterase Inhibitors ; adverse effects ; therapeutic use ; Piperazines ; adverse effects ; therapeutic use ; Sulfones ; adverse effects ; therapeutic use ; Treatment Outcome