In this study, cardiotonic and cardiotoxic effects of Buthus martensi Karsch (BmK) I, a modulator of voltage-gated sodium channels, were investigated on the isolated rat hearts. The results showed that BmK I evoked complex effects characterized by a change in both cardiac mechanical and electrical activity. Langendorff perfusion showed that: (1) maximal left ventricular developed pressure (LVDP(max)) and dp/dt(max) were markedly increased by BmK I (0.5-10 micromol/L) in a dose-dependent manner (n=6, P<0.05), positive chronotropic effects were also induced by BmK I (n=6, P<0.05); (2) negative inotropic action and bradycardia could be elicited at a larger dose of BmK I (20 micromol/L); (3) the coronary flow varied inversely with the positive inotropic effects, coronary flow reduced during positive inotropic effects from 14.5 to 8.6 ml/min after administration of 500 nmol/L BmK I (n=6, P<0.05). In addition, tachycardia and complex cardiac arrhythmias were induced by BmK I (0.5-10 micromol/L). The modulating of BmK I on the heart mechanical, electrical activity could be partially recovered after washing. As propranolol was applied to block the release of catecholamines before administration of BmK I, suggesting that the changes in cardiac mechanical and electrical activity induced by BmK I might not due to catecholamine release from the nerve terminal and subsequent stimulation of the beta-adrenoceptor but attributable to the modulation of BmK I on cardiac voltage-gated sodium channels.
Action Potentials ; drug effects ; Animals ; Electrophysiology ; In Vitro Techniques ; Insect Proteins ; Male ; Myocardial Contraction ; drug effects ; NAV1.5 Voltage-Gated Sodium Channel ; Neurotoxins ; pharmacology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; pharmacology ; Sodium Channel Blockers ; pharmacology ; Sodium Channels ; drug effects

OBJECTIVETo observe the effects of panax quinquefolius saponin (PQS) of stem and leaf on glucose-lipid metabolism and insulin signal transduction in the insulin resistant model of adipocytes.

METHODSThe insulin resistant model of differentiated 3T3-L1 adipocytes was established in vitro with free fatty acid. After induction of insulin resistance, cells were treated with metformin or PQS for 2 days. The glucose consumption in culture fluid was detected by glucose oxidase method; the effects of PQS on the lipolysis induced by tumor necrosis factor (TNF-alpha) was observed using colorimetry; and the phospholation of signal proteins was detected by Western-blot.

RESULTSThe amount of glucose consumption (mmol/L) in the model group (5.250 +/- 2. 671) was significantly lower than that in the normal control group (14.133 +/- 1.305, P < 0.01), it increased in the meformin treated group (11.807 +/- 1.358), and the groups treated with high-, middle- and low-dose PQS dose-dependently (10.784 +/- 2.373, 10.217 +/- 1.237 and 9.984 +/- 2.006, respectively), significantly higher than that in the model group (P < 0.01). Upon TNF-alpha treatment, the concentration of free fatty acid (FFA) (nmol/ microg) in culture medium was 2.479 +/- 0.597, predominantly higher than that in the control group (1.320 +/- 0.538, P < 0.01), while it was 1.210 +/- 0.566 in the metformin group, 1.105 +/- 0.631 in high-dose PQS group, 1.108 +/- 0.260 in the middle-dose PQS group, 1.201 +/- 0.593 in the low-dose PQS group, all were lower than that in the TNF-alpha group (P < 0.05 or P < 0.01), and a dose-dependent tendency of PQS's action was seen. The tyrosine phosphorylation of insulin receptor and IRS-1 as well as Ser473 phosphorylation of PKB were lower in the model group than in the control group; they were insignificantly changed in the low-dose PQS group, but did show significant difference in comparing with those in the high-and middle-dose PQS groups or metformin group.

CONCLUSIONPQS can accelerate the glucose utilization and depress the lipolysis in adipocytes induced by TNF-alpha, which may be correlated with its promoting insulin signal transduction and improving insulin resistance in adipocytes.

3T3-L1 Cells ; Adipocytes ; drug effects ; metabolism ; Animals ; Glucose ; metabolism ; Insulin ; metabolism ; Insulin Resistance ; Lipid Metabolism ; drug effects ; Mice ; Saponins ; pharmacology ; Signal Transduction ; drug effects

Adult ; Angiomatosis ; immunology ; pathology ; surgery ; Antigens, CD ; metabolism ; Diagnosis, Differential ; Female ; Hemangioma ; immunology ; pathology ; Humans ; Hyperplasia ; Spleen ; immunology ; pathology ; Splenectomy ; Splenic Diseases ; immunology ; pathology ; surgery ; Splenic Neoplasms ; immunology ; pathology

Adult ; Aged, 80 and over ; Carcinoma, Hepatocellular ; genetics ; pathology ; DNA Sequence, Unstable ; Female ; Humans ; Liver Neoplasms ; genetics ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; genetics ; Neoplasm Invasiveness

Acupuncture Points ; Adolescent ; Adult ; Aged ; Asthma ; therapy ; Combined Modality Therapy ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Treatment Outcome ; Young Adult

Elevated low density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Studies show that proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulation enzyme and serves a pivotal function in the degradation of low density lipoprotein receptor, which contributes to the decrease in hepatic cholesterol uptake and increase in circulating LDL-C. PCSK9 inhibitor can significantly elevate the surface of low density lipoprotein receptor of liver cells and bond more LDL-C to decrease the level of LDL-C. Thus PCSK9 has emerged as a popular target for the development of new cholesterol lowering drugs and therapeutic intervention of cardiovascular disease. In this article, the history, mechanism of action, metabolic effects of PCSK9 and the clinical outcomes of PCSK9 inhibitors will be briefly reviewed.

Objective To explore the characteristics of dipyridamole 201 Tl myocardial perfusion imaging (MPI) SPECT in patients with dilated cardiomyopathy. Methods Thirty patients with dilated cardiomyopathy underwent pharmacological stress 201Tl MPI SPECT after intravenous infusion of dipyridamole (0. 56 mg/kg) for 4 min. The early and delayed SPECT images were acquired respectively at 10 and 240 min after 201Tl injection. The images were analyzed and reported by two or three experienced nuclear medicine physicians. Results All patients were found to have abnormal perfusion patterns at delay imaging, however 90.00% (27/30) were also abnormal at early images. Six patients had reverse redistribution. Conclusion Dipyridamole 201Tl MPI SPECT imaging may be of some value for the assessment of patients with dilated cardiomyopathy.

Objective To explore the modulatory effect of 5-HT2A receptors on the discharge activities of inspiratory neurons in medial region of nucleus retrofacialis of neonatal rats. Methods Experiments were performed in vitro brainstem slice preparations from neonatal rats. These preparations included the medial region of nucleus retrofacialis with the hypoglossal nerve rootlets retained. The rhythmic discharges of the inspiratory neurons and activities of the hypoglossal nerve rootlets were simultaneously recorded by using microelectrodes and suction electrodes, respectively. Roles of 5-HT2A receptors in modulation of the discharge activities of inspiratory neurons were investigated by administration of the 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodopbenyl)-2-aminopropane (DOI), and its specific antagonist ketanserine dissolved in modified Kreb's solution for perfused slices. Results In DOI group, the inspiratory time (TI) was (0.864±0.07)s, expiratory time (TE) was (10.78±1.06)s, respiratory cycle (RC) was (11.79±1.64)s, integral amplitude (IA) was (357.98±37.21)(μV·s) and the peak discharge frequency (PF) was (37.83±3.66)Hz. In control group, they were (0.68±0.06)s, (13.89±2.14)s, (14.77±1.92)s, (273.57±24.39)(μV·s), and (29.92±4.50)Hz, there were significant differences between the 2 groups (Pa<0.01). In ketanserine group, TI was (0.55±0.07)s, TE and RC were (18.43±3.28)s and (20.17+2.91)s respectively, IA and PF were (214.37±33.52)(μV·s) and (22.17±3.92)Hz, there were significant differences between ketanserine group and DOI, control group (Pa<0.01). Conclusion 5-HT2A receptors take part in modulate the discharge activities of inspiratory neurons in neonatal rat brainstem slices.

Objective To explore the modulation roles of gamma-aminobutyric acid A(GABAA) receptor on respiratory rhythmical discharge activity in brainstem slice of neonatal rats.Methods Experiments were performed on in vitro neonatal rats brainstem slices.The slices containing the medial region of the nucleus retrofacialis(mNRF)with the hypoglossal nerve rootlets retained was prepared in which the respira-tory-related rhythmic discharge activity(RRDA)were recorded from hypoglossal nerve rootlets by suction electrode.The possible role of GABAA receptor on RRDA was investigated by administration of GABA and its antagonist bicuculline in modified Kreb′s solution(MKS),for perfusion of the brainstem slices.Eighteen slices positive of RRDA were randomly divided into three equal groups:the first group of slices was perfused with different concentrations(10,20,40,60 ?mol/L) GABA and the most effective concentration was selected;the second group of slices was perfused with 10 ?mol/L bicuculline;the third group of slices was perfused with 10 ?mol/L bicuculline plus 40 ?mol/L GABA.The RRDA in 3 groups were observed.Results GABA decreased RRDA,40 ?mol/L was the most effective concentration.It shortened inspiratory time(TI),decreased integral amplitude(IA),prolonged respiratory cycle(RC) and expiratory time(TE) respectively.By contrast,10 ?mol/L bicuculline produced opposite effects on RRDA,it prolonged TI,increased IA,shortened RC and TE respectively.40 ?mol/L GABA plus 10 ?mol/L bicuculline had no significant effects on RRDA.Conclusion GABA plays an important role in modulate RRDA of neonatal rats via GABAA receptor.

Objective To compare the relative efficacy and quality of extraction of human fecal DNA using four methods.Methods Real-time PCR were utilized for analysis both quantification and quality of the fecal targeted bacteria(including gut all eubaeterium,Bacteriodes-PrevoteUa group,Bifidobacterium spp Enterobacteriaceae and Enterococcus spp)by using 16s rRNA gene-targeted genus or group-specific primer sets.Results The negative rat of PCR product from method 3(phenol-chloroform plus bead-beating) was about 40%(4/10)by using universal primers,the PCR inhibition disappeared after fecal DNA purified with column.The total fecal 16s rRNA gene copy numbers(per gram of wet weight of feces)as well as the numbers of Bacteriodes-Prevotella group from method 1(QIAamp~DNA stool mini kit)and 4(QIAamp~ DNA stool mini kit combined with bead-beating)was higher significantly than that from method 2(FastDNA ~Kit,Biol01)and 3(P