Treatment of Helicobacter pylori induced chronic atrophic gastritis with traditional Chinese medicine combined standard triple therapy and its mechanisms / 吉林大学学报(医学版)

Objective:To treat the chronic non-atrophic gastritis patients induced by Helicobacter pylori with Qingweizhitong Weiwan combined with standard triple therapy,and to detect the differential expression of related immflammation genes with PCR array,and to clarify its mechanism.Methods: Ten patients with chronic non-atrophic gastritis complicated with Helicobacter pylori infection were used as treatment group and 10 health people were used as health control group. The patients in treatment group were treated with Qingweizhitong Weiwan combined with standard triple therapy for 14 d. The blood samples of the subjects in treatment group and health control group were collected before and after treatment,and QIAGEN human antibacterial response PCR array was performed to test the total RNA inperipheral blood and to analyze the differential expressions of 84 inflammation-related genes.Results:The differential expressions of 20 inflammation-related genes were found.Compared with health control group,the expression levels of 20 genes in treatment group before treatment were up-regulated (Fold-change>2);after treatment,the expression levels of 20 genes were down-regulated,and 11 of them were similar to the level in health control group (Fold-change< 2).More specifically,part of 20 genes was related to NLRP3 inflammasome.Compared with health control group,the gene expression levels of CASP1,IL1B,NLRP3,and PYCARD in treatment group before treatment were up-regulated (P <0.05).Compared with before treatment,the expression levels of CASP1,IL1B,NLRP3,and PYCARD in treatment group after treatment were down-regulated (P <0.05).Conclusion:The mechanism of Qingweizhitong Weiwan combined with standard triple therapy in the treatment of chronic non-atrophic gastritis patients induced by Helicobacter pylori may be related to inhibiting the expressions of NLRP3 inflammasome-related genes and interfering the antimicrobial innate immune response.

A new central anticholinergic anti-motion sickness drug phencynonate hydrochloride / 中国药理学与毒理学杂志

At present scopolamine is the most powerful single anti-motion sickness drug, but with prominent unwanted side effects. Many attempts had been made to decrease the unwanted side effects, but no any approach was considered to be successful. Based on our working hypothesis that central cholinolytic activity of anticholinergics may not be parallel completely to their side effects, a series of alicyclic amino alcohol esters were designed, synthesized and evaluated. One of the best compounds, phencynonate HCl, was obtained by transesteration of methyl α-phenyl-α-cyclopentyl-α-hydroxy acetate with N-methyl-3-azabicyclo(3,3,1)nonan-9α-ol. In animal models it was demonstrated that at equivalent anti-motion sickness dose the side effects of phencynonate were milder than those of two other central anticholinergic anti-motion sickness drugs scopolamine HBr and difenidol HCl. In clinical trials the overall effectiveness rates for prevention of seasickness and carsickness of phencynonate (oral 2-4 mg/person) was very significantly higher than that of placebo, and also significantly higher than that of difenidol (oral 25-50 mg/person). In self controlled rotatory chair experiments in hospital laboratory, the preventive effects of phencynonate and difenidol in reducing the changes in electronystagmus and electrogastrogram were statistically significant. In another self controlled rotation experiment, phencynonate (2-4 mg/person) and scopolamine (0.3-0.6 mg/person) showed significant anti-motion sickness effects in reducing the gastric electric cycles of electrogastrogram and the Graybiel scores of acute motion sickness and significant inhibitory effects on visual-vestibular interaction dose-dependently. The anti-motion sickness effects of phencynonate 2 and 4 mg were correspondent with those of scopolamine 0.3 and 0.6 mg, respectively. Student pilots with high susceptibility to airsickness were stimulated by Coriolis acceleration. The course of desensitization and habituation to airsickness training in phencynonate group (3 mg/person) was significantly shorter than that of placebo. There was no rebounding in sensitivity to Coriolis stimulation after discontinuing phencynonate, which was reported in case of scopolamine. The side effects of phencynonate HCl were mild dry mouth (9.7%) and drowsiness (9.97%). The incidence of drowsiness is significantly lower than that of difenidol. The side effect of drowsiness was only appeared in aboard ship and bus experiments, but not in PhaseⅠ trial in hospital or in laboratory rotation tests. The incidence of drowsiness of phencynonate was also lower than that of dramamine in aboard tank experiment. Phencynonate could effectively control the acute attack of vertigo, especially Meniere′s disease and positional vertigo. In animal models of Parkinson′s disease and parkinsonism, phencynonate showed morepotent antagonistic effects than clinical common used trihexyphendyl. In summary, phencynonate is a new central anticholinergic anti-motion sickness drug with higher efficacy and lower central inhibitory side effect than difenidol and scopolamine in prevention of motion sickness. Phencynonate HCl was approved on Dec 25,1993 by State Food and Drug Administration of China as a Class Ⅰ new drug for the prevention and treatment of motion sickness in the market in China.

Effects of verapamil on the sustained depolarization of rat diaphragm myocyte pretreated with neostigmine or 3,4-diaminopyridine / 中国药理学与毒理学杂志

AIM　To study the effects of verapamil on end-plate potentials(EPPs) in isolated non-uniform stretched muscle preparation(INSMP) of rat diaphragms pretreated with neostigmine or 3,4-diaminopyridine(3,4-DAP). METHODS　Using conventional intracellular microelectrode recording technique. RESULTS A sustained depolarization could be induced at the end-plate area pre-incubated with 0.2－5.0 μmol·L-1 neostigmine or 1.0－4.0 mmol·L-1 3,4-DAP. In normal Tyrode solution, verapamil at a concentration of 1, 5, 10 or 20 μmol·L-1 had no significant effect on evoked endplate potentials and miniature endplate potentials. However, the sustained depolarization due to neostigmine or 3,4-DAP could be antagonized by verapamil at 5－20 μmol·L-1 and the duration of the depolarization was shortened in a concentration-dependent manner. CONCLUSIONL-type calcium ion channels can be activated by accumulated acetylcholine in the synaptic cleft and may be involved in producing sustained depolarization, while they play no role in transmitter release under normal physiological conditions.

THE DIRECT ACTION OF SOMAN ON THE NEUROMUSCULAR JUNCTION OF THE ISOLATED RAT'S DIAPHRAGM / 解放军医学杂志

In the isolated rat's phrenic nerve-diaphragm preparation, 1.5-2.5?10-7M dTC could restore 1.1?10-5'M (2?g/ml) soman-blocked tetany to 40-50% of normal, while ChE remained inhibited. 1.1?10-4M soman could abolish this dTC-restored tetany. The effect of dTC could apparently be inhibited by 1.1?10-(?)M soman given 10 min. before the administration of dTC. In the denervated diaphragm, 1.1?10-(?)M soman could enhance the ACh(5.8?10-(?)M)-induced contraction tension by about 14% owing to its ability of inhibiting ChE. After the inhibition of ChE by pretreatment of soman, the ACh-induced contraction of the denervated diaphragm was decreased by about 30% by 1.1?10-(?)M soman. It is suggested that soman, besides inhibiting ChE, also acts directly on neuro-muscular junctions.