Gut microbiota and Alzheimer′s disease / 国际药学研究杂志

Gut microbiota(GM)consists of a complex community of microorganism species that live in the digestive tracts of animals including humans. Dysbiosis is believed to involve in the development of some diseases. Recently dysbiosis in the patients with Alzheimer′s disease(AD)and AD rat models was reported. GM may influence the pathogenesis and development of AD in several ways. Some neurotoxic substances produced by GM can invade into the brain via circulation and impair the neural functions. These sub?stances include ammonia,cyanobacteria-producedβ-N-methylamino-L-alanine,saxitoxin,anatoxin-αand amyloid. The decrease in brain-derived neurotrophic factor(BDNF)in hippocampus and cerebral cortex induced by dysbiosis contributes to the cognitive dys?function. Dysbiosis related endotoxin can induce inflammation,which is one important risk factor for obesity,insulin resistance(IR) and type 2 diabetes mellitus(TIDM). AD and diabetes have good correlation and similarity. Probiotics,prebiotics and Chinese herbal medicines can rebuild GM and have been reported to ameliorate the memory loss of AD patients or model rats. However ,whether and how their preventative and therapeutic effects on AD mediated by GM are worthy of further investigation.

Phase I study of injectable, depot naltrexone for the relapse prevention treatment of opioid dependence.

BACKGROUND AND OBJECTIVES: We tested long-acting injectable depot naltrexone for its tolerability, pharmacokinetics, and safety in Phase I. METHODS: The Phase I trial enrolled 36 healthy participants in two panels (A, B). In Panel A, 24 subjects were randomly assigned to the high-dosage group (400 mg naltrexone, n=6; placebo, n=6) or low-dosage group (200 mg naltrexone, n=6; placebo, n=6). In Panel B, 12 subjects were randomized to take six doses of monthly injectable naltrexone (400 mg) or placebo. RESULTS: After a single injection of naltrexone 200 and 400 mg, means (SD) of naltrexone plasma concentrations were .57 (.28) ng/ml and 1.5 (.8) ng/ml 30 days post-injection. There was no effect of accumulation after multiple dosing. Eleven of 30 subjects (36.67%) who were administered injectable depot naltrexone reported a total of 12 adverse events (AEs). Seven of these 11 AEs were coded as possibly related with study medication. All treatment-related AEs were mild in severity. No serious treatment-related AEs occurred. DISCUSSION AND CONCLUSIONS: This long-acting formulation of injectable depot naltrexone is well tolerated, results in constant plasma concentration of naltrexone for at least 1 month. SCIENTIFIC SIGNIFICANCE: The tolerability and safety of long-acting injectable depot naltrexone are good.

Advancement of potent narcotic anaIgesics:combination of oxycodone / 中国药理学与毒理学杂志

Oxycodone,an opioid receptor agonist,is one of potent narcotic analgesics. Despite its potent analgesic effect,the tolerant and dependent liability of oxycodone as well as its inhibition on gas-trointestinal motility strongly restricts its clinical application. Since the end of the last century,antipyretic, opioid receptor agonist,opioid receptor antagonist and dopamine receptor antagonist have been used to in combination with oxycodone at different ratios as complex prescriptions,the aim of which is to enhance the effect of oxycodone,decrease the dosage of oxycodone,and prevent the adverse effect and the tendency for misuse. Here we reviewed the development of oxycodone compositions in the recent years,hoping to provide more data for its potential clinical application.