Proton magnetic resonance spectroscopy with metabolite nulling reveals regional differences of macromolecules in normal human brain

PURPOSE: To quantify the macromolecular content in different anatomic brain regions and to evaluate an age dependency of the macromolecular concentrations. MATERIAL AND METHODS: A short echo time Stimulated Echo Acquisition Mode (STEAM) sequence was used without and with inversion recovery metabolite nulling in 8-12 healthy volunteers. Quantitation was achieved by an extended LCModel, and macromolecular resonances at 0.9, 1.4, 2.1, and 3.0 ppm were evaluated. RESULTS: In the cerebellum, the 1.4, 2.1, and 3.0 ppm resonances were highest compared to all other regions (P < 0.02); the 0.9 ppm resonance was significantly higher than that of pons (P < 0.01). In the motor cortex, the 0.9, 1.4, and 2.1 ppm resonances were higher than those of white matter and pons (P < 0.02). Pons and white matter did not differ significantly from each other. A significant correlation of the macromolecular concentrations with the age could not be found. CONCLUSION: There were higher macromolecular concentrations in the cerebellum and motor cortex than in pons or white matter. These were probably due to the higher portions of gray matter in these volumes of interest (VOIs) than in the other regions.     

多剂量口服给药后辅酶Q10缓释片和普通片在健康人体内的血药浓度

目的 比较辅酶Q10缓释片与辅酶Q10普通片多剂量给药后的经时变化过程。方法 将20名男性健康志愿受试者等分为两组，一组受试者每人每天po50mg的辅酶Q10缓释片，连服15d，另一组受试者每天每人po50mg的辅酶Q10普通片，服药期间及服药前后，在规定的时间内采取静脉血，测定血浆中辅酶Q19总含量。血浆经甲醇沉淀蛋白后，以正已烷提取，分离水相和有机相，收集有机相，氮气吹干，将所得残渣溶于100μL无水乙醇中，进行HPLC检测。检测波长为275nm，流动相为乙醇－甲醇（9：1），内标物为辅酶Q9。结果 建立的体内HPLC－UV分析方法简便、稳定、适宜于进行生物样品分析。受试者经过15dpo辅酶Q10缓释片和普通片，每天po一次，每次剂量50mg，测得血浆中总辅酶Q10浓度表明，受试者服缓释片后血浆中辅酶Q10浓度高于对照组普通片后的血药浓度。结论 多次服用缓释片的稳态血药浓度高于普通片的稳态血药浓度，原因在于缓释片可持续释放、持续吸收，从而保持血浆中较高的浓度。     

Inclusion of lignocaine base into a polar lipid formulation--in vitro release, duration of peripheral nerve block and arterial blood concentrations in the rat

BACKGROUND: Slow-release formulations of local anaesthetics may produce nerve blocks of long duration. The present study aimed at investigating the in vitro and in vivo properties of a polar lipid formulation for slow release of lignocaine and the effects on nerve block duration by inclusion of dexamethasone into the system. METHODS: In vitro release of lignocaine from the lipid formulation was studied in a US Pharmacopoeia rotating apparatus. Sciatic nerve blocks were induced in rats by 0.1 ml of test formulations containing lignocaine HCl 20 mg. ml-1 in aqueous solution, lignocaine base 20, 100 or 200 mg. ml-1 in lipid formulation or the last formulation with dexamethasone 0.05, 0.5 or 5 mg. ml-1. The durations of sensory and motor block and the arterial blood concentrations of lignocaine were investigated. RESULTS: In vitro there was a sustained release of lignocaine from the lipid formulation, with 50% release at around 48 h. In vivo lignocaine base 20 mg. ml-1 in lipid formulation produced sciatic nerve blocks of significantly shorter duration than lignocaine HCl 20 mg. ml-1 in aqueous solution, while lignocaine base 100 and 200 mg. ml-1 in lipid formulation produced blocks lasting two and three times longer, respectively, than the lignocaine HCl solution. Addition of dexamethasone did not affect the duration of nerve block. Following administration of lignocaine base 200 mg. ml-1 in lipid formulation, as compared to lignocaine HCl 20 mg. ml-1 in aqueous solution, the maximal blood concentration of lignocaine was only three times higher in spite of the ten-fold difference in dose, and the mean terminal half-life was three times longer, reflecting the slow release from the formulation. CONCLUSIONS: Our findings indicate that lignocaine base in polar lipids acts as a slow-release preparation of local anaesthetic both in vitro and in vivo.     

78株鲍曼不动杆菌的最低抑菌浓度及耐药性分析

目的了解川北地区鲍曼不动杆菌的耐药性。方法细菌耐药性的检测采用琼脂稀释法。收集我院附属医院2005年1月-2007年3月临床分离的鲍曼不动杆菌78株,用琼脂稀释法检测鲍曼不动杆菌对16种抗菌药的最低抑菌浓度(MIC),敏感、中介、耐药的判定采用美国临床实验室标准化协会(CSLI)2006年公布的标准。结果与结论78株鲍曼不动杆菌对亚胺培南全部敏感,对头孢哌酮/舒巴坦和美罗培南耐药率低,分别为37.2%和1.3%,对环丙沙星、庆大霉素、头孢孟多、哌拉西林、头孢他啶、头孢哌酮、头孢噻肟、头孢吡肟、阿米卡星、头孢西丁、氯霉素、四环素、哌拉西林/他唑巴坦等13种抗菌药的耐药率达62.8%-96.2%。     

丁香等中草药有效成分的提取方法和抗菌活性关系的研究

目的探讨8种中药材有效成分的不同提取方法与抗菌活性的关系。方法分别用水煮法、醇提法和超声法提取8种中药材的有效成分，采用试管连续稀释法测定其最小抑菌浓度，探讨不同提取方法的优劣。结果除蜂房外，7种中草药的醇提取物对大肠埃希氏菌和金黄色葡萄球菌的抑菌效果很明显，丁香的醇提物对铜绿假单胞菌抑制效果最佳，各提取液对白色念球菌抑制效果普遍不明显。除蜂房及穿心莲外的其它6种中草药醇提液的最低抑菌浓度（MIC）均显著低于其他提取方法。就抑菌效果和相对稳定性来说，丁香最为明显。结论用不同方法提取中草药有效成分的抑菌效果比较发现，醇提法最优，其次为超声波提取法，水提法最差。     

Pulsatile blood alcohol and CYP2E1 induction during chronic alcohol infusions in rats

Adult male Sprague-Dawley rats were treated with alcohol for 35 days using a total enteral nutrition model. Intragastric cannulae were inserted into rats and they were infused with a diet designed to promote normal growth in male rats. Alcohol was infused at 35% of total calories for 35 days. Urine and blood alcohol concentrations were determined and found to be pulsatile during continuous alcohol infusion, having values between near zero and greater than 500 mg/dl. Twenty-four-hour urine alcohol concentrations were found to be excellent indicators of blood alcohol concentrations (BACs). Cytochrome P450 CYP2E1 was induced in a two-step manner. Step one occurred at BACs below 250 mg/dl and was characterized by significant (p ≤ 0.05) elevations in activities and apoprotein levels with no changes in steady-state mRNA. Step two occurred with BACs greater than 300 mg/dl and resulted in significant (p ≤ 0.05) elevations in steady-state mRNA levels. We propose that the pulsatile BACs are caused by an ethanol concentration-dependent regulation of an ethanol metabolizing system, perhaps CYP2E1.     

Blunted Sensitivity to Sucrose in Autoimmune MRL-lpr Mice: A Curve-Shift Study

Lupus-prone MRL-lpr mice show an autoimmunity-associated behavioral syndrome that has many features similar to the effects of chronic stress. The present study evaluated whether autoimmune MRL-lpr mice show reduced responsiveness to sucrose, as observed in normal animals exposed to chronic mild stress. Sixteen-week old MRL-lpr mice and their age-matched congenic MRL +/+ controls were given 0%, 0.5%, 1%, 2%, 4%, 8%, or 16% sucrose solution to drink every 48 h in a one-bottle test. The MRL-lpr mice drank less than controls at all concentrations, except at 16%. The amount of sucrose consumed vs. solution concentration followed a saturation curve. Estimates were obtained for the concentration yielding the half-maximum response (X₅₀) and the response at saturating concentration of sucrose (R_max). The X₅₀ was significantly higher in MRL-lpr than in MRL +/+ mice, indicating a shift to the right of the concentration-intake curve. The R_max did not differ significantly between substrains, suggesting that the autoimmune process did not affect performance capacity. Pretreatment with the immunosuppressant cyclophosphamide diminished the substrain difference in X₅₀, suggesting that reduced sensitivity to sucrose is related to autoimmune/inflammatory factors. These results support the similarity between autoimmunity-associated behavioral syndrome and behavioral changes produced by chronic stress, and suggest common neuroendocrine mechanisms. Because reduced sensitivity to palatable stimulus may reflect blunted hedonic responsiveness (“anhedonia”), it is hypothesized that an autoimmune/inflammatory factor(s) produces the depression found in human lupus, and some cases of affective disorder. Copyright © 1996 Elsevier Science Inc.     

Brain uptake of mannitol and sucrose after cerebral ischemia: Effect of hyperglycemia

The effect of 10 min cerebral ischemia on blood-brain barrier permeability to mannitol and sucrose was evaluated in normo-and hyperglycemic rats. In the period immediately after ischemia (1–4 min) the PS (permeability-surface area product) for mannitol was 159%± 75 of control (0.17 ± 0.02 ml/100g min) in the normoglycemic rats (plasma glucose 8mM) and 204%± 30 of control (0.09 ± 0.02ml/100g min) in the hyperglycemic rats (plasma glucose 28mM). Two hours after ischemia, PS for mannitol returned to the control levels in the normoglycemic rats and remained elevated in the hyperglycemic animals. The mannitol/sucrose ratios—2.3 ± 0.4 in normoglycemic rats and 2.6 p± 0.I in hyperglycemic rats—remained unchanged after ischemia. As there was no significant difference in the effects of ischemia on normo-and hyperglycemic rats, it was concluded that the deleterious effect of hyperglycemia on clinical recovery after cerebral ischemia in rats (Siemkowicz & Hansen 1978) is not related to enhancement of BBB damage.     

野外γ谱法测定广东高本底地区土壤中放射性核素浓度及照射量率

用一带微型计算机的NaI(T1)γ谱测量系统, 对高本底及对照地区的32个点进行现场γ谱测置.确定各测量点现场土壤中各天然放射性核素的平均浓度及单个核案对照射量率的贡献。并给出各辐射场的总照射量率。现场测量前, 在海面上测定了本底谱。     

Relation between plasma concentrations and cardiovascular effects of oral oxprenolol in man

Summary Oxprenolol, 40, 80 and 160 mg, was administered orally to seven healthy volunteers. Over the following eight hours repeated measurements were made of the plasma concentrations and effects on heart rate, myocardial contractility (PEP_C) and systolic and diastolic blood pressure in recumbency, in the upright position and during physical effort at a work load of 120 watts on a bicycle ergometer. The maximum plasma levels and the area beneath the plasma concentration curves increased roughly in proportion to the dosage increment. No evidence of first-pass inactivation in the liver was found. The half-life of the drug in plasma was approximately 80 minutes, irrespective of the dose administered. Oxprenolol slowed heart rate, prolonged PEP_C and lowered systolic blood pressure, by comparison with values recorded after a placebo. The effects were generally least marked in the recumbent position and most marked during effort, when a clear-cut dose-response relation was found. The pharmacodynamic effects of oxprenolol were compared with its concentration in plasma. Marked beta-receptor blockade still persisted eight hours after dosing, although at this time, after doses of 40 and 80 mg, the drug could not be detected in plasma.