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。     

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.     

Evidence of nonlinearity in digoxin pharmacokinetics

Six normal male volunteers received 0.5 mg label doses of digoxin as (a) a bolus intravenous injection over 2 min, (b) a constant rate intravenous infusion over 1 hr, (c) a constant rate intravenous infusion over 3 hr, and (d) a solution in 5% dextrose given orally. Plasma concentrations of digoxin were measured by radioimmunoassay for a 4 day period and urinary excretion for a 6 day period after the single doses. The mean (coefficient of variation) total areas under the plasma concentration-time curves per 0.5 mg of digoxin were (a) 35.55 (14.8%), (b) 30.20 (27.7%), (c) 25.80 (35.5%), and (d) 15.47 (49.9%); the means differed significantly (0.01>p>0.005). The mean (coefficient of variation) total amounts excreted in the urine as a fraction of the dose were (a) 0.689 (6.31%), (b) 0.517 (20.4%), (c) 0.588 (16.8%), and (d) 0.374 (23.4%); the means differed significantly (p<0.001. Both the total clearance and the nonrenal clearance of digoxin differed significantly with the method of intravenous administration. The slower the rate of input of digoxin to the body, the greater were both the total clearance and the nonrenal clearance of the drug, which strongly suggests nonlinear pharmacokinetics.This work was supported in part by National Institutes of Health Grant 1 R01 HL 23862-01 and in part by National Institutes of Health General Clinical Research Center Grant 5M01 RR421.     

The global obesity epidemic: snacking and obesity may start with free meals during infant feeding

Feeding is vital for survival. The brain has strong hunger and reward mechanisms that ensure optimal food intake for adequate nutrition. The drive for feeding is particularly strong in humans whose large brains require large energy support. This starts immediately after birth; the newborn child being able to taste sucrose and suck the sweet and fat from its mother's milk. At present, mothers are generally advised to breastfeed children as often as they like, which may be up to 15 times a day. At the same time, childhood obesity is rapidly developing. One reason for the rapidly increasing prevalence of childhood obesity may be overfeeding with snack food.

Conclusion: We hypothesize that non-rule breastfeeding favours the development of snacking throughout the day during childhood, a habit which in turn favours the development of obesity.     

Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease

Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3±3.9 mM, and ATP-, 3.6±1.1 mM, (P<0.05) compared with the control group (10.0±4.2 mM and 4.2±0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.