氟比洛芬酯联合罗哌卡因平衡镇痛用于妇科腹腔镜术后镇痛的效果分析

目的观察氟比洛芬酯联合罗哌卡因平衡镇痛用于妇科腹腔镜术后镇痛的效果。方法择期行妇科腹腔镜手术的患者共150例ASAⅠ-Ⅱ级,随机均分为三组,A组为氟比洛芬酯和罗哌卡因联合用药组（n=50例）,B组为罗哌卡因组（n=50例）,C组为对照组（n=50例）。A组患者麻醉诱导前15min静脉注射氟比洛芬酯50mg,在腹壁打孔前用0．375％罗哌卡因行皮肤切口浸润麻醉．各3ml,手术结束前于腹腔内喷洒0．375％罗哌卡因30ml。B组仅用罗哌卡因局部浸润和腹腔内局麻药喷洒,方法同A组。C组不用额外镇痛方法。用视觉模拟评分法（VAS）观察术后1、4、8、12、24h的切口痛（皮肤感觉痛）、内脏痛（如主诉有大小便欲望,胃痛等）,并记录各组术后需要使用镇痛药（哌替啶）的时间、人数和使用的次数。结果A组在术后l、4、8、12h点2个部位疼痛VAS评分均显著低于C组（P〈0．05）;A组和B组比较,只在术后4h和8h时切口VAS评分低于B组（P〈0．05）;B组和C组比较,在术后1、4、8h时,2处VAS评分均显著低于c组（P〈0．05）。A组和B组初次使用哌替啶时间、人数和使用次数均显著低于C组,A组的使用人数和次数显著低于B组（P〈0．05）。术后未观察到与镇痛相关的术后出血、局麻药中毒等副作用。结论氟比洛芬酯联合罗哌卡因平衡镇痛用于妇科腹腔镜术后镇痛有很好的效果。     

液体平衡与血液脑钠肽浓度的变化

目的 研究危重患者液体平衡与血液脑钠肽浓度的变化是否相关.方法 采集2012年5月～2013年5月收入我科的165位危重患者的BNP检查数据,记录患者对应时间段的名义出量和入量.结果 危重患者的液体平衡与血液脑钠肽浓度变化之间仅存在微弱的相关性,r=0.149,P=0.001（Pearson correlation,2-tailed）.结论 液体平衡对容量负荷/BNP水平的影响是复杂的,液体治疗时应该考虑到这种复杂性.     

Advances in anti-obesity therapeutics

Obesity is rapidly becoming an epidemic in developed countries. Currently available anti-obesity therapeutics are only modestly effective and are accompanied by significant adverse effects. In recent years, substantial advances have been made in the basic understanding of brain control of feeding behaviour and metabolism. As a result, several compounds have progressed to Phase III development, with additional compounds at various stages of Phase II development. Most of the late-stage development candidates are CNS agents, which reflects the consensus that the brain exerts a dominant control on feeding behaviour and peripheral metabolism through the autonomic nervous system. Homeostatic mechanisms encompassing hypothalamic/brainstem pathways have long been recognised in obesity research. In addition, non-homeostatic mechanisms encompassing the reward circuit and volitional control need to be targeted to control feeding behaviour and physical activity, especially in humans. While recognising the importance of CNS control, certain peripherally acting agents can affect mitochondrial metabolism, lipolysis, nutrient absorption or the vagal feedback pathway, such that these peripherally acting agents can potentially be combined with CNS agents to achieve maximal efficacy. It is expected that newer generations of anti-obesity therapeutics will be superior to existing agents and will facilitate lifestyle modification.     

Human mass balance,metabolite profile and identification of metabolic enzymes of [14C]ASP015K,a novel oral janus kinase inhibitor

Abstract

1.?The human mass balance of ¹⁴C-labelled ASP015K ([¹⁴C]ASP015K), an orally bioavailable Janus kinase (JAK) inhibitor, was characterized in six healthy male subjects after a single oral dose of [¹⁴C]ASP015K (100?mg, 3.7?MBq) in solution. [¹⁴C]ASP015K was rapidly absorbed with t_max of 1.6 and 1.8?h for ASP015K and total radioactivity in plasma, respectively. Mean recovery in urine and feces amounted to 36.8% and 56.6% of the administered dose, respectively. The main components of radioactivity in plasma and urine were ASP015K and M2 (5′-O-sulfo ASP015K). In feces, ASP015K and M4 (7-N-methyl ASP015K) were the main components.

2.?In vitro study of ASP015K metabolism showed that the major isozyme contributing to the formation of M2 was human sulfotransferase (SULT) 2A1 and of M4 was nicotinamide N-methyltransferase (NNMT).

3.?The in vitro intrinsic clearance (CL_{int_in?vitro}) of M4 formation from ASP015K in human liver cytosol (HLC) was 11-fold higher than that of M2. The competitive inhibitory effect of nicotinamide on M4 formation in the human liver was considered the reason for high CL_{int_in vitro} of M4 formation, while each metabolic pathway made a near equal contribution to the in vivo elimination of ASP015K. ASP015K was cleared by multiple mechanisms.     

Magnetite (Fe 3 O 4) microcapsules prepared using a glass membrane and solvent removal

Fine magnetite powders dispersed in polymer solution were encapsulated from an oil-in-water emulsion prepared by an emulsification process employing a porous glass membrane and subsequent evaporation of the solvent. Styrenebased copolymers were dissolved in a magnetic fluid, and then continuously pushed through the pores of glass membrane into the aqueous phase, which had dissolved polyvinyl alcohol (PVA) and sodium dodecyl sulphate (SDS) as a mixed stabilizer. P(styrene-co-acrylic acid) (PS-AA), P(stryrene-co-butyl acrylate) (PS-BA) and styrene-butadiene rubber (SBR) were dissolved in the specially ordered magnetite fluid (25 wt% magnetite dispersed in toluene) separately or as a mixture, and uniform droplets suspending the magnetic particles were obtained. After the evaporation of toluene, PS-AA capsules retained a spherical shape and uniformity, whereas PS-AA/PS-BA capsules revealed a creased surface and broader size distribution. The microcapsules entrapped 30-40 wt% of magnetite, and the encapsulation yield of magnetite was 20-40%. Glass membranes with 9.5, 5.25 and 1.42 #119 m pore size were employed and 5-40 #119 m microcapsules were obtained depending on the pore size. When magnetite suspended in chloroform was used, magnetite capsules with broader size distributions were obtained because of the sticking of the droplets to the membrane wall. The advantage of the membrane emulsification which provides uniform sized droplets was lost.     

Fluid Dynamics in Man of an Intraperitoneal Drug Delivery Solution: 4% Icodextrin

Interest in targeting drugs into the peritoneal cavity for intra-abdominal cancers or infections is undergoing a revival as recent clinical trials have demonstrated, not only a regional advantage in concentration of the active agent, but also improved long-term outcomes. Solutions currently used for intraperitoneal (IP) drug delivery have short residence times, however, which can limit the exposure of all areas of the peritoneum to the active agent. Icodextrin 4% solution was compared with saline and a glucose-based peritoneal dialysis solution in a clinical study of IP residence time. The study was carried out during the fortnightly rest phase in 9 patients undergoing 5-fluorouracil (5-Fu) IP treatment for colorectal cancer. The volume remaining in the peritoneal cavity was measured at 0, 12, 24, 48, 72, and 96 hr after an instillation of 2 liters of each fluid. Saline (n = 3 dwells) and glucose (n = 3 dwells) peritoneal dialysis solutions were almost fully absorbed by 24 hr, and the patients experienced discomfort when using these solutions. In contrast, icodextrin 4% solution (n = 188 dwells) maintained its instilled volume for up to 48 hr, and half the instilled volume remained after 72 and 96 hr. This result would allow extensive and prolonged coverage of the peritoneal surface. Icodextrin 4% solution may be an effective vehicle to deliver therapeutic agents into the peritoneal cavity.     

Development and Validation of Transtheoretical Model Measures for Bulgarian Adolescent Non-Smokers

The goal of this study was to develop, translate, and evaluate measures for decisional balance and situational temptations for Bulgarian adolescent nonsmokers and to test the predicted relationships with stages of change. Students in the last grades of high school (15–19 years old) recruited in 12 randomly selected schools participated in the study. Data from the 369 nonsmokers (61.8% female, mean age 16.4 years, 97.1% Bulgarian) were used in the measurement development. A two-factor model for decisional balance (CFI =. 94) and a hierarchical three-factor model for temptations (CFI =. 90) demonstrated the best fit. The predicted crossover pattern for decisional balance and decreasing trend for temptations across the stages of change was verified. Both measures demonstrated tau-equivalent invariance across gender, in addition to good psychometric properties. These results, with the caveat of the noted limitations, support the cross-cultural validity of these transtheoretical model (TTM) constructs and indicate that they can be used as a basis for development of smoking prevention interventions.     

A combined experimental and modeling approach to study the effects of high-shear wet granulation process parameters on granule characteristics

The purpose of the current work is to study the effects of high-shear wet granulation process parameters on granule characteristics using both experimental and modeling techniques. A full factorial design of experiments was conducted on three process parameters: water amount, impeller speed and wet massing time. Statistical analysis showed that the water amount has the largest impact on the granule characteristics, and that the effect of other process variables was more pronounced at higher water amount. At high water amounts, an increase in impeller speed and/or wet massing time showed a decrease in granule porosity and compactability. A strong correlation between granule porosity and compactability was observed. A three-dimensional population balance model which considers agglomeration and consolidation was employed to model the granulation process. The model was calibrated using the particle size distribution from an experimental batch to ensure a good match between the simulated and experimental particle size distribution. The particle size distribution of three other batches were predicted, each of which was manufactured under different process parameters (water amount, impeller speed and wet massing time). The model was able to capture and predict successfully the shifts in granule particle size distribution with changes in these process parameters.     

矛盾之中求平衡——矛盾中药配伍刍议

探讨中药矛盾配伍的方法及意义。根据前人的用药经验,临床可分为并用配伍、佐药配伍和去性存用配伍。并用配伍包括寒热并用、散收并用、升降并用,佐药配伍包括寒热互佐、升降互佐、润燥互佐、散敛互佐、补泻互佐、动静互佐等。