腹腔镜下治疗输卵管伞端粘连闭锁伴不孕的比较研究

目的比较PK刀及双极电刀在输卵管伞端粘连闭锁伴不孕中的腹腔镜手术效果。方法 2008年5月～2010年8月因输卵管伞端闭锁伴不孕的Ⅱ、Ⅲ期患者97例,根据引入器械先后不同分双极电刀组55例,PK刀组42例,在腹腔镜下行输卵管造口术。比较手术时间、术中出血量、肛门恢复排气时间和术后妊娠率、分娩率的情况。结果两组手术时间、术中出血量、肛门恢复排气时间,差异均无统计学意义（P〉0.05）。双极组术后妊娠率为25.4%,分娩率为18.2%;PK刀组术后妊娠率为52.4%,分娩率为42.9%,两组比较有显著性差异（P〈0.05）。结论 PK刀热损伤小,较双极电刀更有利于恢复输卵管伞的正常解剖和拾卵功能,提高妊娠率和分娩率。     

左氧氟沙星注射液治疗泌尿系感染疗效分析

目的：在PK/PD参数理论指导下,观察左氧氟沙星静滴每日1次和每日2次治疗泌尿系感染的疗效。方法：选取86例泌尿系感染患者,随机分为治疗组和对照组,每组43例,治疗组用左氧氟沙星400 mg,静脉滴注,1次/d,对照组用左氧氟沙星200 mg,静脉滴注,2次/d。结果：用药3 d后两组血和尿中白细胞数、血中性粒细胞数及体温〉37℃的病例数比较,差异有统计学意义（P〈0.05）。其中,治疗组有效率为95.3%（41/43）,对照组为83.7%（36/43）,两组有效率比较,差异有统计学意义（P〈0.05）。结论：左氧氟沙星治疗泌尿系统感染,静滴每日1次给药疗效优于静滴每日2次。     

Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[(11)C]PK11195 brain PET studies

Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[¹¹C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer''s disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPMV_b). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions (V_b) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of V_b in RPM improved both parametric images and binding potential contrast between groups. Incorporation of V_b within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[¹¹C]PK11195 neurodegeneration studies.     

Identification and human exposure prediction of two aldehyde oxidase-mediated metabolites of a methylquinoline-containing drug candidate

1. Aldehyde oxidase (AO enzymes)-mediated oxidation predominantly occurs at a carbon atom adjacent to the nitrogen on aromatic azaheterocycles. In the current report, we identified that AO enzymes oxidation took place at both the C-2 and C-4 positions of the methylquinoline moiety of Compound A based on data from mass spectrometric analysis, AO enzymes “litmus” test, and comparison with authentic standards.

2. To assess the potential for inadequate coverage for these two AO enzyme-mediated metabolites in nonclinical safety studies, given concerns due to differences in AO enzymes expression between preclinical species and humans, the human circulating levels of the two AO enzyme-mediated metabolites were predicted prospectively using in vitro and in vivo models. Both formation clearance and elimination clearance of the two metabolites were predicted based on in vitro to in vivo correlation and comparison with in vivo data from rats.

3. The result showed that the 4-OH metabolite of Compound A would account for less than 3% of the total drug-related exposure in human plasma, while the exposure to the 2-oxo metabolite would be relatively high (～70%).

4. The predicted human exposure levels for the two metabolites are in similar ranges as those observed in monkeys. These data taken together support the advancement to clinical development of Compound A.     

Model-based clinical drug development in the past,present and future: a commentary

Clinical drug development remains a mostly empirical, costly enterprise, in which decision-making is often based on qualitative assessment of risk, without properly leveraging all the relevant data collected throughout the development programme. Model-based drug development (MBDD) has been proposed by regulatory agencies, academia and pharmaceutical companies as a paradigm to modernize drug research through the quantification of risk and combination of information from different sources across time. We present here a historical account of the use of MBDD in clinical drug development, the current challenges and further opportunities for its application in the pharmaceutical industry.     

A commentary on the development of engineered phage as therapeutics

The use of engineered phages offers a unique opportunity to improve on wild-type (WT) phages to generate ever more successful therapeutics to combat bacterial infections. Here, we discuss how phage engineering could be used to overcome some of the technical challenges of phage therapy, and suggest some areas in which more research will be crucial to the development of further novel phage therapeutics.     

Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial

Purpose

To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC).

Mechanism of Action,Pharmacokinetics, Efficacy,and Safety of Transarterial Therapies Using Ethiodized Oil: Preclinical Review in Liver Cancer Models

Purpose

To systematically review mechanism of action, pharmacokinetics (PKs), efficacy, and safety of ethiodized oil–based locoregional therapy (LRT) for liver cancer in preclinical models.

Fermentation and the properties of some enzymes of carbohydrate metabolism in the trematode Calicophoron ijimai

Glycogen content, glucose consumption and the production of metabolic end products by Calicophoron ijimai were determined under aerobic and anaerobic conditions. The major end products of fermentation were identified as lactic, acetic, propionic, isobutyric and α-methylbutyric acids, propionic acid predominating. The activities and properties of some of the enzymes of carbohydrate metabolism were determined. The worms showed high phosphoenolpyruvate carboxykinase, malate dehydrogenase and malate dehydrogenase (decarboxylating) but relatively low pyruvate kinase and very low lactate dehydrogenase activities. The pH optima, coenzyme, cofactor and ionic requirements of the enzymes were similar to those of other helminths. Malate dehydrogenase had an 8-fold greater affinity for oxaloacetate than malate, and was about 14 times more active for oxaloacetate reduction than malate oxidation. Phosphoenolpyruvate carboxykinase was 2.4 times more active and had a 2-fold greater affinity for phosphoenolpyruvate and dinucleotide than pyruvate kinase. The low activities of lactate dehydrogenase and pyruvate kinase but high activities of malate dehydrogenase and phosphoenolpyruvate carboxykinase suggest that anaerobic carbohydrate catabolism follows the fumarate reductase pathway.