Reduced concentration of hepatic alpha-tocopherol in patients with alcoholic liver cirrhosis.

The concentration of alpha-tocopherol was measured in liver biopsy specimens obtained from 83 patients with alcoholic and non-alcoholic liver diseases. The mean hepatic vitamin E content (as alpha-tocopherol) was significantly lower in 23 patients with alcoholic cirrhosis (17.6 +/- 12.1 nmol/mg wet weight liver), compared with 12 patients with normal liver histology (39.2 +/- 29.7 nmol/mg, P less than 0.01). The mean serum concentration of alpha-tocopherol was lower in patients with alcoholic cirrhosis (13.9 +/- 7.0 mumol/l) than in individuals with alcoholic fatty liver (21.3 +/- 9.3 mumol/l, P less than 0.01) and patients with normal liver histology (23.4 +/- 11.6 mumol/l, P less than 0.01). A decreased ratio of serum alpha-tocopherol/total serum lipids was also observed in patients with alcoholic cirrhosis, compared with patients with normal liver histology (P less than 0.05). There was a significant correlation between concentrations of alpha-tocopherol in liver and serum (r = 0.43, P less than 0.001). Furthermore, serum alpha-tocopherol correlated with retinol (r = 0.53, P less than 0.001), selenium (r = 0.45, P less than 0.001), and albumin (r = 0.37, P less than 0.001) in serum. We suggest that the reduced content of hepatic alpha-tocopherol observed in some patients may play a role in ethanol-induced lipid peroxidation.     

Changes in stem cell populations of rat tracheal epithelial cell cultures at an early stage in neoplastic progression

The development of transformed colonies and concomitant changes in proliferative and nonproliferative cell compartments were studied in rat tracheal epithelial (RTE) cell cultures following exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Primary RTE cells were plated onto 3T3 feeder layers and treated with MNNG (0.25 micrograms/ml) or solvent. Seven days later, the feeder cells were removed to select for enhanced growth variants, which are the transformants of the RTE cell system, usually scored 5 weeks after carcinogen exposure. Most of the RTE cell colonies, which originally formed during the first 7 days of culture, disappeared within 2 weeks after feeder cell removal in control and MNNG-treated cultures. In control cultures, about 3% of the original colonies persisted, while in MNNG-treated cultures, a larger percentage (approximately 9%) of the colonies persisted. These percentages remained constant from 3 to 7 weeks. Based on colony size, cell density, and cell morphology, the persistent colonies were classified into transformed colonies (large colony size, high cell density, high nuclear:cytoplasmic ratio) and untransformed colonies (small size, low cell density, low nuclear:cytoplasmic ratio). In the MNNG-treated cultures, about 50% of all persistent colonies showed transformed morphology. Their frequency remained unchanged between 3 and 7 weeks of culture. In contrast, only 10 to 15% of the persistent colonies in control cultures showed transformed morphology at 3 weeks, but that proportion increased steadily between 3 and 7 weeks. These data suggest that, in control cultures, transformed colonies developed spontaneously as a function of time within untransformed colonies. Autoradiographic studies with [3H]thymidine showed that labeling indices in the early "normal" RTE cell colonies between Days 4 and 7 of culture were very high, ranging between 75 and 90%. In contrast, the labeling indices of persistent colonies, both those without and those with transformed morphology, were low, i.e., between 18 and 25%, indicating that a major proportion of cells was either noncycling or cycling very slowly. The relative compartment sizes of cells with stem cell characteristics and of cells with characteristics of transformed stem cells were estimated before and after transformed colonies appeared.(ABSTRACT TRUNCATED AT 400 WORDS)     

Inhibitory effect of cystic fibrosis serum on pseudomonas phagocytosis by rabbit and human alveolar macrophages.

This report presents experimental observations indicating the presence of an inhibitory activity in cystic fibrosis (CF) serum which impairs phagocytosis of Pseudomonas aeruginosa by rabbit as well as human alveolar macrophages. Of the 49 patient serum samples studied, 40 consistently showed greater than or equal to 60% inhibition, 3 showed no inhibition and 6 were in the range of 20-60% inhibition of Pseudomonas phagocytosis. In parallel studies, the phagocytosis of S. aureus and S. marcescens was found not to be inhibited by CF serum. Mixing of CF serum with normal serum could not overcome the inhibitory effect, indicating the presence of an inhibitory factor rather than the lack of a necessary component. The inhibitory activity is not lost upon exposure of serum to glass, upon freezing the serum once, or upon heating at 56 degrees C for 30 minutes.     

A Collective Review on Mesh-Based Repair of Umbilical and Epigastric Hernias

In accordance with the tension-free principles for other hernias, umbilical and epigastric hernia repair should probably be mesh-based. The number of randomized studies is increasing, most of them showing significantly less recurrences with the use of a mesh. Different devices are available and are applicable by several approaches. The objective of this review was to evaluate recent literature for the different types of mesh for umbilical and epigastric hernia repair and recurrences after mesh repair. A multi-database search was conducted to reveal relevant studies since 2001 reporting mesh-based repair of primary umbilical/epigastric hernia and their outcomes in adult patients. A total of 20 studies were included, 15 of them solely involved umbilical hernias, whereas the remaining studies included epigastric hernias as well. A median of 124 patients (range, 17–384) was investigated per study. Three quarters of the included studies had a follow-up of at least 2 years. Six studies described the results of laparoscopic approach, of which one reported a recurrence rate of 2.7 %; in the remaining studies, no recurrences occurred. Two comparative studies reported a lower incidence of complications and postoperative pain after laparoscopic repair compared to open repair. Seventeen studies reported results of open techniques, of which seven studies showed no recurrence. Other studies reported recurrence rates up to 3.1 %. A wide range of complication rates were reported (0–33 %). This collective review showed acceptable recurrence rates for mesh-based umbilical and epigastric hernia repair. A wide range of devices was investigated. A tendency toward more complications after laparoscopic repair was found compared to open repair.     

Co-assessment of cell cycle and micronucleus frequencies demonstrates the influence of serum on the in vitro genotoxic response to amorphous monodisperse silica nanoparticles of varying sizes

Serum proteins have been shown to modulate the cytotoxic and genotoxic responses to nanomaterials. The aim was to investigate the influence of serum on the induction of micronuclei (MN) by nanoparticles (NPs) of different sizes. Therefore, A549 human lung carcinoma cells and amorphous monodisperse silica nanoparticles (SNPs) were used as models. Assessment of the cell viability, cell cycle changes and induction of MN by SNPs ranging from 12 to 174 nm was performed in presence or absence of serum, applying the in vitro flow cytometry-based MN assay. Here, it has been demonstrated that serum has an influence on these end points, with a lower cell viability in absence of serum compared with the presence of serum. Further, cell cycle changes, specifically, G₁ and S-phase arrest, were observed in absence of serum for four out of six SNPs tested. A size-dependent MN induction was observed: larger SNPs being more active in absence of serum. In addition, the serum influence was characterised by a size-dependency for cytotoxic and genotoxic effects, with a higher influence of serum for smaller particles. The data indicate that the in vitro micronucleus assay in presence and absence of serum could be advised for hazard assessment because it demonstrates a higher sensitivity in serum-free conditions than in conditions with serum. However, this recommendation applies only if the cell line used is able to proliferate under serum-free conditions because cell division is a prerequisite for MN expression.     

缺血预处理程序中心肌环磷酸腺苷含量及环磷酸腺苷依赖蛋白激酶活性的变化

目的:制备大鼠在体缺血再灌注模型,观察缺血预处理程序中心肌环磷酸腺苷含量及环磷酸腺苷依赖蛋白激酶活性的变化。方法:实验于2005-03/2006-10在解放军沈阳军区总医院医学实验动物中心和全军心血管研究所实验室完成。实验分组:选用健康雌性SD大鼠36只,根据预适应程序分为第1,2,3次缺血,第1,2,3次再灌注,每一时间点6只大鼠。实验过程:用手术套管法造成左冠状动脉主干缺血及再灌注。所有实验动物在实验程序结束后,取出心脏迅速置液氮保存备用。实验评估:用放射免疫法测环磷酸腺苷水平,生化法测环磷酸腺苷依赖蛋白激酶活性变化。结果:36只大鼠均进入结果分析。①环磷酸腺苷含量:第1次再灌注组低于第1次缺血组[(0.325±0.015),(0.395±0.024)pmol/g,t=6.06,P<0.001],第2次再灌注组低于第2次缺血组[(0.523±0.017),(0.708±0.067)pmol/g,t=6.56,P<0.001],第3次再灌注组低于第3次缺血组[(0.567±0.031),(0.712±0.038)pmol/g,t=7.24,P<0.001]。②环磷酸腺苷依赖蛋白激酶活性:第1次再灌注组低于第1次缺血组[(10.115±1.000),(16.351±0.849)pkat/g,t=11.12,P<0.001],第2次再灌注组低于第2次缺血组[(11.877±2.213),(14.869±0.619)pkat/g,t=3.31,P<0.01],第3次再灌注组低于第3次缺血组[(11.745±0.987),(14.766±0.329)pkat/g,t=7.09,P<0.001]。③缺血预处理程序中心肌环磷酸腺苷含量及环磷酸腺苷依赖蛋白激酶活性随缺血及再灌注呈周期性波动。在5min缺血预处理时表现为明显增高,而在间隔的再灌注程序中恰呈相反改变,有明显下降的趋势。结论:环磷酸腺苷及环磷酸腺苷依赖蛋白激酶的周期性波动变化可能是激发心肌缺血预处理的机制之一,环磷酸腺苷可能在预处理保护作用中起一些作用。