Cerebromicrovascular endothelial permeability

Summary Permeability of cerebromicrovascular endothelium has been investigated in a new model of cultured cells. The endothelial cells are grown on dextran microcarriers and constitute a barrier for trypan blue (TB) binding to the dextran beads. Changes in the permeability of microcarrier-cultured endothelium have been investigated during the exposure of cells to arachidonic acid or substances involved either in arachidonate metabolism or stimulation of cAMP. The results demonstrate enhanced TB passage through the endothelial barrier during exposure to high concentrations of arachidonic acid and indomethacin, but not to ibuprofen. The effect of indomethacin could be prevented by pretreatment with dexamethasone. Dexamethasone alone did not influence the barrier. Forskolin, a drug which stimulates the catalytic unit of adenylate cyclase, did not affect the endothelial permeability to TB. These findings support the contention that substances derived from a disturbed cellular membrane contribute to the altered blood-brain barrier function found under pathological conditions.Supported in part by a grant from the Deutsche Forschungsgemeinschaft (Ke 3381/1-1) for Dr. Kempski's stay at NIH     

Functional analysis of the marginating pool of human polymorphonuclear leukocytes

The intravascular pool of human polymorphonuclear leukocytes (PMN) is composed of one compartment which is circulating and another that is marginated to the vascular endothelium. Administration of B-adrenergic agonists leads to a rapid demargination with an increase in the circulating PMN pool. The marginating PMN has previously been stated to represent an older PMN based on a higher cytochemical alkaline phosphatase activity. With the understanding that circulating PMN are heterogeneous with respect to function and size we undertook the present study to evaluate the contribution of the marginating PMN to functional and volume-dependent heterogeneity. We found that PMN isolated 7 min after epinephrine administration, presumably enriched by marginating PMN, were not different in volume, biochemically measured alkaline phosphatase activity, stimulated superoxide anion release, degranulation, or phagocytosis. These data suggest that the circulating and marginating pools of PMN are interchangeable and that the marginating PMN are not enriched by a particular subpopulation of PMN.     

促红细胞生成素对实验性肾性贫血的作用

促红细胞生成素(erythropoietin,EPO)是由肾细胞分泌的一种糖蛋白激素。从人胚肾细胞中诱导,经生物化学方法分离、提纯得到此品。本试验用5/6肾切除的方法造成大鼠慢性肾衰性(CRF)贫血,研究不同剂量EPO对CRF贫血的作用。结果表明EPO有显著的促进红细胞生成,改善CRF贫血状态,使其接近或达到正常水平,最佳剂量为1000 U/kg,并可预防实验性贫血,对正常鼠未见明显作用。     

Selective shunt in the management of variceal bleeding in the era of liver transplantation.

This study reports the Emory experience with 147 distal splenorenal shunts (DSRS) and 110 orthotopic liver transplants (OLT) between January 1987 and December 1991. The purpose was to clarify which patients with variceal bleeding should be treated by DSRS versus OLT. Distal splenorenal shunts were selected for patients with adequate or good liver function. Orthotopic liver transplant was offered to patients with end-stage liver disease who fulfilled other selection criteria. The DSRS group comprised 71 Child's A, 70 Child's B, and 6 Child's C patients. The mean galactose elimination capacity for all DSRS patients was 330 +/- 98 mg/minute, which was significantly (p less than 0.01) above the galactose elimination capacity of 237 +/- 82 mg/minute in the OLT group. Survival analysis for the DSRS group showed 91% 1-year and 77% 3-year survival, which was better than the 74% 1-year and 60% 3-year survivals in the OLT group. Variceal bleeding as a major component of end-stage disease leading to OLT had significantly (p less than 0.05) poorer survival (50%) at 1 year compared with patients without variceal bleeding (80%). Hepatic function was maintained after DSRS, as measured by serum albumin and prothrombin time, but galactose elimination capacity decreased significantly (p less than 0.05) to 298 +/- 97 mg/minute. Quality of life, measured by a self-assessment questionnaire, was not significantly different in the DSRS and OLT groups. Hospital charges were significantly higher for OLT (median, $113,733) compared with DSRS ($32,674). These data support a role for selective shunt in the management of patients with variceal bleeding who require surgery and have good hepatic function. Transplantation should be reserved for patients with end-stage liver disease. A thorough evaluation, including tests of liver function, help in selection of the most appropriate therapeutic approach.     

Increased Id-1 expression is significantly associated with poor survival of patients with prostate cancer

The levels of Id-1 (inhibitor of DNA binding or inhibitor of cell differentiation) expression in a series of prostate cell lines and in an archival set of prostate tissues were examined. Western blot analysis showed that the level of Id-1 expressed in the androgen sensitive cell line LNCaP was 1.2 +/- 0.2 times that detected in the benign cell line PNT-2. The level of Id-1 increased further to 1.8 +/- 0.2 and 2.9 +/- 0.3 in the androgen-insensitive cell lines Du-145 and PC-3, respectively. Immunohistochemical staining with Id-1 antibody performed on 113 cases of prostate tissues showed that among the 7 normal cases, 6 (86%) stained either negative or weakly positive whereas only 1 (14%) stained moderately positive. Among the 36 benign prostatic hyperplasia (BPH) samples, 34 (94%) stained either negative or weakly positive; only 1 (3%) stained moderately and 1 (3%) stained strongly. Of the 70 carcinomas, 8 (11.5%) stained weakly, 34 (48.5%) stained moderately, and 28 (40%) stained strongly positive. The intensity of Id-1 staining in carcinomas was significantly stronger than that detected in the normal prostate and BPH (chi(2) test, P < .001) and it was significantly increased as the increasing malignancy of carcinomas measured by Gleason score (chi(2) test, P < .001). The intensity of Id-1 staining was partially associated with the levels of prostate-specific antigen, but not related to the level of androgen receptor. Kaplan-Meier survival curve analysis showed that, similar to Gleason scores, overexpression of Id-1 was significantly associated with the reduced length of patient survival (log-rank test, P = .01). These results suggest that Id-1 is a useful prognostic marker to predict the outcomes of patients with prostate cancer.     

Unemployment, contraceptive behaviour and reproductive outcomes among young Australian women

AIMS: To examine whether unemployment and partnership affects pregnancy, live births and terminations among young Australian women. Unemployment has conventionally been used in epidemiological studies to examine the health effects of loss of opportunity, material resources and satisfaction associated with work. During welfare reform in the 1990s it was argued that unemployment and associated welfare receipt could influence reproductive choice. DESIGN: As part of the Australian Longitudinal Study of Women's Health, information on employment, contraceptive use and pregnancy, live births and terminations was obtained at two time points. Information on partnership, age, parental education, and area economic resources was also obtained. The sample included 9683 women aged 18-23 years in 1996 (time 1) and 2000 (time 2). ANALYSIS: Logistic regressions were conducted to assess the relationship between unemployment and contraceptive use at time 1 and the impact of unemployment at time 1 on pregnancy, live births and terminations at time 2. Analyses accounted for partnership, significant differences in contraception, age, parental education and area economic resources. RESULTS: Despite the absence of differences in overall rates of contraceptive use, rates of pregnancy and live births among young unemployed women were higher than rates among employed women. These differences became non-significant when differences in the need to use contraception and oral contraceptive use were taken into account. There were no differences in terminations due to unemployment overall but partnered unemployed women were more likely to have a termination than other women. CONCLUSIONS: The study did not support the notion that being unemployed provided incentives for single motherhood. However excess terminations suggest that unemployment might provide disincentives to continuing pregnancies among partnered and unemployed women. More detailed examination of contraception and partnership may be key in unraveling inconsistencies in past research.     

原代培养鼠胚脊髓运动神经元活力状态与肌萎灵注射液的干预作用

目的:从细胞水平,观察扶元起萎,养荣生肌的中药制剂肌萎灵注射液对原代培养鼠胚脊髓运动神经元的保护作用。方法:实验于2004-03/2005-03在解放军第三军医大学完成。实验分组:清洁级SD雌性孕鼠,孕期10～14d。应用密度梯度离心法分离鼠胚脊髓运动神经元进行原代培养,运动神经元培养72h后,按培养板及孔分为4.5μg/L肌萎灵组(肌萎灵注射液,含生药0.9g/mL)、9μg/L肌萎灵组、45μg/L肌萎灵组、力如太组(力如太R利鲁唑片,应用时经0.9%NaCl-0.01NHCl溶解)和对照组。实验处理:各组分别加入用新鲜培养基稀释为0.5%(终浓度4.5μg/L)、1%(终浓度9μg/L)、5%(终浓度45μg/L)的肌萎灵注射液,力如太组加入利鲁唑(终浓度10μmo/L),对照组加入等量新鲜培养基。实验评估:①共同培养3d用四甲基偶氮唑盐法观察其对细胞活力的影响,以吸光度表示。②采用NF-200免疫组织化学染色并进行图像分析,测定神经突起主干长度。结果:①培养的运动神经元活力状态比较:4.5,9,45μg/L肌萎灵组培养运动神经元活力显著增强,与对照组相比,差异有显著性意义(0.317±0.054,0.396±0.087,0.329±0.097,0.230±0.130,P<0.05)。力如太组细胞生长与对照组相比无显著差异(0.266±0.141,0.230±0.130,P>0.05)。②脊髓运动神经元突起生长情况结果:4.5μg/L肌萎灵组和9μg/L肌萎灵组可促进其生长,与对照组相比,差异有显著性意义[(315.96±32.32),(373.46±80.24),(159.71±48.95)μm,P<0.05]。结论:肌萎灵注射液可增强运动神经元活力,促进脊髓运动神经元突起的生长。     

An examination of the role of insulin dimerisation and negative cooperativity using the biological properties of the despentapeptide and deshexapeptide insulins

Summary The C-terminus of the insulin B chain is essential for dimerisation and expression of negative cooperativity. In order to evaluate the possible physiological role of these phenomena, we have studied the properties in vivo and in vitro of despentapeptide insulin (B 26–30 deleted), derived from beef insulin, and deshexapeptide insulin (B25–30 deleted), derived from pork insulin. These materials do not dimerise and have 15% and 0% retention of negative cooperativity respectively. Lipogenesis potencies in rat adipocytes were: despentapeptide insulin 19.9±0.3%; deshexapeptide insulin 19.9±1.5%. Binding potencies in adipocytes were: despentapeptide insulin 22.6±7.8%; deshexapeptide insulin 13.2±3.3%. Metabolic clearance rates were reduced compared to insulin (insulin = 19.1±0.9; despentapeptide insulin = 9.7±0.8; deshexapeptide insulin = 6.4±0.6ml·min^–1·kg^–1 at plasma concentration 0.5 nmol/l). Hypoglycaemic potencies were reduced for both analogues (40% and 30%) when calculated on the basis of plasma concentration although both analogues and insulin were equally effective at lowering plasma glucose concentration in equimolar doses. Plasma half-disappearance time was prolonged (despentapeptide insulin=7.3±0.5; deshexapeptide insulin=9.1±0.2 min). Both analogues were full agonists and conformed to the general relationship between in vitro and in vivo properties seen with a wide range of modified insulins. They resemble other analogues with modifications which reduce receptor affinity without impairing dimerisation or negative cooperativity. The results do not support a physiological role for dimerisation or negative cooperativity.     

Endocrine disruptors and asthma-associated chemicals in consumer products

Background: Laboratory and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources.Objectives: We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals.Methods: We selected 213 commercial products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compounds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) filters.Results: We detected 55 compounds, indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concentrations and numbers of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many detected chemicals were not listed on product labels.Conclusions: Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in product composition. Consumers should be able to avoid some target chemicals—synthetic fragrances, BPA, and regulated active ingredients—using purchasing criteria. More complete product labeling would enable consumers to avoid the rest of the target chemicals.