Effects of ethanol consumption on bioactivation and hepatotoxicity of N-nitrosodimethylamine in rats

To study the effects of ethanol on the hepatotoxicity of N-nitrosodimethylamine (NDMA), 5 mg NDMA/kg body weight was injected intraperitoneally 3 times a week for 6 weeks into rats pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrates. Another group of rats was pair-fed with the same diets but injected with saline instead of NDMA. Co-administration of ethanol and NDMA produced much higher elevations of serum alanine and aspartate aminotransferase and glutamic dehydrogenase activities than the administration of either agent alone. The combined treatment also slightly increased focal necrosis, whereas other liver lesions (steatosis and fibrosis) and the functional impairment of mitochondrial respiration were not affected significantly. Microsomal low Km NDMA demethylation, as well as NDMA denitrosation, were inhibited markedly by incubation with an antibody against P450IIE1, suggesting the involvement of this alcohol-inducible P450 in both NDMA bioactivation reactions. The addition of ethanol inhibited P450-dependent demethylation and denitrosation of NDMA in liver microsomes, whereas both activities were enhanced markedly by chronic ethanol administration. At ethanol concentrations similar to those prevailing in the blood of alcohol-fed animals at the time of NDMA administration, hepatic microsomal demethylation and denitrosation remained significantly higher in ethanol-fed rats given NDMA than in controls. Our results suggest that bioactivation plays a critical role in the hepatotoxicity of NDMA and its aggravation by chronic alcohol consumption.     

Tumor necrosis factor-dependent production of human immunodeficiency virus 1 in chronically infected HL-60 cells

Tumor necrosis factor (TNF) may play a central role in proviral activation and release from latency in cells infected with the human immunodeficiency virus (HIV). We studied viral production and its relation to TNF in a HL-60 cell line (J22-HL-60) infected with a monocytotropic strain of HIV-1JR-FL. Viral production was stimulated to similar levels by TNF, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Production of the virus was not suppressed by 3'-azido-3'-deoxythymidine (AZT), indicating that viral production was not caused by superinfection. Low concentrations of TNF (0.1 ng/mL) induced viral production with a short lag period of 8 hours, and this proviral activation was specifically suppressed by anti- TNF antibodies. However, induction of virus production by 1,25(OH)2D3 showed an extended lag period of 2 to 3 days. The effect of 1,25(OH)2D3 on virus production was also blocked by anti-TNF antibodies, which suggests the direct participation of TNF in this process. TNF accumulated in the culture supernatant of cells stimulated with 1,25(OH)2D3 with a kinetics consistent with its involvement in the action of 1,25(OH)2D3 on viral production. The J22-HL-60 cell line produced low levels of virus when cultured in the absence of an external stimulus; however, this basal viral production was suppressed greater than 80% in the presence of anti-TNF antibodies. Corresponding low levels of TNF were detected in the culture supernatants. Viral production decreased slowly with increasing passage of the cells, and no virus was detected in the supernatants of cells maintained in culture for several months. Concomitantly, TNF was no longer detected in the supernatant of these cells, which suggests that endogenous autocrine production of TNF drives viral production in the unstimulated cells. However, viral production was stimulated in these cells by low concentrations (0.1 ng/mL) of added TNF. These results argue for a central role for TNF in HIV proviral activation in chronically infected myeloid cells.     

Quantitation of MR relaxation effects of iron oxide particles in liver and spleen

The relaxation effects and organ distribution of superparamagnetic iron oxide particles for magnetic resonance imaging were measured in rats. T1 and T2 were measured for excised organs, and tissue iron levels were quantified with radiolabeling. Approximately 70% of the injected dose is present in the liver and 10% in the spleen 1 hour after injection. At 20 MHz, the doses required to reduce liver and spleen T2 to half the normal value, as measured with a Carr-Purcell-Meiboom-Gill sequence, were, respectively, 420 and 830 mumol iron injected per kilogram of rat. The transverse relaxation rates increase linearly with injected dose and showed no evidence of saturation. These results suggest that this material is less effective than previously suggested.     

Polycystic ovarian disease: US features in 104 patients

Ultrasonographic (US) study was performed in 25 healthy women and 104 patients with polycystic ovarian disease (PCOD). Although the average size of ovaries in the PCOD patients was much larger than that of the healthy women, 29.7% of ovaries in the PCOD patients were normal in size. The shapes of the ovaries (roundness index) in PCOD patients were not different from those of the healthy women. There was no significant correlation between the size and shape of the ovaries. Bilaterally enlarged, globular-shaped ovaries were rare and usually asymmetric in size. The most important feature of PCOD on US scans is the bilaterally increased numbers of developing follicles (0.5-0.8 cm in size), usually more than five in each ovary. Although maturing follicles (1.5-2.9 cm) are much rarer in PCOD patients (13.5%) than in healthy women (36%), the incidences of follicular cysts (greater than 3 cm) was about the same in both.     

Source of hydrogen peroxide and of chemiluminescence observed in activated human platelet preparations

Human platelet suspensions can be observed to produce small amounts of H2O2 (0.04 nmoles H2O2/min/2.5 X 10(5) cells/cu mm) and measurable chemiluminescence when exposed to target particles for phagocytosis, such as latex spherules. Both H2O2 production and chemiluminescence are characteristic of phagocytosing polymorphonuclear leukocytes (PMN) and analysis of the purified platelets indicates contamination by PMN at the level of 0.2%. The amount of H2O2 produced and the chemiluminescence observed can be duplicated by adding latex spheres to a preparation of PMN at a concentration equivalent to the contaminant in the platelet preparations. We conclude that the H2O2 produced and chemiluminescence observed from activated platelets is due to the presence of small amounts of contaminating PMN. These studies emphasize the importance of controlling for PMN contamination in studies of platelet biochemistry and physiology.     

中国118家实验室精液分析状况的调查

为在实验室内和实验室间实现精液分析标准化和进行质量控制,必须了解目前男科实验室精液分析的状况。为此,对中国大陆地区的部分精液分析实验室进行了调查。设计的"男科实验室精液分析调查表",包含36个问题,涉及精液分析的相关内容。本研究发放调查表145份,回收有效调查表118份。调查显示,53.6%(59/110)的实验室采用目测法检测精液量;对液化不全精液,70.9%(73/103)的实验室未作任何处理;精子密度、活动率、存活率及形态学分析以手工普通光学显微镜分析和计算机辅助精液分析(CASA)系统检测并存;精子染色方法达5种以上;精子自身抗体检测以酶联免疫吸附试验(ELISA)为主;仅有27.1%(32/118)的实验室开展了精浆生化项目检测。而且,在参与调查的所有实验室中,无一家实验室开展精液分析的室内和室间质量控制。总之,在中国大陆,男科实验室精液分析的方法和报告方式很不统一。采用的精液分析方法与《世界卫生组织人类精液分析实验室手册》第4版推荐的方法也不一致。本研究提示,为使不同实验室的检测结果具有可比性且有意义,中国男科实验室目前使用的精液分析方法急需标准化和质量控制。     

定义实验室参考值和决定限:人群,区间范围及其解读

简要概述多种分析人类精液检测结果的方法。参考区间(参考值范围)是最常用的解释临床实验结果的工具。参考值范围概念的发展,有赖于20世纪80年代临床化学专家国际联盟对这一概念的详尽阐述。这些指南要求:健康参考人群至少应包括120个健康个体,并对其进行分类,辨别最外延5%的参考值数据来确定双侧或单侧参考区间的界限值。最近,基于流行病学结果分析得出的决定限,也已用来解读分析检测结果。参考群体必须根据检验项目的临床使用要求严格定义:如果参考值范围用于评估男性生育能力,12个月内使配偶成功妊娠的男性应当是最合适的参考人群;如果用于精液检测结果的流行病学评估,随机选择的健康男性应该是最为理想的参考群体。虽然男性个体精液检测结果基于参考值和决定限无疑会在不久的将来成为解释结果的工具,但从长远看,解释精液检查结果的多因素方法或结合女性有关因素的分析,似乎是检测生育能力低下夫妇妊娠可能性的最佳方式。