The changing faces of glutathione, a cellular protagonist

Glutathione (GSH) has been described for a long time just as a defensive reagent against the action of toxic xenobiotics (drugs, pollutants, carcinogens). As a prototype antioxidant, it has been involved in cell protection from the noxious effect of excess oxidant stress, both directly and as a cofactor of glutathione peroxidases. In addition, it has long been known that GSH is capable of forming disulfide bonds with cysteine residues of proteins, and the relevance of this mechanism ("S-glutathionylation") in regulation of protein function is currently receiving confirmation in a series of research lines. Rather paradoxically, however, recent studies have also highlighted the ability of GSH-and notably of its catabolites-to promote oxidative processes, by participating in metal ion-mediated reactions eventually leading to formation of reactive oxygen species and free radicals. A crucial role in these phenomena is played by membrane bound gamma-glutamyltransferase activity. The significance of GSH as a major factor in regulation of cell life, proliferation, and death, should be regarded as the integrated result of all these roles it can play.     

Information dissemination and use: critical components in occupational safety and health

BACKGROUND: Information dissemination is a mandated, but understudied, requirement of occupational and environmental health laws and voluntary initiatives. Research is needed on the factors that enhance and limit the development, transfer, and use of occupational safety and health information (OSH). Contemporary changes in the workforce, workplaces, and the nature of work will require new emphasis on the dissemination of information to foster prevention. METHODS: Legislative and regulatory requirements and voluntary initiatives for dissemination of OSH information were identified and assessed. Literature on information dissemination was reviewed to identify important issues and useful approaches. RESULTS: More than 20 sections of laws and regulations were identified that mandated dissemination of occupational and environmental safety and health information. A four-stage approach for tracking dissemination and considering the flow of information was delineated. Special areas of dissemination were identified: the information needs of the changing workforce, new and young workers; small businesses; and workers with difficulty in understanding or reading English. CONCLUSIONS: We offer a framework for dissemination of OSH information and underscore the need to focus on the extent to which decision-makers and others receive and use such information. More solid data are also needed on current investments in disseminating, diffusing and applying OSH information and on the utility of that information. Am. J. Ind. Med. 44:515-531, 2003. Published 2003 Wiley-Liss, Inc.     

Infant-mother interaction as a predictor of child's chronic health problems

BACKGROUND: Psychological stress is associated with physical illnesses like asthma or infections. For an infant, situations perceived as stressful are highly dependent on the relationship with the caregiver. Constantly poor mother-infant interaction increases the child's vulnerability to stressful conditions and experiences. The aim of the study was to investigate the impact of the quality of early mother-infant interaction on the subsequent physical health of the child. Poor mother-infant interaction was hypothesized to be associated with chronic or recurrent health problems in the child. PARTICIPANTS: Fifty-seven mother-infant dyads from families at risk of psychosocial problems and 63 from non-risk families, altogether 120 dyads, participated in the study. Families were drawn from normal population, from well-baby clinics in the city of Tampere, Finland. Infants were full-term and healthy, families with severe risks like psychotic illnesses of the parents or a history of child protection concerns were excluded from the study. METHODS: After the initial interview with the mother, the mother-infant interaction was videotaped when the infants were 8-11 weeks of age and the interaction was assessed using the Global Rating Scale for Mother-Infant Interaction (Murray et al. 1996a). After the 2-year follow-up mothers were interviewed again and the health problems of the child were elicited. RESULTS: Poor dyadic mother-infant interaction and infant's poor interactive behaviour assessed at two months were separately associated with the physical health of the child during the two-year follow-up. After adjusting for other factors in the logistic regression analysis infant's poor interactive behaviour remained as a significant predictor of chronic or recurrent health problems in the child. Infant's health problems at the time of the initial interview and day care centre attendance were also significant predictors. CONCLUSIONS: The results suggest that interactional issues between a mother and her infant are related to the child's subsequent physical health. Children with recurrent or chronic health problems may have relationship difficulties with which they need help. Also, early avoidant behaviour of the infant should be regarded as an indicator of the infant's distress with possibly adverse outcomes in the child's physical health, among other consequences.     

Plants for male fertility regulation

The importance of drugs of plant origin in the pursuit of fertility regulating agents for the male from natural products has long been recognized. This review includes 80 plants with 205 references, up to year 2002. The type of extract, dose, animal model and pharmacological activity of these materials have been reviewed in this paper to add impetus to further research and collaboration to resolve the problem of population explosion.     

Ephedra in perspective--a current review

Although the traditional use of Ephedra 'ma huang' has been established for thousands of years, its resurgence in the US as a herbal dietary supplement is currently a matter of national controversy. At the heart of the debate are three important questions: (1) the identity and composition of Ephedra products with regard to ephedrine and related alkaloids; (2) the potential therapeutic utility of Ephedra supplements for weight loss or performance enhancement; and (3) potential health risks associated with such uses of Ephedra, particularly in sensitive individuals or in cases of intentional abuse for its stimulant properties. This review surveys the literature on Ephedra with regard to traditional uses, botany, chemistry, analytics, pharmacological effects and health risks. A brief discussion of the central issues in the current debate on the regulation of Ephedra in the United States is included as this is where most of the problems have occurred to date.     

补肾、健脾、益气、活血法对衰老细胞周期基因表达的调控作用

目的：比较补肾、健脾、益气、活血法对衰老细胞周期基因表达的调控作用。方法：采用上述4种不同的含药血清对衰老的人胚肺二倍体成纤维细胞2Bs细胞株进行处理,通过细胞寿命实验、流式细胞仪、RT—PCR、Westemblot方法研究不同中药对衰老细胞周期及其相关基因(P16^INK4、Cyclin D1及PCNA)的mRNA转录和蛋白表达的影响。结果：补肾、益气中药对衰老细胞周期有一定的促进作用,并可下调衰老细胞增殖抑制基因P16和周期蛋白Cyclin D1的mRNA／蛋白表达;上调细胞周期促进增殖基因PCNAmRNA／蛋白的表达。而健脾、活血中药对细胞周期及其相关基因和蛋白表达的作用不明显。结论：补肾、益气方药对细胞周期有促进作用,其中的作用可能是通过促进P16途径的基因表达来实现。     

Efficacy,safety and cost of new cardiovascular drugs: a survey

To assess the type and degree of innovation of the cardiovascular drugs centrally approved in the European Union between 1995 and 2002. Sources of information were the European Public Assessment Reports and the Summaries of Product Characteristics published by the European Medicines Evaluation Agency. The Agency approved 11 active substances belonging to 5 therapeutic classes: anti-hypertensives, anti-arrhythmics, anti-platelets, anti-coagulants and fibrinolytics. Analysis of the documentation on which the marketing authorisation was based shows few elements of innovation. Moreover, the new drugs usually cost more than similar drugs already available. Cardiovascular drugs approved in Europe in the last few years have contributed little to progress in this area. These approvals provide no real advantage to patients and lay an economic burden on society.S.G. and V.B., respectively, act as member and expert of the CPMP. The views presented in this paper are those of the authors and should not be understood or quoted as being made on behalf of the EMEA and/or its scientific committees.     

Differential up-regulation of striatal dopamine transporter and alpha-synuclein by the pyrethroid insecticide permethrin

The effects of permethrin on striatal dopaminergic biomarkers were assessed in this study. Retired breeder male C57 B1/6 mice were given an ip dose of permethrin (0.1-200 mg/kg) at 7-day intervals, over a 2-week period (Days 0, 7, and 14). Animals were then sacrificed 1 day (t = 1), 14 days (t = 14), or 28 days after the last treatment (t = 28). Dopamine transporter (DAT) protein as assayed by Western blotting was increased to 115% in the 0.8 mg/kg group over that of control mice at t = 1 (P < 0.05). At t = 14, this value increased to 140% of control, and declined slightly to 133% of control at t = 28. The mice given the 1.5 mg/kg dose displayed a significant increase in DAT protein only at t = 28, to 145% of controls. Thus, upregulation of the DAT at low doses of PM is variable 24 h after treatment, and seems to stabilize by t = 28. The threshold dose for increasing DAT expression in Western blots by t = 28 was 0.2 mg/kg permethrin. [(3)H]GBR 12935, used to assay DAT binding, followed the same trend as that for the Western blotting data for 0.8 and 1.5 mg/kg doses of permethrin over the 4 weeks posttreatment. At 200 mg/kg permethrin, DAT protein was unchanged vs controls (t = 1), but had significantly increased by t = 14 and continued to increase at t = 28, suggesting that the reduced dopamine transport at this dose was due to nerve terminal stress and that recovery had occurred. The protein alpha-synuclein was also significantly induced at the 1.5 mg/kg dose at t = 1; however, unlike DAT up-regulation, this effect had declined to control values by t = 14. Maximal induction of alpha-synuclein protein occurred at a dose of 50 mg/kg permethrin. These data provide evidence that the pyrethroid class of insecticides can modulate the dopaminergic system at low doses, in a persistent manner, which may render neurons more vulnerable to toxicant injury.     

Current aspects of lactate exchange: lactate/H+ transport in human skeletal muscle

Skeletal muscle is capable of producing and releasing large amounts of lactate and at the same time taking up lactate and using it as a respiratory fuel. The release and uptake of lactate both involve transmembrane transport, which is mediated mainly by a membrane protein called the monocarboxylate transporter (MCT). MCTs mediate membrane transport with an obligatory 1:1 coupling between lactate and H⁺ fluxes, and is therefore of great importance for pH regulation, especially during intense muscle activity. The total lactate and H⁺ transport capacity is higher in membranes from oxidative fibers than in membranes from more glycolytic fibers. There are two isoforms of MCT present in skeletal muscle, MCT1 and MCT4. In human muscle samples, there is a positive correlation between the proportion of type I fibers and MCT1 density. In contrast, the MCT4 density in human muscle is independent of fiber type and displays a large interindividual variation. Although the two isoforms have identical transport kinetics (K _m), they may have different roles in muscle. MCT1 and MCT4 respond differently to a high-intensity training session, which suggests that these two isoforms are regulated differently. Electronic Publication     

主要组织相容性复合物Ⅱ类分子转录激活因子核酶的克隆及其活性

目的探讨主要组织相容性复合物(MHC)Ⅱ类分子转录激活因子(CⅡTA)核酶抑制MHCⅡ类分子的表达。方法设计并合成针对人类CⅡTA的一组核酶,通过体外制备和活性鉴定,筛选出活性较高的核酶一Rz464。将Rz464克隆到真核表达载体pIRES2-EGFP,简称为pRz464,并稳定转染Daudi细胞株(pRzA64一D),流式细胞术检测经典的MHCⅡ(HLA-DR、-DP、-DQ)类抗原表达,RT—PCR检测CⅡTA mRNA水平。结果 pRz464-D与无关核酶组比较,HLA—DR、-DP、-DQ抗原表达分别降低了88．4％、83．5％、93．4％;同时CⅡTA的mRNA含量明显减少。结论提示抗CⅡTA锤头状核酶抑制了自身mRNA含量,从而阻止了其调控的MHCⅡ类分子的相应表达。