A first molecular epidemiological study of SAT-2 type foot-and-mouth disease viruses in West Africa

Thirty-one viruses causing SAT-2 outbreaks in seven West African countries between 1974 and 1991, and four viruses representative of East and Central Africa were genetically characterized in this study. Four major viral lineages (I-IV) were identified by phylogenetic analysis of an homologous 480 nucleotide region corresponding to the C-terminus end of VP1. Lineage I comprised two West African genotypes with viruses clustering according to year of isolation rather than geographical origin. Lineage II was represented by viruses isolated between 1979 and 1983 in two neighbouring West African countries, Senegal and The Gambia. Viruses from Nigeria and Eritrea, representative of West and East Africa respectively, constituted lineage III, whilst lineage IV, comprising viruses from Central and East Africa, was regionally and genetically distinct. This study revealed that unrestricted animal movement in West Africa is a major factor in disease dissemination and has also provided the first indication of trans-regional virus transmission.     

Mercury persistence in indoor environments in the Amazon region, Brazil

We evaluated the indoor atmospheric Hg contamination in gold trade shops in two Brazilian cities of the Legal Amazon area using the Spanish moss (Tillandsia usneoides, Bromeliaceae) as a sentinel species. Plants inside plastic cages were exposed to a controlled atmosphere to evaluate the rate of Hg retention over time and then distributed in several stores with different characteristics to enable a relative comparison. Hg concentrations were determined by cold vapor atomic absorption spectrophotometry. Plants exposed in active stores with good air circulation exhibited lower levels. Ex-gold trade shops that were kept closed for long periods exhibited higher values. Stores that have been restored before being transformed into new businesses exhibited lower values than nonrestored ones. Direct measurements suggest that indoor Hg air concentrations were below the threshold limit recommended by the World Health Organization to occupational exposure; nevertheless, restoring ex-gold trade shops could ensure a healthier working environment.     

Evaluation of analgesic and anti-inflammatory activities of Nectandra megapotamica (Lauraceae) in mice and rats

The bioactivity-guided phytochemical investigation of the crude hydralcoholic extract of Nectandra megapotamica was carried out using the abdominal constriction test in mice, which led to the isolation of three active compounds: alpha-asarone (1), galgravin (2) and veraguensin (3). The crude extract (EBCA, 300 mg kg(-1)) and isolated compounds 1,2, and 3, at different doses, were evaluated using the acetic acid-induced abdominal constriction test in mice, carrageenan-induced paw oedema in rats, and hot plate tests in rats. The EBCA showed a significant effect in the abdominal constriction and hot plate tests, but did not show activity in the rat paw oedema assay. All isolated compounds displayed activity in the abdominal constriction test, but only compound 1 was active in the hot plate test. Compounds 2 and 3 displayed activity in the anti-inflammatory assay. It was suggested that the analgesic effects obtained for EBCA could be due mainly to the presence of its major compound, alpha-asarone (1).     

Hypericum androsaemum infusion increases tert-butyl hydroperoxide-induced mice hepatotoxicity in vivo

Increasing evidence regarding free radical generating agents indicates that the sustained production of high levels of reactive oxygen species (ROS) can cause hepatotoxicity. Being a short chain analog of lipid peroxide, tert-butyl hydroperoxide (t-BHP) is metabolized into free radical intermediates by cytochrome P450 in hepatocytes, which initiate lipid peroxidation, glutathione depletion and cell damage. The aim of the present study was to evaluate the putative protective effect of Hypericum androsaemum lyophilised infusion against t-BHP-induced mice hepatotoxicity in vivo, which has already been shown to be antioxidant in vitro. However, the results showed that the oral pretreatment with Hypericum androsaemum infusion (4, 20 and 100 mg/kg) for 4 days before a single intraperitoneal dose of t-BHP (1.8 mmol/kg) potentiated the t-BHP-induced hepatotoxicity. In fact, it was observed a potentiation in the depletion of total glutathione and reduced glutathione (GSH) contents and increase in oxidised glutathione (GSSG) level. Also the histopathological evaluation of the mice livers revealed that the infusion raised the incidence of liver lesions induced by t-BHP. These data do not corroborate any effect of Hypericum androsaemum infusion as hepatoprotector, but rather as a potentiator of hepatotoxicity in the present experimental conditions.     

Extratemporal resection for childhood epilepsy

There have been relatively few studies reporting the safety, efficacy, and outcome in children undergoing extratemporal resection for epilepsy. We reviewed the pediatric cases of extratemporal resection for intractable epilepsy performed by the Comprehensive Epilepsy Program at the University of Alberta Hospitals between 1988-1998. Thirty-five patients were studied, 14 male and 21 female. The age at operation ranged from 6 months to 16 years. The operations included frontal excisions (12), parietal (8), occipital (4), hemispherectomies or multilobar resections (10), and one removal of a hypothalamic hamartoma. The pathology at surgery included patients with focal cortical dysplasia (8), brain tumors (6), neurocutaneous syndrome (7), Rasmussen's encephalitis (2), porencephalic cysts (4), hypothalamic hamartoma (1), and nonspecific gliosis (6). Twenty-four of 35 patients (68.5%) had an Engel Class I outcome after surgery and an additional six patients (11%) had a significant decrease in seizure frequency (Engel Class III). Complications were observed in two patients (5%) and there were no deaths. Extratemporal resection is a safe and effective treatment for children with intractable epilepsy. Overall, 68% of patients were seizure-free after surgery, although outcome may be dependent on site and pathology. A wide range of developmental pathology was observed including focal cortical dysplasia, brain tumors, and lesions with neurocutaneous syndromes. Many families reported improvement in behavior and psychosocial function after surgery.     

Hepatotoxicity of 3,4-methylenedioxyamphetamine and α-methyldopamine in isolated rat hepatocytes: formation of glutathione conjugates

The amphetamine designer drugs 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) and its N-demethylated analogue 3,4-methylenedioxyamphetamine (MDA or love) have been extensively used as recreational drugs of abuse. MDA itself is a main MDMA metabolite. MDMA abuse in humans has been associated with numerous reports of hepatocellular damage. Although MDMA undergoes extensive hepatic metabolism, the role of metabolites in MDMA-induced hepatotoxicity remains unclear. Thus, the aim of the present study was to evaluate the effects of MDA and -methyldopamine (-MeDA), a major metabolite of MDA, in freshly isolated rat hepatocyte suspensions. The cells were incubated with MDA or -MeDA at final concentrations of 0.1, 0.2, 0.4, 0.8, or 1.6 mM for 3 h. The toxic effects induced following incubation of hepatocyte suspensions with these metabolites were evaluated by measuring cell viability, the extent of lipid peroxidation, levels of glutathione (GSH) and glutathione disulfide (GSSG), the formation of GSH conjugates, and the activities of GSSG reductase (GR), GSH peroxidase (GPX), and GSH S-transferase (GST). MDA induced a concentration- and time-dependent GSH depletion, but had a negligible effect on lipid peroxidation, cell viability, or on the activities of GR, GPX, and GST. In contrast, -MeDA (1.6 mM, 3 h) induced a marked depletion of GSH accompanied by a loss on cell viability, and decreases in GR, GPX and GST activities, although no significant effect on lipid peroxidation was found. For both metabolites, GSH depletion was not accompanied by increases in GSSG levels; rather, 2-(glutathion-S-yl)--MeDA and 5-(glutathion-S-yl)--MeDA were identified by HPLC-DAD/EC within cells incubated with MDA or -MeDA. The results provide evidence that one of the early consequences of MDMA metabolism is a disruption of thiol homeostasis, which may result in loss of protein function and the initiation of a cascade of events leading to cellular damage.     

Leucoisoprenochrome-o-semiquinone formation in freshly isolated adult rat cardiomyocytes

Sustained high levels of circulating catecholamines can lead to cardiotoxicity. There is increasing evidence that this process may result from metal-catalyzed catecholamine oxidation into semiquinones, quinones, and aminochromes. We have previously shown that Cu2+-induced oxidation of isoproterenol into isoprenochrome induces toxic effects in isolated cardiomyocytes. The aim of this study was to characterize the isoproterenol oxidation process and to locate the formation of semiquinone radicals in cardiomyocyte suspensions. Freshly isolated rat cardiomyocytes were incubated with 1 or 10 mM isoproterenol and 20 microM Cu2+ for 4 h. The formation of an isoproterenol oxidation radical was detected in the extracellular medium, cells, membranes, and heavy organelles by electron spin resonance spectroscopy. An electron spin resonance signal assigned to leucoisoprenochrome-o-semiquinone increased in a time-dependent manner in the extracellular medium. A second electron spin resonance signal, characteristic of an immobilized radical, was also found in the cardiomyocytes. The latter was attributed to leucoisoprenochrome-o-semiquinone immobilized on cellular components such as membranes, cytoskeleton, nucleus, and heavy organelles. In addition, the levels of leucoisoprenochrome-o-semiquinone decreased in the presence of glutathione. Computer simulations of the experimental spectra indicate the formation of two distinct isomeric leucoisoprenochrome-o-semiquinone radicals during isoproterenol oxidation. The present study shows that the isoproterenol oxidation in isolated rat cardiomyocytes correlates with the formation of leucoisoprenochrome-o-semiquinone in the cells and in the extracellular medium, suggesting that it might be involved in cardiotoxicity induced by the oxidation of catecholamines.     

Effect of Mycobacterium leprae lipids on BCG- and carrageenan-induced cellular recruitment in mouse pleurisy

Pathogenic mycobacteria survive inside macrophages and deactivate these cells, using a mechanism that is still poorly understood. Mycobacterial cell wall lipids constitute the first contact with the host cell. Although Mycobaterium leprae and M. bovis BCG share common antigens, they induce opposite inflammatory responses. Apolar M. leprae lipids have been shown to be anti-inflammatory by down-regulating macrophage activation and T-cell functions. We wonder if these lipids would influence cellular migration to BCG or to other inflammatory agent. We investigated the effect of M. leprae, its lipids or delipidated bacteria on acute and chronic BCG- or carrageenan-induced pleurisy. Previous injection of intact or delipidated M. leprae did not alter either the BCG- or carrageenan-induced pleural inflammatory reaction. However, M. leprae lipids enhanced carrageenan-induced acute cellular migration without impairing BCG inflow; moreover, they reduced BCG chronic response. Together these data suggest distinct mechanisms for intracellular deactivation and pleural cell recruitment exerted by mycobacterial structures.     

Willingness to participate in HIV vaccine trials among a sample of men who have sex with men, with and without a history of commercial sex, Rio de Janeiro, Brazil

The study objective was to assess willingness of men who have sex with men (MSM) enrolled in a vaccine preparedness study ('Projeto Rio') to participate in phase III anti-HIV/AIDS vaccine trials. Overall, 57% of Projeto Rio participants stated they would participate in a putative vaccine trial. MSM who reported commercial sex work were significantly (p < 0.05) more likely to engage in risky behaviours than others. In bivariate analysis, commercial sex workers (CSWs) were significantly (p < 0.05) more likely than non-commercial sex workers (NCSWs) to be willing to participate in vaccine trials (62.6% versus 51.4%). Among those willing, CSWs reported significantly more often (p < 0.05) (50.5%) than NCSWs (38.0%) that they would enroll to protect themselves from HIV. In multivariate analyses, variables associated with willingness to participate (WTP) were lower educational level, positive serology for syphilis, and 'engagement, under the influence of alcohol, in risky sexual practices that would normally be avoided', but not commercial sex work. The potential enrollment in vaccine trials of MSM CWSs, as well as participants of low socio-economic status and high risk, seems thus to be possible.