Evidence of species-specific detoxification processes for trace elements in shorebirds

This study investigated sub-lethal effects and detoxification processes activated in free-ranging Red Knots (RKs) (Calidris canutus) from the Pertuis Charentais on the Atlantic coast of France, and compared the results with previous data obtained on another shorebird species, the Black-tailed Godwit (Limosa limosa). The concentrations of 13 trace elements (Ag, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, Zn) were assessed in the liver, kidneys, muscle and feathers. Stable isotope analyses of carbon and nitrogen were carried out to determine whether differences in diet explained variations in elemental uptake. The mRNA expression of relevant genes (cytochrome c oxidase 1, acetyl-CoA carboxylase, Cu/Zn and Mn superoxide dismutase, catalase, metallothionein, malic enzyme), antioxidant enzyme activities (catalase, glutathione peroxidase (GPx), superoxide dismutase), and metallothionein (MT) levels were investigated to shed light on trace element detoxification and toxic effects. Although Red Knots were characterized by elevated As and Se concentrations which were potentially toxic, most elements were usually below toxicity threshold levels. The results strongly suggested a dietary specialization of Red Knots, with individuals feeding on higher trophic status prey experiencing higher As, Hg and Se burdens. Red Knots and Godwits also showed discrepancies in elemental accumulation and detoxification processes. Higher As and Se concentrations in Red Knots enhanced catalase gene expression and enzyme activity, while Godwits had higher Ag, Cu, Fe and Zn levels and showed higher MT production and GPx activity. The results strongly suggest that detoxification pathways are essentially trace element- and species-specific.     

Streptomycin resistance and lineage-specific polymorphisms in Mycobacterium tuberculosis gidB gene

Mutations related to streptomycin resistance in the rpsL and rrs genes are well known and can explain about 70% of this phenotypic resistance. Recently, the gidB gene was found to be associated with low-level streptomycin resistance in Mycobacterium tuberculosis. Mutations in gidB have been reported with high frequency, and this gene appears to be very polymorphic, with frameshift and point mutations occurring in streptomycin-susceptible and streptomycin-resistant strains. In this study, mutations in gidB appeared in 27% of streptomycin-resistant strains that contained no mutations in the rpsL or rrs genes, and they were associated with low-level streptomycin resistance. However, the association of certain mutations in gidB with streptomycin resistance needs to be further investigated, as we also found mutations in gidB in streptomycin-susceptible strains. This occurred only when the strain was resistant to rifampin and isoniazid. Two specific mutations appeared very frequently in this and other studies of streptomycin-susceptible and -resistant strains; these mutations were not considered related to streptomycin resistance, but as a polymorphism. We stratified the strains according to the different phylogenetic lineages and showed that the gidB(16) polymorphism (16G allele) was exclusively present in the Latin American-Mediterranean (LAM) genotype, while the gidB(92) polymorphism (92C allele) was associated with the Beijing lineage in another population. In the sample studied, the two characterized single-nucleotide polymorphisms could distinguish LAM and Beijing lineages from the other lineages.     

Acute hepatitis C in Brazil: results of a national survey

The incidence of acute hepatitis C has decreased in the world. However, new cases are still reported. The objective of this study was to obtain data of acute hepatitis C in Brazil and to identify risk factors of transmission, diagnostic criteria, clinical presentation, evolution, and treatment. A questionnaire was sent to all members of the Brazilian Society of Hepatology. Sixteen centers participated with a total of 170 cases between 2000 and 2008. Among them, 37 had chronic renal failure on hemodialysis and were evaluated separately. The main diagnostic criterion in non‐uremic patients was ALT (alanine aminotransferase) elevation associated with risk factors. In patients with chronic renal failure, anti‐hepatitis C virus (HCV) seroconversion was the most frequent criterion. Among the 133 non‐uremic patients the main risk factors were hospital procedures, whereas in hemodialysis patients, dialysis was the single risk factor in 95% of the cases. Jaundice was more frequent in non‐uremic patients (82% vs. 13%; P < 0.001) and ALT levels were higher in these individuals (P < 0.001). Spontaneous clearance was more frequent in non‐uremic patients (51% vs. 3%; P < 0.001). Sixty‐five patients were treated: 39 non‐uremic patients and 26 on dialysis. Sustained virological response rates were 60% for non‐uremic and 58% for uremic patients (P = 0.98). There was no association of these rates with the study variables. These findings show that cases of acute hepatitis C are still occurring and have been related predominantly to hospital procedures. Measures to prevent nosocomial transmission should be adopted rigorously and followed to minimize this important source of infection observed in this survey. J. Med. Virol. 83:1738–1743, 2011. © 2011 Wiley‐Liss, Inc.     

Lamivudine resistance mutations in European patients with hepatitis B and patients co-infected with HIV and hepatitis B

Evaluation of resistance pattern in patients with chronic hepatitis B. Retrospective study of hepatitis B virus (HBV) resistance mutations in patients found viraemic after first-line treatment. HBV viral load was determined by a real-time polymerase chain reaction and the substitutions in HBV-DNA were studied by polymerase sequencing test. First line treatment had failed in 12 out of 33 patients (36%) receiving anti-HBV drugs. The 12 patients with persistent viraemia were all lamivudine (LAM) experienced and 7 had a polymerase sequencing test available. LAM substitution mutations L180M + M204V/I were found in six out of seven cases, with an accompanying V173L mutation in three cases. These mutations were also related with changes in HBsAg. The use of potent drugs in the first line anti-HBV therapy may reduce the resistance mutations in the future.     

Olfactory ensheathing cells as putative host cells for Streptococcus pneumoniae: evidence of bacterial invasion via mannose receptor-mediated endocytosis

Olfactory ensheathing cells (OECs) are a special glia that ensheath olfactory receptor axons that enter the brain via olfactory phila, thus, providing a potential route for access of pathogens. Streptococcus pneumoniae (Sp), that has a capsule rich in mannosyl residues, is the most common cause of rhinosinusitis that may evolve to meningitis. We have tested whether OECs in vitro express the mannose receptor (MR), and could internalize Sp via MR. Cultures were infected by a suspension of Sp (ATCC 49619), recognized by an anti-Sp antibody, in a 100:1 bacteria:cells ratio. Competition assays, by means of mannan, showed around a 15-fold reduction in the number of internalized bacteria. To verify whether MR could be involved in Sp uptake, OECs were reacted with an antibody against the MR C-terminal peptide (anti-cMR) and bacteria were visualized with Sytox Green. Selective cMR-immunoreaction was seen in perinuclear compartments containing bacteria whereas mannan-treated cultures showed an extremely low percentage of internalized bacteria and only occasional adhered bacteria. Our data suggest the involvement of MR in adhesion of bacteria to OEC surface, and in their internalization. Data are also coherent with a role of OECs as a host cell prior to (and during) bacterial invasion of the brain.     

Antiretrovirals and the use of traditional, complementary and alternative medicine by HIV patients in Kwazulu-Natal, South Africa: a longitudinal study

The aim of this prospective study (20 months) was to assess HIV patients' use of Traditional, Complementary and Alternative Medicine (TCAM) and its effect on ARV adherence at three public hospitals in KwaZulu-Natal, South Africa. Seven hundred and thirty-five (29.8% male and 70.2% female) patients who consecutively attended three HIV clinics completed assessments prior to ARV initiation, 519 after 6 months, 557 after 12 and 499 after 20 months on antiretroviral therapy (ART). Results indicate that following initiation of ARV therapy the use of herbal therapies for HIV declined significantly from 36.6% prior to ARV therapy to 8.0% after 6 months, 4.1% after 12 months and 0.6% after 20 months on ARVs. Faith healing methods (including spiritual practices and prayer) declined from 35.8% to 22.1%, 20.8% and 15.5%, respectively. In contrast, the use of micronutrients (vitamins, etc.) significantly increased from 42.6% to 78.2%. The major herbal remedies that were used prior to ART were unnamed traditional medicine, followed by imbiza (Scilla natalensis planch), canova (immune booster), izifozonke (essential vitamins mixed with herbs), African potato (Hypoxis hemerocallidea), stametta (aloe mixed with vitamins and herbs) and ingwe (tonic). Herbal remedies were mainly used for pain relief, as immune booster and for stopping diarrhea. As herbal treatment for HIV was associated with reduced ARV adherence, patient's use of TCAM should be considered in ARV adherence management.     

Production of interleukin-13 is influenced by the interleukin-4 -34TT and -590TT genotype in patients with aggressive periodontitis

Aggressive periodontitis (AgP) is a specific form of periodontal disease, with rapid destruction of the tissues supporting the teeth in otherwise young healthy individuals. We recently showed a higher frequency of the interleukin-4 (IL-4) -34TT and -590TT genotype in AgP patients compared to controls (P<0.05). Herein, we demonstrated that this specific IL-4 genotype exerts its function by increasing expression of IL-4 and STAT6, and producing higher concentrations of IL-4 in activated CD4+ cells of patients with AgP. In the present study, we investigated the effects of the IL-4-specific genotype on IL-13, IL-2 and IFN-γ expression and production in activated CD4+ cells of patients with AgP and healthy controls. Results revealed higher IFN-γ and IL-2 expression and significantly increased IL-13 production in the cells of the patients who were homozygous for the -34T and -590T alleles in comparison with the patients who were homozygous for the -34C and -590C alleles (P<0.05). Results of controls with the -34C and -590C alleles were similar to those of AgP with the same genotype. To our knowledge, the present study is the first to show an effect of the -34TT and -590TT genotype on IL-13 production. There is an increased production of IL-13 by the T cells of aggressive periodontitis patients with the IL-4 genotype.     

Neuropsychological evidence for three distinct motion mechanisms

The purpose of this study was to investigate the effect of NT-4 on the endoplasmic reticulum (ER) stress-related apoptosis of retinal neurons of isolated retinas. The retinas were isolated from normal and diabetic rats, and the normal retinas were exposed to high glucose (HG). Our results showed that the number of TUNEL-positive, and PERK- and CHOP-positive cells was significantly higher in diabetic and HG exposed retinas than in normal retinas. In diabetic and HG exposed retinas supplemented with NT-4, the number of TUNEL-positive, and PERK- and CHOP-positive cells was significantly lower than in retinas without NT-4. The neuroprotective effect of NT-4 on retinas cultured under diabetic stress was correlated with the suppression in the expression of PERK and CHOP, ER stress-related factors.