Unusual association of NDM-1 with KPC-2 and armA among Brazilian Enterobacteriaceae isolates

We report the microbiological characterization of four New Delhi metallo-beta-lactamase-1 (bla(NDM-1))-producing Enterobacteriaceae isolated in Rio de Janeiro, Brazil. bla(NDM-1) was located on a conjugative plasmid and was associated with Klebsiella pneumoniae carbapenemase-2 (bla(KPC-2)) or aminoglycoside-resistance methylase ( armA), a 16S rRNA methylase not previously reported in Brazil, in two distinct strains of Enterobacter cloacae. Our results suggested that the introduction of bla(NDM-1) in Brazil has been accompanied by rapid spread, since our isolates showed no genetic relationship.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Med, Lab Especial Microbiol Clin, São Paulo, SP, BrazilDASA, Lab Diagnost Amer, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Med, Lab Especial Microbiol Clin, São Paulo, SP, BrazilWeb of Scienc

Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety

Trial Design: Open-label, randomised, controlled, pilot proof-of-concept clinical trial. Methods: Participants: Antiretroviral naive adult males with CD4 count >= 350 cells/mm(3). Interventions: Patients were randomised to receive thalidomide 200 mg QD for 3 weeks (Thalidomide group) or not (Control group) and followed for 48 weeks. Objective: We hypothesized that short-term Thalidomide use would reduce HIV related inflammation and HIV replication among antiretroviral naive HIV infected individuals. Outcome: Viral loads, CD4/CD8 counts, ultra-sensitive C-reactive protein (US-CRP), cell activation markers, and plasma lipopolysaccharide (LPS) were analyzed. Randomisation: Unrestricted randomisation. Blinding: No blinding was used. Results: Numbers randomised: Thirty recruited individuals were randomised to Thalidomide (16 patients) or Control (14 patients) groups. Recruitment: Patients were recruited from April 2011 to January 2013. Outcome: Viral loads remained stable in both groups. During thalidomide treatment, a decrease in CD4/CD8 ratio (p = 0.04), a decrease in CD4 count (p = 0.04), an increase in cell activation calculated by the percentage of CD38 (+)/HLA-DR+ CD8 cells (p < 0.05) and an increase in US-CRP (p < 0.01) were observed in the Thalidomide group, with all parameters returning to baseline levels after thalidomide interruption. We confirmed that thalidomide increased HIV replication in vitro of 6 of 7 samples from long-term antiretroviral suppressed individuals. Harms: No class 3/4 adverse events occurred. Conclusions: Short-termuse of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4(+) cell count without changes to the CD8(+) cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication. (C) 2017 The Authors. Published by Elsevier B.V.Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)Univ Fed São Paulo, Lab Retrovirol, São Paulo, BrazilFiocruz MS, Inst Oswaldo Cruz, Lab Interdisciplinar Pesquisas Med, Rio De Janeiro, BrazilSecretaria Municipal Saude Antonio Ribeiro Neto, Rio De Janeiro, BrazilOncohiv, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Rio De Janeiro, BrazilInst Fed Educ Ciencia & Tecnol Rio de Janeiro IF, Rio De Janeiro, BrazilUniv Fed São Paulo, Lab Retrovirol, São Paulo, BrazilFAPESP: 04/15856-9Web of Scienc

Two Distinct Modes of Hypoosmotic Medium-Induced Release of Excitatory Amino Acids and Taurine in the Rat Brain In Vivo

A variety of physiological and pathological factors induce cellular swelling in the brain. Changes in cell volume activate several types of ion channels, which mediate the release of inorganic and organic osmolytes and allow for compensatory cell volume decrease. Volume-regulated anion channels (VRAC) are thought to be responsible for the release of some of organic osmolytes, including the excitatory neurotransmitters glutamate and aspartate. In the present study, we compared the in vivo properties of the swelling-activated release of glutamate, aspartate, and another major brain osmolyte taurine. Cell swelling was induced by perfusion of hypoosmotic (low [NaCl]) medium via a microdialysis probe placed in the rat cortex. The hypoosmotic medium produced several-fold increases in the extracellular levels of glutamate, aspartate and taurine. However, the release of the excitatory amino acids differed from the release of taurine in several respects including: (i) kinetic properties, (ii) sensitivity to isoosmotic changes in [NaCl], and (iii) sensitivity to hydrogen peroxide, which is known to modulate VRAC. Consistent with the involvement of VRAC, hypoosmotic medium-induced release of the excitatory amino acids was inhibited by the anion channel blocker DNDS, but not by the glutamate transporter inhibitor TBOA or Cd2+, which inhibits exocytosis. In order to elucidate the mechanisms contributing to taurine release, we studied its release properties in cultured astrocytes and cortical synaptosomes. Similarities between the results obtained in vivo and in synaptosomes suggest that the swelling-activated release of taurine in vivo may be of neuronal origin. Taken together, our findings indicate that different transport mechanisms and/or distinct cellular sources mediate hypoosmotic medium-induced release of the excitatory amino acids and taurine in vivo

Unusual association of NDM-1 with KPC-2 and armA among Brazilian Enterobacteriaceae isolates

We report the microbiological characterization of four New Delhi metallo-β-lactamase-1 (blaNDM-1)-producing Enterobacteriaceae isolated in Rio de Janeiro, Brazil. blaNDM-1 was located on a conjugative plasmid and was associated with Klebsiella pneumoniae carbapenemase-2 (blaKPC-2) or aminoglycoside-resistance methylase (armA), a 16S rRNA methylase not previously reported in Brazil, in two distinct strains of Enterobacter cloacae. Our results suggested that the introduction of blaNDM-1 in Brazil has been accompanied by rapid spread, since our isolates showed no genetic relationship