Caffeine Improves GABA Transport in the Striatum of Spontaneously Hypertensive Rats (SHR).

The spontaneously hypertensive rat (SHR) is an excellent animal model that mimics the behavioral and neurochemical phenotype of attention-deficit/hyperactivity disorder (ADHD). Here, we characterized the striatal GABA transport of SHR and investigated whether caffeine, a non-selective antagonist of adenosine receptors, could influence GABAergic circuitry. For this purpose, ex vivo striatal slices of SHR and Wistar (control strain) on the 35th postnatal day were dissected and incubated with [3H]-GABA to quantify the basal levels of uptake and release. SHR exhibited a reduced [3H]-GABA uptake and release, suggesting a defective striatal GABAergic transport system. GAT-1 appears to be the primary transporter for [3H]-GABA uptake in SHR striatum, as GAT-1 selective blocker, NO-711, completely abolished it. We also verified that acute exposure of striatal slices to caffeine improved [3H]-GABA uptake and release in SHR, whereas Wistar rats were not affected. GABA-uptake increase and cAMP accumulation promoted by caffeine was reverted by A1R activation with N6-cyclohexyl adenosine (CHA). As expected, the pharmacological blockade of cAMP-PKA signaling by H-89 also prevented caffeine-mediated [3H]-GABA uptake increment. Interestingly, a single caffeine exposure did not affect GAT-1 or A1R protein density in SHR, which was not different from Wistar protein levels, suggesting that the GAT-1-dependent transport in SHR has a defective functional activity rather than lower protein expression. The current data support that caffeine regulates GAT-1 function and improves striatal GABA transport via A1R-cAMP-PKA signaling, specifically in SHR. These results reinforce that caffeine may have therapeutic use in disorders where the GABA transport system is impaired.

Distribution of virulence determinants in Streptococcus agalactiae recovered from different clinical sources.

Streptococcus agalactiae (group B Streptococcus, GBS) is a pathobiont, a member of human microbiota that can change from commensal to pathogen, causing a large spectrum of diseases. This study assessed virulence determinants of 32 GBS isolates recovered from different clinical sources associated with asymptomatic and symptomatic clinical outcomes that present distinct capsular types and antimicrobial resistance profiles. The ability of a unique strain to colonize and cause infection in different subjects was also evaluated. By PFGE analysis, it was observed that a given strain could be associated with both asymptomatic and symptomatic outcomes. Cell wall anchor proteins ß and alpha C encoding genes (bac and bca, respectively) were detected in all capsular type Ib isolates. bca was more frequent among asymptomatic outcome-related isolates, as well as high expression of ß-hemolysin/cytolysin (ß-H/C). Symptomatic outcome-related isolates produced strong biofilm more frequently. All bacterial isolates recovered from urine were strong biofilm producers. In growth experiments, asymptomatic outcome-related isolates grew faster after 2 h until the end of the log phase. Taken together, these findings show virulence genotypic and phenotypic features of GBS from distinct sources, which may be helpful to understand their pathogenic potential and predict different clinical outcomes.

Low-dose aspirin does not affect the renal function of microalbuminuric type 2 diabetic patients / Aspirina em baixa dosagem não afeta a função renal de pacientes com diabete melito tipo 2 microalbuminuricos

Low-grade inflammation has been implicated in the pathogenesis of diabetic nephropathy, and anti-inflammatory drugs could be potentially useful as a therapeutic tool. The aim of this study was to analyze the effect of low-dose aspirin (300 mg/d) on urinary albumin excretion (UAE) and glomerular filtration rate (GFR) levels of microalbuminuric type 2 DM patients. Methods: in this randomized, double-blind, crossover, placebo-controlled study, 18 microalbuminuric (UAE=30-300 mg/24 h) type 2 DM patients received aspirin (300 mg/d) or identical placebo for 8 weeks, with a 6-week washout period. The patients were aged 56±9 years, had a diabetes duration of 16±7.5 years; 11 (61%) were female, and they were all using enalapril 10 mg bid. GFR was measured by 51Cr-EDTA single-injection method and UAE by immunoturbidimetry. The sample-size calculation showed that 17 patients were needed to detect a 30% change in UAE (α= 0.05 and β= 0.20). Results: after 8 weeks of treatment, there were no significant differences between placebo and aspirin, respectively, regarding UAE [57.7 (8.9-420.0) vs. 63 (8.2-272.0) mg/24 h; P=0.45] and GFR (108±34 vs. 111±47 ml/min/1.73 m2; P=0.90). Glycemic control was stable throughout the C-reactive protein levels [2.72 (0.34-10.3) vs. 2.03 (0.25-10.3) μg/l; P=0.21] were comparable after placebo and aspirin, respectively. There were no period (P=0.41) or carry-over effects (P=0.49). Conclusion: low-dose aspirin did not affect GFR and UAE levels of microalbuminuric type 2 DM. It seems that the putative low-grade inflammation of diabetic nephropathy does not respond to these low doses of the drug

A inflamação em baixo grau tem sido implicada na patogênese da nefropatia diabética e o uso de anti-inflamatórios poderia ser potencialmente útil como terapêutica. Objetivo: o objetivo deste estudo foi analisar o efeito de baixas doses de aspirina sobre a excreção urinária de albumina (EUA) e taxa de filtração glomerular (TFG) de pacientes com diabete melito(DM) tipo 2 microalbuminuricos. Métodos: neste estudo randomizado, duplo-cego, cruzado, controlado com placebo, 18 pacientes DM tipo 2 microalbuminuricos (EUA = 30-300 mg/24 h) receberam aspirina (300 mg/dia) ou placebo idêntico por 8 semanas, com um período de washout de 6 semanas. Os pacientes tinham idade de 56±9 anos, duração diabetes de 16±7,5 anos, 11 (61%) eram do sexo feminino, e todos estavam usando 20 mg de enalapril/dia. A TFG foi medida pelo 51Cr-EDTA e a EUA por imunoturbidimetria. O calculo do tamanho da amostra: 17 pacientes para detectar uma alteração de 30% na EUA (α=0,05 e β=0,20). Resultados: após 8 semanas, não houve diferenças significativas entre placebo e aspirina, respectivamente, em relação a EUA [57,7 (8,9-420,0) vs. 63 (8,2-272,0) mg/24 h;P=0,45] e TFG (108±34 vs. 111±47 ml/min/1,73 m2; P=0,90). O controle glicêmico manteve-se estável. Os níveis de proteína C reativa [2,72 (0,34-10,3) vs. 2,03 (0,25-10,3) mg/l; P=0,21] foram semelhantes após placebo e aspirina, respectivamente. Não houve efeito de período (P=0,41) ou carry-over (P=0,49). Conclusão: a inflamação de baixo grau descrita na patogênese da nefropatia diabética não responde a baixas doses de aspirina