ABSTRACT
A hipertensão é um importante problema de saúde pública associado ao aumento do risco de doenças cardiovasculares. Dentre outros modelos utilizados experimentalmente para estudar a hipertensão arterial, o modelo de hipertensão 2 rins-1clipe (2R1C) está associado à significativa ativação do sistema renina-angiotensina, produzindo alterações vasculares possivelmente decorrentes do aumento do estresse oxidativo e da ativação excessiva de metaloproteinases da matriz extracelular (MMPs). As MMPs são reguladas por vários processos, e a ativação dessas proteases promove degradação excessiva dos componentes da matriz extracelular e desse modo provoca um remodelamento vascular patológico. Entre várias dessas enzimas proteolíticas, asgelatinases (MMP-2 e MMP-9) têm merecido destaque por terem um importante papel nas doenças cardiovasculares. Estudos demonstram que o aumento na atividade e nos níveis de MMP-2 pode prejudicar o relaxamento vascular dependente do endotélio e causar hipertrofia arterial, especialmente da camada média, deposição excessiva decolágeno e elastina e, desse modo, contribuir para disfunção e remodelamento vascular hipertensivo. Portanto, como as MMPs desempenham importante papel no desenvolvimento e progressão de diversas doenças cardiovasculares, a inibição dessas proteases tem sido muito estudada e valorizada como uma importante estratégia terapêutica para o tratamento dessas doenças, inclusive das consequências deletérias da hipertensão arterial.
Hypertension is an important public health problem associated with increased risk of cardiovascular disease. The experimental model of hypertension-2 kidney 1clipe (2K1C) promotes significant activation of the renin-angiotensin system, and produces vascular changes associated with increased oxidative stress and upregulation of extracellular matrix metalloproteinases (MMPs). MMPs can be regulated by several processes, and increased activation of these proteases promotes excessive degradation of extracellular matrix components, thereby causing pathological vascular remodeling. Among these proteolytic enzymes,the gelatinases (MMP-2 and MMP-9), have shown an important role in cardiovascular disease. Studies show that increased activity and levels of MMP-2 may impair the endothelium-dependent vasorelaxation and cause artery wall hypertrophy, excessive deposition of collagen and elastin, thus contributing to dysfunction and hypertensive vascular remodeling. Therefore, as the MMPs play an important role in the development and progression of various cardiovascular diseases, inhibiting these proteases has been valued as a possible therapeutic strategy in the treatment of cardiovascular diseases, including the complications associated with hypertension.
Subject(s)
Humans , Chromatin Assembly and Disassembly , Extracellular Matrix Proteins , Hypertension , Matrix MetalloproteinasesABSTRACT
Despite the importance of gastrointestinal diseases and their global distribution, affecting millions of individuals around the world, the role and antimicrobial susceptibility patterns of anaerobic bacteria such as those in the Bacteroides fragilis group (BFG) are still unclear in young children. This study investigated the occurrence and distribution of species in the BFG and enterotoxigenic strains in the fecal microbiota of children and their antimicrobial susceptibility patterns. Diarrheic (n=110) and non-diarrheic (n=65) fecal samples from children aged 0-5 years old were evaluated. BFG strains were isolated and identified by conventional biochemical, physiological and molecular approaches. Alternatively, bacteria and enterotoxigenic strains were detected directly from feces by molecular biology. Antimicrobial drug susceptibility patterns were determined by the agar dilution method according to the guidelines for isolated bacteria. BFG was detected in 64.3 percent of the fecal samples (55 percent diarrheic and 80.4 percent non-diarrheic), and 4.6 percent were enterotoxigenic. Antimicrobial resistance was observed against ampicillin, ampicillin/sulbactam, piperacillin/tazobactam, meropenem, ceftriaxone, clindamycin and chloramphenicol. The data show that these bacteria are prevalent in fecal microbiota at higher levels in healthy children. The molecular methodology was more effective in identifying the B. fragilis group when compared to the biochemical and physiological techniques. The observation of high resistance levels stimulates thoughts about the indiscriminate use of antimicrobial drugs in early infancy. Further quantitative studies are needed to gain a better understanding of the role of these bacteria in acute diarrhea in children.