RESUMO
Antimicrobial resistance among bacterial strains has emerged out to be a serious threat and contributes to the loss of effectiveness of the common antibiotics. New Delhi metallo-ß-lactamase-1 (blaNDM-1) is an enzyme present in several pathogenic bacteria with a high incidence in Klebsiella pneumoniaie and plays a crucial role in the development of antibacterial resistance. Mur enzymes are also important alternative drug targets in addition to blaNDM-1 which are crucial for the survival of the bacteria. Vitex negundoi is an aromatic medicinaltree with proven antibacterial properties. Fifteen compounds from V. negundo were evaluated for their inhibitory effects on the target proteins blaNDM-1, Mur C, Mur E and Mur F of K. pneumoniae through molecular docking using the Glide (xp) module of Schrodinger. ADME toxicity was also predicted for all the fifteen compounds in the QikProp module. The docking results revealed that the compounds agnuside, negundoside and isoorientin showed promising inhibitory effects on all four targets blaNDM-1, Mur C, Mur E and Mur F of K. pneumoniae with docking scores greater than -7 kcal/mol and reasonable hydrogen bond interactions. The findings of this study provide a lead for developing novel drugs against potent multidrug-resistant K. pneumoniae.
RESUMO
Myocardial ischemia/reperfusion (I/R) injury is the major problem that aggravates cardiac damage. Several established animal models fail to explain the similarity in disease mechanism and progression as seen in humans; whereas guinea pig shows high similarity in cardiovascular parameters. Hence, current study is aimed to develop an animal model using guinea pigs that may best correlate with disease mechanism of human myocardial I/R injury. Male guinea pigs were randomized into three groups: normal diet (ND), high fat diet (HFD) and sham; fed with respective diets for 90â¯days. Myocardial infarction (MI) was induced by ligating left anterior descending artery (LAD) for 30â¯min followed by 24â¯h and 7â¯days of reperfusion in ND and HFD groups. Electrocardiogram (ECG) showed the alterations in electrical conduction during myocardial I/R injury. Elevated levels of lactate dehydrogenase (LDH) and creatine kinase-MB ((CK-MB)) were higher in HFD compared to ND. Inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were up-regulated in I/R injury animals compared to sham. Fold change of these protein expression levels were higher in HFD compared to ND. Elevated lipid profile and increased aortic wall thickness in HFD animals depicts the risk of developing cardiovascular complications. ECG analysis strongly confirmed MI through changes in sinus rhythm that are reflected in infarcted tissue as verified through TTC staining. Thus the combination of HFD followed by I/R injury proved to be an efficient model to study pathophysiology of myocardial I/R injury with minimal tissue damage and surgical mortality.