Gemfibrozil Inhibits Legionella pneumophila and Mycobacterium tuberculosis Enoyl Coenzyme A Reductases and Blocks Intracellular Growth of These Bacteria in Macrophages

We report here that gemfibrozil (GFZ) inhibits axenic and intracellular growth of Legionella pneumophila and of 27 strains of wild-type and multidrug-resistant Mycobacterium tuberculosis in bacteriological medium and in human and mouse macrophages, respectively. At a concentration of 0.4 mM, GFZ completely inhibited L. pneumophila fatty acid synthesis, while at 0.12 mM it promoted cytoplasmic accumulation of polyhydroxybutyrate. To assess the mechanism(s) of these effects, we cloned an L. pneumophila FabI enoyl reductase homolog that complemented for growth an Escherichia coli strain carrying a temperature-sensitive enoyl reductase and rendered the complemented E. coli strain sensitive to GFZ at the nonpermissive temperature. GFZ noncompetitively inhibited this L. pneumophila FabI homolog, as well as M. tuberculosis InhA and E. coli FabI

Prediction of Preclinical Myocardial Dysfunction among Obese Diabetics with Preserved Ejection Fraction Using Tissue Doppler Imaging and Speckle Tracking Echocardiography

Background. Obesity and type 2 diabetes mellitus (T2DM) are two interrelated and preventable disorders. However, they are responsible for significant global mortality from cardiovascular diseases (CVDs). Clinical studies have demonstrated that global longitudinal strain (GLS) using speckle tracking echocardiography (STE), can assess myocardial function accurately in apparently, healthy patients with diabetes and obesity in the settings of acute and chronic ischemia and suspected cardiomyopathy without heart failure. No such studies have been published to date regarding subclinical detection of cardiac dysfunction among obese patients with T2DM. This study aims to investigate the role of STE in the early pre-clinical diagnosis of impairment of diastolic and systolic dysfunction in obese patients with T2DM. This study also investigated whether it is possible to detect early pre-clinical impairment of diastolic and systolic dysfunction in obese T2DM patients, via Tissue Doppler Imaging (TDI), maximum rate of left ventricular pressure development (peak dP/dt) and GLS using STE for comparison. Subjects and Methods. After clearance from the review board of Dibba- Hospital, Alfujairah, UAE, all the available records of patients with the diagnosis of obesity and diabetes were examined. The study included 214 patients presenting with obesity in conjunction with diabetes and 93 age-matched healthy control subjects. STE was performed among all the patients and subjects along with Tissue Doppler Imaging (TDI). This study assessed maximal rate of pressure rise during ventricular contraction (peak dP/dt) and global longitudinal strain (GLS) using STE methods. Transthoracic echocardiography, myocardial Doppler-derived systolic (sm), early diastolic velocity (em) and GLS were also obtained, among all the subjects. Results. The results show that cardiac functions via conventional echocardiography (CE) were similar in the 2 groups. Using TDI and conventional mitral Doppler flow, obese subjects with diabetes showed an evidence of diastolic function abnormalities in the form of lower Ea velocity (9.5 ± 2.9 vs. 18.4 ± 3.5 cm/s, p < 0.0001), an increased Aa velocity (16.5 ± 2.4 vs. 14.1 ± 2.2 cm/s p < 0.05), higher left ventricular filling pressure (E/Ea = 12 ± 4.4 vs 8±3.1), p 35) (n = 26) had reduced LV systolic and diastolic function compared with healthy controls. Regarding, systolic function indices, the findings revealed lower average longitudinal peak systolic strain, sm and reduced em, although, LV ejection fraction remained normal (56.48% ± 8.81). Among subjects with severe obesity (n = 26), the findings reveal that global longitudinal presystolic strain (GLPSS) is highly correlated with maximum rate of pressure development of LV (dp/dt), although the LVEF remained normal, in comparison to systolic strain and dp/dt. (.5% ±1.4 vs -19.54% ± 4.5; p < 0.001), in the age-matched healthy subjects. However, the frequency/grade of DCM detected by STE, among patients having obesity with T2DM, correlated closely with the degree of obesity, metabolic abnormalities and clustering of other major risk factors, especially high blood pressure. The findings also revealed that chest pain due to coronary heart disease (CAD), dyspnea and DCM were more common among female patients compared to men. Conclusion. The results indicate that patients having obesity with T2DM should be advised to undertake early TDI and STE for early diagnosis of decreased cardiac diastolic and systolic dysfunctions and cardiomyopathy, which is likely to be missed by conventional echocardiography. Significant differences in regional and global strain were also identified between the severely obese diabetic (BMI ≥ 35), (GLPSS (-13) patients compared to less obese subjects