Novel carbazolyl-thiazolyl-chromone and carbazolyl-thiazolyl-pyrazole hybrids: synthesis, cytotoxicity evaluation and molecular docking studies.

A simple synthetic method was performed to design a novel series of polycyclic systems consisting of carbazole-thiazolidinone-chromone hybrids 4a-e and carbazole-thiazolidinone-pyrazole hybrids 5a-e in excellent yields. The methodology depended on the one-pot four-component reaction of 3-amino-9-ethylcarbazole, substituted isothiocyanates, ethyl bromoacetate and 6-methyl-3-formylchromone in ethanol under ultrasound waves at 50 °C to give the carbazole-thiazolidinone-chromone hybrids 4a-e. The latter isolated products were treated with hydrazine hydrate in ethanol under ultrasound waves at 50 °C affording the corresponding carbazole-thiazolidinone-pyrazole hybrids 5a-e. Spectral and analytical data confirmed the structures of all the synthesized compounds. The target compounds were screened for their in vitro anticancer activities against HCT116, PC3 and HepG2 cancer cell lines using the standard SRB method. Fortunately, both compounds 5dand5e were the most active against all cancer cell lines compared with doxorubicin and can be promising anticancer agents. Both bioactive products 5band5e were studied by the molecular docking to see how they bind with VEGFR-2 receptor. The results indicated that those compounds exhibited high affinities towards VEGFR-2 and established remarkably similar interactions to those of the powerful VEGFR-2-KDR.

Early postoperative paravalvular leak among Egyptian population: An observational study.

OBJECTIVES: Several reports described the incidence of postoperative paravalvular leakage (PVL) early after valve replacement surgery, however, there is a paucity of data regarding the outcomes and complications correlated to the severity of PVL. The aim of the current study was to evaluate the incidence, causes, and short term outcome of early postoperative PVL. METHODS: Data were collected from patients presenting to the cardiovascular department at Cairo University Hospital for aortic and/or mitral valve replacement surgery from May 2014 to May 2015. Transthoracic echocardiography (TTE) was done for all patients early postoperative. Transesophageal echocardiography (TEE) was done if diagnosis was not confirmed by TTE. All patients with detected PVL were subjected to TTE and TEE after a 3 month follow-up period. RESULTS: Two hundred patients were enrolled in the study. Seventy five percent of patients were known to have rheumatic heart disease, while 16.5% had infective endocarditis. The mitral valve was replaced in 40% of patients, the aortic valve was replaced in 36%, and other patients had both valves replaced. Early postoperative period PVL was detected in 25 patients. The most common underlying etiologies were rheumatic heart disease and infective endocarditis. PVL was common in patients with both valves replaced compared with either mitral or aortic valve replacement. Infective endocarditis as underlying valve disease was significantly high in patients with PVL compared with those without (p < 0.001). CONCLUSION: The incidence of PVL was high in patients with both valves replaced compared with either mitral or aortic valve replacement. Moreover, every patient with PVL should be properly investigated for infective endocarditis. Surgical intervention, although associated with high morbidity and mortality, reduces PVL recurrence.

Evaluation of pulmonary artery pressure and resistance by pulsed Doppler echocardiography in patients with end-stage renal disease on dialysis therapy.

BACKGROUND: Pulmonary hypertension (PH) is one of the most important comorbidities in patients undergoing hemodialysis (HD). The goal of the present work is to determine the possible etiologic factors for its occurrence. METHODS: The prevalence of PH was estimated by Doppler echocardiography in a cohort of 100 patients aged 49.3 ± 13.9 years on regular HD. Mean pulmonary artery pressure was estimated from pulmonary acceleration time by Mahan's regression equation. Pulmonary vascular resistance and pulmonary capillary wedge pressure were calculated. We focused on the effect of HD on left and right ventricle diastolic and systolic function. Right ventricle systolic function was assessed by tricuspid annular systolic excursion and pulsed Doppler myocardial performance index. Since impaired endothelial function was postulated as an underlying cause of PH, we studied the effects of HD on brachial artery endothelial function. RESULTS: The current study found that pulmonary hypertension was prevalent in 70% of patients on dialysis. Left atrium diameter, left ventricle mass indexed to body surface area, and mitral E/E' were increased in the dialysis group (4.4 ± 0.2 cm, 126.5 ± 24.6 g/m(2), and 16.9 ± 4.4, respectively, p < 0.001 for all). Pulmonary artery systolic pressure was positively correlated to duration of dialysis and negatively correlated to glomerular filtration rate (p < 0.001 and r = -0.991). Pulmonary vascular resistance was significantly increased in dialysis patients (1.9 ± 0.2 Wood units vs. 1.2 Wood units in controls, p < 0.001). Endothelial dysfunction, defined as brachial artery flow mediated dilatation <6%, was found in 46% of dialysis group. CONCLUSION: Increased pulmonary artery systolic pressure in the HD population could be attributed to left atrium dilatation and left ventricle diastolic dysfunction. Pulmonary vascular resistance was significantly increased in dialysis group. This might be explained by impaired endothelial nitric oxide synthesis that not only caused systemic vasoconstriction but also affected the pulmonary vasculature.

Early Detection of Subclinical Uremic Cardiomyopathy Using Two-Dimensional Speckle Tracking Echocardiography.

BACKGROUND: Overhydration has a deleterious effect on cardio myocytes. This study was designated to evaluate left ventricular (LV) systolic and diastolic dysfunction in patients with various stages of chronic kidney disease (CKD) using conventional, tissue Doppler and two-dimensional speckle tracking echocardiography (2DSTE). METHODS: Forty controls and 90 CKD patients, aged 49.3 ± 14 years old, were enrolled in the study. Patients were divided into 3 groups depending on their glomerular filtration rate. Group 1 (≥60 mL/min per 1.73 m(2) ), group 2 (≤60 mL/min per 1.73 m(2) ), and group 3 (≤60 mL/min per 1.73 m(2) and on regular dialysis for at least 12 months). Pulsed-Doppler and tissue Doppler studies were used to estimate LV filling pressure E/E'. Using 2DSTE, circumferential, radial, and longitudinal functions of the LV have been measured. RESULTS: LV longitudinal systolic strain, early, and late diastolic strain rates were significantly reduced in CKD patients (-16.9 ± 3.8%, 1.6 ± 0.5%, and 1.3 ± 0.4% in CKD vs. -22.5 ± 0.6%, 2.3 ± 0.2%, and 1.9 ± 0.1% in controls, P < 0.001 for all), and no difference was observed in terms of the circumferential LV functions (-22.4 ± 1.7 vs. -22.5 ± 1.4, P = 0.567). Severity of the kidney dysfunction appears to parallel with the rise of E/E' significantly (P < 0.001). CONCLUSION: In CKD, although the longitudinal and radial systolic functions were reduced, LV ejection fraction may remain within normal limits due to the preservation of the circumferential functions. Early detection of uremic cardiomyopathy might provide useful information for the risk stratification and decide the proper dialysis therapy in these patients.

Detection of Left Atrium Myopathy Using Two-Dimensional Speckle Tracking Echocardiography in Patients with End-Stage Renal Disease on Dialysis Therapy.

BACKGROUND: Left atrium (LA) deformation analysis by two-dimensional speckle tracking echocardiography (2DSTE) has recently been proposed to evaluate left ventricular (LV) filling pressure in dialysis patients. AIM: The purpose of this study was to study the LA function in dialysis patients using two-dimensional speckle tracking echocardiography correlated to prevalence of atrial fibrillation, echocardiographically pulmonary capillary wedge pressure, and right ventricle systolic pressure. METHODS: Hundred adult patients aged 49.3 ± 13.9 years on regular hemodialysis and 40 healthy individuals were enrolled in the study. Left ventricular dimensions, ejection fraction, and mass index were studied. Left atrium volume index (LAVI) was calculated by dividing left atrium volumes by body surface area. Left ventricle filling pressure was evaluated according to E/E'. Left atrium global systolic strain (LASS) was studied using 2DSTE. Left atrium stiffness was calculated noninvasively based on the ratio of E/E' to LASS. Right ventricle systolic pressure was estimated with the Bernoulli equation formula. RESULTS: Left atrium diameter, left ventricle indexed mass, mitral (E/E'), and LA stiffness were increased in dialysis group 4.4 ± 0.2 cm, 126.5 ± 24.6 g/m(2) , 16.9 ± 4.4, and 0.5 ± 0.1, respectively, P < 0.001 for all. Left atrium systolic strain was significantly decreased in dialysis patients (26.6 ± 1.9 vs. 33.7 ± 2.1%, P < 0.001). Left atrium stiffness was significantly higher in dialysis patients with atrial fibrillation (AF) compared to those without AF. CONCLUSION: Assessment of LA deformation parameters predicts LV diastolic dysfunction and right ventricle systolic pressure in dialysis patients. Left atrium function in dialysis patients was impaired before the occurrence of left atrium dilatation.