Protective role of nebivolol via AKT1/Hif-1α/eNOS signaling pathway: nephrotoxicity caused by methotrexate in a rat model.

Methotrexate (MTX) is an antineoplastic and anti-inflammatory agent, which is used in severe diseases. Its use should be limited due to side effects such as nephrotoxicity, myelotoxicity, and hepatotoxicity. Nebivolol (NBV), which is a beta-blocker used in the treatment of hypertension, also contributes to vasodilation in tissues by activating the endothelial nitric oxide synthase (eNOS) enzyme. The purpose of this study is to research the effect of NBV on MTX-induced nephrotoxicity through the AKT1/hypoxia-inducible factor 1-alpha (Hif-1α)/eNOS signaling pathway. The rats were randomly divided into three groups of eight each. The groups were control, MTX, and MTX + NBV. A single dose of 20 mg/kg MTX was given intraperitoneally to the rats on the first day of the study and 10 mg/kg NBV was given orally to the treatment group for 7 days. At the end of the study, rats' blood and kidney tissues were taken for histopathological, immunohistochemical, and biochemical examinations. MTX administration significantly decreased the expression levels of AKT1, eNOS, and Hif-1α compared with the control group (p < 0.001 for all), and NBV treatment increased these values compared with the MTX group (p < 0.001 for all). In conclusion, NBV treatment ameliorated the MTX-induced nephrotoxicity via AKT1/Hif-1α/eNOS signaling pathway.

Total Correction of Tetralogy of Fallot at Early Age: A Study of 183 Cases.

BACKGROUND: Opinions regarding the optimal time for the repair of tetralogy of Fallot vary. A debate also exists about the timing of repair for the asymptomatic infant. METHODS: This study included 183 patients with tetralogy of Fallot. All patients were subjected to clinical examination with measurement of oxygen saturation, 12-lead ECG, plain chest x-ray, and complete laboratory investigation. Echocardiography and cardiac catheterisation were indicated if there was an inability to reach diagnosis by echocardiography, suspicion of coronary anomaly, evaluation of distal pulmonary arteries or suspicion of major aorto-pulmonary collaterals. Complete repair was done in all patients. Patients were divided into two groups for comparison. Group 1 (147 patients, 1-year-old or less), and Group 2 (36 patients older than 1 year). RESULTS: Three patients died in Group1 (2.04%) while there was no early mortality in Group 2 patients. Six patients in Group 1 (4.08%) were reoperated for significant residual or recurrent right ventricular outflow stenosis, three patients (2.04%) were reoperated for residual significant shunt, and three patients (2.04%) were reoperated for residual significant stenosis and residual significant shunt. That is in addition to three patients (2.04%) who had significant tricuspid regurgitation, three more patients (2.04%) who needed a permanent pacemaker implantation, and nine patients (6.1%) who had significant postoperative pulmonary valve regurgitation. On the other hand, for Group 2 patients, there were only three patients who were reoperated for postoperative restenosis and significant shunt, three patients who were reoperated for permanent pacemaker implantation, and another two patients who had insignificant restenosis to be followed up. CONCLUSIONS: Early complete tetralogy of Fallot repair can be accomplished with a low mortality.

Impact of aortic prosthesis-patient mismatch on left ventricular mass regression.

BACKGROUND: Prostheses used for aortic valve replacement may be small in relation to body size, causing prosthesis-patient mismatch and delaying left ventricular mass regression. This study examined the effect of prosthesis-patient mismatch on regression of left ventricular mass after aortic valve replacement. METHODS: We prospectively studied 96 patients undergoing aortic valve replacement between 2007 and 2012. Mean and peak gradients and indexed effective orifice area were measured by transthoracic echocardiography at 3 and 6 months postoperatively. Patient-prosthesis mismatch was defined as indexed effective orifice area ≤0.85 cm(2)·m(-2). RESULTS: Moderate prosthesis-patient mismatch was present in 25% of patients. There were no significant differences in demographic and operative data between patients with and without prosthesis-patient mismatch. Left ventricular dimensions, posterior wall thickness, transvalvular gradients, and left ventricular mass decreased significantly after aortic valve replacement in both groups. The interventricular septal diameter and left ventricular mass index regression, and left ventricular ejection fraction were better in patients without prosthesis-patient mismatch. There was a significant positive correlation between the postoperative indexed effective orifice area of each valve prosthesis and the rate of left ventricular mass regression. CONCLUSIONS: Prosthesis-patient mismatch leads to higher transprosthetic gradients and impaired left ventricular mass regression. A small-sized valve prosthesis does not necessarily result in prosthesis-patient mismatch, and may be perfectly adequate in patient with small body size.

Traumatic intrathoracic tracheobronchial injuries: a study of 78 cases.

BACKGROUND: Tracheobronchial injuries are encountered with increasing frequency because of improvements in pre-hospital care. We reviewed our experience of these injuries to determine how to better recognize them and facilitate their correct management. METHODS: Patients with traumatic non-iatrogenic intrathoracic tracheobronchial injuries managed in 2 tertiary centers in Saudi Arabia between 2000 and 2012, were studied. Clinical presentation, diagnostic evaluation, management, and outcome were reviewed. RESULTS: 78 patients with tracheobronchial injuries were included in this study. They were divided into 2 groups according to the management strategy. Forty-seven patients who were managed conservatively, and 31 underwent surgery. Surgery allowed shorter intensive care unit and hospital stays; otherwise, the results were comparable between the two groups. CONCLUSIONS: Early recognition and expedient appropriate management are essential in these potentially lethal injuries. Operative management can be achieved with acceptable mortality, and conservative treatment should be considered as a valuable alternative to the well-established surgical treatment.

Cytochrome P450-isoenzyme 1A1 in susceptibility to tobacco-related lung cancer.

BACKGROUND: Tobacco smoke contains many carcinogens that may mediate susceptibility to lung cancer. Cytochrome P450 isoenzyme 1A1 activity and expression increases several fold in lung cancer due to smoking. Finding the role of cytochrome P450 1A1 in susceptibility to tobacco-related lung cancer may be important to predict the outcome in early stage cancer, and may result in an improved survival rate. PATIENTS AND METHODS: This study was carried on 2 groups of patients: group A was 20 patients with operable smoking-related lung cancer, who underwent surgery at the time of diagnosis; group B was 20 nonsmokers without lung cancer who underwent chest exploration following road traffic accidents. Specimens were obtained from tumor tissue and surrounding healthy tissue in group A patients, and from healthy lung tissue in group B patients. These specimens were sent for measurement of protein content and cytochrome P450 1A1 activity. RESULTS: There was significantly greater tissue cytochrome P450 1A1 activity in group A compared to group B. Patients with stage II cancer showed significantly higher levels of tissue cytochrome P450 1A1 activity than those with stage I. There was also a significant difference in tissue cytochrome P450 1A1 activity between the tumor tissue and the tissue surrounding the tumor. CONCLUSION: Carcinogens in smoke increase cytochrome P450 1A1 activity, which might be considered to play a role in cigarette smoking-induced lung cancer.

Intraoperative graft verification in coronary surgery: increased diagnostic accuracy adding high-resolution epicardial ultrasonography to transit-time flow measurement.

OBJECTIVES: Transit-time flow measurement (TTFM) allows intraoperative functional assessment of grafts in coronary artery bypass grafting (CABG). The major limitation of this technique is a low positive predictive value (PPV) that could lead to unnecessary graft revisions. A combined approach with high-resolution epicardial ultrasonography (HR-ECUS) and TTFM was evaluated for the first time in terms of diagnostic accuracy. The aim of this study is to evaluate the added value of intraoperative HR-ECUS for an improved graft patency verification. METHODS: From November 2009 to September 2012, 333 patients underwent isolated CABG. A total number of 717 grafts were performed; all grafts were intraoperatively verified by means of both TTFM and HR-ECUS. RESULTS: Among 678 grafts considered functioning at TTFM, 3 (0.4%) were failing at HR-ECUS and promptly redone (2 bilateral internal mammary artery-Y-grafts and 1 left internal mammary artery to left anterior descending (LIMA-LAD)). These were confirmed as true positive at graft revision due to technical error. HR-ECUS confirmed the good functioning of the remaining 675 grafts already demonstrated by TTFM; among them, 8 showed high troponin I release (clinical false negative), whereas the remaining 667 had no high TnI release (clinical true negative). In 2 of 39 grafts malfunctioning at TTFM, HR-ECUS confirmed the graft failure; surgical inspection of the anastomosis during redo procedure (in both cases LIMA-to-LAD graft) showed a technical error leading to define those 2 grafts as 'true positive' on the basis of either direct vision and improved post-redo TTFM parameters. Finally, in 35 cases, HR-ECUS did not confirm TTFM diagnosis demonstrating a full patency of the anastomosis; these grafts had an uneventful clinical course (true negative). The main result of this study is the increase of PPV from 10% with TTFM to almost 100% of TTFM + HR-ECUS, avoiding many unnecessary graft revisions. CONCLUSIONS: HR-ECUS should be considered complimentary to TTFM. Simultaneous use of the two methods during CABG provides morphological and functional information improving considerably diagnostic accuracy of intraoperative graft verification procedure close to 100%.