Differential Effect of Three Macrolide Antibiotics on Cardiac Pathology and Electrophysiology in a Myocardial Infarction Rat Model: Influence on Sodium Nav1.5 Channel Expression.

Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) changes with increased risk in cardiac patients. We aimed to determine the impact of three macrolides, azithromycin, clarithromycin and erythromycin, on cardiac electrophysiology, cardiac enzyme activities, histopathological changes, and sodium voltage-gated alpha subunit 5 (Nav1.5) channel expression. We used eight experimental groups of male albino rats: vehicle, azithromycin (100 mg/kg), clarithromycin (100 mg/kg), erythromycin (100 mg/kg), MI + vehicle, MI + azithromycin (100 mg/kg), MI + clarithromycin (100 mg/kg) and MI + erythromycin (100 mg/kg); each group received chronic oral doses of the vehicle/drugs for seven weeks. ECG abnormalities and elevated serum cardiac enzymes were observed particularly in rats with AMI compared to healthy rats. Microscopic examination revealed elevated pathology scores for rats treated with clarithromycin in both experiments following treatment with erythromycin in healthy rats. Although rats with MI did not show further elevations in fibrosis score on treatment with macrolides, they produced significant fibrosis in healthy rats. Downregulation of cardiac Nav1.5 transcript was observed following macrolides treatment in both groups (healthy rats and rats with MI). In conclusion, the current findings suggested the potential cardiotoxic effects of chronic doses of macrolide antibiotics in rats with MI as manifested by abnormal ECG changes and pathological findings in addition to downregulation of Nav1.5 channels. Furthermore, in the current dose ranges, azithromycin produced the least toxicity compared to clarithromycin and erythromycin.

Simultaneous Determination of Elbasvir and Grazoprevir in Their Pharmaceutical Preparation Using High-Performance Liquid Chromatographic Method.

A high-performance liquid chromatographic method has been developed for simultaneous determination of elbasvir and grazoprevir; two new Food and Drug Administration (FDA) approved drugs. The two drugs were co-formulated for treatment of hepatitis C virus in their combined pharmaceutical dosage form. The chromatographic separation has been achieved using a reversed phase BDS Hypersil C18 column with a mobile phase consists of acetonitrile:methanol (50:50, v/v) at flow rate of 1 mL/min and UV detection at 253 nm. Computational investigation for finding the best stationary phase revealed that C18 column fits better for the simultaneous chromatographic analysis of the studied drugs. Linearity, accuracy and precision have been found to be acceptable over the concentration range of 1-20 µg/mL for the studied drugs. The described method has been successfully applied for simultaneous determination of the studied drugs in their pharmaceutical dosage form.

Respiratory symptoms in rheumatoid arthritis: relation to pulmonary abnormalities detected by high-resolution CT and pulmonary functional testing.

Pulmonary disease is the most frequent and among the most severe extra-articular manifestation of rheumatoid arthritis (RA). However, this issue has not been sufficiently studied in Egyptian patients. The objectives of the present study are to investigate the prevalence and types of pulmonary involvement using high-resolution computed tomography scan (HRCT) and pulmonary function tests (PFT) and evaluate the association between respiratory symptoms and RA-lung disease in a group of Egyptian RA patients. Thirty-six RA patients were recruited; 34 females (94.4%) and 2 males (5.6%) with median age of 48.5 years, and none of them was smoker. Detailed medical and drug histories were obtained. PFT, plain X-ray of the chest, and HRCT were performed to all subjects involved. Nearly 64% of RA patients demonstrated abnormalities in PFT and 47% in HRCT. Mixed restrictive and obstructive pattern was the commonest. Nearly two-thirds of our patients reported one or more pulmonary symptom whether dyspnea, cough, wheezing, or phlegm. Dyspnea was the most frequent symptom. Respiratory symptoms were statistically more common in patients with lung disease. The advanced age, high radiological score, and severity of rheumatoid disease were found to be predictive of lung involvement. Among respiratory symptoms, dyspnea and cough were associated with any pulmonary abnormalities. When specific pulmonary abnormalities were considered, only dyspnea was identified as predictor for restriction. For obstructive abnormality, both cough and wheezing provided valid prediction. We conclude that pulmonary involvement is a common manifestation in Egyptian RA patients, and the pattern of involvement is generally consistent with other studies that were performed worldwide. Specific respiratory symptoms could be used as practical, easy, and cost-effective method, especially in older and with more severe RA patients, to discriminate patients in need of subsequent PFT and HRCT imaging.