The present study evaluated the cardioprotective potential of bosentan, a mixed endothelin type A and B receptor antagonist, in the myocardial ischaemia-reperfusion model of myocardial infarction. Adult male wistar rats (175-225 g) were divided into three groups: sham operated, non-myocardial ischaemia-reperfusion (SHAM); saline-treated myocardial ischaemia-reperfusion control (CON); bosentan-treated myocardial ischaemia-reperfusion (BOS). All animals were anaesthetized and subjected to 40 min. occlusion of left anterior descending coronary artery followed by 120 min. of reperfusion. Saline or drug was administered to the CON or BOS group, respectively, 20 min. after the left anterior descending coronary artery occlusion. Haemodynamic parameters viz. systolic arterial pressure, diastolic arterial pressure and heart rate were recorded throughout the experimental period. Hearts were subsequently excised and processed for histopathological and infarct size evaluation and for biochemical estimation of cardiac specific enzyme creatine kinase-MB (CK-MB) and myocardial malondialdehyde, a lipid peroxidation marker. Myocardial ischaemic reperfusion resulted in severe myocardial injury, depression of haemodynamic function, significant increase in malondialdehyde levels and decline in CK-MB isoenzyme activity in the heart tissue. Administration of bosentan (3 mg/kg, intravenously) slightly improved haemodynamic effects, decreased myocardial oxygen consumption, significantly (PϽ0.01) attenuated the rise in malondialdehyde levels and loss of myocardial CK-MB isoenzyme activity compared to the CON group, whereas bosentan administration significantly reduced the percentage area of fiber loss and infarct area. It is therefore concluded that endothelin-1 may mediate myocardial damage produced by ischaemia and reperfusion and that dual blockade of endothelin A and endothelin B receptors may have potential as a mode of therapy for myocardial infarction.
Endothelin-1 has been shown to be associated with greater myocardial ischemia and reperfusion injury in which oxidative stress plays a key role. The efficacy of bosentan, a mixed ETA-ETB endothelin receptor antagonist, in protecting the myocardium from ischemia-reperfusion injury and oxidative stress was studied in open-chest Wistar rats. Anesthetized adult male rats (175-250 g b wt) underwent sham operation (SHAM group) or were subjected to 40 min of myocardial ischemia (MI) induced by temporary occlusion of the left anterior descending coronary artery (LAD) followed by 2 h reperfusion (R). Rats submitted to the MI-R protocol were administered bosentan at a dose of 3 mg/kg i.v. 20 min (BOS group) or saline (CON group) 20 min post-occlusion of LAD. After the 2 h reperfusion period the animals were euthanized and the heart rapidly excised. Cardiac tissue samples were snap frozen in liquid nitrogen for biochemical assay and were fixed in 10% formalin solution for histologic evaluation. Myocardial I-R resulted in a significant increase (p < 0.05) in the myocardial malondialdehyde levels and a decrease (p < 0.01) in the myocardial reduced glutathione content. These changes were associated with significant decreases in the myocardial activity of antioxidant enzymes superoxide dismutase (p < 0.05) and catalase (p < 0.01) and severe tissue damage in the jeopardized myocardium in the CON group as compared with the non-myocardial ischemia-reperfusion (NMI-R) SHAM group. Bosentan exerted marked tissue protective effect as assessed by histologic evaluation of the myocardium. The drug significantly (p < 0.05) attenuated myocardial oxidative stress and restored the cellular antioxidant defense mechanisms as compared with the saline-treated controls subjected to the MI-R protocol. Furthermore, bosentan also exerted a marked effect on peripheral hemodynamics and heart rate during the reperfusion phase (data reported elsewhere). These results are consistent with the concept that endothelin-1 may be involved in the pathogenesis of myocardial ischemia and infarction. This study demonstrates the antioxidant effect of non-selective endothelin receptor antagonism elucidating that, part of the aetiology of ischemia and reperfusion induced myocardial injury involves impaired antioxidant defenses.
While lymphopenia has been a common finding in COVID-19 infection, particularly in severe cases, febrile neutropenia has been very rarely reported in immunocompetent patients with COVID-19. Herein, we report the case of a 76-year-old hypertensive and diabetic man who was hospitalised with severe COVID-19 infection and developed delayed-onset severe neutropenia with neutropenic fever, which responded to treatment with antibiotics and granulocyte colony-stimulating factor. This case highlights the importance of identifying a rare complication (febrile neutropenia on the fifth week) of COVID-19 infection in hospitalised patients by intensive monitoring and aggressive management for favourable outcomes.
INTRODUCTION: Gall bladder cancer (GBC) accounts for 80%-95% of biliary tract malignancies in the world. There is however striking variability in the global incidence of gallbladder cancer, reaching epidemic levels for some regions and ethnicities. The aim of this study was to evaluate the demographic and clinicopathological profile of the gallbladder cancer patients. MATERIALS AND METHODS: All patients of carcinoma gall bladder presenting to department of surgery in hepatopancreaticobiliary unit from July 2017 to November 2020 were included in this study. A proforma containing all the relevant details including history, examination, blood, radiology, and pathological investigations was filled. RESULTS: A total of 326 patients of GBC were analyzed. The majority (75%) were found to be females with a mean age of 55 years. Pain abdomen was the most common presenting symptom in 81% of patients. The most common stage of presentation was stage IV and only 6 were in stage I. Two hundred and thirty three (71.4%) patients had metastatic disease at presentation. Liver infiltration at the time of diagnosis was present in 89% of patients. The most common site of metastasis was found in the liver (23.3%). GBC was more common in patients with A blood group. Baseline serum albumin levels were found to be significantly associated with the staging of GBC. CONCLUSIONS: Due to the non specific symptoms patients of GBC present at very advanced stages, high index of suspicion and health education seems to play an important role in early detection and improvement of survival.
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