Heart disease is one of the major health problems of advanced as well as developing countries of the world. Extensive research through the last decade has shown beyond doubt that free radicals, particularly, reactive oxygen species play a cardinal role in the pathogenesis of oxidative myocardial damage with consequential cardiac malfunction. This review presents a comprehensive account of the present day knowledge regarding the oxygen free radicals involved in the genesis of ischemic heart disease, the mechanism(s) of oxidative myocardial damage and the endogenous as well as exogenous antioxidant defense systems. Furthermore, the role of ischemic pre-conditioning, some antioxidants and the ability of some cardioprotective drugs in providing protection against the ischemic myocardial damage are also discussed. The text of the article comes to an end with a commentary on the future research perspective in the concerned area, which throws a light on the development of combinatorial therapeutics in the treatment of ischemic myocardial disease.
To understand the mechanism of cardiovascular dysfunction in the hyperthyroid condition, the role of oxidative stress was examined in rats treated with 3,5,3'-triiodo-l-thyronine (T3). Treatment of rats daily with T3 (8 microg/100 g BW) for 15 days resulted in an increase in heart weight to body weight ratio, which was ameliorated by antioxidants, melatonin (2 mg/100 g BW) or vitamin E (4 mg/100 g BW). Both melatonin and vitamin E also inhibited rises of lipid peroxidation and hydroxyl radical generation and prevented the inhibition of Cu,Zn-superoxide dismutase in the hypertrophic heart. The expression of the glucose transporter, GLUT4, was reduced in response to T3, which was completely restored by melatonin and partially by vitamin E. However, neither antioxidant prevented down regulation of peroxisome proliferator-activated receptor-alpha in the hyperthyroid heart. Furthermore, the reduced level of myocyte enhancer factor-2, a regulator of GLUT4 transcription was restored completely by melatonin and partially by vitamin E treatment. Glucose uptake in hypertrophic left ventricular cells was also restored by these antioxidants. The expression of B-type natriuretic peptide, a marker of heart failure, was significantly increased by T3 and ameliorated by melatonin or vitamin E treatments. In general, the beneficial effects of melatonin given as a co-treatment with T3 were better than those induced by vitamin E. These data show that melatonin ameliorates hypertrophic growth of the myocardium induced by hyperthyroidism and provide an insight into the mechanism of reactive oxygen species-mediated down regulation of metabolically important genes such as GLUT4 in the heart.
The antiulcer effect of melatonin on gastric lesions caused by piroxicam was studied with the intent of determining the mechanism of action of this agent. Melatonin dose-dependently lowered piroxicam and indomethacin-induced gastric damage with more than 90% inhibition at a dose of 60 mg/kg BW. Increased lipid peroxidation, augmented protein oxidation and decreased glutathione content of the gastric tissue following piroxicam treatment indicated a possible involvement of oxidative stress in this nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Pretreatment of rats with melatonin prevented these changes. Oral administration of piroxicam to rats caused a threefold increase in the tissue levels of hydroxyl radical generation, a change significantly attenuated by melatonin. Furthermore, a decrease in the activity of gastric peroxidase and an increase in the activity of gastric superoxide dismutase(s) (SOD) because of piroxicam treatment was attenuated by melatonin pretreatment indicating that the indole possibly exerts its gastroprotective effects through its direct as well as indirect antioxidant activities. The results of the present studies also reveal that melatonin may influence the expression of Cu-Zn SOD, catalase, cyclooxygenase as well as alpha-actinin whose levels were found to be altered, following piroxicam treatment. The current studies, therefore, document melatonin's gastroprotective ability against piroxicam-induced gastric damage and the findings raise the possibility of melatonin being considered as a co-therapy with piroxicam or other NSAIDs in reducing the gastropathy when long-term use of these nonsteroidal agents are unavoidable.
Local dissemination of glaucoma screening guidelines with a protocol for referral did not appear to improve the diagnostic accuracy of optometrists in our area. Optometrists who follow the guidelines refer fewer normal individuals on IOP grounds, but false positive visual fields and optic disc interpretation difficulties remain a factor in such referrals. Additional strategies will be necessary to improve the quality and accuracy of referrals for suspect glaucoma by optometrists.
Experiments were carried out to identify the altered genes in hyperthyroid rat heart and their influence on the functions of cardiac myocytes. Chronic treatment of rats with 3,5,3 triiodo--thyronine (T3) resulted in a prominent increase in the size of the left ventricle with increased wall thickness and reduced chamber volume leading to concentric cardiac hypertrophy. The heart weight to body weight ratio (HW/BW) in hyperthyroid rats was increased by about 58% over that of normal rats. Using cDNA microarray comprising 588 genes, we compared the differences in mRNA expression of hyperthyroid and normal rat heart. Based on a threshold of greater than 10% change, about 37 genes were found to be regulated by T3. Further analyses by Western blotting, Northern blotting and real-time quantitative RT-PCR of some of the genes confirmed the microarray results. The T3-altered genes encode various types of proteins related to metabolism, matrix and cytoskeletal structures, growth factors, transcription factors, Ca 2+ -channels etc. The physiological significance of one of these altered proteins in hyperthyroid heart, insulin-responsive glucose transporter (GLUT) type 4 (GLUT4), was studied in detail. The expression of GLUT4 was drastically reduced in the ventricular tissues of hyperthyroid heart. Insulin-induced glucose uptake in hyperthyroid cardiomyocytes was reduced significantly, indicating the impaired glucose transport in cardiac cells. Interestingly, a few genes such as GLUT4, cytochrome P450 isoforms, superoxide dismutase (SOD), collagens, matrix metalloproteinases (MMP), tissue inhibitors of matrix metalloproteinases etc. which had not been reported earlier were found to be altered in hyperthyroid heart. Our results show some new aspects of hyperthyroid heart which will be important in assessing the pathophysiology of hypertrophied cardiomyocytes.
Gallstone ileus is an uncommon cause of small bowel obstruction and is rarely suspected preoperatively. Patients are usually elderly and present with features of small bowel obstruction. Commonest site of impaction of the gallstone is the terminal ileum. We report a case of gallstone ileus in a 37-year-old female who presented with vomiting and anuria, and without any symptoms of intestinal obstruction. Intraoperatively the gallstone was found impacted at the duodeno-jejunal flexure. Impaction of gallstone at the duodeno-jejunal flexure is yet to be reported in literature.
Background: Peptic Ulcer perforation is one of the most important and dreaded complication of peptic ulcer disease. In-spite of recent therapeutic management options available, it is still life threatening catastrophe. Sudden release of gastric and duodenal content in peritoneal cavity leads to devastating sequence of events which if not properly managed may lead to death. Age and Gender adjusted analysis of incidence, morbidity and mortality and the effect of ulcerogenic medications, addictions and H. Pylori infection in prognosis were studied here. Postoperative outcomes were also assessed after giving same type of treatments (Preoperative resuscitation, Graham’s Patch repair, and postoperative care) given by same surgical team.Aims and Objectives: The aims and objectives of this study were to investigate the latest trends of incidence, presentation, morbidity and mortality of benign perforated gastro-duodenal ulcer among the various age groups of population and to further study the risk factors associated with these events and study the association of addiction, ulcerogenic medications and H. Pylori infection.Materials and Methods: This observational descriptive study was conducted in R.G.Kar Medical College, Kolkata between the periods from January 2016 to June 2017 among 102 patients.Results: In this study of 102 patients 97% were male patients, maximum number of patient were from the age group 15 -30 years (45.1%).86.3% were from low socio- economic status and 40.2% residing in urban slum. Maximum number of patients presenting within 72 hrs (71%) having zero mortality. Seventy four percent of patients presented with shock if came between 4-5 days with 17.39% mortality. Patient presenting after 5 days had mortality of 75% and shock was 100% finding. Size <1 cm having 1% mortality but if size is >1 cm then mortality was >50.5%.Conclusion: Perforated peptic ulcer is common among males in second and third decade of their life with patients living in rural and urban slum commonly affected. Most common predisposing factors for PPU among younger population were addictions like smoking or alcohol intake. Among the elderly patients, intake of ulcerogenic medications like NSAID and steroids was the most common predisposing factor for PPU. Among patients of non-NSAID associated PPU, Helicobacter pylori infection was the major cause in the pathogenesis of PPU.Asian Journal of Medical Sciences Vol.9(6) 2018 68-75
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