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H S Sharma

Publications and source records attributed to H S Sharma.

190 records · Page 11Linked to original sources
PubMedDate not supplied

Coordinated expression of heme oxygenase-1 and ubiquitin in the porcine heart subjected to ischemia and reperfusion.

Heme oxygenase (HO) isozymes, HO-1 and HO-2 catalyze the cleavage of heme b to form the antioxidant biliverdin IXa, iron and the putative cellular messenger carbon monoxide (CO). Heat and stress have been reported to induce the expression of HO-1, in analogy to ubiquitin, a protein of 8 kDa involved in ATP dependent proteolysis. Earlier, we have shown in anesthetized pigs that brief periods of coronary artery occlusion followed by reperfusion produce prolonged regional cardiac dysfunction (stunning) associated with altered expression of a number of genes. In the present study, we report on a coordinated expression pattern of HO-1 and ubiquitin in the same porcine model in which the left anterior descending coronary artery (LAD) was occluded for 10 min and reperfused for 30 min (group I) and after a second occlusion of 10 min, reperfused for either 30 min (group II) or 90 min (group III) or 210 min (group IV). Myocardial tissue from LAD (stunned) and left circumflex coronary artery (LCx, control) perfused regions were collected in liquid nitrogen and analysed by Northern and dot blot hybridization techniques. We demonstrated a basal myocardial expression of multiple mRNAs (monomer and polymers) encoding ubiquitin and a single mRNA species (1.8 kb) encoding HO-1. However, the expression of both genes was drastically enhanced in the stunned myocardium as compared to the control in groups II and III with maximum mRNAs levels in group II. These results suggest that the myocardial adaptive response to ischemia involves the coordinated induction of HO-1 and ubiquitin, which may be indicative for the existence of a pathophysiologically important defense mechanism whereby, both degradation of denatured cellular proteins and generation of biologically active products of heme metabolism are accelerated.

Animals↗
PubMedDate not supplied

Cytoprotective mechanisms in cultured cardiomyocytes.

Tumor necrosis factor-alpha (TNF-alpha), a potent cytokine mainly secreted by macrophages exerts pleiotropic effects on different cell types. However, the intracellular mediators of its action are not yet well characterized. To get an insight into endogenous cytoprotective mechanisms, we developed an in vitro model based on cultured cardiomyocytes treated with TNF-alpha at which we examined gene expression of heat shock proteins (HSP-27, HSP-70 and ubiquitin). Cardiomyocytes were isolated from the hearts of 18 day old fetal mice by enzymatic dissociation and grown in minimum essential medium containing 10% fetal calf serum. Spontaneously contractile cells were serum deprived for 24 h and treated with TNF-alpha (25 ng/ml) for 1, 2, 4, 6, 8, 12, and 24 h After each incubation, cells were processed to extract total proteins for Western and total RNA for Northern blot analyses. TNF-alpha induced arrhythmias and cessation of spontaneous contractions in a concentration and time dependent manner. Steady state (ubiquitin) or undetectable mRNA levels (HSP-27, HSP-70) were drastically induced (> 4 fold for all three genes vs untreated control cells) by TNF-alpha, reaching maximal values between 6-8 h of stimulation. Thereafter, the expression of these stress genes declined but remained elevated as compared to control. By Western blot analysis, we found increased multiple bands of ubiquitin protein conjugates in TNF-alpha treated cells whereas no significant change in HSP-27 protein accumulation until 12 h was observed as compared to control. 24 h of TNF-alpha incubation resulted in partial cellular necrosis. Our results indicate that TNF-alpha induces in cardiomyocytes transiently gene expression for cytoprotective molecules like HSP-27, HSP-70 and ubiquitin, suggesting these stress proteins to participate in subsequent defense mechanisms, for example in postischemic myocardial recovery.

Animals↗
PubMedDate not supplied

Hyperthermia induced pathophysiology of the central nervous system.

This review is focused on the pathophysiology of the central nervous system (CNS) associated with mild-to-moderate hyperthermia (body temperature > 37 degrees C but <40 degrees C) induced thermal stress in Human cases as well as whole body hyperthermia (WBH) in animal studies. Pathological changes can be observed in the nerve cells and glial cells in Humans following mild-to-moderate thermal exposure. On the other hand, morphological changes in the axons, nerve cells, glial cells and vascular endothelium is seen at the cellular and the molecular levels in rats subjected to heat exposure at 38 degrees C for 4 h (body temperature > 40 degrees C but <42 degrees C). This effect depends on the age of the animals and their prior thermal experiences. Taken together, heat stress induced hyperthermia, once believed to be non-toxic in the mammalian CNS, do produce specific alterations in the CNS that may have long-term behavioural, physiological and neuropathological consequences. The probable mechanism(s) underlying hyperthermia induced brain pathology is discussed.

Animals↗
PubMedDate not supplied

Influence of ambient temperature and drug treatments on brain oedema induced by impact injury on skull in rats.

The progression and persistence of oedema development following impact-injury on closed skull was studied in anaesthetised as well as in unanaesthetised rats. The degree and rate of oedema development, following trauma, was aggravated in anaesthetised hypothermic animals but was reduced/or delayed by maintenance of body temperature at euthermic level. In general, the unanaesthetised animals showed a greater accumulation of oedema fluid than the corresponding anaesthetised group. The development of oedema corresponded more or less with the accumulation of 5-HT level in plasma and brain. This development of oedema was completely prevented following pretreatment with p-CPA, indomethacin paracetamol and aminophylline in unanaesthetised animals; whereas these drugs were able only to partially reduce the oedema development in euthermic anaesthetised animals. On the other hand the cyproheptadine pretreatment aggravated the oedema development which was more pronounced in unanaesthetised animals. The probable mechanism of the action of these drugs has been discussed.

Acetaminophen↗
PubMedDate not supplied

Role of 5-HT on increased permeability of blood-brain barrier under heat stress.

Exposure of young rats (9-10 wks) to chronic summer heat (36 degrees C) or acute heat (38 degrees C 4hr) increased the BBB permeability to Evans blue albumin complex (MW 68,000) and 131I-sodium (MW 154) in different brain regions which correlated well with the increased level of 5-HT in plasma and brain. This increased permeability of BBB and the increased 5-HT level were prevented by pretreatment with p-CPA, indomethacin and diazepam. Cyproheptadine and vinblastine pretreatment however, prevented only the increased permeability of BBB, the plasma and brain 5-HT level continued to remain high. These results indicate a probable role of 5-HT as one of the factors leading to the increased permeability of BBB in young rats following heat stress.

Animals↗
PubMedDate not supplied

Impairment of blood-brain barrier (BBB) in rat by immobilization stress: role of serotonin (5-HT).

Influence of immobilization stress on blood-brain barrier (BBB) was studied in rats using Evans blue as barrier tracer. 7-9 hr of of immobilization had increased the permeability of BBB mainly in younger rats. This increased permeability was significantly reduced with p-CPA, indomethacin or vinblastine pretreatment. Theophylline treatment caused early extravasation of Evans blue dye. The increased level of serotonin in immobilization and infusion of 5-HT in model experiments suggest a causative role of serotonin in the increased permeability of BBB induced by immobilization stress.

Animals↗
PubMedDate not supplied

Effect of indomethacin (a prostaglandin synthetase inhibitor) on the permeability of blood-brain and blood-CSF barriers in rat.

Effect of indomethacin on the permeability of blood-brain and blood-csf barriers to Evans blue, bromophenol blue and horseradish peroxidase (HRP) was studied by administering the drug through right internal carotid artery, right external jugular vein and through intraperitoneal route in rats. Increased permeability was observed on internal carotid arterial injection but not following jugular vein or intraperitoneal injection. This increased permeability of blood-brain and blood-csf barriers following injection of indomethacin into the internal carotid artery is associated with a steep and sustained rise in mean arterial blood pressure (MABP), a feature not observed in bilateral adrenalectromised animals.

Adrenalectomy↗
PubMedDate not supplied

Relationship of renal transplantation to hypertension in chronic renal failure.

Hypertension is prevalent in 49% of renal transplant recipients. Chronic rejection and impaired renal function may account for mild to moderate hypertension in most patients. The development of severe hypertension following renal transplantation, however, suggests TRAS, which is amenable to surgical correction with a high probability of success. Post-transplant hypertension did not correlate with renal diagnoses, sex, donor source and/or prednisone dose.

Acute Kidney Injury↗