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Biomedical subjects

Vijay Sharma

Publications and source records attributed to Vijay Sharma.

At least 19 recordsLinked to original sources
PubMed2006

AMPK control of myocardial fatty acid metabolism fluctuates with the intensity of insulin-deficient diabetes.

Flexibility in substrate selection is essential for the heart to maintain production of energy and contractile function, and is managed through multiple mechanisms including PPAR-alpha and AMP-activated protein kinase (AMPK). Rats injected with 55 mg/kg STZ (D55) were kept for 4 days (acute diabetes; D55-A) prior to termination. Fatty acid (FA) oxidation increased in D55-A hearts, with no significant change in gene expression of PPAR-alpha, or its downstream targets. However, both AMPK and ACC phosphorylation were significantly higher in these hearts, effects that were reversed by insulin. Unexpectedly, when the duration of diabetes in D55 rats was extended to 6 weeks (chronic diabetes; D55-C), AMPK and ACC phosphorylation were comparable in control and D55-C hearts. In D55-C rat hearts, lack of AMPK activation was closely associated to an overload of plasma and cardiac lipids. To validate the relationship between lipids and cardiac AMPK activation, we either induced more severe diabetes (100 mg/kg STZ to provoke both hyperglycemia and hyperlipidemia acutely; D100-A) or infused intralipid (IL) to enlarge circulating lipids. There was no difference in cardiac AMPK and ACC phosphorylation in D100-A rats compared to control. Measurement of AMPK and ACC phosphorylation in control and D55-A hearts revealed that their phosphorylation was inhibited by acute intralipid infusion. Our data suggest that activation of AMPK is an adaptation that would ensure adequate cardiac energy production when glucose utilization is compromised. However, in severe diabetes, with the addition of augmented plasma and heart lipids, AMPK activation is prevented, and control of FA oxidation is likely through alternate mechanisms. Given that AMPK plays an important role in preventing cardiac ischemic/reperfusion damage, it is possible that in these diabetic hearts, the accelerated damage observed during exposure to ischemia/reperfusion could be a likely outcome of a compromised activation of AMPK.

AMP-Activated Protein Kinases↗
PubMed2006

N-acetylcysteine attenuates TNF-alpha-induced human vascular endothelial cell apoptosis and restores eNOS expression.

The circulatory inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is increased in pathological conditions, such as diabetes, which initiate or exacerbate vascular endothelial injury. Both nitric oxide (NO) and reactive oxygen species may play a dual role (i.e., inhibiting or promoting) in TNF-alpha-induced endothelial cell apoptosis. We investigated the effects of the antioxidant N-acetylcysteine on TNF-alpha-induced apoptosis in human vascular endothelial cell (cell line ECV304) apoptosis, NO production and lipid peroxidation. Cultured vascular endothelial cell (ECV304) were either not treated (control), or treated with TNF-alpha (40 ng/ml) alone or TNF-alpha in the presence of N-acetylcysteine at 30 mmol/l or 1 mmol/l, respectively, for 24 h. Cell viability was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was assessed by flow cytometry. TNF-alpha-induced endothelial cell apoptosis was associated with increased inducible NO synthase but reduced endothelial NO synthase (eNOS) protein expression. NO production and the levels of the lipid peroxidation product malondialdehyde were concomitantly increased. Treatment with NAC at 30 mmol/l restored eNOS expression and further increased NO production as compared to TNF-alpha alone, resulting in improved cell viability and reduced apoptosis. This was accompanied by increased superoxide dismutase activity, increased glutathione peroxidase production and reduced malondialdehyde levels. N-acetylcysteine at 1 mmol/l, however, did not have significant effects on TNF-alpha-induced endothelial cell apoptosis and cell viability despite it slightly enhanced glutathione peroxidase production. N-acetylcysteine attenuation of TNF-alpha-induced human vascular endothelial cell apoptosis is associated with the restoration of eNOS expression.

Acetylcysteine↗
PubMed2006

Bickerstaff's brainstem encephalitis: can it recur?

Bickerstaff's brain-stem encephalitis is usually a monophasic post-viral inflammatory illness characterized by progressive ophthalmoplegia, ataxia and disturbance of consciousness (or hyper-reflexia). Since the clinical spectrum of Bickerstaff encephalitis may overlap with the Miller-Fisher and Guillain-Barré syndromes, the presence of anti- GQ1b antibodies and abnormal brain MRI can help to support its diagnosis. However, absence of anti-GQ1b antibodies and normal MRI do not exclude the diagnosis, which remains based on clinical criteria and exclusion of other etiologies. We report a case of recurrent Bickerstaff's brainstem encephalitis with no identifiable antecedent illness, and overlapping features of Miller Fisher and Guillain-Barré syndromes, in the presence of negative anti-GQ1b antibodies and repeatedly normal MRI of the brain.

Brain Stem↗
PubMed2006

Single photon emission computed tomography and positron emission tomography imaging of multi-drug resistant P-glycoprotein--monitoring a transport activity important in cancer, blood-brain barrier function and Alzheimer's disease.

Overexpression of multi-drug resistant P-glycoprotein (Pgp) remains an important barrier to successful chemotherapy in cancer patients and impacts the pharmacokinetics of many important drugs. Pgp is also expressed on the luminal surface of brain capillary endothelial cells wherein Pgp functionally comprises a major component of the blood-brain barrier by limiting central nervous system penetration of various therapeutic agents. In addition, Pgp in brain capillary endothelial cells removes amyloid-beta from the brain. Several single photon emission computed tomography and positron emission tomography radiopharmaceutical have been shown to be transported by Pgp, thereby enabling the noninvasive interrogation of Pgp-mediated transport activity in vivo. Therefore, molecular imaging of Pgp activity may enable noninvasive dynamic monitoring of multi-drug resistance in cancer, guide therapeutic choices in cancer chemotherapy, and identify transporter deficiencies of the blood-brain barrier in Alzheimer's disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Edema disease caused by a clone of Escherichia coli O147.

Edema disease is a systemic disease of weaned pigs caused by host-adapted strains of Escherichia coli, most commonly belonging to serogroup O138, O139, or O141. In the late 1990s, E. coli O147 strains containing the virulence genes f18, sta, stb, and stx(2) were recovered from outbreaks of edema disease in the United States. Pulsed-field gel electrophoresis (PFGE) was used to determine that the majority of these strains (34/43) were closely related to one another. Subsequent analysis by multilocus restriction typing confirmed the PFGE results and indicated that the cluster of edema disease strains were only distantly related to other E. coli O147 strains. Serogrouping of edema disease isolates from the Iowa State University Veterinary Diagnostic laboratory recovered between 1996 and 2000 indicated that 42% belonged to serogroup O147. Our data suggest that these strains may be a common serotype of edema disease-causing E. coli in the United States.

Animals↗
PubMed2006

The etiology of hypertension in the metabolic syndrome part four: the systemic perspective--the role of the neuroendocrine and immune systems, and the challenge of integration.

Insulin resistance can be regarded to be a cause, a consequence, a sustainer or a marker of the wider neuroendocrine dysfunction within which it occurs. In the final part of our series of reviews, we examine the systemic influences which operate within the metabolic syndrome: the endocrine system, the central nervous system and the immune system. We discuss strategies for integrating the array of information that is being gathered, in particular the need for computer simulation. We also advocate the need to move beyond the linear paradigm of 'cause and effect' and use causal networks to think about this system. We also discuss the need to understand the temperospatial organisation of the factors being studied. Finally, we draw together the data, concepts and hypotheses we have reviewed over the course of these four articles.

Adipose Tissue↗
PubMed2006

The etiology of hypertension in the metabolic syndrome part one: an introduction to the history, the concept and the models.

Hypertension is a complex, multifactorial disorder which is an important cause of morbidity and mortality in the modern world. The study of hypertension in the context of the metabolic syndrome has yielded some important insights into the etiology of the condition. With the recent controversy surrounding the existence of the metabolic syndrome and the clear need for further research, we have undertaken a four part review of the literature in this field to provide a comprehensive overview of experimental and clinical research as it currently stands. In Part One, we review the history of hypertension and the metabolic syndrome, discuss the role of the metabolic syndrome as a concept and a diagnosis, and provide an introduction to insulin resistance and hyperinsulinemia. We also provide a broad overview of the range of animal models which are used to study these conditions.

Animals↗
PubMed2006

The etiology of hypertension in the metabolic syndrome part three: the regulation and dysregulation of blood pressure.

To understand blood pressure is regulated, and how this regulation is disturbed in hypertension, we need to understand how blood volume is regulated and how the distribution of that volume across the vascular tree is regulated. Here we review the literature on blood volume regulation and how it is disturbed in the pre-diabetic and diabetic state. We also provide a comprehensive overview of vascular dysfunction, discussing the key mechanisms, mediators and pathways which are involved. In particular, we focus on the key concept of endothelial dysfunction and how this has shaped our understanding of hypertension.

Animals↗
PubMed2006

The etiology of hypertension in the metabolic syndrome part two: the gene-environment interaction.

The pathogenesis of obesity, insulin resistance and hypertension begins with an interaction between genetic factors and environmental factors. The search for the underlying genetic basis of these conditions has yielded disappointing results. It is possible that the importance of environmental influences has been underestimated. In Part Two of our series of reviews, we discuss the key genetic, environmental and evolutionary influences which lead to the development of these conditions, and provide a detailed account of the mechanisms by which these influences produce their effects.

Animals↗
PubMed2006

Scrub typhus in Himalayas.

Himachal Pradesh state of India is situated in the outer Himalayan ranges. During the rainy season, several cases of acute febrile illness of unknown origin occurred. Orientia tsutsugamushi was identified as the causative agent by microimmunofluorescence and PCR. Two new genotypes of O. tsutsugamushi were identified in the region.

Fever↗
PubMed2005

Amoebic renal cyst: a case report.

Entamoeba histolytica can infect any organ of the body, but only one case of renal involvement has been reported till now in the literature. We report a rare case of amoebic renal cyst in a 78-year showing favorable outcome with metronidazole treatment and therapeutic drainage.

Aged↗
PubMed2005

Vanadium complexes with mixed O,S anionic ligands derived from maltol: synthesis, characterization, and biological studies.

Four mixed O,S binding bidentate ligand precursors derived from maltol (3-hydroxy-2-methyl-4-pyrone) have been chelated to vanadium to yield new bis(ligand)oxovanadium(IV) and tris(ligand)vanadium(III) complexes. The four ligand precursors include two pyranthiones, 3-hydroxy-2-methyl-4-pyranthione, commonly known as thiomaltol (Htma), and 2-ethyl-3-hydroxy-4-pyranthione, commonly known as ethylthiomaltol (Hetma), as well as two pyridinethiones, 3-hydroxy-2-methyl-4(H)-pyridinethione (Hmppt) and 3-hydroxy-1,2-dimethyl-4-pyridinethione (Hdppt). Vanadium complex formation was confirmed by elemental analysis, mass spectrometry, and IR and EPR (where possible) spectroscopies. The X-ray structure of oxobis(thiomaltolato)vanadium(IV),VO(tma)(2), was also determined; both cis and trans isomers were isolated in the same asymmetric unit. In both isomers, the two thiomaltolato ligands are arranged around the base of the square pyramid with the V=O linkage perpendicular; the vanadium atom is slightly displaced from the basal plane [V(1) = 0.656(3) A, V(2) = 0.664(2) A]. All of the new complexes were screened for insulin-enhancing effectiveness in streptozotocin-induced diabetes in rats, and VO(tma)(2) was profiled metabolically for urinary vanadium and ligand clearance by GFAAS and ESIMS, respectively. The new vanadium complexes did not lower blood glucose levels acutely, possibly because of rapid dissociation and excretion.

Animals↗
PubMed2005

Therapeutic drugs for targeting chloroquine resistance in malaria.

While the post-genomic era could lead into new targets for antimalarial drug development, herein few successful targets including medicinals involved in those processes are presented. Further, contribution of bioinorganic chemistry has also started to make its impact in the field of pharmaceuticals. Therefore, metal chelators, selected organometallics, and metalloantimalarials that would offer potential therapeutic drugs are also discussed. Finally, a brief summary on chloroquine-resistance mechanism(s) has been included.

Animals↗
PubMed2005

The emerging roles of leptin and ghrelin in cardiovascular physiology and pathophysiology.

Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the central control of appetite. More recently, it has become clear that these hormones have a range of effects on the cardiovascular system. Leptin increases sympathetic activity, producing a pressor effect when acting on the central nervous system. However, leptin produces vasodilation by an endothelium-dependent mechanism peripherally. Ghrelin decreases sympathetic activity and has a depressor effect when acting on the central nervous system. Peripherally, ghrelin produces vasodilation by an endothelium-independent mechanism. Ghrelin improves left ventricular function and cardiac cachexia in heart failure. Leptin may contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a variety of mechanisms. Leptin has pro-inflammatory, proliferative and calcification promoting effects in the vasculature. Ghrelin has recently been shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro-thrombotic state through stimulation of platelet aggregation and inhibition of coagulation and fibrinolysis. The evidence for and against these effects as well as their pathophysiological significance in obesity hypertension, heart failure, atherosclerosis and thrombosis are discussed.

Animals↗
PubMed2005

Characterization of a 67Ga/68Ga radiopharmaceutical for SPECT and PET of MDR1 P-glycoprotein transport activity in vivo: validation in multidrug-resistant tumors and at the blood-brain barrier.

UNLABELLED: Overexpression of multidrug resistance (MDR1) P-glycoprotein (Pgp) remains an important barrier to successful chemotherapy in cancer patients and impacts the pharmacokinetics of many important drugs, thus evoking a need to noninvasively interrogate Pgp transport activity in vivo. METHODS: Cell tracer transport experiments as well as mouse biodistribution and microPET imaging studies were performed to characterize a nonmetabolized gallium(III) complex, gallium(III)-(bis(3-ethoxy-2-hydroxy-benzylidene)-N,N'-bis(2,2-dimethyl-3-amino-propyl)ethylenediamine) (Ga-[3-ethoxy-ENBDMPI])(+), as a candidate SPECT ((67)Ga) and generator-produced PET ((68)Ga) radiopharmaceutical recognized by MDR1 Pgp. RESULTS: The (67)Ga-complex showed high membrane potential-dependent accumulation in drug-sensitive KB3-1 cells and modulator-reversible low accumulation in MDR KB8-5 cells. In KB8-5 cells, the median effective concentrations (EC(50)) of MDR modulators LY335979, PSC 833, and cyclosporin A were 69 nmol/L, 1 micromol/L, and 3 micromol/L, respectively. Using a variety of cells stably expressing MDR1 Pgp, multidrug resistance-associated proteins (MRP1-MRP6), or the breast cancer resistance protein (BCRP/MXR), the (67)Ga-complex was shown to be readily transported by MDR1 Pgp and, to a much lesser extent, by MRP1, but not MRP2-MRP6 or BCRP/MXR. In a nude mouse xenograft tumor model, the (67)Ga-complex produced a readily detected 3-fold difference between Pgp-expressing tumors and drug-sensitive tumors in the opposite flank. In mdr1a/1b(-/-) gene-deleted mice, the (67)Ga-complex showed 17-fold greater brain uptake and retention compared with wild-type mice with no net difference in blood pharmacokinetics, consistent with transport in vivo by Pgp expressed at the capillary blood-brain barrier. This could be readily observed with microPET using the (68)Ga-complex. Incidentally, wild-type mice showed heart-to-blood ratios of >100 by 1 h after injection and heart-to-liver ratios of 2.2 by 120 min. CONCLUSION: Molecular imaging of the functional transport activity of MDR1 Pgp with ((67/68)Ga-[3-ethoxy-ENBDMPI])(+) may enable noninvasive SPECT/PET monitoring of the blood-brain barrier, chemotherapeutic regimens, and MDR1 gene therapy protocols in vivo. These Pgp-directed properties of the radiopharmaceutical may also translate favorably to myocardial perfusion imaging.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Extraskeletal osteochondroma of the thigh: a case report.

A case of histopathologically proven extraskeletal osteochondroma of the thigh is presented along with its radiographic, CT and MRI findings. This is the first such case reported, to the best of our knowledge. The diagnosis of extraskeletal osteochondroma should be considered when a discrete ossified mass is localised in the soft tissue.

Adolescent↗