Alcoholic Neuropathy: Involvement of Multifaceted Signalling Mechanisms.

Background: Alcoholic neuropathy is a chronic disorder caused by the excessive consumption of alcohol. Damage to the nerves results in unusual sensations in the limbs, decreased mobility and loss of some body functions.

Objective: Alcohol is considered a major cause for exclusively creating the debilitating condition of the neuropathic state.

Mdm2-P53 Interaction Inhibitor with Cisplatin Enhances Apoptosis in Colon and Prostate Cancer Cells In-Vitro.

Objective: To study the effect of RITA (MDM2-p53 interaction inhibitor) and its action along with genotoxic drug cisplatin was evaluated on COLO-205 colon cancer and PC-3 prostate cancer cells.

Method: Various in-vitro parameters to determine cytotoxic and apoptotic potential of RITA with genotoxic drug cisplatin were evaluated. The potentiation of cytotoxic effect was evaluated using MTT assay and colony forming assay, mechanism of cell death by Etbr/AcO assay and the mechanism of apoptosis was determined by caspase-3 release assay.

Preconditioning offers cardioprotection in hyperlipidemic rat hearts: possible role of Dopamine (D2) signaling.

Background: Ischemic preconditioning (IPC) induced cardioprotection has been reported to be blunted in hyperlipidemic subjects. Dopamine, via its D2 receptor signaling, appears to mimic the signaling cascade involved in myocardial preconditioning and is also involved in the inhibition of hyperlipidemia induced mediators. The present study was designed to investigate the possible involvement of D2 receptors in IPC and to see whether dopamine preconditioning can offer cardioprotection in hyperlipidemic rat hearts.

Mild alcohol intake exacerbates metabolic syndrome in rodents: a putative role of GSK-3β.

Metabolic syndrome is characterized with abdominal obesity, insulin resistance, dyslipidemia and hepatic dysfunction. Glycogen synthase kinase-3β (GSK-3β) expression has been observed in adipose tissues in obese and diabetic humans, and in rodents. The aim of study was to investigate role of GSK-3β in modulation of metabolic alterations in alcoholic fed rats.

Protective effect and mechanism of Ginkgo biloba extract-EGb 761 on STZ-induced diabetic cardiomyopathy in rats.

Unlabelled: Diabetes mellitus (DM) is a complex metabolic disorder which leads to development of various long-term complications including cardiomyopathy. Oxidative stress due to hyperglycemia plays a key role in the development and progression of diabetic cardiomyopathy (DC). Oxidative stress causes the opening of mitochondrial permeability transition pore (mPTP) eventually leading to myocardium dysfunction.

Possible modulation of FAS and PTP-1B signaling in ameliorative potential of Bombax ceiba against high fat diet induced obesity.

Background: Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains Lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B.

Mechanism of hyperhomocysteinemia-induced vascular endothelium dysfunction - possible dysregulation of phosphatidylinositol-3-kinase and its downstream phosphoinositide dependent kinase and protein kinase B.

Imbalance of l-arginine/endothelial nitric oxide synthatase (eNOS) activity is the hallmark of vascular endothelium dysfunction. Hyperhomocysteinemia (Hhy) has been identified as a potential risk factor for vascular endothelium dysfunction that leads to cardiovascular disorders. Phosphatidylinositol-3 kinase (PI3K) is a ubiquitous enzyme involved in plethora of cell signaling including the endothelial cells and it has been reported that signaling through this enzyme and its downstream pathway viz phosphoinositide-dependent kinase (PDK)/protein kinase B (Akt) and eNOS is impaired in diseased conditions.

Phosphodiesterases: Regulators of cyclic nucleotide signals and novel molecular target for movement disorders.

Movement disorders rank among the most common neurological disorders. During the last two decades substantial progress has been made in understanding of the pathological basis of these disorders. Although, several mechanisms have been proposed, downregulation of cyclic nucleotide mediated signaling cascade has consistently been shown to contribute to the striatal dysfunctioning as seen in movement disorders.

Anti-inflammatory and anti-hyperalgesic effect of all-trans retinoic acid in carrageenan-induced paw edema in Wistar rats: involvement of peroxisome proliferator-activated receptor-β/δ receptors.

Objective: In this study, we investigated the role of peroxisome proliferator-activated receptors (PPAR)-β/δ receptors in carrageenan-induced inflammation and in the anti-inflammatory effects of all-trans retinoic acid (ATRA).

Materials And Methods: The λ-carrageenan (0.1 ml of 1% w/v) was injected into intra-plantar (i.

Neuroprotective role of PDE4 and PDE5 inhibitors in 3-nitropropionic acid induced behavioral and biochemical toxicities in rats.

Phosphodiesterase inhibitors have been reported to be beneficial in cognitive and motor disorders. In the present study, we have investigated the effects of RO 20-1724 (PDE4 inhibitor) and sildenafil (PDE5 inhibitor) in 3-nitropropionic acid (3-NP) induced experimental Huntington's disease in rats. 3-Nitropropionic acid was administered for 14 days (10 mg/kg i.

Pharmacological inhibition of GSK-3β produces late phase of cardioprotection in hyperlipidemic rat: possible involvement of HSP 72.

The acute, as well as late, phase of cardioprotection induced by ischemic preconditioning is abolished in hyperlipidemic (HL) rat heart. The pharmacological inhibition of glycogen synthase kinase-3β (GSK-3β), has earlier been reported to restore this attenuated acute cardioprotective effect. However, it not known whether GSK-3β inhibitors administered 24 h before the ischemic injury would restore the late cardioprotective in HL rat and, if yes, the role of heat shock protein 72 (HSP 72) in its modulation.

Ameliorative effect of daidzein: a caveolin-1 inhibitor in vascular endothelium dysfunction induced by ovariectomy.

Estrogen deficiency was produced in female Sprague-Dawley rats by surgical removal of both the ovaries and these animals were used 4 weeks later. Endothelium-dependent and endothelium-independent relaxations due to acetylcholine and sodium nitroprusside were observed respectively, in isolated rat thoracic aortic ring preparation. Extent of lipid peroxidation was measured by estimating serum TBARS.

Effect of dipyrone and thalidomide alone and in combination on STZ-induced diabetic neuropathic pain.

Diabetic neuropathy is recognized as one of the most common complications of chronic diabetes, but its pathophysiological mechanism is complex and yet to be completely explored. Monotherapy with conventional analgesics fails to provide adequate pain relief in peripheral diabetic neuropathy. There are a number of evidence suggesting that tumor necrosis factor (TNF-α) plays an important role in the pathogenesis of peripheral diabetic neuropathy.

Possible mechanism of protective effect of thalidomide in STZ-induced-neuropathic pain behavior in rats.

Introduction: Diabetes-induced neuropathic pain is recognized as one of the most difficult type of pain to treat and conventional analgesics are well known to be partially effective or associated with potential toxicity. Recently, it has been demonstrated that thalidomide, besides its teratogenic potential, reduced chronic pain in an SNL experimental pain model.

Objective: The present study was designed to investigate the effect of thalidomide on streptozotocin (STZ)-induced neuropathic pain in rats.

Anti-inflammatory and antihyperalgesic effects of the combination of ibuprofen and hemin in adjuvant-induced arthritis in the Wistar rat.

Aim: Although, pharmacological activation of heme oxygenase (HO)-1 has shown to produce ameliorative effects in various experimental models of inflammation, but such beneficial effects have not been observed in adjuvant-induced arthritis. Further, the upregulated activity of HO-1 has been implicated in the pathogenesis of adjuvant arthritis. The present study was designed to investigate the anti-inflammatory and antihyperalgesic effects of the prophylactic use of hemin alone and/or in combination with ibuprofen using adjuvant-induced arthritis in Wistar rat.

Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart.

Background: Nitric oxide (NO) has been noted to produce ischemic preconditioning (IPC)-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS) by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM).

Possible attenuation of nitric oxide expression in anti-inflammatory effect of Ziziphus jujuba in rat.

The hydroalcoholic extract of fruits of Ziziphus jujuba (ZJ) was investigated for its anti-inflammatory effect using acute and chronic models of inflammation in rat. Wistar albino rats of either sex were employed in the present study (n = 6). Acute inflammation was induced by subplantar administration of carrageenan (1%) in rat hind paw.

Mechanism of attenuation of diabetes mellitus and hypercholesterolemia induced vascular endothelial dysfunction by protein tyrosine phosphatase inhibition.

The study has been designed to investigate downstream mechanisms in the PTPase inhibition mediated attenuation of diabetes mellitus and hypercholesterolemia-induced vascular endothelial dysfunction. Diabetes mellitus was induced in rats using streptozotocin (55 mg/kg, i.v.

Possible involvement of α1-adrenergic receptor and K(ATP) channels in cardioprotective effect of remote aortic preconditioning in isolated rat heart.

Background: Remote preconditioning is a phenomenon in which brief episodes of ischemia and reperfusion to remote organs protect the target organ against sustained ischemia/reperfusion (I/R)-induced injury. Protective effects of remote aortic preconditioning (RAPC) are well established in the heart, but their mechanisms still remain to be elucidated.

Objective: This study has been designed to investigate the possible involvement of α-1-adrenergic receptor (AR) and K(ATP) channels in cardio-protective effect of RAPC in isolated rat heart.

Beneficial effect of insulin in hyperhomocysteinemia and diabetes mellitus-induced vascular endothelium dysfunction: role of phosphoinositide dependent kinase and protein kinase B.

A primary defect in the vascular action of insulin may be the key intermediate mechanism that links endothelial dysfunction with diabetes mellitus and hyperhomocysteinemia. This study investigated the downstream targets of insulin, involved in this process. Hyperhomocysteinemia (serum homocysteine > 10 μm/l) was produced in rats by administering L-methionine (1.

Modulation of the cardioprotective effect of ischemic preconditioning in hyperlipidaemic rat heart.

Ischemic preconditioning (IPC) produces cardioprotection by phosphorylation of glycogen synthaes kinase-3beta (GSK-3beta) that inhibits the opening of mitochondrial permeability transition pore (MPTP), and this cardioprotective action of IPC is attenuated by hyperlipidaemia. The present study investigated the role of GSK-3beta in attenuation of cardioprotective effect of IPC, by hyperlipidaemia in the rat heart. Hyperlipidaemia was produced in rat by feeding high fat diet for six weeks.