Meerpet, India


Meerpet, India
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Mustroph M.L.,Davidson College | Mustroph M.L.,University of Illinois at Urbana - Champaign | King M.A.,University of Florida | King M.A.,Malcom Randall Medical Center | And 2 more authors.
Behavioural Brain Research | Year: 2012

Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics. © 2012 Elsevier B.V.

Van Der Merwe E.,Pharmacology
SA Pharmaceutical Journal | Year: 2010

Hypertension is a major contributor to cardiovascular morbidity and mortality. However, blood pressure control in clinical practice still falls short of treatment recommendations. The reasons for this are manifold and patient noncompliance with medication has been identified as one important factor. In this article we discuss the various reasons for patient noncompliance and look at strategies to improve adherence, for example simplifying the medication regimen and reducing side effects in an asymptomatic disease such as hypertension. In this regard, combination treatment, and specifically fixed-dose combinations, has come a long way in enhancing tolerability, reducing counter-regulatory drug mechanisms and bringing blood pressure closer to target. Furthermore, we investigate the possibility of some combinations having clinical benefits beyond blood pressure control, as this may improve long-term cardiovascular outcomes. On the other hand, certain combinations may only have positive clinical outcomes in carefully selected patient groups and are not recommended for routine management of hypertension. Lastly, issues such as escape mechanisms in the renin angiotensin aldosterone system (RAAS) are discussed - these mechanisms play a role in treatment failure and may require the use of new antihypertensive drug classes, such as direct renin inhibitors. © 2010 Medikredit Integrated Healthcare Solutions (Pty) Ltd.

Atkinson S.M.,Novo Nordisk AS | Nansen A.,Pharmacology
Basic and Clinical Pharmacology and Toxicology | Year: 2017

In this MiniReview, we summarize the body of knowledge on the delayed-type hypersensitivity arthritis (DTHA) model, a recently developed arthritis model with 100% incidence, low variation and synchronized onset in C57BL/6 (B6) mice, and compare it to other murine arthritis models. It is desirable to have robust arthritis models in B6 mice, as many transgene strains are bred on this background. However, several of the most widely used mouse model of arthritis cannot be induced in B6 mice without the drawback of lower incidence, reduced severity and higher variation, if at all. DTHA is induced by modifying a classical methylated bovine serum albumin (mBSA)-induced DTH response by administering a cocktail of anti-type II collagen antibodies (anti-CII) between immunization and challenge. Arthritis affects one, predefined paw in which acute inflammation and severe arthritis rapidly develop and peak after 4–7 days. Disease is self-resolving over the course of around 3 weeks. Disease manifestations resemble those seen in other arthritis models and include bone erosion, cartilage destruction, oedema, pannus and new bone formation. Induction of DTHA is dependent on CD4+ T cells while B cells are dispensable. The DTHA model is set apart from other murine arthritis models in that it can be induced in B6 mice with 100% incidence and with high and consistent severity. This is the clearest advantage of the model, as the mechanisms of disease and clinical manifestations can be found in other arthritis models. The model holds potential for future modifications that may improve the lack of chronicity. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)

Comasco E.,Pharmacology | Comasco E.,Uppsala University | Sylven S.M.,Womens and Childrens Health | Papadopoulos F.C.,Uppsala University Hospital | And 3 more authors.
Psychiatric Genetics | Year: 2011

Objective: Postpartum depression (PPD) is an under diagnosed and under treated mood disorder, with negative impact on both the mother and the infant's health. The aim of this study is to examine whether genetic variations in the monoaminergic neurotransmitter system, together with environmental stressors, contribute to the development of PPD symptoms. Methods: This nested case-control study included 275 women from a population-based cohort of delivering women in Sweden. A questionnaire containing the Edinburgh Postnatal Depression Scale was collected at 6 weeks and 6 months postpartum. Three functional polymorphisms were genotyped, catechol-O-methyltransferase (COMT)-ValMet 158, monoamine oxidase A (MAOA)-upstream variable number tandem repeat (uVNTR) and serotonin transporter linked polymorphic region (5HTT-LPR). Stressful life events, maternity stressors and previous psychiatric contact were considered as potential risk factors. Results: COMT-ValMet 158 was significantly associated with PPD symptoms at 6 weeks, but not at 6 months postpartum. A significant gene-gene interaction effect was present between COMT-ValMet 158 and MAOA-uVNTR. In a gene-environment multivariate model, COMT-ValMet 158, psychiatric contact and maternity stressors were significantly associated with PPD symptoms. Among those with history of psychiatric problems, the COMT-ValMet 158 and 5HTT-LPR risk variants were associated with PPD symptoms, whereas in the absence of previous psychiatric contact only maternity stressors were related to PPD symptoms. Conclusion: The interaction effect between monoaminergic genes and environmental stressors is likely to contribute to vulnerability for PPD. The different patterns of association according to history of psychiatric problems, if replicated, might be helpful in screening strategies. © 2011 Wolters Kluwer Health. Lippincott Williams & Wilkins.

Gosavi Devesh D.,Pharmacology | John P.S.,Mamata Medical College
Asian Journal of Pharmaceutical and Clinical Research | Year: 2012

Introduction: Sushrut samhita, an authentic ayurvedic text mentions the use of Panchagavya Ghrita (PG) in the treatment of mania, epilepsy, fever and hepatitis. In an effort to correlate the ancient knowledge with the modern concepts of research in the pharmacology, we decided to study the effects of Panchagavya Ghrita on some neuropharmacological parameters including anticonvulsant activity in rats. Material and methods: For all the experiments, the animals were divided into four groups of 10 rats each. First three groups received Panchagavya Ghrita in the dose of 1(PG1), 2 (PG2), 4 (PG4) ml per Kg of body weight respectively and the fourth group received normal saline 2 ml per Kg orally twice daily (9am-9pm) for 30 days 1. Effect on general behavior: 2.Maximal electroshock induced convulsions: After screening convulsions were induced by maximal electroshock method. A current of 150 mA was delivered for 0.2 sec using Techno convulsiometer.3. Spontaneous motor activity (SMA): animals were screened for SMA using Actophotometer. Animals were allowed to adjust to the test chamber of the instrument for 30 minutes and then activity was counted using the digital counter for 5 minutes.4.Pentobarbitone induced sleep time:. Test and control animals both were injected with injection Pentobarbitone in the dose of 45-mg/Kg body weight. The animals were observed for loss and recovery of righting reflex for the calculation of duration of sleep Results: 1) PG protected rats from maximal electroshock induced convulsions 2) increased the spontaneous motor activity as measured by Actophotometer. 3) Inhibited the pentobarbitone induced sleep time in rats. There was no effect on the general behavioral profile of the rats except that there was increase in the locomotor activity in the cages. Conclusion: PG appears to be possessing anticonvulsant properties but the degree of protection is not sufficient to use it as single antiepileptic agent. This action of PG appears to be not mediated through GABA receptors.

Tseng C.-L.,National Yang Ming University | Wei J.-W.,Pharmacology
Journal of the Chinese Medical Association | Year: 2012

Background: Information related to histamine-induced cellular responses in C6 glioma cells through second messenger pathways has not been fully studied, especially the involvement of arachidonic acid (AA) metabolism. In addition, specific labeled ligand binding to histamine receptor sites still needs to be clarified. Methods: Labeled mepyramine ligand was used to study its binding sites; [ 3H] inositol was used to detect inositol 4-phosphate (IP 1) formation, and fura-2/AM was used to detect intracellular free calcium ion ([Ca 2+]i) level activated by the phosphatidylinositol-phospholipase C (PI-PLC) pathway. Also, labeled AA was used to detect the metabolism of AA and its metabolites release via the activation of phospholipase A2 in the presence of histamine. Results: C6 glioma cells incubated with histamine in the presence of 10 mM LiCl for 60 minutes induced an increase of IP 1 and glycerophosphoric-inositol (GPI) accumulation. In addition, histamine caused an increase of extracellular AA with its metabolite release, eliciting a transient and sustained increase of free [Ca 2+]i. The sustained increase of [Ca 2+]i was almost or completely blocked by La 3+ and excess ethylene diamine tetraacetic acid. The calcium ion influx associated with the sustained phase required the presence of histamine on the receptor sites, and could be blocked by a H 1 antagonist, chlorpheniramine. Conclusion: C6 glioma cells possess histamine H 1 receptors that have affinity towards [ 3H]mepyramine binding, and are coupled to PI-PLC to generate inositol phosphates and to increase [Ca 2+]i, and they are coupled to phospholipase A2 (PLA2) to generate GPI and AA with its metabolite release. The transient increase in [Ca 2+]i can be attributed to Ca 2+ release from intracellular stores, whereas the sustained increase in [Ca 2+]i is due to influx of extracellular calcium ions. The sustained increase in [Ca 2+]i plays a role in the activation of histamine receptor-coupled PLA2. © 2012.

Tseng C.-L.,National Yang Ming University | Wei J.-W.,Pharmacology
Chinese Journal of Physiology | Year: 2013

Molecular events involved in the homologous desensitization of histamine-mediated signal transduction system in glioma cells are not well understood. The aim of this study was designed to gain further insight into possible events in the process using the C6 glioma cells. Incubation of histamine caused increases in inositol phosphate (IP1) formation and intracellular free-calcium concentration [Ca2+]i in C6 glioma cells via the activation of a G-protein-coupled phospholipase C (PI-PLC). Histamine also caused an increase in extracellular release of arachidonic acid (AA) and formation of glycerophosphoinositol (GPI). These effects are likely to be mediated through the activation of receptor-coupled phospholipase A2 (PLA2). Pretreatment of C6 cells with histamine, from 0.1 μM to 1 mM concentrations, for 10 to 60 min significantly reduced the histamine-induced IP1 production, [Ca2+]i accumulation, AA release and GPI formation, despite repeated wash of the cells with buffer solution. Staurosporine (10 nM), a protein kinase C inhibitor, reversed almost completely IP1 production, or partially for [Ca2+]i, GPI formation and AA release of this homologous desensitization effect of histamine. Pretreatment of C6 cells with phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, at 0.1 nM to 0.1 μM for 2 to 15 min caused a reduction of histamine-induced IP1 formation and [Ca2+]i accumulation, but enhanced histamine-induced AA release and GPI formation. 10 nM staurosporine completely reversed the effect of PMA on histamine-induced IP1 formation and partially on [Ca2+]i accumulation. However, staurosporine potentiated the effect of PMA on histamine-induced AA release and GPI formation, but the effect could be blocked by H7, a calcium-dependent protein kinase C inhibitor. Our results indicate that activation of protein kinase C by histamine in the signal transduction system is involved in the histamine-induced homologous desensitization event. Since PMA pretreatment could not mimic histamine-induced homologues desensitization event in AA release and GPI formation, it is likely due to the dual actions of this protein kinase activator: on calcium independently, and also on calcium dependent via influx of calcium ion through the plasma membrane. The calcium flux effect of PMA is related to the difference between PMA and histamine on the effects of AA release and GPI formation via activation on phospholipase A2. The results of this study provided strong evidence that protein kinase C is involved in this homologous desensitization caused by continuous histamine receptor activation. © 2013 by The Chinese Physiological Society and Airiti Press Inc.

Singla M.,Jawaharlal Institute of Postgraduate Medical Education & Research | Prabhakar S.,Jawaharlal Institute of Postgraduate Medical Education & Research | Modi M.,Jawaharlal Institute of Postgraduate Medical Education & Research | Medhi B.,Pharmacology | And 2 more authors.
Epilepsia | Year: 2011

Purpose: To determine the effect of administration of a short course of prednisolone on seizure and radiologic outcome in patients with solitary cysticercus granuloma (SCG). Methods: One hundred forty-eight subjects presenting with new-onset seizures (<15 days duration) and with SCG demonstrated on imaging studies were randomly allocated to either treatment with prednisolone (40-60 mg/day for 2 weeks) or placebo in addition to standard antiepileptic drug therapy. The subjects were followed up for seizure recurrence for 9 months. Repeat computed tomography (CT, at 3 months) and magnetic resonance imaging (MRI, at 6 months) to evaluate resolution and calcification of the lesion. Key Findings: There was no difference in the proportion of subjects with seizure recurrence during the follow-up period in the treatment (n = 16, 21.9%) and control (n = 19, 25.33%) groups (p = 0.7). However, generalized seizures occurred in a significantly lesser proportion of subjects in the treatment group (n = 3, 15.79%) in comparison to the control group (n = 12, 60.00%) (p = 0.015). There were no significant differences in the proportion of subjects with complete resolution of the SCG on repeat CT at 3 months [treatment group (27, 46.7%) and control group (23, 39.8%); p = 0.453] and repeat MRI at 6 months [treatment group (28, 46.7%) and control group (21, 38.9%); p = 0.402]. Significance: The administration of a short course of prednisolone does not offer significant improvement in seizure control, although a benefit in terms of reducing the likelihood of generalized seizures is possible. Furthermore, it does not improve the chances of resolution of the SCG on follow-up imaging studies. © 2011 International League Against Epilepsy.

Wang Y.,University of Kansas Medical Center | Denisova J.V.,University of Kansas Medical Center | Kang K.S.,Pharmacology | Fontes J.D.,University of Kansas Medical Center | And 2 more authors.
Journal of Neurophysiology | Year: 2010

N-methyl-D-aspartate receptors (NMDARs) play an important role in cell survival versus cell death decisions during neuronal development, ischemia, trauma, and epilepsy. Coupling of neurons by electrical synapses (gap junctions) is high or increases in neuronal networks during all these conditions. In the developing CNS, neuronal gap junctions are critical for two different types of NMDAR-dependent cell death. However, whether neuronal gap junctions play a role in NMDAR-dependent neuronal death in the mature CNS was not known. Using Fluoro-Jade B staining, we show that a single intraperitoneal administration of NMDA (100 mg/kg) to adult wild-type mice induces neurodegeneration in three forebrain regions, including rostral dentate gyrus. However, the NMDARmediated neuronal death is prevented by pharmacological blockade of neuronal gap junctions (with mefloquine, 30 mg/kg) and does not occur in mice lacking neuronal gap junction protein, connexin 36. Using Western blots, electrophysiology, calcium imaging, and gas chromatography-mass spectrometry in wild-type and connexin 36 knockout mice, we show that the reduced level of neuronal death in knockout animals is not caused by the reduced expression of NMDARs, activity of NMDARs, or permeability of the blood- brain barrier to NMDA. In wild-type animals, this neuronal death is not caused by upregulation of connexin 36 by NMDA. Finally, pharmacological and genetic inactivation of neuronal gap junctions in mice also dramatically reduces neuronal death caused by photothrombotic focal cerebral ischemia. The results indicate that neuronal gap junctions are required for NMDAR-dependent excitotoxicity and play a critical role in ischemic neuronal death. Copyright © 2010 The American Physiological Society.

Sandozi T.,Pharmacology
Research Journal of Pharmaceutical, Biological and Chemical Sciences | Year: 2013

To compare the cost analysis of H2 antagonists and proton pump inhibitors (PPIs) prescribed in a tertiary care hospital.A prospective cross sectional study was done for three months. All hospitalized patients prescribed H2 antagonists and PPIs in the medical and surgical wards of the hospital were included in the study. The total number of patients prescribed H2 antagonists and PPIs, their subtypes and the indication for their prescription was noted. The cost analysis of these two groups of anti-secretory (ASD) drugs was determined and compared. 112 patients were prescribed H2 antagonists and PPIs during their hospitalization. PPIs were prescribed more frequently than H2 antagonists. An indication for prescription was present in only 45% of the patients. The cost analysis showed a vast difference in the cost of treatment between (PPIs) and H2 antagonists. This study showed inappropriate prescription of PPIs.

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