Search PubMed⌕ Search

Biomedical subjects

S Pal

Publications and source records attributed to S Pal.

At least 37 records · Page 2Linked to original sources
PubMed2002

Antioxidant activity of the methanol fraction of Pluchea indica root extract.

Studies were carried out to evaluate the influence of the methanol fraction of Pluchea indica Less root extract (PIRE), the dual inhibitors (BW 755C and phenidone) and vitamin on both in vivo and in vitro free radical-scavenging activities, CCl(4)-induced lipid peroxidation and the metabolism of arachidonic acid by lipoxygenase. PIRE produced significant antiinflammatory activity against glucose oxidase-induced paw oedema (in vivo), inhibited hydroxyl radical and superoxide generation, lysis of erythrocytes induced by hydrogen peroxide, CCl(4)-induced lipid peroxidation and also dioxygenase activity of lipoxygenase (both in the presence and absence of hydrogen peroxide). Significantly higher free radical-scavenging activity was observed with BW 755C and phenidone compared with PIRE. However, both BW 755C and phenidone stimulated hydroxyl radical generation compared with the observed inhibitory effects of PIRE and vitamin E.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed2002

Effect of amitriptyline on gastric ulceration.

Amitriptyline significantly inhibited alcohol, aspirin, indomethacin and cold-restraint stress-induced ulceration. Secretory studies conducted in pyloric-ligated rats revealed that the drug, at the doses employed, significantly reduced total acidity and protein content. However, significant reductions of the gastric volume were only observed at the highest dose of the drug. In another set of experiments, when 50% alcohol (v/v) was administered to the pyloric-ligated rats pretreated with amitriptyline, it was observed that the drug significantly reduced the pH, total acidity and protein content.

Amitriptyline↗
PubMed2002

The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease.

BACKGROUND: No formal instruments are available for quantifying sleep problems in Parkinson's disease. OBJECTIVE: To develop a new sleep scale to quantify the various aspects of nocturnal sleep problems in Parkinson's disease, which may occur in up to 96% of affected individuals. METHODS: Employing a multidisciplinary team approach, a visual analogue scale was devised addressing 15 commonly reported symptoms associated with sleep disturbance in Parkinson's disease-the Parkinson's disease sleep scale (PDSS). In all, 143 patients with Parkinson's disease completed the PDSS, covering the entire spectrum of disease from newly diagnosed to advanced stage. As controls, 137 age healthy matched subjects also completed the scale. Test-retest reliability was assessed in a subgroup of subjects. The Epworth sleepiness scale was also satisfactorily completed by 103 of the patients with Parkinson's disease. RESULTS: PDSS scores in the Parkinson group were significantly different from the healthy controls. Patients with advanced Parkinson's disease had impaired scores compared with early/moderate disease. Individual items of the scale showed good discriminatory power between Parkinson's disease and healthy controls. Relevant items of the PDSS correlated with excessive daytime sleepiness. The scale showed robust test-retest reliability. CONCLUSIONS: This appears to be the first description of a simple bedside screening instrument for evaluation of sleep disturbances in Parkinson's disease. A combination of subitems may help identify specific aspects of sleep disturbance, which in turn may help target treatment.

Adult↗
PubMed2002

Thrombocytopenia as the presenting manifestation of sarcoidosis.

Sarcoidosis is a chronic granulomatous disorder characterized by multisystem involvement, however, symptomatic thrombocytopenia as a presenting manifestation is rare. Here we are reporting a case of sarcoidosis presenting with splenomegaly and severe immune thrombocytopenia as a presenting manifestation.

Adrenal Cortex Hormones↗
PubMed2001

Quantitative imaging of glutathione in hippocampal neurons and glia in culture using monochlorobimane.

Glutathione (GSH) is a major antioxidant system in the mammalian central nervous system (CNS). Abnormalities of GSH metabolism have been associated with many disorders of the CNS, including Parkinson's, Alzheimer's, and Huntingdon's diseases and ischaemic/reperfusion injury. Investigation of GSH levels in the CNS generally relies on biochemical assays from cultures enriched for different cell types. Because glia influence neuronal metabolism, we have studied cultures in which neurons and glia are cocultured. This approach demands fluorescence imaging to differentiate between the different cell types in the culture, permitted by the use of monochlorobimane (MCB), which reacts with GSH to produce a fluorescent product. We have defined the conditions required to ensure steady-state MCB loading and show the specificity of MCB for GSH through a reaction catalysed by glutathione-S-transferase (GST). [GSH] was consistently higher in glia than in neurons, and [GSH] in both cell types decreased with time in culture. Inhibition of GSH synthesis by buthionine sulfoximine (BSO) caused a greater proportional depletion of GSH in glia than in neurons. The depletion of GSH induced by BSO was significantly greater in cells cultured for >10 days. Furthermore, release of GSH from glia and its breakdown by the ectoenzyme gamma-glutamyltranspeptidase (gammaGT) maintains [GSH] in neurons. In older cultures, inhibition of gammaGT by acivicin caused significant depletion of neuronal GSH. After inhibition of GSH synthesis by BSO, inhibition of the glia-neuron trafficking pathway by acivicin caused widespread neuronal death. Such neurotoxicity was independent of the endogenous glutamate and nitric oxide synthase, suggesting that it is not due to secondary excitotoxicity.

Animals↗
PubMed2001

Mechanisms of curcumin-induced apoptosis of Ehrlich's ascites carcinoma cells.

Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is a potent antioxidant and anti-inflammatory agent. It has been recently demonstrated to possess discrete chemopreventive activities. However, the molecular mechanisms underlying such anticancer properties of curcumin still remain unrealized, although it has been postulated that induction of apoptosis in cancer cells might be a probable explanation. In the current study, curcumin was found to decrease the Ehrlich's ascites carcinoma (EAC) cell number by the induction of apoptosis in the tumor cells as evident from flow-cytometric analysis of cell cycle phase distribution of nuclear DNA and oligonucleosomal fragmentation. Probing further into the molecular signals leading to apoptosis of EAC cells, we observed that curcumin is causing tumor cell death by the up-regulation of the proto-oncoprotein Bax, release of cytochrome c from the mitochondria, and activation of caspase-3. The status of Bcl-2 remains unchanged in EAC, which would signify that curcumin is bypassing the Bcl-2 checkpoint and overriding its protective effect on apoptosis.

Animals↗
PubMed2001

Central role of p53 on regulation of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in mammary carcinoma.

The process of angiogenic switching is one of the most important factors in the growth and development of breast tumors. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is considered to be the most important directly acting angiogenic protein that has been shown to be up-regulated in breast cancer cells. Hypoxia seems to be an important stimulus for inducing VPF/VEGF mRNA expression in human mammary tumors. Here, we have studied the roles of the tumor suppressor gene p53 and the proto-oncogene c-Src in regulating the transcription of VPF/VEGF in breast cancer cell lines MCF-7 and MDA-MB 435 under both normoxic and hypoxic conditions. p53 significantly inhibited the transcription of VPF/VEGF involving the transcription factor Sp1. Increased binding of Sp1 to the VPF/VEGF promoter has been observed when the cells were exposed to hypoxia. It has been shown that p53 makes a complex with Sp1 and inhibits its binding to the VPF/VEGF promoter to prevent the transcriptional activation. Furthermore, c-Src kinase activity was found to be increased in the hypoxic condition, and in the presence of antisense of Src, there was down-regulation of the total mRNA level and also the promoter activity of VPF/VEGF. The present study indicates that p53 can also inhibit the hypoxic induction of Src kinase activity and thereby may prevent VPF/VEGF transcription. Taken together, our data suggest a central role of p53, through which it can inhibit VPF/VEGF expression by regulating the transcriptional activity of Sp1 and also by down-regulating the Src kinase activity, under both normoxic and hypoxic conditions.

Breast Neoplasms↗
PubMed2001

Long-term alteration of calcium homeostatic mechanisms in the pilocarpine model of temporal lobe epilepsy.

The pilocarpine model of temporal lobe epilepsy is an animal model that shares many of the clinical and pathophysiological characteristics of temporal lobe or limbic epilepsy in humans. This model of acquired epilepsy produces spontaneous recurrent seizure discharges following an initial brain injury produced by pilocarpine-induced status epilepticus. Understanding the molecular mechanisms mediating these long lasting changes in neuronal excitability would provide an important insight into developing new strategies for the treatment and possible prevention of this condition. Our laboratory has been studying the role of alterations in calcium and calcium-dependent systems in mediating some of the long-term neuroplasticity changes associated with epileptogenesis. In this study, [Ca(2+)](i) imaging fluorescence microscopy was performed on CA1 hippocampal neurons acutely isolated from control and chronically epileptic animals at 1 year after the induction of epileptogenesis with two different fluorescent dyes (Fura-2 and Fura-FF) having high and low affinities for [Ca(2+)](i). The high affinity Ca(2+) indicator Fura-2 was utilized to evaluate [Ca(2+)](i) levels up to 900 nM and the low affinity indicator Fura-FF was employed for evaluating [Ca(2+)](i) levels above this range. Baseline [Ca(2+)](i) levels and the ability to restore resting [Ca(2+)](i) levels after a brief exposure to several glutamate concentrations in control and epileptic neurons were evaluated. Epileptic neurons demonstrated a statistically significantly higher baseline [Ca(2+)](i) level in comparison to age-matched control animals. This alteration in basal [Ca(2+)](i) levels persisted up to 1 year after the induction of epileptogenesis. In addition, the epileptic neurons were unable to rapidly restore [Ca(2+)](i) levels to baseline following the glutamate-induced [Ca(2+)](i) loads. These changes in Ca(2+) regulation were not produced by a single seizure and were not normalized by controlling the seizures in the epileptic animals with anticonvulsant treatment. Peak [Ca(2+)](i) levels in response to different concentrations of glutamate were the same in both epileptic and control neurons. Thus, glutamate produced the same initial [Ca(2+)](i) load in both epileptic and control neurons. Characterization of the viability of acutely isolated neurons from control and epileptic animals utilizing standard techniques to identify apoptotic or necrotic neurons demonstrated that epileptic neurons had no statistically significant difference in viability compared to age-matched controls. These results provide the first direct measurement of [Ca(2+)](i) levels in an intact model of epilepsy and indicate that epileptogenesis in this model produced long-lasting alterations in [Ca(2+)](i) homeostatic mechanisms that persist for up to 1 year after induction of epileptogenesis. These observations suggest that altered [Ca(2+)](i) homeostatic mechanisms may underlie some aspects of the epileptic phenotype and contribute to the persistent neuroplasticity changes associated with epilepsy.

Animals↗
PubMed2001

p38 activation is required upstream of potassium current enhancement and caspase cleavage in thiol oxidant-induced neuronal apoptosis.

Oxidant-induced neuronal apoptosis has been shown to involve potassium and zinc dysregulation, energetic dysfunction, activation of stress-related kinases, and caspase cleavage. The temporal ordering and interdependence of these events was investigated in primary neuronal cultures exposed to the sulfhydryl oxidizing agent 2,2'-dithiodipyridine (DTDP), a compound that induces the intracellular release of zinc. We previously observed that tetraethylammonium (TEA), high extracellular potassium, or cysteine protease inhibitors block apoptosis induced by DTDP. We now report that both p38 and extracellular signal-regulated kinase phosphorylation are evident in neuronal cultures within 2 hr of a brief exposure to 100 microm DTDP. However, only p38 inhibition is capable of blocking oxidant-induced toxicity. Cyclohexamide or actinomycin D does not attenuate DTDP-induced cell death, suggesting that posttranslational modification of existing targets, rather than transcriptional activation, is responsible for the deleterious effects of p38. Indeed, an early robust increase in TEA-sensitive potassium channel currents induced by DTDP is attenuated by p38 inhibition but not by caspase inhibition. Moreover, we found that activation of p38 is required for caspase 3 and 9 cleavage, suggesting that potassium currents enhancement is required for caspase activation. Finally, we observed that DTDP toxicity could be blocked with niacinamide or benzamide, inhibitors of poly (ADP-ribose) synthetase. Based on these findings, we conclude that oxidation of sulfhydryl groups on intracellular targets results in intracellular zinc release, p38 phosphorylation, enhancement of potassium currents, caspase cleavage, energetic dysfunction, and translationally independent apoptotic cell death.

2,2'-Dipyridyl↗
PubMed2001

Hippocampal neurons exhibit both persistent Ca2+ influx and impairment of Ca2+ sequestration/extrusion mechanisms following excitotoxic glutamate exposure.

Exposure of neurons to glutamate is an essential element of neuronal function, producing transient elevations in free intracellular calcium ([Ca2+]i) that are required for normal physiological processes. However, prolonged elevations in [Ca2+]i have been observed following glutamate excitotoxicity and have been implicated in the pathophysiology of delayed neuronal cell death. In the current study, we utilized indo-1 and fura-2ff Ca2+ imaging techniques to determine if glutamate-induced prolonged elevations in [Ca2+]i were due to persistent influx of extracellular Ca2+ or from impairment of neuronal Ca2+ extrusion/sequestration mechanisms. By experimentally removing Ca2+ from the extracellular solution following glutamate exposure, influx of Ca2+ into the neurons was severely attenuated. We observed that brief glutamate exposures (<5 min, 50 microM glutamate) resulted in a Ca2+ influx that continued after the removal of glutamate. The Ca2+ influx was reversible, and the cell was able to effectively restore [Ca2+]i to resting levels. Longer, excitotoxic glutamate exposures (> or = 5 min) generated a Ca2+ influx that continued for the duration of the recording period (>1 h). This persistent Ca2+ influx was not primarily mediated through traditionally recognized Ca2+ channels such as glutamate receptor-operated channels or voltage-gated Ca2+ channels. In addition to the persistent Ca2+ influx, longer glutamate exposures also produced a lasting disruption of Ca2+ extrusion/sequestration mechanisms, impairing the ability of the neuron to restore resting [Ca2+]i. These data suggest that glutamate-induced protracted [Ca2+]i elevations result from at least two independent, simultaneously occurring alterations in neuronal Ca2+ physiology, including a persistent Ca2+ influx and damage to Ca2+ regulation mechanisms.

Animals↗
PubMed2001

MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants.

MitoTracker dyes are fluorescent mitochondrial markers that covalently bind free sulfhydryls. The impact of alterations in mitochondrial membrane potential (Delta Psi(m)) and oxidant stress on MitoTracker staining in mitochondria in cultured neurons and astrocytes has been investigated. p-(Trifluoromethoxy) phenyl-hydrazone (FCCP) significantly decreased MitoTracker loading, except with MitoTracker Green in neurons and MitoTracker Red in astrocytes. Treatment with FCCP after loading increased fluorescence intensity and caused a relocalization of the dyes. The magnitude of these effects was contingent on which MitoTracker, cell type and dye concentration were used. H(2)O(2) pretreatment led to a consistent increase in neuronal MitoTracker Orange and Red and astrocytic MitoTracker Green and Orange fluorescence intensity. H(2)O(2) exposure following loading increased MitoTracker Red fluorescence in astrocytes. In rat brain mitochondria, high concentrations of MitoTracker dyes uncoupled respiration in state 4 and inhibited maximal respiration. Thus, loading and mitochondrial localization of the MitoTracker dyes can be influenced by loss of Delta Psi(m) and increased oxidant burden. These dyes can also directly inhibit respiration. Care must be taken in interpreting data collected using MitoTrackers dyes as these dyes have several potential limitations. Although MitoTrackers may have some value in identifying the location of mitochondria within cultured neurons and astrocytes, their sensitivity to Delta Psi(m) and oxidation negates their use as markers of mitochondrial dynamics in healthy cultures.

Aldehydes↗
PubMed2001

Immunobiology of CD28 expression on human neutrophils. I. CD28 regulates neutrophil migration by modulating CXCR-1 expression.

CD28, described as a T cell costimulatory molecule so far, is expressed on human peripheral blood neutrophils, as shown by cell surface staining and immunoprecipitation with anti-CD28 monoclonal antibody, and by reverse transcription PCR. The phorbol 12-myristate 13-acetate-augmented expression of CD28 on these cells can be blocked by actinomycin D, an RNA transcription inhibitor, and staurosporin, a protein kinase inhibitor. Cross-linking of CD28 results in an early increase in IL-8 receptor A (IL-8RA or CXCR-1) expression and a concurrent increase in IL-8-induced chemotaxis. The expression of CXCR-1 is down-regulated by receptor internalization 3 h after CD28 cross-linking with concurrent decrease in IL-8-induced chemotactic migration. Thus, our results demonstrate for the first time that CD28 is expressed on human peripheral blood neutrophils and that CD28 may play an important role in the regulation of IL-8RA expression and migration of neutrophils in response to IL-8.

Adult↗
PubMed2001

Current status of surgery and transplantation in the management of hepatocellular carcinoma: an overview.

Despite many therapeutic advances in the field of hepatocellular carcinoma over the past two decades, this disease continues to be a major cause of cancer-related mortality worldwide. This review focuses on the recent advances in surgical technique, perioperative management, and transplantation of cirrhotic and noncirrhotic patients with hepatocellular carcinoma. Liver resection continues to be the mainstay of curative treatment in noncirrhotic patients and selected cirrhotic patients with small tumors and preserved liver function. Transplantation should be advocated for patients with poor liver function and localized lesions or for patients with large fibrolamellar carcinomas that are otherwise unresectable. Surgery has a definite role in the management of hepatic recurrences in the absence of systemic dissemination. Newer advances in the therapeutic armamentarium, such as cryotherapy, radiofrequency ablation, microwave coagulation, and ethanol injections are discussed, and their overall efficacy assessed.

Carcinoma, Hepatocellular↗
PubMed2001

A study of excessive daytime sleepiness and its clinical significance in three groups of Parkinson's disease patients taking pramipexole, cabergoline and levodopa mono and combination therapy.

OBJECTIVE: To determine if therapy with an ergot and a non-ergot dopamine agonist and levodopa confers an increased risk of excessive daytime sleepiness and secondary "sleep attacks" in Parkinson's disease (PD). METHODS: Comparative study of three clinical groups taking, pramipexole (Group 1, n = 19, 8 monotherapy), cabergoline (Group 2, n = 22, 10 monotherapy), and levodopa monotherapy (Group 3, n = 14). Clinical and demographic characteristics, occurrence of "sleep attacks", and assessment of daytime sleepiness [using the Epworth Sleepiness Scale (ESS)], recorded. RESULTS: No patients reported "sleep attacks". Mean ESS scores: Group 1 (pramipexole) 8.0 +/- 4.5 (range 0-16), Group 2 (cabergoline) 8.1 +/- 3.9 (range 0-19), Group 3 (levodopa), 8.1 +/- 5.5 (range 1-18). There was no significant difference between groups (p = 0.897). Scores of > or = 16 indicating excessive daytime sleepiness (EDS) were evenly distributed throughout treatment groups, particularly in older patients with more advanced disease. CONCLUSIONS: a) EDS is not unique to pramipexole therapy and occurs with both cabergoline and levodopa. b) Increasing age, advanced disease, and higher treatment dose appear important predictors for EDS. c) Driving regulations should be reviewed accordingly.

Adult↗
PubMed2001

Collagen-chitosan polymeric scaffolds for the in vitro culture of human epidermoid carcinoma cells.

A biodegradable polymer scaffold was developed using collagen and chitosan, in the form of interpenetrating polymeric network (IPN), for in vitro culture of human epidermoid carcinoma cells (HEp-2, Cincinnati). Glutaraldehyde was used as cross-linking agent for the development of scaffold. Various types of scaffolds were prepared using different proportionate mixtures of collagen and chitosan solutions in the ratio of 3:7, 4:6, 5:5, 6:4 and 7:3 (collagen:chitosan). These scaffolds were fully characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA). Equilibrium swelling studies were carried out in phosphate buffer of physiological pH (7.4) to study its swelling characteristics at slightly alkaline pH. The scaffold that showed optimum swelling property was selected as the best scaffold for performing in vitro culture studies. In vitro culture studies were carried out using HEp-2 cells, over the selected scaffold and its growth morphology was determined through optical photographs taken at different magnifications at various days of culture. The results of the above studies suggest that the scaffolds prepared from collagen and chitosan can be utilized as a substrate to culture HEp-2 cells and can also be used as an in vitro model to test anticancerous drugs.

Animals↗