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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 253 records · Page 14Linked to original sources
PubMed1999

Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway.

The cell adhesion molecule intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in inflammatory responses. Quercetin (3,3',4',5,7-pentahydroxyflavone), a naturally occurring dietary flavonol, has potent anti-inflammatory properties. The effect of quercetin on ICAM-1 expression induced by agonists phorbol 12-myristate 13-acetate (PMA) and tumor necrosis factor-alpha (TNF-alpha) in human endothelial cell line ECV304 (ECV) was investigated. Quercetin treatment downregulated both PMA- and TNF-alpha-induced surface expression, as well as the ICAM-1 mRNA levels, in ECV cells in a dose-dependent (10-50 microM) manner. Quercetin had no effect on PMA- or TNF-alpha-induced nuclear factor-kappaB (NF-kappaB) activation. However, under similar conditions a remarkable dose-dependent downregulation of activator protein-1 (AP-1) activation was observed. This decrease in AP-1 activation was observed to be associated with the inhibitory effects of quercetin on the c-Jun NH2-terminal kinase (JNK) pathway. These results suggest that quercetin downregulates both PMA- and TNF-alpha-induced ICAM-1 expression via inhibiting both AP-1 activation and the JNK pathway.

Endothelium, Vascular↗
PubMed1999

Cytokine-induced glucose uptake in skeletal muscle: redox regulation and the role of alpha-lipoic acid.

In L6 myotubes, glucose uptake stimulated by interferon (IFN)-gamma or lipopolysaccharides (LPS) and a combination of LPS, IFN-gamma, and tumor necrosis factor (TNF)-alpha was inhibited by the antioxidant pyrrolidinedithiocarbamate and potentiated in reduced glutathione (GSH)-deficient cells. Also, the stimulatory effect of LPS and IFN-gamma individually, and of a combination of LPS, IFN-gamma, and TNF-alpha, on glucose uptake was associated with an increased level of intracellular oxidants (dichlorofluorescein assay) and loss of intracellular GSH. Study of the individual effects of LPS, IFN-gamma, and TNF-alpha as well as of a combination of the three activators provided evidence against a role of nitric oxide in mediating the stimulatory effect of the above-mentioned agents on glucose uptake. We also observed that the insulin-mimetic nutrient alpha-lipoic acid (LA; R-enantiomer) is able to stimulate glucose uptake in cytokine-treated cells that are insulin resistant. This study shows that cytokine-induced glucose uptake in skeletal muscle cells is redox sensitive and that, under conditions of acute infection that is accompanied with insulin resistance, LA may have therapeutic implications in restoring glucose availability in tissues such as the skeletal muscle.

Animals↗
PubMed1999

Alpha-lipoic acid supplementation: tissue glutathione homeostasis at rest and after exercise.

Antioxidant nutrients have demonstrated potential in protecting against exercise-induced oxidative stress. alpha-Lipoic acid (LA) is a proglutathione dietary supplement that is known to strengthen the antioxidant network. We studied the effect of intragastric LA supplementation (150 mg/kg, 8 wk) on tissue LA levels, glutathione metabolism, and lipid peroxidation in rats at rest and after exhaustive treadmill exercise. LA supplementation increased the level of free LA in the red gastrocnemius muscle and increased total glutathione levels in the liver and blood. The exercise-induced decrease in heart glutathione S-transferase activity was prevented by LA supplementation. Exhaustive exercise significantly increased thiobarbituric acid-reactive substance levels in the liver and red gastrocnemius muscle. LA supplementation protected against oxidative lipid damage in the heart, liver, and red gastrocnemius muscle. This study reports that orally supplemented LA is able to favorably influence tissue antioxidant defenses and counteract lipid peroxidation at rest and in response to exercise.

Analysis of Variance↗
PubMed1999

Synchronization of local neural networks in the somatosensory cortex: A comparison of stationary and moving stimuli.

Spontaneous and stimulus-induced responses were recorded from neighboring groups of neurons by an array of electrodes in the primary (SI) somatosensory cortex of intact, halothane-anesthetized cats. Cross-correlation analysis was used to characterize the coordination of spontaneous activity and the responses to peripheral stimulation with moving or stationary air jets. Although synchronization was detected in only 10% (88 of 880) of the pairs of single neurons that were recorded, cross-correlation analysis of multiunit responses revealed significant levels of synchronization in 64% of the 123 recorded electrode pairs. Compared with spontaneous activity, both stationary and moving air jets caused substantial increases in the rate, proportion, and temporal precision of synchronized activity in local regions of SI cortex. Among populations of neurons that were synchronized by both types of air-jet stimulation, the mean rate of synchronized activity was significantly higher during moving air-jet stimulation than during stationary air-jet stimulation. Moving air jets also produced significantly higher correlation coefficients than stationary air jets in the raw cross-correlograms (CCGs) but not in the shift-corrected CCGs. The incidence and rate of stimulus-induced synchronization varied with the distance separating the recording sites. For sites separated by </=300 microm, 80% of the multiunit responses displayed significant levels of synchronization during both types of air-jet stimulation. For sites separated by >/=500 microm, only 37% of the multiunit responses were synchronized by discrete stimulation with a single air jet. Measurements of the multiunit CCG peak half-widths showed that the correlated activity produced by moving air jets had slightly less temporal variability than that produced by stationary air jets. These results indicate that moving stimuli produce greater levels of synchronization than stationary stimuli among local groups of SI neurons and suggest that neuronal synchronization may supplement the changes in firing rate which code intensity and other attributes of a cutaneous stimulus.

Animals↗
PubMed1999

Placement of a spring filter during interventional treatment of deep venous thrombosis to reduce the risk of pulmonary embolism.

PURPOSE: To assess the efficacy of the Spring filter during interventional treatment of deep venous thrombosis in vivo. MATERIAL AND METHODS: A model of inferior vena cava thrombosis was used. Part I: The thrombus was treated by the pulse-spray technique (PT) (urokinase 250,000 IU; n=7) or a rotatory basket catheter, Thrombolizer (MT) (activated with compressed air at 7 atm; n=5). Part II: Following placement of a Spring filter, the animal underwent PT (n=5) or MT (n=5). Based on the results of part I, the treatment protocol was modified (PT, urokinase 500,000 IU; MT, compressed air at 8 atm). Embolus volumes trapped by the filter and found in the lungs were calculated and the filtering efficacy quantified. RESULTS: Part I: Pulmonary emboli (1 to 4 mm in diameter) were observed in 3 animals in the PT group and 1 animal in the MT group, respectively. Median reduction in thrombus volume was 21% and 4% by PT and MT, respectively. Part II: In the PT group, 58% and 100% of the total embolus load was trapped in 2 animals, while the filter failed to trap emboli (1 to 1.5 mm in diameter) in 1 animal. In the remaining 2 animals, no embolus was found trapped by the filter or in the lungs. In the MT group, 55 97% (median 83%) of the embolus load was trapped. Emboli found in the lungs did not exceed 4 mm in diameter. CONCLUSION: Preceding interventional treatment of venous thrombosis with placement of the Spring filter reduced the embolic burden on the lungs.

Angiography↗
PubMed1999

Infectivity and attenuation of Leishmania donovani promastigotes: association of galactosyl transferase with loss of parasite virulence.

During the course of long-term in vitro cultivation of Leishmania donovani parasites, the promastigotes were found to lose their infectivity. Lectin agglutination studies revealed that there is an up-regulation of terminally exposed galactose residues on the noninfective promastigotes. The enzyme galactosyl transferase was absent in the infective form but present in the non-infective form of the parasites. An association between galactosylation and loss of infectivity was also observed. We propose that the enzyme galactosyl transferase is developmentally regulated and induces galactosylation of surface carbohydrates.

Agglutination↗
PubMed1999

Characterization of selective induction and alteration of xenobiotic biotransforming enzymes by vanadium during diethylnitrosamine-induced chemical rat liver carcinogenesis.

Our recent studies have shown that vanadium, a dietary micronutrient, has an inhibitory response against experimentally induced rat liver carcinogenesis. In the present study, the effect of vanadium on hepatic xenobiotic biotransformation in rats exposed to diethylnitrosamine (DENA, 200 mg/kg, IP) was investigated to elucidate a possible mechanism of vanadium-mediated prevention of chemical carcinogenesis. Supplementary vanadium in drinking water at 0.5 parts per million (ppm) was employed ad lib before and after the intiation with DENA, before the initiation only, or during the promotional event. After 20 weeks, there was a significant reduction of hepatocyte nodules (HNs) (P<0.01), nodule multiplicity (P<0.001), and the number of nodules more than 3 mm in size in the long-term vanadium-supplemented rats than their DENA control counterparts. Total cytochrome P450 and b5 contents as well as cytochrome P450 2E1 (CYP2E1, EC 1.5.99), aryl hydrocarbon hydroxylase (AHH, EC 1.14.14.2), and UDP-glucuronyl transferase (UDPGT, EC 2.4.1.17) activities in the microsomal fractions of HNs and nonnodular surrounding parenchyma (NNSP) were found to be significantly decreased in DENA control group compared to untreated normal control. Though supplementary vanadium had little or no influence on the contents of cytochrome P450 and b5 and activities of CYP2E1 and AHH in HNs and NNSP, it substantially elevated the UDPGT activity in both HNs and NNSP liver areas. DENA treatment alone also brought about a sharp decrease in cytosolic UDP-glucose dehydrogenase (EC 1.1.1.22), DT-diaphorase (EC 1.6.99.2), and glutathione S-transferase (EC 2.5.1.18) activities in HNs and NNSP compared to normal liver. Supplementary vanadium was found to exert a marked induction in these cytosolic enzymes in HNs as well as NNSP when compared to DENA control. A positive correlation of phase I and phase II drug metabolizing enzymes in HNs or NNSP was always observed in DENA or DENA plus long-term vanadium-treated group. It is concluded that the chemoprotective effect of vanadium may be attributed to the substantial elevation of phase II conjugating enzymes, which may lead to a move and shift of the metabolic profile that may reduce the intracellular concentration of carcinogen-derived reactive intermediates.

Animals↗
PubMed1999

Deficiency of the transcription factor c-fos increases lipopolysaccharide-induced macrophage interleukin 12 production.

BACKGROUND: Interleukin 12 (IL-12) p70 is a heterodimeric protein (p35, p40 subunits) that promotes T-helper TH1-type cytokine response. In critically ill patients, after severe trauma or sepsis, IL-12 production is markedly impaired. We tested the hypothesis that deficiency of the transcription factor c-fos will increase macrophage IL-12 production. METHODS: We harvested adherent peritoneal macrophages harvested from wild-type (WT), heterozygous c-fos knockout (Hetero KO), or homozygous c-fos knockout (Homo KO) mice and investigated lipopolysaccharide (LPS)-induced IL-12 p70 protein synthesis (by enzyme-linked immunosorbent assay), IL-12 p35 and IL-12 p40 messenger RNA accumulation (mRNA) (by reverse transcriptase-polymerase chain reaction), and the transcription rate (by nuclear runoff). RESULTS: (1) LPS treatment compared with vehicle increases c-fos mRNA accumulation 5-fold and AP-1 DNA protein binding (electrophoretic mobility shift assay), which precedes either IL-12 p35 or IL-12 p40 mRNA accumulation. (2) LPS induces a significant increase in IL-12 p70 protein, IL-12 p40 mRNA, and the transcription rate in the Homo KO group compared with either the Hetero KO or WT groups. (3) Compared with vehicle control, we demonstrate that interferon gamma priming increases LPS-stimulated macrophage IL-12 p70 protein in the Hetero KO or WT groups to the level of the Homo KO group but has no significant effect on the Homo KO group. CONCLUSIONS: These data suggest that deficiency of the transcription factor c-fos increases LPS-induced macrophage IL-12 production, possibly by simulating the effect of interferon gamma priming.

Animals↗
PubMed1999

Development and evaluation of transdermal formulations containing metronidazole and norfloxacin for the treatment of burn wound.

In an attempt for better treatment of partial thickness burn wounds topical ointments containing metronidazole and norfloxacin in different bases were prepared and in vitro release was conducted in phosphate buffer pH 6. It was found that, diffusion of the metronidazole and norfloxacin from the lanolin petrolatum base with 0.25% w/w dimethyl sulfoxide was maximum through hairless rat abdominal skin. Antimicrobial activity of different prepared formulations was found to be more effective both against aerobic and anaerobic bacteria than marketed formulation (1% silver sulfadiazine cream USP). Formulations were significantly effective as compared to that of marketed formulation in wound contraction of the partial thickness burn wound. Histopathological reports supported effectiveness of formulations. It was found that 1% metronidazole and 1% norfloxacin ointments are suitable for treating the partial thickness burn wound.

Administration, Cutaneous↗
PubMed1999

Increased interleukin-6 in aqueous humor of neovascular glaucoma.

PURPOSE: To demonstrate the involvement of proinflammatory cytokines in intraocular neovascularization by detecting the presence of interleukin (IL)-6, IL-2, and tumor necrosis factor (TNF)-alpha in aqueous humor and serum of patients with neovascular glaucoma (NVG) secondary to central retinal vein occlusion (CRVO). METHODS: According to the grade of iris neovascularization (NVI), patients with CRVO were divided into three groups: CRVO without NVI, CRVO with NVI, and CRVO with regressed NVI. Healthy patients with cataract were enrolled as control subjects. Enzyme-linked immunosorbent assay was used to quantitate the concentrations of the cytokines IL-6, IL-2, and TNF-alpha in aqueous humor and serum from patients with NVG and control subjects. RESULTS: In serum, the levels of IL-6, IL-2, and TNF-alpha did not differ among groups. In aqueous humor, only IL-6 showed significant change among groups. IL-6 levels in aqueous humor of group 2, CRVO with NVI (1532.0+/-221.1 pg/ml; P < 0.001), and group 3, CRVO with regressed NVI (234+/-154.6 pg/ml; P < 0.001), were significantly higher. There was no significant difference in IL-6 levels between the control group (26.4+/-21.8 pg/ml) and group 1 (15.6+/-0.9 pg/ml). CONCLUSIONS: The inflammatory cytokine IL-6 in aqueous humor increased spatially and temporally correlated with the grade of NVI in patients of NVG secondary to CRVO. The aqueous IL-6 increased in NVI and decreased after vessels regressed. It is possible that the significantly higher level of IL-6 was due to intraocular synthesis because of the minimal change in serum. The increased level of IL-6 may have a putative role along with other angiogenic factors in angiogenesis of NVG as a possible predictor of NVI.

Aged↗
PubMed1999

The effects of cadmium on the hepatic and renal levels of reduced glutathione, the activity of glutathione S-transferase and gamma glutamyl transpeptidase.

Cadmium chloride, injected subcutaneously in mice at doses of 1.0, 1.5, and 2.0 mg/Kg body weight, resulted in the alteration of body weight and relative liver and kidney weights, the hepatic and renal reduced glutathione levels, and the activity of the enzymes glutathione S-transferase and gamma-glutamyl transpeptidase in a dose-dependent manner. Body weight increased insignificantly with dosage, but significant elevations in relative liver weight (29% of control) and particularly in kidney weight (93% of control) were documented in the cases that received the highest dose of cadmium chloride (2.0 mg/Kg body weight). The treatment significantly lowered hepatic and renal reduced glutathione levels and glutathione S-transferase activity. On the other hand, the gamma-glutamyl transpeptidase activity was found to increase significantly after treatment, with the highest values in the liver (137% of control) and in the kidneys (204% of control). We found that cadmium chloride at 2.0 mg/Km body weight produced the greatest changes in the abovementioned parameters. A significant correlation (r) was observed in some cases among the abovementioned biomolecules between, as well as within, the organs. The present study showed that the effects of cadmium could be correlated with a decreased level of reduced glutathione and glutathione S-transferase activity and an increased activity of gamma-glutamyl transpeptidase in liver and kidney.

Animals↗
PubMed1998

An apyrase from Mimosa pudica contains N5,N10-methenyl tetrahydrofolate and is stimulated by light.

An apyrase (NTP/NDPase) implicated in the response of Mimosa pudica to stimuli, such as touch, has been cloned, sequenced and expressed in Escherichia coli. While purifying and characterizing this enzyme, it was observed that a chromophore is associated with it, having absorption in the ultraviolet-A/blue region of the spectrum. The absorbance maximum of the chromophore, purified from the enzyme complex by gel filtration and HPLC, is around 350 nm. The chromophore has been identified as N5,N10-methenyl tetrahydrofolate (MTHF) by comparing the excitation and emission spectra of synthetic MTHF and the isolated cofactor, and by reconstitution of the enzyme complex with synthetic MTHF. Upon excitation with light (350 nm), an increase of apyrase activity was observed in the purified or reconstituted holoenzyme but not in the apoenzyme. The wavelength dependence of the light stimulation matched well with the fluorescence excitation spectra of the cofactor, MTHF. Possible implications of the results for signal transduction in M. pudica have been discussed.

Amino Acid Sequence↗
PubMed1998

E1A-induced processing of procaspase-8 can occur independently of FADD and is inhibited by Bcl-2.

Expression of the 243-residue form of the adenovirus E1A protein in the absence of other viral proteins triggers apoptosis by a pathway that requires p53. This pathway includes processing and activation of initiator procaspase-8, redistribution of cytochrome c, and activation of procaspase-3. Bcl-2 functions at or upstream of procaspase-8 processing to inhibit all of these events and prevent cell death. This contrasts with the anti-apoptotic influence of Bcl-2 family proteins in the cell death pathway induced by Fas ligand or tumor necrosis factor (TNF), in which Bcl-2 typically acts downstream of Fas/TNFR1-mediated activation of caspase-8. Moreover, E1A induces procaspase-8 processing and cell death in cells deleted of FADD, an adaptor protein critical for Fas/TNFR1 activation of caspase-8. The results indicate that E1A is capable of activating caspase-8 by a Bcl-2-inhibitable pathway that does not involve autocrine stimulation of FADD-dependent death receptor pathways.

Adenovirus E1A Proteins↗
PubMed1998

X-ray analysis of a complex of Escherichia coli uracil DNA glycosylase (EcUDG) with a proteinaceous inhibitor. The structure elucidation of a prokaryotic UDG.

Uracil-DNA glycosylase (UDG), a key highly conserved DNA repair enzyme involved in uracil excision repair, was discovered in Escherichia coli . The Bacillus subtilis bacteriophage, PBS-1 and PBS-2, which contain dUMP residues in their DNA, express a UDG inhibitor protein, Ugi which binds to UDG very tightly to form a physiologically irreversible complex. The X-ray analysis of the E. coli UDG ( Ec UDG)-Ugi complex at 3.2 A resolution, leads to the first structure elucidation of a bacterial UDG molecule. This structure is similar to the enzymes from human and viral sources. A comparison of the available structures involving UDG permits the delineation of the constant and the variable regions of the molecule. Structural comparison and mutational analysis also indicate that the mode of action of the enzyme from these sources are the same. The crystal structure shows a remarkable spatial conservation of the active site residues involved in DNA binding in spite of significant differences in the structure of the enzyme-inhibitor complex, in comparison with those from the mammalian and viral sources. Ec UDG could serve as a prototype for UDGs from pathogenic prokaryotes, and provide a framework for possible drug development against such pathogens with emphasis on features of the molecule that differ from those in the human enzyme.

Bacillus Phages↗
PubMed1998

MU-opioid receptor-knockout mice: role of mu-opioid receptor in morphine mediated immune functions.

The role of the mu-opioid receptor in immune function was investigated using mu-opioid receptor knockout mice (MOR-KO). Morphine modulation of several immune functions, including macrophage phagocytosis and macrophage secretion of TNF-alpha, was not observed in the MOR-KO animals, suggesting that these functions are mediated by the classical mu-opioid receptor. In contrast, morphine reduction of splenic and thymic cell number and mitogen-induced proliferation were unaffected in MOR-KO mice, as was morphine inhibition of IL-1 and IL-6 secretion by macrophages. These latter results are consistent with morphine action on a naloxone insensitive morphine receptor, a conclusion supported by previous studies characterizing a nonopioid morphine binding site on immune cells. Alternatively, morphine may act either directly or indirectly on these cells, by a mechanism mediated by either delta or kappa opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗