Search PubMed⌕ Search

Biomedical subjects

A Singh

Publications and source records attributed to A Singh.

At least 361 records · Page 20Linked to original sources
PubMed1995

Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats.

Seeds of Apium graveolens L. (Apiaceae) and Hygrophila auriculata (K. Schum.) Heine (Syn. Astercantha auriculata Nees, Acanthaceae) are used in Indian systems of medicine for the treatment of liver ailments. The antihepatotoxic effect of methanolic extracts of the seeds of these two plants was studied on rat liver damage induced by a single dose of paracetamol (3 g/kg p.o.) or thioacetamide (100 mg/kg, s.c.) by monitoring several liver function tests, viz. serum transaminases (SGOT and SGPT), alkaline phosphatase, sorbitol dehydrogenase, glutamate dehydrogenase and bilirubin in serum. Furthermore, hepatic tissues were processed for assay of triglycerides and histopathological alterations simultaneously. A significant hepatoprotective activity of the methanolic extract of the seeds of both the plants was reported.

Acetaminophen↗
PubMed1995

Construction of chimeric beta-glucosidases with improved enzymatic properties.

The amino acid sequences of beta-glucosidases from Cellvibrio gilvus and Agrobacterium tumefaciens show about 40% similarity. The pH/temperature optima and stabilities and substrate specificities of the two enzymes are quite different. C. gilvus beta-glucosidase exhibits an optimum pH of 6.2-6.4 and temperature of 35 degrees C, whereas the corresponding values for A. tumefaciens are 7.2-7.4 and 60 degrees C, respectively. The substrate specificity of A. tumefaciens enzyme toward different aryl glycosides is broader than C. gilvus enzyme. To analyze these properties further, three chimeric beta-glucosidases were constructed by substituting segments from the C-terminal homologous region of C. gilvus beta-glucosidase gene with that of A. tumefaciens. The chimeric enzymes were characterized with respect to pH/temperature activity and stability and substrate specificity. Chimeric enzymes exhibited chromatographic behavior similar to that of C. gilvus enzyme. However, enzymatic properties of chimeras were admixtures of those of the two parents. The chimeric enzymes were optimally active at 45-50 degrees C and pH 6.6-7.0. Km values of chimeric enzymes for the various saccharides were admixtures of both parental enzymes. These results suggest that the two domains of C. gilvus and A. tumefaciens enzymes probably can fold independently. The homologous C-terminal region in beta-glucosidase appears to play an important role in determining enzyme characteristics. Changes in the properties on substitution of segments in this region might be related to the enzyme specificity, and beta-glucosidases with improved properties can be prepared by manipulating this region.

Agrobacterium tumefaciens↗
PubMed1995

Postnatal modulation of hepatic biotransformation system enzymes via translactational exposure of F1 mouse pups to turmeric and curcumin.

The potential for the transfer of active principle(s) of turmeric (Curcuma longa L.) and curcumin (major pigment in turmeric) via translactational route and its modulatory influence on the hepatic biotransformation system enzymes in the lactating dams and their suckling offspring was assessed. Turmeric (4 g/kg b.w. per day) and curcumin (0.4 g/kg b.w. per day) induced significant (P < 0.01) increase in the hepatic levels of glutathione S-transferase (GST) and acid soluble sulfhydryl (-SH) after 14 or 21 days treatment in lactating dams and translactationally exposed F1 pups. However the lower dose of curcumin (0.2 g/kg b.w. per day) could modulate hepatic GST activity (P < 0.05) and -SH (P < 0.01) only after 21 days of treatment in dams and pups. Cytochrome b5 and cytochrome P450 levels were significantly elevated (P < 0.05) in the dams as well as their suckling pups of both 14 and 21 days age groups at the selected dose levels of turmeric (4 g/kg b.w.) and curcumin (0.4 g/kg b.w.). The induction in hepatic biotransformation system enzymes in lactating dams and F1 progeny suggests the passage of active constituents and/or metabolites of turmeric and curcumin via the translactational route.

Animals↗
PubMed1995

Effect of arecanut, a masticatory, on hepatic drug metabolizing enzymes -SH content and lipid peroxidation in lactating mothers and their suckling neonates.

The modulation caused by arecanut, a major ingredient of the masticatory substance betel quid, on biotransformation system enzymes, acid soluble sulfhydryl (-SH) content and lipid peroxidation was assessed in lactating mice and their neonates. Following parturition, dams were fed a 1% arecanut diet and F1 mice were nursed by their own mothers during the lactation period of 21 days. Arecanut induced significant increases in the levels of cytochrome b5, cytochrome P-450, glutathione S-transferase and malondialdehyde (MDA) in dams and their pups. However, it decreased the -SH content in lactating mice and F1 progeny; whether the F1 mice were exposed to the translactational dose of arecanut for 21 days or to a similar translactational dose plus a dietary dose of arecanut for additional post weaning period of 21 days, the pattern of changes in the profile of biotransformation system enzymes was essentially similar. The changes elicited by arecanut intake in the levels/activities of enzymes of the biotransformation system, MDA level and -SH content may enhance the susceptibility of neonatal stages of mice to the action of chemical carcinogens.

Animals↗
PubMed1995

Monolayer study of mixtures of diacetylenic phosphatidylcholine and phospholipids containing metal-chelating iminodiacetic acid headgroup.

The mixing behavior of polymerizable diacetylenic phosphatidylcholine (1) with two diacetylenic phospholipids containing the iminodiacetic acid (IDA) functionality in the headgroup region was studied at the air-water interface. All three phospholipids contained tricosa-10,12-diynoyl acyl chains. In phospholipid 2, the choline group (-CH2-CH2-NMe3) was replaced by an -CH2-CH2-N-(CH2-COOH)2 functionality. In phospholipid 3, the IDA unit was linked to the phosphate headgroup via a sulfonate linker, -CH2-CH2-OS(O2)-O-CH2-CH2-. Monolayers were prepared by mixing polymerizable 1,2 bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (1) with metal-chelating IDA phospholipids (2, 3) on a 10 mM CuCl2 subphase. Studies of monolayer properties of mixtures of 2 and 3 with 1 demonstrated that mixtures of 2 with 1 had better mixing behavior than mixtures of phospholipids 1 and 3.

Chelating Agents↗
PubMed1995

Modulatory influence of arecanut on antioxidant 2(3)-tert-butyl-4-hydroxy anisole-induced hepatic detoxification system and antioxidant defence mechanism in mice.

This paper assesses the modificatory potential of arecanut (Areca catechu L.), a popular masticatory substance, on 2(3)-tert-butyl-4-hydroxy anisole (BHA)-induced changes in the hepatic detoxification system and antioxidant defence mechanisms in mice. The modulatory effects on biochemical parameters including glutathione S-transferase (GST), cytochrome b5, cytochrome P-450, acid soluble sulfhydryl (-SH) content and microsomal lipid peroxidation (MDA) levels were assessed. Mice were fed either a normal diet or diets containing 0.25%, 0.5% or 1% (w/w) arecanut for 45 days. During the last 10 days of treatment the feed was supplemented with 0.5% or 1% BHA. Inclusion of BHA in the diet significantly modulated the detoxification system enzymes, -SH content and malondialdehyde (MDA) levels in the liver of the mice. BHA-induced alterations in hepatic GST and -SH content were depressed while cytochrome b5, cytochrome P-450 and MDA levels were further elevated by the arecanut treatment.

Animals↗
PubMed1995

Construction and characterization of a chimeric beta-glucosidase.

The amino acid sequences of beta-glucosidases from Cellvibrio gilvus and Agrobacterium tumefaciens show significant similarity in most of the parts. However, the pH/temperature optima and stabilities of the two enzymes are quite different. C. gilvus beta-glucosidase exhibits an optimum pH of 6.2-6.4 and temperature of 35 degrees C, whereas the corresponding values for A. tumefaciens are 7.2-7.4 and 60 degrees C respectively. To analyse these properties further, a chimeric beta-glucosidase was constructed by replacing a segment from the C-terminal region of C. gilvus beta-glucosidase gene with that of A. tumefaciens. The partially purified chimeric enzyme was characterized with respect to pH/temperature activity and stability and substrate affinity. Our results suggest that C-terminal segment(s) might be important in beta-glucosidase specificity, and shuffling of even a small segment of gene in this region might significantly alter or improve the enzymic properties such as thermal stability.

Agrobacterium tumefaciens↗
PubMed1995

IL-12 reverses cytokine and immune abnormalities in Sezary syndrome.

Cutaneous T cell lymphoma is a lymphoproliferative disorder typically characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature Th cells. Sezary syndrome (SzS) represents an advanced form of cutaneous T cell lymphoma associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by PBMC in SzS characterized by increased IL-4 and deficient IL-2 and IFN-gamma production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, suggesting that the clonal T cell population is derived from the Th 2 subset of helper T lymphocytes. These findings have been associated with a constellation of immune abnormalities that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-gamma production, and causes the activation of cytotoxic lymphocytes, we examined the production of IL-12 by PBMC from SzS patients and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and thus lead to correction of immune defects. Despite normal numbers of peripheral blood monocytes and normal TNF-alpha production, mean Staphyloccus aureus and LPS-induced IL-12 p40 and p70 production by SzS PBMC was significantly decreased compared with PBMC from normal controls. Mean IFN-gamma production by patient PBMC in response to PHA alone was depressed, but increased to levels comparable with normal after addition of 1 ng/ml IL-12. Pretreatment of PBMC for 24 h with IL-12, IFN-alpha, or both together resulted in a decrease in PHA-stimulated IL-4 production from a base line of 1818 pg/ml to 1520, 1350, and 1058 pg/ml, respectively. Lastly, culture of patient PBMC with IL-12 for 24 h also resulted in significant increases in NK activity against K562 cells. These results indicate that PBMC from patients with SzS manifest a defect in IL-12 production and that the cytokine abnormalities associated with SzS can be favorably altered by IL-12.

Cytokines↗
PubMed1995

Squamous cell carcinoma complicating idiopathic inflammatory bowel disease.

Squamous cell carcinoma of the colon and rectum, originating proximal to the transitional zone, is a rare complication of idiopathic inflammatory bowel disease (IIBD). To date there are only 15 single case reports of such an occurrence. This carcinoma develops more commonly in females and in patients with pancolonic disease of more than 8 years' duration. The rectum is affected in two thirds of the cases. Squamous cell changes, in the vicinity of the primary adenocarcinoma, are present in 27% of cases. The carcinoma is in a pathologically advanced stage in one third of the cases. Colectomy is the main therapeutic modality. Survival following surgical resection ranged from 7 months to 21 years. We present an additional case of rectal squamous cell carcinoma (SCC) complicating chronic ulcerative colitis in a 33-year-old woman who had the disease for 15 years. Multiple biopsies of a gross lesion located 5 cm above the dendate line were consistent with invasive basaloid cell carcinoma. The patient received 5-FU, mitomycin C, and radiotherapy prior to a proctocolectomy and ileostomy. The only histopathologic finding at pathologic review of the surgical specimen was severe squamous dysplasia.

Adult↗
PubMed1995

Effect of destruction of serotonin neurons on basal and fenfluramine-induced serotonin release in striatum.

This study examined the relationship between the magnitude of tissue serotonin (5-HT) depletion produced by treatment with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and basal and fenfluramine-induced 5-HT release in the striatum. Separate groups of rats were treated with either vehicle or 5,7-DHT (100 micrograms: 76% striatal 5-HT depletion; or 200 micrograms: 93% striatal 5-HT depletion). Four weeks after treatment, 5-HT release was measured in the ventral striatum using in vivo microdialysis in animals anesthetized with chloral hydrate. Basal 5-HT levels were not significantly altered in any lesion group, whereas basal 5-hydroxyindoleacetic acid levels were dose-dependently reduced by 5,7-DHT. In contrast, the increase of 5-HT release produced by fenfluramine treatment (10 mg/kg) was diminished significantly after 5-HT neuronal destruction in correlation with the reduction of striatal tissue 5-HT content. Fractional 5-HT efflux, a measure of the 5-HT release from surviving striatal nerve terminals, was also significantly elevated when tissue depletion of 5-HT exceeded 95%. This study suggests that compensatory mechanisms may enable surviving 5-HT terminals to maintain basal 5-HT levels in the striatum with as little as 5% of the terminals remaining, but those mechanisms are not sufficient to allow the damaged system to respond to a pharmacological challenge.

5,7-Dihydroxytryptamine↗
PubMed1995

Evaluation of the modifying influence of arecanut on the garlic-modulated hepatic detoxication system enzymes, sulfhydryl content, and lipid peroxidation in mice.

This paper evaluates the potential effects of arecanut (Areca catechu, L.), an important ingredient of betel quid, on the garlic (Allium sativum, L.)-modulated activities of hepatic detoxication system enzymes, acid soluble sulfhydryl content, and lipid peroxidation in mice. Mice were fed on either a normal diet or a diet containing 0.25%, 0.5%, or 1% (w/w) arecanut for 45 days. During the last 10 days of treatment oral administration of garlic at the dose level of 20 or 100 mg/kg body weight/day was supplemented. Significant modulation in the activities of phase I and phase II enzymes, -SH content, and malondialdehyde (MDA) level by garlic was observed. Garlic-modulated alterations in glutathione S-transferase (GST) activity and -SH content were decreased, while cytochrome b5, cytochrome P-450, and MDA levels were further augmented by the arecanut plus garlic treatments.

Animals↗
PubMed1995

Modulatory influence of arecanut on the mouse hepatic xenobiotic detoxication system and skin papillomagenesis.

The modulatory influence of arecanut, a masticatory in several human populations, on the levels of biotransformation system enzymes in mouse liver has been studied. Swiss albino mice of either sex (4 weeks old) were fed on diets containing 0.25%, 0.5%, or 1% arecanut (w/w) for 5 weeks. In addition, a group of mice received a 1% arecanut diet for 36 weeks. The findings revealed a significant increase in hepatic levels of cytochrome b5, cytochrome P-450, malondialdehyde (MDA), and glutathione S-transferase (GST). The hepatic -SH content was depressed by 0.5% and 1% arecanut diets. Long-term feeding of a 1% arecanut diet elicited changes similar to those seen following treatment for 5 weeks. Arecanut-modulated profiles of biotransformation enzymes and antioxidant levels are suggestive of its influence in the process of carcinogenesis induced by bioactivated electrophilic species of potential chemical carcinogens among habitual arecanut chewers. Arecanut was also tested for its potency either to induce or to alter 7,12-dimethylbenz[a]anthracene (DMBA)-induced papillomagenesis in the skin of the mouse. Animals put on a 1% arecanut diet and treated with a standard two-stage protocol for tumor induction developed a 5.41 tumor burden (control value: 5.76) along with 100% incidence of mice bearing papillomas (control value: 94.4%), thus signifying that dietary intake of 1% arecanut for 18 weeks could not induce/alter the mouse skin tumorigenesis pattern.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Pathogenicity of quail's inclusion body hepatitis virus (avian adenovirus-1) for Japanese quails and broiler chicks.

Quail (Coturnix coturnix japonica) and broiler (Gallus domesticus) chicks were inoculated experimentally with IBH virus (avian adenovirus-1) derived from quails to determine its pathogenicity. Quail chicks were inoculated by the intraperitoneal route at 3, 4, 5, 6 or 7 weeks of age. Lesions were encountered most frequently in the liver, kidneys and lungs. These included pale, swollen and mottled liver, swollen nephrotic kidneys, and congested and pneumonic lungs. The lesions were severe in birds inoculated at 5 weeks of age. Large basophilic intranuclear inclusion bodies were seen in hepatocytes and occasionally in the renal epithelium. The results showed that this isolate is pathogenic for quails above 3 weeks of age. Broiler chicks were inoculated at 4 weeks of age by the intraperitoneal route. The lesions produced in these chicks were similar to those of adenovirus-induced inclusion body hepatitis. Viral antigen was also demonstrated by dot-ELISA in suspension of liver tissue from both quail and broiler chicks.

Adenoviridae Infections↗