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Biomedical subjects

D M Vasudevan

Publications and source records attributed to D M Vasudevan.

At least 19 recordsLinked to original sources

Modulation of lecithin activity by vitamin-B complex to treat long term consumption of ethanol induced oxidative stress in liver.

Alcoholic liver disease (ALD) develops as a consequence of priming and sensitizing mechanisms rendered by cross-interactions of primary mechanistic factors and secondary risk factors. Chronic alcohol abuse and its progression to ALD are associated with abnormal metabolism and low tissue or plasma levels, or both, of many micronutrients. Glutathione depletion is considered the most important sensitizing mechanism. In the present study efficacy of lecithin with vitamin-B complex to treat ethanol induced oxidative stress was compared with the effect of lecithin alone, tocopheryl acetate (vitamin E), as well as capacity of hepatic regeneration during abstention. Ethanol (1.6g / kg body weight/ day for 4 weeks) affects body weight in 16-18 week old male albino rats of Wistar strain weighing 200-220 g. Thiobarbituric acid reactive substance level, nitrite content, protein carbonyl group level, redox ratio (oxidized to reduced glutathione ratio), superoxide dismutase activity, and glutathione s-transferase activity significantly increased on ethanol exposure. Whereas reduced glutathione content, and activities of catalase, glutathione reductase and glutathione peroxidase significantly reduced due to ethanol exposure. These changes were reversed by different treatment. The results suggest that tocopheryl acetate (vitamin E) could partially reverse these changes and act as a potential therapeutic agent. However, lecithin with vitamin-B complex treatment is a promising therapeutic approach. Furthermore, preventive measures were more effective than curative treatment. Prevention of oxidative and nitrosative stress along with correction of nutritional deficiency is one of the proposed mechanisms for the therapeutic approach.

Animals↗

Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver.

The production of reactive oxygen species (ROS) is considered to be a major factor in oxidative cell injury. The antioxidant activity or the inhibition of the generation of free radicals is important in providing protection against such hepatic damage. Silymarin, derived from the milk thistle plant, Silybium marianum, has been used in traditional medicine as a remedy for diseases of the liver and biliary tract. In the present study, the effect of hepatoprotective drug silymarin on body weight and biochemical parameters, particularly, antioxidant status of ethanol-exposed rats was studied and its efficacy was compared with the potent antioxidant, ascorbic acid as well as capacity of hepatic regeneration during abstention. Ethanol, at a dose of 1.6 g/kg body wt/day for 4 wks affected body weight in 16-18 week-old male albino rats (Wistar strain weighing 200-220 g). Thiobarbituric acid reactive substance (TBARS) level, superoxide dismutase (SOD), and glutathione-s-transferase (GST) activities were significantly increased, whereas GSH content, and catalase, glutathione reductase (GR) and GPx (glutathione peroxidase) activities significantly reduced, on ethanol exposure. These changes were reversed by silybin and ascorbic acid treatment. It was also observed that abstinence from ethanol might help in hepatic regeneration. Silybin showed a significant hepatoprotective activity, but activity was less than that of ascorbic acid. Furthermore, preventive measures were more effective than curative treatment.

Animals↗

Effect of chronic ethanol administration on testicular antioxidant system and steroidogenic enzyme activity in rats.

In order to find out the effect of chronic ethanol administration on testicular antioxidant system and steroidogenic enzyme activity, male rats fed with ethanol 1.6g/kg body weight per day for four weeks were studied. Besides a drastic reduction in body and testis weight, there was decrease in ascorbic acid, reduced glutathione and activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in the testicular tissue of the treated animals. Simultaneously, there was increase in lipid peroxidation and glutathione S-transferase activity. Activities of 3 beta-hydroxy steroid dehydrogenase and 17 beta-hydroxy steroid dehydrogenase were also found decreased in the treated animals. The results indicate that chronic ethanol administration resulted in increase in oxidative stress and decrease in the activities of steroidogenic enzymes in the rat testes.

17-Hydroxysteroid Dehydrogenases↗

Inhibition of lipid peroxidation by botanical extracts of Ocimum sanctum: in vivo and in vitro studies.

Ocimum sanctum, the Indian holy basil, has significant ability to scavenge highly reactive free radicals. Shade dried leaf powder of the plant was extracted with water and alcohol, and then fractionated with different solvents. Both extracts and their fractions have in vitro anti-lipidperoxidative activity at very low concentrations. In vivo, hypercholesterolemia-induced erythrocyte lipid peroxidation activity was inhibited by aqueous extracts of Ocimum in a dose-dependent manner in male albino rabbits. Aqueous extract feeding also provided significant liver and aortic tissue protection from hypercholesterolemia-induced peroxidative damage.

Analysis of Variance↗

p53 expression in oral cancer: observations of a South Indian study.

Oral cancers constitute a significant proportion of hospital admissions among cancer patients in India. The aim of this study was to elucidate the role of tumour suppressor gene p53 in the pathogenesis of oral squamous cell carcinoma by immunohistochemistry. Though extensive studies on p53 alterations in oral cancers have been done in Western countries and some Asian countries, only a few studies have emerged from India, especially the Southern states. This study would therefore be helpful in providing an Indian perspective, with particular reference to South Indian states. A total of 110 cases of oral squamous cell carcinoma, 35 dysplastic lesions, 15 hyperplastic lesions, and 50 samples of normal mucosa were assessed for p53 expression. Out of 110 cases of oral carcinoma, 40 (36%) were p53 positive. Among 35 cases of dysplastic lesions studied, 6 (17%) showed p53 positive staining. None of the hyperplastic lesions and normal oral lesions showed any evidence of p53 positivity. However, in 9 out of 40 (23%) cases of positive infiltrating squamous cell carcinomas, the adjacent or overlying non-tumourous epithelium demonstrated focal areas of p53 positive staining in the basal and parabasal layers of the epithelium. In addition, in 7 out of 110 (6%) cases, cytoplasmic staining was observed. In these samples, nuclei were not stained. Our results indicate that p53 over-expression may be involved in only a certain proportion of oral carcinomas. The fact that 6% of the dysplastic lesions were p53 positive, and adjacent non-tumourous epithelium of 23% infiltrating squamous cell carcinomas showed positive staining for p53 in the progenitor compartment of the epithelium indicates that p53 immunoreactivity could be used to detect early tumours as well.

Adult↗

Possible role of Granulocyte Macrophage Colony Stimulating Factor receptor (GM-CSF R) in malaria.

Malaria has been reportedly increasing in incidence on the globe. Evidence from clinical studies supports a role for cytokines in the pathogenesis of cerebral malaria. Given the stimulatory effect of the ligand GM-CSF on the synthesis and release of the pyrogenic cytokine TNF alpha, the present study has been undertaken to investigate a possible role of GMCSF receptor in the pathogenesis of both Plasmodium vivax and Plasmodium falciparum malaria. An enzyme immunoassay developed by us at our laboratory for the quantitation of GM-CSF receptor has been used. No changes in the concentration of the receptor have been indicated either at the time of diagnosis or after treatment. In addition, an intercomparison of the receptor concentration between the P. vivax and P. falciparum groups does not show any significant difference. The results suggest that GM-CSF receptor has no significant role in the pathogenesis of either type of malaria.

Adolescent↗

Activity of Ocimum sanctum (the traditional Indian medicinal plant) against the enteric pathogens.

Aqueous & alcoholic extracts of O. sanctum were prepared. Two concentrations of these extracts (30 mg & 60 mg) were tried against the enteric pathogens & candida albicans by Agar diffusion method. Wide zones of inhibition were observed at 60 mg concentration of extract. Aqeous extract showed wider zone of inhibition when compared to alcoholic extract. Aqueous extract showed wider zones of inhibition for Klebisella, E. Coil, Proteus & Staphylococcus aureus. Alcoholic extract showed wider zone for vibrio cholerae.

Candida albicans↗

Viruses in human oral cancers.

The role of viruses in the etiology of human oral cancer is critically reviewed. Available evidences show a positive correlation for human oral cancer with human papilloma virus (HPV), herpes simplex virus (HSV) and human herpes virus type-6 (HHV-6), having strongest association with HPV. These viruses may act alone or in combination with other carcinogens in the genesis of head and neck malignancies.

Adenoviridae Infections↗

Defective interleukin-2 R gene expression in gastric carcinoma patients.

Peripheral blood T lymphocytes from 15 patients with gastric carcinoma and 6 normal healthy controls were evaluated for Interleukin-2 R gene expression. Total RNA was extracted from T cell-enriched fractions of patients as well as from control peripheral blood lymphocytes, with or without mitogenic stimulation. The presence of mRNA for IL-2 R alpha evaluated by Northern blot analysis revealed that unstimulated T cells expressed lower levels of IL-2 R mRNA than PHA stimulated T cells. Expression of both IL-2 R alpha transcripts (3.5 and 1.5 Kb) were either not detectable or only weakly detectable on T lymphocytes from patients even after mitogenic stimulation. In contrast, a significant rise in the expression of both IL-2 R alpha transcripts was observed on T cells from normal controls followed by mitogenic challenge. This paper reports on the defective IL-2 R alpha gene expression in gastric carcinoma patients, which may explain one of the causes of immunodeficiency associated with neoplastic transformation and progression.

Carcinoma↗

WR-1065 as a chemoprotector in Adriamycin chemotherapy.

The protective effect of WR-1065 against the side effects of Adriamycin was studied in tumor bearing mice. It has been noticed that WR-1065 pretreatment improved the Adriamycin toxicities such as increased enzyme levels, pathological lesions in lung, liver and heart and increased rate of lipid peroxidation, without reducing its anticancer property.

Animals↗

Augmentation of murine natural killer cell and antibody dependent cellular cytotoxicity activities by Phyllanthus emblica, a new immunomodulator.

When administered orally, Phyllanthus emblica, an excellent source of vitamin C (ascorbate), has been found to enhance natural killer (NK) cell activity and antibody dependent cellular cytotoxicity (ADCC) in syngeneic BALB/c mice, bearing Dalton's lymphoma ascites (DLA) tumor. P. emblica elicited a 2-fold increase in splenic NK cell activity on day 3 post tumor inoculation. Enhanced activity was highly significant on days 3, 5, 7 and 9 after tumor inoculation with respect to the untreated tumor bearing control. A significant enhancement in ADCC was documented on days 3, 7, 9, 11 and 13 in drug treated mice as compared to the control. An increase in life span (ILS) of 35% was recorded in tumor bearing mice treated with P. emblica. This increased survival was completely abrogated when NK cell and killer (K) cell activities were depleted either by cyclophosphamide or anti-asialo-GM1 antibody treatment. These results indicate: (a) an absolute requirement for a functional NK cell or K cell population in order that P. emblica can exert its effect on tumor bearing animals, and (b) the antitumor activity of P. emblica is mediated primarily through the ability of the drug to augment natural cell mediated cytotoxicity.

Adjuvants, Immunologic↗

Papilloma virus in cervical carcinoma: detection of viral antigen in cancer cells.

Paraffin sections of biopsies from histopathologically confirmed cases of uterine cervical carcinoma, cervical scrapings from dysplasia, chronic cervicitis, tumour cells from carcinoma of the oral cavity and normal tissues from healthy normal cervix and oral cavity scrapings were examined for the presence of Human papilloma virus antigens. The techniques adopted were the Indirect Immunofluorescence Stainig and the Peroxide-Anti-Peroxidase techniques. The HPV-antigen was present in 38 percent and 41 percent of invasive carcinoma cervix, by PAP and IIF methods respectively. In cervical dysplasia 8-13% revealed HPV antigen while oral carcinoma cells and normal tissue samples were totally negative.

Antigens, Viral↗

Detection of herpes simplex virus type-2 DNA and human papilloma virus DNA sequences in cervical carcinoma tissue by molecular hybridization.

Biopsy samples from one hundred and two patients with squamous cell carcinoma of the uterine cervix and tissues from twelve healthy normal cervical tissues (post hysterectomy) were examined for HSV-type 2 and HPV-11 DNA sequences by molecular hybridization technique. In the carcinoma tissue extracts 53% contained HSV-2 DNA, 27% -HSV-1-DNA and 36% showed HPV-11 gene sequences while 5.7% were found to contain both HPV and HSV-2 DNA. Biopsies from healthy cervix were completely negative for HSV-2 and HPV-11 DNA sequences.

Base Sequence↗

Anti-HHV-6 antibodies in normal population and in cancer patients in India.

The prevalence and titre of IgG antibodies to human herpesvirus type 6 (HHV-6) were assayed in the serum samples from normal subjects and patients with Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukaemia (ALL) and oral cancer (OC) using immunofluorescence and immunoperoxidase techniques. This forms the first study on the sero-prevalence and titre of antibodies to HHV-6 in India. There was no considerable difference in the prevalence (76%) and titre (10-160) of the antibodies in normal population from those reported for normal adults in other parts of the world. All the HL and ALL patients studied showed no significant elevation in the antibody titre, though a slight increase in the prevalence (95%) was noted. Antibody titre and prevalence were found highly elevated in OC. OC remained totally unstudied for the presence of anti-HHV-6 antibodies, and this is the first report of elevated levels of the antibody in this cancer. The role of HHV-6, if any, in the pathogenesis of OC is worth investigating.

Antibodies, Viral↗

Effect of a preparation from Viscum album on tumor development in vitro and in mice.

The effect of Iscador, a commercial preparation made from Viscum album was studied on several cell lines using in vitro tissue culture as well as tumor-bearing animals. Iscador was found to be cytotoxic to animal tumor cells such as Dalton's lymphoma ascites cells (DLA cells) and Ehrlich ascites cells in vitro and inhibited the growth of lung fibroblasts (LB cells), Chinese hamster ovary cells (CHO cells) and human nasopharyngeal carcinoma cells (KB cells) at very low concentrations. Moreover, administration of Iscador was found to reduce ascites tumours and solid tumours produced by DLA cells and Ehrlich ascites cells. The effect of the drug could be seen when the drug was given either simultaneously, after tumour development or when given prophylactically, indicating a mechanism of action very different from other chemotherapeutic drugs. Iscador was not found to be cytotoxic to lymphocytes.

Animals↗