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Biomedical subjects

G Ramesh

Publications and source records attributed to G Ramesh.

At least 37 records · Page 2Linked to original sources
PubMed2000

Facile and efficient one-pot synthesis of 4beta-arylaminopodophyllotoxins: synthesis of DNA topoisomerase II inhibitors (NPF and W-68).

A series of 4beta-arylamino-4'-O-demethylepipodophyllotoxins and 4beta-arylaminoepipodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF. W-68 and other DNA topoisomerase II inhibitors are prepared in good to excellent yields by this method and these are active or more active than etoposide in their inhibition of the human DNA topoisomerase II.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Active immunization against riboflavin carrier protein results in peri-implantation embryonic loss leading to pregnancy termination in rats: use of alternate adjuvants.

To investigate the mechanism of pregnancy termination following immuno-neutralization of riboflavin carrier protein (RCP) and to use acceptable adjuvants, we actively immunized female rats with reduced and carboxymethylated RCP (RCM-RCP) using various adjuvants (during primary immunization) such as sodium phthalylated lipopolysaccharide (SPLPS), purified S. typhi outer membrane proteins (porins) and a combination of them. Rats (5-14 per group) were immunized with alugel adsorbed RCM-RCP (100 microg/dose) either alone or with SPLPS or porins or SPLPS+porins. Control animals received RCM-RCP emulsified with Fruend's completelincomplete adjuvants (FCA/FIA). All animals received five boosters at intervals of 21 days. The lowest (4 X 10(-3)) and the highest (> 70 X 10(-3)) anti-RCM-RCP antibody titers were observed in alugel adsorbed-RCM-RCP group and control groups, respectively. Immunized animals showed reduced fertility following 3rd, 4th and 5th boosters. Reduction in fertility was 30-60% in alugel adsorbed RCM-RCP group, 90-100% in FCA-RCM-RCP group and 80-90% in SPLPS+porins group. Fertility reduction was not strictly correlatable with the serum antibody titers. RCP-specific IgG could be localized in the uterine endometrial glands and luminal epithelial cells in the immunized animals. Animals in the FCA/FIA group showed abnormal implantation/resorption sites and their histological sections showed degenerated embryos. But, day 5 preimplantation embryos were normal. These results show that (a) SPLPS+porins can be used as adjuvants in place of FCA/FIA for active immunization against RCM-RCP and (b) early termination of pregnancy in the immunized animals is due largely to the failure of normal embryo implantation.

Abortifacient Agents↗
PubMed1999

Increased plasma nitrite level in cardiac failure.

Increased Plasma Nitrite Level in Cardiac Failure. Nitric oxide is implicated in the pathogenesis of cardiac failure. Plasma nitrite level (an end product of nitric oxide metabolism) is studied in 15 patients of chronic rheumatic valvular heart disease with myocardial contractile dysfunction and cardiac failure (Group I), 15 patients of chronic rheumatic valvular heart disease with similar valvular lesions, normal myocardial contractile function and without cardiac failure (Group II) and 15 healthy controls (Group III). Patients in Group I had higher nitrite level (242.2+/-31.7 n m) compared to Group II (142.6+/-24.4 n m) and Group III (102.7+/-15.9 n m). Among the patients with rheumatic heart disease, increasing nitrite level correlated significantly with worsening of contractile function [Nitrite v End systolic volume/Body surface area (T(xy.z)=0.23), Nitrite v End systolic dimension/Body surface area (T(xy.z)=0.32), Nitrite v left ventricular ejection fraction (T(xy.z)=-0.24), Nitrite v tricuspid annular plane systolic excursion (T(xy.z)=-0. 29)] and worsening New York Heart Association (NYHA) functional class (r(s)=0.5). We conclude that plasma nitrite, a stable end product of nitric oxide metabolism is increased in patients of rheumatic valvular heart disease with cardiac failure, suggesting increased nitric oxide production. Increased level of nitric oxide might be playing a significant role in myocardial contractile dysfunction and alteration of vascular response in cardiac failure.

Female↗
PubMed1998

Effect of cis-unsaturated fatty acids on Meth-A ascitic tumour cells in vitro and in vivo.

Earlier studies performed both by us and by others have demonstrated that some n-3 and n-6 fatty acids can inhibit the growth of tumour cells in vitro. Though studies done with various types of oils rich in n-3 and n-6 fatty acids did show that the tumour incidence and growth can be modified, there were relatively few studies wherein the anti-tumour effects of individual free fatty acids were studied. Here we present results which suggest that free fatty acids (oleic acid (OA), linoleic acid (LA), alpha-linolenic acid (ALA), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) can inhibit the growth of methylcholanthrene-induced sarcoma cells (Meth-A cells) in vitro. The order of potency of various fatty acids on the growth of Meth-A cells was DHA > ALA > EPA > AA > GLA > LA > OA and their ID50 values were 10, 20, 35, 45, 68, 73 and 110 microg/ml/1 x 10(4) cells, respectively. These results indicate that the inhibitory action of different types of n-3, n-6 and n-9 fatty acids on Meth-A cells does not depend on their unsaturation. Vitamin E could partially block the cytotoxicity of these fatty acids indicating a possible role for free radicals. GLA, AA and EPA augmented the generation of superoxide anion and lipid peroxidation in Meth-A cells indicating a possible correlation between the ability of fatty acids to augment free radicals and their tumoricidal action. In an in vivo study, it was observed that OA, LA, ALA, GLA and EPA can prolong the survival of Meth-A-bearing mice when given intraperitoneally. Of all the fatty acids tested, surprisingly, LA was found to be the most potent in enhancing the survival of the tumour-bearing animals at all the concentrations tested. Thus, these studies suggest that free fatty acids can inhibit Meth-A tumour cell proliferation both in vitro and in vivo.

Animals↗
PubMed1998

Effect of evening primrose and fish oils on two stage skin carcinogenesis in mice.

The effect of fish oil (FO, given in the form of MaxEPA) rich in n-3 fatty acids and evening primrose oil (EPO) rich in n-6 fatty acids on two-stage skin carcinogenesis in mice was studied. Both FO and EPO inhibited the papilloma formation to a significant degree only during the promotion stage which was associated with an increase in lipid peroxidation. Both FO and EPO inhibited the binding of benzo(a)-pyrene to skin cell DNA suggesting that this could be one of the mechanism(s) by which these oils could be preventing papilloma development. Neither EPO nor FO influenced epidermal cell proliferation. In the FO group, LA (linoleic acid), AA (arachidonic acid) and DHA (docosahexaenoic acid) were increased, whereas in the EPO group a significant increase in the AA content was noted. No specific changes in the fatty acid pattern were observed in any of the groups that could be attributed to the papilloma incidence. These results suggest that FO and EPO can influence papilloma formation which can be attributed, at least in part, to their ability to prevent benzo(a)pyrene binding to DNA and to an increase the lipid peroxidation process.

Animals↗
PubMed1996

Effect of free fatty acids on two-stage skin carcinogenesis in mice.

The effect of n-3 and n-6 free fatty acids on two stage skin carcinogenesis in mice was studied. Stearic, linoleic, arachidonic, and eicosapentaenoic acids inhibited both initiation and promotion stages of skin carcinogenesis. Although no direct correlation between lipid peroxidation and papilloma formation was observed, a trend towards an increase in the formation of lipid peroxides with the inhibitory effect of fatty acids on papilloma development was noted. In general, the fatty acids applied were incorporated mainly into the phospholipid and free fatty acid pools. All the fatty acids tested, except eicosapentaenoic and docosahexaenoic acids, inhibited the binding of benzo[a]pyrene (BP) to DNA. On the other hand, BP and croton oil-induced skin cell proliferation was not influenced by any of the fatty acids used. In conclusion, the results of the present study suggest that inhibition of papilloma formation by free fatty acids is complex and can be attributed to a limited extent only to their ability to inhibit BP binding to DNA, to block cell proliferation and enhance the lipid peroxidation process.

Animals↗
PubMed1995

Effect of dietary fat on diethylnitrosamine induced hepatocarcinogenesis in Wistar rats.

In a diethylnitrosamine (DEN) induced hepatoma model, the effect of fish oil, a rich source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and ground nut oil, a rich source of oleic acid (OA) and linoleic acid (LA), was studied. Both 20% fish oil and ground nut oil inhibited DEN-induced hepatocarcinogenesis in rats. Contrary to general belief, an inverse correlation was observed between the development of neoplastic nodules and the amount of lipid peroxides formed in the high fat (20% fish oil and ground nut oil) diet groups, indicating that the higher the lipid peroxides formed, the lower the incidence of liver tumours in DEN-treated animals. Results of the analysis of liver fatty acid composition of the phospholipid fraction suggested that DEN and fish oil treatment can inhibit the activity of the delta-6 and 5-desaturases. It is concluded from the results of the present study that a 'high fat' diet and lipid peroxidation can modulate DEN-induced hepatocarcinogenesis in rats.

Animals↗
PubMed1995

Pro-transforming growth factor-alpha processing in human colon carcinoma cells: role of protein kinase C.

The human colon cancer cell lines HCT 116 (poorly differentiated) and GEO (well differentiated) express the mitogenic peptide transforming growth factor alpha (TGF-alpha). The secretion of TGF-alpha was enhanced by phorbol 12-myristate 13-acetate (PMA), indicating the possible role of protein kinase C (PKC) in the formation of mature TGF-alpha. Cells were metabolically labeled with 35S-cysteine and the formation of the mature 6 kDa TGF-alpha polypeptide from the 17 kDa pro-TGF-alpha precursor was determined. The conversion of pro-TGF-alpha was complete in 2-4 hr with the HCT 116 cells showing faster kinetics of TGF-alpha formation than GEO cells. HCT 116 cells secreted more TGF-alpha than GEO cells and the rate and extent of formation of TGF-alpha was enhanced by PMA in both cell lines. The expression of several PKC isozymes by HCT 116 and GEO cells was examined by immunoblotting. The expression of all isozymes examined was higher in HCT 116 cells compared with GEO cells. Calphostin C, an inhibitor of PKC, reduced the enzyme activity and significantly inhibited the PMA-induced secretion of TGF-alpha by both cell lines. Two agonists of PKC that act on specific PKC isozymes, thymeleatoxin and 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), stimulated the release of TGF-alpha into the medium to the same extent as PMA. Since dPPA has been reported to stimulate PKC-beta 1 specifically, our results suggest a potential role for PKC-beta in the processing of pro-TGF-alpha by these 2 human colon carcinoma cell lines.

Colonic Neoplasms↗
PubMed1995

Prostaglandin metabolism during growth and differentiation of the regenerating vertebrate appendage.

House lizards are able to regenerate their tails. This is an ideal model to study the growth and differentiation of an organ. Prostaglandins (PGs) are local hormones having diverse and potent biological activities. In an effort to understand PG metabolism during the growth and differentiation of the regenerating lizard tail, we analysed the fatty acid (FA) composition of phospholipids are free FAs by GC, the activity of two rate-limiting enzymes (phospholipases A and C), the activity of the enzyme responsible for the oxygenation of polyunsaturated fatty acids to PGs (cyclooxygenase) and characterized the endogenous PGs by HPLC. It was observed that on the 20th day, i.e. the tissue differentiation period, there was an increase in phospholipase A activity, together with a sudden fall in the free arachidonic acid (AA) level, an increase in cyclooxygenase activity and the appearance of endogenous PGE2. PGE2 can stimulate cyclic adenosine monophosphate (cAMP) production and it may stimulate a cascade of events associated with tissue differentiation.

Animals↗
PubMed1995

Cloning and characterization of mycobacteriophage I3 promoters.

Restriction fragments of mycobacteriophage I3 DNA capable of initiating transcription have been cloned into a promoter selection vector of Escherichia coli, and selected on the basis of development of resistance to chloramphenicol. The growth pattern of these 'promoter clones' on a concentration gradient of chloramphenicol and the biochemical assays of the chloramphenicol acetyl transferase have permitted the assessment of their relative promoter strengths. DNA sequence analysis revealed significant homology of these promoters to the -35 regions of the mycobacterial--and E. coli promoter consensus, but less so the -10 region. Based on the sequence of phage I3 promoters identified here and the reported sequences of mycobacterial promoters, a promoter consensus for mycobacteria has been generated.

Base Sequence↗
PubMed1994

Essential fatty acid metabolism in south Indians.

Coronary artery disease (CAD), hypertension and diabetes mellitus are more common in Indians compared to their incidence in the Western population. The exact reason for this is not known. One of the risk factors for the development of and complications due to CAD, hypertension and diabetes mellitus could be hyperinsulinemia and insulin resistance and low plasma levels of arachidonic acid and eicosapentaenoic acid, metabolites of dietary essential fatty acids (EFAs), cis-linoleic and alpha-linolenic acids. Fatty acid analysis of the plasma phospholipid (PL) fraction of normal Indians showed that they have low concentrations of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid in comparison to those seen in Canadian and Minnesota (USA) normals. Since insulin can activate EFA metabolism, this alteration in the EFA metabolism may, at least, in part explain the high incidence of CAD, hypertension and diabetes mellitus and insulin resistance and hyperinsulinemia that are common in Indians.

Adult↗
PubMed1993

Prostacyclin is a potent anti-mutagen.

Prostacyclin (PGI2) prevented genetic damage to the bone marrow cells of mice induced by gamma-radiation, benzo(a)pyrene(BP) and cis-platinum(cis-DDP). Carba-PGI2, an analogue of PGI2, was also effective against cis-DDP-induced mutagenicity. In a time-course study it was observed that the geno-protective action of PGI2, can last as long as 24 hr. 6-keto-PGF1 alpha, a major metabolite of PGI2 and c-AMP, a second messenger, were ineffective in bringing about this beneficial action. PGI2 did not influence free radical generation induced by phorbol myristate acetate in human peripheral leukocytes. This suggests that the genoprotective action of PGI2 is not mediated by its metabolite 6-keto-PGF1 alpha and the second messenger cyclic-AMP and is not due to any action on free radical generation. This geno-protective action of PGI2 would be futile if it interfered with the tumoricidal action of cis-DDP. It was observed that the cytotoxic action of cis-DDP against Meth-A tumor cells was not interfered with by PGI2 and carba-PGI2 both in vitro and in vivo. This description of the geno-protective action of PGI2 is important in the development of new strategies in cancer chemotherapy since, it is likely that anticancer drugs, at least cis-DDP can be given along with PGI2 to prevent genetic damage to normal cells without interfering with their tumoricidal action.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Cytotoxic action of cis-unsaturated fatty acids on human cervical carcinoma (HeLa) cells: relationship to free radicals and lipid peroxidation and its modulation by calmodulin antagonists.

Specific fatty acids such as linoleic acid (LA), gamma-linolenic acid (GLA), dihomo gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) showed cytotoxicity towards human cervical (HeLa) cells in vitro. Cyclo-oxygenase inhibitor, indomethacin; lipoxygenase inhibitor, nordihydroguiaretic acid (NDGA); anti-oxidant, vitamin E; and calmodulin antagonists, trifluoperazine (TFP) and chlorpromazine (CPZ) blocked the cytotoxic action of these fatty acids. GLA-induced free radical generation and lipid peroxidation were also inhibited by indomethacin, NDGA, vitamin E, TFP and CPZ. Both indomethacin and NDGA also showed significant anti-oxidant property. These results suggest that fatty acid-induced cytotoxic action against HeLa cells is a free radical dependent process and that it can be modulated by calmodulin antagonists. These results are in contrast to those observed by us earlier with human breast cancer cells where in it was found that the tumoricidal action of fatty acids can be blocked by anti-oxidants but not by cyclo-oxygenase (CO) and lipoxygenase (LO) inhibitors. From these results it can be suggested that though free radicals are the mediators of the tumoricidal action of fatty acids, the mechanism of their production may be different in different types of tumor cells.

Calmodulin↗
PubMed1992

Psoriasis: current concepts and new approaches to therapy.

Psoriasis is a common disorder characterized by marked increases in keratinocyte proliferation, abnormal patterns of keratinocyte differentiation, prominent alterations in dermal capillary vasculature and the presence of dermal and epidermal T cells, monocytes/macrophages and neutrophils. It is now known that psoriasis can occur due to abnormalities in essential fatty acid metabolism, lymphokine secretion, free radical generation, lipid peroxidation and eicosanoid metabolism. It is possible to suppress almost completely psoriatic lesions by judicious use of methotrexate, cyclosporine A, and eicosapentaenoic acid. Our studies have shown that in patients with psoriasis there is an increase in the generation of free radicals with an alteration in essential fatty acid metabolism and that side-effects of anti-cancer drugs can be blocked by essential fatty acids in vivo. Thus, essential fatty acid metabolism seems to play a crucial role both in the pathogenesis and treatment of psoriasis.

Cyclosporine↗
PubMed1991

Reactive oxygen species, lipid peroxides and essential fatty acids in patients with rheumatoid arthritis and systemic lupus erythematosus.

We studied free radical generation, lipid peroxidation and the levels of essential fatty acids and of their metabolites in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Both superoxide and hydrogen peroxide generation by peripheral leukocytes but not malondialdehyde levels, as measured by thiobarbituric acid assay, were found to be significantly enhanced both in RA and SLE. Fatty acid analysis of the plasma PL fraction revealed that both LA and ALA metabolites are significantly decreased in RA and SLE compared to controls. These results suggest that essential fatty acid metabolism is altered in RA and SLE.

Adult↗
PubMed1991

Free radical generation, lipid peroxidation and essential fatty acids in patients with septicemia.

Infections due to gram-negative bacteria and other organisms can lead to septicemia and shock in some patients. Endotoxins, which cause these pathophysiological events, stimulate macrophages to elaborate tumor necrosis factor and other lymphokines. These lymphokines can augment free radical generation by polymorphonuclear leukocytes, macrophages and other cells, which may ultimately produce respiratory distress syndrome, multiorgan failure and irreversible shock seen in septicemia. This is supported by our results presented here that there is indeed an increase in free radical generation and lipid peroxidation in patients with septicemia. In addition, analysis of plasma lipid profile in these patients showed that gamma-linolenic, dihomogamma-linolenic and arachidonic acids of n-6 series and alpha-linolenic and eicosapentaenoic acids of the n-3 series are decreased in their plasma phospholipid fraction. These results suggest that free radicals, lipid peroxides, and alteration in essential fatty acid metabolism may have a role in the pathogenesis of septicemia.

Adolescent↗