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A Saha

Publications and source records attributed to A Saha.

At least 55 records · Page 3Linked to original sources
PubMed2000

Exercise diminishes the activity of acetyl-CoA carboxylase in human muscle.

Studies in rats suggest that increases in fatty acid oxidation in skeletal muscle during exercise are related to the phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), and secondary to this, a decrease in the concentration of malonyl-CoA. Studies in human muscle have not revealed a consistent decrease in the concentration of malonyl-CoA during exercise; however, measurements of ACC activity have not been reported. Thus, whether the same mechanism operates in human muscle in response to physical activity remains uncertain. To investigate this question, ACC was immunoprecipitated from muscle of human volunteers and its activity assayed in the same individual at rest and after one-legged knee-extensor exercise at 60, 85, and 100% of knee extensor VO2max. ACC activity was diminished by 50-75% during exercise with the magnitude of the decrease generally paralleling exercise intensity. Treatment of the immunoprecipitated enzyme with protein phosphatase 2A restored activity to resting values, suggesting the decrease in activity was due to phosphorylation. The measurement of malonyl-CoA in the muscles revealed that its concentration is 1/10 of that in rats, and that it is diminished (12-17%) during the higher-intensity exercises. The respiratory exchange ratio increased with increasing exercise intensity from 0.84 +/- 0.02 at 60% to 0.99 0.04 at 100% VO2max. Calculated rates of whole-body fatty acid oxidation were 121 mg/min at rest and 258 +/- 35, 264 +/- 63, and 174 +/- 76 mg/min at 60, 85, and 100% VO2max, respectively. The results show that ACC activity, and to a lesser extent malonyl-CoA concentration, in human skeletal muscle decrease during exercise. Although these changes may contribute to the increases in fat oxidation from rest to exercise, they do not appear to explain the shift from mixed fuel to predominantly carbohydrate utilization when exercise intensity is increased.

Acetyl-CoA Carboxylase↗
PubMed2000

Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis.

BACKGROUND: Plant-derived flavonoids, which occur abundantly in our daily dietary intake, possess antitumor, antibacterial, and free radical scavenging properties. They form active constituents of a number of herbal and traditional medicines. Several flavonoids have been shown to exert their action by interacting with DNA topoisomerases and promoting site-specific DNA cleavage. Therefore, flavonoids are potential candidates in drug design. We report here that, although the flavonoids luteolin and quercetin are potent antileishmanial agents, luteolin has great promise for acting as a lead compound in the chemotherapy of leishmaniasis, a major concern in developing countries. MATERIALS AND METHODS: Kinetoplast DNA (kDNA) minicircle cleavage in drug-treated parasites was measured by electrophoresis of the total cellular DNA, followed by Southern hybridization using 32P labeled kDNA as a probe. Cell cycle progression and apoptosis were measured by flow cytometry using propidium iodide and fluorescein isothiocyanate (FITC)-labeled Annexin V. RESULTS: Luteolin and quercetin inhibited the growth of Leishmania donovani promastigotes and amastigotes in vitro, inhibited DNA synthesis in promastigotes, and promoted topoisomerase-II-mediated linearization of kDNA minicircles. The IC50 values of luteolin and quercetin were 12.5 microM and 45.5 microM, respectively. These compounds arrest cell cycle progression in L. donovani promastigotes, leading to apoptosis. Luteolin has no effect on normal human T-cell blasts. Both luteolin and quercetin reduced splenic parasite burden in animal models. CONCLUSION: Luteolin and quercetin are effective antileishmanial agents. Quercetin has nonspecific effects on normal human T cells, but luteolin appears nontoxic. So, luteolin can be a strong candidate for antileishmanial drug design.

Animals↗
PubMed2000

Ethinyl estradiol: its interaction on blood-lipid.

Lipophilicity (log P) of the drug plays an important role when drug reaches in the critical reaction site, i.e., active site cum receptors where the major constituent is lipid moieties. The drug molecule may be responsible for altering the lipid constituents, which is measured in terms of phosphorus content and can be explained by their fatty acid changes that are linked with biological effect of the drug. Having considered the lipophilicity of ethinyl estradiol (log P = 3.67), its interactions with the whole lipid of goat blood have been investigated along with fatty acid changes and lipid peroxidation phenomena. There was significant loss of phosphorus content of phospholipid and change of fatty acid constituents of whole lipid. This may be ascribed to binding affinity of ethinyl estradiol with lipid constituents in blood. Lipid binding potential of the drug may have role in its therapeutic effect. The peroxidation induced by drug has been quantitatively measured along with its suppression by using antioxidant. The results reveal that ethinyl estradiol caused significant extent of lipid peroxidation. Ascorbic acid, a promising antioxidant could significantly reduce drug induced lipid peroxidation.

Animals↗
PubMed2000

Effect of aspirin on blood-lipid interaction and lipid peroxidation phenomena in relation to partition coefficient and biological activity.

Considering the lipophilicity of aspirin (log P = -1.15), a significant contributor to its action mechanism, interaction of the drug with the whole lipids of goat blood have been investigated using phospholipid binding and lipid peroxidation phenomena as the parameters under investigation. The lipid content change along with the peroxidation induced by aspirin and its suppression with ascorbic acid had been quantitatively measured. Significant loss in phospholipid was observed after incubation of whole blood with aspirin in varying periods of time. This may be ascribed to binding affinity of aspirin with lipid constituents in blood, which may have potential role in its therapeutic effect. Lipid peroxidation induction potential of aspirin caused significant extent of peroxidation. Ascorbic acid, an antioxidant could significantly reduce aspirin induced lipid peroxidation.

Animals↗
PubMed1999

Leishmania donovani parasites interact with gamma/delta+ human peripheral blood T cells and induce susceptibility to NK cell-mediated lysis.

We recently reported that Leishmania donovani infect the human T-cell line in vitro. To examine whether primary human T cells could be infected by this parasite, a direct interaction of the peripheral blood T cells with L. donovani was examined. The percentage of gamma/delta+ T cells was markedly increased when in vitro generated normal human T-cell blasts were cultured with L. donovani amastigotes. About 30% of the gamma/delta+ T cells in the parasite exposed T-cell blasts expressed parasite antigens intracellularly without detectable intracellular parasites. Parasite exposed T-cell blasts had a reduced surface expression of HLA-DR and were lysed by the sorted CD56+ cells. In contrast, neither L. donovani amastigotes nor T-cell blasts exposed to heat killed amastigotes and/or were sensitive to the NK cell-mediated lysis. Of interest is that about 10% CD3+ peripheral blood T cells in two out of three Indian Kala-azar patients tested expressed intracellular L. donovani antigens.

Animals↗
PubMed1999

Use of ridge regression for improved estimation of kinetic constants from PET data.

The estimation of parameters in radio-tracer models from positron emission tomography (PET) data by nonlinear least squares (NLS) often leads to results with unacceptable mean square error (ME) characteristics. The introduction of constraints on parameters has the potential to address this problem. We examine a ridge-regression technique that augments the standard NLS criterion by the addition of a term which penalizes estimates which deviate from physiologically reasonable values. A variation on a plug-in methodology of Hoerl et al. [7] is examined for data-dependent selection of the degree of reliance to place on the penalizing term. A simulation study is carried out to evaluate the performance of this approach in the context of estimation of kinetic constants in the three-compartment model used to analyze data from PET studies with fluoro-deoxyglucose (FDG). Results show that over a range of realistic noise levels, the ridge-regression procedure can be expected to reduce the root ME of parameter estimates by 60%. This result is not found to be substantially dependent on the precise formulation of the penalty function used. Thus, the use of ridge regression for estimation of kinetic parameters in PET studies is considered to be a promising tool.

Brain Neoplasms↗
PubMed1999

Colposcopy and treatment of cervical intra-epithelial neoplasia: are national standards achievable?

OBJECTIVE: To assess whether consensus based national standards for colposcopy and treatment of cervical intra-epithelial neoplasia are achievable in practice. DESIGN: Identification of 100 consecutive cases of first assessment colposcopy from each gynaecological unit in the former North West region from 1 January 1994 and follow up of their outcome after one year. SETTING: All 19 gynaecological colposcopy clinics in the former North West region. SAMPLE: In one hospital data were available on only 39 women and therefore information was analysed on 1839 women. MAIN OUTCOME MEASURES: Waiting times for colposcopy, different modalities of treatment used for premalignant conditions of the cervix and type of anaesthesia used for treatments. With regard to follow up, time of occurrence, whether or not colposcopy was performed and efficacy of treatment as judged by cervical cytology. RESULTS: Waiting times for colposcopy varied in the individual hospitals studied, but overall 56% of patients were seen within eight weeks. Diathermy loop excision was the most popular treatment modality accounting for 44% of cases. At six months after treatment, 9.98% of patients had a smear of mild dyskaryosis or worse. Colposcopy, as well as cytology, was used at the first follow up visit in 43% of cases. CONCLUSION: At a local level individual hospitals can identify areas where improvements in the service they provide need to be made. The practicality of the current guidelines in today's health service needs questioning.

Anesthesia↗
PubMed1998

Determination of optimal conditions for synthesis of peroxynitrite by mixing acidified hydrogen peroxide with nitrite.

The measured parameters for the formation of peroxynitrous acid via the reaction of acidified hydrogen peroxide with nitrous acid and its self-decomposition corroborate with an earlier suggested mechanism in which H2NO2+ nitrosates H2O2. The activation energies for the formation and decay of peroxynitrous acid have been determined to be 15 and 19 kcal/mol, respectively. We found that perchlorate, nitrate, sulfate and phosphate ions have no effect on the formation and decay rates, whereas chloride ions enhance the rate of the formation of peroxynitrous acid at low peroxide concentrations, and have no effect at high peroxide concentrations. This suggests that at relatively low concentration of H2O2, Cl- competes with H2O2 for H2NO+ to yield NOCl, which may also nitrosate H2O2. Simulation of the experimentally observed parameters for the decay and formation rates suggests that it is not possible to obtain 100% yield of peroxynitrite under any condition. High yields of peroxynitrite were obtained at room temperature using an efficient double mixer where acidified peroxide was mixed with nitrite; after an appropriate delay, the reaction was quenched with strong alkali. An excess of more than 10% of H2O2 over nitrite, or vice versa, is sufficient to get ca. 85-90% of peroxynitrite, almost free from nitrite or H2O2, respectively. The results also suggest that conventional use of ice-cold solutions of the reactants and the alkali solutions is not required if an efficient mixer and appropriate quenching times are available.

Cold Temperature↗
PubMed1998

Studies on the anticlastogenic effect of turmeric and curcumin on cyclophosphamide and mitomycin C in vivo.

Turmeric and its main constituent curcumin were assessed in vivo for their anticlastogenic potential. In one experimental set, Swiss albino male mice were given turmeric (8, 12 and 16 mg/kg body weight) or curcumin (2, 4 and 8 mg/kg body weight) as a single intraperitoneal injection. In another set, the mice were given 8 mg/kg body weight of turmeric or one of three concentrations of curcumin (2, 4 and 8 mg/kg body weight) as a dietary supplement by gavage for 7 consecutive days. 30 min after the last dose the mice were administered a single acute dose of two known clastogens, cyclophosphamide (CP) (20 mg/kg body weight) or mitomycin C (MMC) (1.5 mg/kg body weight). After 18 hr, chromosome preparations were made from bone marrow cells. The endpoints studied were chromosome aberrations and damaged cells. Clastogenicity of the chemicals was compared using turmeric- or curcumin-primed and non-primed animals. As single agents turmeric and curcumin were not clastogenic even after 7 days of priming. Turmeric/curcumin could not inhibit CP- or MMC-induced clastogenicity. Although curcumin is reported to be the active chemopreventive principle in turmeric effective against a number of potential carcinogens in several experimental systems, it was virtually ineffective against the clastogenicity of CP or MMC at the doses tested.

Animals↗
PubMed1998

Genotoxicity of sennosides on the bone marrow cells of mice.

Preparations of a number of plants which contain hydroxyanthraquinones as active constituents are used worldwide for their laxative effect. Anthraquinone glycosides of Cassia angustifolia and C. fistula were investigated for their ability to induce a clastogenic effect on the bone marrow cells of Swiss albino mice. The endpoints screened were chromosomal aberrations and frequency of aberrant cells. Oral exposure to doses of these anthraquinones and their equivalent amount in leaf and pod extracts did not induce significant numbers of chromosomal aberrations or aberrant cells. The results indicate that anthraquinone sennoside B and rhein are weakly genotoxic.

Administration, Oral↗
PubMed1997

Photo-induced inactivation of dihydroorotate dehydrogenase in dilute aqueous solution.

The inactivation of dihydroorotate dehydrogenase was studied by irradiating at selective wavelengths, namely 280 nm and 450 nm, using a steady-state Xenon lamp as a light source. The activity of the enzyme decreased exponentially as a function of the absorbed dose under both aerated and deaerated conditions. The inactivation in deaerated conditions is higher than that in aerated conditions when enzyme solutions were irradiated at 450 nm, whereas inactivation under aerated conditions was slightly higher compared with that in Ar-saturated condition when irradiated at 280 nm. No change in fluorescence spectral shape was observed, however, intensity of emission maximum was found to decrease, except in one case. The fluorescence intensity of flavin was found to increase with absorbed dose when the enzyme was irradiated at 280 nm in aerated solution. Changes in the kinetic parameters (Michaelis-Menten constant, Km, and maximal velocity, Vmax) due to irradiation at 280 nm suggests that the substrate-binding site is modified in deaerated conditions but not in aerated conditions.

Dihydroorotate Dehydrogenase↗
PubMed1997

Enhancement of membrane damage by saponins isolated from Acacia auriculiformis.

Acaciaside A and B, two acylated triterpenoid bisglycosides isolated from the funicles of Acacia auriculiformis, are known to have antihelmintic activity. Since the saponins contain a conjugated unsaturated system that is highly susceptible to peroxidation, we investigated the interaction of saponins and membrane using rat liver microsomes as our model. Microsomal membranes were incubated with saponins at 30 degrees C for 2 hr. Following incubation, lipid peroxidation was measured in terms of malondialdehyde and conjugated diene. Our results showed that incubation of microsomal membranes with saponins increased both malondialdehyde and conjugated diene. The results suggest that in our model, saponins enhance the membrane lipid peroxidation.

Acacia↗
PubMed1997

Radiation-induced double-strand modification in calf thymus DNA in the presence of 1,2-dihydroxy-9,10-anthraquinone and its Cu(II) complex.

When cells or DNA is exposed to ionizing radiation, the radicals produced in the irradiated sample will modify the base-pair region of the double strands. Effects of 1,2-dihydroxy-9,10-anthraquinone (DHA) and its Cu(II) complex on the radiation-induced modification of double-strands in calf thymus DNA were studied using ethidium bromide as a fluorescent probe. Our results show that the Cu(II)-DHA complex is more efficient in modifying the base-pair region in double-stranded DNA compared to free DHA.

Animals↗