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Biomedical subjects

M Sharma

Publications and source records attributed to M Sharma.

At least 433 records · Page 24Linked to original sources
PubMed1975

Testosterone production by XYY subjects.

A study of plasma concentration (P1T, ng/ml), metabolic clearance rate (MCRT, L/day) and blood production rate (PBT, mg/day) was done on seven XYY subjects of various ages and four pair-matched control XY subjects by a radioinfusion technique of 1,2-3H-testosterone. Although MCRT showed no significant difference between the groups, P1T and PBT were significantly lower (P less than 0.05) in XYY subjects. Therefore, increased aggressive behavior of the XYY subjects can not be attributed to increased levels or production rates of testosterone.

Adolescent↗
PubMedDate not supplied

Trends in neonatal outcome with low Apgar scores.

Trends in incidence and neonatal outcome following low Apgar scores (1 min Apgar score < 6) were prospectively studied during the years (1981, 1983, 1986 and 1988. The incidence of birth asphyxia was 7.6% of live births during the study period; it was 5.8% in 1981, increased to highest of 8.9% in 1986 with slight reduction to 7.2% in 1988. Birth weight distribution of asphyxiated babies and 1 min Apgar score < 3 (severe asphyxia) remained unchanged. A significant decline in neonatal mortality with asphyxia was noted from 46.0% to 28.4% during 1981 and 1988 respectively. Aetiological factors for asphyxia could be identified in nearly 90% of infants during 1988, and all but 2 of 12 factors studied registered significant differences from control non-asphyxiated group.

Apgar Score↗
PubMedDate not supplied

Serum IgG at birth in preterm appropriate- and small-for-gestational age newborns.

Serum IgG at birth was estimated in 31 preterm and 33 full term newborns, grouped according to their weight-for-gestational age. Preterm small-for-gestational age neonates were found to have significantly reduced IgG levels as compared to preterm appropriate-for-gestational age and full term small-for-gestational age newborns. It is suggested that preterms with intra-uterine growth retardation are most suitable for exogenous IgG supplementation to reduce neonatal and postneonatal susceptibility to infections.

Agammaglobulinemia↗
PubMedDate not supplied

Knowledge, attitude and practice of immunization in an urban educated population.

A KAP evaluation of urban educated parents revealed suboptimal, superficial transfer of immunization knowledge. Poorer dose-related knowledge as compared to vaccine awareness contributed to partial immunization. Non-availability of vaccine contributed to 18.7% unprotected children, and therefore all logistics must be overcome to remedy service default. The unacceptable level of knowledge found in final year nursing and medical students, points out the need to restructure immunization related teaching in our hospitals. Incorporation of immunization based knowledge in high school curriculum is also recommended. It is important that areas of relevant information and education must be delineated time to time with increasing vaccination coverage.

Educational Status↗
PubMedDate not supplied

Comparative bioavailability and in-vitro antimicrobial activity of two different brands of rifampicin.

A comparative bioavailability study was undertaken between a new formulation of rifampicin 'Famcin' and a standard formulation of rifampicin 'R-cin' in eight healthy male volunteers at two dose levels: 300 mg and 450 mg given orally under both single dose and steady state conditions. Plasma rifampicin was assayed spectrophotometrically. The study documented comparable rate and extent of bioavailability. (Cmax, Tmax and AUC0-infinity) and elimination half-lives (t1/2) of the two brands of rifampicin when compared at similar dose levels. The study establishes the bioequivalence of Famcin to that of the standard brand R-cin. Further, a comparative in vitro microbiological sensitivity of the two brands of rifampicin was undertaken against several strains of two test micro-organism viz. Staphylococcus aureus and Mycobacterium tuberculosis. For both the micro-organisms the minimal inhibitory concentration of Famcin was lower than that of R-cin, suggesting a somewhat greater potency of Famcin in suppressing the growth of test micro-organisms.

Administration, Oral↗
PubMedDate not supplied

Effect of chronic treatment of melatonin on learning, memory and oxidative deficiencies induced by intracerebroventricular streptozotocin in rats.

Intracerebroventricular (ICV) streptozotocin (STZ) has been shown to cause cognitive impairment, which is associated with free radical generation in the brain of rats. Melatonin is a potent free radical scavenger and antioxidant. In the present study, the effect of melatonin was investigated against ICV STZ induced cognitive impairment and oxidative stress in rats. Adult male Wistar rats were injected with ICV STZ (3 mg/kg) bilaterally. The rats were treated with STZ twice, on days 1 and 3. The learning and memory behavior was assessed using passive avoidance paradigms, elevated plus maze and the closed field activity while the parameters of oxidative stress assessed were malondialdehyde (MDA) and glutathione. The rats were treated chronically with melatonin for 21 days starting from day 1 of STZ injection. The learning and memory behavior was evaluated on days 17, 18 and 19 and the rats were sacrificed on day 21 for estimation of MDA and glutathione. The rats treated with melatonin showed significantly less cognitive impairment. There was also insignificant increase in brain MDA and decrease in glutathione levels in melatonin-treated ICV STZ rats as compared to the vehicle-treated ICV STZ animals. The study demonstrates the effectiveness of melatonin in preventing the cognitive deficits as well as the oxidative stress caused by ICV STZ in rats and suggests it's potential in age and age-related neurodegenerative disorders where oxidative stress and cognitive impairment are involved.

Animals↗
PubMedDate not supplied

A novel technique to assay adducts of DNA induced by anticancer agent cis-diamminedichloroplatinum(II).

The dideoxynucleotides d(pGpG) and d(pApG) and the tetradeoxynucleotide d(CpTpApG) were synthesized in solution phase by a modified phosphotriester technique and reacted with the anticancer agent cis-diamminedichloroplatinum(II) (cisplatin). The major products were isolated by HPLC and characterized by NMR and mass spectrometry as cross-link adducts of cisplatin with the neighboring purine bases. The cross-link adducts of d(pGpG) and d(pApG) were dansylated through a 5'-phosphoramidate linkage with ethylenediammine. The labeling efficiency of the adducts was quantitative as in the case of the normal dinucleotides. The modified tetramer was digested with nuclease P1. The excised adduct was enriched by HPLC and labeled with dansyl chloride. The analysis of the postlabeled adduct by HPCL, using a fluorescence detector, detected a peak with retention time corresponding to that of the dansylated cis-Pt(NH3)2d(pApG). Cochromatography with the authentic marker confirmed the identification. The same overall procedure was used to assay calf thymus DNA exposed to cisplatin. The major adducts were identified as cis-Pt(NH3)2d(pGpG) and cis-Pt(NH3)2d(pApG). The quantitative labeling efficiency of platinum adducts combined with highly sensitive fluorescence detection technique (subfemtomol) suggests that fluorescence postlabeling assay could be a novel approach for real-time analysis of DNA modification induced by platinated drugs in biological system.

Animals↗
PubMedDate not supplied

Quantitative analysis of 3'-azido-3'-deoxythymidine incorporation into DNA in human colon tumor cells.

We have previously reported that 3'-azido-3'-deoxythymidine (AZT) can possess significant antineoplastic activity in vitro and in vivo when combined with agents which inhibit de novo thymidylate synthesis. Under these conditions cytotoxicity is closely associated with the degree to which AZT is incorporated into DNA. We now report a fluorescence postlabeling technique by which AZT incorporation into DNA can be quantitated without employing radiolabeled AZT. Cultured human colon tumor (HCT-8) cells were exposed to various concentrations of AZT alone and in combination with 5-fluorouracil (FUra). Control cells received the same amount of medium. DNA was isolated from harvested cell pellets (2 x 10(7)). Enzymatic digestion of DNA to the mononucleotide level followed by HPLC analysis of the digest showed that the DNA preparation was free of RNA contamination. The DNA digest was conjugated with dansyl chloride in situ via the phosphoramidate derivative with ethylenediamine. HPLC analysis of the postlabeled nucleotides using fluorescence detection detected 105, 245, and 479 fmol of 5'-monophosphate of AZT (AZTMP) per microg of DNA from cells exposed to 20, 50, and 100 microM AZT, respectively. FUra (3 microM) doubled the AZT incorporation per microg of DNA in cells exposed to 50 and 100 microM AZT. These findings generally support our previously reported data which quantitated (3H)AZT incorporation into cellular DNA and are discussed in light of the potential clinical utility of this technique in assessing the relationship between AZT incorporation into DNA and therapeutic action.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Radiation-induced formation of 3,4-dihydroxyphenylalanine in tyrosine-containing peptides and proteins as a function of X-irradiation dose.

Radiation-induced formation of 3,4-dihydroxyphenylalanine (DOPA) in Tyr and Tyr-containing peptides and proteins was investigated as a function of X-irradiation dose. Irradiated Tyr (0-30 Gy) and the acid hydrolysates of irradiated peptide and protein (0-240 Gy) were conjugated with dansyl chloride. The dansylated amino acids were analyzed by reversed-phase HPLC using fluorescence detection. Formation of DOPA, determined by integrated peak area, increased with dose. Analysis of the major product from irradiated tripeptide Tyr-Gly-Gly detected Gly and DOPA (2:1). Extension of the model study to irradiated BSA and RNase A showed correlation of DOPA formation with Tyr modification up to 120 Gy. Higher dose induced further transformation of DOPA. The fluorescence signal of dansylated DOPA was linear from 1.5 nmol to 0.5 pmol (correlation coefficient of 0.999, n = 3). The detection limit allows the detection of 1 molecule of DOPA/300 molecules of BSA in 5 micrograms of dansylated hydrolysate. Most standard amino acid analysis techniques are limited to detect normal residues of protein. Protein-bound DOPA has been suggested to have a role in the replenishment of reduced transition metal ion involved free-radical-generating system in vivo. Sensitive analysis of protein-bound DOPA will be useful to study amplification of the radical-damaging event.

Animals↗
PubMedDate not supplied

Conjugation of glutathione and other thiols with bioreductively activated mitomycin C. Effect of thiols on the reductive activation rate.

Mitomycin C (MC), a clinically used natural antitumor agent, was shown to form three monoconjugates (11a-13a) and two bisconjugates (14a, 15a) with GSH upon reductive activation by rat liver microsomes, purified NADPH-cytochrome c reductase, or NADH-cytochrome c reductase or chemical reduction using H2/PtO2. Rat liver cytosol/NADH activated MC only at acidic pH (5.8), resulting in the formation of a single GSH-MC monoconjugate, 13a. The reductase responsible for cytosolic activation of MC to form this conjugate was DT-diaphorase. GSH itself did not reduce MC, and unreduced MC did not form conjugates with GSH. A moderate catalytic effect by glutathione S-transferase was demonstrated on the cytosol-activated reaction. Mercaptoethanol and N-acetylcysteine gave analogous sets of five MC-thiol conjugates under cytochrome c reductase or H2/PtO2 activation conditions. The structures of all 15 MC-thiol conjugates (five each with GSH, mercaptoethanol, and N-acetylcysteine, respectively) were determined, using 1H-NMR, UV, and mass spectroscopies, combined with analytical chemical and radiolabeling methods. The mechanism of formation of the conjugates features SN2 displacement of the carbamate of the reduced MC by GS-. The MC-GSH conjugates were noncytotoxic to the tumor cells tested. The conjugation of GSH with activated MC is likely to represent detoxication in mammalian cells. As another effect, GSH accelerates the rate of reduction of MC by "slow" reducing agents such as cytochrome c reductases and H2/PtO2. A mechanism is proposed to explain this effect, which involves further reduction of the initially formed MC semiquinone free radical by GSH.

Acetylcysteine↗