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Biomedical subjects

R K Gupta

Publications and source records attributed to R K Gupta.

At least 865 records · Page 48Linked to original sources
PubMedDate not supplied

Molecular similarity analysis between insect juvenile hormone and N, N-diethyl-m-toluamide (DEET) analogs may aid design of novel insect repellents.

Molecular similarity analysis of stereoelectronic properties between natural insect juvenile hormone (JH), -a synthetic insect juvenile hormone mimic (JH-mimic, undecen-2-yl carbamate), and N, N-diethyl-m-toluamide (DEET) and its analogs reveals similarities that may aid the design of more efficacious insect repellents and give a better insight into the mechanism of repellent action. The study involves quantum chemical calculations using the AM1 semi-empirical computational method enabling a conformational search for the lowest and most abundant energy conformers of JH, JH-mimic, and 15 DEET compounds, followed by complete geometry optimization of the conformers. Similarity analyses of stereoelectronic properties such as structural parameters, atomic charges, dipole moments, molecular electrostatic potentials, and highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were performed on JH, JH-mimic and the DEET compounds. The similarity of stereoelectronic attributes of the amide/ester moiety, the negative electrostatic potential regions beyond the van der Waals surface, and the large distribution of hydrophobic regions in the compounds appear to be the three important factors leading to a similar interaction with the JH receptor. The similarity of electrostatic profiles beyond the van der Waals surface is likely to play a crucial role in molecular recognition interaction with the JH receptor from a distance. This also suggests electrostatic bioisosterism of the amide group of the DEET compounds and JH-mimic and, thus, a model for molecular recognition at the JH receptor. The insect repellent property of the DEET analogs may thus be attributed to a conflict of complementarity for the JH receptor binding sites.

Algorithms↗
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Etoposide in combination with intermediate dose cytosine arabinoside (ID ARA C) given with the intention of further myeloablative therapy for the treatment of refractory or recurrent hematological malignancy.

Thirty-four patients with refractory or recurrent high grade non-Hodgkin's lymphoma (NHL) or acute leukemia were treated with a combination of etoposide, 100 mg/m2 daily, and ara C, 1 g/m2 twice daily, for 5 days (VPARAC). This therapy was given in the anticipation that remissions thus achieved would be 'consolidated' with myeloablative therapy supported by bone marrow transplantation (BMT). The complete remission rate (CR) in patients with NHL was 3/18 (17 per cent) with partial responses (PR) seen in a further four patients, giving an overall response rate of 39 per cent. Four patients (three in CR, one in PR) proceeded to the planned consolidation treatment. Complete remission was achieved in 2/8 (25 per cent) patients with acute myelogenous leukemia (AML) and in 2/8 patients with acute lymphoblastic leukemia (ALL). Three of these patients subsequently had myeloablative consolidation therapy with BMT. There were four treatment-related deaths (NHL, two; AML, one; ALL, one). In poor risk patients with high grade NHL and acute leukemia, VPARAC is an effective remission induction programme in 21 per cent of patients. Seven of the original 34 patients received the intended 'curative' therapy, of whom only four are alive and well 1 year later.

Adolescent↗
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Mutagenic potential of nitroguanidine and nitrosoguanidine in the Drosophila melanogaster sex-linked recessive lethal assay.

Nitroguanidine (NG) and its degradation product nitrosoguanidine (NSG) were evaluated for their mutagenic potential by using Drosophila melanogaster sex-linked recessive lethal (SLRL) assay. Following 72 h of feeding exposure, NG and NSG at concentrations of 4-8 micrograms ml-1 and 15-20 mg ml-1, respectively, were not mutagenic in the test system. The frequencies of mutations for NG and the negative control were 0.188% and 0.096%, respectively. The frequencies of mutations for NSG and the negative control experiments were 0.049% and 0.05%, respectively. The positive control mutation frequencies were 15% and 17.8% for the two assays. The differences between the mutation frequencies of NG and NSG and their negative controls were not significant.

Animals↗
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Hydrogen-1, sodium-23, and carbon-13 MR spectroscopy of cartilage degradation in vitro.

Viable bovine nasal cartilage was examined with magnetic resonance (MR) spectroscopy. Digestion of the proteoglycan matrix by papain or trypsin was accompanied by substantial changes in carbon-13, sodium-23, and hydrogen-1 MR spectra and relaxation parameters, with C-13 MR spectra showing the most pronounced changes. These results indicate the potential of MR spectroscopy (and imaging) for noninvasive evaluation of cartilage disease and monitoring of patients with degenerative joint diseases.

Animals↗
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Use of proton MR spectroscopy and MR imaging to assess obesity.

We used 1H MR spectroscopy and MR imaging at 9.4-T to quantify and localize fat and water in the abdominal regions of 12 lean, normal, and obese mice. The D2O dilution method which measures also the equilibrium plasma D2O concentration by 2H MR spectroscopy was used to quantify body water and fat. In obese mice, the intensity of the fat 1H resonance was about 120% that of the water 1H resonance, about threefold higher than its value (about 45%) in normal mice. In lean mice, the fat/water intensity ratio was about 1:4, about half that in normal mice. Total body water was similar in obese and normal mice (19.9 +/- 1.5 and 18.7 +/- 1.3 mL) despite their very different body weights (50.1 +/- 3.1 g and 30.2 +/- 3.1 g, respectively), but slightly lower in lean mice (14.8 +/- 1.2 mL water; 22.1 g +/- 2.0 g weight). Selective methylene-proton images showed marked accumulation of fat in the abdomen and the retroperitoneal and subcutaneous spaces of obese mice. Selective water-proton images allowed clear resolution of the renal cortex, medulla, papilla, and urinary pelvis. The readily measurable resonance intensity ratio of abdominal fat to water is a sensitive index by which to characterize obesity.

Adipose Tissue↗
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Measurement of magnetization transfer in different stages of neurocysticercosis.

The purpose of this study was to establish magnetization transfer ratio (MTR) in different stages of neurocysticercosis. A total 2,532 cysticerci were studied prospectively in 15 cases. MTR from different regions of the lesions (ie, the cyst, the protoscolex or mural nodule, the granuloma wall) were calculated in different stages of evolution/degeneration in all cases. Of a total 2,532 lesions studied, 2,261 (89.29%) were seen on routine spin-echo (SE) imaging. The rest of the lesions were only seen on magnetization transfer (MT) SE imaging. Maximum MTR was calculated from healing lesions (mean + SD = 31.0+/-2.8) and from the core of SE invisible lesions (30.0+/-5.1). Innocuous cystic lesions, which were hyperintense on T2-weighted images, did not show any MT (MTR = 5.10+/-1.2), whereas degenerating T2 hyperintense lesions showed MTR of 26.40+/-2.7. Nondegenerating and degenerating scolices showed an intermediate MTR of 21.7+/-3.3 and 15.0+/-4.5, respectively. MT varies between different parts of the lesion and also from the same part in different stages of evolution/degeneration of the lesion. The visibility of a lesion on MT-SE sequence was dependent on its MTR and its location at a particular site (cortical gray matter, white matter, or deep gray matter). The difference in MTR of the lesion and the surrounding brain parenchyma decides the resulting contrast and visibility of the lesion.

Adolescent↗
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Enhancement of complement-dependent cytotoxicity by polyvalent melanoma cell vaccine (CancerVax): correlation with survival.

BACKGROUND: Case control studies have demonstrated that administration of CancerVax, a polyvalent melanoma cell vaccine (PMCV), after complete resection of melanoma metastases produces a significant improvement in disease-free survival (DFS). Because PMCV has no direct cytotoxic effect on melanoma cells, the authors hypothesized that it prolongs survival by enhancing antibody-mediated antimelanoma cytotoxicity. METHODS: One hundred melanoma patients participating in a trial of PMCV adjuvant therapy following complete resection of regional node metastases were randomly selected for study. Serum samples obtained immediately before (T0) and 4, 8, 12, and 16 weeks after initiation of PMCV adjuvant therapy were adsorbed with L-14 lymphoblastoid cells and then tested for in vitro complement-dependent cytotoxicity (CDC) against M-14 cells, a melanoma cell line not used in PMCV. CDC was expressed as percentage of total cells (n = 10,000) killed. Survival curves were estimated by the Kaplan-Meier method. Statistical analysis was performed by the signed rank sum test, Spearman test, log-rank test, and Cox proportional hazard regression. RESULTS: Median CDC at T0 was 4.5% (range, 0% to 40%). Within 16 weeks after initiation of PMCV therapy, CDC had increased in 82 (82%) patients. The median increase of 7.5% (range, -9% to 39%) represented a highly significant change (signed rank sum test; P = .0001). At a median follow-up of 29 months (range, 6 to 92 months), the maximum increase in CDC (deltaCDC) as a continuous variable was significantly correlated with DFS (P = .0001). Median survival and 5-year DFS were more than 54 months and less than 54%, respectively, for patients with deltaCDC > or =10% (n = 44) but only 7 months and 14%, respectively, for those with deltaCDC <10% (n = 56; P = .0001). Multivariate analysis confirmed deltaCDC as the most significant independent variable associated with DFS following initiation of PMCV therapy (P = .0001). CONCLUSION: PMCV therapy greatly enhances serum CDC against melanoma cells. This enhancement is directly correlated with DFS following initiation of vaccine therapy.

Adult↗
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Impact of television on children.

Television viewing has a great impact on various aspects of child's life. This study was carried out at Sir Padampat Mother & Child Health Institute, Jaipur (Rajasthan). The aim was to study the effects of television viewing on a child's eating habits, general physical health, physical activities, interest in study and school performance. Only 250 children of 3-10 years age groups were studied for a period of nine months (January 1992 to September 1992). Average duration of television exposure to an individual child was 18.5 hours per week in the study. Significant changes were observed in a childs' eating habits, weight, physical activity, sleep pattern, interest in study and general physical health. Increase in weight was observed in 19.6% children suggesting that the television viewing may predispose to childhood obesity. In 30.4% cases decrease in physical activity was found, 18.4% children showed decreased interest in study, while 10% children showed decrease in school performance, and sleep pattern was disturbed in 24% children. Medical problems were found in 11.6% children. Significantly two children had precipitation of fits on television viewing.

Child↗
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Stereoselective reduction of C-2 substituted steroid C-3 ketones with lithium tris-(R,S-1,2-dimethylpropyl)-borohydride and sodium borohydride.

The effect of C-2 substitution on the stereoselective reduction of steroid C-3 ketones with lithium tris-(R,S-1,2-dimethylpropyl)-borohydride and sodium borohydride was investigated. The C-2 mono- and di-substituted chloro and methyl derivatives were predominantly reduced to one of the epimeric alcohols. The 2 alpha-chloro and 2 alpha-methyl derivatives of 17 beta-acetoxy-5 alpha-androstan-3-one undergo stereoselective reduction with lithium tris-(R,S-1,2-dimethylpropyl)-borohydride to the axial (3 alpha) alcohol as observed in the unsubstituted compound, whereas sodium borohydride gives predominantly the equatorial (3 beta) alcohol. The 2 beta-chloro, 2 beta-methyl, 2,2-dichloro, and 2,2-dimethyl derivatives are reduced predominantly to the equatorial (3 beta) alcohol by both reagents.

Borohydrides↗
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Role of brain [Mg2+]i in alcohol-induced hemorrhagic stroke in a rat model: a 31P-NMR in vivo study.

One hundred percent of anesthetized rats administered 6.6 gm/kg of ethanol IP died within 10-35 min of alcohol injection; upon autopsy of the brain all demonstrated profound subarachnoid and intracranial bleeding, clear signs of hemorrhagic stroke. Pretreatment of rats with 4 mumol/min MgCl2, but not saline, via IV administration (for 30-45 min), prevented hemorrhagic stroke in all animals so treated with 6.6 gm/kg ethanol. Administration of the stroke dose of alcohol resulted in rapid (within 3-5 min) and marked deficits in whole brain intracellular free Mg ([Mg2++]i) as observed by in vivo 31P-NMR spectroscopy. Intracellular pH (pHi) and the phosphocreatine [PCr]/[ATP] ratio also fell following a significant fall in brain [Mg2+]i). Brains of rats that exhibited strokelike events, upon death and autopsy, demonstrated continued and marked intracellular acidosis with progressive fall in the [PCr]/[ATP] ratio and elevation of inorganic phosphate (Pi) and [H+]i; these events were not accompanied by any rises in systemic arterial blood pressure. Rats pretreated with MgCl2 exhibited relatively stable brain [Mg2+]i, and essentially unchanged pHi, [PCr], [ATP], or [Pi] following alcohol administration, although such animals exhibited threefold alterations in plasma Mg2+, as measured by ion selective electrodes. These observations suggest that high alcohol ingestion can result in severe vasospasm, ischemia, and rupture of blood vessels probably as a consequence of depletion of brain [Mg2+]i, events that can be prevented by Mg2+ pretreatment.

Animals↗
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Beneficial vs. detrimental actions of ethanol on heart and coronary vascular muscle: roles of Mg2+ and Ca2+.

Epidemiologic studies suggest that daily ingestion of small amounts of alcohol may protect the heart, whereas higher intake may be detrimental. We studied: 1) cardiac performance, bioenergetics, and [Mg2+]i of isolated working rat hearts during perfusion with Krebs-Henseleit medium containing different concentrations of ethanol (EtOH), 2) mechanical responses. Ca2+ metabolism and Mg content of isolated coronary arteries obtained from dogs, sheep, and piglets subjected to varying concentrations of EtOH and [Mg2+]o and 3) intracellular free Ca2+ of isolated rat cardiac myocytes. In intact hearts, EtOH produced a biphasic hemodynamic change, depending upon concentration; 15 mM EtOH (0.07 g/dl) and 45 mM EtOH (0.21 g/dl) were stimulatory: 90 (0.42 g/dl), 135 (0.63 g/dl), and 170 mM (0.79 g/dl) EtOH were depressive. EtOH 15 and 45 mM increased coronary flow up to 150%, cardiac output up to 130%, stroke volume up to 135%, and oxygen consumption (VO2) up to 130%. However, 90 mM and higher EtOH depressed most hemodynamic parameters (except for heart rate) dose dependently. Lactic acid, lactic acid dehydrogenase, and creatine phosphokinase levels in the perfusate tended to be elevated progressively with increasing duration of EtOH perfusion and pH tended to be reduced (p < 0.05). [31P]NMR spectroscopy on hearts revealed that EtOH > or = 90 mM resulted in rises in Pi/ATP concentration ratio with no significant change in PCr/ATP ratio; [Mg2+]i levels fell and cytosolic pH tended to become slightly acidotic [19F]NMR spectroscopy of isolated myocytes revealed that [Ca2+]i rises at high concentrations of EtOH. With respect to coronary vascular muscle (CVM), low concentrations of EtOH resulted in a concentration-dependent reduction in contractions induced by K+, angiotensin II, and 5-HT; concentration-effect curves were shifted rightward to higher concentrations. Low [Mg2+]o potentiated contractions of CVM induced by EtOH. Low EtOH also resulted in reductions in exchangeable and membrane-bound 45Ca in CVM; medium to high concentrations of EtOH reduced Mg content in CVM and increased 45Ca. In the absence of [Ca2+]o, caffeine and EtOH induced similar, transient contractions followed by relaxation in K(+)-depolarized coronary arterial tissues. EtOH-induced contractions were completely abolished by pretreatment of tissues with caffeine. These results on isolated coronary vessels suggest that in addition to a need for [Ca2+]o, an intracellular release of Ca2+ is needed for EtOH to induce contractions. Overall, the data indicate that low concentrations of EtOH (15, 45 mM) are beneficial on cardiac performance, at least in the intact rat heart and coronary arteries: higher concentrations of EtOH (90, 135 mM) are detrimental. High concentrations of EtOH decrease coronary flow, lead to loss of cellular Mg2+, hypoxia, metabolic acidosis of the myocardium, cell membrane damage, and Ca2+ overload, which could result in cardiac failure. Cellular loss of Mg2+ appears to be causative in the detrimental actions of EtOH on the heart.

Animals↗