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Biomedical subjects

A Sarkar

Publications and source records attributed to A Sarkar.

At least 55 records · Page 3Linked to original sources

Conformationally restricted analogues of 1N,12N-bisethylspermine: synthesis and growth inhibitory effects on human tumor cell lines.

Eight analogues of 1N,12N-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1, 2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained (three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). 1N,12N-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the 4N, 9N-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1, 2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action.

Antineoplastic Agents↗

Correction to flow rate--pressure drop relation in coronary angioplasty: steady streaming effect.

The changed flow pattern of pulsatile blood flow in a catheterized stenosed artery has been studied through a mathematical model. The study takes into account the effect of the movement of the flexible catheter influenced by the pulsatile nature of the flow. The contribution of the steady streaming effect brings into focus the existence of a non-zero mean pressure drop in addition to the one predicted by the linear theory -- a fact overlooked by the previous authors. Thus our results are intended to provide a correction to the mean pressure drop usually calculated by neglecting the non-linear inertia terms. The calculations based on the geometry and the flow conditions representing a real physiological situation as closely as possible suggest that depending upon the values of k (where k is the ratio of the catheter size to vessel size) ranging from 0.2 to 0.5 mean pressure drop increases for any frequency parameter. In addition, it is found that depending upon the material properties, a thin catheter experiencing small oscillations due to the flow conditions is likely to influence in the same way as a thicker catheter which remains fairly stationary inside the artery. The results are sensitive to the shape of the wall geometry and will be different for different wall geometries even if the cross-sectional area reduction at the peak of stenosis is kept the same. Interesting streamline patterns depict distinct boundary layer characteristics both at the artery wall and catheter wall. Finally, the effect of catheterization and its movement on various physiologically important flow characteristics-mean pressure drop, impedance, wall stress is studied for different range of catheter size and frequency parameter.

Angioplasty, Balloon, Coronary↗

Comparison between two different modes of oxygen therapy during immediate postoperative period following mitral commisurotomy.

Hypoxaemia is a common postoperative problem after thoracotomy. Oxygen therapy with continuous monitoring by pulse oximetry should be a routine practice. This study was conducted to compare the efficacy between nasal cannula and ventimask for post-thoracotomy oxygen supplementation on 20 patients divided into 2 groups of 10 each undergoing closed mitral commisurotomy. The study period was of 5 months duration from March to July, 1996. The mean oxygen saturation remained above 98% in both the groups receiving oxygen either by nasal cannula or ventimask. As there was adequate oxygenation, the cost benefit ratio favours the use of nasal cannula for routine postoperative oxygen supplementation in the closed mitral commisurotomy patients.

Adolescent↗

Chloroma.

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Acute Disease↗

The Hermes element from Musca domestica can transpose in four families of cyclorrhaphan flies.

Transgenic insect technology will provide opportunities to explore the basic biology of a broad range of insect species in ways that will prove insightful and important. It is also a technology that will provide opportunities to manipulate the genotypes of insects of practical significance to the health and welfare of humans. The Hermes transposable element from the housefly, Musca domestica, is a short inverted repeat-type element related to hobo from Drosophila melanogaster, Ac from Zea mays, and Tam3 from Antirrhinum majus. It has potential to become a versatile and efficient broad host-range insect transformation vector. The ability of Hermes to transpose when introduced into five species of diptera from four divergent families was tested using an in vivo, interplasmid transpositional recombination assay. Hermes was capable of transposing in all species tested, demonstrating that Hermes has a broad host-range. In addition, the rates of transposition were sufficiently high in all species tested to suggest that Hermes will be an efficient gene transfer vector in a wide range of insect species. The Hermes element also revealed a pattern of integration into the target substrate that permitted factors determining integration site selection to be identified. Primary nucleotide sequence of the integration site played a role as did proximity to preferred integration sites and the nucleosomal organization of the target.

Animals↗

A modification of split-skin graft.

A modification of the conventional split-skin graft is presented. This modification provides a gain in the length of the donor skin up to a maximum of 1:1.92. The gain in length is achieved in a very short period during an emergency operation. No special instrument is required. This technique has been proved to be useful in burn cases having much less donor site than recipient area. Earlier recovery, shortened hospital stay, earlier rehabilitation, less scar contracture and less morbidity could be achieved with this type of simple modification of a sheet graft.

Burns↗

Transposition of the Hermes element in embryos of the vector mosquito, Aedes aegypti.

Using a plasmid-based transpositional recombination assay in vivo, we have demonstrated that Hermes, a short inverted repeat type transposable element from Musca domestica, can transpose in Aedes aegypti embryos. Hermes transpositions in Ae. aegypti have all the characteristics observed during Hermes transposition in its host M. domestica and in related species. These characteristics include an absolute dependence on the expression of the Hermes transposase and a preference for the integration site GTNCAGAC (P < 0.05). In addition, the rate of Hermes transposition in Ae. aegypti (0.286 transpositions per 10,000 donor plasmids screened) was comparable to that observed in Drosophila melanogaster under similar conditions. These results suggest that Hermes can be developed into a gene vector and genetic engineering tool for Ae. aegypti and related mosquitoes.

Aedes↗

Beta-carotene inhibits rat liver chromosomal aberrations and DNA chain break after a single injection of diethylnitrosamine.

Beta-carotene (BC) has recently been found to possess potent anti-tumour activity in chemically induced rat liver carcinogenesis. In the present study, attempts have been made to understand the basic cytogenetic and molecular mechanism of the anti-tumour effect of BC by monitoring its effect on rat liver chromosomal aberrations (CAs) and DNA chain breaks during the early preneoplastic stage of diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male rats. DNA chain breaks, however, can be detected with great sensitivity by exposing crude cell lysates to alkaline solutions and monitoring the rate of strand unwinding so that one strand break per chromosome can easily be detected. Supplementary BC, in basal diet (120 mg kg[-1]), was given to rats 15 days before carcinogenic threat with DEN. Under these experimental conditions, BC was found to afford a unique protection against DEN-induced CAs 96 h after DEN injection. Long-term treatment with BC also triggered a protective effect on induction of CAs 15, 30 or 45 days after DEN treatment, which was maximal on structural aberrations followed by numerical and physiological types. BC treatment for 15 days before DEN injection was found to offer a significant (P < 0.001) protection in the generation of single-strand breaks compared with DEN control. Thus, BC ranks as a potential chemopreventive agent for the future so far as chemical rat liver carcinogenesis is concerned.

Animal Nutritional Physiological Phenomena↗

Cloning, characterization, and expression of a calcitonin receptor from guinea pig brain.

A calcitonin receptor was cloned from guinea pig brain by using a degenerate reverse transcription-polymerase chain reaction (RT-PCR) strategy. When the cloned guinea pig calcitonin receptor was transfected into COS 1 cells, salmon calcitonin stimulated intracellular cyclic AMP accumulation with an EC50 of 0.1 nM, whereas human calcitonin was >250-fold less potent (EC50 27.6 nM). Related neuropeptides rat alphaCGRP and rat amylin did not activate the guinea pig calcitonin receptor at physiologic concentrations. Stimulation of the transfected guinea pig calcitonin receptor by salmon calcitonin also resulted in phosphatidylinositol hydrolysis with an EC50 of 2.5 nM. Expression of the calcitonin receptor was mapped by a combination of RT-PCR, northern analysis, and expression in Xenopus oocytes. The guinea pig calcitonin receptor was most highly expressed in diencephalon and a single subtype was detected.

Amino Acid Sequence↗

Transgene expression in the rhesus cervix mediated by an adenovirus expressing beta-galactosidase.

OBJECTIVES: More than 90% of cervical cancers are positive for human papillomavirus, which functionally represses p53 and pRb. The remainder have been found to contain p53 mutations. Gene therapy involves insertion of a functioning gene into a patient to correct a genetic abnormality. STUDY DESIGN: The ability of a beta-galactosidase adenovirus to mediate transgene expression in the rhesus cervix was evaluated. Three different doses and two different entry techniques of virus were investigated. RESULTS: The ideal dose determined by X-galactosidase staining was 2 x 10(10) plaque-forming units, and the injection method yielded better staining than did abrasion with topical application. Increased adenoviral-specific immunoglobulin G antibody response in the injected monkeys confirmed the results. CONCLUSION: High transduction efficiency by use of adenoviral vectors can be achieved in the cervix. Reversing the effects of human papillomavirus and p53 mutations with gene therapy may become a novel therapy for invasive and preinvasive cervical cancer.

Adenoviridae↗

Cervical human papillomavirus infection and intraepithelial neoplasia: a review.

Cervical human papillomavirus (HPV) infections and intraepithelial neoplasias are precursors to cervical cancer, the second most common cancer in women worldwide. HPV satisfies the epidemiologic criteria for causality; the role of other cofactors is under study. Natural history studies show that most low-grade lesions (productive HPV infections) regress or persist, whereas high-grade lesions (those with integrated HPV DNA) progress. Immunobiologic studies demonstrate that infection peaks in the early 20s, leading to a 10- to 20-year period of persistent infection, before finally progressing to a preinvasive or invasive lesion. Papanicolaou (Pap) screening has lowered the morbidity and mortality from cervical cancer in every country in which screening programs have been introduced. The diagnostic strategy for an abnormal Pap smear includes colposcopy; the role of HPV DNA testing in screening or diagnosis remains unclear. Patients are treated with cervical ablation, cone biopsy, or chemopreventive agents. Efforts to strengthen screening and prevention, as well as new directions for research, are needed.

Female↗

Biochemical basis of selenomethionine-mediated inhibition during 2-acetylaminofluorene-induced hepatocarcinogenesis in the rat.

Supplementation of selenium in the form of selenomethionine (8 ppm) in drinking water daily has been found to be highly effective in reducing cancer incidence in male Sprague-Dawley rats fed 2-acetylaminofluorine (2-AAF) (0.05%) in the basal diet daily for 16 weeks. Selenomethionine treatment before initiation, during initiation or during the selection/promotion phases of hepatocarcinogenesis has been found to be effective in elevating hepatic microsomal cytochrome b5, cytochrome P-450 contents, triphosphopyridine nucleotide-cytochrome c-reductase and cytosolic aryl hydrocarbon hydroxylase activities to a statistically significant level measured either in the hyperplastic nodules or in the non-nodular surrounding liver parenchyma compared with 2-AAF control rats. Moreover, selenomethionine treatment throughout the study also decreased the cytosolic 1-chloro-2,4-dinitrobenzene conjugated glutathione-S-transferase and microsomal UDP-glucuronyl transferase activities to a significant level when compared with 2-AAF control rats. Furthermore, direct correlations between hyperplastic nodules and non-nodular liver areas were observed with the hepatic selenium content and also with the rates and patterns of hepatic drug metabolism. Selenomethionine was also found to protect and improve the histopathological indices without any toxic side effects as revealed from the haematoxylin and eosin staining. Our results establish the fact that selenium is particularly protective in limiting the action of 2-AAF during the initiation phase of hepatocarcinogenesis.

2-Acetylaminofluorene↗

Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver.

The effect of carrot extract on carbon tetrachloride (CCl4)-induced acute liver damage was evaluated. The increased serum enzyme levels (viz., glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, sorbitol and glutamate dehydrogenase) by CCl4-induction were significantly lowered due to pretreatment with the extract. The extract also decreased the elevated serum bilirubin and urea content due to CCl4 administration. Increased activities of hepatic 5'-nucleotidase, acid phosphatase, acid ribonuclease and decreased levels of succinic dehydrogenase, glucose-6-phosphatase and cytochrome P-450 produced by CCl4 were reversed by the extract in a dose-responsive way. Results of this study revealed that carrot could afford a significant protective action in the alleviation of CCl4-induced hepatocellular injury.

Alanine Transaminase↗

Inhibition of 3'-methyl-4-dimethylaminoazobenzene-induced hepatocarcinogenesis in rat by dietary beta-carotene: changes in hepatic anti-oxidant defense enzyme levels.

The dietary administration of beta-carotene (BC) daily has been found to be highly effective in reducing hepatocarcinogenesis in male Sprague-Dawley rats fed 3'-methyl-4-dimethylaminoazobenzene (3'-Met-DAB). The anti-cancer efficacy of BC was evaluated by estimating some possible pre-neoplastic and neoplastic hepatic anti-oxidant markers such as glutathione (GSH) and related enzymes, namely glutathione S-transferases (GSHT, with varying substrate specificities), gamma-glutamyl transpeptidase (GGT), glutathione peroxidase (GPX) and reductase. BC proved to be an effective anti-neoplastic substance in long-term treatment. Furthermore, BC limited the exponential increase of GSH, GGT, GSH-T and GPX both in the hyperplastic nodules (HNs) and surrounding liver (NNSP) areas compared with carcinogen control (3'-Met-DAB) rats during long-term treatment. Early marginal changes in GSH, GGT and GSHT (with 1-chloro-2,4-dinitrobenzene as a substrate) activities in BC-treated groups for 10 days compared with carcinogen (3'-Met-DAB once) control rats entail the participation of BC in the initial stages of hepatocarcinogenesis. A decrease in the number of hyperplastic nodules and the total liver parenchyma they occupy was observed in BC-treated groups. HNs and NNSP liver areas are directly correlated with hepatic BC and vitamin A content and with rates and patterns of hepatic anti-oxidant defense enzymes. Our results confirm that BC is protective in limiting the action of 3'-Met-DAB during the initiation phase of hepatocarcinogenesis.

Animals↗

Beta-carotene prevents lipid peroxidation and red blood cell membrane protein damage in experimental hepatocarcinogenesis.

The anti-cancer efficacy of dietary beta-carotene (BC, 120 mg/kg diet, daily) was evaluated during diethylnitrosamine (DEN, 200 mg/kg body weight)-induced hepatocarcinogenesis in male Sprague-Dawley rats. BC treatment was carried out throughout the study, before initiation or selection/promotion phase of hepatocarcinogenesis in a defined experimental protocol. In red blood cells (RBC) and microsomal fractions from hepatic nodular and non-nodular surrounding parenchyma, the enzymatic lipid peroxidation increased significantly by more than 3-fold, 9- to 10-fold and 4- to 7-fold respectively 18 weeks following initiation by DEN as compared to normal control animals. RBC membrane protein damage was estimated by alanine release and was found to increase more than 5-fold in the same time period in DEN control rats. A decrease in hepatic cytosolic and microsomal glucose-6-phosphatase activities was observed, whereas the activities of the oxygen-derived free-radical scavenger enzymes, like cytosolic catalase and superoxide dismutase, were shown to increase significantly at the same time point. However, BC exposure in the different phases to hepatocarcinogenesis substantially changed all the above parameters in limiting the action of DEN. Results showed that the most significant beneficial effect of BC during hepatocarcinogenesis was exerted mainly in long term continuous and/or the initiation phase of carcinogenicity, rather than in the selection/promotion phase. Moreover, the volumetric and numerical densities of the preneoplastic lesions were all appreciably reduced by exposure to BC. We conclude that long term intake of BC could reduce cancer risk by preventing hepatic lipid peroxidation and RBC membrane protein damage due to its antioxidant actions.

Animals↗

Comparative efficacy of furazolidone and nalidixic acid in the empirical treatment of acute invasive diarrhea: randomized clinical trial.

Efficacy of furazolidone and nalidixic acid was compared in a randomized trial involving 72 children with acute invasive diarrhea. Thirty six children received furazolidone (7.5 mg/kg/day) and 36 children received nalidixic acid (55 mg/kg/day). Clinical characteristics of the two treatment groups were comparable on admission. Of these, 34 children in furazolidone treated group and 29 children in nalidixic acid treated group completed the full course of treatment and were analyzed finally for clinical efficacy. Clinical cure was observed in 29(85.3%) children treated with furazolidone and 29(100.0%) children treated with nalidixic acid. Nalidixic acid treated group had statistically significantly higher cure rate (p = 0.039) as compared to furazolidone treated group. However, 85% cure rate in furazolidone treated group may be potentially useful for the treatment of acute invasive diarrhea because of decreasing efficacy of nalidixic acid against shigellosis in many countries.

Anti-Infective Agents↗