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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 1,531 records · Page 85Linked to original sources

Effect of estrogen on hypoglycemia-induced neurological impairment in ovariectomized rats.

The risk of hypoglycemia and the resulting functional derangement of the brain are one of the major complications with stringently controlled diabetes mellitus. Ovarian steroid hormones, particularly estradiol, play a modulatory role in the ability of the female brain to utilize glucose. In the present study, the effects of estrogen on hypoglycemia-induced neurological impairment were done in ovariectomized rats. Animals received either vehicle or estradiol benzoate treatment. Hypoglycemia (Blood glucose levels <50 mg/dl) was induced in all the rats by insulin (2 U/kg, IP). Neurological functions were assessed using an 18 point scale at different time intervals of hypoglycemia. Estradiol benzoate (100 microg/kg IP) significantly (p<0.05) deteriorated the neurological functions in ovariectomized rats during hypoglycemia. The present study thus reveals that estradiol benzoate is responsible for further aggravation of neurological impairment induced by insulin hypoglycemia in female rats.

Animals↗

Chemotherapy of filariasis--on the search of new agents effective on the reproductive system of female adult worms.

The design and synthesis of a series of alkyl 5(6)-substituted benzimidazole-2-carbamates (1-13), 7-chloro-4-(4-substituted phenyl)aminoquinolines (14-16), 1,2-dimethyl-3-methoxy-carbonyl-4,5-disubstituted pyrroles (17-19) and some compounds belonging to the class pimelonitrile (20), dihydroquinoline (21), pyridine (22), pyridoquinoline (23) and tetrahydro-pyrimidine (24) have been carried out as possible antifilarial agents. All these compounds have been evaluated for their activity against male and female adult worms of Litomosoides carinii in cotton rats. The effect of these compounds was also observed on the reproductive system (condition of developing microfilariae and their release from uterus) of adult female worms. In this study, three types of compounds were discovered: (a) those which showed activity on both the male and female adult worms and also had sterilizing effects on surviving adult females (1-3, 6-9, 13, 19), (b) those which only sterilized the adult females (14-16, 21, 24), and (c) those which had no effect on female reproduction but killed only adult worms (4, 5, 11, 12, 17, 18, 20, 22, 23). This tends to open up a new avenue in the chemotherapy of filariasis and the future scope of work on chemosterilization of adult females has been discussed.

Animals↗

Studies in enteric anthelmintics: activity profile of prodrug of a bisbenzimidazole [1].

The comparative anthelmintic activity of a possible prodrug, 2,2'-dicarbomethoxyamino-5,5'-dibenzimidazolyl methanol (2) with its parent compound 2,2'-dicarbomethoxyamino-5,5'-dibenzimidazolyl ketone (1) and the reference drug mebendazole (3a) is reported. At a dose of 25 mg/kg, compound 2 was 100% effective against Ancylostoma ceylanicum in hamsters. Compound 2 also exhibited a similar order of activity against Syphacia obvelata, Hymenolepis nana and H. diminuta at a dose of 100 mg/kg. The drug exhibited lethal effects against metamorphic forms of A. ceylanicum at a dose of 100 mg/kg. However the trichostrongylids, Nippostrongylus brasiliensis remained unaffected up to a dose of 250 mg/kg of 2. Both 1 and 3a exhibited inferior activity than 2 except against adult A. ceylanicum. The activity of 1 and 2 has been explained on the basis of their ability to resist systemic hydrolysis resulting in higher concentration of the active drug in biophase.

Animals↗

Lung adenocarcinomas metastatic to the brain with and without ultrastructural evidence of rootlets: an electron microscopic and immunohistochemical study using cytokeratins 7 and 20 and villin.

Adenocarcinomas metastatic to brain from lung or colon may pose differentiation difficulties. Ultrastructurally, both may have brush borders with rootlets. This study examines the ultrastructural morphology and immunohistochemical expression of villin (associated with rootlets), cytokeratin 7 (present in lung adenocarcinomas), and cytokeratin 20 (present in colon adenocarcinomas) in 19 formalin-fixed sequential surgical biopsies of lung adenocarcinomas metastatic to brain as compared to 13 colonic adenocarcinoma metastases. Of lung tumor metastases, mucinous differentiation with rootlets was most common [6/19(32%)]. All colon tumor metastases were cytokeratin 7(-), 20(+), and profusely villin(+). Well-formed rootlets were seen. All lung metastases were cytokeratin 7(+) and 20(-). 5/6(83%) lung metastases with rootlets were focally villin(+). 12/13(95%) without rootlets were villin(-). Rootlets are extremely common in lung adenocarcinoma metastatic to brain. Villin immunoreactivity closely correlates with rootlets. Its distribution is a useful adjunct to cytokeratin 7 and 20 in differentiation of lung versus colon adenocarcinomas metastatic to the brain.

Adenocarcinoma↗

Side-effects of local hyperthermia: results of a prospectively randomized clinical study.

In 1986, 25 patients with stage II and III carcinoma of the cervix were treated by a combination of radiation and local hyperthermia using an endotract intravaginal applicator. Another 25 patients were treated with radiation alone. Both groups were followed up for a minimum period of 18 months. The acute and long-term toxicity of local hyperthermia was closely monitored. Our study shows that whereas local hyperthermia adds significantly to the local control achieved with radiation alone, it is not in any way associated with any significant short- or long-term toxicity, and does not enhance the radiation reactions.

Combined Modality Therapy↗

Recovery of coal fines from washery and power plant effluents by integrated technique of oil agglomeration and biofilm formation.

The possibility of applying an integrated technique of oil agglomeration and biofilm formation for recovery of coal fines from coal washeries and power plants effluents has been explored. Laboratory experiments with simulated slurries of different Indian coal fines demonstrate that vegetable oils are satisfactory agglomerating agents for recovery of most of the coal fines depending on the nature of coal and type of oil. The agglomeration behaviour of coal fines was assessed in terms of % yield, % organic matter recovery and % ash rejections. Maximum 85% agglomerate recovery was obtained in the agglomeration stage. Residual oil concentrations in some cases were found to exceed the permissible limit. Recovery of residual coal fines and reduction in residual oil concentration in the resultant slurry after oil agglomeration have been attempted using biofilm formation. A laboratory scale treatment reactor was put under complete recirculation to facilitate attached microbial growth on coal particles as carrier under aerobic conditions. The influence of various parameters on attached growth and stable biofilm formation were studied. The growth patterns of attached cell in suspension and consumption pattern of carbon substrate (oil) have been investigated. Steady decline in residual substrate concentration in the slurry with corresponding increase in the growth of attached and free cell mass is observed. The growth process was favoured in pH range of 6.5-7.0. The attached growth was found to be expanded in size in due course of time ultimately leading to the formation of stable biofilm in the treatment reactor which was subjected to the influent total suspended solids loading resulting from oil agglomeration step. Performance of the biofilm reactor in terms of % reduction in total suspended solids and residual oil concentration in the influent slurry was assessed in continuous mode. Complete recovery of coal fines and 60% degradation of oil was observed in the final effluent discharged from the treatment reactor.

Biofilms↗

Alcohol ablation of symptomatic vertebral hemangiomas.

BACKGROUND AND PURPOSE: Many therapeutic techniques have been used for the treatment of symptomatic vertebral hemangiomas (SVH), and each has its own limitations. Our objective was to evaluate the therapeutic efficacy of alcohol ablation for treating these lesions. METHODS: Fourteen patients with SVH were treated by injection of absolute alcohol into the lesion via the percutaneous transpedicular route under CT guidance. Symptoms before treatment included neurologic deficit in 13 patients and debilitating pain in one. All patients underwent preprocedural MR imaging. All patients had clinical and MR imaging follow-up (14 patients at 48-96 hours and 2 months; six at 9-15 months). Results were divided into excellent (resumption of work, alleviation of pain), good (significant improvement), and failure of treatment categories on the basis of subjective assessment of clinical improvement. Clinical improvement/deterioration was correlated with MR-revealed changes. RESULTS: All patients showed transient deterioration of neurologic status after alcohol ablation. Subsequently, excellent results were seen in five patients and eight were in the good category. One patient in whom treatment failed also developed a complication (paravertebral abscess). Four of the eight patients with good results had preprocedural cord changes. Total follow-up ranged from 5 to 31 months, with 11 patients showing stable improvement. One patient developed recurrent hemangioma within a month. Another patient became symptomatic after initial good response, secondary to the collapse of the involved vertebral body. Good correlation was found between clinical improvement and reduction of epidural soft-tissue masses on MR images. Cord signal alteration seen on MR images in four treated patients, however, did not show any change after treatment. CONCLUSION: Alcohol ablation is an effective management option for symptomatic vertebral hemangiomas. Although encouraging results were seen in almost 86% of our patients, a longer follow-up period still is needed to assess the stability of improvement. Potential complications include vertebral collapse and infection.

Adolescent↗

Lipemia retinalis.

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Adult↗

Evaluation of glutaraldehyde and povidone iodine for sterilization of wide-field contact vitrectomy lenses.

BACKGROUND AND OBJECTIVE: Wide-field vitrectomy contact lenses are currently sterilized with ethylene oxide gas, and other lenses with autoclaving. To maintain a large inventory or possibly run the risk of loss of lens quality with repeated autoclaving, glutaraldehyde 2% and povidone iodine 5% solution were evaluated as possible sterilizing agents. MATERIALS AND METHODS: Ethylene oxide presterilized lenses were contaminated with known concentrations (10(5) organisms/mL) of bacteria (S. epidemidis, P. aeruginosa, B. subtilis), and fungi (A. flavus, C. albicans) for 5 minutes. The test lenses were treated with glutaraldehyde or povidone iodine for 5, 10, 30, 60, and 120 minutes, and controls with sterilized water for a similar duration. Following treatment, both test and control lenses were sampled with sterile cotton swabs. The swabs were cultured for bacteria (tryptone soya broth 48 hours), and fungi (Saubourd's dextrose broth 5 days). RESULTS: The culture was negative for both glutaraldehyde- and povidone iodine-treated lenses against all organisms at all time points except B subtilis, which needed 120 minutes treatment. CONCLUSION: Two hours contact time with glutaraldehyde 2% or providone iodine 5% can sterilize vitrectomy contact lenses against common bacteria and fungi without affecting lens quality.

Bacteria↗

Enhancement of catalytic activity of enzymes by heating in anhydrous organic solvents: 3D structure of a modified serine proteinase at high resolution.

For the first time, it is demonstrated that exposure of an enzyme to anhydrous organic solvents at optimized high temperature enhances its catalytic power through local changes at the binding region. Six enzymes, namely, proteinase K, wheat germ acid phosphatase, alpha-amylase, beta-glucosidase, chymotrypsin and trypsin were exposed to acetonitrile at 70 degrees C for three hr. The activities of these enzymes were found to be considerably enhanced. In order to understand the basis of this change in the activity of these enzymes, proteinase K was analyzed in detail using X-ray diffraction method. The overall structure of the enzyme was found to be similar to the native structure in aqueous environment. The hydrogen bonding system of the catalytic triad remained intact after the treatment. However, the water structure in the substrate binding site underwent some rearrangement as some of the water molecules were either displaced or completely absent. The most striking observation concerning the water structure was the complete deletion of the water molecule which occupied the position at the so-called oxyanion hole in the active site of the native enzyme. Three acetonitrile molecules were found in the present structure. All the acetonitrile molecules were located in the recognition site. Interlinked through water molecules, the sites occupied by acetonitrile molecules were independent of water molecules. The acetonitrile molecules are involved in extensive interactions with the protein atoms. The methyl group of one of the acetonitrile molecules (CCN1) interacts simultaneously with the hydrophobic side chains of Leu 96, Ile 107 and Leu 133. The development of such a hydrophobic environment at the recognition site introduced a striking conformation change in Ile 107 by rotating its side chain about C alpha-C beta bond by 180 degrees to bring about the delta-methyl group within the range of attractive van der Waals interactions with the methyl group of CCN1. A similar change had earlier been observed in proteinase K when it was complexed to a substrate analogue, lactoferrin fragment.

Acetonitriles↗

A quantitative angiogenesis model for efficacy testing of chemopreventive agents.

One of the approaches in chemoprevention to prevent or delay the progression of precancerous lesions, is to apply chemopreventive agents that can potentially block angiogenesis. A quantitative in vivo angiogenesis inhibition assay was developed to test the efficacy of twelve chemopreventive agents that represent different chemical classes and multiple biological activities, using the chick chorioallantoic membrane (CAM) model and an oncogene-transfected angiogenic cell line (6 Ti ras/SV myc # 4). These tumorigenic cells held by a primary agarose pellet, were placed alone or with a secondary pellet incorporating five concentrations of the test agent, on an exposed CAM of 7-day-old chick embryo for 72 hours in a humidified chamber at 35 degrees C. The cell-induced angiogenic blood vessels, including the microvessels radiating from the cell pellet focal area, were scored using a computerized custom image analysis system. The results show that nonsteroidal antiinflammatory drugs (NSAIDS); aspirin, sulindac, sulindac sulfide and sulindac sulfone, were effective inhibitors of cell-induced angiogenesis (23-66%). Aspirin displayed a dose-dependent response with the highest inhibition at 300 microM and an EC50 (the effective molar concentration that inhibits angiogenesis by 50%) of 26 microM. Sulindac sulfone was more effective than sulindac with an EC50 of 5 microM versus 85 microM. However, sulindac sulfide showed an intermediate response with an EC50 of 41 microM. The retinoids; all-trans-retinoic acid (ATRA), 9-cis-retinoic acid (9-cis-RA), and 13-cis-retinoic acid (13-cis-RA) were also highly effective inhibitors of cell-mediated CAM-angiogenesis. 13-cis-RA with an EC50 of 3.6 nM, has been the most efficacious test agent. > 400-fold more effective than 9-cis-RA (1.5 microM). ATRA exhibited an intermediate response between 9-cis-RA and 13-cis-RA with an EC50 of 0.3 microM, and was 100-fold more efficacious than 9-cis-RA. However, the synthetic retinoid, N-(4-hydroxyphenyl) retinamide (4-HPR), was not an effective inhibitor of CAM angiogenesis. Thalidomide, a compound with multiple biological activities, exhibited dose-dependent inhibition ranging from 10-1000 microM with an EC50 of 19 microM. Other agents that exhibited dose-dependent inhibition included Bowman-Birk inhibitor (BBI), EC50: 10 microg/ml, tamoxifen, EC50, 0.05 microM and difluoromethyl omithine (DFMO), with an EC50 of 13 microM. These results suggest that tumor-associated angiogenesis can be modulated by non-toxic concentrations of chemopreventive agents representing multiple biological activities and multiple targets.

Angiogenesis Inhibitors↗