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Biomedical subjects

G Sharma

Publications and source records attributed to G Sharma.

At least 19 recordsLinked to original sources

Liposomes as targeted drug delivery systems in the treatment of breast cancer.

Solid tumors such as breast cancer have historically provided many challenges to anti-cancer therapy. Therapeutic hurdles to drug penetration in solid tumors include heterogeneous vascular supply and high interstitial pressures within tumor tissue, particularly in necrotic zones, lower pH and presence of leaky vasculature leading to reduced therapeutic response. Liposome based drug delivery systems offer the potential to enhance the therapeutic index of anti-cancer agents, either by increasing the drug concentration in tumor cells and/or by decreasing the exposure in normal tissues exploiting enhanced permeability and retention effect phenomenon and by utilizing targeting strategies. This review discusses recent trends in liposome-based drug delivery system both for diagnosis and treatment of breast cancer.

Animals↗

Oral manifestations in HIV/AIDS infected patients from India.

OBJECTIVES: To assess types and prevalence of HIV-related oral lesions among HIV-infected individuals in south India and to correlate common oral findings with co-morbidities, gender, age and medication. SUBJECTS AND METHODS: One hundred and one patients with HIV infection or AIDS at infectious diseases units of Attavar Hospital, Mangalore, and medical wards of Kasturba Medical College, Manipal, were selected. Sociodemographic information was obtained using a structured questionnaire. Oral lesions were diagnosed according to the presumptive criteria of EEC-Clearinghouse Classification. Clinical history was retrieved from patient's medical records. RESULTS: Erythematous candidiasis (44.5%), melanotic hyperpigmentaion (34.6%) and xerostomia (29.7%) were among the most common oral manifestations. A significant association was found between oral candidiasis and advanced immunosuppression (P < 0.05). Oral hairy leukoplakia (OHL) was predominant in individuals <35 years (P < 0.05). Melanotic hyperpigmentation was significantly associated with highly active antiretroviral therapy (P < 0.05). OHL was more frequent in patients with HIV-associated tuberculosis. Linear gingival erythema was more predominant in females. CONCLUSIONS: Oral hairy leukoplakia showed a positive relationship with patients younger than 35 years. Oral candidiasis can act as a marker for immunosuppression. Angular cheilitis was predominant in the symptomatic stage.

Adolescent↗

Eruption disturbances: an aetiological-cum-management perspective.

Failure of permanent teeth to erupt without any known cause is a rare incident. We report a case of multiple unerupted permanent teeth and make an effort to predict all possible causes of non-eruption of permanent teeth clinically and radiographically. It is essential to diagnose and treat eruption disturbances as early as possible because treatment at a later stage is usually more complicated due to the tendency of malocclusion to increase with time and reduced ability of remaining dentition to adjust.

Adult↗

Anti-diabetic activity and mechanism of action of chromium chloride.

Though supplementation of chromium has been found to improve deranged carbohydrate and lipid metabolism associated with suboptimal chromium intake in patients, its usefulness in the treatment of diabetes mellitus of variable etiology remains questionable. In the present investigation, the effect of 6 wk oral administration of chromium chloride (CC) on the glucose and lipid metabolism was studied in streptozotocin (STZ) diabetic and neonatal-STZ (nSTZ) diabetic rats. Further, its cellular mechanism was studied using 3T3-L1 adipocyte and C2C12 myoblast cell lines. Treatment with CC significantly improved the impaired glucose tolerance and insulin sensitivity of both STZ diabetic and nSTZ diabetic rats without any change in basal or glucose stimulated insulin response indicating insulin-sensitizing action of chromium. CC treatment also significantly improved deranged lipid metabolism. CC per se did not produce any effect in vitro, however, significantly increased insulin stimulated glucose uptake in C2C12 myoblasts and differentiation of 3T3-L1 preadipocytes into mature adipocytes supporting the in vivo insulin-sensitizing action of chromium. This study shows that CC exhibited significant anti-diabetic potential in chemically-induced diabetes in rats, the mechanism of which appears to be potentiation of insulin actions at the target tissues leading to improved peripheral insulin sensitivity.

Adipocytes↗

First-trimester screening for aneuploidy with fetal nuchal translucency in a United States population.

OBJECTIVE: To examine the detection rate of chromosomal abnormalities using a combination of nuchal translucency (NT) and maternal age in a United States population. METHODS: A total of 2131 pregnancies with 2339 fetuses underwent NT screening from April 2000 to April 2002 in our ultrasound unit. Nuchal translucency was measured from 11 to 14 weeks' gestation. Fetal crown-rump length (CRL) was also measured. The risk for trisomy 21 was calculated from a combination of maternal age and fetal NT with the use of software provided by The Fetal Medicine Foundation (FMF). Sensitivity and false-positive rates were calculated for different risk cut-offs. RESULTS: Chromosomal defects were diagnosed in 32 cases, including 12 cases of trisomy 21 and 10 cases of trisomy 18. The estimated risk based on maternal age and fetal NT was 1 in 300 or greater in 195 (8.3%) cases and these included 10/12 (83.3%) pregnancies with trisomy 21 and 9/10 (90.0%) pregnancies with trisomy 18. CONCLUSION: A combination of maternal age and fetal NT provides an effective method of screening for chromosomal defects. Using ultrasound techniques and risk algorithms from The FMF, the performance of the test in an American population is similar to that described in international populations.

Adult↗

Thyroid hormones levels in infants during and after cardiopulmonary bypass with ultrafiltration.

OBJECTIVE: The aim of this study was to find out if infants after cardiopulmonary bypass develop non-thyroidal illness and if illness severity after cardiopulmonary bypass depends on hormone concentration in ultrafiltrate. METHODS: Thyroid hormone status was assessed in 20 infants with congenital heart defects undergoing cardiac surgery (age range 7 days-11 months). Blood samples were collected preoperatively, during cardiopulmonary bypass, after cardiopulmonary bypass, and also postoperatively in 1, 2, 3, and 8 day after cardiac surgery. Plasma thyrotropin, thyroxine, free thyroxine, triiodothyronine, free triiodothyronine and reverse triiodothyronine were measured in blood samples and also in ultrafiltrate. RESULTS: All patients had reduction in serum thyrotropin, thyroxine, free thyroxine, triiodothyronine, free triiodothyronine, and elevation of reverse triiodothyronine after cardiac surgery. In all patients we performed ultrafiltration. Patients were divided in to two groups. (with and without prolonged recovery). In the group of patients with prolonged recovery we noticed significantly higher amount of triiodothyronine per kilogram body weight. One of these patients died. The average level of total thyroxine decreased from the level 126 nmol/l before bypass to the minimal level 73 nmol/l after bypass, free thyroxine from the level 18 pmol/l before bypass to the minimal level 12 pmol/l after bypass. The average level of total triiodothyronine decreased from the level 1.54 nmol/l before bypass to the minimal level 0.42 nmol/l after bypass, free triiodothyronine from the level 6.12 pmol/l before bypass to the minimal level 3.21 pmol/l after bypass. The average level of TSH decreased from the level 4.31 mU/l before bypass to the level 0.64 mU/l after bypass. The average level of reverse-triiodothyronine increase from the level 0.83 nmol/l before bypass to the maximal level 1.94 nmol/l after bypass. CONCLUSIONS: We conclude that non-thyroidal illness occurs in all infants after cardiopulmonary bypass. The amount of free triiodothyronine that is filtrated during cardiopulmonary bypass may influence postoperative recovery.

Cardiopulmonary Bypass↗

Performance of an age series of alnus-cardamom plantations in the Sikkim Himalaya: productivity, energetics and efficiencies.

Biomass, net primary productivity, energetics and energy efficiencies were estimated in an age series of Alnus-cardamom plantations in the eastern Himalaya. The impact of stand age (5, 10, 15, 20, 30 and 40 years) on the performance of mixtures of N2-fixing (Alnus nepalensis) and non-N2-fixing (large cardamom) plants was studied. Large cardamom (Amomum subulatum) is the most important perennial cash crop in the region and is cultivated predominantly under Alnus trees. Net primary productivity was lowest (7 t ha(-1) per year) in the 40-year-old stand and was more than three times higher (22 t ha(-1) per year) in the 15-year-old stand. Agronomic yield of large cardamom peaked between 15 and 20 years of age. Cardamom productivity doubled from the 5- to the 15-year-old stand, and then decreased with plantation age to reach a minimum in the 40-year-old stand. Performance of cardamom in association of N2-fixing Alnus remained beneficial until 20 years of age. Annual net energy fixation was highest (444 x 10(6) kJ ha(-1) per year) in the 15-year-old stand, being 1.4 times that of the 5-year-old stand and 2.9-times that of the 40-year-old stand. Inverse relationships of production efficiency, energy conversion efficiency and energy utilized in N2-fixation against stand age, and a positive relationship between production efficiency and energy conversion efficiency suggest that the younger plantations are more productive. The Alnus-cardamom plantation system will be sustainable by adopting a rotational cycle of 15 to 20 years.

Algorithms↗

Performance of an age series of Alnus-cardamom plantations in the Sikkim Himalaya: nutrient dynamics.

Nutrient cycling, nutrient use efficiency and nitrogen fixation in an age series of Alnus-cardamom plantations were studied in the eastern Himalaya. The impact of stand age (5, 10, 15, 20, 30 and 40 years) on the nutrient dynamics of mixtures of N2-fixing (Alnus nepalensis) and non-N2-fixing (large cardamom) plants was assessed. Foliar nutrient concentrations of Alnus decreased with advancing age groups of plantations and showed an inverse relationship with stand age. Annual N fixation increased from the 5-year-old stand (52 kg ha(-1)), peaking in the 15-year-old stand (155 kg ha(-1)) and then decreased with increasing plantation age. Nitrogen and phosphorus uptake was lowest in the 40-year-old stand, and highest in the 15- and 5-year-old stand, respectively. Nutrient storage in understorey cardamom was very high: up to 31 % N and 59 % P of the stand total in the 15-year-old stand. Nutrient use efficiency was higher (with faster turnover times) in younger stands and decreased (with slower turnover times) in older plantations. Nitrogen retranslocation showed a strong positive relationship with stand age, while that of P was inversely related to stand age. Nutrient standing stock, uptake and return were also highest in the 15-year-old stand. Nitrogen and P cycling in Alnus-cardamom plantations was functionally balanced. Nutrient cycling and dynamics indicated that Alnus-cardamom plantations performed sustainably up to 15-20 years. The management practice should be altered to incorporate replantation after this age.

Algorithms↗

Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores.

In this report we provide evidence that neuronal nicotinic acetylcholine receptors (nAChRs) are present on hippocampal astrocytes and their activation produces rapid currents and calcium transients. Our data indicate that these responses obtained from astrocytes are primarily mediated by an AChR subtype that is functionally blocked by alpha-bungarotoxin (alpha Bgt) and contains the alpha7 subunit (alpha Bgt-AChRs). Furthermore, their action is unusual in that they effectively increase intracellular free calcium concentrations by activating calcium-induced calcium release from intracellular stores, triggered by influx through the receptor channels. These results reveal a mechanism by which alpha Bgt-AChRs on astrocytes can efficiently modulate calcium signaling in the central nervous system in a manner distinct from that observed with these receptors on neurons.

Animals↗

Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial.

CONTEXT: Patients with chronic fatigue syndrome (CFS) are more likely than healthy persons to develop neurally mediated hypotension (NMH) in response to prolonged orthostatic stress. OBJECTIVE: To examine the efficacy of fludrocortisone acetate as monotherapy for adults with both CFS and NMH. DESIGN: Randomized, double-blind, placebo-controlled trial conducted between March 1996 and February 1999. SETTING: Two tertiary referral centers in the United States. PATIENTS: One hundred individuals aged 18 to 50 years who satisfied Centers for Disease Control and Prevention criteria for CFS and had NMH provoked during a 2-stage tilt-table test. Eighty-three subjects had adequate outcome data to assess efficacy. INTERVENTION: Subjects were randomly assigned to receive fludrocortisone acetate, titrated to 0.1 mg/d (n = 50) or matching placebo (n = 50) for 9 weeks, followed by 2 weeks of observation after discontinuation of therapy. MAIN OUTCOME MEASURE: Proportion of subjects in each group with at least a 15-point improvement on a 100-point global wellness scale. RESULTS: Baseline demographic and illness characteristics between the groups were similar; CFS had been present for at least 3 years in 71%. Using an intention-to-treat analysis, 7 subjects (14%) treated with fludrocortisone experienced at least a 15-point improvement in their wellness scores compared with 5 (10%) among placebo recipients (P =.76). No differences were observed in several other symptom scores or in the proportion with normal follow-up tilt test results at the end of the treatment period. CONCLUSIONS: In our study of adults with CFS, fludrocortisone as monotherapy for NMH was no more efficacious than placebo for amelioration of symptoms. Failure to identify symptomatic improvement with fludrocortisone does not disprove the hypothesis that NMH could be contributing to some of the symptoms of CFS. Further studies are needed to determine whether other medications or combination therapy are more effective in treating orthostatic intolerance in patients with CFS.

Adult↗

Development of Dot-ELISA for the detection of human rotavirus antigen and comparison with RNA-PAGE.

AIMS: Development of a simple, specific, rapid and inexpensive Dot-ELISA test for diagnosis of rotaviral antigen in stool samples. METHODS AND RESULTS: Hyperimmune rabbit antisera raised against SA-11 (Simian Agent-11) strain was used as primary antibody. The secondary antibody conjugate used was the goat anti-rabbit IgG alkaline phosphatase, and BCIP/NBT solution was used as substrate. Faecal extracts were diluted 10-fold and used for the detection of rotavirus antigen. RNA-PAGE was performed to compare the specificity and sensitivity of the diagnostic tests. Dot-ELISA positive samples were further confirmed by Western blot analysis. CONCLUSIONS: This Dot-ELISA test could be used as an alternative method for diagnosing rotaviral samples in the field. SIGNIFICANCE AND IMPACT OF THE STUDY: The Dot-ELISA test is simple, specific, rapid and cost effective. It is suitable for identifying a large number of samples obtained from epidemiological studies and hence, reducing the death rate of rotavirus-infected patients.

Antigens, Viral↗

Temperature stability of vaginal specimens for Chlamydia trachomatis detection by Amplicor polymerase chain reaction assay.

Vaginal introital specimens were collected from 17 women - 10 positive and 7 negative for Chlamydia trachomatis, and kept in Amplicor collection medium at ambient temperature. Aliquots were removed at intervals for up to 34 days and frozen at -80 degrees C. Samples were thawed and assayed for C. trachomatis by polymerase chain reaction (PCR). The results of all specimens remained unchanged over this time interval.

Chlamydia Infections↗

Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype.

Uridine-diphosphoglucuronate glucuronosyltransferases (UGTs) are a family of enzymes that conjugate various endogenous and exogenous compounds with glucuronic acid and facilitate their excretion in the bile. Bilirubin-UGT(1) (UGT1A1) is the only isoform that significantly contributes to the conjugation of bilirubin. Lesions in the gene encoding bilirubin-UGT(1), lead to complete or partial inactivation of the enzyme causing the rare autosomal recessively inherited conditions, Crigler-Najjar syndrome type-1 (CN-1) and type 2 (CN-2), respectively. Inactivation of the enzyme leads to accumulation of unconjugated bilirubin in the serum. Severe hyperbilirubinemia seen in CN-1 can cause bilirubin encephalopathy (kernicterus). Kernicterus can be fatal or may leave behind permanent neurological sequelae. Here, we have compiled more than 50 genetic lesions of UGT1A1 that cause CN-1 (including 9 novel mutations) or CN-2 (including 3 novel mutations) and have presented a correlation of structure to function of UGT1A1. In contrast to Crigler-Najjar syndromes, Gilbert syndrome is a common inherited condition characterized by mild hyperbilirubinemia. An insertional mutation of the TATAA element upstream to UGT1A1 results in a reduced level of expression of the gene. Homozygosity for the variant promoter is required for Gilbert syndrome, but not sufficient for manifestation of hyperbilirubinemia, which is partly dependent on the rate of bilirubin production. Several structural mutations of UGT1A1, for example, a G71R substitution, have been reported to cause mild reduction of UGT activity toward bilirubin, resulting in mild hyperbilirubinemia, consistent with Gilbert syndrome. When the normal allele of a heterozygote carrier for a Crigler-Najjar type structural mutation contains a Gilbert type promoter, intermediate levels of hyperbilirubinemia, consistent with the diagnosis of CN-2, may be observed.

Animals↗

Symptomatic human rotavirus subgroups, serotypes & electropherotypes in Hyderabad, India.

A total of 352 stool specimens obtained from children under 2 yr of age with acute diarrhoea, between January 1998 and March 1999, were screened for the presence of rotavirus by RNA-PAGE. Symptomatic human rotaviruses were detected in 57 of 352 (16.19%) specimens by RNA-PAGE. These 57 samples were tested for rotavirus double stranded RNA pattern and among these, 46 samples were tested for subgroup and serotype specificities. Among the 46 strains tested, 29 strains were found to be subgroup II and remaining 17 strains were subgroup I, indicating that subgroup II strains are more predominant than subgroup I strains. Subgroup I and II strains were circulating concurrently throughout the study period. Seventeen strains with 'short' RNA pattern and subgroup I specificity could not be assigned as serotype 2 strains as they exhibited cross-reactivity to MAbs specific for more than one serotype. Of the 29 subgroup II strains with 'long' RNA pattern, 16 (55.17%) were serotype 1, 8 (27.58%) were serotype 4. Five (17.24%) showed dual reactivity to serotypes 1 and 3. Our results indicated that serotype 1 and G2-like strains are predominant in Hyderabad. None of the virus strains showed an unusual RNA pattern.

DNA, Viral↗

Detection of influenza virus induced DNA damage by comet assay.

Influenza virus A2/HK/68 is known to be a biological mutagen and teratogen. Reports are available implicating influenza virus as a causative agent of chromosomal aberrations in cells in culture and also in circulating leukocytes of humans. Also, an increased incidence of abortions, prenatal mortality and congenital abnormalities during the periods of epidemics has also been reported. In view of these reports, it would be worthwhile to screen persons especially pregnant women exposed to influenza virus for possible DNA damage. The present study reports the use of Comet assay to measure influenza virus induced DNA damage. We have carried out in vitro infection experiments using human leukocytes. Our results clearly indicate that influenza virus A2/HK/68 induces DNA damage in leukocytes right from 2-h post-infection. Maximum damage was observed at 24-h post-infection. However, at 48-h post-infection, a slight decrease was observed which can be attributed to the DNA repair occurring in the cells. Thereafter, irreparable damage was noticed. Cell viability results have shown lack of cytotoxicity till 72-h post-infection. However, significant cytotoxicity was observed only at 96-h post-infection. The occurrence of DNA damage without cell death may result in chromosomal aberrations or mutations. Therefore, it is most advisable to get screened for the possible DNA damage especially persons frequently infected with influenza and pregnant women.

Abortion, Spontaneous↗

Evaluation of a new recombinant DNA hepatitis B vaccine (Shanvac-B).

We assessed the efficacy and safety of Shanvac-B, a new recombinant hepatitis B vaccine developed in India. Eighty-one healthy volunteers (75 women, 6 men; aged 18-40 yr), negative for markers for hepatitis B and HIV, received 20 microg of the vaccine intramuscularly at 0, 1 and 2 months. Forty-three (53%) seroconverted at one month after dose 1; of these, 26% were seroprotected (anti-HBs> 10 mIU/mL). Seroprotection at one month after doses 2 and 3 was 99% and 100%, respectively. Geometric mean titres of anti-HBs in subjects who seroconverted were 11 (range 2-366), 266 (8-7469) and 2246 (102-23680) mIU/mL, respectively. One subject developed urticarial rash after the second dose; there was no other adverse event. We conclude that this vaccine is safe and efficacious, providing significant protection even after two doses.

Adolescent↗