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Biomedical subjects

M K Gupta

Publications and source records attributed to M K Gupta.

At least 19 recordsLinked to original sources
PubMed2005

Biodegradable microparticulate system of captopril.

Albumin microparticles have found many applications in diagnosis and treatment in recent years and more than 100 diagnostic agents and drugs have been incorporated into albumin microparticles. In the present study, bovine serum albumin (BSA) based microparticles bearing captopril were prepared by an emulsification-heat stabilization technique. Four batches of microparticles with varying ratio of drug and polymer were prepared. The prepared microparticles were studied for drug loading, particle size distribution, in vitro release characteristics, in vivo tissue distribution study and stability studies. The microparticles had mean diameter between 2 and 11 microm of which more than 70% were below 5 microm and incorporation efficiency of 41-63% was obtained. In vitro release profile for formulations containing captopril-loaded albumin microparticles with heat stabilizing technique shows slow controlled release up to 24 h. The in vivo result of drug-loaded microparticles showed preferential drug targeting to liver followed by lungs, kidneys and spleen. Stability studies showed that maximum drug content and closest in vitro release to initial data were found in the formulation stored at 4 degrees C. In the present study, captopril-loaded BSA microparticles were prepared and targeted to various organs to a satisfactory level and were found to be stable at 4 degrees C.

Animals↗
PubMed2005

Topological descriptors in modeling the HIV inhibitory activity of 2-aryl-3-pyridyl-thiazolidin-4-ones.

The HIV-1 RT inhibitory activity of 2-(2,6-dihalophenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones has been analyzed with different topological descriptors obtained from DRAGON software. Here, simple topological descriptors (TOPO), Galvez topological charge indices (GVZ) and 2D autocorrelation descriptors (2DAUTO) have been found to yield good predictive models for the activity of these compounds. The correlations obtained from the TOPO class descriptors suggest that less extended or compact saturated structural templates would be better for the activity. The participating GVZ class descriptors suggest that they have same degree of influence on the activity. In 2DAUTO class, the large participation of descriptors of lags seven and three indicate the association of activity information with the seven and three centered structural fragments of these compounds. The physicochemical weighting components of these descriptors suggest homogeneous influence of mass, volume, electronegativity and/ or polarizability on the activity.

Anti-HIV Agents↗
PubMed2004

Pathology of benzalkonium chloride toxicity and its effect on body weight gain in broiler birds.

Four groups comprising 16 broiler birds each were given benzalkonium chloride (BC) at 100, 300, 500 and 700 ppm in drinking water for 40 days and one group of 16 birds (control) was kept on plain water. Clinical signs in higher dose groups were respiratory distress, drooling of saliva, difficulty in deglutition, inappetence, apathy, lethargy and loss of body weight. Better body weight gain was recorded in 100 ppm dose rate. At 300 ppm, no significant body weight variation was recorded, whereas, at 500 and 700 ppm dose rates, significantly poor body weight gain was recorded. Major pathological changes were seen in 500 and 700 ppm groups, which exhibited formation of yellow diphtheritic plaques in the buccal cavity, swollen and pale commissures of beak and shortening of tongue. Minute necrotic and ulcerative foci were seen in oesophagus and crop. Hyperplastic and hypertrophic alterations were seen in mucosa of the upper digestive tract. Crop of 300 ppm group revealed formation of well developed epithelial nest with pseudoepitheliomatous hyperplasia at the margin of the lesion. Serum alanine transaminase, urea and uric acid in 500 and 700 ppm groups were elevated whereas no significant variations were observed in the 100 and 300 ppm groups. BC could enhance performance of broiler birds at 100 ppm dose rate. It should not be used beyond 300 ppm.

Alanine Transaminase↗
PubMed2003

Effect of low-dose testosterone treatment on androgen regulated proteins prostate specific antigen and sex hormone binding globulin in short prepubertal boys: lack of initiation of puberty.

The efficacy of testosterone undecanoate (TU) treatment in constitutional delay of growth (CHD) is well recognized. We investigated its role in initiating puberty. Sera taken prior to, just after 6 months on and after 6 months off treatment with TU (20 mg daily) were analyzed from eight boys and compared to results from eight boys receiving placebo. Prostate specific antigen (PSA) and sex hormone binding globulin (SHBG), sleep-entrained pulsatility and mean overnight luteinizing hormone (mLH), and morning testosterone (T) levels were measured. Free androgen index (FAI) was calculated. Testicular volume (TV) and growth parameters were assessed. During treatment, there was a significant increase in height velocity in boys taking TU vs placebo (mean +/- SD: 5.7 +/- 2.0 vs 3.2 +/- 0.9 cm/year, p = 0.008) but no significant differences were observed in regard to LH pulsatility, mLH, T, SHBG, FAI, PSA and TV values. PSA was detectable in four patients (two each in the TU and placebo groups) at 6 months off treatment indicating pubertal progression. Among the hormones measured, only pretreatment mLH levels were significantly higher in the PSA-positive patients compared to 12 PSA-negative patients (mean +/- SEM: 1.5 +/- 0.39 vs 0.37 +/- 0.06 IU/l, p < 0.001). In conclusion, TU treatment shows no significant effect on initiation or advancement of puberty despite its resultant growth acceleration. Among the hormonal changes studied, mLH levels were the earliest indicator of pubertal initiation.

Adolescent↗
PubMed2001

Evidence that androgens are the primary steroids produced by Xenopus laevis ovaries and may signal through the classical androgen receptor to promote oocyte maturation.

Steroid-induced maturation of Xenopus oocytes has long served as a model for studying meiosis. Progesterone has been considered the relevant steroid controlling maturation, perhaps through interactions with classical progesterone receptors. In this study, we provide evidence that androgens, rather than progesterone, are the physiologic mediators of Xenopus oocyte maturation. Androgens were equal or more potent activators of maturation in vitro relative to progesterone and were significantly more abundant in the serum and ovaries of beta-human chorionic growth hormone-stimulated frogs. Androgen action appeared to be mediated by classical androgen receptors (ARs) expressed in oocytes, as androgen-induced maturation and signaling was specifically attenuated by AR antagonists. Interestingly, we found that progesterone was rapidly converted to the androgen androstenedione in isolated oocytes by the enzyme CYP17, suggesting that androgens may be promoting maturation even under conditions typical for "progesterone-mediated" maturation assays. Androgens are thought to play an important role in ovarian development as well as pathology, and signaling through the AR may prove to be a major regulatory mechanism mediating these processes.

Androgen Receptor Antagonists↗
PubMed2001

Histamine--can it cause an acute coronary event?

Myocardial infarction (MI) occurring during the course of an allergic urticarial reaction in the absence of systemic hypotension has been rarely reported. This paper reports the case of a 28-year-old woman with no significant risk factors for coronary artery disease who presented with generalized urticaria associated with chest pain and had electrocardiographic and enzymatic evidence of an acute MI. Review of the literature suggests that local histamine release may induce spasm of the coronary vasculature, thus leading to myocardial ischemia and infarction.

Adult↗
PubMed2001

Enhanced drug dissolution and bulk properties of solid dispersions granulated with a surface adsorbent.

A combination of solid dispersion and surface adsorption techniques was used to enhance the dissolution of a poorly water-soluble drug, BAY 12-9566. In addition to dissolution enhancement, this method allows compression of the granulated dispersion into tablets. Gelucire 50/13 (polyglycolized glycerides) was used as the solid dispersion carrier. Hot-melt granulation was performed to adsorb the melt of the drug and Gelucire 50/13 onto the surface of Neusilin US2 (magnesium alumino silicate), the surface adsorbent. Dispersion granules using various ratios of drug-Gelucire 50/13-Neusilin US2 were thus prepared. The dissolution profiles of BAY 12-9566 from the dispersion granules and corresponding physical mixtures were evaluated using USP Type II apparatus at 75 rpm. The dissolution medium consisted of 0.1 N hydrochloric acid (HCl) with 1% w/v sodium lauryl sulfate (SLS). Dissolution of BAY 12-9566 from the dispersion granules was enhanced compared to the physical mixture. The dissolution of BAY 12-9566 increased as a function of increased Gelucire 50/13 and Neusilin US2 loading and decreased with increased drug loading. In contrast to the usually observed decrease in dissolution on storage, an enhancement in dissolution was observed for the dispersion granules stored at 40 degrees C/75% relative humidity (RH) for 2 and 4 weeks. Additionally, the flow and compressibility properties of dispersion granules were improved significantly when compared to the drug alone or the corresponding physical mixture. The ternary dispersion granules were compressed easily into tablets with up to 30% w/w drug loading. The extent of dissolution of drug from these tablets was greater than that from the uncompressed dispersion granules.

Adsorption↗
PubMed2001

Effect of 131 iodine therapy on the course of Graves' ophthalmopathy: a quantitative analysis of extraocular muscle volumes using orbital magnetic resonance imaging.

There remains uncertainty as to the effect of radioactive iodine (131I) therapy on the associated ophthalmopathy (GO). Twenty newly diagnosed patients with Graves' hyperthyroidism treated with 131I (median dose, 15.5 mCi) were followed with ophthalmologic evaluations (OE) and magnetic resonance imaging (MRI) at baseline, 2, and 6 months, and with OE alone at 3 years. For MRI, the superior, inferior, and medial rectus muscle volumes and total muscle volumes (TMV) were measured. Replacement levothyroxine was initiated as low thyroxine (T4) levels were noted. At baseline, 10 patients (50%) showed evidence of mild GO by OE and/or MRI. There was a significant difference in TMV between the 20 patients with Graves' hyperthyroidism and 10 controls (mean +/- standard error [SE]; 2,652 +/- 118 vs. 2,046 +/- 96 mm3; P = 0.002) and between the 10 patients with and 10 without GO (3,006 +/- 96 vs. 2,298 +/- 61 mm3; P = 0.001). TMV correlated with the Hertel score (r = 0.56, P = 0.01). TMV showed no significant change at 2 or 6 months posttreatment. The inferior rectus volume increased slightly at 2 months posttreatment (P = 0.03) but remained stable at 6 months. Furthermore, no significant changes occurred in Hertel scores or in clinical assessments up to 3 years posttreatment and none showed worsening or new development of GO. In conclusion, our results show no significant risk for radioiodine-induced initiation or progression of mild GO.

Adult↗
PubMed2001

Pitfalls in characterizing P450c17 mutations associated with isolated 17,20-lyase deficiency.

The cytochrome P450c17 enzyme system performs both the 17alpha-hydroxylase and 17,20-lyase reactions in the human adrenal glands and gonads. This 17,20-lyase activity is required for the biosynthesis of dehydroepiandrosterone, the C(19) precursor of sex steroids. Considerable evidence supports the idea that the 17,20-lyase activity of this system is particularly sensitive to alterations in the interactions between P450c17 and its cofactor proteins P450-oxidoreductase and cytochrome b(5). We have described two patients with the clinical phenotype of isolated 17,20-lyase deficiency in whom single amino acid replacement mutations in the redox partner binding site of P450c17 (R347H and R358Q) selectively ablate 17,20-lyase activity while preserving most 17alpha-hydroxylase activity. We have shown by computer modeling and detailed biochemical studies that mutations R347H and R358Q impair the interactions of P450c17 with P450-oxidoreductase and cytochrome b(5) (redox partners). Another mutation reported to cause isolated 17,20-lyase deficiency (F417C) does not map within the redox partner binding site, but might nonetheless alter the interaction of the mutant protein with redox partners. To study the interaction of the F417C mutation with P450 oxidoreductase and cytochrome b(5), we expressed the cDNA for this protein in yeast microsomes, a heterologous expression system in which the composition of redox partner proteins can be varied systematically. Although the full-length protein was expressed in quantities comparable to those of wild-type P450c17 in this system, the F417C mutation did not form a classical P450 difference spectrum and was devoid of both 17alpha-hydroxylase and 17,20-lyase activities. To ensure that this result was not unique to the yeast expression system, we also expressed wild-type P450c17 and the F417C mutation in COS-7 cells, and we again found that the F417C mutation was expressed, but was not active. To conclusively demonstrate that a particular mutation in P450c17 causes isolated 17,20-lyase deficiency, accurate enzymatic studies of the mutant protein must reproducibly show activities consistent with the diagnosis. Mutations R347H and R358Q are the only two such mutations found in humans proven to cause isolated 17,20-lyase deficiency.

Animals↗
PubMed1999

Serum prostate specific antigen, sex hormone binding globulin and free androgen index as markers of pubertal development in boys.

OBJECTIVE: Prostate specific antigen (PSA) expression in the prostate gland is regulated by androgens. Serum levels of PSA are undetectable by routine assays in normal boys. Measurable values could serve as a marker for pubertal development. In order to explore this question, we measured serum PSA levels in normal boys throughout puberty and examined the interrelationships with various hormonal and physical developmental changes. DESIGN: Sera from 77 normal boys in Tanner stages I to V (T-I to T-V) were analysed for PSA levels by a sensitive time-resolved fluoro-immunometric assay (sensitivity: 0.012 microgram/l). In addition, sex hormone binding globulin (SHBG), insulin like growth factor I (IGF-I), IGF binding protein 3(IGFBP-3) and testosterone were measured. RESULTS: PSA was detectable in 0% of Stage T-I (n = 16), 33% of T-II (n = 18), 65% of T-III (n = 17) and 100% of T-IV (n = 10) and T-V (n = 16) boys. PSA levels rose significantly according to stage (P < 0.05). Also, there were significant (P < 0.05) increments in serum testosterone, IGF-I and IGFBP-3 levels from stages T-I to T-IV. PSA showed a positive correlation with testosterone (r = 0.86, P < 0.001), IGF-I (r = 0.66, P < 0.001), and IGFBP-3 (r = 0.34, P = 0.004) levels. Both PSA and these analytes, however, showed significant overlap between stages T-I and T-II with only 6/18 (33%) and 12/18 (66%) of T-II subjects having PSA and testosterone levels, respectively, above the T-I range. In contrast, serum SHBG levels decreased markedly from stages I to II (P < 0.001). At the calculated best cut-off point for SHBG of 50 nmol/l, 16/18 T-II subjects had values below the T-I range (sensitivity = 89%). Because of this decrement of SHBG and the increasing testosterone secretion in early puberty, the Free Androgen Index (FAI = Testosterone/SHBG) could even better differentiate the onset of puberty with all except one of the T-II subjects having FAI levels above the T-I range (sensitivity = 94.4%). The decrease of SHBG in T-II subjects coincided with an increase in total body weight (P = 0.001) and body mass index (BMI, P = 0.0003). Despite the continuing pubertal rise in testosterone, SHBG levels showed a rebound increment from T-II-T-III subjects (P = 0.02) with a concomitant decrease in BMI (P = 0.0014). CONCLUSIONS: Prostate specific antigen closely reflects serum free androgen activity during puberty. However, it was unable to differentiate the earliest pubertal development. In comparison, SHBG levels and Free Androgen Index are more sensitive markers for the onset of puberty in boys. The inverse association between SHBG levels and BMI in pubertal stages Tanner stages, I to III suggests that body fatness, via its effect on insulin sensitivity, may play an important role in the regulation of SHBG production during early pubertal development.

Adolescent↗
PubMed1999

Epitope heterogeneity of thyrotropin receptor-blocking antibodies in Graves' patients as detected with wild-type versus chimeric thyrotropin receptors.

The stable transfectants of wild-type (W25) and mutant thyrotropin-receptor (TSH-R) allow detection of the bioactivities of TSH-R antibodies in Graves' patients. A mutant Chinese hamster ovary (CHO) cell line (Mc1+2) transfected with a chimeric construct, where residues 8 to 165 of the TSH-R are replaced with residues 10 to 166 of the lutropin/choriogonadotropin (LH/CGR) receptor, lacks the cyclic adenosine monophosphate (cAMP) response to most thyrotropin stimulating antibodies (TSAb), yet retains the response to TSH and acquires the response to LH/CG. We compared Mc1+2 cells with wild-type W25 cells for their ability to detect TSAb as well as thyrotropin-blocking antibodies (TBAb) in Graves' sera. Eighteen normal and 39 Graves' sera were tested for TSAb and TBAb levels by in vitro bioassays using W25 and Mc1+2 cells. In addition, these sera were also tested for thyrotropin-binding inhibitory activity (TBII) by a radioreceptor assay. Eighteen (47%) Graves' sera had TBAb activity measured with W25 cells but not with Mc1+2 cells. These TBAbs were, therefore, a population of antibodies with functional epitopes on the N-terminus of the extracellular domain. This TBAb activity by W25 cells exhibited a high degree of correlation with TBII levels by a radioreceptor assay (r = 0.70, p = 0.001). Ten (25.6%) Graves' sera had positive TBAb activity in both W25 and Mc1+2 cells; moreover, their activity in both assays was similar (r = 0.83, p < 0.001). The TBAb activity in these sera, however, did not correlate with TBII activity. Eleven (28%) Graves' sera had no TBAb activity. Overall, thyroid-stimulating antibodies were detected in 87% and 28% of the 39 Graves' sera by W25 and Mc1 +2 cells, respectively. Thus, using the 2 cell lines, at least 2 distinct populations of TBAbs were detected. One is detected in a similar fashion by both W25 and Mc1+2 cell lines and likely interacts with the epitopes residing in the unaltered C-terminus of the TSH-R. The other is reactive in W25 cells only, indicating the loss of TBAb epitope in the chimeric receptor located in the N-terminus of the TSH-R. Furthermore, our results indicate that the TBAb binding epitope in 8-165 residues of the native TSH-R is highly associated with TBII activity in Graves' disease. These results indicate that patients with Graves' disease harbor TBAbs with epitope heterogeneity and favor the notion that there are different sites and mechanisms by which TBAbs act in Graves' patients. It remains to be determined whether or not TBAb subtyping will have a useful predictive role in the management of patients with Graves' disease.

Adult↗
PubMed1998

Combined nested RT-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in prostate cancer patients: correlation with pathological stage.

Nested reverse transcription (RT)-PCR for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) can detect circulating prostatic cells in patients with prostate cancer. We evaluated the role of a combined screening approach for PSA and PSM in prostate cancer staging. We examined the peripheral blood samples from 136 patients with adenocarcinoma of the prostate (PCA), 15 patients with benign prostatic hyperplasia, 15 normal male subjects, and 5 female subjects. The controls (benign prostatic hyperplasias, normal males, and normal females) were negative for both PSA and PSM. In patients with metastatic PCA (n = 11), 100% were positive by combined PSA/PSM (64% by PSA and 91% by PSM). In biochemical failure PCA patients (n = 18), 39% were positive by PSM, compared to only 6% by PSA. In patients with clinically localized PCA (n = 107), 48% were positive by combined PSA/PSM approach (43% by PSM and 14% by PSA). These results show that PSM is a more sensitive marker than PSA in detecting circulating prostatic cells (P < 0.0001). We correlated preoperative RT-PCR results with final pathological stages in 67 prostatectomy patients. RT-PCR positivity was 81.5% in patients with non-organ-confined disease versus 37.5% in organ-confined disease (P = 0.001). PSA/PSM RT-PCR had an odds ratio of 7.3 (95% confidence interval, 2.3-23.4; P = 0.001) in predicting tumor extracapsular extension. PSA/PSM RT-PCR was a better predictor of tumor extracapsular extension than initial serum PSA, clinical stage, and biopsy Gleason score. Our data show that PSA/PSM nested RT-PCR may provide the staging information unavailable from the current modalities. The ultimate impact of this technique in the management of patients with prostate cancer will require continued investigation.

Adenocarcinoma↗
PubMed1997

Studies on aluminium leaching from cookware in tea and coffee and estimation of aluminium content in toothpaste, baking powder and paan masala.

Studies were conducted in order to assess the level of aluminium (Al) in samples of Indian tea, coffee, toothpaste, paan masala (mouth freshener) and baking powder. Leaching of Al from cookware while preparing tea and coffee was also studied. Experiments were also conducted to study the sequential leaching of Al from cookware by preparing tea and coffee in the presence of standard size Al sheets (coupons). A small amount of Al was found to have leached from coupons during preparation of tea. Tea leaves, were found to be a rich source of Al and a maximum of 2.2% Al is extracted in tea infusions. Coffee powder on the other hand was not found to be a rich source of Al. Baking powder was found to be a rich source of Al and 1 kg of cake prepared with 1-3 teaspoon of baking powder may contain 2-12.7 mg of Al in each serving (25 g). Toothpaste also contains a significant quantity of Al, more so, when packed in Al tubes. Ingestion pattern of Al from these items by humans is also discussed.

Alum Compounds↗
PubMed1997

Insulin antibodies and hypoglycemia in diabetic patients. Can a quantitative analysis of antibody binding predict the risk of hypoglycemia?

We report a noninsulin-dependent diabetes mellitus (NIDDM) patient with spontaneous, severe hypoglycemic reactions and the presence of insulin antibodies. He had a remote antecedent history of beef-pork insulin therapy as well as exposure to hydralazine. Detailed insulin binding kinetic studies were performed in this patient as well as in six other insulin-treated diabetic patients with anti-insulin antibodies (three with and three without an obvious cause of hypoglycemia). Sera from the current patient and five of the six other diabetic patients (one NIDDM, four IDDM) revealed two types of binding sites: high-affinity with low capacity (Kd, 0.4-12.4 x 10(-9) mol/L; binding capacity, 0.6-659 mU/L) and low-affinity with high capacity (Kd, 0.3 to 35.7 x 10(-7) mol/L; binding capacity; 202-113,680 mU/L). One NIDDM patient had only high-affinity antibodies (Kd, 22.9 x 10(-9) mol/L; binding capacity of 78 mU/L). Type of diabetes mellitus, insulin antibody titers or their binding capacities, insulin levels (total, bound, or free), and bioavailable insulin were not related to hypoglycemic reactions. Two calculated values by the method described tended to discriminate patients with and without hypoglycemia. The calculated amount of low-affinity antibody bound insulin ranged from 69.4-2090 mU/L vs < 4-70.6 mU/L in patients with and without hypoglycemia, respectively. The best discrimination was afford by the percent saturation of low-affinity binding sites; values were clearly higher in the patients with hypoglycemia (2.5-34.4%) than in those without hypoglycemia (not detectable, 0.06, 0.15%). Consideration of the possible drug-associated insulin antibody formation in insulin-treated diabetics and the novel quantitative analysis of the antibody binding kinetics should prove helpful in evaluating patients with high insulin antibody titers and assessing the risk of hypoglycemia.

Adult↗