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N Gupta

Publications and source records attributed to N Gupta.

At least 37 records · Page 2Linked to original sources
PubMed2001

Role of glucocorticoids in the maturation of the rat renal Na+/H+ antiporter (NHE3).

BACKGROUND: Neonates have a lower Na+/H+ antiporter activity on the apical membrane of proximal tubule than that of adults. The maturational increase in Na+/H+ antiporter activity occurs at the time when there is a rise in serum glucocorticoid levels in rats. The purpose of the present study was to examine whether glucocorticoids are responsible for the postnatal increase in Na+/H+ antiporter activity. METHODS: Nine-day-old Sprague-Dawley rats were compared with rats studied at 30 days of age who had either a sham operation or adrenalectomy (ADX) at nine days of age and with rats that had an adrenalectomy and physiologic corticosterone replacement (ADX-Cort) to determine whether glucocorticoid deficiency prevented the maturational increase in Na+/H+ antiporter activity. Na+/H+ antiporter activity was measured in proximal convoluted tubules perfused in vitro by the change in cell pH (pHi) following luminal sodium removal. NHE3 mRNA abundance was measured using Northern blot analysis, and NHE3 protein abundance was measured by immunoblot. RESULTS: Na+/H+ antiporter activity was 93.8 +/- 17.7, 157.0 +/- 18.0, 356.7 +/- 29.9, and 402.5 +/- 14.5 pmol/mm. min in nine-day-old, ADX, ADX-Cort, and sham control groups, respectively. The ADX-Cort and sham control were higher than the 9-day-old and the 30-day-old ADX group (P < 0.05). Brush-border membrane NHE3 protein abundance in the nine-day-old and ADX groups were sixfold less than ADX-Cort and sham control groups (P < 0.001). Nine-day-old neonates had fivefold less renal cortical NHE3 mRNA than the ADX, ADX-Cort, and sham-operated control groups (P < 0.01). CONCLUSIONS: These data demonstrate that glucocorticoids play a role in the postnatal maturation of the proximal tubule Na+/H+ antiporter activity and brush-border membrane NHE3 protein abundance. Glucocorticoid deficiency does not completely prevent the maturational increase in Na+/H+ antiporter activity and does not affect NHE3 mRNA abundance.

Adrenalectomy↗
PubMed2001

Prospects for viral-based strategies enhancing the anti-tumor effects of ionizing radiation.

Ionizing radiation (IR) has been extensively used to treat a variety of solid tumors to improve local control and overall survival in patients. Gene therapy strategies represent one experimental direction to improve radiocurability. These gene therapy strategies include (1) replacement of mutated or deleted tumor-suppressor genes, (2) delivery of prodrugs, (3) transduction of genes under the control of radiation-inducible promoters, and (4) genetically engineered viruses that replicate preferentially in tumor cells after IR. Although any one of these viral-based gene therapy approaches is unlikely to succeed independently, experimental results suggest that clinically important antitumor can be achieved when these strategies are combined with IR. Several of these strategies are currently being or soon will be evaluated in clinical trials. This review focuses on molecular mechanisms and potential clinical application of these viral-based gene therapy strategies to improve the therapeutic index of IR.

Animals↗
PubMed2001

Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma.

BACKGROUND: A recombinant humanized anti-IgE mAb, omalizumab, forms complexes with free IgE, blocking its interaction with mast cells and basophils; as a consequence, it might be effective in the treatment of asthma. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of omalizumab in the treatment of inhaled corticosteroid-dependent asthma. METHODS: In this phase III, double-blinded, placebo-controlled trial, 525 subjects with severe allergic asthma requiring daily inhaled corticosteroids were randomized to receive placebo or omalizumab subcutaneously every 2 or 4 weeks, depending on baseline IgE level and body weight. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment and tapered during a further 12-week treatment period. RESULTS: Omalizumab treatment resulted in significantly fewer asthma exacerbations per subject and in lower percentages of subjects experiencing an exacerbation than placebo treatment during the stable steroid phase (0.28 vs 0.54 [P =.006] and 14.6% vs 23.3% [P =.009], respectively) and during the steroid reduction phase (0.39 vs 0.66 [P =.003] and 21.3% vs 32.3% [P =.004], respectively). Beclomethasone dipropionate reduction was significantly greater with omalizumab treatment than with placebo (median 75% vs 50% [P <.001]), and beclomethasone dipropionate discontinuation was more likely with omalizumab (39.6% vs 19.1% [P <.001]). Improvements in asthma symptoms and pulmonary function occurred along with a reduction in rescue beta-agonist use. Omalizumab was well tolerated, with an adverse-events profile similar to that of placebo. CONCLUSION: The addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use.

Adolescent↗
PubMed2001

Angiostatin effects on endothelial cells mediated by ceramide and RhoA.

Angiostatin is a cleavage product of plasminogen that has anti-angiogenic properties. We investigated whether the effects of angiostatin on endothelial cells are mediated by ceramide, a lipid implicated in endothelial cell signaling. Our results demonstrate that angiostatin produces a transient increase in ceramide that correlates with actin stress fiber reorganization, detachment and death. DNA array expression analysis performed on ceramide-treated human endothelial cells demonstrated induction of certain genes involved in cytoskeleton organization. Specifically, we report that treatment with angiostatin or ceramide results in the activation of RhoA, an important effector of cytoskeletal structure. We also show that treatment of endothelial cells with the antioxidant N-acetylcysteine abrogates morphological changes and cytotoxic effects of treatment with angiostatin or ceramide. These findings support a model in which angiostatin induces a transient rise in ceramide, RhoA activation and free radical production.

Angiostatins↗
PubMed2001

Garlic and garlic-derived compounds inhibit human squalene monooxygenase.

Although extracts of garlic inhibit cholesterol biosynthesis in cultured hepatocytes, the inhibitory components of garlic and the site or sites of inhibition in the cholesterol biosynthetic pathway have not been established. To elucidate potential mechanisms of inhibition, we examined the effect of fresh garlic extract and 16 water- or lipid-soluble compounds derived from garlic on purified recombinant human squalene monooxygenase. Squalene monooxygenase catalyzes the second and likely rate-limiting step in the downstream pathway for cholesterol biosynthesis. A 50% inhibitory concentration (IC(50)) of squalene epoxidation was achieved with 1 g/L of fresh garlic extract; of the 16 garlic compounds tested, only selenocystine (IC(50) = 65 micromol/L), S-allylcysteine (IC(50) = 110 micromol/L), alliin (IC(50) = 120 micromol/L), diallyl trisulfide (IC(50) = 195 micromol/L), and diallyl disulfide (IC(50) = 400 micromol/L) substantially inhibited the enzyme. Kinetic analysis showed that the inhibition by garlic and by these compounds was slow and irreversible, suggestive of covalent binding to the enzyme; the ability of thiol-containing compounds such as glutathione and 2,3-dimercaptopropanol to prevent and reverse the inhibition indicated that the garlic compounds were reacting with sulfhydryl groups on the protein. Dithiols were better reversal agents than monothiols, further suggesting that these inhibitors bind to the proposed vicinal sulfhydryls present on this enzyme. These results indicate that squalene monooxygenase may be one of the target enzymes through which garlic inhibits cholesterol biosynthesis.

Cysteine↗
PubMed2001

Development and calculation of an energy dependent normal brain tissue neutron RBE for evaluating neutron fields for BNCT.

In Boron Neutron Capture Therapy (BNCT) of malignant brain tumors, the energy dependence of a clinically relevant Relative Biological Effectiveness (RBE) for epithermal neutrons, RBE(En), is important in neutron field design. In the first half of this paper, we present the development of an expression for the energy dependent normal-tissue RBE, RBE(En). We then calculate a reasonable estimate for RBE(En) for adult brain tissue. In the second half of the paper, two separate RBE expressions are developed, one for the RBE of the neutrons that interact in tissue via the 14N(n,p)14C reaction, denoted RBE(N), and one for the RBE of the neutrons which interact in tissue via the 1H(n,n')1H reaction, denoted RBE(H). The absorbed-dose-averaged values of these expressions are calculated for the neutron flux spectrum in phantom for the Brookhaven Medical Research Reactor (BMRR) epithermal neutron beam. The calculated values, [RBE(norm)N] = 3.4 and [RBE(norm)H] = 3.2, are within 6% of being equal, and support the use of equal values for RBEN and RBE(H) by researchers at Brookhaven National Laboratory (BNL). Finally, values of [RBE(norm)N] and [RBE(norm)H], along with the absorbed-dose-averaged RBE for brain, [RBE(norm)b], were calculated as a function of depth along the centerline of an ellipsoidal head phantom using flux spectra calculated for our Accelerator-Based Neutron Source (ABNS). These values remained essentially constant with depth, supporting the use of constant values for RBE, as is done at BNL.

Absorption↗
PubMed2001

Psychiatric morbidity in vitiligo and psoriasis: a comparative study from India.

In a tertiary-care teaching hospital in India, dermatology outpatients with vitiligo (N=113) and psoriasis (N=103) were studied for psychiatric morbidity. The two groups were similar with regard to education, locality, religion, and attitude to appearance (ATT). Psoriasis cases were older, more often male, and more often married. The General Health Questionnaire (GHQ) assessed psychiatric morbidity rates at 33.63% and 24.7% for vitiligo and psoriasis, respectively. The ICD-10 psychiatric diagnoses in GHQ positive cases were: adjustment disorder (56% vs 62%), depressive episode (22% vs 29%) and dysthymia (9% vs 4%) in vitiligo and psoriasis, respectively. The Comprehensive Psychopathological Rating Scale (CPRS) assessed that depression, anxiety, and total psychopathology levels were similar in the two GHQ positive subgroups. Significant correlations were noted between psychopathology (GHQ CRPS), dysfunction as per Dysfunction Analysis Questionnaire (DAQ), and behavior change as per Impact of Skin Disease Scale (IMPACT), and all were more prominent in vitiligo.

Adaptation, Psychological↗
PubMed2001

A comparison of neutron beams for BNCT based on in-phantom neutron field assessment parameters.

In this paper our in-phantom neutron field assessment parameters, T and DTumor, were used to evaluate several neutron sources for use in BNCT. Specifically, neutron fields from The Ohio State University (OSU) Accelerator-Based Neutron Source (ABNS) design, two alternative ABNS designs from the literature (the Al/AIF3-Al2O3 ABNS and the 7LiF-AI2O3 ABNS), a fission-convertor plate concept based on the 500-kW OSU Research Reactor (OSURR), and the Brookhaven Medical Research Reactor (BMRR) facility were evaluated. In order to facilitate a comparison of the various neutron fields, values of T and DTumor were calculated in a 14 cm x 14 cm x 14 cm lucite cube phantom located in the treatment port of each neutron source. All of the other relevant factors, such as phantom materials, kerma factors, and treatment parameters, were kept the same. The treatment times for the OSURR, the 7LiF-Al2O3 ABNS operating at a beam current of 10 mA, and the BMRR were calculated to be comparable and acceptable, with a treatment time per fraction of approximately 25 min for a four fraction treatment scheme. The treatment time per fraction for the OSU ABNS and the Al/AlF3-Al2O3 ABNS can be reduced to below 30 min per fraction for four fractions, if the proton beam current is made greater than approximately 20 mA. DTumor was calculated along the bean centerline for tumor depths in the phantom ranging from 0 to 14 cm. For tumor depths ranging from 0 to approximately 1.5 cm, the value of DTumor for the OSURR is largest, while for tumor depths ranging from 1.5 to approximately 14 cm, the value of DTumor for the OSU-ABNS is the largest.

Boron Neutron Capture Therapy↗
PubMed2001

Absorbed dose estimates to structures of the brain and head using a high-resolution voxel-based head phantom.

The purpose of this article is to demonstrate the viability of using a high-resolution 3-D head phantom in Monte Carlo N-Particle (MCNP) for boron neutron capture therapy (BNCT) structure dosimetry. This work describes a high-resolution voxel-based model of a human head and its use for calculating absorbed doses to the structures of the brain. The Zubal head phantom is a 3-D model of a human head that can be displayed and manipulated on a computer. Several changes were made to the original head phantom which now contains over 29 critical structures of the brain and head. The modified phantom is a 85 x 109 x 120 lattice of voxels, where each voxel is 2.2 x 2.2 x 1.4 mm3. This model was translated into MCNP lattice format. As a proof of principle study, two MCNP absorbed dose calculations were made (left and right lateral irradiations) using a uniformly distributed neutron disk source with an 1/E energy spectrum. Additionally, the results of these two calculations were combined to estimate the absorbed doses from a bilateral irradiation. Radiobiologically equivalent (RBE) doses were calculated for all structures and were normalized to 12.8 Gy-Eq. For a left lateral irradiation, the left motor cortex receives the limiting RBE dose. For a bilateral irradiation, the insula cortices receive the limiting dose. Among the nonencephalic structures, the parotid glands receive RBE doses that were within 15% of the limiting dose.

Boron Neutron Capture Therapy↗
PubMed2001

Inhibition of glioma cell growth and tumorigenic potential by CCN3 (NOV).

AIMS: To establish whether the ectopic expression of CCN3 (NOV) in glioma cells can interfere with their tumorigenic potential and assess its potential value in molecular medicine. METHODS: Glioma cell lines were used to assess whether differences in the degree of intracellular communication induced by the expression of the gap junction protein connexin 43 (Cx43) is related to the differential expression of CCN3 (NOV). The antiproliferative activity of rat CCN3 (rCCN3; NOV) in glioma cells, has been assessed both in vitro and in vivo with glioma cell lines expressing different amounts of CCN3 (NOV). RESULTS: Upon ectopic expression of Cx43, the growth of C6 glioma cells is decreased. An increase of CCN3 (NOV) expression matches the reduced tumorigenic potential of these transfected cells. The localisation of CCN3 (NOV) is affected by the increased expression of Cx43 in the Cx-13 transfected cells, in which it is detected at areas of cell-cell contact. In a xenograft model, CCN3 (NOV) transfected glioma cells were found to induce tumours to a lesser degree than their parental counterparts, which do not express detectable amounts of CCN3 (NOV). CONCLUSIONS: Previous observations had suggested an inverse relation between CCN3 (NOV) expression in glioma cells and their tumorigenicity. These results establish a direct association between the establishment of functional gap junctional intercellular communication and the expression of rCCN3 (NOV). In addition to a negative effect on murine and human cell growth, CCN3 (NOV) has antiproliferative activity on tumour cells in vivo. Thus, the antiproliferative activity of the CCN3 (NOV) protein might involve reorganisation of cellular contacts that play a crucial role in tumorigenesis. The antiproliferative activity of CCN3 (NOV) established in this work sets the stage for the potential use of CCN proteins in molecular oncology.

Animals↗
PubMed2001

The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics.

The clinical benefit and steroid-sparing effect of treatment with the anti-immunoglobulin-E (IgE) antibody, omalizumab, was assessed in patients with moderate-to-severe allergic asthma. After a run-in period, 546 allergic asthmatics (aged 12-76 yrs), symptomatic despite inhaled corticosteroids (500-1,200 microg daily of beclomethasone dipropionate), were randomized to receive double-blind either placebo or omalizumab every 2 or 4 weeks (depending on body weight and serum total IgE) subcutaneously for 7 months. A constant beclomethasone dose was maintained during a 16-week stable-steroid phase and progressively reduced to the lowest dose required for asthma control over the following 8 weeks. The latter dose was maintained for the next 4 weeks. Asthma exacerbations represented the primary variable. Compared to the placebo group, the omalizumab group showed 58% fewer exacerbations per patient during the stable-steroid phase (p<0.001). During the steroid-reduction phase, there were 52% fewer exacerbations in the omalizumab group versus the placebo group (p<0.001) despite the greater reduction of the beclomethasone dosage on omalizumab (p<0.001). Treatment with omalizumab was well tolerated. The incidence of adverse events was similar in both groups. These results indicate that omalizumab therapy safely improves asthma control in allergic asthmatics who remain symptomatic despite regular use of inhaled corticosteroids and simultaneous reduction in corticosteroid requirement.

Acute Disease↗