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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 271 records · Page 15Linked to original sources

Predicting anti-HIV activity: computational approach using a novel topological descriptor.

The discriminating power of a novel topological descriptor termed as eccentric adjacency index in the estimation of anti-HIV activity, for a data set of 107 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives was investigated in the present study. The value of eccentric adjacency index of each derivative was computed and active range was identified using moving average analysis. Subsequently, each derivative was assigned a biological activity which was then compared with the reported anti-HIV activity. The accuracy of prediction was found to be more than ninety percent in the active range using eccentric adjacency index. The proposed index offers a vast potential for structure-activity/property studies.

Anti-HIV Agents↗

Anti-P-glycoprotein antibody-induced apoptosis of activated peripheral blood lymphocytes: a possible role of P-glycoprotein in lymphocyte survival.

P-glycoprotein (P-gp) is a 170-kDa glycoprotein encoded by the MDR-1 gene. In tumor cells overexpression of P-gp is associated with resistance to chemotherapy-induced apoptosis. P-gp is also expressed on cells of the immune system; however, its role in lymphocyte physiology remains unclear. Therefore, in this investigation, we examined a possible role of P-gp in the survival of in vitro activated peripheral blood mononuclear cells (MNCs). MNCs were activated with anti-CD3 monoclonal antibody (mAb) for 96 hr in the presence or absence of anti-P-gp mAb or isotype control and examined for apoptosis by TUNEL assay. Activation of caspase was determined by colorimetric assay. Activated lymphocytes (96 hr) are resistant to apoptosis. However, anti-P-gp mAb-induced apoptosis in anti-CD3 activated MNC. Induction of apoptosis was associated with increased expression of CD95L; activation of caspase 3, however, did not affect the expression of Bcl-2 and Bcl-xL. Furthermore, both recombinant Fas-Fc fusion protein, a blocker of CD95-CD95L interactions, and Z-DEVD-FMK, a cell-permeable caspase 3 inhibitor, reversed anti-P-gp-induced apoptosis. These data demonstrate that anti-P-gp mAb promotes apoptosis in activated T lymphocytes by up-regulating CD95L expression and via CD95-CD95L interactions and suggest a possible role of P-gp in lymphocyte survival.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Use of olanzapine for elderly patients with psychotic disorders: a review.

The number of elderly persons with psychosis will increase with the increasing geriatric population. Olanzapine is one of the newer atypical antipsychotics with efficacy for positive and negative symptoms and safer side effect profile compared to conventional antipsychotics. The manuscript describes the pharmacology, efficacy and tolerability studies, adverse effects and dosing considerations in the elderly. Further studies are needed to fully assess the efficacy and safety of olanzapine in the elderly. Current research supports a role for olanzapine in treating elderly patients with schizophrenia, schizoaffective disorder and behavioral and psychological symptoms of dementia.

Aged↗

Evaluation of the conformational propensities of peptide isosteres as a basis for selecting bioactive pseudopeptides.

Our aim was to compare the repertoires of conformers formed by the model zwitterionic peptides AA and AAA in aqueous solution with the conformational profiles of a range of their peptide isosteres, so as to facilitate selection of isosteres for synthesis and testing as biologically stable surrogates of bioactive di- and tripeptides. Comparisons were based upon the results of conformational analysis using a random search approach implemented within the SYBYL molecular modelling package, using zwitterionic molecules, simulated aqueous solvation using a dielectric constant of 80 and allowing all torsions to vary. For each compound, individual conformers were grouped on the basis of specific combinations of psi, phi and omega torsions and, using their energies, the aggregated percentage for each group was calculated using a Boltzmann distribution and displayed using a 3D pseudo Ramachandran plot relating percentage conformer to psi and phi torsions. Retroamide, N-methylamide and thioamide isosteres showed the best match to natural peptides and to the molecular recognition parameters defined for substrates of peptide transporters. The results should aid rational design of therapeutic agents in various areas, e.g. oral delivery of drugs by peptide transporters and of peptidase inhibitors. This approach may usefully be applied to various biochemical and pharmaceutical topics.

Dipeptides↗

Differential effects of serotonin reuptake inhibitors on erectile responses, NO-production, and neuronal NO synthase expression in rat corpus cavernosum tissue.

Increased incidence of impotence is associated with some selective serotonin-reuptake-inhibitors (SSRIs), but the pathophysiological mechanism is unknown. Paroxetine and citalopram are extensively used SSRIs, but only paroxetine has been shown to inhibit nitric oxide synthase (NOS) activity. NO is a key mediator of penile erection. Thus, the aim of this study was to determine the effects of paroxetine and citalopram on erectile function and NO production, in a rat model. Application of cavernosal nerve electrical stimulation produced frequency-related intracavernosal pressure (ICP) increases, which were inhibited by the NOS inhibitor, N(G)-nitro-L-arginine (0.3 mg x kg(-1)). Acute or chronic (2 weeks) paroxetine-treatment (10 mg x kg(-1)) reduced ICP-responses, while citalopram did not. Paroxetine, but not citalopram, significantly reduced nitrite+nitrate plasma levels by 61.4% and inhibited penile neuronal NOS (nNOS) protein expression by 31.2% after chronic treatment. The results show that paroxetine inhibits erectile responses in rats. We propose that this effect is due to reduced NO production and nNOS expression.

Animals↗

Single chain Fv: a ligand in receptor-mediated gene delivery.

We have used an anti-human polymeric immunoglobulin receptor (pIgR) single chain Fv (scFv) to deliver reporter genes to epithelial cells in vitro. The scFv was constructed from a monoclonal antibody directed against pIgR and a cysteine residue was added at the carboxyl end to facilitate its conjugation to polylysine (polyK) via the heterobifunctional cross-linker SPDP. ScFv-cys was expressed in Drosophila S2 cells and purified to homogeneity using conventional column chromatography. ScFv-polyK, and polyK as control, were condensed with a DNA expression plasmid containing the luciferase reporter gene driven by the CMV promoter into unimolecular (with respect to DNA) complexes under high salt conditions. Target cells were MDCK cells transfected with human pIgR and repeatedly sorted for high-level receptor expression, with untransfected MDCK cells as control. Receptor-bearing MDCK cells were readily transfected by scFv-cys containing, pIgR directed complexes, and expression could be blocked by addition of excess human secretory component (SC), the extracellular portion of pIgR. In contrast, MDCK cells that did not express pIgR were not transfected. Nontargeted complexes were not effective in transfecting MDCK cells with or without pIgR. Targeted complexes also transfected human tracheal epithelial cells in primary culture, corroborating the pIgR-mediated gene delivery. These data indicate that a scFv directed against human pIgR can direct foreign genes specifically into receptor-bearing cells in vitro. We have expressed and purified a ligand that is efficient and specific in pIgR-mediated gene delivery.

Animals↗

Negative pressure pulmonary oedema after cryotherapy for tracheal obstruction.

We report a patient who suffered negative pressure pulmonary oedema because of tracheal obstruction after cryotherapy to granulation tissue in the trachea. The pathophysiology and clinical course of negative pressure pulmonary oedema is described. Though there are reports of negative pressure pulmonary oedema after airway obstruction, to our knowledge this is the first case reported after cryotherapy.

Aged↗

Spinal endoscopy in chronic low back pain with radiculopathy. A prospective case series.

All 38 patients listed for day-case spinal endoscopy over a 12-month period (April 1998 - April 1999), who had chronic severe low back pain with a radiculopathic element, were studied prospectively. The mean [range] pain duration before treatment was 10.9 [2-26] years and 50% had failed back surgery syndrome. In all patients in whom treatment was completed (n = 34), the pain-generating nerve roots were located through symptom interaction with the patient. All had epidural scar tissue, 14 (41%) having dense adhesions. Mobilisation of adhesions around the nerve root (neuroplasty) was performed so that a pocket was formed for the subsequent placement of bupivacaine, Depomedrone and clonidine. No intra-operative complications occurred and side-effects were minimal. Follow-up over a 12-month period showed statistically significant reductions in pain scores and disability. Spinal endoscopy may be the diagnostic method of choice for epidural fibrosis. It has substantial therapeutic and research potential. Prospective randomised studies are required.

Ambulatory Surgical Procedures↗

Covert fears and anxiety in asthma and congenital heart disease.

AIM: To compare anxiety, fears and behavioural problems in children with asthma and children with congenital heart disease, and with the normative population. To also review the influence of maternal anxiety, time since diagnosis and severity of disease. DESIGN: Children administered Fear Survey Scale (FSSC-R) and Child Manifest Anxiety Scale (R-CMAS). Mothers given Child Behaviour Checklist (CBCL) and State Trait Anxiety Scale (STAI-S and STAI-T). Normative means and SDs compared with means and SDs for both medical groups. The mother's scores on the STAI-S and STAI-T scales were correlated with the child's scores on the FSSC-R and the R-CMAS. SETTING: Outpatient Asthma and Cardiology multidisciplinary Clinics at a tertiary care paediatric facility, Alberta Children's Hospital. SUBJECTS: Forty children with asthma (aged 6--17 years) were compared with 39 children with congenital heart disease. Intake questionnaires and interviews determined these children to be without obvious psycho-social problems. RESULTS: Children with asthma and children with congenital heart disease had more medical fears, and more physiological anxiety than normative samples. Increased maternal anxiety was correlated in both groups with increased child anxiety, medical fears and behavioural problems in the child. Similarly, increased severity of asthma or cardiac problems was associated with more physiological anxiety and more fears. Less time since diagnosis of the disease adversely affected social interactions in both groups of children. CONCLUSION: Physiological anxiety, medical fears and maternal anxiety are important issues requiring attention in asthma and cardiac disease, even in the absence of obvious psychosocial problems. There may be specific problems with a recent diagnosis of a chronic illness.

Adult↗

Microfilariae in association with neoplastic lesions: report of five cases.

Microfilariae and adult filarial worms have occasionally been detected in association with neoplastic lesions in cytological smears. The presence of microfilariae along with neoplasms is generally regarded as a chance association, yet some authors suggest that such parasitic infestations may be a causative factor for tumourigenesis. There are only a few reported cases in cytology literature documenting this association. We report the presence of microfilariae in routine cytology smears from one benign and four malignant tumours. Microfilariae could not be identified on histopathology available in four of these cases.

Adult↗

Blunt abdominal trauma with delayed rupture of splenic haematoma in a haemophiliac patient.

A 13-year-old haemophilia A patient presented with pain in the abdomen, 4 days after a blunt abdominal trauma. The computed tomography scan of the abdomen showed a large splenic haematoma. The patient was initially managed with factor VIII replacement therapy, but 4 weeks later he had a delayed rupture of the splenic haematoma with haemoperitoneum and shock. An elective splenectomy under factor VIII therapy was successfully performed.

Abdominal Injuries↗

Intralesional cryosurgery using lumbar puncture and/or hypodermic needles for large, bulky, recalcitrant keloids.

BACKGROUND: Keloids are notoriously difficult to treat. A variety of treatment modalities are currently in use, indicating that none is totally satisfactory. Surface cryosurgery is effective for smaller keloids, but not for larger ones. It often results in widespread depigmentation over the surface of the keloids, which may not be desirable, especially in patients with dark skin. OBJECTIVES: To determine the efficacy of intralesional (IL) cryosurgery in large, bulky keloids unresponsive to IL steroids, and to observe the extent of depigmentation and other complications produced by the technique. METHODS: Twelve patients with large, bulky, symptomatic keloids unresponsive to at least five injections of IL triamcinolone acetonide were included in the study. The age of the patients and the duration of the keloids were in the range 19-50 years and 1-12 years, respectively. The IL cryosurgery device was assembled using a small liquid nitrogen Dewar cylinder, a rubber and a plastic tube taken from a drip-set, adhesive tape, and hypodermic and lumbar puncture needles. The lumbar puncture or injection needle was introduced through the lesion until it appeared at the other side. Liquid nitrogen was then passed through the needle. The freezing time was between 20 and 30 s. The procedure was repeated for a second freeze-thaw cycle in the same session. RESULTS: The patients underwent a minimum of five up to a maximum of 10 sessions of IL cryosurgery. Seven out of 12 patients showed > 75% flattening. Depigmentation was observed along the tracks of the needles in all the patients, which improved during follow-up due to pigment spread from the normally pigmented areas in between. At the end of follow-up, 1-25% of the area remained hypo- or depigmented in four patients, 26-50% in six patients, and 51-75% in the remaining two patients. CONCLUSIONS: IL cryosurgery should be the preferred mode of therapy for large, bulky keloids, which are unresponsive to IL steroids.

Adult↗

"Pot-lid" technique for aesthetic removal of small lipoma on the face.

BACKGROUND: Patients presenting with an asymptomatic subcutaneous facial lipoma desire its removal in order to restore the contour of the face. The standard treatment for lipoma is excision, with the size of the incision being about one-half of that of the tumor itself. The long linear scar resulting from simple excision may fail to improve the appearance of the patient. The removal of the lipoma through a small incision or a punch hole decreases the size of the resulting scar, but does not eliminate it completely. OBJECTIVE: To improve the aesthetic outcome of the commonly used technique for lipoma removal, known as the narrow hole extrusion technique (NHET), by modification. METHODS: Four patients (three men and one woman) with small lipomas on the face (three on the forehead and one on the cheek) were selected for the procedure. A 5-mm punch was inserted deep into the center of the lesion to create a circular hole. The punched-out piece of skin was kept in normal saline. The lipoma was extruded with the help of a hemostat and by squeezing pressure. This resulted in the formation of a subcutaneous cavity. After achieving hemostasis, two absorbable buried subcutaneous sutures were placed to create support for the graft. The punched-out piece of skin was then positioned to cover the defect, like a "lid on a pot" and dressed. RESULTS: The color and texture match of the graft with the surrounding skin were excellent in three of the four patients by the end of 6 months. The graft, which was depressed in the fourth patient, improved through spot dermabrasion. CONCLUSION: The proposed modification of the NHET for lipoma removal improves the cosmetic outcome.

Adult↗