Biomedical subjects

S K Gupta

Publications and source records attributed to S K Gupta.

At least 181 records · Page 10Linked to original sources

PubMed2000

Studies on the relationships between the synonymous codon usage and protein secondary structural units.

The relationship between the synonymous codon usage and protein secondary structural elements (alpha helices and beta sheets) were reinvestigated by taking structural information of proteins from Protein Data Bank (PDB) and their corresponding mRNA sequences from GenBank for four different organisms E. coli, B. subtilis, S. cerevisiae, and Homo sapiens. It was observed that synonymous codon families have non-random codon usage, but there does not exist any species invariant universal correlation between the synonymous codon usage and protein secondary structural elements. The secondary structural units of proteins can be distinguished from the occurrences of bases at the second codon position.

Amino Acids↗

PubMed2000

Modeling of ion permeation in calcium and sodium channel selectivity filters.

Structure-function studies have shown that it is possible to convert a sodium channel to a calcium-selective channel by a single amino acid substitution in the selectivity filter locus. Ion permeation through the "model selectivity filter" was modeled with a reduced set of functional groups representative of the constituent amino acid side chains. Force-field minimizations were conducted to obtain the energy profile of the cations as they get desolvated and bind to the "model selectivity filter." The calculations suggest that the ion selectivity in the calcium channel is due to preferential binding, whereas in the sodium channel it is due to exclusion. Energetics of displacement of a bound cation from the calcium "model selectivity filter" by another cation suggest that "multi-ion mechanism" reduces the activation barrier for ion permeation. Thus, the simple model captures qualitatively most of the conduction characteristics of sodium and calcium channels. However, the computed barriers for permeation are fairly large, suggesting that ion interaction with additional residues along the transport path may be essential to effect desolvation.

Calcium Channels↗

PubMed2000

Lung injury, inflammation, and inflammatory stimuli in rats exposed to ozone.

The effects of ozone (O3) on airway epithelia, inflammation, and expression of inflammatory stimuli were investigated to delineate the mechanisms of inflammatory reactions relevant to lung injury. Because the airway responses to O3 develop gradually, this investigation included a time-sequence analysis. Rats exposed for 3 h to 1 ppm O3 were studied at 4-h intervals up to 20 h postexposure. Bronchoalveolar lavage fluid (BAL) was analyzed for albumin as an indicator of increased permeability, polymorphonuclear leukocytes (PMNs) to assess the inflammatory status, macrophage inflammatory protein-2 (MIP-2, an inflammatory chemokine), and cell adhesion molecules for their role in inflammation and PMN functions. The time-related increase in albumin was matched by a similar significant increase for PMNs, MIP-2, and intercellular adhesion molecule-1 (ICAM-1). However, no marked change occurred for beta-2 integrin (CD-18) and leukotriene B4 (LTB4). The results establish a temporal correlation of epithelial permeability with changes in inflammatory activity and stimuli responsible for PMN recruitment in the lung. The observations of elevated MIP-2 and ICAM-1 levels are consistent with their role in injury and inflammation. An early expression of MIP-2 mRNA in BAL cells, that is, immediately post O3 exposure, and the peak increase in BAL MIP-2 levels 4 h later support the chemotactic role of MIP-2 in PMN recruitment at 4- and 12-h time points. The rapid drop in MIP-2 and ICAM-1 levels appears to signal the termination of inflammatory cell recruitment, which is accompanied by an onset of recovery.

Air Pollution↗

PubMed2000

Induction of chromosome aberrations, micronucleus formation and sperm abnormalities in mouse following carbofuran exposure.

Carbofuran was tested to study in vivo cytogenetic effects in mouse bone marrow cells and morphological alterations in sperms. The acute oral and intraperitoneal (i.p.) LD(50) of carbofuran was determined to be 9.5 or 2.0 mg/kg b.w. in mice, respectively. The animals were orally administered 1.9, 3.8 or 5.7 mg/kg b.w. (20, 40 and 60% of LD(50)) of carbofuran for 24 h or 1.9 mg/kg b.w. for 4 consecutive days (cumulative 7.6 mg/kg or 80% of LD(50)) to analyse chromosome aberrations (CAs). For micronucleus test (MT) animals were orally exposed to 5.7 mg/kg b.w. for 24 and 48 h or 1.9 mg/kg b.w. for 4 consecutive days. For reference mice were exposed to peanut oil (negative control) and cyclophosphamide (20 mg/kg) or ethyl methanesulfonate (EMS: 100 mg/kg) positive control for CAs and MT respectively. To analyse the effect on sperm morphology mice were exposed to single i.p. dose of 1 and 2 mg/kg b.w. of carbofuran and repeatedly to 0.5 mg/kg for 5 consecutive days. Cytogenetic analysis revealed that all the test doses induced mitotic inhibition, CAs, micronucleus (MN) formation and sperm abnormalities in a dose dependent manner. Present observations concurrent with earlier reports substantiate the genotoxic potential of carbofuran and possible risk to human beings.

Animals↗

PubMed2000

Development and validation of a new high-performance liquid chromatographic estimation method of meloxicam in biological samples.

A simple, HPLC method was developed to estimate meloxicam (COX-2 inhibitor) using piroxicam as the internal standard. The mobile phase containing methanol, acetonitrile and an aqueous solution of diammonium hydrogenorthophosphate (50 mM) in the ratio of 4:1:5 was pumped at the rate 1 ml/min. Lichrocart RP-18 (125 x 4 mm) was used as an analytical column and the analytes were detected at 364 nm using a UV detector. Acidified plasma samples were extracted with chloroform, evaporated to dryness, reconstituted in the mobile phase and then a volume of 10 microl of the prepared sample was injected in the column. The retention time of meloxicam and piroxicam was found to be 2.7 and 1.9, respectively. This method showed an accuracy of 102.3% at 0.52 microg/ml and was capable of detecting a minimum concentration of 0.029 microg/ml meloxicam from biological samples. The analytical method was successfully utilized for estimating meloxicam in biological samples.

Animals↗

PubMed2000

DNA flow cytometry of non-Hodgkin's lymphomas: correlation with cytologic grade and clinical relapse.

In this prospective study, we correlated cytological grading and clinical follow-up of non-Hodgkin's lymphomas (NHL) with DNA flow cytometry (FCM) data from fine-needle aspiration biopsy (FNAB) material. FNAB was performed from 34 successive cases of NHL, and the aspirated material was analyzed by DNA FCM. Cytological subtyping and grading were done by modified Working Formulation. Cases were followed up for 2.5 yr, and cytological grading, clinical follow-up, and DNA FCM data were correlated. There were 8 cases of low, 14 intermediate, and 12 high-grade NHL. None of the cases of low-grade NHL showed DNA aneuploidy. Of the 8 DNA aneuploid cases, 5 were of intermediate and 3 were of high-grade NHL. Mean growth fraction (GF) of low-grade, intermediate-grade, and high-grade NHL was 6.1, 9.4, and 19.4, respectively. DNA aneuploidy was statistically significant (P < 0.05) between low- vs. intermediate- and high-grade NHL. Growth fraction was also statistically significant between low- vs. high-grade NHL. Six cases showed clinical recurrence, and one case died within 6 mo of diagnosis, due to widespread involvement of NHL. DNA aneuploidy and mean GF of recurrent and nonrecurrent cases were statistically significant (P < 0.05) irrespective of grading of NHL. DNA aneuploidy and GF are not well-correlated with morphological grading (by the Working Formulation). However, these two criteria are important for assessment of early clinical relapse of NHL.

Aneuploidy↗

PubMed2000

Effect of food on the pharmacokinetics of osmotic controlled-release methylphenidate HCl in healthy subjects.

The effect of a high-fat meal on the pharmacokinetics of OROS(R) (methylphenidate HCl), an osmotic controlled-release formulation of methylphenidate HCl, was investigated in healthy subjects. Mean peak methylphenidate plasma concentrations occurred slightly later and peak methylphenidate plasma concentrations and AUC values were slightly higher (approximately 10-30%) in the presence of food than in the absence of food. There was no difference in the plasma elimination half-life of methylphenidate between the fed and fasted state. Similarly, peak concentrations and AUC values for alpha-phenyl-2-piperidine acetic acid (PPA; ritalinic acid), the major metabolite of methylphenidate, were slightly higher in the presence of food than in its absence. The 90% confidence interval (CI) for the treatment ratio (fed/fasted) for C(max) was 120.6%-140. 0% for the 18-mg dose and 105.4-119.3% for a 36-mg dose. The 90% CI for the treatment ratio for AUC(infinity) was 114.6-125.7% for the 18-mg dose and 115.1-124.6% for the 36-mg dose. PPA levels were measured following the 18-mg dose and the 90% CI of the treatment ratio was 106.8-115.4% for C(max) and 97.9-103.6% for AUC(infinity). These results indicate the absence of dose dumping from OROS (methylphenidate HCl) in the presence of food. Food does not impede drug absorption and OROS (methylphenidate HCl) may be administered in the fed or fasted state. There were no differences in the adverse event profile between the fed and fasted state.

Administration, Oral↗

PubMed2000

Application of in vitro-in vivo correlations (IVIVC) in setting formulation release specifications.

An in vitro-in vivo correlation (IVIVC) was established for an osmotic controlled-release dosage form by deconvolution using data from an immediate-release treatment as the characteristic response. The established IVIVC was evaluated internally (predicting data used to develop the IVIVC) and externally (predicting data not originally included in developing the IVIVC), and the application of the IVIVC in product development was demonstrated. The estimated in vivo dissolution profile compared favorably with the in vitro drug release profile. Good agreement was demonstrated between the estimated and observed cumulative drug release across the entire time course (level A correlation) with low (<10%) predictive error for both C(max) and AUC(infinity). External validation using lots not initially included in the model development compared very well with the observed in vivo profile, with mean prediction errors less than 10% for both C(max) and AUC(infinity). The proposed method demonstrates a schema for developing IVIVCs using data from biostudies routinely conducted during formulation development. The method should facilitate product optimization and can support setting in vitro dissolution specification.

Algorithms↗

PubMed2000

Misuse of corticosteroids in some of the drugs dispensed as preparations from alternative systems of medicine in India.

Screening for corticosteroids carried out on 120 samples of alternative medicines which were dispensed to patients suffering mainly from asthma, arthritis, etc., showed that 38.32% of them were adulterated with steroids. Most of these samples were submitted for screening by either a medical practitioner or the patients themselves, who suspected effects of steroids from these drugs. The percentage of steroid positivity was determined in ayurvedic drugs, homeopathic drugs, and unknown or other category of drugs. The presence of steroids in these drugs given for different ailments such as asthma, arthritis, and unknown/other ailments was also tabulated. The results show that a high percentage of these samples contained corticosteroids, however, the distribution of positivity amongst groups was not statistically significant. The lack of proper quality control mechanisms to verify ingredients or efficacy of 'alternative medicines' has led to the proliferation of the practice of dispensing spurious drugs containing corticosteroids as alternative medicines. This study aims to highlight the existence of 'quick fix' remedies dispensed as 'alternative medicines' which not only cause extensive adverse health effects to the patients but also bring alternative systems of medicines into disrepute. The deliberate contamination of corticosteroids with alternative systems of medicine by some practitioners is a cause of great concern. Such practices may not only disgrace alternative systems of medicine but may also lead to adverse side-effects on chronic exposure.

Adrenal Cortex Hormones↗

PubMed2000

Comparative anti-nociceptive, anti-inflammatory and toxicity profile of nimesulide vs nimesulide and piperine combination.

Piperine is an inhibitor of various hepatic and other enzymes involved in the biotransformation of drugs. Preliminary pharmacokinetic studies conducted by us suggested the increased bioavailability of nimesulide co-administered with piperine. The present study was, thus, conducted to evaluate the antinociceptive, anti-inflammatory and toxicity profile of a new nimesulide-piperine combination administered orally as compared with nimesulide alone. Antinociceptive efficacy was tested using an acetic acid writhing test and tail flick latency test (TFL). The ED50 value of a nimesulide-piperine combination in writhing test was calculated to be significantly lower (1.5 mg kg(-1)) as compared to (11.2 mg kg(-1)) of nimesulide alone. The antinociceptive effect was lesser in the tail flick latency test as compared to what was observed in the writhing test indicating the peripheral action of the Non-Steriodal Anti-Inflammatory Drug (NSAID). In carrageenan-induced inflammatory tests, the nimesulide-piperine combination was found to be dose-to-dose superior than nimesulide alone. Acute toxicity studies on mice revealed a reduction in lethal dose (LD50) of the combination (980 mg kg(-1)) as compared to nimesulide (1500 mg kg(-1)) alone. Results from the present study suggest a better therapeutic index for the nimesulide-piperine combination indicating that this combination would further reduce the frequency of adverse effects associated with nimesulide alone.

Administration, Oral↗

PubMed2000

Etoposide encapsulated in positively charged liposomes: pharmacokinetic studies in mice and formulation stability studies.

Etoposide is an antineoplastic agent which acts by forming a ternary complex with topoisomerase II and DNA, causing DNA breaks and cell death. In recent studies we have demonstrated that encapsulation in liposomes increases the antitumour efficacy and reduces the adverse effects associated with etoposide. The present study was thus conducted to evaluate whether encapsulation in cationic liposomes altered the pharmacokinetics of etoposide and to study the effect of cholesterol incorporation on the stability of the liposomes. Etoposide-encapsulated unilammellar liposomes were synthesized by thin film hydration followed by extrusion. The drug was administered to Swiss albino mice at a dose of 10 mg kg(-1). The concentration of the drug in plasma was analysed at different time points till 360 min after injection, using a h.p.l.c. method. The terbium chloride-dipicolinic acid interaction method was applied to study the stability of the formulation in mouse serum and also following storage at 0( composite function)C over a period of time. The effect of the free and liposomal drug on myelosuppression was evaluated at 10 mg m(-2)and 40 mg m(-2)dose levels by quantifying blood cell counts on day 15 and day 21 following a 5 day course of therapy. Encapsulation in cationic liposomes increased the area under the concentration vs time curve to 42.98 microghml(-1)from 24.18 microghml(-1)in the case of the free drug. Half-life (beta) was 58. 62 and 186 min in the case of free and liposomal etoposide, respectively. In the stability studies, incorporation of cholesterol progressively stabilized the formulation in serum. The use of sucrose at increasing concentrations as a cryoprotectant also increased the shelf stability of the formulation at 0( composite function)C. Toxicity studies using a dose of pure drug revealed that though myelosuppression was evident in both liposomal- and free drug-treated groups on day 15 it was reversed by day 21 following initiation of therapy. The present findings suggest that liposomes could serve as an alternative mode of delivery for etoposide.

Analysis of Variance↗

PubMed2000

Popliteal venous aneurysms: report of an unusual presentation and literature review.

Aneurysms of the popliteal vein represent a rare clinical finding. Most patients with popliteal venous aneurysms present with pulmonary emboli. We describe a case report of a 69-year-old female who presented with popliteal fossa pain. A popliteal venous aneurysm was detected following extensive diagnostic work-up that included magnetic resonance imaging (MRI), venous duplex, and venography. At operation, the aneurysm was found to be compressing the tibial nerve. Tangential aneurysmectomy and lateral venorrhaphy was performed. A PTFE sleeve was placed around the site of venous repair to prevent recurrence of the aneurysm and to keep the tibial nerve free of the repair site. The postoperative course was uneventful, and duplex studies at 18 months after the procedure remain normal. The etiology of popliteal venous aneurysms is discussed here, and presentation, diagnostic work-up, and treatment options are reviewed. We demonstrate that pain in the popliteal fossa should be considered a presenting symptom for venous aneurysms.

Aged↗

PubMed2000

Bypass surgery using a radial artery graft for bilateral extracranial carotid arteries occlusion.

A patient presenting with recurrent ischemic attacks was demonstrated to have complete occlusion of the right common and left internal carotid arteries. An external carotid angiogram showed a large left superficial temporal artery (STA) supplying both sides of the scalp. 123I-IMP single photon emission computed tomography (SPECT) revealed hypoperfusion of the both hemispheres, especially the left cerebral hemisphere. An extracranial-intracranial (EC-IC) bypass was performed using a radial artery graft interpositioned between the proximal part of the STA and the M2 segment, thus preserving blood flow to the scalp through the STA. Postoperative angiography after 1 year showed good circulation through the anastomosis, and 123I-IMP SPECT studies demonstrated increased cerebral perfusion. The patient improved clinically. The surgical technique is described below.

Carotid Artery Diseases↗

PubMed2000

Studies on codon usage in Entamoeba histolytica.

Codon usage bias of Entamoeba histolytica, a protozoan parasite, was investigated using the available DNA sequence data. Entamoeba histolytica having AT rich genome, is expected to have A and/or T at the third position of codons. Overall codon usage data analysis indicates that A and/or T ending codons are strongly biased in the coding region of this organism. However, multivariate statistical analysis suggests that there is a single major trend in codon usage variation among the genes. The genes which are supposed to be highly expressed are clustered at one end, while the majority of the putatively lowly expressed genes are clustered at the other end. The codon usage pattern is distinctly different in these two sets of genes. C ending codons are significantly higher in the putatively highly expressed genes suggesting that C ending codons are translationally optimal in this organism. In the putatively lowly expressed genes A and/or T ending codons are predominant, which suggests that compositional constraints are playing the major role in shaping codon usage variation among the lowly expressed genes. These results suggest that both mutational bias and translational selection are operational in the codon usage variation in this organism.

Animals↗

PubMed2000

Chemopreventive activity of Ocimum sanctum seed oil.

The seed oil of Ocimum sanctum was evaluated for chemopreventive activity against subcutaneously injected 20-methylcholanthrene induced-fibrosarcoma tumors in the thigh region of Swiss albino mice. Supplementation of maximal tolerated dose (100 microl/kg body weight) of the oil significantly reduced 20-methylcholanthrene induced tumor incidence and tumor volume. The enhanced survival rate and delay in tumor incidence was observed in seed oil supplemented mice. Liver enzymatic (superoxide dismutase, catalase, glutathione-S-transferase), non-enzymatic antioxidants (reduced glutathione) and lipid peroxidation end product, malondialdehyde levels were significantly modulated with oil treatment as compared to untreated 20-methylcholanthrene injected mice. The results of this study suggest that the potential chemopreventive activity of the oil is partly attributable to its antioxidant properties. The chemopreventive efficacy of 100 microl/kg seed oil was comparable to that of 80 mg/kg of vitamin E.

Animals↗

PubMed2000

Efficacy of fluconazole and liposome entrapped fluconazole for C. albicans induced experimental mycotic endophthalmitis in rabbit eyes.

PURPOSE: To study the efficacy of intravitreally injected plain and liposome encapsulated fluconazole in the doses of 100 and 200 microg in Candidal endophthalmitis in rabbit eyes. METHOD: Endophthalmitis was induced by injecting Candida albicans (1000 CFU/0.1 ml). Seventy two hours after inoculation, plain and liposome encapsulated fluconazole (REVs) were injected. At day 16 sterility was studied using vitreous culture. RESULTS: In the 100 & 200 microg plain fluconazole group, vitreous sterility was seen in 62.5% and 75%, respectively. In the liposome entrapped fluconazole a culture sterility of 25% and 50% for 100 microg and 200 microg, respectively, was seen. CONCLUSION: Plain fluconazole in the dose of 100 and 200 microg was equally effective against Candidal endophthalmitis in rabbits, but a failure of 25-37.5% of the eyes to respond, discourages one from using fluconazole as a sole therapy. Liposome entrapped fluconazole was found to be inferior to plain fluconazole in this model.

Animals↗

PubMed2000

Refolding, structural transition and spermatozoa-binding of recombinant bonnet monkey (Macaca radiata) zona pellucida glycoprotein-C expressed in Escherichia coli.

An internal cDNA fragment (978 bp) corresponding to bonnet monkey (Macaca radiata) zona pellucida glycoprotein-C (bmZPC), excluding the N-terminal signal sequence and the C-terminal transmembrane-like domain, was cloned in pQE-30 vector and the protein expressed as inclusion bodies in Escherichia coli. Recombinant bmZPC (r-bmZPC) was solubilized from purified inclusion bodies in the absence of a high concentration of chaotropic agents and was subsequently refolded. Use of a low concentration of urea (2 M) during solubilization of r-bmZPC helped to minimize the extent of protein aggregation during refolding of the recombinant protein, and retain the existing native-like secondary structure that was essential for proper folding. Purified r-bmZPC appeared as a dominant band of 43 kDa on SDS/PAGE and Western blot. Although it lacked carbohydrate moieties, the purified and refolded r-bmZPC bound to the head region of bonnet monkey spermatozoa, confirming the existence of a native-like conformation. CD revealed a maximum at 200 nm and a single broad minimum extending from 209 to 216 nm, indicating the presence of both alpha-helical and beta-sheet conformations in the refolded r-bmZPC. Two different phases of transition were observed by urea-gradient electrophoresis, suggesting the existence of multiple intermediate stages during the unfolding of r-bmZPC. The availability of refolded r-bmZPC will help in elucidating its role during the complex cascade of events during fertilization.

Animals↗

PubMed2000

Intravitreal pefloxacin therapy in postoperative endophthalmitis.

PURPOSE: To study the efficacy of intravitreal pefloxacin in the management of suspected bacterial endophthalmitis. METHODS: Twenty eyes with suspected postoperative bacterial endophthalmitis were given an intravitreal injection of pefloxacin (200 microg in 0.1 mL). If required the injection was repeated after 24 h. The main parameters evaluated were visual acuity, response to intravitreal therapy and any complications due to intravitreal pefloxacin. RESULTS: Fourteen eyes (70%) responded to intravitreal pefloxacin therapy alone, while an additional pars plana vitrectomy was required in six eyes (30%). Nineteen eyes retained a visual acuity of 6/60 or better at 3 months after the initiation of therapy. A retinal detachment developed in one of the eyes which received intravitreal therapy. CONCLUSIONS: Intravitreal pefloxacin may be a useful aternative therapy in bacteria endophthalmitis.

Aged↗