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Biomedical subjects

G Sridhar

Publications and source records attributed to G Sridhar.

18 recordsLinked to original sources
PubMed2005

A stability indicating LC method for zolmitriptan.

A gradient, reversed-phase liquid chromatographic (RP-LC) assay method was developed for the quantitative determination of zolmitriptan, used to treat severe migraine headaches. The developed method is also applicable for the related substances determination in bulk drugs. The chromatographic separation was achieved on a Waters X Terra RP18, 250 mm x 4.6 mm, 5 microm column. The gradient LC method employs solutions A and B as mobile phase. The solution A contains a mixture of phosphate buffer pH 9.85:methanol:acetonitrile (70:20:10, v/v/v) and solution B contains a mixture of phosphate buffer, pH 9.85:acetonitrile (30:70). The flow rate was 1.0 ml/min and the detection wavelength was 225 nm. In the developed HPLC method, the resolution between zolmitriptan and its potential impurities, namely Imp-1, Imp-2 and Imp-3 was found to be greater than 3. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in alkaline medium and oxidative stress conditions. Degradation product formed during base hydrolysis was found to be Imp-3. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.

Acetonitriles↗
PubMed2005

A validated chiral LC method for the enantiomeric separation of Zolmitriptan key intermediate, ZTR-5.

A new and accurate chiral liquid chromatographic method was described for the enantiomeric separation of ZTR-5 [(4S)-4-(4-aminobenzyl)-2-oxazolidinone, (S)-isomer], a key intermediate of Zolmitriptan in bulk drugs. The enantiomers of ZTR-5 were baseline resolved on a Chiralpak AD-H (250 mm x 4.6 mm, 5 microm) column using a mobile phase system containing hexane:ethanol (70:30, v/v). The resolution between the enantiomers was not less than four and interestingly distomer was eluted prior to eutomer. The limit of detection and limit of quantification of (4R)-4-(4-aminobenzyl)-2-oxazolidinone [(R)-isomer] were found to be 250 and 750 ng/ml, respectively, for 10 microl injection volume. The percentage recovery of (R)-isomer ranged from 92.0 to 105.6 in the bulk drug samples of ZTR-5. The validated method yielded good results regarding precision, linearity, accuracy and ruggedness. The proposed method was found to be suitable and accurate for the quantitative determination of (R)-isomer in bulk drug samples of ZTR-5.

Amylose↗
PubMed2004

A validated chiral LC method for the determination of zolmitriptan and its potential impurities.

A new, accurate and reliable chiral HPLC method was developed for the determination of Zolmitriptan, (4S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] methyl]-2-oxazolidinone an antimigraine agent and its potential impurities namely (4R)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] methyl]-2-oxazolidinone [(R)-enantiomer] and (4S)-4-(4-aminobenzyl)-2-oxazolidinone (Imp-1) in pharmaceutical formulations and in bulk drugs. HPLC separation was carried out by normal phase chromatography with a mobile phase composed of hexane:isopropanol:methanol:diethylamine in the ratio (75:10:15:0.1, v/v/v/v) pumped at a flow rate of 1.0 ml/min on a Chiralpak AD-H column. Zolmitriptan and its potential impurities were baseline resolved in the optimized method. The presence of diethylamine in the mobile phase has played a key role in achieving chromatographic resolution between the enantiomers and also in enhancing chromatographic efficiency. The developed method was also found to be selective under exposed conditions UV light and 60 degrees C. The developed method was completely validated and proved to be robust. The values of the limit of detection (LOD) and limit of quantification (LOQ) of (R)-enantiomer and Imp-1 were 100, 250 ng/ml and 30, 1000 ng/ml, respectively, for 10 microl injection volume. The validated method yielded good results regarding selectivity, linearity, precision, accuracy and ruggedness. Zolmitriptan sample solution and mobile phase are found to be stable for at least 24 h. The proposed method was found to be suitable and accurate for the quantitative determination of Zolmitriptan and its impurities namely (R)-enantiomer and Imp-1 in bulk drugs and commercial formulations.

Chromatography, Liquid↗
PubMed2001

A bioactive metabolite of benzo[a]pyrene, benzo[a]pyrene-7,8-dione, selectively alters microsomal Ca2+ transport and ryanodine receptor function.

Polycyclic aromatic hydrocarbons are environmental pollutants known to be carcinogenic and immunotoxic. In intact cell assays, benzo[a]pyrene (B[a]P) disrupts Ca(2+) homeostasis in both immune and nonimmune cells, but the molecular mechanism is undefined. In this study, B[a]P and five metabolites are examined for their ability to alter Ca(2+) transport across microsomal membranes. Using a well-defined model system, junctional SR vesicles from skeletal muscle, we show that a single o-quinone metabolite of B[a]P, B[a]P-7,8-dione, can account for altered Ca(2+) transport across microsomal membranes. B[a]P-7,8-dione induces net Ca(2+) release from actively loaded vesicles in a dose-, time-, and Ca(2+)-dependent manner. In the presence of 5 microM extravesicular Ca(2+), B[a]P-7,8-dione exhibited threshold and EC(50) values of 0.4 and 2 microM, respectively, and a maximal release rate of 2 micromol of Ca(2+) min(-1) mg(-1). The mechanism by which B[a]P-7,8-dione enhanced Ca(2+) efflux was further investigated by measuring macroscopic fluxes and single RyR1 channels reconstituted in bilayer lipid membranes and direct measurements of SERCA catalytic activity. B[a]P-7,8-dione (< or = 20 microM) had no measurable effect on initial rates of Ca(2+) accumulation in the presence of ruthenium red to block ryanodine receptor (RyR1), nor did it alter Ca(2+)-dependent (thapsigargin-sensitive) ATPase activity. B[a]P-7,8-dione selectively altered the function of RyR1 in a time-dependent diphasic manner, first activating then inhibiting channel activity. Considering that RyR1 and its two alternate isoforms are broadly expressed in mammalian cells and their important role in Ca(2+)-signaling, the present results reveal a mechanism by which metabolic bioactivation of B[a]P may mediate RyR dysfunction of pathophysiological significance.

Animals↗
PubMed2000

Ventilatory responses to hypercapnia and hypoxia in relatives of patients with the obesity hypoventilation syndrome.

BACKGROUND: It is unclear why some morbidly obese individuals have waking alveolar hypoventilation while others with similar obesity do not. Some evidence suggests that patients with the obesity hypoventilation syndrome (OHS) may have a measurable premorbid impairment of ventilatory chemoresponsiveness. Such an impairment of ventilatory chemoresponsiveness in OHS, however, may be an acquired and reversible consequence of severe obstructive sleep apnoea (OSA). We hypothesised that, in patients with OHS who do not have coincident severe OSA, there may be a familial impairment in ventilatory responses to hypoxia and hypercapnia. METHODS: Sixteen first degree relatives of seven patients with OHS without severe OSA (mean (SD) age 40 (16) years, body mass index (BMI) 30 (6) kg/m(2)) and 16 subjects matched for age and BMI without OHS or OSA were studied. Selection criteria included normal arterial blood gas tensions and lung function tests and absence of sleep apnoea on overnight polysomnography. Ventilatory responses to isocapnic hypoxia and to hyperoxic hypercapnia were compared between the two groups. RESULTS: The slope of the ventilatory response to hypercapnia was similar in the relatives (mean 2.33 l/min/mm Hg) and in the control subjects (2.12 l/min/mm Hg), mean difference 0.2 l/min/mm Hg, 95% confidence interval (CI) for the difference -0.5 to 0.9 l/min/mm Hg, p=0.5. The hypoxic ventilatory response was also similar between the two groups (slope factor A: 379.1 l/min * mm Hg for relatives and 373.4 l/min * mm Hg for controls; mean difference 5.7 l/min * mm Hg; 95% CI -282 to 293 l/min * mm Hg, p=0.7; slope of the linear regression line of the fall in oxygen saturation and increase in minute ventilation: 2.01 l/min/% desaturation in relatives, 1.15 l/min/% desaturation in controls; mean difference 0. 5 l/min/% desaturation; 95% CI -1.7 to 0.7 l/min/% desaturation, p=0. 8). CONCLUSION: There is no evidence of impaired ventilatory chemoresponsiveness in first degree relatives of patients with OHS compared with age and BMI matched control subjects.

Adult↗
PubMed2000

Role of respiratory function in exercise limitation in chronic heart failure.

OBJECTIVE: To test the hypothesis that respiratory function contributes to limit maximal exercise performance in patients with chronic heart failure by using the technique of dead space loading during exercise. DESIGN: Blinded subjects underwent two maximal incremental exercise tests in random order on an upright bicycle ergometer: one with and one without added dead space. SETTING: : Tertiary-care university teaching hospital. SUBJECTS: Seven patients with stable chronic heart failure (mean +/- SEM left ventricular ejection fraction, 27 +/- 3%). RESULTS: Subjects were able to significantly increase their peak minute ventilation during exercise with added dead space when compared with control exercise (57.4 +/- 5.9 vs 50.0 +/- 5.6 L/min; p < 0.05). Peak oxygen uptake, workload, heart rate, and exercise duration were not significantly different between the added dead space and control tests. Breathing pattern was significantly deeper and slower at matched levels of ventilation during exercise with added dead space. CONCLUSION: Because patients with chronic heart failure had significant ventilatory reserve at the end of exercise and were able to further increase their maximal minute ventilation, we conclude that respiratory function does not contribute to limitation of exercise in patients with chronic heart failure.

Adult↗
PubMed1999

Pyknodysostosis: a report of two siblings with unusual manifestations.

We report pyknodysostosis presenting as extramedullary haematopoiesis in one of two siblings and as obstructive airway disease in the other. Visceral manifestations are rare and have been reported in only two cases in the Indian literature. They have often been mistaken for osteopetrosis, haemolytic anaemia and other osteochondrodystrophies. The cases we report illustrate that, though the physical characteristics may be similar, it is the radiological features that are typical and help establish the diagnosis.

Child↗
PubMed1999

Positional treatment vs continuous positive airway pressure in patients with positional obstructive sleep apnea syndrome.

OBJECTIVES: The aim of this study was to compare the relative efficacy of continuous positive airway pressure (CPAP) and positional treatment in the management of positional obstructive sleep apnea (OSA), using objective outcome measures. DESIGN: A prospective, randomized, single blind crossover comparison of CPAP and positional treatment for 2 weeks each. SETTING: A university teaching hospital. PATIENTS: Thirteen patients with positional OSA, aged (mean+/-SD) 51+/-9 years, with an apnea-hypopnea index (AHI) of 17+/-8. MEASUREMENTS: (1) Daily Epworth Sleepiness Scale scores; (2) overnight polysomnography, an objective assessment of sleep quality and AHI; (3) maintenance of wakefulness testing; (4) psychometric test battery; (5) mood scales; (6) quality-of-life questionnaires; and (7) individual patient's treatment preference. RESULTS: Positional treatment was highly effective in reducing time spent supine (median, 0; range, 0 to 32 min). The AHI was lower (mean difference, 6.1; 95% confidence interval [CI], 2 to 10.2; p = 0.007), and the minimum oxygen saturation was higher (4%; 95% CI, 1% to 8%; p = 0.02) on CPAP as compared with positional treatment. There was no significant difference, however, in sleep architecture, Epworth Sleepiness Scale scores, maintenance of wakefulness testing sleep latency, psychometric test performance, mood scales, or quality-of-life measures. CONCLUSION: Positional treatment and CPAP have similar efficacy in the treatment of patients with positional OSA.

Cross-Over Studies↗
PubMed1998

Continuous positive airway pressure requirement during the first month of treatment in patients with severe obstructive sleep apnea.

OBJECTIVES: (1) To compare the continuous positive airway pressure (CPAP) requirement at the time of diagnosis (T0), after 2 weeks (T2), and after 4 weeks (T4) of CPAP treatment, in patients with severe obstructive sleep apnea (OSA); and (2) to assess whether any alteration in CPAP requirement over the first 4 weeks of CPAP treatment would influence daytime alertness, subjective sleepiness, or mood. DESIGN: A prospective, controlled, single-blind crossover study. SETTING: University teaching hospital. PATIENTS: Ten patients with newly diagnosed and previously untreated severe OSA (aged 52+/-9 years, apnea hypopnea index [AHI] of 99+/-31) and subsequently 10 control patients (aged 52+/-11 years, AHI 85+/-17). MEASUREMENTS: Overnight polysomnography with CPAP titration to determine the CPAP requirement, which was standardized for body position and sleep stage, on all three occasions (T0, T2, T4). Objective sleep quality, daytime alertness, subjective sleepiness (Epworth Sleepiness Scale), and mood (Hospital Anxiety and Depression Scale). RESULTS: CPAP requirement decreased from T0 to T2 (median difference, 1.5 cm H2O, 95% confidence interval [CI], 1.1 to 2.7 cm H2O, p=0.0004) and did not differ between T2 and T4. Use of the lower CPAP pressure during T2 to T4 was associated with a decrease in Epworth scale (mean difference, 2.6, 95% CI, 1.2 to 4; p=0.01) and anxiety (median change, 2; 95% CI, 0.5 to 2.9, p=0.03) scores, as compared with the first 2 weeks. Daytime alertness did not differ between T0 to T2 and T2 to T4. CONCLUSION: CPAP requirement falls within 2 weeks of starting CPAP treatment. A change to the lower required CPAP was not associated with any deterioration in daytime alertness but was associated with small subjective improvements in sleepiness and mood.

Cross-Over Studies↗
PubMed1996

Role of hypoxemia and pulmonary mechanics in exercise limitation in interstitial lung disease.

We have previously shown that respiratory factors (arterial hypoxemia and/or pulmonary mechanics) contribute to limit maximal incremental exercise in interstitial lung disease (ILD). In this study, we tested the hypothesis that arterial hypoxemia, not pulmonary mechanics, primarily limits maximal exercise in subjects with ILD. Seven subjects with ILD underwent two incremental exercise tests in random order. Test 1: breathing room air (RA); Test 2: breathing 60% O2 with added external dead space (O2VD). Added VD was used to prevent the fall in minute ventilation (VI) while breathing O2. All subjects demonstrated impaired exercise performance (maximal oxygen uptake [VO2], 56 +/- 13% predicted) while breathing RA. There was a significant increase in peak VI (RA, 64.9 +/- 22.3 L/min versus O2VD, 71.0 +/- 20.6; p < 0.05), maximal work rate (RA, 99 +/- 12 watts versus O2VD, 109 +/- 15 watts; p < 0.01), exercise duration (RA, 383 +/- 67 s versus O2VD; 426 +/- 72 s; p < 0.0005) and maximal VO2 (RA, 1.25 +/- 0.21 L/min versus O2VD, 1.39 +/- 0.26; p < 0.05) during the O2VD exercise test. There was a significant correlation between the percent increase in exercise duration during the O2VD test and the DLCO (r = -0.813, p < 0.05). At matched levels of ventilation, subjects demonstrated a significantly deeper and slower pattern of breathing during the O2VD test. Because subjects with ILD were able to further improve their exercise and further increase their VI during the O2VD exercise study, we conclude that arterial hypoxemia, and not respiratory mechanics, predominantly limits maximal incremental exercise in subjects with ILD.

Exercise Test↗
PubMed1995

Low-dose nebulized morphine does not improve exercise in interstitial lung disease.

Recent reports have suggested that low-dose nebulized morphine may improve exercise tolerance in patients with interstitial lung disease (ILD) by acting on peripheral opioid-sensitive pulmonary receptors. We therefore examined whether the administration of low-dose nebulized morphine would influence dyspnea or the breathing pattern during exercise of subjects with ILD and improve their exercise performance. Each of six subjects with ILD underwent three maximal incremental cycle ergometer tests, each test separated from the last by at least 3 d. Each exercise test was similar except that 30 min before exercise, the subjects received nebulized saline (control), morphine 2.5 mg, or morphine 5.0 mg, respectively, in double-blinded fashion. No significant differences were noted in exercise duration, maximal workload, or sense of dyspnea at the end of exercise in the control test and the tests with either morphine 2.5 mg or morphine 5.0 mg. Nor were significant differences noted in resting, submaximal, or end-exercise measurements of oxygen uptake (VO2), carbon dioxide output (VCO2), end-tidal CO2 (PETCO2), oxygen saturation (SaO2), minute ventilation (VI), respiratory frequency (f), tidal volume (VT), or heart rate (HR) in the three tests. Low-dose nebulized morphine did not alter the subjects' breathing pattern or affect the relationship between dyspnea and ventilation during exercise. No significant side effects were noted. The administration of low-dose nebulized morphine to subjects with ILD neither relieves their dyspnea during exercise nor improves their maximal exercise performance.

Double-Blind Method↗
PubMed1994

Reactivation disease: the commonest form of tuberculous pleural effusion in Edinburgh, 1980-1991.

From 1980-1991 82 (7.2%) of 1134 tuberculosis notifications in Edinburgh were for pleural effusion. Study of the available records of 62 cases satisfying defined diagnostic criteria identified 14 cases (6 M, 8 F) with a mean age of 27.6 years (range 11-51 years) of primary tuberculous effusion and 25 cases (21 M, 4 F) with a mean age of 51 years (range 19-79 years) with pleural effusion due to reactivation disease. Twenty-three patients (19 M, 4 F) with a mean age of 48.9 years (range 25-85 years) defied classification. Symptoms, associated and diagnostic test findings were similar in all three groups of patients. Parenchymal radiographic shadowing was seen in 1/14 primary, 16/25 reactivation and 3/25 unclassified pleural effusions. Twenty-three of 30 patients treated with corticosteroids showed no residual radiographic abnormality compared to 17/30 not so treated (P < 0.06). Reactivation disease is currently a commoner cause of tuberculous pleural effusion than primary disease in Edinburgh. We suggest that the unclassified cases, so similar in age and sex to the defined reactivation disease cases, also represent largely extrapulmonary reactivation disease occurring in middle age.

Adrenal Cortex Hormones↗
PubMed1994

Lung volumes and expiratory flow limitation during exercise in interstitial lung disease.

Lung volumes were measured at rest and during exercise by an open-circuit N2-washout technique in patients with interstitial lung disease (ILD). Exercise tidal flow-volume (F-V) curves were also compared with maximal F-V curves to investigate whether these patients demonstrated flow limitation. Seven patients underwent 4 min of constant work rate bicycle ergometer exercise at 40, 70, and 90% of their previously determined maximal work rates. End-expiratory lung volume and total lung capacity were measured at rest and near the end of each period of exercise. There was no significant change in end-expiratory lung volume or total lung capacity when resting measurements were compared with measurements at 40, 70, and 90% work rates. During exercise, expiratory flow limitation was evident in four patients who reported stopping exercise because of dyspnea. In the remaining patients who discontinued exercise because of leg fatigue, no flow limitation was evident. In all patients, the mean ratio of maximal minute ventilation to maximal ventilatory capacity (calculated from maximal F-V curves) was 67%. We conclude that lung volumes during exercise do not significantly differ from those at rest in this population and that patients with ILD may demonstrate expiratory flow limitation during exercise. Furthermore, because most patients with ILD are not breathing near their maximal ventilatory capacity at the end of exercise, we suggest that respiratory mechanics are not the primary cause of their exercise limitation.

Airway Obstruction↗
PubMed1994

Oxygen improves maximal exercise performance in interstitial lung disease.

We examined whether arterial hypoxemia impairs incremental exercise performance in subjects with interstitial lung disease (ILD). Seven subjects underwent two incremental exercise tests on a bicycle ergometer in random order; one while breathing room air (RA), and the other while breathing 60% O2. Maximal exercise performance was impaired in all subjects: maximal oxygen uptake (peak VO2) was 56 +/- 4% predicted (+/- SEM); and all subjects demonstrated significant arterial oxygen desaturation during exercise breathing RA (mean 11 +/- 1%). Breathing 60% O2 during exercise resulted in a significant increase in peak VO2 (RA: 1.32 +/- 0.05 L/min; O2: 1.58 +/- 0.08 L/min; p < 0.05), exercise duration (RA: 390 +/- 21 s; O2: 458 +/- 24 s; p < 0.01) and maximal work load (RA: 112 +/- 6 watts; O2: 129 +/- 6 watts; p < 0.005). There was no significant difference in maximal minute ventilation (VI) achieved at the end of both tests. At matched ventilation (90% peak VI from the RA test), respiratory frequency (f) was significantly higher (RA: 33 +/- 2 breaths/min; O2: 35 +/- 2 breaths/min; p < 0.05), and tidal volume (VT) significantly lower (RA: 1.72 +/- 0.15 L; O2: 1.64 +/- 0.12; p < 0.05) when subjects exercised breathing oxygen. We conclude that arterial hypoxemia significantly impairs incremental exercise performance in subjects with ILD, but that mechanisms other than arterial oxygen desaturation are responsible for the rapid, shallow breathing pattern these subjects adopt during exercise.

Adult↗
PubMed1994

Dot blot hybridization assay for the detection of duck hepatitis B virus DNA among healthy Indian country ducks.

A DNA molecular hybridization technique employing Duck Hepatitis B Virus (DHBV) DNA of 3.0 kilobase pairs as a probe was used to screen for the presence of DHBV DNA in blood samples, collected from 90 apparently healthy Indian country ducks. Six out of 90 ducks showed positivity for DHBV DNA in serum (5.4%) and only 4 out of 6 DHBV DNA positive ducks answered in Counter Immuno Electrophoresis (CIEP) using specific antibody against DHBV surface antigen raised in Guinea pig. The results indicate the pilot observation that (a) DHBV carrier status exists to a tune of 5.4% among apparently healthy Indian country ducks also and (b) DHBV probe can be employed as a sensitive and reliable assay for DHBV DNA detection in DHBV infected ducks.

Animals↗
PubMed1993

Duck hepatitis B virus (DHBV) infection in Indian domestic ducks: a pilot study.

One hundred and two apparently healthy Indian domestic ducks from the Poultry Research Station, Madras were screened for duck hepatitis B virus (DHBV) infection by; 1. screening for the duck hepatitis B virus surface antigen (DHBsAg) in their sera using hepatitis B virus (HBV) reagents, 2. screening for DHBsAg using specific duck hepatitis B virus (DHBV) reagents and 3. demonstration of DHBV DNA using DHBV DNA probe by dot blot hybridisation. While 5 ducks (4.9%) were consistently positive with HBV reagents, use of DHBV reagents showed a total of 4 ducks (including 3 of the above 5) to be positive for DHBsAg. DNA hybridisation showed 6 ducks to be positive for DHBV DNA. On clinical examination, 5 out of these 6 ducks did not reveal abnormalities, the other one showed hepatomegaly and ascites. Post-mortem studies showed the presence of nodules on the surface of the liver in all 5 which were positive with HBV reagents including the one with hepatomegaly. On histopathological evaluation, they were found to be hepatocellular carcinoma with or without bile duct carcinoma. The present study is a pilot report on the occurrence of DHBV infection in Indian domestic ducks and the possibility of antigenic cross reactivity between human HBV and duck hepatitis B virus antigens.

Animals↗
PubMed1990

In vitro effect of intravenous immunoglobulin on serum opsonic activity in normal & intrauterine growth retarded neonates.

In vitro effect of intravenous immunoglobulin (IVIG), Intraglobin F, on serum opsonic activity against Staphylococcus aureus was studied in 26 full term normal healthy neonates and 18 intrauterine growth retarded (IUGR) neonates by the polymorphonuclear leucocyte overlay method (requiring only a few drops of blood). Cord IgG and IgM levels were determined by single radial immunodiffusion. Serum opsonic activity against Staph. aureus was significantly lower in the IUGR neonates (49.1 +/- 0.89), as compared to that in normal neonates (61.96 +/- 0.73; P less than 0.001). Immunoglobulin supplementation in vitro at a concentration of 5 g/dl significantly enhanced the opsonic activity of IUGR neonate sera. Cord IgG levels of IUGR neonates were significantly lower (P less than 0.01) than IgG levels of normal neonates. No significant difference was observed in cord IgM levels between the normal and IUGR neonates.

Blood Bactericidal Activity↗