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Biomedical subjects

N Chand

Publications and source records attributed to N Chand.

At least 19 recordsLinked to original sources
PubMed2004

Sleep dysfunction in patients with gastro-oesophageal reflux disease: prevalence and response to GERD therapy, a pilot study.

BACKGROUND: There is little information on the prevalence of pathological sleep disorders in patients with gastro-oesophageal reflux disease and whether pharmacological treatment of patients with gastro-oesophageal reflux disease will lead to improvement in sleep. AIMS: This pilot study determined the prevalence of sleep disorder in patients with erosive gastro-oesophageal reflux disease, correlated subjective (questionnaire) and objective (actigraphy - a watch worn on the wrist that monitors motion to help differentiate sleep from awake states) assessment of sleep dysfunction and determined whether therapeutic resolution of oesophageal symptoms was associated with an improvement in sleep. METHODS: Eighteen patients with erosive gastro-oesophageal reflux disease received esomeprazole 40 mg once daily for 8 weeks. Assessments at 0, 4 and 8 weeks included: Gastrointestinal Symptoms Rating Scale, Pittsburgh Sleep Quality Index questionnaire and ambulatory wrist actigraphy. RESULTS: Unrecognized sleep disturbance occurred in 81% of this cohort of patients with gastro-oesophageal reflux disease and erosive oesophagitis. Median reflux syndrome score (heartburn and acid regurgitation) on Gastrointestinal Symptoms Rating Scale decreased from 2 at baseline to 0 at weeks 4 and 8 (P </= 0.0001). Median global Pittsburgh Sleep Quality Index score decreased from 8.50 at baseline to 4.50 at week 4 (P = 0.002) and to 7.00 at week 8 (P = 0.043). There were no significant changes in actigraphy measurements. CONCLUSIONS: Sleep disturbance is common in patients with gastro-oesophageal reflux disease with erosive oesophagitis. This study which is the first to evaluate sleep abnormalities and gastro-oesophageal reflux disease using a validated questionnaire, demonstrates that in patients with gastro-oesophageal reflux disease, sleep improvement, may be effected by gastro-oesophageal reflux disease therapy. Actigraphy may be inappropriate for measurement of sleep disturbance in gastro-oesophageal reflux disease patients.

Anti-Ulcer Agents↗
PubMed1999

Optimization and interaction of media components in ethanol production using Zymomonas mobilis by response surface methodology.

Ethanol production using Zymomonas mobilis strains with medium optimized by response surface methodology (RSM) was studied. A significant improvement in the ethanol yield (0.50 g/g ethanol) was demonstrated, resulting in very low residual sugar and fewer by-products. The five-factor and five-response full factorial design have shown that glucose and yeast extract are the key media components that influence ethanol production, followed by the inoculum concentration and ammonium sulfate, with phosphate showing little or no effect. The composition (all in g/l) of the optimized medium was glucose 120.4, ammonium sulfate 0.96, potassium dihydrogen phosphate 0.02, yeast extract 6.5, and magnesium sulfate 0.5. The optimum inoculum concentration was log10 8.4 cells.

Journal Article↗
PubMed1995

Azelastine--a novel in vivo inhibitor of leukotriene biosynthesis: a possible mechanism of action: a mini review.

Leukotrienes have been proposed as important chemical mediators of allergic inflammation, and there is evidence that azelastine (Astelin) can affect leukotriene-mediated allergic responses. One of the enzymes required for the synthesis of leukotrienes from arachidonic acid is 5-lipoxygenase (5-LO). Azelastine, which is preferentially taken up by the lung and alveolar macrophages, inhibits leukotriene generation in the airways. This property of azelastine may contribute to its therapeutic efficacy in the long-term treatment and management of rhinitis and asthma. Azelastine does not directly inhibit 5-LO in disrupted murine peritoneal cells and rat basophilic leukemia cells (IC50 > 100 microM), but does have moderate 5-LO inhibitory activity in intact murine peritoneal cells (IC50 = 10 microM, 5 min) and in chopped guinea pig liver (IC50 = 14 microM, 2 hr). The generation and release of leukotrienes in human neutrophils and eosinophils is also inhibited by azelastine (IC50 = 0.9-1.1 microM). Furthermore, azelastine is a potent and specific inhibitor of allergen-induced generation of leukotrienes in the nose of the guinea pig (ID50 < 100 micrograms/kg, im, 20 min) as well as in patients with rhinitis (2 mg, po, 4 hr; ID50 < 30 micrograms/kg). Azelastine also inhibits allergen-induced, leukotriene-mediated, pyrilamine-resistant bronchoconstriction (oral ID50 = 60 micrograms/kg, 2 hr and 120 micrograms/kg, 24 hr). This profile suggests that azelastine may be a novel inhibitor of Ca(2+)-dependent translocation of 5-lipoxygenase from cytosol to the nuclear envelope or a FLAP inhibitor rather than a direct 5-LO inhibitor.

Animals↗
PubMed1995

Synergistic protective effects with azelastine and salbutamol in a guinea pig asthma model.

Azelastine prevents down-regulation of beta 2-receptors and adenylate cyclase and upregulation of alpha 1-adrenoceptors induced by repeated allergen challenge in the guinea pig lung. In the present study the protective effects of azelastine and salbutamol and a combination of both drugs was investigated using aeroallergen-induced acute allergic bronchoconstrictor responses in conscious, actively sensitized guinea pig. The drugs were given orally 1 h prior to challenge. The oral PD50 was 230 micrograms/kg for azelastine and 1200 micrograms/kg for salbutamol. Both drugs showed a synergistic protective effect with a PD50 of 60 micrograms/kg of azelastine plus 120 micrograms/kg of salbutamol indicating a reduction in the PD50 of azelastine by a factor of 4 and of salbutamol by a factor of 10. These findings may explain the reduction in the use of salbutamol and theophylline with azelastine by chronic asthmatics.

Administration, Oral↗
PubMed1994

Effect of PAF-antagonists on aeroallergen-induced bronchial eosinophilia in guinea pigs: a therapeutic approach.

Aeroallergen-induced eosinophilia in actively sensitized guinea pigs was used as a marker of bronchial inflammation in this study. Drugs were administered p.o. therapeutically, i.e., four hours after aeroallergen challenge. Allergic bronchial eosinophilia in guinea pigs was sensitive to dexamethasone. Thus, the therapeutic approach appears to be a reliable, predictable, and sensitive for the evaluation and selection of potential bronchial anti-inflammatory compounds. PAF-antagonists (WEB-2086, WEB-2170, and E-6123) and a 5-lipoxygenase inhibitor (E-6080) did not influence allergen-induced eosinophil infiltration in the bronchoalveolar lavage fluid. These observations seem to suggest that therapeutic administration of PAF antagonists and leukotriene synthesis inhibitors exert little or no inhibitory effect on the progression of late-phase allergic bronchial inflammation in this model.

Administration, Oral↗
PubMed1994

Azelastine inhibits acute allergic dyspnea in a conscious guinea pig asthma model.

A simple, noninvasive, bias-flow ventilated wholebody plethysmographic technique and noninvasive pulmonary analyzer (Buxco dyspnea monitor) were used to quantitate allergic dyspnea in chronically sensitized freely moving guinea pigs. In this study, the effect of azelastine on aeroallergen-induced dyspnea in allergic guinea pigs was investigated. Aeroallergen challenge produced severe dyspnea which was characterized by a 390% increase in the amplitude of pseudo flow signal, a 93% increase in box pressure (delta P) and a 68% decline in relaxation time; these changes signify a tremendous increase in the effort of breathing. The oral administration of azelastine (1 mg/kg) two hours before aeroallergen provocation significantly inhibited allergic dyspnea in this acute allergic asthma model. This technique permits quantitative measurement of the severity of the airway allergic responses in freely moving guinea pigs.

Aerosols↗
PubMed1993

Mucolytic activity of azelastine in mice and rats.

The mucolytic activity of azelastine, an antiallergic/antiasthmatic drug, in mice and rats was investigated. The oral administration of test compounds 30 min before phenol red i.p. injection stimulated dye secretion in the trachea of mice. The resulting oral ED50's (mg/kg) were: azelastine, 0.16; salbutamol, 2.5; N-acetylcysteine, 61.8; S-Carboxymethyl-l-cysteine, < 100; bromhexine, > 100; and potassium iodide, approximately 200. In rats, several drugs stimulated secretion of fluorescein sodium (FINa) in the tracheobronchial lumen. The resulting oral ED50's (mg/kg) were: azelastine, 0.33; terbutaline, 0.3; salbutamol, 0.89; and S-carboxymethyl-l-cysteine, 56.8. Terfenadine and diphenhydramine (1-10 mg/kg, p.o.) did not stimulate tracheal secretion in rats and mice. The mucolytic activity of azelastine may contribute to its overall effectiveness, including antitussive activity in asthmatics. Finally, this activity seems to be dissociated from its H1-histamine receptor blocking activity.

Acetylcysteine↗
PubMed1993

Computer-aided modeling and optimization for capsaicinoid production by immobilized Capsicum frutescens cells.

Production of capsaicinoids by immobilized cell cultures of Capsicum entrapped in calcium alginate matrix is influenced by several factors related to immobilization techniques, including media composition and the biosynthetic capability of cells. Central composite rotatable design (CCRD), one of the response surface methodologies, was used to arrive at optimal conditions for maximizing the yields of capsaicinoids in only 53 experiments, instead of 15,625. Immobilization of cells in 2.5% sodium alginate with 15 min contact time in 60 mM calcium chloride and culture in Murashige and Skoog medium supplemented with 3 mg l-1 2,4-dichlorophenoxyacetic acid and 0.2% curdlan gave the highest yield of 220 micrograms g-1 in 3 days.

Alginates↗
PubMed1993

Aeroallergen-induced dyspnea in freely moving guinea pigs: quantitative measurement by bias flow ventilated whole body plethysmography.

Guinea pigs were sensitized and boostered with i.p. injections of ovalbumin (OA) 10 micrograms + Al(OH)3 100 mg. Thirteen days after the last injection animals (800-1100 g) were placed in bias flow ventilated whole body plethysmographs and allowed to stabilize for 2 h. Lung function was recorded for up to 2 h before and 5 h after aeroallergen challenge (OA 20 mg/ml, 60 s, 20 psi) by a noninvasive pulmonary analyzer for unrestrained rodents. Aeroallergen challenge produced immediate dyspnea and gasping (peaking between 8 and 17 min). Gasping was associated with an increase in amplitude in the box pressure fluctuations (93%), and in the slope of the fluctuations (391%). Respiratory rate increased (103 to 175 breaths/min, 78%), the product of breathing rate times box pressure amplitude increased (161 to 432, 180%). Relaxation time (the time it takes the box pressure signal to drop from its peak to 1/3 of its peak value) declined (0.16 to 0.05 s, 72%). All of these lung dysfunction changes were highly significant (p < 0.001). Lung dysfunction persisted for 60 to 120 min after challenge. One of 8 animals tested died within 10 min. None of the animals exhibited late asthmatic responses during the 5 h post-challenge period. Based on these data we conclude that this technique allows quantitative analysis of dyspnea, gasping, and an abnormal pattern (waveform) of breathing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Allergic bronchial eosinophilia: a therapeutic approach for the selection of potential bronchial anti-inflammatory drugs.

Aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) in guinea pigs was used as a marker of bronchial inflammation. Drugs were administered orally 4 h after aeroallergen challenge. Allergic bronchial eosinophilia in guinea pigs was inhibited by orally administered dexamethasone and methylprednisolone. Terfenadine (a newer H1-receptor antagonist), theophylline (a nonspecific phosphodiesterase inhibitor), and salbutamol (a beta 2-agonist) did not influence allergic eosinophilic infiltration. Many of these agents, administered prophylactically, have been reported to suppress allergic eosinophilic infiltration in the BALF of guinea pigs. Methylprednisolone, a steroid, inhibits allergic bronchial eosinophilia regardless of the time of administration; that is, 2 h before or 4 h after aeroallergen challenge. The therapeutic approach used in this study may facilitate drug discovery for bronchial inflammation/asthma.

Albuterol↗
PubMed1993

Pharmacodynamic and pharmacokinetic studies with azelastine in the guinea pig: evidence for preferential distribution into the lung.

The correlation between the antiasthma activity of azelastine and the concentrations of azelastine and its major metabolite, desmethylazelastine, in the blood and lung were investigated in guinea pigs. Blood and lung tissue samples collected at 15 min after aeroallergen (ovalbumin, 0.5 mg/ml, 30 s, 15 psi) challenge, i.e., 2-1/4 h after oral administration of the drug, were analyzed for azelastine and its desmethyl metabolite by specific HPLC assay. Azelastine afforded protection against immediate allergic responses (IAR, characterized by gasping and bronchospasmic convulsions). Based on the reduction of the severity of IAR, the ID50 was 0.04 mg/kg. It also delayed the onset of IAR and prevented mortalities. A positive correlation (r2 = 0.944) between the antiallergic activity and the sum concentrations of azelastine and desmethylazelastine in the lung was observed. Preferential uptake of azelastine and desmethylazelastine by the lung was demonstrated by the mean lung/blood ratio of about 22 and 146, respectively. The selective uptake of azelastine and its active metabolite by the lungs could contribute to its antiasthmatic/antiallergic activity in guinea pigs.

Animals↗
PubMed1992

Anti-IL-5 monoclonal antibody inhibits allergic late phase bronchial eosinophilia in guinea pigs: a therapeutic approach.

In this study the effect of purified rat anti-mouse IL-5 monoclonal antibody on aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid of guinea pigs was studied. The i.p. injection of anti-IL-5 antibody 4 h after aeroallergen challenge inhibited eosinophil infiltration in a dose-dependent fashion. The resulting ED50 was 10 (3.4-32.8) micrograms/kg. The clinical therapeutic usefulness of anti-IL-5 or anti-IL-5-producing cells in asthma/allergy treatment remains to be an intriguing possibility.

Animals↗
PubMed1992

Repeated aeroallergen challenge induces lung dysfunction but not bronchial hyperresponsiveness in conscious guinea pigs.

Adult male Hartley-strain guinea pigs were sensitized by 10 min exposure to aerosolized 1% ovalbumin (OA; 10 mg/ml in normal saline containing 4% heat-killed B. pertussis vaccine and 0.02% antifoam B emulsion). One week after sensitization, animals were placed in an exposure chamber and challenged (nebulized OA 0.5%) until each animal showed labored breathing. Maximal exposure time was 10 min. Diphenhydramine (20 mg/kg, i.p.) was given 1 h before each OA challenge to protect the animals from bronchospasmic death. Antigen challenge was repeated twice a week for 2 weeks. The specific airway resistance (sR(aw)) changes in response to increasing concentrations of aerosolized acetylcholine (Ach) were determined. The data obtained in this study demonstrated that repeated antigen challenge produced a significant bronchial tone i.e. an increase in sR(aw) and a decline in specific airway conductance (sG(aw)) and failed to induce bronchial hyperreactivity to aerosolized acetylcholine (Ach) in conscious guinea pigs.

Acetylcholine↗
PubMed1992

Characterization of aeroallergen-induced dyspnea in unrestrained guinea pigs by bias-flow-ventilated whole body plethysmography.

Aeroallergen-induced dyspnea in guinea pigs was associated with an increase in amplitude in the box pressure fluctuations (212%) and pseudo-flow signal (604%) and an 80% decline (from 0.19 to 0.04 s) in relaxation time (the time it takes the box pressure signal to drop from its peak to 1/3 of its peak value). All of these lung dysfunction changes were highly significant (P < 0.001). Pyrilamine (1 mg/kg, p.o., -2 h) inhibited dyspnea (delta P and delta F) by 50-53%. This technique allows quantitative analysis of allergic dyspnea in conscious, unrestrained guinea pigs.

Aerosols↗
PubMed1992

Inhibition of aeroallergen-induced bronchial eosinophilia by azelastine in guinea pigs.

The ability of azelastine to influence allergic bronchial eosinophil infiltration in guinea pigs was studied. Aeroallergen challenge of actively sensitized guinea pigs produces eosinophil infiltration in bronchoalveolar lavage fluid collected 20-24 h after aeroallergen exposure. Azelastine and methylprednisolone, administered orally 2 h before challenge, inhibited eosinophilic infiltration yielding the ED50s of 1.55 and 4.48 mg/kg, respectively. WEB-2086, a platelet-activating factor antagonist (3 mg/kg), and theophylline, a phosphodiesterase inhibitor (30 mg/kg), also suppressed allergic bronchial infiltration of eosinophils by 44%. The data obtained in this study demonstrate that azelastine exerts direct bronchial anti-inflammatory activity in guinea pigs.

Administration, Oral↗