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Biomedical subjects

A Raychaudhuri

Publications and source records attributed to A Raychaudhuri.

At least 19 recordsLinked to original sources
PubMed2005

A population based survey of the prevalence and types of glaucoma in rural West Bengal: the West Bengal Glaucoma Study.

AIM: To determine (i) the prevalence of glaucoma in people aged > or =50 years, (ii) the proportions of different types of glaucoma, (iii) the distributions of intraocular pressure and vertical cup disc ratio. METHOD: Population based prevalence survey in rural West Bengal. People aged > or =50 years in randomly selected villages in 24 Parganas South district. The main outcome measures were diagnosis of glaucoma, based on criteria described by the International Society for Geographic and Epidemiological Ophthalmology. RESULTS: 1594 people aged > or =50 years were enumerated in nine villages; 1324 (83.1%) were surveyed and 1269 people adequately examined. 42 definite cases of glaucoma were identified, with prevalence increasing from 2.7% (95% CI 1.7 to 3.7) in people aged 50-59 years to 6.5% (95% CI 0.0 to 14.1) in those aged > or =80 years. The age standardised estimate for the prevalence of all glaucoma in people aged > or =50 years was 3.4%. Only three cases of primary angle closure glaucoma (PACG) were identified, giving a crude ratio of primary open angle glaucoma (POAG) to PACG of more than 10:1. Three people with glaucoma were blind in one eye but none was blind in both eyes. CONCLUSION: Compared to other surveys of glaucoma in India, the age standardised prevalence observed was less than in Hyderabad, but similar to Tamil Nadu and Dhaka. The ratio of POAG to PACG was much higher than found previously, suggesting that PACG may be less prevalent in Bengalis than in Indian populations living in south India. The authors conclude that ophthalmic services in West Bengal should focus on detecting POAG. Since there is still no satisfactory method of screening for POAG, there is no alternative to case detection (opportunistic screening) in eye clinics.

Age Distribution↗
PubMed2004

Angiogenesis inhibition by the novel VEGF receptor tyrosine kinase inhibitor, PTK787/ZK222584, causes significant anti-arthritic effects in models of rheumatoid arthritis.

OBJECTIVE AND DESIGN: To examine the effects of PTK787/ZK222584, a novel angiogenesis inhibitor, in a series of in vivo models of arthritis and inflammation. MATERIALS: The granulomatous air pouch and antigen-induced arthritis models were established in female OFA-1 mice. Female DBA/1LacJ mice were used for the collagen-induced arthritis model and male OFA rats were used for the carrageenan oedema and hyperalgesia tests. TREATMENT: PTK787/ZK222584 was administered p.o., once daily, at various concentrations. Diclofenac (3 mg/kg) and DUP697 (0.5 mg/kg) were also given p.o, once daily. METHODS: The anti-angiogenic effects of PTK787/ZK222584 were directly assessed in the granulomatous air pouch model using the carmine red assay. The anti-arthritic effects of this compound were further examined in the mouse antigen-induced and collagen-induced models of arthritis, using macroscopic observations (calliper measurements of joints) and histological scores (as assessed by degree of cellularity, cell infiltration and erosions and proteoglycan loss). All compounds were administered orally. PTK787/ZK222584 at 10, 30, 50 and 100 mg/kg and positive control compounds, diclofenac and DUP697 at 3 mg/kg and 0.5 mg/kg, respectively. In addition, the effects of PTK787/ZK222584 in the rat carrageenan oedema model and Randall Selitto hyperalgesia test were observed. RESULTS: PTK787/ZK222584 treatment caused dose dependent reduction in the vascularity of the granulomatous air pouch model. It inhibited knee swelling by 40% in antigen-induced arthritis, at the dose of 30 mg/kg p.o., once daily (s.i.d). and inhibited both severity scores (by 51%) and global histological scores in mice with collagen-induced arthritis following oral treatment (45 mg/kg p.o.), as compared to control animals. PTK787/ZK222584 demonstrated no effects on inflammatory mediators in the VEGF-independent rat carrageenan model and displayed interesting analgesic activity in the Randall Selitto test in the acute setting. CONCLUSIONS: The anti-arthritic effects of this specific, receptor tyrosine kinase inhibitor compound appear to be mediated by anti-angiogenic actions. This study represents a new indication for PTK787/ZK222584, namely, rheumatoid arthritis and further supports the belief that angiogenesis inhibition is likely to be beneficial in the therapy of this condition.

Angiogenesis Inhibitors↗
PubMed1999

Carboxy-substituted cinnamides: a novel series of potent, orally active LTB4 receptor antagonists.

A series of carboxy-substituted cinnamides were investigated as antagonists of the human cell surface leukotriene B4 (LTB4) receptor. Binding was determined through measurement of [3H]LTB4 displacement from human neutrophils. Receptor antagonism was confirmed through a functional assay, which measures inhibition of Ca2+ release in human neutrophils. Potent antagonists were discovered through optimization of a random screening hit, a p-(alpha-methylbenzyloxy)cinnamide, having low-micromolar activity. Substantial improvement of in vitro potency was realized by the attachment of a carboxylic acid moiety to the cinnamide phenyl ring through a flexible tether, leading to identification of compounds with low-nanomolar potency. Modification of the benzyloxy substituent, either through ortho-substitution on the benzyloxy phenyl group or through replacement of the ether oxygen with a methylene or sulfur atom, produced achiral antagonists of equal or greater potency. The most potent compounds in vitro were assayed for oral activity using the arachidonic acid-induced mouse ear edema model of inflammation. Several compounds in this series were found to significantly inhibit edema formation and myeloperoxidase activity in this model up to 17 h after oral administration. Representatives of this series have been shown to be potent and long-acting orally active inhibitors of the LTB4 receptor.

Administration, Oral↗
PubMed1998

A loglogistic model for altitude decompression sickness.

BACKGROUND: Altitude decompression sickness (DCS) is a potential hazard encountered during high altitude flights or during extravehicular activity in space. In this study, the loglogistic distribution was used to model DCS risk and symptom onset time. METHODS: The Air Force Research Laboratory, Brooks AFB, TX, has conducted studies on human subjects exposed to simulated altitudes in hypobaric chambers. The dataset from those studies was used to develop the DCS models and consisted of 975 subject-exposures to various altitudes, preoxygenation times, and exercise regimens. Since the risk of DCS is known to increase over time at altitude, and then decrease because of denitrogenation, the loglogistic model was fit to the data. The model assumes that the probability of DCS depends on several risk factors. Maximum likelihood estimates of the parameters were obtained using the statistical software package SAS. Cross validation techniques were provided to examine the goodness of fit of the model. RESULTS: The fitted model indicated that altitude, ratio of preoxygenation to exposure time, and exercise were the most significant risk factors. The model was used to predict the risk of DCS for a variety of exposure profiles. The predicted probability of DCS agreed very closely with the actual percentages in the database. CONCLUSION: The loglogistic distribution was found to be appropriate for modeling the risk of DCS. Based on the cross validation and validation results, we conclude that this model provides good estimates of the probability of DCS over time.

Adolescent↗
PubMed1997

Analysis of lognormal survival data.

The failure rate and the mean residual life function (MRLF) of a lognormal distribution are known to be nonmonotonic. It is of interest to study the point at which the monotonicity changes (the change point). In this article we study the change points of the failure rate and the MRLF for the lognormal distribution. It is shown that the change points are the solutions of certain nonlinear equations. We apply these results to estimate the change points for survival data on guinea pigs given by Bjerkedal. The standard deviation of the estimate is obtained using bootstrap and jackknife methods. Finally confidence bands for the failure rate and the MRLF are also provided to illustrate the behavior of the estimates.

Animals↗
PubMed1997

Inhibition of LTB4 biosynthesis in situ by CGS 23885, a potent 5-lipoxygenase inhibitor, correlates with its pleural fluid concentrations in an experimentally induced rat pleurisy model.

An intrapleural injection of carrageenan in rats induced LTB4 and LTC4/D4/E4 biosynthesis, exudate formation, and cellular influx in the pleural cavity. An injection of calcium ionophore (A23187, 100 nmol) 16-18 h after carrageenan injection augmented leukotriene biosynthesis and exudate formation, but not cellular influx. The carrageenan-induced pleurisy model modifid by A23187 administration was used to study the oral effect of CGS 23885 (N-hydroxy-N-[(6-phenoxy-2H-1-benzopyran-3-yl)-methyl]urea), a potent 5-lipoxygenase (5-LO) inhibitor, on inflammatory parameters. CGS 23885 dose-dependently (1 to 30 mg/kg) inhibited the enhanced LTB4 and LTC4/D4/E4 (1 to 10 mg/kg) biosynthesis, but had no effect on enhanced exudate formation. An inhibitory effect of CGS 23885 of small magnitude on cellular influx due to carrageenan stimulation was seen at 30 mg/kg. The concentrations of CGS 23885 in the pleural fluid were dose-related, and a positive correlation (r2=0.989) between pleural fluid concentration of LTB4 and CGS 23885 was observed. The results confirm that CGS 23885 is a specific, orally active 5-LO inhibitor which can achieve concentrations in the pleural cavity sufficient to inhibit production of LTB4 and LTC4/D4/E4 in an ongoing inflammatory response.

Animals↗
PubMed1993

New adenosine kinase inhibitors with oral antiinflammatory activity: synthesis and biological evaluation.

Several 5-iodotubercidin analogues in the pyrazolo[3,4-d]pyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials. The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor. First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity. The order of potency was: iodotubercidin > hydroxyl > amino > or = deoxy > fluoro > chloro >> azido. The Ki values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively. The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out. Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds. The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective. Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally. Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts. Results indicated that the two most potent inhibitors in the pyrazolo[3,4-d]pyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.

Adenosine Kinase↗
PubMed1993

Effect of 5-lipoxygenase inhibitors on in situ LTB4 biosynthesis following calcium ionophore stimulation in the rat pleural cavity.

The intrapleural injection of carrageenan in the rat induces exudate formation, cellular influx and leukotriene generation in the pleural cavity. We have demonstrated that the inflammatory response (exudate volume, and LTB4 levels) is increased in situ by the intrapleural administration of calcium ionophore A 23187 (100 nmol/rat) at 4, 16, 24, 48, and 72 h after the injection of carrageenan and that the A 23187-induced increase is dose-dependent. The oral administration of A-64077 and MK-886, two 5-lipoxygenase inhibitors (5-LOIs), at 10 mg/kg causes marked decreases in LTB4 release at the above-mentioned time intervals. However, A 23187-induced augmented exudate formation is not affected by the treatment with 5-LOIs. The results suggest that the use of 5-LOIs to inhibit LTB4 biosynthesis may be beneficial in various LTB4-dependent pathological conditions.

Animals↗
PubMed1993

Effect of anti-inflammatory compounds on edema formation and myeloperoxidase activity in the arachidonic acid-induced ear model in the mouse.

The arachidonic acid (AA)-induced ear edema model in the mouse has been demonstrated as an effective in vivo experimental tool to screen compounds showing anti-inflammatory activity. Since neutrophil influx is a component of the inflammatory reaction, we have modified this assay by quantitating myeloperoxidase (MPO) levels which reflect neutrophil accumulation in the edematous biopsies of the mouse ear. Our work has shown that orally administered 5-lipoxygenase inhibitors, dual inhibitors (CO/LO), and steroids dose-dependently inhibit both edema formation and MPO activity, whereas oral activity is not seen with NSAID's. There is a good correlation between the inhibition of edema formation and of MPO activity by these compounds. Thus, measurement of MPO, in addition to the AA-induced edema in the mouse ear, can provide another parameter to profile potential anti-inflammatory compounds.

Administration, Oral↗
PubMed1993

LTB4-induced transient neutropenia in the rat: a model for evaluating efficacy and bioavailability of LTB4 receptor antagonists.

An animal model of leukotriene B4- (LTB4) induced neutropenia has been developed to evaluate LTB4 receptor antagonists in vivo. LTB4, a potent chemotactic inflammatory mediator, when administered intravenously, induces a profound, rapid, and transient redistribution of blood neutrophils from the circulating pool to the marginated pool. This phenomenon is applied in the neutropenia model whereby circulating blood neutrophil counts prior to and after intravenous infusion of LTB4 are compared. Kinetics of LTB4-induced neutrophil responses are determined through the use of a Technicon H*1 automated blood cell analyzer. LTB4 receptor antagonists are identified by inhibition of LTB4-induced neutropenia. Standard antiinflammatory compounds including BW-755C, Abbott A-64077 (zileuton), dexamethasone-21-acetate, indomethacin, and naproxen did not affect LTB4-induced neutropenia. A potent LTB4 receptor antagonist, designated "RPR," inhibited LTB4-induced neutropenia following oral administration in a dose-dependent fashion.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗