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Biomedical subjects

S Mukhopadhyay

Publications and source records attributed to S Mukhopadhyay.

At least 19 recordsLinked to original sources

Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex.

Protein kinase C (PKC) is an important constituent of the signaling pathways involved in apoptosis. We report here that like staurosporine, withaferin A is a potent inhibitor of PKC. In Leishmania donovani, the inhibition of PKC by withaferin A causes depolarization of DeltaPsim and generates ROS inside cells. Loss of DeltaPsim leads to the release of cytochrome c into the cytosol and subsequently activates caspase-like proteases and oligonucleosomal DNA cleavage. Moreover, in treated cells, oxidative DNA lesions facilitate the stabilization of topoisomerase I-mediated cleavable complexes, which also contribute to DNA fragmentation. However, withaferin A and staurosporine cannot induce cleavable complex formation in vitro with recombinant topoisomerase I nor with nuclear extracts from control cells. Taken together, our results indicate that inhibition of PKC by withaferin A is a central event for the induction of apoptosis and that the stabilization of topoisomerase I-DNA complex is necessary to amplify apoptotic process.

Animals↗

Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol.

BACKGROUND: The homozygous presence of the arginine-16 variant of the beta(2) adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting beta(2) agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting beta(2) agonists. METHODS: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. RESULTS: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. CONCLUSIONS: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.

Adolescent↗

Prediction of obstructive sleep apnea in patients presenting to a tertiary care center.

The objective of this prospective observational clinical study is to derive and validate a diagnostic model for prediction of obstructive sleep apnea (OSA) in subjects presenting with non-sleep-related complaints in a tertiary care center in north India. We included 102 subjects (group I, range 31-70 years) presenting to the hospital with non-sleep-related complaints. None of the subjects had any significant comorbid illness such as respiratory or congestive cardiac failure. All subjects underwent detailed evaluation including polysomnography (PSG). Various parameters were compared between the cases (apnea-hypopnea index, AHI > or =15/h) and controls (AHI <15/h). Using multivariate logistic regression analysis, a diagnostic model for prediction of OSA was derived. Subsequently, using similar selection criteria, 104 subjects (group II, range 32-68 years) were included for validation of the newly derived diagnostic model. Body mass index [BMI; OR (95% CI), 1.14(1.1-1.2)], male gender 5.0(1.4-27.1), relative-reported snoring index (SI) 2.8(1.7-5.0), and choking index (ChI) 8.1(1.4-46.5) were significant, independent predictors of OSA. Diagnostic model was computed as score = [1.61 x (gender)] + [1.01 x (S1)] + [2.09 x (ChI)] + [0.1 x (BMI)] where, gender: 0 = female, 1 = male and SI, ChI, BMI are actual values. The diagnostic model had an area under the receiver operator characteristics curve of 89.6%. A cutoff of 4.3 for the score was associated with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 91.3, 68.5, 70.5, and 92.3%, respectively. Misclassification rate with the application of the diagnostic model on group II subjects was 13.5% (14/104). Sensitivity, specificity, PPV, and NPV of the model for predicting OSA in this group were 82, 90.7, 89.1, and 84.5%, respectively. BMI, male gender, SI, and ChI are independent predictors of OSA. Diagnostic model derived from these parameters is useful for predicting presence of OSA and screening subjects for PSG.

Adult↗

Effect of reduction in tube current on reader confidence in paediatric computed tomography.

BACKGROUND: Computed tomography (CT) contributes significantly to the total radiation dose derived from medical imaging in children. As the number of CT examinations increases there is renewed interest in possible ways to minimize such radiation. AIM: To study the effect of decremental reduction in tube current settings on structural resolution and on reader confidence in being able to reach a final diagnosis. MATERIALS AND METHODS: The study involved spiral CT of children aged 0-13 years. CT performed at reduced mA settings (60-75, 76-90 and 91-130 mA for thoracic, abdominal and pelvic examinations, and 76-90 and 91-130 mA for cranial examinations) were compared with similar investigations at conventional settings (180-240 mA). Images were scored by two blinded readers for structural resolution and diagnostic confidence. Structural resolution was scored on a binary (adequate or not) scale for six structures each in cranial, thoracic and pelvic examinations and for eight structures in abdominal studies, and reader confidence was scored on a four-point scale as 25-100%. Scores from the two readers were averaged for comparison in subgroup analyses. RESULTS: Reduction of tube current settings to 75-90 mA for thoracic, abdominal and pelvic examinations and to 90-130 mA for cranial examinations was not associated with any significant deterioration in image quality. The number of scans considered satisfactory were comparable even at 60-75 mA, although the total relative scores for structural resolution at this setting were lower. CONCLUSION: Tube current settings can be significantly reduced in all paediatric age groups, in all regions. In younger children the impact of such reduction in tube current is likely to be greater. Cranial scans are more sensitive to such reductions as compared to thoracic or abdominopelvic examinations.

Adolescent↗

Deaf child--a general practitioner's responsibility.

The power of a child's speaking language never develops if he is deaf. Deafness persists if it is not detected early. Childhood deafness is either congenital or acquired. At birth, doctors or attendants can detect deafness by arousing the baby with sudden loud noise. At 4 months onwards mothers and doctors can detect deafness. The baby at this age can turn its head or eyes towards the source of the sound. By 12 months to 2 years of age it is very difficult to detect deafness. By the age of 3 years children again become co-operative and it becomes easier to detect deafness. Children should always be screened for deafness while being admitted to nursery classes. In school going age ie, 5 years onwards loss of tests can be employed to detect deafness. If a child is suspected be deaf, a general practitioner's responsibility is to refer him to an ENT specialist earlier. Any child whose mother believes her child is deaf should be given due attention. Otitis media with effusion, enlarged adenoid, chronic suppurative otitis media, recurrent otitis media are some diseases to be carefully looked into by the general practitioners. Now-a-days cochlear implantation surgery is gaining popularity to give hearing to deaf child. Moreover regular screening for deafness should be included school heath programme.

Child, Preschool↗

A stepped approach for prediction of obstructive sleep apnea in overtly asymptomatic obese subjects: a hospital based study.

BACKGROUND AND PURPOSE: Prevalence of obstructive sleep apnea (OSA) is high in obese subjects, many of whom may not be overtly symptomatic. Polysomnography (PSG) is a costly and time-consuming investigation. Since it is not feasible to subject all obese individuals to PSG, it is useful to define predictors of OSA among these subjects. PATIENTS AND METHODS: One hundred and eighteen obese subjects [body mass index (BMI)> or =25 kg/m(2)] presenting to the hospital with non-sleep related complaints were included, of which 53 subjects with PSG evidence of OSA [apnea-hypopnea index (AHI)> or =15/h] were defined as cases and 65 subjects without any evidence of OSA (AHI<15/h) were defined as controls. Anthropometry, biochemical investigations, blood gas analysis, pulmonary function tests, and PSG were performed for all subjects. RESULTS: Waist hip ratio (WHR) (as percentage of a standard) [odds ratio (95% CI): 1.07 (1.00-1.14); P = 0.049] male gender [odds ratio (95% CI): 3.97 (0.99-15.81); P = 0.046] and neck circumference (NC) [odds ratio (95% CI): 1.23 (1.03-1.47); P = 0.023] were found to be independent predictors of OSA. Overnight oxygen desaturation data were evaluated in patients selected as having OSA on the basis of these clinical markers, and the best cut-off for level of desaturation (10%) was defined. The stepped approach had a specificity, sensitivity, positive and negative predictive value of 89.2, 88.5, 86.8 and 90.6%, respectively, for the diagnosis of OSA. CONCLUSIONS: Male gender, WHR and NC are independent predictors of OSA in overtly asymptomatic obese subjects. A stepped approach to diagnose OSA should be used, as it is accurate and cost-effective.

Adult↗

Damodar river pollution and health hazards.

Damodar river is one of the most polluted rivers in this country. Chemical pollution and bacteriological pollution, both are high--leading to rising trend in different industrial health hazards in the Damodar basin.

Environmental Monitoring↗

Primary osteosarcoma of the skull. A report of 3 cases.

Osteosarcomas are malignant bone tumors, which commonly affect the long bones of young adults. Primary osteosarcomas of the skull are exceedingly rare. We herein report 3 cases of primary osteosarcoma of the skull involving the calvaria, diagnosed over a period of 8 years at the Department of Pathology of our Institute.

Adolescent↗

Isolated extra-cranial internal carotid artery aneurysm in a young adult with Eale's disease.

A young male patient, a known case of Eale's disease presented with a large isolated aneurysm of the extra-cranial part of internal carotid artery. Detailed investigation failed to establish the etiology of the aneurysm, and it is possible that the underlying pathology may be the same as that of Eale's disease. Eale's disease is an idiopathic vascular disease of the peripheral retina and we hypothesize that aneurysm in this patient may be associated with Eale's disease of the eye.

Adult↗

X-linked Charcot-Marie-Tooth disease with myokymia: report of a family.

The clinical and electrophysiologic profiles of two brothers suffering from Charcot-Marie-Tooth disease are presented. Both had widespread muscle twitching in the legs which showed electrophysiologic features of myokymia. Pedigree analysis suggested an x-linked recessive form of inheritance. This appears to be the first report of an Indian family with x-linked Charcot-Marie-Tooth disease.

Adolescent↗

Effect of arsenic on cell growth of the cellular slime mould, Dictyostelium discoideum.

The growing D. discoideum cells were killed in a dose-dependent manner when exposed to 100 and 140 ppm of arsenic (As2O3) at mid-log phase for 20 min. Reduced plaque sizes and changed cell and colony morphologies were observed in the treated cells. Endocytotic functions (both phagocytosis and pinocytosis) were also inhibited in the treated cells. Arsenic treated cell showed a lower DNA and protein synthetic activities. These findings are discussed in relation to known mechanism of action of the heavy metal on growth-related cellular functions.

Animals↗

Lung function and asthma symptoms in children: relationships and response to treatment.

UNLABELLED: The aim of this study was to determine the relationships between the forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF) and asthma symptom scores, as well as their response to treatment, in children with no recent exacerbations of asthma. Asthma symptom scores, FEV1 and PEF were characterised, and their relationships and changes at follow-up studied in 64 children (mean age 9.5 y) referred to asthma outpatients. The mean FEV1 and PEF at the initial clinic visit were 94% of predicted values. At follow-up, mean FEV1 and PEF were similar. However, symptom scores (maximum obtainable score for each variable = 3) for exercise, nocturnal cough and morning cough were abnormal at the initial visit (mean +/- SD, exercise 1.0 +/- 0.7, nocturnal cough 1.7 +/- 1.2, morning cough 1.6 +/- 1.2) and improved significantly at follow-up (exercise 0.8 +/- 0.7, nocturnal cough 0.9 +/- 1.1, morning cough 1.0 +/- 1.2) (p < 0.05). A significant relationship was not observed between lung function and total symptom score, at either the initial or follow-up clinic visit. Neither FEV1 nor PEF significantly correlated with individual symptom scores. While symptom control improved, no significant relationships between change in asthma symptom scores and change in FEV1 and PEF between the initial and follow-up visits were observed. CONCLUSION: Clinic ("office") spirometry, currently performed world-wide, cannot be uniformly regarded as an indicator of asthma status. In addition to the measurement of lung function, quantitative symptom scoring may be a helpful tool for physicians in the assessment of childhood asthma status.

Adolescent↗

Quercetin: critical evaluation as an antileishmanial agent in vivo in hamsters using different vesicular delivery modes.

Chemotherapy is still a major challenge for in vivo drug targeting to macrophages. Toxicity remains the major obstacle for the most potent drugs already known in the therapy of leishmaniasis. Thus, new drugs and new delivery systems are sought. By using different vesicular delivery modes e.g. liposomes, niosomes, microspheres and nanoparticles, attempts have been made to deliver an indigenous antileishmanial compound, quercetin, to treat experimental leishmaniasis in the hamster model so as to increase its efficacy as well as to reduce the toxicity. At equivalent quercetin concentration, the nanocapsulated quercetin was found to be the most potent in reducing the parasite burden in the spleen as well as in reducing hepatotoxcity and renaltoxicity compared to free drug or drug in other vesicular forms. An inverse relationship between the efficacy and the size of the vesicles was established. Such a drug vehicle formulation especially in the nanocapsulated form may be considered for clinical trials.

Algorithms↗