Inhibition of Contractility of Isolated Caprine Detrusor by the Calcium Channel Blocker Cilnidipine and Reversal by Calcium Channel Openers.

Background: Cilnidipine is a fourth-generation calcium channel blocker that is clinically used to treat hypertension. It is a dihydropyridine that blocks L- and N-type calcium channels. The inhibitory effect of cilnidipine on isolated detrusor muscle contractility has not been studied. This study investigated the inhibitory effect of cilnidipine on isolated caprine (goat) detrusor muscle contractility and the reversal of the inhibition by calcium channel openers. Methods: Fourteen caprine detrusor strips were made to contract using 80 mM potassium chloride before and after addition of three concentrations (20, 40, and 60 µM) of cilnidipine. Two reversal agents, the L-type calcium channel opener FPL64716, and the N-type calcium channel opener GV-58, were investigated for their ability to reverse the inhibitory effect of 40 µΜ cilnidipine on potassium chloride-induced detrusor contractility. Results: Cilnidipine caused a dose-dependent and statistically significant inhibition of detrusor contractility at all concentrations of cilnidipine used (20, 40, and 60 µΜ). The inhibitory effect of 40 µM cilnidipine on detrusor contractility was significantly reversed by the addition of FPL64716 and GV-58. Conclusions: Cilnidipine inhibits the contractility of the isolated detrusor by blocking L- and N-type calcium channels. Cilnidipine could be evaluated for treating clinical conditions requiring relaxation of the detrusor such as overactive bladder.

Surface decorated spinel-oxide electrodes for mixed-potential ammonia sensor: Performance and DRT analysis.

The mixed-potential gas sensors appeared as the most promising sensing technology for the in-situ quantification of exhaust pollutants due to their simple configuration, low-cost, and thermochemical stability. Presently, high sensitivity and selectivity supplemented by long-term stability is the bottleneck challenge for these sensors to commercialize. Herein, highly sensitive and ammonia (NH3) selective mixed-potential gas sensors were developed using surface decorated CuFe2O4 (CFO)-MOX (M = Sn, Ni, Zn) composite sensing electrodes (SE). The CFO-NiO SE enriched of the surface oxygen vacancies produced a maximum response of -62 mV to 80 ppm NH3, supported by excellent sensitivity at 650 ℃. The comprehensive analysis of the response behavior and current-voltage (I-V) characteristics verified the sensing mechanism to be based upon the mixed-potential model conforming to the reaction-rate limited Butler-Volmer NH3 oxidation kinetics. Finally, the distribution of relaxation times (DRT) analysis of impedance spectra confirmed that the overall polarization resistance was invariable of the mass-transport processes and solely governed by the extent of interfacial redox reactions proceeding at the triple-phase boundaries (TPB). Moreover, the high sensitivity, selectivity, and exceptional stability over five months substantiate the suitability of the presented sensor as a potential candidate for in-situ ammonia quantifications in industrial and automotive applications.

Quantitative estimation of isoniazid content in the commercially available and government-supplied formulations.

BACKGROUND: Multi-drug resistant tuberculosis is on the rise, resulting in treatment failure. One potential reason for drug resistance is the substandard quality of manufactured antituberculous drugs. This study aims at finding out the difference in the quantity of isoniazid between government-supplied tablets and commercially available tablets. METHOD: Tablets from the single most commonly used brand of isoniazid manufactured by a pharmaceutical company and from RNTCP DOTS providing centre were obtained for the estimation of concentration using a spectrophotometer. The results were analysed using Un-paired Student's t-test. RESULTS: Of the 98 isoniazid tablets from each arm studied, none had the strength that deviated from the WHO limit of 90-110%, i.e. 270-330 mg. The mean strength ±SD of the commercial preparation of isoniazid tablets was found to be 295.16 ± 12.14. The mean strength ± SD of DOTS isoniazid tablets was found to be 298.69 ± 9.55. The difference observed in the strengths of isoniazid tablets between DOTS and commercial preparation was statistically insignificant (p = 0.1704). CONCLUSION: This method to estimate the strength of isoniazid tablets is inexpensive, relatively easy, and considerably accurate to perform, and hence can be employed in primary or secondary care centres to ensure the standard strengths of tablets dispensed from such centres.

Avanafil Inhibits the Contractility of the Isolated Caprine Detrusor Muscle.

CONTEXT: Avanafil is a smooth muscle relaxant that is clinically used to treat erectile dysfunction. It is an inhibitor of phosphodiesterase-5 (PDE5), the enzyme that catalyzes the metabolism of cyclic guanosine monophosphate (cGMP). The inhibitory effect of avanafil on isolated detrusor muscle contractility has not been studied. AIMS: This study investigated the inhibitory effect of avanafil on isolated caprine (goat) detrusor muscle contractility and the possible mechanisms involved. SETTINGS AND DESIGN: 80 mM potassium chloride (KCl)-induced contractility of the isolated goat detrusor was studied using a physiograph. MATERIALS AND METHODS: Ten caprine detrusor strips were made to contract using 80 mM KCl before and after addition of three concentrations (10, 30, and 60 µM) of avanafil. Three reversal agents, ODQ, a guanylyl cyclase inhibitor; glibenclamide, an adenosine triphosphate (ATP)-sensitive potassium channel blocker; and iberiotoxin, a calcium-sensitive potassium (BKCa) channel blocker, were investigated for their ability to reverse the inhibitory effect of 30 µM avanafil on KCl-induced detrusor contractility. STATISTICAL ANALYSIS USED: The nonparametric statistical test, Kruskal-Wallis test, was used for the analysis of the data. RESULTS: Avanafil caused a statistically significant inhibition of detrusor contractility at 30 and 60 µM concentrations. The inhibitory effect of 30 µM avanafil on detrusor contractility was significantly reversed by the addition of ODQ, glibenclamide, and iberiotoxin. CONCLUSIONS: Avanafil inhibits the contractility of the isolated detrusor by inhibiting PDE5, leading to raised cellular levels of cGMP. The raised levels of cGMP could have inhibited detrusor contractility by activating cGMP-dependent protein kinase, by opening ATP-sensitive potassium channels, and by opening BKCa. Avanafil could be evaluated for treating clinical conditions requiring relaxation of the detrusor like overactive bladder.

Epigenetic Drugs for Mood Disorders.

There is increasing evidence that changes in epigenetic mechanisms of gene expression are involved in the pathogenesis of mood disorders. Such evidence stems from studies conducted on postmortem brain tissues and peripheral cells or tissues of patients with mood disorders. This article describes and discusses the epigenetic changes in the mood disorders (major depressive disorder and bipolar disorder) found to date. The article also describes and discusses preclinical drug trials of epigenetic drugs for treating mood disorders. In addition, nonrandomized and randomized controlled trials of nutritional drugs with effects on epigenetic mechanisms of gene expression in patients with major depressive disorder and bipolar disorder are discussed. Trials of epigenetic drugs and nutritional drugs with epigenetic effects are showing promising results for the treatment of mood disorders. Thus, epigenetic drugs and nutritional drugs with epigenetic effects could be useful in the treatment of patients with these disorders.

Insights into the binding interaction between copper ferrite nanoparticles and bovine serum albumin: An effect on protein conformation and activity.

The binding affinity between bovine serum albumin (BSA) and copper ferrite (CuFe2 O4 ) nanoparticles in terms of conformation, stability and activity of protein was studied using various spectroscopic methods. The quenching involved in BSA-CuFe2 O4 NP interaction was static quenching as analysed by different techniques (steady-state and time-resolved fluorescence along with temperature-dependent fluorescence measurements). Among all types of possible interactions, it was revealed that the major binding forces were van der Waals interaction and hydrogen bonding, which were explored from negative values of enthalpy change (∆H = -193.85 kJ mol-1 ) and entropy change (∆S = -588.88 J mol-1  K-1 ). Additionally, synchronous, circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy measurements confirmed the conformational changes in BSA upon the addition of CuFe2 O4 NP. Furthermore, thermal denaturation observations were consistent with the circular dichroism results. The interaction of CuFe2 O4 NP with BSA decreased the esterase activity in the BSA assay, revealing the affinity of copper ferrite towards the active site of BSA.

Retraction: Association Between 5-HTR2C -759C/T (rs3813929) and -697G/C (rs518147) Gene Polymorphisms and Risperidone-Induced Insulin Resistance Syndrome in an Indian Population.

The above article from the Journal of Clinical Pharmacology, first published online on 22 September 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement among the authors, the journal Editor in Chief, Joseph Bertino, and Wiley Periodicals, Inc. The retraction has been agreed upon due to the article having been submitted by the lead author without agreement from all co-authors. Having been alerted to this irregularity, the journal was also advised by the Senior Author of inaccuracies in the genotyping data. Reference Das, S., Dey, J. K., Prabhu SS, N., David, S., Kumar, A., Braganza, D. and Shanthi FX, M. (2017), Association Between 5-HTR2C -759C/T (rs3813929) and -697G/C (rs518147) Gene Polymorphisms and Risperidone-Induced Insulin Resistance Syndrome in an Indian Population. The Journal of Clinical Pharmacology. doi:10.1002/jcph.1012.

A retrospective study on non-drug related poisoning in the community among children from south India.

OBJECTIVES: This retrospective study was performed to determine the incidence, demographic distribution, types and outcomes across various non-drug related poisonings among children attending a tertiary care center in south India. METHODS: All children from 0-16 years who presented to the Paediatric Emergency Department, Christian Medical College, Vellore with non-drug related poisoning from October 2004 to September 2013 were included. RESULTS: Out of the total 997 cases of poisoning, 629 (63.1%) cases were contributed by chemicals and plants: mainly hydrocarbons (kerosene) 309 (49.1%); organophosphates 72 (11.5%); corrosive acids and alkalis 57 (9.1%); insecticides 51 (8.1%); and plant poisons 20 (3.2%). Males (62.79%) and children < 5 years (77.42%) were mostly affected. Although many children developed complications requiring intensive care unit admissions, the total mortality was only 9 (1.4%). The incidence of poisoning showed a decreasing trend over the last 4 years. CONCLUSION: This study for the first time gives an elaborative insight on non-drug related pediatric poisoning from a tertiary care center in south India for almost a decade.

Greener Route for Synthesis of aryl and alkyl-14H-dibenzo [a.j] xanthenes using Graphene Oxide-Copper Ferrite Nanocomposite as a Recyclable Heterogeneous Catalyst.

A facile, efficient and environmentally-friendly protocol for the synthesis of xanthenes by graphene oxide based nanocomposite (GO-CuFe2O4) has been developed by one-pot condensation route. The nanocomposite was designed by decorating copper ferrite nanoparticles on graphene oxide (GO) surface via a solution combustion route without the use of template. The as-synthesized GO-CuFe2O4 composite was comprehensively characterized by XRD, FTIR, Raman, SEM, EDX, HRTEM with EDS mapping, XPS, N2 adsorption-desorption and ICP-OES techniques. This nanocomposite was then used in an operationally simple, cost effective, efficient and environmentally benign synthesis of 14H-dibenzo xanthene under solvent free condition. The present approach offers several advantages such as short reaction times, high yields, easy purification, a cleaner reaction, ease of recovery and reusability of the catalyst by a magnetic field. Based upon various controlled reaction results, a possible mechanism for xanthene synthesis over GO-CuFe2O4 catalyst was proposed. The superior catalytic activity of the GO-CuFe2O4 nanocomposite can be attributed to the synergistic interaction between GO and CuFe2O4 nanoparticles, high surface area and presence of small sized CuFe2O4 NPs. This versatile GO-CuFe2O4 nanocomposite synthesized via combustion method holds great promise for applications in wide range of industrially important catalytic reactions.

Drug poisoning in the community among children: a nine years' experience from a tertiary care center in south India.

OBJECTIVES: This study was performed to determine the incidence, demographic distribution, types and outcomes across various drug poisonings among children from south India. METHODS: This retrospective study included children less than 16 years who presented to the Pediatric Emergency Department with drug poisoning from the 1st of October 2004 to the 30th of September 2013. RESULTS: Out of the total 997 poisoning cases, 366 (36.71%) were contributed by drugs; mainly antiepileptics, central nervous system depressants, psychotropics, analgesic-antipyretics and natural drugs. Males and children of < 5 years were mostly affected. Although many children developed complications and required intensive care unit admissions, the total mortality rate was less than 1%. The incidence of drug poisoning showed a decreasing trend over the last 4 years. CONCLUSION: This study for the first time gives an elaborative insight into pediatric drug poisoning over a nine-year period from a Pediatric Emergency Department tertiary care center in south India.

Prevalence of Hepatotoxicity From Antituberculosis Therapy: A Five-Year Experience From South India.

BACKGROUND: Antituberculosis (ATT) drug-induced liver injury (DILI) is a common and serious adverse effect of tuberculosis (TB) treatment. This retrospective study was carried out to study the prevalence of DILI among patients who had received anti-TB medications and to study some of the known risk factors responsible for causing DILI. MATERIALS AND METHODS: This longitudinal descriptive study was performed to evaluate cases of DILI with predefined criteria. Patients of all ages, diagnosed and treated for smear positive pulmonary TB from January 1, 2008 to December 31, 2012 and those who came for regular follow-up were included in the study. Multiple logistic regression analysis was performed to determine the association of different risk factors and DILI. The confounders considered were age, sex, weight, body mass index, doses of drugs (fixed or per kg), ATT regimens (daily or intermittent), and treatment categories. RESULTS: Of the 253 patients analyzed, 24 (9.48%) developed DILI. Associations of different risk factors were insignificant; including chronic alcohol consumption, hepatitis B infection, hepatitis C infection, HIV infection, and existing chronic TB. CONCLUSION: DILI was not significantly associated with known risk factors in our settings.

Drug Prescribing Pattern During Intranatal Period in a Secondary Care Hospital in South India: A Retrospective Study.

BACKGROUND: During delivery, drugs being prescribed cause concerns due to their harmful effects on lactation as well as potential adverse reactions on the mother. This retrospective study was performed to evaluate the drug prescribing pattern during normal delivery in a secondary care hospital in India. MATERIALS AND METHODS: This cross-sectional retrospective study included 3 months of patient's medical records. RESULTS: A total of 2222 drugs, comprising 51 different types of drugs were prescribed to 313 mothers undergoing normal delivery. Most of these drugs are safe in lactation. Ten types of drugs would have been better avoided, but they possibly did not cause harm because of their limited short-term use only during the intranatal period. CONCLUSION: This study reflects a good, safe, and rational medication practice during normal delivery for various common ailments in a secondary care hospital and can be cited as an example for similar settings.

Drug prescribing pattern in pregnancy in a secondary care hospital in south India: a retrospective study.

BACKGROUND: In pregnancy drug treatment presents a special concern due potential teratogenic effects and physiologic alterations in mother. This retrospective study was performed to evaluate the drug prescribing pattern in pregnancy among pregnant women in a secondary care hospital in India. MATERIALS AND METHODS: This cross-sectional retrospective study was done for 3 months using pre-formatted forms and patient's records. RESULTS: A total of 326 drugs, including 46 different types of drugs, were prescribed to 606 gravid women. Eight different types of medications were started before being seen at the antenatal clinic. Most of these drugs fall under US FDA pregnancy categories B and C and few under categories A, X and N. CONCLUSION: This study reflects a good, safe and rational medication practice during pregnancy in various common disorders in a secondary care hospital and can be cited as an example to similar primary and secondary care hospitals.

Socio-economic patterning of cardiometabolic risk factors in rural and peri-urban India: Andhra Pradesh children and parents study (APCAPS).

AIM: To assess the prevalence of cardiometabolic risk factors by socio-economic position (SEP) in rural and peri-urban Indian population. SUBJECTS AND METHODS: Cross-sectional survey of 3,948 adults (1,154 households) from Telangana (2010-2012) was conducted to collect questionnaire-based data, physical measurements and fasting blood samples. We compared the prevalence of risk factors and their clustering by SEP adjusting for age using the Mantel Hansel test. RESULTS: Men and women with no education had higher prevalence of increased waist circumference (men: 8 vs. 6.4 %, P < 0.001; women: 20.9 vs. 12.0 %, P = 0.01), waist-hip ratio (men: 46.5 vs. 25.8 %, P = 0.003; women: 58.8 vs. 29.2 %, P = 0.04) and regular alcohol intake (61.7 vs. 32.5 %, P < 0.001; women: 25.7 vs. 3.8 %, P < 0.001) than educated participants. Unskilled participants had higher prevalence of regular alcohol intake (men: 57.7 vs. 38.7 %, P = 0.001; women: 28.3 vs. 7.3 %, P < 0.001). In contrast, participants with a higher standard of living index had higher prevalence of diabetes (top third vs. bottom third: men 5.2 vs. 3.5 %, P = 0.004; women 5.5 vs. 2.4 %, P = 0.003), hyperinsulinemia (men 29.5 vs. 16.3 %, P = 0.002; women 31.1 vs. 14.3 %, P < 0.001), obesity (men 23.3 vs. 10.6 %, P < 0.001; women 25.9 vs. 12.8 %, P < 0.001), and raised LDL (men 16.8 vs. 11.4 %, P = 0.001; women 21.3 vs. 14.0 %, P < 0.001). CONCLUSIONS: Cardiometabolic risk factors are common in rural India but do not show a consistent association with SEP except for higher prevalence of smoking and regular alcohol intake in lower SEP group. Strategies to address the growing burden of cardiometabolic diseases in urbanizing rural India should be assessed for their potential impact on social inequalities in health.

Cohort profile: Andhra Pradesh Children and Parents Study (APCAPS).

The Andhra Pradesh Children and Parents Study (APCAPS) was originally established to study the long-term effects of early-life undernutrition on risk of cardiovascular disease. Its aims were subsequently expanded to include trans-generational influences of other environmental and genetic factors on chronic diseases in rural India. It builds on the Hyderabad Nutrition Trial (HNT) conducted in 1987-90 to compare the effects on birthweight of a protein-calorie supplement for pregnant women and children. The index children of HNT and their mothers were retraced and examined in 2003-05, and the children re-examined as young adults aged 18-21 years in 2009-10. The cohort was expanded to include both parents and siblings of the index children in a recently completed follow-up conducted in 2010-12 (N=∼6225 out of 10,213 participants). Recruitment of the remaining residents of these 29 villages (N=∼55,000) in Ranga Reddy district of Andhra Pradesh is now under way. Extensive data on socio-demographic, lifestyle, medical, anthropometric, physiological, vascular and body composition measures, DNA, stored plasma, and assays of lipids and inflammatory markers on APCAPS participants are available. Details of how to access these data are available from the corresponding author.

Ethnicity, obesity and health pattern among Indian population.

OBJECTIVE: To study the relationship of ethnicity with overweight/obesity, variation in adiposity levels, regional distribution of fat and its impact on cardio-respiratory health among selected ethnic groups. MATERIALS AND METHODS: A cross-sectional study was carried out among 300 young adults of three ethnic groups from different geographical regions of India ranging in age from 20 to 30 years. Stature, weight, circumferences, body fat percentage, and skinfold thicknesses were measured. Obesity indices like body mass index (BMI), grand mean thickness (GMT), waist hip ratio (WHR), waist height ratio (WHtR), and conicity index (CI) were computed. Cardio-respiratory health indicators such as lung functions including forced expiratory volume in 1 s (FEV(1.0)), forced vital capacity (FVC), forced expiratory ratio (FER), peak expiratory flow rate (PEFR), breath holding time (BHT), and systolic and diastolic BP (blood pressure) were taken and associated with obesity indices. RESULTS: General body fat deposition, assessed by BMI, GMT, and fat percentage, was found to be the highest among Delhi females and males. However, central adiposity as assessed from WHR, WHtR, and CI was found to be significantly higher among the Manipur subjects signifying a relatively more androidal pattern of fat deposition. Most of the inter-group differences for adiposity indices were significant; however, it was not so in the case of blood pressure among different ethnic groups. On the other hand, the respiratory efficiency varied significantly between different ethnic groups. Ethnicity, adiposity, and cardio-respiratory health were found to be interrelated. CONCLUSIONS: Subjects belonging to three ethnic groups showed marked differences in different body dimension, adiposity indices, and cardio-respiratory health. Central obesity has been found to be a better pointer for cardiovascular health risk. There were ethnic and gender differences with respect to adiposity measures and cardio-respiratory health indicators.