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   Table of Contents - Current issue
Coverpage
May-June 2017
Volume 49 | Issue 3
Page Nos. 221-259

Online since Wednesday, September 27, 2017

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EDITORIAL  

Photopharmacology p. 221
Phulen Sarma, Bikash Medhi
DOI:10.4103/0253-7613.215730  
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RESEARCH ARTICLES Top

Adverse drug reaction monitoring in patients on antiretroviral therapy in a tertiary care hospital in Eastern India p. 223
Shatavisa Mukherjee, Nikhil Era, Bibhuti Saha, Santanu Kumar Tripathi
DOI:10.4103/ijp.IJP_304_16  
Background: Besides unparalleled benefits, highly active antiretroviral therapy is also associated with wide range of potential adverse drug reactions (ADRs), which hinders treatment adherence. The present study was thus designed to monitor and explore the pattern of occurrence of ADRs to various antiretroviral therapy (ART) regimens in a tertiary care ART setup. Materials and Methods: A prospective, observational clinical study was carried out in the outpatient setting of nodal ART center of Eastern India. A total of 610 patients on various ART regimens were studied for suspected ADRs over 12 months. Adverse event history, medication history, and other relevant details were captured. Causality and severity of each reported ADR were duly assessed. Results: 32.45% patients of total study participants presented with a total of 330 ADRs. Patients from zidovudine-based regimens presented with majority of ADRs such as anemia (up to 36%), central nervous system (CNS), and gastrointestinal (GI) side effects. Tenofovir-based regimens were, however, found to be mildly safer. The combination with Efavirenz was associated with majorly CNS side effects while that of nevirapine was associated with rash and pigmentation of nails. Atazanavir boosted second-line regimens were notably associated with increased serum lipid levels followed by other GI and CNS adverse effects. Increased liver enzymes were found in atazanavir-based second-line ART. Conclusion: The study enables to obtain information on the incidence and pattern of ADRs associated with various antiretroviral regimens, thereby reducing its occurrence and protecting the patient population from avoidable harm. Need of intensive monitoring for ADRs in ARTs thus seems to be a mandate.
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In vitro antioxidant and in vivo antidepressant activity of green synthesized azomethine derivatives of cinnamaldehyde p. 229
Sridevi Chigurupati, Sohrab Akhtar Shaikh, Jahidul Islam Mohammad, Kesavanarayanan Krishnan Selvarajan, Appala Raju Nemala, Chu How Khaw, Chun Foo Teoh, Ting Hei Kee
DOI:10.4103/ijp.IJP_293_16  
Objectives: In this study, three (CS-1 to CS-3) azomethine derivatives of cinnamaldehyde were green synthesized, characterized, and their antioxidant and antidepressant activities were explored. Materials and Methods: The antioxidant effect of these compounds was initially performed in vitro using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay methods before subjecting them to in vivo experiments. Compounds showing potent antioxidant activity (CS-1 and CS-2) were investigated further for their antidepressant activity using the forced swim test (FST) and tail suspension test (TST). Ascorbic acid (AA) and fluoxetine (20 mg/kg, p.o) were used as reference drugs for comparison in the antioxidant and antidepressant experiments, respectively. Results: It was observed that CS-2 and CS-3 exhibited highest DPPH (half maximal inhibitory concentration [IC50]: 16.22 and 25.18 μg/mL) and ABTS (IC50: 17.2 and 28.86 μg/mL) radical scavenging activity, respectively, compared to AA (IC50: 15.73 and 16.79 μg/mL) and therefore, both CS-2 and CS-3 were tested for their antidepressant effect using FST and TST as experimental models. Pretreatment of CS-2 and CS-3 (20 mg/kg) for 10 days considerably decreased the immobility time in both the FST and TST models. Conclusion: The antioxidant and antidepressant effect of CS-2 and CS-3 may be attributed to the presence of azomethine linkage in the molecule.
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The impact of antidepressant treatment on brain-derived neurotrophic factor level: An evidence-based approach through systematic review and meta-analysis p. 236
Vijayakumar Arumugam, Vini Susan John, Nisha Augustine, Taniya Jacob, Sagar Maliakkal Joy, Suchandra Sen, Tuhinadri Sen
DOI:10.4103/ijp.IJP_700_16  
Objectives: Antidepressant treatment alters brain-derived neurotrophic factor (BDNF) levels, but it is not well established whether BDNF can be used as a marker to prove the efficacy of antidepressant treatment. The present systematic review and meta-analysis aim at assessing the influence of antidepressant treatment on BDNF level and the Hamilton Depression Rating Scale (HDRS) score, thereby to establish the rationale of utilizing BDNF as a predictive biomarker and HDRS score as an indicator for antidepressant treatment efficacy. Materials and Methods: Search was conducted in PubMed, Science Direct, and Cochrane databases using the key words “BDNF” and “Depression” and “Antidepressants.” On the basis of the inclusion and exclusion criteria, studies were filtered and finally 6 randomized controlled trials were shortlisted. Results: Comparison of serum BDNF level before and after antidepressant treatment was performed and the result showed that antidepressant treatment does not significantly affect the BDNF levels (confidence interval [CI]: −0.483 to 0.959; standard mean difference [SMD]: 0.238, P = 0.518). Egger's regression test (P = 0.455) and heterogeneity test (I2 = 88.909%) were done. Similarly, comparison of HDRS scores before and after antidepressant treatment indicated improvement in HDRS score suggesting positive outcome (CI: 1.719 to 3.707; SMD: 2.713, P < 0.001). Egger's regression test (P = 0.1417) and heterogeneity test (I2 = 89.843%) were performed. Publication bias was observed by funnel plot. Conclusion: Changes in BDNF levels do not occur uniformly for all the antidepressants. Hence, to use BDNF as a biomarker, it needs to be seen whether the same is true for all antidepressants.
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Congenital malformation and autism spectrum disorder: Insight from a rat model of autism spectrum disorder p. 243
Rakesh K Ruhela, Phulen Sarma, Shringika Soni, Ajay Prakash, Bikash Medhi
DOI:10.4103/ijp.IJP_183_17  
Aims and Objectives: The primary aim was an evaluation of the pattern of gross congenital malformations in a rat model of autism spectrum disorder (ASD) and the secondary aim was characterization of the most common gross malformation observed. Materials and Methods: In females, the late pro-oestrous phase was identified by vaginal smear cytology, and then, they were allowed to mate at 1:3 ratio (male: female). Pregnancy was confirmed by the presence of sperm plug in the vagina and presence of sperm in the vaginal smear. In the ASD group, ASD was induced by injecting valproic acid 600 mg/kg (i.p.) to pregnant female rats (n = 18) on day 12.5 (single injection). Only vehicle (normal saline) was given in the control group (n = 12). After delivery, pups were grossly observed for congenital malformations until the time of sacrifice (3 months) and different types of malformations and their frequency were noted and characterized. Results: In the ASD group, congenital malformation was present in 69.9% of the pups, whereas in the control group, it was 0%. Male pups were most commonly affected (90% in males vs. only 39.72% in female pups). The tail deformity was the most common malformation found affecting 61.2% pups in the ASD group. Other malformations observed were dental malformation (3.82%), genital malformation (3.28%) and paw malformation (1.1%). Hind limb paralysis was observed in one pup. The tail anomalies were characterized as per gross appearance and location of the malformation. Conclusion: In this well-validated rat model of ASD, congenital malformation was quite common. It seems screening of congenital malformations should be an integral part of the management of ASD, or the case may be vice versa, i.e., in the case of a baby born with a congenital deformity, they should be screened for ASD.
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SHORT COMMUNICATION Top

Correlation of long-term glycemic control as measured by glycated hemoglobin with serum angiopoietin-like 6 protein levels in type 2 diabetes mellitus patients p. 250
Vikaas Sharma, Ghan Shyam Pangtey, Rachna Gupta, Harmeet Singh Rehan, Lalit Kumar Gupta
DOI:10.4103/ijp.IJP_261_16  
Aims: Angiopoietin-like growth factors (ANGPTLs) regulate glucose, lipid homeostasis, and insulin sensitivity. This study aimed to find whether long-term glycemic control (glycated hemoglobin [HbA1c]) has any correlation with serum ANGPTL6 levels in patients of type 2 diabetes mellitus. Materials and Methods: It was an open-label, observational, prospective clinical study. Sixty-five participants (41 diabetic patients receiving daily dose of oral metformin for a minimum of 3 months and 24 matched controls) completed the study. A single venous blood sample was taken from each participant to determine serum HbA1cand serum ANGPTL6 levels. Comparison of serum ANGPTL6 levels according to the HbA1clevels, in groups A, B, and C ranging from 6.5%–8%, 8.1%–9.5%, and >9.5%, respectively, was done using Kruskal–Wallis H-test followed by pairwise comparisons. Results: Serum HbA1cand serum ANGPTL6 levels were raised significantly (P < 0.05) in diabetic patients when compared with control participants. A positive correlation was observed between serum HbA1cand serum ANGPTL6 levels (r = 0.88, 95% confidence interval 0.81, 0.92). Mean ANGPTL6 level for Group A (n = 20) was 394.3 pg/ml, for Group B (n = 8) 692.8 pg/ml, and for Group C (n = 13) 896.2 pg/ml. Conclusions: Serum ANGPTL6 levels were significantly higher in type 2 diabetic patients in comparison with healthy controls. Poor glycemic control in diabetes mellitus as reflected by higher serum HbA1clevels is associated with raised serum ANGPTL6 levels.
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DRUG WATCH Top

Topiramate-induced acute liver injury: A rare adverse effect p. 254
Archish Khivsara, Jeffrey Pradeep Raj, Divya Hegde, Mangala Rao
DOI:10.4103/ijp.IJP_414_16  
Idiosyncratic drug-induced liver injury (DILI) is damage to liver occurring at recommended dose of a drug in contrast to toxic or predictable DILI. Although it is common in first-generation antiepileptic drugs (AEDs), it is rare in newer AEDs such as topiramate. Topiramate commonly causes neurological adverse effects such as psychomotor slowing and somnolence. Hepatotoxicity by topiramate is rare and has been previously reported in combination with other drugs such as valproate and carbamazepine. Here, we report a case of topiramate-induced asymptomatic elevation of liver enzymes in an adult man diagnosed with alcohol dependence syndrome and alcohol withdrawal complicated with seizures.
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Gingival hyperplasia: Should drug interaction be blamed for? p. 257
Pramod Kumar Sharma, Arup Kumar Misra, Ankita Chugh, Vinay Kumar Chugh, Nitesh Gonnade, Surjit Singh
DOI:10.4103/ijp.IJP_57_17  
Gingival overgrowth (GO) is one of the common findings in clinical practice. There could be several causes including drugs associated with the GO. Carbamazepine (CBZ) and amlodipine are the drugs which are infrequently documented as a cause in inducing the gingival hyperplasia. Certain drugs in the body fluid might limit the population of plaque bacteria and alter their metabolism that in turn induce the inflammatory mediators and also activate the genetic and biochemical factors responsible for gingival fibroblast growth. Drug-induced GO is a side effect with a multifactorial etiology that seems to orchestrate the interaction between drugs and fibroblasts in the gingiva. We describe a case of trigeminal neuralgia with hypertension treated with multiple drugs including amlodipine and CBZ. Although amlodipine is known to be infrequently associated with GO, an association of CBZ with GO is even rarer. Causality analysis on the World Health Organization Uppsala Monitoring Centre's scale indicates a probable association with offending drugs.
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