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   Table of Contents - Current issue
Coverpage
January-February 2015
Volume 47 | Issue 1
Page Nos. 1-127

Online since Friday, January 30, 2015

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EDITORIAL  

Time to sensitize medical graduates to the Indian Systems of Medicine and Homeopathy p. 1
Vandana Roy
DOI:10.4103/0253-7613.150301  
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REVIEW ARTICLE Top

Diabetes-associated depression: The serotonergic system as a novel multifunctional target Highly accessed article p. 4
Visakh Prabhakar, Deepali Gupta, Prateek Kanade, Mahesh Radhakrishnan
DOI:10.4103/0253-7613.150305  
Diabetes associated depression is a largely understudied field which nonetheless carries a significant disease burden. The very low therapeutic efficacy of the existing conventional drugs with poor outcome may be, in part, due to uncertainty of the mechanism involved that clearly explains the existing comorbidity. The main purpose of this review was to address the sophisticated mechanisms of this comorbidity with a view of developing potential novel targets with higher efficacy and specificity. Data were collected from database searches including PubMed, references from relevant English language research/review articles and other official publications. Articles from 1990 to 2013 were included, and a broad search term criteria were followed for data mining so that relevant information was not missed out. Some of the search terms used included; diabetes-induced depression, diabetes and serotonin, hypothalamic-pituitary-adrenal (HPA) axis and diabetes and glucocorticoids in diabetes. Neuropathologically, depletion of brain monoaminergic activity specifically the serotonin (5-hydroxytryptamine [5-HT]) system, due to chronically persisting diabetic state may lead to the mood and behavioral complications that further add on worsening the quality life years. The 5-HT system through multifunctional tasks regulates neurogenesis and plasticity and by complex receptor mechanism controls the emotional and behavioral activity. Persisting hyperglycemia leads to impaired neurogenesis, decreased synaptic plasticity, undesired neuro-anatomical alterations, neurochemical deficits, and reduced neurotransmitter activity. The neurotrophic factors and secondary messenger functions affected at molecular and genetic levels indicate the impact of diabetes-mediated dysregulation on neuronal circuits. HPA activity, glycogen synthase kinase 3, and insulin signaling controls were also found to be hampered, interlinked to 5-HT system following diabetic progression.
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EDUCATIONAL FORUM Top

The Tamiflu fiasco and lessons learnt Highly accessed article p. 11
Yogendra Kumar Gupta, Meenakshi Meenu, Prafull Mohan
DOI:10.4103/0253-7613.150308  
Oseltamivir (Tamiflu), a neuraminidase inhibitor, was approved for seasonal flu by US Food and Drug Administration in 1999. A number of randomized controlled trials, systematic reviews, and meta-analysis emphasized a favorable efficacy and safety profile. Majority of them were funded by Roche, which also first marketed and promoted this drug. In 2005 and 2009, the looming fear of pandemic flu led to recommendation by prominent regulatory bodies such as World Health Organization (WHO), Centers for Disease Control and Prevention, European Medicines Agency and others for its use in treatment and prophylaxis of influenza, and it's stockpiling as a measure to tide over the crisis. Serious Adverse Events, especially neuropsychiatric events associated with Tamiflu started getting reported leading to a cascade of questions on clinical utility of this drug. A recent Cochrane review and related articles have questioned the risk-benefit ratio of the drug, besides raising doubts about the regulatory decision of approving it. The recommendations for stockpiling the said drug as given by various international organizations viz WHO have also been put to scrutiny. Although many reviewers have labeled the Tamiflu saga as a "costly mistake," the episode leaves us with some important lessons. This article takes a comprehensive relook on the subject, and we proceed to suggest some ways and means to avoid a similar situation in the future.
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RESEARCH ARTICLES Top

Protective effect of simvastatin and rosuvastatin on trinitrobenzene sulfonic acid-induced colitis in rats p. 17
Rajesh A Maheshwari, R Balaraman, Girish U Sailor, Dhanya B Sen
DOI:10.4103/0253-7613.150311  
Objective: Statins have anti-inflammatory effects that are not directly related to their cholesterol lowering activity. This study was carried out to evaluate the effect of simvastatin or rosuvastatin on the extent of colonic mucosal damage and on the inflammatory response in trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis. Materials and Methods: Ulcerative colitis was induced by single intrarectal injection of 120 mg/kg TNBS. Test groups were treated with simvastatin (10 mg/kg, p.o.) or rosuvastatin (10 mg/kg, p.o.). Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically. Result: Disease activity index score in TNBS-treated rats, as determined by weight loss, stool consistency, fecal occult blood, were significantly lowers in simvastatin or rosuvastatin-treated rats than TNBS-treated animals. Simvastatin or rosuvastatin counteracted the reduction in colon length, decreased colon weight, neutrophil accumulation, and tumor necrosis factor-alpha level in TNBS-induced colitis. Simvastatin and rosuvastatin also inhibited the increase in oxidative stress levels after TNBS administration. Conclusions: These results suggest that simvastatin and rosuvastatin significantly ameliorate experimental colitis in rats, and these effects could be explained by their anti-inflammatory and antioxidant activity.
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Lead-induced adverse effects on the reproductive system of rats with particular reference to histopathological changes in uterus p. 22
Udayraj Premdas Nakade, Satish Kumar Garg, Abhishek Sharma, Soumen Choudhury, Rajkumar Singh Yadav, Kuldeep Gupta, Naresh Sood
DOI:10.4103/0253-7613.150317  
Objectives: This study was undertaken to elucidate the adverse effect of lead on female reproductive system following in vivo exposure in rats. Materials and Methods: Animals of Group II, III and IV received lead acetate in drinking water (30, 100 and 300 ppm, respectively) for 28 days whereas Group I served as control. Lead levels in digested blood and bone samples were measured using atomic absorption spectrophotometer. Results: Marked and a significant decrease in per cent body weight gain was observed in rats of Group IV and III, respectively, compared to that in the control group. Relative uterine weights were found to decrease by 27% in Group III and IV compared to control and low dose lead treated (30 ppm) rats. Lead levels were found to increase in a linear manner in blood along with a marked increase in bone levels in 100 ppm exposure group while there was a decrease in both the blood and bones levels at 300 ppm exposure. Compared to plasma progesterone levels in rats of the control group, a nonsignificant (12.46-21.13%) reduction in plasma progesterone were observed in different lead-treated groups. No apparent gross pathological lesions were observed in any of the vital organs, including uterus. However, histopathological examination of uteri of different groups revealed lead-induced dose-dependent inflammatory changes, which were characterized by thickening of the endometrium, narrowing of uterine lumen, damage to endometrial glands and vacuolar degeneration in endometrial epithelial cells. Conclusion: Findings of this study suggest lead-induced pathophysiological alterations in myometrium, which in turn may affect the reproductive efficiency of animals.
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Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy p. 27
Xiaowen Chen, Shengnan Peng, Huihong Zeng, Aixiang Fu, Qingxian Zhu
DOI:10.4103/0253-7613.150319  
Objectives: The objective was to investigate the protective effects of rhein on renal histology change and the effects of rhein on renal tissue toll-like receptor (TLR) 4, TLR9, transforming growth factor-β1 (TGF-β1) expression in immunoglobulin A nephropathy (IgAN) rats. Materials and Methods: Bovine serum albumin-lipopolysaccharide-carbon tetrachloride 4 method was used to establish IgAN model. Thirty-two male sprague dawley rats were randomly divided into the control group, IgAN model group, rhein-prevented group, and rhein-treated group. 24-h urinary protein (UP), creatinine, urea, alanine aminotransferase (ALT), total protein (TP) contents in the serum of rats were detected with automatic biochemical analyzer and renal pathological changes were observed by the hematoxylin and eosin and periodic acid-Schiff staining. The glomerular deposition of IgA was measured by immunofluorescence staining. Real-time polymerase chain reaction and immunohistochemistry were used to detect renal tissue contents of TLR4, TLR9, TGF-β1 messenger ribonucleic acid and protein expression. Results: The biochemical parameters results of IgAN model rats showed that the 24-h UP excretion and ALT concentration were much higher, and TP concentration was much lower than those of the control group (P < 0.05). Granule-like or mass-like IgA depositions in the mesangial area, glomerular hypercellularity, hyperplasia of mesangial matrix, and tubulointerstitial fibrosis were found in IgAN group. Rhein-prevented and rhein-treated both improved the biochemical parameters and relieved renal pathological injury. The expressions of renal tissue TLR4, TGF-β1, but not TLR9 were significantly elevated in IgAN model rats (P < 0.05). Rhein-prevented and rhein-treated both inhibited TLR4 and TGF-β1 expressions. Conclusion: Rhein significantly improved the serum and urine biochemical parameters, and attenuated the glomerular pathological changes and tubulointerstitial fibrosis in IgAN rats. The mechanism may involve inhibition of renal TLR4 and TGF-β1 secretion.
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Evaluation of effects of T and N type calcium channel blockers on the electroencephalogram recordings in Wistar Albino Glaxo/Rij rats, an absence epilepsy model p. 34
Nedim Durmus, Sefa Gültürk, Tijen Kaya, Tuncer Demir, Mesut Parlak, Ahmet Altun
DOI:10.4103/0253-7613.150324  
Objectives: It is suggested that excessive calcium entry into neurons is the main triggering event in the initiation of epileptic discharges. We aimed to investigate the role of T and N type calcium channels in absence epilepsy experimental model. Materials and Methods: Wistar Albino Glaxo/Rij (WAG/Rij) rats (12-16 weeks old) were randomly allocated into four groups; sham, mibefradil (T type calcium channel blocker), w-Conotoxin MVIIA (N type calcium channel blocker), and mibefradil + w-Conotoxin MVIIA. Beta, alpha, theta, and delta wave ratios of EEG recordings and frequency and duration of spike wave discharges (SWDs) were analyzed and compared between groups. Results: Beta and delta recording ratios in 1 μM/5 μl mibefradil group was significantly different from basal and other dose-injected groups. Beta, alpha, and theta recordings in 0.2 μM/5 μl w-Conotoxin MVIIA group was significantly different from basal and other dose-injected groups. In w-Conotoxin MVIIA after mibefradil group, beta, alpha, and theta recording ratios were significantly different from basal and mibefradil group. Mibefradil and w-Conotoxin MVIIA significantly decreased the frequency and duration of SWDs. The decrease of frequency and duration of SWDs in mibefradil group was significantly different from w-Conotoxin MVIIA group. The frequency and duration of SWDs significantly decreased in w-Conotoxin MVIIA after mibefradil group compared with basal, mibefradil, and w-Conotoxin MVIIA groups. Conclusions: We concluded that both T and L type calcium channels play activator roles in SWDs and have positive effects on frequency and duration of these discharges. These results are related with their central effects more than peripheral effects.
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Combination of Spirulina with glycyrrhizin prevents cognitive dysfunction in aged obese rats p. 39
Sowmya Madhavadas, Sarada Subramanian
DOI:10.4103/0253-7613.150327  
Objectives: To evaluate the cognition enhancing effect of the combination of Spirulina and glycyrrhizin in monosodium glutamate (MSG)-induced obese aged rats. Materials and Methods: Obesity was induced in rats by administration of MSG (intraperitoneally, 4 mg/g body weight) for 14 consecutive days from day 1 after birth. Subsequently, the animals were allowed to grow for 18 months with food and water ad libitum. Hypercholesterolemia, hyperglycemia, leptin resistance, were monitored in these animals. Cognitive status was assessed by Barne's maze task and hippocampal acetylcholinesterase (AChE) levels. Further, the animals were treated with Spirulina (Sp) (oral route, 1 g/Kg body weight, for 30 days) alone or glycyrrhizin (Gly) alone (intraperitoneal route, 0.1 mg/Kg, on day 15 and day 21), or their combination (SpGly). Counting of the treatment days was done by considering first day of Sp administration as day 1. After the completion of 30 days of Spirulina treatment or 2 doses of Gly administration or the combination (SpGly) treatment, the animals were left for 3 weeks. They were then were assessed for their biochemical and cognitive changes. Results: The combination of Sp with Gly showed a significant reduction (P < 0.0001) in glucose, cholesterol, leptin levels in the serum with improvement in cognitive functions with concomitant reduction in AChE activity in the hippocampal tissue homogenates (P < 0.0001) of the obese rats. Conclusion: SpGly combination has a potential role in reversing cognitive dysfunctions associated with aging and obesity.
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Effects of valproate on the carotid artery intima-media thickness in epileptics p. 45
Xinming Luo, Ming Zhang, Liying Deng, Jing Zhao
DOI:10.4103/0253-7613.150328  
Objective: The objective was to explore the effects of valproate (VPA) on the carotid artery intima-media thickness (CA-IMT) in epileptics. Materials and Methods: A total of 30 epileptic patients treated with VPA was included as disease group, while 33 healthy people who matched general basic demographic details were the control group. The IMTs of the left and right carotids of the both groups were measured, and the average CA-IMT was calculated. The IMT-related risk factors were acquired for the univariate and multivariate analysis. Results: The bilateral carotid and average CA-IMTs of the disease group were significantly higher than the control group (P < 0.001). The multivariant gradual regressive analysis screened out two CA-IMT-related factors, namely the disease duration and the drug administration duration were positively correlated with the average CA-IMT. The epileptic patients with disease course of more than 3 years had much higher average CA-IMT than that of the epileptics with ≤3 years disease (P < 0.001). The average CA-IMT of the patients with VPA-administration duration >1 year was also higher than that of the patients with VPA-administration duration <1 year, while the difference was not statistically significant (P = 0.196). Conclusions: The average CA-IMT of the epileptic patients treated with VPA was higher than that of healthy people.
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Resuscitation with hydroxyethyl starch 130/0.4 attenuates intestinal injury in a rabbit model of sepsis p. 49
Wei-Hua Lu, Xiao-Ju Jin, Xiao-Gan Jiang, Zhen Wang, Jing-Yi Wu, Guang-Gui Shen
DOI:10.4103/0253-7613.150333  
Objective: Improvement of mucosal barrier function and reduction of bacterial translocation are important in the management of sepsis. The mechanisms that underlie the protective effects of colloids on the intestinal mucosal barrier are unclear. The study aims to investigate the effect of fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 against intestinal mucosal barrier dysfunction in a rabbit model of sepsis. Materials and Methods: Thirty healthy rabbits were randomly and equally divided into a sham-operated control, a sepsis model, or a sepsis + HES treatment group. The sepsis model and sepsis + HES treatment groups were subjected to a modified colon ascendens stent peritonitis (CASP) procedure to induce sepsis. Four hours after the CASP procedure, fluid resuscitation was performed with 6% HES 130/0.4. Arterial and superior mesenteric vein blood samples were collected 4 and 8 h after the CASP procedure for blood gas analysis and measuring tumor necrosis factor-α, interleukin-10, and D-lactate levels. The rabbits were euthanized 8 h after CASP, and sections of the small intestine were stained to evaluate histopathological changes. Results: Respiratory rate and blood pressure were stable during the resuscitation period. Fluid resuscitation with 6% HES 130/0.4 alleviated pathological changes in the abdominal cavity, improved blood gas parameters and inflammatory mediator levels, decreased plasma D-lactate levels, and reduced intestinal mucosal injury compared with the non-treated sepsis model. Conclusions: Fluid resuscitation with 6% HES 130/0.4 protects against intestinal mucosal barrier dysfunction in rabbits with sepsis, possibly via mechanisms associated with improving intestinal oxygen metabolism and reducing the release of inflammatory mediators.
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Effects of bleomycin A5 on caspase-3, P53, bcl-2 expression and telomerase activity in vascular endothelial cells p. 55
Yi-Deng Huang, Ping Li, Xiao Tong, Yue He, Yang Zhuo, Si-Wen Xia, Xing-Hua Luo
DOI:10.4103/0253-7613.150337  
Objective: The aim of this study was to investigate the molecular mechanism of bleomycin A5 in inducing the apoptosis of human umbilical vein endothelial cells (ECV304). Materials and Methods: ECV304 cells were cultured and passaged, and then were divided into control group and three treatment groups. The later three groups were treated with 15, 75, and 150 μg/ml bleomycin A5 for 24 hours, respectively. The expressions of caspase-3, p53, and bcl-2 in ECV304 cells were detected by flow cytometry, and the activity of telomerase was determined using telomere repeat amplification protocol (TRAP)-silver staining method. Results: After treatment with different concentrations of bleomycin A5, the expression of caspase-3 in ECV304 cells was increased. It was significantly decreased with the increase of bleomycin A5 concentration, but the difference between 75 μg/ml and 150 μg/ml groups was not significant. Bleomycin A5 could significantly increase the expression of p53, with concentration dependence. It had no obvious effect on bcl-2 expression. There was high expression of telomerase in control group. After treatment with different concentration of bleomycin A5, the telomerase activity was significantly decreased. Conclusion: Bleomycin A5 can increase caspase-3 and p53 levels and inhibit telomerase activity to induce ECV304 apoptosis.
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Evaluation of anti-osteoarthritic activity of Vigna mungo in papain induced osteoarthritis model p. 59
Dhaval V Patel, Mrunal Ghag Sawant, Ginpreet Kaur
DOI:10.4103/0253-7613.150340  
Aim: This study was carried out to evaluate the effect of Vigna mungo hydroalcoholic extract (VMHA) by papain induced osteoarthritis (OA) in the rat model. Materials and Methods: OA was induced by intra-articular injection of papain (4% w/v) along with cysteine (0.03 M) on day 1, 4 and 7 in rats and VMHA was administered orally in three doses (100, 200 and 400 mg/kg) after last papain injection. The anti-osteoarthritic activity was evaluated by measuring knee joint diameter, grip strength, locomotion activity and hanging time. Histopathological analysis and acute toxicity study were also performed. Results: VMHA improved inflammatory condition with all the doses, but significant (P < 0.05) attenuation of inflammation was present only with 400 mg/kg dose. The grip strength, locomotion activity and hanging time were also significantly (P < 0.05) improved at dose level of 100 mg/kg however other two doses (200 mg/kg and 400 mg/kg) were not found to be effective. VMHA did not show any mortality or any toxic clinical signs after oral administration of 2 g/kg dose. Conclusion: VMHA improved arthritic condition by significantly reducing pain and inflammation.
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Under-reporting of adverse drug reactions: A challenge for pharmacovigilance in India p. 65
Vishal R Tandon, Vivek Mahajan, Vijay Khajuria, Zahid Gillani
DOI:10.4103/0253-7613.150344  
Aim: The aim was to evaluate the extent and factors responsible for underreporting (UR) of adverse drug reactions (ADRs) in India. Materials and Methods: A retrospective observational, cross-sectional prospective questionnaire-based analysis was undertaken to evaluate the extent and factors for UR of ADRs in pharmacovigilance. Results: At the time, this report was prepared, 90 ADR Monitoring Centers (AMC) were operational in India. Indian AMC functional rate was 56.45%. The average number of Individual Case Safety Reports reported by our center via VigiFlow per month was 48.038. In a period of the 3 years the total number of ADRs reported was 3024. The average number of reports per month was 80.08. Active surveillance versus spontaneous reporting contributed 66.13% versus 33.86% of the total ADRs (P < 0.0001). Outpatient Department (OPD) contribution was 76.05% and indoor contribution was 23.94% of total reports (P < 0.0001). Department of Medicine (33%), followed by oncology (19.27%) and chest disease (13.49%) contributed maximally. The contribution of Pharmacology ADR monitoring OPD was 16.20%. Eye, ear, nose and throat and surgery, private Medical Colleges, hospitals in periphery, sub-district and district contributed no ADRs. ADR detection rates by clinical presentation, biochemical investigation and diagnostic tools were 84.33%, 14.57%, and 1.09% respectively (P < 0.0001). Reporting by postgraduate, registrars, consultants and nurses were 72.65%, 6.58%, 16.56% and 4.19% respectively (P < 0.0001). PG students in Pharmacology contributed an average number of 5.61 ADR reports/month. The lack of knowledge and awareness about Pharmacovigilance Programme of India (PvPI), lethargy, indifference, insecurity, complacency, workload, lack of training were the common factors responsible for UR. Major academic activity, exams, thesis and synopsis submission time influenced reporting of ADRs by postgraduate students. Conclusion: UR is a matter of concern PvPI. Multiple interventions are needed to improve ADR reporting.
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Safety and efficacy of Qurse-e-istisqua in chronic hepatitis C Infection: An exploratory study p. 72
Harmeet Singh Rehan, Deepti Chopra, Madhur Yadav, Neeta Wardhan, Seema Manak, KM Siddiqui, Mohd Aslam
DOI:10.4103/0253-7613.150347  
Background: Qurse-e-istisqua (Q-e-I), an Unani medicine commonly prescribed to treat liver disorders. Objectives: To study efficacy and safety of Q-e-I in hepatitis C virus (HCV) infection. Methods : In this randomized double-blind exploratory study, 60 naive patients of HCV infection were assigned to receive either interferonα2a (IFNα2a) (3 mIU, subcutaneous, thrice weekly), ribavirin (RBV) (1000 mg, orally, twice daily in divided doses) and placebo (n = 30) or IFNα2a, RBV and Q-e-I (5 g, orally, thrice daily in divided doses) (n = 30). HCV RNA levels, serum hyaluronic acid (SHA), ultrasound image scoring for fibrosis, liver and renal function test, prothrombin time, were done at the baseline and thereafter periodically. Results: Early virologic response (EVR), end of treatment response (ETR) and sustained virologic response (SVR) were 90%, 96.6% and 90% in the control group and 86.6%, 90.0% and 83.3% in the treatment group. SHA level was lower in the treatment group at the end of the treatment as compared to the control group. Mean end of follow-up ultrasound image scoring for fibrosis in the control and the treatment group was 1.37 ± 0.07 and 1.22 ± 0.06 respectively. Aspartate aminotransferase (AST) levels were significantly lower in the treatment group than the control group at 1-month. Commonly observed adverse drug reactions included fever, hair fall, fatigue, anemia, and diarrhea. Conclusion: Q-e-I was well tolerated and showed anti-fibrotic activity. EVR, ETR and SVR suggested that Q-e-I do not have any anti-HCV activity. Early recovery in AST and inhibition of progress of fibrosis in Q-e-I group was probably due to the anti-inflammatory and antioxidant activity of its ingredients.
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Effects of combination of aliskiren and pentoxyfylline on renal function in the rat remnant kidney model of chronic renal failure p. 80
Hitesh M Soni, Praful P Patel, Savan Patel, Akshyaya C Rath, Aviseka Acharya, Harshkant D Trivedi, Mukul R Jain
DOI:10.4103/0253-7613.150351  
Objectives: The aim was to investigate the nephroprotective effect of combination of aliskiren (ASK), a direct renin inhibitor and pentoxifylline (PTX), inhibitor of tumor necrotic factor-alpha (TNF-alpha), in rat remnant kidney model of chronic kidney disease (CKD). Materials and Methods: Nephrectomized (NPX) rats were treated with ASK (10 mg/kg, p.o.), PTX (100 mg/kg, p.o.), and combination of PTX + ASK once daily for 28 days. We have performed analysis of various renal injury parameters after 4 weeks of treatment. Results: Treatment with PTX, ASK and combination showed significant improvement in urea, creatinine and total protein in plasma when compared with vehicle treated group in NPX rats. ASK and combination of PTX + ASK elicited significant reduction in blood pressure but PTX alone did not produce blood pressure reduction. ASK treatment showed significant elevation in TNF-alpha, whereas PTX and ASK + PTX showed significant reduction in TNF-alpha in plasma. Histopathologically, the extent of the kidney injury was similar in NPX + vehicle and NPX + ASK-treated rats. PTX and ASK + PTX-treated group showed lesser extent of kidney injury. There was good correlation of mRNA expression levels of kidney injury molecule-1 and bradykinin B1 receptor data with histopathological findings in kidney samples and elevated TNF-alpha levels in plasma. Conclusions: We conclude that combination of PTX + ASK may be better therapeutic intervention for nephroprotection in CKD patients.
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Protective effect of rutin on impairment of cognitive functions of due to antiepileptic drugs on zebrafish model p. 86
Shagun Dubey, Aditya Ganeshpurkar, Divya Bansal, Nazneen Dubey
DOI:10.4103/0253-7613.150357  
Aim: The severity of adverse reactions due to antiepileptics is observed during initiation and early treatment in which impairment of cognitive effects are common. Since long time, herbal medicine is a natural remedy to treat neural symptoms. Phytochemicals have been proven to be potent neuro-protective agents. Rutin, a bioflavonoid is established to be nootropic in many studies. In this study, we aimed to determine the protective effect of rutin in zebrafish against the side effects produced by AEDs. Materials and Methods: Seizures were induced in zebrafish by phenylenetetrazole. Rutin pretreatment (50 mg/kg, single injection, i.p.) was done before commencement of the study. Behavioral studies were performed as: latency to move high in the tank, locomotion effects, color effect, shoal cohesion, light/dark test on Zebrafish. Results: Treatment with rutin reverted the locomotor behavior to normal. Treatment with AEDs caused fishes to move in all regions while, in case of treatment with rutin, the response reverted to normal. Treatment with AEDs altered swimming behavior of zebrafish, however, rutin showed a positive effect over this behavior. Treatment with AEDs resulted in restricted movement of zebrafish to the dark zone. Treatment with rutin caused increased latency of zebrafish to move in the light compartment. Similarly, time spent in the light compartment by zebrafish treated with rutin was significantly (P < 0.01) higher as compared to zebrafish treated with AEDs. Conclusion: The results suggest a protective role of rutin on cognition impaired by AEDs.
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A comparison of enoxaparin with unfractionated heparins in patients with coronary heart disease in an emergency department in rural South Indian tertiary care teaching hospital p. 90
Akram Ahmad, Isha Patel, Himani Asani, M Jagadeesan, S Parimalakrishnan, S Selvamuthukumaran
DOI:10.4103/0253-7613.150360  
Aim: Antithrombotic therapy with heparin plus antiplatelets reduces the rate of ischemic events in patients with coronary heart disease. Low molecular weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, does not require monitoring and is associated with less ADRs.The purpose of the present study was to evaluate and compare the clinical and cost outcomes of Enoxaparin with a standard unfractionated heparin in patients with coronary heart disease. Materials and Methods: This was a noninvasive prospective observational descriptive study carried out at a multi-specialty tertiary care teaching hospital situated in rural Tamil Nadu, India. Male and female coronary heart disease (CHD) patients aged 35-75 years newly diagnosed or those having a history of CHD were included. The intervention group received enoxaparin for 5 days. A series of resting the electrocardiogram, prothrombin time and ADRs were measured in all patients during days 1 and 21 respectively. Results: Compared to unfractionated heparin group of patients, the average prothrombin time was significantly higher (P < 0.0001) whereas hypokalemia was significantly lower (P < 0.02) in enoxaparin group of patients. Even though recurrence of angina and ADRs such as bleeding, nausea, headache and sudden cough occurred less frequently in the enoxaparin group of patients compared to unfractionated heparin group of patients, the differences were not significant. Conclusions: Antithrombotic therapy with enoxaparin plus aspirin was safer and more effective than unfractionated heparin plus aspirin, in reducing the incidence of ischemic events in patients with unstable angina or myocardial infarction in the early phase.
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Comparison of colistin monotherapy and non-colistin combinations in the treatment of multi-drug resistant Acinetobacter spp. bloodstream infections: A Multicenter retrospective analysis p. 95
Ilker Inanc Balkan, Ayse Batirel, Oguz Karabay, Canan Agalar, Serife Akalin, Ozlem Alici, Emine Alp, Fatma Aybala Altay, Nilgun Altin, Ferhat Arslan, Turan Aslan, Nural Bekiroglu, Salih Cesur, Aygul Dogan Celik, Mustafa Dogan, Bulent Durdu, Fazilet Duygu, Aynur Engin, Derya Ozturk Engin, Ibak Gonen, Ertugrul Guclu, Tumer Guven, Cigdem Ataman Hatipoglu, Salih Hosoglu, Mustafa Kasim Karahocagil, Aysegul Ulu Kilic, Bahar Ormen, Davut Ozdemir, Serdar Ozer, Nefise Oztoprak, Nurbanu Sezak, Vedat Turhan, Nesrin Turker, Hava Yilmaz
DOI:10.4103/0253-7613.150383  
Objectives: To compare the efficacy of colistin (COL) monotherapy versus non-COL based combinations in the treatment of bloodstream infections (BSIs) due to multidrug resistant Acinetobacter spp.(MDR-A) . Materials and Methods: Retrospective data of 107 MDR-A BSI cases from 27 tertiary centers in Turkey were included. Primary End-Point: 14-day mortality. Secondary End-Points: Microbial eradication and clinical improvement. Results: Thirty-six patients in the COL monotherapy (CM) group and 71 in the non-COL based combinations (NCC) group were included in the study. Mean age was 59.98 ± 20 years (range: 18-89) and 50.5% were male. Median duration of follow-up was 40 days (range: 9-297). The 14-day survival rates were 52.8% in CM and 47.23% in NCC group (P = 0.36). Microbiological eradication was achieved in 69% of CM and 83% of NCC group (P = 0.13). Treatment failure was detected in 22.9% of cases in both CM and NCC groups. Univariate analysis revealed that mean age (P = 0.001), Charlson comorbidity index (P = 0.03), duration of hospital stay before MDR-A BSI (P = 0.04), Pitt bacteremia score (P = 0.043) and Acute Physiology and Chronic Health Evaluation II score (P = 0.05) were significant in terms of 14-day mortality. Advanced age (P = 0.01) and duration of hospital stay before MDR-A BSI (P = 0.04) were independently associated with 14-day mortality in multivariate analysis. Conclusion: No significant difference was detected between CM and non-COL based combinations in the treatment of MDR-A BSIs in terms of efficacy and 14-day mortality.
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Effects of Ginkgo biloba extract on the apoptosis of oxygen and glucose-deprived SH-SY5Y cells and its mechanism p. 101
Xiao-Hong Ba, Lian-Qiu Min
DOI:10.4103/0253-7613.150372  
Objective: The aim was to observe the effects of the extract of Ginkgo biloba (EGb761) on the apoptosis of oxygen and glucose-deprived (OGD) human neuroblastoma cells (SH-SY5Y) cells and explore its mechanism. Materials and Methods: SH-SY5Y cells were divided into normal control group, OGD group, OGD for 4 h and EGb761-pretreated groups including very low-concentration (20 μg/ml), low-concentration group (25 μg/ml), moderate-concentration group (50 μg/ml) and high-concentration group (100 μg/ml). Twenty four hours after reoxygenation, cell viability was determined with 3-[4, 5-dimehyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide assay, apoptosis rate was detected with annexin V-fluorescein isothiocyanate/propidium iodide double staining flow cytometry and the protein level of apoptosis-inducing factor (AIF) was observed with immunofluorescence technique in each group. Results: Cell viability was significantly lower in OGD group than in EGb761-pretreated groups, especially in moderate-concentration group (50 μg/ml) (P < 0.005). Apoptosis rate was significantly lower in EGb761-pretreated groups than in OGD group (P < 0.001). Immunofluorescent staining showed that there was AIF nuclear translocation in both EGb761-pretreated groups and OGD group, but AIF nuclear translocation was less in EGb761-pretreated groups than in OGD group. Conclusion: EGb761 can reduce the apoptosis of OGD SH-SY5Y cells probably through inhibiting AIF nuclear translocation. This study provides a theoretical basis for the application of EGb761 in clinical practice.
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SHORT COMMUNICATIONS Top

A questionnaire-based survey to ascertain the views of clinicians regarding rational use of antibiotics in teaching hospitals of Kolkata p. 105
Dattatreyo Chatterjee, Sukanta Sen, Sabnam Ara Begum, Anjan Adhikari, Avijit Hazra, Anup Kumar Das
DOI:10.4103/0253-7613.150373  
Objectives: The objective was to assess the views of clinicians in teaching hospitals of Kolkata regarding the use of antibiotics in their own hospitals, focusing on perceived misuse, reasons behind such misuse and feasible remedial measures. Materials and Methods: A total of 200 clinicians from core clinical disciplines was approached in six teaching hospitals of Kolkata through purposive sampling. A structured, validated questionnaire adopted from published studies and modified to suit the responding population was completed by consenting respondents through face-to-face interaction with a single interviewer. Respondents were free to leave out questions they did not wish to answer. Results: Among 130 participating clinicians (65% of approached), all felt that antibiotic misuse occurs in various hospital settings; 72 (55.4% of the respondents) felt it was a frequent occurrence and needed major rectification. Cough and cold (78.5%), fever (65.4%), and diarrhea (62.3%) were perceived to be the commonest conditions of antibiotic misuse. About half (50.76%) felt that oral preparations were more misused compared to injectable or topical ones. Among oral antibiotics, co-amoxiclav (66.9%) and cefpodoxime (63.07%) whereas among parenteral ones, ceftriaxone and other third generation cephalosporins (74.6%) followed by piperacillin-tazobactam (61.5%) were selected as the most misused ones. Deficient training in rational use of medicines (70.7%) and absence of institutional antibiotic policy (67.7%) were listed as the two most important predisposing factors. Training of medical students and interns in rational antibiotic use (78.5%), implementation of antibiotic policy (76.9%), improvement in microbiology support (70.7%), and regular surveillance on this issue (64.6%) were cited as the principal remedial measures. Conclusions: Clinicians acknowledge that the misuse of antibiotics is an important problem in their hospitals. A system of clinical audit of antibiotic usage, improved microbiology support and implementation of antibiotic policy can help to promote rational use of antimicrobial agents.
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Interaction of aqueous leaf extract of Aegle marmelos (L.) Corr. with cholinergic, serotonergic and adrenergic receptors: An ex vivo study p. 109
Sanjeev Kumar, Rakesh Kumar Mahaseth, Mukesh Tiwari, Ratika Sehgal, Preety Rajora, Rajani Mathur
DOI:10.4103/0253-7613.150374  
Objectives: The aim was to study interaction of aqueous leaf extract of Aegle marmelos (AM) with cholinergic, serotonergic, and adrenergic receptor systems using appropriate rat tissues-ileum, fundus and tracheal chain, respectively. Materials and Methods: Cumulative concentration-response curves (CRC) were constructed at various doses on each tissue for AM and respective standard agonist. The CRC was again plotted in presence and absence of respective standard antagonist to confirm the interaction of receptor system and AM. Results: AM induced concentration-dependent contractions in isolated rat ileum (0.2-6.4 mg/ml) and fundus (0.2-3.2 mg/ml) that were inhibited significantly (P < 0.05) in the presence of atropine (10−7 M) and ketanserin (10−6 M), respectively. The relaxant effect, produced by AM (0.2 mg/ml) on carbachol (10−5 M) precontracted rat tracheal chain, was also inhibited significantly (P < 0.05) by propranolol (1 ng/ml). Conclusion: It may be concluded that AM possesses agonistic activity on cholinergic, serotonergic and adrenergic receptors.
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Aminoglycosides induce fragility of human red cell membrane: An in vitro study p. 114
Abdulkadir A Alnakshbandi,
DOI:10.4103/0253-7613.150375  
Objectives: It is well-known that aminoglycosides are ototoxic and nephrotoxic. Recent advances in pharmacology research suggest that the red cell used as a carrier of aminoglycosides. This study aimed to find the effect of aminoglycosides on the human red cell membrane using osmotic fragility test. Materials and Methods: This study was conducted in Rizgari Teaching Hospital in Erbil, Iraq. The effect of aminoglycosides, namely gentamicin, amikacin, and spectinomycin, on human red cells was investigated. The effects of aminoglycosides were evaluated by osmotic fragility test using fresh human blood in the presence of aminoglycosides in concentrations of 10-160 μg/mL. Results: The results showed that aminoglycosides drugs shifted the osmotic fragility curve to some extent, and this effect was well observed with spectinomycin. The hemolysis did not depend on the concentration of aminoglycosides. The concentration of sodium chloride to induced 50% hemolysis is higher in presence of gentamicin, amikacin and spectinomycin (at 160 μg/mL) than corresponding control and this account to an increment in hemolysis percents of 1.88, 1.5 and 1.06%, respectively. Conclusion: Aminoglycosides induce human red cell membrane fragility in a concentration-independent manner.
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Effect of adiponectin on expression of vascular endothelial growth factor and pigment epithelium-derived factor: An in vitro study p. 117
Vidhya Srinivasan, KN Sulochana
DOI:10.4103/0253-7613.150376  
Aim: This study was carried out to identify the role of adiponectin (APN) in modulating the expression of vascular endothelial growth factor (VEGF) and pigment epithelial-derived factor (PEDF) in relation to ocular angiogenesis. Materials and Methods: Human retinal pigment epithelial cell lines (ARPE-19) were cultured in Dulbeco's minimum essential medium with 10% fetal bovine serum (FBS) and exposed to varying concentrations of recombinant adiponectin (5-5 ng/ml) for 1 h. Analysis of VEGF and PEDF mRNA was done by reverse transcriptase and further quantified by quantitative polymerase chain reaction. VEGF and PEDF protein expression were studied using enzyme-linked immune sorbent assay (ELISA). Statistical Analysis: Unpaired Student's t-test was used to analyze the significance. P < 0.05 was accepted as statistically significant. Results: ARPE cells exposed to APN showed decreased expression of VEGF mRNA, protein whereas PEDF protein is unaltered and PEDF mRNA was increased. Conclusion: Our in vitro study on ARPE exposed to APN showed a negative correlation with VEGF levels. Thus indicating the protective role for APN in angiogenesis-related diseases.
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DRUG WATCH Top

Reversible bilateral ototoxicity in a patient with chronic hepatitis B during peginterferon alpha-2a treatment p. 121
Hasan Tahsin Gozdas, Oguz Karabay
DOI:10.4103/0253-7613.150377  
Peginterferon alpha-2a (PEG IFN α-2a) is frequently used in chronic hepatitis B (CHB)treatment. Numerous adverse events can be noted during this therapy such as flu-like disease, rash, weight loss and depression. However, PEG IFN α-2a related ototoxicity seems to be an uncommon entity. Ototoxicity can be detected objectively by audiometry. In this paper, we present a case of CHB who developed reversible bilateral ototoxicity during PEG IFN α-2a treatment. Due to ototoxicity detected objectively by audiogram, treatment was ceased at sixth month and ototoxicity completely recovered one month after stopping the drug.
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Pustular drug hypersensitivity syndrome due to allopurinol p. 123
Chaker Ben Salem, Wafa Saidi, Sofiene Larif, Neila Fathallah, Raoudha Slim, Houssem Hmouda
DOI:10.4103/0253-7613.150378  
Allopurinol hypersensitivity syndrome (AHS) is a severe drug reaction. It is characterized by rash, fever, and internal organ involvement. It may present in different clinical forms. We present a case of acute generalized exanthematous pustulosis occurring as a manifestation of AHS.
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LETTERS TO THE EDITOR Top

Cost-effectiveness of the baclofen versus chlordiazepoxide in alcohol withdrawal syndrome p. 125
Sim Sai Tin, Viroj Wiwanitkit
DOI:10.4103/0253-7613.150379  
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Reply p. 125
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A cross-sectional study of adverse drug reactions reporting among doctors of a private medical college in Bihar, India p. 126
Buddhadev Panja, S Bhowmick, VR Chowrasia, Shipra Bhattacharya, RN Chatterjee, Arindam Sen, Manjula Sarkar, AK Ram, PK Mukherjee
DOI:10.4103/0253-7613.150382  
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