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   Table of Contents - Current issue
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November-December 2016
Volume 48 | Issue 6
Page Nos. 615-742

Online since Tuesday, November 29, 2016

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EDITORIAL  

Online pharmacies: A boon or bane? p. 615
Chetna Desai
DOI:10.4103/0253-7613.194865  
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REVIEW ARTICLE Top

Pain on propofol injection: Causes and remedies p. 617
Kalindi Anil Desousa
DOI:10.4103/0253-7613.194845  
Pain on propofol injection (POPI) is a minor problem that all anesthetists face every day. Introduction of several new formulations and hundreds of clinical trials have failed to find its remedy with just one intervention in all patients. This article highlights the causes of POPI and interventions that are used to eliminate this pain in current practice. Relevant articles from Medline and Embase databases were searched and included in this descriptive review with the following conclusions: (1) POPI is due to irritation of venous adventitia leading to release of mediators such as kininogen from kinin cascade. (2) When two or more drugs or measures are used, the incidence of POPI decreases considerably. Hence, the approach to eliminating POPI should be multimodal. (3) Any regimen that includes a drug having local anesthetic effect combined with central sedative/analgesic and rapid injection into a large vein should definitely reduce the risk of POPI to negligible levels.
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EDUCATIONAL FORUM Top

Pharmacovigilance Programme of India: Recent developments and future perspectives Highly accessed article p. 624
Vivekanandan Kalaiselvan, Prasad Thota, Gyanendra Nath Singh
DOI:10.4103/0253-7613.194855  
Promoting safe use of medicines is a priority of Indian Pharmacopoeia Commission that functions as the National Coordination Center (NCC) for Pharmacovigilance Programme of India (PvPI). One hundred and seventy-nine adverse drug reactions (ADRs) monitoring centers currently report ADRs to NCC. Current India contribution to global safety database reaches 3% and the completeness score is 0.93 out of 1. NCC is taking several measures to enhance patient safety including capacity building for monitoring, surveillance, collaboration with national health programs and other organizations to increase ADR reporting and to ensure that PvPI is a vital knowledge database for Indian regulators. The Central Drugs Standard Control Organization has notified important safety label changes on drugs such as carbamazepine and piperacillin + tazobactam in the year 2015, other drugs are under monitoring for regulatory interventions.
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Novel strategies for Alzheimer's disease treatment: An overview of anti-amyloid beta monoclonal antibodies Highly accessed article p. 629
Katarzyna Rygiel
DOI:10.4103/0253-7613.194867  
Alzheimer's disease (AD) is a multifactorial, progressive neurodegenerative disorder with a poor prognosis, and thus, novel therapies for AD are certainly needed in a growing population of elderly patients or asymptomatic individuals, who are at risk for AD, worldwide. It has been established that some AD biomarkers such as amyloid-beta load in the brain, precede the onset of the disease, by approximately 20 years. Therefore, the therapy to prevent or effectively treat AD has to be initiated before the emergence of symptoms. A goal of this review is to present the results of recent clinical trials on monoclonal antibodies against amyloid beta, used for the treatment of AD and also to address some of the current challenges and emerging strategies to prevent AD. In recent trials, a monoclonal antibody, i.e. solanezumab has shown some beneficial cognitive effects among mild AD patients. Ongoing studies with gantenerumab and crenezumab will examine when exactly the AD treatment, aimed at modifying the disease course has to be started. This review was based on Medline database search for trials on passive anti-AD immunotherapy, for which the main timeframe was set from 2012 to 2015.
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RESEARCH ARTICLES Top

Genistein synergizes centchroman action in human breast cancer cells p. 637
Shweta Kaushik, Hari Shyam, Ramesh Sharma, Anil K Balapure
DOI:10.4103/0253-7613.194852  
Objectives: Despite the progress in the diagnosis and treatment of breast cancer, it remains a major health problem in women. Natural flavones along with chemotherapeutic agents enhance therapeutic response and minimize toxicity of chemical agents. Centchroman (CC) colloquially called as ormeloxifene, is a nonsteroidal oral contraceptive categorized as selective estrogen receptor modulator with anti-breast cancer activity. Genistein (GN), an isoflavone found mainly in soy products possesses anti-cancerous potential against a number of cancers including breast. The present study aims at investigating the combination of CC and GN in human breast cancer cell lines (HBCCs). Materials and Methods: Cytotoxic effect of CC and GN separately and in combination were assessed by sulforhodamine B (SRB) assay in MDA MB-231, MDA MB-468, MCF-7, T-47D HBCCs, and nontumorigenic human mammary epithelial cell (HMEC) MCF-10A. The drug interaction was analyzed using CompuSyn software through which combination index and dose reduction index were generated. Results: Combination of CC plus GN exerts significantly higher cytotoxicity compared to each drug per se in HBCCs, whereas HMEC-MCF-10A remains unaffected. Conclusion: On an overall basis, the drugs in combination enhanced cell killing in malignant cells. Therefore, the combination of CC with GN may offer a novel approach for the breast cancer.
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Oropharyngeal aspiration of bleomycin: An alternative experimental model of pulmonary fibrosis developed in Swiss mice p. 643
Swarna Bale, Manoj Sunkoju, Shiva Shankar Reddy, Veerabhadra Swamy, Chandraiah Godugu
DOI:10.4103/0253-7613.194859  
Objective: Pulmonary fibrosis (PF) is a progressive and predominantly lethal form of several interstitial lung diseases with limited current therapeutics; it is, therefore, essential to develop a simple, homogeneous, and noninvasive disease model to investigate possible anti-fibrotic approaches. The present study is designed to develop oropharyngeal aspiration (OPA) model of bleomycin (BLM)-induced PF as a simple and alternative to intratracheal (IT) administration of BLM in Swiss mice strain. Materials and Methods: Mice were divided into two groups, BLM-treated and normal control. BLM via OPA (2 IU/kg) was used to induce PF. Water for injection was used as a vehicle in control animals. Body weights were measured once in a week, and the study was continued for 21 days. At the end of the study, animals were euthanized and bronchoalveolar lavage fluid was collected and subjected to lymphocytes count, estimation of albumin and protein levels. Lung tissues were collected, and various biochemical assays (malondialdehyde, glutathione, nitric oxide, hydroxyproline) and molecular techniques including ELISA and Western blot were performed to investigate the effect of OPA-BLM. Further, histopathology and Masson's trichrome staining techniques were performed in lung sections. Results: OPA administration of BLM in Swiss mice significantly induced PF, evident from lung index and morphology. Several oxidative stress parameters and hydroxyproline assay revealed the significant (P < 0.05) induction of PF. Further results obtained from histopathology, Masson's trichrome staining, ELISA, and Western blot confirmed the significant induction of PF via OPA-BLM. Conclusion: BLM administration by OPA route in Swiss mice can be used as a simple, homogeneous, and noninvasive model of inducing PF and to investigate the effect of various anti-fibrotic agents as an alternative to IT-BLM.
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Comparison of efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine in patients of allergic rhinitis: A randomized, double-blind clinical trial p. 649
Mohini Sachin Mahatme, Ganesh Natthuji Dakhale, Kanchan Tadke, Sachin Keshaorao Hiware, SD Dudhgaonkar, Sumit Wankhede
DOI:10.4103/0253-7613.194854  
Objectives: Allergic rhinitis (AR) is a global health problem. Almost 10%–25% of population worldwide is affected by AR. Oral/intranasal H1-antihistamine, decongestants, leukotriene receptor antagonists, and intranasal corticosteroids are the pillars in the management of AR. The combination therapy of montelukast with antihistaminic provides enhancing and complimentary effects, thereby reducing the symptoms effectively, but there are scanty data regarding the comparisons of combinations. Therefore, we aimed to compare the efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine combination in patients of AR. Materials and Methods: Seventy patients with AR participated in a prospective, randomized, double-blind, parallel, active-controlled, comparative 4-week trial. The patients between the age group of 18–65 years of either gender having moderate-severe intermittent or mild persistent AR were included in the study. The study inclusion criteria required the patients with total nasal symptom score (TNSS) of 5 or higher. The patients were randomly divided into two treatment groups with montelukast-levocetirizine (10 mg and 5 mg) in one group and montelukast-fexofenadine (10 mg and 120 mg) in another group. TNSS parameter was the main effectiveness parameter. Results: Evaluation of TNSS revealed significant difference (P < 0.05) when compared from baseline to 4th week in both groups. The mean change of TNSS, i.e., 9.46 was significant (P < 0.05) in montelukast-fexofenadine group. The cost-effectiveness ratio was less in montelukast-levocetirizine group than in montelukast-fexofenadine group. Conclusion: The decrease in TNSS was more in montelukast-fexofenadine group, but the cost-effectiveness is more with montelukast-levocetirizine combination.
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Randomized, double-blind, comparative study of oral metronidazole and tinidazole in treatment of bacterial vaginosis p. 654
Indu M Raja, Asha Basavareddy, Deepali Mukherjee, Bikash Ranjan Meher
DOI:10.4103/0253-7613.194843  
Objective: To compare the efficacy and tolerability of oral metronidazole and tinidazole in patients with bacterial vaginosis (BV) using Amsel's criteria. Patients and Methods: This was a randomized double-blind study, conducted by the Departments of Pharmacology and Gynecology of a tertiary care teaching hospital. Patients diagnosed with BV received either tablet metronidazole 500 mg twice daily for 5 days or tablet tinidazole 500 mg once daily + one placebo for 5 days and instructed to come for follow-up at the 1st week and 4th week. They were categorized as cured, partially cured, and not cured based on Amsel's criteria at the end of the study and compared between two groups using Chi-square test. Results: A total 120 women were enrolled in the study, of which 114 completed the study. The treatment arms were comparable. The cure rate with low-dose tinidazole was significantly more compared to metronidazole at 4th week (P = 0.0013), but not at 1st week (P = 0.242). The adverse drug reactions were less with tinidazole compared to metronidazole. Conclusion: Tinidazole at lower dose offers a better efficacy than metronidazole in long-term cure rates and in preventing relapses with better side effect profile.
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Efficacy and tolerability of topical sertaconazole versus topical terbinafine in localized dermatophytosis: A randomized, observer-blind, parallel group study p. 659
Dattatreyo Chatterjee, Sudip Kumar Ghosh, Sukanta Sen, Saswati Sarkar, Avijit Hazra, Radharaman De
DOI:10.4103/0253-7613.194850  
Objective: Epidermal dermatophyte infections most commonly manifest as tinea corporis or tinea cruris. Topical azole antifungals are commonly used in their treatment but literature suggests that most require twice-daily application and provide lower cure rates than the allylamine antifungal terbinafine. We conducted a head-to-head comparison of the effectiveness of the once-daily topical azole, sertaconazole, with terbinafine in these infections. Materials and Methods: We conducted a randomized, observer-blind, parallel group study (Clinical Trial Registry India [CTRI]/2014/09/005029) with adult patients of either sex presenting with localized lesions. The clinical diagnosis was confirmed by potassium hydroxide smear microscopy of skin scrapings. After baseline assessment of erythema, scaling, and pruritus, patients applied either of the two study drugs once daily for 2 weeks. If clinical cure was not seen at 2 weeks, but improvement was noted, application was continued for further 2 weeks. Patients deemed to be clinical failure at 2 weeks were switched to oral antifungals. Results: Overall 88 patients on sertaconazole and 91 on terbinafine were analyzed. At 2 weeks, the clinical cure rates were comparable at 77.27% (95% confidence interval [CI]: 68.52%–86.03%) for sertaconazole and 73.63% (95% CI 64.57%–82.68%) for terbinafine (P = 0.606). Fourteen patients in either group improved and on further treatment showed complete healing by another 2 weeks. The final cure rate at 4 weeks was also comparable at 93.18% (95% CI 88.75%–97.62%) and 89.01% (95% CI 82.59%–95.44%), respectively (P = 0.914). At 2 weeks, 6 (6.82%) sertaconazole and 10 (10.99%) terbinafine recipients were considered as “clinical failure.” Tolerability of both preparations was excellent. Conclusion: Despite the limitations of an observer-blind study without microbiological support, the results suggest that once-daily topical sertaconazole is as effective as terbinafine in localized tinea infections.
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Impact of oral contraceptive pills on central corneal thickness in young women p. 665
Bengi Ece Kurtul, Besime Inal, Pinar Altiaylik Ozer, Emrah Utku Kabatas
DOI:10.4103/0253-7613.194860  
Objectives: Hormonal changes during oral contraceptive pill (OCP) use may affect central corneal thickness (CCT) values. We aimed to evaluate the impact of OCP use on CCT values in healthy young women. Materials and Methods: Fifty women subjects who use OCP for contraception (Group 1) and forty control subjects (Group 2) who do not use OCP were included in this prospective study. None of the patients had any history of systemic or ocular diseases. The CCT values measured by ultrasonic pachymeter (Nidek US-4000 Echoscan, Japan) and the intraocular pressure (IOP) values were measured by noncontact tonometer (Reichert 7 CR Corneal Response Technology, USA) at the time of admission to our clinic. The demographic findings and body mass index (BMI) scores of participants were also recorded. Results: The mean ages were 32.8 ± 5.6 for OCP + patients (Group 1) and 31.3 ± 6.9 for OCP-patients (Group 2) (P = 0.28). The mean CCT values were significantly higher in Group 1 when compared to that of the Group 2 (540.9 ± 30.4 μm and 519.6 ± 35.6 μm, respectively) (P = 0.003). The mean IOP value was 14.3 ± 2.5 mmHg in Group 1 and 14.4 ± 2.7 mmHg in Group 2 (P = 0.96). The mean BMI scores were 24.4 ± 5.8 kg/m2 in Group 1 and 24.6 ± 3.5 kg/m2 in Group 2 (P = 0.83). Conclusion: Our findings revealed that CCT values were significantly higher in patients with OCP use. Ophthalmologists should be aware of potential elevated CCT levels in these patients.
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Antifertility activity of Thevetia peruviana (Pers.) K. Schum leaf in female Sprague-Dawley rat p. 669
Jhuma Samanta, Snehendu Bhattacharya, Avtar C Rana
DOI:10.4103/0253-7613.194861  
Objectives: Thevetia peruviana (Pers.) K. Schum. (Apocynaceae) is known to possess cardioactive glycoside such as thevetin A, thevetin B, neriifolin, peruvoside, thevetoxin, and ruvoside. Traditionally, T. peruviana leaves are used as abortifacient. The aim of the present study is to evaluate antifertility potential of T. peruviana leaves. Subjects and Methods: Cardiac glycoside freed leaves of T. peruviana were extracted with methanol using maceration method. The dried cardiac glycoside-free methanolic extract of T. peruviana leaves (TPL-Me-G) was screened for phytoconstituents and evaluated for its effect on estrogen-primed female Sprague-Dawley rat uterus model. It was further studied for effects on the estrous cycle, implantation, and effect on estrogen and progesterone. Statistical Analysis Used: Statistical analysis was done by ANOVA followed by Dunnett's t-test. Results: Alkaloids, flavonoids, essential oils, carbohydrates, and amino acids were found to be present in the glycoside-free extract. Thin-layer chromatography (TLC) in n-butanol: acetone: water (4:1:5) revealed the presence of quercetin and kaempferol. The presence of flavonoids (quercetin 0.0326% and kaempferol 0.138% on dry weight basis) was reconfirmed by high-performance TLC analysis. The extract was able to induce uterine contractions (EC50, 0.170 mg/ml) in a dose-dependent manner. Further investigation showed significant (P < 0.001) extension of estrous cycle and anti-implantation activity of the extract by reduction of the progesterone level. Conclusions: Methanolic extract of T. peruviana leaves (TPL-Me-G) containing quercetin 0.0326% and kaempferol 0.138% possesses a significant (P < 0.001) antifertility potential by virtue of decreasing the progesterone level.
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Modulation of hippocampal gene expression of microRNA-146a/microRNA-155-nuclear factor-kappa B inflammatory signaling by troxerutin in healthy and diabetic rats p. 675
Raana Yavari, Reza Badalzadeh, Mohammad Reza Alipour, Seyed Mahmoud Tabatabaei
DOI:10.4103/0253-7613.194847  
Objectives: Inflammation plays a critical role in the progression of diabetic complications such as neurological disorders. Previous reports have indicated the memory-improving effect of troxerutin, in rat hippocampus, but the underlying mechanisms are unclear. Hence, we have investigated the effect of troxerutin pretreatment on gene expressions of inflammation-related microRNAs (miRs), miR-146a and miR-155, and nuclear factor-kappa B (NF-κB) signaling pathway in the hippocampus of healthy and diabetic rats. Materials and Methods: Wistar rats were randomly divided into four groups (control, control + troxerutin, diabetic, and diabetic + troxerutin). Diabetes was induced by a single i.p. injection of streptozotocin (50 mg/kg). Troxerutin (150 mg/kg) was orally administered in animals for 1 month. After 10 weeks of diabetes, animals were anesthetized and decapitated for the isolation of hippocampus. The expression of miR-146a and miR-155 and the messenger RNA (mRNA) expressions of NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), and tumor necrosis factor receptor-associated factor-6 (TRAF-6) were analyzed by real-time polymerase chain reaction. Results: Diabetes significantly increased hippocampal mRNA levels of NF-κB, IRAK-1, and TRAF-6 compared with nondiabetic rats (P < 0.05); however, pretreatment with troxerutin decreased them in both diabetic and nondiabetic animals, independent of its glycemic effect (P < 0.05). The expression levels of miR-146a and miR-155 were decreased in diabetic group as compared to the control (P < 0.01). Conclusion: These findings showed that troxerutin could inhibit the inflammatory NF-κB pathway in the hippocampus of diabetic rats, which may be due to the negative feedback loop regulated by miR-146a.
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Anxiolytic activity of aqueous extract of Camellia sinensis in rats p. 681
Rajeshwari Shastry, Sheetal Dinkar Ullal, Shreyas Karkala, Seema Rai, Akash Gadgade
DOI:10.4103/0253-7613.194864  
Objectives: The present study was undertaken to evaluate anxiolytic effect of Camellia sinensis (CS) and possible mechanism on acute and chronic administration in rats. Materials and Methods: Eight groups of rats with six in each group were used. Group I served as control. Group II received diazepam (1 mg/kg). Groups III, IV, and V received CS in doses of 3.3, 16.5, and 33 mg/kg, respectively. Three pharmacologically validated experimental models – elevated plus maze (EPM), light and dark box (LDB), and open field tests (OFT) – were employed. Each animal was tested initially in the EPM and then in the LDB, followed by the OFT in a single setting. In EMP, number of entries into, time spent in, and number of rears in each arm in a 5-min period were noted. In LDB, number of entries and time spent in bright arena, number of rears, and duration of immobility were noted. In OFT, number of peripheral and central squares crossed, time spent, and number of rears in central squares were observed for a 5-min period. One-way ANOVA followed by post hoc least significant difference test was performed. Results: In EPM and LDB, CS at 3.3, 16.5, and 33 mg/kg (acute and chronic models) increased the number of entries and time spent and rearing in the open arms and bright arena, respectively, compared to control. In the OFT, CS at 16.5 and 33 mg/kg significantly increased the number of squares crossed, time spent, and the number of rears in the central squares compared to control. Anxiolytic effect was dose dependent in EPM and LDB and CS at 33 mg/kg showed better anxiolytic activity compared to diazepam (1 mg/kg) in all models. Flumazenil (0.5 mg/kg) and bicuculline (1 mg/kg) completely inhibited while picrotoxin (1 mg/kg) partially inhibited the anxiolytic effect of CS. Diazepam and CS at 33 mg/kg reduced the locomotor activity in rats. Conclusion: CS has dose-dependent anxiolytic activity which is comparable to diazepam. Anxiolytic action of CS is likely mediated through GABAA-benzodiazepine receptor – Cl − channel complex – since flumazenil and bicuculline inhibited the anxiolytic effect.
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Neuroprotective effect of Celastrus paniculatus on chronic stress-induced cognitive impairment p. 687
V Bhagya, Thomas Christofer, BS Shankaranarayana Rao
DOI:10.4103/0253-7613.194853  
Objective: Several studies report that chronic stress results in impaired spatial learning and working memory and enhanced anxiety-like behavior. However, not many studies have looked into the possible ways of reversing stress-induced deficits. Celastrus paniculatus (CP), a traditional ayurvedic herbal medicine, was used to treat cognitive deficits in mentally retarded children. CP oil has been reported to have neuroprotective and antioxidant activities. However, the effects of CP oil on chronic stress-induced cognitive deficits are unclear. In the present study, we intended to analyze the neuroprotective effects of CP oil on stress-associated cognitive dysfunctions. Materials and Methods: Chronic stress was induced by subjecting rats to restrainers for 6 h a day for 21 days. CP oil (400, 600 mg/kg) or vehicle was administered intraperitoneally (i.p.) after stress protocol once a day over the next 14 days. Groups used in the present study: normal control, stress, stress + vehicle, stress + CP oil at 2 different doses (400 and 600 mg/kg, i.p.). After the drug treatment, open field and elevated plus maze (EPM) were used to analyze anxiety-like behavior, and partially baited radial arm maze (RAM) and T-maze were used to evaluate spatial learning and memory capabilities. Analysis has been done using two-way ANOVA followed by Bonferroni's post hoc test and one-way ANOVA followed by Tukey's post hoc test. Results: Stressed rats showed enhanced anxiety-like behavior in EPM (P < 0.001) and impaired performance in RAM (P < 0.001) and T-maze tasks (P < 0.001) compared to normal animals. In contrast, CP oil treatment to these rats improved their performance in both RAM (P < 0.001) and T-maze (P < 0.001). In addition, CP oil significantly reduced stress-induced anxiety behavior (P < 0.001). Conclusion: Chronic treatment with CP oil is to improve cognitive abilities in chronically stressed rats. The current study provides a novel perspective on beneficial effect of herbal therapy on stress-induced cognitive dysfunctions.
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Cerebroprotective activity of Pentapetes phoenicea on global cerebral ischemia in rats p. 694
Koneru Naga Sravanthi, Nadendla Rama Rao
DOI:10.4103/0253-7613.194849  
Objectives: The study was performed to evaluate the cerebroprotective activity of methanolic extract (ME) of Pentapetes phoenicea - a folk medicine used as anti-inflammatory and in central nervous system ailments. It has high phenolic and flavonoid contents including rutin. Materials and Methods: Global cerebral ischemia was induced in male albino Wistar rats by temporary bilateral carotid artery occlusion (BCAO) for 30 min, followed by 4 h reperfusion. Groups of rats were pretreated for 10 days with 100, 200, and 400 mg/kg of ME of P. phoenicea and 3 mg/kg of edaravone, a marketed cerebroprotective agent, as standard. Antioxidant enzymes such as, the levels of malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and hydrogen peroxide (H2O2), protein content, brain water content, cerebral infarct size and the histopathological changes were measured. Results: P. phoenicea-pretreated groups restored the biochemical parameters significantly in a dose-dependent manner. The ischemic changes were involved with an increase in the concentration of MDA and H2O2, followed by decreased SOD, CAT, GPx, GR, and GST activity in rat brain. The neurodegenaration and its attenuation by P. phoenicea were confirmed by examination of triphenyl tetrazolium chloride staining and histopathological changes in the cerebral ischemic rat brains. Similarly, P. phoenicea reversed the brain water content in the ischemia-reperfusion animals. Conclusion: The result of the study indicates that the treatment with P. phoenicea enhances the antioxidant defense against BCAO-induced global cerebral ischemia/reperfusion and exerts cerebroprotection.
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Assessment of impact of pharmacophilia and pharmacophobia on medication adherence in patients with psychiatric disorders: A cross-sectional study p. 701
Mini Johnson Christudas, Balaji Sathyanarayana Gupta, Krishna Undela, Noel M Isaac, Dushad Ram, Madhan Ramesh
DOI:10.4103/0253-7613.194858  
Aims: To investigate the impact of pharmacophilia and pharmacophobia on medication adherence among patients with psychiatric disorders. Materials and Methods: A cross-sectional, observational study was conducted in the Department of Psychiatry over a period of 2 months. Patients above 18 years of age with a psychiatric diagnosis as per the International Classification of Diseases 10 and receiving at least one psychotropic medication (any medication capable of affecting the mind, emotions, and behavior) for >1 month were enrolled in the study. Patients who were critically ill, on magico-religious treatment (beliefs prevalent in a particular culture concerning various supernatural influences operating in the environment), diagnosis of dementia, or mental retardation and patients from whom reliable history of illness cannot be obtained were excluded from the study. Drug attitude inventory scale was used to classify patients into pharmacophilic and pharmacophobic groups. Medication adherence rating scale was used to identify the extent of medication adherence. Results: Among 176 patients included, 110 were found to be pharmacophilic and 54 were pharmacophobic. The number of hospitalizations (P < 0.03) and adverse drug reactions (P < 0.001) were found to be higher in pharmacophobic group as compared to pharmacophilic group. Antipsychotics were found to be most commonly prescribed medications among pharmacophobic group (P < 0.001). In this study, patients who had pharmacophilia were found to be have higher adherence score (mean score: 6.98) than patients with pharmacophobia (mean score: 2.9), with P< 0.001. Conclusions: This study concluded that pharmacophobia toward psychopharmacological agents can significantly reduce the medication adherence among patients with psychiatric disorders.
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SHORT COMMUNICATIONS Top

Clinical effectiveness and safety of low cost versus innovator brand amlodipine in hypertension: A single-blinded, randomized, crossover, noninferiority trial p. 706
Alak Kumar Das, Suparna Chatterjee, Jyotirmoy Pal
DOI:10.4103/0253-7613.194844  
Objectives: A single-blinded, randomized, crossover, noninferiority trial was conducted to evaluate clinical effectiveness and safety of low-cost brand (LCB) versus innovator brand (IB) amlodipine in essential hypertension. Materials and Methods: The primary end-point was change of systolic blood pressure (BP) from baseline to study end. Adult patients with Stage 1 hypertension or isolated systolic hypertension were randomized to receive 5 mg amlodipine LCB or IB once daily for 6 weeks in each period in a 2 × 2 crossover manner with three follow-up visits in each sequence. In 28 evaluable patients, the reduction of systolic BP (SBP), diastolic BP, and safety profile between two brands was comparable. Results: The lower bound of the 95% confidence interval of the difference in reduction of SBP (−5.04 mmHg) was within the noninferiority margin of 10 mmHg. Conclusion: LCB amlodipine is noninferior to IB in terms of BP reduction and is a cost-effective alternative as it is less expensive than IB.
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In vitro effectiveness of triterpenoids and their synergistic effect with antibiotics against Staphylococcus aureus strains p. 710
Muhammad Hamza, Maha Nadir, Nadir Mehmood, Adeel Farooq
DOI:10.4103/0253-7613.194851  
Objectives: The aim of this study is to evaluate the effect of four triterpenoids such as oleanolic acid, ursolic acid, cycloastragenol, and beta-boswellic acid alone and in combination with antibiotics against Staphylococcus aureus strains. Materials and Methods: Sixteen clinical strains of S. aureus from infected wounds were isolated. Eight were methicillin-sensitive S. aureus (MSSA), and the other eight were methicillin-resistant S. aureus (MRSA). The activity was also seen in reference S. aureus American Type Culture Collection strains. The activity of all the triterpenoids and antibiotics against S. aureus was evaluated by broth microdilution method. The effectiveness was judged by comparing the minimum inhibitory concentrations (MICs) of the compounds with antibiotics. The combination of antibiotics with compounds was evaluated by their fractional inhibitory concentrations (FIC). Results: Against both clinical and reference MSSA strains, none of the compounds exhibited comparable activity to antibiotics vancomycin or cefradine except for ursolic acid (MIC 7.8 μg/ml). Against MRSA, all compounds (MIC 16–128 μg/ml) showed lesser activity than vancomycin (MIC 5.8 μg/ml). Among triterpenoid-antibiotic combinations, the most effective were ursolic acid and vancomycin against clinical strain MSSA (FICS 0.17). However, overall, different combinations between triterpenoids and antibiotics showed 95%–46% (P < 0.05) reduction in MICs of antibiotics compared to when antibiotics were used alone. Cefradine, a drug not suitable for treating MRSA (MIC = 45 μg/ml), showed a remarkable decrease in its MIC (87% P< 0.01) when it was used in combination with oleanolic acid or ursolic acid in both clinical and reference strains. Conclusion: The tested triterpenoids are relatively weaker than antibiotics. However, when used in combination with antibiotics, they showed remarkable synergistic effect and thus can help in prolonging the viability of these antibiotics against S. aureus infections. Furthermore, reduction in MIC of cefradine with oleanolic acid indicates their potential use against MRSA.
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Lactogenic activity of Teramnus labialis (Linn.) fruit with special reference to the estimation of serum prolactin and cortisol level in nursing rats p. 715
Himanshu Bhusan Sahoo, Amrita Bhaiji, Dev Das Santani
DOI:10.4103/0253-7613.194856  
Aim: The objective of the study was to investigate the lactogenic activity of methanolic extract of Teramnus labialis (L.) fruit (MTLF) on rats. Subjects and Methods: Nursing rats (200–250 g) with their suckling pups were selected and were divided into five groups (n = 6). Group I treated as control (distil water); Group II treated as standard (domperidone), and Group III, IV, and V were orally administered with MTLF at 200, 400, and 600 mg/kg body weight, respectively and continued for l4th day of parturition. Milk yield, the pups as well as mother's weight were measured daily. On 15th day, the total protein/carbohydrate contents from mammary tissue and serum prolactin/cortisol level from blood sample were measured and compared with control. Results: Oral administration of MTLF increases the milk yield, body weight of pups as well as mother rat, glycogen, and protein content as well as serum prolactin and cortisol level as compared to the control animals. In addition, the lactogenic effect of MTLF was followed dose-dependent manner as compared to control. Conclusions: The present study was revealed that the MTLF possesses significant lactogenic activity by enhancing milk production and prolactin concentration in nursing rats.
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Antigenotoxic and apoptotic activities of essential oil of Atalantia monophylla Correa p. 720
Ramaraj Thirugnanasampandan, Gunasekar Ramya, Madusudhanan Gogulramnath
DOI:10.4103/0253-7613.194866  
Objective: To study antigenotoxic and apoptotic activities of hydrodistilled essential oil from the leaves of Atalantia monophylla Correa. Materials and Methods: Antigenotoxic activity of essential oil was tested against hydrogen peroxide (100 μM)-induced deoxyribonucleic acid (DNA) damage in 3T3-L1 cells. Cervical cancer cell (HeLa) growth inhibitory effect of essential oil was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI), Hoechst 33258, and acridine orange/ethidium bromide (AO/EtBr) staining techniques were used to identify apoptosis. Results: DNA protecting the activity of A. monophylla essential oil was high at 125 μg/mL. HeLa cell growth was inhibited dose-dependently and inhibitory concentration 50% was calculated as 43.08 ± 0.02 μg/mL. Annexin V-FITC/PI double staining showed membrane breakage and nuclei staining. Further, Hoechst 33258 and AO/EtBr stain also confirmed the apoptosis in essential oil-treated HeLa cells. Conclusion: The results obtained suggest that A. monophylla essential oil is a promising natural agent which may be used in preparation of herbal medicine to treat cancer and other diseases.
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Comparison of the knowledge, attitude, and practices of doctors, nurses, and pharmacists regarding the use of expired and disposal of unused medicines in Delhi p. 725
Kriti Bhayana, Harmeet Singh Rehan, Tarun Arora
DOI:10.4103/0253-7613.194846  
Objectives: The use of out-of-date medicines and improper disposal of pharmaceutical products harm consumers and environment. To limit pharmaceutical load on the environment, it is important that healthcare professionals (HCPs) are aware of and have good practices toward their disposal. Materials and Methods: A pretested instructor administered questionnaire containing 21 questions was used to assess knowledge, attitude, and practices (KAP) of 300 HCPs toward use and disposal of unwanted/expired medicines. Results: Nurses (76%) had significantly (P < 0.01) better knowledge over doctors regarding the methods of drug disposal, whereas both doctors (63%) and nurses (64%) knew significantly (P < 0.05) more than pharmacists about type of formulations not to be incinerated. The majority (88%) of overall respondents were unaware of validity of dispensing medicines before 15 days of mentioned expiry date. A large proportion of HCPs had a positive attitude toward checking the expiry date of medicines (96%), and a significant proportion of doctors and nurses believed that drug disposal is everyone's responsibility. Only 8% of the HCPs received unused/expired drugs back from the consumers. Nurses (59%) had better (P < 0.01) practice than pharmacists regarding the disposal of expired medicines. Nearly half (44%) of all HCPs agreed that there existed a system for removing expiry and unused medicines from the inventory. Conclusions: The KAP of HCPs toward use and disposal of out-of-date and unused medicines need upgrading. The existing guidelines should be implemented to ensure patients' safety and to preserve the ecosystem.
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Perception of pharmacists regarding over-the-counter medication: A survey p. 729
Abinaya Ravichandran, Asha Basavareddy
DOI:10.4103/0253-7613.194857  
Objective: To assess knowledge, attitude, and practice of the pharmacists toward dispensing the over-the-counter (OTC) medications using questionnaire. Materials and Methods: cross-sectional questionnaire-based study was conducted to assess the knowledge, attitude, and practice among pharmacists regarding OTC medications. Eighty out of hundred filled questionnaires were received from various pharmacists from medical shops in and around Kolar. Data were analyzed using descriptive statistics. Results: A total of 74.6% responded to the questionnaire. Most of the dispensers (97.3%) at pharmacy were qualified with a D.Pharma/B.Pharma degree. Pharmacists with B.Pharma (80%) were able to define OTC. Majority of them had more than ten consumers taking OTC per week. Among the OTCs dispensed, common were analgesics (75%), antacids (48%), antihistaminics (40%), and others (35%). The choice of OTC brand was made by pharmacists (58.7%) and consumers (41.2%). Most of them (96.5%) asked the consumer's complaints before dispensing the drug, but only few (51%) counseled them regarding the instructions to administer medication. The brand of OTC was influenced by prescriptions of local doctor (60%), consumer's choice (31.2%), cost of the drug (16.7%), and medical representatives (5%). OTCs were safe to dispense, according to 90% of the pharmacists; however, among them, 50% expressed that the consumers should first consult doctor. Conclusion: Majority of the pharmacists were qualified to dispense medication, but only few knew about OTC drugs. Analgesics were most commonly used OTC. These drugs were safe to dispense, however, consulting doctor before taking medications was suggested by some of them.
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Antidepressants triggering suicidal ideation: An area of concern p. 733
Himali Rajgadhi, Sapna Gupta, Supriya Deepak Malhotra, Advait Thakor, Pankaj Patel
DOI:10.4103/0253-7613.194842  
This is a report of four cases of possible suicidal ideation with the use of antidepressants in Indian population. The patients presented to emergency department of a tertiary care hospital with attempted suicide. All of them were prescribed at least one antidepressant. The association of increased suicidal attempts/ideation with antidepressant drugs themselves has been reported in the West, but data in the Indian population are lacking. Antidepressants are widely used not only for treatment of depression but also many other psychiatric illnesses; it is yet unclear whether suicidal ideation is because of these drugs or the progression of the disease. Hence, careful prescribing of these medicines is warranted.
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Seizure following chemotherapy (paclitaxel and cisplatin) in a patient of carcinoma cervix p. 736
Rohitashwa Dana, RK Spartacus, Shweta Mutha, Prashanth Bhat
DOI:10.4103/0253-7613.194863  
Cisplatin and paclitaxel both can cause peripheral neurotoxicity as an adverse effect; however, central nervous system neurotoxicity in the form of seizures is rare. We report a case of a 36-year-old female patient of metastatic carcinoma cervix, who developed seizure shortly after cisplatin infusion. Her laboratory investigations were within normal limits. Computed tomography scan and magnetic resonance imaging of the brain did not reveal brain primary metastasis or meningeal carcinomatosis. She had no complaints of fever, no signs and symptoms of infection, and no history of seizure nor was she on any medication predisposing to such an event. Excluding several causes, seizure was thought to be most likely related to the chemotherapy and cisplatin was the more likely agent in view of observed temporal relationship with the adverse event.
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Ibuprofen-induced Henoch–Schönlein purpura nephritis: First reported case p. 739
Christopher Lim Thiam Seong, Malini Shanmuganathan
DOI:10.4103/0253-7613.194848  
Ibuprofen is a nonsteroidal anti-inflammatory drug that is used widely in treating pain, fever, and inflammation. Its side effects are mainly due to acute renal impairment and gastric discomfort. We hereby report a rare case of Henoch–Schönlein purpura nephritis secondary to ibuprofen consumption which has not been reported in literature before.
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Eyelid and feet edema induced by pemetrexed p. 741
Sarrah Kastalli, Ons Charfi, Rym Sahnoun, Ghozlane Lakhoua
DOI:10.4103/0253-7613.194862  
Pemetrexed is an anti-metabolite that targets multiple enzymes in folate pathway. The main toxicities associated with pemetrexed are asthenia, nausea, diarrhea, myelosuppression, and rash. Few cases of pemetrexed induced cutaneous adverse event have been reported, mainly periorbital-facial edema and edema of the limbs. We report a case of pemetrexed-induced edema of the eyelid and feet in a patient with adenocarcinoma of the lung.
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