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Year : 2011  |  Volume : 43  |  Issue : 7  |  Page : 197--201

G-Achari Prize Paper Abstracts


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. G-Achari Prize Paper Abstracts.Indian J Pharmacol 2011;43:197-201

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. G-Achari Prize Paper Abstracts. Indian J Pharmacol [serial online] 2011 [cited 2021 Jan 21 ];43:197-201
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G Achari Prize -1

Evaluation of antidepressant activity of simvastatin and lovastatin in male swiss mice - an experimental study

Anupama Gudadappanavar , S.V. Hiremath, S.S. Torgal

Department of Pharmacology, J.N. Medical College, KLE University, Belgaum - 590 010, Karnataka.

Objective: To investigate the effect of simvastatin and lovastatin for their antidepressant activity using forced swim test and tail suspension test on behavioral models of depression in male swiss mice. Materials and Methods: The in vivo antidepressant activity of simvastatin and lovastatin was studied using forced swim test and tail suspension test behavior models of depression. Group mean immobility time was calculated in treated and control groups for comparison. Results: Simvastatin and Lovastatin used in the present study showed significant antidepressant activity in both behavioral models of depression. Conclusion : The antidepressant activity of simvastatin as well as lovastatin, could be of therapeutic potential for patients with major depression, especially those who have dyslipidaemia or comorbidities relating to cardiovascular diseases. They can also be of benefit in the treatment of other neuropsychiatric disorders associated with disturbed BDNF (Brain-derived Neurotropic Factor) signaling, such as attention-deficit hyperactivity disorder and Rett syndrome. Key words : Amitriptyline, BDNF, depression, lovastatin, simvastatin

G Achari Prize -2

Single nucleotide polymorphisms of CYP3A5 AND P2Y12 contributes to clopidogrel resistance in coronary artery disease patients

Priyadharsini R, Subraja K, Satheesh S 1 , Sridhar MG 2 , Dkhar SA, Adithan C, Shewade DG

Departments of Pharmacology, 1 Cardiology, and 2 Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry - 605 006, India

Objectives: Clopidogrel is one of the antiplatelet agents used for treatment and prophylaxis of coronary artery disease. Clopidogrel resistance is an emerging situation in clinical settings. The aim of the study is to assess the effect of genetic polymorphisms of CYP3A5 and P2Y12 on clopidogrel resistance. Materials and Methods: 152 patients from outpatient departments of Cardiology on 75 mg/day clopidogrel were recruited from January 2010 to July 2011. All subjects gave written informed consent to participate in the study. DNA extraction was done using phenol chloroform extraction procedure and genotyping by standard PCR-RFLP and qRT- PCR method. Platelet aggregation was done at the end of 7 th and 14 th day by using chronolog lumi aggregometer. Impedance value of ≥5 ohms at the end of 6 minutes considered as clopidogrel resistance. Results: 147 subjects were analysed for CYP3A5*3 and 149 for P2Y12 polymorphism, of which 49 (33%) were found to be clopidogrel resistant. Homomutants of CYP3A5*3 gene had 2.78 fold risk and heteromutants had 2.45 fold risk of developing clopidogrel resistance. Carriers of defective allele G of CYP3A5 *3 had higher propensity to cause clopidogrel resistance with an odds ratio of 1.63. CT and CC genotypes of P2Y12 had a 2.2 fold risk of developing clopidogrel resistance and subjects with defective C allele had a 2 fold risk. Further, the combinations of C and G allele had 1.62 fold risk of developing clopidogrel resistance. Conclusion: Variant alleles and genotypes of CYP3A5*3 and P2Y12 genetic polymorphisms contributed significantly to clopidogrel resistance with a higher hazard ratio. Thus, pharmacogenomics paves way for the emergence of stratified medicine in clopidogrel therapy and personalised pharmacotherapy in ischaemic heart disease

G Achari Prize -3

A role for neuropeptide Y in morphine induced reward and reinforcement

Ashish P. Bharne, Sagar J. Desai, Manoj A. Upadhya, Dadasaheb M. Kokare, Nishikant K. Subhedar 1

Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur - 440 033, 1 Indian Institute of Science Education and Research (IISER), Central Tower, Sai Trinity Building, Garware Circle, Sutarwadi, Pashan, Pune - 411 021, Maharashtra, India.

Objectives : To investigate the role of neuropeptide Y (NPY) Y1 receptor in morphine induced reward and reinforcement in the framework of nucleus accumbens shell (AcbSh). Materials and Methods : Intra-AcbSh cannulated rats were trained in the operant chamber for self-stimulation in medial fore brain bundle (MFB) and the number of lever pressings as a sign of reward and repeated behavior indicating reinforcement. The status of endogenous NPY was evaluated in trained rats using immunocytochemistry. Results : While bilateral intra-AcbSh morphine, NPY or [Leu 31 , Pro 34 ]-NPY (NPY Y1/Y5 receptors agonist) treatment significantly increased self-stimulation, BIBP3226 (selective NPY Y1 receptors antagonist) treatment prevented the same. This effect of morphine was significantly potentiated by NPY or [Leu 31 , Pro 34 ]-NPY and antagonized by BIBP3226. Furthermore, NPY-immunoreactivity in the AcbSh, arcuate nucleus of hypothalamus and lateral part of bed nucleus of stria terminalis was increased in the rats that self-stimulated MFB in operant chamber as compared to that in the control. However, NPY-immunoreactivity was significantly decreased in all these regions following morphine treatment as compared to that in the self-stimulated rats. On the other hand, NPY-immunoreactive fibers in the hypothalamic paraventricular nucleus did not respond either to self-stimulation or morphine administration . Conclusions : The results of the present study suggest a role for endogenous NPY, via NPY Y1 receptor, in the reward and reinforcement actions of morphine within the frame work of AcbSh.

G Achari Prize -4

Effect of rifampicin, isoniazid and pyrazinamide on acute and subacute inflammation in male wistar rats- An experimental study

Priya Gandigawad, Anil P. Hogade, Hiremath SV, Torgal SS, Patil PA, Malur PR 1

Departments of Pharmacology, and 1 Pathology, J.N. Medical College, Belgaum - 590 010, India.

Objective: To study the effect of rifampicin , isoniazid , pyrazinamide on acute and subacute models of inflammation in male Wistar rats. Materials and Methods: The in vivo anti-inflammatory activity of rifampicin, isoniazid, pyrazinamide was studied using acute (carrageenan paw edema) and sub-acute (cotton pellet granuloma and histopathologic examination of grass pith) models of inflammation. Results: Rifampicin and Isoniazid used in the present study showed significant anti-inflammatory activity in acute as well as subacute models of inflammation whereas pyrazinamide failed to show significant anti-inflammatory activity. Conclusion: Rifampicin and Isoniazid when administered to treat tuberculosis can reduce complications of tuberculosis like pulmonary fibrosis, constrictive pericarditis etc by virtue of their anti-inflammatory activity. So daily dosing of these drugs may be more useful than thrice weekly dosing. Key words: Aspirin, inflammation, isoniazid, pyrazinamide, rifampicin

G-Achari Prize -5

Evaluation of antidepressant activity of piracetam in experimental models of behavioral despair

Gokhale VS, Bhide SS, Jalgaonkar SV, Marathe PA, Khan MF, Rege NN.

Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Mumbai, India

Objective: To evaluate the effect of Piracetam in animal models of behavioural despair. Materials and Methods: Following Animal Ethics Committee approval, 36 Wistar rats were divided into 6 groups for 2 parts of the study i.e. acute forced swimming test (FST) and chronic FST (3 groups/ part). Groups pretreated with distilled water (vehicle control), fluoxetine 20 mg/kg (positive control) and piracetam 500 mg/kg (test drug); daily for 7 days were tested on day 7 in acute FST. For chronic FST, rats were treated for 14 days with test drugs with daily pretest and subjected to FST on day 14 Swiss albino mice (n = 18, 3 groups); pretreated with respective test drugs for 7 days were subjected to TST on day 7. Immobility time in seconds was noted in all models and the groups were compared using one-way ANOVA with post-hoc Tuckey's test (level of significance P<0.05). Results: In acute FST, the mean immobility time was significantly lower (P<0.01) in piracetam (149.17 ± 26.48) and fluoxetine (139.5 ± 19.38) groups as compared to the vehicle control (208.5 ± 48.46). In TST, immobility time was reduced significantly (P<0.01) in both piracetam (155.83 ± 45.04) and fluoxetine treated groups (154.50 ± 38.68) compared to control (240.83 ± 31.02). In chronic FST too, piracetam (155.67 ± 36.18) and fluoxetine (173.33 ± 33.47) showed significantly reduced immobility (P<0.01) than control group (239.83 ± 49.66). The duration of immobility was comparable between piracetam and fluoxetine groups in all the models. Conclusion: Piracetam at the dose of 500mg/kg was effective in models of behavioural despair.

G-Achari Prize -6

Study on effects of Piper Betle leaves (Paan) extract on Pharmacodynamic and Biochemical parameters

Pooja Reddy , R.K. Gupta

Department of Pharmacology, MGIMS, Sevagram - 442 102, Wardha District, Maharashtra, India

Piper betle leaf, commonly known as 'paan' has long been known for its various medicinal properties and has been used very commonly in traditional medicine, for e.g. in infections and in gastric ulcer, etc. Still some of its properties remain unexplored or less studied. Hence, in this study its various pharmacodynamic and biochemical properties like antinociceptive, anti-inflammatory, immunomodulatory and antioxidant activities were studied. Hydroalcoholic extract of Piper betle leaves (HEPBL) was extracted using soxhlet apparatus and was used for the study. Wistar rats and Albino mice were used for all the experiments. Before commencing the study, qualitative phytochemical constituents were observed. Acute toxicity study was also done according to OECD guideline no.425 and the test doses were decided accordingly. The experimental models used were tail-flick method and acetic acid induced writhing for analgesic study, carrageenan induced paw edema and cotton pellet granuloma for anti-inflammatory study, cyclophosphamide induced neutropenia and haemagglutination for immunomodulation, Satoh and Marklund methods for anti-oxidant activities. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Dunnett's test. HEPBL showed significant results in all the experiments in the doses of 100mg/kg and 200mg/kg in a dose-dependent manner. Although these results can be attributed to its phytochemical constituents, HEPBL needs further studies for evaluation of its mechanisms of action. In view of its various pharmacodynamic and biochemical parameters, HEPBL might prove useful in the treatment of various ailments

G-Achari Prize -7

Status of dyslipidemia management with statins, in in-patients with known coronary artery disease confirmed by angiographic findings

Vijay T , Baruah DK, Ushakiron P, Sudha J, Sudhakar K, Srinivas A.

Department of Pharmacology, Andhra Medical College, Visakhapatnam, India.

Objectives : To study whether the lipid parameters (LDL-C) are within desired levels in In-patients with known Coronary Artery Disease confirmed by angiographic findings. Materials and Methods : Retrospective analysis of data collected from the electronic medical records (in a corporate cardiac centre) in terms of the age, sex, and Coronary Artery Disease (CAD) status, associated risk factors, statin usage and lipid parameters. Results : Among a sample of 92 known CAD in-patients, 81.5% achieved LDL-C goal of <100 mg/dl as recommended by Third Report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III [ATP III] for CAD and CAD risk equivalents. Success rates among males and females are 79.7% and 85% respectively. 78.2% of 69 patients on Atorvastatin, 85% of 20 patients on Rosuvastatin and 100% of 3 patients on Simvastatin achieved LDL-C goal. If the target LDL-C level is kept at <70 mg/dl as defined as optional goal for very high risk CAD and CAD risk equivalents, the success rate is only 31.5%. Conclusion : The LDL-C goal (<100 mg/dl) achievement rate is satisfactory. But the major concern here is even with desired LDL-C levels 61% of these in-patients suffered with a recurrent CAD leaving an opportunity to reconsider the target LDL-C to still lower levels (<70 mg/dl) which is mentioned just as an optional for very high risk candidates in NCEP ATP-III guidelines. Further larger, prospective, randomised controlled clinical trials and multi-centric Indian trials involving both in-patients and out-patients have to be conducted to find the success rates, CAD recurrence rates and to fix new target levels of LDL-C and the best Statin that suits Indian scenario.

G-Achari Prize -8

Study of barriers faced by the investigators during informed consent process and comprehension of the informed consent document by the participants in a teaching hospital: questionnaire based survey

Tanuj Chawla , H.S. Rehan, Ravinder Sah, Vikram Patil,

Deepti Chopra

Department of Pharmacology, Lady Hardinge Medical College, Shaheed Bhagat Singh Marg, Opp. Shivaji Stadium, New Delhi - 110 001, India.

Objectives: There is no report in the literature assessing the informed consent (IC) taken by medical postgraduate (PG) students while doing MD/MS dissertation research work. The aim of the study was to evaluate the comprehension of the participants regarding IC document and the barriers faced by medical PG students during IC process. Materials and Methods : A total of 76 participants and 30 medical PG students were asked to answer a self administered structured questionnaire on IC procedure, for being involved in dissertation research work. Results : All the participants and PG students completed questionnaire and were enrolled. In this survey, majority of the participants (97.3%) were unaware of their involvement in the research, nature of study, risks involved and did not remember signing any IC document, hence not understood the IC process. Majority (64%) of participants received education till 10 th grade. Majority of PG students (90%) claimed that they had obtained written IC from their participants and all of them discussed the study details. PG students (66%) informed that risks involved in the study was frequently asked question by the participants followed by study procedure related queries (43%). Commonly reported barriers by the PG students were poor comprehension by the participants (70%), lack of time in explaining IC document (46%), detailed IC document (33%) and language (30%). Conclusion: The current IC process is insufficient and not understandable by the participants. The barriers for poor understanding of the participants need to be addressed

G-Achari Prize -9

In-silico and in-vivo validation of herbal and nutraceutical combination as anti-inflammatory agent

Chetan C. Nimgulkar, Raju Naik Vankudavath, Sudip Ghosh, K. Bhaskarachary, B. Dinesh Kumar

Food and Drug Toxicology Research Centre, National Institute of Nutrition, Indian Council of Medical Research (ICMR) Jamai Osmania, Hyderabad 500 007, India.

E-mail: [email protected]

Introduction : Among the various advances in technology, use of in-silico molecular modeling of active compounds is gaining attention in Advance Pharmacology. An attempt is made to validate anti-inflammatory potential of common nutraceuticals, herbals and their combination using in-vivo and in-silico models. Materials and Methods : The hydro-alcoholic extracts of nutraceuticals (Allium sativum, Zingiber officinale, Curcuma longa) and herbals (Terminalia arjuna, Cyprus rotundus) complying with WHO / Indian Pharmacopeia (IP) monograph were combined in equal ratio and Poly-Herbal and Nutraceutical (PHN) formulation was prepared. Anti-inflammatory activity of individual nutraceuticals, herbals and PHN was assessed by both carrageenan induced paw edema (acute) and cotton pellet granuloma (chronic) inflammation in C57Bl/6 mice. The inflammatory biomarkers (IL1-β, IL-6, TNF-α, IL-10, CRP) were assessed to understand the mechanism of action. In in-silico modeling, NF-κB and COX-2 proteins were docked with phytochemical ligand using Accelrys Discovery Studio v2.1. Results : Anti-inflammatory activity of PHN was found to be more potent at lower dose than individual test material hydro-alcoholic extracts in both acute and chronic inflammatory models. The hydro-alcoholic extracts of all the test material significantly inhibited carrageenan-induced paw edema in second phase of acute inflammation. While cotton pellet induced chronic inflammation was inhibited and it follows C. longa (41.8%), T. arjuna (40.5%), A. sativum (40.7%), C. rotundus (38.3%) and Z. officinale (35.5%) at respective individual dosages (800mg/Kg, 200mg/Kg, 800mg/Kg, 600mg/Kg and 800mg/Kg). Similarly Pro-inflammatory interleukins biomarkers like IL1-β, IL-6, TNF-α, IL-10 and CRP were reduced significantly as compared with positive control. In-silico results suggest that COX-2 enzyme protein was docked by Curcumin, Dimethoxy curcumin and Alliin, whereas poly-phenols like Gallic acid, Ellagic acid, Gallo catechin and Alliin docked NF-κB protein with an average binding at 8 sites. The pilot observations suggest comparative anti-inflammatory activity in both in-vivo and in-silico. Conclusion : The PHN formulation developed as per the traditional approaches certifies potential anti-inflammatory activity both in-silico and in-vivo models. The study results with reference to in-silico modeling suggest it as major tools for Reverse Pharmacology.

G-Achari Prize -10

Pharmacokinetics of single oral dose (15mg) of primaquine in special populations and normal, healthy participants

Taur SR , Kadam PK, Gogtay NJ, Bhatia SJ 1 , Hase NK 2 , Thatte UM

Departments of Clinical Pharmacology, 1 Gastroenterology, and 2 Nephrology, Seth GS Medical College and KEM Hospital, Parel, Mumbai - 400 012, India.

Objective: To study pharmacokinetics and safety of single oral dose (15mg) of Primaquine in patients with hepatic dysfunction and chronic kidney disease and compare with normal, healthy participants. Materials and Methods: The Institutional Ethics Committee approved the study and written, informed consent was obtained from all participants. Ten healthy participants, 12 patients with mild and 6 with moderate hepatic dysfunction, and 11 of stage IV & 12 of stage V chronic kidney disease were given a single oral dose 15 mg of primaquine phosphate in fed state and 5 ml of blood was collected at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 h post-dose. Plasma primaquine concentration was analyzed by High Performance Liquid Chromatography (HPLC). Results: The pharmacokinetics of primaquine showed marked interindividual variability but were comparable between healthy participants, patients with mild hepatic and stage IV and V chronic kidney disease. The pharmacokinetic parameters were significantly lower in moderate hepatic dysfunction than healthy participants [median (range) and P <0.05: C max , ng/ml, 14.4 (5.9, 29.9) vs 33.4 (14.6, 104.3), AUC 0-∞, ng-h/ml, 85 (52, 274.5) vs 342.6 (86.4, 685.3) and Cl/F, h/ml, 183.71 (54.64, 288.41) vs 45.61 (21.89, 173.525)]. None of the participants experienced adverse events. Conclusion: Marked interindividual differences were seen in the various pharmacokinetic parameters. Pharmacokinetics of primaquine was significantly altered in patients with moderate hepatic dysfunction but was comparable between mild hepatic and chronic kidney disease, and healthy participants. Evaluation of steady state kinetics and metabolite levels will help optimize dosing regimens in these special populations.

G-Achari Prize -11

Evaluation of antidiabetic and antihyperlipidemic activity of aqueous extract of Terminalia paniculata bark in streptozotocin-nicotinamide induced diabetic rats

Subramaniam Ramachandran , Aiyalu Rajaseakaran 1 , K.T. Manisenthilkumar

Departments of Pharmacology, and 1 Pharmaceutical Chemistry, KMCH College of Pharmacy, Coimbatore - 641048, Tamil Nadu, India. E-mail: [email protected]

Objective : To study the antidiabetic and antihyperlipidemic activity of aqueous extract of Terminalia paniculata bark in streptozotocin-nicotinamide (STZ-NIC)-induced diabetic rats.

Materials and Methods : The aqueous extract of Terminalia paniculata bark (AETPB) was prepared and its acute toxicity was performed in rats by administration of AETPB (2 g/kg; oral) to determine the dose to evaluate its antidiabetic activity. In rats, type 2 diabetes was induced by injection of STZ-NIC (65 mg/kg-110 mg/kg; i.p). In diabetic rats, AETPB was orally given for 28 days and its action on fasting blood glucose and body weights were determined on 14th and 28th days. At the end of the experimental day, fasting blood samples were collected to estimate the haemoglobin (Hb), glycosylated haemoglobin (HbA1c), serum creatinine, urea and insulin levels. Also, serum high density lipoprotein (HDL), total cholesterol (TC) and triglycerides (TG) were estimated. Results : In rats, AETPB did not showed toxicity and death at 2 g/kg dose after its oral treatment. In diabetic rats, AETPB (100 and 200 mg/kg) treatment significantly (P < 0.001) lowered blood glucose, HbA1c, creatinine and urea levels in diabetic rats compared to diabetic control rats. The diabetic rats body weight, total protein, insulin and Hb levels were increased significantly (P < 0.001) after the treatment of AETPB than diabetic control rats. Also, in diabetic rats, significant (P < 0.001) reduction of elevated lipid profile levels were observed after the AETPB treatment compared to diabetic control rats. Conclusion : Our study data revealed that AETPB has significant antidiabetic and antihyperlipidemic activity in type 2 diabetic rats. Keywords Antidiabetic, antihyperlipidemic, streptozotocin, terminalia paniculata