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|Year : 2011 | Volume
| Issue : 7 | Page : 203-205
O. D. Gulati Prize Paper Abstracts
|Date of Web Publication||13-Dec-2011|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. O. D. Gulati Prize Paper Abstracts. Indian J Pharmacol 2011;43, Suppl S1:203-5
OD Gulati Prize -1
Genetic polymorphisms of CYP2C19 and MDR1 reduce the antiplatelet response in patients on maintenance therapy with clopidogrel
Subraja K , Priyadharsini R, Dkhar SA, Satheesh S 1 , Sridhar MG 2 , Adithan C.
Departments of Pharmacology, 1 Cardiology, and 2 Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, (JIPMER), Puducherry - 605 006, India.
Objectives: Nearly 3-40% of patients showed impaired response to clopidogrel. Genetic factors are one of the major determinants for this impaired response. While MDR1 expression affects the absorption, CYP2C19 helps in the conversion of the prodrug clopidogrel to an active metabolite. The expression of MDR1 protein and the activity of CYP2C19 are genetically influenced by polymorphisms in their genes. Hence, the study was intended to evaluate the association of CYP2C19 and MDR1 polymorphisms on the response to clopidogrel. Materials and Methods: A total of 149 ischemic heart disease patients on a 75 mg dose of clopidogrel were recruited. We measured residual platelet activities expressed as impedance (ohms). Higher values of impedance denote increased residual platelet activities. Genotyping for CYP2C19 and MDR1 polymorphisms were done. The study subjects were grouped according to their metabolic status based on CYP2C19 genotypes and MDR1 genotypes to compare the residual platelet activities. The plasma levels of inactive carboxy metabolite of clopidogrel were compared across the MDR1 genotypes. Results: Poor metabolizers with defective alleles of CYP2C19 (*2,*3) had a higher value of impedance (4.33±0.46 vs. 2.83±0.47; p= 0.03) than the extensive metabolizers without any defective alleles. Individuals with TT genotype of MDR1 had a higher impedance value (4.0±0.52 vs. 2.5±0.51; p= 0.04) than CC genotype. The levels of inactive metabolite were not found to be statistically different across MDR1 genotypes. Conclusion: In ischemic heart disease patients of south Indian origin on maintenance therapy of clopidogrel, genetic polymorphisms of CYP2C19 and MDR1 were found to be associated with reduced antiplatelet response to clopidogrel.
OD Gulati Prize -2
Evaluation of efficacy of different antiplatelet drug regimens in patients with the cardiovascular disease- an observational study
K. Manju Nath N. , P. Usha Rani, Ramesh Kumar
Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082, India.
E-mail: [email protected]
Objective: To compare the efficacy of different antiplatelet drug regimens in cardiovascular disease patients. Materials and Methods: Consecutive blood samples of 331 patients (Male: Female ratio- 274: 57) with mean age of 55.2 ±10.86 yrs who underwent Platelet aggregation test [by Light transmission aggregometry (LTA) method] were analysed . Results: Patients were either on aspirin, clopidogrel, prasugrel, cilostazol or a combination of these drugs in different dosages. Of the 331 patients, 40, 166 and 125 patients were on single, dual and triple antiplatelet drug regimen respectively. Percentages of responders were 62.5%, 87.35% and 76.8% in single, dual and triple drug regimens respectively. Dual antiplatelet regimens were associated with greater inhibition of platelet aggregation when compared to triple antiplatelet regimens. This may be due to the preferential presence of Prasugrel in the dual but not in the triple antiplatelet therapy regimen. Percentages of Poor responders (30- 40% inhibition of platelet aggregation) were- 20% in single, 6.63% in dual and in 12% triple antiplatelet drug regimens. Percentage of non-responders (less than 30% of inhibition of platelet aggregation) in single, dual and triple drug regimens were 17.5%, 6.02% and 11.2 respectively. Prasugrel was found to be more effective when compared with Clopidogrel in the background of aspirin treatment in the dual antiplatelet regimens (87.67% Vs78.75%). Inhibition of platelet aggregation was variable in the smokers in the different drug regimens. Conclusions : In this study, dual antiplatelet therapy containing Prasugrel was found to be more effective, however further studies are needed to confirm this.
OD Gulati Prize -3
Correlation of invasive and non-invasive central aortic pressures in patients undergoing diagnostic coronary angiogram
Padmaja Mekala, Gopi Krishna Rayidi 1 , Jyotsna Maddury 1 , Ramesh Kumar Rao Takallapalli
Departments of Clinical Pharmacology and Therapeutics, and 1 Cardiology, Nizam's Institute of Medical Sciences, Hyderabad - 500 082, India.
E-mail: [email protected]
Objective: Recent studies demonstrated the importance of central aortic pressures over the peripheral blood pressure recording by Sphygmomanometer. The main objective of the study was to determine central aortic pressures (CAP) by non-invasive technique and to compare with invasive CAP measurements in patients undergoing diagnostic coronary angiogram. Materials and Methods: Non-invasive CAP was recorded using applanation tonometry with SphygmoCor® over the right radial artery. The readings were taken 3 times with patient in supine position. Invasive opening aortic pressures were recorded during cardiac catheterization via right femoral artery using Recor pressure Recording system. The data was analysed by using Bland-Altman plots and the strength of the association was assessed by Pearson correlation coefficient. Results: 50 patients (36 males and 14 females), aged 52.06 ± 7.15 years and BMI of 25.04 ± 3.62 Kg/m2 who were to undergo diagnostic coronary angiogram were recruited into the study. The mean systolic CAP by non-invasive and invasive techniques were 116.1± 15.18 & 121.04 ± 16.6 mmHg respectively and the mean diastolic CAP by non-invasive and invasive techniques were 76.66 ± 9.32 mmHg & 78.14 ± 7.58mmHg respectively. Non-invasive CAP measured by SphygmoCor® underestimated catheter-measured central systolic pressure by 4.9 mmHg and diastolic pressure by 1.5 mmHg as analysed by Bland-Altman plot. There was a high correlation between non-invasive and invasive systolic blood pressures (r = 0.74, P<0.0001) and also between the non-invasive and invasive diastolic blood pressures (r = 0.74, P<0.0001). Conclusion: SphygmoCor® derived non-invasive CAP was found to be in agreement with invasive CAP (gold standard technique) recorded during cardiac catheterization. However, the utility of non-invasive measurement of CAP by SphygmoCor® needs to be verified in a large sample.
OD Gulati Prize -4
Cocaine- and amphetamine-regulated transcript (cart) serves as neuroprotective peptide in various neurodegenerative disorders
Harshita R. Trivedi , 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), First Floor, Central Tower, Sai Trinity Building, Garware Circle, Sutarwadi, Pashan, Pune - 411 021, Maharashtra, India.
Objectives : To investigate the role of neuropeptide cocaine- and amphetamine-regulated transcript (CART) in Alzheimer's, Parkinson's or Huntington's diseases. Materials and Methods: Rats were administered colchicine (15 μg/rat; intracerebroventricular, icv), 6-hydroxydopamine (6-OHDA, 8 μg/rat; substantia nigra, SN) or 3-nitropropionic acid (3-NP, 20 mg/kg; intraperitoneal, ip) to induce Alzheimer's, Parkinson's or Huntington's diseases, respectively. The effect of CART (25-100 ng/rat, icv) was assessed using Morris Water Maze (MWM) in Alzheimer's, apomorphine induced rotations in Parkinson's, and footprint analysis and locomotor activity in Huntington's. The status of endogenous CART was evaluated using immunocytochemistry in the rat brains following these neurological conditions. Results : Alzheimer's induced rats showed increased escape latency and spent less time in the target quadrant in probe test, however CART treatment reversed the effect. Similarly, Parkinson's induced rats treated with apomorphine showed contralateral rotations in the rotational test chambers. Rats treated with 3-NP for 4 days showed significant decrease in the stride length and foot print length and number of locomotions and crossovers as compared to those in the control rats. CART treatment prior to 6-OHDA or 3-NP reduced the apomorphine rotations and prevented the motor deficits in rats. Further, CART-immunoreactivity was significantly reduced in hypothalamic arcuate and paraventricular nuclei, dentate gyrus, SN, locus coeruleus and striatum in Alzheimer's, Parkinson's, and Huntington's induced rat brains as compared to control. Conclusions : These observations for the first time suggest a role for endogenous CART as a neuroprotective agent in the prevention of severe neurodegenerative deficits like Alzheimer's, Parkinson's and Huntington's diseases.
OD Gulati Prize -5
Involvement of ventral tegmental neuropeptide y in ethanol induced reward and reinforcement using operant chamber in rats
Atmaram D. Kale, Chandrashekhar D. Borkar, Manoj A. Upadhya, Dadasaheb M. Kokare
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur- 440 033
Objectives: To study the involvement of ventral tegmental neuropeptide Y (NPY) in ethanol induced reward and reinforcement effect using operant chamber in rats. Materials and Methods: Intra-ventral tegmental area (VTA) cannulated rats were used in the study. Rats were trained for intra-VTA ethanol self-infusion in the operant chamber and the numbers of lever pressings were assessed as a parameter for reward. The modulation of this effect was observed following administration of NPYergic agents like NPY, [Leu 31 , Pro 34 ]-NPY (NPY Y1/Y5 receptors agonist) or BIBP3226 (selective NPY Y1 receptors antagonist) by intra-VTA route prior to ethanol. The involvement of endogenous NPY in ethanol self-infusion was assessed by immunocytochemistry technique. Results : Rats cannulated in the VTA showed increased ethanol self-infusion as compared to that with aCSF control. While prior treatment of NPY or [Leu 31 , Pro 34 ]-NPY treatment increased the number of intra-VTA ethanol infusion, BIBP3226 decreased the number of lever pressings. Furthermore, NPY-immunoreactivity in the nucleus accumbens shell, hypothalamic arcuate nucleus, central nucleus of amygdala and lateral part of bed nucleus of stria terminalis was significantly increased in the rats that self-infused ethanol in VTA as compared to that in the control rats. However, NPY in the prefrontal cortex did not respond to ethanol self-infusion. Conclusions : We suggest that endogenous NPY, via NPY Y1 receptor in the VTA, might play a role in the reward and reinforcement actions of ethanol and that the activation of NPYergic system in the VTA might help in reducing the dose and undesirable consequences related to ethanol.
OD Gulati Prize -6
Effect of refeeding on starved rats on the brain cart peptide and plasma cortisol levels
Dadasaheb M. Kokare , Kartik T. Nakhate, Praful S. Singru 1 , Nishikant K. Subhedar 2
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur- 440 033, 1 School of Biological Sciences, National Institute of Science Education and Research (NISER), Institute of Physics Campus, Sachivalaya Marg, PO Sainik School, Bhubaneswar - 751 005, 2 Indian Institute of Science Education and Research (IISER), First Floor, Central Tower, Sai Trinity Building, Garware Circle, Sutarwadi, Pashan, Pune- 411 021, Maharashtra, India.
Objectives : To investigate the effect of refeeding, following fasting, on neuropeptide cocaine- and amphetamine-regulated transcript (CART) and plasma cortisol . Materials and Methods: Adult male rats were food deprived for 64 h and subjected to refeeding with either normal chow feed or high energy diet (HED) for 24 h. While the brains of these rats were processed for immunohistochemical analysis of CART, the cortisol levels were measured in the blood. Results : Food deprivation reduced CART-immunoreactivity in nucleus accumbens shell (AcbSh) and in hypothalamic arcuate (ARC) and paraventricular (PVN) nuclei. Refeeding with chow or HED restored CART to normal within 4 h in ARC cells and AcbSh fibers. However, re-introduction of normal chow did not restore CART in ARC fibers and cells/fibers of PVN, though HED fully restored CART-immunoreactivity in ARC and PVN at 24 h time-point. While fasting increased plasma cortisol, the levels were restored after refeeding. Conclusions : While energy depletion by fasting may be associated with inhibition of CART in the PVN, reduction in AcbSh may be a consequence of aversion. Since chow and HED restored CART in AcbSh, immediately after refeeding, the rewarding aspect may not depend on food composition. CART in PVN was not restored immediately after re-introduction of either foods, and therefore may not be involved in early satiety. Refeeding with HED, but not chow, restored CART contents in PVN at 24 h time-point; suggesting the role of PVN CART in replenishment of depleted fuel store. Moreover, fasting might produce stress as indicated by increased plasma cortisol levels, which may subside on refeeding.
OD Gulati Prize -7
Altered maternal and neurobehaviour in pregnant dams and progeny exposed to methylmethimazole, monocrotophos and lead
B. Kala Kumar, A. Gopala Reddy, M. Alpha Raj, M. Usha Rani, P. Ravi kumar, K. Kondal Reddy .
Department of Pharmacology and Toxicology, College of Veterinary Science, R'nagar, Hyderabad - 500 030, India.
Objectives : Monocrotophos a widely used pesticide, lead an ubiquitous heavy metal and methimazole a thyroid disruptor were evaluated for their effects on maternal behaviour and neonatal mortality. Materials and Methods : Thirty pregnant female rats were divided into five groups and exposed perinatally. Group I was Sham, Methimazole (II), monocrotophos (III), and lead acetate (IV) were administered singly and a combination of monocrotophos and lead to assess the interaction (V) were administered from day 3 of gestation to postnatal day 21. Maternal behaviour, litter size, neonatal mortality and behavior of the progeny were studied. Results: Maternal behaviour was significantly (P<0.01) interfered in III and V. Perinatally exposed pups were subjected to neurobehavioural tests after 90 days. Acoustic response decreased in monocrotophos and lead acetate treated groups singly and in combination. Rope descent was affected with methimazole and lead acetate treatment. Conclusion: Thus, it is concluded that monocrotophos could affect the maternal behaviour of the dams. The neurobehaviour of the F1 adults was affected in acoustic response in group III-V and rope descent in group II, IV and V.