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   2008| July-August  | Volume 40 | Issue 4  
    Online since September 29, 2008

 
 
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REVIEW ARTICLE
Role of pharmacogenomics in drug discovery and development
A Surendiran, SC Pradhan, C Adithan
July-August 2008, 40(4):137-143
DOI:10.4103/0253-7613.43158  PMID:20040945
Pharmacogenetics and pharmacogenomics are two major emerging trends in medical sciences, which influence the success of drug development and therapeutics. In current times, though pharmacogenetic studies are being done extensively for research, its application for drug development needs to get started on a large scale. The major determinants of success of a new drug compound, viz safety and efficacy, have become more predictable, with the advent of pharmacogenetic studies. There is a need felt for pharmacogenomic studies, where the effects of multiple genes are assessed with the study of entire genome. Pharmacogenetic studies can be used at various stages of drug development. The effect of drug target polymorphisms on drug response can be assessed and identified. In clinical studies, pharmacogenetic tests can be used for stratification of patients based on their genotype, which corresponds to their metabolizing capacity. This prevents the occurrence of severe adverse drug reactions and helps in better outcome of clinical trials. This can also reduce attrition of drug compounds. Further, the variations in drug response can be better studied with the wider application of pharmacogenomic methods like genome wide scans, haplotype analysis and candidate gene approaches. The cost of pharmacogenetic testing has become very low, with the advent of newer high throughput genotyping systems. However, the cost of pharmacogenomic methods continues to be very high. As the treatment with several drugs is being more and more pharmacogeneticaly guided (e.g. warfarin and irinotecan), the FDA has laid down guidelines for pharmaceutical firms regarding submission of pharmacogenetic data for their drug products in labelling.
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RESEARCH ARTICLES
Burn wound healing property of Cocos nucifera: An appraisal
Pallavi Srivastava, S Durgaprasad
July-August 2008, 40(4):144-146
DOI:10.4103/0253-7613.43159  PMID:20040946
Objectives: The study was undertaken to evaluate the burn wound healing property of oil of Cocos nucifera and to compare the effect of the combination of oil of Cocos nucifera and silver sulphadiazine with silver sulphadiazine alone. Materials and Methods: Partial thickness burn wounds were inflicted upon four groups of six rats each. Group I was assigned as control, Group II received the standard silver sulphadiazine. Group III was given pure oil of Cocos nucifera , and Group IV received the combination of the oil and the standard. The parameters observed were epithelialization period and percentage of wound contraction. Results: It was noted that there was significant improvement in burn wound contraction in the group treated with the combination of Cocos nucifera and silver sulphadiazine. The period of epithelialization also decreased significantly in groups III and IV. Conclusion: It is concluded that oil of Cocos nucifera is an effective burn wound healing agent.
  9,704 748 14
In vitro antioxidant activity of pet ether extract of black pepper
Ramnik Singh, Narinder Singh, BS Saini, Harwinder Singh Rao
July-August 2008, 40(4):147-151
DOI:10.4103/0253-7613.43160  PMID:20040947
Objective: To investigate the in vitro antioxidant activity of different fractions (R1, R2 and R3) obtained from pet ether extract of black pepper fruits (Piper nigrum Linn.) Materials and Methods: The fractions R1, R2 and R3 were eluted from pet ether and ethyl acetate in the ratio of 6:4, 5:5 and 4:6, respectively. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radical, superoxide anion radical, nitric oxide radical, and hydroxyl radical scavenging assays were carried out to evaluate the antioxidant potential of the extract. Results: The free radical scavenging activity of the different fractions of pet ether extract of P. nigrum (PEPN) increased in a concentration dependent manner. The R3 and R2 fraction of PEPN in 500 g/ml inhibited the peroxidation of a linoleic acid emulsion by 60.483.33% and 58.892.51%, respectively. In DPPH free radical scavenging assay, the activity of R3 and R2 were found to be almost similar. The R3 (100g/ml) fraction of PEPN inhibited 55.684.48% nitric oxide radicals generated from sodium nitroprusside, whereas curcumin in the same concentration inhibited 84.274.12%. Moreover, PEPN scavenged the superoxide radical generated by the Xanthine/Xanthine oxidase system. The fraction R2 and R3 in the doses of 1000g/ml inhibited 61.045.11% and 63.564.17%, respectively. The hydroxyl radical was generated by Fenton's reaction. The amounts of total phenolic compounds were determined and 56.98 g pyrocatechol phenol equivalents were detected in one mg of R3. Conclusions: P. nigrum could be considered as a potential source of natural antioxidant.
  7,609 1,174 11
Intrathecal tramadol added to bupivacaine as spinal anesthetic increases analgesic effect of the spinal blockade after major gynecological surgeries
Susmita Chakraborty, Jayanta Chakrabarti, Dipasri Bhattacharya
July-August 2008, 40(4):180-182
DOI:10.4103/0253-7613.43166  PMID:20040953
The analgesic effect of the centrally acting opioid, tramadol, is well-known. It has been shown in clinical studies that using tramadol epidurally can provide longer duration of analgesia, without the common side effects of opioids. The study was undertaken to evaluate the duration of analgesia and/or pain free period produced by intrathecal tramadol added to bupivacaine in patients undergoing major gynecological surgery in a randomized double blind placebo controlled protocol. Fifty patients ASA I & II scheduled for Wardmayo's operation and Fothergill's operation were randomly allocated to two equal groups. Group A (n=25) received 3 ml of 0.5% hyperbaric bupivacaine (15 mg) with 0.2 ml of normal saline and Group B (n=25) received 3 ml 0.5% hyperbaric bupivacaine and 0.2 ml (20 mg) tramadol by intrathecal route at L3-4 inter space. Standard monitoring of the vital parameters was done during the study period. Levels of sensory block and sedation score were recorded every two minutes for the first 20 minutes, and then every ten minutes for the rest of the surgical procedure. Assessment of pain was done using Visual Analogue Scale (VAS). The study was concluded when the VAS was more than 40 mm, postoperatively. The patient was medicated and the time was recorded. Duration of analgesia or pain free period was estimated from the time of completion of spinal injection to administration of rescue analgesic or when the VAS score was greater than 40 mm. In Group B patients, the VAS score was significantly lower, as compared to Group A patients. The duration of analgesia was 210 10.12 min in Group A; whereas, in Group B, it was 380 11.82 min, which was found to be significant.
  5,547 347 7
Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice
Dinesh Dhingra, Vaibhav Kumar
July-August 2008, 40(4):175-179
DOI:10.4103/0253-7613.43165  PMID:20040952
Objectives: The present study was undertaken to investigate the effect of the ethanolic extract of Allium sativum L. (Family: Lilliaceae), commonly known as garlic, on depression in mice. Materials and Methods: Ethanolic extract of garlic (25, 50 and 100 mg/kg) was administered orally for 14 successive days to young Swiss albino mice of either sex and antidepressant-like activity was evaluated employing tail suspension test (TST) and forced swim test (FST). The efficacy of the extract was compared with standard antidepressant drugs like fluoxetine and imipramine. The mechanism of action of the extract was investigated by co-administration of prazosin (α1-adrenoceptor antagonist), sulpiride (selective D2-receptor antagonist), baclofen (GABA B agonist) and p-CPA (serotonin antagonist) separately with the extract and by studying the effect of the extract on brain MAO-A and MAO-B levels. Results: Garlic extract (25, 50 and 100 mg/kg) significantly decreased immobility time in a dose-dependent manner in both TST and FST, indicating significant antidepressant-like activity. The efficacy of the extract was found to be comparable to fluoxetine (20 mg/kg p.o.) and imipramine (15 mg/kg p.o.) in both TST and FST. The extract did not show any significant effect on the locomotor activity of the mice. Prazosin, sulpiride, baclofen and p-CPA significantly attenuated the extract-induced antidepressant-like effect in TST. Garlic extract (100 mg/kg) administered orally for 14 successive days significantly decreased brain MAO-A and MAO-B levels, as compared to the control group. Conclusion: Garlic extract showed significant antidepressant-like activity probably by inhibiting MAO-A and MAO-B levels and through interaction with adrenergic, dopaminergic, serotonergic and GABAergic systems.
  4,890 569 5
The effect of aqueous extract of Embelia ribes Burm on serum homocysteine, lipids and oxidative enzymes in methionine induced hyperhomocysteinemia
Uma Bhandari, M Nazam Ansari, F Islam, CD Tripathi
July-August 2008, 40(4):152-157
DOI:10.4103/0253-7613.43161  PMID:20040948
Objective: The present study was designed to evaluate the effect of the aqueous extract of Embelia ribes Burm fruits on methionine-induced hyperhomocysteinemia, hyperlipidemia and oxidative stress in albino rats. Materials and Methods: Adult male Wistar albino rats were fed with the aqueous extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days. Hyperhomocysteinemia was induced by methionine treatment (1 g/kg, p.o.) for 30 days and folic acid (100 mg/kg, p.o.) was used as a standard drug. The animals were evaluated for various biochemical parameters in serum and brain homogenates, followed by histopathological studies at the end of the study. Results: Administration of methionine (1 g/kg, p.o.) for 30 days to vehicle control rats produced significant increase (P <0.01) in homocysteine, lactate dehydrogenase (LDH), total cholesterol, triglycerides, low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C) levels in serum and lipid peroxides (LPO) levels in brain homogenates, with reduction in high density lipoprotein (HDL-C) levels in serum, and glutathione (GSH) content in brain homogenates, as compared to vehicle control rats. Administration of the aqueous extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days, to hyperhomocysteinemic rats, significantly (P <0.01) decreased the levels of homocysteine, LDH, total cholesterol, triglycerides, LDL-C and VLDL-C and increased the HDL-C levels in serum. In addition, a significant (P <0.01) decrease in LPO levels with increase in GSH content was observed in hyperhomocysteinemic rats treated with the aqueous extract of Embelia ribes. The results were comparable to those obtained with folic acid, a standard antihyperhomocysteinemic drug. Conclusion: The present results provide clear evidence that the aqueous extract of Embelia ribes treatment enhances the antioxidant defense against methionine-induced hyperhomocysteinemia, hyperlipidemia and oxidative stress in brain.
  4,843 580 8
Hypoglycemic effect of aqueous extract of Parthenium hysterophorus L. in normal and alloxan induced diabetic rats
Vijay S Patel, V Chitra, P Lakshmi Prasanna, V Krishnaraju
July-August 2008, 40(4):183-185
DOI:10.4103/0253-7613.43167  PMID:20040954
Objectives: To study the effects of Parthenium hysterophorus L. flower on serum glucose level in normal and alloxan induced diabetic rats. Materials and Methods: Albino rats were divided into six groups of six animals each, three groups of normal animals receiving different treatments consisting of vehicle, aqueous extract of Parthenium hysterophorus L. flower (100 mg/kg) and the standard antidiabetic drug, glibenclamide (0.5 mg/kg). The same treatment was given to the other three groups comprising alloxan induced diabetic animals. Fasting blood glucose level was estimated using the glucose oxidase method in normal and alloxan induced diabetic rats, before and 2 h after the administration of drugs. Results: Parthenium hysterophorus L. showed significant reduction in blood glucose level in the diabetic (P <0.01) rats. However, the reduction in blood glucose level with aqueous extract was less than with the standard drug glibenclamide. The extract showed less hypoglycemic effect in fasted normal rats, (P<0.05). Conclusion: The study reveals that the active fraction of Parthenium hysterophorus L. flower extract is very promising for developing standardized phytomedicine for diabetes mellitus.
  4,664 652 7
The effects of topical (gel) astemizole and terfenadine on wound healing
D Srikanth, Rekha R Shenoy, C Mallikarjuna Rao
July-August 2008, 40(4):170-174
DOI:10.4103/0253-7613.43164  PMID:20040951
Objective: To develop topical gel preparations of astemizole and terfenadine and to investigate the actions of the gels on the healing of incision and excision wounds in male albino rats. Materials and Methods: Gels containing 1% astemizole, with varying concentrations of carbopol 934 (polymer), were prepared. Similarly, 1% terfenadine gels were made. The formulations were evaluated for release rate and stability. Incision and excision wounds were inflicted on male albino rats under ketamine anesthesia, taking aseptic precautions. The animals were divided into two groups. They were given a topical application of either astemizole or terfenadine gel, at a dose of 100 mg per wound, once daily, for 10 days in the case of incision wounds and till the time of complete closure in the case of excision wounds. On the 11 th day, breaking strength of the incision wound was measured. In the excision wound model, wound closure rate, epithelization time, scar features and hydroxyproline content of scar tissue were studied from the day of wounding till the day of the scab falling off, with no residual raw area. Results: Gels prepared using 0.8% carbopol 934 and 1% of drug in gel base were found to be stable. The gels of astemizole and terfenadine significantly (P < 0.05) promoted the phases of healing such as collagenation (in incision wounds), wound contraction and epithelization (in excision wounds). Conclusion: The gels of astemizole and terfenadine might play an important role in wound management program.
  4,551 539 3
SHORT COMMUNICATION
Ondansetron induced fatal ventricular tachycardia
R Chandrakala, CN Vijayashankara, K Kushal Kumar, N Sarala
July-August 2008, 40(4):186-187
DOI:10.4103/0253-7613.43168  PMID:20040955
Ondansetron is a serotonin receptor antagonist used widely in the prophylaxis and treatment of postoperative nausea and vomiting (PONV) and vomiting associated with cancer chemotherapy. The common side effects of ondansetron are fever, malaise, diarrhoea, constipation, and allergic reactions. Extra-pyramidal reactions are rare and cardiovascular side effects are even rarer. Even though its clinical safety has been established in a large number of studies, its adverse effects have been reported and these include cardiovascular events like acute myocardial ischemia and arrhythmias in adults. [1] Studies of its adverse effects in children are few. We report a rare adverse effect of ondansetron in a 14-year-old girl, presenting as ventricular tachycardia.
  4,151 347 7
RESEARCH ARTICLES
Effect of methomyl on hepatic mixed function oxidases in rats
Jyotsna A Patil, Arun J Patil, Ajit V Sontakke, Sanjay P Govindwar
July-August 2008, 40(4):158-163
DOI:10.4103/0253-7613.43162  PMID:20040949
Objective: To study the effect of the methomyl on mixed function oxidase system in rats. Materials and Methods: The effect of the methomyl on mixed function oxidase was studied using different dosages, durations and sex. Microsomes were isolated using the calcium precipitation method. The levels of cytochrome P 450 , and cytochrome b 5 were determined using extinction coefficient of 91 and 85 mM -1 respectively. The activities of drug metabolizing enzymes, hemoglobin content, liver function enzymes, and serum cholinesterase activity were assayed by using standard methods. Results: Intraperitoneal administration of methomyl (4 mg/kg body weight) showed significant decrease in the level of cytochrome P 450 , and the activities of aminopyrine N-demethylase and aniline hydroxylase on the third day of the treatment. Methomyl (4 mg/kg) treatment of old male rat and adult female rat also showed a decrease in the level of cytochrome P 450 , and aminopyrine N-demethylase activity. The serum samples from methomyl treated rats (male and female), when analyzed for alanine aminotransferase (SGPT) and aspartate aminotransferase (SGOT) as markers of the liver toxicity, showed significant increase in the activity. The activities of SGPT and SGOT were significantly higher in the treated rats (2 and 4 mg/kg) than in the control group. A significant decrease in the level of hemoglobin and serum cholinesterase activity was observed, when there was an increase in the dose level. A significant increase was observed in alkaline phosphatase activity at all dose levels. Conclusion: Methomyl influences mixed function oxidase and creates abnormality of liver functions in the rats. This effect depends on the dose and duration of methomyl.
  3,893 234 1
BOOK REVIEW
Practical manual of pharmacology
Chetna Desai
July-August 2008, 40(4):188-188
  3,212 596 -
RESEARCH ARTICLES
Sample purification procedure for confirmation of 3'-hydroxy stanozolol by gas chromatography/high resolution mass spectrometry
S Ahi, IM Reddy, A Beotra, R Lal, S Jain, T Kaur
July-August 2008, 40(4):164-169
DOI:10.4103/0253-7613.43163  PMID:20040950
Objective: To improve the detection limit of 3'-hydroxy-stanozolol by using the double extraction procedure, specific for basic drugs. Materials and Methods: The urine samples were spiked in four replicates with 3'-hydroxy-stanozolol at different concentrations of 1, 2, 5 and 10 ng/mL, processed by two different methods and injected into gas chromatography/high resolution mass spectrometry (GC-HRMS) instrument. The data was analyzed by comparing the recovery values and the ion match criterion of the two procedures. Results: The results show that the recovery percentage and ion match criterion of 3'-hydroxy-stanozolol at lower concentrations has a significant improvement when Solid phase extraction was performed, instead of Liquid-liquid extraction in the second extraction procedure. Conclusion: The sample preparation procedure using Oasis-MCX cartridges allows confirmation of 3'-hydroxy-stanozolol at the minimum required performance limit (MRPL) decided by the World Anti Doping Agency. This procedure may be used for the confirmation of suspicious samples found in routine testing, as it efficiently fulfills the ion-matching criterion laid down by the World Anti Doping Agency.
  3,166 179 2
EDITORIAL
Writing an effective manuscript: Editor's perspective
Mira Desai
July-August 2008, 40(4):135-136
DOI:10.4103/0253-7613.43157  PMID:20040944
  2,599 571 -
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