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   2012| May-June  | Volume 44 | Issue 3  
    Online since May 17, 2012

 
 
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EDUCATIONAL FORUM
Antiretroviral drugs: Critical issues and recent advances
Mira Desai, Geetha Iyer, RK Dikshit
May-June 2012, 44(3):288-298
DOI:10.4103/0253-7613.96296  
Human immunodeficiency virus (HIV) infection is now recognized as a chronic illness. Although the success of highly active antiretroviral therapy is beyond question, several issues still persist. Since the drugs cannot eradicate the virus, cure is not yet possible, and patients have to maintain a lifelong adherence with the risk of toxic effects, drug-drug interactions and drug resistance. A clear understanding of the viral replication and its interaction with host cell factors has led to the development of a large number of effective antiretroviral drugs (ARVs). New drugs in the existing class such as apricitabine, elvucitabine and etravirine have shown promising results against HIV isolates resistant to first line drugs. These drugs have offered a new choice for patients with drug resistant disease. However, the impact of their long term use on safety is yet to be assessed. Novel drugs with unique mechanism of action such as CD4 receptor attachment inhibitors, maturation inhibitors, pharmacokinetic enhancers, capsid assembly inhibitors and lens epithelium derived growth factor inhibitors are still under development. Currently, ARVs, especially tenofovir and emtricitabine, are also being evaluated for prevention of sexual transmission of HIV-1. The initial results of an HIV prevention trial network are encouraging and have recommended the use of ARVs for pre-exposure prophylaxis. Thus, ARVs form the key component of HIV prevention and treatment strategy. This article discusses the challenges associated with HIV-1 treatment and updates several major advances in the development of ARVs.
  11,691 1,281 3
REVIEW ARTICLE
Molecular mechanism of alcoholic fatty liver
Karuna Rasineni, Carol A Casey
May-June 2012, 44(3):299-303
DOI:10.4103/0253-7613.96297  
Ethanol abuse and chronic ethanol consumption remains a major public health problem and is responsible for a high rate of morbidity. Alcohol-induced fatty liver generally begins as hepatic steatosis, and if the cause persists, this invariably progresses to steatohepatitis and cirrhosis. The original biochemical explanation for an alcoholic fatty liver centered on the ability of ethanol metabolism to shift the redox state of the liver and inhibit fatty acid oxidation. Subsequent studies found repression of fatty acid oxidation and that the induction of lipogenesis can occur in alcoholic conditions. Ethanol activates sterol regulatory element binding protein 1, inducing a battery of lipogenic enzymes. These effects may be due in part to inhibition of AMP-dependent protein kinase, reduction in plasma adiponectin or increased levels of TNF-α the liver. They in turn activate lipogenic pathways and inhibit fatty acid oxidation. Besides the fatty acid synthesis and oxidation, ethanol also alters lipid droplet (LD, the storage form of triglycerides, TG) metabolism in hepatocytes and very low-density lipoprotein (VLDL) secretion from liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology provides new therapeutic targets to reverse the alcoholic fatty liver.
  7,785 592 6
RESEARCH ARTICLES
Antidiabetic and antihiperlipidemic effect of Andrographis paniculata (Burm. f.) Nees and andrographolide in high-fructose-fat-fed rats
Agung Endro Nugroho, Mohamad Andrie, Ni Kadek Warditiani, Eka Siswanto, Suwidjiyo Pramono, Endang Lukitaningsih
May-June 2012, 44(3):377-381
DOI:10.4103/0253-7613.96343  
Objectives: Andrographis paniculata (Burm. f.) Nees originates from India and grows widely in many areas in Southeast Asian countries. Andrographis paniculata (Burm. f.) Nees has shown an antidiabetic effect in type 1 DM rats. The present study investigates the purified extract of the plant and its active compound andrographolide for antidiabetic and antihyperlipidemic effects in high-fructose-fat-fed rats, a model of type 2 DM rats. Materials and Methods: Hyperglycemia in rats was induced by high-fructose-fat diet containing 36% fructose, 15% lard, and 5% egg yolks in 0.36 g/200 gb.wt. 55 days. The rats were treated with the extract or test compound on the 50 th day. Antidiabetic activity was measured by estimating mainly the pre- and postprandial blood glucose levels and other parameters such as cholesterol, LDL, triglyceride, and body weight. Results: The purified extract and andrographolide significantly (P<0.05) decreased the levels of blood glucose, triglyceride, and LDL compared to controls. However, no changes were observed in serum cholesterol and rat body weight. Metformin also showed similar effects on these parameters. Conclusions: Andrographis paniculata (Burm. f.) Nees or its active compound andrographolide showed hypoglycemic and hypolipidemic effects in high-fat-fructose-fed rat.
  5,529 358 16
Antiosteoporotic activity of phytoestrogen-rich fraction separated from ethanol extract of aerial parts of Cissus quadrangularis in ovariectomized rats
Urmila M Aswar, V Mohan, Subhash L Bodhankar
May-June 2012, 44(3):345-350
DOI:10.4103/0253-7613.96310  
Objective: Cissus quadrangularis L. (C. quadrangularis L.) (Vitaceae) has been reported in Ayurveda for its antiosteoporotic activity. The study separated the phytoestrogen-rich fraction (IND-HE) from aerial parts of C. quadrangularis L. and evaluated its effect on osteoporosis caused by ovariectomy in rats. Materials and Methods: IND-HE was separated from the ethanol extract of C. quadrangularis. Ovariectomized female Wistar rats were divided into four groups (n = 6). Group 1: Control (distilled water), Group II: IND-HE (75 mg/kg p.o.), Group III: IND-HE (100 mg/kg p.o.) were treated once daily for 8 weeks and Group IV: standard estradiol group, received estrogen (1 mg/kg, s.c. bi-weekly). The effects on body weight were determined. DEXA (Dual energy-emission X-ray absorptimatory analysis) of whole body bone and femur was carried out. Blood was removed and analyzed for biochemical parameters. After sacrificing the animals, biomechanical study of right tibia and histopathology of pelvic bone was carried out. Results: IND-HE showed presence of phytoestrogen-rich fraction. IND-HE (75 and 100 mg/ kg) and estrogen treatment showed statistically significant increase in bone thickness, bone density and bone hardness. IND-HE (75 and 100 mg/kg) and estrogen treatment significantly increased serum estradiol. IND-HE (100 mg/kg) (P<0.05) and estrogen treatment increased serum vitamin D3 and serum calcium compared to control. Alkaline phosphatase was significantly reduced by IND-HE (100 mg/kg p.o.) and estrogen treatment. Histopathology and DEXA results indicated that IND-HE (75 and 100 mg/kg) prevented bone loss. Discussion and Conclusion: These findings confirm that phytoestrogen-rich fraction (IND- HE) possess good antiosteoporotic activity.
  5,254 291 7
BOOK REVIEW
Fundamentals of Experimental Pharmacology
JD Bhatt
May-June 2012, 44(3):430-430
  4,019 349 -
RESEARCH ARTICLES
Efficacy of alternate-day versus everyday dosing of atorvastatin
Sushobhan Pramanik, Asoke Kumar Das, Milan Chakrabarty, Susanta Kumar Bandyopadhyay, Mainak Ghosh, Chanchal Kumar Dalai
May-June 2012, 44(3):362-365
DOI:10.4103/0253-7613.96326  
Background: Atorvastatin has a longer duration of action than other hydroxymethylglutaryl coenzyme A reductase inhibitors. Objectives: The objective was to evaluate the efficacy of alternate day vs. daily dosing of atorvastatin for the treatment of hyperlipidemia. Materials and Methods: In this prospective, open label, crossover study, 40 patients with plasma low-density cholesterol (LDL-C) of more than 130 mg/dl and total cholesterol (TC) more than 200 mg/dl were recruited. After baseline tests, they were randomly allocated to two groups. Group A received 20 mg atorvastatin on alternate days and group B received 20 mg atorvastatin daily for 12 weeks. After 4 weeks of washout period, the groups were crossed over to the other treatment regimen for another 12 weeks. Fasting plasma lipid profile and serum alanine transaminase (ALT) and aspartate transaminase (AST) were measured for both groups at 6 th , 12 th , 16 th , 22 nd , and 28 th weeks. Results were pooled across the periods and data between the two groups were compared using unpaired t-test. Results: Among the 40 enrolled subjects, 38 completed the study. Both treatment regimens significantly reduced LDL-C and TC compared to baseline. There was no statistically significant difference between the two groups in terms of reduction of plasma LDL-C and TC at 6 and 12 weeks of treatment. Both the regimens were well tolerated. Conclusion: Alternate-day treatment with atorvastatin is comparable in efficacy and safety to the established daily treatment regimen, thus being a cost effective alternative.
  3,862 463 -
Alcea rosea root extract as a preventive and curative agent in ethylene glycol-induced urolithiasis in rats
Marzieh Ahmadi, Abolfazl Khajavi Rad, Ziba Rajaei, Mousa-Al-Reza Hadjzadeh, Nema Mohammadian, Nafiseh Sadat Tabasi
May-June 2012, 44(3):304-307
DOI:10.4103/0253-7613.96298  
Introduction: Alcea rosea L. is used in Asian folk medicine as a remedy for a wide range of ailments. The aim of the present study was to investigate the effect of hydroalcoholic extract of Alcea rosea roots on ethylene glycol-induced kidney calculi in rats. Materials and Methods: Male Wistar rats were randomly divided into control, ethylene glycol (EG), curative and preventive groups. Control group received tap drinking water for 28 days. Ethylene glycol (EG), curative and preventive groups received 1% ethylene glycol for induction of calcium oxalate (CaOx) calculus formation; preventive and curative subjects also received the hydroalcoholic extract of Alcea rosea roots in drinking water at dose of 170 mg/kg, since day 0 or day 14, respectively. Urinary oxalate concentration was measured by spectrophotometer on days 0, 14 and 28. On day 28, the kidneys were removed and examined histopathologically under light microscopy for counting the calcium oxalate deposits in 50 microscopic fields. Results: In both preventive and curative protocols, treatment of rats with hydroalcoholic extract of Alcea rosea roots significantly reduced the number of kidney calcium oxalate deposits compared to ethylene glycol group. Administration of Alcea rosea extract also reduced the elevated urinary oxalate due to ethylene glycol. Conclusion: Alcea rosea showed a beneficial effect in preventing and eliminating calcium oxalate deposition in the rat kidney. This effect is possibly due to diuretic and anti-inflammatory effects or presence of mucilaginous polysaccharides in the plant. It may also be related to lowering of urinary concentration of stone-forming constituents.
  3,870 320 3
Antihyperglycemic effect of Annona squamosa hexane extract in type 2 diabetes animal model: PTP1B inhibition, a possible mechanism of action?
Joseph Alex Davis, Suchitra Sharma, Shivani Mittra, S Sujatha, Anil Kanaujia, Gyanesh Shukla, Chandrakant Katiyar, BS Lakshmi, Vinay Sheel Bansal, Pradip Kumar Bhatnagar
May-June 2012, 44(3):326-332
DOI:10.4103/0253-7613.96304  
Aim: The mechanism of action of Annona squamosa hexane extract in mediating antihyperglycemic and antitriglyceridimic effect were investigated in this study. Materials and Methods: The effects of extract on glucose uptake, insulin receptor-β (IR-β), insulin receptor substrate-1 (IRS-1) phosphorylation and glucose transporter type 4 (GLUT4) and phosphoinositide 3-kinase (PI3 kinase) mRNA expression were studied in L6 myotubes. The in vitro mechanism of action was tested in protein-tyrosine phosphatase 1B (PTP1B), G-protein-coupled receptor 40 (GPR40), silent mating type information regulation 2 homolog 1 (SIRT1) and dipeptidyl peptidase-IV (DPP-IV) assays. The in vivo efficacy was characterized in ob/ob mice after an oral administration of the extract for 21 days. Results: The effect of extract promoted glucose uptake, IR-β and IRS-1 phosphorylation and GLUT4 and PI3 kinase mRNA upregulation in L6 myotubes. The extract inhibited PTP1B with an IC 50 17.4 ΅g/ml and did not modulate GPR40, SIRT1 or DPP-IV activities. An oral administration of extract in ob/ob mice for 21 days improved random blood glucose, triglyceride and oral glucose tolerance. Further, the extract did not result in body weight gain before and after treatment (29.3 vs. 33.6 g) compared to rosiglitazone where significant body weight gain was observed (28.4 vs. 44.5 g; *P<0.05 after treatment compared to before treatment). Conclusion: The results suggest that Annona squamosa hexane extract exerts its action by modulating insulin signaling through inhibition of PTP1B.
  3,818 364 -
Comparative evaluation of intrathecal midazolam and low dose clonidine: Efficacy, safety and duration of analgesia. A randomized, double blind, prospective clinical trial
Suchita A Joshi, Venkatesh V Khadke, Rajesh D Subhedar, Arun W Patil, Vijay M Motghare
May-June 2012, 44(3):357-361
DOI:10.4103/0253-7613.96321  
Background: The study was planned to assess the comparative efficacy, safety and duration of analgesia produced by low-dose clonidine and midazolam when used as adjuvant for spinal anesthesia. Materials and Methods: This is a randomized, participant and observer blind, prospective, parallel group clinical trial. Fifty ASA grade I and II patients posted for lower abdominal surgery were randomly allocated into two groups. BC group received spinal clonidine 30 μg and BM group received preservative-free midazolam 2 mg with 15 mg hyperbaric bupivacaine. Postoperative analgesia, analgesic requirement in 24 hours, onset and duration of block, hemodynamic stability and adverse effects were observed (P<0.05 - considered significant, P<0.01 considered highly significant). Results: The duration of postoperative analgesia was prolonged in BM group (391.64 ± 132.98 min) than BC group (296.60 ± 52.77 min) (P<0.01). The mean verbal rating pain score was significantly less in BM group than BC group (P<0.01). The number of analgesic doses in 24 hours were significantly less in BM group (P<0.05). Nine patients (36%) in BC group required additional analgesia as against none in BM group (P<0.01). The onset of sensory block and peak sensory level was significantly earlier in BM group as compared to BC group. Duration of sensory block was longer in BM group (P<0.05). Subjects in BC group(36%) had bradycardia as compared to none in BM group (P<0.01). Hypotension was observed in 44% patients in BC group as against 16% in BM group (P<0.05). Conclusion: Postoperative analgesia with clonidine is short lived with some bradycardia. Intrathecal midazolam provides superior analgesia without clinically relevant adverse effects.
  3,768 324 2
DRUG WATCH
Cefditoren pivoxil associated rash and arthralgia in a child
Manab Nandy, Ananya Mandal, Santanu K Tripathi, Abhiram Chakrabarti
May-June 2012, 44(3):419-420
DOI:10.4103/0253-7613.96354  
Cefditoren pivoxil is an oral antimicrobial used increasingly in pediatric bacterial infections. We report a case of rash and arthralgia following administration of cefditoren pivoxil for lower respiratory tract infection in a four-year-old female child. On discontinuation of the antibiotic, the child recovered full function of the knee joint within seven days. The causality of the event assessed as per the WHO-UMC system for standardized case causality assessment criteria can be considered as 'probable'. Analyzed by the Naranjo's ADR probability scale, the score was 7, which also makes it a 'probable' event.
  3,883 113 -
Allopurinol-induced DRESS syndrome
Selcuk Yaylaci, Mustafa Volkan Demir, Tayfun Temiz, Ali Tamer, Mustafa Ihsan Uslan
May-June 2012, 44(3):412-414
DOI:10.4103/0253-7613.96351  
A 70-year-old man was admitted to our clinic with complaints of fever, jaundice, dyspnea, and generalized rash after 3 months of allopurinol treatment for gout. On physical examination, he was found to have fever (38.5°C), jaundice, and generalized maculopapular rash. Leukocytosis, eosinophilia, elevation of liver enzymes, and hyperbilirubinemia were detected in his blood analysis. Skin biopsy was consistent with drug-induced hypersensitivity. He was diagnosed as Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). Allopurinol treatment was stopped and steroid treatment was launched. At day 24 of admission, the patient died because of multiple organ failure.
  3,784 185 3
EDITORIAL
Quality assurance in medical education
Medha A Joshi
May-June 2012, 44(3):285-287
DOI:10.4103/0253-7613.96295  
  3,441 500 -
SHORT COMMUNICATIONS
Evaluation of antiasthmatic activity of ethanolic extract of Elephantopus scaber L. leaves
Rakesh Sagar, HB Sahoo
May-June 2012, 44(3):398-401
DOI:10.4103/0253-7613.96347  
Aims: The aim of study was to evaluate the scientific basis for the traditional use of Elephantopus scaber leaves. Materials and Methods: In the present study, ethanol extract of Elephantopus scaber leaves was evaluated for preliminary phytochemical screening and antiasthmatic activity using histamine and acetylcholine-induced bronchospasm, mast cell degranulation and histamine induced constriction on isolated guinea pig tracheal chain at different dose levels. Student's t-Test and Dunett's test were used for statistical analysis. Results: The result of present investigation showed that the ethanolic extract of E. scaber significantly (P<0.001) decreased the bronchospasm induced by histamine, acetylcholine and protected mast cell degranulation as compared to control groups. It also decreased the histamine induce constriction on isolated guinea pig trachea in dose-dependent manner. Phytochemical studies revealed the presence of steroids, saponin, flavonoids, and phenolic compounds in the extract. Conclusions: The present study concludes that the antiasthmatic activity of ethanolic extract of E. scaber leaves may be due to the presence of flavonoids or steroids. Antiasthmatic action of the E. scaber could be due to its antihistaminic, anticholinergic and mast-cell-stabilizing property.
  3,272 304 3
Propofol pharmacokinetics in young healthy Indian subjects
Avinash Puri, Bikash Medhi, Nidhi B Panda, GD Puri, Sanju Dhawan
May-June 2012, 44(3):402-406
Objectives: To analyze population pharmacokinetics of Propofol in Indian patients after single bolus dose of Propofol using WINNONLIN program. Materials and Methods: Population pharmacokinetics of Propofol was investigated in Indian subjects in 26 elective surgical patients (14 males and 12 females) following single bolus dose of 2 mg/kg propofol. A total of 364 samples were estimated by High Performance Liquid Chromatography and pharmacokinetic parameters were derived using WINNONLIN (5.2). The effect of demographic characters of the study population on pharmacokinetic parameters was investigated. Results: Three-compartment model was used to describe the pharmacokinetic data of Propofol in Indian subjects. Initial volume of distribution (V1) clearance (Cl) and steady state volume of distribution (Vd ss ) was 13.5 ± 3.3 l, 1.08 ± 0.42 l/min, and 77.69 ± 48.0 l, respectively. Body weight best described the volume of central compartment (V1) as well as elimination clearance (P<0.01). Conclusion: Pharmacokinetics of Propofol in young healthy Indian subjects show lower volume of distribution and clearance as compared with most of the western data. Body weight best describes the V1, Vd ss , and Clearance in this group.
  3,360 155 2
Evaluation of anti-ulcer effect of amlodipine in gastric ulcer models in rats
Amol N Patil, Manjari G Advani, SN Mali, Sudhir Pawar, Sanket B Raut
May-June 2012, 44(3):387-389
DOI:10.4103/0253-7613.96344  
Aims: To study anti-ulcer effect of Amlodipine and compared it with ranitidine in indomethacin, alcohol and pyloric ligation-induced gastric ulcers in wistar rats. Materials and Methods: Gastric ulcers were induced in Wistar albino rats by oral administration of indomethacin (200 mg/kg), alcohol (80%, 1 ml/100 gm) and by pyloric ligation. Antiulcer activity of amlodipine (0.5 mg/kg, i.p.) was observed either alone or in combination with ranitidine (15 mg/kg, i.p.), on ulcer index, gastric pH and gastric volume. Statistical analysis was done by ANOVA and unpaired one tailed 't ' test. P<0.05 was considered statistically significant. Results: Amlodipine produced significant (P<0.05) decrease in ulcer index and gastric pH as compared to control. It also produced significant (P<0.05) increase in gastric volume as compared to ranitidine. The anti-ulcer effects of ranitidine were significantly higher than that of amlodipine. Combination of amlodipine and ranitidine did not show significant increase in anti-ulcer activity as compared with ranitidine alone. Conclusions: Amlodipine produced significant anti-ulcer effects in all 3 experimental models. Amlodipine increased the volume of gastric secretions as compared to ranitidine.
  3,002 356 1
RESEARCH ARTICLES
An audit of first prescription of new patients attending a psychiatry walk-in-clinic in north India
Sandeep Grover, Vineet Kumar, Ajit Avasthi, Parmanand Kulhara
May-June 2012, 44(3):319-325
DOI:10.4103/0253-7613.96302  
Background: Although almost all psychotropic medications available worldwide are readily available in India, there is meager data in this country on the prescription patterns of psychiatrists. Aim: To study the first prescription handed over to patients attending the psychiatry outpatient clinic of a tertiary care hospital. Materials and Methods: Data of all patients (for the period of January 1, 2009 to November 30, 2010; diagnosed with an ICD-10 diagnosis of F2-F4) were extracted from the computer-based registry and analyzed. Results: Ten thousand two hundred and fourteen (10 214) patients were diagnosed to have a diagnosis of F2-F4 ICD-10 category. In all diagnostic groups, olanzapine was the most commonly prescribed antipsychotic followed by risperidone. Very few patients (8%) received typical antipsychotic medication. In all diagnostic groups, escitalopram was the most commonly prescribed antidepressant; other frequently prescribed antidepressants were sertraline, paroxetine, and venlafaxine. Among the mood stabilizers, valproate was preferred over lithium. In all the groups, more than half of the patients were prescribed benzodiazepines, clonazepam being the most commonly prescribed agent, followed by lorazepam. The mean number of psychotropic medications was highest in the bipolar disorder group. Very few patients received the combination of same group of drugs. Conclusions: Olanzapine, escitalopram, and clonazepam are the most commonly prescribed antipsychotic, antidepressants, and benzodiazepines, respectively. Valproate was preferred over lithium as a mood stabilizer. In general, the prescription trends were in accordance to the recommendations of various treatment guidelines, except for the use of benzodiazepines, which was higher.
  3,001 314 3
SHORT COMMUNICATIONS
Effect of beta-1-blocker, nebivolol, on central aortic pressure and arterial stiffness in patients with essential hypertension
Radhika Soanker, M.U.R Naidu, Sree Bhushan Raju, A Krishna Prasad, T Ramesh Kumar Rao
May-June 2012, 44(3):407-411
DOI:10.4103/0253-7613.96349  
Introduction: Blood pressure (BP) reduction is the major determinant of benefit provided by antihypertensive treatment. Although different drugs reduce peripheral BP to some extent, there may be a significant difference in their effect on central BP reduction. It has been shown that beta-blockers are efficient in reducing peripheral, but not central BP. This study was done to assess the effect of beta-1-blocker, nebivolol, in patients with essential hypertension on central aortic pressures and arterial stiffness. Materials and Methods: In this single arm, open-labeled study, 13 patients were given nebivolol, 5 mg orally once daily for 15 days. Primary outcome was change in central aortic pressure, and other measures of efficacy included changes in brachial BP, augmentation index (AIx%), AIx%@75 HR, augmentation pressure (AP), heart rate (HR), and carotid femoral pulse wave velocity (PWVcf). Results: Nebivolol 5 mg significantly reduced central aortic pressures [systolic BP, 131.5-111.6 mmHg; diastolic BP, 96.3-81.7 mmHg; Mean Arterial Pressure (MAP), 111.3-94.0 mmHg (all P<0.0001), and Pulse Pressure (PP), 35.2-29.7 mmHg (P<0.01)]. AIx%@75 HR reduced from 29 to 21.6 (P<0.001) and PWVcf reduced from 8.6 to 7.2 m/s (P<0.001). One subject was lost to followup. Conclusion: Nebivolol 5 mg demonstrated antihypertensive efficacy in patients with essential hypertension by reducing not only peripheral brachial pressures, but also significantly reducing central aortic pressures, augmentation index, and carotid femoral pulse wave velocity, which is the marker of arterial stiffness.
  2,957 197 7
RESEARCH ARTICLES
The effect of inhaled corticosteroids on hypothalamic-pituitary-adrenal axis
Keivan Gohari Moghaddam, Negin Rashidi, Hamidreza Aghaei Meybodi, Nader Rezaie, Mahdi Montazeri, Ramin Heshmat, Zohreh Annabestani
May-June 2012, 44(3):314-318
DOI:10.4103/0253-7613.96300  
Objectives: The aim of this study was to compare systemic effects of high-dose fluticasone propionate (FP) and beclomethasone dipropionate (BDP) via pressurized metered dose inhaler on adrenal and pulmonary function tests. Materials and Methods: A total of 66 patients with newly diagnosed moderate persistent asthma without previous use of asthma medications participated in this single blind, randomized, parallel design study. FP or BDP increased to 1 500 μg/d in 62 patients who had not received oral or IV corticosteroids in the previous six months. Possible effects of BDP and FP on adrenal function were evaluated by free cortisol level at baseline and after Synacthen test (250 μg). Fasting plasma glucose and pulmonary function tests were also assessed. Similar tests were repeated 3 weeks after increasing dose of inhaled corticosteroids to 1 500 μg/d. Results: No statistically significant suppression was found in geometric means of cortisol level post treatment in both groups. After treatment in FP group, mean forced expiratory volume in one second (FEV1) and mean forced vital capacity (FVC) values improved by 0.17 l (5.66% ± 13.91, P=0.031) and 0.18 l (5.09% ± 10.29, P=0.010), respectively. Although FEV1 and FVC improved in BDP group but was not statistically significant. Oral candidiasis and hoarseness were observed in 6.5% patients receiving BDP, but hoarseness was found in 3.2% patients in FP group (P=0.288). Conclusions: The results indicate that safety profiles of high doses of BDP and FP with respect to adrenal function are similar, but FP is more efficacious than that of BDP in improving pulmonary function test.
  2,831 257 1
Influence of pioglitazone on experimental heart failure and hyperlipidemia in rats
Arghya Biswas, Syed Imam Rabbani, Kshama Devi
May-June 2012, 44(3):333-339
DOI:10.4103/0253-7613.96305  
Objectives: To investigate the effect of pioglitazone on isoproterenol-induced heart failure and high-fructose diet-induced metabolic changes in rats. Materials and Methods: Three doses of pioglitazone (Pio - 3, 10, 30 mg/kg, po) were tested in male Wistar rats. In the Heart Failure (HF) group, treatment was followed by Isoproterenol (ISO) injection. The markers for HF, such as enzyme estimation, relative heart weight, and antioxidant status, were evaluated. In another group, metabolic disturbances were induced by High Fructose Diet (HFD). The influence of Pio treatment on Systolic Blood Pressure (SBP), serum glucose, Triglycerides (TG), Total Cholesterol (TC), and High-Density Lipoprotein (HDL)-cholesterol (HDL-c) were determined. Results: The results indicated that Pio at 10 mg increased significantly (P<0.05) the Lactate Dehydrogenase (LDH), Creatinine Kinase-MB (CK-MB), and antioxidant enzyme levels as compared to ISO. The high dose of Pio (30 mg) enhanced (P<0.05) Aspartate Transaminase (AST), Alanine Transaminase (ALT), Lipid Peroxidation (LPO),and relative heart weight in addition to increased LDH, CK-MB, and antioxidant enzyme activity. In the HFD group, a dose-dependent inhibitory effect was observed. Pio at 3 mg significantly reduced (P<0.05) elevated glycemia, TG, and SBP as compared to HFD rats. Further, the higher doses of Pio (10 and 30 mg) enhanced the inhibitory effect on glucose, TG, and SBP besides elevating the HDL-c levels. However, none of the tested doses of Pio significantly altered the TC level in HFD rats. Conclusion: The observations suggest that Pio exhibits anti-diabetic and anti-hypertensive effects and also partially corrected the hyperlipidemia, but the treatment augmented the cardiac damage associated with ISO. The antioxidant property of Pio appears to have a limited role in protecting the ISO-mediated heart damage.
  2,751 288 2
Citrus flavonoid naringenin improves aortic reactivity in streptozotocin-diabetic rats
Faramarz Fallahi, Mehrdad Roghani, Sanaz Moghadami
May-June 2012, 44(3):382-386
DOI:10.4103/0253-7613.96350  
Background and Objective: Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of naringenin was investigated on aortic reactivity of streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Male diabetic rats (n=32) were divided into control, naringenin-treated control, diabetic, and naringenin-treated diabetic groups of eight animals each. The latter group received naringenin for 5 weeks at a dose of 10 mg/kg/day after diabetes induction. The contractile responses to potassium chloride (KCl) and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Meanwhile, participation of nitric oxide (NO) and endothelial vasodilator factors in response to ACh were evaluated using N (G)-nitro-l-arginine methyl ester (L-NAME) and indomethacin (INDO), respectively. Results: Maximum contractile response of endothelium-intact rings to KCl and PE was significantly (P<0.05) lower in naringenin-treated diabetic rats as compared to untreated diabetics. Endothelium-dependent relaxation to ACh was significantly (P<0.05-0.01) higher in naringenin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N (G)-nitro-l-arginine methyl ester (L-NAME) significantly (P<0.001) attenuated the observed response. Conclusion: Chronic treatment of diabetic rats with naringenin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and endothelium integrity is necessary for this beneficial effect.
  2,806 172 4
Pharmacological investigation of memory restorative effect of riluzole in mice
Puneet Rinwa, Amteshwar Singh Jaggi, Nirmal Singh
May-June 2012, 44(3):366-371
DOI:10.4103/0253-7613.96337  
Objective: Streptozotocin (STZ) and sodium nitrite (NaNO 2 ) treatment have been positively correlated with higher incidence of memory loss and experimental dementia. The present study was designed to investigate the potential of the Riluzole, an inhibitor of glutamatergic neurotransmission and activator of TWIK-Related K + channels with incidences of memory deficits associated with dementia in mice. Materials and Methods: Dementia was induced in Swiss albino mice by intracerebroventricular STZ (ICV) and by subcutaneous NaNO 2 in separate groups of animals. Morris water maze was employed to assess learning and memory of the animals. Biochemical analysis of brain homogenate was performed so as to assess brain acetyl cholinesterase (AChE) activity. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured to assess total oxidative stress. Results: Treatment of ICV STZ and NaNO 2 produced a significant decrease in water maze performance of mice hence reflecting loss of learning and memory. Furthermore, higher levels of brain AChE activity and oxidative stress were observed in these animals. Administration of riluzole (5 and 10 mg/kg intraperitoneally) successfully attenuated memory deficits as well as ICV STZ- and NaNO 2 -induced changes in the levels of brain AChE, TBARS, and GSH. Conclusion: The memory restorative effects of riluzole in dementia may involve its multiple functions including anti-oxidative and anticholinesterase properties.
  2,523 245 3
Evaluation of protective effect of Aegle marmelos Corr. in an animal model of chronic fatigue syndrome
Vanphawng Lalremruta, Gurunath S Prasanna
May-June 2012, 44(3):351-356
DOI:10.4103/0253-7613.96316  
Objective: To evaluate ethanolic extract of leaves of Aegle marmelos in an experimental animal model of chronic fatigue syndrome for potential therapeutic benefit. Materials and Methods: Age/weight-matched female Wistar albino rats were grouped into five groups. (Group I- V) (n = 8). Group I served as naïve control and II served as stress control. Except for group I animals, other group animals were subjected to forced swimming every day for 15 minutes to induce a state of chronic fatigue and simultaneously treated with ethanolic extract of Aegle marmelos (EEAM) 150 and 250 mg/kg b.w. and Imipramine (20 mg.kg b.w.), respectively. Duration of immobility, anxiety level and locomotor activity were assessed on day 1, 7, 14 and 21 followed by biochemical estimation of oxidative biomarkers at the end of the study. Results: Treatment with EEAM (150 and 250 mg/kg b.w.) resulted in a statistically significant and dose dependent reduction (P <0.001) in the duration of immobility, reduction in anxiety and increase in locomotor activity. Dose dependent and significant reduction in LPO level and increase in CAT and SOD was observed in extract treated animals. Conclusion: The results are suggestive of potential protective effect of A. marmelos against experimentally induced CFS.
  2,464 265 2
Reversal of reserpine-induced orofacial dyskinesia and catalepsy by Nardostachys jatamansi
Rupali A Patil, Yogesh A Hiray, Sanjay B Kasture
May-June 2012, 44(3):340-344
DOI:10.4103/0253-7613.96307  
Context: Reserpine-induced orofacial dyskinesia is an animal model of tardive dyskinesia which may be associated with neurodegeneration and free radical damage. Aim: The aim was to assess the neuroprotective potential and in vivo antioxidant status of alcoholic extract of roots and rhizomes of Nardostachys jatamansi (ANJ) and its triterpenes (TNJ) in reserpine-induced orofacial dyskinesia. Materials and Methods: In the present study, repeated treatment with reserpine (1.0 mg/kg) on each other day for a period of 5 days (days 1, 3, and 5) significantly induced vacuous chewing movements (VCMs) and tongue protrusions (TPs) in rats. The effect on reserpine-induced catalepsy was also studied. The effect of ANJ and TNJ on levels of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) and inhibition of lipid peroxidation (LPO) in the forebrain region was assessed. Statistical Analysis: All observations were expressed as mean ± SEM. Statistical analysis was performed by the one-way ANOVA followed by Dunnett's test. P<0.05 was regarded as statistically significant. Results: At the end of the treatment schedule, ANJ and TNJ significantly inhibited reserpine-induced VCM, TP, and catalepsy, and significantly increased the locomotion and rearing in the open-field test. Treatment with ANJ and TNJ exhibited significant elevation in the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) and inhibition of lipid peroxidation (LPO) in forebrain region compared to the reserpine treated group. Conclusions: The study concludes that ANJ and TNJ significantly protected animals against reserpine-induced orofacial dyskinesia as well as catalepsy suggesting its potential value in the treatment of neuroleptic-induced orofacial dyskinesia and Parkinson's disease.
  2,476 246 2
A low dose of doxorubicin improves antioxidant defence system and modulates anaerobic metabolism during the development of lymphoma
Nibha Verma, Manjula Vinayak
May-June 2012, 44(3):308-313
DOI:10.4103/0253-7613.96299  
Objective: The objective of the present study is to find low dose of doxorubicin (DOX) with cancer preventive activity and to check the implication of this low dose of DOX on antioxidant defence system during lymphoma growth in mice, as the clinical utility of anthracycline anticancer drugs, especially DOX is limited by a progressive cardiotoxicity linked to mitochondrial damage. Materials and Methods: We selected a dose of DOX (0.90 mg/kg body weight of mouse), which is about 20 folds lower than clinically used dose for cancer treatment. The cancer preventive action is monitored by modulation of anaerobic metabolism. The effect of this dose on antioxidant defence system is analyzed by testing the activities of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST). The activities of these enzymes were monitored at different intervals during the growth of lymphoma in mice. Results: The activities of antioxidant enzymes, such as CAT, SOD, and GST, were found to decrease gradually during the growth of lymphoma in mice. The anaerobic metabolism was increasing with lymphoma growth. We report that about 20 folds lower dose of DOX enhances the activities of antioxidant enzymes and decreases anaerobic metabolism during the development of lymphoma. These enzymes of antioxidant defence system suppress oxidative stress and mitochondrial damage, whereas a decrease in anaerobic metabolism checks cancer growth. Conclusions: The result suggests that dose cumulative cellular toxicity of DOX may be avoided by treating cancer in animals with lower doses of DOX in combination with other drugs.
  2,386 204 1
SHORT COMMUNICATIONS
Propofol pharmacokinetics in China: A multicentric study
Hong-bo Ye, Jin-heng Li, Jian-zhong Rui, Hong Zheng, Xin-an Zhang, Xin-jin Chi, Wen-ying Chen, Jian-guo Xu
May-June 2012, 44(3):393-397
DOI:10.4103/0253-7613.96346  
Objective : A multicenter population pharmacokinetics study of propofol was performed to establish a new population model. Materials and Methods : Three thousand two hundred and fifty-nine blood samples of 220 participants were measured by HPLC-UV or HPLC-FLU or GC-MS. Target-controlled infusion after single bolus or continuous infusion was applied for propofol anesthesia. The samples were taken from 2 to 1500 min. The concentration-time profiles were analyzed by nonlinear mixed effect model (NONMEM) with first order estimation method. The inter-individual variability and the residual variability were described by exponential model and constant coefficient variation model. The stepwise modeling strategy using PsN was applied for covariate modeling. The criteria of forward addition and backward elimination were (α = 0.01 and α = 0.005, χ2, df = 1). The final model was evaluated by bootstrap using PDx and visual predictive check using PsN. 500 bootstraps and 1000 simulation were run. Result : The propofol population model was described by 3-compartment model with inter-individual variability of CL, V 1 , Q 2, and Q 3 describing by exponential model. The inter-individual variability of V 2 , V 3 were not included because it is reported that the parameter was near its boundary. The typical value of CL, V1, Q2, V2, Q3 and V3 were 1.28 L · min-1 , 10.1 × (age/44)-0.465 × (1 + 0.352 × sex) L, 0.819 L · min-1 , 36.0 L, 0.405 × (bodyweight/60)1.58 L · min-1 and 272 L, respectively. Coefficients of inter-individual variability of CL, V1, Q2 and Q3 were 30.5%, 35.6%, 43.7% and 66.9%, respectively, and the coefficients of variation of HPLC-UV, GC-MS and HPLC-FLU were 13.3%, 16.9% and 24.2%, respectively. The bootstrap evaluation showed that the final model parameter estimates were within ± 3.39% compared with bootstrap median. The curves of observations percentiles were distributed within the corresponding 95 prediction percentiles by the visual predictive check. Conclusion: The three-compartment model with first-order elimination could describe the pharmacokinetics of propofol fairly well. The involved fixed effects are age, body weight and sex. The population model was evaluated to be stable by bootstrap and visual predictive check.
  2,457 90 1
DRUG WATCH
Successful treatment of excessive dose of carbamazepine
Selcuk Yaylaci, Mustafa Volkan Demir, Bilgehan Acar, Savas Sipahi, Ali Tamer
May-June 2012, 44(3):417-418
DOI:10.4103/0253-7613.96353  
Carbamazepine is used in the treatment of epilepsy; it is also prescribed for treatment of neuralgic pain syndromes and certain affective disorders. Carbamazepine intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, arrhythmia, hemodynamic instability, and death. There is no specific antidote. Multiple-dose activated charcoal and hemodialysis are the main treatment for carbamazepine intoxication. In this paper, we report the case of a 19-year-old woman with excessive dose carbamazepin intoxication and our successful treatment with multiple-dose activated charcoal and hemodialysis.
  2,249 109 2
RESEARCH ARTICLES
Improvement of abnormal liver enzymes after rosiglitazone treatment in Chinese type 2 diabetes
Jing-Quan Zheng, Kun Wang, Dee Pei, Yen-Lin Chen, Yen-Lin Chang, Chun-Hsien Hsu, Tsan-Ming Huang, Mei-Yu Lin, Pao-Ying Lin, Jiunn-Diann Lin
May-June 2012, 44(3):372-376
DOI:10.4103/0253-7613.96340  
Objectives: Insulin resistance is one of the important underlying abnormalities of type 2 diabetes. The effect of thiazolidinedione on liver functions has been controversial in different studies. In this study, we evaluated the effect of rosiglitazone on liver enzymes in subjects with type 2 diabetes with and without abnormal liver function. Materials and Methods: Seventy-three patients with type 2 diabetes taking rosiglitazone 4 mg daily were enrolled in this 3-month study. Forty-two of them had normal liver function (NLF), and 31 had abnormal liver function (ABLF). Blood biochemistries were collected monthly during the treatment period. Results: At baseline, other than age and liver enzymes, there were no differences in body mass index, fasting plasma glucose, hemoglobin A1c (HbA1c), and lipid profiles between the NLF and ABLF groups. At the end of the treatment, HbA1c was lowered in both groups, but only significantly in the ABLF group ( P = 0.027). More importantly, serum concentrations of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the ABLF group decreased significantly (AST: 57.8 ± 26.5 to 47.5 ± 20.2 U/L, P = 0.006; ALT 66.6 ± 35.0 to 51.9 ± 23.5 UL, P = 0.004), while in the NLF group, a similar change was not found. Conclusion: After 3-month rosiglitazone treatment in subjects with type 2 diabetes with mildly elevated liver enzymes, significant improvement in AST and ALT were observed. Our study provides some hints that rosiglitazone might not be contraindicated in subjects with diabetes with abnormal liver function as previously thought, but further well-designed studies are necessary to clarify this issue.
  2,163 128 -
DRUG WATCH
Paraphenylene diamine poisoning
AC Jesudoss Prabhakaran
May-June 2012, 44(3):423-424
DOI:10.4103/0253-7613.96356  
The commonest constituent of all hair dyes is paraphenylene diamine (PPD). Hair dye poisoning is emerging as one of the emerging causes of intentional self-poisoning to commit suicide. In this article, we report a case of PPD poisoning and the importance of clinical of hair dye poisoning. The lack of specific diagnostic tests, a specific antidote for paraphenylene diamine poisoning and the importance of early supportive treatment modalities are also discussed.
  2,125 124 -
Norfloxacin-induced hypoglycemia and urticaria
Ajay Mishra, Nikhil Dave
May-June 2012, 44(3):415-416
DOI:10.4103/0253-7613.96352  
Fluoroquinolone-induced hypoglycemia is not a common adverse drug reaction. However, it has been reported with most of the available agents and appears to be more common in elderly patients with a history of type 2 diabetes who are receiving oral sulfonylureas. The exact mechanism of this effect is unknown but is postulated to be a result of blockage of Adenosine 5'-Triphosphate (ATP)-sensitive potassium channels in pancreatic β-cell membranes. This report highlights hypoglycemia with urticaria as an adverse drug reaction of norfloxacin in a middle aged non-diabetic patient. Clinicians should be alert about the possibility of its potential adverse effect in patients who are receiving norfloxacin therapy.
  2,051 166 1
SHORT COMMUNICATIONS
Effect of Terminalia catappa on lipid profile in transplanted fibrosarcoma in rats
Pandya Naitik, Tigari Prakash, Dupadahalli Kotresha, Nadendla Rama Rao
May-June 2012, 44(3):390-392
DOI:10.4103/0253-7613.96345  
To evaluate the effect of an antitumor activity of Terminalia catappa on lipid lowering activity in transplanted fibrosarcoma in Wistar albino rats. Methylcholantherene-induced fibrosarcoma was transplanted in rats. After 30 th day when tumor became palpable, started the treatment of ethanolic extract of Terminalia catappa by orally (250 and 500 mg/kg) for a period of 20 days. The blood sample was collected on 21 st day, and the liver and the kidney were also removed for studying the lipid profile in serum and the tissues. The levels of total cholesterol, triglycerides and very low density lipoprotein (VLDL) were markedly elevated and high density lipoprotein (HDL) was markedly decreased in the serum of tumor bearing rats. Significant alterations were also observed in the lipid profile of liver and kidney. These changes were significantly reversed in Terminalia catappa (500 mg/kg) treated animals. The reversal of altered lipid levels to normal values in rats with experimentally induced tumor was showed antitumor activity by Terminalia catappa.
  2,065 116 2
LETTERS TO THE EDITOR
Uncontrolled penile erection and increased sexual desire with intravenous moxifloxacin
Abdulkadir Kucukbayrak, Zulkuf Perdeci, Zeynep Seckin Kucukbayrak, Ersin Günay
May-June 2012, 44(3):426-427
DOI:10.4103/0253-7613.96359  
  1,960 119 -
DRUG WATCH
Unilateral tremor induced by risperidone in a patient with acute mania: Vitamin B12 deficiency as possible mediating factor
Shivanand Kattimani, Sushanta Kumar Padhy, Indukumar Annamalai
May-June 2012, 44(3):421-422
DOI:10.4103/0253-7613.96355  
Identification and management of drug-induced movement disorders is a clinical challenge, more so when the clinical presentation is atypical. A young male with acute mania was under treatment with sodium valproate and risperidone. He developed tremors of right hand and neck. These were present at rest and exacerbated by mental activity, when under observation and during voluntarily initiated activity. There were no associated extra pyramidal symptoms or cerebellar signs. Investigations for other common causes of tremors did not reveal any evidence except for low value of serum vitamin B12 levels. The tremors persisted after the withdrawal of valproate, but resolved following the withdrawal of risperidone. It is a common dictum that drug-induced tremors are bilateral. This may not be true always as we found out in our case. These movements were probably induced by risperidone. This atypical presentation could be due to concurrent use of valproate and low serum vitamin B12 levels.
  1,714 114 -
LETTERS TO THE EDITOR
Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuvant-induced arthritis and hematological indices in rats
Mahendra K Patel, Manish J Barvaliya, Tejas K Patel
May-June 2012, 44(3):425-425
DOI:10.4103/0253-7613.96357  
  1,637 115 1
Steven-Johnson syndrome may NOT be due to ayurvedic drugs - 1
G Pallavi, KL Virupaksha Gupta
May-June 2012, 44(3):427-428
DOI:10.4103/0253-7613.96360  
  1,475 120 -
Steven-Johnson syndrome may NOT be due to ayurvedic drugs - 3
Ramesh Babu Devalla
May-June 2012, 44(3):429-429
DOI:10.4103/0253-7613.96362  
  1,327 101 -
Steven-Johnson syndrome may NOT be due to ayurvedic drugs - 2
Galib Ruknuddin
May-June 2012, 44(3):428-428
DOI:10.4103/0253-7613.96361  
  1,130 109 -
ERRATUM
Erratum

May-June 2012, 44(3):332-332
  950 81 -
LETTERS TO THE EDITOR
Authors' reply
Raghu Prasada M Shivamurthy, Ravindra Kallappa, Shashikala G.H Reddy, Druva Kumar B Rangappa
May-June 2012, 44(3):429-429
  930 84 -
Author's reply
D Banji
May-June 2012, 44(3):426-426
  932 60 -
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