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   2010| July-August  | Volume 42 | Issue 4  
    Online since August 13, 2010

 
 
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RESEARCH ARTICLES
Nature of action of sitagliptin, the dipeptidyl peptidase-IV inhibitor in diabetic animals
Joseph A Davis, Shuchita Singh, Sachin Sethi, Subhasis Roy, Shivani Mittra, Geetavani Rayasam, Vinay Bansal, Jitendra Sattigeri, Abhijit Ray
July-August 2010, 42(4):229-233
DOI:10.4103/0253-7613.68425  PMID:20927248
Objective : The aim of this study was to evaluate the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin with respect to mode of inhibition and its in vivo duration of inhibition and efficacy in type 2 diabetes animal model. Materials and Methods : DPP-IV enzyme assay was carried out in human plasma (10 μL) or human recombinant enzyme (10 ng) using H-Gly-Pro-AMC as a substrate. The competitive nature was estimated by plotting IC 50 values measured at different substrate concentrations on the Y axis and substrate concentration on the X axis. The tight binding nature was estimated by plotting IC 50 values measured at different plasma volumes on the Y axis and plasma volumes on the X axis. Fast binding kinetics was assessed by progressive curves at different inhibitor concentrations in the DPP-IV assay. The reversibility of the inhibitor was assessed by a dissociation study of the DPP-IV-sitagliptin complex. Durations of DPP-IV inhibition and efficacy were shown in ob/ob mice dosed at 10 mg/kg, p.o. Results : Sitagliptin is a competitive, reversible, fast and tight binding DPP-IV inhibitor. In ob/ob mice, 10 mg/kg, (p.o.) showed a long duration of inhibition of > 70% at 8 h. The duration was translated into long duration of efficacy (~ 35% glucose excursion at 8 h) in the same model and the effect was comparable to vildagliptin. Conclusion : The DPP-IV inhibitor sitagliptin behaves as a competitive, tight, and fast binding inhibitor. Sitagliptin differs mechanistically from vildagliptin and exhibits comparable efficacy to that of latter. The finding may give an understanding to develop-second generation DPP-IV inhibitors with desired kinetic profiles.
  9 6,780 351
EDUCATIONAL FORUM
Adaptive design clinical trials: Methodology, challenges and prospect
Rajiv Mahajan, Kapil Gupta
July-August 2010, 42(4):201-207
DOI:10.4103/0253-7613.68417  PMID:20927243
New drug development is a time-consuming and expensive process. Recently, there has been stagnation in the development of novel compounds. Moreover, the attrition rate in clinical research is also on the rise. Fearing more stagnation, the Food and Drug Administration released the critical path initiative in 2004 and critical path opportunity list in 2006 thus highlighting the need of advancing innovative trial designs. One of the innovations suggested was the adaptive designed clinical trials, a method promoting introduction of pre-specified modifications in the design or statistical procedures of an on-going trial depending on the data generated from the concerned trial thus making a trial more flexible. The adaptive design trials are proposed to boost clinical research by cutting on the cost and time factor. Although the concept of adaptive designed clinical trials is round-the-corner for the last 40 years, there is still lack of uniformity and understanding on this issue. This review highlights important adaptive designed methodologies besides covering the regulatory positions on this issue.
  7 11,627 1,324
RESEARCH ARTICLES
Antidiabetic activity of Cassia occidentalis (Linn) in normal and alloxan-induced diabetic rats
Laxmi Verma, Anirudh Khatri, Basant Kaushik, Umesh K Patil, Rajesh S Pawar
July-August 2010, 42(4):224-228
DOI:10.4103/0253-7613.68422  PMID:20927247
Objective : To evaluate the hypoglycemic activity of various extracts, petroleum ether, chloroform and aqueous extract of Cassia occidentalis in normal and alloxan-induced diabetic rats. Materials and Methods : Petroleum ether, chloroform and aqueous extract of whole plant of Cassia occidentalis were orally tested at the dose of 200 mg/kg for hypoglycemic effect in normal and alloxan-induced diabetic rats. In addition, changes in body weight, serum cholesterol, triglyceride and total protein levels, assessed in the ethanol extract-treated diabetic rats, were compared with diabetic control and normal animals. Histopathological observations during 21 days treatment were also evaluated. Results : Aqueous extract of C. occidentalis produced a significant reduction in fasting blood glucose levels in the normal and alloxan-induced diabetic rats. Apart from aqueous extract, petroleum ether extract showed activity from day 14 and chloroform extract showed activity from 7 days. Significant differences were observed in serum lipid profiles (cholesterol and triglyceride), serum protein, and changes in body weight by aqueous extract treated-diabetic animals, when compared with the diabetic control and normal animals. Concurrent histopathological studies of the pancreas of these animals showed comparable regeneration by extract which were earlier necrosed by alloxan. Conclusion : Aqueous extract of C. occidentalis exhibited significant antihyperglycemic activity in normal and alloxan-induced diabetic rats. They also showed improvement in parameters like body weight and serum lipid profiles as well as histopathological studies showed regeneration of β-cells of pancreas and so might be of value in diabetes treatment.
  7 9,973 817
Effects of ethanol extract of Ficus bengalensis (bark) on inflammatory bowel disease
Manish Amerutlal Patel, Paras Kantibhai Patel, Manish B Patel
July-August 2010, 42(4):214-218
DOI:10.4103/0253-7613.68420  PMID:20927245
Objective : The present study was designed to evaluate the effects of ethanol extract of Ficus bengalensis Linn. bark (AEFB) on inflammatory bowel disease (IBD). Materials and Methods : Effects of AEFB were studied on 2,4,6-trinitrobenzenesulfonic acid (TNBS, 0.25 ml 120 mg/ml in 50% ethanol intrarectally, on first day only) induced IBD in rats. The effects of co-administration of prednisolone (2 mg/kg) and AEFB (250, 500 mg/kg) for 21 days were evaluated. Animals sacrificed at end of the experiment and various histopathological parameters like colon mucosal damage index (CMDI) and disease activity index (DAI) were assessed. In the colon homogenate malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and nitric oxide (NO) levels and in mesentery % mast cell protection was also measured. Results : Rats treated with only TNBS showed more score of CMDI and DAI, higher MDA, NO, MPO, and lower SOD activity as compared to the control group. Treatment with AEFB significantly declined both indices scores and decreased the MPO, MDA, NO, and increased the SOD activity. AEFB also increased the % mast cell protection compared to alone TNBS-treated animals. Conclusion : In our study, we found that AEFB has a significant protective effect in the IBD in rats that is comparable to that of prednisolone and may be because of the presence of flavonoids, terpenoids, and phenolic compounds.
  4 4,717 319
CASE REPORTS
Unusual nail pigmentation following cyclophosphamide-containing chemotherapy regimen
Santosh Kumar, Rakesh Dixit, Saurabh Karmakar, Sayan Paul
July-August 2010, 42(4):243-244
DOI:10.4103/0253-7613.68433  PMID:20927252
Cyclophosphamide therapy may rarely cause pigmentation of the nails which is of different patterns. We report a patient who developed pigmentation of nails after six cycles of cyclophosphamide, methotrexate, and 5-flourouracil chemotherapy, each repeated after 28 days for breast cancer. The patient developed nail pigmentation that started proximally and spread distally and involved all the nails of both hands and feet except the second and third toenails of right foot. Using Naranjo ADR Probability Scale, the case revealed a "probable" association with cyclophosphamide.
  3 5,980 158
RESEARCH ARTICLES
Mechanism of cardioprotective effect of erythropoietin-induced preconditioning in rat heart
Kavita Garg, Harlokesh N Yadav, Manjeet Singh, PL Sharma
July-August 2010, 42(4):219-223
DOI:10.4103/0253-7613.68421  PMID:20927246
Objective : The cardioprotective potential of human recombinant erythropoietin (alpha) (Epo) against ischemia-reperfusion-induced injury is well known. But, the underlying mechanisms are not well elucidated. The aim of this study was to characterize the mechanism involved in the cardioprotective effect of Epo-induced preconditioning in isolated rat heart. Materials and Methods : The heart was mounted on a Langendorff apparatus. After 10 min of stabilization, four cycles of ischemic preconditioning (IPC) were given followed by 30 min of global ischemia and 120 min of reperfusion. Epo preconditioning was induced by four cycles of 5-min perfusion of K-H solution containing Epo (1.0 U/ml) followed by 5 min perfusion with K-H solution. Myocardial infarct size was estimated macroscopically using the triphenyltetrazolium chloride staining technique. The extent of myocardial injury was measured by release of lactate dehydrogenase and creatine kinase-MB in the coronary effluent. Results : The present study demonstrates that Epo preconditioning was almost as effective as IPC. Administration of Wortmannin (100 nM), a PI-3K inhibitor, or Chelerythrine (1 μM), a protein kinase-C (PKC) inhibitor, or AG490 (5 μM), a JAK-2 inhibitor, significantly attenuated the cardioprotective effects of Epo-induced preconditioning. Conclusion : Our result suggest that the cardioprotective potential of Epo-induced preconditioning in isolated rat heart was due to an interplay of the JAK-2, PI-3K and PKC pathways. Inhibition of any one of the three pathways was sufficient to block the cardioprotective effect of Epo-induced preconditioning in isolated rat heart.
  3 3,377 241
CASE REPORTS
Propofol and priapism
Subramanian Senthilkumaran, Sweni Shah, Ganapathysubramanian , Namasivayam Balamurgan, Ponniah Thirumalaikolundusubramanian
July-August 2010, 42(4):238-239
DOI:10.4103/0253-7613.68430  PMID:20927250
Propofol-induced priapism in a 25-year-old male confirmed by rechallenge is reported for its rarity and to create awareness among practitioners, because propofol is used frequently in India for the induction and maintenance of anesthesia or sedation. The probable mechanisms are highlighted. Because propofol causes low-flow priapism, early alleviation is essential to minimize and/or avert the long-term complications.
  2 4,791 154
Capreomycin-induced optic neuritis in a case of multidrug resistant pulmonary tuberculosis
Rahul Magazine, Mahuya Pal, Bharti Chogtu, Veena Nayak
July-August 2010, 42(4):247-248
DOI:10.4103/0253-7613.68436  PMID:20927254
A patient of multidrug-resistant pulmonary tuberculosis was prescribed an anti-tubercular regimen containing capreomycin. Patient developed optic neuritis 3 months after starting treatment. Investigations did not reveal any specific cause for this ocular condition and on discontinuing capreomycin his vision recovered. We conclude that capreomycin is the cause of reversible optic neuritis in our case.
  2 2,707 137
RESEARCH ARTICLES
Evaluation of Cassia occidentalis for in vitro cytotoxicity against human cancer cell lines and antibacterial activity
Madhulika Bhagat, Ajit Kumar Saxena
July-August 2010, 42(4):234-237
DOI:10.4103/0253-7613.68428  PMID:20927249
Objective : To evaluate the in vitro cytotoxicity and antibacterial properties of Cassia occidentalis (whole plant) via alcoholic, hydro-alcoholic, and aqueous extracts against eight human cancer cell lines from six different tissues and four bacterial strains. Material and Methods : In vitro cytotoxicity against the human cancer cells, cultured for 48h in presence of different concentrations C. occidentalis extracts and percentage of cell viability, was evaluated using the sulforhodamine-B (SRB) assay. The antibacterial activity was performed using the standard protocol against bacterial strains. Results : It was observed that aqueous extract of C. occidentalis (whole plant) had more potential than hydro-alcoholic and alcoholic extracts against HCT-15, SW-620, PC-3, MCF-7, SiHa, and OVCAR-5 human cancer cell lines at 100, 30, and 10 μg/ml in a dose-dependent manner. The hydro-alcoholic extract showed potential against Bacillus subtillis. Conclusion : The plant can be explored for the possible development of lead molecules for drug discovery.
  2 4,577 382
CASE REPORTS
Rifampicin-induced thrombocytopenia
Ajay Kumar Verma, Arpita Singh, Amol Chandra, Santosh Kumar, Rajesh Kumar Gupta
July-August 2010, 42(4):240-242
DOI:10.4103/0253-7613.68432  PMID:20927251
In the treatment of tuberculosis there are special therapeutic problems related to adverse effects of drugs, compliance to treatment, and microbial resistance. Thrombocytopenia is an uncommon but potentially fatal adverse effect of certain anti-tubercular drugs when the incriminating drug is taken by a susceptible individual. We report a case of rifampicin-induced thrombocytopenia, which although rare, needs attention.
  1 4,041 253
Diffuse skeletal pain after administration of alendronate
Nihal Ozaras, Aylin Rezvani
July-August 2010, 42(4):245-246
DOI:10.4103/0253-7613.68435  PMID:20927253
Background : Osteoporosis is caused by bone resorption in excess of bone formation, and bisphosphonates, are used to inhibit bone resorption. Alendronate, a biphosphonate, is effective for both the treatment and prevention of osteoporosis in postmenopausal women. Side effects are relatively few and prominently gastrointestinal. Musculoskeletal pain may be an important side effect in these patients. We presented a patient admitted to our out-patient clinic with diffuse skeletal pain after three consecutive administration of alendronate. Conclusion : We conclude that patients with osteoporosis can report pain, and bisphosphonate-related pain should also be considered before ascribing this complaint to osteoporosis.
  1 2,779 124
RESEARCH ARTICLES
Renal effects of Mammea africana Sabine (Guttiferae) stem bark methanol/methylene chloride extract on L-NAME hypertensive rats
Elvine Pami Nguelefack-Mbuyo, Theophile Dimo, Telesphore Benoit Nguelefack, Alain Bertrand Dongmo, Pierre Kamtchouing, Albert Kamanyi
July-August 2010, 42(4):208-213
DOI:10.4103/0253-7613.68418  PMID:20927244
Objective : The present study aims at evaluating the effects of methanol/methylene chloride extract of the stem bark of Mammea africana on the renal function of L-NAME treated rats. Material and Methods : Normotensive male Wistar rats were divided into five groups respectively treated with distilled water, L-NAME (40 mg/kg/day), L-NAME + L-arginine (100 mg/kg/day), L-NAME + captopril (20 mg/kg/day) or L-NAME + M. africana extract (200 mg/kg/day) for 30 days. Systolic blood pressure was measured before and at the end of treatment. Body weight was measured at the end of each week. Urine was collected 6 and 24 h after the first administration and further on day 15 and 30 of treatment for creatinine, sodium and potassium quantification, while plasma was collected at the end of treatment for the creatinine assay. ANOVA two way followed by Bonferonni or one way followed by Tukey were used for statistical analysis. Results : M. africana successfully prevented the rise in blood pressure and the acute natriuresis and diuresis induced by L-NAME. When given chronically, the extract produced a sustained antinatriuretic effect, a non-significant increase in urine excretion and reduced the glomerular hyperfiltration induced by L-NAME. Conclusions : The above results suggest that the methanol/methylene chloride extract of the stem bark of M. africana may protect kidney against renal dysfunction and further demonstrate that its antihypertensive effect does not depend on a diuretic or natriuretic activity.
  1 3,468 326
SHORT COMMUNICATION
Drug safety monitoring in patients of movement disorders of a tertiary care hospital
Ananya Mandal, Suparna Chatterjee, Shyamal Kumar Das, Amar Mishra
July-August 2010, 42(4):249-251
DOI:10.4103/0253-7613.68437  PMID:20927255
Background : Movement disorders (MD) are neurological conditions that affect the speed, fluency, quality, and ease of movement and commonly include Parkinson's disease, tremor and dystonias. Drugs are important causes of MD, and the incidence and prevalence of such disorders are possibly underappreciated because of the lack of recognition. Objectives : To assess the incidence of all adverse drug reactions (ADRs) and estimate the prevalence of drug-induced MD among patients attending the clinic. Materials and Methods : This prospective observational study was conducted at an outpatient referral MD clinic of a tertiary care hospital for 1 year. The demographic data, drug intake, diagnosis, and ADRs experienced by the subjects were recorded. Causality assessment was done by Naranjo's scale. Results : Incidence of ADR among patients who attended this clinic was 19.7% (151 out of 768 patients experienced at least one ADR). A total of 299 ADRs were detected out of which 30.8% were gastrointestinal, 28.4% psychiatric, and 26% MD effects. The commonly implicated suspect drugs were levodopa (37.8%) and trihexyphenidyl (25.1%). The prevalence of drug-induced MD was 10.15% and drug-induced dyskinesias and dystonias were the most common. Conclusion : MDs are clinically important neurological disorders which are often caused by drugs and interestingly drugs used for its management are also associated with high incidence of ADRs. Hence these ADRs should be carefully monitored.
  1 3,070 237
EDITORIAL
Embedding clinical trials in clinical practice: Harvesting experience and winnowing evidence
Arun S Nanivadekar
July-August 2010, 42(4):199-200
DOI:10.4103/0253-7613.68416  PMID:20927242
  - 2,263 426
LETTERS TO THE EDITOR
Pharmacovigilance on olanzapine
Anand Lingeswaran, Harsha Shetty, Kigshuk Lahon, Amit Paramel, Gyaneshwar Sharma
July-August 2010, 42(4):252-253
DOI:10.4103/0253-7613.68438  PMID:20927256
  - 2,327 275
A survey on postgraduate pharmacology education in India
Ananya Chakraborty
July-August 2010, 42(4):253-254
DOI:10.4103/0253-7613.68439  PMID:20927257
  - 2,271 284
The need for introducing medication vials tailored for pediatric use. Where do we stand?
T Arun Babu, C Venkatesh
July-August 2010, 42(4):254-254
DOI:10.4103/0253-7613.68441  PMID:20927258
  - 1,850 102
Effect of participation in a clinical trial on glycemic control in type 2 diabetic patients
Mukta N Chowta, Prabha M Adhikari, Nithyananda K Chowta, Susan D'Souza, Ashok K Shenoy
July-August 2010, 42(4):255-256
DOI:10.4103/0253-7613.68442  PMID:20927259
  - 2,026 152
THE JOURNAL CLUB
The Journal Club

July-August 2010, 42(4):257-257
  - 1,781 193
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