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   2009| July-August  | Volume 41 | Issue 4  
    Online since September 26, 2009

 
 
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SHORT COMMUNICATION
Bromocriptine mesylate: FDA-approved novel treatment for type-2 diabetes
Rajiv Mahajan
July-August 2009, 41(4):197-198
DOI:10.4103/0253-7613.56070  PMID:20523873
  7,704 1,568 5
RESEARCH ARTICLES
Analgesic and anti-inflammatory activity of Argyreia speciosa root
RS Bachhav, VS Gulecha, CD Upasani
July-August 2009, 41(4):158-161
DOI:10.4103/0253-7613.56066  PMID:20523865
Objective: To study analgesic and anti-inflammatory activities of a methanolic extract (ME) of Argyreia speciosa (AS) root powder. Materials and Methods: The study was carried out using male albino mice (20-25 gm) and male wistar rats (100-150gm). The ME was prepared using soxhlet extraction process. The effect of ME of A. speciosa was investigated for analgesic activity using acetic acid-induced abdominal constriction, tail immersion method and hot plate method. The anti-inflammatory activity of ME of AS roots was studied using carrageenan-induced rat paw edema. Result: The ME of A. speciosa root was used in pain and inflammation models. The analgesic activity of AS at the dose of (30,100, and 300 mg/kg p.o) showed significant (P< 0.01) decrease in acetic acid-induced writhing, whereas ME of A. speciosa at the dose of (100, 300 mg/kg p.o) showed significant (P<0.01) increase in latency to tail flick in tail immersion method and elevated mean basal reaction time in hot plate method. The ME of the A. speciosa at doses (30, 100, and 300mg/kg) showed significant (P < 0.01) inhibition of carrageenan induced hind paw edema in rats. Conclusion: The ME of A. speciosa showed significant analgesic and anti-inflammatory activity in mice and rat.
  5,125 1,561 5
REVIEW ARTICLE
Recent advances in pharmacotherapy of atrial fibrillation
J Singh, JS Braich
July-August 2009, 41(4):153-157
DOI:10.4103/0253-7613.56064  PMID:20523864
Atrial fibrillation (AF) is the most common sustained arrhythmia associated with increased morbidity and mortality. Efficacy and safety of currently employed antiarrhythmic drugs (AADs) continue to be less optimal in AF. Development of newer AADs has recently been made possible through a greater understanding of electro-pathophysiology of AF. Highly specific drugs acting on atria are currently being explored, although there is little data available on effectiveness of atrial specific agents in maintaining sinus rhythm. Combining AADs and non-AADs such as angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase effectiveness of AADs in patients with AF. Controlled clinical trials are required to precisely define the efficacy of single agents versus various combinations in maintaining sinus rhythm in patients with AF. This review describes some of the most promising therapeutic approaches that may overcome some of the limitations of drugs used at present for the management of AF.
  4,680 1,206 1
RESEARCH ARTICLES
Determination of drug-like properties of a novel antileishmanial compound: In vitro absorption, distribution, metabolism, and excretion studies
Susanta Kumar Mondal, Nirup B Mondal, Sukdeb Banerjee, Upal Kanti Mazumder
July-August 2009, 41(4):176-181
DOI:10.4103/0253-7613.56075  PMID:20523869
In drug discovery research, the compounds should not only to be potent and selective but also must possess acceptable pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) to increase success rate in clinical studies. Objective: Exploration of drug-like properties of 2-(2-methylquinolin-4-ylamino)-N-phenyl acetamide, a potent antileishmanial compound by performing some in vitro ADME experiments along with validation of such studies. Materials and Methods: Experimental protocols were established and validated for stability (in PBS pH7.4, simulated gastric and intestinal fluid), solubility, permeability, distribution coefficient (Log D), plasma protein binding and metabolism by rat liver microsomes by using spectrophotometer or HPLC. Methods were considered valid if the results of the standard compounds matched with reported results or within acceptable range or with proper ranking (high-medium-low). Results: The compound was found to be stable (>95% remaining) in all stability studies and aqueous solubility was 299.7 ± 6.42 μM. The parallel artificial membrane permeability assay (PAMPA) indicated its medium permeability (Log Pe = -5.53 ± 0.01). The distribution coefficients (Log D) in octanol/PBS and cyclohexane/PBS systems were found to be 0.54 and -1.33, respectively. The plasma protein binding study by the equilibrium dialysis method was observed to be 78.82 ± 0.13% while metabolism by Phase-I enzymes for 1 hour at 37°C revealed that 36.07 ± 4.15% of the compound remained after metabolism. Conclusion: The methods were found to be very useful for day-to-day ADME studies. All the studies with the antileishmanial compound ascertained that the compound bears optimum pharmacokinetic properties to be used orally as a potential drug for the treatment of leishmaniasis.
  5,016 491 4
CASE REPORTS
Severe irritant contact dermatitis induced by povidone iodine solution
Mangala Bhaskar Murthy, Bhaskar Krishnamurthy
July-August 2009, 41(4):199-200
DOI:10.4103/0253-7613.56069  PMID:20523874
Albeit uncommon occurrence, irritant contact dermatitis induced by povidone iodine can be an unfortunate adverse reaction complicating its use as an antiseptic. We hereby present the case report of a patient who suffered such a reaction as a result of exposure to povidone iodine, employed as an antiseptic during spinal anesthesia. On conservative management with soframycin ointment, the lesions resembling chemical burns healed in a month without extensive scarring or other complications.
  4,390 361 3
RESEARCH ARTICLES
Reduced exposure of imatinib after coadministration with acetaminophen in mice
Inthisham Nassar, Thanikachalam Pasupati, John Paul Judson, Ignacio Segarra
July-August 2009, 41(4):167-172
DOI:10.4103/0253-7613.56071  PMID:20523867
Purpose: Imatinib is an efficacious drug against chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) due to selective inhibition of c-KIT and BCR-ABL kinases. It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated. However, a few severe drug-drug interactions have been reported in cancer patients taking acetaminophen. Materials and Methods: Male ICR mice were given 100 mg/kg single dose of imatinib orally or imatinib 100 mg/kg (orally) coadministered with acetaminophen intraperitoneally (700 mg/kg). Mice were euthanized at predetermined time points, blood samples collected, and imatinib plasma concentration measured by HPLC. Results: Imatinib AUC 0-12 was 27.04 ± 0.38 mg·h/ml, C max was 7.21 ± 0.99 mg/ml and elimination half-life was 2.3 hours. Acetaminophen affected the imatinib disposition profile: AUC 0-12 and C max decreased 56% and 59%, respectively and a longer half-life was observed (5.6 hours). Conclusions: The study shows a pharmacokinetic interaction between acetaminophen and imatinib which may render further human studies necessary if both drugs are administered concurrently to cancer patients.
  4,186 410 12
Cholinergic influence on memory stages: A study on scopolamine amnesic mice
Rahul Agrawal, Ethika Tyagi, Gunjan Saxena, Chandishwar Nath
July-August 2009, 41(4):192-196
DOI:10.4103/0253-7613.56072  PMID:20523872
Objectives: The study was planned to determine cholinergic influence on different stages of memory - acquisition, consolidation and recall in scopolamine-induced amnesia (memory impairment) in mice. Materials and Methods: To study acquision, consolidation and recall stages of memory, we administered scopolamine (0.75, 1.5 and 3 mg/kg ip) 30 minutes and five minutes prior to first trial acquisition and consolidation and 30 minutes prior to second trial recall of passive avoidance (PA) test, respectively, in separate groups. Tacrine (5 mg/kg po) and rivastigmine (5 mg/kg po) were administered one hour prior to first trial in separate groups which received scopolamine (3 mg/kg ip) 30 minutes and five minutes prior to first trial where as the control group received vehicle only. Results: In the control group, there was a significant (P < 0.01) increase in transfer latency time (TLT) in the second trial compared to first indicating successful learning. In scopolamine treated groups, administering scopolamine 30 minutes or five minutes prior to first trial did not show any significant (P > 0.05) change in TLT whereas mice treated with scopolamine 30 minutes prior to second trial showed significant (P < 0.01) increase in TLT in second trial as compared to the first. Both tacrine and rivastigmine administration in scopolamine treated mice showed significant (P < 0.05-0.01) increase in TLT in second trial as compared to first trial while the rivastigmine treated group showed greater percentage retention compared to tacrine treated group. Conclusion: Results show that acquisition and consolidation are more susceptible to the scopolamine effects than recall. Thus, it may be concluded that cholinergic influence is more on acquisition and consolidation as compared to recall.
  3,898 535 14
EDITORIAL
Changing face of pharmacology practicals for medical undergraduates
Mira Desai
July-August 2009, 41(4):151-152
DOI:10.4103/0253-7613.56062  PMID:20523863
  3,448 811 5
RESEARCH ARTICLES
Effect of lanthanum carbonate and calcium acetate in the treatment of hyperphosphatemia in patients of chronic kidney disease
P Thomas Scaria, Reneega Gangadhar, Ramdas Pisharody
July-August 2009, 41(4):187-191
DOI:10.4103/0253-7613.56074  PMID:20523871
Objectives: The tolerability and efficacy of lanthanum carbonate has not been studied in the Indian population. This study was, therefore, undertaken to compare the efficacy and tolerability of lanthanum carbonate with calcium acetate in patients with stage 4 chronic kidney disease. Design: A randomized open label two group cross-over study. Materials and Methods: Following Institutional Ethics Committee approval and valid consent, patients with stage 4 chronic kidney disease were randomized to receive either lanthanum carbonate 500 mg thrice daily or calcium acetate 667 mg thrice daily for 4 weeks. After a 4-week washout period, the patients were crossed over for another 4 weeks. Serum phosphorous, serum calcium, serum alkaline phosphatase, and serum creatinine were estimated at fixed intervals. Results: Twenty-six patients were enrolled in the study. The mean serum phosphorous concentrations showed a declining trend with lanthanum carbonate (from pre-drug levels of 7.88 ± 1.52 mg/dL-7.14 ± 1.51 mg/dL) and calcium acetate (from pre-drug levels of 7.54 ± 1.39 mg/dL-6.51 ± 1.38 mg/dL). A statistically significant difference was seen when comparing the change in serum calcium produced by these drugs (P < 0.05). Serum calcium levels increased with calcium acetate (from pre-drug levels of 7.01 ± 1.07-7.46 ± 0.74 mg dL), while it decreased with lanthanum carbonate (from pre-drug levels 7.43 ± 0.77-7.14 ± 0.72 mg/ dL). The incidence of adverse effects was greater with lanthanum carbonate. Conclusion: Lanthanum carbonate and calcium acetate are equally effective phosphate binders with trends obvious in the first 4 weeks of therapy. The decrease in serum calcium levels with lanthanum carbonate when compared to the increase in serum calcium levels due to calcium acetate is statistically significant. The drawback of lanthanum carbonate is its high cost and relatively higher incidence of adverse events during treatment.
  3,696 395 2
Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride
Dhaval K Gavali, Kala S Kulkarni, Amal Kumar, Bhaswat S Chakraborty
July-August 2009, 41(4):162-166
DOI:10.4103/0253-7613.56068  PMID:20523866
Background: Propranolol hydrochloride, one of the most widely used β-blocker in the treatment of hypertension since 1960s, shows a number of serious and non-serious adverse events. Objective: Major objectives of this study were to extract the Canadian Adverse Drug Reaction Monitoring Program (CADRMP) database for possible toxic signal detection (SD) of propranolol hydrochloride, evaluate the frequency of the bradycardia associated with it in different stratified groups for a putative signal, and generate awareness in healthcare professionals regarding usefulness of SD. Materials and Methods: Appropriate statistical methods were used for adverse drug reaction (ADR) signal detection such as, proportional reporting ratio (PRR); reporting odds ratio (ROR); the Chi-square (λ2 ) statistic method; the 95% confidence interval (CI); the observed to expected ratio (O/E); and Du Mouchel method were used to calculate the possible signals. Significance of λ2 and other calculated statistics, e.g., PRR and ROR, was based on a composite criterion of regulatory guidelines and not on any particular statistical level of significance. Results: Calculated statistics by different methods were compared with the regulatory criteria of a statistic value ≥4.0 for λ2 , and ≥3.0 for the rest for SD to be declared significant. The PRR statistic was found to be 2.5054; by the ROR method it was 2.5820; the λ2 statistic was 3.2598, whereas the lower and upper limits of 95% CI of PRR were found to be 0.0778 and 1.9104, respectively, by the O/E ratio was found to be 2.3978, and PRR with the help of Du Mouchel was found to be 2.3979. Thus, the bradycardia-propranolol signals calculated in this study were not significant. Conclusions: The therapeutic class specific signal of bradycardia associated with propranolol hydrochloride was not found potent enough to cause bradycardia. However, since the calculated statistics were very high albeit not significant, the possibility of bradycardia-propranolol pairing should still be analyzed from larger databases.
  3,547 393 -
Effect of an isolated active compound (Cg-1) of Cassia glauca leaf on blood glucose, lipid profile, and atherogenic index in diabetic rats
Papiya Mitra Mazumder, Mamta Farswan, V Parcha
July-August 2009, 41(4):182-186
DOI:10.4103/0253-7613.56076  PMID:20523870
Objectives: The objective of present study was to evaluate the effect of active principle (Cg-1) from Cassia glauca leaf on serum glucose and lipid profile in normal and diabetic rats. Materials and Methods: Diabetes was induced by streptozotocin in neonates. Oral administration of petroleum ether, chloroform, acetone, and methanol of C. glauca leaf (100 mg/kg, p.o.) for 21 days caused a decrease in fasting blood glucose (FBG) in diabetic rats. Among all the extracts, acetone extract was found to lower the FBG level significantly in diabetic rats. Glibenclamide was used as standard antidiabetic drug (5 mg/kg, p.o). Acetone extract was subjected to column chromatography that led to isolation of an active principle, which was given trivial name Cg-1. Cg-1 (50 mg/kg, p.o.) was studied for its hypoglycemic and hypolipidemic potential. The unpaired t-test and analysis of variance (ANOVA) followed by post hoc test was used for statistical analysis. Results: Cg-1 caused a significant reduction in FBG level. It also caused reduction in cholesterol, triglycerides, and LDL levels and improvement in the atherogenic index and HDL level in diabetic rats. Conclusion: Improvement in the FBG and the atherogenic index by Cg-1 indicates that Cg-1 has cardioprotective potential along with antidiabetic activity and provides a scientific rationale for the use as an antidiabetic agent.
  3,091 713 3
In-vitro red blood cell partitioning of doxycycline
PV Deshmukh, PC Badgujar, MM Gatne
July-August 2009, 41(4):173-175
DOI:10.4103/0253-7613.56073  PMID:20523868
Objective: In-vitro red blood cell (RBC) partitioning of doxycycline was studied to determine whether doxycycline penetrates RBC and its concentration was assayed keeping in view its high lipophilicity. Materials and Methods: Standardization of doxycycline was performed in whole blood and plasma of cattle by microbiological assay using Bacillus subtillis ATCC 6633 as indicator organizm. Actual concentration of the drug was obtained by comparing zone inhibition with standard graph and the extent of partitioning was mathematically calculated. Results: The R 2 value of standard graph for doxycycline was 0.9934 and 0.9727 for plasma and whole blood, respectively. Overall, RBC partitioning of doxycycline was found to be 18.40 ± 1.70%. Conclusions: Overall RBC partitioning of doxycycline indicated low penetration into RBC. Plasma is the fluid suggested for pharmacokinetic evaluation of doxycycline.
  3,048 315 -
CASE REPORTS
Relapse of tardive dyskinesia due to reduction in clozapine dose
Meena Shrivastava, Bhupendra Solanke, Ganesh Dakhale, Abhishek Somani, Pravir Waradkar
July-August 2009, 41(4):201-202
DOI:10.4103/0253-7613.56067  PMID:20523875
Clozapine is a second-generation (atypical) antipsychotic agent, which has been proven efficient against the positive and negative symptoms of schizophrenia, with a low propensity to induce tardive dyskinesia (TD). Compared with typical antipsychotics, it has a greater affinity for dopamine D4 than D2 receptors and additional action on serotonin 5-HT 2A receptors. Due to its weak D 2 blocking action, it produces few extra pyramidal side effects and TD is rare. TD is one of the muscular side effects of antipsychotic drugs, especially the older generation like haloperidol. TD does not occur until after many months or years of taking antipsychotic drugs. TD is primarily characterized by abnormal involuntary movements of the tongue, lips or jaw, as well as facial grimacing or extremities that develop in association with the use of antipsychotic medications. TD can be embarrassing to the affected patient in public. The movements disappear during sleep and women are at greater risk than men for developing TD.
  2,497 256 3
LETTER TO THE EDITOR
Medicinal plant-based health products: Where is the medicinal constituent?
R Mathur, T Velpandian
July-August 2009, 41(4):205-206
DOI:10.4103/0253-7613.56063  PMID:20523877
  2,193 483 3
CASE REPORTS
Docetaxel-induced photolichenoid eruption
Biju Vasudevan, M.P.S. Sawhney, Nitu Sharma
July-August 2009, 41(4):203-204
DOI:10.4103/0253-7613.56065  PMID:20523876
A 58-year-old man presented with complaints of blackish discoloration of forearms and face of five months duration. The lesions occurred episodically after taking anti-cancer medications, each episode lasting for two weeks. Histopathology confirmed a lichenoid eruption. Photolichenoid eruption to docetaxel is a dermatological adverse effect not reported in literature earlier.
  2,244 240 2
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