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   2013| July-August  | Volume 45 | Issue 4  
    Online since July 15, 2013

 
 
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RESEARCH ARTICLES
A comparative study of efficacy and safety of gabapentin versus amitriptyline as coanalgesics in patients receiving opioid analgesics for neuropathic pain in malignancy
Manasi Banerjee, Santanu Pal, Biswamit Bhattacharya, Balaram Ghosh, Shirsendu Mondal, Joydeep Basu
July-August 2013, 45(4):334-338
DOI:10.4103/0253-7613.115000  PMID:24014906
Objective: To assess the efficacy and safety of gabapentin and amitriptyline along with opioids in patients suffering from neuropathic pain in malignancy. Materials and Methods: Eighty-eight adult patients between 18 and 70 years of age with neuropathic pain in stage III malignant disease, matched for baseline charactistics, were randomly assigned to two groups. Group A received oral tramadol and gabapentin and group B received oral tramadol and amitriptyline. The treatment duration of each patient was 6 months. Visual analog scale (VAS) was the primary efficacy parameter. Verbal rating scale (VRS) score, percentage of pain relief (PPR), and global pain score (GPS) were the secondary efficacy parameters. Oral morphine tablets or fentanyl transdermal patch were used as rescue medication. Data analysis was carried out in Graph Pad instat. Results: There was decline in VAS pain score from baseline in both the groups in the early phase of the study though there was no statistically detectable difference between them at any study point. Similar changes were seen in the secondary efficacy parameters too. Thus both the drugs were effective in providing relief to cancer patients with neuropathic pain though there was no statistically detectable difference in efficacy between them. Six patients in group A and eight patients in group B required rescue medication. A total of 12 subjects in the gabapentin group and 15 subjects in the amitriptyline group experienced adverse events which were of mild to moderate grades. Conclusions: Amitriptyline may be a suitable alternative for management of neuropathic pain in cancer patients although gabapentin is widely used for this purpose. The lower cost of amitriptyline may favor patient compliance with lesser number of drop-outs.
  4 4,691 433
LETTERS TO THE EDITOR
Rutin exerts antiulcer effect by inhibiting the gastric proton pump
Shagun Dubey, Aditya Ganeshpurkar, Abhishek Shrivastava, Divya Bansal, Nazneen Dubey
July-August 2013, 45(4):415-417
DOI:10.4103/0253-7613.115011  PMID:24014928
  3 2,730 140
RESEARCH ARTICLES
Amelioration of cisplatin-induced nephrotoxicity by statins
Rajesh A Maheshwari, Girish U Sailor, Lalji Patel, R Balaraman
July-August 2013, 45(4):354-358
DOI:10.4103/0253-7613.115016  PMID:24014910
Objectives: This study aimed to investigate the protective effect of simvastatin (SIM) and rosuvastatin (RST) on cisplatin (CIS)-induced nephrotoxicity. Materials and Methods: Adult female Wistar rats were divided into six groups: Control group (Group 1) received 0.5% sodium carboxy methyl cellulose, group 2 and group 3 received SIM and RST for 10 days, respectively, and group 4 was injected single dose of CIS (7 mg/kg, i.p.). Group 5 and 6 were treated with SIM (10 mg/kg, p.o.) and RST (10 mg/kg, p.o.) for 10 days, respectively. All groups received cisplatin on the 5 th day of treatment. Renal function tests like serum creatinine, urea, BUN, albumin, calcium, uric acid and magnesium, serum lipids, and markers of oxidative stress such as renal malondialdehyde (MDA) level and superoxide dismutase (SOD) and catalase (CAT) activities were measured. All tissues were investigated for histopathological changes. Result: CIS reduced the renal function, which was reflected with significant increase in serum urea, BUN, serum creatinine, uric acid and also significant decrease serum calcium, magnesium, albumin levels. In addition, cisplatin caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity, and elevation of serum lipids. SIM or RST ameliorate CIS induced renal damage due to improvement in renal function, oxidative stress, suppression of serum lipids, and histological alteration. Conclusions: This finding suggests that simvastatin and rosuvastatin may have a protective effect against cisplatin-induced kidney damage via amelioration of lipid peroxidation as well as due to improvement of renal function, and lipid-lowering effects.
  3 2,975 274
DRUG WATCH
Unexpected death due to cefuroxime-induced disulfiram-like reaction
Hongmei Dong, Ji Zhang, Liang Ren, Qian Liu, Shaohua Zhu
July-August 2013, 45(4):399-400
DOI:10.4103/0253-7613.114991  PMID:24014919
Cefuoxime, a second-generation cephalosporin, is used in the treatment of Gram-positive infections. Here, we report a case cefuroxime-induced disulfiram-like reaction which led to sudden death of the patient.
  2 3,541 119
A case of thrombocytopenia caused by rifampicin and pyrazinamide
Rekha Bansal, Parveen K Sharma, Aradhna Sharma
July-August 2013, 45(4):405-407
DOI:10.4103/0253-7613.114998  PMID:24014922
A 32-year-old male patient was diagnosed as having pulmonary tuberculosis and put on category II antitubercular regime since he had a history of antituberculosis treatment 10 years ago. Within 3 weeks, patient presented with ulcers in mouth, and blood picture confirmed thrombocytopenia. Rifampicin-induced thrombocytopenia was suspected and antitubercular treatment stopped. Patient improved and was re-exposed to the drugs one by one. After re-exposure with pyrazinamide, the platelet count decreased drastically and oral mucosal ecchymoses reappeared, while with rifampicin, thrombocytopenia was accompanied with petechiae on legs and forearms. Isoniazid, ethambutol, and streptomycin were continued.
  2 3,489 120
Inflamed psoriatic plaques: Drug toxicity or disease exacerbation?
Nidhi Jindal, Kshama Arora, Pooja Jindal, Vijay Kumar Jain, Sangita Ghosh
July-August 2013, 45(4):410-411
DOI:10.4103/0253-7613.115001  PMID:24014924
We are presenting a case of Methotrexate treated stable plaque psoriasis, in whom inflamed psoriatic plaques of drug toxicity were misdiagnosed as disease exacerbation. Erosive psoriatic plaques were present in the absence of biochemical or hematological derangements. Ulceration of psoriatic plaques in the presence of disturbed hematological profile is well described as a harbinger of methotrexate toxicity, but this kind of erosions in the absence of any systemic involvement is the first report of its kind.
  2 2,112 96
RESEARCH ARTICLES
Evaluation of anti-inflammatory effect of statins in chronic periodontitis
Snophia Suresh, Satya Narayana, P Jayakumar, Uma Sudhakar, V Pramod
July-August 2013, 45(4):391-394
DOI:10.4103/0253-7613.115017  PMID:24014917
Objectives: Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Materials and Methods: Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of Department of Periodontics, Thaimoogambigai Dental College and Hospital, Chennai. Thirty patients selected were grouped into two groups, Group-I consists of patients with generalized chronic periodontitis and on statin medication and Group-II consists of patients with generalized chronic periodontitis. Clinical parameters were recorded and gingival crevicular fluid (GCF) samples were analyzed for interleukin (IL)-1β using commercially available enzyme-linked immunosorbent assay. Results: The mean GCF IL-1® levels in generalized chronic periodontitis patients who are on statin medication (Group-I) were lower than the generalized chronic periodontitis patients without statin medication (Group-II). Conclusion: Reduction of GCF IL-1β levels in statin users indicate that statins have anti-inflammatory effect on periodontal disease.
  2 4,020 241
DRUG WATCH
Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS)
Shaman Gill, Amitabh Sagar, S Shankar, Velu Nair
July-August 2013, 45(4):401-402
DOI:10.4103/0253-7613.114993  PMID:24014920
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, dapsone, and antiretroviral agents such as abacavir and nevirapine. We describe a rare case of nevirapine-induced hypersensitivity syndrome that was successfully treated with oral steroids.
  1 2,937 127
Terlipressin-induced hyponatremic seizure in a child
Syed Ahmed Zaki
July-August 2013, 45(4):403-404
DOI:10.4103/0253-7613.114995  PMID:24014921
Terlipressin, an analog of the natural hormone arginine-vasopressin, is a splanchnic constrictor that is used to control variceal bleeding in portal hypertension. It has a very good safety profile compared to vasopressin. Although rare, adverse effects such as hyponatremia and seizure can occur. We describe a 7-year-old male child who developed hyponatremia induced by infusion of terlipressin which resulted in a generalized seizure. After withdrawal of terlipressin, the serum sodium level became normal. Through this case, we emphasize the importance of monitoring patient's electrolyte levels during the course of terlipressin therapy.
  1 3,048 95
Severe photosensitivity reaction induced by topical diclofenac
Pramod B Akat
July-August 2013, 45(4):408-409
DOI:10.4103/0253-7613.114999  PMID:24014923
Albeit uncommon, photosensitivity reaction induced by diclofenac can be an unfortunate adverse reaction complicating its use as a topical analgesic. We here present a case of a patient who suffered such a reaction as a result of exposure to diclofenac, employed as a topical analgesic for low backache. The lesions healed with conservative management without extensive scarring or other complications.
  1 3,654 136
EDITORIAL
Regulatory changes in conduct of clinical trials: A need for review
Suparna Chatterjee
July-August 2013, 45(4):323-324
DOI:10.4103/0253-7613.114990  PMID:24014903
  1 3,498 565
LETTERS TO THE EDITOR
Effects of Withania somnifera in patients of schizophrenia: A randomized, double blind, placebo controlled pilot trial study
Akshay P Agnihotri, Smita D Sontakke, Vijay R Thawani, Anand Saoji, Vaidya Shishir S Goswami
July-August 2013, 45(4):417-418
DOI:10.4103/0253-7613.115012  PMID:24014929
  1 3,292 132
RESEARCH ARTICLES
Effect of methylprednisolone on bone mineral density in rats with ovariectomy-induced bone loss and suppressed endogenous adrenaline levels by metyrosine
Mehmet Yilmaz, Unal Isaoglu, Turan Uslu, Kadir Yildirim, Bedri Seven, Fatih Akcay, Ahmet Hacimuftuoglu
July-August 2013, 45(4):344-347
DOI:10.4103/0253-7613.115008  PMID:24014908
Objectives: In this study, effect of methylprednisolone on bone mineral density (BMD) was investigated in rats with overiectomy induced bone lose and suppressed endogenous adrenalin levels, and compared to alendronate. Materials and Methods: Severity of bone loss in the examined material (femur bones) was evaluated by BMD measurement. Results: The group with the highest BMD value was metyrosinemetyrosine + methylprednisolone combination (0.151 g/cm 2 ), while that with the lowest BMD was methylprednisolone (0.123 g/cm 2 ). Alendronate was effective only when used alone in ovariectomized rats (0.144 g/cm 2 ), but not when used in combination with methylprednisolone (0.124 g/cm 2 ). In the ovariectomized rat group which received only metyrosine, BMD value was statistically indifferent from ovariectomized control group. Conclusions: Methylprednisolone protected bone loss in rats with suppressed adrenaline levels because of metyrosinemetyrosine.
  1 3,742 117
Antidepressant-like effect of novel 5-HT3 receptor antagonist N-n-butyl-3-ethoxyquinoxalin-2-carboxamide (6p): An approach using rodent behavioral antidepressant tests
Shvetank Bhatt, Radhakrishnan Mahesh, Thangaraj Devadoss, Ankur Kumar Jindal
July-August 2013, 45(4):348-353
DOI:10.4103/0253-7613.115014  PMID:24014909
Objective: The present study was designed to investigate the antidepressant potential of N-n-butyl-3-ethoxyquinoxalin-2-carboxamide ( 6p ), a novel 5-HT 3 receptor antagonist in rodent behavioral models of depression. Materials and Methods: The compound 6p was examined in various behavioral models like forced swim test (FST), tail suspension test (TST), mechanistic models [5-hydroxytryptophan (5-HTP)-induced head twitch and reserpine-induced hypothermia (RIH)], and in chronic surgery model-olfactory bulbectomy in rats. Results: Compound 6p (1, 2, and 4 mg/kg, i.p.) exhibited antidepressant-like effect in FST and TST after acute treatment without having an effect on baseline locomotor activity. Moreover, 6p (2 mg/kg, i.p.), potentiated the 5-HTP-induced head twitch responses in mice and inhibited the RIH in rats. Chronic treatment (14 days) with 6p (1 and 2 mg/kg, p.o.) and paroxetine (10 mg/kg, p.o.) in rats significantly reversed the behavioral anomalies induced by bilateral olfactory bulbectomy using open field exploration. Conclusion: The preliminary studies reveal that compound 6p exhibits antidepressant-like effect in behavioral rodent models of depression.
  1 4,142 185
Antioxidative effects of hesperetin against lead acetate-induced oxidative stress in rats
Jicang Wang, Huali Zhu, Zijun Yang, Zongping Liu
July-August 2013, 45(4):395-398
DOI:10.4103/0253-7613.115015  PMID:24014918
Objectives: Oxidative stress with subsequent lipid peroxidation (LP) has been suggested as a mechanism for lead-induced toxicity. The current study was carried out to evaluate antioxidant activity of hesperetin against lead acetate-induced oxidative stress. Materials and Methods: The male rats were treated with hesperetin in combination with lead acetate (500 mg/L). Results: The results indicated that hesperetin alone did not induce any significant changes in the biochemistry of serum, liver, and kidney tissues. On the other hand, lead-induced oxidative stress as indicated by significant changes in serum biochemical parameters, including increased lipid peroxide and decreased reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels in liver and kidney tissues. Hesperetin succeeded in improving these biochemical parameters towards the normal values of control. Conclusions: It suggests that hesperetin shows antioxidant activity and plays a protective role against lead-induced oxidative damage in liver and kidney of rats.
  1 3,213 166
Involvement of opioid and monoaminergic pain pathways in Aegle marmelos induced analgesia in mice
Saroj Kothari, Anjali Kushwah, Dilip Kothari
July-August 2013, 45(4):371-375
DOI:10.4103/0253-7613.115020  PMID:24014913
Objective: To study analgesic activity and to evaluate the involvement of opioid and monoamines in the antinociceptive activity of methanol extract of leaves of Aegle marmelos. Materials and Methods: Analgesic activity of methanol extract (ME) of A. marmelos alone (75,150 and 300mg/kg orally) and in combination with morphine or venlafaxine (subanalgesic) were studied using tail flick test and acetic acid-induced writhing in mice. The effect of pre-treatment with opioid antagonist naltrexone 1mg/kg was also studied on antinociception induced due to ME. Result: ME produced a dose-dependent significant antinociceptive activity in the tail flick test and acetic acid-induced writhing in mice. (P<0.05) Administration of subanalgesic dose of ME with morphine or venlafaxine also resulted in significant (P<0.05) antinociceptive activity in both the pain models. Pre-treatment with naltrexone inhibited analgesic activity induced by ME alone and combination with morphine or venlafaxine. Conclusion: A.marmelos in induced antinociception is mediated through both opioid and monoaminergic pain pathways, suggest its possible use in chronic pain.
  1 3,030 166
Cytotoxic activity of aqueous extracts of Anogeissus leiocarpus and Terminalia avicennioides root barks against Ehrlich Ascites Carcinoma cells
Amadu Kayode Salau, Musa Toyin Yakubu, Adenike Temidayo Oladiji
July-August 2013, 45(4):381-385
DOI:10.4103/0253-7613.115023  PMID:24014915
Objectives: Folkloric claims on the use of a mixture of Anogeissus leiocarpus and Terminalia avicennioides root barks in tumor management exist without scientific evidence. This study aimed at investigating the phytochemical constituents and in vitro antiproliferative activity of these plants and their mixture. Materials and Methods: Phytochemical screening was carried out on the aqueous extracts after which various concentrations (0 to 1 000 μg/ml) were incubated with Ehrlich ascites carcinoma cell lines for 3 and 24 hours. Results: The extracts contained alkaloids, tannins, flavonoids, phenolics, saponins, phlobatannins, and terpenes. The separate extracts and their 1:1 mixture significantly (P<0.05) decreased the computed percentage viability of the cell lines in a dose- and time-dependent manner. Conclusions: The antiproliferative activity may be due to the presence of the bioactive compounds in the extracts and has a potential in the management of tumor.
  1 2,393 159
BOOK REVIEW
Principles of Medical Education
Medha A Joshi
July-August 2013, 45(4):419-419
  - 1,313 153
LETTERS TO THE EDITOR
Integration can lead to efficiencies as well as costs
Kieran Walsh
July-August 2013, 45(4):412-412
DOI:10.4103/0253-7613.115002  PMID:24014925
  - 2,324 76
Chronic fluoxetine treatment and sexual behavior in male and female albino rats
Ranjita Santra, Patralekha Raychaudhuri, Chiranjib Bagchi, Santanu Kumar Tripathi
July-August 2013, 45(4):412-414
DOI:10.4103/0253-7613.115004  PMID:24014926
  - 2,681 85
Detection of complete Dihydropyrimidine Dehydrogenase deficiency in a Tunisian family using a simple phenotypic test
Arij Mani, Manel Nouira, Slim Ben Ahmed, Saad Saguem
July-August 2013, 45(4):414-415
DOI:10.4103/0253-7613.115010  PMID:24014927
  - 2,373 57
RESEARCH ARTICLES
Antidepressant-like action of the hydromethanolic flower extract of Tagetes erecta L. in mice and its possible mechanism of action
Aarti Khulbe, Savita Pandey, Sangeeta Pilkhwal Sah
July-August 2013, 45(4):386-390
DOI:10.4103/0253-7613.115026  PMID:24014916
Objective: Tagetes erecta, the marigold, has commercial and ethnomedicinal use; however, reports concerning its efficacy for the treatment of depression are lacking. This study was carried out to elucidate the antidepressant effect of hydromethanolic flower extract of T. erecta. Materials and Methods: Hydromethanolic extract of flowers of Tagetes erecta was subjected to preliminary phytochemical screening. The extract (12.5, 25, and 50 mg/kg, i.p.) was evaluated for antidepressant effect using forced swim test in mice. The mechanism of antidepressant action was further examined using different drugs and imipramine was used as standard drug. Results: T. erecta significantly inhibited the immobility period in forced swim test in mice P<0.05). T. erecta (25 mg/kg, i.p.) enhanced the anti-immobility effect of antidepressant drugs like imipramine, fluoxetine, and p-chlorophenylalanine, an inhibitor of serotonin synthesis significantly attenuated its antidepressant effect. The antidepressant effect of T. erecta in the forced swim test was prevented by pretreatment with L-arginine and sildenafil, whereas pretreatment of mice with nitric oxide synthase inhibitors potentiated the action. Pentazocine, a high-affinity sigma receptor agonist, produced synergism with effective dose of T. erecta while progesterone, a sigma receptor antagonist, reversed the antidepressant effect of T. erecta. However, the locomotor activity was not affected at tested doses. Conclusions: Serotonergic, nitrergic pathway, and sigma receptors are possibly involved in mediating antidepressant action of T. erecta in mouse forced swim test.
  - 3,510 233
Protective effect of Clerodendrum colebrookianum Walp., on acute and chronic inflammation in rats
Lokesh Deb, Amitabha Dey, G Sakthivel, Subrat Kumar Bhattamishra, Amitsankar Dutta
July-August 2013, 45(4):376-380
DOI:10.4103/0253-7613.115021  PMID:24014914
Aim: To evaluate antioxidant, anti-inflammatory potential of the aqueous extracts and its aqueous, n-butanol, ethyl-acetate, and chloroform fractions of Clerodendrum colebrookianum Walp. leaves. Materials and Methods: In this present study, all the test samples were evaluated on in-vivo inflammatory model such as carrageenan and histamine-induced acute-inflammation and cotton pellet induced granuloma formation in albino male rats. Test samples were also employed in in-vitro assays like DPPH* free radical scavenging activity and COX inhibition assay. Results: The test samples at the dose of 200mg/kg/p.o. were found to cause significant inhibition of carrageenan and histamine-induced inflammation and cotton pallet-induced granuloma formation on acute and chronic inflammation in rats. The test samples, except n-butanol fraction, exhibited inhibitory effect for both COX-1 and COX-2, in in-vitro assay but their percentage of inhibition values differs from each other. The test samples (aqueous extracts, aqueous, n-butanol, ethyl-acetate, and chloroform fractions) at 100 μg concentration exhibits 54.37%, 33.88%, 62.85%, 56.28%, and 57.48% DPPH* radical-scavenging effect respectively in in-vitro antioxidant study. Conclusion: These observations established the anti-inflammatory effect of C. colebrookianum leaves in acute and chronic stages of inflammation by free radical scavenging and inhibition of COX-1 and COX-2.
  - 2,110 182
Anticoagulant effect of Huisheng oral solution in a rat model of thrombosis
Shuang-Qing Liu, Jian-Ying Guo, Jun Du, Qun Deng, Zhong-Jie He, Hong-Yuan Lin, Shu-Hong Lei
July-August 2013, 45(4):359-364
DOI:10.4103/0253-7613.115018  PMID:24014911
Objective: To investigate whether Huisheng Oral Solution has an anticoagulant effect in a rat model of thrombosis. Materials and Methods: A total of 40 male SD rats were equally and randomly divided into four groups: blank group, model group, and two treatment groups (A and B). Rats were subcutaneously injected with carrageenan to induce thrombosis. Rats in the treatment group A were intragastrically administered with Huisheng Oral Solution at a dose of 2 ml/100 g body weight (once per 8 hours), 72 hours after carrageenan injection, while those in the treatment group B were administered with Huisheng Oral Solution both 72 hours before and after induction of thrombosis. Blood samples were collected 24, 48, and 72 hours after carrageenan injection for measurements of prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen (FIB), prothrombin activity (PTA), platelets (PLT), fibrin degradation products (FDPs), and D-dimer. Lung, liver, and mesentery samples were taken 72 hours after carrageenan injection for histopathological analysis. The numbers of microthrombi in sections of different tissue samples were counted under a microscope. Blood parameters among each group were compared using the Welch test, the Kruskal-Wallis test, or the SNK test after testing for normality, while the number of microthrombi was compared using the Bonferroni test. Results: Compared to those in the model group, PT, APTT, and INR were significantly prolonged or increased while FIB was significantly reduced at the majority of time points in the two treatment groups (P < 0.05 for all). The levels of FDPs and D-dimer and PLT counts at the majority of time points were significantly lower (P < 0.05 for all), and the numbers of microthrombi in lung, liver, and mesentery samples were significantly decreased (P < 0.05 for all) in the two treatment groups. The above parameters at the majority of time points showed no significant differences between the two treatment groups. Conclusions: Huisheng Oral Solution can significantly improve coagulation parameters, fibrinolysis parameters, and PLT count, and reduce blood hypercoagulability and microthrombosis, suggesting that Huisheng Oral Solution has an anticoagulant effect in a rat model of thrombosis.
  - 4,280 107
A study to investigate capsaicin-induced pressure response in vagotomized rats
Abhaya Dutta, Aparna Akella, Shripad B Deshpande
July-August 2013, 45(4):365-370
DOI:10.4103/0253-7613.115019  PMID:24014912
Objectives: Capsaicin is used to evoke pulmonary C reflexes and produces complex pressure responses along with apnea/tachypnea, and bradycardia. In the present study, the mechanisms involved in capsaicin-induced pressure responses were explored. Materials and Methods: Tracheal, jugular venous, and femoral artery cannulations were performed in anesthetized adult rats. Blood pressure, respiratory excursions, and electrocardiogram were recorded. Cardiorespiratory reflex changes evoked by jugular venous injection of capsaicin (10 μg/kg) were recorded in vagotomized and antagonist pretreated animals. Results: Capsaicin produced triphasic pressure response exhibiting immediate hypotension, intermediate recovery, and delayed hypotension. Time-matched respiratory changes showed apnea, bradypnea, and tachypnea, respectively. Bradycardia occurred at immediate and intermediate phases. After vagotomy, immediate hypotension was abolished; the intermediate recovery was potentiated as hypertensive response; and the delayed hypotension persisted. In case of respiration, the immediate bradypnea persisted and delayed tachypnea was abolished; while heart rate changes at immediate and intermediate phases were abolished. Antagonists of α1 -adrenoceptor (prazosin or terazosin, 0.5 mg/kg), β-adrenoceptor (propranolol, 1 mg/kg), AT 1 receptor (losartan, 10 mg/kg) and Ca 2+ channel (diltiazem, 1 mg/kg) failed to block the capsaicin-induced intermediate hypertensive response in vagotomized animals. Conclusions: These observations implicate the existence of mechanisms other than adrenergic, angiotensinergic, or Ca 2+ channel-dependent mechanisms for mediating the capsaicin-induced intermediate hypertensive response in vagotomized animals.
  - 3,763 88
Development of an in vitro cell culture model to study milk to plasma ratios of therapeutic drugs
Maithili A Athavale, Anurupa Maitra, Shahnaz Patel, Vijay R Bhate, Villi S Toddywalla
July-August 2013, 45(4):325-329
DOI:10.4103/0253-7613.114994  PMID:24014904
Objective: To create an in vitro cell culture model to predict the M/P (concentration of drug in milk/concentration in maternal plasma) ratios of therapeutic drugs viz. rifampicin, theophylline, paracetamol, and aspirin. Materials and Methods: An in vitro cell culture model using CIT3 cells (mouse mammary epithelial cells) was created by culturing the cells on transwells. The cells formed an integral monolayer, allowing only transcellular transport as it happens in vivo. Functionality of the cells was confirmed through scanning electron microscopy. Time wise transfer of the study drugs from plasma to milk was studied and compared with actual (in vivo) M/P ratios obtained at reported t max for the respective drugs. Results: The developed model mimicked two important intrinsic factors of mammary epithelial cells viz. secretory and tight-junction properties and also the passive route of drug transport. The in vitro M/P ratios at reported t max were 0.23, 0.61, 0.87, and 0.03 respectively, for rifampicin, theophylline, paracetamol, and salicylic acid as compared to 0.29, 0.65, 0.65, and 0.22, respectively, in vitro. Conclusion: Our preliminary effort to develop an in vitro physiological model showed promising results. Transfer rate of the drugs using the developed model compared well with the transfer potential seen in vivo except for salicylic acid, which was transferred in far lower concentration in vitro. The model has a potential to be developed as a non-invasive alternative to the in vitro technique for determining the transfer of therapeutic drugs into breast milk.
  - 3,880 227
Pharmacokinetics of single-dose primaquine in patients with chronic kidney dysfunction
Shaunak P Kulkarni, Sanjana R Shah, Prashant P Kadam, Kannan Sridharan, Nivrutti K Hase, Partha P Shetty, Urmila M Thatte, Nithya J Gogtay
July-August 2013, 45(4):330-333
DOI:10.4103/0253-7613.114997  PMID:24014905
Aim: The pharmacokinetics of primaquine has not been studied in special populations. Being a basic compound, preferential binding to alpha-1 acid glycoprotein and substrate for P-glycoprotein, may predispose the drug for an altered pharmacokinetics in states of renal dysfunction. This study attempts to evaluate the pharmacokinetics of a single oral dose (15 mg) of primaquine in severely impaired renal function and end stage renal dysfunction patients compared to healthy participants. Materials and Methods: Twelve patients each with chronic kidney disease classified as either Stage IV or V (not on dialysis) were recruited. Data from 12 healthy participants was used as concurrent controls. Serial blood collections were performed following a single dose 15 mg Primaquine orally. Primaquine concentrations were measured in the plasma using a validated HPLC method. Results: The C max [median (range) in ng/ml] was 29.3 (14.6-104.3), 40.3 (14.8 - 78.6), and 49.8 (15 - 169.6) and the t max [median (range) in hours] was 3.0 (1.0- 6.0), 2.0 (1.5 - 8) and 2.0 (1.0 - 4.0) for healthy and stage IV, V (not on dialysis) CKD participants, respectively. No statistically significant difference was observed in any of the pharmacokinetic parameters between healthy, stage IV and V CKD participants. Conclusion: Pharmacokinetics of single oral dose primaquine (15 mg) does not appear to be altered in patients with severely impaired renal function and end stage renal dysfunction. A change in dose or frequency of the drug administration perhaps may not be required in this population.
  - 4,414 318
Effect of thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat kidney
Durdu Altuner, Nihal Cetin, Bahadir Suleyman, Zeynep Aslan, Ahmet Hacimuftuoglu, Mine Gulaboglu, Neslihan Isaoglu, Ismail Demiryilmaz, Halis Suleyman
July-August 2013, 45(4):339-343
DOI:10.4103/0253-7613.115005  PMID:24014907
Objectives: The biochemical effects of thiamine pyrophosphate on ischemia-reperfusion (IR) induced oxidative damage and DNA mutation in rat kidney tissue were investigated, and compared to thiamine. Materials and Methods: Rats were divided into four groups: Renal ischemia-reperfusion (RIR); thiamine pyrophosphate + RIR (TPRIR); thiamine + RIR (TRIR); and sham group (SG). Results: The results of biochemical experiments have shown that malondialdehyde (MDA) levels in rat kidney tissue after TRIR and TPRIR treatment were 7.2 ± 0.5 (P > 0.05) and 3.3 ± 0.3 (P < 0.0001) μmol/g protein, respectively. The MDA levels in the SG rat kidney tissue and in RIR group were 3.6 ± 0.2 (P < 0.0001) and 7.6 ± 0.6 μmol/g protein, respectively. Total glutathione (tGSH) levels in TRIR, TPRIR, SG, and RIR animal groups were 2.2 ± 0.3 (P > 0.05), 5.8 ± 0.4 (P < 0.0001), 6.2 ± 0.2 (P < 0.0001), and 1.7 ± 0.2 nmol/g protein, respectively. In the TRIR, TPRIR, SG, and RIR animal groups; 8-hydroxyguanine (8-OHGua)/Gua levels, which indicate mutagenic DNA, were 1.75 ± 0.12 (P > 0.05), 0.93 ± 0.1 (P < 0.0001), 0.85 ± 0.08 (P < 0.0001), and 1.93 ± 0.24 pmol/L, respectively. Conclusions: It has been shown that thiamine pyrophosphate prevents increase in mutagenic DNA in IR induced oxidative damage, whereas thiamine does not have this effect.
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