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   2011| September-October  | Volume 43 | Issue 5  
    Online since September 15, 2011

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Inverse agonism and its therapeutic significance
Gurudas Khilnani, Ajeet Kumar Khilnani
September-October 2011, 43(5):492-501
DOI:10.4103/0253-7613.84947  PMID:22021988
A large number of G-protein-coupled receptors (GPCRs) show varying degrees of basal or constitutive activity. This constitutive activity is usually minimal in natural receptors but is markedly observed in wild type and mutated (naturally or induced) receptors. According to conventional two-state drug receptor interaction model, binding of a ligand may initiate activity (agonist with varying degrees of positive intrinsic activity) or prevent the effect of an agonist (antagonist with zero intrinsic activity). Inverse agonists bind with the constitutively active receptors, stabilize them, and thus reduce the activity (negative intrinsic activity). Receptors of many classes (α-and β-adrenergic, histaminergic, GABAergic, serotoninergic, opiate, and angiotensin receptors) have shown basal activity in suitable in vitro models. Several drugs that have been conventionally classified as antagonists (β-blockers, antihistaminics) have shown inverse agonist effects on corresponding constitutively active receptors. Nearly all H 1 and H 2 antihistaminics (antagonists) have been shown to be inverse agonists. Among the β-blockers, carvedilol and bucindolol demonstrate low level of inverse agonism as compared to propranolol and nadolol. Several antipsychotic drugs (D 2 receptors antagonist), antihypertensive (AT 1 receptor antagonists), antiserotoninergic drugs and opioid antagonists have significant inverse agonistic activity that contributes partly or wholly to their therapeutic value. Inverse agonism may also help explain the underlying mechanism of beneficial effects of carvedilol in congestive failure, naloxone-induced withdrawal syndrome in opioid dependence, clozapine in psychosis, and candesartan in cardiac hypertrophy. Understanding inverse agonisms has paved a way for newer drug development. It is now possible to develop agents, which have only desired therapeutic value and are devoid of unwanted adverse effect. Pimavanserin (ACP-103), a highly selective 5-HT 2A inverse agonist, attenuates psychosis in patients with Parkinson's disease with psychosis and is devoid of extrapyramidal side effects. This dissociation is also evident from the development of anxioselective benzodiazepines devoid of habit-forming potential. Hemopressin is a peptide ligand that acts as an antagonist as well as inverse agonist. This agent acts as an antinociceptive agent in different in vivo models of pain. Treatment of obesity by drugs having inverse agonist activity at CB 1/2 receptors is also underway. An exciting development is evaluation of β-blockers in chronic bronchial asthma-a condition akin to congestive heart failure where β-blockade has become the standard mode of therapy. Synthesis and evaluation of selective agents is underway. Therefore, inverse agonism is an important aspect of drug-receptor interaction and has immense untapped therapeutic potential.
  13,653 870 18
An evaluation of antioxidant, anti-inflammatory, and antinociceptive activities of essential oil from Curcuma longa. L
Vijayastelter B Liju, Kottarapat Jeena, Ramadasan Kuttan
September-October 2011, 43(5):526-531
DOI:10.4103/0253-7613.84961  PMID:22021994
Objectives : This study was aimed to evaluate the chemical composition, antioxidant potential in vitro and in vivo, anti-inflammatory, and antinociceptive activity of turmeric oil. Materials and Methods : Chemical analysis of turmeric oil was done by gas chromatography/mass spectrometry. Antioxidant activities in vitro was done by six different methods and in vivo antioxidant activity was determined by measuring superoxide generation from macrophages treated with phorbol-12-myristate-13-acetate (PMA) as well as determining antioxidant level after feeding the oil orally for one month. Anti-inflammatory activity was studied in mice using carrageenan, dextran, and formalin. Antinociceptive activity was evaluated by using acetic acid-induced writhing movement in mice. Results : The main constituent of essential oil of turmeric was found to be ar-turmerone (61.79%), curlone (12.48%), and ar-curcumene (6.11%). Turmeric oil was found to have in vitro antioxidant activity and IC 50 for scavenging superoxides, hydroxyl radicals, and lipid peroxidation were 135 mg/ml, 200 mg/ml, and 400 mg/ml, respectively. The ferric-reducing activity for 50 mg of turmeric essential oil was found to be 5 mM. Intraperitoneal administration of oil was found to inhibit PMA-induced superoxide radicals elicited by macrophages. Oral administration of turmeric oil for one month to mice significantly increased superoxide dismutase, glutathione, and glutathione reductase enzyme levels in blood and glutathione-S-transferase and superoxide dismutase enzymes in liver. Turmeric oil showed significant reduction in paw thickness in carrageenan, dextran-induced acute inflammation, and formalin-induced chronic inflammation. The drug produced significant antinociceptive activity (P < 0.001) at all doses studied. Conclusions : These results demonstrated that turmeric oil has potential health benefits as it can scavenge the free radicals and produce significant anti-inflammatory and antinociceptive activities.
  11,937 470 64
Anti-anxiety activity of Coriandrum sativum assessed using different experimental anxiety models
Poonam Mahendra, Shradha Bisht
September-October 2011, 43(5):574-577
DOI:10.4103/0253-7613.84975  PMID:22022003
Interest in alternative medicine and plant-derived medications that affect the "mind" is growing. The aim of present study was to explore the anti-anxiety activity of hydroalcoholic extract of Coriandrum sativum (Linn.) using different animal models (elevated plus maze, open field test, light and dark test and social interaction test) of anxiety in mice. Diazepam (0.5 mg/kg) was used as the standard and dose of hydroalcoholic extract of C. sativum fruit (50, 100 and 200 mg/kg) was selected as per OECD guidelines. Results suggested that extract of C. sativum at 100 and 200 mg/kg dose produced anti-anxiety effects almost similar to diazepam, and at 50 mg/kg dose did not produce anti-anxiety activity on any of the paradigm used. Further studies are needed to identify the anxiolytic mechanism(s) and the phytoconstituents responsible for the observed central effects of the hydroalcoholic extract of C. sativum.
  8,419 431 23
Evaluation of anti-ulcer activity of Samanea saman (Jacq) merr bark on ethanol and stress induced gastric lesions in albino rats
Suresh Arumugam, Senthil Velan Selvaraj, Suresh Velayutham, Senthil Kumar Natesan, Karthikeyan Palaniswamy
September-October 2011, 43(5):586-590
DOI:10.4103/0253-7613.84978  PMID:22022006
Objective : To evaluate the antiulcer activity of Samanea saman (Jacq) Merr bark on ethanol and stress induced gastric lesions in albino rats. Materials and Methods : Gastric lesions were induced in rats by oral administration of absolute ethanol (5 ml/kg) and stress induced by water immersion. The antiulcer activity of methanolic extract of Samanea saman (Jacq) Merr bark (100 mg/kg, 200 mg/kg, 400 mg/kg) was compared with standard drugs. The parameters studied were ulcer index, gastric juice volume, pH, free acidity and total acidity. Result : Samanea saman (Jacq) Merr showed a dose dependent curative ratio compared to ulcer control groups. The extract at 400 mg/kg showed significant anti ulcer activity which is almost equal to that of the standard drug in both models. The volume of acid secretion, total and free acidity was decreased and pH of the gastric juice was increased compared to ulcer control group. Conclusions : The present study indicates that Samanea saman (Jacq) Merr bark extracts have potential anti ulcer activity.
  8,013 319 6
Antioxidant activities of bark extract from mangroves, Bruguiera cylindrica (L.) Blume and Ceriops decandra Perr
M Krishnamoorthy, JM Sasikumar, R Shamna, C Pandiarajan, P Sofia, B Nagarajan
September-October 2011, 43(5):557-562
DOI:10.4103/0253-7613.84972  PMID:22022000
Objectives : The antioxidant activities of two Indian mangrove plants, Bruguiera cylindrica and Ceriops decandra, were investigated. Materials and Methods : Total phenolics and total flavonoid contents of the mangroves were determined using folin-ciocalteu reagent method and aluminium chloride method, respectively. Antioxidant capacity was assessed by the following methods: 1,1-diphenyl-2-picryl hydroxyl (DPPH.) quenching assay; 2,2'- azinobis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS. + ) cation decolorization test; scavenging capacity towards hydroxyl ion radicals (.OH); reductive capacity; and antihemolytic activity. Results : The mangroves yielded 233.3 ± 0.062 and 283.31 ± 0.04 mg gallic acid equivalent/g phenolic contents and 11.6 ± 0.12 and 15.1 ± 0.02 mg quercetin equivalent/g flavonoid contents. The methanol extracts of both mangroves exhibited high antiradical activity against DPPH., ABTS. + , and .OH radicals. The reductive capacity of the extracts increased with increasing concentration of samples. The extracts also inhibited H 2 O 2 induced hemolysis in cow blood erythrocytes. The antioxidant activities were found stronger than that of the reference standard, butylated hydroxy toluene (BHT). The antioxidant activity of mangrove plants was correlated with total phenolics and flavonoid contents. Conclusion : Both plants can be considered as good sources of natural antioxidants for medicinal uses. Further studies are necessary to isolate active principles responsible for the overall antioxidant activity of the extracts.
  7,207 369 12
Cardioprotective effect of fenugreek on isoproterenol-induced myocardial infarction in rats
Madhesh Murugesan, Ramalingam Revathi, Vaiyapuri Manju
September-October 2011, 43(5):516-519
DOI:10.4103/0253-7613.84957  PMID:22021992
Objectives : This study is designed to evaluate the cardioprotective effect of fenugreek on isoproterenol- induced myocardial infarction and is investigated by an in vivo method in rats. Materials and Methods : Male Wistar albino rats were divided into four groups (n=10). Group I received 0.5% CMC treated as normal control group. Group II received isoproterenol (85 mg/kg body weight) intraperitoneal (i.p.) for two consecutive days (14 th and 15 th days). Group III received fenugreek (250 mg/kg body weight) intragastric intubation for 15 days. Group IV rats received fenugreek as in Group III and additionally isoproterenol was given for two consecutive days (14 th and 15 th days). Results : The results described the cardioprotective effect that observed in Group IV showed significantly (P< 0.05) decreased levels of TBARS and enhanced the activities of both enzymatic and non-enzymatic antioxidants (SOD, CAT, GPx and GSH) in myocardial infarcted rats when compared to Groups II and III. Histopathological studies were also co-relating with the above biochemical parameters. Conclusion : These findings concluded the cardioprotective effect of fenugreek on lipid peroxidation and antioxidant defense system during isoproterenol-induced myocardial infarction in rats.
  7,137 422 17
A textbook of Pharmacy Practice
I Patel, J Chang, R Balkrishnan
September-October 2011, 43(5):619-620
  7,249 268 -
The functional role of the alpha-1 adrenergic receptors in cerebral blood flow regulation
Sushmita Purkayastha, Peter B Raven
September-October 2011, 43(5):502-506
DOI:10.4103/0253-7613.84950  PMID:22021989
Cerebral vasculature is richly innervated by the α-1 adrenergic receptors similar to that of the peripheral vasculature. However, the functional role of the α-1adrenergic receptors in cerebral blood flow (CBF) regulation is yet to be established. The traditional thinking being that during normotension and normocapnia sympathetic neural activity does not play a significant role in CBF regulation. Reports in the past have stated that catecholamines do not penetrate the blood brain barrier (BBB) and therefore only influence cerebral vessels from outside the BBB and hence, have a limited role in CBF regulation. However, with the advent of dynamic measurement techniques, beat-to-beat CBF assessment can be done during dynamic changes in arterial blood pressure. Several studies in the recent years have reported a functional role of the α-1adrenergic receptors in CBF regulation. This review focuses on the recent developments on the role of the sympathetic nervous system, specifically that of the α-1 adrenergic receptors in CBF regulation.
  6,991 489 13
Cardioprotective effect of ascorbic acid on doxorubicin-induced myocardial toxicity in rats
A.H.M Viswanatha Swamy, U Wangikar, BC Koti, A.H.M Thippeswamy, P.M Ronad, DV Manjula
September-October 2011, 43(5):507-511
DOI:10.4103/0253-7613.84952  PMID:22021990
Objective : To investigate the preventive and curative role of ascorbic acid on doxorubicin (dox)-induced myocardial toxicity in rats. Materials and Methods : Animals were divided into five groups of six animals each. Group I served as normal control and received saline 5 ml/kg/day intraperitoneal (i.p.) for a period of 15 days. Group II animals received ascorbic acid 20 mg/kg per oral (p.o.) for 15 days as a pretreatment control (PR). Group III animals received dox 2.5 mg/kg body weight (b.w.), i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg b.w. Group IV animals received ascorbic acid 20 mg/kg p.o. for 15 days as a pretreatment followed by dox 2.5 mg/kg b.w., i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg body weight. Group V animals received dox 2.5 mg/kg b.w., i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg b.w. followed by ascorbic acid 20 mg/kg p.o for 15 days as post-treatment control (CR). The biochemical parameters such as tissue glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), and enzyme biomarkers such as creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were monitored. Results : Pretreatment with ascorbic acid (20 mg/kg p.o.) significantly protected the myocardium from the toxic effect of dox (PR), by increasing the levels of antioxidant enzymes such as GSH, SOD, and CAT toward normal and decreased the levels of MDA, CPK, LDH, AST, and ALT as compared with dox-treated rats. Post-treatment with ascorbic acid to dox-treated group (CR) significantly increased the levels of tissue GSH, SOD, CAT and significantly decreased the level of MDA as compared with dox-treated group. It also reduced the severity of cellular damage of the myocardium as confirmed by histopathology. The restoration of the endogenous antioxidant system clearly depicts that ascorbic acid produced its protective effect by scavenging the reactive oxygen species. Conclusion : The results obtained in this study provide evidence for the usefulness of the ascorbic acid as a cardioprotective agent.
  6,812 386 38
Hepatoprotective activity of aqueous extract of Portulaca oleracea in combination with lycopene in rats
M Anusha, M Venkateswarlu, V Prabhakaran, S Shareen Taj, B Pushpa Kumari, D Ranganayakulu
September-October 2011, 43(5):563-567
DOI:10.4103/0253-7613.84973  PMID:22022001
Objective : To investigate the hepatoprotective activity of the aqueous extract of the aerial parts of Portulaca oleracea (P. oleracea) in combination with lycopene against carbon tetrachloride induced hepatotoxicity in rats. Materials and Methods : Hepatotoxicity was induced in male Wistar rats by intraperitoneal injection of carbon tetrachloride (0.1 ml/kg b.w for 14 days). The aqueous extract of P. oleracea in combination with lycopene (50 mg/kg b.w) was administered to the experimental animals at two selected doses for 14 days. The hepatoprotective activity of the combination was evaluated by the liver function marker enzymes in the serum [aspartate transaminases (AST), alanine transaminases (ALT), alkaline phosphatase (Alk.P), total bilirubin (TB), total protein (TP) and total cholesterol (TC)], pentobarbitone induced sleeping time (PST) and histopathological studies of liver. Results : Both the treatment groups showed hepatoprotective effect against carbon tetrachloride induced hepatotoxicity by significantly restoring the levels of serum enzymes to normal which was comparable to that of silymarin group. Besides, the results obtained from PST and histopathological results also support the study. Conclusions : The oral administration of P. oleracea in combination with lycopene significantly ameliorates CCl 4 hepatotoxicity in rats.
  6,436 282 37
Availability of essential medicines: A primary health care perspective
Rohit Dixit, M Vinay, T Jayasree, Shaikh Ubedulla, VS Manohar, N Chandrasekhar
September-October 2011, 43(5):599-600
DOI:10.4103/0253-7613.84981  PMID:22022009
The present study was undertaken to assess the availability of the essential medicines to the people of Kunijarla, Khammam district, AP. This was done in two steps: 1) Comparison of PHC-EML (primary health care essential medicines list) with AP-EML (Andhra Pradesh essential medicines list) and NEML (National essential medicines list); and 2) Assessment of availability of the listed medicines in adequate quantity to meet the needs of people of kunijarla. Results showed that the PHC-EML is on par with AP-EML and NEML. The hospital has 100% availability of the listed medicines; however, there was a need for certain add-on drugs like phenytoin tablets, valproic acid, and activated charcoal since they were prescribed frequently and were not included in PHC-EML. All the drugs which were listed in PHC-EML were being used and none were considered as non-utility supply. Suggestions were given for the revision of PHC-EML according to the criteria for identifying medicines for inclusion in the revised list which was mentioned in NEML.
  6,487 184 4
Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuvant-induced arthritis and hematological indices in rats
David Banji, Jyothi Pinnapureddy, Otilia J.F Banji, A Ranjith Kumar, K Narsi Reddy
September-October 2011, 43(5):546-550
DOI:10.4103/0253-7613.84970  PMID:22021998
Objective : To evaluate the concomitant administration of methotrexate and curcumin for antiarthiritic activity in rats. Materials and Methods : Arthritis was induced in rats following a single subplantar injection of Freund's complete adjuvant (0.1 ml). Rats were divided into six groups of six animals each. Group I and II were control injected with saline and Freund's complete adjuvant (0.1 ml), respectively. Group III arthritic rats were treated with curcumin (100 mg/kg, i.p.) on alternate days. Group IV received methotrexate (MTX) (2 mg/kg, i.p.) once in a week. Group-V and VI were treated with MTX (1 mg/kg, i.p.) once in a week and after 30 min received curcumin (30 mg/kg and 100 mg/kg, thrice a week, i.p.) from 10 th to 45 th days, respectively. Body weight and the paw volume was measured on 9 th , 16 th , 23 rd , 30 th , 37 th , and 45 th days. Determination of complete blood cell counts, hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration was determined on the 46 th day. Results : An improvement in body weight and a significant (P < 0.05) reduction in arthritis was observed with the combination treatment as compared to the positive control. A significant improvement in the hematological profile was also observed in rats treated with curcumin and methotrexate. Conclusion : The study showed a significant anti-arthritic action and protection from hematological toxicity with the combination treatment of methotrexate and curcumin.
  5,875 267 15
Clinical pharmacology: Prospects and development in India
Nilima Kshirsagar, Vijay Kumar
September-October 2011, 43(5):489-491
DOI:10.4103/0253-7613.84946  PMID:22021987
  5,401 721 1
Piperacillin-tazobactam-induced hypokalemia and metabolic alkalosis
Syed Ahmed Zaki, Vijay Lad
September-October 2011, 43(5):609-610
DOI:10.4103/0253-7613.84986  PMID:22022014
Piperacillin/tazobactam is a commonly prescribed antibiotic and is generally considered safe. We report a case of a 2-year-old girl who developed hypokalemic metabolic alkalosis and bradycardia after receiving intravenous piperacillin-tazobactam for bronchopneumonia. Upon withdrawal of the drug, serum potassium normalized in 2 days. Hypokalemia is a serious adverse effect of piperacillin-tazobactam and should be suspected while treating patients with this drug. Early recognition and prompt withdrawal of the drug will result in lesser morbidity.
  5,914 127 9
In vivo investigation of the neuroprotective property of Convolvulus pluricaulis in scopolamine-induced cognitive impairments in Wistar rats
Syed Waseem Bihaqi, Avninder Pal Singh, Manisha Tiwari
September-October 2011, 43(5):520-525
DOI:10.4103/0253-7613.84958  PMID:22021993
Aim : To investigate the neuroprotective effect of Convolvulus pluricaulis aqueous extract (AE) against scopolamine (1 mg/kg body weight (bwt))-induced neurotoxicity in the cerebral cortex of male Wistar rats. Materials and Methods : The study was carried out on male Wistar rats (age matched, weight 250 ± 20 g). The present study investigated cognitive-enhancing property of AE using Elevated plus maze (EPM) (transfer latency [TL]) and Morris water maze (MWM). Besides evaluating the effect of extract on neurochemical enzymes, in vivo antioxidant and free radical scavenging activities were also screened. All the measured parameters were compared with rivastigmine tartrate (1 mg/kg bwt) which was taken as standard. Results : Pretreatment of rats with AE (150 mg/kg bwt) significantly reduced scopolamine-induced increase in the TL in EPM, whereas in MWM, administration of extract improved the impairment of spatial memory induced by scopolamine. The activity of acetylcholinesterase (AChE) was significantly inhibited by extract within the cortex and hippocampus. Reduced activities or contents of glutathione reductase, superoxide dismutase, and reduced glutathione within the cortex and hippocampus induced by scopolamine were elevated by the extract. Taken together, it could be postulated that extract may exert its potent-enhancing activity through both anti-AChE and antioxidant action. Conclusion : AE possesses neuroprotective potential, thus validating its use in alleviating toxic effects of scopolamine.
  5,613 379 23
Protective effect of an aphrodisiac herb Tribulus terrestris Linn on cadmium-induced testicular damage
B Rajendar, K Bharavi, GS Rao, P.V.S Kishore, P Ravi Kumar, C.S.V Satish Kumar, T Pankaj Patel
September-October 2011, 43(5):568-573
DOI:10.4103/0253-7613.84974  PMID:22022002
Aim : The aim of the present study was to investigate whether Tribulus terrestris Linn (TT) could protect the cadmium (Cd)-induced testicular tissue peroxidation in rats and to explore the underlying mechanism of the same. Materials and Methods : In vitro and in vivo studies were conducted to know the protective effect of ethanolic extract of TT (eTT) in Cd toxicity. In in vitro studies, total antioxidant and ferrous metal ion chelating activity of TT was studied. In vivo studies were conducted in rats. A total of 40 Wistar strain adult male rats were divided into four groups. Group 1 served as control, while group 2 to 4 received CdCl 2 (3 mg/kg b. wt. s/c once a week). In addition to Cd, group 3 and 4 rats also received eTT (5 mg/kg b.wt. daily as oral gavage) and α-tocopherol (75 mg/kg daily by oral gavage), respectively. At the end of 6th week, all the rats were sacrificed and the separated testes were weighted and processed for estimation of tissue peroxidation markers, antioxidant markers, functional markers, and Cd concentration. The testes were also subjected to histopathological screening. Results : In in vitro studies, the percentage of metal ion chelating activity of 50 μg/ml of eTT and α-tocopherol were 2.76 and 9.39, respectively, and the antioxidant capacity of eTT was equivalent to 0.063 μg of α-tocopherol/μg of eTT. In in vivo studies, administration of Cd significantly reduced the absolute and relative testicular weight, antioxidant markers such as superoxide dismutase and glutathione, and functional markers such as LDH and ALP, along with significant increase in peroxidation markers such as malondialdehyde and protein carbonyls in testicular tissue. Testes of Cd only-treated group showed histological insults like necrotic changes in seminiferous tubules and interstitium, shrunken tubules with desquamated basal lamina, vacuolization and destruction of sertoli cells, and degenerating Leydig cells. This group also had higher Cd levels in testicular tissue. Co-treatment with eTT and α-tocopherol significantly reduced the Cd burden in the testes along with reversal of the Cd-induced changes. Conclusions : eTT exhibited protective effect against Cd-induced testicular damage. The protective effect appears to be mediated through inhibition of testicular tissue peroxidation by antioxidant and metal chelator activity and also, may be indirectly by stimulating the testosterone production from Leydig cells.
  5,628 216 14
Pharmacological investigations of Punica granatum in glycerol-induced acute renal failure in rats
Amrit Pal Singh, Amteshwar Jaggi Singh, Nirmal Singh
September-October 2011, 43(5):551-556
DOI:10.4103/0253-7613.84971  PMID:22021999
Objective : The present study was designed to investigate the ameliorative potential and possible mechanism of hydroalcoholic extract of flowers of P. granatum in glycerol-induced acute renal failure (ARF) in rats. Materials and Methods : The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 ml/kg) and the animals were sacrificed after 24 hours of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury. Results : Pretreatment with hydroalcoholic extract of flowers of P. granatum (125 and 250 mg/kg p.o. twice daily for 3 days) significantly attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner. BADGE (Bisphenol-A-diglycidyl ether) (30 mg/kg), a peroxisome proliferator-activated receptor (PPAR)-γ antagonist, and N(omega)-nitro-l-arginine-methyl ester (L-NAME) (10, 20, and 40 mg/kg), nitric oxide synthase inhibitor, were employed to explore the mechanism of renoprotective effects of Punica granatum. Administration of BADGE (30 mg/kg) and L-NAME (40 mg/kg) abolished the beneficial effects of P. granatum in glycerol-induced renal dysfunction. Conclusion : Hydroalcoholic extract of flowers of P. granatum has ameliorative potential in attenuating myoglobinuric renal failure and its renoprotective effects involve activation of PPAR-γ and nitric oxide-dependent signaling pathway.
  5,534 234 12
Comparison of the efficacy of carbamazepine, gabapentin and lamotrigine for neuropathic pain in rats
Bharti Chogtu, KL Bairy, D Smitha, Supurna Dhar, P Himabindu
September-October 2011, 43(5):596-598
DOI:10.4103/0253-7613.84980  PMID:22022008
Background : Neuropathic pain in cancer patients remain a treatment challenge. Many of the anticancer drugs have to be abandoned because patients develop neuropathic pain. Several antiepileptic drugs like carbamazepine, phenytoin, lamotrigine, felbamate are effective in neuropathic pain and trigeminal neuralgia. However, their efficacy varies. Aim : The aim of this study is to compare the efficacy of antiepileptic drugs in neuropathic pain induced by anticancer drugs. Materials and Methods : Neuropathic pain was induced in rats by injecting 4 doses of paclitaxel. The rats were divided into four groups of six animals each. Group I was treated with oral carbamazepine (cbz) 100 mg/kg, group II received oral gabapentin (gbp) 60 mg/kg, and group III was treated with oral lamotrigine (lam) 40 mg/kg and group IV was the control group. Behavioural testing for thermal hyperalgesia and mechanical hyperalgesia was assessed from 26 th day of paclitaxel administration to next five days by hot plate method and Randall Siletto test, respectively, in all the four groups. One way analysis of variance followed by Scheffe's post hoc test was used for statistical analysis. Results : In thermal hyperalgesia lam treated group was found to be significantly (P < 0.001) superior to cbz and gbp treated group. In mechanical hyperalgesia, lam group showed significant response (P < 0.05) as compared to gbp group. However, the gbp treated group showed a significant (P < 0.01) improvement after three days of treatment. Conclusions : In paclitaxel induced neuropathic pain, lamotrigine appears to be a promising drug. The difference in responses shown by different antiepileptics' depends on the etiology of the underlying mechanisms in neuropathic pain.
  5,222 232 6
Evaluation of the role of erythropoietin and methotrexate in multiple sclerosis
Sandipan Dasgupta, Bhaskar Mazumder, Y Roja Ramani, Subhra Prakash Bhattacharyya, Mukesh K Das
September-October 2011, 43(5):512-515
DOI:10.4103/0253-7613.84955  PMID:22021991
Background : Erythropoietin, originally recognized for its role in erythropoiesis, has been shown to improve neurological outcome after stroke. Low-dose methotrexate is effective against certain inflammatory diseases, such as severe psoriasis and rheumatoid arthritis as well as Crohn's disease. Immunosuppressive effect of methotrexate also reduces the proportion of patients with chronic progressive multiple sclerosis with modest clinical benefits. Combination of erythropoietin and methotrexate can target neuroinflammation along with immunosupression. Objective : To evaluate the role of erythropoietin and methotrexate in experimental autoimmune encephalomyelitis, a commonly used animal model of several degenerative human diseases like multiple sclerosis. Materials and Methods : In the present study, C57BL/J6 mice were immunized with 200 mg of myelin basic protein (MBP) emulsified in complete Freund's adjuvant (CFA) supplemented with 1 mg/ml of killed mycobacterium tuberculosis (MBP: CFA in 1:1 ratio). These animals were given a combination of methotrexate and erythropoietin. Neurological function tests were scored daily by grading of clinical signs. Cerebral histopathology was performed to detect inflammatory infiltrates and demyelination. Results : Treatment with erythropoietin and methotrexate significantly improved the neurological function recovery, reduced inflammatory infiltrates, and demyelination as compared to controls possibly by stimulating oligodendrogenesis and down-regulating proinflammatory infiltrates. Conclusion : The findings suggest an adjunctive use of methotrexate in demyelinating disease.
  4,792 241 2
Steroid-induced central serous retinopathy
Samidh P Shah, Chetna K Desai, Mira K Desai, RK Dikshit
September-October 2011, 43(5):607-608
DOI:10.4103/0253-7613.84985  PMID:22022013
A-24 year-old male was prescribed prednisolone (60 mg/day) for left sided facial palsy. After three days of therapy, the patient complained of black spots in his vision in right eye. Fluorescein angiography of right eye showed evidence of central serous retinopathy (CSR). Prednisolone dose was withdrawn gradually and the patient improved within a week. There were no other systemic or ophthalmic diseases reported by the patient, which could have caused this condition. An improvement after dechallenge confirmed steroid-induced CSR. Recurrent CSR is known to cause permanent loss of vision. Hence, awareness regarding this adverse drug reaction (ADR) with steroids and its reporting can minimize this complication and help in better patient management.
  4,698 152 7
Assessment of antidiabetic potential of Cinnamomum tamala leaves extract in streptozotocin induced diabetic rats
Shradha Bisht, SS Sisodia
September-October 2011, 43(5):582-585
DOI:10.4103/0253-7613.84977  PMID:22022005
Objective : To establish the effect of Cinnamomum tamala leaves extract on diabetes and diabetes induced dyslipidemia in streptozotocin-induced diabetic rats. Materials and Methods : Diabetes was induced by a single intravenous injection of streptozotocin (50 mg/kg body weight). Group I and II were kept as control and diabetic control respectively. And group III was further treated with ethanolic leaf extract of C. tamala (200 mg/kg body weight, orally) for a period of 40 days. Oral glucose tolerance test was performed before starting the experiment and blood glucose level was estimated. Statistical analysis was performed using one-way Analysis of Variance (using Statistical Package for the Social Sciences [SPSS] version 10.0) and student's 't'- test (Sigma Plot version 8.0). The values of P < 0.05 were considered as statistically significant. Results : Treatment of diabetic animals with Cinnamomum tamala extract significantly lowered the blood glucose level, and maintained body weight and lipid-profile parameters towards near normal range. Conclusion : The extract exhibited antidiabetic and antidyslipidemic effect. Further, chemical and pharmacological investigations are required to elucidate the exact mechanism of action of this extract and to isolate the active principles responsible for these effects.
  4,550 290 8
Metabolic syndrome among patients receiving clozapine: A preliminary estimate
Sandeep Grover, Naresh Nebhinani, Subho Chakrabarti, Ajit Avasthi, Parmanand Kulhara
September-October 2011, 43(5):591-595
DOI:10.4103/0253-7613.84979  PMID:22022007
Objective : To study the prevalence of metabolic syndrome in patients receiving clozapine. Materials and Methods : For this study, 100 patients attending the psychiatry outpatient clinic of a tertiary care hospital who were receiving clozapine for more than three months were evaluated for the presence of metabolic syndrome using the International Diabetes Federation (IDF) and modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) criteria. Results : Forty-six patients fulfilled IDF criteria and 47 met modified NCEP ATP-III criteria of metabolic syndrome. There was significant correlation between these two sets of criteria used to define the metabolic syndrome (Kappa value -0.821, P < 0.001). Among the individual parameters studied, increased waist circumference was the most common abnormality, followed by abnormal blood glucose levels and elevated triglyceride levels. All these abnormalities were seen in more than half (52-61%) of the patients. When the sample was divided into two groups, i.e., those with and without metabolic syndrome, patients with metabolic syndrome had significantly higher body mass index and had spent more time in school. Logistic regression analysis revealed that these two variables together explained about 19% of the variance in metabolic syndrome (adjusted r 2 = 0193; F = 12.8; P < 0.001). Conclusion : The findings of the present study suggest that metabolic syndrome is highly prevalent in subjects receiving clozapine.
  4,492 154 20
Effect of folic acid supplementation on oxidative gastric mucosa damage and acid secretory response in the rat
KO Ajeigbe, SB Olaleye, EO Oladejo, AO Olayanju
September-October 2011, 43(5):578-581
DOI:10.4103/0253-7613.84976  PMID:22022004
Objective : This study investigated the antioxidative and antisecretory properties of folic acid in the rats' stomach. Materials and Methods: Male Wistar rats were treated with 2 mg/kg diet of folic acid for 21 days. Gastric ulceration was induced by indomethacin, scored, and assayed to determine the concentration of total protein, mucus, malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) in homogenized samples. Normal saline and Ranitidine treated group served as negative and positive control, respectively. Basal and stimulated acid secretion was measured by continuous perfusion method. Result : Indomethacin caused severe damage to the rats' stomach with an ulcer index of 4.32 ± 0.13, increase in MDA concentration and reduction in the concentration of protein, mucus, catalase and superoxide dismutase (P < 0.001). Pre-treatment with folic acid prevented the formation of ulcers by 32%, and attenuated the inhibition of mucus by 14%, CAT, 51% and SOD, 150%. Ranitidine afforded 56% prevention in ulcer formation with 67%, 55% and 78% attenuation of the inhibition of mucus, CAT and SOD, respectively, by indomethacin. While indomethacin-induced lipid peroxidation was attenuated by 58% reduction in MDA concentration on pretreatment with folic acid, Ranitidine offered 65% reduction. Basal and stimulated acid secretions were significantly reduced in the treated when compared with control animals. Folic acid produced a 21% reduction in the basal acid output when compared with the control animals (P < 0.05), and 140% reduction in histamine-induced acid response. Conclusion : The results indicate the gastroprotective activity of folic acid due its antioxidative and anti-secretory properties.
  4,410 124 5
Evaluation of Chinese medicine Qian-Yu for chronic bacterial prostatitis in rats
Jinhu Wu, Qianying Yuan, Daohua Zhang, Xiaoyan Zhang, Lijun Zhao, Xiaohua Zhang, Jinlan Ruan
September-October 2011, 43(5):532-535
DOI:10.4103/0253-7613.84964  PMID:22021995
Objectives : Qian-Yu (QY), a Chinese medicine formula, has anti-inflammatory and broad spectrum anti-bacterial activity. This study is undertaken to evaluate the anti-inflammatory effects of Qian-Yu (QY) in chronic bacterial prostatitis (CBP). Materials and Methods : The potential of QY in the treatment of CBP was evaluated using a CBP animal model by examining the anti-inflammatory activity. Its consequences were analyzed by immunological and histopathological methods. Experimental chronic bacterial prostatitis was induced by instillation of bacterial suspension of Escherichia coli 7.5 ΄ 10 5 CFU/ml into the prostatic urethra. Animals were followed up for four weeks and then treated with either 7 mg/kg QY or 7 mg/kg positive control agent-Qianlietai (QLT) or 1 ml of phosphate-buffered saline (PBS) for the controls. Ten rats in each group were sacrificed at the end of four weeks. The inhibition of inflammation and its consequences were analyzed histologically. Prostatic IL-8, SIgA and zinc concentrations were measured by ELISA, RIA and ICP-AES, respectively. The data was expressed as mean ± S.D. Least-significant difference (LSD) of one-way ANOVA (SPSS 12.0) was used to determine the differences of scores. Results : The histopathology showed resolving prostatitis in QY-and QLT-treated groups and the immunology showed reduction of IL-8 and increment of SIgA contents in prostatic tissues as compared to the control groups. The prostatic zinc levels were higher in the QY-and QLT-treated groups than those in the controls. These results suggested that QY is effective in CBP treatment.
  4,126 92 -
Diuretics induced uremia and nonrecovery of renal function in a patient with acute renal failure caused by sepsis
PK Sahu, A Pal, J Panda, S Patnaik
September-October 2011, 43(5):603-604
DOI:10.4103/0253-7613.84983  PMID:22022011
Sepsis is a clinical syndrome related to severe infection and is characterized by systemic inflammation and injury to multiple organs and functional systems. Sepsis is one of the main causes of acute renal failure (ARF). Diuretics are frequently administered during ARF. However, there is scant evidence that diuretics provide any benefit to the patients with ARF. This case report highlights the occurrence of uremia and nonrecovery of renal function after administration of diuretics in a patient with ARF caused by sepsis. It is suggested that physicians should be cautious in prescribing diuretics to patients with ARF due to septicemia. Diuretics cause uremia and may lead to false diagnosis of chronic renal failure and nonrecovery of renal function. The patient may unnecessarily require prolonged dialysis.
  3,973 129 -
Evaluation of Cynanchum otophyllum glucan sulfate against human immunodeficiency virus and herpes simplex virus as a microbicide agent
Jian Tao, Jing Yang, Chaoyin Chen, Xiaomei Cao, Shenglan Zhao, Kunlong Ben
September-October 2011, 43(5):536-540
DOI:10.4103/0253-7613.84967  PMID:22021996
Objective : The root ofCynanchum otophyllum -also known as Qing Yang Sheng-is a traditional ethnical Chinese medicine. The objective of this study was to evaluate in vitro activities and safety of C. otophyllum glucan sulfate (PS20) against Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV). Materials and Methods : Anti-HIV activity was detected with syncytial formation assay and quantitative P24 Enzyme-Linked Immunosorbent Assay (ELISA). Anti-HSV activity was detected with plaque reduction assay; cytotoxicity was tested with MTT colorimetric assay; and anti-bacterial activity was tested with microdilution method. Anti-HIV mechanism was investigated with fusion inhibition, time of addition, and pretreatment. Results : The 50% Inhibition Concentration (IC 50 ) of PS20 for HIV-1 IIIB , HIV- Ada-M , HIV-1 Bal , HSV-I, and -II were 0.26 ± 0.02 mM, 0.46 ± 0.02 mM, 0.90 ± 0.04 mM, 3.45 ± 0.85 mM, and 0.70 ± 0.22 mM, respectively. Selectivity Indices (SI) were 653, 50, 39, 85, and 362, respectively. Studies on anti-HIV mechanism of PS20 showed that the target molecule should be the envelope protein. The 50% Cytotoxicity Concentrations (CC 50 ) of PS20 for HeLa and ME-180 cell lines and human foreskin fibroblast cells was more than 70 mM. The Minimum Inhibitory Concentration (MIC) for vaginal lactobacilli was more than 1000 mM. Conclusion : PS20 possesses anti-HIV and HSV effect and low cytotoxicity to epithelium cells and vaginal lactobacilli. It may be considered as a potential microbicide agent for further investigation.
  3,967 104 1
Cefotaxime-induced near-fatal anaphylaxis in a neonate: A case report and review of literature
Thirunavukkarasu Arun Babu, Vijayan Sharmila
September-October 2011, 43(5):611-612
DOI:10.4103/0253-7613.84987  PMID:22022015
A case of 7-day-old male neonate with cefotaxime-induced near-fatal anaphylaxis is being reported. Child was started on intravenous cefotaxime on day 3 of life in view of early-onset sepsis with pneumonia, following which there was clinical improvement. Child was then shifted out of intensive care to general ward for completion of antibiotic course. One day prior to the planned discharge, child suddenly developed poor sensorium, flaccidity, apnea, and cyanosis within seconds of receiving intravenous cefotaxime and was found to have bradypnea with bradycardia. Prompt resuscitation was carried out with artificial ventilation, adrenaline, and steroids. Spontaneous breathing reappeared and the clinical condition improved.
  3,901 144 7
The effect of chronic administration of L-arginine and L-NAME on morphine-induced antinociception in ovariectomized rats
Mahmoud Hosseini, Zahra Taiarani, Reza Karami, Azam Alavi Nezhad Khalil Abad
September-October 2011, 43(5):541-545
DOI:10.4103/0253-7613.84969  PMID:22021997
Objective : The role of ovarian hormones and nitric oxide on morphine-induced antinociception and their interaction have been widely investigated. The results of previous study showed that nitric oxide synthase inhibition differently affects morphine-induced antinociception in male and female rats. The present study was carried out to evaluate the different effects of chronic administration of L-arginine (LA) and L-NAME (LN) on morphine-induced antinociception in ovariectomized (OVX) and naive female rats. Materials and Methods : Sixty female rats were randomly divided into six groups (n = 10) as follows: (1) sham, (2) OVX, (3) sham-LA (4) sham-LN (5) OVX-LA, and (6) OVX-LN. The animals of sham-LA and OVX-LA groups received daily injection of 200 mg/kg LA (i.p.) during 6 weeks, while in sham-LN and OVX-LN groups, the animals were treated with 10 mg/kg LN (i.p.). The animals of sham and OVX groups received 2 ml/kg saline (i.p.) instead of LA and LN. Finally, all the animals were tested on the hot plate test (52 ± 0.2°C; cut-off time 80 seconds) for evaluating the antinociceptive effects of morphine. The hot plate test was performed as three base records with a 15-min interval before the injection of morphine (10 mg/kg; s.c.) following which it was repeated every 15 min after injection. Analgesic effect of morphine was quantified as maximal percent effect (MPE). Base reaction latency times (seconds) before the injection of morphine and MPE after the injection of morphine were compared using repeated-measure analysis of variance (ANOVA) followed by post-hoc Tukey's test. Differences were considered statistically significant when P < 0.05. Results : Before injection of morphine, there was no significant difference observed between sham and OVX groups in three recorded base reaction latency times. The base reaction latency times in sham-LA group were significantly higher than those of sham group (P < 0.001). In sham-LN group, the base reaction latency times were nonsignificantly lower than those of sham group (P = 0.095). There was no significant difference between OVX-LA group and OVX group. In OVX-LN group, three base reaction latency times were nonsignificantly lower than those of OVX group (P = 0.077). MPE in sham-LN group was higher than that of sham group (P < 0.05); however, there was no significant difference between sham-LA and sham groups. Conclusion : It is concluded that NO has a role in pain perception and the analgesic effect of morphine. The effect of NO might be differing in the presence or absence of ovarian hormones, but further investigations need to be done.
  3,728 108 2
Gingival enlargement due to Cyclosporine A therapy in aplastic anaemia
Girish R Sabnis, Niteen D Karnik, Uma Sundar, Sikandar Adwani
September-October 2011, 43(5):613-614
DOI:10.4103/0253-7613.84988  PMID:22022016
  3,433 98 -
Enalapril induced severe hyponatremia and altered sensorium in a child
Syed Ahmed Zaki, Swapnil Bhongade, Preeti Shanbag
September-October 2011, 43(5):605-606
DOI:10.4103/0253-7613.84984  PMID:22022012
Enalapril is an angiotensin converting enzyme inhibitor widely used in children for treatment of hypertension and congestive cardiac failure. We report a 5-year-old boy who developed severe hyponatremia and altered sensorium on enalapril therapy. The serum sodium gradually became normal within 3 days. The patient's sensorium improved significantly on correction of hyponatremia. Through this case, we highlight the importance of monitoring serum sodium in patients on enalapril therapy.
  3,333 113 -
Quadriparesis and dysarthria due to tetrabenazine therapy in a child with rheumatic chorea
Syed Ahmed Zaki, Vijay Lad, Preeti Shanbag
September-October 2011, 43(5):601-602
DOI:10.4103/0253-7613.84982  PMID:22022010
Tetrabenazine (TBZ) is widely used to treat hyperkinetic movement disorders in adults; however, published experience with the drug in children is limited. Common side effects of TBZ include drowsiness, sedation, weakness, Parkinsonism, depression, and acute akathisia, all of which are reversible with decreased doses. We report here a 7-year-old girl with rheumatic chorea who developed acute akinesia of all four limbs and dysarthria due to TBZ therapy. Withdrawal of the drug led to rapid improvement within 18 hours.
  3,211 85 1
In vitro antigiardial and antirotaviral activity of Psidium guajava L. leaves
Tannaz J Birdi, Poonam G Daswani, S Brijesh, Pundarikakshudu Tetali
September-October 2011, 43(5):616-617
DOI:10.4103/0253-7613.84990  PMID:22022018
  2,992 106 5
Effect of memantine on lithium chloride induced head twitches in rats
Amarinder Singh, Arijit Ghosh, Vijay R Dhumal, Abhijeet V Tilak
September-October 2011, 43(5):614-616
DOI:10.4103/0253-7613.84989  PMID:22022017
  2,941 109 -
DRESSing up to phenytoin
Dilip Gude, Sashidhar Chennamsetty, Ratan Jha, K Rajitha
September-October 2011, 43(5):617-618
DOI:10.4103/0253-7613.84991  PMID:22022019
  2,891 124 1
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