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September-October 2008
Volume 40 | Issue 5
Page Nos. 189-238
Online since Friday, November 21, 2008
Accessed 84,215 times.
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GUEST EDITORIAL
Early phase studies in India: Are we too early to explore?
p. 189
Anupama Ramkumar
DOI
:10.4103/0253-7613.44149
PMID
:20040956
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EDUCATIONAL FORUM
Partial nicotinic acetylcholine (α4β2) agonists as promising new medications for smoking cessation
p. 191
J Singh, Salil Budhiraja
DOI
:10.4103/0253-7613.44150
PMID
:20040957
Objective:
To review the pharmacology, clinical efficacy and safety of partial agonists of a4β 2 nicotinic acetylcholine receptor.
Data Sources:
Primary literature and review articles were obtained via a PUBMED search (1988-August 2006) using the key terms smoking cessation, partial agonist alpha4beta2 nicotinic acetylcholine receptor, varenicline, cytisine and SSR591813. Additional studies and abstracts were identified from the bibliographies of reviewed literature.
Study Selection and Data Extraction:
Studies and review articles related to varenicline, cytisine and the partial agonist alpha4beta2 nicotinic acetylcholine receptor were reviewed.
Data Synthesis:
Smoking is widely recognized as a serious health problem. Smoking cessation has major health benefits. According to the US Public Health Services, all patients attempting to quit smoking should be encouraged to use one or more effective pharmacotherapy. Currently, along with nicotine replacement therapy, bupropion, nortriptyline and clonidine, are the mainstay of pharmacotherapy. More than ¾ of patients receiving treatment for smoking cessation return to smoking within the first year. Nicotine, through stimulating α4β 2 nAChR, releases dopamine in the reward pathway. Partial agonist of α4β 2 nAChR elicits moderate and sustained release of dopamine, which is countered during the cessation attempts; it simultaneously blocks the effects of nicotine by binding with α4β 2 receptors during smoking. Recently, varenicline, a partial agonist at α4β 2 nAChR, has been approved by the FDA (Food and Drug Administration) for smoking cessation.
Conclusion:
Partial agonist α4β 2 nAChR appears to be a promising target in smoking cessation. Varenicline of this group is approved for treatment of smoking cessation by the FDA in May 2006.
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REVIEW ARTICLE
Recent advances in pharmacotherapy of glaucoma
p. 197
SK Gupta, Niranjan D Galpalli, SS Agrawal, Sushma Srivastava, Rohit Saxena
DOI
:10.4103/0253-7613.44151
PMID
:20040958
Glaucoma is a slow progressive degeneration of the retinal ganglion cells (RGCs) and the optic nerve axons, leading to irreversible blindness if left undiagnosed and untreated. Although increased intraocular pressure is a major risk factor of glaucoma, other factors include increased glutamate levels, alterations in nitric oxide (NO) metabolism, vascular alterations and oxidative damage caused by reactive oxygen species. Glaucoma is the second leading cause of blindness globally, accounting for 12.3% of the total blindness. Glaucoma has been broadly classified as primary or secondary open-angle or angle-closure glaucoma. The primary goal in management of glaucoma is to prevent the risk factor, especially elevated intraocular pressure (IOP), using medications, laser therapy or conventional surgery. The first-line treatment of glaucoma usually begins with the use of a topical selective or nonselective blocker or a prostaglandin analog. Second-line drugs of choice include alpha-agonists and topical carbonic anhydrase inhibitors. Cholinergic agonists are considered third-line treatment options. When a single therapy is not sufficient to lower the IOP, a combination therapy is indicated. To enhance the patient compliance, drug delivery systems like electronic devices, ocular inserts, tansdermal and mechanical drug delivery systems have been developed. Use of viscoelastic agents in ophthalmic formulations, emulsions and soluble ophthalmic drug inserts (SODI) enhance patience compliance and ocular drug delivery in patients in long-term glaucoma therapy. For patients who do not respond to antiglaucoma medications, laser trabeculoplasty and incisional surgery are recommended. Several nutrients and botanicals hold promise for the treatment of glaucoma, but most studies are preliminary, and larger, controlled studies are required. Future directions for the development of a novel therapy glaucoma may target glutamate inhibition, NMDA receptor blockade, exogenously applied neurotrophins, open channel blockers, antioxidants, protease inhibitors and gene therapy.
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RESEARCH ARTICLES
Antiulcer activity of cod liver oil in rats
p. 209
Salaj Khare, Mohammed Asad, Sunil S Dhamanigi, V Satya Prasad
DOI
:10.4103/0253-7613.44152
PMID
:20040959
Objective:
Cod liver oil is used widely as a dietary supplement. The present study was carried out to evaluate the effect of cod liver oil (0.5 g/kg, p.o. and 1 g/kg, p.o.) on gastric and duodenal ulcers.
Materials and Methods:
The study was carried out on different gastric ulcer models such as acetic acid induced chronic gastric ulcers, pylorus ligation, indomethacin induced ulcers, stress induced ulcers and ethanol induced ulcers. The duodenal ulcers were induced using cysteamine hydrochloride (HCl). Ranitidine (50 mg/kg p.o.) and misoprostol (100 µg/kg, p.o.) were used as standard drugs.
Results:
Both doses of cod liver oil showed gastric ulcer healing effect in acetic acid induced chronic gastric ulcers, produced gastric antisecretory effect in pylorus-ligated rats and also showed gastric cytoprotective effect in ethanol-induced and indomethacin-induced ulcer. Cod liver oil also produced a significant reduction in the development of stress induced gastric ulcers and cysteamine induced duodenal ulcer. The high dose of cod liver oil (1 g/kg, p.o.) was more effective compared to the low dose (0.5 g/kg, p.o.).
Conclusion:
Cod liver oil increases healing of gastric ulcers and prevents the development of experimentally induced gastric and duodenal ulcers in rats.
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Protective effect of aqueous extract of
Embelia ribes
Burm fruits in middle cerebral artery occlusion-induced focal cerebral ischemia in rats
p. 215
Uma Bhandari, M Nazam Ansari
DOI
:10.4103/0253-7613.44153
PMID
:20040960
Objective:
The present study was carried out to evaluate the neuroprotective effect of the aqueous extract of
Embelia ribes
, in focal ischemic brain.
Materials and Methods:
Adult male Wistar albino rats were fed with the aqueous extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days. After 30 days of feeding, all the animals were anaesthetized with chloral hydrate (400 mg/kg, i.p.). The right middle cerebral artery was occluded with a 4-0 suture for 2 h. The suture was removed after 2 h, to allow reperfusion injury. The animals were used for grip strength measurement, biochemical estimation in serum and brain tissue (hippocampus and frontal cortex) and cerebral infarct size measurement.
Results:
In the ischemic group, a significant (
P
<0.01) alteration in the markers of oxidative damage (thiobarbituric acid reactive substances (TBARS); reduced glutathione (GSH); glutathione peroxidase (GPx); glutathione reductase (GR); and, glutathione-S-transferase (GST)) was observed in the hippocampus and frontal cortex, as compared to sham operated rats. We observed that the animals treated with the aqueous extract of
Embelia ribes
had a significant (
P
<0.01) increase in the poststroke grip strength activity. Further, supplementation with aqueous extract of
Embelia ribes
reversed the levels/activities of the above mentioned biochemical parameters significantly (P<0.01) and also resulted in decreased cerebral infarct area, as compared to the ischemic group.
Conclusion:
The results of our study, for the first time, provide clear evidence that aqueous extract of
Embelia ribes
pretreatment ameliorates cerebral ischemia/reperfusion injury and enhances the antioxidant defense against middle cerebral artery occlusion-induced cerebral infarction in rats; it exhibits neuroprotective property.
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Anti-dopaminergic effect of the methanolic extract of
Morus alba
L. leaves
p. 221
Adhikrao V Yadav, Vandana S Nade
DOI
:10.4103/0253-7613.44154
PMID
:20040961
Objective:
To evaluate the effect of methanolic extract of Morus alba L. leaves on dopaminergic function.
Materials and Methods:
The effect of the methanolic extract of Morus alba L. leaves was evaluated on haloperidol and metoclopramide induced catalepsy, foot shock-induced aggression, amphetamine-induced stereotyped behavior and phenobarbitone induced sleeping in mice. In each of these tests, the extract was administered in doses of 50, 100 and 200 mg/kg, i.p., 30 min before performing the test in mice. Further, the inhibitory effect of the extract on dopamine was studied using isolated rat vas deferens.
Results:
The extract produced significant dose dependent potentiation of haloperidol (1 mg/kg, i.p.) and metoclopramide (20 mg/kg, i.p.) induced catalepsy in mice. The extract significantly reduced number of fights and increased latency to fights in foot shock-induced aggression; it also decreased amphetamine (1 mg/kg, i.p.) induced stereotyped behavior in a dose dependent manner. The sleeping time induced by phenobarbitone (50 mg/kg, i.p.) too was prolonged. The extract inhibited contractions produced by dopamine on isolated rat vas deferens.
Conclusion:
The results suggest that the methanolic extract of Morus alba L. possesses antidopaminergic activity. Further neurochemical investigation can explore the mechanism of action of the plant drug with respect to antidopaminergic functions and help to establish the plant as an antipsychotic agent.
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Preliminary isolation and
in vitro
antiyeast activity of active fraction from crude extract of
Gracilaria changii
p. 227
Sreenivasan Sasidharan, Ibrahim Darah, Mohd Kassim Mohd Jain Noordin
DOI
:10.4103/0253-7613.44155
PMID
:20040962
Objective:
To isolate the active fraction from crude extract of Gracilaria changii and to determine its
in vitro
antifungal activity.
Materials and Methods:
The active fraction was isolated from the crude extract of
G. changii
by various purification procedures such as column chromatography, thin layer chromatography, bioauthograph etc. The
in vitro
antifungal activity (
Candida albicans
) of the active fraction (1.00, 0.50, and 0.25 mg/ml) was studied by disc diffusion method and the effect of the active fraction on the morphology of yeast was done by scanning electron microscope (SEM) studies.
Results:
An active fraction with remarkable antifungal activity was separated from the crude extract. The active fraction was effective as a fungicide against
C. albicans
and showed a dose-dependent antifungal activity. A Scanning Electron Microscope (SEM) study confirmed the fungicidal effect of
G. changii
active fraction on
C. albicans
, by changing the normal morphology of C. albicans.
Conclusion:
From
G. changii
crude extract, an active fraction with remarkable in vitro antifungal activity has been isolated.
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Antibiotic susceptibility patterns of
Pseudomonas aeruginosa
at a tertiary care hospital in Gujarat, India
p. 230
Viren A Javiya, Somsuvra B Ghatak, Kamlesh R Patel, Jagruti A Patel
DOI
:10.4103/0253-7613.44156
PMID
:20040963
Objectives:
The present study was undertaken to assess the antibiotic susceptibility patterns of
Pseudomonas aeruginosa
at a tertiary care hospital in Gujarat, India. Due to significant changes in microbial genetic ecology, as a result of indiscriminate use of anti-microbials, the spread of anti-microbial resistance is now a global problem.
Materials and Methods:
Out of 276 culture positive samples, 56 samples of Pseudomonas aeruginosa were examined and 10 different types of specimen were collected. Microbial sensitivity testing was done using disk diffusion test with
Pseudomonas species
NCTC 10662, as per CLSI guidelines.
Results:
The highest number of
Pseudomonas infections
was found in urine, followed by pus and sputum. Pseudomonas species demonstrated marked resistance against monotherapy of penicillins, cephalosporins, fluoroquinolones, tetracyclines and macrolides. Only combination drugs like Ticarcillin + Clavulanic acid, Piperacillin + Tazobactum, Cefoperazone + Sulbactum, Cefotaxime + Sulbactum, Ceftriaxome + Sulbactum and monotherapy of amikacin showed higher sensitivity to Pseudomonas infections; however, the maximum sensitivity was shown by the Carbapenems.
Conclusion:
From the present study, we conclude that urinary tract infection was the most common hospital acquired infection. Also, co-administration of β -lactamase inhibitors markedly expanded the anti-microbial sensitivity of semi-synthetic penicillins and cephalosporins. The aminoglycoside group of antibiotics - amikacin - demonstrated maximum sensitivity against pseudomonas species. Therefore, use of amikacin should be restricted to severe nosocomial infections, in order to avoid rapid emergence of resistant strains. Periodic susceptibility testing should be carried out over a period of two to three years, to detect the resistance trends. Also, a rational strategy on the limited and prudent use of anti-Pseudomonal agents is urgently required.
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SHORT COMMUNICATION
Effect of fresh
Triticum aestivum
grass juice on lipid profile of normal rats
p. 235
Saroj Kothari, Anand K Jain, Swaroop C Mehta, Shrinivas D Tonpay
DOI
:10.4103/0253-7613.44157
PMID
:20040964
Objective:
To study the hypolipidemic activity of fresh grass juice of
Triticum aestivum
in normal rats.
Materials and Methods:
Freshly prepared
Triticum aestivum
grass juice was administered to normal rats at the dose of 5 ml/kg and 10 ml/kg orally once daily for 21 days. Blood samples were collected after 24 hours of last administration and used for estimation of lipid profile. Fresh grass juice was also subjected to preliminary phytochemical screening.
Results:
Fresh grass juice administration produced dose related significant (
P
<0.05) reduction in total chloesterol,triglycerides,low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol levels in normal rats as compared to control.Preliminary phytochemical screening revealed presence of alkaloids,tannins, saponins and sterols in
Triticum aestivum
grass.
Conclusion:
The results of the present study lndicate hypolipidemic activity of fresh
Triticum aestivum
grass juice.
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CASE REPORT
Olanzapine induced tardive dystonia
p. 237
Ashish Aggarwal, RC Jiloha
DOI
:10.4103/0253-7613.44158
PMID
:20040965
Advent of atypical antipsychotics was thought to be a major advancement in the psychopharmacology for schizophrenia. It was thought that these drugs would have low propensity to induce extrapyramidal symptoms including tardive movements. Olanzapine is a thienobenzodiazepine derivative, second generation (atypical) antipsychotic agent. Compared to typical antipsychotics, it has a greater affinity for serotonin 5-HT2A than dopamine D2 receptors, with preferential action at mesolimbic than nigrostriatal dopaminergic pathways. However, only few reports of olanzapine induced tardive dystonia (TD) are available in the literature. We wish to report another case of TD, in a male patient with schizophrenia, which developed after 15 months of treatment with olanzapine.
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