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2012| November-December | Volume 44 | Issue 6
Online since
November 8, 2012
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RESEARCH ARTICLES
Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats
Sawsan A Zaitone, Dina M Abo-Elmatty, Shimaa M Elshazly
November-December 2012, 44(6):774-779
DOI
:10.4103/0253-7613.103300
PMID
:23248410
Objective:
To evaluate the neuroprotective effect of the nootropic drugs, piracetam (PIR) and vinpocetine (VIN), in rotenone-induced Parkinsonism in rats.
Materials and Methods:
Sixty male rats were divided into 6 groups of 10 rats each. The groups were administered vehicle, control (rotenone, 1.5 mg/kg/48 h/6 doses, s.c.), PIR (100 and 200 mg/kg/day, p.o.) and VIN (3 and 6 mg/kg/day, p.o.). The motor performance of the rats was evaluated by the open field and pole test. Striatal dopamine level, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor-α (TNF-α) were assayed. Histopathological study of the substantia nigra was also done.
Results:
Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field test. In addition, GSH level was decreased whereas MDA and TNF-α increased in striata of rotenone-treated rats as compared to vehicle-treated rats. Marked degeneration of the substantia nigra pars compacta (SNpc) neurons and depletion of striatal dopamine was also observed in the rotenone-treated rats. Treatment with PIR or VIN significantly reversed the locomotor deficits and increased striatal dopamine level. Treatment with VIN significantly (
P
< 0.05) reduced the striatal level of MDA and GSH in comparison to rotenone group whereas TNF-α production was found to be significantly decreased in PIR group (
P
< 0.05).
Conclusion:
VIN and PIR exhibit neuroprotective activity in rotenone-induced Parkinsonism. Hence, these nootropic agents may be considered as possible candidates in the treatment of Parkinson's disease.
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EDUCATIONAL FORUM
The treatment strategies of autoimmune disease may need a different approach from conventional protocol: A review
S Chandrashekara
November-December 2012, 44(6):665-671
DOI
:10.4103/0253-7613.103235
PMID
:23248391
Autoimmune disease (AD) is one of the emerging noncommunicable diseases. Remission is a possibility in AD, but current treatment strategies are not able to achieve this. We have well-established protocols for infections, oncology, metabolic diseases, and transplantation which are often used as models for the management of AD. Studies and observations suggest that in contrast to diseases used as a role model, AD has wide variability, different causative and pathogenic process, which is highly dynamic, making the current treatment strategies to fall short of expected complete remission. In this brief review, it is attempted to highlight the current understanding of AD and the probable gaps in the treatment strategies. Few hypothetical suggestions to modify the treatment protocols are presented.
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RESEARCH ARTICLES
Shatavarins (containing Shatavarin IV) with anticancer activity from the roots of
Asparagus racemosus
Shankar K Mitra, Neswi S Prakash, Ramachandran Sundaram
November-December 2012, 44(6):732-736
DOI
:10.4103/0253-7613.103273
PMID
:23248403
Objectives:
The anticancer activity of shatavarins (containing shatavarin IV) isolated from the roots of
Asparagus racemosus
(Wild) was evaluated using
in vitro
and
in vivo
experimental models.
Material and Methods:
The shatavarin IV was isolated from ethyl acetate insoluble fraction (AR-2B) of chloroform:methanol (2:1) (AR-2) extract of
A. racemosus
roots. The cytotoxicity (
in vitro
) of shatavarin IV and other shatavarins rich fraction was carried out using of MTT assay using MCF-7 (human breast cancer), HT-29 (human colon adenocarcinoma), and A-498 (human kidney carcinoma) cell lines. The
in vivo
anticancer activity of shatavarins (containing shatavarin IV) was evaluated against Ehrlich ascites carcinoma (EAC) tumor bearing mice.
Results:
The isolated shatavarin IV (84.69 %) along with shatavarins rich fraction, coded AR-2B containing 5.05% shatavarin IV showed potent cytotoxicity. Oral administration of AR-2B to tumor bearing mice at doses of 250 and 500 mg/kg body weight for 10 days, showed significant reduction in percent increase in body weight, tumor volume, packed cell volume, viable tumor cell count, and increased non-viable cell count when compared to the untreated mice of the EAC control group. The restoration of hematological parameters towards normalcy was also observed.
Conclusion:
The result suggests that the shatavarins (containing shatavarin IV) rich fraction (AR-2B) exhibits significant anticancer activity in both
in vitro
and
in vivo
experimental models.
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413
Antiurolithiatic and antioxidant activity of
Hordeum vulgare seeds
on ethylene glycol-induced urolithiasis in rats
Jignesh G Shah, Bharat G Patel, Sandip B Patel, Ravindra K Patel
November-December 2012, 44(6):672-677
DOI
:10.4103/0253-7613.103237
PMID
:23248392
Objective:
The objective was to investigate the antiurolithiatic and antioxidant activity of ethanolic extract of
Hordeum vulgare seeds
(EHV) on ethylene glycol-induced urolithiasis in Wistar albino rats.
Materials and Methods:
Urolithiasis was produced in Wistar albino rats by adding 0.75% v/v ethylene glycol (EG) to drinking water for 28 days. The ethanolic extract of
Hordeum vulgare seeds
(EHV) was assessed for its curative and preventive action in urolithiasis. In preventive treatment, the EHV given from 1st day to 28th day, while in the curative regimen, the EHV was given from 15th day to 28th day. Various renal functional and injury markers such as urine volume, calcium, phosphate, uric acid, magnesium, urea, and oxalate were evaluated using urine, serum, and kidney homogenate. Antioxidant parameters such as lipid peroxidation, superoxide dismutase, and catalase were also determined.
Results:
The EHV treatment (both preventive and curative) increased the urine output significantly compared to the control. The EHV treatment significantly reduced the urinary excretion of the calcium, phosphate, uric acid, magnesium, urea, and oxalate and increased the excretion of citrate compared to EG control. The increased deposition of stone forming constituents in the kidneys of calculogenic rats were significantly lowered by curative and preventive treatment with EHV. It was also observed that the treatment with EHV produced significant decrease in lipid peroxidation, and increased levels of superoxide dismutase and catalase.
Conclusion:
These results suggest the usefulness of ethanolic extract of
Hordeum vulgare seeds
as an antiurolithiatic and antioxidant agent.
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Evaluation of the wound-healing activity of
Hibiscus rosa sinensis
L (Malvaceae) in Wistar albino rats
Anusha Bhaskar, V Nithya
November-December 2012, 44(6):694-698
DOI
:10.4103/0253-7613.103252
PMID
:23248396
Objective:
To investigate the wound-healing potency of the ethanolic extract of the flowers of
Hibiscus rosa sinensis
.
Materials and Methods:
The wound-healing activity of
H. rosa sinensis
(5 and 10% w/w) on Wistar albino rats was studied using three different models viz., excision, incision and dead space wound. The parameters studied were breaking strength in incision model, granulation tissue dry weight, breaking strength and collagen content in dead space wound model, percentage of wound contraction and period of epithelization in excision wound model. The granulation tissue formed on days 4, 8, 12, and 16 (post-wound) was used to estimate total collagen, hexosamine, protein, DNA and uronic acid. Data were analyzed by Analysis of Variance (ANOVA) test.
P
<0.05 was considered statistically significant.
Results:
The extract increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, total protein and total collagen content of granulation tissues. The extract-treated wounds were found to heal much faster as indicated by improved rates of epithelialization and wound contraction. The extract of
H. rosa sinensis
significantly (
P
<0.001) increased the wound-breaking strength in the incision wound model compared to controls. The extract-treated wounds were found to epithelialize faster, and the rate of wound contraction was significantly (
P
<0.001) increased as compared to control wounds. Wet and dry granulation tissue weights in a dead space wound model increased significantly (
P
<0.001). There was a significant increase in wound closure rate, tensile strength, dry granuloma weight, wet granuloma weight and decrease in epithelization period in
H. rosa sinensis
-treated group as compared to control and standard drug-treated groups.
Conclusion:
The ethanolic extract of
H. rosa sinensis
had greater wound-healing activity than the nitrofurazone ointment.
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SHORT COMMUNICATIONS
Cutaneous adverse drug reaction profile in a tertiary care out patient setting in Eastern India
Abanti Saha, Nilay Kanti Das, Avijit Hazra, Ramesh Chandra Gharami, Satyendra Nath Chowdhury, Pijush Kanti Datta
November-December 2012, 44(6):792-797
DOI
:10.4103/0253-7613.103304
PMID
:23248414
Background:
Cutaneous adverse drug reactions (CADR) are the most frequent of all manifestations of drug sensitivity and manifest with varied and diverse morphology.
Aims:
To study the prevalence and clinical spectrum of CADR among patients attending outpatient department (OPD) in a tertiary care hospital.
Materials and Methods:
An observational study was undertaken over a 1-year period in dermatology OPD of a tertiary care teaching hospital in Eastern India. Patients presenting with suspected drug-related cutaneous lesions were included if drug identity could be ascertained. Clinical profiling was done. Drug history was recorded in a format specified in Indian National Pharmacovigilance Programme and causality assessment carried out as per World Health Organization-Uppsala Monitoring Centre (WHO-UMC) criteria.
Results:
Commonest CADR in our study was morbilliform eruption (30.18%), followed by fixed drug eruption (24.52%), Stevens-Johnson syndrome (SJS)-Toxic epidermal necrolysis (TEN) and overlap of two (24.50%), exfoliative dermatitis (7.54%), urticaria (5.6%), phototoxic drug reaction (3.8%), pityriasis rosea-like eruptions (1.89%), and severe mucositis (1.80%). Drugs implicated were sulfonamides (17%), fixed-dose combinations of fluoroquinolones with nitroimidazoles (11.30%), analgesics (11.30%), antiepileptics (11.30%), beta-lactam antibiotics (9.40%), fluoroquinolones alone (7.50%), allopurinol (7.50%), and azithromycin (5.70%). Reaction latency varied from 1 to 43 days. Causality assessment was certain and probable for 18.9% and 41.5% of the reactions, respectively, and reactions were serious in 33.96% (95% confidence interval 21.21-46.71%).
Conclusions:
Cutaneous adverse drug reaction profile in this study is similar in many ways to studies conducted earlier in India. Incidence of life-threatening reactions like SJS-TEN was higher compared with studies conducted abroad. Reaction time and lesion patterns are helpful in identifying an offending drug in the setting of multiple drug therapy.
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RESEARCH ARTICLES
Evaluation of anti-inflammatory effect of anti-platelet agent-clopidogrel in experimentally induced inflammatory bowel disease
Samir H Patel, Manish A Rachchh, Pinakin D Jadav
November-December 2012, 44(6):744-748
DOI
:10.4103/0253-7613.103278
PMID
:23248405
Aim:
To evaluate the anti-inflammatory effect of antiplatelet agent, clopidogrel, in experimentally induced inflammatory bowel disease (IBD).
Materials and Methods:
TNBS induced Crohn's disease model and oxazolone induced ulcerative colitis model were used to evaluate the role of clopidogrel in IBD. Spargue Dawley female and Wistar male rats were used respectively. The colitis was induced by a single intra-colonic application of TNBS (0.25 ml, 120 mg/ml in 50% ethanol) and oxazolone (450 μl 5% oxazolone in 50% ethanol). Rats were divided into four groups (n=6) in each model namely normal control, sham control, test and standard group. Drug treatment was carried out for 21 days. After 21 days, animals were sacrificed and evaluated for weight change, colon mucosal damage index (CMDI), disease activity Index (DAI) and myeloperoxidase (MPO) activity.
Results:
Results showed that clopidogrel provided significant protection against mucosal damage in both the models of IBD. It significantly reduced (
P
<0.05) the decrease in body weight and CMDI, DAI and MPO scores.
Conclusion:
The results indicate that clopidogrel may be effective in treatment of Crohn's disease and ulcerative colitis. Platelet inhibition may be one of the mechanism for effectiveness of clopidogrel in the treatment of IBD.
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Protective effect of methanolic extract of
Garcinia indica
fruits in 6-OHDA rat model of Parkinson's disease
Bhaveshkumar V Antala, Manishkumar S Patel, Satish V Bhuva, Shiv Gupta, Samir Rabadiya, Mangala Lahkar
November-December 2012, 44(6):683-687
DOI
:10.4103/0253-7613.103242
PMID
:23248394
Context:
Several studies have reported that antioxidants play an important role in Parkinson's disease (PD).
Garcinia indica
extract is a natural antioxidant, the present study was undertaken to evaluate the neuroprotective effect of methanolic extract of
Garcinia indica
(GIM) against 6-hydroxydopamine (6-OHDA) neurotoxicity for striatal dopaminergic neurons in the rat.
Materials and Methods:
Thirty adult Wistar rats were randomly divided into five groups namely control, 6-OHDA model, and GIM (100, 200, and 400 mg/kg body weight suspended in one ml of 0.1% carboxymethyl cellulose). The treatment was started three days before surgery and continued for next 14 days. The surgery was done on third day in all groups for administration of 6-OHDA into the right striatum and right substantia nigra, whereas control group injected with 6-OHDA vehicle. Various behavior and biochemical tests (Apomorphine-induced rotational behavior, Stepping test, Initiation time, Postural balance test, and Disengage time) were used to evaluate the neuroprotective effect of GIM. One-way analysis of variance (ANOVA) followed by Dunnett's test was used to compare inter-group differences.
P
<0.05 was considered as statistically significant.
Results:
GIM had significant (
P
<0.05,
P
<0.01) preventive effect in biochemical tests,
i.e.
, dopamine and its metabolites measurement and in various behavior tests,
i.e.
, apomorphine-induced rotational behavior, stepping test, initiation time, postural balance test, and disengage time as compared to 6-OHDA-treated rats.
Conclusions:
Our results demonstrated that GIM acted as an effective neuroprotective agent for striatal dopaminergic neurons in 6-OHDA lesioned rat model of PD.
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Effect of lithium chloride and antineoplastic drugs on survival and cell cycle of androgen-dependent prostate cancer LNCap cells
Vajihe Azimian-Zavareh, Ghamartaj Hossein, Ehsan Janzamin
November-December 2012, 44(6):714-721
DOI
:10.4103/0253-7613.103265
PMID
:23248400
Objective:
Glycogen synthase kinase-3β (GSK-3β) has been reported to be required for androgen receptor (AR) activity. This study sought to determine the usefulness of lithium chloride (LiCl) as a highly selective inhibitor of GSK-3β to increase the sensitivity of LNCap cells to doxorubicin (Dox), etoposide (Eto), and vinblastine (Vin) drugs.
Materials and Methods:
Thiazolyl Blue Tetrazolium Blue (MTT) assay was used to determine the cytotoxic effect to LiCl alone or in combination with low dose and IC
50
doses of drugs. Subsequently, cell cycle analysis was performed by using flow cytometry.
Results:
LiCl showed cytotoxic effect in a dose- and time-dependent manner (
P
<0.001). Both Dox (100 or 280 nM) and Vin IC
50
(5 nM) doses caused G2/M-phase arrest (
P
<0.001) compared with control. However, low dose (10 μM) or IC
50
(70 μM) Eto doses showed G2/M or S-phase arrests, respectively (
P
<0.001). Combination of low dose or IC
50
dose of Eto with LiCl showed increased apoptosis as revealed by high percent of cells in SubG1 (
P
<0.05,
P
<0.01, respectively). Moreover, Eto (10 μM) led to decreased percent of cells in G2/M phase when combined with LiCl (
P
<0.05).
Conclusion:
This study showed that LiCl increases apoptosis of (LNCap) Lymph Node Carcinoma of the Prostate cells in the presence of Eto, which is S- and G2-phase-specific drug.
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Comparison of knowledge, attitude and practices of resident doctors and nurses on adverse drug reaction monitoring and reporting in a tertiary care hospital
HS Rehan, Ravinder Kumar Sah, Deepti Chopra
November-December 2012, 44(6):699-703
DOI
:10.4103/0253-7613.103253
PMID
:23248397
Background:
Lack of knowledge of pharmacovigilance (PhV) and adverse event (AE) reporting culture among the healthcare providers have been identified as major factors for under reporting of AE in developing countries. Hence, this study was planned to assess and compare the knowledge, attitude, and practices (KAP) of resident doctors and nurses about PhV and AE reporting.
Material and Methods:
This cross-sectional, questionnaire-based study was conducted to compare KAP of 100 doctors and 100 nurses on PhV and AE reporting.
Results:
All the respondents felt that AE reporting is necessary and two-thirds were aware of the existing PhV Program of India. Significantly, higher proportion of doctors had correct understanding regarding PhV (
P
<0.05) and knew what should be reported (
P
<0.05) but nurses (75%) knew better about where to report (
P
<0.001). Significantly (
P
<0.001), more doctors (98%) felt that the patients are benefited by reporting AE. Nurses (96%) felt the need for information on drugs causing AE and their management strategy (
P
<0.001). Around 60% of all the respondents were in favor of mandatory PhV and feedback on the submitted AE. Doctors (67%) (
P
<0.05) had a practice of inquiring patients for any untoward outcome of therapy. Higher proportion (
P
<0.05) of nurses (55%) mentioned that observed AE are recorded in patient's case record, but random screening of 1000 patients' record did not reveal it. Nurses mentioned that they never reported any AE (
P
<0.05) and witnessed discussions on ADRs during the ward rounds (
P
<0.001). All the respondents preferred phone as the convenient method for reporting AE followed by drop box kept in the ward/OPD and felt the need of frequent workshops and continuing medical education.
Conclusion:
Resident doctors and nurses had good knowledge and awareness on AE reporting and PhV but their practices need to be improved.
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Analgesic effects of stem bark extracts of
Trichilia monadelpha
(Thonn.) JJ De Wilde
Eric Woode, Ama Kyeraa Amoh-Barimah, Wonder Kofi Mensah Abotsi, George Kwaw Ainooson, George Owusu
November-December 2012, 44(6):765-773
DOI
:10.4103/0253-7613.103299
PMID
:23248409
Objectives:
Various parts of
Trichilia monadelpha
(Thonn) JJ De Wilde (Fam. Meliaceae) are used in Ghanaian traditional medicine for the treatment of painful and inflammatory conditions. The present study examined the analgesic properties of the petroleum ether (PEE), ethyl acetate (EAE), and the hydro-ethanolic (HAE) extract of the stem bark of the plant in murine models.
Materials and Methods:
PEE, EAE, and HAE were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models. The possible mechanisms of the antinociceptive action were also examined with various antagonists in the formalin test.
Results:
HAE, EAE, and PEE, each at doses of 10-100 mg/kg orally, and the positive controls (morphine and diclofenac) elicited significant dose-dependent antinociceptive activity in the chemical (acetic acid abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models in rodents. The antinociceptive effect of HAE was partly or wholly reversed by systemic administration of atropine, naloxone, and glibenclamide. The antinociceptive effects of EAE and PEE were inhibited by atropine.
Conclusion:
The extracts HAE, EAE, and PEE caused dose-related antinociception in chemical, thermal, and mechanical models of pain in animals. The mechanism of action of HAE involves an interaction with muscarinic cholinergic, adenosinergic, opioidergic pathways, and ATP-sensitive K
+
channels while that of EAE and PEE involve the muscarinic cholinergic system.
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SHORT COMMUNICATIONS
Evaluation of anti-inflammatory activity of
Typha angustifolia
pollen grains extracts in experimental animals
Saroj S Varpe, Archana R Juvekar, Mukta P Bidikar, Parikshit R Juvekar
November-December 2012, 44(6):788-791
DOI
:10.4103/0253-7613.103303
PMID
:23248413
Objective:
This study was designed to evaluate the anti-inflammatory activity of aqueous and 70% methanolic extracts of pollen grains of
Typha angustifolia
.
Materials and Methods:
Female Sprague Dawley rats were used for the study. The acute anti-inflammatory activity of pollen grains of
T. angustifolia
was studied using the carrageenan as phlogistic agent, whereas its chronic anti-inflammatory effect was investigated by the percentage inhibition of cotton pellet-induced granuloma.
Results:
Both aqueous and 70% methanolic extracts of pollen grains of
T. angustifolia
showed significant dose-dependent inhibition of carrageenan-induced paw edema as compared to the control (
P
<0.001). It was observed that both the extracts at dose of 125 mg/kg inhibited the granuloma formation by 44.30% which is higher than at dose of 500, 250 mg/kg, thus causing a significant (
P
<0.001) non-dose-related inhibition of granuloma formation.
Conclusion:
The results of this study indicate that extracts of pollen grains of
T. angustifolia
are effective in the treatment of both acute and chronic inflammatory conditions and thus support its traditional utilization.
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197
RESEARCH ARTICLES
Neuroprotective activity of
Stereospermum suaveolens
DC against 6-OHDA induced Parkinson's disease model
MH Shalavadi, VM Chandrashekhar, SP Avinash, C Sowmya, A Ramkishan
November-December 2012, 44(6):737-743
DOI
:10.4103/0253-7613.103275
PMID
:23248404
Objectives:
To evaluate the neuroprotective effect of
Stereospermum suaveolens
DC on 6-hydroxy dopamine induced Parkinson's disease model.
Materials and Methods:
The study was conducted on Sprague-Dawley rats where parkinson's disease was induced by producing the striatal 6-hydroxy dopamine lesions. The test animals received methanolic extract of
Stereospermum suaveolens
at dose of 125, 250 and 500 mg/kg for 42 days. Behavioral assessment, spontaneous locomotor activity and muscular coordination were studied. Antioxidant levels, striatal infraction area were assessed and histopathological studies were carried out.
Results:
The
Stereospermum suaveolens
DC methanolic extract showed significant dose dependent increase in behavioral activity, improved muscular coordination. Significant reduction of lipid peroxidation (LPO), increased antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and non-enzymatic activity of glutathione (GSH) and total thiol levels in extract treated groups was observed in test groups as compared to control group. Striatal infarction area was significantly reduced in extract treated groups as compared to control group.
Conclusion:
The methanolic extract of
Stereospermum suaveolens
DC showed neuroprotective activity against 6-hydroxy dopamine induced Parkinson's disease in rats.
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333
SHORT COMMUNICATIONS
Comparison of safety and efficacy of papaya dressing with hydrogen peroxide solution on wound bed preparation in patients with wound gape
Mangala B Murthy, Bhasker K Murthy, Sanjay Bhave
November-December 2012, 44(6):784-787
DOI
:10.4103/0253-7613.103302
PMID
:23248412
Objective:
Indian papaya or Carica papaya is known to have de-sloughing and wound-healing properties due to the presence of protease enzymes. The present study was done to compare the efficacy and safety of papaya dressing with hydrogen peroxide solution for preparation of wound bed in patients of postoperative wound gape.
Materials and Methods:
A randomized, open-labeled interventional study was carried out over a period of 8 months at a tertiary care hospital on post-caesarean section patients with wound gape. The efficacy parameters studied were duration of time required to induce development of healthy granulation tissue and total duration of hospitalization. Safety parameters studied were adverse effects reported by patients and development of hypersensitivity reaction.
Results:
A total of 64 patients were enrolled, of which 32 patients received hydrogen peroxide dressing and 31 patients received papaya dressing (one patient withdrew after randomization). Time required to induce the development of healthy granulation tissue and total duration of hospitalization were 6.2 ± 1.6 days vs 2.5 ± 0.5 days and 19.2 ± 5.8 days vs 12.92 ± 4.6 days in papaya and hydrogen peroxide dressing groups, respectively. Both primary efficacy parameters were significantly shorter in papaya dressing group. The incidence of adverse effects like local irritation and itching were comparable in both groups and the difference was not statistically significant.
Conclusion:
Papaya dressing is more efficacious and equally safe as compared to hydrogen peroxide dressing when used for wound bed preparation in patients with postoperative wound gape.
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169
DRUG WATCH
Zidovudine-induced nail pigmentation in a 12-year-old boy
Sanjeevani M Chawre, Shraddha M Pore, Manish B Nandeshwar, Nausheen M Masood
November-December 2012, 44(6):801-802
DOI
:10.4103/0253-7613.103306
PMID
:23248416
Zidovudine is an important component of first-line antiretroviral treatment (ART) regimens used to manage pediatric HIV. Nail pigmentation with zidovudine is a well-documented occurrence in adults, especially dark-skinned individuals. But it has so far not been reported in children. Here, we report a pediatric case of zidovudine-induced nail pigmentation. A 12-year-old boy receiving ART with zidovudine, lamivudine, and nevirapine presented to dermatology OPD with complaint of diffuse bluish-brown discoloration of all fingernails. The pigmentation was noticed by the patient after 3 months of initiating zidovudine-based regimen. It first appeared in thumb nails, gradually involved all fingernails, and increased in intensity over time. Though harmless and reversible, psychological aspects of this noticeable side effect may hamper adherence to therapy and may lead to unnecessary investigations and treatment for misdiagnosis such as cyanosis or melanoma.
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171
RESEARCH ARTICLES
A study of the effect of
Nigella sativa
(Black seeds) in isoniazid (INH)-induced hepatotoxicity in rabbits
Anwar S Hassan, Jawad H Ahmed, Sawsan S Al-Haroon
November-December 2012, 44(6):678-682
DOI
:10.4103/0253-7613.103239
PMID
:23248393
Objective:
To investigate the possibility of hepatoprotective effect of
Nigella sativa
(NS) in INH-induced hepatotoxicity.
Materials and Methods:
The experiments were carried out on 24 male rabbits. They were divided into 4 groups (6 each); rabbits in group 1 were treated with INH following a standard protocol to induce hepatotoxicity. Rabbits in group 2 received starch. Group 3 received NS 1 g/kg/day before INH treatment. Group 4 rabbits were treated with NS only. Phenobarbital sodium (IP) was given to induce metabolism of INH. INH and NS were given orally. The experiment continued for 12 days; at day 13, animals were sacrificed. Liver function tests, malondialdehyde (MDA) were estimated in serum and in liver homogenates. Liver histopathological examinations were performed.
Results:
Histopathological changes of hepatotoxicity were found in all INH-treated rabbits. The histopathological findings were normal in three rabbits treated with NS before INH, very mild in two, and with moderate changes in one rabbit. Serum alanine aminotransferase (S.ALT) was elevated after INH treatment and returned back to the control value when NS was given before INH. Similar pattern of effect was noticed with serum aspartate aminotransferase (S.AST), S. total bilirubin, S. MDA, and Serum alkaline phosphatase. In liver homogenate, AST, ALT, and MDA were increased with INH treatment compared to the control, then decreased with NS treatment given before INH.
Conclusions:
NS has hepatoprotective effects against INH-induced hepatotoxicity in rabbits. NS 1 g/kg proved safe, no adverse effects; no histopathological or biological abnormalities were seen.
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304
DRUG WATCH
Lamotrigine induced DRESS syndrome
Kikkeri Narayanasetty Naveen, Mysore Satyanarayana Ravindra, Varadraj V Pai, Vijetha Rai, Sharatchandra B Athanikar, Meravanige Girish
November-December 2012, 44(6):798-800
DOI
:10.4103/0253-7613.103305
PMID
:23248415
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and life-threatening delayed drug hypersensitivity reaction characterized by skin eruption, fever, lymphadenopathies, and visceral involvement. Here, we are presenting a 12 year old boy, who developed rare but life threatening DRESS syndrome due to Lamotrigine. Early detection and treatment led to his rapid recovery. This case is presented to highlight the importance of early detection of rare fatal syndrome.
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3
5,670
221
RESEARCH ARTICLES
Comparison of efficacy and safety of oseltamivir and zanamivir in pandemic influenza treatment
Nazan Tuna, Oguz Karabay, Mehmet Yahyaoglu
November-December 2012, 44(6):780-783
DOI
:10.4103/0253-7613.103301
PMID
:23248411
Aim:
In 2009, a flu pandemic caused panic worldwide. Oseltamivir and zanamivir were widely used in this pandemic. Currently, there are a limited number of studies comparing the efficacy and tolerability of these two drugs. This study aimed to compare the efficacy and tolerability of these two drugs in the treatment of influenza.
Materials and Methods:
Patients diagnosed with influenza at our infectious disease outpatient clinic during the influenza season between October 1, 2009 and February 1, 2010 were included in the study. Study data were obtained retrospectively from files for consecutive patients. A total of 136 subjects were selected. After exclusion criteria were applied, 56 subjects were discarded. The information for 80 patients in whom oseltamivir or zanamivir therapy was initiated (40 for each therapy) was compiled, and the efficacy and tolerability of the drugs were compared.
Results:
There was no significant difference in efficacy for the two drugs (
P
> 0.05). Temperature normalization was significantly faster in patients taking zanamivir (
P
= 0.0157). Drowsiness was the most frequent adverse event for both drugs (38% for the oseltamivir group, and 22% for the zanamivir group). Respiratory distress was observed in five patients in the zanamivir group, whereas it was not observed in patients in the oseltamivir group (
P
< 0.05). One patient had to discontinue therapy in the zanamivir group due to respiratory distress.
Conclusion:
Efficacy (in terms of symptom relief and duration to resumption of work) and adverse events were similar for zanamivir and oseltamivir, but temperature normalization was much more rapid in patients using zanamivir. Patients using zanamivir should be monitored for respiratory distress.
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3,741
337
Health care personnel and risk of H1N1-chemoprophylaxis with oseltamivir
Tanvir Samra, Mridula Pawar
November-December 2012, 44(6):754-758
DOI
:10.4103/0253-7613.103292
PMID
:23248407
Objectives:
To evaluate the efficacy of chemoprophylactic dose of oseltamivir in preventing H1N1 by comparing the rates of acute respiratory illness and H1N1 positivity of respiratory specimens between HCP with and without consumption of oseltamivir working in swine flu ICU.
Materials and Methods:
The study was conducted on HCP posted in "Swine Flu Intensive Care Unit" from October 2009 to March 2010. Data on infection control measures, chemoprophylactic use of oseltamivir, flu-like illness, ADRs to oseltamivir, and contact history in family and neighborhood were collected by face-to-face interview conducted by investigator using a set of prespecified items in a questionnaire.
Results:
All HCP used infection control measures like using long-sleeved cuffed gown, gloves, cap, shoe cover, and N95 mask, and frequent hand washing. There was no history of any unprotected contact with an H1N1-positive case. Out of 100 HCP, 69% took chemoprophylaxis. There was no significant difference in incidence of flu-like illness between HCP who took chemoprophylaxis (48%) and those who did not (29%,
P
= 0.18). H1N1 testing was done on 17 HCP, but all tested negative. Incidence of adverse effects to chemoprophylactic dose of oseltamivir was high (57%). The most commonly reported adverse effects were nausea (54%), gastritis (51%), and headache (38%).
Conclusion:
Chemoprophylaxis with oseltamivir is not recommended for HCP working in areas of high aerosol generation like ICU if infection control measures are adopted as there is no significant difference in the incidence of flu-like illness in HCP with and without intake of oseltamivir. This protects HCP from various adverse effects of the drugs, like nausea, gastritis, and headache.
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3
2,937
172
Effect of bromocriptine on cardiovascular complications associated with metabolic syndrome in fructose fed rats
Vandana S Nade, Laxman A Kawale, Umesh B Todmal, Anjali B Tajanpure
November-December 2012, 44(6):688-693
DOI
:10.4103/0253-7613.103248
PMID
:23248395
Objective:
The objective of the present study was to evaluate the effect of bromocriptine on cardiovascular complications associated with type-2 diabetes mellitus (DM).
Materials and Methods:
Metabolic syndrome or type 2 DM was induced by administration of fructose (66% solution, p.o.) in rats. Bromocriptine mesylate (10 mg/kg, i.p.) was given in fructose-treated rats for a period of 6 weeks after induction of diabetes. After drug treatment, the parameters such as body weight, food and water intake, serum glucose, triglycerides, cholesterol, insulin, and blood pressure (BP) were measured weekly and at the end of study. At the end of treatment, BP was determined by invasive method and vascular reactivity was tested with adrenaline (Adr), noradrenaline (NA), and phenylephrine (PE). Acetylcholine-induced vasorelaxation was tested on isolated rat aorta and histopathology of hearts was also done.
Results:
Fructose-fed rats showed significant weight gain, hyperglycemia, hyperlipidemia, hyperinsulinemia, and rise of BP. Administration of bromocriptine at a dose 10 mg/kg, i.p. significantly decreased weight gain, serum glucose, triglyceride, cholesterol and insulin levels in rats fed on fructose. Bromocriptine also significantly reduced elevated BP in fructose-fed hypertensive rats. Chronic treatment with bromocriptine significantly improved the relaxant response to acetylcholine on fructose-fed hyperinsulinemic rat aorta and also reduced the pressor response to Adr, NA, and PE. Bromocriptine also showed a protection from hypertrophy and degenerative changes in myocardium.
Conclusion:
Bromocriptine has beneficial effect in reduction of cardiovascular complications associated with metabolic syndrome.
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3
3,753
280
DRUG WATCH
Accidental haloperidol poisoning in children
Mona P Gajre, Dimple Jain, Alka Jadhav
November-December 2012, 44(6):803-804
DOI
:10.4103/0253-7613.103307
PMID
:23248417
Haloperidol, a butyrophenone neuroleptic drug, is an antipsychotic used in the treatment of adult schizophrenia and mania. It is used in children with neurological disorders like chorea and developmental disorders such as hyperactivity. With the advent of newer selective neuroleptics use of haloperidol is now on decline. However, in adults it is still the preferred drug especially in resource challenged settings. Extrapyramidal reactions occur frequently with haloperidol predominantly as parkinsonian symptoms. There are few case reports of accidental haloperidol poisoning in children and this one of them.
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3,272
144
RESEARCH ARTICLES
Biological evaluation of RBx-0128, a potent and selective dipeptidyl peptidase-IV inhibitor in type 2 diabetes genetic model
Joseph A Davis, Pucha S Kumar, Shuchita Singh, A Surender, Subhasis Roy, Vivek Khanna, Sachin Sethi, Chanchan Pal, Lalima Sharma, Biju Benjamin, Shivani Mittra, Jitendra Sattigeri, Vinay S Bansal
November-December 2012, 44(6):759-764
DOI
:10.4103/0253-7613.103298
PMID
:23248408
Aim:
Dipeptidyl peptidase IV (DPP-IV) inhibition to modulate the incretin effect is a proven strategy to treat type 2 diabetes mellitus. The present study describes the pharmacological profile of a novel DPP-IV inhibitor RBx-0128, as an antidiabetic agent.
Material and Methods:
DPP-IV assay was carried out to evaluate
in vitro
potency of RBx-0128 using human, mouse, and rat plasma as an enzyme source. Selectivity was assessed with various serine proteases. In vivo efficacy was assessed in ob/ob mice. The pharmacokinetic (PK) profile was performed in Wistar rats.
Results:
RBx-0128 inhibited human, mouse, and rat plasma DPP-IV activity with IC
50
values of 10.6, 18.1, and 56.0 nM respectively, selective over various serine proteases (900-9000-fold). The inhibition was reversible and competitive in nature. In ob/ob mice, RBx-0128 significantly (
P
< 0.05) inhibited plasma DPP-IV and stimulated GLP-1 and insulin at 10 mg/kg. In the oral glucose tolerance test (OGTT), glucose lowering effect was better than sitagliptin (23 vs. 17%) at 10 mg/kg. The effect was sustained till 8 hours (30-35%) at 10 mg/kg with favorable PK profile (plasma clearance: 39.3 ml/min/kg;
C
max
790 ng/ml;
t
1/2
1.6 hours;
t
max
4.8 hours,
V
ss
3.24 l/kg and
F
oral
55%) in Wistar rats.
Conclusions:
The present study showed that RBx-0128 is a novel, DPP-IV inhibitor with an antihyperglycemic effect. It can be a promising candidate for the treatment of type 2 diabetes mellitus.
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2,920
170
Comparison of reservoir effect of topical corticosteroids in an experimental animal model by histamine-induced wheal suppression test
Afroz Abidi, Farida Ahmad, Satyendra K Singh, Anil Kumar
November-December 2012, 44(6):722-725
DOI
:10.4103/0253-7613.103267
PMID
:23248401
Introduction:
Topical corticosteroids used in various dermatological diseases are available in different potencies and different formulations. The reservoir effect of different potency corticosteroids in the stratum corneum will help the clinicians to choose an appropriate topical steroid to maximize their efficacy and safety as therapeutic agents.
Aims:
This study was designed to compare the duration of reservoir of different potency topical corticosteroids experimentally in rabbits using histamine-induced wheal suppression test.
Materials and Methods:
The study was carried out in albino rabbits (as their skin is similar to humans) using four different concentrations of topical steroids, namely mometasone furoate ointment (0.1%), fluticasone propionate ointment (0.005%), betamethasone valerate cream (0.1%), and hydrocortisone butyrate cream (0.1%). These were applied on the back of rabbit on one side and the vehicle was applied on the other. One hour later, histamine-induced wheal suppression test was performed on both sides and wheal area was measured at 10 min for 7 days. Statistical analysis was done by ANOVA followed by
post hoc
test.
Results:
Maximum wheal suppression was seen on day 1 (
P
<0.001) in all four groups, both at test and at control sites. Interday comparison of mean wheal size by topical steroids showed that the reservoir of mometasone furoate ointment (0.1%) persisted till day 4 in the stratum corneum of the skin. In case of fluticasone propionate ointment (0.005%) and betamethasone valerate cream (0.1%), the reservoir persisted till day 2 and for hydrocortisone butyrate cream (0.1%), the reservoir was present only on day 1.
Conclusions:
It is concluded that the duration of reservoir depends on the potency of topical steroids. Higher the potency more is the duration of reservoir in stratum corneum and vice versa.
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3,509
147
A study to evaluate the price control of antifungal medicines and its practical applicability
Amrita Sil, Nilay Kanti Das, Pramit Ghosh, Pijush Kanti Datta, Chowdhury Nazrul Islam, Santanu Kumar Tripathi
November-December 2012, 44(6):704-709
DOI
:10.4103/0253-7613.103257
PMID
:23248398
Background:
Superficial fungal infections are common and treatment imposes economic burden on the patients. Government of India had introduced price control over griseofulvin and tolnaftate in 1995; however, this measure can only benefit the needy if the policy is harmonized with the health-care service provider, that is, dermatologists. The aim of this study was to evaluate the existing Government mechanisms over price control of antifungal medications and its reach to the people-in-need.
Materials and Methods:
A questionnaire-based, cross-sectional study was carried out over a period of 6 months. Questionnaire was mailed to members of a state branch of Indian Association of Dermatologists, Venereologists, and Leprologists. Responses reaching investigators within 2 months from the date of mailing were finally analyzed.
Results:
Among 93 (41.33%) respondents, only 6 (6.5%) were aware of existing price control over griseofulvin but none about tolnaftate. Thirty-nine (41.9%) respondents were in favor of introducing price control on terbinafine and 42 (45.2%) for itraconazole. The topically preferred antifungals were primarily azoles and terbinafine, while among systemic antifungals, dermatologists mostly preferred fluconazole and terbinafine. The choice of antifungals by the dermatologists matched with the evidence-based dermatology data.
Conclusion:
Currently, price-controlled antifungal drugs are less commonly used by practitioners. Although the dermatologists favor price control, the initiative undertaken by the Government has not reached them. This shows the need to bridge the gap between policy makers and health-care service providers to help the ailing population.
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4,257
251
BOOK REVIEW
Pharmacology: An Illustrated Review
Vinayak Bhavsar
November-December 2012, 44(6):807-807
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204
EDITORIALS
Animal experiments: Confusion, contradiction, and controversy
RK Dikshit
November-December 2012, 44(6):661-662
DOI
:10.4103/0253-7613.103232
PMID
:23248389
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3,822
861
Ethics committee: Critical issues and challenges
Mira Desai
November-December 2012, 44(6):663-664
DOI
:10.4103/0253-7613.103233
PMID
:23248390
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4,313
848
LETTER TO THE EDITOR
Is dronedarone really safer than amiodarone?
Shreya M Shah, Megha Shah
November-December 2012, 44(6):805-806
DOI
:10.4103/0253-7613.103308
PMID
:23248418
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2,956
150
RESEARCH ARTICLES
Influence of antioxidant complex on the adhesion of leukocytes in chronic venous insufficiency of lower limbs in rats
Mark Plotnikov, Ivan Ivanov, Anastasia Sidehmenova, Oleg Aliev, Nonna Tykavkina
November-December 2012, 44(6):710-713
DOI
:10.4103/0253-7613.103260
PMID
:23248399
Objectives:
In this study, we have evaluated the influence of antioxidant complex (AOC) (dihydroquercetin and lipoic acid) on pool of nonadhesive leukocytes and leukocytes with low and high adhesion in chronic venous insufficiency (CVI) of lower limbs in rats.
Materials and Methods:
Model of CVI of lower limbs was created by blood flow restriction in caudal vena cava. AOC was administered at 100 mg/kg b.w./day for 14 days p.o. The venous pressure in vena cava and adhesion of leukocytes were estimated on the 14
th
day of the experiment.
Results:
On the 14
th
day, the venous pressure in groups of animals (experimental and control) was in 2.7-2.9-fold higher. In the control group, the significant increase of leukocytes pool with high adhesion was detected. Intragastric administration of AOC reduced the number of leukocytes with high adhesion and increased the number of nonadhesive leukocytes and leukocytes with a low adhesion.
Conclusions:
Model of CVI of lower limb is accompanied by increased venous pressure and raised adhesion activity of leukocytes. Administration of AOC for 14 days reduces the adhesive activity of leukocytes.
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3,726
105
Detection of interleukin -1β from isolated human lymphocyte in response to lipopolysaccharide and lipoteichoic acid
Niveditha Lekshmi, Chandrika S Geetha, Parayanthala V Mohanan
November-December 2012, 44(6):726-731
DOI
:10.4103/0253-7613.103269
PMID
:23248402
Aim:
To detect the interleukin -1β levels from single and pooled isolated human lymphocytes in response to lipolysaccharide and lipoteichoic acid.
Materials and Methods:
Blood collected from healthy individuals (O +ve, A +ve, B +ve, and AB +ve) were subjected to gradient centrifugation to isolate lymphocytes. Different lymphocyte concentrations were used for
in vitro
pyrogen assay. Lymphocytes isolated were challenged with 5 EU of Gram negative (LPS) and 1 μg/μl of Gram positive (LTA) pyrogens
in vitro
and the inflammatory cytokine, Interleukin 1β (IL-1β) release was measured by Sandwich ELISA method.
Results:
The results indicated that the release of IL-1β increases immediately after the initiation of incubation and reaches a maximum at 4 to 6
th
hour and then stabilizes for both the pyrogens. Furthermore, IL-1β release by 5 EU of LPS and 1 μg/μl of LTA is dependent on lymphocytes concentration. It was also observed that the difference in blood group did not interfere with the IL-1β release.
Conclusion:
The isolated lymphocyte system can be used as an alternative to the
in vivo
rabbit pyrogen assay.
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2,980
113
Gender differences in response to chronic treatment with 17β-oestradiol and 17β-aminoestrogen pentolame on hemostasis in rats
Cristina Lemini, Ruth Jaimez, Martha Medina-Jiménez, María Estela Ávila
November-December 2012, 44(6):749-753
DOI
:10.4103/0253-7613.103287
PMID
:23248406
Objectives:
This work evaluated chronic treatment with 17β-oestradiol (E
2
) and 17β-aminoestrogen pentolame (AEP) on prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen concentration (FIB). Male (M) and ovariectomized (Ovx) Wistar rats were used to explore gender differences in the pharmacological response.
Materials and Methods:
Rats (
n
= 12-18) were treated every third day during three months with E
2
(1, 10, 100 μg/kg), AEP (1, 10, 100, 500 μg/kg) or vehicle (propylenglycol 1 ml/ kg). PT, aPTT, TT, and FIB were measured using standardized techniques.
Results:
Chronic treatment with E
2
in male rats increased PT (4-7%;
P
< 0.05), decreased aPTT (9%; 100 μg/kg;
P
< 0.05) and decreased TT (5% at 100 μg/Kg;
P
< 0.05). Chronic treatment with E
2
in ovariectomized female rats decreased PT (3-4%;
P
< 0.05), did not induce significant changes on aPTT and decreased TT in a dose dependent manner (12-27%;
P
< 0.05). Chronic treatment with AEP in male rats did not alter PT, increased aPTT in a dose dependent manner (5-16%;
P
< 0.05), and decreased TT (5%; 500 μg/Kg;
P
< 0.05) while in female ovariectomized rats it decreased PT (5-9%;
P
< 0.05), increased aPTT (8-13%;
P
< 0.05) and decreased TT (6-13%;
P
< 0.05). E
2
and AEP decreased FIB in M and Ovx animals. Decreases in FIB by E
2
were more pronounced in male (15-18%
P
< 0.05) than in ovariectomized rats (10-14%
P
< 0.05). E
2
showed more potency than AEP, lowering FIB at 1 and 10 μg/kg doses. Both estrogens decreased FIB in ovariectomized animals (E
2
, 10-14%,
P
< 0.05; AEP, 9%
P
< 0.05) and were reverted by increasing dosage.
Conclusions:
Gender influenced response to chronic treatment with E
2
and AEP on hemostatic parameters. PT and aPTT were the most affected parameters, demonstrating non-equivalence in the pharmacological response of M and Ovx rats.
[ABSTRACT]
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2,876
99
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