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   Table of Contents - Current issue
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March-April 2014
Volume 46 | Issue 2
Page Nos. 145-237

Online since Monday, March 24, 2014

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EDITORIAL  

Clinical trials for children: Some concerns p. 145
Trupti Rekha Swain
DOI:10.4103/0253-7613.129300  
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RESEARCH ARTICLES Top

Protective effect of ketamine against hemorrhagic cystitis in rats receiving ifosfamide p. 147
Ali A Ozguven, Omer Yilmaz, Fatma Taneli, Cevval Ulman, Seda Vatansever, Ali Onag
DOI:10.4103/0253-7613.129301  
Objective: To investigate the possible protective effect of a single dose of ketamine and the synergistic effect between ketamine and 2-mercaptoethane sulfonate (mesna) against ifosfamide-induced hemorrhagic cystitis. Materials and Methods: 35 adult female wistar rats were divided into five groups and pretreated with ketamine at 10 mg/kg and/or mesna 400 mg/kg 30 minutes before intraperitoneal injection of IFS (400 mg/kg) or with saline (control group). Hemorrhagic cystitis was evaluated 24 hours after IFS injection according to bladder wet weight (BWW), and microscopic changes, i.e. edema, hemorrhage, cellular infiltration, and urothelial desquamation. The markers of oxidative damage including nitric oxide (NO) and malondialdehyde (MDA) levels and the expressions of tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1β), inducible nitric oxide synthase (i-NOS) and endothelial nitric oxide synthase (e-NOS) were also assayed in the bladder tissues. Results: Pretreatment with ketamine alone or ketamine in combination with mesna reduced the IFS-induced increase of BWW (58,47% and 63,33%, respectively, P < 0.05). IFS- induced microscopic alterations were also prevented by ketamine with or without mesna (P < 0.05). In addition, also statistically insignificant, the bladder tissue expressions of IL-1β were lower in ketamine and/or mesna-receiving groups (P > 0,05). The parameters of oxidative stress, the NO and the MDA contents of the bladder tissues of the study groups were not different. Conclusion: The results of the present study suggest that a single dose of ketamine pretreatment attenuates experimental IFS-induced bladder damage. It is therefore necessary to investigate ketamine locally and systematically with various dosing schedulesin order to reduce the bladder damage secondary to oxazaphosphorine-alkylating agents and these results may widen the spectrum of ketamine.
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A study of potential drug-drug interactions among hospitalized cardiac patients in a teaching hospital in Western Nepal p. 152
Sushmita Sharma, Himal Paudel Chhetri, Kadir Alam
DOI:10.4103/0253-7613.129303  
Aim: Drug-drug interaction (DDI) is of major concern in patients with complex therapeutic regimens. The involvement of cardiovascular medicines in drug interaction is even higher. However, reports of DDI between these groups of drugs are few. The study aims to identify the potential DDI among hospitalized cardiac patients. Furthermore, we assessed the possible risk factors associated with these interactions. Subjects and Methods: The Type of study prospective observational study was conducted from May 2012 to August 2012 among hospitalized cardiac patients. Cardiac patients who were taking at least two drugs and who had a hospital stay of at least 24 h were enrolled. The medications of the patients were analyzed for possible interactions using the standard drug interaction database - Micromedex -2 (Thomson Reuters) × 2.0. Results: From a total of 150 enrolled patients, at least one interacting drug combination was identified among 32 patients. The incidence of potential DDI was 21.3%. A total of 48 potentially hazardous drug interactions were identified. Atorvastatin/azithromycin (10.4%), enalapril/metformin (10.4%), enalapril/potassium chloride (10.4%), atorvastatin/clarithromycin (8.3%) and furosemide/gentamicin (6.3%) were the most common interacting pairs. Drugs most commonly involved were atorvastatin, enalapril, digoxin, furosemide, clopidogrel and warfarin. Majority of interactions were of moderate severity (62.5%) and pharmacokinetic (58.3%) in nature. Increased number of medicines, prolonged hospital stays and comorbid conditions were the risk factors found associated with the potential DDI. Conclusions: This study highlighted the need of intense monitoring of patients who have identified risk factors to help detect and prevent them from serious health hazards associated with drug interactions.
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Effects of delayed puerarin treatment in long-term neurological outcomes of focal ischemic stroke in rats p. 157
Minghua Wu, Sen Liang, Li Ma, Yang Han, Xiusheng Zhang, Chengcheng Xu
DOI:10.4103/0253-7613.129305  
Objective: The present study aimed at investigate the therapeutic effects of delayed puerarin treatment in neurological outcomes after middle cerebral artery occlusion (MCAO) in rats. Materials and Methods: Male Wistar rats were subjected to MCAO for 120 min followed by reperfusion for 14 days. Puerarin (0, 50, 100, 200 mg/kg, intra-peritoneally) was administered at 24 h after stroke onset and repeated daily for 14 days. Neurological deficits were evaluated at 1, 4, 7, 14 days after stroke. Brain infarct volume and peri-infarct context vessel density were examined at 14 days after stroke. Results: Puerarin significantly improved neurological functions up to 14 days after stroke and decreased the infarct volume with doses of 50 mg/kg and 100 mg/kg compared with saline controls. Puerarin treatment also significantly increased peri-infarct context vessel density at 14 days after stroke. Conclusions: Delayed treatment of puerarin initiated at 24 h after stroke is beneficial with improved long-term neurological outcomes and reduced infarction volume in focal ischemic stroke in rats. Enhanced vascular remodeling by puerarin might at least partially contribute to its beneficial effects.
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Mechanism of testicular protection of carvedilol in streptozotocin-induced diabetic rats p. 161
Maggie M Ramzy, Azza A. K El-Sheikh, Maha Y Kamel, Soha A Abdelwahab, Mohamed A Morsy
DOI:10.4103/0253-7613.129307  
Aims: Male sub-fertility and infertility are major complications of diabetes mellitus. The non-selective β-blocker carvedilol has been reported to have favorable effects on some of the diabetic complications based on its antioxidant and anti-apoptotic effects. This study aims to evaluate the possible testicular protective effect of carvedilol in streptozotocin (STZ)-induced diabetic rat model and its possible mechanisms. Materials and Methods: Diabetes was induced by a single i.p. dose of 65 mg/kg of STZ. In parallel groups of diabetic rats, carvedilol in low and high doses (1 and 10 mg/kg/day orally) were administered for 4 weeks. Oxidative stress markers as reduced glutathione (GSH) and the product of lipid peroxidation; malondialdehyde (MDA) were evaluated in testicular homogenate. The level of expression of the apoptotic marker; caspase 3, was assessed using western blot, followed by densitometric analysis. Results: Induction of diabetes caused distortion of histological normal testicular structure, with decrease (P < 0.05) in GSH and increase (P < 0.05) in MDA, as well as induction of caspase 3 expression. Carvedilol in low or high doses reverted diabetes-induced histological damage, restored antioxidant activity and ameliorated caspase 3 expression. Conclusion: Carvedilol confers testicular protection against diabetes-induced damage through antioxidant and anti-apoptotic mechanisms.
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Mentha piperita in nephrotoxicity - a possible intervention to ameliorate renal derangements associated with gentamicin p. 166
Naveed Ullah, Mir Azam Khan, Taous Khan, Afzal Haq Asif, Waqar Ahmad
DOI:10.4103/0253-7613.129309  
Objective: Free radical generation has a strong role in the pathogenesis of renal damage associated with the use of gentamicin. Therefore, the present study was carried out to evaluate the renoprotective effect of Mentha piperita against gentamicin induced nephrotoxicity. Materials and Methods: A total of 24 male rabbits were divided into 4 groups receiving normal saline, gentamicin, M. piperita extract and co-therapy of extract and gentamicin respectively. Gentamicin was provided as 80 mg/kg/day intramuscularly and extract was given 200 mg/kg/day orally for a period of 21 days. Serum and urinary biochemical parameters and histological changes were studied for each group. The impact of the extract on the antibacterial action of gentamicin was also evaluated. Results: Animals treated with gentamicin showed derangements in serum and urinary biochemical parameters. These alterations were reversed by treatment with M. piperita extract. The histological changes showed in gentamicin group were also reverted by treatment with the extract. Further the plant did not influence the efficacy of gentamicin with respect to its antimicrobial properties. Conclusion: Co-therapy of M. piperita with gentamicin successfully attenuated biochemical kidney functioning derangements and morphological changes associated with gentamicin.
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Evaluation of aqueous extract of Murraya koenigii in unilateral renal ischemia reperfusion injury in rats p. 171
Priyanka Punuru, D Sujatha, B Pushpa Kumari, V. V. L Charisma
DOI:10.4103/0253-7613.129310  
Aim: The aqueous extract of leaves of Murraya koenigii was studied for its renoprotective potential against unilateral renal ischemia reperfusion (RIR) injury in male Wistar rats. Materials and Methods: Healthy adult male Wistar rats were divided into five groups (n = 8) and were treated with 200 mg/kg., p.o. of aqueous extract of M. koenigii (AEMK) for 30 days to assess both preventive and curative effects of AEMK. Except Group I, RIR was induced to all the groups by clamping the left renal artery using artery clamp for 1 h followed by reperfusion by removing the clamp. Groups II and III underwent RIR at 30 th day whereas RIR was induced in Groups IV and V at 1 st day of treatment schedule. Biochemical parameters (serum creatinine, blood urea nitrogen, serum total protein and serum Na + ), urinary parameters (urine output, urinary creatinine, urinary urea, urinary total protein, urinary Na + ), in vivo anti-oxidants, renal myeloperoxidase (MPO) activity and histopathology of kidneys were monitored. Statistical significance was set at P < 0.05. Results: Rats were treated with AEMK significantly (P < 0.05) restored the serum and urinary parameters with significant (P < 0.05) improvement in endogenous anti-oxidants such as superoxide dismutase, catalase and reduced glutathione and decreased levels of malondialdehyde and renal MPO when compared with the control groups. Histopathological examination also supported the biochemical and urinary tests. Conclusions: Aqueous extract of M. koenigii possesses both preventive and curative effects against RIR injury.
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Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy dopamine induced Parkinsonism p. 176
Jayasankar Kosaraju, Santhivardhan Chinni, Partha Deb Roy, Elango Kannan, A Shanish Antony, M. N. Satish Kumar
DOI:10.4103/0253-7613.129312  
Objective: The present study investigates the neuroprotective activity of ethanol extract of Tinospora cordifolia aerial parts against 6-hydroxy dopamine (6-OHDA) lesion rat model of Parkinson's disease (PD). Materials and Methods: T. cordifolia ethanol extract (TCEE) was standardized with high performance thin layer chromatography using berberine. Experimental PD was induced by intracerebral injection of 6-OHDA (8 μg). Animals were divided into five groups: sham operated, negative control, positive control (levodopa 6 mg/kg) and two experimental groups (n = 6/group). Experimental groups received 200 and 400 mg/kg of TCEE once daily for 30 days by oral gavage. Biochemical parameters including dopamine level, oxidative stress, complex I activity and brain iron asymmetry ratio and locomotor activity including skeletal muscle co-ordination and degree of catatonia were assessed. Results: TCEE exhibited significant neuroprotection by increasing the dopamine levels (1.96 ± 0.20 and 2.45 ± 0.40 ng/mg of protein) and complex I activity (77.14 ± 0.89 and 78.50 ± 0.96 nmol/min/mg of protein) at 200 and 400 mg/kg respectively when compared with negative control group. Iron asymmetry ratio was also significantly attenuated by TCEE at 200 (1.57 ± 0.18) and 400 mg/kg (1.11 ± 0.15) when compared with negative control group. Neuroprotection by TCEE was further supported by reduced oxidative stress and restored locomotor activity in treatment groups. Conclusion: Results show that TCEE possess significant neuroprotection in 6-OHDA induced PD by protecting dopaminergic neurons and reducing the iron accumulation.
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Hepatotoxicity of Teucrium chamaedrys L. decoction: role of difference in the harvesting area and preparation method p. 181
Cristina Nencini, Paola Galluzzi, Francesco Pippi, Andrea Menchiari, Lucia Micheli
DOI:10.4103/0253-7613.129313  
Aim: Two recurrent cases of severe acute liver injury attributed to the use of a wild germander decoction, prepared with some variation in traditional method has been reported. The aim of the present study was to correlate the hepatotoxic effect observed in patients who consumed germander decoction with teucrin A levels. Antioxidant properties were analyzed to assess any possible differences between the decoction used traditionally by the family (without negative consequences) and the decoction taken by the patients. Materials and Methods: Different types of germander decoctions were prepared in the laboratory by simulating the same conditions for preparing the decoction by the patients and their family members. The levels of teucrin A, the polyphenols and the antioxidant power were determined. One-way analysis of variance was used to test for differences between the groups. Results and Conclusions: The extract consumed by the patients had higher concentration of teucrin A, lower antioxidant activity and lower content of polyphenols compared with the traditional decoction, revealing an inverse relationship between teucrin A content and antioxidant capacity. These case reports emphasize that more information is needed on the safety and quality of these natural products.
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An evaluation of vardenafil as a calcium channel blocker in pulmonary artery in rats p. 185
Edibe Minareci, Gulay Sadan
DOI:10.4103/0253-7613.129315  
Objective: Vardenafil was reported to relax rat pulmonary artery through endothelium-dependent mechanisms. The aim of this in vitro study was to investigate other related mechanisms for this effect. Materials and Methods: Endothelium-intact and denuded artery rings were suspended in order to record isometric tension. In the rings with or without endothelium, the concentration-response curves for vardenafil were generated. In the rings without endothelium the contractile response induced by phenylephrine (Phe) or KCl was assessed in the presence or absence of vardenafil. In the last set of experiments, pulmonary artery rings were exposed to calcium-free isotonic depolarizing solution and the contractile response induced by the addition of calcium was evaluated in the presence or absence of vardenafil, nifedipine, verapamil or 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ). Results: Vardenafil attenuated pulmonary artery contraction induced by phenylephrine in the presence and absence of endothelium. In addition, vardenafil attenuated both Phe or KCl-induced contraction but, it's effect on the KCl dose-response curve was more significant. Vardenafil also inhibited the contractile response induced by calcium in a dose-dependent manner. Addition of nifedipine or verapamil did not significantly alter this effect while ODQ incubation significantly inhibited vardenafil-induced relaxation. Conclusion: From these findings, it was proposed that vardenafil relaxed rat pulmonary artery through inhibiting calcium influx.
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Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (6g) on chronic unpredictable mild stress-induced changes in behavioural and brain oxidative stress parameters in mice p. 191
Shvetank Bhatt, Mahesh Radhakrishnan, Ankur Jindal, Thangaraj Devadoss, Arghya Kusum Dhar
DOI:10.4103/0253-7613.129316  
Aim: The aim of the study was to evaluate a novel 5 HT 3 receptor antagonist (6g) on chronic stress induced changes in behavioural and brain oxidative stress parameter in mice. A complicated relationship exists among stressful stimuli, body's reaction to stress and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to human depression, and such animal models can be used for the preclinical evaluation of antidepressants. Materials and Methods: In the present study, a novel and potential 5-HT 3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) with good Log P (3.08) value and pA 2 (7.5) values, synthesized in our laboratory was investigated to study the effects on chronic unpredictable mild stress (CUMS)-induced behavioural and biochemical alterations in mice. Mice were subjected to different stress paradigms daily for a period of 28 days to induce depressive-like behaviour. Results: The results showed that CUMS caused depression-like behaviour in mice, as indicated by the significant (P < 0.05) decrease in sucrose consumption and locomotor activity and increase in immobility the forced swim test. In addition, it was found that lipid peroxidation and nitrite levels were significantly (P < 0.05) increased, whereas glutathione levels, superoxide dismutase and catalase activities decreased in brain tissue of CUMS-treated mice. '6g' (1 and 2 mg/kg, p.o., 21 days) and fluoxetine treatment (20 mg/kg, p.o., 21 days) significantly (P < 0.05) reversed the CUMS-induced behavioural (increased immobility period, reduced sucrose preference and decreased locomotor activity) and biochemical (increased lipid peroxidation; decreased glutathione levels, superoxide dismutase and catalase activities). However fluoxetine treatment (20 mg/kg, p.o., 21 days) significantly decreased the nitrite level in the brain while '6g' (1 and 2 mg/kg, p.o., 21 days) did not show significant (P < 0.05) effect on the nitrite levels in brain. Conclusion: Compound '6g' exerted antidepressant-like effects in behavioural despair paradigm in chronically stressed mice by restoring antioxidant mechanisms.
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Hepatoprotective activity of Tephrosia purpurea against arsenic induced toxicity in rats p. 197
Ravuri Halley Gora, Sushma Lalita Baxla, Priscilla Kerketta, Subhasree Patnaik, Birendra Kumar Roy
DOI:10.4103/0253-7613.129317  
Aim: The present study was conducted to evaluate the hepatoprotective activity of Tephrosia purpurea (TP) against sodium arsenite (NaAsO2) induced sub-acute toxicity in rats. Materials and Methods: Twenty four wistar albino rats of either sex were randomly divided into three groups. Group II and III were orally administered with sodium arsenite (10 mg/kg) daily in drinking water for 28 days. Additionally Group III was orally treated with hydro-alcoholic extract of Tephrosia purpurea (TP) @ 500 mg/kg daily for the same time period, whereas only deionized water was given to Group I (control). Serum biomarker levels, oxidative stress parameters and arsenic concentration were assessed in liver. Histopathology was also conducted. Results: It has been seen that TPE (500 mg/kg) significantly (P < 0.01) reduced serum ALT, AST, ALP activity and increased total protein and reduced necrosis and inflammation in liver of group III compared to group II. A significantly (P < 0.01) higher LPO and lower GSH levels without change in SOD activity in liver was also observed in group II compared to group III, though there was no significant difference in arsenic accumulation between them. The plant extract also protects the animals of group III from significant (P < 0.01) reduction in body weight. Conclusion: Our study shows that supplementation of Tephrosia purpurea extract (500 mg/kg) could ameliorate the hepatotoxic action of arsenic.
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Population pharmacokinetics of bupivacaine in combined lumbar and sciatic nerve block p. 201
Hanene Eljebari, Nadia Jebabli, Issam Salouage, Emna Gaies, Mohamed Lakhal, Mehdi Boussofara, Anis Klouz
DOI:10.4103/0253-7613.129318  
Objectives: The primary aim of this study was to establish the population pharmacokinetic (PPK) model of bupivacaine after combined lumbar plexus and sciatic nerve blocks and secondary aim is to assess the effect of patient's characteristics including age, body weight and sex on pharmacokinetic parameters. Materials and Methods: A total of 31 patients scheduled for elective lower extremity surgery with combined lumbar and sciatic nerve block using plain bupivacaine 0.5% were included. The total bupivacaine plasma concentrations were measured before injection and after two blocks placement and at selected time points. Monitoring of bupivacaine was made by high performance liquid chromatography (HPLC) with ultraviolet detection. Non-linear mixed effects modeling was used to analyze the PPK of bupivacaine. Results: One compartment model with first order absorption, two input compartments and a central elimination was selected. The Shapiro-Wilks test of normality for normalized prediction distribution errors for this model (P = 0.156) showed this as a valid model. The selected model predicts a population clearance of 930 ml/min (residual standard error [RSE] = 15.48%, IC 95% = 930 ± 282.24) with inter individual variability of 75.29%. The central volume of distribution was 134 l (RSE = 12.76%, IC = 134 ± 33.51 L) with inter individual variability of 63.40%. The absorption of bupivacaine in two sites Ka1 and Ka2 were 0.00462/min for the lumbar site and 0.292/min for the sciatic site. Age, body weight and sex have no effect on the bupivacaine pharmacokinetics in this studied population. Conclusion: The developed model helps us to assess the systemic absorption of bupivacaine at two injections sites.
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Effect of trapidil in myocardial ischemia-reperfusion injury in rabbit p. 207
MingJie Liu, Qi Sun, Qiang Wang, Xiuying Wang, Peng Lin, Ming Yang, Yuanyuan Yan
DOI:10.4103/0253-7613.129320  
Objectives: To evaluate the cardioprotective effects of trapidil on myocardial ischemia-reperfusion injury (MIRI) in rabbits. Materials and Methods: Rabbits were subjected to 40 min of myocardial ischemia followed by 120 min of reperfusion. Blood for superoxide dismutase (SOD) and malondialdehyde (MDA) were estimated. At the end of reperfusion, the rabbits were sacrificed and the hearts were isolated for histological examination. An apoptotic index (AI) was determined using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) method. The expression of apoptosis-related proteins Bax and Bcl-2 was analyzed using immunohistochemistry. Statistical analyses were performed by one-way analysis of variance (ANOVA), P < 0.05 considered statistically significant Results: Trapidil caused a significant (P < 0.05) increase in SOD activity, as decreased MDA levels and significantly (P < 0.05) reduced the expression of Bax as compared with the ischemia-reperfusion (IR) control group. Conclusion: Trapidil may attenuate the myocardial damage produced by IR injury and offer potential cardioprotective action.
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Hepatoprotective and antioxidant activity of N-acetyl cysteine in carbamazepine-administered rats p. 211
Eswaran Maheswari, Ganesan Raja Lekshmi Saraswathy, Thakur Santhranii
DOI:10.4103/0253-7613.129321  
Objectives: The present study evaluates the hepatoprotective activity of N-acetyl cysteine (NAC) against carbamazepine (CBZ)-induced hepatotoxicity. Materials and Methods: Rats were treated with CBZ (50 mg/kg p.o.) and CBZ supplemented with NAC 50, 100 and 200 mg/kg for 45 days, after which blood samples were collected and subjected to liver function tests. Animals were killed, liver was separated, weighed and the levels of antioxidants and liver enzymes were estimated. In addition, histopathological investigation was also performed. Results: Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate (SGOT) transaminase, alkaline phosphatase (ALP), bilirubin, lipid peroxidation, absolute and relative liver weights were significantly (P < 0.05) elevated, whereas serum levels of albumin, total protein and body weight were decreased in the CBZ-treated animals. CBZ also produced vacuolar degeneration, centrilobular congestion and hepatic necrosis as evidenced from histopathological report. NAC significantly reduced the levels of serum transaminase, ALP, bilirubin and liver weight and increased the levels of total protein, albumin and body weight. Conclusion: It was observed that NAC increased the glutathione (GSH) content, reduced lipid peroxidation and reversed the CBZ-induced histopathological abnormalities. CBZ-induced hepatotoxicity may be due its toxic epoxide metabolite-induced oxidative stress.
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SHORT COMMUNICATIONS Top

Anti-fibrosis effects of Huisheng oral solution in CCl 4 -induced hepatic fibrosis in rat p. 216
Wenting Li, Yuanbo Wu, Chuanlong Zhu, Zheng Wang, Rentao Gao, Quan Wu
DOI:10.4103/0253-7613.129323  
Aim: Some gradient of Huisheng oral solution (HOS) has been reported to have anti-fibrosis activity. This study was designed to investigate whether HOS could inhibit liver fibrosis and to elucidate its molecular mechanism of action. Materials and Methods: Hepatic fibrosis model in rat was induced by subcutaneous injection of CCl 4 . Rats in the treatment group were administrated with HOS intragastrically. Hematoxylin and eosin (H and E) staining and Masson's trichrome staining were used to examine the changes in liver pathology. Levels of ALT, AST, LDH, hyaluronic acid (HA) and laminin (LN) in serum and hydroxyproline (Hyp) in liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of Smad3, TGF-β1, α-SMA and TIMP-1 were observed and the active TGF-β1 was tested. Results: Our data demonstrated that HOS alleviated CCl 4 -induced collagen deposition in liver tissue, improved liver condition and liver function in rats. HOS also significantly reduced the expression and distribution of Smad3, TGF-β1, α-SMA and TIMP-1 as well as decreased active TGF-β1. Conclusions: This study revealed that HOS attenuates the development of liver fibrosis through suppressing the TGF-β1 pathway. It provides us a new approach to treatment of liver fibrosis.
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Variation of adverse drug reaction profile of platinum-based chemotherapy with body mass index in patients with solid tumors: An observational study p. 222
Dattatreyo Chatterjee, Somnath Roy, Avijit Hazra, Partha Dasgupta, Subir Ganguly, Anup Kumar Das
DOI:10.4103/0253-7613.129325  
Objectives: Toxicity of cancer chemotherapy may be affected by nutritional status of patients which is reflected in the body mass index (BMI). We sought to assess whether the adverse drug reaction (ADR) profile of platinum-based chemotherapy varies with BMI status. Materials and Methods: Adult patients of either sex, suffering from a solid tumor (lung, head and neck, ovary, gall bladder, stomach, colon) and started on platinum-based chemotherapy as initial treatment were included. BMI at chemotherapy commencement was obtained from medical records. Events were recorded and graded as per Eastern Co-operative Oncology Group Common Toxicity Criteria-patients' complaints; clinically evident signs and laboratory reports were considered. Frequencies of individual adverse events were compared between low BMI (<18.5 kg/m 2 ) and satisfactory BMI groups. Similar comparisons were done for events with grades 2 or 3 severities. Results: A total of 50 patients were observed over a 3-month period of whom 17 (34%) belonged to the low BMI group. Nausea, vomiting, diarrhea, stomatitis, anemia, alopecia, tinnitus and paresthesia were the commonly observed ADRs. The frequencies of anemia (P = 0.152) and vomiting (P = 0.140) and severity of grades of nausea (P = 0.066), anemia (P = 0.120) and paresthesia (P = 0.128) showed a higher trend in the low BMI group though differences were not statistically significant. The frequencies of tinnitus (P = 0.021) and paresthesia overall (P = 0.036) were significantly higher in the low BMI group. Conclusion: ADR profile of primary platinum-based chemotherapy appears to be partly influenced by BMI. This suggests the importance of maintaining adequate nutrition in patients and the need for greater vigilance in those with low BMI.
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DRUG WATCH Top

Docetaxel-induced palmoplantar erythrodysesthesia syndrome and long-lasting multiple nail changes p. 225
Gulsen Akoglu
DOI:10.4103/0253-7613.129326  
Palmoplantar erythrodysesthesia syndrome (PPES) and nail changes are common presentations of cutaneous toxicity of docetaxel chemotherapy, which deteriorate the quality of life of patients. Herein, we describe a female patient who developed PPES and multiple nail changes due to docetaxel treatment for infiltrative ductal carcinoma. Cold application and elevation of extremities during docetaxel infusion, potent topical steroids and oral pyridoxine increased the tolerance to chemotherapy and provided regression of painful cutaneous lesions without cessation of the treatment.
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Lorazepam-induced diplopia p. 228
Jisha M Lucca, Madhan Ramesh, Gurumurthy Parthasarathi, Dushad Ram
DOI:10.4103/0253-7613.129328  
Diplopia - seeing double - is a symptom with many potential causes, both neurological and ophthalmological. Benzodiazepine induced ocular side-effects are rarely reported. Lorazepam is one of the commonly used benzodiazepine in psychiatric practice. Visual problems associated with administration of lorazepam are rarely reported and the frequency of occurrence is not established. We report a rare case of lorazepam-induced diplopia in a newly diagnosed case of obsessive compulsive disorder.
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Delayed onset renal failure in a patient on tenofovir based antiretroviral regimen p. 230
M Murali Krishna, M. V. S. Subbalaxmi, Megha Uppin, S Radhika
DOI:10.4103/0253-7613.129330  
Tenofovir is recommended as one of the first line agents in combination with other antiretroviral drugs for management of human immunodeficiency virus (HIV). It is known to cause renal failure after exposure for a median duration of 5 months. We report tenofovir induced adverse drug reaction in a 56-year-old female patient who was diagnosed to have HIV 1 infection since 10 years. The combination antiretroviral treatment included tenofovir, emtricitabine and ritonavir/lopinavir regimen since the last 6 years. She presented with recent onset renal failure and renal biopsy showed interstitial nephritis which could probably attributable to tenofovir.
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Acute generalized exanthematous pustulosis induced by piroxicam: A case report p. 232
Y Cherif, Moez Jallouli, M Mseddi, H Turki, Z Bahloul
DOI:10.4103/0253-7613.129332  
Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous reaction characterized by an acute episode of sterile pustules over erythematous-edematous skin. The main triggering drugs are antibiotics, mainly beta-lactam and macrolides. Non-steroid anti-inflammatory drugs may rarely be responsible. We describe a case of a woman with AGEP, who presented with generalized pustulosis lesions after the use of piroxicam for renal colic. The diagnosis was confirmed by the clinical and histological correlations and the dermatosis resolved after withdrawal of the drug.
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Anaphylaxis following intravenous ranitidine: A rare adverse reaction of a common drug p. 234
Deepti Chopra, Pooja Arora, Shamimullah Khan, Shridhar Dwivedi
DOI:10.4103/0253-7613.129334  
Ranitidine hydrochloride is a widely used drug that is generally well-tolerated. Anaphylaxis is rarely observed with ranitidine. We report a case who developed severe anaphylaxis following single dose of intravenous ranitidine. The article highlights the importance of recognition of this serious adverse event and re-emphasizes the need for cautious use of drugs, especially in those with known history of allergy.
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Clinical trials: A Beginner's Guide p. 237
P Usha Rani
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