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   2019| July-September  | Volume 10 | Issue 3  
    Online since November 19, 2019

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Effect of calcium channel blockers on the seizures, oxidative stress, and histoarchitecture in the rats
K Saniya, BG Patil, C Madhavrao, KG Prakash
July-September 2019, 10(3):93-99
Objective: To evaluate the anticonvulsant and antioxidant actions of diltiazem, nimodipine, and flunarizine in the Wistar albino rats using the maximum electroshock-induced seizure (MES) model. Materials and Methods: Thirty inbred Wistar rats were divided into five groups of six rats in each group. Groups 3, 4, and 5 were pretreated with diltiazem (20 mg/kg), nimodipine (20 mg/kg), and flunarizine (10 mg/kg), respectively. Group 2 served as a standard group and received phenytoin (25 mg/kg). All groups were subjected to MES. Twenty-four hours after the MES, hemisections of the rat brain were homogenized, and oxidative markers (glutathione [GSH], lipid peroxidation [LPO], and myeloperoxidase [MPO]) and neurotransmitters (dopamine, serotonin, gamma-aminobutyric acid, acetylcholine, and glutamate levels) were estimated. Histological changes were studied with hematoxylin and eosin-stained hemisection of rat brain. Apoptotic marker heat shock protein (HSP) was used for immunohistochemical changes. Results: Rats pretreated with diltiazem, nimodipine, and flunarizine showed a statistically significant reduction in duration of hind limb extension phase and clonic seizures. GSH, LPO, and MPO changes indicate better oxidative stress outcomes in rat brains pretreated with diltiazem and flunarizine. Neurotransmitters showed variable and significant changes. There were histoarchitectural changes such as cerebral edema, vacuole formation, and intracytoplasmic granules with all three calcium channel blockers in acute phase. HSP was positive in temporal lobe sections of rats pretreated with nimodipine. Conclusions: Diltiazem, nimodipine, and flunarizine showed an anticonvulsant action among Wistar rats in MES model. Diltiazem and flunarizine have antioxidant actions as well.
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Comparison of adherence to ARRIVE guidelines in animal research articles published in the years 2009 and 2016 in pharmacology journals: An observational study
Sharmila Jalgaonkar, Tausif Mapara, Apoorv Verma, Mohsin Sayyed
July-September 2019, 10(3):77-84
Objective: To evaluate and compare the adherence of the ARRIVE guidelines before and after its introduction by the articles published by two leading journals publishing animal research articles. Materials and Methods: Literature of original research articles of animal studies was obtained from two leading open-access journals. A combined total of 100 articles were selected from these journals from the years 2009 and 2016 (50 articles from each year). Each article was assessed by two investigators independently. The percentage of articles adhering to each item in the ARRIVE guidelines was calculated for both 2009 and 2016. The percentage of overall adherence of the articles to all recommendations was calculated. Completeness of reporting of an article was also assessed. The percentage of overall adherence of the articles to all recommendations was calculated. The adherence to the ARRIVE guidelines in the two journals was statistically compared using Chi-square test. P = 0.05 was considered as a measure of statistical significance. Results: A combined total of 100 articles from the two journals, Indian Journal of Pharmacology and Journal of Pharmacology and Experimental Therapeutics, during the years 2009 and 2016 (50 articles from each year) were studied for adherence to ARRIVE and completeness of studies. Despite introduction of the ARRIVE guidelines, 8 of 38 unreported items in articles of 2009 are still unreported in 2016. A statistically insignificant improvement was observed in total adherence to 22 of 38 recommendations of the ARRIVE checklist by >50% of the articles in 2016. A statistically significant improvement was observed in completeness of reporting on 14/38 recommendations, 6 years after the introduction of the ARRIVE guidelines. The study revealed that ~58% of recommendations of the ARRIVE guidelines are being followed by the articles selected from 2016. Conclusion: No significant improvement in quality of reporting of animal research published by two reputed journals was observed even 6 years after the introduction of the ARRIVE guidelines. However, the study revealed improvement in the completeness of reporting of an animal research article. Active endorsement of the ARRIVE guidelines by editors of journals publishing animal research is recommended.
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Curcumin recovers the toxic effects of nicotine on hippocampus cornu ammonis 1 in rats
Mohammad Reza Salahshoor, Amir Abdolmaleki, Shiva Roshankhah, Amir Jalali, Cyrus Jalili
July-September 2019, 10(3):85-92
Objective: To evaluate the effects of curcumin (CUM) against Nicotine (NIC) induced damage to the hippocampal cortex of rats. Materials and Methods: In this study, 48 Wistar male rats were randomly assigned to eight groups: normal group, NIC group (0.5 mg/kg), CUM groups (10, 30, and 60 mg/kg), and NIC + CUM groups (10, 30, and 60 mg/kg). Treatments were administered intraperitoneally (i. p) daily for 28 days. Golgi and cresyl violet staining techniques were employed to investigate the number of neurons and dendritic spines. The techniques of Griess, ferric reducing/antioxidant power, and hippocampal malondialdehyde (MDA) were used. Results: NIC administration significantly increased the nitrite oxide (NO) and MDA levels and decreased the total antioxidant capacity (TAC) as well as the number of neuronal dendritic spines and neurons compared to the normal group (P < 0.01). In all the CUM and NIC + CUM groups, the number of neurons, neuronal dendritic spines, and TAC increased significantly compared to the NIC group, whereas the NO level and MDA diminished significantly compared to the NIC group (P < 0.01). Conclusions: It seems that CUM administration improves the hippocampal NIC-induced injuries in the CA1 region of rats.
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Determination of thiopurine S-methyltransferase activity using reverse-phase high-performance liquid chromatography assay with ultraviolet detection: Reference values for the Indian population
Ratna Prabha, Sumith K Mathew, AJ Joseph, Binu Susan Mathew
July-September 2019, 10(3):105-110
Objective: To determine thiopurine S-methyltransferase (TPMT) activity and the range of TPMT activity values for the Indian population. Methods: An isocratic reversed-phase high-performance liquid chromatography method with ultraviolet detection for the determination of TPMT activity in red blood cells was developed and validated. TPMT activity (nmol of 6-methylmercaptopurine [6-MMP]/h/ml erythrocytes) was measured based on the conversion of 6-mercaptopurine to 6-MMP with S-adenosyl-l-methionine. The stability of erythrocyte lysate at −20°C and the whole-blood specimens for TPMT activity were determined at 4°C. TPMT enzyme activity was measured in 150 patients who were not on azathioprine (AZA), and population difference in TPMT enzyme activity was evaluated. Results: The assay was linear from 1.0 to 60.14 nmol 6-MMP concentrations. The chromatogram peaks obtained were baseline separated for 6-MMP and the internal standard. The bias and precision of low-, medium-, and high-quality controls (QC) were within acceptable limits. Stock and lysate specimens were found to be stable in −20°C. The Indian populations have a considerable number of patients with low- and intermediate-TPMT activity. The wide range of TPMT activity in the study population (3.85–35.68 nmol/h/ml erythrocytes) is suggestive of high inter-individual variability in the formation of 6-thioguanine nucleotide formation, and therefore clinical efficacy and safety of AZA. Conclusion: A simple isocratic method was developed and validated for measuring TPMT activity in erythrocytes. Measuring TPMT activity before initiating AZA may help to decide the initial dose of AZA in patient management.
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Impact of gender variation on calculated plasma concentration of propofol (Cp50calc) to prevent movement response to surgical stimulus in South Indian population: A comparative study
Sudar Codi Ramarajan, M Ravishankar, K Manimekalai, Sameera Jahagirdhar
July-September 2019, 10(3):100-104
Objective: To find out the gender differences in Cp50calc of propofol required to prevent movement response to surgical stimulus in South Indian population. Materials and Methods: A comparative study was performed on sixty American Society of Anesthesiologists I–II patients of both sexes undergoing elective surgery at a tertiary care institution. A bolus dose of 1.5 mg/kg propofol for 2 min, followed by a 150 μg/kg infusion for 10 min was administered and movement response to surgical incision was noted. Propofol maintenance infusion rate was determined by Dixon's up-and-down method, increased by 10 μg/kg/min for patient movement on surgical stimulus and reduced by 10 μg/kg/min for no movement for successive patient. The plasma concentration (Cpcalc) was calculated by formula used in the marsh pharmacokinetic model using Rugloop II propofol calculation validation Excel Spreadsheet by feeding patient's age, weight, and propofol dose. Cp50calc of propofol, the calculated plasma concentration of propofol, at which 50% of patients anesthetized with propofol do not respond to standard surgical stimulus is calculated by the mean of the midpoint concentration of all independent pair of patients who manifested a consecutive three crossovers from movement-to-no movement response to ensure reaching steady state. Results: No statistically significant difference observed in hemodynamic parameters between the groups. Cp50calc of propofol was 6.336 + 0.14 μg/ml in males and 5.664 + 0.14 μg/ml in females, which was statistically significant (P < 0.05). Conclusion: Males require more propofol than women for anesthetic induction. Hence, gender variable can also be incorporated in the target-controlled pumps for accurate prediction.
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