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   Table of Contents - Current issue
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July-September 2018
Volume 8 | Issue 3
Page Nos. 115-156

Online since Friday, February 1, 2019

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ORIGINAL RESEARCH ARTICLES  

Study on the quality control analysis of antiepileptic drugs using high-performance liquid chromatography p. 115
Manzoor Ahmad Mir, Najwa Shabir, Umar Mehraj, Younis Mohd Rather, Samina Farhat
DOI:10.4103/jphi.JPHI_45_18  
Background: Epilepsy is the second most common neurological condition, and antiepileptic drugs (AEDs) are used as a prophylactic measure. Any amount of poor-quality medicine is unacceptable because it increases morbidity and mortality, thus an assessment of quality of AEDs are important in developing countries like India. Phenytoin (PHT) has become a major first-line AED in the treatment of partial and secondarily generalized seizures, but like other pharmaceuticals, PHT too may develop impurities at various stages of development, transportation, and storage which make the pharmaceutical risky. Hence, the objective of the study was to test PHT concentrations in various injectable medicines available in the local markets of Kashmir Valley. Materials and Methods: Quality analysis of PHT by high-performance liquid chromatography (HPLC) is more precise and accurate than using other analytical methods such as enzyme-based assays and immunoassay as the use of HPLC technique in the analytical field helps in structure elucidation and quantitative determination of impurities. In this study, we studied the different parameters of quality of various PHT drugs available in the local markets using HPLC and compared the results obtained with that of the standard. Results: We observed that all the tested PHT sodium injections available in the local market have standard concentrations as all the samples under study showed the peak exactly where the standard PHT peak was supposed to be. Hence, our results suggest that the quality of various PHT drugs used in Kashmir Valley is satisfactory and safe. Conclusion: It is clear from our results that there is a need for a quick and effective drug quality analysis method. As shown from the experiments performed in this study, HPLC is not only a suitable but also efficient system to carry out drug quality evaluation and help curb or at least keep in check the rampant sale of substandard drugs that go unabated in developing countries like India.
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Anti-osteoporotic activity of isoflavones from Iris germanica targeting NF-kappaB p. 122
Afroze Alam, Monika Verma, Kamlesh Kumar Naik, Disha Choudhary, Shailendra Kumar
DOI:10.4103/jphi.JPHI_36_18  
Background: Most of the available anti-osteoporotic drugs are costly and possess great threat of severe side effects. Thus, an alternative approach is required to develop new therapeutic drugs. Materials and Methods: An attempt was made to isolate two novel compounds followed by its analog synthesis from Iris germanica. All the compounds were subjected for in vitro anti-osteoporotic activities; % stimulation on osteoblast-like cells, % inhibition on osteoclast-like multinucleated cells (RAW264.7), cytotoxicity against RAW264.7 cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra assay, % tartrate-resistant acid phosphatase (TRAP) activity on RAW264.7 cell lines, and docking study into the active site of NF-kappaB. Results: Out of six compounds, the compounds 1a, 1c, and 2a exhibited significant % stimulation (90%–98%) compared to standard drug diazedine (100%) while % inhibition was found in the range of 142–165, when compared with standard drug elcitonin. Cytotoxic assay results revealed that compound 1c and 1a have showed pronounced activity with IC50values 4.2 and 5.2 against preosteoclastic RAW 264.7 cell lines. All the compounds showed significant inhibition of TRAP in NF-kappaB ligand-induced osteoclastic RAW 264.7 cells, with values ranging from 14.39% ± 2.62% to 66.67% ± 2.76%. Furthermore, all the compounds were docked into the active site of NF-kappa B and 1a exhibited docking score (−7.98 kcal/mole). Conclusion: In vitro screening of all compound were carried out for anti-osteoporotic activity using NF-kappa B as a target. Isolated isoflavones showed excellent interactions with NF-kappaB and established a noticeable correlation between in silico score and in vitro anti-osteoporotic study.
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Molecular docking studies of ephedrine, eugenol, and their derivatives as arginase inhibitors: Implications in asthma p. 130
Suhasini Donthi, Jayasree Ganugapati, Vijayalakshmi Valluri, Ramesh Macha, Krovvidi S.R Sivasai
DOI:10.4103/jphi.JPHI_25_18  
Background: Arginine being a common substrate for arginase and nitric oxide synthase (NOS) an imbalance between enzymes could lead to a shift in airway responses. Reports suggest that increased arginase reduces the substrate availability to NOS and attributes to the airway hyperresponsiveness. Hence, inhibition of arginase might enhance the bioavailability of arginine to NOS and generates nitric oxide (NO) a bronchodilator. Molecules from Ephedra and Eugenia caryophyllus are documented for bronchodilator properties. However, the mechanism of action of these molecules for enhancing bronchodilation is not well characterized. The objective of the present study is to assess whether these molecules could inhibit the arginase by binding at its active site and helps in bronchodilation using in silco approach. Methods: The crystal structures of the arginase and NOS enzymes were selected from the protein database. The molecules from Ephedra and Eugenia caryophyllus were obtained from Pubchem. Drug likeliness and bioactivity of the molecules were assessed by Molinspiration. The successful molecules were docked with active sites of enzymes using docking software, and the docked complexes were analyzed using Accelrys Discovery Studio. Results: Molecules from Ephedra and Eugenia caryophyllus were able to interact to arginase at the active site whereas away from the active site in case of NOS. The molecules showed differential binding affinities, and some of them had higher binding affinity than substrate arginine. Conclusion: In silico study suggests that molecules of Ephedra and Eugenia were capable of blocking the active site of arginase. We speculate that if these molecules are used as therapeutics, they could inhibit the arginase activity and this might increase arginine availability to NOS to produce NO which acts as bronchodilator. Our study suggests that molecules which bind to active site of arginine and do not affect the active site of NOS might be the potential molecules for arginase associated asthma.
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Synthesis, antimicrobial activity, and docking study of some N3, N6-diphenylpyridazine-3,6-diamine derivatives as dihydrofolate reductase inhibitors p. 138
Athar Javed, Sameer Sapra, Afroze Alam
DOI:10.4103/jphi.JPHI_37_18  
Objective: The present study focussed on the synthesis of pyridazine analogs to explore broad-spectrum antimicrobial study. Since pyridazine analogs are not conventionally found in nature, and hence, its analogs are studied later. Materials and Methods: All the synthesized compounds were characterized by spectroscopic techniques, namely, UV, IR,1HNMR, and mass spectrometry. Antimicrobial activity was screened by serial dilution method and absorbance was recorded using ELISA reader, subsequently minimum inhibitory concentrations were determined. Docking study was done into the active site of dihydrofolate reductase using Auto Dock 4.2. Results: The present investigation about synthesis, characterization, and biological studies of some new pyridazine analogs were carried out to obtain potent and pharmacologically active compounds. The free energy of binding was in the range of −5.12 to −8.97 kcal/mole. In silico study report was in good tune with laboratory experiments. Conclusions: Most of the compounds were moderate-to-good toward the antimicrobial activity. Compound AJ27 was found to be most active. Results of anti-microbial activity establishes the importance of N3, N6-diphenylpyridazine-3,6-diamine as the basic skeleton required for the antimicrobial activity.
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The effectiveness of Valeriana officinalis on sleep disturbance in patients with chronic heart failure p. 145
Fatemeh Aliakbari, Mahmoud Rafieian
DOI:10.4103/jphi.JPHI_43_18  
Background: Sleep disturbances are common problems in patients with chronic heart failure (CHF) and are a significant contributing factor to fatigue and poor quality of life. The aim of the present study was to evaluate the effectiveness of Valeriana officinalis on sleep disturbance in patients with CHF. Materials and Methods: A randomized, controlled trial design was used for this study. Eighty patients with CHF experiencing insomnia were designated to intervention and control groups. The patients in the intervention group went through conventional treatment while taking 12cc V. officinalis syrup, 1 h before sleeping every night for 4 weeks. The control group received routine medication such as alprazolam. A demographic data form and the Pittsburgh Sleep Quality Index were used to collect data. Questionnaires were completed by all participants before and after the intervention. Results: The results indicated that regarding the duration of waiting for falling into sleep, there was a significant difference after intervention so that it was less in intervention groups compared to that of the control group (P = 0.001). In view of the hours during which the participants were fully asleep, there was a significant difference after the intervention between control and intervention groups, considerably higher among three intervention groups compared to that in the control group (P < 0.05). Conclusions: V. officinalis improves the quality of sleep in patients with CHF who experience insomnia. The findings from this study support the reported effectiveness of V. officinalis in the clinical management of insomnia.
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Intensive monitoring of adverse drug reactions to antipsychotic medications in the inpatient psychiatry department of a secondary care hospital of UAE p. 151
Haneen Abou R. Aburamadan, Sathvik Belagodu Sridhar, Talaat Matar Tadross
DOI:10.4103/jphi.JPHI_46_18  
Background: Antipsychotics are a class of medications used primarily for the treatment of psychotic disorders. However, these medications are associated with potential adverse drug reactions (ADRs). Aim: To monitor the incidence and nature of ADRs in the psychiatric inpatient department of a secondary care hospital of Ras Al Khaimah, UAE. Materials and Methods: This was an observational, prospective, noninterventional study, conducted in the psychiatric inpatient setting of a secondary care hospital. Psychiatric inpatients of all age groups and both the gender, diagnosed with any psychotic disorder, and hospitalized in the psychiatry ward and managed with at least one antipsychotic medication were included in the study. The causality, severity, and preventability of ADRs were assessed using different assessment scales. Results: Out of 170 patients, 38 patients reported at least one ADR with an incidence rate of 22.3%. The most common ADRs were weight gain 15 (29.4%) due to olanzapine, followed by pseudo-parkinsonism 11 (21.6%) due to parenteral haloperidol. Schizophrenia (18, 35.3%), followed by bipolar I disorder (10, 19.6%) was the most common condition associated with ADRs. Female gender and duration of hospital stay were found to be significant (P < 0.05) predictors of occurrence of ADRs. Conclusion: A high incidence of ADRs was observed in the inpatients of psychiatry department, especially of mild nature and probably preventable types. The study highlights the importance of intensive monitoring by pharmacists to identify high ADR risk psychiatric inpatients. To reduce the ADR risk, specific and frequent monitoring for antipsychotics is recommended such as weight and extrapyramidal symptoms.
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