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EDITORIAL |
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Principles and practice of plagiarism: Perpetrators' perspective |
p. 61 |
Amitav Banerjee DOI:10.4103/0976-500X.155480 PMID:25969650 |
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REVIEW ARTICLES |
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Scientific concepts and applications of integrated discrete multiple organ co-culture technology |
p. 63 |
Loganathan Gayathri, Dharumadurai Dhanasekaran, Mohammad A Akbarsha DOI:10.4103/0976-500X.155481 PMID:25969651Over several decades, animals have been used as models to investigate the human-specific drug toxicity, but the outcomes are not always reliably extrapolated to the humans in vivo. Appropriate in vitro human-based experimental system that includes in vivo parameters is required for the evaluation of multiple organ interaction, multiple organ/organ-specific toxicity, and metabolism of xenobiotic compounds to avoid the use of animals for toxicity testing. One such versatile in vitro technology in which human primary cells could be used is integrated discrete multiple organ co-culture (IdMOC). IdMOC system adopts wells-within-well concept that facilitates co-culture of cells from different organs in a discrete manner, separately in the respective media in the smaller inner wells which are then interconnected by an overlay of a universal medium in the large containing well. This novel in vitro approach mimics the in vivo situation to a great extent, and employs cells from multiple organs that are physically separated but interconnected by a medium that mimics the systemic circulation and provides for multiple organ interaction. Applications of IdMOC include assessment of multiple organ toxicity, drug distribution, organ-specific toxicity, screening of anticancer drugs, metabolic cytotoxicity, etc. |
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Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis |
p. 71 |
Marianne Frieri, William Heuser, Joshua Bliss DOI:10.4103/0976-500X.155482 PMID:25969652Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis. Lupus nephritis is a major complication of systemic lupus erythematosus (SLE) that can lead to significant illness or even death without proper intervention and treatment. With vast implications through a novel mechanism, belimumab offers a new standard of treatment for physicians in the complications associated with SLE, specifically lupus nephritis. By targeting B cell signaling and maturation, belimumab is able to mitigate the underlying pathological complications surrounding SLE. Phase 3 clinical trials with belimumab have depicted clinically efficacious applications, suggesting belimumab as a revolutionary breakthrough in the treatment armamentarium for practicing clinicians. This article explains the precise mechanism of action of belimumab on the soluble protein BlyS that plays a major role in the pathogenesis of lupus nephritis. In addition, the extensive pharmacokinetics and clinical implications are exemplified in this review with belimumab's comparison with standard therapeutic guidelines for the treatment of lupus nephritis. |
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RESEARCH PAPERS |
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Identification of core active disaccharides in heparin for HGF-inducing activity |
p. 77 |
Takashi Kato, Ryoichi Sakiyama, Kiyomasa Oka, Toshikazu Nakamura DOI:10.4103/0976-500X.155483 PMID:25969653Objectives: To ascertain the positions of sulfated groups for HGF-inducing activity using differently sulfated heparin disaccharides and to investigate whether the heparin disaccharide elevates HGF levels in plasma in vivo and exerts protective effects on acute liver injury. Materials and Methods: The heparin disaccharides ΔUA-GlcNS, ΔUA (2S)-GlcN, ΔUA-GlcNAc (6S), ΔUA-GlcNS (6S), ΔUA (2S)-GlcNS, ΔUA (2S)-GlcNAc (6S), ΔUA-GlcNAc and ΔUA (2S)-GlcNS (6S) were added to MRC-9 fibroblasts and HGF concentrations in culture media were determined by enzyme-linked immunosorbent assay. Furthermore, ΔUA-GlcNS (100 μg/head) was injected into C57BL/6 mice and plasma levels of HGF measured at 12 h. After acute hepatitis was induced by CCl 4 (15 mg/kg) in mice, liver specimens were stained with hematoxylin and eosin (H and E). Levels of aspartate aminotransferase and alanine aminotransferase were measured at 24 h. Results: Among the disaccharides investigated, ΔUA-GlcNS, ΔUA-GlcNAc (6S) and ΔUA-GlcNS (6S) stimulated HGF production in MRC-9 fibroblasts. However, none of the 2-O-sulfated disaccharides [ΔUA (2S)-GlcNS, ΔUA (2S)-GlcNAc (6S) and ΔUA (2S)-GlcNS (6S)] showed any activity despite the presence of N-sulfated and/or 6-O-sulfated disaccharides. Thus, 2-O-sulfation of hexuronic acid has an inhibitory effect. Moreover, ΔUA-GlcNS administration increased plasma levels of HGF in normal mice and prevented CCl 4 -induced liver injury in mice. Conclusions: N-sulfation and/or 6-O-sulfation of glucosamine with nonsulfated hexuronic acid provides a structural basis for the HGF-inducing activity of disaccharides. ΔUA-GlcNS increases plasma levels of HGF and protects against CCl 4 -induced acute liver injury. |
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Prescription errors in cancer chemotherapy: Omissions supersede potentially harmful errors |
p. 83 |
Jayanthi Mathaiyan, Tanvi Jain, Biswajit Dubashi, K Satyanarayana Reddy, Gitanjali Batmanabane DOI:10.4103/0976-500X.155484 PMID:25969654Objective: To estimate the frequency and type of prescription errors in patients receiving cancer chemotherapy. Settings and Design: We conducted a cross-sectional study at the day care unit of the Regional Cancer Centre (RCC) of a tertiary care hospital in South India. Materials and Methods: All prescriptions written during July to September 2013 for patients attending the out-patient department of the RCC to be treated at the day care center were included in this study. The prescriptions were analyzed for omission of standard information, usage of brand names, abbreviations and legibility. The errors were further classified into potentially harmful ones and not harmful based on the likelihood of resulting in harm to the patient. Descriptive analysis was performed to estimate the frequency of prescription errors and expressed as total number of errors and percentage. Results: A total of 4253 prescribing errors were found in 1500 prescriptions (283.5%), of which 47.1% were due to omissions like name, age and diagnosis and 22.5% were due to usage of brand names. Abbreviations of pre-medications and anticancer drugs accounted for 29.2% of the errors. Potentially harmful errors that were likely to result in serious consequences to the patient were estimated to be 11.7%. Conclusions: Most of the errors intercepted in our study are due to a high patient load and inattention of the prescribers to omissions in prescription. Redesigning prescription forms and sensitizing prescribers to the importance of writing prescriptions without errors may help in reducing errors to a large extent. |
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RESEARCH LETTERS |
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Parents' awareness and perspective on off-label medicines use in children |
p. 88 |
Mohd Masnoon Saiyed, Aarohi Prajapati, Gaurang Shah DOI:10.4103/0976-500X.155485 PMID:25969655 |
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Comparison of agreement and rational uses of the WHO and Naranjo adverse event causality assessment tools |
p. 91 |
Niti Mittal, Mahesh C Gupta DOI:10.4103/0976-500X.155486 PMID:25969656 |
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COMMENTARY |
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Violation of publication ethics in manuscripts: Analysis and perspectives |
p. 94 |
Subramani Parasuraman, Ramasamy Raveendran, KK Mueen Ahmed DOI:10.4103/0976-500X.155487 PMID:25969657 |
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CASE REPORTS |
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Hypokalemia and rhabdomyolysis |
p. 98 |
Henrik Horwitz, Vidar A Woeien, Linda Wiuff Petersen, Espen Jimenez-Solem DOI:10.4103/0976-500X.155488 PMID:25969658The adverse drug event manager of the Capital Region of Denmark received a report of a 65-year-old male with type II diabetes and long-lasting treatment with indapamide. In addition, he had a history of a high consumption of licorice. For 2 weeks, the patient suffered from myalgia, which the general practitioner suspected to be polymyalgia rheumatica and referred him to the hospital. Initial blood samples revealed a reduced potassium concentration of 1.5 mmol/L (reference value: 6.6-4.6 mmol/L) and an elevated creatine kinase of 18,400 IU/L (reference value: 40-280 IU/L). We believe that the patient developed rhabdomyolysis due to severe hypokalemia, possibly induced by a pharmacodynamic interaction between licorice and indapamide. |
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Intravenous ranitidine: Rapid bolus can lead to cardiac arrest |
p. 100 |
Kamlesh J Upadhyay, Sarita J Parmar, Rohan Pravinbhai Parikh, Prashant K Gauswami, Nikunj Dadhaniya, Abhilash Surela DOI:10.4103/0976-500X.155489 PMID:25969659This is a rare case report of a 30-year-old male, who was admitted to the Maxillofacial Surgery Department of the Dental College for a malunited fracture of the mandible and zygomatic bones. He was given oral medications namely, cefixime, metronidazole, ondansetron, and ranitidine for three days prior to the operation with complete normal preoperative workup. He had no significant past medical or family history. On the day of the operation, he was given injectable dexamethasone, cefotaxime, ondansetron, ranitidine, and metronidazole half-an-hour prior to the operation. In less than five minutes of giving a bolus ranitidine injection, the patient developed a cardiac arrest and was resuscitated by the anesthetist team on duty. He was transferred to the Intensive Care Unit (ICU) on a ventilator, which was soon removed and the patient was off vasopressors, with stable vitals for 24 hours after the event. He was then transferred to the general ward of Medicine Department and observed for a further two days during which the patient remained uneventful and was finally transferred back to the Dental Department. |
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Dexamethasone-induced withdrawal seizure |
p. 103 |
Santwana Mahar, Mahima Malhotra DOI:10.4103/0976-500X.155490 PMID:25969660Dexamethasone-induced withdrawal seizure, which is a very rare and uncommon event, occurred after discontinuation of steroid therapy that was taken to increase weight by the patient. The pathogenesis is not well understood. In this submission, we have highlighted the fact that withdrawal of steroid has a propensity to cause seizure as a rare withdrawal phenomenon. |
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Hypersensitivity reaction with deferasirox |
p. 105 |
Atul Sharma, Ekta Arora, Harmanjit Singh DOI:10.4103/0976-500X.155491 PMID:25969661Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case. |
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Telmisartan aggravates pustular psoriasis |
p. 107 |
Subramaniam Keerthi, Murugaiyan Rangaraj, Kaliaperumal Karthikeyan DOI:10.4103/0976-500X.155492 PMID:25969662Pustular psoriasis is characterized by abrupt onset of macroscopic pustules associated with erythema and symptoms of burning pain and constitutional symptoms. There are several precipitating factors, both physiological such as pregnancy and routinely prescribed drugs like antihypertensives, antifungals, corticosteroids and progesterone. We present a case of a 50-year-old male patient with pustular psoriasis, well controlled on oral methotrexate, who presented with sudden exacerbation of pustular psoriasis following the use of telmisartan. This case is presented due to the absence of prior reports of telmisartan aggravating pustular psoriasis. |
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Adrenal suppression following herbal remedy for rheumatoid arthritis |
p. 110 |
Balasekar Premkumar, Muppavarapu Srinivasa Murthy, Karuppasamy Rajagopal, Vadivelmurugan Nagasubramani Nagaprabu, Sree Madhuri Ponugupati DOI:10.4103/0976-500X.155493 PMID:25969663A patient suffering from rheumatoid arthritis who had extreme adrenal suppression as a result of chronic use of herbal medicines presented with complications of adrenal suppression such as muscle weakness. He also had psychiatric disturbances such as confusion and suicidal tendency. Steroids in the herbal medication were found and hence there exists a need for investigation into their safety and efficacy. |
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Olanzapine-induced tender pitting pre-tibial edema |
p. 114 |
Kaliaperumal Mathan, Venkatesan Muthukrishnan, Vikas Menon DOI:10.4103/0976-500X.155494 PMID:25969664Antipsychotic-induced edema is uncommonly encountered in clinical practice. We report a case of tender pitting pre-tibial edema with olanzapine in a woman with no medical comorbidities. The peculiar distribution of edema resulted in diagnostic confusion necessitating specific investigations. Eventually, the edema resolved following complete stoppage of the drug, but caused distress to the patient and the caregiver. |
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CORRESPONDENCE |
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VACCRaksha Calc: A computer program for the calculation of vaccine potency |
p. 116 |
SaiMahesh Reddy Avula, Venkata Subba Reddy Avula DOI:10.4103/0976-500X.155495 PMID:25969665 |
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MOLECULES OF THE MILLENNIUM |
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Suvorexant: The first orexin receptor antagonist to treat insomnia |
p. 118 |
Ashok K Dubey, Shailendra S Handu, Pramod K Mediratta DOI:10.4103/0976-500X.155496 PMID:25969666Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, have often been associated with adverse effects, such as, day-time somnolence, amnesia, confusion, and gait disturbance, apart from the risk of dependence on chronic use. Suvorexant has not shown these adverse effects because of its unique mechanism of action. It also appears to be suitable as a chronic therapy for insomnia, because of minimal physical dependence. The availability of this new drug as an effective and safe alternative is an important and welcome development in insomnia management. |
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ERRATUM |
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Adverse drug reactions of imatinib in patients with chronic myeloid leukemia: A single-center surveillance study: Erratum |
p. 122 |
DOI:10.4103/0976-500X.155497 PMID:25969667 |
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