This drug is contraindicated in renal compromised cases as it causes severe renal impairment (eGFR less than 30 mL/ min/1.73 m²), end stage renal disease (ESRD). FDA determined that an analysis of spontaneous postmarketing adverse events reported till now is not sufficient to assess signals of serious risks of malignancy (pheochromocytoma, Leydig cell tumor, renal cell carcinoma), pancreatitis, hypersensitivity reactions, photosensitivity reactions, hepatotoxicity, bone fractures, nephrotoxicity, and adverse pregnancy outcomes in patients treated with Canagliflozin. FDA has suggested that enhanced pharmacovigilance should continue for 10 years from the date of approval for malignancies and 5 years for all other events. Use of Canagliflozin in some specific populations seems important. Use during pregnancy can be done only if the potential benefit justifies the potential risk to the fetus. There are inadequate studies conducted in pregnant women to show the safety profile. Nursing mothers should discontinue Canagliflozin. In geriatrics, a higher incidence of adverse reactions related to reduced intravascular volume was seen. In renal impaired populations, also a higher incidence of adverse reactions was encountered. Moreover, Canagliflozin is not recommended with severe hepatic impairment.[1,4] Others drugs in this class are Dapagliflozin, Ipragliflozin, and Empagliflozin. Dapagliflozin, approved in November 2012 is already available in Europe.Canagliflozin has approval for being marketed in North America, South America, Europe, the Middle East, Africa, Australia, New Zealand, and parts of Asia excluding Japan. (Mitsubishi Tanabe Pharma is currently conducting a development Phase III for Type 2 Diabetes Mellitus in Japan.) The benefit and risk profile of Canagliflozin can be conclusive. The benefits outweigh the risks associated with the drug. The risks reported are mostly dose‑related higher incidence of reduced volume‑related events, increase in Low Density Lipoprotein (LDL) cholesterol and a small reduction in the bone mineral density (BMD). However, the benefits are a low incidence of hypoglycemia, an unique mechanism of action of the drug complementary with other antihypoglycemic agents, improves beta‑cell function, simple to administer with once daily oral dosing and a flexible dosing of 100 and 300 mg. Canagliflozin is an important addition to the comprehensive platform of offerings for patients with diabetes from the Johnson and Johnson Family of Companies.
Sunil Kumar Pandey, Deepanjana Dass
Department of Pharmacology, Sikkim Manipal Institute of Medical Sciences, Tadong, Gangtok, Sikkim, India E‑mail: [email protected]
National diabetes fact sheet: National estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA. U.S. Department of Health and Human Services, Centers
Journal of Pharmacy and Bioallied Sciences April-June 2014 Vol 6 Issue 2
for Disease Control and Prevention 2011‑ Available from: http://www. diabetes.org/in‑my‑community/local‑offices/miami‑florida/assets/ files/national‑diabetes‑fact‑sheet.pdf [Last cited 2013 Apr 20]. Available from: http://www.idf.org/diabetesatlas/5e/the‑global‑burden [Last accessed on 2013 Apr 13]. Coelln‑Hough J. Endocrinologic and Metabolic Drugs Advisory Committee. 2013. Janssen Pharmaceuticals. Available from: http://www.fda.gov/ downloads/AdvisoryCommittees/CommitteesMeetingMaterials/ Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/ UCM336236.pdf [Last accessed on 2013 Apr 13 ]. Accessdata.fda.gov [Internet]. NDA Approval of Canagliflozin. Department of Health and Human Services: Available from: http://www.accessdata. fda.gov/drugsatfda_docs/nda/2013/204042Orig1s000Approv.pdf [Last accessed on 2013 Apr 16]. US FDA approves Canagliflozin (TA‑7284) for the treatment of adult patients with Type 2 Diabetes. Mitsubishi Tanabe Pharma Corporation. Press release 2013.
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Website: www.jpbsonline.org DOI: 10.4103/0975-7406.129179
Platelet rich concentrates: A quick healer Sir, Platelet rich plasma (PRP) has an extremely broad range of clinical applications in oral and maxillofacial surgery, periodontal surgery, otolaryngology, cardiovascular surgery, burns, wound healing, cosmetic surgery, orthopedic surgery etc., PRP has also been used in combination with mesenchymal stem cells to promote bone regeneration and can also be mixed with fat cells for breast reconstruction, and to correct painful adherent scars. In contrary, some studies even suggest that PRP could even be harmful to tissue repair. There is still no consensus about the ideal platelet concentration that could optimize the tissue repair process. The mechanism of action of growth factors is very complex, because each growth factor may have a different effect on the signal transduction of bone matrix mineralization. Growth factors may also interact with each other and consequently may form a cascade of different signal proteins with multiple pathways, which will ultimately lead to activation of gene expression followed by protein production. PRP is unique as it acts on multiple signal pathways at the same time. Platelet rich fibrin (PRF) has been vastly used in dentistry in treatment of periodontal regeneration, bone regeneration, dental implants, dental pulp regeneration. when used in periodontal regeneration PRF had two major benefits firstly the promotion of soft tissue healing as explained by the effect of PRF on progenitor proliferation and migration and secondly the induction of new alveolar bone formation as possibly facilitated by the fibrin mediated effect of PRF 133
on runt‑related transcription factor 2 (a key transcription factor associated with osteoblast differentiation) and matrix mineralization and also by the enhancing alkaline phosphatase activity. It also reduces expression of the matrix gla protein (a mineralization inhibitor), preferentially in alveolar bone osteoblast progenitors. Limitations of PRF are (1) the availability in larger quantity is limited, (2) PRF possesses the circulating immune cells and antigenic molecules that prevent its use as an allogenic material, (3) dehydration of PRF may inactivate the growth factors, (4) contamination of membrane during handling.
B. S. Deepak, D. B. Nandini1
Department of Conservative Dentistry and Endodontics, Bapuji Dental College and Hospital, 1Department of Oral and Maxillofacial Pathology, College of Dental Sciences, Davangere, Karnataka, India E‑mail: [email protected]
References 1. 2. 3. 4. 5.
Lucarelli E, Beretta R, Dozza B, Tazzari PL, O’Connel SM, Ricci F, et al. A recently developed bifacial platelet‑rich fibrin matrix. Eur Cell Mater 2010;20:13‑23. Choi BH, Im CJ, Huh JY, Suh JJ, Lee SH. Effect of platelet‑rich plasma on bone regeneration in autogenous bone graft. Int J Oral Maxillofac Surg 2004;33:56‑9. Sandy J, Davies M, Prime S, Farndale R. Signal pathways that transduce growth factor‑stimulated mitogenesis in bone cells. Bone 1998;23:17‑26. Li Q, Pan S, Dangaria SJ, Gopinathan G, Kolokythas A, Chu S, et al. Platelet‑rich fibrin promotes periodontal regeneration and enhances alveolar bone augmentation. Biomed Res Int 2013;2013:638043. Khiste SV, Tari RN. Platelet‑rich fibrin as a biofuel for tissue regeneration. ISRN Biomater 2013, Article ID 627367, p. 1‑6.
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Website: www.jpbsonline.org DOI: 10.4103/0975-7406.129180
Negative animal studies published in Indian Medical Journal: Are they methodologically strong enough to conclude what they are concluding? Sir, Negative studies refer to the studies where authors formally conclude that any statistical significant difference amongst
the variables under study could not be found. Published negative study should be methodologically strong as it usually discourages other researcher to further research same topic. Published negative study should also report all statistical and methodological parameters, which can help a reader to critically appraise the negative study for the results and conclusion. It is observed that negative studies published in various peer reviewed journals do not report statistical and methodological parameters, which are in fact essential in critical appraisal of published study. More so, studies concluding with “No significant difference” should have adequate power to detect the difference, for which appropriate methodology and statistics is required. There is a paucity of data regarding methodological and statistical reporting standard of negative animal studies published in Indian Medical Journals. The present study attempts to reflect on validity of such studies with primary objective of assessing negative animal studies published in medical journals from India in terms of reporting of various statistical and methodological parameters. Study was conducted at Department of Pharmacology, Govt. Medical College, Surat (Gujarat), India in collaboration of Indian Institute of Public Health Gandhinagar. Study was initiated in July 2012 and ended in February 2013. It was a cross sectional study based on animal negative studies published in Indian medical journals from Science Citation Index (SCI). A two stage Delphi technique was utilized to develop consensus on tool to be used for data collection. The members participated in the Delphi process included selected journal editors, peer reviewers, member of academia and researchers from Gujarat state and other part of India. A roundtable was done with journal editors, researchers and academicians after the Delphi process to decide the final tool and inclusion criteria for journals and studies to be included in the present work. Original articles published during 2000‑2011, dealing with negative animal studies and published in 15 SCI indexed Indian journals were downloaded and included in the present study. Studies dealing with two or three groups (drug with placebo or with active comparator) were included in the final analysis. The Journals which were finally included as per the eligible criteria included Indian Pediatrics (IP), Annals of Indian Academy of Neurology (AIAN), Indian Journal of Dermatology, Venereology and Leprology (IJDVL), Indian Journal of Medical Microbiology (IJMM), Indian Journal of Ophthalmology (IJO), Indian Journal of Pharmacology (IJP), Journal of Postgraduate Medicine (JPGM), Neurology India (NI), Indian Journal of Orthopedics (IJO), Journal of Anatomical Society of India (JASI), Indian Journal of Medical Research (IJMR), Indian Journal of Otolaryngology and Head and Neck Surgery, Indian Journal of Pathology and Microbiology (IJPM), Indian Journal of Pediatrics (IJP) and International Journal of Diabetes in Developing Countries (IJDD). Operational definition to suffice any study as negative included studies which reported 1. Difference between primary endpoint as non‑significant. 2. If there was no primary endpoint reported in reference to the difference in endpoint which was considered for sample Journal of Pharmacy and Bioallied Sciences April-June 2014 Vol 6 Issue 2
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