DocumentsDate added
Review article
Nagaraj B Malipatil1,*, Kiran M Haridas1, Shruthi D Prithvi2
Affiliation:
1Clinical Pharmacologist, Bangalore, Karnataka, India
2Former Post-graduate, Department of Orthodontics and Dentofacial Orthopedics, DayanandSagar College of Dental Sciences, Bangalore - 560078, Karnataka, India
Address reprint requests to
Dr. Nagaraj B Malipatil.
Clinical Pharmacologist,
Bangalore, Karnataka, India
Article citation:
Malipatil NB, Haridas KM, Shruthi DP. Biosimilars and regulations: A review. J Pharm Biomed Sci. 2015; 05(06):453-468. Available at www.jpbms.info
ABSTRACT:
Currently, all biologics in India, including innovative and bioequivalent biologics (also known as similar biologics in India), are approved as new drugs. Recently in 2012, the Department of Biotechnology (DBT) and Central Drugs Standard Control Organization (CDSCO) issued the “guidelines on similar biologics”. The guidance outlined an abridged procedure for the regulatory requirements for marketing authorization of similar biologics in India.
Due to limited R & D capabilities, most domestic companies manufacture simple biologics. However, companies have increasingly begun to shift their focus to the development of both novel and copy versions of monoclonal antibodies and second-generation biologics, which though more expensive and complex to develop can be priced at a premium, and compete in a much less crowded market than that faced by first-generation biologics.
A number of factors facilitate the development and uptake of Biosimilars in India. Poor patent enforcement in India provides opportunities for domestic biologics manufacturers, while publicprivate sector partnerships promote biologics development. Since there are less stringent regulatory requirements and low R&D costs, domestic biologics are priced much lower in India compared to originators, further driving uptake, as well as offering huge potential for contract manufacturing of biosimilars and for exports. Domestic companies are also entering into partnerships to facilitate development of biologics for the Indian and global market.
However, despite the low price of Biosimilars compared to originator brands, the domestic market is restricted by limited health insurance coverage and therefore poor access to biologic drugs. Also, issues regarding the quality and safety of some domestically manufactured biologics remain a concern among patients and physicians.
KEYWORDS: Biosimilars; Biologics; Regulations; Similar biologic.
REFERENCES:
1.BioSpectrum ABLE Biotech Industry Survey. The eighth survey of Indian biotech industry. 2010. [Accessed on 05 Apr 2015] Available from <http://www.ableindia.org/html/resources/eighth_biospectrum_June_10.pdf.
2.Sheppard A. Modified Biologics: the global outlook Biosimilars, A presentation at Biosimilar Asia Conference 2011, 24-26 May 2011, Grand Hyatt Shanghai, China.
3.Biospectrum- Erythropoietin. 2005. [Accessed on 06 Apr 2015] Available from < http://biospectrumindia.ciol.com/content/BioBusiness/10509062.asp.
4.Business Standard. Angel Broking - Cadila Healthcare - 3QFY2011. 2011. [Accessed on 07 Apr 2015] Available from http://www.business-standard.com/content/research_pdf/cadila_210111_01.pdf.
5.Desai JP. Bridges to Bloom: The Future of Indian Biosimilars” by Universal Consulting India (Pvt) Ltd., September 2009. [Accessed on 08 Apr 2015] Accessed from http://www.universalconsulting.com/pdf/The%20Future%20of%20Indian%20Biosimilars.pdf.
6.CDSCO. Draft guidance on approval of clinical trials and new drugs. 2011. [Accessed on 07 Apr 2015] http://cdsco.nic.in/Guidance_for_New_Drug_Approval-23.07.2011.pdf
7.Shirodkar SN. DBT completes draft guidelines on preclinical trial data for similar biologics. 2011 [Accessed on 08 Apr 2015] Available from http://www.pharmabiz.com/PrintArticle.aspx?aid=63640&sid=1
8.EGA. Global Development, The Way Forward The EGA’s Perspective. 2010a. [Accessed on 08 Apr 2015] Available from: http://www.egagenerics.com/doc/ega_biosimilars_Schwarzenberger_090424.pdf.
9.EGA. 8th EGA Annual International Symposium On Biosimilar Medicines. 2010b. [Accessed on 08 Apr 2015] Available from: http://www.egagenerics.com/bio-articles.htm.
10.Chen H. Requirements For China To Globalize Success Seen In Domestic Biosimilars Market. 2009. [Accessed on 08 Apr 2015] Available from: http://www.genengnews.com/analysis-and-insight/requirements-for-china-toglobalize-success-seen-in-domestic-biosimilars-market/59580243
11.Alexander J. Expert Panel to Recommend Regulatory Guidelines for Biosimilars Soon. 2011. [Accessed on 06 Apr 2015] Available from: http://www.pharmabiz.com/NewsDetails.aspx?aid=60815&sid=1.
12.Dicicco R. Developing Biosimilars in Regulated/Semi-Regulated and Unregulated Markets, A presentation at Informa Life Sciences Biosimilars Conference 2010, June 2010.
13.GaBi. EMA to Revise Overarching Biosimilar Guidelines. 2012. [Accessed on 08 Apr 2015] Available from: http://gabionline.net/Guidelines/EMA-to-revise-overarching-biosimilar-guidelines
14.Kubrekar V. Innovations in drug delivery for biologics to enhance efficacy, A presentation at the Biosimilars India Conference 2011, 14-15 July 2011 Mumbai, India.
15.Tessensohn JA, Yamamoto S. Patent term extensions for biologic innovators in Japan. Nat Biotechnol. 2011; 29(1):34-7.
16.Nomura. Coming of age: generic-centered players flourishing and preparing to go global. 2011 [Accessed on 08 Apr 2015] http://www.nomura.com/europe/resources/upload/Korean_biopharmaceuticals.pdf.
17.Department of Biotechnology. Guidelines on similar biologics. 2012. [Accessed on 08 Apr 2015] Accessed from http://www.igmoris.nic.in/Files2/Guidelines_SimilarBiologics.pdf.
18.Controller General of India. [Accessed on 08 Apr 2015] Available from http://igmoris.nic.in/clinical_trials.asp
19.Clinical Trials Registry – India. Search for trials. 2011. [Accessed on 08 Apr 2015] Available from <http://ctri.nic.in/Clinicaltrials/pubview.php.
20.Department of Industrial Policy & Promotion. Industrial Policy – Industrial licensing. 2011. [Accessed on 08 Apr 2015] Available from <http://dipp.nic.in/inv_opp/manul.pdf.
21.Government of India. Web directory–Union government ministries. 2011. [Accessed on 08 Apr 2015] Available from http://goidirectory.nic.in/union_categories.php?ct=E002.
22.Ministry of Chemicals & Fertilizers. Pharmaceutical policy - 2002. [Accessed on 08 Apr 2015] Available from < http://chemicals.nic.in/pharma4.htm.
23.Ministry of Environment & Forests. Rules for the manufacture, use, import, export and storage of hazardous microorganisms genetically engineered organisms or cells. 1989. [Accessed on 08 Apr 2015] Available from http://envfor.nic.in/legis/hsm/hsm3.html.
24.Parliamentary Standing Committee - 45th report. Issues relating to availability of generic, Generic-branded and branded medicines, their formulation and therapeutic efficacy and effectiveness. 2010. [Accessed on 05 Apr 2015] Available from <http://164.100.47.5/newcommittee/reports/EnglishCommittees/Committee%20on%20Health%20and %20Family%20Welfare/45th%20report.pdf.
25.Ministry of Health and Family Welfare. Drugs and Cosmetics rules 1988 (eighth amendment).1988. [Accessed on 05 Apr 2015] Available from http://dbtbiosafety.nic.in/act/_Annex-7.htm.
26.Tharu R. Clinical Trials in India - Boon or Bane? 2008. [Accessed on 05 Apr 2015] Available from:http://www.medindia.net/news/healthwatch/clinical-trials-in-india-boon-or-bane414191.htm#ixzz3YlVgw7wi.
27.Ariyanchira S. The Opportunity for India in The Global Biosimilars Market. 2010. [Accessed on 05 Apr 2015] Available from: http://www.pharmaphorum.com/2010/06/21/the-opportunity-for-india-in-the-global-biosimilarsmarket/
28.CDSCO. Import or manufacture of a new drug for clinical trials or marketing. 2010. [Accessed on 05 Apr 2015] Available from <http://cdsco.nic.in/html/Sec_122_A.htm
29.Ministry of Health & Family Welfare. Schedule Y - Requirements and guidelines for permission of import and / or manufacture of new drugs for sale or to undertake clinical trials. 2005. [Accessed on 05 Apr 2015] Available from http://dbtbiosafety.nic.in/act/Schedule_Y.pdf
30.Tripathi KK. General approval procedures for biotech medicines - Regulatory approaches and criteria for approvals of biotech medicines in India. 2009. [Accessed on 08 Apr 2015] Accessed from http://www.grips.ac.jp/docs/tripathi.pdf.
31.Ministry of Environment & Forests. Notification regarding adoption of the recommendations of the task force on r-pharma under the chairmanship of Dr. R A Mashelkar, DG-CSIR with effect from 1.4.2006. 2006. [Accessed on 08 Apr 2015] Available from http://envfor.nic.in/divisions/csurv/geac/rpharma_tf.pdf.
32.Subramaniam KV. India as a global leader in biosimilars, A presentation at the Biosimilars India Conference 2011, 14-15 July 2011 Mumbai, India.
33.Arnum PV. Opportunities in the Biosimilars Market. 2010. [Accessed on 05 Apr 2015] Available from:<http://pharmtech.findpharma.com/pharmtech/Ingredients/Opportunities-in-the-BiosimilarsMarket/ArticleStandard/Article/detail/660530>
34.Bourgoin A. What you need to know about the follow-on biologic market in the US: Implications, strategies and impact - competitive landscape. 2011. [Accessed on 05 Apr 2015] Available from <http://thomsonreuters.com/content/science/pdf/ls/newport-biologics.pdf
35.The New Trends of Drug Development Outsourcing in China and India. 2012. [Accessed on 06 Apr 2015] Available from:http://www.researchandmarkets.com/reports/2238850/the_new_trends_of_drug_development_outsourcing_in#pos-0[36 Ghangurde A. Biocon plans biosimilars R&D and production unit in Malaysia. 2010. [Accessed on 05 Apr 2015] Available from http://www.scripintelligence.com/business/Biocon-plans-biosimilars-RandD-and-production-unit-in-Malaysia-305021.
37.Gale J, Bhattacharjee A. Dr. Reddy's is developing eight more drugs. 2007. [Accessed on 06 Apr 2015] Available from http://www.bloomberg.com/apps/news?pid=newsarchive&sid=an605eC_iu.c&refer=home
38.Bhattacharjya AS, Sapra PK. Health Insurance In China And India: Segmented Roles For Public And Private Financing. Health Aff 2008; 27(4):1005-1015.
39.Tandon VR, Mahajan A, Khajuria V, Kapoor V. Biologics and challenges ahead for the physicians. JIACM 2006; 7(4): 334-43.
40.Dey S. 1 insulin price cap for all brands. 2012. [Accessed on 06 Apr 2015] Available from: http://www.business-standard.com/article/companies/1-insulin-price-cap-for-all-brands-112112100017_1.html.
41.WHOSIS. Global Health Observatory. 2010. [Accessed on 08 Apr 2015] Available from: <http://apps.who.int/ghodata/.
42.Joshi SR, Biosimilar peptides: Need for pharmacovigilance. J Assoc Physicians India. 2011 Apr; 59 Suppl: 44-7.
43.Joshi SR. Biosimilar insulins: Are they really 'similar'? 2009. [Accessed on 06 Apr 2015] Available from http://www.japi.org/february_2009/biosimilar_insulins.html.
44.Mody, Goradia, Gupta. How Similar Are Biosimilars In India? 2010. [Accessed on 06 Apr 2015] Available from:http://www.pharmafocusasia.com/research_development/blind-comparative-study.html.
45.Werner R. How biosimilar drugs compare to the original substance - International experts workshop on early treatment strategies for AMI. 2009. Kuala Lumpur. [Accessed on 06 Apr 2015] Available from http://www.metalyse.com/img/download/mi_news_kualalumpur2009.pdf.
46.Yang P. Roche – an innovator’s perspective and position on biosimilars. 2009. [Accessed on 06 Apr 2015] Available from < www.roche.com/irp101005.pdf
47.Patwardhan A. Dr. Reddy’s Position on Biosimilars, A presentation at the FDA Part 15 Public Hearing, November 2010.
48.Kliche W. There Is No Biosimilar ToMetalyse, A presentation at Informa Life Sciences Biosimilars Conference, 2010, June 2010.
49.FDA. Guidance for Industry: Quality Consideration in Demonstrating Biosimilarity to a Reference Protein Product. 2012a. [Accessed on 08 Apr 2015] Available from:http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291 134.pdf.
50.FDA. Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. 2012b. [Accessed on 08 Apr 2015] Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291 128.pdf.
Source of funding: None
Competing interest / Conflict of interest: The author(s) have no competing interests for financial support, publication of this research, patents and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript.
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Malipatil NB, Haridas KM, Shruthi DP. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Original article
D.DalyaThamer Ahmad*
Affiliation:
College of medicine, Al – Iraqia University, Adhamiyah, Baghdad, Iraq
The name of the department(s) and institution(s) to which the work should be attributed:
College of medicine, Al – Iraqia University, Adhamiyah, Baghdad, Iraq
Address reprint requests to
Dr.D.DalyaThamer Ahmad
College of medicine, Al–Iraqia University, Adhamiyah, Baghdad, Iraq
Article citation: Ahmad DT. Placental dysfunction disorders after prior miscarriages in a sample of Iraqi womens. J Pharm Biomed Sci. 2015; 05(06):440-448. Available at www.jpbms.info
ABSTRACT:
Objective: The aim of this study was to investigate the association between prior miscarriages and the risks of placental dysfunction disorders, including preeclampsia, stillbirth, birth of a small for gestational age (SGA) infant, placental abruption, and spontaneous preterm birth.
Study Design: In a population-based cohort study including 72 primiparous women, we estimated risks of placental dysfunction disorders for women with 1(n = 24 ), 2 (n = 20 ) and 3 or more (n = 18 ) self-reported prior miscarriages. Risks were calculated as odds ratios by unconditional logistic regression analysis and adjustments were made for maternal age, early pregnancy body mass index, smoking habits, years of formal education, in vitro fertilization, chronic hypertension, pregestational diabetes, hypothyroidism, systemic lupus erythematosis and fetal sex .
Results: Compared with women with no prior miscarriage, women with 1 prior miscarriage had almost no increased risks. Women with 2 prior miscarriages had increased risks of spontaneous preterm birth, preterm (<37 weeks) SGA infant, and placental abruption. The rates of all disorders were higher for women with 3 or more prior miscarriages compared with women without prior miscarriages: preeclampsia, 50% vs 30%; stillbirth, 22.22 % vs 0%, SGA infant, 22.22 % vs 10 %, placental abruption, 27.78 % vs 10 %; and spontaneous preterm birth, 27.78 % vs 10 %. The adjusted odds ratios for preterm (<37 weeks) disorders in women with 3 prior miscarriages were approximately 3.4, neonatal death, 11.11 % vs 0%.
Conclusion: History of 2 or more miscarriages is associated with an increased risk of placental dysfunction disorders and should be regarded as a risk factor in antenatal care
KEYWORDS: Intrauterine growth restriction; miscarriage; placental abruption; preeclampsia, spontaneous preterm birth; stillbirth.
REFERENCES
1.Julia Shelley. Miscarriage and time to next pregnancy : British Medical Journal 2010;341:c4181.
2.Eleanor R Love, Siladitya Bhattacharya, Norman C Smith, Sohinee Bhattacharya. Research Effect of interpregnancy interval on outcomes of pregnancy after miscarriage: retrospective analysis of hospital episode statistics in Scotland.BMJBritish Medical Journal, 2010;341:c3967.
3.Brosens, I., Pijnenborg, R., Vercruysse, L., and Romero, R. The “Great Obstetrical Syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol. 2011; 204: 193–201.
4.Jivraj, S., Anstie, B., Cheong, Y.C., Fairlie, F.M., Laird, S.M., and Li, T.C. Obstetric and neonatal outcome in women with a history of recurrent miscarriage: a cohort study. Hum Reprod. 2001; 16: 102–106.
5.Weintraub, A.Y., Sergienko, R., Harlev, A. et al. An initial miscarriage is associated with adverse pregnancy outcomes in the following pregnancy. Am J Obstet Gynecol. 2011; 205: 286.E1–286.E5.
6.Sheiner, E., Levy, A., Katz, M., and Mazor, M. Pregnancy outcome following recurrent spontaneous abortions. Eur J ObstetGynecolReprod Biol. 2005; 118: 61–65.
7. Oliver-Williams C, Fleming M, Wood AM, Smith GCS. Previous miscarriage and the subsequent risk of preterm birth in Scotland, 1980–2008: a historical cohort study. BJOG 2015; DOI: 10.1111/1471-0528.13276.
8.Buchmayer, S.M., Sparén, P., and Cnattingius, S. Previous pregnancy loss: risks related to severity of preterm delivery. Am J Obstet Gynecol. 2004; 191: 1225–1231.
9.Cara Bicking Kinsey, Kesha Baptiste-Roberts, Junjia Zhu, Kristen H. Kjerulff .Effect of Previous Miscarriage on the Maternal Birth Experience in the First Baby Study.JOGNN . Journal of Obstetric, Gynecologic, & Neonatal Nursing . 2013; 42: 4: 442–450.
10.Rasmussen, S. and Irgens, L.M. History of fetal growth restriction is more strongly associated with severe rather than milder pregnancy-induced hypertension. Hypertension. 2008; 51: 1231–1238.
11.Wikstrom, A.K., Stephansson, O., and Cnattingius, S. Previous preeclampsia and risks of adverse outcomes in subsequent nonpreeclamptic pregnancies. Am J Obstet Gynecol. 2011; 204: 148.e1–148.e6.
12.Kulandavelu, S., Whiteley, K.J., Bainbridge, S.A., Qu, D., and Adamson, S.L. Endothelial NO synthase augments fetoplacental blood flow, placental vascularization, and fetal growth in mice. Hypertension. 2013; 61: 259–266.
13.Espinoza, J., Uckele, J.E., Starr, R.A., Seubert, D.E., Espinoza, A.F., and Berry, S.M. Angiogenic imbalance: the obstetric perspective. Am J Obstet Gynecol. 2010; 203: 17.e1–17.e8.
14.Torry, D.S., Leavenworth, J., Chang, M. et al. Angiogenesis in implantation. J Assist Reprod Genet. 2007; 24: 303–315.
15.Rabbani, M.L. and Rogers, P.A. Role of vascular endothelial growth factor in endometrial vascular events before implantation in rats. Reproduction. 2001; 122: 85–90.
16.Plaisier, M. Decidualisation and angiogenesis. Best Pract Res ClinObstetGynaecol. 2011; 25: 259–271.
17.Plaisier, M., Dennert, I., Rost, E., Koolwijk, P., van Hinsbergh, V.W., and Helmerhorst, F.M. Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions. Hum Reprod. 2009; 24: 185–197. 18.Jauniaux, E., Hempstock, J., Greenwold, N., and Burton, G.J. Trophoblastic oxidative stress in relation to temporal and regional differences in maternal placental blood flow in normal and abnormal early pregnancies. Am J Pathol. 2003; 162: 115–125.
19.Su, M.T., Lin, S.H., and Chen, Y.C. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod Update.2011; 17: 803–812
20.Galazios, G., Papazoglou, D., Tsikouras, P., and Kolios, G. Vascular endothelial growth factor gene polymorphisms and pregnancy. J Matern Fetal Neonat. 2009; 22: 371–378.
21.Bhattacharya, S., Townend, J., Shetty, A., and Campbell, D. Does miscarriage in an initial pregnancy lead to adverse obstetric and perinatal outcomes in the next continuing pregnancy?.BJOG. 2008; 115: 1623–1629.
22.Basso, O., Olsen, J., and Christensen, K. Risk of preterm delivery, low birthweight and growth retardation following spontaneous abortion: a registry-based study in Denmark. Int J Epidemiol. 1998; 27: 642–646.
23.Trogstad, L., Magnus, P., Skjaerven, R., and Stoltenberg, C. Previous abortions and risk of pre-eclampsia.Int J Epidemiol. 2008; 37: 1333–1340.
24.El-Bastawissi AY, Sorensen TK, Akafomo CK, Frederick IO, Xiao R, Williams MA. History of fetal loss and other adverse pregnancy outcomes in relation to subsequent risk of preterm delivery.Matern Child Health J. 2003 Mar;7(1):53-8.
25.Hammoud AO, Merhi ZO, Diamond M, Baumann P. Recurrent pregnancy loss and obstetric outcome. Int J GyneacolObstet 2007;96:28-29.
26.McCarthy FP1, Khashan AS, North RA, Rahma MB, Walker JJ, Baker PN, Dekker G, Poston L, McCowan LM, O'Donoghue K, Kenny LC. Pregnancy loss managed by cervical dilatation and curettage increases the risk of spontaneous preterm birth. Humrep 2013 Dec;28(12):3:197-206.
27. R.H.F. van Oppenraaij, E. Jauniaux, O.B. Christiansen, J.A. Horcajadas, R.G. Farquharson and N. Exalto1,6 on behalf of the ESHRE Special Interest Group for Early Pregnancy (SIGEP). Predicting adverse obstetric outcome after early pregnancy events and complications. Oxford Journals2009 ;15; 4: 409-421.
28.Lang JM, Lieberman E, Cohen A. A comparison of risk-factors for preterm labor and term small-for-gestational-age birth. Epidemiology 1996;7:369-376.
29.Voigt M1, Olbertz D, Fusch C, Krafczyk D, Briese V, Schneider KT . The influence of previous pregnancy terminations, miscarriages and still-births on the incidence of babies with low birth weight and premature births as well as a somatic classification of newborns . Z GeburtshilfeNeonatol [Article in German]. 2008 Feb;212(1):5-12.
30.Moreau C, Kaminski M, Ancel PY, Bouyer J, Escande B, Thiriez G, Boulot P, Fresson J, Arnaud C, Subtil D, et al.; EPIPAGE Group. Previous induced abortions and the risk of very preterm delivery: results of the EPIPAGE study. Br J ObstetGynaecol 2005;112:430-437.
31.Raatikainen K, Heiskanen N, Heinonen S. Induced abortion: not an indepedent risk factor for pregnancy outcome, but a challenge for health counselling. Ann Epidemiol 2006;16:587-592.
32.Parazzini F, Cipriani S, Chiaffarino F, Sandretti F, Bortolus R, Chiantera V. Induced abortion and risk of small-for-gestational-age birth. Br J ObstetGynaecol 2007;114:1414-1418.
33.Reime B, Schücking BA, Wenzlaff P. Reproductive outcomes in adolescents who had a previous birth or an induced abortion compared to adolescents’ first pregnancies. BMC Pregnancy Childbirth 2008;31:4.
Source of funding: None
Statement of Originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
Competing interest / Conflict of interest: The author(s) have no competing interests for financial support, publication of this research, patents and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript.
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Ahmad DT. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Case report
Tanima Bose, PhD*
Affiliation:
Leibniz Institute for Neurobiology, Brenneckestrasse 6, D-39118 Magdeburg, Germany
The name of the department(s) and institution(s) to which the work should be attributed:
Leibniz Institute for Neurobiology, Brenneckestrasse 6, D-39118 Magdeburg, Germany
Address reprint requests to
Tanima Bose, PhD
Leibniz Institute for Neurobiology,
Brenneckestrasse 6, D-39118 Magdeburg, Germany
Article citation: Bose T. Azathiorpine-induced Idiosyncratic Liver-injury. J Pharm Biomed Sci. 2015; 05(06):449-452. Available at www.jpbms.info
ABSTRACT:
Autoimmune hepatitis is a rare autoimmune disorder. The regular treatments for this disease is the administration of regular immunosuppressants like Azathiorpine, Metabolic Mycophenolic Acid in addition to steroids. The adverse effects of these immunosuppressants are poorly described in the literature. Here is the description of one case report where the patient had maximum level of severity of autoimmune hepatitis within weeks of exposure to Azathiorpine.
KEYWORDS: Autoimmune hepatitis; Azathiorpine.
ACKNOWLEDGEMENT
I would like to acknowledge Dr. Subhra Mandal, Nijmegen, Netherlands for her continuing support in writing this Case Report. There is no source of funding for this work. There is no financial conflict with the subject matter discussed in the manuscript.
REFERENCES
1.Watanabe A, Hobara N, Tobe K, Endo H, Nagashima H. Biochemical and morphological study on hepatotoxicity of azathioprine in rat. Acta medica Okayama 1979, 33(1): 5-14.
2.Okan G, Vural P, Peker O, Colakoglu E, Saruc M. Azathioprine-induced liver injury in a patient with multiple autoimmune syndrome. The Journal of dermatological treatment 2010, 21(6): 357-360.
3.Du Vivier A, Munro DD, Verbov J. Treatment of psoriasis with azathioprine. British medical journal 1974, 1(5897): 49-51.
4.Harvey C, Dixon JS, Bird HA. Serum IgA concentration and hepatotoxicity in rheumatoid arthritis treated with azathioprine. Br Med J (Clin Res Ed) 1983, 287(6391): 534.
5.Blogowski W, Marlicz W, Smereczynski A, Lawniczak M, Lewosiuk A, Starzynska T. Nodular regenerative liver hyperplasia as a complication of azathioprine-containing immunosuppressive treatment for Crohn's disease. Immunopharmacology and immunotoxicology 2011, 33(2): 398-402.
6.Lopez-Martin C, Chaparro M, Espinosa L, Bejerano A, Mate J, Gisbert JP. Adverse events of thiopurine immunomodulators in patients with inflammatory bowel disease. Gastroenterologia y hepatologia 2011, 34(6): 385-392.
7.Ware AJ, Luby JP, Hollinger B, Eigenbrodt EH, Cuthbert JA, Atkins CR, et al. Etiology of liver disease in renal-transplant patients. Annals of internal medicine 1979, 91(3): 364-371.
8.Ramalho HJ, Terra EG, Cartapatti E, Barberato JB, Alves VA, Gayotto LC, et al. Hepatotoxicity of azathioprine in renal transplant recipients. Transplantation proceedings 1989, 21(1 Pt 2): 1716-1717.
9.Lemarchand P, Desrumeaux B, Bercoff E, Manchon ND, Chassagne P, Deshayes P, et al.Cholestasis and sinusoidal dilatation following treatment with azathioprine. Gastroenterologie clinique et biologique 1986, 10(12): 853-854.
10.Barrowman JA, Kutty PK, Ra MU, Huang SN. Sclerosing hepatitis and azathioprine. Digestive diseases and sciences 1986, 31(2): 221-222.
Statement of Originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
Source of funding: None
Competing interest / Conflict of interest: The author(s) have no competing interests for financial support, publication of this research, patents and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript.
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Bose T. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Original article
Dakshita Joy Sinha1, Agrima Vasudeva2,*, Owais Gowhar2,¥ , Paridhi Garg2,¥,Ashish Sinha1,±, Prem Prakash2
Affiliation:
1Reader, Department of Conservative Dentistry and Endodontics, Kothiwal Dental College and Research centre, Moradabad, Uttar Pradesh-244001, India
2PG student, Department of Conservative Dentistry and Endodontics, Kothiwal Dental College and Research Centre, Moradabad, Uttar Pradesh-244001, India
2,¥PG student, Department of Oral Pathology and Microbiology, Kothiwal Dental College and Research Centre, Moradabad, Uttar Pradesh-244001, India
1,±Reader, Department of Pedodontics, Kothiwal Dental College and Research Centre, Moradabad, Uttar Pradesh-244001, India
The name of the department(s) and institution(s) to which the work should be attributed:
Kothiwal Dental College and research centre, Moradabad, Uttar Pradesh-244001, India
Address reprint requests to
Dr. Agrima Vasudeva*.
PG student, Department of Conservative Dentistry and Endodontics, Kothiwal dental college and research centre, Moradabad, Uttar Pradesh-244001 or at agvasu2000@yahoo.com
Article citation:
Sinha DJ, Vasudeva A, Gowhar O, Garg P, Sinha A, Prakash P. Comparison of antimicrobial efficacy of Propolis, Azadirachta indica (Neem), Melaleuca alternifolia (Tea tree oil), Curcuma longa (Turmeric) and 5% Sodium hypochlorite on Candida albicans biofilm formed on tooth substrate: An in-vitro study. J Pharm Biomed Sci. 2015; 05(06):469-474. Available at www.jpbms.info
ABSTRACT:
Aim: To determine the antimicrobial efficacy of Propolis, Azadirachta indica (Neem), Melaleuca alternifolia (Tea tree oil) ,Curcuma longa(Turmeric) and 5% Sodium hypochlorite on Candida albicans biofilm.
Materials and methods: Extracted human mandibular premolars were biomechanically prepared, vertically sectioned, placed in tissue culture wells exposing the root canal surface to C. albicans grown on Sabouraud Dextrose Agar to form a biofilm. At the end of 2 days, all groups were treated with test solutions and control for 10 min and evaluated for Candida growth and number of colony forming units were calculated. The readings were subjected to statistical analysis using ANOVA and Tukey’s post hoc test. Results: Sodium hypochlorite and propolis groups exhibited highest antimicrobial efficacy against C. albicans with no statistically significant difference. It was followed by Melaleuca alternifolia (Tea tree oil), Curcuma longa(turmeric) group. A.india (Neem) had limited antifungal action followed by the negative control group of saline. Conclusion: According to the results of this study, propolis can be used as an effective antifungal agent similar to that of sodiumhypochlorite, although long-term in vivo studies are warranted.
KEYWORDS: Antimicrobial efficacy; Azadirachta indica; Candida albicans; Curcuma longa; Melaleuca alternifolia; propolis.
References:
1.Saleh IM, RytlerLE, HaapasaloD. Survival of Enterococcus faecalis in infected dentinal tubules after root canal filling with different root canal sealers: in vitro study. J Endod 2004 37;193-198.[PubMed]
2 Lee Y1, Han SH, Hong SH, Lee JK, Ji H, Kum KY. Antimicrobial efficacy of a polymeric chlorhexidine release device using in vitro model of Enterococcus faecalis dentinal tubule infection. J Endod 2008;34:855-858.[PubMed]
3.Hess W. Anatomy of root canals in the teeth of permanent dentition. New York: William Wood & co.1925: 82-85.
4.Baumgartner JC, Watts CM, Xia T. Occurrence of Candida albicans in infections of endodontic origin. J Endod 2000;26 :695-698.[PubMed]
5.Siqueira JF Jr., Rôças IN. Diversity of endodontic microbiota revisited. J Dent Res 2009;88: 969-981. doi: 10.1177/0022034509346549.[PubMed]
6.Waltimo TM, Haapasalo M, Zehnder M, Meyer J. Clinical aspects related to endodontic yeast infections. Endod Topics2004;9:66-78.
7.Spangberg L, Engström B, Langeland K. Biologic effects of dental materials. 3. Toxicity and antimicrobial effect of endodontic antiseptics in vitro. Oral Surg Oral Med Oral Pathol 1973;36: 856-871.[Pubmed]
8.McComb D, Smith DC.A preliminary scanning electron microscopic study of root canals after endodontic procedures. J Endod1975; 1:238-242.[PubMed]
9.Mohammadi Z. Sodium hypochlorite in endodontics: An update review. Int Dent J 2008; 58: 329-341.[PubMed]
10.Vermani K, Garg S. Herbal medicines for sexually transmitted diseases and AIDS. J Ethnopharmacol 2002; 80: 49-66.[PubMed]
11.Hyun Koo, Pedro L. Rosalen, Jaime A. Cury, Yong K. Park, and William H. Bowen. Effects of Compounds Found in Propolis on Streptococcus mutans Growth and on Glucosyltransferase activity. Antimicrob Agents Chemother2002 ;46: 1302-1309.
12.OzantOncag, Dilsah Cogulu, AtacUzel, KadriyeSorkun. Efficacy of propolis as an intracanal medicament against Enterococcus faecalis. Gen Dent 2006;.54: 319-322.[Pubmed]
13.Subapriya R, Nagini S. Medicinal properties of neem leaves: A review. Curr Med Chem Anticancer Agents 2005; 5:149-156.[PubMed]
14.Sadr Lahijani MS, RaoofKateb HR, Heady R, Yazdani D. The effect of German chamomile [Marticariarecutitia L.] extract and tea tree [ Melaleucaalternifolia L.] oil used as irrigants on removal of smear layer: a scanning electron microscopy study. IntEndod 2006; 39:190-195.[PubMed]
15.Chaturvedi TP. Uses of turmeric in dentistry –an update. Indian J Dent Res 2009; 20:107-109.[PubMed]
16.NeelakantanP, Subbarao C, Subbarao CV. Analysis of Antibacterial Activity of Curcumin against Enterococcus faecalis. Int J Curr Res Rev 2011; 3: 37-42.
17.Shingare P, Chaugule V. Comparative evaluation of antimicrobial activity of miswak, propolis, sodium hypochlorite and saline as root canal irrigants by microbial culturing and quantification in chronically exposed primary teeth. Germs 2011;1:12-21.[PubMed]
18.Irshad S , Butt M, Younis H. In-Vitro antibacterial activity of two medicinal plants Neem (Azadirachta indica) and Peppermint Intl. R. J. of Pharmaceuticals 2011;1: 9-14.
19.Garg P, Tyagi SP, Sinha DJ, Singh UP, Malik V, Maccune ER. Comparison of antimicrobial efficacy of propolis, Morindacitrifolia, Azadirachta indica, triphala, green tea polyphenols and 5.25% sodium hypochlorite against Enterococcus faecalis biofilm. Saudi Endod J 2014;4:122-7.[PDF]
20.JhaHarit, Anand Barapatre, Mithlesh Prajapati, Keshaw Ram Aadil and Sunil Senapati. Antimicrobial Activity of rhizome of selected Curcuma Variety. Int J Life Sc Bt & Pharm Res 2013; 2:183-189.
21.Uday Kamath, Hina Sheth, Sai Ramesh, Keshav Singla. Comparison of the Antibacterial Efficacy of Tea Tree Oil with 3% Sodium Hypochlorite and 2% Chlorhexidine against E. faecalis: An in vitro Study. J Contemp Dent 2013 ;3: 117-20.[PDF]
22.Pujar M, Patil C, Kadam A. Comparison of antimicrobial efficacy of triphala, green tea polyphenols and 3% of sodium hypochlorite on Enterococcus faecalis biofilms formed on tooth substrate: In vitro. JIOH 2011; 3: 23-29.[PDF]
23. Prabhakar J, Senthilkumar M, Priya MS, Mahalakshmi K, Sehgal PK, Sukumaran VG.Evaluation of antimicrobial efficacy of herbal alternatives (Triphala and green tea polyphenols), MTAD, and 5% sodium hypochlorite against Enterococcus faecalis biofilm formed on tooth substrate: an in vitro study.J Endod. 2010 Jan;36(1):83-6. doi: 10.1016/j.joen.2009.09.040. [PubMed]
24.Baillie GS,DouglasLJ.Role of dimorphism in the development of Candida albicans biofilms. J Med Microbiol 1999;48: 671-679.[PubMed]
25.Nikawa H, Nishimura H, Hamada T, Makihira S, Samaranayake LP. Relationship between thigmotropism and candida biofilm formation in vitro. Mycopathologia 1998;144:125-129.[PubMed]
26.Davies JM, Stacey AJ, Gilligan CA. Candida albicanshyphal invasion: Thigmotropism or chemotropism? FEMS Microbiol Lett1999;171:245-249.[PubMed]
27.Ayhan H, Sultan N, Cirak M, Ruhi MZ, Bodur H. Antimicrobial effects of various endodontic irrigants on selected microorganisms. IntEndod J 1999;32: 99-102.[PubMed]
28. Vinothkumar TS, Rubin MI, Balaji L, Kandaswamy D. In vitro evaluation of five different herbal extracts as an antimicrobial endodontic irrigant using real time quantitative polymerase chain reaction. J Conserv Dent 2013;16:167-70.[HTML]
29.Takaisi-Kikuni NB, Schilcher H. Electron microscopic and microcalorimetric investigations of the possible mechanism of the antibacterial action of a defined propolis provenance. Planta Med 1994;60:222-227.[PubMed]
30.Kujumgiev A, Tsvetkova I, Serkedjieva Y, Bankova V, Christov R, Popov S. Antibacterial, antifungal and antiviral activity of propolis of different geographic origin. J Ethnopharmacol 1999; 64:235-240.[PubMed]
31.Ivančajić S, Mileusnić I, Milošević DC. In vitro antibacterial activity of propolis extracts on 12 different bacteria in conditions of 3 various pH values. Arch BiolSci Belgrade 2010;62:915-934.
32.Tyagi SP, Sinha DJ, Garg P, Singh UP, Mishra CC, Nagpal R. Comparison of antimicrobial efficacy of propolis, Morindacitrifolia, Azadirachtaindica(Neem) and 5% sodium hypochlorite on Candida albicansbiofilm formed on tooth substrate: An in-vitro study. J Conserv Dent. 2013 Nov;16(6):532-5. doi: 10.4103/0972-0707.120973.[PubMed]
33.Polaquini SR, Svidzinski TI, Kemmelmeier C, Gasparetto A. Effect of aqueous extract from neem (Azadirachtaindica A. Juss) on hydrophobicity, biofilm formation and adhesion in composite resin by Candida albicans. Arch Oral Biol 2006;5:482-490.[PubMed]
34.Nayak A, Nayak RN, Soumya GB, Bhat K, Kudalkar M. Evaluation of antibacterial and anticandidal efficacy of aqueous and alcoholic extract of neem (Azadirachta indica): An in vitro study. IJRAP 2011;2: 230-235.
35.Bohora A, Hedge V, Kokate S. Comparison of the antibacterial efficiency of neem leaf extract and 2% sodium hypochlorite against E. faecalis, C.albicans and mixed culture - An in vitro study. Endodontology 2010; 22: 8-12.
36.Cox, S. D., C. M. Mann, and J. L. Markham. Interactions between components of the essential oil of Melaleucaalternifolia. J. Appl. Microbiol 2001;.91:492–497.[PubMed]
37.D’Auria, F. D., L. Laino, V. Strippoli, M. Tecca, G. Salvatore, L. Battinelli,and G. Mazzanti. In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi. J. Chemother 2001;13:377–383.[PubMed]
38.Hammer, K. A., C. F. Carson, and T. V. Riley. Melaleuca alternifolia (tea tree) oil inhibits germ tube formation by Candida albicans. Med. Mycol 2010;38:355–362.[PubMed]
39.Nadia G, Talat Y M, Nayyar J, Samia A. Studies On The Antibacterial Effect Of Different Fractions Of Curcuma Longa Against Urinary Tract Infection Isolates. Pak J Bio Sci. 2004; 7: 2055-2060.
Statement of Originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
Competing interest/Conflict of interest: The author(s) have no competing interests for financial support, publication of this research, patents and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript.
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Sinha DJ, Vasudeva A, Gowhar O, Garg P, Sinha A, Prakash P. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Case report
Bharath Bhushan1, Anju Bhushan1,*, Elizabeth Moirangthem1±, Nitin Sharma1,¥,
Neha Bhargava1,£, Tarun Sethi1,£, Chiranjeev Saini1,≠
Affiliation:
1Professor and Head of Department of Pediatric and Preventive Dentistry,1,*Professor and Head of Department of Oral Pathology and Microbiology,1,±Post Graduate Student, Department of Pediatric and Preventive Dentistry,1,¥ Reader, Department of Pediatric and Preventive Dentistry, 1,£Senior Lecturer, Department of Pediatric and Preventive Dentistry, 1,£Senior Lecturer, Department Of Pediatric and Preventive Dentistry, 1,≠Post Graduate Student, Department of Orthodontics and Dentofacial Orthopedics, Rajasthan Dental College and Research Centre, Bagru Khurd, Jaipur, NH-8, Rajasthan, India
The name of the department(s) and institution(s) to which the work should be attributed:
Rajasthan Dental College and Research Centre, Bagru Khurd, Jaipur, Nh-8, Rajasthan, India
Address reprint requests to
*Dr Elizabeth Moiranthem.
Rajasthan Dental College and Research Centre,
Girls Hostel, Bagru Khurd, Jaipur, Nh-8, India
Article citation: Bhushan B, Bhushan A, Moirangthem E, Sharma N, Bhargava N, Sethi T et al. Peripheral ossifying fibroma in mandible: A rare case report. J Pharm Biomed Sci. 2015; 05(06):475-479. Available at www.jpbms.info
ABSTRACT:
Peripheral ossifying fibroma is one of many localized reactive lesions occurring on the gingiva which includes focal fibrous hyperplasia, pyogenic granuloma and peripheral giant cell granuloma. It is a solitary overgrowth of the gingiva known to arise from the cells of the periodontal ligament. As lesions with similar clinical presentation makes it difficult to diagnose, it makes histo-pathological investigation essential to positively identify the lesion. The present case report highlights the diagnosis and management of peripheral ossifying fibroma in the anterior mandible region of a female child patient.
KEYWORDS: Peripheral ossifying fibroma; calcification; central-ossifying fibroma.
REFERENCES
1.Varshal J. Barot, SarathChandran, Shivlal L. Vishnoi. Peripheral ossifying fibroma: A case report. Journal of Indian Society of Periodontology 2013; 17(6) Nov-Dec
2.Eversole LR, Rovin S. Reactive lesions of the gingiva. J Oral Pathol 1972;1:30‑8.
3.Jose A. Garcia de Marcos, Maria J. Garcia de Marcos, Susana Arroyo Rodriguez, Jaime ChiarriRodrigo.Peripheral ossifying fibroma: A clinical and immunohistochemical study of four cases. Journal of Oral Science 2010; 52(1):95-99.
4.Nazareth, B, Arya, H, Ansari, S & Arora, R. Peripheral ossifying fibroma: A clinical report. Int. J. Odontostomat 2011;5(2):153-156.
5.K. S. Poonacha, Anand L. Shigli, DayanandShirol. Peripheral ossifying fibroma: A clinical report. Contemporary Clinical Dentistry 2010 1(1)Jan-Mar.
6.TrasadVA ,Devarsa GM, Subba Reddy VV, Shashikiran ND. Peripheral ossifying fibroma in the maxillary arch. Journal of Indian Society of Pedodontics and Preventive Dentistry 2011; 29(3) Jul – Sept.
7.Kumar SK, Ram S, Jorgensen MG, Shuler CF, Sedghizadeh PP. Multicentric peripheral ossifying fibroma. J Oral Sci 2006;48:239-43.
8.Santosh Hunasgi, VandanaRaghunath. A Clinicopathological Study of Ossifying Fibromas and Comparison between Central and Peripheral Ossifying Fibromas. The Journal of Contemporary Dental Practice 2012;13(4):509-514 July-August.
9.Merin George, S Karthigakannan, Giju Baby George, Renji K Paul, Leena Johnson Arakkal, Sam Jose. Journal of Indian Academy of Oral Medicine and Radiology, October-December 2013;25(4):330-332.
10.Srikanth A Choudary, Archana R Naik, Madhukeshwara S Naik, Anvitha D. Multicentric variant of peripheral ossifying fibroma. Indian Journal of Dental Research, 2014;25(2).
11.Sumona Pal,ShruthiHegde,VidyaAjila. The varying clinical presentations of peripheral ossifying fibroma: A report of three cases. Rev Odonto Cienc 2012;27(3):251-255.
12.NehaBhargava,Gaurav Gupta,Manohar Bhat,Farzan Rahman, Rajesh Sharma. A paediatric gingival over growth. A tickling time bomb. Indian J Stomatol, 2013;4(1) 54-57.
Statement of Originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
Source of funding: None
Competing interest / Conflict of interest: The author(s) have no competing interests for financial support, publication of this research, patents and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript.
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Bhushan B,Bhushan A,Moirangthem E,Sharma N,Bhargava N,Sethi T et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.