DocumentsDate added
Original article
Aslam Mohd.a, Maurya Shesh Prakash b*, Khan Shadab Ahmed c,
Habib Anwar d, Das Ashimae,Mehrotra Ginni f
Affiliation:-
a,b,e SHKM Government Medical College, Mewat, Haryana, India
c,dJawahar Lal Nehru Medical College, Aligarh, India
fInstitute of IBSBT, CSJM University, Kanpur, India.
Author’s contributions- Aslam Mohd contributes towards concept, design, literature search, clinical studies, data acquisition, statistical analysis, manuscript writing and editing. Maurya Shesh Prakash helps in literature search, data analysis, manuscript editing, and writing. Khan Shadab Ahmed and Habib Anwar contribute towards data analysis and manuscript review. Das Ashima & Mehrotra Ginni analysed, collected the data and helped in manuscript writing.
Abstract:
Background and objectives: Stroke is a worldwide health problem and contributes significantly to morbidity and mortality. Currently prevention of stroke is the best treatment. Once a stroke has occurred, then major goal in the treatment of acute ischemic stroke is to minimize the irreversible brain damage. One strategy of preserving neuronal function is to increase cerebral blood flow. Use of calcium antagonists during the “open therapeutic window” may result in neuronal function improvement. This study endeavours to establish therapeutic role of Nimodipine in acute ischemic stroke.
Material and methods: The study was carried out in 75 patients of acute Ischemic stroke over a period of 1 year. Patients were randomly allocated to receive either nimodipine (120 mg/day) orally within 24 hrs of stroke onset or only best medical care consisting of antithrombotics. Neurological deficit was assessed using modified Mathew scale at admission and then on 3rd and 7th day. The patients comprised of two groups with score of either >65 or ≤65.
Results: Total numbers of patients with score ≤65 were 39 out of which 20 patients received nimodipine. There was no significant improvement on giving nimodipine on the 3rd day of admission (P>0.05), but there was significant improvement on the 7th day ((P<0.05). Total number of patients with base line score of >65 were 36 out of which 20 patients received nimodipine. There was no significant improvement either on the 3rd (P>0.05) or 7th (P>0.05) day.
Conclusion: These results suggest that patients of acute ischaemic stroke would benefit from nimodipine if started as early as possible.
Keywords:Calcium channel antagonists, Ischemic stroke, Modified Mathew scale, Nimodipine.
Article citation:-
Aslam Mohd. et al. Therapeutic role of Nimodipine in acute ischemic stroke. Journal of pharmaceutical and biomedical sciences (J Pharm Biomed Sci.) 2013 August; 33(33): 1577-1581 .Available at http://www.jpbms.info
Copyright © 2013 Aslam Mohd. 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.
Original article
M. A. Salama*, Md. Azharul Arafathb & M. A. Affanc
Affiliation:-
aBangladesh Petroleum Exploration and Production Co. Ltd. (BAPEX), 80/A-B, Siddeshwari Circular Road, Malibag, Dhaka-1217, Bangladesh.
bDepartment of Chemistry, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh.
cFaculty of Resource Science and Technology, Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak, Malaysia.
Author’s contributions-All authors contributed equally to this paper.
Abstract:
Four new tin(IV)/organotin(IV) complexes with 2-acetylpyridine-N(4)-cyclohexylthiosemicarbazone [(HL), (1)] of the type [SnCl3(L)] (2), [MeSnCl2(L)] (3), [BuSnCl2(L)] (4) and [PhSnCl2(L)] (5) have been synthesized in 1:1 molar ratio. All tin(IV)/organotin(IV) complexes were characterized by elemental analyses, molar conductivity, UV-Vis, FT-IR, 1H, 13C and 119Sn NMR spectral studies. The molecular structure of complex 4 has been determined by X-ray single crystal diffraction analyses. Its X-ray structure revealed that there are two independent molecules in the asymmetric unit and the central tin(IV) atom is six-coordinate in distorted octahedral geometry. In all the complexes, tin(IV) was coordinated via pyridine-N, azomethine-N, and thiolato-S from uninegative tridentate ligand (1). The synthesized ligand (1) and its tin(IV)/organotin(IV) complexes (2-5) were screened for their in vitro antibacterial activity. The antibacterial results indicated the profound activity of the compounds (2-5) against various strains of bacteria. Among the compounds, phenyltin(IV) derivative (5) was found more active than other compounds (1-4).
Keywords: 2-acetylpyridine-N(4)-cyclohexyl thiosemicarbazone; Tin (IV)/organotin (IV) complexes; Spectral analyses; Crystal structure; Antibacterial activity.
REFERENCES
1.Wang, B. D.,Yang,Z.Y.,Lü,M.H.,Hai,J., Wang, Q., Chen, Z. N. J. Organomet. Chem. 2009; 694:4069-4075.
2.Baldini, M.,Ferrari, M. B., Bisceglie, F,Pelosi, G.,Pinelli, S.,Tarasconi,P.Inorg.Chem.2003;42:2049-2055.
3.Padhye, S.,Afrasiabi, Z.,Sinn, E.,Fok, J.,Mehta, K., Rath, N. Inorg.Chem.2005;44:1154-1156.
4.Padhye,S.B.,Kauffman,G.B.Coord.Chem. Rev.1985;63:127-160.
5.West, D.X.,Liberta, A.E.,Padhye,S.B.,Chikate, R.C.,Sonawane,P.B.,Kumbhar, A.S.,Xerande,R.G.Coord.Chem. Rev. 1993;123:49-71.
6.Baldini, M.,Belicchi-Ferrari, M.,Bisceglie, F.,Pelosi, G., Pinelli, S.,Tarasconi,P. Inorg.Chem.2003;42:2049-2055.
7.Padhye, S., Afrasiabi, Z., Sinn, E.,Fok,J.,Mehta,K., Rath, N. Inorg. Chem. 2005;44;1154-1156.
8.Kowol,C.R.,Trondl,R.,Heffeter,P.,Arion, V.B.,Jakupec, M.A.,Roller,A.,Galanski, M.,Berge,W.,Kepple,B.K.J.Med. Chem. 2009;52:5032-5043.
9.Blower,P.J.,Ditworth,J.R.Coord. Chem.Rev.1987;76:121-185.
10.Winter, G.Inorg.Chem. Rev.1980;2:253-342.
11.Hill J.O.,Magee, R.J. Inorg. Chem.Rev.1981;3:141-197.
12.Lin, X., Liu, Q., Chen Z., Wang, D. J. Rare Earths 2007; 25:396-400.
13.Teoh, S. G., Ang, S. H., Fun, H. K., Ong, C. W. J. Organomet. Chem. 1999; 580: 17-21.
14.Gielen, M., Biesemans, M., Willen, R. Appl. Organomet. Chem. 2005;19:440-450.
15.Momeni, B. Z., Shahbazi, S., Khavasi, H. R. Polyhedron 2010;29:1393-1398.
16.Wiecek, J., Dokorou, V., Zbigniew, C., Kovala-Demertzi, D. Polyhedron 2009;28: 3298-3304.
17.Choudhary, M. I., Abbas, G., Ali, S., Shuja, S., Khalid, N., Khan, K. M., Rahman, A., Basha, F. Z. J. Enzyme Inhib. Med. Chem. 2011;26:98-103.
18.Shujah, S., Rehman, Z., Muhammad, N., Ali, S., Khalid, N., Tahir, M. N. J. Organomet Chem. 2011;696:2772-2781.
19.Beraldo, H., Gambino, D. Mini Rev. Med. Chem, 2004;4:31-39.
20.Li, M. X., Zhang, D., Zhang, L. Z., Niu, J. Y., Ji, B.S.J. Organomet. Chem. 2011;696: 852-858.
21.Salam, M. A., Affan, M. A., Ahmad, F. B., Hitam, R. B.,Gal, Z., Oliver, P. J. Coord. Chem. 2011;64: 2409-2418.
22.Affan, M. A., Salam, M. A., Ahmad, F. B., Ismai, J.,Shamsuddin, M. B., Ali, H. M. Inorg. Chim Acta 2011; 366: 227-232.
23.Affan, M. A., Salam, M. A., Ahmad, F. B., Hitam, R. B., White, F. Polyhedron 2012;33: 19–24.
24.Armarego, W. L. F., Perrin, D. D. Purification of Laboratory Chemicals 4th Edition Butterworth-Heineman Publication: Great Britain (1996).
25.Rahman, A., Choudry, M. I., Thomsen, W. J. Bioassay Techniques for Drug Development, Harwood Academic Publishers, The Netherlands, 2001.
26.Sharaby,C. M. Spectrochim. Acta A 2007;66:1271-1278.
27.Rebolledo, A. P., de Lima, G. M., Gambi, L. N., Speziali, N. L., Maia, D. F., Pinheiro, C. B., Ardisson, J. D.,Corte´s, M. E., Beraldo, H. Appl. Organomet. Chem. 2003; 17: 945- 951.
28.Maurya, R. M., Jayaswal, M. N., Puranik, V. G., Chakrabarti, P., Gopinathan, S., Gopinathan, C. Polyhedron 1997;16: 3977-3983.
29.Costa, F. F., Rebolledo, A. P., Matencio, T., Calado, H. D. R., Ardisson, J. D., Cortes, M. E., Rodrigues, B. L., Beraldo, H. J. Coord. Chem. 2005;58: 1307-1319.
30.Garg, B. S., Kurup, M. R. P., Jain, S. K., Bhoon,Y. K.Transition met. Chem. 1988;13:309-312.
31.Mendes, I. C., Moreira, J. P., Mangrich, A. S., Balena, S. P., Rodrigues, B. L.; Beraldo, H. Polyhedron 2007:26;3263-3270.
32.Mendes, I. C., Moreira, J. P., Speziali, L. N., Mangrich, A. S., Takahashi, J. A., Beraldo, H. J. Braz. Chem. Soc. 2006;17;1571-1577.
33.Yin, H. D., Chen, S. W., Li, L. W., Wang, D. Q. Inorg. Chim.Acta 2007; 360: 2215-2223.
34.Salam, M. A., Affan, M. A., Ahmad, F. B., Jusoh, I., Shamsuddin, M. B., Yamin B., Farina, Y. J. Organomet. Chem. 2012;696: 4202-4206.
35.Lockhart, T. P., Manders, W. F. Inorg. Chem. 1986; 25: 892–895.
36.Lycka, A., Holeˆcek, J., Nadvornik, M., Handlir, K. J. Organomet. Chem. 1985; 280: 323-329.
37.Casas, J. S., Castineiras, A., Martinez, E. G., Gonzalez, A. S. Sanchez, A., Sordo, J. Polyhedron 1997;16:795-800.
38.Ali, S., Ahmad, S. U., Rehman, S., Shahzadi, S., Purvez, M., Mazhar, M. Appl. Organomet. Chem. 2005;19:200.
39.Yin, H. D., Chen, S. W. Inorg. Chem. Acta 2006; 359: 3330-3338.
40.Mendes I. C., Corta, F. B.,de Lima, G. M., Ardisson, J. D., Santos, I. G., Castineiras, A., Beraldo, H. Polyhedron 2009;28:1179-1185.
41.Refat, M. S., Deen, I. M. E., Anwer, Z. M., Ghol, S. E. J. Mol. Struct. 2009; 920: 149-162.
Article citation:-
M. A. Salama, Md. Azharul Arafath & M. A. Affan. Synthesis, characterization, crystal structure and in vitro antibacterial activity of tin (IV)/organotin(IV) complexes from N,N,S, donor ligand 2-acetylpyridine-N(4)-cyclohexylthiosemicarbazone. Journal of pharmaceutical and biomedical sciences (J Pharm Biomed Sci.) 2013 August; 33(33): 1558-1566 .Available at http://www.jpbms.info
Copyright © 2013 G. M. A. Salam, Md. Azharul Arafath & M. A. Affan. 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.
Research article:
*1Ambica Khetarpal,2Sarika Chaudhary,3Rakesh Sharma,
4Sangeeta Talwar, & 5Mahesh Verma
Affiliation:
1Senior Research Associate,2Associate Professor, 4Professor and Head, Department of Conservative Dentistry and Endodontics, 3Senior Research Associate, Department of Oral and maxillofacial surgery,5Director-principal, Maulana Azad Institute of Dental Sciences, Bahadur Shah Zafar Marg, New Delhi – 110002 Delhi, India.
Abstract:
Extrusion of an endodontic filling material can be a consequence of apical transportation or over-enlargement of the apical root canal because of over-instrumentation. Suspicion of endodontic material extrusion after acute endodontic pain on a dental intervention should favour early diagnosis and prompt management, reducing the risk of permanent tissue damage. Endodontically overfilled canals that remain symptomatic may require apical surgery for resolution. The aim of this paper is to report a surgical management of case of endodontic filling material extrusion into the periapical area using novabone a bone graft material and biodentine as a retrofilling material.
Key words: endodontic procedurals errors; surgical; Biodentine; Novabone; extrusion.
References:
1.Seltzer S, Naidorf IJ. Flare-ups in endodontics: I—etiological factors. J Endod 1985; 11:472–8.Link
2.Serper A, Ucer O, Onur R, Etikan I. Comparative neurotoxic effects of root canalfilling materials on rat sciatic nerve. J Endod 1998; 24:592–4.
3.Gutierrez JH, Brizuela C, Villota E. Human teeth with periapical pathosis after overstrumentation and overfilling of the root canals: a scanning electron microscopic study. Int Endod J 1999; 32: 40-8.Pubmed
4.Bergenholtz G, Lekholm U, Milthon R, et al. Influence of apical overinstrumentation and overfilling on re-treated root canals. J Endod 1979; 5: 310-14.Pubmed
5.Holland R, De Souza V, Nery MJ, et al. Tissue reactions following apical plugging of the root canal with infected dentin chips. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1980; 49: 366-9.Pubmed
6.Costerton JW, Stewart PS, Gerenberg EP. Bacteria biofilms: a common cause of persistent infections. Science 1999; 284: 1318-22.Pubmed
7.Laurent P, Camps J, De Méo M, Déjou J, About I. Induction of specific cell responses to a Ca(3)SiO(5)-based posterior restorative material. Dent Mat 2008 Nov; 24:1486-94. Epub 2008 Apr 29.Pubmed
8.Nair PN. Non-microbial etiology: foreign body reaction maintaining post-treatment apical periodontitis. Endod Topics 2003; 6(1):114–34.
9. Pascon EA, Leonardo MR, Safavi K, Langeland K. Tissue reactions to endodontic materials: criteria, assessment and and observations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1991; 72: 222-37.Pubmed
10.Dahl JE. Toxicity of endodontics filling materials. Endod Top 2005; 12: 39-43.Link
11.Ørstavik D. Materials used for root canal obturation technical, biological and clinical testing. Endod Top 2005; 12: 25-38.Link
12.Ho YC, Huang FM, Chang YC. Mechanism of citotoxicity of eugenol in human osteoblastic cells in vitro. Int Endod J 2006; 39: 389-93.Pubmed
13.Salthouse TN, Matlaga BF. Microspectophotometery of macrophage lysosomal enzyme activity: A measure of polymer implant tissue toxicity. Toxicol Appl Pharmacol 1973; 25:201.Pubmed
14.Seltzer S, Turkenkopf S. Histological evaluation of periapical repair following positive and negative root canal cultures. Oral Surg 1964; 17:507.Pubmed
15.Erausquin J, Muruzabal M. Root canal filling with zinc oxide eugenol cements in rat molars. Oral Surg 1967; 24:547.Pubmed
16.Wang X, Sun H & Chang J. Characterization of Ca3SiO5/CaCl2 composite cement for dental application. Dent Mater 2008; 24:74-82.Pubmed
Article citation:-
Khetarpal Ambica, Chaudhary Sarika,Sharma Rakesh,Talwar Sangeeta, Verma Mahesh. Surgical management of a case of severely extruded endodontic filling material using Novabone and Biodentin. Journal of Pharmaceutical and Biomedical Sciences (J Pharm Biomed Sci.) 2013 August; 33(33): 1486-1490.Available at http://www.jpbms.info
Copyright © 2013 Khetarpal Ambica, Chaudhary Sarika,Sharma Rakesh,Talwar Sangeeta,Verma Mahesh. 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.
Research article
Dalal Nasser Eldin ElKaffash1 , Aymen Abdel Hay2 ,Nermine Hossam Zakaria1* & Mounir Elhag 4
Affiliation:-
1Clinical Pathology Department, Faculty of Medicine, Alexandria University, Faculty of Medicine, Alexandria University, Egypt.
2Cardiology Department Faculty of Medicine, Alexandria University, Egypt.
3Clinical Pathology Department, Faculty of Medicine, Alexandria University Faculty of Medicine, Alexandria University, Egypt.
4Resident in Clinical Pathology Department, Faculty of Medicine, Alexandria University, Egypt.
Abstract:
Warfarin is the therapeutic drug of choice for treatment and maintenance of anticoagulation therapy. The dosage required to achieve the therapeutic effect varies between individuals. These differences in drug response and the narrow therapeutic window lead to increased risk of life threatening hemorrhagic adverse events. The standard treatment monitoring is the international normalized ratio (INR).Warfarin activity is determined by polymorphisms in CYP29C and VKORC1 genes. The CYP2C9 gene encodes enzyme that catalyzes the conversion of Warfarin to inactive metabolites. Polymorphisms of CYP2C9 includes the variant alleles *2 and *3; which have decreased enzymatic activity than the wild type CYP2C9*1. When Warfarin is given to patients with*2or*3variants it will be metabolized less efficiently and will remain in circulation longer, so lower Warfarin doses will be needed to achieve anticoagulation.VKORC1gene encodes the molecular target of coumarin type anticoagulant, vitamin Kepoxide reductase (VKORC1).It recycles vitamin K 2, 3 epoxide to vitamin K hydroquinone, which functions as the essential cofactor for the carboxylation of coagulation factors II, VII, IX, and X; proteins C, S. In the VKORC1 1639 single nucleotide polymorphism, the common G allele is replaced by the A allele. Because A allele produce less VKORC1 than do those with the G allele, lower Warfarin doses are needed to inhibit VKORC1 and to produce an anticoagulant effect. The aim of this study was to assess CYP2C9 and VKORC1 polymorphisms among Egyptian patients on chronic Warfarin therapy and determine its relation to Warfarin dosing protocol; study the CYP2C9 and VKORC1 alleles and genotypes frequency among sample of Egyptian patients.Subjects and Methods: The study was conducted on forty Egyptian male patients on stable Warfarin dose with a stable INR within the therapeutic range of 2.0 - 3.0.The CYP2C9 and VKORC1 genotypes were determined by PCR amplification reverse hybridization technique. Results: The frequency of CYP2C9 genotypes were; 65% for *1/*1, 10% for*1/*2. 15% for *1/*3, 5% for *2/*2 and 5% for*3/*3, genotype *2/*3 was not detected among studied patients. CYP2C9 alleles frequencies were; 77.5% for *1 allele, 10% for *2 allele and 12.5% for *3 allele. VKORC1 AA frequency was 7.5%, AG 65% and GG 27.5%. VKORC1 allele frequency: VKORC1 G allele 60% and VKORC1 A allele 40%. For CYP2C9 and Warfarin dose; the majority of low dose responders 76.9% was made by CYP2C9*3 and CYP2C9*2 while CYP2C9*1 made the rest 23.1%. In the intermediate dose responders, CYP2C9*1made 78.6% and CYP2C9*2 made 21.4%, and in high dose responder the CYP2C9*1 made 100%. As VKORC1 genotypes and Warfarin dose; the majority of low dose responders 76.9% was made by AG, while VKORC1 AA made 23,1%. In the intermediate dose responders, VKORC1 GG made 28.6%, AG made71.4% and AA not detected .in high dose responder the VKORC1 GG made 54.6 %, AG made 45.4% and AA not detected. For CYP2C9/VKORC1 haplotypes and Warfarin dose our findings was as follows: In group I low dose responder (Warfarin dose < 4 mg / day) *1/*3/AG haplotype made 38.5% ,*3/*3/AG haplotype made 15.4% ,*1/*1/AG haplotype made 15.4% and haplotypes *1/*1/AA, *1/*2/AG, *1/*3/AA and*2/*2/AA made 7.7% for each. In group II intermediate dose responders *1/*1/AG made 57.1%,*1/*1/GG 21.4%,*1/*2/AG 14.3% and *1/*2/GG made 7.1%. In High dose responders Haplotype *1/*1/GG made 63.6% and *1/*1/AG 36.4%. Conclusions: CYP2C9 common variant alleles CYP29C*2 and CYP29C*3 were detected in this study sample. CYP29C*2 frequency was comparable with Caucasians, while CYP29C*3 was higher. CYP29C*2 and CYP29C*3 were associated with lower mean daily doses of Warfarin than CYP2C9*1 wild type. VKORC1 mutant A and wild type G alleles were detected in a frequency similar to Caucasian. People with VKORC1 mutant allele A in the present study was associated with lower Warfarin doses than wild type G. Polymorphism in CYP2C9 and VKORC1 genes significantly affect individual response to Warfarin therapy, and could explain some of interindividual variations in Warfarin therapy.
Key words: Warfarin, vitamin Kepoxide reductase (VKORC1), INR; International Normalized Ratio, PCR amplification reverse hybridization technique.
References:
1.Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest. 2001;119(1 suppl):8S.Pubmed
2.Bernard JM BJ, Kokseng CU.et al. Warfarin sodium.Practitioner beware. AmPodiatr Med Assoc. 1992;82:345.Pubmed
3.Brummel KE, Paradis SG, Branda RF, Mann KG. Oral anticoagulation thresholds. Circulation. 2001;104(19):2311.Pubmed
4.Schelleman H, Limdi NA, Kimmel SE. Ethnic differences in warfarin maintenance dose requirement and its relationship with genetics. Pharmacogenomics.2008;9(9):1331-46.Pubmed
5.Chow W , Chow T , Tse T , Tai Y , Lee W . Anticoagulation instability with life threatening complication after dietary modification. Postgraduate medical journal . 1990; 66(780):855.Pubmed
6.Lee SH, Ahn YM, Ahn SY, Doo HK, Lee BC. Interaction between warfarin and Panax ginseng in ischemic stroke patients. The Journal of Alternative and Complementary Medicine. 2008;14(6):715-21.Pubmed
7.Zhao F, Loke C , Rankin S.C , Guo J.Y, Lee H.S , Wu T.S , et al. Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose. Clin Pharmacol Ther. 2004;76:210–9.Pubmed
8.Rane A, Lindh JD. Pharmacogenetics of anticoagulants. Hum Genomics Proteomics. 2010 Sep 13;2010:754919. doi: 10.4061/2010/754919.Pubmed
9.Krynetskiy E, McDonnell P. Building individualized medicine: prevention of adverse reactions to warfarin therapy. Journal of Pharmacology and Experimental Therapeutics. 2007;322(2):427.Pubmed
10.Majerus P, Broze G, Miletich J, Tollefsen D. Anticoagulant, thrombolytic, and antiplatelet drugs. Goodman and Gilman’s The pharmacological basis of therapeutics. 1995:1341-59.
11.Zhang K, Young C, Berger J. Administrative claims analysis of the relationship between warfarin use and risk of hemorrhage including drug-drug and drug-disease interactions. Journal of Managed Care Pharmacy. 2006;12(8):640.Pubmed
12.Harrison L, Johnston M, Massicotte MP, Crowther M, Moffat K, Hirsh J. Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy. Annals of Internal Medicine. 1997;126(2):133.Pubmed
13.Lamb GC. Loading Dose and Monitoring of Warfarin Therapy-Reply. JAMA: The Journal of the American Medical Association. 1997;278(7):548.Pubmed
14.Kovacs MJ, Rodger M, Anderson DR, Morrow B, Kells G, Kovacs J, et al. Comparison of 10-mg and 5-mg warfarin initiation nomograms together with low-molecular-weight heparin for outpatient treatment of acute venous thromboembolism. Annals of Internal Medicine. 2003;138(9):714.Pubmed
15.Fennerty A, Campbell I, Routledge P. Anticoagulants in venous thromboembolism. British Medical Journal. 1988;297(6659):1285.Pubmed
16.Smellie WSA, Hampton K, Bowlees R, Martin S, Shaw N, Hoffman J, et al. Best practice in primary care pathology: review 8. Journal of clinical pathology. 2007;60(7):740.Pubmed
17.Lenzini PA, Grice GR, Milligan PE, Dowd MB, Subherwal S, Deych E, et al. Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients. Journal of Thrombosis and Haemostasis. 2008;6(10):1655-62.Pubmed
18. Bennett S. Monitoring Anticoagulant Therapy. Laboratory Hemostasis. 2007:167-205.Link
19.Schulman S. Care of patients receiving long-term anticoagulant therapy. N Engl J Med. 2003 Aug 14;349(7):675-83..Pubmed
20.Greenblatt DJ, von Moltke LL. Interaction of warfarin with drugs, natural substances, and foods. The Journal of Clinical Pharmacology. 2005;45(2):127.Pubmed
21.Horstkotte D, Piper C, Wiemer M. Optimal frequency of patient monitoring and intensity of oral anticoagulation therapy in valvular heart disease. Journal of thrombosis and thrombolysis. 1998;5:19-24.Pubmed
22.Ansell J, Jacobson A, Levy J, Völler H, Hasenkam JM. Guidelines for implementation of patient self-testing and patient self-management of oral anticoagulation. International consensus guidelines prepared by International Self-Monitoring Association for Oral Anticoagulation. International journal of cardiology. 2005 Mar 10 ;99(1):37-45.Pubmed
23.Sconce EA, Khan TI, Wynne HA, Avery P, Monkhouse L, King BP, et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood. 2005 Oct 1;106(7):2329. Pubmed
24.Yin T, Miyata T. Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1--Rationale and perspectives. Thrombosis research. 2007;120(1):1-10.Pubmed
25. Sanderson S, Emery J, Higgins J. CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: A HuGEnet (TM) systematic review and meta-analysis. Genetics in Medicine. 2005;7(2):97.Pubmed
26.Takahashi H, Echizen H. Pharmacogenetics of warfarin elimination and its clinical implications. Clinical pharmacokinetics. 2001;40(8):587-603.
27.Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW. Identification of the gene for vitamin K epoxide reductase. Nature. 2004;427(6974):541-4.Pubmed
28.Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hörtnagel K, Pelz HJ, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004;427(6974):537-41.Pubmed
29.Oldenburg J. VKORC1: the little big protein. Blood. 2005;106(12):3683.Link
30.Flockhart DA, O’Kane D, Williams MS, Watson MS, Gage B, Gandolfi R, et al. Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genetics in Medicine. 2008;10(2):139.Pubmed
31.Schwarz UI, Ritchie MD, Bradford Y, Li C, Dudek SM, Frye-Anderson A, et al. Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med.2008;358(10):999-1008.Pubmed
32.Loebstein R, Yonath H, Peleg D , Almog S, Rotenberg M , Lubetsky A , et al. Interindividual variability in sensitivity to warfarin—nature or nurture? Clin Pharmacol Ther. 2001;70:159–64.Pubmed
33.Gladstone DJ, Bui E, Fang J, Laupacis A, Lindsay MP, Tu JV. et al. Potentially preventable strokes in high-risk patients with atrial fibrillation who are not adequately anticoagulated. Stroke. 2009 Jan;40(1):235-40.Pubmed
34.Geisen C, Watzka M, Sittinger K, Steffens M, Daugela L, Seifried E,et al. VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation. Thromb Haemost. 2005;94(4):773-9.Pubmed
35. Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, Rettie AE . Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA. 2002 Apr 3;287(13):1690-8.Pubmed
36.Vecsler M LR, Almog S, Kurnik D, Goldman B, Halkin H, Gak E. Combined genetic profiles of components and regulators of the vitamin K dependent gamma-carboxylation system affect individual sensitivity to warfarin. Thromb Haemost. 2006;95:205-11.Pubmed
37.Takahashi H, Wilkinson G.R, Caraco Y, Muszkat M, Kim R.B., Kashima T, et al. Population differences in S-warfarin metabolism between CYP2C9 genotype-matched Caucasian and Japanese patients. Clin Pharmacol Ther. 2003;73:253–63.Pubmed
38.Hill CE, Duncan A, Wirth D, Nolte FS. Detection and identification of cytochrome P-450 2C9 alleles *1, *2, and *3 by high-resolution melting curve. Am J Clin Pathol. 2006;125:584-91.Pubmed
39.Gage BF, Eby C, Milligan PE, Banet GA, Duncan JR, McLeod HL. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther.2008;84(3):326-31.Pubmed
40.Hamdy SI, Hiratsuka M, Narahara K, Endo N, ElEnany M, Moursi N, et al. Genotyping of four genetic polymorphisms in the CYP1A2 gene in the Egyptian population. British journal of clinical pharmacology. 2003;55(3):321-4.Pubmed
41.Scott SA, Khasawneh R, Peter I, Kornreich R, Desnick RJ. Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups. Pharmacogenomics. 2010;1(6):781-91.Pubmed
42.Scordo MG, Pengo V, Spina E, Dahl ML, Gusella M, Padrini R. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance&ast. Clinical Pharmacology & Therapeutics. 2002;72(6):702-10.Pubmed
43.Takahashi H, Kashima T, Nomizo Y, Muramoto N, Shimizu T, Nasu K, et al. Metabolism of warfarin enantiomers in Japanese patients with heart disease having different CYP2C9 and CYP2C19 genotypes&ast. Clinical Pharmacology & Therapeutics. 1998;63(5):519-28.
44.Taube J, Halsall D, Baglin T. Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood. 2000;96(5):1816-9.Pubmed
45. Limdi N, McGwin G, Goldstein J, Beasley T, Arnett D, Adler B, et al. Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin. Clinical Pharmacology & Therapeutics. 2007;83(2):312-21.Pubmed
46. Rosemary J, Adithan C. The pharmacogenetics of CYP2C9 and CYP2C19: ethnic variation and clinical significance. Current clinical pharmacology. 2007;2(1):93-109.Pubmed
47.Borgiani P, Ciccacci C, Forte V, Romano S, Federici G, Novelli G. Allelic variants in the CYP2C9 and VKORC1 loci and interindividual variability in the anticoagulant dose effect of warfarin in Italians. Pharmacogenomics. 2007;8(11):1545-50.Pubmed
48.Rosemary J, Adithan C. The pharmacogenetics of CYP2C9 and CYP2C19: ethnic variation and clinical significance. Current clinical pharmacology. 2007;2(1):93-109.Pubmed
49. Obayashi K, Nakamura K, Kawana J, Ogata H, Hanada K, Kurabayashi M, et al. VKORC1 gene variations are the major contributors of variation in warfarin dose in Japanese patients&ast. Clinical Pharmacology & Therapeutics. 2006;80(2):169-78.Pubmed
50.Takahashi H, Echizen H. Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin. The pharmacogenomics journal. 2003;3(4):202-14.Pubmed
51.Moyer TP, O'Kane DJ, Baudhuin LM, Wiley CL, Fortini A, Fisher PK, et al. Warfarin sensitivity genotyping: a review of the literature and summary of patient experience Mayo Clin Proc. 2009 Dec;84(12):1079-94. doi: 10.4065/mcp.2009.0278.Pubmed
52.Yuan HY, Chen JJ, Lee MTM, Wung JC, Chen YF, Charng MJ, et al. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Human molecular genetics. 2005;14(13):1745-51.Pubmed
53.Xie HG, Prasad H.C, Kim R.B. and Stein C.M. CYP2C9 allelic variants: ethnic distribution and functional significance. Adv Drug Delivery Rev.54:1257–70.Pubmed
54.Elizabeth A. Sconce, Tayyaba I. Khan, Hilary A. Wynne, Peter Avery, et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirement: proposal for a new dosing regimen. Blood. 2005;106:2329–33.Pubmed
55.Sanderson S , Emery j, Higgins J . CYP29 gene variants , drug dose ,and bleeding risk in warfarin treated patients: HuGent ™ systematic review and metaanalysis . Genetics in Medicine .2005; 792):97.Pubmed
56. Mark J. Rieder, Alexander P. Reiner, Brian F. Gage, Deborah A, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med. 2005;352:2285–93.Pubmed
57. Rost S, Fregin A, Ivaskevicius V, Conzelmann E , Hortnagel K, Pelz H.J , et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004;427:537–41.Pubmed
58. Kamali F, Khan TI, King BP, Frearson R, Kesteven P, Wood P, et al. Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin&ast. Clinical Pharmacology & Therapeutics. 2004;75(3):204-12.Pubmed
59.Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA: The Journal of the American Medical Association. 2002;287(13):1690-8.Pubmed
60.Meckley LM, Wittkowsky AK, Rieder MJ, Rettie AE, Veenestra DL. An analysis of the relative effects of VKORC1 and CYP2C9 variants on. ThrombHaemost. 2008;100:220–39.Pubmed
61.Rieder MJ, Reiner AP, Gage BF, Nickerson DA, Eby CS, McLeod HL, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. New England Journal of Medicine. 2005;352(22):2285-93.Pubmed
62. Tatarūnas V, Lesauskaitė V, Veikutienė A, Jakuška P, Benetis R. The Influence of CYP2C9 and VKORC1 Gene Polymorphisms on Optimal Warfarin Doses After Heart Valve Replacement. Medicina (Kaunas). 2011;47(1):25-30.Pubmed
63.Gan GG, Phipps ME, Lee MMT, Lu LS, Subramaniam RY, Bee PC, et al. Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations. Annals of Hematology. 2011;90(6):635-41.Pubmed
64.H Echizen H Ta. Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin. Pharmacogenomics.2003;3:202–14.Pubmed
65.Limdi NA, Wadelius M, Cavallari L, Eriksson N, Crawford DC, Lee MT, et al. Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. Blood. 2010 May 6;115(18):3827-34.Pubmed
66.Ensom MHH, T. K. H. Chang , and P. Patel. Pharmacogenetics: the therapy drug monitoring of the future? Clin Pharmacokinet. 2001;40:783–802.Pubmed
67.Dorothy M. Adcock CK, Domnita Crisan and Frederick L. Kiechle. Effect of Polymorphisms in the Cytochrome P450 CYP2C9 Gene on Warfarin Anticoagulation. Archives of Pathology & Laboratory Medicine. 2004 December;128(12):1360-3.Pubmed
68.Mannuci PM. Genetic control of anticoagulation. Lancet. 1999;353:688–9.Pubmed
69.Poller I A .Mckernan, J M Thomson and M Elstein . Fixed mini dose warfarin:a new approach to prophylaxis against venous thromboembolism after major surgery .Br Med J. 1987; 295:1309-12.Pubmed
Article citation:-
Dalal Nasser Eldin ElKaffash,Aymen Abdel Hay,Nermine Hossam Zakaria & Mounir Elhag Role of CYP2C9 and VKORC1 polymorphism in dose dependent Warfarin therapy management. Journal of Pharmaceutical and Biomedical Sciences (J Pharm Biomed Sci.) 2013 August; 33(33): 1468-1485.Available at http://www.jpbms.info
Copyright © 2013 Dalal Nasser Eldin ElKaffash,Aymen Abdel Hay,Nermine Hossam Zakaria & Mounir Elhag. 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
* 1Naik Irfan (Msc, Ph.D), 2Fomda Bashir A (MBBS, MD), 1Tenguria Rajesh K (Msc, M.phil, Ph.D), 2Sikander C (MBBS, MD), 3Peer Maroof (MBBS, MD) & 3Nasir Reyaz (MBBS, MD).
Affiliation:-
1Department of Microbiology, Govt. Motilal Vigyan Mahavidyalya Bhopal-462 008 (MP) India.
2Departments of Microbiology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar- Jammu and Kashmir-190 011 India.
3Department of Microbiology, Govt. Medical College Srinagar- Jammu and Kashmir-190 010 India.
Author’s contributions-All authors contributed equally to this paper.
Abstract:
Background & objectives: Extended spectrum β-lactamase (ESBL) and AmpC β-lactamase are important mechanisms of betalactam resistence among Enterobacteriaceae. The purpose of this study was to simultaneously screen for Extended-spectrum β-lactamases (ESBL) and AmpC β-lactamases in gram negative clinical isolates from tertiary care hospital and further to compare two detection methods, three-dimensional extraction method and AmpC disk test for AmpC β-lactamases. Materials and Methods: A total of 342 isolates were screened for ESBL and AmpC β-lactamase by modified double disk approximation method (MDDM). Synergy observed between disks of ceftazidime and clavulanate were considered as ESBL producer. Isolates showing reduced susceptibility to ceftazidime, ceftazidime clavulanic acid, cefepime, aztreonam and cefoxitin were considered as presumptive AmpC producers and further confirmed by three-dimensional extraction method and AmpC disk test. Results: A total of 215 (63%) of the isolates were found to be ESBL positive and 74 (22%) showed resistant to cefoxitin. ESBL was detected in 96 (63%) isolates of E. coli and 79 (73%) of Klebsiella spp. The occurrence of AmpC β-lactamases was found to be 9% (32) of the total isolates and the two detection methods for AmpC β-lactamase showed concordant results. Conclusion: Screening for ESBL and AmpC can be simultaneously done by MDDM method and confirmation for AmpC β-lactamase should be carried out routinely in tertiary care hospitals by AmpC disk test, as it is a simple and rapid procedure.
Key words: ESBL, AmpC β –lactamases; phenotypic methods; Disk test.
References:
1.Stapleton, P. D., K. P. Shannon, and G. L. French. 1999. Construction and characterization of mutants of the TEM-1 β-lactamase containing amino acid substitutions associated with both extended-spectrum resistance and resistance to β-lactamase inhibitors. Antimicrob. Agents Chemother. 43:1881-1887.[Pubmed],[PMC free article]
2.Quale JM, Landman D, Bradford PA, Visalli M, Ravishankar J, Flores et al. Molecular epidemiology of a citywide outbreak of extended-spectrum β-lactamase producing Klebsiella pneumoniae infections. Clin Infect Dis 2002; 35: 834-41. [Pubmed]
3.Coudron PE, Moland ES, Sanders CC. The occurrence and the detection of extended- spectrum β-lactamases in members of the family, Enterobacteriaceae at a Veterans Medical Center: seek and you may find. J Clin Microbiol 1997; 35: 2593-97. [Pubmed][PMC free article][JCM]
4.Pitout JDD, Reisbig MD, Venter EL, Church DL, Hanson ND, Modification of the double disk test for the detection of Enterobacteriaceae which produced the extended-spectrum and the AmpC β-lactamases. J Clin Microbiol 2003; 41: 3933-35.
5. Manchanda V, Singh NP..Occurrence and detection of AmpC beta-lactamases among Gram-negative clinical isolates using a modified three-dimensional test at Guru Tegh Bahadur Hospital, Delhi, India.J Antimicrob Chemother. 2003 Feb;51(2):415-8.[Pubmed]
6.Black JA, Moland ES, HossainA, Lockhart TJ, Olson LB, Thomson KS, et al. Prevalence of Plasmid-mediated AmpC β-lactamases in Klebsiella pneumoniae (KP), Klebsiella oxytoca (KO), Proteus mirabilis (PM) , and Salmonella (S) isolates from 42 ICU and 21 non-ICU sites in the United States. Poster (C2-2034) in 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICCAC) 2003.
7.Thomson KS. Controversies about extended-spectrum and AmpC beta-lactamases. Emerging Infect Dis 2001; 7: 333-6.[Pubmed][PMC free article][ Emerg Infect Dis]
8.Gheldre YD, Avesani V, Berhin C, Delmee M, Glupczynski Y. Evaluation of oxoid combination disks for detection of extended spectrum b-lactamases J Antimicrob Chemother 2003;52 :591-7.[PMC Free article] [ jcm.asm]
9.National Committee for Clinical Laboratory Standardards. Performance Standards for Antimicrobial Susceptibility Testing-twelfth informational supplement: Wayne, PA, USA: NCCLS; 2002;M 100-S12. [Link]
10.Philippon A, Arlet G, Jacoby GA. Plasmid-determined AmpC-type b-lactamases. Antimicrob Agents Chemother 2002; 46 :1-11.[Pubmed][PMC Free article][aac.acm.org]
11.Shahid M, Malik A, Sheeba. Multi drug resistant Pseudomonas aeruginosa strains harboring R-plasmids and AmpC b-lactamases isolated from hospitalized burn patients in a tertiary care hospital of North India. FEMS Microbiology Letters 2003; 228 :181-6.[IJCM][Free in PMC]
Article citation:-
Naik Irfan et al. Phenotypic detection of extended-spectrum and AmpC β lactamases in gram negative clinical isolates from tertiary care hospital. Journal of pharmaceutical and biomedical sciences (J Pharm Biomed Sci.) 2013 August; 33(33): 1537-1541.Available at http://www.jpbms.info
Copyright © 2013 Naik Irfan 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.