Search results for: P. K. Sreeja
4 Impact of CYP3A5 Polymorphism on Tacrolimus to Predict the Optimal Initial Dose Requirements in South Indian Renal Transplant Recipients
Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai
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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP
Procedia PDF Downloads 3013 Collision Avoidance Maneuvers for Vessels Navigating through Traffic Separation Scheme
Authors: Aswin V. J., Sreeja S., R. Harikumar
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Ship collision is one of the major concerns while navigating in the ocean. In congested sea routes where there are hectic offshore operations, ships are often forced to take close encounter maneuvers. Maritime rules for preventing collision at sea are defined in the International Regulations for Preventing Collision at Sea. Traffic Separation Schemes (TSS) are traffic management route systems ruled by International Maritime Organization (IMO), where the traffic lanes indicate the general direction of traffic flow. The Rule 10 of International Regulations for Preventing Collision at Sea prescribes the conduct of vessels while navigating through TSS. But no quantitative criteria regarding the procedures to detect and evaluate collision risk is specified in International Regulations for Preventing Collision at Sea. Most of the accidents that occur are due to operational errors affected by human factors such as lack of experience and loss of situational awareness. In open waters, the traffic density is less when compared to that in TSS, and hence the vessels can be operated in autopilot mode. A collision avoidance method that uses the possible obstacle trajectories in advance to predict “collision occurrence” and can generate suitable maneuvers for collision avoidance is presented in this paper. The suitable course and propulsion changes that can be used in a TSS considering International Regulations for Preventing Collision at Sea are found out for various obstacle scenarios.Keywords: collision avoidance, maneuvers, obstacle trajectories, traffic separation scheme
Procedia PDF Downloads 762 Assessment of Alteration in High Density Lipo Protein, Apolipoprotein A1, Serum Glutamic Pyruvic Transaminase and Serum Glutamic Oxaloacetic Transaminase in Oral Submucous Fibrosis Patients
Authors: Marina Lazar Chandy, N. Kannan, Rajendra Patil, Vinod Mathew, Ajmal Mohamed, P. K. Sreeja, Renju Jose
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Introduction- Arecoline, a major constituent of arecanut has shown to have some effect on liver. The use of arecanut is found to be the most common etiological factor for the development of Oral Submucous fibrosis (O.S.M.F). The effect of arecanut usage on liver in patients with O.S.M.F needs to be assessed. Lipids play a role in structural maintenance of cell. Alterations of lipid profile were noted in cancer patients. O.S.M.F being a precancerous lesion can have some effect on the level of lipids in the body. Objectives: This study was done to assess the alterations in liver enzymes (Serum Glutamic Pyruvic Transaminase(S.G.P.T ,Serum Glutamic Oxaloacetic Transaminase(S.G.O.T)) and lipid metabolism (High Density Lipoprotien(H.D.L) and Apo Lipoprotien A1 (Apo A1)) in patients with O.S.M.F. Methods-130 patients were taken for the study,100 patients with O.S.M.F and 30 as control group without O.S.M.F. Fasting blood sugar levels were taken, centrifuged and analyzed for S.G.P.T,S.G.O.T, H.D.L and Apo A1 using semi automated spectrophotometer. Results: After statistical analysis, it was concluded that there is an elevation of levels of S.G.P.T, S.G.O.T, and decreased levels of H.D.L, Apo A1 for O.S.M.F group when compared with control group. With increased grade of O.S.M.F. and duration of habit, S.G.P.T. & S.G.O.T. increased whereas, H.D.L. & Apo A1 decreased. All the values were statistically significant at p<0.01.Keywords: apolipoprotien A1, high density lipoprotien, oral submucous fibrosis, serum glutamic oxaloacetic transaminase
Procedia PDF Downloads 3251 Genetic and Phenotypic Variability Among the Vibrio Cholerae O1 Isolates of India
Authors: Sreeja Shaw, Prosenjit Samanta, Asish Kumar Mukhopadhyay
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Cholera is still a global public health burden and is caused by Vibrio cholerae O1 and O139 serogroups. Evidence from recent outbreaks in Haiti and Yemen suggested that circulating V. cholerae O1 El Tor variant strains are continuously changing to cause more ruinous outbreaks worldwide, and most of them have emerged from the Indian subcontinents. Therefore, we studied the changing virulence characteristics along with the antibiotic resistance profile of V. cholerae O1strains isolated from seasonal outbreaks in three cholera endemic regions during 2018, Gujarat and Maharashtra in Western India (87 strains), and to compare those features with the isolates of West Bengal in Eastern India (48 strains) collected during the same period. All the strains from Western India were of Ogawa serotype, polymyxin B-sensitive, hemolytic, and contained a large fragment deletion in VSP-II genomic region similar with Yemen outbreak strains and carried more virulent Haitian genetic alleles of major virulence associated genes ctxB, tcpA, and rtxA. Conversely, 14.6% (7/48) of the strains from Eastern India were belong to the Inaba serotype, polymyxin B-resistant, non-hemolytic, harbored intact VSP-II region, classical ctxB, Haitian tcpA, and El Tor rtxA alleles. Interestingly, resistance to tetracycline and chloramphenicol was seen in isolates from both regions, which are not very common among V. cholerae O1 isolates in India. Therefore, this study indicated West Bengal as a diverse region where two different types of El Tor variant hypervirulent strains are co-existed, probably competing for their better environmental survival, which may result in severe irrepressible disease outcome in the future.Keywords: cholera, vibrio cholerae, polymyxin B, Non-hemolytic, ctxB, tcpA, rtxA, VSP-II
Procedia PDF Downloads 165