Advances in immunosuppressive therapy allowed renal transplantation to become the treatment of choice for suitable candidates with (end stage renal disease) ESRD. The post-transplant therapeutic strategy is difficult due to narrow therapeutic indices for the currently used immunosuppressive drugs. Inter-individual differences in drug bioavailability are related to genetic and non genetic factors. The idea of targeted and personalized therapy is to achieve therapeutic success. The empirical dose has lost its value in the post-transplant therapy and an individualized dosage regimen must be established. Interindividual heterogeneity in expression of ABCB1 and CYP3A4 has been suspected to be one of the factors resulting in cyclosporine (CsA) pharmacokinetic variation. This study aimed to investigate the impact of inter-individual CYP3A4 rs4646437C>T and MDR1 G2677T/A polymorphisms on cyclosporine dose requirements among a sample of renal transplant Egyptian recipients. Fifty adult Egyptian patients on CsA were genotyped for CYP3A4 rs4646437C>T and MDR1 G2677T/A and correlated with CsA dose requirement and dose-adjusted CsA (C0) blood levels at 3, 6, and 9 months post transplantation. CYP3A4 rs4646437C>T influenced significantly cyclosporine kinetics, the T carriers requiring higher cyclosporine dose. Daily dose requirements were also significantly higher in T allele MDR1 2677G>T GG genotype as compared to GT/TT genotypes at 3, 6, and 9 months post transplantation. Genotyping of both CYP3A4 and MDR1 SNPs may be helpful in providing pre-transplant pharmacogenetic information to individualize CsA dosing. Heterozygous CT genotype is the most frequent CYP3A4 rs4646437C>T genotype in the studied group of Egyptian population (48 %) followed by CC genotype and TT genotype. Daily dose requirements were significantly higher in T allele MDR1 2677G>T GG genotype as compared to GT/TT genotypes at 3, 6, and 9 months post transplantation.

Background: Methotrexate is the most commonly used disease-modifying anti-rheumatic drug (DMARD) and it is considered the first-line treatment in the management of rheumatoid arthritis (RA). MTX treatment outcome regarding response to the drug and adverse effects in RA patients are not universal. Therefore, it would be beneficial if we could predict the response of patients to MTX before starting MTX treatment in order to determine the patient ' s drug-treatment plan. Objectives: The present study aimed to evaluate the impact of MTHFR A1298C SNP (rs1801131) on the clinical outcome of MTX treatment as regards treatment efficacy and toxicity in a cohort of Egyptian rheumatoid arthritis patients. Patients and methods: Fifty rheumatoid arthritis patients were included in the present study. Data about patient related variables such as age and sex, disease related variables such as disease duration as well as treatment related variables such as treatment duration, dose of MTX, its route of administration and concomitant use of other drugs (NSAIDs) were obtained. DAS28 was calculated to all patients to assess drug response. MTHFR A1298C polymorphism was investigated using real time 5 0 nuclease allelic discrimination assay. Results: Multivariate regression analysis for factors predicting MTX drug response showed that MTHFR A1298C SNP and MTX dose were the most significant independent predictors for MTX treatment response (p = .016, OR = 39.113, 95% C.I = 1.970-776.558, p = .003, OR = 1.667, C.I = 1.184-2.348, respectively). Considering clinicopathological variables; longer disease duration, positive anti-CCP, NSAIDs users, higher MTX doses and longer treatment durations were significantly associated with nonresponse to MTX. Regarding MTX drug toxicity, MTHFR 1298 CC genotype, MTX dose and concomitant use of NSAIDs were significantly associated with MTX drug toxicity (MC p = .003, p = .031, p = .029, respectively). Conclusion: Our study proved that MTHFR A1298C SNP can predict clinical outcome of MTX treatment as regards treatment efficacy and toxicity in Egyptian rheumatoid arthritis patients.

Background: Ovarian cancer is the seventh most common cancer in females with the highest mortality rate of all gynecological cancers due to its late discovery and ambiguous symptoms. Thus, there is a need for new promising strategies to diagnose ovarian cancer. We aimed at finding a characteristic plasma proteome pattern that could be used for the detection of epithelial ovarian cancer, in comparison with benign ovarian masses and healthy controls. We also aimed at differentiating between profiling of plasma proteins in early and advanced stages of ovarian cancer and between serous and non-serous histopathological types. Methods: The combination of MagSi-proteomics C8 beads, Ultraflextreme MALDI-TOF and ClinPro Tools software was used to compare the plasma protein spectra from 50 patients with epithelial ovarian cancer, 20 patients with benign ovarian masses and 50 age matched healthy females. Results: A plasma proteome profile of 21 peaks differentiated patients with epithelial ovarian cancer from healthy controls with a sensitivity of 73 % and a specificity of 82.8% upon external validation, while a 5-peak profile differentiated patients with epithelial ovarian cancer from patients with benign ovarian masses with a sensitivity of 81% and a specificity of 73.7%. A 20 peak profile was generated to discriminate between early and late stages of the disease with 88.3% recognition capability and 70% cross validation. Conclusion: MALDI-TOF proteomic profiling represents a promising potential tool for diagnosing epithelial ovarian cancer, discriminating between early and advanced stages and between serous and non-serous types.

Background: Many animal studies suggested that the uremic toxin indoxyl sulphate can add to renal damage following induced nephrotoxicity and this effect has not been proved in patients with such complication. Methods: This is a prospective, case-control, and an observational study conducted on 74 critically ill patients with acute nephrotoxicity. It was designed to measure serum levels of indoxyl sulphate on the day of enrollment and over the course of their illness using high performance liquid chromatography (HPLC-UV) and to test the correlation between these levels and patient's demographics, clinical characteristics, physiological variables, and their outcomes. Results: Critically ill patients with acute nephrotoxicity had significantly higher total (tIS) and free (fIS) indoxyl sulphate than healthy controls and significantly lower than patients with end-stage renal disease (ESRD). Although, no correlation was found between tIS or fIS and mortality, among survivors, tIS, fIS, creatinine and eGFR were independently associated with no renal recovery. Conclusions: Serum indoxyl sulphate levels were elevated in critically ill patients with acute nephrotoxicity. There is an association between high levels of indoxyl sulphate and no renal-recovery outcome among survivors of acute nephrotoxicity. Early removal of indoxyl sulphate from patients' blood may improve their outcomes.

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