Evaluation of Genetic Polymorphisms of N-acetyltransferase 2 and Relation with Chronic Myeloid Leukemia.

OBJECTIVES: The N-Acetyltransferase 2 (NAT2) gene encodes a key enzyme involved in xenobiotic metabolism, which contributes to the detoxification of numerous cancer therapy-induced products. However, the NAT2 genotype/phenotype is not fully understood and few studies have reported its relationship with CML. The aim of this study was to determine whether its polymorphisms (C481T, G590A, 803A>G and 857G>A) have a role in chronic myeloid leukemia susceptibility (CML) in Sudanese population. METHODS: We performed a case- control study. DNA from 200 CML patients and 100 controls was analyzed for the NAT2 polymorphisms using PCR-RFLP assay. RESULTS: The study showed NAT2 polymorphisms 803AG are associated with CML protection by a factor of 2.3, (OR = 0.044, 95% CI: 0.020-0.095, p = 0. 000). The study indicated that the heterozygous (GA) and mutant (AA) variants of the G857A genotype also offer protection, (OR = 0.002, 95% CI: 0.002-0.019, p = 0. 000) and (OR = 0.018, 95% CI: 0.002-0.133, p = 0. 000), respectively. CONCLUSION: There was no significant difference in CML diagnosis among Sudanese cases with the 481C→T and 590G→A polymorphisms. But patients with the compound NAT2 genotypes 481CT/803 AG, 590AG/ 803AG, 590AG/ 803GG, 590AA/ 803AG and 590GG/ 803AG were found to have a reduced risk. The current study demonstrates that polymorphisms of NAT2 A803G and G857A might also act as protective factors against developing the disease.

Applying Telemedicine Technology in Treating Prolactinomas: A Case Report.

Despite being considered a relatively new concept, telemedicine has already been associated with improved outcomes and reduced healthcare utilization in the management of several high-risk diseases. However, no reports to date have examined the effectiveness of telemedicine in managing prolactinomas. We report a case of a young male with a macroprolactinoma who was reviewed initially in a face-to-face encounter, however, continued his subsequent management virtually using telemedicine methods with satisfactory clinical outcomes.

CYP1A1 and CYP2D6 Polymorphisms and Susceptibility to Chronic Myelocytic Leukaemia.

BACKGROUND: CYP1A1 and CYP2D6 are both xenobiotic metabolizing enzymes belonging to the CYP450 enzyme family. Polymorphisms in these genes vary between individuals, resulting in dissimilar patterns of susceptibility to the effects of carcinogenic substances and drugs. OBJECTIVE: In a prospective study, the influence of CYP1A1*2C and CYP2D6*4 gene polymorphisms on the susceptibility to chronic myelocytic leukaemia (CML) were investigated. METHODS: Prevalence of CYP1A1*2C and CYP2D6*4 was detected in blood specimens from three hundred participants - two hundred patients and a hundred healthy individuals as a control group, using PCR-RFLP. RESULTS: CYP1A1 Ile/Val and Val/Val genotype frequency in our study population was 82% & 15% in CML patients and 55% & 8% in controls, respectively. This suggests that carriers had an elevated risk (OR=18.38, 95% CI=7.364-45.913, p value; =0.000 and OR=23.125,95 % CI=7.228-73.980, p value=0.000, respectively). Individuals carrying the CYP2D6 heterozygous genotype (IM) were notably fewer in number within the CML group at 43.5%, as opposed to 93% of the controls. This suggests that the IM genotype may have a prophylactic function in lowering CML risk (OR=0.036, 95% CI=0.005-0.271, p value =0.001). In spite of the distribution of the homozygous mutant (PM) genotype being higher in cases with CML (87% as opposed to 6% in the control), this difference was deemed non-significant (OR=0.558, 95% CI=0.064-4.845, p value =0.597). CONCLUSION: These findings indicate that polymorphic CYP1A1 and CYP2D6 genes affect the susceptibility to CML.

Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia.

BACKGROUND: The development of cancer results from an imbalance between exposure to carcinogens and the capacity of various enzyme systems engaged in activation or in the detoxification of xenobiotics. The aim of the present study is to investigate the association of GSTP1, GSTM1 and GSTT1 gene polymorphisms in susceptibility to Chronic Myeloid Leukaemia (CML). METHODS: A total of 200 CML patients and 100 controls were enrolled in a case-control study with GSTM1 and GSTT1 analysis with PCR and GSTP1 analysis with PCR-RFLP. RESULTS: The GSTT1 null genotype was significantly higher among CML patients suggesting that this genotype is associated with an increased risk of CML. It was found in 42% of cases as compared with 21% of the controls, (OR =2.78, 95% CI: 1.59 - 4.85; p-value =0.000). The presence of the GSTT1 genotype may thus be considered a protective factor for CML. The frequency of individuals carrying GSTM1 null genotype was slightly higher in the control group but this difference was not statistically significant. The GSTM1 null genotype was present in 35% of control cases and 34% of the CML patients, (OR=0.975, 95%CI: 0.58-1.58;p-value=0.863). Individuals with a combined GSTM1 null/GSTT1null genotype had an estimated 2.85-fold increased risk of CML, but no associated risk between GSTP1 Ile 105 Val polymorphism and CML was found (OR=1.99, 95% CI: 0.40 - 9.32; p-value = 0.417). CONCLUSIONS: No association between GSTP1 and GSTM1 with susceptibility to CML was found. GSTT1 genotype may be a protective factor for CML, while the null genotype shows association with developing CML.
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Intra-articular injection of expanded autologous bone marrow mesenchymal cells in moderate and severe knee osteoarthritis is safe: a phase I/II study.

BACKGROUND: Knee osteoarthritis (KOA) is a major health problem especially in the aging population. There is a need for safe treatment that restores the cartilage and reduces the symptoms. The use of stem cells is emerging as a possible option for the moderate and severe cases. This study aimed at testing the safety of autologous bone marrow mesenchymal stem cells (BM-MSCs) expanded in vitro when given intra-articularly to patients with stage II and III KOA. As a secondary end point, the study tested the ability of these cells to relieve symptoms and restore the knee cartilage in these patients as judged by normalized knee injury and Osteoarthritis Outcome Score (KOOS) and by magnetic resonance imaging (MRI). METHODS: Thirteen patients with a mean age of 50 years suffering from KOA stages II and III were given two doses of BM-MSCs 1 month apart totaling 61 × 106 ± 0.6 × 106 by intra-articular injection in a phase I prospective clinical trial. Each patient was followed for a minimum of 24 months for any adverse events and for clinical outcome using normalized KOOS. Cartilage thickness was assessed by quantitative MRI T2 at 12 months of follow-up. RESULTS: No severe adverse events were reported up to 24 months follow-up. Normalized KOOS improved significantly. Mean knee cartilage thickness measured by MRI improved significantly. CONCLUSION: BM-MSCs given intra-articularly are safe in knee osteoarthrosis. Despite the limited number of patients in this study, the procedure described significantly improved the KOOS and knee cartilage thickness, indicating that they may enhance the functional outcome as well as the structural component. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02118519.