Frequency of the C677T Polymorphism of MTHFR, G20210A of Prothrombin and R506Q of Factor V Leiden in Type 2 Diabetics in Abidjan

In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.

Distribution and Contamination of Arsenic in Fish, Gastropods and Bivalves in the Aby and Tendo Lagoons in East of Ivory Coast

Lagoons are ecosystems for biodiversity and the livelihoods of coastal communities. The main objective of the study was to analyze the variability of arsenic concentrations in gastropods and bivalves in the Aby and Tendo lagoons, taking into account spatial, seasonal and hydrological variations. The study was carried out in four stages spread over two successive hydroclimatic cycles, including two seasons during the rainy season and two more during the dry season. The samples were taken in two areas of the Aby and Tendo lagoons. Arsenic levels were measured by ICP-MS. The results showed that mean arsenic concentrations in the muscles of organisms in Aby Lagoon ranged from 0.01 to 1.26 μg As/g, with a mean and median of 0.17 and 0.06 μg As/g, respectively. Fish had the highest levels of arsenic, followed by crustaceans, while molluscs and plants had lower and comparable concentrations of As. Arsenic concentrations in tilapia and jawbones varied significantly between sites and seasons, with higher concentrations at Tendo and during the rainy season. Arsenic concentrations in gastropods and bivalves were significantly higher than those of other species, with averages of 0.74 and 1.03 mg As/kg, respectively.

Safety, Tolerability and Anti-Diarrhoeal Activity of “Diarra”, a Preparation of Medicinal Plants Used in Ivorian Traditional Medicine

Background: “Diarra”, a traditional herbal remedy made from five (5) medicinal plants, might be endowed with anti-diarrhoeal properties according to its owner. However, scientific evidence of its safety, tolerability and activity has not been established. Objective: This study aimed to assess the safety, tolerability and anti-diarrhoeal activity of “Diarra” in experimental rats. Materials and Methods: Safety was assessed by acute (OECD 423) and sub-acute (OECD 407) toxicity studies at doses of 5, 10 and 20 mg/kg. Clinical tolerability was assessed for 28 days. On day 29, a blood sample was taken to evaluate biological tolerability. The anti-diarrhoeal activity was investigated in a castor oil-induced diarrhoea model. Rats were given the remedy at doses of 5, 10 and 20 mg/kg and then castor oil 1 hour later. They were observed for 4 hours and diarrhoeal stools were collected. The Percentage of diarrhoeal inhibition was calculated. Results: A single dose of “Diarra” at a dose of 2000 mg/kg did not induce any lethality, behavioural or weight change in rats for 14 days. When administered once daily for 28 days, “Diarra” did not cause lethality or significant behavioural disorders or significant weight loss in rats. No biological disorders were observed. The treatment of rats with “Diarra” at doses of 5 mg/kg, 10 mg/kg and 20 mg/kg in a single administration inhibited the occurrence of diarrhoeal stools. The respective percentages of inhibition were 60%, 50% and 62%, similar to those of loperamide at a dose of 2 mg/kg (68%). Conclusion: “Diarra” has an anti-diarrheal activity in rats. It is also safe to use this remedy as such.

Influence of Haptoglobin and Hemoglobin Phenotypic Polymorphisms on Sickle Cell Disease Morbidity

Objectives: Sickle cell disease (SCD) has a varied clinical and biological expression depending on the hemoglobin phenotype: SSFA2, SFA2, SAFA2 and SC. Considering the antioxidant properties of the different haptoglobin phenotypes (Hp 1-1, Hp 2-1, Hp 2-2), it seemed relevant to know their influence on the morbidity of the different hemoglobin phenotype of SCD. Thus, the objective of this study was to identify associations between haptoglobin phenotype and morbidity of different SCD phenotypes. Methods: In a retrospective cross-sectional descriptive and analytical study, with a cohort of 170 black African carriers of hemoglobin S, in Ivory Coast, West Africa, hemoglobin and haptoglobin phenotypes were determined by electrophoretic methods. Results: The three major phenotypes of haptoglobin polymorphism were found in the SCD cohort: Hp 1-1 (24.1%), Hp 2-1 (56.5%), Hp 2-2 (19.4%). Vaso-occlusions were associated with haptoglobin phenotype Hp 1-1, (OR = 2.03;CI95% = [1.06 - 3.9];p Conclusions: Haptoglobin phenotype was associated to morbidity-adjusted hemoglobin phenotype. The study revealed a greater probability of a worse morbidity when the hemoglobin phenotype is homozygous. Unexpectedly, the worse morbidity is associated to Hp 1-1 haptoglobin phenotype, the most powerful antioxidant within the different haptoglobin phenotypes. Associations found were not systematic and need further studies to enlighten the determinism of SCD morbidity.

Application of Sigma Metric Analysis to Evaluate the Performance of the Biochemistry Analytical System in a Medical Biology Laboratory in Côte d’Ivoire

Introduction: The Six Sigma methodology is an opportunity for a better understanding of the performance of analytical methods and for a better adaptation of the quality control management policy of the medical biology laboratory. Using the sigma metric, this study assessed the performance of the Biochemistry analytical system of a medical biology laboratory in Côte d'Ivoire. Methods: Six Sigma methodology was applied to 3 analytes (alanine aminotransferase, glucose and creatinine). Performance indicators such as measurement imprecision and bias were determined based on the results of internal and external quality controls. The sigma number was calculated using the total allowable error values proposed by Ricos et al. Results: For both control levels, ALT had a sigma number greater than 6 (7.6 for normal control and 7.9 for pathological control). However, low sigma numbers, less than or equal to 2 for creatinine (1.4 for normal control and 2 for pathological control) and less than 1 for glucose were found. Conclusion: This study revealed good analytical performance of ALT from the point of view of 6 sigma analysis. However, modifications to the overall quality control procedure for glucose and creatinine are needed to improve their analytical performance. The study should be extended to the entire laboratory’s analytes in order to modify the strategies of quality control procedures based on metric analysis for an overall improvement in analytical performance.

Biomarkers of cetuximab resistance in patients with head and neck squamous cell carcinoma

Objective:In patients with head and neck squamous cell carcinoma(HNSCC),cetuximab[a monoclonal antibody targeting epidermal growth factor receptor(EGFR)]has been shown to improve overall survival when combined with radiotherapy in the locally advanced setting or with chemotherapy in first-line recurrent and/or metastatic(R/M)setting,respectively.While biomarkers of resistance to cetuximab have been identified in metastatic colorectal cancer,no biomarkers of efficacy have been identified in HNSCC.Here,we aimed to identify biomarkers of cetuximab sensitivity/resistance in HNSCC.Methods:HNSCC patients treated with cetuximab at the Curie Institute,for whom complete clinicopathological data and formalin-fixed paraffin-embedded(FFPE)tumor tissue collected before cetuximab treatment were available,were included.Immunohistochemistry analyses of PTEN and EGFR were performed to assess protein expression levels.PIK3 CA and H/N/KRAS mutations were analyzed using high-resolution melting(HRM)and Sanger sequencing.We evaluated the predictive value of these alterations in terms of progression-free survival(PFS).Results:Hot spot activating PIK3 CA and KRAS/HRAS mutations were associated with poor PFS among HNSCC patients treated with cetuximab in the first-line R/M setting,but not among HNSCC patients treated with cetuximab in combination with radiotherapy.Loss of PTEN protein expression had a negative predictive value among HNSCC patients treated with cetuximab and radiotherapy.High EGFR expression did not predict cetuximab sensitivity in our patient population.Conclusions:Hot spot activating PIK3 CA and RAS mutations predicted cetuximab resistance among HNSCC patients in the firstline R/M setting,whereas loss of PTEN protein expression predicted resistance to cetuximab when combined to radiotherapy.

GenoType MTBDRplus as a Complementary Tool for the Typing of Mycobacterium tuberculosis

The aim of this study was to investigate the usefulness of combining profiles obtained by using a line probe assay (LPA) originally intended to characterize the resistance of two major anti-tuberculosis drugs to the association of spoligotyping and MIRU-VNTR, in order to improve its discriminatory power. For this purpose, 74 strains of Mycobacterium tuberculosis belonging to the same cluster after spoligotyping were further typed by using the 24 loci MIRU/VNTR. These strains were then tested by the GenoType MTBDRplus, and profiles obtained were analyzed within previously obtained clusters. The combination of spoligotying and MIRU-VNTR led to the consolidation of 56 of them (75.7%) in 9 clusters. Most of the strains (54, 96.4%) were multidrug resistant (MDR). From the 9 initial clusters, the addition of GenoType MTBDRplus helped to define 26 profiles including 11 unique profiles, and 3 original clusters remained undifferentiated. Results obtained express the relevance of combining this method which improved quite significantly the discriminatory power in typing Mycobacterium tuberculosis.

Genetic Diversity and Antiretroviral Drug Resistance among Drug-Naive HIV-1 Infected Pregnant Women Attending Antenatal Clinics in Abidjan, Cote d'Ivoire

To clarify the distribution of HIV-1 subtypes and drug resistance-related mutations, we collected and analysed serum from pregnant women who are ARV drug-naive in Abidjan. The prevalence of HIV-1 subtypes and mutations associated with antiretroviral drug resistance among drug-na?ve HIV-1 infected pregnant women was investigated from plasma of 90 young pregnant primigravida. The HIV-1 pol and env genes were amplified by using primers recognizing conserved viral sequences and sequenced by employing BigDye chemistry. Positions 1 - 99 of the PR and 1 - 350 of the RT genes were analyzed for mutations based on the international AIDS society USA panel. In 39 strains which both genes were sequenced including CFR02_AG 30 (76.9%), subtype A 3 (7.7%), CFR06_cpx 2 (5.1%), CFR09_cpx 1 (2.6%), and discordant sequences suggesting the presence of a few number of recombinant involving CRF02-AG and subtype A 3 (7.7%). None of the major drug resistance mutations was detected. The frequent minor mutations associated drug resistance observed were M36I (52%/96.3%), L10I/R/V (19%/35.2%) and L63P (7%/12.9%). The M36I mutation was widespread in all subtypes. Our result demonstrated first a significant level of viral heterogeneity and then only the presence of minor resistance associated mutations. Our study emphasizes the need of HIV sentinel survey in C?te d'Ivoire and shows that pregnant women who are candidates for receiving antiretroviral drug therapies do not contain naturally occurring or preexisting drug resistance mutations. So such drug therapies are likely to be highly effective in this setting.