A Metabolomic Signature of Ischemic Stroke Showing Acute Oxidative and Energetic Stress.

Metabolomics is a powerful data-driven tool for in-depth biological phenotyping that could help identify the specific metabolic profile of cryptogenic strokes, for which no precise cause has been identified. We performed a targeted quantitative metabolomics study in West African patients who had recently suffered an ischemic stroke, which was either cryptogenic (n = 40) or had a clearly identified cause (n = 39), compared to a healthy control group (n = 40). Four hundred fifty-six metabolites were accurately measured. Multivariate analyses failed to reveal any metabolic profile discriminating between cryptogenic ischemic strokes and those with an identified cause but did show superimposable metabolic profiles in both groups, which were clearly distinct from those of healthy controls. The blood concentrations of 234 metabolites were significantly affected in stroke patients compared to controls after the Benjamini-Hochberg correction. Increased methionine sulfoxide and homocysteine concentrations, as well as an overall increase in saturation of fatty acids, were indicative of acute oxidative stress. This signature also showed alterations in energetic metabolism, cell membrane integrity, monocarbon metabolism, and neurotransmission, with reduced concentrations of several metabolites known to be neuroprotective. Overall, our results show that cryptogenic strokes are not pathophysiologically distinct from ischemic strokes of established origin, and that stroke leads to intense metabolic remodeling with marked oxidative and energetic stresses.

Biomarkers of sickle cell nephropathy in Senegal.

Sickle cell anemia (SCA) is caused by a single point variation in the ß-globin gene (HBB): c.20A> T (p.Glu7Val), in homozygous state. SCA is characterized by sickling of red blood cells in small blood vessels which leads to a range of multiorgan complications, including kidney dysfunction. This case-control study aims at identifying sickle cell nephropathy biomarkers in a group of patients living with SCA from Senegal. A total of 163 patients living with SCA and 177 ethnic matched controls were investigated. Biological phenotyping included evaluation of glycemia, glucosuria, albuminuria, proteinuria, tubular proteinuria, serum creatinine, urine creatinine, urine specific gravity and glomerular filtration rate. Descriptive statistics of biomarkers were performed using the χ2 -test, with the significance level set at p<0.05. Patients living with SCA had a median age of 20 years (range 4 to 57) with a female sex frequency of 53.21%. The median age of the control participants was 29 years (range: 4-77) with a female sex frequency of 66.09%. The following proportions of abnormal biological indices were observed in SCA patients versus (vs.) controls, as follows: hyposthenuria: 35.3%vs.5.2% (p<0.001); glomerular hyperfiltration: 47.66%vs.19.75% (p<0.001), renal insufficiency: 5.47%vs.3.82% (p = 0.182); microalbuminuria: 42.38%vs.5.78% (p<0.001); proteinuria: 39.33%vs.4.62% (p<0.001); tubular proteinuria: 40.97%vs.4.73% (p<0.001) and microglucosuria: 22.5%vs.5.1% (p<0.001). This study shows a relatively high proportion of SCA nephropathy among patients living with SCA in Senegal. Microglucosuria, proteinuria, tubular proteinuria, microalbuminuria, hyposthenuria and glomerular hyperfiltration are the most prevalent biomarkers of nephropathy in this group of Senegalese patients with SCA.

Effects of Senegal haplotype (Xmn1-rs7412844), alpha-thalassemia (3.7kb HBA1/HBA2 deletion), NPRL3-rs11248850 and BCL11A-rs4671393 variants on sickle cell nephropathy.

OBJECTIVE: Sickle cell anemia (SCA) can cause substantial kidney dysfunction resulting in sickle cell nephropathy, which may be affected by the presence of modifier genes. This study evaluates the effects of some modifier genes on sickle cell nephropathy. METHODS: Patients living with SCA were recruited. Alpha-thalassemia (3.7kb HBA1/HBA2 deletion) was genotyped using gap PCR multiplex. Senegal haplotype (Xmn1-rs7412844), BCL11A-rs4671393 and NPRL3-rs11248850 were genotyped using Mass Array. The effects of variants on kidney dysfunction were then evaluated using multivariate analysis. RESULTS: The number of patients living with SCA included in this study was 162 with a median age of 20 years [minimum-maximum: 4-57] and a female frequency of 53.21%. Senegal haplotype, BCL11A-rs4671393 variant were protective factors against albuminuria stage A2 with an odds ratio (OR) of 0.22 (95% CI 0.05-0.90) and 0.27 (95% CI 0.08-0.96) respectively. The combination NPRL3-rs11248850 variant - 3.7kb HBA1/HBA2 deletion was a protective factor against albuminuria stage A2 (OR = 0.087, 95% Cl 0.01-0.78) but it was a risk factor for glomerular hyperfiltration (OR = 17.69, 95% CI 1.85-169.31). CONCLUSIONS: All four variants displayed a protective effect against albuminuria stage A2. The combination alpha-thalassemia - NPRL3-rs11248850 variant is a risk factor for glomerular hyperfiltration.

[Blood biomarkers of early diagnosis for neonatal bacterial infections: back from Senegal cohort]. / Biomarqueurs sanguins du diagnostic précoce des infections néonatales bactériennes : retour d'expérience d'une cohorte sénégalaise.

In Senegal, reducing neonatal mortality remains a challenge. The management of neonatal infections remains problematic and presents a strong clinical focus. Indeed, like all developing countries, the difficulty of acquiring state-of-the-art infrastructure and the financial cost impact on the routine use of biomarkers. It is in this context that we conducted this study to identify the best biological strategy for making a reliable diagnosis. Ninety-nine newborns were recruited at the pediatric service of the Diamniadio Children's Hospital (Senegal). CRP was assayed by latex immuno-agglutination method, IL-6 and IL-8 using Luminex® technology, PCT by chemiluminescence, orosomucoid by immunoturbidimetry and SAA by ELISA technique. 20 newborns had probable infection and six established infection. Deaths and complications were significantly greater in these groups. With an optimal decision threshold of 16.3 mg/L, CRP performed better (compared to the other tested blood biomarkers) with AUC, sensitivity and specificity of 94%, 88% and 99%, respectively. With the performance obtained from CRP in the diagnosis of neonatal bacterial infections, the installation of panels with other biomarkers with advanced and expensive technology is not necessary. Thus, optimal care and within a reasonable timeframe can be done in our health facilities, with this accessible marker that is CRP.