A Comparison of three Methods to Estimate the Glomerular Filtration Rate in Diabetic Patients at the Ngaoundere Regional Hospital (Cameroon)

Estimation of Glomerular Filtration Rate (GFR) can be done using different methods. The cheaper and most available are those with formulas to determine the estimated GFR. The majority of these formulas have been developed among extra- African populations. In Sub-Saharan Africa, 3 formulas are almost used to estimate GFR which are MDRD, CG and CKD-EPI. This present study was conducted to assess the importance of these formulas as estimators of GFR for diabetic among African Populations. The study was conducted at the Ngaoundere Regional Hospital. Only diabetics from 30 to 78 years attending the regional hospital were enrolled in the study. After enrolment, diabetics with very high values of urea and/or creatinine were excluded. We evaluated CG, MDRD and CKD–EPI as estimators of GFR. Creatinine clearance of 24 hours has been considered as gold standard method. 60 participants were included for sex ratio (M/F) 1.5. The average eGFR of diabetics with high Blood Pressure was lower (91.2 ml / min) than diabetics with lower Blood Pressure (102 ml / min) according to ClCr24. A significant correlation (0.975) between MDRD and CKD-EPI was found when measuring eGFR. It was less significant between CG and MDRD (0.663) and; between CG and CKD-EPI (0.729). A strong similarity was noticed between MDRD and CKD-EPI (92%) while it was smaller between MDRD and CG (55%) and between CKD-EPI and CG (63%) when estimating the stage of kidney diseases. Compared to ClCr24, similarity in half results was found with MDRD (50%) and less than half with CKD-EPI (48%) and CG (38%). The study shown higher value of fasting blood glucose of diabetics attending the Ngaoundere Regional Hospital (212.1 ± 83.0 mg / dl) than the normal recommandation (127-144 mg / dl) for diabetic patients. The average value of the eGFR with MDRD (76.6 ± 20.0 mL / min) was closer to CKD-EPI (78.8 ± 20.4 ml / min) (P<0,001 ; X2=0,976). eGFR was lower in diabetics with high Blood Pressure compared to diabetics with low Blood Pressure. Estimation of CKD stages using MDRD and CKD shown significant similarity. In conclusion, CKD-EPI and MDRD estimated better the GFR. MDRD presented values that were closer to the Creatinine clearance of 24 hours. Further studies are needed with more participants to evaluate the best formula between MDRD and CKD-EPI for the estimation of GFR in Sub-Saharan diabetic population

Constitutive Overexpression of Muscarinic Receptors Leads to Vagal Hyperreactivity

BACKGROUND: Alterations in muscarinic receptor expression and acetylcholinesterase (AchE) activity have been observed in tissues from Sudden Infant Death Syndrome (SIDS). Vagal overactivity has been proposed as a possible cause of SIDS as well as of vasovagal syncopes. The aim of the present study was to seek whether muscarinic receptor overexpression may be the underlying mechanism of vagal hyperreactivity. Rabbits with marked vagal pauses following injection of phenylephrine were selected and crossed to obtain a vagal hyperreactive strain. The density of cardiac muscarinic receptors and acetylcholinesterase (AchE) gene expression were assessed. Blood markers of the observed cardiac abnormalities were also sought. METHODOLOGY/PRINCIPAL FINDINGS: Cardiac muscarinic M(2) and M(3) receptors were overexpressed in hyperreactive rabbits compared to control animals (2.3-fold and 2.5-fold, respectively) and the severity of the phenylephrine-induced bradycardia was correlated with their densities. A similar overexpression of M(2) receptors was observed in peripheral mononuclear white blood cells, suggesting that cardiac M(2) receptor expression can be inferred with high confidence from measurements in blood cells. Sequencing of the coding fragment of the M(2) receptor gene revealed a single nucleotide mutation in 83% of hyperreactive animals, possibly contributing for the transcript overexpression. Significant increases in AchE expression and activity were also assessed (AchE mRNA amplification ratio of 3.6 versus normal rabbits). This phenomenon might represent a compensatory consequence of muscarinic receptors overexpression. Alterations in M(2) receptor and AchE expression occurred between the 5th and the 7th week of age, a critical period also characterized by a higher mortality rate of hyperreactive rabbits (52% in H rabbits versus 13% in normal rabbits) and preceeded the appearance of functional disorders. CONCLUSIONS/SIGNIFICANCE: The results suggest that cardiac muscarinic receptor overexpression plays a critical role in the development of vagal hyperreactivity, whereas AchE hyperactivity appears as a compensatory consequence of it. Since similar vagal disorders were observed recently by us in SIDS, muscarinic receptor overexpression could become a marker of risk of vasovagal syncopes and SIDS

Hepatic Stem-like Phenotype and Interplay of Wnt/β-Catenin and Myc Signaling in Aggressive Childhood Liver Cancer

SummaryHepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/β-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. β-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

L’alimentation hydraulique de Saint-Romain-en-Gal (Rhône), quartier de Vienne antique (Isère)

International audienceThe distribution of water in Vienna, duplex urbs, presents different features according to which bank of the river is considered. Six aqueducts, all located on the left bank of the Rhône, supplied the centre and the southern district of the city. The water supply to the right bank was subject to variations over time. After the use of wells and spring water capture during the Augustan period, from the time of Tiberius neighbourhoods obtained water originating from the left bank through the presence of a bridge over the Rhône. The good state of preservation of the network of supply pipes allows us to follow the evolution of the management of these systems from the beginning of the 1st century AD until the 3rd century AD.La distribution de l’eau à Vienne/Vienna, duplex urbs, présente des aspects différents selon la rive du fleuve. Six aqueducs, tous situés en rive gauche du Rhône, alimentaient le centre et le quartier sud de la ville durant l’Antiquité. Quant à l’approvisionnement en eau de la rive droite, il a subi des variations selon les époques : après l’utilisation de puits et le captage de sources au cours de l’époque augustéenne, les quartiers ont bénéficié de l’eau issue de la rive gauche grâce à la présence au nord de la ville d’un pont sur le Rhône à partir de l’époque de Tibère. Une excellente conservation du réseau des canalisations d’adduction permet de suivre l’évolution de la gestion de ces réseaux du début du Ier s. apr. J.-C. jusqu’au IIIe s. apr. J.-C

The sodium/iodide symporter: State of the art of its molecular characterization

International audienceThe sodium/iodide symporter (NIS or SLC5A5) is an intrinsic membrane protein implicated in iodide uptake into thyroid follicular cells. It plays a crucial role in iodine metabolism and thyroid regulation and its function is widely exploited in the diagnosis and treatment of benign and malignant thyroid diseases. A great effort is currently being made to develop a NIS-based gene therapy also allowing the radiotreatment of nonthyroidal tumors. NIS is also expressed in other tissues, such as salivary gland, stomach and mammary gland during lactation, where its physiological role remains unclear. The molecular identity of the thyroid iodide transporter was elucidated approximately fifteen years ago. It belongs to the superfamily of sodium/solute symporters, SSS (and to the human transporter family, SLC5), and is composed of 13 transmembrane helices and 643 amino acid residues in humans. Knowledge concerning NIS structure/function relationship has been obtained by taking advantage of the high resolution structure of one member of the SSS family, the Vibrio parahaemolyticus sodium/galactose symporter (vSGLT), and from studies of gene mutations leading to congenital iodine transport defects (ITD). This review will summarize current knowledge regarding the molecular characterization of NIS

Mandibular buccal bifurcation cyst treatment: report of two cases and literature review

The mandibular bifurcation cyst is an uncommon lesion that was first described by Stoneman and Worth in 1983. It is a site and age-specific lesion affecting the first or second permanent mandibular molar in children between 6 and 13 years old. Even if the clinical and radiological signs are well defined, this lesion can be misdiagnosed in particular with forms which would have a spontaneous resolution. The patient care is less well defined, the range of treatments being rather wide, from the simple follow-up to the extraction of the involved tooth. Both two clinical cases presented will illustrate the diagnostic criterias associated to the buccal bifurcation cyst. The etiopathogenesis and the therapeutic decision criterias will be discussed through a literature review

Preliminary phytochemical screening and protective effect of Erythrina Senegalensis in an in vivo mouse model of Alzheimer's disease

International audienceErythrina senegalensis is a therapeutic plant selective extracts from bark of of the African Pharmacopoeia, widely used E. senegalensis by identification tests, and by populations in the treatment many evaluated its anti-radical activity (DPPH pathologies, including mental disorders and test) and compared to vitamin C. Finally, we cognitive impairments. We qualitatively examined its neuroprotective potential in analyzed crude methanol, acidic extracts and vivo in a pharmacological mouse model of Alzheimer's disease at the behavioral and biochemical level. The neuroprotective activity was evaluated in vivo in mice intracerebroventricularly injected with oligomeric amyloid-β25-35 peptide. The different tests were analyzed and compared to donepezil, anacetylcholinesteraseinhibitor. Sterols, terpenes, coumarins, alkaloids, flavonoids, polyphenolstannins were identified in the plant. The best inhibitory profile of DPPH radical was observed for the chloroform extract. The crude methanol extract had high neuroprotective activities in vivo