Assessment of soil trace metal contamination of an uncontrolled landfill and its vicinity: the case of the city of ‘Targuist’ (Northern Morocco)

This study aims to assess, for the first time, soil Trace Metal Elements (TME) contamination level in an uncontrolled landfill and its vicinity of 'Targuist' (town in northern Morocco). Soil samples were collected at two depths (20 and 40cm) from 16 sampling sites. Samples were characterized for their physicochemical parameters (pH, electrical conductivity (EC), organic matter (OM) and total organic carbon (TOC)) and for their TME (copper (Cu), zinc (Zn), cadmium (Cd) and chromium (Cr)) using atomic absorption spectroscopy (ASS). The results show no significant differences between soils sampled at 20cm or 40cm depths regarding the tested parameters. While significant differences between sampling sites In landfill and Out landfill is observed particularly regarding pH, CaCO3, TOC, and Cd. Overall, our results show that soil physicochemical properties follow a spatial variability with decreasing values moving away from the landfill. Regarding TME soil contents, our results show contamination levels in most of the sampling sites of the study area. Furthermore, the total TME concentrations in soils vary according to the type of the studied metal and to the sampling site. Zn, Cu and Cd show significant positive correlations with pH. However, Cd has no correlation with any other trace elements or soil physicochemical properties. Meanwhile, Cr shows a significant negative correlation with Zn and Cu. OM, TOC, CaCO3 and EC are strongly and positively correlated. These results are well illustrated in the outcomes of the Principal Components Analysis and Hierarchical Cluster Analysis

Tuberculose uro-génitale : A propos de 95 cas

Objectif: Préciser les aspects cliniques, iconographiques et thérapeutiques de la tuberculose urogénitale. Patients et méthodes: D’avril 1992 à avril 2007, 95 patients atteints de tuberculose uro-génitale ont été vus. Il s’agissait de 53 hommes et 42 femmes âgés de 18 à 72 ans. Tous nos malades ont bénéficié d’un interrogatoire, avec recherche des antécédents de tuberculose extra urinaire, d’un examen clinique, d’une créatinémie, d’une urographie intra veineuse (UIV), d’une échographie et/ou tomodensitométrie, de la recherche du bacille de Koch (BK) dans les urines, d’un ECBU, d’une cystoscopie, et d’une analyse histologique des fragments biopsiques et/ou de la pièce d’exérèse. Résultats: Le diagnostic était basé sur un faisceau d’arguments cliniques, bactériologiques et radiologiques. L’irritation vésicale représentait la manifestation clinique la plus fréquente (51,5%). L’atteinte génitale isolée était présente chez 17,8% des patients. 16,8% de nos malades avaient une insuffisance rénale inaugurale (créatinine moyenne de 24 mg/l). La recherche de BK a été réalisée chez tous les patients et n’a été positive que dans 9,4% des cas. Les anomalies à l’UIV concernaient 86% des malades avec un rein muet dans 42% des cas. On a traité tous nos patients par une chimiothérapie antibacillaire associée à la chirurgie (85,2%) et/ou à des manoeuvres endo-urologiques (20%). Avec un recul moyen de 3 ans (extrêmes allant de 1 à 9 ans), la plupart de nos patients ont bien évolué sous traitement. L’amélioration clinique a été spectaculaire avec disparition des signes cliniques chez 88% des patients. La fonction rénale a été normalisée chez 70% des cas. Conclusion: La tuberculose reste une maladie grave par son évolution latente et le diagnostic tardif. L’amélioration de son pronostic passe par la prévention et par une bonne prise en charge diagnostique et thérapeutique.Mots clés : Tuberculose uro-génitale, diagnostic, traitemen

L’exstrophie vésicale chez l’adulte: A propos de 5 cas

RésuméButle but de cette étude est d’analyser les particularités de l’exstrophie vésicale chez l’adulte, sur les plans psycho-social et chirurgical.Patients et méthodesil s’agit d’une étude rétrospective de 5 patients, âgés entre 18 et 25ans, hospitalisés pour prise en charge d’une exstrophie vésicale. Les scores ICIQ-SF et MCS-SF36 ont été utilisés pour évaluer respectivement la continence urinaire et la qualité de vie avant et après réalisation d’une urostomie de type de vessie iléo-coecale continente VICC.Résultatsune amélioration significative a été notée sur les plans de continence et qualité de vie: l’ICIQ-SF après 6 mois était de 4,2+- 4,02 contre 18,8+- 2,28 avant chirurgie (p=0,0003), et le MCS-SF à 6 mois était de 57,15+/-13,37 contre 37,2+/-13,22 avant chirurgie (p=0,045). Des complications stomiales à long terme ont été enregistrées.Conclusionl’urostomie continente à type de VICC améliore la qualité de vie et la continence des patients adultes ayant une exstrophie vésicale, mais au prix de complications stomiales à long terme.AbstractObjectivethe aim of this study is to analyze sexual, psycho-social and surgical particularities of bladder exstrophy in adulthood.Patients and methodsa retrospective study was performed including 5 patients, from 18 to 25 years old, admitted for management of bladder exstrophy. ICIQ-SF and MCS-SF36 scores were used to assess respectively urinary continence and quality of life before and after continent ileo-coecal bladder.Resultsa significant improvement was noted in both urinary continence and quality of life: the ICIQ-SF after 6 months was 4.2+/- 4.02 against 18.8+/- 2.28 before surgery (p=0.0003), and MCS-SF at 6 months was 57.15+/-13.37 against 37.2+/-13.22 before surgery (p=0.045). Stomal complications were recorded in the long term.Conclusionthe continent ileocoecal bladder improves the quality of life and urinary continence in adult patients with bladder exstrophy, but at the cost of long-term stomal complications

Abord trans-symphysaire des ruptures posttramatiques de l’urètre postérieur chez l’adulte

Objectif: Etudier la place de la voie trans-symphysaire dans le traitement des ruptures posttraumatiques de l’urètre postérieur vues tardivement et en évaluer ses résultats. Patients et méthodes: Cinq malades ayant une rupture complète post-traumatique de l’urètre postérieur (> 2,5 cm et/ou échec d’un traitement antérieur) ont été traités dans notre service au stade de sténose urétrale. Tous les patients ont eu une urétrorraphie termino-terminale par voie trans-symphysaire seule. Une description technique et une évaluation clinique et paraclinique des résultats sur le plan mictionnel et sexuel ont été réalisées dans ce travail. Résultats: Les résultats ont été évalués avec un suivi médian de 19 mois. Aucune complication post-opératoire immédiate (saignement, fistule, douleur) n’a été rapportée. Sur le plan mictionnel, on a constaté dans tous les cas une miction satisfaisante, sans troubles de la continence et un cas de dysfonction érectile améliorée par le traitement médical. Aucun patient ne s’est plaint de troubles de la statique pelvienne. Conclusion: La voie trans-symphysaire constitue un excellent abord pour le traitement des lésions complexes de l’urètre postérieur vues tardivement. Cette technique permet d’avoir un abord direct sur l’urètre postérieur et de réaliser une suture termino-terminale sans tension. Les résultats sont satisfaisants et les inconvénients sont plus théoriques que réels.Mots clés : Rupture de l’urètre postérieur, sténose de l’urètre postérieur, urétrorraphie, voie transsymphysair

How much dystrophin is enough: the physiological consequences of different levels of dystrophin in the mdx mouse

Splice modulation therapy has shown great clinical promise in Duchenne muscular dystrophy, resulting in the production of dystrophin protein. Despite this, the relationship between restoring dystrophin to established dystrophic muscle and its ability to induce clinically relevant changes in muscle function is poorly understood. In order to robustly evaluate functional improvement, we used in situ protocols in the mdx mouse to measure muscle strength and resistance to eccentric contraction-induced damage. Here, we modelled the treatment of muscle with pre-existing dystrophic pathology using antisense oligonucleotides conjugated to a cell-penetrating peptide. We reveal that 15% homogeneous dystrophin expression is sufficient to protect against eccentric contraction-induced injury. In addition, we demonstrate a >40% increase in specific isometric force following repeated administrations. Strikingly, we show that changes in muscle strength are proportional to dystrophin expression levels. These data define the dystrophin restoration levels required to slow down or prevent disease progression and improve overall muscle function once a dystrophic environment has been established in the mdx mouse model

Isolation of Exosomes from Blood Plasma: Qualitative and Quantitative Comparison of Ultracentrifugation and Size Exclusion Chromatography Methods

BACKGROUND: Exosomes are emerging targets for biomedical research. However, suitable methods for the isolation of blood plasma-derived exosomes without impurities have not yet been described. AIM: Therefore, we investigated the efficiency and purity of exosomes isolated with potentially suitable methods; differential ultracentrifugation (UC) and size exclusion chromatography (SEC). METHODS AND RESULTS: Exosomes were isolated from rat and human blood plasma by various UC and SEC conditions. Efficiency was investigated at serial UC of the supernatant, while in case of SEC by comparing the content of exosomal markers of various fractions. Purity was assessed based on the presence of albumin. We found that the diameter of the majority of isolated particles fell into the size range of exosomes, however, albumin was also present in the preparations, when 1h UC at 4 degrees C was applied. Furthermore, with this method only a minor fraction of total exosomes could be isolated from blood as deduced from the constant amount of exosomal markers CD63 and TSG101 detected after serial UC of rat blood plasma samples. By using UC for longer time or with shorter sedimentation distance at 4 degrees C, or UC performed at 37 degrees C, exosomal yield increased, but albumin impurity was still observed in the isolates, as assessed by transmission electron microscopy, dynamic light scattering and immunoblotting against CD63, TSG101 and albumin. Efficiency and purity were not different in case of using further diluted samples. By using SEC with different columns, we have found that although a minor fraction of exosomes can be isolated without significant albumin content on Sepharose CL-4B or Sephacryl S-400 columns, but not on Sepharose 2B columns, the majority of exosomes co-eluted with albumin. CONCLUSION: Here we show that it is feasible to isolate exosomes from blood plasma by SEC without significant albumin contamination albeit with low vesicle yield

Interleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cells

IL-21 is known to promote anti-tumour immunity due to its ability to promote T cell responses and counteract Treg-mediated suppression. It has also been shown to limit Treg frequencies during tumour-antigen stimulations. However, whether this represents inhibition of FOXP3 induction in naïve CD4 T cells or curtailed expansion of natural Treg remains unclear. Moreover, whether this effect is maintained in an environment of tumour-derived immunosuppressive factors is not known. Here, we show that in the context of a number of cancers, naïve CD45RA+ CD4 T cells are induced to express high levels of FOXP3, and that FOXP3 expression correlates with inhibition of T cell proliferation. FOXP3 expression was most potently induced by tumours secreting higher levels of total and active TGFβ1 and this induction could be potently counteracted with IL-21, restoring T cell proliferation. We conclude that Treg induction in naïve T cells is a common phenomenon amongst a number of different cancers and that the ability of IL-21 to counteract this effect is further evidence of its promise in cancer therapy

Monitoring of Regulatory T Cell Frequencies and Expression of CTLA-4 on T Cells, before and after DC Vaccination, Can Predict Survival in GBM Patients

PURPOSE: Dendritic cell (DC) vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL) subsets in glioblastoma patients treated with DC vaccination at UCLA. EXPERIMENTAL DESIGN: Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival. RESULTS: The change in regulatory T cell (CD3(+)CD4(+)CD25(+)CD127(low)) frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623) after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+)CD4(+) T cells (p = 0.0191; hazard ratio = 2.840) and CD3(+)CD8(+) T cells (p = 0.0273; hazard ratio = 2.690), while that of activation markers (CD25, CD69) was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves. CONCLUSIONS: Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future prospective immunotherapy trials to further evaluate its predictive validity

The biogenesis and characterization of mammalian microRNAs of mirtron origin

Mirtrons, short hairpin pre-microRNA (miRNA) mimics directly produced by intronic splicing, have recently been identified and experimentally confirmed in invertebrates. While there is evidence to suggest several mammalian miRNAs have mirtron origins, this has yet to be experimentally demonstrated. Here, we characterize the biogenesis of mammalian mirtrons by ectopic expression of splicing-dependent mirtron precursors. The putative mirtrons hsa-miR-877, hsa-miR-1226 and mmu-miR-1224 were designed as introns within eGFP. Correct splicing and function of these sequences as introns was shown through eGFP fluorescence and RT–PCR, while all mirtrons suppressed perfectly complementary luciferase reporter targets to levels similar to that of corresponding independently expressed pre-miRNA controls. Splicing-deficient mutants and disruption of key steps in miRNA biogenesis demonstrated that mirtron-mediated gene knockdown was splicing-dependent, Drosha-independent and had variable dependence on RNAi pathway elements following pre-miRNA formation. The silencing effect of hsa-miR-877 was further demonstrated to be mediated by the generation of short anti-sense RNA species expressed with low abundance. Finally, the mammalian mirtron hsa-miR-877 was shown to reduce mRNA levels of an endogenous transcript containing hsa-miR-877 target sites in neuronal SH-SY5Y cells. This work confirms the mirtron origins of three mammalian miRNAs and suggests that they are a functional class of splicing-dependent miRNAs which are physiologically active