Involvement of heparanase in the pathogenesis of acute kidney injury: Nephroprotective effect of PG545

Despite the high prevalence of acute kidney injury (AKI) and its association with increased morbidity and mortality, therapeutic approaches for AKI are disappointing. This is largely attributed to poor understanding of the pathogenesis of AKI. Heparanase, an endoglycosidase that cleaves heparan sulfate, is involved in extracellular matrix turnover, inflammation, kidney dysfunction, diabetes, fibrosis, angiogenesis and cancer progression. The current study examined the involvement of heparanase in the pathogenesis of ischemic reperfusion (I/R) AKI in a mouse model and the protective effect of PG545, a potent heparanase inhibitor. I/R induced tubular damage and elevation in serum creatinine and blood urea nitrogen to a higher extent in heparanase over-expressing transgenic mice vs. wild type mice. Moreover, TGF-\u3b2, vimentin, fibronectin and \u3b1-smooth muscle actin, biomarkers of fibrosis, and TNF\u3b1, IL6 and endothelin-1, biomarkers of inflammation, were upregulated in I/R induced AKI, primarily in heparanase transgenic mice, suggesting an adverse role of heparanase in the pathogenesis of AKI. Remarkably, pretreatment of mice with PG545 abolished kidney dysfunction and the up-regulation of heparanase, pro-inflammatory (i.e., IL-6) and pro-fibrotic (i.e., TGF-\u3b2) genes induced by I/R. The present study provides new insights into the involvement of heparanase in the pathogenesis of ischemic AKI.Our results demonstrate that heparanase plays a deleterious role in the development of renal injury and kidney dysfunction,attesting heparanase inhibition as a promising therapeutic approach for AKI

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Les conséquences des pluies exceptionnelles de janvier 1994 sur le milieu dans les bassins et les montagnes du Rif oriental marocain

An exceptional precipitation event occurred during three consecutive days (17, 18 and 19 janvier 1994) in the East of the Rifian region, Morocco. The records enregistrated in all the climatological stations of the region exceeded 150 mm. A maximum of 237 mm is reached in the Boudinar station. Despite its low occurrence, a such event gives an exceptional opportunity to observe the behaviour of terrains under cultures, bare terrains and soil and water conservation techniques. The purpose of this paper is to evaluate the role of human activities in a region having a fragile ecosystem equilibrium. The methodology adopted is based on direct observations of all kinds of phenomena acting on the previous terrains and techniques. We had also made some field mesures to evaluate the degree of degradation phenomena and its costs.Des précipitations exceptionnelles se sont abattues pendant trois jours consécutifs, les 17, 18 et 19 janvier 1994 sur le Rif oriental marocain. Les totaux enregistrés par les stations pluviométriques de la région sont sans précédent, ce qui donne une occasion unique pour observer l 'évolution de la surface sous des conditions pluviométriques extrêmes. Les observations qui font l'objet de cet article portent sur le comportement des terrains de culture et les aménagements de conservation des eaux et des sols, mis en place par les populations locales. L'objectif consiste en une meilleure appréhension de l'impact anthropique sur ce milieu à équilibre fragile et profondément transformé par l'homme. L'approche méthodologique adoptée s'appuie sur l'observation et sur la confrontation des diverses situations observées, sur des mesures ponctuelles menées sur les champs et sur des enquêtes auprès des populations locales pour évaluer l'importance et le coût des dégâts.El Abbassi Hassan. Les conséquences des pluies exceptionnelles de janvier 1994 sur le milieu dans les bassins et les montagnes du Rif oriental marocain. In: Méditerranée, tome 86, 1-2-1997. Impact anthropique en milieu méditerranéen. pp. 67-76

Quelques aspects des transformations récentes dans les campagnes du Rif oriental marocain : mécanismes, formes et incidences sur le milieu

Situated in semi-arid and arid environment and having a fragile equilibrium of their ecosystems, the rural regions of the Eastern Rif in Morocco, are subjected to various mutations which could be noted in all fields at different levels. These transformations are directly linked to emigration. On the social level, a decrease of the population is observed in all the parts of the region. This triggers a deficiency of workmanship and changes in farming modes. Only about 10 % of the farmers continue cultivating the totality of their lands directly. Several parcels of fertile lands are abandoned and some of them are planted with olive trees. Consequently, the extension of the uncultivated land induces high surface runoff which causes many damages to the landscape. Farming represents the most adequate way to reduce land erosion in the Rif. The presence of man in this region is a fundamental factor for its environmental stability. On the other hand, the traditional techniques of soil and water conservation are abandoned, which causes them to deteriorate. The rural habitat undergoes several transformations : dispersion, architectural modifications, etc. The whole of these mutations always has ambivalent consequences on environmental stability.Les campagnes du Rif oriental marocain font actuellement face à de nombreuses transformations qui se répercutent directement sur le milieu naturel. Ces mutations sont largement liées à l'émigration internationale du travail. Sur le plan social, une diminution nette de la population se manifeste dans la quasi-totalité des communes rurales de la région, entraînant un écrémage de la main-d'œuvre et des changements dans les modes de faire-valoir agricole. De nombreux terrains cultivés sont abandonnés, ce qui se manifeste par l'extension de la friche qui transforme de larges secteurs en surface de concentration rapide des eaux. Les techniques traditionnelles de conservation des eaux et du sol mises en place par la population autochtone se dégradent. L'habitat rural connaît des changements remarquables : dispersion, modification de l'architecture, etc. Ces mutations ont souvent des conséquences ambivalentes pour la stabilité du milieu naturel.El Abbassi Hassan. Quelques aspects des transformations récentes dans les campagnes du Rif oriental marocain : mécanismes, formes et incidences sur le milieu . In: Annales de Géographie, t. 106, n°597, 1997. pp. 479-501

Les oasis de la région de Tata (Maroc) : abandon de la vie oasienne traditionnelle et adaptation à la vie urbaine

Barathon Jean-Jacques, El Abbassi Hassan, Lechevalier Claude. Les oasis de la région de Tata (Maroc) : abandon de la vie oasienne traditionnelle et adaptation à la vie urbaine. In: Annales de Géographie, t. 114, n°644, 2005. pp. 449-461

Caractérisation de la corrosion d’acier par la méthode ultrasonore en mode de réflexion

La méthode ultrasonore est très largement utilisée pour détecter et caractériser des défauts internes, mais aussi pour mesurer des épaisseurs résiduelles en présence de phénomènes corrosifs ou érosifs. Dans ce travail, Nous avons exploité : la technique ultrasonore en réflexion servant d’un transducteur de fréquence centrale 5MHz, dont le but de déduire les paramètres ultrasoniques des échantillons, et du traçage du coefficient de réflexion expérimentale correspondant à chaque échantillon. Ce travail a mis en évidence la fiabilité et l’aptitude des techniques ultrasonores pour montrer l’influence de la durée d’immersion dans une solution corrosive. La corrosion résultante sur l’acier corrodé est analysée par le suivi de l’évolution des paramètres ultrasonores. Nous confirmons certains résultats trouvés par d’autres chercheurs ([1] (K. Niboucha, 2006); [2] (Benjamin L. Ervin, 2009); [3] (Vervisch-Fortuné Isabelle, 2009) ; [4] (S. Sharma, 2010), sur l’influence du processus de corrosion des aciers avec des méthodes de contrôle non destructif

Caractérisation de la corrosion d’acier par la méthode ultrasonore en mode de réflexion

La méthode ultrasonore est très largement utilisée pour détecter et caractériser des défauts internes, mais aussi pour mesurer des épaisseurs résiduelles en présence de phénomènes corrosifs ou érosifs. Dans ce travail, Nous avons exploité : la technique ultrasonore en réflexion servant d’un transducteur de fréquence centrale 5MHz, dont le but de déduire les paramètres ultrasoniques des échantillons, et du traçage du coefficient de réflexion expérimentale correspondant à chaque échantillon. Ce travail a mis en évidence la fiabilité et l’aptitude des techniques ultrasonores pour montrer l’influence de la durée d’immersion dans une solution corrosive. La corrosion résultante sur l’acier corrodé est analysée par le suivi de l’évolution des paramètres ultrasonores. Nous confirmons certains résultats trouvés par d’autres chercheurs ([1] (K. Niboucha, 2006); [2] (Benjamin L. Ervin, 2009); [3] (Vervisch-Fortuné Isabelle, 2009) ; [4] (S. Sharma, 2010), sur l’influence du processus de corrosion des aciers avec des méthodes de contrôle non destructif

Heat waves and health impact on human in Baghdad

This investigation aim to evaluate the effect of heat wave on health of human, so to achieve this 40 blood samples for person exposed to heat wave were drawn most patients were attend to specialists in hospital laboratories (Medical City, Ibn al-Baladi, Sheikh Zayed, Kadhimiya Educational). The patients aged 10–60 years, male (20) and female (20). CBC analyzes was performed. The result of the presents study recorded a highly signifi cant difference in total (mean and percent) as compared with the normal value of the CBC analyze the result for total (mean and percent) for male the factors CRP, ESR, WBC, PCV, PL (15.5, 43, 11.35, 28.5, 215) respectively (100%, 100%, 100%, 100%, 100%) and the result for total (mean and percent) for female the factors CRP, ESR, WBC, PCV, PL (15, 43.5, 11.35, 31, 220.5) respectively (100%, 100%, 100%, 100%, 100%). According to the result we can conclude that there was a highly significant deferent in mean value for patient compared with the normal value which is the mean cause of hard attack which lead to death. The study is the first of its kind in the Department of Atmospheric Sciences in Iraq

The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus

Objective(s):Silver nanoparticles (Ag-NPs) are used widely in bedding, water purification, tooth paste and toys. These nanoparticles can enter into the body and move into the hippocampus. The aim of this study was to investigate the neurotoxicity of silver nanoparticles in the adult rat hippocampus. Materials and Methods:12 male Wistar rats were randomly divided into two experimental and control groups (6 rats in each group). Animals in the experimental group received Ag-NPs (30 mg/kg) orally (gavage) for 28 consecutive days. Control group in the same period was treated with distilled water via gavage. At the end of experiment, animals were deeply anesthetized, sacrificed, and their brains were collected from each group. Finally the brain sections were stained using toluidine blue and TUNEL. Then to compare the groups, dark neurons (DNs) and apoptotic neurons were counted by morphometric method. Results: Results showed that the num­bers of DNs and apoptotic cells in the CA1, CA2, CA3, and dentate gyrus (DG) of hippocampus significantly increased in the Ag-NPs group in comparison to the control group (