[Realities for a Sickle Cell Disease Control Strategy in the World Health Organization African Region]. / Réalités pour une stratégie de lutte contre la drépanocytose dans la région africaine de l'Organisation Mondiale de la Santé: Compte rendu du 7e Symposium International du Réseau d'Étude de la Drépanocytose en Afrique Centrale (REDAC https://www.redacnetwork.org/) Antananarivo, Madagascar. 13 - 15 juin 2018.

The Network for the Study of Sickle Cell Disease in Central Africa or REDAC, is a network of African, European and American researchers whose aim is to combat sickle cell disease. Its congresses take place every year in the partner countries with international symposia alternating with workshops. REDAC enables host countries to obtain from local authorities a real involvement in the fight through resolutions in line with national strategies of fight. The Seventh International Symposium of REDAC was held in 2018 in Antananarivo, Madagascar under the auspices of the Malagasy Minister of Health and the Malagasy Senate Authorities. The theme chosen was that of strategies to combat sickle cell disease recommended by the WHO. The presentations focused on neonatal screening, early diagnosis, management of sickle cell disease and new therapies (marrow transplant, gene therapy and treatment with hydroxyurea).

Perfluorocarbons: new tool for islets preservation in vitro.

Pancreatic islet transplantations to treat type 1 diabetes often fail to function because of hypoxia. Perfluorocarbons (PFCs) exhibit a high oxygen solubility coefficient and maintain high oxygen partial pressure for extended times. They also serve as oxygen "reservoirs" for harvested organs in pancreas organ transplantation. Previous studies have shown the PFCs display antiadhesive effects on beta cells. The aim of this study was to evaluate the effects of PFC on islet viability and functionality and on extracellular matrix (ECM) disruption of islets via inhibition of adhesion. Primary cultures of rat islets were incubated for 24 hours in the presence or absence of 3.5% (weight/volume) PFCs in culture media. We studied viability (FDA/PI), stimulation index linked to insulin secretion (ELISA), and expression of insulin and laminin messenger RNAs (mRNAs). Immunostaining was performed on insulin and laminin. Islet viability was similar in the presence or absence of PFCs (about 80%). Stimulation index showed preservation of islet functionality in the presence of PFC (4.9 +/- 0.7) as compared with controls (2.8 +/- 0.5). Moreover, laminin mRNA expression was lower compared with controls (55% of PFC incubated vs control islets). Immunohistochemistry studies showed preservation of ECM inside the islets in the presence of PFCs versus controls at 24 hours after islet isolation. In conclusion, PFCs preserved islet viability and functionality and prevented ECM disruption. PFCs may represent a new tool for islet preservation in vitro.

Influence of rapamycin on rat macrophage viability and chemotaxis toward allogenic pancreatic islet supernates.

The aim of this work was to evaluate the effects of rapamycin on rat macrophage viability and chemotaxis toward allogereic pancreatic islet supernates. Macrophages were isolated from rats by peritoneal lavage at 3 days after intraperitoneal injection of thioglycolate. Macrophage viability was studied after 7 days of culture by Cell Titer assays in the presence of rapamycin at 0.1, 1, and 10 ng/mL (n = 6). After 48 hours of culture, pancreatic rat islet supernates were studied for there chemotactic properties toward freshly isolated macrophages in the presence of rapamycin at 0.1, 1, and 10 ng/mL. Chemotaxis was expressed as a migration index defined as the number of macrophages attracted by the test solution (islet supernate +/- rapamycin)/number of macrophages attracted by the supernate (n = 6). After 3 days of culture, macrophage viability decreased significantly by 22%, 36%, and 32% in the presence of 0.1, 1, and 10 ng/mL rapamycin, respectively (P = .008). Macrophage viability remained stable at about 70% after 7 days of culture. In the presence of islet supernates, macrophage migration increased two-fold compared with those obtained by culture medium. Rapamycin did not influence macrophage migration toward culture medium. However, the drug significantly reduced the migration of macrophages toward islet supernates from 2 +/- 0.6 to 0.9 +/- 0.4, 0.7 +/- 0.3, or 0.8 +/- 0.4 in the presence of 0.1, 1, or 10 ng/mL rapamycin, respectively (P = .04). Rapamycin decreased the survival of cultured rat macrophages and their migration toward allogenic islet supernates. These results suggested that, besides its anti-proliferative effect on T cells, rapamycin reduced macrophage attraction to the graft site.

Rat nerve regeneration with the use of a polymeric membrane loaded with NGF.

Exogenous neurotrophic factors, delivered by various systems, are used to improve nerve regeneration. This study tested the effectiveness of a polymeric membrane loaded with Nerve Growth Factor (NGF) on mental nerve regeneration after a crush injury in rats. We tested NGF application, known to play a role in afferent fiber repair in dental neurobiology, to see if it could improve the regeneration. Afferent neurogram recordings and histological analyses of the trigeminal ganglion neurons were performed. One month after the crush injury, early regeneration was observed independently of exogenous NGF. However, as compared with the activity level recorded before the injury, the afferent activity was reduced by 28.5% without NGF, and the mean number of labeled neurons decreased. With NGF, activity was increased by 30.8%, with no significant histological difference compared with animals without lesions. NGF application through a polymeric membrane can influence degenerative and/or regenerative processes after a crush injury.

Compensatory mechanism of motor defect in SOD1 transgenic mice by overactivation of striatal cholinergic neurons.

Expression of a mutant superoxide dismutase 1 (SOD1) gene in transgenic mice induces a gradual degeneration of cholinergic motor neurons in the spinal cord, causing progressive muscle weakness and hindlimb paralysis. Transgenic mice over-expressing the human SOD1 gene containing a Gly-->Ala substitution at position 93 (G93A) were employed to explore the effects of the SOD1 mutation on choline acetyltransferase (ChAT) expression in the striatum, and in the lumbar and cervical spinal cord. These mice showed a progressive loss of their spinal cord motor neurons, and at 130 days of age showed an up-regulation of ChAT mRNA expression in the striatum. On the other hand, ChAT mRNA decreased in cervical and lumbar motor neurons. These findings suggest that cholinergic interneurons in striatum in SOD1 transgenic mice are over-activated in an attempt to compensate for the death of spinal motor neurons.