Rapid Wolff–Kishner reductions in a silicon carbide microreactor

Wolff–Kishner reductions are performed in a novel silicon carbide microreactor. Greatly reduced reaction times and safer operation are achieved, giving high yields without requiring a large excess of hydrazine. The corrosion resistance of silicon carbide avoids the problematic reactor compatibility issues that arise when Wolff–Kishner reductions are done in glass or stainless steel reactors. With only nitrogen gas and water as by-products, this opens the possibility of performing selective, large scale ketone reductions without the generation of hazardous waste streams.Novartis-MIT Center for Continuous ManufacturingNatural Sciences and Engineering Research Council of Canada (post-doctoral fellowship

Mesenchymal Stromal Cells Engage Complement and Complement Receptor Bearing Innate Effector Cells to Modulate Immune Responses

Infusion of human third-party mesenchymal stromal cells (MSCs) appears to be a promising therapy for acute graft-versus-host disease (aGvHD). To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46) and DAF (CD55), but were protected from complement lysis via expression of protectin (CD59). Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18)-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells

Désulfuration sélective du gaz soutiré d'un stockage souterrain Selective Desulfurization of Gas Withdrawn from an Underground Storage Facility

La présence d'H2S constatée dès les premiers soutirages de gaz au stockage souterrain en nappe aquifère de Chémery avait nécessité la mise en place d'unités de désulfuration. Le gaz injecté étant exempt de gaz carbonique, le procédé par voie liquide utilisant la monoéthanolamine avait été retenu. Depuis 1977, le gaz injecté contenant des quantités appréciables de gaz carbonique a rendu inutilisable ce procédé. Parallèlement à l'injection de ce composé acide, la production d'H2S a fortement augmenté. La mise en oeuvre d'une amine sélective (MDEA) a permis d'éliminer les composés soufrés en laissant pratiquement inchangée la composition du gaz chargé en C02. Les installations existantes ont pu être conservées, la banalisation des circuits facilitant l'utilisation de cette nouvelle amine. La communication présente les études et essais réalisés ainsi que les résultats d'exploitation qui se sont révélés particulièrement intéressants tant au point de vue technique qu'économique <br> The presence of H2S in the first gas withdrawn from the underground storage aquifer at Chémery, France, required the installation of desulfurization units. Since there was no carton dioxide in the injected gas, a liquid process using monoethanolamine was selected. This process has become unusable since 1977 because the injected gas contains appreciable amounts of carton dioxide. At the same time as the injection of this acid compound, the production of H2S has considerably increased. A selective amine (MDEA) was used tg eliminate the sulfur-containing compounds while leaving the composition of the C02-containing gas almost unchanged. The existing installations have been maintained as the result of the standardizing of the circuits for this new amine. This article describes the research and tests performed as well as the operational results which have turned out to be particularly intersting from both the technical and economic stand point

Thrombotic disease in systemic lupus erythematosus is associated with a maintained systemic platelet activation

Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis. Platelet-induced extracellular phosphorylation of plasma proteins suggests that this is due to persistent activation of the platelets. We examined 30 SLE patients (15 with thrombotic disease), 18 non-SLE patients with deep vein thrombosis (DVT) and 50 healthy controls by analysing beta-thromboglobulin, activated factor XI-antithrombin complexes and fibrinogen-bound phosphate. All parameters were elevated in SLE patients, particularly those with thrombosis, but normal in DVT cases and healthy controls. We conclude that thrombotic disease in SLE patients is associated with a persistent systemic platelet activation that may lower the threshold for induction of thrombosis

Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation.

The instant blood-mediated inflammatory reaction (IBMIR) is triggered in clinical islet transplantation when human pancreatic islets come in contact with blood and may explain the initial tissue loss associated with this procedure. Low molecular weight dextran sulfate (LMW-DS; MM 5000), today available for clinical use, inhibits both complement and coagulation activation. In a tubing loop model, LMW-DS at concentrations ranging from 0.01 to 1 g/L showed a dose-dependent inhibition of IBMIR with an inhibition of coagulation and complement activation and less consumption of platelets and other blood cells. In blood or plasma APTT was demonstrated to be an excellent method for monitoring the LMW-DS concentration both in vitro and in vivo in a nonhuman primate model. The toxicity was assessed using a glucose challenge test and the pharmacokinetics was tested in the nonhuman primate model. Here, we present a tentative protocol for using LMW-DS in clinical islet transplantation

Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation

Background Intraportal transplantation of pancreatic islets offers improved glycaemic control and insulin independence in type 1 diabetes mellitus, but intraportal thrombosis remains a possible complication. The thrombotic reaction may explain why graft loss occurs and islets from more than one donor are needed, since contact between human islets and ABO-compatible blood in vitro triggers a thrombotic reaction that damages the islets. We investigated the possible mechanism and treatment of such thrombotic reactions. Methods Coagulation activation and islet damage were monitored in four patients undergoing clinical islet transplantation according to a modified Edmonton protocol. Expression of tissue factor (TF) in the islet preparations was investigated by immunohistochemistry, immunoprecipitation, electron microscopy, and RT-PCR. To assess TF activity in purified islets, human islets were mixed with non-anticoagulated ABO-compatible blood in tubing loops coated with heparin. Findings Coagulation activation and subsequent release of insulin were found consistently after clinical islet transplantation, even in the absence of signs of intraportal thrombosis. The endocrine, but not the exocrine, cells of the pancreas were found to synthesise and secrete active TF. The clotting reaction triggered by pancreatic islets in vitro could be abrogated by blocking the active site of TF with specific antibodies or site-inactivated factor Vlla, a candidate drug for inhibition of TF activity in vivo. Interpretation Blockade of TF represents a new therapeutic approach that might increase the success of islet transplantation in patients with type 1 diabetes, in terms of both the risk of intraportal thrombosis and the need for islets from more than one donor