Methods of diagnosis and triage using cell activation measures

A - Human Necessities – 61 – K

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A61K 38/57 (2006.01) C12N 5/071 (2010.01) A61K 31/235 (2006.01) A61K 35/39 (2006.01) A61K 38/55 (2006.01) C12Q 1/00 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2322618

Diagnostic methods that rely on the use of one or more assays that assess cellular activation are provided. The assays are performed on whole blood or leukocytes (neutrophils), and indicate individually or in combination the level of cardiovascular cell activation, which is pivotal in many chronic and acute disease states. These results of the assays are used within a clinical framework to support therapeutic decisions such as: further testing for infectious agents, anti-oxidant or anti-adhesion therapy, postponement and optimal re-scheduling of high-risk surgeries, classifying susceptibility to and progression rates of chronic disease such as diabetes, organ rejection, atherogenesis, and venous insufficiency; extreme interventions in trauma cases of particularly high risk and activation-lowering therapies. Also provided is composition derived from a pancreatic homogenate that contains circulating cell activating factors, which can serve as targets for drug screening to identify drug candidates for use in activation lowering therapies. Methods for lowering cell activation by administering protease inhibitors, particularly serine protease inhibitors, are also provided. Kits for performing the methods are also provided.

La présente invention concerne des techniques de diagnostic faisant intervenir au moins un essai de confirmation de l'activation cellulaire. Ces essais sont menés sur le sang total ou les leucocytes, et plus particulièrement les neutrophiles. En outre, ces essais indiquent individuellement ou combinés à d'autres le niveau d'activation cellulaire cardio-vasculaire qui est un indicateur clé de nombreux états pathologiques chroniques ou aigus. On utilise les résultats de ces essais dans un cadre clinique pour venir en appui de décisions thérapeutiques telles que la poursuite de la recherche d'agents infectieux, les thérapies antioxydants ou anti-adhésion, le report et la reprogrammation optimale des interventions chirurgicales à haut risque, la classification de la susceptibilité d'affections chroniques (et de leur taux de progression) telles que le diabète, le rejet d'organe, l'athérogénèse et les insuffisances veineuses interventions extrêmes en traumatologie à haut risque et thérapies à abaissement de l'activation. L'invention concerne également une composition dérivée d'un homogénat pancréatique qui contient des facteurs d'activation de cellules circulantes, et qui peut servir de cibles pour la recherche systématique de médicaments de façon à identifier les candidats médicaments à utiliser pour les thérapies d'abaissement de l'activation. L'invention concerne en outre des techniques d'abaissement de l'activation cellulaire consistant à administrer des inhibiteurs de protéases, et notamment des inhibiteurs de protéines sériques. L'invention concerne enfin des nécessaires pour la mise en oeuvre de ces techniques.

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