Safety and efficacy of platelet glycoprotein VI inhibition in acute ischaemic stroke (ACTIMIS): a randomised, double-blind, placebo-controlled, phase 1b/2a trial.

Background: Antagonists of glycoprotein VI-triggered platelet activation used in combination with recanalisation therapies are a promising therapeutic approach in acute ischaemic stroke. Glenzocimab is an antibody fragment that inhibits the action of platelet glycoprotein VI. We aimed to determine and assess the safety and efficacy of the optimal dose of glenzocimab in patients with acute ischaemic stroke eligible to receive alteplase with or without mechanical thrombectomy.

Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT017, an Antiplatelet GPVI (Glycoprotein VI) Fab.

Objective- ACT017 is a novel, first in class, therapeutic antibody to platelet GPVI (glycoprotein VI) with potent and selective antiplatelet effects. This first-in-human, randomized, placebo-controlled phase 1 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT017 in healthy subjects. Approach and Results- Six cohorts of 8 healthy male and female subjects each received ascending single doses of ACT017 (n=6) or placebo (n=2) as a 6-hour intravenous infusion, with ¼ of the total dose administered within 15 minutes and the rest of the dose (¾ of the total dose) administered within 5 hours and 45 minutes.

Design, development and characterization of ACT017, a humanized Fab that blocks platelet's glycoprotein VI function without causing bleeding risks.

Glycoprotein VI is a platelet-specific collagen receptor critical for in vivo formation of arterial thrombosis. It is also considered as an attractive target for the development of anti-thrombotic drugs because blocking glycoprotein (GP)VI inhibits platelet aggregation without inducing detrimental effects on physiologic hemostasis. Here, we present data on the identification, in vitro and ex vivo pharmacology of a humanized Fab fragment designated as ACT017.

Engineered erythrocytes: influence of P50 rightward shift and oxemia on oxygen transport to tissues.

The red blood cell (RBC) membrane may be reversibly opened using a lysis-resealing continuous flow method. The technology was adapted to the internalisation of an allosteric effector of haemoglobin, Inositol-Hexaphosphate (IHP). This molecule, occupying the allosteric site of 2,3 Bis-Phosphoglycerate with a very large affinity, induces a rightward shift of the oxyhaemoglobin dissociation curve (ODC).

Acute and chronic haemodynamic effects of naftazone in portal hypertensive rats.

It has been demonstrated that hyperproduction of nitric oxide (NO) plays a major role in the vasodilatation of cirrhosis; thus, the vasodilatation might be reversed by an inhibition of NO production. Experimental studies in isolated aortic rings showed that naftazone inhibits the effects of NO production. The aim of this study was to evaluate the haemodynamic effects of acute and chronic administration of naftazone in rats with portal hypertension.

[Comparison of two skin antiseptics in blood transfusion. Comparison with the results of the bacteriologic control of labile blood products].

The comparison of two skin antiseptics (70 degrees alcohol and 0,5% alcoholic chlorhexidine solution) was carried out by the method of in vivo impressions. The study used 45 healthy volonteers from whom a bacteriological sample was taken from both bends of the elbow, without use of an antiseptic, and after the application of one according to usual sample taking methods. The subjects were divided into two sets according to the antiseptic being tested.

[In vitro evaluation and study of the survival of erythrocytes preserved in a saline-adenine-glucose-mannitol medium for 35 days].

The saline-adenine-glucose-mannitol (SAGM) solution for resuspension of red cells was evaluated on 30 blood units tested over 42 days and compared to 5 red cell concentrates collected on the conventional CPD medium. Total and extra-cellular hemoglobin, potassium, pH, ATP and DPG concentrations, osmotic fragility, schizocyte formation, and red cell antigenicity were studied through the storage period. Chromium survival studies of autologous donated red cells were performed in 10 donors.

Large scale detection of IgA deficient blood donors.

An automated technique using passive haemagglutination inhibition was developed on Groupamatic equipment for the screening of IgA deficient blood donors. Positive controls were also assayed by a manual haemagglutination inhibition test and solid-phase radioimmunoassay. Fourty-two blood donors totally deficient in IgA were detected in the systematic screening of 108,000 blood samples.

Preparation of varicella-herpes zoster immunoglobulin.

The efficacy of zoster immunoglobulin in prophylaxis of varicella and herpes zoster is reported by many authors. The screening for zoster's antibodies is performed in the blood donor population and in persons convalescing from herpes zoster. The results show that 25 per cent of blood donors and 83.

[Anti-varicella-zona immunoglobulins. Discovery of antibodies and method of formation].

The screening of zoster's antibodies has been performed in blood donors population and persons convalescing from herpes zoster. The results show that 25% of blood donors and 83,5% of convalescents have respectively a titer of CF antibody of 8. Plasma units were pooled and the pool had a final titer of CF antibody of 16.

[The prevention of chickenpox in high risk children. Comparison of the effectiveness of specific immunoglobulins and of defibrinated convalescent plasma. 414 cases (author's transl)].

Comparison between 157 children treated with defibrinated convalescent plasma and 257 children treated with specific immunoglobulins revealed the improved effectiveness of the latter treatment in the prevention of chickenpox. Specific Herpes Zoster-Chickenpox immunoglobulins are prepared by caprylic acid fractionation of convalescent plasma. The prevention obtained in more than 90% of cases would appear to be clinically and biologically total as shown by serological surveillance of certain children with particularly severe immune depression.

[Detection of antitetanic antibodies. Technics (electrosyneresis, Laurell, latex) applied to a high-antibody population].

The human serum of about twenty years old men, recently vaccinated has been tested by Laurell's method (Mesnier and Piquet variant). Purified antitetanic equine serum from Pasteur Institute (P.I.