ABSTRACT
Objective To investigate expression and role of protease catenin-1(PN-1), thrombin(thrombin), protease activated receptor-1(PAR-1) in rats brain edema tissue after intracerebral hemorrhage(ICH).Methods Adult male SD rats 80 were randomly divided into sham group,ICH group after number, 40 in each group, ICH group autologous arterial method of making a rat model of experimental ICH in the right caudate nucleus unit injection.The degree of neurological dysfunction between 2 groups was evaluated at 12 h,24 h and 120 h after post-operation.Observed the morphology of brain cells by HE staining.Changes of PN-1,thrombin, PAR-1 index in rat brain tissue at 3,6,10,12,24,48 and 120 h were detected by Western blot.Results Neurological dysfunction score ICH rats after modeling 12,48,120 h were significantly lower than the sham group(P<0.05);ICH in rats after modeling 3,6,10,12,24,48 and 120 h of brain tissue PN-1, thrombin, PAR-1 compared with sham-operated group were significantly increased (P<0.05); ICH rat brain tissue PN-1, thrombin, PAR-1 appeared in 12 h after modeling shwed a gradual downward trend (P<0.05). Conclusion ICH hematoma surrounding brain tissue in rats PN-1 has the effect of inhibiting thrombin and PAR-1 overexpression, cause nerve damage.
ABSTRACT
The objective of this study was to develop stable lyophilized product of Bivalirudin, a direct thrombin inhibitor with good reconsti-tution time, % yield of good vials and cake quality. The % loss of crystallinity was determined by DSC for any crystallographic changes of the bulking agent after freeze drying. The glass transition temperature of 5% w/v of Bivalirudin, 3% w/v of mannitol and 0.03% of sodium acetate was approximately -31°C and the collapse temperature was approximately -28°C. Tubular vials were found to withstand the thermal transition during freeze drying. Water content was inversely proportional to the primary drying set point. Reconstitution time was inversely proportional to annealing temperature and vacuum set point. The % yield of good vials and cake quality was directly proportional to annealing time and primary drying set point. The % loss of crystallinity by DSC was independ-ent of all factors and directly proportional to annealing time. Drying at -10°C results in transition of β form of mannitol, whereas drying at -7.5°C and -5°C results in α and δ form of mannitol respectively. On annealing at -7°C for 54 minutes and drying at -6.5°C at 215mT lyophilized product with less than 2% water content, reconstitution time less than 10 seconds, with high yield of more than 95% yield of good vials with best cake quality was obtained.
ABSTRACT
The objective of this study was to develop stable lyophilized product of Bivalirudin, a direct thrombin inhibitor with good reconsti-tution time, % yield of good vials and cake quality. The % loss of crystallinity was determined by DSC for any crystallographic changes of the bulking agent after freeze drying. The glass transition temperature of 5% w/v of Bivalirudin, 3% w/v of mannitol and 0.03% of sodium acetate was approximately -31°C and the collapse temperature was approximately -28°C. Tubular vials were found to withstand the thermal transition during freeze drying. Water content was inversely proportional to the primary drying set point. Reconstitution time was inversely proportional to annealing temperature and vacuum set point. The % yield of good vials and cake quality was directly proportional to annealing time and primary drying set point. The % loss of crystallinity by DSC was independ-ent of all factors and directly proportional to annealing time. Drying at -10°C results in transition of β form of mannitol, whereas drying at -7.5°C and -5°C results in α and δ form of mannitol respectively. On annealing at -7°C for 54 minutes and drying at -6.5°C at 215mT lyophilized product with less than 2% water content, reconstitution time less than 10 seconds, with high yield of more than 95% yield of good vials with best cake quality was obtained.
ABSTRACT
La fibrilación auricular es la arritmia cardiaca más frecuente en la práctica clínica. El valor de la anticoagulación con antagonistas de la vitamina K -como la warfarina-en la prevención de los fenómenos embólicos está ampliamente demostrada, pero también su difícil manejo por las conocidas interacciones con otros fármacos e incluso los alimentos. En la búsqueda del anticoagulante ideal, en los últimos años han aparecido nuevos agentes antitrombóticos y otros se encuentran en fases avanzadas de investigación. En la presente revisión, se describe los resultados del desarrollo de los nuevos agentes anticoagulantes y sus expectativas, oportunidades y desafíos, que enfrentarán estos nuevos agentes, los inhibidores directos de la trombina y del factor Xa.
Atrial fibrillation is the most frequent cardiac arrhythmia in clinical practice. The value of anticoagulation with vitamin K antagonists like warfarin in the prevention of embolic phenomena is widely demonstrated but managing is difficult because of its known interactions with other drugs and even food. Looking for the ideal anticoagulant in the last years new antithrombotic agents have appeared and others are in advanced phases of investigation. In the current review results of new anticoagulant agents development and expectations, opportunities and challenges are described in regards to direct thrombin and Xa factor inhibitors.