ContextIntravenous tissue-type plasminogen activator can be beneficial to some
patients when given within 3 hours of stroke onset, but many patients present
later after stroke onset and alternative treatments are needed.ObjectiveTo determine the clinical efficacy and safety of intra-arterial (IA)
recombinant prourokinase (r-proUK) in patients with acute stroke of less than
6 hours' duration caused by middle cerebral artery (MCA) occlusion.DesignPROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized,
controlled, multicenter, open-label clinical trial with blinded follow-up
conducted between February 1996 and August 1998.SettingFifty-four centers in the United States and Canada.PatientsA total of 180 patients with acute ischemic stroke of less than 6 hours'
duration caused by angiographically proven occlusion of the MCA and without
hemorrhage or major early infarction signs on computed tomographic scan.InterventionPatients were randomized to receive 9 mg of IA r-proUK plus heparin
(n = 121) or heparin only (n = 59).Main Outcome MeasuresThe primary outcome, analyzed by intention-to-treat, was based on the
proportion of patients with slight or no neurological disability at 90 days
as defined by a modified Rankin score of 2 or less. Secondary outcomes included
MCA recanalization, the frequency of intracranial hemorrhage with neurological
deterioration, and mortality.ResultsFor the primary analysis, 40% of r-proUK patients and 25% of control
patients had a modified Rankin score of 2 or less (P
= .04). Mortality was 25% for the r-proUK group and 27% for the control group.
The recanalization rate was 66% for the r-proUK group and 18% for the control
group (P<.001). Intracranial hemorrhage with neurological
deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of
control patients (P = .06).ConclusionDespite an increased frequency of early symptomatic intracranial hemorrhage,
treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke
caused by MCA occlusion significantly improved clinical outcome at 90 days.

https://jamanetwork.com/journals/jama/articlepdf/192156/JOC91323.pdf

Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial

The molecular basis of blood coagulation

Background and Purpose—To test the safety and recanalization efficacy of intra-arterial local delivery of plasminogen activators in acute ischemic stroke, a randomized trial of recombinant pro-urok...

PROACT: A Phase II Randomized Trial of Recombinant Pro-Urokinase by Direct Arterial Delivery in Acute Middle Cerebral Artery Stroke

Intra-arterial Prourokinase for Acute Ischemic Stroke

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some Physiology Blut ist ein ganz besondrer Saft1

http://www.jbc.org/content/260/22/12377.full.pdf

Proteolytic cleavage of single-chain pro-urokinase induces conformational change which follows activation of the zymogen and reduction of its high affinity for fibrin.

Primary structure of single-chain pro-urokinase.

The invention provides a method of producing a water-soluble complex comprising a water-insoluble drug and a phospholipid, comprising the steps of (1) dissolving a water-insoluble drug and a phospholipid in an organic solvent, (2) removing the solvent to leave behind a drug-containing phospholipid film, (3) suspending the resulting film in an aqueous solution, (4) ultrasonicating the film, (5) centrifuging the resulting suspension, and (6) recovering the lowermost layer of the resulting sediment to yield the water-soluble complex. The above complex can be administered parenterally as well as by the oral and other routes, and is so rich in the drug component that a remarkably increased drug activity can be realized.

Water soluble drug complex and method for production of same

There is provided a fat emulsion of an ester of flurbiprofen having the formula ##STR1## wherein R is a group of the formula ##STR2## wherein R1 is a hydrogen atom or a C1 -C3 alkyl group, R2 is a C1 -C15 alkyl group or a C2 -C8 alkenyl group, and m is zero or an integer of 1; or a lactone group of the formula ##STR3## wherein R3 and R4 are same as or different from each other and are a hydrogen atom or a C1 -C3 alkyl group, and n is an integer of 1 or 2. The emulsion containing particles of a vegetable oil dissolving the ester can be orally or parenterally administered to human or animal for analgesia, antiphlogosis and antipyresis in various diseases and exhibits a high activity with small amounts in terms of flurbiprofen as compared with flurbiprofen itself.

Tadakazu Suyama

Papers

Proteolytic cleavage of single-chain pro-urokinase induces conformational change which follows activation of the zymogen and reduction of its high affinity for fibrin.

Primary structure of single-chain pro-urokinase.

Water soluble drug complex and method for production of same

Ester of flurbiprofen and emulsion containing the same

Molecular cloning of cDNA coding for human preprourokinase.