Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urokinase is a plasminogen activator of human origin which breaks up the fibrin base of blood clots. When given as an intravitreal injection it produces hypopyon and glaucoma, both of which transient. In a series of 27 patients (34 eyes) with unresolved vitreous haemorrhage, this simple and relatively atraumatic treatment has produced marked objective improvement in 10, and greatly improved the life styles of a further 9. This series brings the total of reported cases to 93. When compared with recent American reports of surgical vitrectomy for vitreous haemorrhage, intravitreal urokinase appears to have a higher success rate, with a lower complication rate both in the short and long term. This study suggests that, despite the high cost of the purified enzyme, urokinase should be come the first line of attack in vitreous haemorrhage, vitrectomy being reserved for those patients who fail to respond.
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PMID:Urokinase in the management of vitreous hemorrhage. 91 29

The primary cause of failure in glaucoma filtration surgery is fibroblastic proliferation and subconjunctival fibrosis at the bleb site resulting in decreased aqueous flow. We evaluated New Zealand white rabbits in a masked, placebo controlled pilot study to determine the potential reduction of episcleral fibrosis at the surgical bleb site utilizing 0.3 mls of: balanced salt solution (n = 11); an inert gel delivery vehicle (n = 13); the gel delivery vehicle with incorporated recombinant tissue plasminogen activator (tpa; n = 14), 1 mg/ml. Statistical analysis of computer assisted area measurements from multiple histologic sections demonstrated a significant decrease in episcleral fibrosis in the t-PA group as compared to the two other groups (p less than 0.05). Results from the t-PA group did not demonstrate an effect on intraocular pressure. There was no clinical evidence of toxicity or healing complications in the t-PA group.
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PMID:Subconjunctival high dose plasminogen activator in rabbit filtration surgery. 190 44

Maintenance of patency of the trabecular meshwork, the major outflow channel of the anterior chamber of the eye, is necessary to prevent an excessive rise in intraocular pressure. Obstruction of flow due to clot formation results in severe glaucoma and damage to the optic nerve. We have found that human trabecular meshwork cells which have been passaged in tissue culture synthesize large amounts of tissue plasminogen activator (t-PA), based on functional, immunologic and molecular weight analysis. Trabecular cells express substantially more t-PA activity than vascular endothelium which produces t-PA for clot dissolution in the systemic circulation. Vascular cells produce excess t-PA inhibitor while trabecular cells make comparatively little. Trabecular meshwork cells are the first normal cell type reported in which the balance between t-PA and inhibitor is weighted towards the activator, indicating that fibrinolysis may be more important than clotting in the anterior chamber of the eye.
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PMID:Tissue plasminogen activator in cultured human trabecular meshwork cells. Predominance of enzyme over plasminogen activator inhibitor. 312 23

Fibrinolytic activity of aqueous humor was tested by the Astrup fibrin plate lysis technique in 7 patients who had chronic simple glaucoma and was compared with a control group of 7 patients with senile cataract. The plasminogen activator content of aqueous humour in glaucoma patients was remarkably reduced; it was not demonstrable in as many as six out of seven patients. The lysis zones in the control group ranged from 110 to 900 mm2 with an average of 423 mm2. The want of aqueous fibrinolytic activity may have a pathogenetic implication for glaucoma since deposition of fibrin in the angle of the eye to depressed fibrinolytic activity could increase resistance to aqueous flow.
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PMID:Reduced fibrinolytic activity in aqueous humor of chronic simple glaucoma. 653 99

Tissue-type plasminogen activator (t-PA), a serine protease that catalyzes the conversion from plasminogen to plasmin, plays an important role in the fibrinolytic system and has also in recent years attracted attention in the field of ophthalmology. In order to examine the role of t-PA in the physiology of the anterior segment, we detected t-PA in aqueous humor by using immunoassays. The samples were taken by keratocentesis prior to cataract or glaucoma surgery. The sample volumes ranged from 50-200 microliters. The quantities of t-PA Ag and plasminogen-activator inhibitor (PAI) Ag were determined by using enzyme-linked immunosorbent assays. We determined t-PA and PAI in the aqueous humor of 54 patients between 32 and 87 years of age. The t-PA Ag levels ranged from 0.2 to 1.9 ng/ml (average 0.8 ng/ml), PAI-Ag from 0.2 to 1.7 ng/ml (average 0.9 ng/ml). The values measured in men were slightly higher than those measured in women. No association between t-PA and PAI levels and accompanying diseases or metabolic disorders was noted. Precise knowledge about the presence of t-PA in aqueous humor is a prerequisite for the recognition of pathological events following intraocular fibrin formation and may be an important basis for the therapeutic use of rt-PA in the intraocular inflammatory process.
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PMID:[Plasminogen activator and PAI. Detection in aqueous humor of the human eye]. 844 55

After glaucoma filtering surgery subconjunctival injection of human recombinant tissue plasminogen activator may promote the function of glaucoma filter bleb and increase outflow facility. It can also increase postoperative complications, such as corneal damage. The aim of our research was to determine corneal endothelial permeability (Pac) in subjects with glaucoma filter bleb protected by a plasminogen activator (Actilyse, Boehringer) when haemorrhagic clots obstructing a glaucoma filtering site had occurred. Two weeks, three months and six months after goniotrephining with scleral cover, in groups with and without subconjunctival injection of 25 mg human tissue plasminogen activator, Pac was calculated. In both groups, no significant differences in the level of Pac measured by fluorophotometry were found.
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PMID:Corneal endothelial permeability in protection glaucoma filter bleb with tissue plasminogen activator. 853 90

An occlusion of the central retinal artery (CRAO) leads to a unilateral acute painless loss of vision. The individual etiology remains unclear in many cases. Potential pathomechanisms are embolism, vasoobliteration and vascular compression. Emboli (calcified, thrombotic, myxomatous, bacterial or cholesterol) are of carotid or cardiac origin. Atherosclerotic plaques, giant-cell arteritis and other types of vasculitis may cause vasoobliteration. A retrobulbar mass (hematoma, neoplasms, retrobulbar injections) may lead to an optic nerve and central retinal artery compression. Funduscopic signs of CRAO are described. Late development of iris neovascularization and neovascular secondary glaucoma may occur in up to 15 percent of cases. The prognosis of CRAO has been poor. A spontaneous remission and recovery of visual function is rare. It has been shown experimentally that the retinal damage is irreversible after 100 minutes of non-perfusion. The initial treatment should include an immediate paracentesis of the anterior chamber, digital massage of the globe, and i.v. administration of 500 mg azetazolamide in order to stimulate retinal reperfusion by lowering the intraocular pressure. This procedure is recommended for the first 6 (up to 24) hours after onset of CRAO. More promising success rates have recently be reported by a selective intra-arterial fibrinolysis with Urokinase (100,000-1,000,000 IU) or recombinant plasminogen activator (rtPA). In a personal series of 18 cases, intra-arterial fibrinolysis with Urokinase was performed. A final visual acuity of 6/10 to 6/6 was achieved in 30 percent of the cases.
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PMID:[Central retinal artery occlusion--etiology, clinical picture, therapeutic possibilities]. 1121 85

Intracameral tissue plasminogen activator (t-PA) application in a child with previously unrecognized sickle cell anemia, post-traumatic hyphema, thrombosis in trabecular mashwork and consecutive acute glaucoma showed positive results. Thirteen year-old boy, son of African father and Caucasian mother, was admitted to hospital, with symptoms of acute glaucoma and partial hyphema after right eye trauma. Visual acuity of affected eye was 0.5 and intraocular pressure (IOP) 46 mm Hg. Despite a common therapy three days later clinical condition of patient's right eye was getting worst. Visual acuity was only hand motion (HM) and IOP 53 mmHg. At this point rose suspicion of sickle cell disease (SCD) and decision about injecting t-PA (20 microg) into anterior chamber was made. Cytological examination of aqueous humor revealed 10% sickled erythrocytes. Hemoglobin electrophoresis discovered hemoglobin S so that diagnosis of SCD was confirmed. Intraocular application of t-PA showed excellent results in post-traumatic hyphema with trabecular mashwork thrombosis in the patient with sickle cell anemia. Two-years follow up confirmed permanent normalisation of IOP and visual acuity. Successful outcome with anterior chamber paracentesis and intracameral injection of t-PA is promising novel approach, which we recommend in treatment of post-traumatic hyphema in SCD.
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PMID:Treatment of post-traumatic trabecular mashwork thrombosis and secondary glaucoma with intracameral tissue plasminogen activator in previously unrecognized sickle cell anemia. 1619 93

It is estimated that 2.2 million people have glaucoma in the US and 67 million people worldwide. The majority of cases are associated with elevated intraocular pressure (IOP) and decreasing IOP eliminates or greatly reduces degeneration in most cases, including cases in which the IOP is in the normal range but optic neuropathy occurs. Timolol maleate has the longest record of safety and efficacy to lower IOP and is administered via eye drops one or more times per day. Unfortunately, compliance is poor across patient populations leading to degeneration. Patients typically see their ophthalmologist once every 3-4 months. If one could administer a long-acting treatment while in the doctor's office, one might overcome the compliance issue and effectively preserve sight. The critical step is to develop a formulation for timolol maleate that leads to sustained delivery for greater than 90 days and would permit a different treatment paradigm, namely subconjunctival administration once every 3-4 months. By using a 50 : 50 blend of PLGA 502H and PLA, this study was able to fabricate microspheres that delivered timolol maleate continually over 107 days, well within the time frame needed to make subconjunctival administration feasible and permit a new approach to treating glaucoma and diseases of the eye more broadly.
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PMID:Sustained delivery of timolol maleate from poly(lactic-co-glycolic acid)/poly(lactic acid) microspheres for over 3 months. 1846 88

The 2010 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), held in Fort Lauderdale, FL, USA, included topics covering new therapeutic developments in the field of eye and vision research. This conference report highlights selected presentations on the development of FOV-2304 (Fovea Pharmaceuticals SA) for the potential treatment of diabetic macular edema; PHA-666859 (Pfizer Inc) for diabetic retinopathy; GTx-878 (GTx Inc) and FCFD-4514S (Genentech Inc) for age-related macular degeneration; SYL-040012 (Sylentis Sau) for ocular hypertension associated with open-angle glaucoma; PEG-PLA-TNP-470 (Harvard Medical School) for ocular neovascularization; recombinant galectin-3 (Senju Pharmaceutical Co Ltd) for corneal injury; and CellBead Neuro (CellMed Inc) for neurological trauma and neurodegeneration.
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PMID:Association for Research in Vision and Ophthalmology (ARVO)--2010 Annual Meeting. For Sight: The Future of Eye and Vision Research--part 1. 2058 62


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