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)

Poly(dl-lactide) (PLA) microspheres containing quinidine or quinidine sulphate were prepared by the emulsification-solvent evaporation technique. The in vitro release profile of quinidine or quinidine sulphate from the microspheres was characterized by three phases: a lag time, a rapid release phase (burst), and a slow release phase. Drug release was studied as a function of the ionic strength of the dissolution medium, to demonstrate the importance of the water imbition into the microspheres which induced the drug release. The lag time increased with increasing ionic strength. The microspheres stayed intact during the dissolution study as shown by scanning electron microscopy (SEM). Disintegration of microspheres which was initially observed was an artifact introduced during the SEM procedure. The high vacuum applied either during the coating of the microspheres with gold-palladium or during the actual observation in the scanning electron microscope caused the microspheres to collapse or rupture.
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PMID:Polylactic acid microspheres containing quinidine base and quinidine sulphate prepared by the solvent evaporation method. III. Morphology of the microspheres during dissolution studies. 323 52

REV 3164 has been evaluated in a variety of intact rodent models to reveal potential utility in the prophylactic treatment of asthma. REV 3164 was found a potent, orally active inhibitor of rat (IgE) passive cutaneous anaphylaxis (PCA, ED50 = 0.9 mg/kg). By contrast, at 50-200 mg/kg p.o., it did not affect guinea-pig (IgG1) PCA. In PCA rats, both REV 3164, 1-36 mg/kg i.p., and the known inhibitor of mast cell mediator release, disodium cromoglycate (DSCG), 2-54 mg/kg i.p., blocked cutaneous wheals caused by i.v. antigen challenge but not by intradermal serotonin or histamine. Neither REV 3164 (0.1-10 mg/kg i.p.) nor DSCG (2-54 mg/kg i.p.) affected Compound 48/80-induced wheals. REV 3164 (0.01-1 mg/kg i.v. or 10 mg/kg i.p.) abolished rat (IgE) passive lung anaphylaxis (PLA, ED50 = 0.05 mg/kg i.v. for inhibition of elevated airway resistance). At 10 mg/kg i.p., REV 3164 did not affect active lung anaphylaxis in guinea-pigs pharmacologically manipulated to enhance the production and action of slow reacting substance of anaphylaxis (SRS-A), nor did it exhibit anticholinergic activity in the rat. REV 3164 (100 mg/kg i.p.) did not protect conscious guinea-pigs from histamine aerosol-induced collapse. It is concluded that REV 3164 is an oral inhibitor of IgE-dependent immediate hypersensitivity in the rat with biological activities in rats and guinea-pigs similar to DSCG.
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PMID:In vivo anti-allergic and bronchopulmonary pharmacology of REV 3164 in rats and guinea-pigs. 649 6

The purpose of this study was to investigate whether barrier membranes that were earlier shown to promote bone healing in the craniofacial skeleton are capable of producing bone healing in long bone. defects by themselves or in combination with recombinant human bone morphogenetic protein 2 (rhBMP-2). Segmental defects (10 mm long) in the rabbit radius, known to heal as pseudoarthrosis-like defects, were used as the experimental model. Treatment with expanded polytetrafluoroethylene membranes (GORE-TEX Membrane) (n = 10) resulted in only minor amounts of bone formation within the defect and collapse of the membranes was common. When placement of membranes was combined with implantation of rhBMP-2 in a beaded biodegradable copolymeric PLA/PGA carrier, total bony bridging of the defects was accomplished within 10 weeks (n = 5). Osteopromotive membranes combined with mBMP-2 can therefore bring about complete healing of long bones. The membranes exclude soft tissue from the defect and at the same time keep the growth-stimulatory implant in place and maintain the anatomical contour of the bone. The combination of osteopromotive membranes and rhBMP-2 may be of. value in reconstructive bone surgery.
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PMID:Treatment of segmental defects in long bones using osteopromotive membranes and recombinant human bone morphogenetic protein-2. An experimental study in rabbits. 923 93

Metal implants employed in orthopaedic surgery have certain disadvantages. Intensive research work is therefore being done in the field of biodegradable implants, the behavior of which in the case of possible contamination or infection at the operation site has not yet been studied. In-vitro experiments on PLA-test bodies were performed to clarify the influence of bacteria on the polymer degradation. The investigated parameters were germ growth, course of the pH-value of the culture media, bending stiffness of the PLA-test bodies and the decrease in their molecular weight. The experiments performed did not demonstrate an accelerated degradation of PLA specimen in vitro incubated in different bacterial contaminated media. Therefore bacterial contamination may possibly not lead to a premature collapse of the PLA used in connection with fracture treatment by biodegradable osteosynthesis implants.
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PMID:The influence of bacterial contaminations on the biodegradation of PLA implants. 1014 17

The Papuan taipan (Oxyuranus scutellatus canni) is the third most venomous terrestrial snake in the world, however, little is know about the pharmacology of the venom. In the chick biventer cervicis muscle, venom (10 microg/ml) abolished nerve-mediated twitches (time to 90% inhibition (t90) 44+/-5 min, n = 9). This inhibition was unaffected by prior incubation of the venom with the phospholipase A inhibitor 4-bromophenacyl bromide (4-BPB; 0.72 mM) (t90 48+/-7 min, n = 8). The mouse phrenic nerve diaphragm preparation displayed greater sensitivity to venom (10 microg/ml) (t90 25+/-1 min, n = 6). In the chick biventer muscle, venom (10 microg/ml) significantly inhibited responses to acetylcholine (1 mM) and carbachol (20 microM), but not KCI (40 mM), indicating activity at post-synaptic nicotinic receptors. Venom (10 microg/ ml) did not affect direct muscle stimulation. Venom (3-30 microg/ml) produced dose-dependant contractions of the guinea-pig ileum. Contractile responses were significantly inhibited by indomethacin (1 microM) or prior incubation of the venom with 4-BPB (0.72 mM) indicating involvement of a PLA component. In rat phenylephrine (0.3 microM) precontracted aortae, venom (3-100 microg/ml) produced endothelium-independent relaxation which was unaffected by prior incubation of venom (30 microg/ml) with 4-BPB (0.72 mM). In anaesthetised rats, 10 microg/kg (i.v.) venom produced rapid respiratory and cardiovascular collapse while 5 microg/kg (i.v.) venom produced only a small transient decrease in mean arterial blood pressure. Prior administration of 5 microg/kg (i.v.) venom enabled subsequent administration of 10 and 100 microg/kg (i.v.) venom without respiratory or cardiovascular collapse. Further work is required to identify specific toxins with the above pharmacological activity.
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PMID:A pharmacological examination of venom from the Papuan taipan (Oxyuranus scutellatus canni). 1051 50

The studies presented here explore intracellular signals resulting from the action of repellents on growth cones. Growth cone challenge with thrombin or thrombin receptor-activating peptide (TRAP) triggers collapse via a receptor-mediated process. The results indicate that this involves activation of cytosolic phospholipase A(2) (PLA(2)) and eicosanoid synthesis. The collapse response to repellents targets at least two functional units of the growth cone, the actin cytoskeleton and substratum adhesion sites. We show in a cell-free assay that thrombin and TRAP cause the detachment of isolated growth cones from laminin. Biochemical analyses of isolated growth cones reveal that thrombin and TRAP stimulate cytosolic PLA(2) but not phospholipase C. In addition, thrombin stimulates synthesis of 12- and 15-hydroxyeicosatetraenoic acid (HETE) from the released arachidonic acid via a lipoxygenase (LO) pathway. A selective LO inhibitor blocks 12/15-HETE synthesis in growth cones and inhibits thrombin-induced growth cone collapse. Exogenously applied 12(S)-HETE mimics the thrombin effect and induces growth cone collapse in culture. These observations indicate that thrombin-induced growth cone collapse occurs by a mechanism that involves the activation of cytosolic PLA(2) and the generation of 12/15-HETE.
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PMID:Thrombin-induced growth cone collapse: involvement of phospholipase A(2) and eicosanoid generation. 1059 66

Consensus regarding the use of thrombolysis to treat acute pulmonary embolism has not yet been reached. There is good evidence that thrombolytic agents dissolve clot more rapidly than heparin. However, proving that this benefit reduces the death rate from pulmonary embolism has been difficult. Each of the 3 thrombolytic agents (tissue type-plasminogen activator, streptokinase and urokinase) is equally efficacious at dissolving clot, but all are associated with an increased risk of major hemorrhage when compared with heparin. One evolving position is that, in addition to patients presenting in circulatory collapse, for whom thrombolysis has been demonstrated to be life-saving, a subgroup of patients may be identified by echocardiography, through its ability to assess right ventricular dysfunction, who should also be considered for thrombolytic therapy. It remains to be seen whether this approach can reduce the death rate associated with pulmonary embolism.
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PMID:Thrombolytic therapy for pulmonary embolism. 1112 28

During thrombolytic therapy and after recanalization is achieved, reduction in the volume of mural thrombi is desirable. Mural thrombi are known to contribute to rethrombosis and reocclusion. The lysis rate of mural thrombi has been demonstrated to increase with fluid flow in different experimental models, but the mechanisms responsible are unknown. An experimental and a theoretical study were developed to determine the contribution of outer convective transport to the lysis of mural fibrin clots. Normal human plasma containing recombinant tissue-type plasminogen activator (tPA; 0.5 microg/mL) was (re)perfused over mural fibrin clots with fluorescently labeled fibrin at low arterial, arterial, or higher wall shear stresses (4, 18, or 41 dyn/cm(2), respectively) and lysis was monitored in real time. Flow accelerated lysis, but significantly only at the highest shear stress: The average lysis front velocity was 3 x 10(-5) cm/s at 41 dyn/cm(2) vs. almost half of that at the lower shear stresses. Confocal microscopy showed fibrin fibers dissolving only in a narrow region close to the surface when permeation velocity was predicted to be low. A heterogeneous transport-reaction finite element model was used to describe mural fibrinolysis. After scaling the effects of outer and inner convection, inner diffusion, and chemical reactions, a simplified inner diffusion/reaction model was used. Correlation to fibrin lysis data in purified systems dictated higher rates of plasmin(ogen) and tPA adsorption onto fibrin and a decreased catalytic rate of plasmin-mediated fibrin degradation, compared with published parameters. At each shear stress, the model predicted a temporal pattern of lysis of mural fibrin (similar to that observed experimentally), and protease accumulation in a narrow fibrin region and significant lysis inhibition by plasma alpha(2)-antiplasmin (according to the literature). Increasing outer convection accelerated mural fibrinolysis, but the model did not predict the big increase in lysis rate at the highest shear stress. At higher than arterial flows, additional mechanisms not accounted for in the current model, such as fibrin collapse at the fibrin front, may regulate the lysis of mural clots and determine the outcome of thrombolytic therapy.
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PMID:An experimental and theoretical study on the dissolution of mural fibrin clots by tissue-type plasminogen activator. 1178 13

We describe a case of sudden and severe pulseless electrical activity in a 30 year old woman which was managed successfully with reteplase and heparin one day following an anterior cruciate ligament repair. The presentation of a sudden collapse with ECG findings of S1Q3T3, early precordial lead ST depression and partial right bundle branch block were indicative of an acute pulmonary embolus. The cardiopulmonary collapse necessitated rapid treatment in the absence of confirmatory investigations. Reteplase (10 U stat followed by 10 U at 30 minutes) led to a dramatic improvement in the cardiovascular status of the patient. One day following the cardiac arrest the patient was extubated and responding normally. A spiral CT performed later confirmed multiple small embolic defects in the lower pulmonary arteries of both lower lung zones. This case highlights the utility of reteplase in the management of an acute pulmonary embolism and in an emergency, recent surgery is not necessarily a contraindication to its use.
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PMID:Life threatening massive pulmonary embolism treated with reteplase: a case report. 1659 9

No means exist to evaluate the activity status, turnover, and prognosis of idiopathic osteonecrosis of the femoral head (IONFH) except for X-ray evidence of segmental collapse as a very good marker for prognosis. Moreover, the only current method for diagnosis of this disease is through physical examination and diagnostic imaging results, and no serum biochemical markers exist. A comparative analysis of serum proteomes was performed to discover proteins associated with osteonecrosis of the femoral head. Two-dimensional electrophoresis (2-DE) patterns of human sera from 10 patients with IONFH and 10 normal subjects were analyzed. The differentially expressed spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and 7 proteins were found. The expression levels of tissue-type plasminogen activator (t-PA), bone-carboxyglutamate protein (BGP), c-sis, and an unknown protein were downregulated in the sera of patients with IONFH, whereas the other 3 proteins, including plasminogen activator inhibitor type 1 (PAI-1), crosslaps, and anti-p53 antibody, were upregulated. To examine their applicability as diagnostic markers, levels of the 6 identified proteins in serum were validated from patients with IONFH, osteoarthritis (OA), rheumatoid arthritis (RA), and fracture using the enzyme-linked immunosorbent assay (ELISA) method. It was found that only serum levels of t-PA, PAI-1, crosslaps, and anti-p53 antibody in patients with IONFH were always significantly different from those in patients with OA, RA, and fracture. These results suggest that serum levels of t-PA, PAI-1, crosslaps, and anti-p53 antibody could be used as noninvasive diagnostic biomarkers for IONFH.
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PMID:Comparative analysis of serum proteomes: discovery of proteins associated with osteonecrosis of the femoral head. 1693 48


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