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)

In the course of a pilot study, the effects of fibrinolysis treatment with rt-PA (Actilyse, Thomae, Biberach; 100 mg) on the recovery of hearing and hemorheologic parameters were investigated in 12 patients suffering from sudden hearing loss. The authors' approach was based on two considerations, (1) the possibility that, in cases of sudden hearing loss, the oxygen supply to the cochlea is totally or partially blocked by a microthrombus which could be dissolved by rt-PA and (2) the fact that lysis markedly improves the flow characteristics of the blood (as has been demonstrated in studies with streptokinase and urokinase). This human-plasminogen activator, produced by genetic engineering, is superior (also in terms of possible side-effects) to other lysin enzyme preparations (streptokinase, urokinase) because of its highly selective effects on thrombi (low activation of plasma plasminogen) and its short half-life (approx. 4 min). In nine of 12 patients, the treatment brought about a marked improvement in hearing or its complete restitution (three of the patients has initially been deaf in the affected ear). In the three nonresponders there was serologic evidence of an inner-ear infection (neuroborreliosis, cytomegaly, influenza B). The most interesting rheologic effect was the reduction of plasma viscosity (average decrease about 18%), since such a reduction cannot be attained with other, comparable rheologic measures (isovolemic or hypervolemic hemodilution). In spite of the convincing hemorheologic effects, fibrinolysis cannot yet be recommended as treatment for sudden hearing loss. Further studies have still to be done on spontaneous healing, the effects of hemorheologic measures on the blood circulation of the inner ear, and on the oxygen requirements of the ear affected by hearing loss.
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PMID:[Fibrinolytic therapy in sudden deafness with recombinant tissue-type plasminogen activator. Hemorheologic and therapeutic effects]. 191 Mar 64

Influenza virus hemagglutinin (HA) possesses anticoagulant and fubrinolytic activities and affects such blood clotting factors as fibrinogen and factor XIII in vitro and in vivo. Computer analysis of HA structure of avian, animal, and human type 1 influenza viruses showed 1 or 2 sites of amino acid sequences similar to plasminogen activator. These sites proved to be highly conservative for each virus subtype, irrespective of the source and year of isolation of the strain. Evolution relationships with respect to this sign were detected between the studied viruses.
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PMID:[The role of influenza virus hemagglutinin in blood anticoagulation processes]. 899 75

Lamellar particles and microspheres were produced by precipitation from solutions of resorbable, biocompatible, semi-crystalline poly(L-lactide)[PLA] and amorphous poly(DL lactide co-glycolide)[PLG] copolymer, respectively, to investigate their adjuvanticity towards adsorbed influenza virus. Both types of substrate were capable of adsorbing large quantities of virus (> 15% w/w) and retaining virus (> 60% of the initial load) over an 8 week time scale in-vitro. Potent immune responses were obtained in mice after the intra-muscular injection of adsorbed vaccine systems. The response to virus adsorbed on PLA lamellar particles was almost five times that obtained using PLG microspheres and fourteen times that using aqueous vaccine. The lamellar forms of PLA may function as an immunomodulator enhancing phagocytic activity due to their irregular shape and may be useful in improving the immune response to a variety of protein and viral antigens.
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PMID:Resorbable lamellar particles of polylactide as adjuvants for influenza virus vaccines. 969 6

Sixty patients meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.: American Psychiatric Association, 1994) criteria for generalized social phobia were assigned to cognitive therapy (CT), fluoxetine plus self-exposure (FLU + SE), or placebo plus self-exposure (PLA + SE). At posttreatment (16 weeks), the medication blind was broken. CT and FLU + SE patients then entered a 3-month booster phase. Assessments were at pretreatment, midtreatment, posttreatment, end of booster phase, and 12-month follow-up. Significant improvements were observed on most measures in all 3 treatments. On measures of social phobia, CT was superior to FLU + SE and PLA + SE at midtreatment and at posttreatment. FLU + SE and PLA + SE did not differ. CT remained superior to FLU + SE at the end of the booster period and at 12-month follow-up. On general mood measures, there were few differences between the treatments
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PMID:Cognitive therapy versus fluoxetine in generalized social phobia: a randomized placebo-controlled trial. 1527 19

Phospholipase A(2) (PLA(2)) not only plays a role in the membrane vesiculation system but also mediates membrane-raft budding and fission in artificial giant liposomes. This study aimed to demonstrate the same effects in living cells. Differentiated Caco-2 cells were cultured on filter membranes. MDCK cells were challenged with Influenza virus. The MDCK cultures were harvested for virus titration with a plaque assay. Alkaline phosphatase (ALP), a membrane-raft associated glycosylphosphatidylinositol (GPI)-anchored protein, was 70% released by adding 0.2 mmol/l lysophosphatidylcholine, which was abolished by treatment with a membrane-raft disrupter, methyl-beta-cyclodextrin. Activation of calcium-independent PLA(2) (iPLA(2)) by brefeldin A increased the apical release of ALP by approximately 1.5-fold (p<0.01), which was blocked by PLA(2) inhibitor bromoenol lactone (BEL). BEL also reduced Influenza virus production into the media (<10%) in the MDCK culture. These results suggest that cells utilize inverted corn-shaped lysophospholipids generated by PLA(2) to modulate plasma membrane structure and assist the budding of raft-associated plasma membrane particles, which virus utilizes for its budding. Brush borders are enriched with membrane-rafts and undergo rapid turnover; thus, PLA(2) may be involved in the regulatory mechanism in membrane dynamism. Further, iPLA(2) may provide a therapeutic target for viral infections.
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PMID:A possible role of lysophospholipids produced by calcium-independent phospholipase A(2) in membrane-raft budding and fission. 1964 79

The plasminogen activator receptor (uPAR) is required for lung infiltration by innate immune cells in respiratory bacterial infections. In order to verify if this held true for respiratory viruses, wild type (WT) and uPAR knockout (uPAR(-/-)) mice were inoculated intranasally with the human respiratory syncytial virus (HRSV) and the influenza A virus. At several days post-infection (dpi), viral titers in the lungs were determined while cell infiltrates in the bronchoalveolar lavage (BAL) were analyzed by flow cytometry. In the case of influenza A, body weight loss and mortality were also monitored. Only minor differences were observed between infected WT and uPAR(-/-) mice, primarily in influenza virus replication and pathology. These results indicate that uPAR does not play a major role in limiting virus replication or in orchestrating the innate immune response against HRSV or influenza infections in mice. This suggests that there are fundamental differences in the immune control of the viral infections studied here and those caused by bacteria.
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PMID:Urokinase receptor-deficient mice mount an innate immune response to and clarify respiratory viruses as efficiently as wild-type mice. 2611 63

Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A2 (PLA2), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV). Additionally, BV and MLT also inhibited the replication of non-enveloped viruses such as Enterovirus-71 (EV-71) and Coxsackie Virus (H3). Such antiviral properties were mainly explained by virucidal mechanism. Moreover, MLT protected mice which were challenged with lethal doses of pathogenic influenza A H1N1 viruses. Therefore, these results provides the evidence that BV and MLT could be a potential source as a promising antiviral agent, especially to develop as a broad spectrum antiviral agent.
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PMID:Inhibitory effects of bee venom and its components against viruses in vitro and in vivo. 2812 Jan 96

Targeted delivery of drug-encapsulated nanoparticles is a promising new approach to safe and effective therapeutics for cancer. Here we investigate the pharmacokinetics and biodistribution of a prostate-specific membrane antigen (PSMA)-targeted nanoparticle based on a poly(lactic acid)-polyethylene glycol copolymer by utilizing single photon emission computed tomography (SPECT) and fluorescence imaging of a low-molecular-weight, PSMA-targeting moiety attached to the surface and oriented toward the outside environment. Tissue biodistribution of the radioactive, PSMA-targeted nanoparticles in mice containing PSMA(+) PC3 PIP and PSMA(-) PC3 flu (control) tumors demonstrated similar accumulation compared to the untargeted particles within all tissues except for the tumor and liver by 96 h postinjection. For PSMA(+) PC3 PIP tumor, the targeted nanoparticle demonstrated retention of 6.58% injected dose (ID)/g at 48 h and remained nearly at that level out to 96 h, whereas the untargeted nanoparticle showed a 48 h retention of 8.17% ID/g followed by a significant clearance to 2.37% ID/g at 96 h (P < 0.02). On the other hand, for control tumor, both targeted and untargeted particles displayed similar 48 h retentions and rates of clearance over 96 h. Ex vivo microscopic analysis with near-infrared versions of the nanoparticles indicated retention within PSMA(+) tumor epithelial cells as well as tumor-associated macrophages for targeted particles and primarily macrophage-associated uptake for the untargeted particles. Retention in control tumor was primarily associated with tumor vasculature and macrophages. The data demonstrate the utility of radioimaging to assess nanoparticle biodistribution and suggest that active targeting has a modest positive effect on tumor localization of PSMA-targeted PLA-PEG nanoparticles that have been derivatized for imaging.
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PMID:111In- and IRDye800CW-Labeled PLA-PEG Nanoparticle for Imaging Prostate-Specific Membrane Antigen-Expressing Tissues. 2800 64

Hepatitis C virus (HCV), dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the family Flaviviridae. Their viral particles have the envelope composed of viral proteins and a lipid bilayer acquired from budding through the endoplasmic reticulum (ER). The phospholipid content of the ER membrane differs from that of the plasma membrane (PM). The phospholipase A2 (PLA2) superfamily consists of a large number of members that specifically catalyse the hydrolysis of phospholipids at a particular position. Here we show that the CM-II isoform of secreted PLA2 obtained from Naja mossambica mossambica snake venom (CM-II-sPLA2) possesses potent virucidal (neutralising) activity against HCV, DENV and JEV, with 50% inhibitory concentrations (IC50) of 0.036, 0.31 and 1.34 ng/ml, respectively. In contrast, the IC50 values of CM-II-sPLA2 against viruses that bud through the PM (Sindbis virus, influenza virus and Sendai virus) or trans-Golgi network (TGN) (herpes simplex virus) were >10,000 ng/ml. Moreover, the 50% cytotoxic (CC50) and haemolytic (HC50) concentrations of CM-II-sPLA2 were >10,000 ng/ml, implying that CM-II-sPLA2 did not significantly damage the PM. These results suggest that CM-II-sPLA2 and its derivatives are good candidates for the development of broad-spectrum antiviral drugs that target viral envelope lipid bilayers derived from the ER membrane.
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PMID:Broad-spectrum antiviral agents: secreted phospholipase A2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane. 2916 67

Instillation of intrapleural (IP) fibrinolytics has been used in patients with complicated parapneumonic pleural effusions to improve fluid drainage and decrease the need for surgical intervention. However, clinical trials have not included certain special populations such as pregnant females and there are currently no published case reports of this practice in this group. We describe the case of a 35-year-old female, G2P1 at 32 weeks of gestation, with a complicated pleural effusion due to influenza pneumonia with superimposed bacterial pneumonia. Her parapneumonic pleural effusion was successfully treated with intercostal tube drainage and IP alteplase [tissue plasminogen activator (tPA)] administration and systemic antibiotics with no harm to her or her fetus, sparing this patient from more invasive surgical procedures. This is the first reported case of successful IP tPA administration for a complicated parapneumonic pleural effusion in a pregnant patient.
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PMID:Safe administration of intrapleural alteplase during pregnancy. 2922 47


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