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)

Administration of anthracyclines, a family of highly effective anticancer drugs, is associated with a cumulative dose-related cardiomyopathy, the etiology of which remains poorly understood. We have discovered that administration of the anthracyclines leads to a marked inhibition of membrane-associated calcium-independent phospholipase A(2) (iPLA(2)) both in vitro and in vivo. To elucidate the clinical relevance of this effect and to correlate it with known cardiotoxicity of the individual anthracyclines, we have compared four anthracycline analogues: doxorubicin, daunorubicin, idarubicin, and epirubicin for their ability to inhibit iPLA(2). Isolated adult rat cardiomyocytes were treated with each analogue at concentrations of 0.1-100 micro M, and PLA(2) activity was assessed in cytosolic and membrane fractions using (16:0, [(3)H]18:1) plasmenylcholine in the absence of calcium. For all of the examined analogues, iPLA(2) inhibition was concentration and time dependent, preceded detectable changes in cell viability, and was specific to the membrane-associated enzyme. The degree of iPLA(2) inhibition by equimolar concentrations of epirubicin and idarubicin was significantly less than that of doxorubicin or daunorubicin, which correlates with the reported in vivo cardiotoxicity of these drugs. Because membrane iPLA(2) represents the majority of myocardial PLA(2) activity, its inhibition by anthracyclines would critically impair the ability of cardiomyocytes to repair oxidized phospholipids. Indeed, anthracycline-pretreated myocytes become more susceptible to the low-level oxidative stress imposed by repetitive additions of tert-butyl peroxide. The results suggest that iPLA(2) inhibition may be the initial step in a chain of events leading to chronic cardiotoxicity of the anthracyclines.
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PMID:Inhibition of membrane-associated calcium-independent phospholipase A2 as a potential culprit of anthracycline cardiotoxicity. 1452 26

Patients with end stage liver disease (ESLD) have complex problems such as cirrhotic cardiomyopathy, coronary artery disease, hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), hepatic encephalopathy, intracranial hypertension, (ICP), left ventricular outflow tract obstruction (LVOTO), high Model of end liver disease (MELD) scores, hyponatremia, and coagulopathies. The anesthesia management for liver transplantation can be very complex, dynamic and challenging. Anesthesia agents affect hepatic blood flow and anesthetic drug distribution, metabolism and elimination maybe altered in end stage liver disease. Other non-anesthetic agents such as nitric oxide, epoprosterenol, THAM, hypertonic saline, fibrinogen concentrates, fresh frozen plasma, platelets, packed red blood cells, recombinant plasminogen activator, calcium chloride, epinephrine etc. may play a vital role in the perioperative management of these patients. Intraoperative hemostasis and coagulation management can be very arduous as these patients may bleed or be at risk for thrombosis. Monitoring modalities such as Thromboelastography (TEG), Transcranial Doppler (TCD), Transesophageal Echocardiography (TEE), Bispectral Index (BIS) and Optic Nerve Sheath Diameter (ONSD) ultrasound play a significant role in various circumstances. Surgical techniques include complete or partial occlusion of the inferior vena cava (IVC) with or without use of venovenous bypass (VVBP) or portocaval shunts. Post reperfusion syndrome (PRS) is a crucial event in this procedure, where patients may experience arrhythmia and/or cardiac arrest. Anesthetic handling of this phase has been recapitulated in detail. Provision of anesthesia services to the living liver transplant donor and pain management has been outlined.
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PMID:Anesthesia for liver transplantation. 2611 26

A 79-year-old man presented with left hemiparesis and disturbance of consciousness. Brain magnetic resonance(MR)imaging revealed an infarction in the right insular cortex. MR angiography showed a defect in the inferior trunk of the right middle cerebral artery. The patient was treated with alteplase about 2.5 h after onset. Immediately after the intravenous alteplase administration, the hemiparesis improved. However, his respiratory condition unexpectedly worsened 10 h after onset. Chest radiography demonstrated an infiltrative shadow in both lung fields. Transthoracic echocardiogram showed a dysfunction in the left ventricle and no contraction at the apex of the heart, consistent with a type of cardiomyopathy, known as takotsubo cardiomyopathy(TCM). Gradually, the patient's respiratory and cardiac function improved. Here, we describe a very rare case of TCM and neurogenic pulmonary edema(NPE)following an acute cerebral infarction, which was treated with alteplase intravenous administration. TCM and NPE have a poor prognosis, therefore diagnosis, management, and treatment in the acute phase is required.
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PMID:[Takotsubo Cardiomyopathy and Neurogenic Pulmonary Edema Following Fibrinolytic Therapy for Embolic Stroke:A Case Report]. 2936 81