Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morbidity and mortality rates of ARDS (acute respiratory distress syndrome) are high in patients with a history of chronic alcohol abuse. In addition to susceptibility to lung infection, alteration of local cellular functions in the lung has recently been proposed as a new mechanism of exacerbation of ARDS in patients with a history of chronic alcohol abuse. Clinical studies and studies using animal experiments have shown that a decrease in lung glutathione levels is associated with exacerbation of ARDS in chronic alcohol abuse. In the alcoholic lung, depletion of glutathione increases oxidative stress derived from activated neutrophils, resulting in decreased surfactant production, apoptosis and increased permeability of alveolar epithelial type II cells, in which TGF-beta1 may be involved. Acetoaldehyde has been suggested to be involved in the mechanism of exacerbation of ARDS by inducing lung remodeling through stimulation of fibronectin expression following nicotinic acetylcholine receptor stimulation and CREB activation in chronic alcohol abuse. More recently, antagonists of angiotensin II type-1 receptor (AT1 receptor) have been shown to prevent glutathione depletion, increase in TGF-beta1 expression and lung edema in endotoxemic rats with chronic alcohol administration. On the other hand, macrophage-derived prostaglandin E2 plays a protective role at an initial phase of ARDS by inhibiting cytokine production by macrophages and extravascular invasion of activated neutrophils. Our recent studies have shown that LPS-induced COX-2 expression and subsequent prostaglandin E2 production in rat alveolar macrophages are inhibited by ethanol incubation in vitro and ethanol administration in vivo. Only a decade has passed since alcohol abuse was demonstrated to be associated with increased mortality of ARDS and future studies are needed to clarify the mechanism underlying alcohol-induced exacerbation of ARDS.
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PMID:[Alcohol abuse as a risk factor for ARDS]. 1717 45

Adenosine is a purine nucleoside that regulates cell function through G protein-coupled receptors that activate or inhibit adenylyl cyclase. Based on the understanding that cAMP regulates alveolar epithelial active Na(+) transport, we hypothesized that adenosine and its receptors have the potential to regulate alveolar ion transport and airspace fluid content. Herein, we report that type 1 (A(1)R), 2a (A(2a)R), 2b (A(2b)R), and 3 (A(3)R) adenosine receptors are present in rat and mouse lungs and alveolar type 1 and 2 epithelial cells (AT1 and AT2). Rat AT2 cells generated and produced cAMP in response to adenosine, and micromolar concentrations of adenosine were measured in bronchoalveolar lavage fluid from mice. Ussing chamber studies of rat AT2 cells indicated that adenosine affects ion transport through engagement of A(1)R, A(2a)R, and/or A(3)R through a mechanism that increases CFTR and amiloride-sensitive channel function. Intratracheal instillation of low concentrations of adenosine (< or =10(-8)M) or either A(2a)R- or A(3)R-specific agonists increased alveolar fluid clearance (AFC), whereas physiologic concentrations of adenosine (> or =10(-6)M) reduced AFC in mice and rats via an A(1)R-dependent pathway. Instillation of a CFTR inhibitor (CFTR(inh-172)) attenuated adenosine-mediated down-regulation of AFC, suggesting that adenosine causes Cl(-) efflux by means of CFTR. These studies report a role for adenosine in regulation of alveolar ion transport and fluid clearance. These findings suggest that physiologic concentrations of adenosine allow the alveolar epithelium to counterbalance active Na(+) absorption with Cl(-) efflux through engagement of the A(1)R and raise the possibility that adenosine receptor ligands can be used to treat pulmonary edema.
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PMID:Adenosine regulation of alveolar fluid clearance. 1736 Apr 81

Antibody-mediated rejection (AMR) in heart transplants in the absence of anti-HLA donor-specific antibody (DSA) is not well studied or documented. This case reviews hyperacute fulminant graft dysfunction suspected to be mediated by non-HLA antibodies. After cross clamp removal, the patient developed severe pulmonary edema, profound coagulopathy, and biventricular failure. The patient's presumed AMR, cardiogenic shock, and coagulopathy were treated with extracorporeal membrane oxygenation (ECMO), plasmapheresis, intravenous immunoglobulin (IVIG), multiple blood products, and prothrombin complex concentrate. The recipient was 0% panel-reactive antibody (PRA), ABO, and crossmatch compatible. Intraoperative biopsy sample revealed a thrombotic process suggestive of a coagulation pathway activated by AMR; however, no C4d deposition was detected. Postmortem biopsies also suggested AMR. Retrospective testing of the patient's pretransplant serum revealed strong antiangiotensin II type 1 receptor (AT1R) antibodies and a strongly positive endothelial cell crossmatch. Anti-AT1R antibodies are known to be AT1 receptor agonists and may trigger inflammation and activate the extrinsic coagulation pathway. Given the potential effects of signaling through the AT1R, the patient's preexisting anti-AT1R antibodies and procoagulant therapy may have adversely affected the patient's clinical course.
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PMID:Hyperacute graft dysfunction in an orthotopic heart transplant in the presence of non-HLA antibodies. 3140 Feb 58