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)

In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, control, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with anti-C5a antibodies did not die and did not develop decreased oxygenation (P less than 0.05) or increased extravascular lung water (P less than 0.05). They also had a marked recovery in their mean arterial blood pressure (P less than 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.
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PMID:Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. 371 36

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium moniliforme and F. proliferatum, induces liver damage and pulmonary edema in swine. We examined the temporal and dose-response features of FB1 toxicosis in male weanling crossbred pigs fed nutritionally balanced diets, containing corn screenings naturally contaminated with fumonisins, for 14 days. Total fumonisins (FB1 and FB2) in diets 1 through 6 were assayed at 175, 101, 39, 23, 5, and < 1 ppm (below detectable concentrations), respectively. Clinical signs, serum biochemical alterations, and morphologic changes were evaluated. Pigs were weighed, and bled for hematologic and clinical chemistry evaluation on days 5 and 14. They were euthanized on day 14, or earlier if respiratory distress was observed. Respiratory distress developed in 3/5 pigs fed diet 1 between days 4 and 6 due to severe pulmonary edema and pleural effusion. Histologic evidence of hepatic injury was present in all pigs fed diets 1 and 2, 3/5 on diet 3, and 1/5 on diet 4. Serum bilirubin and cholesterol concentrations, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and arginase (ARG) activities were elevated in pigs fed diets 1 and 2. Based on liver histopathology, the no observed adverse effect level (NOAEL) for fumonisin toxicity in swine was < 23 ppm total fumosins for the 14-day period. Based on regression analyses of the clinical chemistry profiles at 14 days, the NOAEL was < 12 ppm, with ALP being the most sensitive parameter. In conclusion, pulmonary edema occurred only at the highest fumonisin concentration (175 ppm), while liver damage occurred at much lower concentrations with a NOAEL of < 12 ppm.
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PMID:Temporal and dose-response features in swine fed corn screenings contaminated with fumonisin mycotoxins. 805 90

Features of acute lung injury include neutrophil influx and increased vascular permeability with resultant pulmonary edema. Inhibition of p38 mitogen-activated protein kinase (MAPK) in in vivo models of endotoxin-induced inflammation results in reduction of organ injury as well as symptomatic relief. In this study, mice received an oral dose (100 mg/kg) of the p38 MAPK inhibitor, SB203580, followed by intratracheal instillation of an agent of complement origin, C5a des arg, at a concentration (10 microg) that induced acute lung injury. Neutrophil and protein content of bronchoalveolar lavage fluid as indicators of leukocyte influx and vascular permeability respectively were assessed. Animals that received C5a-instillation had a significant influx of neutrophils into the lungs (49+/-8%) while mice receiving C5a-instillation and prior treatment with SB203580 exhibited diminished influx (16+/-5%). Similarly, pretreatment with oral SB203580 resulted in decreased vascular permeability (241+/-34 microg/ml) than the positive control animals (407+/-135 microg/ml). Activity analysis of total lung p38 MAPK revealed that p38 activity was increased at 4 h after C5a-instillation and that SB203580-treated C5a-instilled mouse lungs had lower p38 activity than did the C5a-instilled control. These data indicate that oral administration of an agent inhibitory for p38 MAPK offers a protective effect in the lungs from both neutrophil influx and protein leak associated with acute lung injury.
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PMID:Blockade of p38 map kinase inhibits complement-induced acute lung injury in a murine model. 1627 22

Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Ym1 and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 "healer" phenotype. Comparative multiplex analysis of MSC- and fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-I.
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PMID:Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. 2302 71

This study aimed to investigate the differential expression of plasma proteins in patients suffering from high-altitude pulmonary edema (HAPE) at different phases. A complete proteomic analysis was performed using two-dimensional gel electrophoresis followed by mass spectrometry in three patients with HAPE at the acute stage and recovery phase. Comparisons between the expression patterns of the patients with HAPE at the two different phases led to the identification of eight protein spots with a >1.5-fold difference in expression between the acute and recovery phases. These differentially expressed proteins were apolipoproteins, serum amyloid P component, complement components and others. Apolipoprotein A-I (Apo A-I), serum amyloid P component and fibrinogen were overexpressed in the patients with HAPE in the acute stage compared with their expression levels in the recovery phase. However, Apo A-IV and antithrombin-III were overexpressed in the patients with HAPE in the recovery phase compared with their expression levels in the acute stage. The results indicate that the differential plasma proteome in patients with HAPE may be associated with the occurrence of HAPE, and the expression changes of Apo A-I and A-IV may offer further understanding of HAPE to aid its prognosis, diagnosis and treatment.
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PMID:Differential plasma proteome analysis in patients with high-altitude pulmonary edema at the acute and recovery phases. 2494 Apr 4