elastin and Sepsis

Sepsis is a potentially life-threatening medical condition induced by viral, bacterial or fungal infection, which is characterized by systemic inflammation, hypotension and vasodilation that can lead to cardiovascular collapse. Increased activity of elastases, enzymes which degrade the extracellular matrix components including elastin, has been demonstrated in plasma of septic patients. Since elastin peptides (EP), by binding to an elastin-laminin receptor on vascular endothelial and smooth muscle cells, induce dose-dependent vasodilation, we hypothesized that elevated circulating EP could contribute to the vasodilation that occurs in septic patients.. Blood for measurement of EP was collected from not-septic and septic patients admitted to the intensive care unit (ICU), as well as from healthy subjects. Plasma EP concentrations were measured using a competitive ELISA technique.. The plasma EP level in the septic patients was approximately half that of the not-septic patients and the healthy controls, with similar EP levels in the latter two groups. There was no apparent association between EP levels and age or gender in any of the groups.. Plasma EP levels were actually decreased in septic patients, possibly indicating that the balance between EP production vs. elimination favors elimination. This result further suggests that circulating EP may not be important in the development of the vasodilation and hypotension that occurs in septic shock. Alternatively, however, increased degradation of EP by elastase or other enzymes could lead to the appearance of biologically active EP, which may not be recognized by the ELISA assay.

Topics: Adult; Aged; Aged, 80 and over; Aging; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Peptide Fragments; Reference Values; Sepsis

Matrix metalloproteinases (MMPs) are degradative enzymes, which act to remodel tissue. Their activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). An imbalance in the degradation/inhibition activities has been associated with many diseases, including sepsis. We have previously shown that TIMP-3 knockout animals develop spontaneous, progressive air space enlargement. The objectives of this study were to determine the effects of a septic lung stress induced by cecal ligation and perforation (CLP) on lung function, structure, pulmonary surfactant, and inflammation in TIMP-3 null mice. Knockout and wild-type animals were randomized to either sham or CLP surgery, allowed to recover for 6 h, and then euthanized. TIMP-3 null animals exposed to sham surgery had a significant increase in lung compliance when compared with sham wild-type mice. Additionally, the TIMP-3 knockout mice showed a significant increase in compliance following CLP. Rapid compliance changes were accompanied by significantly decreased collagen and fibronectin levels and increased gelatinase (MMP-2 and -9) abundance and activation. Additionally, in situ zymography showed increased airway-associated gelatinase activity in the knockout animals enhanced following CLP. In conclusion, exposing TIMP-3 null animals to sepsis rapidly enhances the phenotypic abnormalities of these mice, due to increased MMP activity induced by CLP.

Topics: Animals; Collagen; Elastin; Female; Fibronectins; Immunohistochemistry; Interleukin-6; Lung Compliance; Lung Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Alveoli; Pulmonary Surfactants; Sepsis; Tissue Inhibitor of Metalloproteinase-3; Tumor Necrosis Factor-alpha

Endopatch E-F is a new product elaborated with natural human and animal proteins. Its synthesis originates in a covalent link between elastin and fibrin monomers. Numerous experimental studies carried out in animal have previously shown its ability to reinforce healing process of digestive wall. The results reported herein have been obtained in very selected patients in whom a digestive anastomosis had to be done in spite of unfavorable circumstances, such as intra-abdominal infection, radiated bowel or ascitis. From October 1990 to October 1992, 21 digestive anastomosis have been performed in 18 patients. All were reinforced by Endopatch E-F. Two deaths have been observed (mortality: 11.1%), which do not look like a consequence of the use of the product (One myocardial infarction and one cirrhotic failure). There were 2 post-operative fistulas (9.5% of the whole anastomosis). No patients had any reaction of intolerance. These preliminary results confirm experimental data, and suggest that Endopatch EF can be used in order to reinforce digestive sutures when performed under unfavorable circumstances.

Topics: Adult; Aged; Aged, 80 and over; Biocompatible Materials; Elastin; Female; Fibrin; Humans; Male; Middle Aged; Postoperative Complications; Sepsis; Sutures; Wound Healing