6-ketoprostaglandin-f1-alpha and Systemic-Inflammatory-Response-Syndrome

The 'systemic inflammatory response syndrome' (SIRS) may represent the underlying cause of complications after bone marrow transplantation (BMT). This study was conducted to determine whether blocking the etiologic factors of SIRS could improve the complications of BMT. Sixteen consecutive patients with unrelated donors were allocated alternately to two groups. Seven patients received 1.8 g/day of eicosapentaenoic acid (EPA) orally from 3 weeks before to about 180 days after transplantation, while nine patients did not. These two groups were compared with respect to complications, survival, and various cytokines and factors causing vascular endothelial damage. All seven patients receiving EPA survived and only two had grade III graft-versus-host disease (GVHD). Among the nine patients not receiving EPA, three had grade III or IV GVHD. In addition, thrombotic microangiopathy developed in four patients and cytomegalovirus disease occurred in four. Five patients died in this group. The levels of leukotriene B(4), thromboxane A(2), and prostaglandin I(2) were significantly lower in patients receiving EPA than in those not receiving it (all P < 0.01). Cytokines such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-10 were also significantly decreased by EPA (P < 0.05), as were factors causing vascular endothelial damage such as thrombomodulin and plasminogen activator inhibitor-1 (P < 0.05). The survival rate was significantly higher in the group given EPA (P < 0.01). EPA significantly reduced the complications of BMT, indicating that these complications may be manifestations of the systemic inflammatory response syndrome.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Adult; Anemia, Aplastic; Bone Marrow Transplantation; Cytokines; Cytomegalovirus Infections; Eicosapentaenoic Acid; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukins; Leukemia; Life Tables; Lung Diseases, Interstitial; Male; Survival Analysis; Systemic Inflammatory Response Syndrome; Transplantation, Homologous; Tumor Necrosis Factor-alpha; Vascular Diseases

These serial clinical and experimental studies were designed to clarify the pathogenesis of postburn MODS. Both animal and clinical studies were performed. In animal experiments, 46 male cross-bred dogs were cannulated with Swan-Ganz catheters and 39 of them were inflicted with 50% TBSA third degree burns (7 were used as controls). The burned dogs were randomly divided into 4 groups: immediate infusion, delayed infusion, delayed fast infusion and delayed fast infusion combined with ginsenosides. All dogs were kept under constant barbiturate sedation during the whole study period. Hemodynamics, visceral MDA, mitochondrial respiratory control rate (RCR) and ADP/O ratio, ATP, succinic dehydrogenase (SDH), organ water content as well as light and electron microscopy of visceral tissues were determined. In the clinical study, 61 patients with extensive deep burns were chosen, of which 16 sustained MODS. Plasma TXB2/6-keto-PGF1alpha ratio, TNF, SOD, MDA, circulatory platelet aggregate ratio (CPAR), PGE2, interleukin-1, total organ water content and pathological observations of visceral tissues from patients who died of MODS were carried out. Results demonstrated that ischemic-reperfusion damage due to severe shock, sepsis and inhalation injury are three main causes of postburn death. All inflammatory mediators increased markedly in both animals and patients who sustained organ damage or MODS. SDH, RCR, ADP/O and ATP decreased significantly. These findings suggested that ischemic damage and systemic inflammatory response syndrome (SIRS) initiated by mediators or cytokines might be important in the pathogenesis of postburn MODS.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Adenosine Triphosphate; Adult; Animals; Body Water; Burns; Central Nervous System Agents; Dinoprostone; Dogs; Female; Fluid Therapy; Ginsenosides; Hemodynamics; Humans; Hypnotics and Sedatives; Interleukin-1; Male; Malondialdehyde; Mitochondria; Multiple Organ Failure; Oxygen Consumption; Panax; Plants, Medicinal; Platelet Aggregation; Random Allocation; Reperfusion Injury; Saponins; Sepsis; Shock; Succinate Dehydrogenase; Superoxide Dismutase; Syndrome; Systemic Inflammatory Response Syndrome; Thromboxane B2; Tumor Necrosis Factor-alpha

Thromboxane, prostacyclin, and the leukotrienes are eicosanoids that have been implicated as mediators of the host inflammatory response to infection and injury. Commercial enzyme-linked immunosorbent assays (ELISA) are being increasingly utilized to quantitate plasma eicosanoid concentrations in both clinical and experimental systemic inflammatory conditions. The objectives of this study were to 1) critically examine the performance characteristics of commercial ELISA kits for thromboxane B2, 6 keto-prostaglandin F1 alpha, leukotriene B4, and leukotrienes C4, D4, and E4; 2) apply the four ELISA kits in obtaining actual eicosanoid plasma values under both baseline and septic conditions; and 3) recommend quality control measures for general use. Although averages of multiple standard curves from individual assays were variable, there was a strong linear regression relationship between the backfit dose and nominal dose for each level of standard. Precision profiles constructed for each assay type defined a working range where the intra-assay coefficient of variation is less than 10%. Backfit doses deviated most from nominal doses at both extremes of the standard curves and this variation is reflected in the higher percentage errors in these regions. Recovery of each eicosanoid analyte was 96-103%. Calculated sensitivities were somewhat higher than the manufacturer's specifications. When applied to actual measurements in human and porcine plasma, the assays yielded values that fell within the working ranges of the standard curves with the exception of leukotriene B4. Thus, the ELISAs examined were reproducible, precise, and accurate within a specific working range for each assay type. However, internal controls were lacking in the commercial kits examined, which made assessment of intra- and inter-assay variation difficult.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Animals; Eicosanoids; Enzyme-Linked Immunosorbent Assay; Evaluation Studies as Topic; Female; Humans; Leukotrienes; Male; Middle Aged; Quality Assurance, Health Care; Reagent Kits, Diagnostic; Reproducibility of Results; Sensitivity and Specificity; Swine; Systemic Inflammatory Response Syndrome; Thromboxane B2