Nitrosative and Oxidative Stresses Contribute to Post-Ischemic Liver Injury Following Severe Hemorrhagic Shock: The Role of Hypoxemic Resuscitation

Purpose: Hemorrhagic shock and resuscitation is frequently associated with liver ischemia-reperfusion injury. The aim of the study was to investigate whether hypoxemic resuscitation attenuates liver injury. Methods: Anesthetized, mechanically ventilated New Zealand white rabbits were exsanguinated to a mean arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia (Normox-Res group, n = 16, PaO2 = 95–105 mmHg) or hypoxemia (Hypox-Res group, n = 15, PaO 2 = 35–40 mmHg) followed, modifying the FiO 2. Animals not subjected to shock constituted the sham group (n = 11, PaO 2 = 95–105 mmHg). Indices of the inflammatory, oxidative and nitrosative response were measured and histopathological and immunohistochemical studies of the liver were performed. Results: Normox-Res group animals exhibited increased serum alanine aminotransferase, tumor necrosis factor- alpha, interleukin (IL)-1b and IL-6 levels compared with Hypox-Res and sham groups. Reactive oxygen species generation, malondialdehyde formation and myeloperoxidase activity were all elevated in Normox-Res rabbits compared with Hypox-Res and sham groups. Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was up-regulated and nitrotyrosine immunostaining increased in animals resuscitated normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals demonstrated a less prominent histopathologic injury which was similar to sham animals. Conclusions: Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory respons

Gastrointestinal stromal tumor

<p>Abstract</p> <p>Background</p> <p>GISTs are a subset of mesenchymal tumors and represent the most common mesenchymal neoplasms of GI tract. However, GIST is a recently recognized tumor entity and the literature on these stromal tumors has rapidly expanded.</p> <p>Methods</p> <p>An extensive review of the literature was carried out in both online medical journals and through Athens University Medical library. An extensive literature search for papers published up to 2009 was performed, using as key words, GIST, Cajal's cells, treatment, Imatinib, KIT, review of each study were conducted, and data were abstracted.</p> <p>Results</p> <p>GIST has recently been suggested that is originated from the multipotential mesenchymal stem cells. It is estimated that the incidence of GIST is approximately 10-20 per million people, per year.</p> <p>Conclusion</p> <p>The clinical presentation of GIST is variable but the most usual symptoms include the presence of a mass or bleeding. Surgical resection of the local disease is the mainstay therapy. However, therapeutic agents, such as Imatinib have now been approved for the treatment of advanced GISTs and others, such as everolimus, rapamycin, heat shock protein 90 and IGF are in trial stage demonstrate promising results for the management of GISTs.</p

Remarks on Andrew Lang's World Trade Law After Neo-Liberalism

No abstract available

Rethinking stasis and utopianism: empty placards and imaginative boredom in the Greek crisis-scape

This chapter traces specific modalities for performing stasis and rethinking utopianism against the backdrop of the recent financial crisis in Greece and, generally, of conditions shaped within the totalizing order Mark Fisher has called “capitalist realism.” Boletsi probes the ways two works deal with the (im)possibility of resistance from within the neoliberal “now”: the short story “Placard and Broomstick” (Ikonomou) and an Athenian wall writing that translates as “I am bored imaginatively.” The empty placard that takes center stage in Ikonomou’s story and the imaginative boredom registered on the walls of Athens test different modalities of stasis against alienation, dispossession, and the contracting of the future. Boletsi argues that both works disengage from conceptions of subjectivity that rest on the binary of either a passive or an active subject—either an acquiescent victim or a revolutionary hero who challenges power from its outside. The story stages the desire for alternative languages by registering a crisis of representation and the inadequacy of existing narratives. The wall writing taps into the modality of the “middle voice” to reconfigure one of the symptoms of capitalist realism—the boredom of unemployment, consumerism, or an indebted life—into a potential resource for different modes of being that carry glimpses of utopianism. Both works, albeit differently, challenge neoliberal imperatives of acquiescence, normalization, or “moving forward.” Although they stage the limited possibilities for resistance within a totalizing system, they also enable alternative configurations of subjectivity, agency, and futurity.Modern and Contemporary Studie

Year in review in Intensive Care Medicine 2009: II. Neurology, cardiovascular, experimental, pharmacology and sedation, communication and teaching

N/

Bile canaliculi are defective in hepatic involvement of organ failure and recovery of liver function is due to their secondary regeneration

Objective: To investigate the morphological changes in the liver in patients with organ failure and hyperbilirubinemia and to correlate them to the outcome. Design: A case series prospective study. Setting: Intensive care units of two general hospitals. Patients: Twelve patients in organ failure with predominant hepatic involvement, aged 16 to 69 years (mean 56 years). Interventions: Liver biopsy was performed on all patients 3-15 days after organ failure. A second biopsy was also performed on all four surviving patients, as well as on 3 patients just before death at a mean time of 16 days (6-32) and 31 days (14-55), respectively, after the first biopsy. The samples were studied by electron microscopy and findings were assessed according to Rappaport&apos;s designation. Measurements and main results: In the first biopsy it was shown that in zone III there was complete degeneration of bile canaliculi and hepatocytes in contrast to zone I. The grade of histological severity for zone III is positively correlated to the bilirubin concentration (p = 0.001). In the specimens from the second biopsy, it was shown that numerous, newly formed secondary bile canaliculi per 20 consecutive hepatocytes had developed in zone III in the surviving patients, whereas there was a complete absence of such canaliculi in the patients who died (mean ± SD: 9.6 ± 3.2 vs 0). Conclusions: It appears that the destruction of primary bile canaliculi is a striking anatomical defect in patients with organ failure and impaired bilirubin excretion. The restoration of liver function coincides with adequate formation of new secondary bile canaliculi in zone III, giving credence to the hypothesis that this formation is an important structural change responsible for the improvement in liver function

The regional production of cytokines and lactate in sepsis-related multiple organ failure

In order to explore whether an organ-specific pattern in cytokine and lactate concentrations exists in patients with multiple organ failure (MOF), we measured the cytokines interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and lactate in blood taken from the hepatic vein, pulmonary capillaries, and peripheral veins of 10 patients with MOF with hepatic involvement (MOF-HI), eight patients with MOF and adult respiratory distress syndrome (MOF-ARDS), and five head-injured patients (controls). Ten additional patients participated in a study of arteriovenous pulmonary concentration gradients of these substances. For statsitical analysis, nonparametric tests and analysis of variance (ANOVA) were used. The regional concentrations of these substances exhibited a different pattern in the two MOF groups. in the MOF-HI group, mean rt SD cytokines IL-1 beta and IL-6 (pg/ml) were respectively 216 +/- 100 and 461 +/- 343 in the hepatic sinusoidal blood; 149 +/- 52 and 293 +/- 204 in pulmonary capillary blood; and 148 +/- 105 and 234 +/- 162 in peripheral venous blood. In the MOF-ARDS group the corresponding levels were 180 +/- 103 and 235 +/- 124; 235 +/- 94 and 280 +/- 108; and 130 +/- 77 and 194 +/- 127. The TNF-alpha levels also exhibited the same pattern. The mean +/- SD corresponding levels (mmol/L) for lactate in the MOF-HI group were 3.1 +/- 1.8, 1.5 +/- 0.3, and 1.2 +/- 0.6, and in the MOF-ARDS group were 1.1 +/- 0.9, 1.8 +/- 1.1, and 1.0 +/- 0.2, respectively. The differences in the levels of all substances between the liver and lungs in the two MOF groups were statistically significant (p &lt; 0.003). In the study of transpulmonary gradients it was shown that the levels of cytokine and lactate were lower in arterial blood than in mixed venous blood in MOF-HI patients, whereas the opposite was true in MOF-ARDS patients. In this study, we found that in MOF, cytokines and lactate are secreted from the most severely affected organs