Induction of intestinal ischemia reperfusion injury by portal vein outflow occlusion in rats

Background  

Intestinal ischemia can occur from mesenteric artery (MA) occlusion and portal vein (PV) occlusion. The degree and mechanisms of ischemia/reperfusion (I/R) injury in these conditions may differ. Metabolic changes are seen early in I/R. This study compares tissue histology, inflammation, and metabolic response during small bowel I/R due to superior MA or PV occlusion.     

Ischemia-reperfusion injury is more severe in older versus young rat livers

BACKGROUND: Hepatic warm ischemia during surgery remains a significant problem, particularly in organs with possible baseline dysfunction. The objective of this study was to investigate whether age influences the degree of warm ischemia-reperfusion injury in rat livers. MATERIALS AND METHODS: The left and median lobes of young (3 months) and adult (9 months) male rats were exposed to 75 min of ischemia followed by reperfusion. Each age group was divided into two sub-groups. One sub-group was observed for 8 h, whereas the other was allowed to survive. Animals in the 8-h groups (young and adult) were sacrificed, and blood and tissue were taken to determine liver enzymes, neutrophil accumulation, and blood metabolic profiles and to examine the histology. RESULTS: Hepatocellular injury was significantly greater in adult rats after 8 h of reperfusion, as determined by hepatic enzyme levels and histology. Liver enzyme levels were massively elevated in adult rats and were significantly higher compared with those of young rats. The degree of necrosis and neutrophil accumulation was significantly higher in adult rats. After 8 h of reperfusion, the metabolic profiling of the blood revealed elevated levels of creatine, creatinine, allantoin, and amino acids (tyrosine, methionine) in the adult rats. At 24 h of reperfusion, all adult rats died, in contrast to young rats, which all survived. CONCLUSIONS: Aging in rats is associated with greater hepatocellular injury and poor survival rate after 75 min of warm hepatic ischemia.     

Toxicity of the quinalphos metabolite 2-hydroxyquinoxaline: growth inhibition, induction of oxidative stress, and genotoxicity in test organisms

The quinalphos metabolite 2-hydroxyquinoxaline (HQO), previously shown to photocatalytically destroy antioxidant vitamins and biogenic amines in vitro, was tested for toxicity in several small aquatic organisms and for mutagenicity in Salmonella typhimurium. In the rotifer Philodina acuticornis, HQO caused the disappearance of large individuals and increased hydroperoxide concentration. The latter effect was not only observed in animals kept in a light/dark cycle, but also in constant darkness, indicating that HQO can assume a reactive state and/or form reactive intermediates under the influence of either light or redox-active metabolites, in particular, free radicals. Cell proliferation was inhibited in the ciliate Paramecium bursaria. In the dinoflagellate Lingulodinium polyedrum, which allows early detection of cellular stress on the basis of bioluminescence measurements, strong rises in light emission became apparent on the 2nd day of exposure to HQO and continued until cells died between 12 and 18 days of treatment. Oxidative damage of protein by HQO was demonstrated by measuring protein carbonyl in L. polyedrumin vivo as well as in light-exposed bovine serum albumin in vitro. In an Ames test of mutagenicity, HQO proved to be genotoxic in both light- and dark-exposed bacteria. HQO appears as a source of secondary quinalphos toxicity, which deserves further attention.     

Region selective alterations of soluble guanylate cyclase content and modulation in brain of cirrhotic patients

Modulation of soluble guanylate cyclase (sGC) by nitric oxide (NO) is altered in brain from experimental animals with hyperammonemia with or without liver failure. The aim of this work was to assess the content and modulation of sGC in brain in chronic liver failure in humans. Expression of the alpha-1, alpha-2, and beta-1 subunits of sGC was measured by immunoblotting in autopsied frontal cortex and cerebellum from cirrhotic patients and controls. The contents of alpha-1 and alpha-2 subunits of guanylate cyclase was increased both in cortex and cerebellum, whereas the beta-1 subunit was not affected. Addition of the NO-generating agent S-nitroso-N-acetyl-penicillamine (SNAP) to homogenates of frontal cortex from controls increased the activity of sGC 87-fold, whereas, in homogenates from cirrhotic patients, the increase was significantly higher (183-fold). In contrast, in cerebellum, activation of guanylate cyclase by NO was significantly lower in patients (156-fold) than in controls (248-fold). A similar regional difference was found in rats with portacaval anastomosis. In conclusion, these findings show that the NO-guanylate cyclase signal transduction pathway is strongly altered in brain in patients with chronic liver failure and that the effects are different in different brain areas. Given that activation of sGC by NO in brain is involved in the modulation of important cerebral processes such as intercellular communication, learning and memory, and the sleep-wake cycle, these changes could be implicated in the pathogenesis of hepatic encephalopathy in these patients.     

Phasic control of the transmission in the excitatory and inhibitory reflex pathways from cutaneous afferents to α-motoneurones during fictive locomotion in cats

In high spinal paralyzed cats the effect of cutaneous nerve stimulation on lumbar motoneurons was investigated during fictive locomotion. EPSPs evoked from the cutaneous afferents were generally larger during the active phase of the motoneurones, while IPSPs tended to increase during the reciprocal phase. In some cases EPSPs occurred during the active phase, while IPSPs dominated during the reciprocal phase. Apparently, the transmission in the excitatory and inhibitory segmental reflex pathways from cutaneous afferents to α-motoneurones depends on the phase of the step cycle, but there is no general phase dependent alternating switching between these two pathways.     

Schrittmacherimplantation: transthorakaler oder retrosternaler Zugang?

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