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  • 1
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The factors regulating liver regeneration were studied by measuring changes in the liver volume and serum hepatocyte growth factor (HGF) levels after hepatectomy. Changes in the liver volumes were studied in 68 hepatectomized patients, including (A) hepatoma patients who had chronic hepatitis or liver cirrhosis (n=44) and (B) metastatic liver cancer patients who had normal liver parenchyma (n=24). The hepatic volume increased by 13.8% of the remnant hepatic volume in group A and by 49.1% in group B. The examined factors included the percentage of resected liver volume (%RLV) and the results of laboratory tests. Regression analysis showed that in group A, both %RLV (β=0.46) and the serum total bilirubin (T-Bil) level (β=−0.33) correlated significantly with the extent of liver regeneration and that in group B, only %RLV (β=0.78) correlated significantly with the regeneration. Serum HGF levels after hepatectomy were studied in 21 hepatectomized patients, including 11 hepatoma patients and 10 patients with some types of metastatic liver cancer. Serum HGF levels increased significantly after surgery in all 21 patients. Regression analysis, however, showed that the change in HGF was related to liver cirrhosis (β=0.46) and to the maximal postoperative T-Bil level (β=0.51) but not to the extent of liver regeneration after hepatectomy. These results suggest that liver regeneration is regulated primarily by factors relating to the percentage of the resected liver parenchyma and that serum HGF levels do not directly relate to liver regeneration after surgery.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1573-2568
    Schlagwort(e): HEPATOCYTE TRANSPLANTATION ; EISAI HYPERBILIRUBINEMIC RAT ; JAUNDICE ; RECOMBINANT HUMAN HEPATOCYTE GROWTHFACTOR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Hepatocyte transplantation may offer anattractive treatment for inborn errors of livermetabolism. However, factor(s) are required as stimulito induce proliferation of the limited number ofhepatocytes transplanted. The Eisai hyperbilirubinemic rat(EHBR) is a SpragueDawley (SD) mutant rat withconjugated hyperbilirubinemia. EHBRs have impairedcanalicular excretory transport of organic anions, bileacid glucuronide, and sulfate. Recombinant humanhepatocyte growth factor (rhHGF) (100 μg/kg) wasinjected intravenously at 2-hr intervals for 10 hr,immediately and 35 days following the intraportalinjection of 1 × 107 wild-type SD rathepatocytes. Serum bilirubin concentrations decreasedsignificantly within 35 days and were maintained atsignificantly reduced levels for 120 days followingtransplantation. Biliary excretion was demonstrated by the biliarytransport of indocyanine green and sulfobromophthaleinsodium into the bile. These results indicate thathepatic transport of bile acid conjugates in EHBRs can be restored by hepatocyte transplantationcombined with repeated administration of exogenousrhHGF, in conjunction with functioning of therecipient's excretory biliary system.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1573-2568
    Schlagwort(e): Ki-1 lymphoma ; liver ; involvement ; cytokine ; interleukin-6 ; granulocyte colony-stimulating factor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1573-2568
    Schlagwort(e): FACTOR XA INHIBITOR ; MONOCYTE CHEMOATTRACTANT PROTEIN-1 ; REPERFUSION INJURY
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Activated factor X (FXa) is a trypsinlike serineprotease involved in the cascade of blood coagulation.The monocyte chemoattractant protein-1 (MCP-1) may beimportant in the pathophysiology of liverischemia-reperfusion injury. We investigated the effects of aselective FXa inhibitor, DX-9065a, on MCP-1 expressionafter ischemia-reperfusion in the rat liver. Liverischemia was induced in rats by occluding the portalvein for 30 min. DX-9065a was injected intravenously5 min before vascular clamping. Serum concentrations ofMCP-1 were measured by enzyme-linked immunosorbentassay. The levels of MCP-1 mRNA in the liver after reperfusion were determined by northern blotanalysis. In vitro MCP-1 production by peritonealmacrophages in response to alpha-thrombin was examined.Serum concentrations of MCP-1 increased and peaked at 6 hr after reperfusion. However,pretreatment of animals with DX-9065a resulted insignificantly smaller increases in the serumconcentration of MCP-1 after reperfusion in adose-dependent manner. Pretreatment with DX-9065a significantly reduced MCP-1 mRNAlevels in the liver after ischemia-reperfusion. In vitroMCP-1 production by peritoneal macrophages was enhancedby alpha-thrombin. In addition, DX-9065a significantly reduced tissue factor mRNA levels in peripheralmonocytes after ischemiareperfusion, compared tountreated animals. In conclusion, a selective inhibitorof FXa, DX-9065a, limited MCP-1 production after ischemia-reperfusion of the ratliver.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    ISSN: 1573-2568
    Schlagwort(e): cytokine-induced neutrophil chemoattractant ; coagulation ; ischemia-reperfusion injury ; liver ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    ISSN: 1573-2568
    Schlagwort(e): PANCREATITIS ; SEPTIC COMPLICATION ; CYTOKINE-INDUCED NEUTROPHIL ; CHEMOATTRACTANT ; MACROPHAGE ; LUNG COMPLIANCE
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The role of bronchoalveolar macrophages (BAMs)in the aggravation of cerulein-induced pancreatitis wasstudied by measuring expression of cytokine-inducedneutrophil chemoattractant (CINC) in vitro. Pancreatitis was induced by four intramuscular injections ofcerulein (50 μg/kg at 1-hr intervals). Pancreatitisrats were injected intraperitoneally with 30 mg/kglipopolysaccharide (LPS) 6 hr following the first cerulein injection as a septic challenge. Ratswere divided into four groups: group I, nonpancreatitiswithout LPS; group II, pancreatitis without LPS; groupIII, nonpancreatitis with LPS; and group IV, pancreatitis with LPS. Hyperactivity of BAMs inresponse to LPS was assessed as a function of in vitroCINC production. CINC concentrations of the serum andbronchoalveolar lavage fluid in group IV were significantly higher than those in groups I,II, and III. BAMs in group II harvested 6 hr followingthe first cerulein injection had significantly greaterCINC production than those in group I. Northern blot analysis revealed abundant CINC mRNAtranscripts in BAMs from groups III and IV.Additionally, myeloperoxidase activity in the lung ofgroup IV rats 8 and 12 hr following the first ceruleininjection was significantly higher than that in group I,II, and III rats. Significant differences in static lungcompliance in group IV were found compared with groupsI, II, and III. These results indicate that BAMs from rats with cerulein-inducedpancreatitis were primed and had enhanced release ofCINC following LPS exposure. Enhanced expression of CINCmay modulate the pathogenesis of pancreatitis-associated lung injury complicated with sepsis.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1573-2568
    Schlagwort(e): PANCREATITIS ; CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT ; PERITONEAL MACROPHAGES
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Pancreatitis complicated with infection oftenresults in the development of multiple organ failure. Weinvestigated the role of altered intracellular calciumas a priming signal for cytokine-induced neutrophil chemoattractant expression in this process.Agents modulating cytosolic Ca2+ wereutilized to study the in vivo and in vitrocytokine-induced neutrophil chemoattractant expressionfor macrophages in rats with cerulein-induced pancreatitis afterintraperitoneal administration of lipopolysaccharide asa septic challenge. Pretreatment with the calciumchannel blocker verapamil significantly reduced serumcytokine-induced neutrophil chemoattractant concentrations inrats with cerulein-induced pancreatitis after septicchallenge. Lipopolysaccharide-stimulated in vitrocytokine-induced neutrophil chemoattractant (CINC)production by peritoneal macrophages was significantlyenhanced by pretreatment with thapsigargin (an inhibitorof the endoplasmic reticulum-resident Ca2+-ATPase), but not by A23187 (acalcium-specific ionophore, extracellular Ca2+ influx). Pretreatment withU73122 (a phospholipase C inhibitor) inhibitedlipopolysaccharide-stimulated but not basalcytokine-induced neutrophil chemoattractant production,while verapamil (a calcium channel blocker), TMB-8 (an inhibitor ofcalcium release from endoplasmic reticulum), and W7(calmodulin antagonist) completely abrogated thechemoattractant production. Altered intracellularcalcium, due to Ca2+ efflux from intracellularstores, may be involved in the “priming” ofmacrophages to release cytokine-induced neutrophilchemoattractant following triggering withlipopolysaccharide during acute cerulein pancreatitis.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1573-2568
    Schlagwort(e): calcium channel blocker ; verapamil hydrochloride ; cytokine-induced neutrophil chemoattractant ; reperfusion injury ; rat ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We investigated the effects of the calcium-channel blocker verapamil hydrochloride on the production of cytokine-induced neutrophil chemoattractant (CINC) following reperfusion injury in rat liver. Ischemia was induced for 30 min by portal vein occlusion. Animals were pretreated with intravenous injection of verapamil hydrochloride (2.5 mg/kg) 5 min before vascular clamp. Verapamil hydrochloride limited increases in the chemoattractant compared with nonpretreated rats. Most cells immunostained for chemoattractant were ED2-positive macrophages in sinusoids. In vitro chemoattractant production by Kupffer cells isolated from animals pretreated with verapamil hydrochloride was significantly lower than by Kupffer cells from nonpretreated animals. Expression of transcripts in liver for chemoattractant peaked 3 hr after reperfusion in nonpretreated animals, while pretreatment with verapamil hydrochloride significantly decreased chemoattractant mRNA levels. In vitro chemoattractant production could be induced in naive Kupffer cells after stimulation with oxygen radicals generated by hypoxanthine and xanthine oxidase, but verapamil hydrochloride prevented these increases. We concluded that the calcium-channel blocker verapamil hydrochloride significantly attenuates chemoattractant release by Kupffer cells after ischemia–reperfusion in the rat liver.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 9
    ISSN: 1573-2568
    Schlagwort(e): rat hepatic allograft ; interleukin-12 ; interleukin-18 ; donor-specific blood transfusion ; immunologic unresponsiveness ; Th-2-type cytokine ; interferon-γ
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Interferon-γ is a key immunoregulatory cytokine involved in acute graft rejection. Immunologic unresponsiveness to organ allografts has been induced by pretransplantation donor-specific blood transfusion, both experimentally and clinically. We investigated interferon-γ production and intragraft gene expression of type-1 T-helper cytokines such as interleukin-12 and -18 and type-2 T-helper cytokines such as interleukin-10 and transforming growth factor-β in rats receiving hepatic allografts after such transfusions. The animals were divided into four groups: group I received isografts; group II received allografts; group III received allografts after donor-specific transfusion; and group IV received allografts and was treated with FK 506. Donor blood given seven days prior to transplantation significantly prolonged allograft survival. The serum interferon-γ concentrations in group II increased, peaking on day 5 and then decreasing. Serum interferon-γ concentrations in groups I, III, and IV were significantly lower than those observed in group II, as were levels of interleukin-12 and interleukin-18 mRNA in the graft. Transforming growth factor-β and interleukin-10 mRNA levels in grafts in transfused animals were significantly greater than those in the untreated allograft group. Interleukin-12 and -18 mRNA transcripts in an allogeneic mixed lymphocyte reaction were inhibited by interleukin-10 and transforming growth factor-β. These results suggest that interleukin-12 and -18 expression in hepatic allografts is inhibited in the immunologically unresponsive state induced by donor-specific transfusion.
    Materialart: Digitale Medien
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