Gastroenterology
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Body temperature may critically affect mechanisms of liver injury in acetaminophen (APAP) hepatotoxicity. In addition, mild hypothermia is used to treat intracranial hypertension in human liver failure without detailed information on its effects on the injured liver itself. Therefore, we investigated the effects of body temperature on the progression of APAP-induced liver injury in mice. ⋯ Mild hypothermia improved survival and attenuated liver injury and apoptosis in APAP-treated mice by reducing hepatic congestion and improving glycogen recovery without affecting hepatic regeneration. Results of the study underscore the need for a strict control of body temperature in animal models of liver failure and suggest that the benefits of mild hypothermia in liver failure may extend beyond those related to reduced cerebral complications.
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Methylenetetrahydrofolate reductase (MTHFR) is involved in intracellular folate homeostasis and metabolism. We assessed 2 polymorphisms in the MTHFR gene (C677T and A1298C) in relation to colorectal adenoma recurrence and conducted analyses to investigate their joint effects with plasma and dietary markers of folate status. ⋯ We propose that the effect of the MTHFR genotypes on increasing risk of adenoma recurrence in the presence of a low folate status is through their increase in homocysteine concentrations, which in turn could result in DNA hypomethylation via pathways involving S-adenosylhomocysteine.
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Activating mutations in platelet-derived growth factor receptor alpha (PDGFRA) have been reported in a subset of gastrointestinal stromal tumor (GIST) patients who do not express the mutant stem cell factor receptor c-kit. The responsiveness of mutant PDGFRA-positive GIST to imatinib depends on the location of the PDGFRA mutation; for example, the V561D juxtamembrane domain mutation is more sensitive to imatinib than the D842V kinase domain mutation. In this study, we compare the effects of 3 tyrosine kinase inhibitors, PKC412 and nilotinib, and imatinib, on 2 GIST-related PDGFRA mutants, V561D and D842V, which possess differential sensitivity to imatinib. ⋯ Our findings support the clinical testing of PKC412 for treatment of mutant PDGFRA-GIST. The data also support the use of nilotinib as a treatment option for V561D-PDGFRA-associated GIST, although the reduced sensitivity of D842V-PDGFRA probably limits the potential of nilotinib monotherapy for D842V-PDGFRA-associated GIST.
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Comparative Study
Effects of mouse and human lipocalin homologues 24p3/lcn2 and neutrophil gelatinase-associated lipocalin on gastrointestinal mucosal integrity and repair.
The lipocalin superfamily, including the mouse and human homologues 24p3/lcn2 and neutrophil gelatinase-associated lipocalin, show great functional diversity including roles in olfaction, transportation, and prostaglandin synthesis in mammals. Their potential role in maintaining gastrointestinal mucosal integrity and repair is, however, unclear. ⋯ 24p3/lcn2 facilitates mucosal regeneration by promoting cell migration.
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Comparative Study
Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients.
To elucidate the survival of the patients with unresectable hepatocellular carcinoma (HCC) who underwent transcatheter arterial lipiodol chemoembolization (TACE) and to analyze the factors affecting the survivals. ⋯ TACE showed safe therapeutic modality with a 5-year survival of 26% for unresectable HCC patients. The degrees of liver damage, TNM stage, and alpha-fetoprotein values were independent risk factors for patient survival.