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  • 1
    ISSN: 1432-2277
    Keywords: Key words Geranylgeranylacetone ; Heat-shock protein 72 ; Liver transplantation ; Warm ischemic injury ; Ischemia reperfusion injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is well known that heat-shock proteins (HSPs) have a cytoprotective function as “molecular chaperones” when cells are exposed to several stress conditions. Geranylgeranylacetone (GGA) is an antiulcer drug that was developed in Japan and it has recently been reported to induce HSP72 in rat gastric mucosa. In this experiment, we investigated the induction of HSP72 in rat liver in response to oral administration of GGA and assessed its ability to induce tolerance to warm ischemic injury by this approach. We prepared donor rats by orally administering GGA to them and compared HSP72 expression in graft liver, survival rates, and serum TNF-α concentrations after liver transplantation with the findings in controls. The survival rates were significantly increased when the livers were obtained from donor rats given GGA. Western blotting revealed expression of HSP72 in graft livers given GGA, and the serum TNF-α levels were significantly suppressed in the rats given GGA. Oral administration of GGA induced HSP72 in graft livers, and they were better able to tolerate warm ischemic injury. Oral administration of GGA appears to provide a promising new strategy for preventing ischemia-reperfusion injury.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Serotonin receptor ; 5HT2A ; M100907 ; [11C]M100907 ; Positron emission tomography ; PET ; Human brain ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Selective drugs are required to test the hypothesis whether antipsychotic effects may be induced or modulated by 5HT2A receptor antagonism. M100907 (previously known as MDL 100,907) is a highly selective 5HT2A antagonist in clinical development. Objective: To test if the suggested clinical dose of 20 mg M100907 daily induces high 5HT2A receptor occupancy in patients with schizophrenia. Methods: The 5HT2A receptor occupancy was determined in two patients with schizophrenia treated with M100907, 20 mg once a day. Positron emission tomography (PET) with 11C-labeled M100907, was performed prestudy and under steady state conditions. Clinical ratings were performed weekly. Results: Clinical treatment with M100907, 20 mg daily induced a very high 5HT2A receptor occupancy in the frontal cortex of both patients (〉90%). M100907 was well tolerated. One patient improved minimally and one patient became minimally worse during treatment. Conclusions: The results confirm that an oral dose of 20 mg per day ensures adequate 5HT2A receptor occupancy for clinical proof of concept. The sample is too small to allow conclusions about the clinical effect.
    Type of Medium: Electronic Resource
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