Based on these data, we conclude that the Fas- and TNFR1-mediated apoptotic pathways are directly involved in the pathogenesis of cisplatin-induced RTC death process.
The rapid hydrogenation of simple aromatic ketones is accomplished by using a combination of (η 5 -C 5 (CH 3 ) 5 )Ru complexes and primary amines as a catalyst in 2-propanol. In particular, 1,2-diamines with primary and tertiary amino groups at both ends exhibit a significant ligand acceleration effect. Isotope-labeling experiments using D 2 and 2-propanol-d n reveal that 2-propanol participates in the activation of H 2 based on a metal/NH bifunctional effect to facilitate the hydrogenation. Asymmetric hydrogenation of prochiral simple ketones with the chiral version of the catalysts provides optically active secondary alcohols with up to 95% ee.
We have recently demonstrated the direct involvement of the death receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell (RTC) death. Reactive oxygen species are thought to be a major cause of cellular damage in such injury. The aim of this study was to examine the mechanism through which antioxidants ameliorate cisplatin-induced RTC death, with special emphasis on death receptor-mediated apoptotic pathways. Cisplatin was added to cultures of normal rat kidney (NRK52E) cells or injected in rats. NRK52E cells and rats were also treated with dimethylthiourea (DMTU), a hydroxyl radical scavenger. We then examined the mRNA levels of death ligands and receptors, caspase-8 activity, cell viability, cell death, renal function, and histological alterations. RT-PCR indicated cisplatin-induced upregulation of Fas, Fas ligand, and TNF-alpha mRNAs and complete inhibition by DMTU in vitro and in vivo. Cisplatin increased caspase-8 activity of NRK52E cells, and DMTU prevented such activation. Exposure to cisplatin reduced viability of NRK52E cells, examined by WST-1 assay, and increased apoptosis and necrosis of the cells, examined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and fluorescence-activated cell sorter analysis. DMTU abrogated cisplatin-induced changes in cell viability and apoptosis and/or necrosis. Cisplatin-induced renal dysfunction and histological damage were also prevented by DMTU. DMTU did not hinder cisplatin incorporation into RTCs. Our results suggest that antioxidants can ameliorate cisplatin-induced acute renal failure through inactivation of the death receptor-mediated apoptotic pathways.
Terminal epoxides are hydrogenolyzed to give
secondary alcohols with high regioselectivity using the
ternary catalyst system of Cp*RuCl(cod)−2-(diphenylphosphino)ethylamine (1a)−KOH (Cp* = η5-C5(CH3)5,
cod = 1,5-cyclooctadiene) in 2-propanol under mild
conditions.
We conclude that hyperglycemia in diabetes, independent of plasma aldosterone concentration, induces podocyte injury through MR-mediated ROS production and leads to proteinuria. SPL inhibits hyperglycemia-induced podocyte injury by attenuating ROS production.
Brain metastases from gynecological cancers were retrospectively investigated in 18 patients who were treated between 1985 and 2006. Six patients received surgical resection followed by radiotherapy, and 12 patients received only radiotherapy. The median survival for all patients was 4.1 months (range 0.7-48.2 months), and the actuarial survival rates were 11% at both 12 months and 24 months. Univariate analysis showed that treatment modality, extracranial disease status, total radiation dose, number of brain metastases, and Karnofsky performance status (KPS) all had statistically significant impacts on survival. Two patients survived for more than 2 years, and both had single brain metastasis, inactive extracranial disease, 90-100% KPS, and were treated with surgical resection followed by radiotherapy. Improvements in neurological symptoms were observed in 10 of the 12 patients treated with palliative radiotherapy, with median duration of 3.1 months (range 1.5-4.5 months). The prognoses for patients with brain metastases from gynecological cancers were generally poor, although selected patients may survive longer with intensive brain tumor treatment. Palliative radiotherapy was effective in improving the quality of the remaining life for patients with unfavorable prognoses.
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