Geomorphic and geologic controls of geohazards induced by Nepal's 2015 Gorkha earthquake.

The Gorkha earthquake (magnitude 7.8) on 25 April 2015 and later aftershocks struck South Asia, killing ~9000 people and damaging a large region. Supported by a large campaign of responsive satellite data acquisitions over the earthquake disaster zone, our team undertook a satellite image survey of the earthquakes' induced geohazards in Nepal and China and an assessment of the geomorphic, tectonic, and lithologic controls on quake-induced landslides. Timely analysis and communication aided response and recovery and informed decision-makers. We mapped 4312 coseismic and postseismic landslides. We also surveyed 491 glacier lakes for earthquake damage but found only nine landslide-impacted lakes and no visible satellite evidence of outbursts. Landslide densities correlate with slope, peak ground acceleration, surface downdrop, and specific metamorphic lithologies and large plutonic intrusions.

Cisplatin urinary pharmacokinetics and nephrotoxicity: a common circadian mechanism.

Renal toxicity and urinary pharmacokinetics following a nonlethal dose (5 mg/kg) of cisplatin were investigated in female F344 (Fischer) rats that were on a standardized light-dark schedule, with water freely available. Circadian timing of drug administration had a major effect on the BUN increase (P less than 0.01), the urine volume increase (P less than 0.025), and the urinary concentration of cisplatin following drug administration (P less than 0.01). Renal toxicity was positively correlated with the peak urinary concentration of cisplatin and with the area under the curve of urinary concentration over the first 20 hours after drug administration (P less than 0.01). Drug administration near the normal circadian maximum of urinary volume prior to treatment resulted in the least renal toxicity, lowest peak, and smallest area of urinary concentration of cisplatin.

Effect of diethyldithiocarbamate rescue on tumor response to cis-platinum in a rat model.

The nephrotoxic effects of cis-dichlorodiamineplatinum(II) (NSC-119875) (DDP) in female F344 rats were effectively inhibited by administration of sodium diethyldithiocarbamate (DDTC) in doses of 750 mg/kg intraperitoneally or 100 mg/kg intravenously 2 hr after administration of DDP. Rats were inoculated with mammary tumor 13762 and treated after 10 days with DDP (2.0 or 8.0 mg/kg) with or without DDTC rescue (750 mg/kg intraperitoneally or 100 mg/kg intravenously). Initial reductions in tumor size were identical with or without rescue in all experiments. High-dose intraperitoneal rescue, however, resulted in earlier relapse and more rapid progressions at both DDP doses than was observed in the absence of rescue. Low-dose intravenous rescue led to a tumor response identical to that observed without rescue. Urinary excretion of free DDTC was increased by prior administration of acetazolamide; however, this combination was more toxic to rats after DDP administration than was DDTC alone. Intravenous administration of DDTC appeared to be the most effective route for delivery of this ligand to the kidney. These results support our earlier mechanistic hypothesis and demonstrate the feasibility of inhibition of cis-platinum toxicity by DDTC without inhibition of the antitumor effect.

Inhibition of cis-platinum nephrotoxicity by diethyldithiocarbamate rescue in a rat model.

The nephrotoxic effects of cis-dichlorodiammineplatinum(II) (NSC-119875) administered to male F344 rats at the median lethal dose (LD50; 7.5 mg/kg) were inhibited by treatment with sodium diethyldithiocarbamate (500 or 750 mg/kg) between 1 and 4 hr after cis-platinum administration. Those animals receiving cis-platinum alone had mean serum blood urea nitrogen levels of 234 mg/dl at the time of maximal toxicity (day 5); kidney sections revealed large areas of degeneration and necrosis. When dithiocarbamate rescue was carried out after cis-platinum treatment, mean blood urea nitrogen levels were in the range 56-95 mg/dl; kidney sections were grossly normal with a barely discernible band of degeneration at the corticomedullary junction. Gastrointestinal toxicity was observed in greater than 95% of the cis-platinum-treated rats but was totally absent in those receiving subsequent rescue treatment. A significant decrease in weight loss was also observed in the dithiocarbamate-rescued rats. Based on the chemistry of platinum-sulfur interactions and the observed time-dependence of the rescue treatment, it is suggested that dithiocarbamate exerts its effects via competitive chelation and removal of platinum coordinated to protein-bound sulfhydryl groups of the kidney tubule cells.