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1.
Sci Data ; 11(1): 598, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844775

ABSTRACT

In the arid and semi-arid Western U.S., access to water is regulated through a legal system of water rights. Individuals, companies, organizations, municipalities, and tribal entities have documents that declare their water rights. State water regulatory agencies collate and maintain these records, which can be used in legal disputes over access to water. While these records are publicly available data in all Western U.S. states, the data have not yet been readily available in digital form from all states. Furthermore, there are many differences in data format, terminology, and definitions between state water regulatory agencies. Here, we have collected water rights data from 11 Western U.S. state agencies, harmonized terminology and use definitions, formatted them for consistency, and tied them to a Western U.S.-wide shapefile of water administrative boundaries.

2.
Toxicol Sci ; 120(2): 269-83, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21258088

ABSTRACT

Drug-induced kidney injury (DIKI) results in attrition during drug development; new DIKI urinary biomarkers offer potential to detect and monitor DIKI progression and regression, but frequently only in rats. The triple reuptake inhibitor (TRI) PRC200-SS represents a new class of antidepressants that elevate synaptic levels of serotonin, norepinephrine, and dopamine and is expected to produce more rapid onset and better antidepressant efficacy than single or dual inhibitors. Although preclinical studies and recent clinical trials lend support to this concept of superior efficacy for TRIs, there is little information on the safety profile of this class of compounds. Using histopathology and DIKI biomarkers, in single- and repeat dose toxicological studies in cynomolgus monkeys, PRC200-SS demonstrated dose-proportional kidney toxicity. Characterization of the histopathological lesions, using a combination of immunohistochemistry (IHC) and urinary biomarker analysis, indicated that the compound is a distal tubule and collecting duct toxicant. Segment specificity for the lesions was shown using a newly developed triple IHC combination method with antibodies against calbindin D28, aquaporin 2, and aquaporin 1. Urinary biomarker analyses, using multiplex immunoassays, confirmed a dose-proportional increase in the excretion of calbindin D28 and clusterin in compound-treated monkeys with levels returning to baseline during the drug-free recovery period. These results constitute the validation of distal nephron DIKI biomarkers in the cynomolgus monkey and demonstrate the utility of calbindin D28 and clusterin to monitor the progression of distal nephron DIKI, representing potential early biomarkers of DIKI for the clinic.


Subject(s)
Antidepressive Agents/toxicity , Biomarkers , Kidney Diseases/chemically induced , Naphthalenes/toxicity , Neurotransmitter Uptake Inhibitors/toxicity , Propanolamines/toxicity , Animals , Antidepressive Agents/pharmacokinetics , Biomarkers/blood , Biomarkers/urine , Biotransformation , Cells, Cultured , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Hepatocytes/drug effects , Hepatocytes/metabolism , Humans , Immunohistochemistry , Kidney Diseases/blood , Kidney Diseases/pathology , Kidney Diseases/urine , Macaca fascicularis , Male , Naphthalenes/pharmacokinetics , Neurotransmitter Uptake Inhibitors/pharmacokinetics , Organ Size/drug effects , Pilot Projects , Propanolamines/pharmacokinetics
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