Glover C.,ITR Laboratories 19601 Clark |
Ochoa R.,Niantic Inc.
Toxicologic Pathology | Year: 2015
Examination of H&E-stained tongue samples from a 26-week intravenous infusion study of Beagle dogs, utilizing a compound with no recognized effect on mineral metabolism, exhibited superficial stratum corneum calcification in both treated and control animals. This resulted in the search for possible causes of the finding to help clarify confounding issues. Retrospective examination of 11 studies performed before the signal case indicated that the problem existed in the testing facility but was not recognized. Prior to 2008, this finding was not observed, perhaps indicating the requirement for a change in procedures or suppliers. Based on the hypothesis that the calcium salts were deposited from bone during processing, a series of tests was performed by fixing tongue and femur along with different tissues, processed routinely to slide, and stained with H&E and von Kossa stains. We conclude that the presence of superficial stratum corneum calcification of the tongue in dogs demonstrated in toxicology studies is an artifactual change related to the processing of tissues, specifically the fixation of tongue in the same container as bone and stomach. This change should not be confused with compound-related effects, even when the incidence varies between controls and treated animals. Copyright © 2014 by The Author(s).
Ochoa R.,Niantic Inc.
Toxicologic Pathology | Year: 2013
Adding a few animals to a toxicology study in order to document whether any lesions observed are reversible and at what level is a common practice but it is often unjustified, as most of the findings observed, particularly in the early stages of drug development, are easily categorized in regard to reversibility potential. The scientific application of all knowledge regarding the compound and the lesion in question is necessary to develop specific studies to address reversibility when this is a necessary step. © 2013 by The Author(s).
Tepper J.,Tepper Nonclinical Consulting |
Ochoa R.,Niantic Inc. |
Rix P.,Vector Preclinical Solutions |
Elliott G.,Galenic Strategies LLC |
And 4 more authors.
International Journal of Toxicology | Year: 2014
Historically, nitrogen oxides (NOx) in food, drinking water, as well as in the atmosphere have been believed to be associated with adverse health consequences. More recently, NOx have been implicated in normal homeostatic regulation, and exogenous administration has been associated with health benefits. One such potential health benefit is the prospect that inhaled nitrite will lower pulmonary blood pressure (BP) in patients with pulmonary arterial hypertension (PAH), a disease with poor prognosis due to the lack of effective treatment. To characterize potential chronic toxicity associated with inhaled AIR001 (sodium nitrite) for use in the treatment of PAH, 26-week exposures to AIR001 were carried out by inhalation administration in rats and by intravenous infusion in dogs. The studies revealed that methemoglobinemia was the primary adverse effect in both species. Methemoglobin levels less than 40% were well tolerated in both species, while levels greater than 50% methemoglobin caused death in some rats. Additionally, a decrease in systemic BP was also observed with inhaled AIR001 exposure in dogs. These acute secondary and exaggerated pharmacological effects occurred daily throughout the 26-week treatment period. Chronic exposure did not alter the magnitude of either methemoglobinemia or hypotension or result in additional toxicity or compensatory responses. Based on the exposure levels that produced these pharmacodynamic responses in animals, relative to those measured in early clinical studies, it appears that an adequate margin of safety exists to support the continued clinical development of inhaled AIR001. © 2014 The Author(s).
Niantic Inc. | Entity website
Niantic Inc. and Google | Date: 2016-07-19
Computer software for detecting a users location and displaying relevant local information of general interest; computer software enabling users to view information about locations, events, and points of interest; computer game software; downloadable computer game software for use on wireless devices; video game programs; interactive video game programs; downloadable electronic game programs and computer software platforms for social networking. Entertainment services, namely, providing online computer and electronic games; providing a web-based system and on-line portal for users to play online computer and electronic games; providing virtual environments in which users can interact through social games for recreational, leisure or entertainment purposes.