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D. Mukherjee, S. E. Nissen and E. J. Topol, "Risk of cardiovascular events associated with selective COX-2 inhibitors," JAMA, Vol. 286, 2001, pp. 954-959.

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• TITLE: Isobolographic Method and Invertebrate (Planarian) Model for Evaluating Combinations of Waterways Pollutants

  AUTHORS: Robert B. Raffa, Deborah A. Gallo, Christopher S. Tallarida, Scott M. Rawls, Ronald J. Tallarida

  KEYWORDS: Combinations; Isobolographic Analysis; Methods; Pollutants; Planarians

  JOURNAL NAME: Pharmacology & Pharmacy, Vol.3 No.4, October 29, 2012

  ABSTRACT: Agricultural, pharmaceutical, and other biologically active substances are emptied or leach into waterways and groundwater, where they can dose-relatedly cause pharmacologic or toxic effects on the resident or dependent animal species. Standard methods can be used to evaluate the effects of individual substances, but evaluation of combinations of substances is more difficult. The mathematically rigorous method of isobolographic analysis was coupled with a simple in vivo invertebrate model. Planarians were selected because they are the lowest extant species with a centralized nervous system. Neostigmine bromide and monopotassium phosphate (KH2PO4) were selected as representative of two types of potential pollutants. Neostigmine bromide and KH2PO4 individually produced dose-related lethality over a 60-minute observation period with LD50 values of 122 and 70 mM, respectively. The LD50 value of a 1:1 combination of the two was significantly different (p