No abstract

The relations between ATP depletion, increased cytosolic free calcium concentration [( Cai]), contracture development, and lethal myocardial ischemic injury, as evaluated by enzyme release, were examined using 19F nuclear magnetic resonance to measure [Cai] in 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA)-loaded perfused rat hearts. Total ischemia at 37 degrees C was induced in beating hearts, potassium-arrested hearts, magnesium-arrested hearts, and hearts pretreated with 0.9 microM diltiazem to reduce but not abolish contractility. In the beating hearts, time-averaged [Cai], which is intermediate between the systolic and the basal [Cai], was 544 +/- 74 nM. In contrast, in the potassium- and magnesium-arrested hearts, the time-averaged values are lower than in beating hearts (352 +/- 88 nM for potassium arrest, 143 +/- 22 nM for magnesium arrest). During ischemia, ATP depletion, contracture, and a rise in [Cai] are delayed by cardiac arrest, but all occur more rapidly in the potassium-arrested hearts than in the magnesium-arrested hearts. The diltiazem-treated hearts were generally similar to the magnesium-arrested hearts in their response to ischemia. Under all conditions, contracture development was initiated after tissue ATP had fallen to less than 50% of control; invariably, there was a progressive rise in [Cai] during and following contracture development. Reperfusion with oxygenated perfusate shortly after peak contracture development resulted in a return of [Cai] to its preischemic level, resynthesis of creatine phosphate, no significant enzyme release, and no substantial loss of 5F-BAPTA from the heart. The data demonstrate that an increase in [Cai] precedes lethal myocardial ischemic injury. This rise in [Cai] may accelerate the depletion of cellular ATP and may directly contribute to the development of lethal ischemic cell injury.

Current environmental monitoring approaches focus primarily on chemical occurrence. However, based on concentration alone, it can be difficult to identify which compounds may be of toxicological concern and should be prioritized for further monitoring, in-depth testing, or management. This can be problematic because toxicological characterization is lacking for many emerging contaminants. New sources of high-throughput screening (HTS) data, such as the ToxCast database, which contains information for over 9000 compounds screened through up to 1100 bioassays, are now available. Integrated analysis of chemical occurrence data with HTS data offers new opportunities to prioritize chemicals, sites, or biological effects for further investigation based on concentrations detected in the environment linked to relative potencies in pathway-based bioassays. As a case study, chemical occurrence data from a 2012 study in the Great Lakes Basin along with the ToxCast effects database were used to calculate exposure-activity ratios (EARs) as a prioritization tool. Technical considerations of data processing and use of the ToxCast database are presented and discussed. EAR prioritization identified multiple sites, biological pathways, and chemicals that warrant further investigation. Prioritized bioactivities from the EAR analysis were linked to discrete adverse outcome pathways to identify potential adverse outcomes and biomarkers for use in subsequent monitoring efforts.

Table I. Mineral Element Content of Ten Kinds of Raw, Mature, Dry Legumes' mg/100 g edible portion Kind of legume Calcium Copper Iron Magnesium Manganese Phosphorus Potassium Sodium Zinc Phaseolus vulgaris Navy beans 135.5 ± 2.0 0.80 ± 0.02 5.34 ± 0.02 162.8 ± 2.3 1.02 ± 0.01 453 ± 6 820.8 i 15.0 1.66 ± 0.03 2.17 i 0.04 Great northern beans 181.2 ± 2.9 0.82 ± 0.02 6.87 ± 0.08 178.3 ± 4.7 1.52 ± 0.02 458 ± 3 1087.3 ± 21.1 3.60 ± 0.04 2.12 i 0.04 Pinto beans 111.7 ± 3.6 0.67 ± 0.06 7.04 i 0.15 170.8 ± 7.9 1.52 ± 0.13 510 ± 69 1156.2 ± 43.4 2.51 ± 0.10 2.21 t 0.05 Red kidney beans 59.5 t 2.6 0.69 * 0.01 7.47 ± 0.23 123.0 ± 5.1 1.43 ± 0.10 374 ± 13 1300.7 ± 11.7 2.45 ± 0.03 2.52 ± 0.04 Signif. of diff.b