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1.
Toxicol Sci ; 54(2): 509-16, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10774834

ABSTRACT

Acetaminophen overdose induces severe liver injury and hepatic failure. There is evidence that inflammatory cells may be involved in the pathophysiology. Thus, the aim of this investigation was to characterize the neutrophilic inflammatory response after treatment of C3Heb/FeJ mice with 300 mg/kg acetaminophen. A time course study showed that neutrophils accumulate in the liver parallel to or slightly after the development of liver injury. The number of neutrophils in the liver was substantial (209 +/- 64 PMN/50 high-power fields at 12 h) compared to baseline levels (7 +/- 1). Serum levels of TNF-alpha and the C-X-C chemokines KC and MIP-2 increased by 28-, 14-, and 295-fold, respectively, over levels found in controls during the injury process. In addition, mRNA expression of MIP-2 and KC were upregulated in livers of acetaminophen-treated animals as determined by ribonuclease protection assay. However, none of these mediators were generated in large enough quantities to account for neutrophil sequestration in the liver. There was no upregulation of Mac-1 (CD11b/ CD18) or shedding of L-selectin on circulating neutrophils. Moreover, an anti-CD18 antibody had no protective effect against acetaminophen overdose during the first 24 h. These results indicate that there is a local inflammatory response after acetaminophen overdose, including a substantial accumulation of neutrophils in the liver. Because of the critical importance of beta2 integrins for neutrophil cytotoxicity, these results suggest that neutrophils do not contribute to the initiation or progression of AAP-induced liver. The inflammation observed after acetaminophen overdose may be characteristic for a response sufficient to recruit neutrophils for the purpose of removing necrotic cells but is not severe enough to cause additional damage.


Subject(s)
Acetaminophen/toxicity , Analgesics, Non-Narcotic/toxicity , Hepatitis, Animal/immunology , Liver/drug effects , Neutrophils/physiology , Animals , CD18 Antigens/metabolism , CD18 Antigens/pharmacology , Chemokines, CXC/blood , Chemokines, CXC/genetics , Drug Overdose/etiology , Drug Overdose/immunology , Flow Cytometry , Hepatitis, Animal/chemically induced , Hepatitis, Animal/pathology , L-Selectin/blood , Macrophage-1 Antigen/blood , Male , Mice , Mice, Inbred C3H , Necrosis , RNA, Messenger/metabolism , Time Factors , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation
2.
Health Phys ; 77(3): 303-8, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10456502

ABSTRACT

As an element of the joint IAEA-EPA International Radon Metrology Evaluation Program, a climatic test of long-term integrating radon detectors was conducted at the U.S. EPA Radiation and Indoor Environments National Laboratory. The objective of this study was to test the performance of commonly used commercially available long-term 222Rn detector systems under extreme climatological conditions using filtered polycarbonate CR-39 plastic analyzed by the manufacturer using the track-etch method, unfiltered LR-115 film analyzed by the manufacturer, and Teflon based electrets analyzed in the field by EPA using the manufacturer's equipment. The EPA environmental radon chambers were used to expose detectors to extreme cold and dry (less than 4.0 degrees C air temperature and 25% relative humidity) and hot and humid (greater than 35 degrees C air temperature and 85% relative humidity) climatic conditions. During phase I detectors were exposed to low temperatures and low humidities, and during phase II detectors were exposed to high temperatures and high humidities. Typical indoor equilibrium fractions (near 50%) and radon concentrations of about 150 Bq m(-3) were maintained for each phase, which lasted 90 d. The results indicated that the optimal detector for extreme climatic conditions is dependent on the relative importance of bias and precision. Overall, however, the filtered track-etch type detector produced the most reliable results under the extreme conditions.


Subject(s)
Radiometry/instrumentation , Radon/analysis , Air Microbiology , Evaluation Studies as Topic , Fungi/isolation & purification , Health Physics , Humidity , International Agencies , Quality Control , Radiometry/standards , Temperature , United States , United States Environmental Protection Agency
3.
Health Phys ; 66(4): 433-8, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8138410

ABSTRACT

Measurements of radon at 50 sites with varying geology indicate that outdoor air in Nevada is comparable to that measured nationwide by Hopper et al. (1991). The statewide median of 15 Bq m-3 (0.4 pCi L-1) is essentially the same as the nationwide median. The range is considerable: from 2.6-52 Bq m-3 (0.07-1.40 pCi L-1). Variations in these measurements can generally be correlated with different concentrations of radon in soils and uranium and its progeny in rocks. Silica-rich igneous rocks (rhyolites and granites) appear to be the main sources of high levels of radon in outdoor air in Nevada. Concentrations of radon in outdoor air generally correlate with levels of radon in soil gas. Measurements taken from heights of 0.5, 1.0, and 2.0 m above the ground suggest that radon in outdoor air reflects the local geology throughout this range of heights. Towns for which > 20% of the homes have indoor-air radon concentrations > 48 Bq m-3 (4 pCi L-1) generally have relatively high soil-gas radon, relatively high outdoor-air radon, or both.


Subject(s)
Air Pollutants, Radioactive/analysis , Radon/analysis , Nevada , Soil Pollutants, Radioactive/analysis , Uranium/analysis
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