摘要:

The effects of ozone (O3) on airway epithelia, inflammation, and expression of inflammatory stimuli were investigated to delineate the mechanisms of inflam matory reactions relevant to lung injury. Because the airway responses to O3develop gradually, this investigation included a time-sequence analysis. Rats exposed for 3 h to 1 ppm O3were studied at 4-h intervals up to 20 h postexposure. Bronchoalveolar lavage fluid (BAL) was analyzed for albumin as an indicator of increased permeability, polymorphonuclear leukocytes (PMNs) to assess the inflammatory status, macrophage inflammatory protein-2 (MIP-2, an inflammatory chemokine), and cell adhesion molecules for their role in inflammation and PMN functions. The time-related increase in album in was matched by a similar significant increase for PMNs, MIP-2, and intercellular adhesion molecule-1 (ICAM-1). However, no marked change occurred for b-2 integrin (CD-18) and leukotriene B4(LTB4). The results establish a temporal correlation of epithelial permeability with changes in inflammatory activity and stimuli responsible for PMN recruitment in the lung. The observations of elevated MIP-2 and ICAM-1 levels are consistent with their role in injury and inflammation. An early expression of MIP-2 mRNA in BAL cells, that is, immediately post O3exposure, and the peak increase in BAL MIP-2 levels 4 h later support the chem otactic role of MIP-2 in PMN recruitm ent at 4- and 12-h time points. The rapid drop in MIP-2 and ICAM-1 levels appears to signal the termination of inflammatory cell recruitment, which is accompanied by an onset of recovery.

ISSN:1528-7394    

DOI:10.1080/009841000156899

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

The concentrations of organochlorine (OC) compounds in the substantia nigra (SN) were compared in Parkinson's disease (PD) with concentrations in brain from cortical Lewy body dementia (CLBD), Alzheimer's disease (AD), and nondemented nonparkinsonian controls (CON). The levels of the gamma isomer of hexachlorocyclohexane (g HCH, lindane) were significantly higher in PD tissues (mean +/- SD: 0.56 +/- 0.434 mug/g lipid) than in the other three groups (CLBD 0.052 +/- 0.101 mug/g lipid; AD none detected; CON 0.125 +/- 0.195; all differences from PD significant at p < .05, Mann-Whitney U-test). Dieldrin (HEOD) was higher in PD brain than in AD or control brain, while 1,1'-(2,2-dichloroethenyl diene)-bis(4-chlorobenzene) (p,p-DDE) and total Aroclor-matched polychlorinated biphenyls (matched PCBs) were only higher in PD substantia nigra when these concentrations were compared with those of CLBD. These findings are not inconsistent with the hypothesis derived from epidemiological work and animal studies that organochlorine insecticides produce a direct toxic action on the dopaminergic tracts of the substantia nigra and may contribute to the development of PD in those rendered susceptible by virtue of cytochrome P-450 polymorphism, excessive exposure, or other factors.

ISSN:1528-7394    

DOI:10.1080/009841000156907

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

Sediment ingestion has recently been identified as an important exposure route for toxicants in waterfowl. The effects of lead-contaminated sediment from the Coeur d'Alene River Basin (CDARB) in Idaho on posthatching development of Canada geese (Branta canadensis) were examined for 6 wk. Day-old goslings received either untreated control diet, clean sediment (48%) supplemented control diet, or CDARB sediment (3449 mug/g lead) supplemented diets at 12%, 24%, or 48%. The 12% CDARB diet resulted in a geometric mean blood lead concentration of 0.68 ppm (ww), with over 90% depression of red blood cell ALAD activity and over fourfold elevation of free erythrocyte protoporphyrin concentration. The 24% CDARB diet resulted in blood lead of 1.61 ppm with decreased hematocrit, hemoglobin, and plasma protein in addition to the effects just described. The 48% CDARB diet resulted in blood lead of 2.52 ppm with 22% mortality, decreased growth, and elevated plasma lactate dehydrogenase-L (LDH-L) activity. In this group the liver lead concentration was 6.57 ppm (ww), with twofold increases in hepatic lipid peroxidation (thiobarbituric acid-reactive substances, TBARS) and in reduced glutathione concentration; associated effects included elevated glutathione reductase activity but lower protein-bound thiols concentration and glucose-6-phosphate dehydrogenase (G-6-PDH) activity. The kidney lead concentration in this group was 14.93 ppm with subacute renal tubular nephrosis in one of the surviving goslings. Three other geese in this treatment group exhibited calcified areas of marrow, and one of these displayed severe chronic fibrosing pancreatitis. Lead from CDARB sediment accumulated less readily in gosling blood and tissues than reported in ducklings but at given concentrations was generally more toxic to goslings. Many of these effects were similar to those reported in wild geese and mallards within the Coeur d'Alene River Basin.

ISSN:1528-7394    

DOI:10.1080/009841000156916

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

Previous studies using the freshwater snailLymnaea stagnalishave indicated significant accumulation of aluminum (Al) from simple salts (chloride or nitrate) or Al lactate \[Al(lactate)3] preparations, but not from the Al maltol complex \[Al(maltol)3]. This is in contrast to findings in mammalian systems, where uptake and neurotoxicity are greatest for the soluble and lipophilic Al(maltol)3complex. This study was undertaken to investigate the direct effects of extracellular Al (100 muM) from three Al preparations \[AlCl3, Al(lactate)3and Al(maltol)3] on electrophysiological parameters of an identified neuron, the right parietal dorsal 1 (RPD1) neuron, ofL. stagnalisin vitro. The effects of the corresponding counterion/ligand on the solubility and availability of Al in solution were also examined. Significant effects of Al on electrical properties, including membrane depolarization, increased firing activity, and abnormal firing patterns, were seen in the presence of AlCl3and Al( lactate)3, which formed polyhydroxy and labile Al species in aqueous solution, but not with Al(maltol)3, which remained as the soluble monomeric complex. Qualitative differences were also observed between the response to AlCl3and Al(lactate)3, despite their similar chemistry. The extent of action potential broadening was greater with Al(lactate)3, suggesting some interaction between Al and lactate in their cellular uptake and/or toxicity. It is suggested that polyhydroxy Al species are toxic to molluscan neurons, possibly via disruption of intracellular Ca2+homeostasis.

ISSN:1528-7394    

DOI:10.1080/009841000156925

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

To further elucidate the physiological mechanisms that may contribute to the dichotomy of effect of indole-3-carbinol (I3C) on cancer development, we examined immune functions representative of the three major branches of the imm une system in rats fed either a high (150 mg/kg) or low (50 mg/kg) dose of I3C. Animals fed the high dose of I3C daily for 7 wk had significantly reduced natural killer cell activity. In contrast, T-cellmediated delayed-type hypersensitivity was significantly elevated. Antibody production in response to the antigen keyhole limpet hemocyanin was not significantly altered compared to controls. These results indicate that exposure to I3C may have differential effects on major immune responses. The significance of these immune function alterations in tumor development will require additional investigation of the effects of dietary I3C on immune functions in appropriate tumor models.

ISSN:1528-7394    

DOI:10.1080/009841000156934

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor