摘要:

AbstractTwo commonly employed solvents,n-hexane and carbon disulfide (CS2), although chemically dissimilar, result in identical neurofilament-filled swellings of the distal axon in both the central and peripheral nervous systems. Whereas CS2is itself a neurotoxicant, hexane requires metabolism to theγ-diketone, 2,5-hexanedione (HD). Both HD and CS2react with protein amino functions to yield initial adducts (pyrrolyl or dithiocarbamate derivatives, respectively), which then undergo oxidation or decomposition to an electrophile (oxidized pyrrole ring or isothiocyanate), that then reacts with protein nucleophiles to result in protein cross-linking. It is postulated that progressive cross-linking of the stable neurofilament during its anterograde transport in the longest axons ultimately results in the accumulation of neurofilaments within axonal swellings. Reaction with additional targets appears to be responsible for the degeneration of the axon distal to the swellings.

ISSN:1040-8444    

DOI:10.3109/10408449509021609

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractIt has become increasingly apparent that cocaine abuse can provoke lethal cardiac events, including myocardial infarction and ventricular fibrillation. The mechanisms responsible for these cardiotoxic actions of cocaine largely remain to be determined. Cocaine has two primary pharmacological properties that can adversely affect the heart and vasculature. Cocaine acts both as a local anesthetic (sodium and potassium channel blockade) and as a powerful cardiac stimulant that accentuates the actions of the sympathetic nervous system (inhibition of central and peripheral neuronal catecholamine uptake). The local anesthetic properties could impair impulse conduction, as well as elicit inhomogeneities in repolarization (refractory period), which creates an ideal substrate for reentrant arrhythmias. In addition, high doses of cocaine can depress contractile function due to inhibition of sodium/calcium exchange that results from decreased sodium influx (local anesthetic action). These actions are particularly obvious when sympathomimetic effects of cocaine are blunted. In a similar manner, the cocaine-induced accumulation of catecholamines potentiates the activation ofα- andβ-adrenergic receptors, which can provoke coronary vasospasm (myocardial ischemia and infarction), increased contractile force (increased metabolic demand), and cardiac arrhythmias. The activation of adrenergic receptors will elicit a cascade of second messengers, ultimately provoking an increase in cytosolic calcium. These elevations in cytosolic calcium can provoke oscillations in membrane potential, triggering sustained action potential generation and extrasystoles. In particular, activation of theαIA-adrenergic receptor subtype and corresponding increase in calcium influx via voltage sensitive (L type) channels may play a critical role in the genesis of malignant arrhythmias. Thus, the adrenergic and local anesthetic properties of cocaine could act synergistically to elicit toxic actions on the heart.

ISSN:1040-8444    

DOI:10.3109/10408449509021610

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractPolychlorinated biphenyls (PCBs) are a mixture of 209 different chlorinated biphenyl congeners (forms) of which 36 are environmentally relevant. PCBs are lipid (fat)-soluble, stable compounds. PCBs may be contaminated with more highly toxic polychlorinated dibenzofurans (PCDFs). Some PCDFs were primarily responsible for the two poisoning outbreaks—Yusho and Yu-Cheng.Based on the reports on workers and the general population, no clear and convincing evidence that PCB exposures were casually associated with adverse health effects was advanced; this included cancer for a wide range of body burdens and exposures for serum PCB concentrations>1000 ppb (µ.g/1) and adipose PCB levels>400 ppm (mg/kg). No meaningful reproductive problems have been identified in female capacitor workers. In the opinion of the review author, the available evidence for cancer and for reproductive effects is inconclusive.Adverse neurobehavioral effects in infants and young children have been reported in a study of women in the general population and a study of fish eaters and their offspring. The adverse effects observed in the two studies were not the same; the exposure assessments in both studies are not well defined and have many uncertainties.Subhuman primates appear to be more sensitive to reproductive and other adverse effects of PCBs than humans. Obvious external clinical signs are observed in the offspring of subhuman primates at dosage levels below those experienced by female capacitor workers and members of the general population prior to the control of PCBs.

ISSN:1040-8444    

DOI:10.3109/10408449509021611

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractThe mammalian lung is exposed to and affected by many airborne and bloodborne foreign compounds. This review summarizes the role of lung in accumulation and metabolism of xenobiotics, some of which are spontaneously reactive or are metabolically activated to toxic intermediates. The specific architectural arrangement of mammalian lung favors that so-called pneumophilic drugs are filtered out of the blood and are retained within the tissue as shown in particular for amphetamine, chlorphentermine, amiodarone, imipramine, chlorpromazine, propranolol, local anaesthetics, and some miscellaneous therapeutics.There is strong evidence that intrapulmonary distribution activity and regulation of drug-metabolizing enzymes in lung is distinct from liver. This review focuses on the metabolic rate of selected compounds in lung such as 5-fluoro-2″-deoxyuridine, local anesthetics, nicotine, benzo(a)pyrene, ipomeanol, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone.It is widely accepted that the formation of radical species is a key event in the pneumotoxic mechanisms induced by bleomycin, paraquat, 3-methylindole, butylhydroxytoluene, or nitrofurantoin.Finally, methodological approaches to assess the capacity of lung to eliminate foreign compounds as well as biochemical features of the pulmonary tissue are evaluated briefly.

ISSN:1040-8444    

DOI:10.3109/10408449509021612

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor