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Tinnitus is the perceived sensation of sound in the absence of acoustic stimulation. Individuals who suffer from it are commonly between the ages of 40 and 80 years. Tinnitus is often classified as objective or subjective, yet the pathophysiologic cause is still unknown. Subjective tinnitus is largely identified with hearing loss. Management of tinnitus is based on an individual approach; there is no single treatment or regimen for it. 相似文献
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Caspases (ICE/ Ced3 proteases) are a closely related family of cysteine proteases that play a key role in apoptotic cell death. We examined the role of caspases in DNA damage and cell death in response to the mitochondrial inhibitor, antimycin A. LLC-PK1 cells contain caspase activity that was markedly inhibited by cleavage site-based peptide inhibitors of caspases but not by inhibitors of serine, cysteine, aspartate or metalloproteinases. The caspase activity increased within five minutes of exposure to antimycin A, preceding any evidence of DNA damage and cell death. The specific caspase inhibitors. Ac-Tyr-Val-Ala-Asp-aldehyde (inhibitor I) and Ac-Asp-Glu-Val-Asp-aldehyde (inhibitor II) prevented, in a dose dependent manner, antimycin A-induced DNA strand breaks as determined by DNA unwinding assay (residual double stranded DNA in control, 94 +/- 2%; antimycin A alone, 48 +/- 3%; antimycin A + inhibitor I at 50 microM, 93 +/- 2%; antimycin A + inhibitor II at 50 microM, 89 +/- 5%; N = 3 to 4, P < 0.001). These inhibitors also prevented antimycin A-induced DNA fragmentation as determined by agarose gel electrophoresis and by in situ labeling of cell nuclei by the terminal deoxynucleotidyl transferase (TdT) nick end labeling (TUNEL) method. The caspase inhibitors markedly prevented antimycin A-induced cell death in a dose-dependent manner as measured by trypan blue exclusion (control 6 +/- 1%, antimycin A alone 40 +/- 1%, antimycin A + inhibitor I at 50 microM 16 +/- 1%, antimycin A + inhibitor II at 50 microM 16 +/- 1%; N = 4 to 7, P < 0.001). These data indicate that the caspase family of enzymes play an important role in DNA damage and cell death in response to the mitochondrial inhibitor, antimycin A. 相似文献
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Environmental estrogens and reproductive health: a discussion of the human and environmental data 总被引:1,自引:0,他引:1
GP Daston JW Gooch WJ Breslin DL Shuey AI Nikiforov TA Fico JW Gorsuch 《Canadian Metallurgical Quarterly》1997,11(4):465-481
Estrogenic activity of certain xenobiotics is an established mechanism of toxicity that can impair reproductive function in adults of either sex, lead to irreversible abnormalities when administered during development, or cause cancer. The concern has been raised that exposure to ambient levels of estrogenic xenobiotics may be having widespread adverse effects on reproductive health of humans and wildlife. The purpose of this review is to evaluate (a) the nature of the evidence supporting this concern, and (b) the adequacy of toxicity screening to detect, and risk assessment procedures to establish safe levels for, agents acting by this mechanism. Observations such as adverse developmental effects after maternal exposure to therapeutic levels of the potent estrogen diethylstilbestrol or male fertility problems after exposure to high levels of the weak estrogen chlordecone clearly demonstrate that estrogenicity is active as a toxic mechanism in humans. High level exposures to estrogenic compounds have also been shown to affect specific wildlife populations. However, there is little direct evidence to indicate that exposures to ambient levels of estrogenic xenobiotics are affecting reproductive health. Reports of historical trends showing decreasing reproductive capacity (e.g., decreased sperm production over the last 50 years) are either inconsistent with other data or have significant methodologic inadequacies that hinder interpretation. More reliable historical trend data show an increase in breast cancer rate, but the most comprehensive epidemiology study to data failed to show an association between exposure to persistent, estrogenic organochlorine compounds and breast cancer. Clearly, more work needs to be done to characterize historical trends in humans and background incidence of abnormalities in wildlife populations, and to test hypotheses about ambient exposure to environmental contaminants and toxic effects, before conclusions can be reached about the extent or possible causes of adverse effects. It is unlikely that current lab animal testing protocols are failing to detect agents with estrogenic activity, as a wide array of estrogen-responsive endpoints are measured in standard testing batteries. Routine testing for aquatic and wildlife toxicity is more limited in this respect, and work should be done to assess the validity of applying mammalian toxicology data for submammalian hazard identification. Current risk assessment methods appear to be valid for estrogenic agents, although the database for evaluating this is limited. In conclusion, estrogenicity is an important mechanism of reproductive and developmental toxicity; however, there is little evidence at this point that low level exposures constitute a human or ecologic health risk. Given the potential consequences of an undetected risk, more research is needed to investigate associations between exposures and effects, both in people and animals, and a number of research questions are identified herein. The lack of evidence demonstrating widespread xenobiotic-induced estrogenic risk suggests that far-reaching policy decisions can await these research findings. 相似文献
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FB Mochales RB Castelló JC Marqués LD Rodríguez XG Alemany JA Rodríguez EP Beato BP Gorricho EP Trallero GP Pastor 《Canadian Metallurgical Quarterly》1995,69(6):445-461
This document represents the recommendations of a panel of Spanish experts on antibiotic use and resistance. In a Task Force, under the auspices of the Spanish Ministry of Health and Consumer Affairs that took place in 1994 in Madrid, the members were gravely concerned about the national increase in antibiotic resistance. They analysed the development, evolution and spread of antibiotic resistance among community-acquired human bacterial pathogens in Spain, its relation with antibiotic consumption, and they proposed future surveillance strategies for monitoring the patterns of antibiotic use and consumption. Success will require a collective action among the producers (pharmaceutical industry), prescribers (doctors, veterinarians), dispensers (pharmacists), and consumers (patients). Two similar documents have been recently published by the American Society of Microbiology and the World Health Organization showing the global concern about this topic. 相似文献
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RE Marc RF Murry SK Fisher KA Linberg GP Lewis M Kalloniatis 《Canadian Metallurgical Quarterly》1998,39(9):1685-1693
PURPOSE: To establish a nomogram of amino acid signatures in normal neurons, glia, and retinal pigment epithelium (RPE) of the cat retina, guided by the premise that micromolecular signatures reflect cellular identity and metabolic integrity. The long-range objective was to provide techniques to detect subtle aberrations in cellular metabolism engendered by model interventions such as focal retinal detachment. METHODS: High-performance immunochemical mapping, image registration, and quantitative pattern recognition were combined to analyze the amino acid contents of virtually all cell types in serial 200-nm sections of normal cat retina. RESULTS: The cellular cohorts of the cat retina formed 14 separable biochemical theme classes. The photoreceptor --> bipolar cell --> ganglion cell pathway was composed of six classes, each possessing a characteristic glutamate signature. Amacrine cells could be grouped into two glycine- and three gamma-aminobutyric acid (GABA)-dominated populations. Horizontal cells possessed a distinctive GABA-rich signature completely separate from that of amacrine cells. A stable taurine-glutamine signature defined Müller cells, and a broad-spectrum aspartate-glutamate-taurine-glutamine signature was present in the normal RPE. CONCLUSIONS: In this study, basic micromolecular signatures were established for cat retina, and multiple metabolic subtypes were identified for each neurochemical class. It was shown that virtually all neuronal space can be accounted for by cells bearing characteristic glutamate, GABA, or glycine signatures. The resultant signature matrix constitutes a nomogram for assessing cellular responses to experimental challenges in disease models. 相似文献