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Bradley J Catalone Shendra R Miller Mary Lee Ferguson Dan Malamud Tina Kish-Catalone Nina J Thakkar Fred C Krebs Mary K Howett Brian Wigdahl 《Biomedicine & Pharmacotherapy》2005,59(8):430-437
C31G, which has potent activity against the human immunodeficiency virus type 1 (HIV-1) and an established record of safety in animal studies and human trials, is a microbicidal agent comprised of a buffered equimolar mixture of two amphoteric, surface-active agents: an alkyl amine oxide (C14AO) and an alkyl betaine (C16B). Studies of long-term in vitro exposure to C31G and its constituents have suggested that the components of C31G may contribute differentially to its toxicity and efficacy. In the present studies, in vitro assays of cytotoxicity and anti-HIV-1 activity demonstrated that C16B was slightly less cytotoxic compared to either C31G or C14AO, whereas the anti-HIV-1 activities of C31G and its individual constituents were similar. In the murine model of cervicovaginal microbicide toxicity, in vivo exposure to C14AO resulted in severe cervical inflammation followed by a delayed disruption of the columnar epithelium. In contrast, exposure to C16B caused severe cervical epithelial disruption and a secondary, less intense inflammatory response. These results demonstrate that (i) there are both mechanistic and temporal differences in toxicity associated with the components of C31G not necessarily predicted by in vitro assessments of cytotoxicity and (ii) contributions of each component to the anti-HIV-1 activity of C31G appear to be equal. In addition, these findings indicate that direct and indirect mechanisms of in vivo toxicity can be observed as separate but interrelated events. These results provide further insight into the activity of C31G, as well as mechanisms potentially associated with microbicide toxicity. 相似文献
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Workplace status and risk of hypertension among hourly and salaried aluminum manufacturing employees
Jane Ellen Clougherty Ellen A. Eisen Martin D. Slade Ichiro Kawachi Mark R. Cullen 《Social science & medicine (1982)》2009
An inverse relationship between workplace status and morbidity is well established; higher job status has been associated with reduced risks of heart disease, hypertension, and injury. Most research on job status, however, has focused on salaried populations, and it remains unclear whether job status operates similarly among hourly workers. Our objectives were to examine whether hourly status itself influences risk of hypertension after adjustment for socioeconomic confounders, and to explore the role of fine-scale job grade on hypertension incidence within hourly and salaried groups. We examined data for 14,999 aluminum manufacturing employees in 11 plants across the U.S., using logistic regression with adjustment for age, sex, race/ethnicity and other individual characteristics. Propensity score restriction was used to identify comparable groups of hourly and salaried employees, reducing confounding by sociodemographic characteristics. Job grade (coded 1 through 30, within hourly and salaried groups) was examined as a more refined measure of job status. Hourly status was associated with an increased risk of hypertension, after propensity restriction and adjustment for confounders. The observed effect of hourly status was stronger among women, although the propensity-restricted cohort was disproportionately male (96%). Among salaried workers, higher job grade was not consistently associated with decreased risk; among hourly employees, however, there was a significant trend, with higher job grades more protective against hypertension. Increasing the stringency of hypertension case criteria also increased the risk of severe or persistent hypertension for hourly employees. 相似文献
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David M Raffel Robert A Koeppe Roderick Little Chia-Ning Wang Suyu Liu Larry Junck Mary Heumann Sid Gilman 《Journal of nuclear medicine》2006,47(11):1769-1777
Scintigraphic imaging with (123)I-metaiodobenzylguanidine ((123)I-MIBG) has demonstrated extensive losses of cardiac sympathetic neurons in idiopathic Parkinson's disease (IPD). In contrast, normal cardiac innervation has been observed in (123)I-MIBG studies of multiple-system atrophy (MSA) and progressive supranuclear palsy (PSP). Consequently, it has been hypothesized that cardiac denervation can be used to differentiate IPD from MSA and PSP. We sought to test this hypothesis by mapping the distribution of cardiac sympathetic neurons in patients with IPD, MSA, and PSP by using PET and (11)C-meta-hydroxyephedrine ((11)C-HED). Also, the relationship between cardiac denervation and nigrostriatal denervation was investigated by measuring striatal presynaptic monoaminergic nerve density with PET and (11)C-dihydrotetrabenazine ((11)C-DTBZ). METHODS: (11)C-HED and (11)C-DTBZ scans were obtained for patients with IPD (n = 9), MSA (n = 10), and PSP (n = 8) and for age-matched control subjects (n = 10). Global and regional measurements of (11)C-HED retention were obtained to assess the extent of cardiac sympathetic denervation. (11)C-DTBZ binding was measured in the caudate nucleus, anterior putamen, and posterior putamen. RESULTS: As expected, extensive cardiac denervation was observed in several of the patients with IPD. However, substantial cardiac denervation was also seen in some patients with MSA and PSP. (11)C-DTBZ studies demonstrated striatal denervation in all patients with IPD and in most patients with MSA and PSP. No correlation was found between cardiac (11)C-HED retention and striatal (11)C-DTBZ binding. CONCLUSION: Cardiac sympathetic denervation was found to occur not only in IPD but also in other movement disorders, such as MSA and PSP. This finding implies that scintigraphic detection of cardiac sympathetic denervation cannot be used independently to discriminate IPD from other movement disorders, such as MSA and PSP. Cardiac sympathetic denervation was not correlated with striatal denervation, suggesting that the pathophysiologic processes underlying cardiac denervation and striatal denervation occur independently in patients with parkinsonian syndromes. These findings provide novel information about central and peripheral denervation in patients with neurodegenerative disorders. 相似文献
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