Amanda M. Burns

Bio: Amanda M. Burns is an academic researcher from Pennsylvania State University. The author has contributed to research in topics: Peroxisome proliferator-activated receptor & Peroxisome. The author has an hindex of 12, co-authored 22 publications receiving 664 citations. Previous affiliations of Amanda M. Burns include University of North Carolina at Chapel Hill.

Role of peroxisome proliferator-activated receptor-α (PPARα) in bezafibrate-induced hepatocarcinogenesis and cholestasis

Abstract: Prolonged administration of peroxisome proliferators to rodents typically leads to hepatocarcinogenesis. Peroxisome proliferator-activated receptor-alpha (PPARalpha) is required to mediate alterations in PPARalpha target gene expression, repress apoptosis, enhance replicative DNA synthesis, oxidative stress to DNA and hepatocarcinogenesis induced by the relatively specific PPARalpha agonist, Wy-14,643. Interestingly, administration of the less specific PPARalpha agonist, bezafibrate, leads to a modest induction of PPARalpha target genes in the absence of PPARalpha expression. In these studies, the role of PPARalpha in modulating hepatocarcinogenesis induced by long-term feeding of 0.5% bezafibrate was examined in wild-type (+/+) and PPARalpha-null (-/-) mice. The average liver weight was significantly higher in (+/+) and (-/-) mice fed bezafibrate than controls, but this effect was considerably less in (-/-) mice as compared with similarly treated (+/+) mice. Increased levels of mRNA encoding cell cycle regulatory proteins and DNA repair enzymes were found in (+/+) mice fed bezafibrate, and this effect was not found in (-/-) mice. In mice fed bezafibrate for 1 year, preneoplastic foci, adenomas and a hepatocellular carcinoma were found in (+/+) mice, while only a single microscopic adenoma was found in one (-/-) mouse. This effect was observed in both Sv/129 and C57BL/6N strains of mice, although only preneoplastic foci were observed in the latter strain. Interestingly, hepatic cholestasis was observed in 100% of the bezafibrate-fed (-/-) mice, and this was accompanied by significantly elevated hepatic expression of mRNA encoding bile salt export pump and lower expression of mRNA encoding cytochrome P450 7A1, consistent with enhanced activation of the bile acid receptor, farnesoid X receptor. Results from these studies demonstrate that the PPARalpha is required to mediate hepatocarcinogenesis induced by bezafibrate, and that PPARalpha protects against potential cholestasis.

Outbreak of norovirus illness associated with a swimming pool

Abstract: On 3 February 2004, the Vermont Department of Health received reports of acute gastroenteritis in persons who had recently visited a swimming facility. A retrospective cohort study was conducted among persons attending the facility between 30 January and 2 February. Fifty-three of 189 (28%) persons interviewed developed vomiting or diarrhoea within 72 h after visiting the facility. Five specimens tested positive for norovirus and three specimen sequences were identical. Entering the smaller of the two pools at the facility was significantly associated with illness (RR 5·67, 95% CI 1·5–22·0, P=0·012). The investigation identified several maintenance system failures: chlorine equipment failure, poorly trained operators, inadequate maintenance checks, failure to alert management, and insufficient record keeping. This study demonstrates the vulnerability of recreational water to norovirus contamination, even in the absence of any obvious vomiting or faecal accident. Our findings also suggest that norovirus is not as resistant to chlorine as previously reported in experimental studies. Appropriate regulations and enforcement, with adequate staff training, are necessary to ensure recreational water safety.

Peroxisome proliferator-activated receptor α target genes

Abstract: Peroxisome proliferator-activated receptors (PPARs) are nuclear proteins that belong to the superfamily of nuclear hormone receptors. They mediate the effects of small lipophilic compounds such as long-chain fatty acids and their derivatives on transcription of genes commonly called PPAR target genes. Here we review the involvement of PPARalpha in peroxisomal and mitochondrial fatty acid oxidation, microsomal fatty acid hydroxylation, lipoprotein, bile and amino acid metabolism, glucose homeostasis, biotransformation, inflammation control, hepato-carcinogenesis and other pathways, through a detailed analysis of the different known or putative PPARalpha target genes.

Therapeutic Roles of Peroxisome Proliferator–Activated Receptor Agonists

Abstract: Peroxisome proliferator-activated receptors (PPARs) play key roles in the regulation of energy homeostasis and inflammation, and agonists of PPARalpha and -gamma are currently used therapeutically. Fibrates, first used in the 1970s for their lipid-modifying properties, were later shown to activate PPARalpha. These agents lower plasma triglycerides and VLDL particles and increase HDL cholesterol, effects that are associated with cardiovascular benefit. Thiazolidinediones, acting via PPARgamma, influence free fatty acid flux and thus reduce insulin resistance and blood glucose levels. PPARgamma agonists are therefore used to treat type 2 diabetes. PPARalpha and -gamma agonists also affect inflammation, vascular function, and vascular remodeling. As knowledge of the pleiotropic effects of these agents advances, further potential indications are being revealed, including roles in the management of cardiovascular disease (CVD) and the metabolic syndrome. Dual PPARalpha/gamma agonists (currently in development) look set to combine the properties of thiazolidinediones and fibrates, and they hold considerable promise for improving the management of type 2 diabetes and providing an effective therapeutic option for treating the multifactorial components of CVD and the metabolic syndrome. The functions of a third PPAR isoform, PPARdelta, and its potential as a therapeutic target are currently under investigation.

Surveillance for waterborne disease and outbreaks associated with recreational water use and other aquatic facility-associated health events-- United States, 2005-2006; and, Surveillance for waterborne disease and outbreaks associated with drinking water and water not intended for drinking-- United States, 2005-2006

Abstract: PROBLEM/CONDITION Since 1971, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have collaboratively maintained the Waterborne Disease and Outbreak Surveillance System for collecting and reporting data related to waterborne-disease outbreaks (WBDOs) associated with drinking water. In 1978, WBDOs associated with recreational water (natural and treated water) were added. This system is the primary source of data regarding the scope and effects of disease associated with recreational water in the United States. In addition, data are collected on individual cases of recreational water-associated illnesses and infections and health events occurring at aquatic facilities but not directly related to water exposure. REPORTING PERIOD Data presented summarize WBDOs and case reports associated with recreational water use that occurred during January 2005--December 2006 and previously unreported disease reports and outbreaks during 1978--2004. DESCRIPTION OF THE SYSTEM Public health departments in the states, territories, localities, and the Freely Associated States (i.e., the Republic of the Marshall Islands, the Federated States of Micronesia, and the Republic of Palau, formerly parts of the U.S.-administered Trust Territory of the Pacific Islands) have primary responsibility for detecting, investigating, and voluntarily reporting WBDOs to CDC. Although the surveillance system includes data for WBDOs and cases associated with drinking water, recreational water, and water not intended for drinking, only cases and outbreaks associated with recreational water and health events at aquatic facilities are summarized in this report. RESULTS During 2005--2006, a total of 78 WBDOs associated with recreational water were reported by 31 states. Illness occurred in 4,412 persons, resulting in 116 hospitalizations and five deaths. The median outbreak size was 13 persons (range: 2--2,307 persons). Of the 78 WBDOs, 48 (61.5%) were outbreaks of gastroenteritis that resulted from infectious agents or chemicals; 11 (14.1%) were outbreaks of acute respiratory illness; and 11 (14.1%) were outbreaks of dermatitis or other skin conditions. The remaining eight were outbreaks of leptospirosis (n = two), primary amebic meningoencephalitis (n = one), and mixed or other illnesses (n = five). WBDOs associated with gastroenteritis resulted in 4,015 (91.0%) of 4,412 illnesses. Fifty-eight (74.4%) WBDOs occurred at treated water venues, resulting in 4,167 (94.4%) cases of illness. The etiologic agent was confirmed in 62 (79.5%) of the 78 WBDOs, suspected in 12 (15.4%), and unidentified in four (5.1%). Thirty-four (43.6%) WBDOs had a parasitic etiology; 22 (28.2%), bacterial; four (5.1%), viral; and two (2.6%), chemical or toxin. Among the 48 gastroenteritis outbreaks, Cryptosporidium was confirmed as the causal agent in 31 (64.6%), and all except two of these outbreaks occurred in treated water venues where Cryptosporidium caused 82.9% (29/35) of the gastroenteritis outbreaks. Case reports associated with recreational water exposure that were discussed and analyzed separately from outbreaks include three fatal Naegleria cases and 189 Vibrio illnesses reported to the Cholera and Other Vibrio Illness Surveillance System. For Vibrio reporting, the most commonly reported species were Vibrio vulnificus, V. alginolyticus, and V. parahaemolyticus. V. vulnificus illnesses associated with recreational water exposure had the highest Vibrio illness hospitalization (77.6%) and mortality (22.4%) rates. In addition, 32 aquatic facility-related health events not associated with recreational water use (e.g., pool chemical mixing accidents) that occurred during 1983--2006 were received from New York. These events, which caused illness in 364 persons, are included in this report but analyzed separately. INTERPRETATIONS The number of WBDOs summarized in this report and the trends in recreational water-associated disease and outbreaks demonstrate a substantial increase in number of reports from previous years. Outbreaks, especially the largest ones, occurred more frequently in the summer at treated water venues and caused gastrointestinal illness. Deficiencies leading to WBDOs included problems with water-quality, venue design, usage, and maintenance. Case reports of illness associated with recreational water use expand our understanding of the scope of waterborne illness by further underscoring the contribution of less well-recognized swimming venues (e.g., oceans) and illness (e.g., nongastrointestinal illness). Aquatic facilities are also a focus for injuries involving chemicals or equipment used routinely in the operation of swimming venues, thus illustrating the lack of training of some aquatics staff. PUBLIC HEALTH ACTIONS CDC uses WBDO surveillance data to 1) identify the etiologic agents, types of aquatic venues, water-treatment systems, and deficiencies associated with outbreaks and case reports; 2) evaluate the adequacy of efforts (i.e., regulations and public awareness activities) to provide safe recreational water; 3) expand the scope of understanding about waterborne disease and health events associated with swimming and aquatics facilities; and 4) establish public health prevention priorities, data, and messaging that might lead to improved regulations, guidelines, and prevention measures at the local, state, and federal levels.