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1.
Nutr Cancer ; 70(2): 278-287, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29313726

RESUMO

The association between a Western Diet and colon cancer suggests that dietary factors and/or obesity may contribute to cancer progression. Our objective was to develop a new animal model of obesity and the associated pathophysiology to investigate human cancer independent of dietary components that induce obesity. A novel congenic rat strain was established by introducing the fa allele from the Zucker rat into the Rowett Nude rat to generate a "fatty nude rat". The obese phenotype was first characterized in the new model. To then examine the utility of this model, lean and obese rats were implanted with HT-29 human colon cancer xenografts and tumor growth monitored. Fatty nude rats were visibly obese and did not develop fasting hyperglycemia. Compared to lean rats, fatty nude rats developed fasting hyperinsulinemia, glucose intolerance, and insulin resistance. Colon cancer tumor growth rate and final weight were increased (P < 0.05) in fatty nude compared to lean rats. Final tumor weight was associated with p38 kinase phosphorylation (P < 0.01) in fatty nude rats. We have established a novel model of obesity and pre-type 2 diabetes that can be used to investigate human cancer and therapeutics in the context of obesity and its associated pathophysiology.


Assuntos
Glucose/metabolismo , Obesidade/etiologia , Ratos Endogâmicos/genética , Alelos , Animais , Animais Congênicos , Modelos Animais de Doenças , Ingestão de Alimentos , Feminino , Glucose/genética , Células HT29 , Humanos , Resistência à Insulina , Masculino , Camundongos Nus , Obesidade/metabolismo , Ratos Zucker , Receptores para Leptina/genética , Ensaios Antitumorais Modelo de Xenoenxerto
2.
J Agromedicine ; 23(1): 20-24, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28952899

RESUMO

In 2013, the Occupational Safety and Health Administration announced a Local Emphasis Program targeted at New York farmers. This program involved random inspections of dairy farms across the state. This article provides an overview of the efforts made in New York to prepare farmers for these inspections. As a result of this program launch, several safety services offered by the New York Center for Agricultural Medicine and Health were significantly impacted, and required expansion and modification in order to meet the needs of New York farmers.


Assuntos
Indústria de Laticínios/normas , Saúde Ocupacional/normas , Gestão da Segurança/normas , United States Occupational Safety and Health Administration , Criação de Animais Domésticos/métodos , Indústria de Laticínios/métodos , Fidelidade a Diretrizes , Humanos , New York , Saúde Ocupacional/educação , Estados Unidos
3.
Nutr Res ; 36(12): 1325-1334, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27866828

RESUMO

Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth. Homozygous Rag1tm1Mom mice were fed either a low-fat Western diet or a high-fat Western diet (HFWD), then human colon cancer xenografts were implanted subcutaneously or orthotopically. Tumors were analyzed to detect changes in receptor tyrosine kinase-mediated signaling and expression of inflammatory-associated genes in epididymal white adipose tissue. In both models, mice fed an HFWD weighed more and had increased intra-abdominal fat, and tumor weight was greater compared with in the low-fat Western diet-fed mice. They also displayed significantly higher levels of leptin; however, there was a negative correlation between leptin levels and tumor size. In the orthotopic model, tumors and adipose tissue from the HFWD group displayed significant increases in both c-Jun N-terminal kinase activation and monocyte chemoattractant protein 1 expression, respectively. In conclusion, this study suggests that human colon cancer growth is accelerated in animals that are obese and insulin resistant due to the consumption of an HFWD.


Assuntos
Neoplasias do Colo , Dieta Hiperlipídica/efeitos adversos , Dieta Ocidental/efeitos adversos , Gorduras na Dieta/efeitos adversos , Resistência à Insulina , Obesidade/complicações , Tecido Adiposo Branco/metabolismo , Animais , Quimiocina CCL2/metabolismo , Neoplasias do Colo/etiologia , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Epididimo/metabolismo , Xenoenxertos/crescimento & desenvolvimento , Humanos , Inflamação/genética , Insulina/sangue , Gordura Intra-Abdominal/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Leptina/sangue , Masculino , Camundongos Endogâmicos , Obesidade/sangue , Obesidade/metabolismo , Fosforilação , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais
4.
J Agromedicine ; 20(2): 195-204, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25906278

RESUMO

Agriculture and forestry rank among industries with the highest rates of occupational fatality and injury. Establishing a nonfatal injury surveillance system is a top priority in the National Occupational Research Agenda. Recently, new sources of data such as Pre-Hospital Care Reports (PCRs) and hospitalization data have transitioned to electronic databases. Using narrative free text and location codes from Maine PCRs, along with International Classification of Diseases (ICD)-9 External Cause of Injury Codes (E-codes) in Maine hospital data, researchers are designing a surveillance system to track farm and forestry injury that utilizes electronic match-merging of the two data sources. For 2008, PCR records produced a total of 104 true agricultural cases. Of these, 66 (63%) were identified from the keyword/visual inspection process alone, 25 (24%) were identified by the farm checkbox only, and the remaining 13 (13%) by both methods. For the 150 unique injury events found in hospitalization data, 146 had the initial episode of care documented in only one of the three hospital files. The emergency department (ED) file had the largest number of these (123/146 = 84.2%), followed by the outpatient file (12/146 = 8.2%) and the inpatient file (11/146 = 7.5%). Of the 250 unique agricultural injuries identified (100 PCR only + 146 hospital only + 4 from both), 66 (26%) would not have been identified without free text review of PCR narrative. The false-positive rate (97.14%) keyword searches underscores that without visual inspection, it is not an effective strategy. Both sources of data (PCR and hospital data) need to be used in a continued surveillance system.


Assuntos
Acidentes de Trabalho/estatística & dados numéricos , Agricultura/estatística & dados numéricos , Agricultura Florestal/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Maine/epidemiologia , Ferimentos e Lesões/epidemiologia
5.
Biochem Biophys Res Commun ; 450(4): 1619-25, 2014 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-25035929

RESUMO

PKCδ has been linked to key pathophysiological features of non-alcoholic fatty liver disease (NAFLD). Yet, our knowledge of PKCδ's role in NAFLD development and progression in obese models is limited. PKCδ(-/-)/Lepr(db)(/)(db) mice were generated to evaluate key pathophysiological features of NAFLD in mice. Hepatic histology, oxidative stress, apoptosis, gene expression, insulin signaling, and serum parameters were analyzed in Lepr(db)(/)(db) and PKCδ(-/-)/Lepr(db)(/)(db) mice. The absence of PKCδ did not abrogate the development of obesity in Lepr(db)(/)(db) mice. In contrast, serum triglyceride levels and epididymal white adipose tissue weight normalized to body weight were reduced in PKCδ(-/-)/Lepr(db)(/)(db) mice compared Lepr(db)(/)(db) mice. Analysis of insulin signaling in mice revealed that hepatic Akt and GSK3ß phosphorylation were strongly stimulated by insulin in PKCδ(-/-)/Lepr(db)(/)(db) compared Lepr(db)(/)(db) mice. PKCδ may be involved in the development of obesity-associated NAFLD by regulating hepatic lipid metabolism and insulin signaling.


Assuntos
Insulina/metabolismo , Fígado/metabolismo , Proteína Quinase C-delta/metabolismo , Transdução de Sinais , Triglicerídeos/metabolismo , Animais , Peso Corporal , Fígado Gorduroso/metabolismo , Expressão Gênica , Metabolismo dos Lipídeos/genética , Camundongos , Tamanho do Órgão , Estresse Oxidativo , Reação em Cadeia da Polimerase
6.
PLoS One ; 9(1): e85848, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24454937

RESUMO

Steatosis, oxidative stress, and apoptosis underlie the development of nonalcoholic steatohepatitis (NASH). Protein kinase C delta (PKCδ) has been implicated in fatty liver disease and is activated in the methionine and choline-deficient (MCD) diet model of NASH, yet its pathophysiological importance towards steatohepatitis progression is uncertain. We therefore addressed the role of PKCδ in the development of steatosis, inflammation, oxidative stress, apoptosis, and fibrosis in an animal model of NASH. We fed PKCδ(-/-) mice and wildtype littermates a control or MCD diet. PKCδ(-/-) primary hepatocytes were used to evaluate the direct effects of fatty acids on hepatocyte lipid metabolism gene expression. A reduction in hepatic steatosis and triglyceride levels were observed between wildtype and PKCδ(-/-) mice fed the MCD diet. The hepatic expression of key regulators of ß-oxidation and plasma triglyceride metabolism was significantly reduced in PKCδ(-/-) mice and changes in serum triglyceride were blocked in PKCδ(-/-) mice. MCD diet-induced hepatic oxidative stress and hepatocyte apoptosis were reduced in PKCδ(-/-) mice. MCD diet-induced NADPH oxidase activity and p47(phox) membrane translocation were blunted and blocked, respectively, in PKCδ(-/-) mice. Expression of pro-apoptotic genes and caspase 3 and 9 cleavage in the liver of MCD diet fed PKCδ(-/-) mice were blunted and blocked, respectively. Surprisingly, no differences in MCD diet-induced fibrosis or pro-fibrotic gene expression were observed in 8 week MCD diet fed PKCδ(-/-) mice. Our results suggest that PKCδ plays a role in key pathological features of fatty liver disease but not ultimately in fibrosis in the MCD diet model of NASH.


Assuntos
Apoptose , Fígado Gorduroso/enzimologia , Metabolismo dos Lipídeos , Estresse Oxidativo , Proteína Quinase C-delta/fisiologia , Animais , Biomarcadores/metabolismo , Células Cultivadas , Deficiência de Colina/enzimologia , Dieta , Estresse do Retículo Endoplasmático , Ativação Enzimática , Feminino , Expressão Gênica , Hepatócitos/fisiologia , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/enzimologia , Masculino , Metionina/deficiência , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica , Cultura Primária de Células
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