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1.
FASEB J ; 34(6): 8611-8624, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32359100

RESUMO

Obesity is a risk factor for breast cancer in postmenopausal and high-risk premenopausal women. Changes within the obese breast microenvironment may increase breast cancer risk. Transforming growth factor beta-1 (TGFß1) is a major regulator of mammary epithelial stem/progenitor cells, and its activity is dysregulated under conditions of obesity. Using a high-fat diet model of obesity in mice and breast tissue from women, we observed that TGFß1 activity is reduced in breast epithelial cells in obesity. Breast ducts and lobules demonstrated increased decorin in the extracellular matrix (ECM) surrounding epithelial cells, and we observed that decorin and latent TGFß1 complexed together. Under conditions of obesity, macrophages expressed higher levels of decorin and were significantly increased in number surrounding breast epithelial cells. To investigate the relationship between macrophages and decorin expression, we treated obese mice with either IgG control or anti-F4/80 antibodies to deplete macrophages. Mice treated with anti-F4/80 antibodies demonstrated reduced decorin surrounding mammary ducts and enhanced TGFß1 activity within mammary epithelial cells. Given the role of TGFß1 as a tumor suppressor, reduced epithelial TGFß1 activity and enhanced TGFß1 within the ECM of obese mammary tissue may enhance breast cancer risk.


Assuntos
Células Epiteliais/metabolismo , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Humanas/metabolismo , Obesidade/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adolescente , Adulto , Animais , Mama/metabolismo , Neoplasias da Mama/metabolismo , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Matriz Extracelular/metabolismo , Feminino , Humanos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos/metabolismo , Pessoa de Meia-Idade , Células-Tronco/metabolismo , Microambiente Tumoral/fisiologia , Adulto Jovem
2.
Health Promot Pract ; 18(6): 854-861, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-27872273

RESUMO

Providing access to nutritious foods is crucial for low-income populations, but increasing nutrition-related skills and attitudes such as food preparation, feeding practices, and positive perceptions around healthy foods to establish sustainable behavior change are paramount for the development of healthy lifestyles. This qualitative study was designed to evaluate the What's Cooking pilot program. A total of 15 participants were recruited from two Head Start schools through flyers, text messages, and e-mails. Two focus group sessions were audiotaped to obtain information related to the program implementation and perceived outcomes and behavior change. Recordings of the sessions were transcribed and analyzed using constant comparative analysis. Resulting themes included children's asking behavior for healthy foods, family connection, parent comfort in cooking, and development of child attitude, knowledge, and skills. The qualitative analysis provided foundational information for the development of a framework for other nutrition program providers to understand the role of the child in a cooking class as a mediator for lifestyle change. The What's Cooking program increased the implementation of sustainable food practices and healthy nutrition behaviors through educating families on how to involve their children in positive mealtime practices.


Assuntos
Culinária , Dieta , Educação em Saúde/organização & administração , Pobreza , Instituições Acadêmicas/organização & administração , Relações Familiares , Conhecimentos, Atitudes e Prática em Saúde , Estilo de Vida Saudável , Humanos
3.
Crit Care ; 15(4): R195, 2011 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-21834973

RESUMO

INTRODUCTION: Activated protein C (APC) induces release of microparticles (MP) from primary physiological cells, which are found in patients undergoing treatment with recombinant human APC (rhAPC) for severe sepsis. We hypothesised that APC on these circulating MPs activate endothelial protease-activated receptor 1 (PAR1) to induce anti-apoptotic and anti-inflammatory properties that can improve patient outcome. METHODS: This was an experimental study on clinical samples in an intensive care setting, and included patients with severe sepsis who fulfilled criteria for treatment with rhAPC. The number of CD13+ MPs from the patients were analysed to determine their origin. They were also quantified for endothelial protein C receptor (EPCR) and APC expression. Clinical relevance of these MPs were ascertained by comparing survival between the group receiving rhAPC (n = 25) and a control group of untreated patients (n = 25). MPs were also incubated with endothelial cells to analyse apoptotic gene expression, cytoprotection and anti-inflammatory effects. RESULTS: rhAPC treatment induced a significant increase in circulating MP-associated EPCR by flow cytometry (P < 0.05) and by quantitative ELISA (P < 0.005). APC expression also showed significant increases (P < 0.05). Numerically, CD13+ MPs were higher in rhAPC-treated survivors versus non-survivors. However, the number of non-survivors was low and this was not significantly different. APC on MPs was demonstrated to induce anti-apoptotic and endothelial barrier effects through the activation of endothelial PAR1. CONCLUSIONS: rhAPC treatment in patients with sepsis significantly increases circulating EPCR + MPs. These MPs were noted to express APC, which has specific anti-apoptotic and anti-inflammatory effects, with a non-significant correlative trend towards survival. This suggests that MPs could disseminate APC function and activate endothelial PAR1 at distal vascular sites.


Assuntos
Anti-Infecciosos/uso terapêutico , Fatores de Coagulação Sanguínea/farmacologia , Micropartículas Derivadas de Células/metabolismo , Proteína C/uso terapêutico , Sepse/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Apoptose , Fatores de Coagulação Sanguínea/uso terapêutico , Micropartículas Derivadas de Células/efeitos dos fármacos , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Sepse/fisiopatologia , Índice de Gravidade de Doença , Análise de Sobrevida
4.
Cancers (Basel) ; 13(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670906

RESUMO

Obesity is correlated with increased incidence of breast cancer metastasis; however, the mechanisms underlying how obesity promotes metastasis are unclear. In a diet-induced obese mouse model, obesity enhanced lung metastasis in both the presence and absence of primary mammary tumors and increased recruitment of myeloid lineage cells into the lungs. In the absence of tumors, obese mice demonstrated increased numbers of myeloid lineage cells and elevated collagen fibers within the lung stroma, reminiscent of premetastatic niches formed by primary tumors. Lung stromal cells isolated from obese tumor-naïve mice showed increased proliferation, contractility, and expression of extracellular matrix, inflammatory markers and transforming growth factor beta-1 (TGFß1). Conditioned media from lung stromal cells from obese mice promoted myeloid lineage cell migration in vitro in response to colony-stimulating factor 2 (CSF2) expression and enhanced invasion of tumor cells. Together, these results suggest that prior to tumor formation, obesity alters the lung microenvironment, creating niches conducive to metastatic growth.

5.
NASN Sch Nurse ; 35(5): 250-253, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32356491

RESUMO

Intellectual disability may affect the access school children have to curriculum and social experiences. While these children often have difficulty with social relationships, academic functioning, and communication, they also may experience pain on a daily basis. Communication difficulties present challenges for school nurses to identify and assess pain in students with intellectual disability. Although considered a gold standard for pain assessment, self-report cannot always be used for students with intellectual disability. School nurses must find methods other than self-reports of pain intensity to adequately assess these children's pain, such as collaborating with the student's caregiver(s), observing the student in the classroom, or assuming pain is present and offering an appropriate pain management intervention.


Assuntos
Deficiência Intelectual , Serviços de Enfermagem Escolar , Cuidadores , Criança , Humanos , Deficiência Intelectual/diagnóstico , Medição da Dor , Estudantes
6.
Cancers (Basel) ; 12(8)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731354

RESUMO

Obesity is correlated with breast tumor desmoplasia, leading to diminished chemotherapy response and disease-free survival. Obesity causes chronic, macrophage-driven inflammation within breast tissue, initiated by chemokine ligand 2 (CCL2) signaling from adipose stromal cells. To understand how CCL2-induced inflammation alters breast tumor pathology, we transplanted oncogenically transformed human breast epithelial cells with breast stromal cells expressing CCL2 or empty vector into murine mammary glands and examined tumor formation and progression with time. As tumors developed, macrophages were rapidly recruited, followed by the emergence of cancer-associated fibroblasts (CAFs) and collagen deposition. Depletion of CD11b + myeloid lineage cells early in tumor formation reduced tumor growth, CAF numbers, and collagen deposition. CCL2 expression within developing tumors also enhanced recruitment of myeloid progenitor cells from the bone marrow into the tumor site. The myeloid progenitor cell population contained elevated numbers of fibrocytes, which exhibited platelet-derived growth factor receptor-alpha (PDGFRα)-dependent colony formation and growth in vitro. Together, these results suggest that chronic inflammation induced by CCL2 significantly enhances tumor growth and promotes the formation of a desmoplastic stroma through early recruitment of macrophages and fibrocytes into the tumor microenvironment. Fibrocytes may be a novel target in the tumor microenvironment to reduce tumor fibrosis and enhance treatment responses for obese breast cancer patients.

7.
Cancer Res ; 80(20): 4465-4475, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32868380

RESUMO

Obesity enhances breast cancer risk in postmenopausal women and premenopausal women with genetic or familial risk factors. We have shown previously that within breast tissue, obesity increases macrophage-driven inflammation and promotes expansion of luminal epithelial cell populations that are hypothesized to be the cells of origin for the most common subtypes of breast cancer. However, it is not clear how these changes within the microenvironment of the breast alter cancer risk and tumor growth. Using a high-fat diet to induce obesity, we examined preneoplastic changes associated with epithelial cell-specific loss of Trp53. Obesity significantly enhanced the incidence of tumors of diverse histotypes and increased stromal cells within the tumor microenvironment. Obesity also promoted the growth of preneoplastic lesions containing elevated numbers of luminal epithelial progenitor cells, which were surrounded by macrophages. To understand how macrophage-driven inflammation due to obesity enhances tumor formation, mice were treated with IgG or anti-F4/80 antibodies to deplete macrophages during preneoplastic growth. Unexpectedly, depletion of macrophages in obese mice enhanced mammary epithelial cell stem/progenitor activity, elevated expression of estrogen receptor alpha, and increased DNA damage in cells. Together, these results suggest that in obesity, macrophages reduce epithelial cells with DNA damage, which may limit the progression of preneoplastic breast lesions, and uncovers complex macrophage function within the evolving tumor microenvironment. Understanding how obesity alters the function of macrophages during tumor formation may lead to chemoprevention options for at-risk obese women. SIGNIFICANCE: Understanding how obesity impacts early tumor growth and response to macrophage-targeted therapies may improve therapeutics for obese patients with breast cancer and identify patient populations that would benefit from macrophage-targeted therapies.


Assuntos
Macrófagos/patologia , Glândulas Mamárias Animais/patologia , Obesidade/patologia , Células-Tronco/patologia , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Dano ao DNA , Dieta Hiperlipídica/efeitos adversos , Células Epiteliais/patologia , Células Epiteliais/transplante , Feminino , Glândulas Mamárias Animais/citologia , Camundongos Endogâmicos , Camundongos Mutantes , Obesidade/etiologia , Lesões Pré-Cancerosas , Células Estromais/patologia , Proteína Supressora de Tumor p53/genética
8.
J Nutr Educ Behav ; 39(1): 2-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17276320

RESUMO

OBJECTIVE: To determine the reliability and validity of a questionnaire measuring fruit and vegetable (FV) self-efficacy and social norms during school lunch among 5th graders. DESIGN: In this cross-sectional study, students completed lunch food records and a psychosocial questionnaire measuring school lunch FV self-efficacy and social norms regarding consumption during the fall and spring semesters. Test-retest reliability was assessed between fall and spring semesters. The measurement model was cross-validated in the spring data. SETTING: One middle school in Houston, Texas. PARTICIPANTS: 275 fifth graders in the 1998 fall semester and 262 of these fifth graders in the 1999 spring semester. MAIN OUTCOME MEASURES: FV consumption and psychosocial variables. ANALYSES: Principal components analyses, confirmatory factor analyses and bivariate correlations. RESULTS: Three scales were identified: Fruit Self-Efficacy, Vegetable Self-Efficacy, and FV Social Norms. FV self-efficacy were positively correlated with low-fat vegetable and fruit consumption. Social norms were positively correlated with total vegetable, low-fat vegetable, fruit and total FV consumption. CONCLUSIONS AND IMPLICATIONS: Self-efficacy and norms for eating FV at school lunch are related to lunch FV consumption. Increasing self-efficacy and social norms about consuming FV at school appears to be important targets to improve FV consumption.


Assuntos
Frutas , Autoeficácia , Inquéritos e Questionários/normas , Verduras , Criança , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Análise de Componente Principal , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Exp Neurol ; 277: 96-102, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26708558

RESUMO

Complex regional pain syndrome (CRPS) is thought to have an auto-immune component. One such target recently proposed from the effects of auto-immune IgGs on Ca(2+) transients in cardiac myocytes and cell lines is the α1-adrenoceptor. We have tested whether such IgGs exerted comparable effects on nociceptive sensory neurons isolated from rat dorsal root ganglia. Depolarisation-induced [Ca(2+)]i transients were generated by applying 30 mM KCl for 2 min and monitored by Fura-2 fluorescence imaging. No IgGs tested (including 3 from CRPS patients) had any significant effect on these [Ca(2+)]i transients. However, IgG from one CRPS patient consistently and significantly reduced the K(+)-induced response of cells that had been pre-incubated for 24h with a mixture of inflammatory mediators (1 µM histamine, 5-hydroxytryptamine, bradykinin and PGE2). Since this pre-incubation also appeared to induce a comparable inhibitory response to the α1-agonist phenylephrine, this is compatible with the α1-adrenoceptor as a target for CRPS auto-immunity. A mechanism whereby this might enhance pain is suggested.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Síndromes da Dor Regional Complexa/sangue , Síndromes da Dor Regional Complexa/imunologia , Gânglios Espinais/citologia , Imunoglobulina G/farmacologia , Neurônios/efeitos dos fármacos , Análise de Variância , Animais , Animais Recém-Nascidos , Células Cultivadas , Feminino , Humanos , Masculino , Potássio/farmacologia , Ratos , Ratos Sprague-Dawley
10.
Nurs Times ; 101(18): 46-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15892505

RESUMO

Incontinence is defined as any loss of urine or faeces that is involuntary (Abrahams et al, 2002). It can affect anyone at any age. The prevalence of incontinence increases with age, and in women it is often associated with childbearing and the menopause. Incontinence can have devastating effects on an individual's life (Laycock et al, 2001), with both emotional and financial costs (Paddison, 2002). In the UK, conservative estimates suggest that 424 million pounds per year is spent on urinary incontinence alone (Continence Foundation, 2000).


Assuntos
Procedimentos Clínicos/organização & administração , Incontinência Fecal/enfermagem , Avaliação em Enfermagem/organização & administração , Incontinência Urinária/enfermagem , Doença Aguda , Algoritmos , Benchmarking/organização & administração , Efeitos Psicossociais da Doença , Árvores de Decisões , Documentação , Incontinência Fecal/diagnóstico , Incontinência Fecal/epidemiologia , Controle de Formulários e Registros , Humanos , Disseminação de Informação , Auditoria de Enfermagem , Pesquisa em Avaliação de Enfermagem , Registros de Enfermagem , Educação de Pacientes como Assunto , Projetos Piloto , Fatores de Risco , Reino Unido/epidemiologia , Incontinência Urinária/diagnóstico , Incontinência Urinária/epidemiologia
11.
Nutr Rev ; 62(4): 132-41, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15141428

RESUMO

Epidemiologic evidence suggests that dietary monounsaturated fatty acids (MUFA) may have a beneficial health effect. Twenty-four-hour dietary intake data collected on 10-year-olds from 1978 to 1994 and on children and adults (ages 0-30 years) were examined for time, age, gender, ethnic, and geographic location differences in MUFA intake. Children's percent energy from MUFA decreased significantly from 1978 (14.1%) to 1994 (11.9%) with intake of oleic acid decreasing from 33.9 g/day (1973) to 25.7 g/day (1994). In 1994-96, percent energy from MUFA was 13% for children and adults aged 12 to 30 years, with 5% from palmitoleic acid and 93% from oleic acid. Males and blacks had significantly higher MUFA intake across all age groups than females and whites. Intakes of MUFA increased from 0 to 11 years of age to young adulthood (12-19 years), with no further increase at 20 to 30 years of age. Intakes of MUFA were lowest in the Northeast and highest in the Midwest. There were differences in food sources of MUFA by age group. For children 0 to 5 years of age, major sources were whole milk, peanut butter, 2% milk, and French fries; for children 6 to 11 years of age, major sources were whole milk, peanut butter, French fries, and 2% milk; for children 12 to 19 years of age, French fries, salt snacks, whole milk, and meat pizza were the major sources; for adults, French fries, whole milk, potato chips, and ground beef were the most common sources of MUFA. U.S. children and adults displayed temporal trends and demographic differences in intakes and food sources of MUFA. The implications of these changes and differences on biologic risk factors for specific chronic diseases warrant further investigation.


Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Adolescente , Adulto , Fatores Etários , População Negra , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Inquéritos Nutricionais , Fatores Sexuais , Estados Unidos , População Branca
12.
J Nutr Educ Behav ; 35(3): 115-23, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12773282

RESUMO

OBJECTIVE: To understand diet, physical activity, and inactivity influences among preadolescent African American girls at risk of becoming obese. DESIGN: Interviews and group qualitative discussions (i.e., mixed qualitative research method) were conducted separately with 8- to 10-year-old African American girls and their parents. SETTING: Greater Houston, Texas. PARTICIPANTS: Eight- to 10-year-old African American girls above the 50th percentile body mass index with a home computer (n = 82) and a parent (n = 74). VARIABLES MEASURED: Influences on dietary practices and physical activity/inactivity among preadolescent African American girls. ANALYSIS: Discussions were audiotaped, manually recorded, transcribed, and coded. The primary coder analyzed the transcribed notes. The secondary coder reviewed and critiqued the initial coding. RESULTS: Parents and girls were concerned about overweight and viewed physical activity as a weight control practice. Mothers facilitated daughters' physical activity, while fathers and siblings were coparticipants. Girls had access to physical activity equipment and facilities. Snack food items and carbonated beverages were often limited by the parents, and water consumption was encouraged. Discrepancies were apparent between girls' and parents' responses. CONCLUSIONS AND IMPLICATIONS: Parental convenience and girls' food preferences influenced dietary intake. Obesity prevention programs should capitalize on parental motivation for their child's health and provide practical strategies to facilitate healthful eating and physical activity.


Assuntos
Negro ou Afro-Americano , Dieta , Exercício Físico/fisiologia , Obesidade/etiologia , Índice de Massa Corporal , Criança , Comportamento Alimentar/etnologia , Feminino , Grupos Focais , Preferências Alimentares/etnologia , Humanos , Obesidade/etnologia , Obesidade/prevenção & controle , Pais
13.
Diaeta (B. Aires) ; 37(169): 18-26, oct.-dic. 2019.
Artigo em Espanhol | BINACIS, UNISALUD, LILACS | ID: biblio-1100616

RESUMO

Introducción: la población argentina exhibe una elevada prevalencia de enfermedad celíaca (1/100) y la alimentación es su único tratamiento, por ende, el costo de la dieta es un factor clave para la adherencia. Objetivos: calcular el costo diferencial de la dieta de una mujer adulta celíaca vs. no celíaca basado en la Canasta Básica de Alimentos (CBA) y en el patrón alimentario propuesto por las Guías Alimentarias para la Población Argentina (GAPA). Estimar la proporción que representa en base al Salario Mínimo Vital y Móvil (SMVM) en ambos casos. Materiales y método: se tomaron alimentos trazadores extraídos de la plataforma digital de un hipermercado durante el mes de septiembre y diciembre del 2018 para realizar los cálculos de costo de la dieta, considerando los alimentos de más bajo precio. Resultados: el costo de la alimentación propuesta por las GAPA arrojó una diferencia de un 55,27% superior para la población celíaca (+ $1410,08) para septiembre y de un 48,60% (+ $1537,63) para el mes de diciembre. El costo mensual representó un incremento de 13,18% del SMVM para septiembre y de 13,61% para diciembre para la población celíaca. Tomando la CBA, el costo diferencial de la dieta mensual fue mayor (89,27% más cara, equivalente a 1182,76 pesos más) para el mes de septiembre, y 46,81% que equivalen a $886,10 para diciembre. Representó un incremento de 11,06% del SMVM para septiembre y de 7,84% para diciembre. Conclusiones: la alimentación para una mujer adulta celíaca representa un costo mayor que para una mujer adulta no celíaca en la CABA. Este es uno de los factores que contribuye a la no adherencia al tratamiento de la enfermedad, siendo la alimentación la única estrategia para tratarla(AU).


Introduction: Argentinian population exhibits a high prevalence of celiac disease (1/100) and feeding is the only treatment; therefore, the cost of diet is a key factor for adherence. Objectives: to calculate the differential cost of the diet of an adult celiac woman vs. non-celiac one, based on the Basic Food Basket (BFB) and on the dietary pattern proposed by the Dietary Guidelines for the Argentine Population (GAPA). Estimate the proportion that represents based on the Minimum Living Wage (MLW) in both cases. Materials and method: tracers extracted from the digital platform of an hypermarket were taken during September and December 2018 to calculate the cost of the diet, considering the lowest-priced foods. Results: the cost of food proposed by GAPA showed a difference of 55.27% higher for the celiac population ($ 1410.08 more) in September and of 48.60% ($ 1537.63 more) in December. The monthly cost represented an increase of 13.18% for the MLW in September and 13.61% in December for the celiac population. Taking the BFB, the differential cost of the monthly diet was higher (89.27% more expensive, equivalent to 1182.76 pesos more) in September, and 46.81%, equivalent to $ 886.10, in December. It represented an increase of 11.06% for the MLW in September and of 7.84% in December. Conclusions: the food for a celiac adult woman is higher than for a nonceliac adult woman in CABA. This is one of the factors that contributes to non-adherence to the treatment of the disease; food being the only strategy to treat it(AU).


Assuntos
Doença Celíaca , Custos e Análise de Custo , Alimentos
14.
Pain ; 155(2): 299-308, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24145209

RESUMO

The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS.


Assuntos
Síndromes da Dor Regional Complexa/induzido quimicamente , Síndromes da Dor Regional Complexa/patologia , Modelos Animais de Doenças , Hiperalgesia/induzido quimicamente , Hiperalgesia/patologia , Imunoglobulina G/toxicidade , Adulto , Animais , Autoanticorpos/biossíntese , Autoanticorpos/sangue , Síndromes da Dor Regional Complexa/sangue , Feminino , Humanos , Hiperalgesia/sangue , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Medição da Dor/métodos , Projetos Piloto
15.
Pain ; 155(11): 2408-17, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25250722

RESUMO

Complex regional pain syndrome (CRPS) is a limb-confined posttraumatic pain syndrome with sympathetic features. The cause is unknown, but the results of a randomized crossover trial on low-dose intravenous immunoglobulins (IVIG) treatment point to a possible autoimmune mechanism. We tested purified serum immunoglobulin G (IgG) from patients with longstanding CRPS for evidence of antibodies interacting with autonomic receptors on adult primary cardiomyocytes, comparing with control IgG from healthy and diseased controls, and related the results to the clinical response to treatment with low-dose IVIG. We simultaneously recorded both single-cell contractions and intracellular calcium handling in an electrical field. Ten of 18 CRPS preparations and only 1/57 control preparations (P<0.0001) increased the sensitivity of the myocytes to the electric field, and this effect was abrogated by preincubation with α-1a receptor blockers. By contrast, effects on baseline calcium were blocked by preincubation with atropine. Interestingly, serum-IgG preparations from all 4 CRPS patients who had responded to low-dose IVIG with meaningful pain relief were effective in these assays, although 4/8 of the nonresponders were also active. To see if there were antibodies to the α-1a receptor, CRPS-IgG was applied to α-1a receptor-transfected rat-1 fibroblast cells. The CRPS serum IgG induced calcium flux, and fluorescence-activated cell sorting showed that there was serum IgG binding to the cells. The results suggest that patients with longstanding CRPS have serum antibodies to α-1a receptors, and that measurement of these antibodies may be useful in the diagnosis and management of the patients.


Assuntos
Autoanticorpos/sangue , Síndromes da Dor Regional Complexa/sangue , Síndromes da Dor Regional Complexa/imunologia , Receptores Adrenérgicos alfa 1/imunologia , Adulto , Animais , Atropina/farmacologia , Cálcio/metabolismo , Células Cultivadas , Síndromes da Dor Regional Complexa/terapia , Estudos Cross-Over , Dioxanos/farmacologia , Feminino , Humanos , Imunoglobulina G/farmacologia , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Potenciais da Membrana/efeitos dos fármacos , Pessoa de Meia-Idade , Antagonistas Muscarínicos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Técnicas de Patch-Clamp , Ligação Proteica/efeitos dos fármacos , Ratos , Transfecção , Adulto Jovem
16.
Mol Cancer Res ; 11(5): 541-54, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23505068

RESUMO

B-cell receptor (BCR) signals promote survival of chronic lymphocytic leukemia (CLL) cells, and it is believed that overexpressed and constitutively active Lyn mediates this signaling. Here, we show that CLL cells express lymphocyte-specific protein tyrosine kinase (LCK) and that inhibition of this Src family tyrosine kinase with the specific inhibitor [4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[3,2-d]pyrimidin-7-yl-cyclopentane (Lck-i)], or reduction of its expression with siRNA, blocks the induction of CD79a, Syk, inhibitor of IκB kinase (IKK), Akt, and extracellular signal-regulated kinase (ERK) phosphorylation by BCR cross-linking in these cells. Furthermore, we show that CLL cells with high levels of LCK expression have higher levels of BCR-mediated IKK, Akt, and ERK phosphorylation as well as cell survival than CLL cells with low levels of LCK expression. We also show that treatment of CLL cells with Lck-i inhibits BCR cross-linking-induced cell survival. Taken together, these data show a major role for LCK in proximal and distal BCR-mediated signaling in CLL cells and suggest that LCK expression is important in the pathogenesis of this disease. On a clinical level, these studies advocate the use of specific LCK inhibitors in the treatment of progressive CLL.


Assuntos
Leucemia Linfocítica Crônica de Células B/enzimologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/imunologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/imunologia , Transdução de Sinais , Transfecção
17.
PLoS One ; 6(10): e26106, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22022527

RESUMO

Osteosarcoma is an aggressive malignancy of the bone and an increase in serum alkaline phosphatase concentration has clinical prognostic value in both humans and canines. Increased serum alkaline phosphatase concentration at the time of diagnosis has been associated with poorer outcomes for osteosarcoma patients. The biology underlying this negative prognostic factor is poorly understood. Given that activation of the Wnt signaling pathway has been associated with alkaline phosphatase expression in osteoblasts, we hypothesized that the Wnt/ß-catenin signaling pathway would be differentially activated in osteosarcoma tissue based on serum ALP status. Archived canine osteosarcoma samples and primary canine osteosarcoma cell lines were used to evaluate the status of Wnt/ß-catenin signaling pathway activity through immunohistochemical staining, western immunoblot analyses, quantitative reverse-transcription polymerase chain reaction, and a Wnt-responsive promoter activity assay. We found no significant difference in ß-catenin expression or activation between OSA populations differing in serum ALP concentration. Pathway activity was mildly increased in the primary OSA cell line generated from a patient with increased serum ALP compared to the normal serum ALP OSA cell line. Further investigation into the mechanisms underlying differences in serum ALP concentration is necessary to improve our understanding of the biological implications of this negative prognostic indicator.


Assuntos
Fosfatase Alcalina/sangue , Doenças do Cão/sangue , Doenças do Cão/enzimologia , Osteossarcoma/veterinária , Via de Sinalização Wnt , beta Catenina/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Doenças do Cão/genética , Cães , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Imuno-Histoquímica , Luciferases/metabolismo , Osteossarcoma/sangue , Osteossarcoma/enzimologia , Osteossarcoma/genética , Transporte Proteico , Extratos de Tecidos , Via de Sinalização Wnt/genética , beta Catenina/genética
18.
Simul Gaming ; 41(4): 587-606, 2010 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-20711522

RESUMO

Serious video games for health are designed to entertain players while attempting to modify some aspect of their health behavior. Behavior is a complex process influenced by multiple factors, often making it difficult to change. Behavioral science provides insight into factors that influence specific actions that can be used to guide key game design decisions. This article reports how behavioral science guided the design of a serious video game to prevent Type 2 diabetes and obesity among youth, two health problems increasing in prevalence. It demonstrates how video game designers and behavioral scientists can combine their unique talents to create a highly focused serious video game that entertains while promoting behavior change.

19.
Public Health Nutr ; 11(4): 421-6, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17666158

RESUMO

OBJECTIVE: To determine the reliability and validity of scales measuring low-fat milk consumption self-efficacy and norms during school lunch among a cohort of 5th graders. DESIGN: Two hundred and seventy-five students completed lunch food records and a psychosocial questionnaire measuring self-efficacy and norms for school lunch low-fat milk consumption during the fall and spring semesters of the 1998-1999 academic year. Test-retest reliability was assessed in participants who also completed the questionnaire in the spring semester (n = 262). Principal component analyses identified and confirmatory factor analyses confirmed latent variables. Bivariate correlations measured construct validity. SETTING: Houston-area middle school. SUBJECTS: Fifth graders (n = 275) from one middle school in southeast Texas. RESULTS: Two scales measuring psychosocial influences of low-fat milk consumption were identified and proved reliable in this population: milk self-efficacy and milk norms. Milk self-efficacy and norms were positively correlated with milk consumption and negatively correlated with consumption of sweetened beverages. CONCLUSIONS: These questionnaires can be used in similar interventions to measure the impact of self-efficacy and norms for drinking low-fat milk during school lunch.


Assuntos
Serviços de Alimentação/estatística & dados numéricos , Leite , Autoeficácia , Inquéritos e Questionários/normas , Animais , Bovinos , Criança , Estudos de Coortes , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Análise de Componente Principal , Psicometria , Reprodutibilidade dos Testes , Instituições Acadêmicas , Sensibilidade e Especificidade , Texas
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