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2.
Neuroimage Clin ; 27: 102240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32361633

RESUMO

We present a Human Connectome Project study tailored toward adolescent anxiety and depression. This study is one of the first studies of the Connectomes Related to Human Diseases initiative and is collecting structural, functional, and diffusion-weighted brain imaging data from up to 225 adolescents (ages 14-17 years), 150 of whom are expected to have a current diagnosis of an anxiety and/or depressive disorder. Comprehensive clinical and neuropsychological evaluations and longitudinal clinical data are also being collected. This article provides an overview of task functional magnetic resonance imaging (fMRI) protocols and preliminary findings (N = 140), as well as clinical and neuropsychological characterization of adolescents. Data collection is ongoing for an additional 85 adolescents, most of whom are expected to have a diagnosis of an anxiety and/or depressive disorder. Data from the first 140 adolescents are projected for public release through the National Institutes of Health Data Archive (NDA) with the timing of this manuscript. All other data will be made publicly-available through the NDA at regularly scheduled intervals. This article is intended to serve as an introduction to this project as well as a reference for those seeking to clinical, neurocognitive, and task fMRI data from this public resource.


Assuntos
Transtornos de Ansiedade/diagnóstico por imagem , Ansiedade/diagnóstico por imagem , Encéfalo/fisiopatologia , Depressão/diagnóstico por imagem , Neuroimagem , Adolescente , Transtornos de Ansiedade/fisiopatologia , Boston , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Conectoma/métodos , Depressão/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodos
3.
Phys Rev Lett ; 121(14): 142701, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30339438

RESUMO

The ^{12}C(α,γ)^{16}O reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced α width, γ_{11}, of the bound 1^{-} level in ^{16}O is particularly important to determine the cross section. The magnitude of γ_{11} is determined via sub-Coulomb α-transfer reactions or the ß-delayed α decay of ^{16}N, but the latter approach is presently hampered by the lack of sufficiently precise data on the ß-decay branching ratios. Here we report improved branching ratios for the bound 1^{-} level [b_{ß,11}=(5.02±0.10)×10^{-2}] and for ß-delayed α emission [b_{ßα}=(1.59±0.06)×10^{-5}]. Our value for b_{ßα} is 33% larger than previously held, leading to a substantial increase in γ_{11}. Our revised value for γ_{11} is in good agreement with the value obtained in α-transfer studies and the weighted average of the two gives a robust and precise determination of γ_{11}, which provides significantly improved constraints on the ^{12}C(α,γ) cross section in the energy range relevant to hydrostatic He burning.

4.
Phys Rev Lett ; 115(5): 052701, 2015 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-26274414

RESUMO

The production of 26Al in massive stars is sensitive to the 23Na(α,p)26Mg cross section. Recent experimental data suggest the currently recommended cross sections are underestimated by a factor of ∼40. We present here differential cross sections for the 23Na(α,p)26Mg reaction measured in the energy range E(c.m.)=1.7-2.5 MeV. Concurrent measurements of Rutherford scattering provide absolute normalizations that are independent of variations in target properties. Angular distributions are measured for both p0 and p1 permitting the determination of total cross sections. The results show no significant deviation from the statistical model calculations upon which the recommended rates are based. We therefore retain the previous recommendation without the increase in cross section and resulting stellar reaction rates by a factor of 40, impacting the 26Al yield from massive stars by more than a factor of 3.

5.
Surg Endosc ; 21(4): 625-8, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17364152

RESUMO

BACKGROUND: Endoscopic endoluminal radiofrequency ablation using the Barrx device is a new technique to treat Barrett's esophagus. This procedure has been used in patients who have not had antireflux surgery. This report is presents an early experience of the effects of endoluminal ablation on the reflux symptoms and completeness of ablation in post-fundoplication patients. METHODS: Seven patients who have had either a laparoscopic or open Nissen fundoplication and Barrett's esophagus underwent endoscopic endoluminal ablation of the Barrett's metaplasia using the Barrx device (Barrx Medical, Sunnyvale, CA). Preprocedure, none of the patients had significant symptoms related to gastroesophageal reflux disease. One to two weeks after the ablation, patients were questioned as to the presence of symptoms. Preprocedure and postprocedure, they completed the GERD-HRQL symptom severity questionnaire (best possible score, 0; worst possible score, 50). Patients had follow-up endoscopy to assess completeness of ablation 3 months after the original treatment. RESULTS: All patients completed the ablation without complications. No patients reported recurrence of their GERD symptoms. The median preprocedure total GERD-HRQL score was 2, compared to a median postprocedure score of 1. One patient had residual Barrett's metaplasia at 3 months follow-up, requiring re-ablation. CONCLUSIONS: This preliminary report of a small number of patients demonstrates that endoscopic endoluminal ablation of Barrett's metaplasia using the Barrx device is safe and effective in patients who have already undergone antireflux surgery. There appears to be no disruption in the fundoplication or recurrence of GERD-related symptoms. Nevertheless, longer-term follow-up with more patients is needed.


Assuntos
Esôfago de Barrett/cirurgia , Ablação por Cateter/métodos , Fundoplicatura/métodos , Refluxo Gastroesofágico/cirurgia , Adulto , Idoso , Esôfago de Barrett/complicações , Esôfago de Barrett/diagnóstico , Biópsia por Agulha , Ablação por Cateter/efeitos adversos , Terapia Combinada , Endoscopia/métodos , Esofagoscopia/métodos , Feminino , Seguimentos , Fundoplicatura/efeitos adversos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/mortalidade , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Probabilidade , Medição de Risco , Estudos de Amostragem , Estatísticas não Paramétricas , Resultado do Tratamento
6.
Int J Obes (Lond) ; 30(9): 1347-55, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16534530

RESUMO

BACKGROUND: Chemotactic cytokines, referred to as chemokines, play an important role in leukocyte trafficking. The circulating levels of chemokines have been shown to increase in inflammatory processes including obesity-related pathologies (e.g. atherosclerosis and diabetes). However, little is currently known about the relationship between chemokines and human obesity. In the present study, we investigated the circulating levels of selected chemokines (monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), leukotactin-1, interleukin-8 (IL-8)) and the association between the chemokine levels and obesity-related parameters: body mass index (BMI), waist circumference, fasting glucose and insulin levels, lipids profile, and the level of C-reactive protein (CRP). METHODS: A total of 100 subjects, 50 obese (BMI>or=25 kg/m2) and 50 who were not obese (BMI<25 kg/m2) participated in the present study. The levels of chemokines and CRP were measured in a fasting state serum by sandwich enzyme-linked immunosorbent assay. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, glucose, and insulin levels were measured by enzymatic analysis and immunoassay. RESULTS: The circulating levels of MCP-1 and IL-8 in the serum were significantly (P<0.05) higher in obese subjects (BMI>30 kg/m2) compared with those of nonobese controls (BMI<25 kg/m2). The levels of CRP were positively correlated with BMI (P<0.001) or waist circumference (P<0.0001). The levels of MCP-1 and IL-8 were positively related to BMI (MCP-1, P<0.02; IL-8, P<0.01) and/or waist circumference (MCP-1, P<0.009; IL-8, P<0.03). The levels of MCP-1 were positively related to the levels of CRP (P<0.007) or interleukin-6 (IL-6) (P<0.0001), and negatively related to the levels of HDL-cholesterol (P<0.01). Homeostasis model assessment (HOMA) score was positively related to the levels of MCP-1 (P<0.02) or IL-8 (P<0.03) in obese subject. DISCUSSION: Our data demonstrated that the circulating levels of MCP-1 and IL-8 are related to obesity-related parameters such as BMI, waist circumference, CRP, IL-6, HOMA and HDL-cholesterol. These findings suggest that the circulating MCP-1 and/or IL-8 may be a potential candidate linking obesity with obesity-related metabolic complications such as atherosclerosis and diabetes.


Assuntos
Quimiocina CCL2/sangue , Interleucina-8/sangue , Obesidade/sangue , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , HDL-Colesterol/sangue , Feminino , Humanos , Masculino , Relação Cintura-Quadril
7.
Artigo em Inglês | MEDLINE | ID: mdl-11728162

RESUMO

We have previously shown that dietary (n-3) fatty acids decrease mammary tumor vascularization and PGE(2) production. One possible mechanism may be the modulation of vascular endothelial growth factor (VEGF) production by PGE(2). Macrophages are major producers of VEGF, and thus we assessed the role of PGE(2) in vitro and in vivo on their VEGF production. When added to macrophages, pharmacological (10(-7) M) but not physiological (10(-9) to 10(-11) M) concentrations of PGE(2) increased VEGF mRNA and protein levels. That increased expression was relatively rapid and sustained up to 8 hrs, but declined by 24 hrs. Similarly, dibutryl cAMP increased production of VEGF protein which was completely inhibited by H89. Addition of cAMP-elevating agents further potentiated the production of VEGF by PGE(2). Next, (n-3) and (n-6) fatty acids were added to macrophages in vitro or provided in the diet. Macrophages of mice fed safflower oil (n-6) had 2- to 4-fold greater copy number of VEGF transcripts after lipopolysaccarhide (LPS) stimulation compared to fish oil (n-3). A decreasing trend was seen in LPS-induced VEGF secretion from macrophages in vitro after docosahexaenoic acid or eicosapentaenoic acid incubation compared to arachidonic acid. While pharmacological concentrations of PGE(2) modulate VEGF expression, physiological alterations did not alter VEGF protein production by macrophages.


Assuntos
Dinoprostona/farmacologia , Fatores de Crescimento Endotelial/biossíntese , Linfocinas/biossíntese , Macrófagos/metabolismo , Sulfonamidas , Ativação Transcricional , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Células Cultivadas , AMP Cíclico/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Relação Dose-Resposta a Droga , Fatores de Crescimento Endotelial/genética , Inibidores Enzimáticos/farmacologia , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6 , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/farmacologia , Feminino , Isoquinolinas/farmacologia , Cinética , Linfocinas/genética , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Inibidores de Fosfodiesterase/farmacologia , RNA Mensageiro/biossíntese , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
8.
Artigo em Inglês | MEDLINE | ID: mdl-11993722

RESUMO

Assessing the regulation of macrophage receptors for prostaglandin (PGE2) is essential to understanding the control which that potent lipid mediator has in modulating macrophage activities. The purpose of this study was to assess the differential mRNA expression of PGE2 receptor subtypes (EP) during macrophage exposure to activating and transducing agents. RAW 264.7 macrophages constitutively expressed mRNA for EP2,EP3 and EP4 receptor subtypes. Messenger RNA for EP4 was expressed at a much higher level when compared to EP2 in unstimulated macrophages as assessed by kinetic quantitative RT-PCR. When macrophages were stimulated with LPS, EP2 m RNA levels were 12-fold higher when compared to unstimulated macrophages, while EP4 m RNA remained unchanged. Conversely, mRNA levels of both EP2 and EP4 receptors were lower after macrophages were treated with IFN-gamma. Messenger RNA levels of both receptors were lower in macrophages after treatment with PGE2 or dibutyryl (db) cAMP Addition of the PKA inhibitor H89 reversed the effects of PGE2 and dbcAMP to varying degrees. Proteosome and p38 MAP kinase inhibitors blocked the LPS-stimulated increase in EP2 mRNA levels. Those inhibitors had no effect on EP4 mRNA.Thus, activating agents such as LPS and IFN-gamma may differentially regulate mRNAfor PGE2 receptor types in macrophages but the ligand and its associated signal transducing factors probably have similar regulatory effects.


Assuntos
Macrófagos/fisiologia , Receptores de Prostaglandina/genética , Sulfonamidas , Animais , Células Cultivadas , AMP Cíclico/metabolismo , Proteína Quinase Tipo II Dependente de AMP Cíclico , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dinoprostona/metabolismo , Interferon gama/farmacologia , Isoquinolinas/farmacologia , Leupeptinas/farmacologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Receptores de Prostaglandina/metabolismo , Receptores de Prostaglandina E/efeitos dos fármacos , Receptores de Prostaglandina E/genética , Receptores de Prostaglandina E/metabolismo , Receptores de Prostaglandina E Subtipo EP2 , Receptores de Prostaglandina E Subtipo EP3 , Receptores de Prostaglandina E Subtipo EP4 , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Transcrição Gênica
9.
Vis Neurosci ; 18(4): 641-56, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11829310

RESUMO

The goal of the present study was to relate the dark and light-adapted flash sensitivity of the scotopic threshold response (STR) and rod b-wave of the electroretinogram (ERG) to behaviorally measured rod increment threshold responses. Small amplitudes of the dark-adapted STR and b-wave, the latter after application of NMDA, were found to increase in proportion to flash intensity. The value obtained for the sensitivity of the b-wave would be expected if signals from rods were summed linearly by the rod bipolar cell. The sensitivity of the STR could not be accounted for in terms of rod signal convergence as the source of this ERG component is still unknown. Increment threshold responses of rats were measured behaviorally in an operant conditioning chamber. At absolute threshold, on average I in 2400 rods were activated by the test flash. Comparison of the adaptive effects of background lights on behaviorally measured scotopic sensitivity and rod ERG sensitivity suggest that the increment threshold sensitivity of rat is regulated at three different sites in the retina.


Assuntos
Adaptação Ocular/fisiologia , Comportamento Animal/fisiologia , Adaptação à Escuridão/fisiologia , Animais , Condicionamento Operante , Limiar Diferencial , Eletrorretinografia , Masculino , Modelos Biológicos , Ratos , Ratos Sprague-Dawley , Células Fotorreceptoras Retinianas Bastonetes/fisiologia
10.
J Infect Dis ; 182 Suppl 1: S5-10, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10944478

RESUMO

Micronutrients such as zinc, selenium, iron, copper, beta-carotene, vitamins A, C, and E, and folic acid can influence several components of innate immunity. Select micronutrients play an important role in alteration of oxidant-mediated tissue injury, and phagocytic cells produce reactive oxidants as part of the defense against infectious agents. Thus, adequate micronutrients are required to prevent damage of cells participating in innate immunity. Deficiencies in zinc and vitamins A and D may reduce natural killer cell function, whereas supplemental zinc or vitamin C may enhance their activity. The specific effects of micronutrients on neutrophil functions are not clear. Select micronutrients may play a role in innate immunity associated with some disease processes. Future studies should focus on issues such as age-related micronutrient status and innate immunity, alterations of micronutrients in disease states and their effect on innate immunity, and the mechanisms by which micronutrients alter innate immunity.


Assuntos
Deficiências Nutricionais/imunologia , Imunidade , Micronutrientes , Vitaminas , Humanos
11.
J Nutr ; 130(2S Suppl): 403S-409S, 2000 02.
Artigo em Inglês | MEDLINE | ID: mdl-10721915

RESUMO

Probiotics, microorganisms that have a favorable influence on physiologic and pathological processes of the host by their effect on the intestinal flora, may play a role in improving human health. One of the putative effects is the modulation of immune function. Thus, the mucosal immune system and methods to assess its function are reviewed briefly. Probiotic modulation of humoral, cellular and nonspecific immunity is reviewed, with emphasis placed on immune response in disease models. There are very few reports of human intervention studies with probiotics. However, some of the possible future directions for research with respect to probiotics, immunity, and human health are discussed. Although the application of probiotics has demonstrated trends with respect to altered aspects of immune response, the underlying mechanisms by which that occurs are unclear.


Assuntos
Sistema Imunitário/imunologia , Intestinos/imunologia , Probióticos , Animais , Modelos Animais de Doenças , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/microbiologia , Imunidade nas Mucosas/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Probióticos/farmacologia
12.
Cancer Lett ; 150(1): 93-100, 2000 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-10755392

RESUMO

Recent studies have shown that conjugated linoleic acid (CLA) can inhibit the initiation and thus, incidence of mammary tumors in rodents. The concentration of CLA required for these effects was as low as 0.1% of the diet, with no increased effects above 1%. To date, there is little evidence that CLA has any effect on growth or metastasis of mammary tumors. In this report, we demonstrate that CLA, at the concentrations used in previous studies, had a significant effect on the latency, metastasis, and pulmonary tumor burden of transplantable murine mammary tumors grown in mice fed 20% fat diets. The latency of tumors from mice fed CLA was significantly increased when compared with the 0% CLA control diet. The volume of pulmonary tumor burden, as a result of spontaneous metastasis, decreased proportionately with increasing concentrations of dietary CLA. With 0.5 and 1% CLA, pulmonary tumor burden was significantly decreased compared to mice treated with the eicosanoid inhibitor, indomethacin and fed diets containing no CLA. Tumors of mice fed as little as 0.1% CLA and as much as 1% had significantly decreased numbers of pulmonary nodules when compared with diets containing no CLA. The decrease in the number of pulmonary nodules by CLA was nearly as effective as indomethacin, a known suppressor of tumor growth and metastasis in this malignant model. These data suggest that effects of CLA on mammary tumorigenesis may go beyond the reported alterations in tumor incidence and effect later stages, especially metastasis.


Assuntos
Ácido Linoleico/farmacologia , Neoplasias Mamárias Experimentais/prevenção & controle , Metástase Neoplásica/prevenção & controle , Animais , Gorduras Insaturadas na Dieta/administração & dosagem , Gorduras Insaturadas na Dieta/farmacologia , Relação Dose-Resposta a Droga , Feminino , Ácido Linoleico/administração & dosagem , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Tempo , Células Tumorais Cultivadas
13.
Cancer Lett ; 150(1): 101-9, 2000 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-10755393

RESUMO

We have previously shown that mice fed a high (n-3) fatty acid-containing diet with 20% (w/w) total fat had significantly slower mammary tumor growth, decreased numbers of metastatic pulmonary nodules, and decreased total metastatic load. In this study we sought to determine whether tumor vascularization was altered in mice fed diets varying in concentrations of (n-3) and (n-6) fatty acids. Several direct or indirect parameters of vascularization were tested. With 20% dietary fat, fish oil (FO) or a mixture of FO and safflower oil (FS) significantly reduced blood vascular area, mast cell number and macrophage infiltration in solid mammary tumors compared to tumors grown in mice fed safflower oil (SO). A decreasing trend was seen in the percent area of vessels positive for CD31 and vascular endothelial growth factor (VEGF) in the 20% FO and 20% FS compared to the 20% SO dietary groups. VEGF concentrations were twice as high in smaller tumors (100 mm3) from all dietary groups as compared to larger tumors (500 mm3). A two-fold increase in VEGF levels was found in the 20% SO dietary group compared to the 20% FO group in 100-mm3 but not larger tumors. We conclude that at 20% total fat, the n-3 fatty acids found in fish oil may inhibit primary mammary tumor growth through modulation of select determinants of vascularization.


Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Neoplasias Mamárias Experimentais/prevenção & controle , Neovascularização Patológica/prevenção & controle , Animais , Contagem de Células/efeitos dos fármacos , Gorduras Insaturadas na Dieta/administração & dosagem , Fatores de Crescimento Endotelial/análise , Endotélio Vascular/química , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Óleos de Peixe/administração & dosagem , Óleos de Peixe/química , Imuno-Histoquímica , Linfocinas/análise , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Óleo de Cártamo/farmacologia , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
14.
Int J Obes Relat Metab Disord ; 23(8): 896-903, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10490793

RESUMO

OBJECTIVE: Our objective was to determine the effects of prolonged exposure to tumor necrosis factor-alpha (TNF-alpha) on leptin secretion from and leptin (OB) gene expression in isolated adipocytes. Because glucose uptake and the metabolism of glucose beyond lactate are important determinants of leptin production in adipocytes, we examined the effects of TNF-alpha on glucose uptake and lactate production and their relationship to leptin secretion. DESIGN AND METHODS: Isolated rat adipocytes were anchored in a defined matrix of basement membrane components and cultured with media containing 5 mM glucose, 0.16 nM insulin and several concentrations of TNF-alpha. Leptin secretion, steady-state levels of leptin mRNA levels, glucose uptake, and lactate production were assessed over 96 h. RESULTS: TNF-alpha at concentrations of 0.024, 0.24, 2.4 and 24 ng/ml did not affect leptin secretion over 24 h. TNF-alpha at concentrations of 0.24 to 24 ng/ml significantly inhibited leptin secretion over 96 h by 19-60%. TNF-alpha at concentrations of 0.024 to 24 ng/ml significantly decreased steady-state levels of leptin mRNA after 96 h by 32-95%. In addition, TNF-alpha at concentrations of 2.4 and 24 ng/ml significantly increased glucose uptake and lactate production over 96 h by 30-57%. TNF-alpha at a concentration of 0.024 ng/ml did not affect leptin secretion, glucose uptake or lactate production. Overall, for the TNF-alpha concentrations tested, leptin secretion was inversely related to the percent of glucose carbon released as lactate; however, TNF-alpha did not induce a proportional increase of lactate production from glucose. CONCLUSION: Short-term (24 h) exposure of isolated adipocytes to TNF-alpha does not affect leptin secretion. Prolonged exposure to TNF-alpha produces a concentration-dependent inhibition of leptin secretion and gene expression. This suggests that the acute effect of TNF-alpha to increase circulating leptin levels in vivo may be indirect. TNF-alpha at higher concentrations increases glucose uptake, but does not increase the conversion of glucose to lactate. Therefore, TNF-alpha appears to induce a dissociation between adipocyte glucose metabolism and leptin production.


Assuntos
Adipócitos/metabolismo , Expressão Gênica , Glucose/metabolismo , Proteínas/genética , Proteínas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Northern Blotting , Células Cultivadas , Insulina/metabolismo , Ácido Láctico/metabolismo , Leptina , Masculino , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
15.
J Trauma ; 46(5): 900-6, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10338410

RESUMO

BACKGROUND: Depression of myocardial contractility occurs in septic shock. METHODS: Fourteen pigs were instrumented to measure cardiopulmonary dynamics after a challenge of Escherichia coli endotoxin (lipopolysaccharide endotoxin, LPS). A volumetric Swan-Ganz catheter was placed via the jugular vein, and a carotid arterial line was placed into the aortic root. Eight pigs received LPS alone and six pigs received tumor necrosis factor monoclonal antibody (TNF MAb) 15 minutes before the administration of LPS. Pulmonary artery and aortic root blood were sampled for amounts of TNF. Ninety minutes after LPS administration, thoracotomy was performed to biopsy the right and left ventricles for TNF levels. Contractility was determined from the end systolic pressure-volume relationships of pressure-volume diagrams. RESULTS: Right ventricular end diastolic volume index nearly doubled and myocardial contractility decreased by 40% from baseline in the pigs receiving only LPS. Pigs that received TNF MAb had no change in myocardial contractility or right ventricular end diastolic volume index from baseline. There was a higher level of TNF in the aortic sample than in the pulmonary samples at 60 minutes. Right ventricular tissue TNF levels were significantly higher in the LPS-alone group. There was no such difference in left ventricular tissue. CONCLUSION: The left and right ventricles have different susceptibilities to TNF MAb. TNF may decrease myocardial contractility in sepsis. Blockade of TNF with TNF MAb reverses the depression of myocardial contractility and the right ventricular dilatation associated with septic shock.


Assuntos
Endotoxemia/fisiopatologia , Contração Miocárdica/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Anticorpos Monoclonais/administração & dosagem , Pressão Sanguínea , Débito Cardíaco , Endotoxinas/administração & dosagem , Escherichia coli , Lipopolissacarídeos/administração & dosagem , Miocárdio/química , Artéria Pulmonar , Volume Sistólico , Suínos , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologia , Função Ventricular
16.
J Surg Res ; 78(1): 1-6, 1998 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-9733608

RESUMO

The immunosuppressive effect of portal venous blood transfusions in organ transplantation has been well established and may be mediated by increased Kupffer cell production of the immunosuppressive arachidonic acid metabolite prostaglandin E2 (PGE2). In this study, butyrate, a short-chain fatty acid known to enhance gene transcription, is hypothesized to enhance Kupffer cell PGE2 production by altering cyclooxygenase or phospholipase A2 (PLA2) activity, thus augmenting the immunosuppressive effect of portal venous transfusion. Lewis rats were given a portal venous transfusion of Wistar-Firth blood or saline 1 h prior to Kupffer cell harvest. The in vitro effects of butyrate on Kupffer cell PGE2 production, cyclooxygenase, and PLA2 activity were assessed. Kupffer cell tumor necrosis factor-alpha (TNFalpha) production was also assessed due to its sensitivity to PGE2 and its proinflamatory effects. Kupffer cells from portally transfused animals produced significantly more PGE2 than saline-transfused controls. Addition of butyrate to the culture medium further increased PGE2 production by as much as sevenfold in Kupffer cells of portally transfused animals. Other short-chain fatty acids, propionate and hexanoate, did not increase PGE2 production. Butyrate added to Kupffer cells from transfused animals slightly upregulated inducible cyclooxygenase (COX-2) mRNA levels as measured by both Northern blot and reverse-transcriptase polymerase chain reaction and increased PLA2 activity fivefold as measured by Western blot. Kupffer cell immune function was also affected by in vitro butyrate treatment with a significant decrease in the production of TNFalpha. Thus, butyrate may be a useful immunoregulatory agent in organ transplantation protocols which seek to enhance transcription of immunosuppressive molecules.


Assuntos
Butiratos/farmacologia , Dinoprostona/biossíntese , Antagonistas dos Receptores Histamínicos/farmacologia , Sistema Imunitário/efeitos dos fármacos , Células de Kupffer/enzimologia , Animais , Ácido Butírico , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Dinoprostona/análise , Regulação Enzimológica da Expressão Gênica , Sistema Imunitário/metabolismo , Imunossupressores/farmacologia , Isoenzimas/genética , Isoenzimas/metabolismo , Células de Kupffer/química , Células de Kupffer/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Proteínas de Membrana , Peroxidases/metabolismo , Fosfolipases A/análise , Fosfolipases A/biossíntese , Fosfolipases A2 , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos WF , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/biossíntese
17.
Transplantation ; 65(10): 1294-8, 1998 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-9625008

RESUMO

BACKGROUND: Enhanced Kupffer cell production of the immunosuppressive arachidonic acid metabolite prostaglandin E2 (PGE2) has been shown to be a mechanism of the immunosuppressive effect of portal venous transfusions (PVT). Butyrate, a four-carbon short-chain fatty acid, has received increased attention because of its ability to enhance gene transcription. This study tested the hypothesis that the intrahepatic delivery of butyrate enhances Kupffer cell PGE2 production and thus augments the immunosuppressive effect of PVT. METHODS: Butyrate was incorporated into liposomes and administered intravenously to Lewis rats. Control rats were administered liposomes without butyrate. Twenty-four hours after liposome injection, rats were administered a PVT of 1 ml of Wistar-Furth blood. Kupffer cells were isolated, and PGE2 and tumor necrosis factor-alpha levels were measured in the culture medium after 24 hr. Additionally, Kupffer cells from butyrate-treated and control animals were added to one-way mixed lymphocyte reaction cultures. RESULTS: Intrahepatic delivery of butyrate via liposomes increased Kupffer cell PGE2 (3800+/-1220 vs. 1010+/-119 pg/ml, P<0.05) and decreased tumor necrosis factor-alpha (1670+/-81 vs. 3360+/-415 pg/ml, P<0.01) production as compared with controls. Butyrate also augmented the Kupffer cell-mediated immunosuppression as demonstrated by significant depression of the mixed lymphocyte reaction (690+/-119 vs. 3850+/-148 cpm, P<0.01). CONCLUSION: The results support the hypothesis that intrahepatic delivery of butyrate enhances Kupffer cell PGE2 production, and specific targeting of Kupffer cells with liposomes containing immunomodulating agents such as butyrate may be a useful means of augmenting immunosuppression protocols in organ transplantation.


Assuntos
Transfusão de Sangue , Butiratos/administração & dosagem , Terapia de Imunossupressão/métodos , Células de Kupffer/efeitos dos fármacos , Veia Porta , Animais , Butiratos/farmacologia , Ácido Butírico , Dinoprostona/biossíntese , Portadores de Fármacos , Sistema Imunitário/fisiologia , Células de Kupffer/metabolismo , Células de Kupffer/fisiologia , Lipossomos , Teste de Cultura Mista de Linfócitos , Masculino , Ratos , Ratos Endogâmicos WF , Fator de Necrose Tumoral alfa/biossíntese
18.
Cancer Lett ; 124(1): 1-7, 1998 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-9500184

RESUMO

We and others have previously shown that dietary fat can alter the growth and metastasis of rodent mammary tumors. Few transplantable tumor models have been used to study the effects of dietary n-6 versus n-3 fatty acids on mammary tumorigenesis. Here we study the effects of fish oil and safflower oil on the growth and metastasis of an animal model that in several ways parallels the human disease. Tumor latency, growth and metastasis were studied in mice fed diets that contained either 10 or 20% total fat which was varied in the type of fat with either menhaden fish oil (FO), safflower oil (SO) or a 50/50 mixture of the two. Tumor latency was significantly longer and tumor growth was significantly slower in mice fed the 20% FO diet. When spontaneous metastasis was assessed, mice fed diets containing FO had significantly decreased numbers of pulmonary nodules and total metastatic load. Likewise, mice fed FO diets had a lower level of implantation and survival of pulmonary metastases. Thus, in our animal model, diets containing n-3 fatty acids in fish oil significantly decrease primary breast tumor growth and its metastasis.


Assuntos
Adenocarcinoma/dietoterapia , Antineoplásicos/farmacologia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Óleos de Peixe/administração & dosagem , Neoplasias Mamárias Experimentais/dietoterapia , Óleo de Cártamo/administração & dosagem , Adenocarcinoma/patologia , Animais , Divisão Celular/efeitos dos fármacos , Dieta , Modelos Animais de Doenças , Ácidos Graxos Ômega-6 , Feminino , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Metástase Neoplásica , Transplante de Neoplasias , Células Tumorais Cultivadas
19.
J Leukoc Biol ; 62(6): 845-51, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9400826

RESUMO

Expression of major histocompatibility complex class II molecules, Ia, can be significantly augmented by interferon-gamma (IFN-gamma) in macrophages. In this study we demonstrate that platelet-activating factor (PAF) was also a potent inducer of Ia antigen expression on macrophages. PAF-induced Ia expression was both time- and dose-dependent. Maximal Ia expression was induced with 25 nM PAF after 3-h exposure to PAF. Ia expression in macrophages stimulated with PAF for 24 h was not significantly greater than unstimulated macrophages. Treatment of macrophages with IFN-gamma and PAF did not affect either the kinetics or concentration required for maximal Ia expression induced by either IFN-gamma or PAF. PAF-induced Ia expression was inhibited by the specific PAF receptor antagonists, WEB 2086, Ro 24-0238, and Ro 24-4637, indicating a receptor-mediated event. Like IFN-gamma-induced Ia expression, PAF activity was inhibited by prostaglandin E2 (PGE2). However, that expression was only inhibited after 24 h when macrophages were treated with the PGE2 synthesis inhibitors, flurbiprofen and indomethacin. These findings demonstrate that PAF, along with its role as a potent proinflammatory mediator, was also capable of inducing Ia expression on macrophages through the PAF receptor and that expression was altered by PGE2.


Assuntos
Antígenos de Histocompatibilidade Classe II/biossíntese , Macrófagos Peritoneais/imunologia , Fator de Ativação de Plaquetas/farmacologia , Animais , Células Cultivadas , Dinoprostona/farmacologia , Feminino , Interferon gama/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
20.
Transplantation ; 64(1): 135-9, 1997 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-9233713

RESUMO

Portal venous transfusions (PVTs) of blood have been shown to induce significant immunosuppression in animal models of organ transplantation. A proposed mechanism of PVT-induced immunosuppression is via alteration of Kupffer cell arachidonic acid metabolism with increased secretion of the suppressive metabolite prostaglandin E2 (PGE2). This study assessed the hypothesis that PVT increases Kupffer cell PGE2 production via up-regulation of Kupffer cell phospholipase A2 (PLA2) as well as constitutive (COX1) and inducible (COX2) cyclooxygenase. Kupffer cells from Lewis rats were harvested 1 hr after PVT with either 1 ml of Wistar-Furth blood, systemic transfusion (SVT), or saline via portal vein (PVSal). After lipopolysaccharide stimulation, 24-hr Kupffer cell supernatant fractions were assayed for PGE2. PGE2 was increased after SVT (1465+/-234 pg/ml) compared with PVSal (597+/-99; P<0.01). PVT increased Kupffer cell PGE2 (5370+/-533; P<0.001 vs. SVT and vs. PVSal) even more substantially. Kupffer cells from PVT-treated rats were then cultured in the presence of inhibitors of PLA2, COX1, or COX2. When Kupffer cells were treated with mepacrine to inhibit PLA2 (5575+/-453 pg/ml), PGE2 production was not different from that by PVSal-treated controls (6467+/-614 pg/ml), but when Kupffer cells were incubated in the presence of the COX1 inhibitor flurbiprofen (3512+/-407 pg/ml) or the COX2 inhibitor nimesulide (2800+/-830 pg/ml), production was decreased 46.7% and 56.7%, respectively, over control activity without added inhibitor. PVT also increased Kupffer cells COX1 and COX2 mRNA as measured by Northern blot. Heart transplants were then performed from Wistar-Furth donors into Lewis recipients at the time of PVT, SVT, PVSal, or PVT + indomethacin (COX1/2 inhibitor). PVT prolonged allograft survival (12.0+/-0.9 days) compared with PVSal (6.3+/-0.3; P<0.01) or SVT (6.3+/-0.3; P<0.04). Indomethacin shortened graft survival when given with PVT (6.5+/-0.3 days). In summary, PVT increased Kupffer cell PGE2 production, up-regulated transcription of Kupffer cells COX1 and COX2 mRNA, and prolonged cardiac allograft survival. COX1/2 inhibition abrogated the effect of PVT. The results indicated that the immunosuppressive effect of PVT may be mediated by up-regulation of Kupffer cell COX1 and COX2. Manipulation of Kupffer cell arachidonic acid metabolism may be useful in augmentation of PVT-induced immunosuppression.


Assuntos
Transfusão de Sangue , Células de Kupffer/enzimologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Dinoprostona/metabolismo , Sobrevivência de Enxerto/fisiologia , Transplante de Coração/imunologia , Tolerância Imunológica , Células de Kupffer/metabolismo , Masculino , Veia Porta , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/fisiologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos WF , Regulação para Cima
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