RESUMEN
The nuclear two-photon or double-gamma (2γ) decay is a second-order electromagnetic process whereby a nucleus in an excited state emits two gamma rays simultaneously. To be able to directly measure the 2γ decay rate in the low-energy regime below the electron-positron pair-creation threshold, we combined the isochronous mode of a storage ring with Schottky resonant cavities. The newly developed technique can be applied to isomers with excitation energies down to â¼100 keV and half-lives as short as â¼10 ms. The half-life for the 2γ decay of the first-excited 0^{+} state in bare ^{72}Ge ions was determined to be 23.9(6) ms, which strongly deviates from expectations.
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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.
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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 â¼40. 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.
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This article describes primary data and resources available from the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, a novel arm of the Human Connectome Project (HCP). Data were collected from 215 adolescents (14-17 years old), 152 of whom had current diagnoses of anxiety and/or depressive disorders at study intake. Data include cross-sectional structural (T1- and T2-weighted), functional (resting state and three tasks), and diffusion-weighted magnetic resonance images. Both unprocessed and HCP minimally-preprocessed imaging data are available within the data release packages. Adolescent and parent clinical interview data, as well as cognitive and neuropsychological data are also included within these packages. Release packages additionally provide data collected from self-report measures assessing key features of adolescent psychopathology, including: anxious and depressive symptom dimensions, behavioral inhibition/activation, exposure to stressful life events, and risk behaviors. Finally, the release packages include 6- and 12-month longitudinal data acquired from clinical measures. Data are publicly accessible through the National Institute of Mental Health Data Archive (ID: #2505).
Asunto(s)
Ansiedad , Conectoma , Depresión , Humanos , Adolescente , Masculino , Femenino , Trastornos de Ansiedad , Trastorno Depresivo , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagenRESUMEN
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.
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Trastornos de Ansiedad/diagnóstico por imagen , Ansiedad/diagnóstico por imagen , Encéfalo/fisiopatología , Depresión/diagnóstico por imagen , Neuroimagen , Adolescente , Trastornos de Ansiedad/fisiopatología , Boston , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Conectoma/métodos , Depresión/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Neuroimagen/métodosRESUMEN
The variation in trace element abundance patterns indicates that lunar igneous rocks are the product of extensive igneous fractionation. Variations in the Sr(87)/ Sr(86) ratio indicate that these rocks crystallized 3.5+/-0.3 x 10(9) years ago.
RESUMEN
A chemically distinct group of lunar rocks with the trace element characteristics of basaltic lunar rocks is apparently ubiquitous on the lunar surface. Such rocks have been found at the Apollo 15, Apollo 16, and Luna 20 landing sites. They may be derived from the plains-forming material that has been designated Cayley Formation.
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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.
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Esófago de Barrett/cirugía , Ablación por Catéter/métodos , Fundoplicación/métodos , Reflujo Gastroesofágico/cirugía , Adulto , Anciano , Esófago de Barrett/complicaciones , Esófago de Barrett/diagnóstico , Biopsia con Aguja , Ablación por Catéter/efectos adversos , Terapia Combinada , Endoscopía/métodos , Esofagoscopía/métodos , Femenino , Estudios de Seguimiento , Fundoplicación/efectos adversos , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/mortalidad , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Probabilidad , Medición de Riesgo , Muestreo , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
The influence of quantitative differences in dietary linoleic acid (18:2) on the metastasis as well as the development of line 4526 mouse mammary tumors was investigated. High fat diets (20%, w/w) that contained either 1, 2, 4, 8, or 12% 18:2 by weight, were prepared by using mixtures of coconut and safflower oil and fed to female BALB/c mice that were subsequently inoculated with 10(4) 4526 tumor cells s.c., either at the lateral abdominal wall (LAW) or in the mammary fat pad (MFP). Latency of LAW tumors was influenced by the level of dietary 18:2, whereas the latency of MFP tumors was not. When metastasis was assessed, mice with MFP tumors fed 1, 2, 4, or 8% 18:2 diets had 62-73% fewer lung surface tumor nodules than similar mice fed 12% 18:2. Mice in all dietary groups with LAW tumors had fewer metastatic lung nodules than mice with MFP tumors; mice with LAW tumors fed diets containing 1, 2, or 4% 18:2 had 52-69% fewer nodules than similar mice fed diets containing 8 or 12% 18:2. There were no significant differences in the rate of increase of body weight or the daily mean tumor volumes when compared with dietary 18:2 level. Fatty acid composition of the tumor, particularly the level of 18:2, was significantly altered by diet. This study demonstrates that while the level of dietary 18:2 does not enhance the growth rate of primary 4526 tumors and does or does not affect the latency depending on the primary site, it does significantly alter the metastasis. These results stress the importance of metastasis assessment in future studies involving dietary fat effects on tumorigenesis.
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Grasas de la Dieta , Ácidos Linoleicos , Neoplasias Mamarias Experimentales/patología , Metástasis de la Neoplasia/inducido químicamente , Animales , Peso Corporal , Ácidos Grasos/análisis , Femenino , Ácido Linoleico , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Trasplante de NeoplasiasRESUMEN
The mechanism(s) by which dietary linoleic acid (18:2n-6) enhances mammary tumor growth and metastasis is not known. Since arachidonic acid (20:4n-6)-derived prostaglandins (PG) may play a role in the metastatic dissemination of tumor cells, the ability of two murine mammary tumor cell lines, 4526 (metastasis positive) and line 168 (spontaneous metastasis negative), to convert 18:2n-6 into prostaglandins was examined. Cells were initially incubated with [14C]18:2n-6 and after 8-24 h the [14C]fatty acids were quantitated by high-performance liquid chromatography following transesterification. [14C]18:2n-6 was metabolized primarily to [14C]dihomogammalinolenic acid (20:3n-6) in line 4526 cells and [14C]20:4n-6 in line 168 cells. Examination of cellular fatty acid levels revealed a 20:3n-6/20:4n-6 ratio of 1.79 +/- 0.36 and 0.20 +/- 0.02 in line 4526 and 168 cells, respectively. These data are consistent with an inherently lower delta 5 desaturase activity in line 4526 relative to 168. To assess the metabolism of 18:2n-6 into eicosanoid products, the cell lines were prelabeled with [14C]18:2n-6 or 0-40 microM nonradiolabeled 18:2n-6 overnight and subsequently stimulated with calcium ionophore A23187 for 1 h. Total PGE production, as determined by radioimmunoassay, was greater in 168 relative to 4526 cells at all 18:2n-6 concentrations. 14C-prostaglandins detected by high-performance liquid chromatography and argentation thin-layer chromatography were: PGF1 alpha and PGE1 (derived from 20:3n-6) and PGF2 alpha and PGE 2 (derived from 20:4n-6) from line 4526; PGE1 and PGE2 from line 168. PGE1/PGE2 ratios were 1.43 +/- 0.07 and 0.23 +/- 0.03 for 4526 and 168 lines, respectively. Neither cell line synthesized lipoxygenase products following [14C]18:2n-6 or [3H]-20:4n-6 incubations under the conditions employed. Additional studies are warranted in order to define the biological properties of 1- and 2-series cyclooxygenase products as they relate to tumor cell metastasis.
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Ácidos Linoleicos/metabolismo , Neoplasias Mamarias Experimentales/metabolismo , Metástasis de la Neoplasia/metabolismo , Animales , Ácido Araquidónico , Ácidos Araquidónicos/metabolismo , Ácidos Grasos Insaturados/metabolismo , Femenino , Ácido Linoleico , Neoplasias Mamarias Experimentales/patología , Ratones , Prostaglandina-Endoperóxido Sintasas/metabolismo , Prostaglandinas/biosíntesis , Células Tumorales CultivadasRESUMEN
Modifying the fatty acid composition of macrophages through diet can significantly alter some of their functions, such as tumoricidal capacity and tumor necrosis factor alpha (TNF-alpha) production. The mechanism of that modification, however, is unknown. In this report, we provide evidence that fatty acids added to macrophages in culture can significantly alter macrophage TNF-alpha production. For example when inflammatory macrophages were incubated with various doses of arachidonic acid [20:4(n-6)] during activation with lipopolysaccharide (LPS), we observed a dose-dependent decrease in the level of bioactive TNF-alpha with complete inhibition at 2-5 microM. This inhibition was specific for 20:4(n-6) because in vitro treatment with other fatty acids, such as eicosapentaenoic [20:5(n-3)] or docosahexaenoic [22:6(n-3)] acids, had differential effects. The inhibitory action of 20:4(n-6) did not involve toxicity because cell viability was not affected and in vitro interferon-gamma and lipopolysaccharide (LPS) activation of macrophages for killing of P815 tumor targets was not altered. Inhibition by 20:4(n-6) occurred posttranscriptionally, and could be reversed when macrophages were treated with indomethacin during activation. Arachidonic acid treatment also significantly increased the production of immunoreactive prostaglandin E2 (PGE2) by LPS-treated and untreated macrophages. These results suggest that in vitro treatment of macrophages with 20:4(n-6) may inhibit TNF-alpha production through an alteration in the levels of PGE2 at a posttranscriptional level. These results provide evidence that some dietary fats may affect macrophage activity through modification of eicosanoid synthesis.
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Ácido Araquidónico/farmacología , Macrófagos/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesis , Animales , Ácido Araquidónico/antagonistas & inhibidores , Dinoprostona/biosíntesis , Ácidos Grasos/farmacología , Femenino , Técnicas In Vitro , Indometacina/farmacología , Cinética , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Cavidad Peritoneal/citología , Factor de Necrosis Tumoral alfa/efectos de los fármacosRESUMEN
Inflammatory macrophages from mice fed diets containing menhaden fish oil (MFO) have a reduced capacity for cytotoxicity of mastocytoma cells upon activation with interferon-gamma (IFN gamma) and lipopolysaccharide due to an altered responsiveness to IFN gamma. In an effort to elucidate further how dietary MFO effects macrophage function, we have studied the maturation of inflammatory macrophages from mice fed MFO compared with mice fed safflower oil (SFO) using several processes that serve as markers of the activational state. No significant differences in the recruitment or percentage of peritoneal exudate cells as macrophages after thioglycollate injection and no differences in spreading, binding, or phagocytosis of sheep erythrocytes or phagocytosis of yeast by inflammatory macrophages were observed when the dietary groups were compared. However, MFO macrophages had an altered capacity for peroxide release when stimulated with unopsonized zymosan (10-200 micrograms/ml). Furthermore, to elucidate how MFO feeding could alter IFN gamma-induced responses of inflammatory macrophages, we assessed phorbol-12-myristate-13-acetate-induced hydrogen peroxide production and expression of class II MHC determinants (Ia). There were no differences between macrophages from mice fed the two diets with respect to the production of peroxide when they were preincubated with 0.1-10 U/ml of IFN gamma. However, MFO macrophages had greater peroxide production after enhancement with 100 U/ml of IFN gamma. With respect to Ia induction, the percentage of macrophages responding to IFN gamma was not altered by diet, and there were no differences in expression of Ia induced by 24 hr exposure to IFN gamma. Thus the differential effect of MFO compared with SFO is probably mediated not by an alteration in the maturation of inflammatory macrophages but rather through the alteration of IFN gamma-induced functions such as peroxide production.
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Grasas Insaturadas en la Dieta/farmacología , Aceites de Pescado/farmacología , Inflamación/patología , Macrófagos/fisiología , Administración Oral , Animales , Adhesión Celular/efectos de los fármacos , Adhesión Celular/fisiología , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Células Cultivadas , Grasas Insaturadas en la Dieta/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Aceites de Pescado/administración & dosificación , Antígenos de Histocompatibilidad Clase II/metabolismo , Inflamación/fisiopatología , Interferón gamma/farmacología , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/patología , Ratones , Peróxidos/metabolismo , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiología , Aceite de Cártamo/administración & dosificación , Aceite de Cártamo/farmacología , Acetato de Tetradecanoilforbol/farmacología , Zimosan/farmacologíaRESUMEN
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.
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Antígenos de Histocompatibilidad Clase II/biosíntesis , Macrófagos Peritoneales/inmunología , Factor de Activación Plaquetaria/farmacología , Animales , Células Cultivadas , Dinoprostona/farmacología , Femenino , Interferón gamma/farmacología , Activación de Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BLRESUMEN
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.
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Transfusión Sanguínea , Macrófagos del Hígado/enzimología , Prostaglandina-Endoperóxido Sintasas/metabolismo , Animales , Dinoprostona/metabolismo , Supervivencia de Injerto/fisiología , Trasplante de Corazón/inmunología , Tolerancia Inmunológica , Macrófagos del Hígado/metabolismo , Masculino , Vena Porta , Prostaglandina-Endoperóxido Sintasas/genética , Prostaglandina-Endoperóxido Sintasas/fisiología , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas WF , Regulación hacia ArribaRESUMEN
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.
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Transfusión Sanguínea , Butiratos/administración & dosificación , Terapia de Inmunosupresión/métodos , Macrófagos del Hígado/efectos de los fármacos , Vena Porta , Animales , Butiratos/farmacología , Ácido Butírico , Dinoprostona/biosíntesis , Portadores de Fármacos , Sistema Inmunológico/fisiología , Macrófagos del Hígado/metabolismo , Macrófagos del Hígado/fisiología , Liposomas , Prueba de Cultivo Mixto de Linfocitos , Masculino , Ratas , Ratas Endogámicas WF , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
We have previously shown that a high fat diet (20% w/w) containing 12% linoleic acid (18:2) can significantly increase the metastasis of mammary tumor cells when compared with high fat diets that contain 8% or less 18:2 with a constant level of oleic acid (18:1). This effect may have been due to an alteration of eicosanoid metabolism because the cyclooxygenase inhibitor, indomethacin, abolished the increase. Because 18:1 may interfere with the metabolism of 18:2 to 20:4, we have now tested whether the 18:1 that supplements the 18:2 diet can have an effect on spontaneous or experimental metastasis of the line 4526 murine mammary tumor. For this, six 20% fat diets were formulated with 1%, 6%, and 12% 18:2 and either high or low levels of 18:1. Our results indicate that the amount of select fatty acids other than 18:2 at 12% has no significant effect on mouse growth, tumor growth, or tumor latency. When spontaneous metastatic burden was calculated, no significant differences between mice fed diets containing 1% and 6% 18:2 were observed. However, 4 to 5 times more of a metastatic burden was observed in mice fed diets containing 12% 18:2. No significant differences were observed between high and low 18:1 diets when the 18:2 content was 1 or 12%. However, at 6% 18:2, 18:1 significantly decreased metastatic burden. When experimental metastasis was assessed, relatively low levels of surface lung nodules were observed at 1% and 6% 18:2, but significantly higher levels were observed at 12% 18:2.(ABSTRACT TRUNCATED AT 250 WORDS)
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Grasas de la Dieta/farmacología , Ácidos Linoleicos/farmacología , Neoplasias Pulmonares/metabolismo , Neoplasias Mamarias Experimentales/patología , Metástasis de la Neoplasia/patología , Ácidos Oléicos/farmacología , Animales , Ácidos Grasos/análisis , Femenino , Ácido Linoleico , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ácido OléicoRESUMEN
The effect of dietary fat concentration and saturation on cell composition and structure of line 168 mouse mammary tumors in vivo was studied using morphometry and electron microscopy. Both the concentration and saturation of fat fed to mice had a significant influence on the volume ratio of mast cells infiltrating line 168 tumors. Tumors of mice fed diets containing a high concentration (20%) of either safflower oil (SO) or palm oil (PO) had 2-3 times the volume ratio of mast cells than mice fed diets containing a low concentration (5%) of either fat. There were no significant differences among diets with respect to other inflammatory cell populations. Mice fed either one of the high fat diets had tumor cells with inclusions that ultrastructurally, appeared to consist of lipid. Dietary fat, however, had no observable affect on cell junctions or other morphological characteristics. Greater infiltration of mast cells in tumors of mice fed high fat diets and the eventual formation of new blood capillaries may explain the decreased latency of tumor onset and enhanced growth of tumors in mice fed diets with high concentrations of fat.
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Grasas de la Dieta/administración & dosificación , Neoplasias Mamarias Experimentales/patología , Animales , Línea Celular/efectos de los fármacos , Aceite de Maíz/administración & dosificación , Grasas de la Dieta/farmacología , Ácidos Grasos/análisis , Ácidos Grasos Esenciales/administración & dosificación , Cuerpos de Inclusión/ultraestructura , Metabolismo de los Lípidos , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/ultraestructura , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Aceite de Palma , Aceites de Plantas/administración & dosificación , Aceite de Cártamo/administración & dosificaciónRESUMEN
High levels of dietary linoleic acid (18:2) have been shown to increase the spontaneous metastasis of line 4526 mouse mammary tumors. In this report, the influence of 18:2 on specific events of tumor metastasis, namely, lodgement, proliferation and survival, were studied using spontaneous and experimental metastasis assays with line 4526 cells. A significantly greater number of radiolabeled tumor cells lodged in the lungs of mice fed 4, 8 and 12% 18:2 when compared with mice fed lower levels of 18:2. The effect of dietary 18:2 appeared to be on the host tissue (lungs) and not the tumor cells. Lodgement of tumor cells first cultured in serum of mice fed 18:2 then injected into mice fed 1% 18:2 was not affected. There were no significant differences in the percentage of [3H]thymidine labeled metastatic cells from lungs of mice fed different levels of 18:2. However, the number of surface lung nodules that appeared in mice 21 days after injection of unlabeled line 4526 cells increased in mice fed 8 and 12% 18:2 compared with those fed lower levels of 18:2. Thus, dietary 18:2 may increase metastasis by influencing the lodgement, implantation and survival but not proliferation of line 4526 mouse mammary tumor cells.
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Grasas de la Dieta/farmacología , Ácidos Linoleicos/farmacología , Neoplasias Mamarias Experimentales/patología , Animales , Adhesión Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Femenino , Ácido Linoleico , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Metástasis de la Neoplasia , Trasplante de NeoplasiasRESUMEN
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.