RESUMEN
Diets rich in soy phytoestrogens have many potential health benefits but isoflavones such as genistein may suppress cell mediated immune function. The effect of dietary phytoestrogens on the host response to infection has not been extensively examined. Mice were fed a diet containing soy phytoestrogens and infected with Mycobacterium avium to establish a chronic infection and inflammatory response. As phytoestrogens may act through classical oestrogen receptors (ER), mice deficient in ERalpha signalling and wild type mice were evaluated for a panel of Type 1-associated cytokines (IFNgamma, IL-12 and IL-18) in the spleen. IFNgamma production in the spleen was increased approximately 4-fold in ERalpha-deficient mice fed a casein-based diet over wild type mice fed a casein-based diet (P < 0.05), suggesting a role for ERalpha in suppressing IFNgamma production. IL-18 levels in spleens of wild type mice were decreased compared to ERalpha-deficient mice on a casein diet. Splenic IL-12 and IL-18 levels were not affected in wild type and ERalpha-deficient mice on the phytoestrogen containing diets, with the exception that whole soy increased IL-12 levels in the tissues of ERalpha deficient mice. We conclude that ERalpha and dietary phytoestrogens can influence production of key regulatory cytokines in response to chronic bacterial infection.
Asunto(s)
Glycine max/efectos adversos , Inmunosupresores/administración & dosificación , Interferón gamma/biosíntesis , Isoflavonas/administración & dosificación , Mycobacterium avium/inmunología , Preparaciones de Plantas/administración & dosificación , Receptores de Estrógenos/inmunología , Tuberculosis/inmunología , Animales , Caseínas/administración & dosificación , Cromatografía Líquida de Alta Presión/métodos , Recuento de Colonia Microbiana , Suplementos Dietéticos/efectos adversos , Inhibidores Enzimáticos/sangre , Genisteína/administración & dosificación , Genisteína/sangre , Inmunidad Celular/inmunología , Inmunosupresores/efectos adversos , Interleucina-12/análisis , Interleucina-18/análisis , Isoflavonas/efectos adversos , Ratones , Ratones Endogámicos C57BL , Fitoestrógenos , Preparaciones de Plantas/efectos adversos , Transducción de Señal/inmunología , Bazo/inmunologíaRESUMEN
Zinc deprivation results in decreased and cyclic food intake in rats. We determined the response of zinc-deprived rats to neuropeptide Y (NPY). In a preliminary experiment, rats were fed a low (-Zn; <1 mg/kg) or adequate zinc diet (+Zn; 100 mg/kg) for 4 days. NPY (5 or 10 microg) was then administered via an intracerebroventricular (ICV) cannula and food intake measured for 4 h. NPY stimulated food intake in all rats, but the difference in food intake due to zinc deprivation persisted. In a subsequent experiment, rats were fed the low zinc and adequate zinc diets for 4, 5 or 6 days. Food intake was suppressed in rats fed the low zinc compared to the adequate zinc diet on all of these days. When NPY (10 microg) was administered at the onset of the light cycle, the food intake was approximately 2.5-fold greater regardless of dietary zinc status, but the amount of food consumed by rats fed low zinc was approximately one-half the quantity consumed by NPY-stimulated zinc-adequate rats. NPY administered at the onset of dark failed to stimulate food intake in either dietary group although the total intake difference due to zinc status persisted. ICV administration of 5 nmol of zinc prior to NPY injection failed to correct the food intake response of the zinc-deficient rats. We conclude that the basis of the reduced food intake of zinc-deficient rats does not relate to NPY quantity or release, or to impairment of its signal transduction. There appears to be another undefined factor that limits food intake in zinc deficiency.
Asunto(s)
Ingestión de Alimentos/efectos de los fármacos , Neuropéptido Y/farmacología , Zinc/deficiencia , Animales , Inyecciones Intraventriculares , Masculino , Estado Nutricional , Ratas , Ratas Wistar , Zinc/administración & dosificaciónRESUMEN
Dietary supplements containing concentrates of plant-derived estrogens are being increasingly used by consumers as alternatives for hormone replacement therapy, for treatment of menopausal symptoms, and as cancer preventives. The effect of dietary genistein on dimethylbenz[a]anthracene (DMBA)-induced mammary tumor development was investigated in wild-type (ER alpha WT) and estrogen receptor-alpha knockout (ER alpha KO) mice. ER alpha WT and ER alpha KO mice were fed a casein-based diet containing 0 or 1 g genistein/kg diet from weaning. Tumors were induced by oral administration of DMBA and subscapular implantation of medroxyprogesterone acetate. No tumors were observed in ER alpha KO mice. In ER alpha WT mice, dietary intake of genistein influenced tumor development, enhancing anaplasia of mammary cancer. Mice consuming genistein expressed malignant mammary adenocarcinoma, whereas benign adenomas were observed in mice fed the control diet. Dietary intake was also influenced by genistein, with ER alpha WT and ER alpha KO mice fed genistein consuming less food (p < 0.0001) and subsequently weighing less than mice fed the control diet (p < 0.0001). Significant differences in food intake by genotype were also observed (p = 0.0017), with ER alpha KO mice consuming less than ER alpha WT mice. Overall, this study found no protective effect of genistein on DMBA-induced mammary tumors in mice and suggests a potential adverse effect on tumor development when high levels of genistein are consumed.
Asunto(s)
9,10-Dimetil-1,2-benzantraceno , Adenocarcinoma/inducido químicamente , Dieta , Genisteína/administración & dosificación , Neoplasias Mamarias Experimentales/inducido químicamente , Receptores de Estrógenos/deficiencia , Animales , Caseínas/administración & dosificación , Estradiol/sangre , Receptor alfa de Estrógeno , Femenino , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Acetato de Medroxiprogesterona/administración & dosificación , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Tamaño de los Órganos , Ovario/patología , Receptores de Estrógenos/genética , Receptores de Estrógenos/fisiología , Neoplasias Cutáneas/inducido químicamente , Útero/patología , Aumento de PesoRESUMEN
The inhibition of growth is a cardinal symptom of zinc deficiency. In animals fed a zinc-inadequate diet, both food intake and growth are reduced within 4-5 d. Despite the concomitant reduction in food intake and growth, reduced energy intake is not the limiting factor in growth, because force-feeding a zinc-inadequate diet to animals fails to maintain growth. Hence, food intake and growth appear to be regulated by zinc through independent, although well coordinated, mechanisms. Despite the long-term study of zinc metabolism, the first limiting role of zinc in cell proliferation remains undefined. Zinc participates in the regulation of cell proliferation in several ways; it is essential to enzyme systems that influence cell division and proliferation. Removing zinc from the extracellular milieu results in decreased activity of deoxythymidine kinase and reduced levels of adenosine(5')tetraphosphate(5')-adenosine. Hence, zinc may directly regulate DNA synthesis through these systems. Zinc also influences hormonal regulation of cell division. Specifically, the pituitary growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis is responsive to zinc status. Both increased and decreased circulating concentrations of GH have been observed in zinc deficiency, although circulating IGF-I concentrations are consistently decreased. However, growth failure is not reversed by maintaining either GH or IGF-I levels through exogenous administration, which suggests the defect occurs in hormone signaling. Zinc appears to be essential for IGF-I induction of cell proliferation; the site of regulation is postreceptor binding. Overall, the evidence suggests that reduced zinc availability affects membrane signaling systems and intracellular second messengers that coordinate cell proliferation in response to IGF-I.
Asunto(s)
Crecimiento/fisiología , Zinc/fisiología , Animales , División Celular/efectos de los fármacos , ADN/biosíntesis , Hormona de Crecimiento Humana/efectos de los fármacos , Hormona de Crecimiento Humana/fisiología , Humanos , Factor I del Crecimiento Similar a la Insulina/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/fisiología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Zinc/deficiencia , Zinc/metabolismoRESUMEN
IGF-I and IGF-II receptors are expressed in the small intestine of mammalian species, as are the genes to synthesize both peptides. IGF binding proteins are also expressed in the intestine. IGF-I and IGF-II mRNA are highest in fetal and newborn tissues and decrease with age. IGF-I mRNA is present in the adult small intestine, and is associated with the submucosal regions and crypt cells. IGF-I and IGF-II receptor binding to the small intestine is higher in newborn animals and decreases with age. Both receptors are more concentrated in the crypt than villus regions, but IGF-II binding is higher than IGF-I in all regions. IGF-I receptors are associated with the submucosal region of the small intestine, whereas IGF-II receptors are more abundant in the mucosal cells. Administration of IGF-I either orally or by osmotic pump generally has no affect on small intestinal weight or length, but does increase mucosal cellularity. LR3-IGF-I administration by osmotic pump affects the small intestine similarly to IGF-I, although with a higher potency. In the few studies in which IGF-II was administered, increased gut mass was observed in adult rats, but not newborn rats or pigs. Significant effects on mucosal expression of disaccharidases was achieved with either oral or subcutaneous IGF-I or oral IGF-II. Administration of IGF in models of intestinal hypertrophy and atrophy are also reviewed.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Factor II del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/genética , Intestino Delgado/citología , Animales , División Celular/fisiología , Intestino Delgado/crecimiento & desarrolloRESUMEN
Growth failure in zinc-deficient animals is associated with decreased DNA synthesis; zinc deprivation of 3T3 cells, by use of diethylenetrinitrilopentaacetate (DTPA), impairs thymidine incorporation when the cells are stimulated with fetal bovine serum (FBS). The purpose of this study was to determine the step of cell cycle progression that is affected by zinc deprivation. Swiss murine 3T3 cells were cultured for 3 d in complete media and then for 2 d in low serum media. Cells were then placed in serum-free media and stimulated in sequence with platelet-derived growth factor (PDGF; 3 h), epidermal growth factor (EGF; 0.5 h) and insulin-like growth factor-I (IGF-I; 16 h). The combination of growth factors stimulated thymidine incorporation to the same extent as 10% FBS, and DTPA or EDTA (0.6 mmol/L) inhibited thymidine incorporation. Inhibition was prevented by addition of zinc, but not calcium, iron or cadmium (0.4 mmol/L). When DTPA was present during all stages with no addition of zinc, or zinc added during the competency-priming (PDGF and EGF) step, the IGF-I step, or both steps, the zinc effect occurred at the IGF-I step. Zinc addition 4 h before the measurement of thymidine incorporation had no ameliorative effect, but the presence of zinc during the prior 12 h increased incorporation. Thus zinc exerts its major effect on DNA synthesis during the IGF-I stimulatory phase of the cell cycle. The total zinc concentration of 3T3 cells treated with DTPA for 16 h was not different from that of untreated cells; hence only a small compartment of the cell is affected by DTPA.
Asunto(s)
Células 3T3/efectos de los fármacos , Células 3T3/metabolismo , Quelantes/toxicidad , ADN/biosíntesis , Factor I del Crecimiento Similar a la Insulina/farmacología , Ácido Pentético/toxicidad , Timidina/metabolismo , Zinc/deficiencia , Animales , Células Cultivadas , Factor de Crecimiento Epidérmico/farmacología , Ratones , Factor de Crecimiento Derivado de Plaquetas/farmacología , Zinc/farmacología , Zinc/fisiologíaRESUMEN
Depletion of zinc inhibits growth in animals and proliferation of cultured cells. Additionally, zinc can serve as an antioxidant protecting many compounds, including proteins, from oxidation. Regulation of cell division also involves insulin-like growth factor type I (IGF-I) and its receptor, especially during late G1 phase, allowing progression of the cell to S phase with subsequent DNA synthesis. We examined the effects of zinc depletion from the culture media of Swiss 3T3 cells on the cell cycle and IGF-I receptor expression. Cells were exposed to reduced fetal bovine serum concentrations to induce growth arrest, then returned to normal fetal bovine serum concentrations with the divalent cation chelator diethylenetriamine pentaacetic acid. Reducing the fetal bovine serum concentration did not induce quiescence in the cells as previously suggested. Zinc depletion reduced the proliferative fraction (S and G2/M phases) of the cell cycle. The addition of glutathione to the zinc-depleted media partially returned the proliferative fraction to the control level. Fetal bovine serum deprivation reduced IGF-I receptor expression whereas the absence of zinc had little effect on receptor expression. We conclude that depletion of zinc from culture media inhibits 3T3 cell proliferation independent of insulin-like growth factor-I receptor expression, and part of this inhibition is due to the antioxidant capacity of this divalent cation.
Asunto(s)
Células 3T3/fisiología , Receptor IGF Tipo 1/metabolismo , Zinc/deficiencia , Animales , Bovinos , División Celular , Separación Celular/métodos , Quelantes/farmacología , Citometría de Flujo/métodos , Glutatión/farmacología , Ratones , Ácido Pentético/farmacología , Albúmina Sérica Bovina/farmacología , Zinc/metabolismoRESUMEN
OBJECTIVE: To determine seasonal variations in circulating concentrations of growth hormone and IGF-I in healthy, free-living elderly and to identify correlates between dietary intake, growth hormone and IGF-I concentrations in this population. METHODS: Seven-day diet records and plasma samples were collected throughout a 1-year period. Plasma growth hormone and IGF-I were determined by RIA. Dietary macronutrient intake was determined using Nutritionist IV. RESULTS: The dietary intake of the population corresponded to the established recommendations for percentage of fat, carbohydrate and protein. Carbohydrate intake differed significantly during the year, but protein and fat did not. Hormone concentrations were constant throughout the year, with no significant differences observed. No correlation between plasma growth hormone and IGF-I was observed. Growth hormone and IGF-I concentrations did not correlate with macronutrient intake, however subjects with the lowest energy intakes tended to have higher growth hormone and lower IGF-I than those with higher energy intakes. CONCLUSIONS: This study provides important information on the dietary intake and hormone concentrations in normal, healthy elderly which will be useful in comparison with persons of similar age with complicating illnesses or nutrient deficiencies.
Asunto(s)
Hormona del Crecimiento/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Estado Nutricional , Anciano , Anciano de 80 o más Años , Registros de Dieta , HumanosRESUMEN
Epidemiologic data and animal models have demonstrated a correlation between dietary fat composition and colon cancer risk. We have previously found that dietary fat alters cell proliferation in rat colon, which may influence the risk of colon cancer. Growth factors, including insulin-like growth factor (IGF) I and II, regulate the cell cycle in most mammalian tissues. Hence, we measured IGF-I and IGF-II receptor expression in colonocytes from Sprague-Dawley rats fed diets containing either beef tallow (BT) or corn oil (CO) at 12, 30 or 37% of energy for 4 wk. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using an internal standard was used to examine the relative expression of both IGF-I and II receptor mRNA in three sections of the colon. The IGF-I receptor protein was also measured by Western immunoblot. In the distal colon, IGF-I receptor gene expression and protein increased significantly as the percentage of CO increased. In both proximal and middle colon, an increased percentage of BT resulted in significantly increased IGF-II receptor expression. In the proximal colon, IGF-II receptor expression decreased with increasing CO concentration, whereas in the middle colon, rats fed 37% CO had significantly higher IGF-II receptor expression than rats fed 12 or 30% CO. IGF-II receptor gene expression in proximal colon decreased with increased fat quantity, independently of fat source, whereas in the middle colon, increased fat quantity resulted in increased IGF-II receptor expression. Thus IGF-I and IGF-II receptor mRNA and IGF-I receptor protein level in colon mucosa were significantly altered by dietary fat source and quantity, thereby suggesting a potential influence of dietary fat on the endocrine regulation of colon cell mitogenesis.
Asunto(s)
Colon/efectos de los fármacos , Grasas de la Dieta/farmacología , Receptor IGF Tipo 1/efectos de los fármacos , Receptor IGF Tipo 2/efectos de los fármacos , Animales , Bovinos , Colon/metabolismo , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/genética , Aceite de Maíz/administración & dosificación , Aceite de Maíz/farmacología , Grasas de la Dieta/administración & dosificación , Relación Dosis-Respuesta a Droga , Expresión Génica , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 2/genética , Receptor IGF Tipo 2/metabolismoRESUMEN
Zinc deficiency in rats results in impaired growth accompanied by decreased and cyclic food intake. These signs are associated with decreased plasma insulin-like growth factor-I (IGF-I), a major mediator of growth. The purpose of this study was to determine the relationship between decreased plasma IGF-I and the impairment of appetite and growth in zinc deficiency. Immature male rats were fed free choice a low zinc (<1 mg/kg) diet (-Zn) or a zinc adequate (100 mg/kg) control diet (+Zn). Plasma IGF-I concentrations were normalized in zinc-deficient rats by the following two methods: osmotic pump infusion of IGF-I (2.4 mg/kg body weight daily) and oral administration (50 mg/kg body weight twice daily) of the synthetic progestin, megestrol acetate (MA). Infusion of IGF-I for 8 d sustained plasma IGF-I concentrations in zinc-deficient rats at control levels but had no effect on either food intake or growth rate. MA administration for 8 d maintained the plasma IGF-I of deficient rats and significantly increased food intake. The early aspects of cyclic food intake were eliminated, and, after a few days, food intake of deficient rats given MA was not different than that of controls. MA increased food intake and fat deposition regardless of zinc status, but it had no effect on the growth rate of deficient rats. MA significantly decreased body weight of controls, uncoupling energy intake and gain. The results suggest that reduced food intake precedes the decreased plasma IGF-I concentration and that IGF-I is not responsible for the decreased growth and food intake of zinc-deficient rats. The appetite and growth impairment of zinc-deficient rats may arise from disrupted function of IGF-I receptors in the brain and peripheral tissues, but not from low circulating levels of IGF-I.
Asunto(s)
Estimulantes del Apetito/farmacología , Ingestión de Alimentos/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/farmacología , Acetato de Megestrol/farmacología , Zinc/deficiencia , Tejido Adiposo , Animales , Composición Corporal , Dieta , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Ratas , Ratas Wistar , Aumento de Peso/efectos de los fármacos , Zinc/administración & dosificaciónRESUMEN
The consumption of yogurt has been associated with a reduced incidence of colon cancer in population groups. Bioactive peptides produced during bacterial fermentation may alter the risk of colon cancer via modification of cell proliferation in the colon. Using our previously described cell culture model system, we have isolated a yogurt fraction that decreases cell proliferation. Yogurt was fractionated using 10,000- and 500-Da membrane dialysis. When the yogurt fraction was incubated with IEC-6 or Caco-2 cells, cell division was decreased compared with control treatments, as determined by thymidine incorporation. Cell division was not inhibited in response to a similarly produced milk fraction or in response to solutions of lactic acid. The determination of cell kinetics by flow cytometry revealed a decrease in the number of cells in the initial growth phase in response to the yogurt fraction for the IEC-6 cells, but not the Caco-2 cells. Alpha-Lactalbumin inhibited cell division of both cell lines, but beta-casein did not.
Asunto(s)
División Celular , Diálisis , Yogur , Animales , Células CACO-2 , Caseínas/farmacología , Ciclo Celular , División Celular/efectos de los fármacos , Línea Celular , ADN/biosíntesis , Electroforesis en Gel de Poliacrilamida , Fermentación , Citometría de Flujo , Humanos , Concentración de Iones de Hidrógeno , Lactalbúmina/farmacología , Péptidos/análisis , Péptidos/farmacología , Yogur/análisisRESUMEN
We have previously observed changes in colon cell proliferation in growing rats fed different levels of dietary fat as beef tallow or corn oil. Here we measured cellular proliferation at 18 and 30 weeks in the colon of rats fed beef tallow or corn oil and treated with the chemical carcinogen azoxymethane. Additionally, we assessed colon cell membrane lipid composition after 18 weeks on the defined diets and tumor incidence at 30 weeks. Dietary fat type and quantity significantly affected colon cell proliferation. Membrane phospholipids and free fatty acids were significantly affected by fat type. Tumor incidence was not affected by diet type. We conclude that dietary fat induces changes in cell membrane lipid composition and proliferation in the colon and these changes may be related to the development of tumors.
Asunto(s)
Colon/metabolismo , Neoplasias del Colon/metabolismo , Grasas de la Dieta/farmacología , Lípidos de la Membrana/metabolismo , Antígeno Nuclear de Célula en Proliferación/biosíntesis , Animales , División Celular/efectos de los fármacos , Colon/citología , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Masculino , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
An experiment was conducted to characterize the effects of postruminal administration of casein, glutamine, cornstarch, and water on protein turnover and in vitro muscle cell proliferation. Four MARC III steers (205 kg) were fed a protein-restricted bromegrass hay-based diet (2.86 Mcal of DE/kg and 13.6 g of N/kg). Using a 4 x 5 Latin square arrangement balanced for residual effects, casein and glutamine, equal to 50% of basal dietary nitrogen intake, cornstarch, isocaloric with casein infusion, or an equal volume of water was continuously infused into the abomasum of steers. Blood samples, collected every 2 h for 24 h after 7 d of infusion, were tested for the effect on cell cycle kinetics and myotube protein turnover. Urine and feces were also collected for 4 d after blood sampling for nitrogen balance and fractional skeletal muscle degradation. The mitogenic activity and ability of serum to influence rate of myoblast proliferation in a dose-dependent manner was influenced (P < .05) by infusate: casein > cornstarch > glutamine = water. Abomasal infusion of casein and cornstarch increased (P < .05) in vitro muscle protein synthesis and decreased (P < .05) in vitro muscle protein degradation, whereas abomasal glutamine infusion only increased (P < .05) in vitro muscle protein synthesis. Abomasal glutamine infusion decreased (P < .05) fractional skeletal muscle protein degradation and synthesis; however, fractional muscle protein accretion tended to increase due to a greater decline in fractional muscle protein degradation. In contrast, abomasal casein infusion increased (P < .05) fractional skeletal muscle protein synthesis, breakdown, and accretion. These results suggest that muscle hypertrophy may be regulated by serum constituents whose activity is affected by postruminal amino acid flow.
Asunto(s)
Aminoácidos/farmacología , Proteínas Musculares/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Aminoácidos/metabolismo , Animales , Caseínas/metabolismo , Caseínas/farmacología , Bovinos , División Celular/efectos de los fármacos , División Celular/fisiología , Línea Celular , Relación Dosis-Respuesta a Droga , Duodeno/metabolismo , Ácidos Grasos no Esterificados/sangre , Heces/química , Glutamina/metabolismo , Glutamina/farmacología , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Nitrógeno/análisis , Nitrógeno/orina , Ratas , Albúmina Sérica Bovina/farmacología , Almidón/metabolismo , Almidón/farmacología , Factores de TiempoRESUMEN
Previous studies examining the response of brain lipids to dietary fat modification have not quantified neutral lipids such as diacylglycerols (DG) and triacylglycerols (TG). In this study we measured the concentrations of neutral lipids and phospholipids, and their fatty acid profiles, in the cerebra of rats fed defined diets containing either beef tallow (BT) or corn oil (CO) at 12% or 37% of energy. The diets were fed to rat pups beginning at 18 d of age and continued for 31 wk. The proportion of brain linoleic acid [18:2(n-6)] in TG from CO-fed rats was two- to fourfold greater than in BT-fed rats. Although 18:2(n-6) levels were higher in serum and brain TG of rats fed CO, differences in other TG fatty acid concentrations in serum were not reflected in the brain. Rats fed CO diets had higher concentrations of 18:2(n-6) in brain phospholipids as well as neutral lipids compared with rats fed BT diets, and the differences were greater in rats fed 37% rather than 12% of energy as fat. Differences in other polyunsaturated fatty acids associated with dietary fat composition were also found among the brain phospholipids. Most notably, the concentration of docosapentaenoic acid [22:5(n-6)] in brain phospholipids was highest in rats fed diets containing the lowest concentrations of alpha-linolenic acid [18:3(n-3)]. A concentration of 0.1 mg 18:3(n-3)/g diet appeared to be adequate to prevent elevation of 22:5(n-6) in brain phospholipids. These results demonstrate that consumption of a low fat diet (12% of energy) primarily comprised of saturated fats may potentiate an 18:3(n-3) deficiency in brain of rats.
Asunto(s)
Encéfalo/metabolismo , Aceite de Maíz/farmacología , Grasas de la Dieta/farmacología , Grasas , Metabolismo de los Lípidos , Fosfolípidos/metabolismo , Animales , Bovinos , Diglicéridos/metabolismo , Ingestión de Energía , Ácidos Grasos/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Masculino , Fosfolípidos/sangre , Ratas , Ratas Sprague-Dawley , Triglicéridos/sangre , Triglicéridos/metabolismoRESUMEN
Consumption of fermented dairy foods has been linked to reduced incidence of colon cancer in population groups. Recently, biologically active compounds have been isolated from these products. Bacterial proteinases, produced by dairy starter cultures, generate a variety of peptides from casein. Some of these casein-derived peptides are likely to alter intestinal cell kinetics. Effects on colon cell kinetics because of the presence of casein-derived peptides may be a mechanism through which fermented dairy foods reduce the risk of colon cancer. We have used two intestinal cell lines (IEC-6 cells, derived from normal rat intestine, and Caco-2 cells, derived from human colon adenocarcinoma) to identify casein peptides that affect intestinal cell kinetics. Cell culture media containing casein were inoculated with three commercial starter cultures and incubated for 4, 8, or 24 h. The bacteria-conditioned media were then filter-sterilized and incubated with the intestinal cells for 6 or 24 h. Rates of [3H]thymidine incorporation and cell cycle kinetics determined by flow cytometry were affected by the culture-modified media in both cell lines. The IEC-6 cells tended to reduce, and Caco-2 cells to increase, rates of cell division after exposure to the media. Intestinal cell response varied among the starter cultures. The results support the use of intestinal cell cultures to identify casein peptides generated by dairy starter cultures, which affect intestinal cell kinetics.
Asunto(s)
Bacterias/metabolismo , Caseínas/metabolismo , Péptidos/metabolismo , Adenocarcinoma , Animales , Ciclo Celular , Línea Celular , Neoplasias del Colon , Medios de Cultivo Condicionados , ADN/biosíntesis , Humanos , Hidrólisis , Cinética , Lactobacillus/metabolismo , Metilnitronitrosoguanidina/farmacología , Ratas , Streptococcus/metabolismo , Células Tumorales CultivadasRESUMEN
Holstein steers fed protein-restricted diets were used to evaluate protein realimentation and site of serum collection on the ability of calf serum to affect proliferation, protein synthesis and degradation in L6 myoblast cell culture bioassay. In Experiment 1, five steers (average weight 227 kg) received continuous abomasal infusion of 4 L of water or casein (50% of basal dietary nitrogen intake) in a switchback design. Serum was collected 2 d before and after 1, 3, 5, 7 and 9 d of infusion. Abomasal casein infusion increased serum mitogenic activity, nitrogen retention (119%) and total post-ruminal amino acid flow (78%). In Experiment 2, serum was collected from the jugular and femoral veins and the carotid artery before and after 7 d of abomasal casein infusion. Serum from calves abomasally infused with casein increased myoblast proliferation (jugular > femoral > carotid) and protein synthesis and decreased protein degradation in cultured myotubes. The addition of test calf serum inhibited the mitogenic activity of control calf serum. Results suggest that post-ruminal amino acid flow and site of serum collection alter the ability of serum to influence cell culture bioassays.
Asunto(s)
Fenómenos Fisiológicos Sanguíneos , Caseínas/farmacología , Bovinos/crecimiento & desarrollo , Mitosis/efectos de los fármacos , Músculos/citología , Aminoácidos/sangre , Animales , Bioensayo , Sangre/efectos de los fármacos , Arterias Carótidas , Caseínas/administración & dosificación , Bovinos/sangre , Ciclo Celular/efectos de los fármacos , Células Cultivadas , Cromo/análisis , Proteínas en la Dieta/administración & dosificación , Proteínas en la Dieta/farmacología , Heces/química , Vena Femoral , Infusiones Parenterales/veterinaria , Factor I del Crecimiento Similar a la Insulina/análisis , Venas Yugulares , Masculino , Desarrollo de Músculos , Proteínas Musculares/metabolismo , Músculos/efectos de los fármacos , Músculos/metabolismo , Nitrógeno/análisis , Distribución AleatoriaRESUMEN
The effects of corn oil and beef tallow on the proliferation of colon mucosal cells in rats were investigated. In protocol 1, rats were fed diets containing 12 or 38% kJ from fat supplied by either corn oil or beef tallow. Colon crypt column cell number was examined histologically. The source of dietary fat had no effect on the number of cells per crypt column, but rats fed 38% fat had significantly fewer cells per crypt column in the proximal colon than rats fed 12%. Protocol 2 examined the effects of diets containing corn oil or beef tallow at 12, 30, or 37% kJ on the percentage of colon cells in phases of the cell cycle using flow cytometry and expression of proliferating cell nuclear antigen (PCNA). Rats fed corn oil had more cells in S phase compared to rats fed beef tallow. Rats fed 30 or 37% fat had more cells in G1 and fewer cells in G2 + M compared to rats fed 12%. Animals consuming the 12% corn oil diet or the 37% beef tallow diet had the fewest colon cells expressing PCNA, while those animals consuming the 37% corn oil diet or the 12% beef tallow diet had the greatest number of cells expressing PCNA. Based on combined interpretation of PCNA and cell cycle phases, the results suggest that diets high in saturated fat result in reduced colon cell proliferation whereas diets high in unsaturated fat do not.
Asunto(s)
Colon/citología , Grasas de la Dieta/farmacología , Animales , Peso Corporal , Bovinos , División Celular/efectos de los fármacos , Colon/química , Colon/fisiología , Aceite de Maíz/administración & dosificación , Aceite de Maíz/farmacología , Grasas de la Dieta/administración & dosificación , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos , Grasas/administración & dosificación , Grasas/farmacología , Citometría de Flujo , Masculino , Microvellosidades/efectos de los fármacos , Microvellosidades/ultraestructura , Antígeno Nuclear de Célula en Proliferación/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
This study was undertaken to correlate changes in insulin, IGF-1, and IGF-2 receptors in enterocytes both during the phase of active hyperplasia (protocol 1) and the phase of initiation of hyperplasia (protocol 2) induced by 60% proximal jejunoileal resection in rats. Hormone binding to purified receptor preparations, indirect immunofluorescence analysis by flow cytometry, and immunohistochemistry were used to identify receptor changes. Insulin and IGF-2 receptor binding were increased in the intestine two days after surgery and prior to increased cell mass. The number of cells expressing insulin and IGF-1 receptors increased two- and three-fold between 12 and 36 hr after resection, whereas IGF-2 receptors were maintained throughout the 48-hr period. A significant increase in immunoreactive IGF-2 receptors in both the villus and crypt regions of the jejunum and ileum was observed 12 hr after resection, and this increase was maintained in the crypt region of the jejunum through 48 hr. Therefore, insulin and IGF-2 receptors appear to be important in the initiation of cellular hyperplasia following resection.
Asunto(s)
Insulina/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/patología , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 2/metabolismo , Animales , División Celular , Citometría de Flujo , Hiperplasia/metabolismo , Hiperplasia/patología , Inmunohistoquímica , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Intestino Delgado/cirugía , Masculino , Ratas , Ratas WistarRESUMEN
The electrical interaction between the heart and an artificial pacemaker is often complex. Because of the sophistication and diversity of dual-chamber device algorithms, even experienced cardiologists can have difficulty interpreting paced electrocardiograms (ECG's). In order to study heart-pacemaker interaction (HPI), a computer model of the cardiac conduction system has been developed which includes the effects of artificial pacemaker function and failure. The stochastic network model of cardiac conduction consists of five vertices, each representing a functional electrophysiologic element. Electrophysiologic multidimensional conditional probability functions determine the depolarization status of each vertex. The atrioventricular (AV) node is emulated using a mathematical model which includes the influence of past cycle lengths on AV nodal conduction time. Twenty-three classes of arrhythmias may be simulated and, for pacing simulation, one of 12 antibradycardia pacing modes may be chosen. Random effects of pacemaker malfunction including oversensing, undersensing, or failure-to-capture may be simulated through the use of probability distribution functions. This model should prove useful in the development of pacemaker algorithms, determining patient-specific pacemaker therapy, and predicting causes for apparent pacemaker malfunction. The model has been used in the development of an expert system to analyze paced ECG's for pacemaker function and malfunction.
Asunto(s)
Simulación por Computador , Electrocardiografía , Modelos Cardiovasculares , Marcapaso Artificial , Procesos Estocásticos , Algoritmos , Arritmias Cardíacas/fisiopatología , Diseño de Equipo , Falla de Equipo , Sistemas Especialistas , Sistema de Conducción Cardíaco/fisiología , Frecuencia Cardíaca , Humanos , Marcapaso Artificial/efectos adversosRESUMEN
It is presently recommended that the general US population reduce the consumption of dietary lipid in order to reduce the risk of several chronic diseases, although the mechanism(s) through which dietary factors alter cellular function remain unclear. Dietary lipid composition has been shown to alter the plasma membrane lipid composition of adipocytes, muscle and other tissues. These changes in membrane lipid composition have been correlated with altered insulin receptor binding and signal transduction. Insulin receptors are present on mucosal cells of the intestinal tract, although their role in this tissue is not fully understood. We have fed rats diets containing 6, 31.4 or 76% of calories from lard (Protocol 1) and found insulin binding to be increased in the duodenum and decreased in the colon of rats fed the high-fat diet. Additionally, we compared diets containing either 12 or 37.6% of calories from beef tallow (saturated fatty acids or SFA) or corn oil (polyunsaturated fatty acids or PUFA; Protocol 2) and found insulin binding in the jejunum to be significantly decreased by a low SFA or high PUFA diet relative to the low PUFA diet. These results suggest that intestinal insulin receptors are responsive to dietary lipid quantity and quality which may have implications as to the role of dietary factors in modifying nutrient transport and/or risk of intestinal disease.