RESUMEN
PURPOSE: Differences in resting energy expenditure (REE) between men and women mainly result from sex-related differences in lean body mass (LBM). So far, a little is known about whether REE and LBM are reflected by a distinct human metabolite profile. Therefore, we aimed to identify plasma and urine metabolite patterns that are associated with REE and LBM of healthy subjects. METHODS: We investigated 301 healthy male and female subjects (18-80 years) under standardized conditions in the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study. REE was determined by indirect calorimetry and LBM by dual X-ray absorptiometry. Fasting blood and 24 h urine samples were analyzed by targeted and non-targeted metabolomics methods using GC × GC-MS, GC-MS, LC-MS, and NMR. Data were evaluated by predictive modeling of combined data using different machine learning algorithms, namely SVM, glmnet, and PLS. RESULTS: When evaluating data of men and women combined, we were able to predict REE and LBM with high accuracy (> 90%). This, however, was a clear effect of sex, which is supported by the high degree of overlap in identified important metabolites for LBM, REE, and sex, respectively. The applied machine learning algorithms did not reveal a metabolite pattern predictive of REE or LBM, when analyzing data for men and women, separately. CONCLUSIONS: We could not identify a sex independent predictive metabolite pattern for REE or LBM. REE and LBM have no impact on plasma and urine metabolite profiles in the KarMeN Study participants. Studies applying metabolomics in healthy humans need to consider sex specific data evaluation.
Asunto(s)
Metabolismo Basal/fisiología , Composición Corporal/fisiología , Metaboloma/fisiología , Absorciometría de Fotón , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Factores Sexuales , Adulto JovenRESUMEN
To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.
Asunto(s)
Biomarcadores , Inflamación/metabolismo , Fenómenos Fisiológicos de la Nutrición , Biomarcadores/sangre , Biomarcadores/metabolismo , Dieta/efectos adversos , Alimentos/efectos adversos , Humanos , Inflamación/patologíaRESUMEN
The use of protective, probiotic cultures in poultry farming may serve as a useful strategy to improve food product safety from the beginning of the food chain and thus to protect consumer health. The objective of this study was to investigate the effect of the probiotic strain Bifidobacterium longum PCB133 on innate and adaptive immune responses in turkeys beginning at 2 wk of age, under farming conditions. The vaccination efficiency against Newcastle disease virus served as the primary endpoint. At 2 wk of age, male turkeys (British United Turkey Big 6 strain) were randomly assigned to the control (n = 25) or probiotic group (n = 25). Turkeys in the probiotic group received the probiotic B. longum PCB133 (at least 3 × 10(7) cfu/d) incorporated into the daily feed ration for 5 wk, until slaughter at 7 wk of age. At the beginning of the probiotic intervention, birds in both groups were vaccinated against Newcastle disease. Birds were weighed weekly throughout the intervention period, and finally blood sera and heparinized blood were collected for immune function tests (lymphocyte proliferation, phagocytosis, respiratory burst), and for the determination of Newcastle disease virus antibody titers. No effects on BW gain and on the proliferation of blood lymphocytes were elicited by the 5-wk intervention with the probiotic. Concerning the primary endpoint of the study (i.e., specific antibody production as a response to vaccination against Newcastle disease), no adjuvant effect of the probiotic could be determined. In addition, innate immune functions tested were not significantly affected. In conclusion, first scientific evidence on the application of the probiotic strain B. longum PCB133 in turkeys beginning at 2 wk of age does not support an improvement in live performance, humoral immunity, or innate immunity.
Asunto(s)
Inmunidad Adaptativa , Bifidobacterium , Inmunidad Innata , Probióticos/administración & dosificación , Pavos/inmunología , Animales , Dieta , Activación de Linfocitos/inmunología , Masculino , Enfermedad de Newcastle/inmunología , Enfermedad de Newcastle/prevención & control , Virus de la Enfermedad de Newcastle/inmunología , Vacunación/veterinariaRESUMEN
The therapeutic efficacy of pooled bovine colostrum for the control of cryptosporidiosis was investigated during murine acquired immunodeficiency syndrome in female C57Bl/6 mice. Mice were infected with LP-BM5 murine leukemia retrovirus for four months and then inoculated with Cryptosporidium parvum oocysts. Persistent cryptosporidiosis was established in all retrovirus immunosuppressed mice, while control mice were refractory to infection. Parasite colonization of intestinal villi was significantly (P < 0.05) reduced in immunosuppressed animals that received dietary supplemental pooled bovine colostrum compared with to those that did not receive colostrum treatment. Similarly, shedding of oocysts in the feces of immunosuppressed animals that received dietary pooled bovine colostrum was significantly (P < 0.05) reduced compared with those that did not at 26 days post-parasite challenge. Since the nonimmune bovine colostrum contained no anti-Cryptosporidium antibodies, this suggests that passively transferred antibodies alone are unlikely to have provided the improved resistance shown in this study.
Asunto(s)
Calostro/inmunología , Criptosporidiosis/prevención & control , Cryptosporidium parvum/inmunología , Síndrome de Inmunodeficiencia Adquirida del Murino/inmunología , Animales , Bovinos , Criptosporidiosis/complicaciones , Criptosporidiosis/inmunología , Heces/parasitología , Femenino , Mucosa Intestinal/parasitología , Ratones , Ratones Endogámicos C57BL , Microvellosidades/parasitología , Síndrome de Inmunodeficiencia Adquirida del Murino/complicacionesRESUMEN
Aflatoxin B1 (AFB1) is toxic to the systemic immune system in various animal species, whereas little is known about its effect on the gut-associated lymphoid tissue (GALT). It may be hypothesized that the toxicity of AFB1 and its locally generated metabolites in the intestinal tissue may result in a disturbed intestinal integrity and, subsequently, in an impaired immune response towards dietary proteins. The objective of our study was to investigate the toxic effect of short-term moderate AFB1 exposure on the intestinal epithelium and on the immune cells associated with the intestinal tract. The toxicological potential of AFB1 and its metabolites to the intestinal epithelium was determined by measuring viability and genotoxic damage in isolated jejunal epithelial cells (comet assay) after 30 min incubation in vitro. In vivo toxicology studies were carried out with Brown Norway (BN) rats, which were exposed orally once a week with AFB1 (1 x 100 microg/kg body weight (b.w.)/week) for 5 consecutive weeks. Viability and genotoxicity were measured in explanted jejunal epithelial cells. For studying the effectiveness of AFB1 on immunological parameters BN rats were treated with a high (study 1: 1 x 1 mg/kg b.w./week) or a low (study 2: 1 x 100 microg/kg b.w./week) AFB1 dose for 5 consecutive weeks with or without ovalbumin (OVA). Mesenteric lymphocytes were isolated and proliferative responsiveness, secretion of interferon-gamma, and changes in lymphocyte subpopulations as well as mucosal mast cell specific protease and anti-OVA specific antibody concentrations were measured. In vitro, AFB1 ( >30 microM) induced genotoxicity in rat jejunal epithelial cells. The oral administration of AFB1 (1 x 100 microg/kg b.w./week) did not induce DNA damage in jejunal epithelial cells. The high AFB1 dose increased the number of CD8+ and CD8/CD71 + cells in mesenteric lymph nodes. The immune response towards OVA was not affected. The low AFB1 dose only reduced the proliferative responsiveness of mesenteric lymphocytes (P < 0.05). Serum concentrations of anti-OVA specific IgE antibody, of RMCPII, and the capacity of mesenteric lymphocytes to produce interferon-gamma were not impaired by AFB1. In conclusion, exposure to moderate doses of AFB1 does not damage the intestinal epithelium and has only minor effects on the GALT. The low exposure, as it may predominantly occur in western countries, does not appear to increase the risk for sensitization to dietary antigens.
Asunto(s)
Aflatoxina B1/toxicidad , Mucosa Intestinal/efectos de los fármacos , Ganglios Linfáticos/efectos de los fármacos , Aflatoxina B1/inmunología , Aflatoxina B1/metabolismo , Animales , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocinas/biosíntesis , Daño del ADN , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Técnica del Anticuerpo Fluorescente , Inmunoglobulina E/análisis , Inmunoglobulina E/inmunología , Inmunoglobulina G/análisis , Inmunoglobulina G/inmunología , Interferones/biosíntesis , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Yeyuno/citología , Yeyuno/efectos de los fármacos , Yeyuno/inmunología , Ganglios Linfáticos/citología , Ganglios Linfáticos/inmunología , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Masculino , Mastocitos/enzimología , Mesenterio , Metaloendopeptidasas/metabolismo , Pruebas de Mutagenicidad , Ovalbúmina/inmunología , Ratas , Ratas Endogámicas BNRESUMEN
Cocaine acts directly on lymphoid cells and indirectly modulates the immune response by affecting the level of neuroendocrine hormones. In vitro, very high concentrations of cocaine inhibit different immune responses, while plasma levels following cocaine use have no effect. The results of the few published in vivo studies are contradictory, showing stimulatory, suppressive or no effect on lymphoid cells. The indirect effects of cocaine on the immune system could be mediated by ACTH, beta-endorphin and corticosterone. Anorectic effect associated with nutritional deficiencies of drug users could additionally affect the immune response by cocaine.
Asunto(s)
Cocaína/farmacología , Hormonas/metabolismo , Sistema Inmunológico/efectos de los fármacos , Animales , Humanos , Sistema Inmunológico/metabolismo , Linfocitos/efectos de los fármacos , Sistemas Neurosecretores/efectos de los fármacos , Estado Nutricional , Trastornos Relacionados con Sustancias/metabolismoRESUMEN
C57BL/6 female mice were fed a liquid ethanol (ETOH) diet (27% of calories derived from ETOH) for 5 months as an animal model of chronic alcohol use. A isocaloric liquid diet supplemented with maltose dextran was fed to controls. Splenocytes from ETOH-treated and control mice, and purified macrophages from normal mice and retrovirus infected mice were exposed in vitro to various concentrations of ETOH (0.1-1.0% v/v). The effect of chronic ETOH exposure in vivo, and of in vitro treatment with ETOH on tumor necrosis factor (TNF) and gamma-interferon (IFN) production by cultured murine splenocytes and purified macrophages was investigated. Dietary ethanol did not significantly affect in vitro TNF or IFN production. However, TNF and IFN production by splenocytes from mice fed either the ETOH or control diet decreased significantly when the cells were cultured with ETOH and stimulated with LPS or Con A in vitro. Thus ETOH in vitro directly down regulates TNF and IFN secretion by LPS- or Con A-stimulated spleen cells. ETOH treatment in vitro did not significantly change TNF production by purified peritoneal macrophage (PM) and thioglycollate-induced peritoneal macrophage (TPM) from normal mice, but increased TNF production by alveolar macrophage (AM). Although murine retrovirus infection per se increased TNF production it did not change the responsive pattern in TNF production of PM and TPM to ETOH in vitro and reduced the TNF production of AM.
Asunto(s)
Etanol/farmacología , Interferón gamma/efectos de los fármacos , Macrófagos/efectos de los fármacos , Bazo/efectos de los fármacos , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Animales , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Interferón gamma/biosíntesis , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Bazo/citología , Bazo/inmunología , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
An experimental model which resembles human drug addiction was developed to study the effect of chronic drug (cocaine or morphine) administration on the immune system. As malnutrition has been associated with drug use, a low protein diet has been evaluated for its contribution to the impairment of the immune system during cocaine/morphine addiction. Female C57BL/6 mice that received a 20% or 4% casein diet were studied. Both drugs were administered intraperitoneally daily for 11 weeks and drugs were administered in increasing daily doses, beginning after 3 weeks of diet consumption. Doses of cocaine began with 5 mg/kg body weight and reached the maximum dose of 40 mg/kg/day at the fourth week. Doses of morphine gradually increased from 10 mg/kg to 75 mg/kg body weight with the maximum dose reached after 5 weeks of treatment. Cocaine administration reduced body weight, particularly in the low protein diet group, and spleen weight in protein malnourished mice. Cocaine as well as saline injected mice showed a decrease in the percentage of CD4+ CD8+ and Mac-1+ cells and an increase in B cells in the spleens of well nourished mice. Morphine-treated mice showed similar results to those observed in cocaine or saline treated mice. These results suggest that cocaine, morphine or saline injection can alter the percentage of cells that express a defined phenotype independently of the nutritional status of the subject. Moreover, the effect appears dependent on a stress mediated process.
Asunto(s)
Cocaína/farmacología , Subgrupos Linfocitarios/inmunología , Morfina/farmacología , Trastornos Nutricionales/inmunología , Bazo/inmunología , Trastornos Relacionados con Sustancias/inmunología , Animales , Antígenos de Superficie/inmunología , Modelos Animales de Enfermedad , Femenino , Recuento de Leucocitos , Subgrupos Linfocitarios/efectos de los fármacos , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Trastornos Nutricionales/patología , Tamaño de los Órganos/efectos de los fármacos , Bazo/citologíaRESUMEN
OBJECTIVE: To investigate whether the daily intake of red wine (RW) at a dose which inversely correlates with cardiovascular disease (CVD) risk modulates immune functions in healthy men. DESIGN: Randomized single-blind trial with four intervention periods. SETTING: The Institute of Nutritional Physiology, Federal Research Centre for Nutrition, Karlsruhe, Germany. SUBJECTS: A total of 24 healthy males with moderate alcohol consumption patterns were recruited and all completed the study. INTERVENTION: Participants consumed 500 ml of RW (12% ethanol (ETOH)) or 500 ml of a 12% ETOH dilution per day for a period of 2 weeks. To control the potential effects of RW polyphenols, accordingly 500 ml/day of dealcoholized red wine (DRW) and of red grape juice (RGJ) were given. The following immune parameters were measured before beverage consumption and at 1 and 2 weeks following beverage consumption: phagocytic activity of neutrophils and monocytes, production of tumor necrosis factor-alpha (TNFalpha), interleukin-2 and -4, transforming growth factor-beta, TNFalpha mRNA, lymphocyte proliferation, lytic activity of natural killer cells, and percentage of apoptotic lymphocytes. RESULTS: Consumption of a moderate volume of alcohol with RW and with a 12% ETOH dilution had no effect on immune functions in healthy males. Consumption of polyphenol-rich beverages (DRW and RGJ) did not affect immunity-related parameters. CONCLUSIONS: Daily moderate consumption of alcohol and of RW for 2 weeks at doses which inversely correlate with CVD risk has no adverse effects on human immune cell functions. Polyphenol-rich beverages such as RGJ and DRW further do not suppress immune responses in healthy men.
Asunto(s)
Consumo de Bebidas Alcohólicas/inmunología , Citocinas/biosíntesis , Inmunidad Celular/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Vino , Adulto , Estudios Cruzados , Flavonoides/administración & dosificación , Humanos , Masculino , Fenoles/administración & dosificación , Polifenoles , Método Simple CiegoRESUMEN
Food contaminants may contribute to the recent increased incidence of food allergies. We have investigated this hypothesis experimentally. It was our objective to determine whether toxicity to the intestinal tissue by orally applied mercury (Hg) could modulate the immune response to food allergens. Effective mechanisms were studied with functional immunological and toxicological parameters. Brown Norway rats were immunized intraperitoneally by ovalbumin (OVA). Before oral challenge with OVA, immunized and non-immunized animals were exposed to HgCl2. Immunological responses were measured by enzyme-linked immunosorbent assays [anti-OVA-IgE and-IgG, rat mast cell protease II (RMCPII), interferon-gamma, interleukin-4, lymphocyte proliferation] and by flow cytometry (lymphocyte subpopulations). Toxicity of Hg to the intestinal barrier was determined by measuring viability, DNA damage and induction of glutathione S-transferase in isolated intestinal epithelial cells and lymph node cells, and by measuring permeability, short-circuit current and tissue conductance of the intact intestinal epithelium. A single high oral dose of HgCl2 enhanced the serum concentrations of anti-OVA-IgE and IgG (P < 0.05) and of RMCPII (P < 0.05) in immunized rats. The treatment resulted in a higher number of CD4/CD25+ T cells in the lymph nodes (P < 0.05). The multiple application of low HgCl2 doses (5 x 0.2 mg/kg body weight) only resulted in an elevated RMCPII serum concentration (P < 0.05). Neither treatment schedules impaired proliferation and cytokine production of lymphocytes. In non-immunized rats only minor immunological changes were observed. Oral HgCl2 induced genotoxic damage in lymph node cells and in jejunal epithelial cells (P < 0.05). Moreover, HgCl2 increased the permeability of intestinal epithelial tissue and of Caco-2 monolayers and was genotoxic and cytotoxic to isolated intestinal epithelial cells in vitro. In conclusion, these studies indicate that the food contaminant Hg can stimulate the immune response to OVA in immunized rats. One possible mechanism could be the toxicity of Hg to the intestinal epithelial and the lymph node cells. Whether humans with allergies respond to high oral doses of Hg in a similar way needs to be investigated in further studies.
Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Hipersensibilidad a los Alimentos/inmunología , Inmunidad Mucosa/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Mastocitos/efectos de los fármacos , Mercurio/toxicidad , Ovalbúmina/inmunología , Animales , Antígenos de Superficie/biosíntesis , Células CACO-2 , Permeabilidad de la Membrana Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Inducción Enzimática/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Fluoresceína/metabolismo , Glutatión Transferasa/metabolismo , Humanos , Interferón gamma/biosíntesis , Interleucina-4/biosíntesis , Activación de Linfocitos , Masculino , Mesenterio/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Serina Endopeptidasas/sangreRESUMEN
The objective of this study was to determine if chronic ethanol consumption could modify cell populations in the Peyer's patches (PP), which could favor pathogenic or opportunistic infections in mice, as seen in chronic alcohol addicts. Young C57BL/6 mice receiving the Lieber-DeCarli diet (36% of calories as ethanol) for 5 weeks presented a significant decrease in the total number of cells in the PP. Mature FVB mice receiving the Lieber-DeCarli diet for 19 weeks presented a highly significant decrease in the total number of cells and in the absolute number of T and B cells in the PP. Young C57BL/6 mice receiving the 100% NRC (30% ethanol) or the 60% NRC (30% ethanol) diets for 7 weeks presented alterations in the T and B cell phenotype comparable with the alterations observed in mice receiving the Lieber-DeCarli diet for 19 weeks. As less alcohol for a shorter time caused similar changes to those seen with a highly micronutrient enriched diet with more alcohol for a longer consumption period, micronutrient supplementation may overcome some immune damage found in animal models of alcoholism. Our data indicated that ethanol administration altered the mucosal immune system at the level of the PP, the site for antigen presentation and induction of a mucosal immune response.
Asunto(s)
Etanol/administración & dosificación , Recuento de Linfocitos , Ganglios Linfáticos Agregados/citología , Fenotipo , Alcoholismo/inmunología , Animales , Linfocitos B , Dieta , Ingestión de Energía , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Linfocitos TRESUMEN
Alcoholics have frequent bronchial and intestinal bacterial-associated infections compromising the mucosal-associated lymphoid tissues. Alcoholics also suffer undernutrition due to changes in their lifestyles. Thus, we studied the intestinal mucosa-associated lymphoid tissues using two types of diets in young and mature mice. The objective was to elucidate if ethanol consumption alters the T and B cell populations in the intestine, and if the alteration could be associated with the age and/or the nutritional status of the host. There was an increase in the number of CD8+ cells per field in the intestinal lamina propria (ILP) of young mice consuming ethanol, with no change in CD4+ and IgA+ cells in the ILP and CD4+ and CD8+ cells in the intestinal intraepithelium (IE). There was also an increase in the number of CD4+ and CD8+ cells in the ILP of well-nourished mature mice consuming ethanol, and an increase in the number of CD4+ cells in the ILP of undernourished mice. An increase in the number of CD8+ cells in the IE was also detected in the well-nourished group consuming ethanol. Therefore, we conclude that ethanol administration alters the intestinal mucosa-associated lymphoid tissue.
Asunto(s)
Envejecimiento/inmunología , Etanol/farmacología , Sistema Inmunológico/efectos de los fármacos , Mucosa Intestinal/inmunología , Animales , Linfocitos B/inmunología , Antígenos CD4/análisis , Antígenos CD8/análisis , Dieta , Femenino , Inmunoglobulina A/análisis , Mucosa Intestinal/citología , Ratones , Ratones Endogámicos C57BL , Linfocitos T/inmunologíaRESUMEN
The D-A-CH reference value (D-A-CH arises from the initial letters of the common country identification for the countries Germany (D), Austria (A) and Switzerland (CH)) for folate equivalents had been set at 400 µg/d for adults in the year 2000. By that time, the prevention of cardiovascular diseases through reduction of homocysteine was considered an important target of the reference value. Since that time a number of research papers revealed that in spite of an inverse association between folate-rich diet and chronic diseases, a preventive effect of folic acid intake on cardiovascular events was not supported by randomized controlled trials, and the reduction of plasma homocysteine levels to around 10-12 µmol/l did not reduce the risk for thromboembolic and cardiovascular diseases in persons already affected by these diseases. These results together with the observation that folate intakes below 400 µg/d result in a sufficient folate status justified a review of the current literature and-consequently-a reduction of the reference value to 300 µg/d for adults. This reference value is expressed as dietary folate equivalents that take into account the difference in bioavailability between folic acid and all types of folates in food. The recommendation to take a daily supplement of 400 µg of synthetic folic acid for women who intend to get pregnant and until the end of the first trimester of pregnancy is maintained.
Asunto(s)
Dieta , Suplementos Dietéticos , Deficiencia de Ácido Fólico/prevención & control , Ácido Fólico/administración & dosificación , Política Nutricional , Necesidades Nutricionales , Adolescente , Adulto , Austria , Disponibilidad Biológica , Niño , Preescolar , Femenino , Alemania , Humanos , Lactante , Masculino , Estado Nutricional , Atención Preconceptiva , Embarazo , Complicaciones del Embarazo/prevención & control , Suiza , Adulto JovenAsunto(s)
Cannabidiol/farmacología , Citocinas/metabolismo , Dronabinol/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Adulto , Anciano , Dimetilsulfóxido/farmacología , Humanos , Interferón gamma/metabolismo , Interleucina-1/metabolismo , Interleucina-2/metabolismo , Leucocitos Mononucleares/metabolismo , Activación de Linfocitos/efectos de los fármacos , Persona de Mediana Edad , Mitógenos/farmacología , Factor de Necrosis Tumoral alfa/metabolismoAsunto(s)
Síndrome de Inmunodeficiencia Adquirida , Cantaxantina/farmacología , Modelos Animales de Enfermedad , Inmunocompetencia/efectos de los fármacos , Melanoma Experimental/complicaciones , Síndrome de Inmunodeficiencia Adquirida del Murino/complicaciones , Animales , Peso Corporal , Citocinas/metabolismo , Femenino , Fibrosarcoma/complicaciones , Fibrosarcoma/inmunología , Fibrosarcoma/patología , Rechazo de Injerto/efectos de los fármacos , Interferón gamma/metabolismo , Virus de la Leucemia Murina/patogenicidad , Melanoma Experimental/inmunología , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL/inmunología , Síndrome de Inmunodeficiencia Adquirida del Murino/inmunología , Síndrome de Inmunodeficiencia Adquirida del Murino/patología , Trasplante de Neoplasias , Tamaño de los Órganos/efectos de los fármacos , Bazo/patologíaAsunto(s)
Grano Comestible/efectos adversos , Inhibidores Enzimáticos/efectos adversos , Lectinas/efectos adversos , Medios de Comunicación de Masas , Ácido Fítico/efectos adversos , Aglutininas del Germen de Trigo/efectos adversos , Niño , Grano Comestible/química , Inhibidores Enzimáticos/análisis , Humanos , Lectinas/análisis , Valor Nutritivo , Ácido Fítico/análisis , Factores de Riesgo , Aglutininas del Germen de Trigo/análisisRESUMEN
Clear (CleA) and cloudy (CloA) apple juices containing different amounts of analyzed procyanidins and pectin were investigated for preventive effects of colon cancer and underlying molecular mechanisms in F344 rats given intraperitoneal injections of 1,2-dimethylhydrazine (DMH; 20 mg/kg body wt) once a week for 4 weeks. Rats received either water (Cont), CleA or CloA (ad libitum) for 7 weeks starting 1 week before the first DMH injection. CloA inhibited DMH induced genotoxic damage in mucosa cells of the distal colon compared with Cont as investigated by single-cell microgel electrophoresis assay. The mean tail intensity in mucosa cells of DMH-treated controls (Cont/DMH: 6.1+/-0.9%) was significantly reduced by CloA (2.4+/-0.8%; P<0.01) but not by CleA intervention (4.1+/-1.2%; P>0.05). The crypt cell proliferation index induced by DMH (Cont/NaCl: 10.0+/-0.7%; Cont/DMH: 19.9+/-1.0%; P<0.001) was significantly decreased by CleA (15.7+/-0.7%; P<0.001) and CloA intervention (11.9+/-0.4%; P<0.001). CloA but not CleA significantly reduced the number of large aberrant crypt foci (ACF) consisting of more than four aberrant crypts (AC) (Cont/DMH: 37.4+/-5.4; CleA/DMH: 32.8+/-4.4, P>0.05; CloA/DMH: 18.8+/-2.5 ACF; P<0.05) and the overall mean ACF size in the distal colon (Cont/DMH: 2.31+/-0.09; CleA/DMH: 2.27+/-0.05; CloA/DMH: 2.04+/-0.03 AC/ACF; P<0.05). After treatment with DMH and/or apple juices there were no changes in transcript levels of colonic cyclooxygenase isoforms (COX-1, COX-2) or glutathione-associated enzymes (GST-M2, gamma-GCS, GST-P), the splenocyte natural killer cell activity and plasma antioxidant status. However, CloA but not CleA prevented the DMH-induced reduction of splenocyte CD4/CD8 (T-helper cells to cytotoxic lymphocytes) ratio. Since both formulations contained comparable concentrations and types of monomeric polyphenols, complex polyphenols or non-polyphenolic compounds, such as pectin might be responsible for the stronger cancer-preventive effect by CloA.
Asunto(s)
Anticarcinógenos/farmacología , Bebidas , Carcinógenos/toxicidad , División Celular/efectos de los fármacos , Colon/patología , Daño del ADN/efectos de los fármacos , Dimetilhidrazinas/toxicidad , Mucosa Intestinal/patología , Malus , Animales , Colon/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas F344RESUMEN
Nutritional status is an important determinant of the host resistance against infections and tumors. Alcohol interferes in various ways with the complex system of nutritional immunomodulation. Alcohol acts directly on mechanical barriers in the gastrointestinal tract and increases permeability of intestinal walls, which results in a reduced exclusion of immunogenic material in the intestine. Alcohol further affects granulocytopoiesis and suppresses various immune functions. Indirect effects on the immune response are caused by alcohol-induced malnutrition. Heavy alcohol abuse is associated with a high energy intake derived by alcohol and an inadequate intake of protein, vitamins and minerals. In addition, alcohol abuse impairs absorption, utilization, storage and excretion of nutrients, which together with inadequate nutrient intakes results in nutritional immunosuppression. The high incidence of infections in alcoholics could be one consequence of the alcohol-induced immunosuppression.
Asunto(s)
Alcoholismo/complicaciones , Trastornos Nutricionales/inmunología , Alcoholismo/inmunología , Animales , Infecciones por VIH/inmunología , Humanos , Trastornos Nutricionales/etiología , Factores de RiesgoRESUMEN
Immunosuppression observed in chronic alcohol users is caused by multiple factors including the amount of alcohol consumed and alcohol-induced nutritional deficiencies. Investigators of the immunotoxic effects of ethanol (ETOH) frequently concentrate on the effects of ETOH and neglect nutrition as a confounding variable. This study investigated the immunotoxic effects of ETOH under variable dietary nutritional conditions. Mice were fed diets containing various levels of nutrients and ethanol for 7 weeks. Spleen cell number, and interleukin-2 and tumor necrosis factor (TNF) secretion were independent of the diet consumed, but were affected by consumption of ETOH. Body and spleen weights, and interferon-gamma secretion were modulated by ETOH as well as by diet. The results indicate that the nutritional composition of the diet consumed during concurrent administration of ETOH modulates the immunotoxic effects of chronic ETOH ingestion. We conclude that the levels of various nutrients in animal diets have to be planned and controlled carefully in order to identify directly the immunotoxic effects of ETOH.