RESUMEN
Chronic inflammation is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC). The causes of inflammation in ESCC, however, are undefined. Dietary zinc (Zn)-deficiency (ZD) increases the risk of ESCC. We have previously shown that short-term ZD (6 weeks) in rats induces overexpression of the proinflammatory mediators S100a8 and S100a9 in the esophageal mucosa with accompanying esophageal epithelial hyperplasia. Here we report that prolonged ZD (21 weeks) in rats amplified this inflammation that when combined with non-carcinogenic low doses of the environmental carcinogen, N-nitrosomethylbenzylamine (NMBA) elicited a 66.7% (16/24) incidence of ESCC. With Zn-sufficiency, NMBA produced no cancers (0/21) (P<0.001). At tumor endpoint, the neoplastic ZD esophagus, as compared with Zn-sufficient esophagus, had an inflammatory gene signature with upregulation of numerous cancer-related inflammation genes (CXC and CC chemokines, chemokine receptors, cytokines and Cox-2) in addition to S100a8 and S100a9. This signature was already activated in the earlier dysplastic stage. Additionally, time-course bioinformatics analysis of expression profiles at tumor endpoint and before NMBA exposure revealed that this sustained inflammation was due to ZD rather than carcinogen exposure. Importantly, Zn replenishment reversed this inflammatory signature at both the dysplastic and neoplastic stages of ESCC development, and prevented cancer formation. Thus, the molecular definition of ZD-induced inflammation as a critical factor in ESCC development has important clinical implications with regard to development and prevention of this deadly disease.
Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Esófago/metabolismo , Inflamación/genética , Zinc/administración & dosificación , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Análisis por Conglomerados , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dieta , Dimetilnitrosamina/análogos & derivados , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/metabolismo , Esófago/efectos de los fármacos , Esófago/patología , Perfilación de la Expresión Génica , Inmunohistoquímica , Inflamación/etiología , Inflamación/metabolismo , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Sprague-Dawley , Receptores de Quimiocina/genética , Receptores de Quimiocina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Destete , Zinc/deficienciaRESUMEN
Based on the Inventory of Interpersonal Problems (IIP), the IIP-PD and the IIP-C screening scales were developed to distinguish personality disorder (PD) from non-PD and Cluster C from other PD, respectively, in a clinic population. Two studies were conducted to determine (a) validity and reliability of these IIP scales for PD screening in a nonclinical population, (b) specificity of IIP-C for identifying Cluster C, and (c) usefulness of the IIP scales for screening Cluster A. College students were screened using the IIP scales (Study 1, N = 454, Study 2, N = 87). High and low scorers completed PD-related questionnaires in Study 1 and a clinical interview for PD symptomatology in Study 2. Results indicated strong test-retest reliability, internal consistency, and factorial, convergent, and external validity. The scales tapped a common deficit in interpersonal relatedness, with some distinction between externalizing and internalizing dimensions, respectively, and both scales were positively and significantly associated with schizotypal traits. In conclusion, the IIP-PD and IIP-C are useful and valid screening instruments for identifying any versus no PD in nonclinical populations.
Asunto(s)
Tamizaje Masivo/métodos , Trastornos de la Personalidad/diagnóstico , Inventario de Personalidad , Psicometría/métodos , Adolescente , Adulto , Anciano , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Personalidad/psicología , Reproducibilidad de los Resultados , Trastorno de la Personalidad Esquizotípica/psicología , Estados UnidosRESUMEN
The purpose of this work was to clarify the essentiality of glucose production from amino acids in obese subjects undergoing prolonged starvation and to provide an explanation for death after the depletion of lean body mass when some body fat is still available to meet body energy requirements. Five obese subjects fasted for 21 d. Nitrogen balance studies were combined with measurements of blood metabolite and hormone concentrations, indirect calorimetry, determination of body-composition changes, and catheterization techniques. Phenylacetate was administered from day 19 to day 21 to remove glutamine from the body and to assess this perturbation on energy requirements, ammoniagenesis, ureagenesis, gluconeogenesis, and ketogenesis. The obese subjects lost body fat and fat-free mass in parallel and resting metabolic energy requirements per mass remained constant during starvation. Urinary nitrogen excretion reflected continuous demands for amino acid oxidation. Phenylacetate administration decreased blood glutamine concentrations, increased plasma epinephrine concentrations, and increased urinary nitrogen loss through phenylacetylglutamine excretion; urinary excretion rates of urea, ammonium, urate, creatinine, and ketone bodies remained unchanged. The essentiality of amino acid oxidation was therefore shown. Late in prolonged starvation, aminogenic oxidation amounted to 7% and fat provided the remaining energy requirements. Hepatic and renal gluconeogenesis were not curtailed. Blood glutamate served as a vehicle for carbon and nitrogen transport; the contribution of glycerol to gluconeogenesis equaled that of all amino acids combined. The minimal quantities of amino acid (0.27 +/- 0.08 and 0.52 +/- 0.10 g) and fat (1.53 +/- 0.21 and 2.98 +/- 0.15 g) oxidized per kg body wt or fat-free mass/d, respectively, were determined. Included within amino acid and fat oxidation were the minimal amounts of precursors needed for synthesizing the essential quantity of glucose (0.34 +/- 0.14 and 0.66 +/- 0.20 g) oxidized per kg body wt or fat-free mass, respectively.
Asunto(s)
Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Necesidades Nutricionales , Obesidad/fisiopatología , Adulto , Aminoácidos/metabolismo , Antimetabolitos Antineoplásicos , Composición Corporal , Ingestión de Energía , Epinefrina/sangre , Femenino , Gluconeogénesis , Glutamina/sangre , Humanos , Masculino , Persona de Mediana Edad , Nitrógeno/metabolismo , Nitrógeno/orina , Fenilacetatos/farmacologíaRESUMEN
Oxidative and nonoxidative macronutrient disposal rates were measured in lean and obese males randomly fed mixed meals containing 0, 33, 67, 100, and 134 kJ/kg fat-free mass (0, 8, 16, 24, and 32 kcal/kg). Body composition, preprandial and postprandial energy expenditure, and macronutrient concentrations in the extracellular space were measured. Relationships among carbohydrate, fat, and protein disposal rates; body weight; and body composition were examined. Oxidative and nonoxidative disposals of macronutrients were not different between the lean and obese groups. Glucose was preferentially oxidized and fat was preferentially stored after nutrient ingestion. Macronutrient storage increased linearly with caloric intake. Oxidative and nonoxidative macronutrient disposals were completed within 8 h after ingesting the meals. Serum insulin concentrations rose to 3000-6000 pmol/L in two obese men after their two largest meals. Eight hours after nutrient ingestion, concentrations of macronutrient substrates, metabolic products, and insulin were indistinguishable from preprandial values.
Asunto(s)
Carbohidratos de la Dieta/metabolismo , Grasas de la Dieta/metabolismo , Proteínas en la Dieta/metabolismo , Metabolismo Energético , Obesidad/metabolismo , Adulto , Nitrógeno de la Urea Sanguínea , Composición Corporal , Calorimetría Indirecta , Ingestión de Energía , Espacio Extracelular/metabolismo , Ácidos Grasos no Esterificados/sangre , Alimentos , Glucosa/metabolismo , Humanos , Insulina/sangre , Masculino , Oxidación-ReducciónRESUMEN
The accuracy of body mass indices (BMIs), such as Quetelet's index, for the definition of obesity was investigated in a large sample of healthy humans. Two hundred thirteen women and 150 men with a wide spectrum of weights, heights, and ages underwent densitometric analysis for the determination of percent body fat (%BF). %BF was then contrasted with various well-established BMIs. Although %BF was correlated with all the BMIs (r = 0.60-0.82), applying objective definitions of obesity based on BMIs or %BF by densitometry often produced conflicting results. It was also found that the 95% confidence intervals for predicting %BF by using Quetelet's index were very wide. Because of the wide variation for individuals between densitometrically determined body fat and body fat as estimated by BMIs, we conclude that BMIs should be used with caution as indicators of obesity.
Asunto(s)
Constitución Corporal/fisiología , Índice de Masa Corporal , Obesidad/clasificación , Tejido Adiposo/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estatura , Peso Corporal , Densitometría , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Delgadez/clasificaciónRESUMEN
Indirect calorimetry was used to measure resting metabolic rates (RMR), and densitometry and anthropometry were used to measure body fat and fat-free masses of 32 adults with very short stature. Twenty-seven of them were achondroplastic dwarfs. Their results were compared to those obtained from 103 lean and obese adults with normal heights. All 32 dwarfs had distinctly greater RMR per kg fat-free mass by densitometry than adults with average stature. However, there was a wide variation in the RMR among dwarfs, which was independent of leanness or obesity. In spite of increased RMR, obesity among dysplastic adult dwarfs was twice as prevalent as among average-height adults. Increased abdominal:hip ratios were prevalent among dwarfs, but these ratios do not reflect body fat. Body mass indices were worthless, and skinfold thicknesses and other anthropometric measurements were of very limited value in predicting the body fat of dwarfs. Although our new and specific equations for estimating RMR and body composition give reasonable values, we recommend that the caloric requirements and body compositional variables be measured if nutritional therapy is needed to induce weight loss or gain in Little People.
Asunto(s)
Acondroplasia/metabolismo , Metabolismo Basal , Composición Corporal , Acondroplasia/patología , Tejido Adiposo/patología , Adulto , Antropometría , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Grosor de los Pliegues CutáneosRESUMEN
A systemic reappraisal of the thermic effect of food was done in lean and obese males randomly fed mixed meals containing 0, 8, 16, 24, and 32 kcal/kg fat-free mass. Densitometric analysis was used to measure body composition. Preprandial and postprandial energy expenditures were measured by indirect calorimetry. The data show that the thermic effect of food was linearly correlated with caloric intake, and that the magnitude and duration of augmented postprandial thermogenesis increased linearly with caloric consumption. Postprandial energy expenditures over resting metabolic requirements were indistinguishable when comparing lean and obese men for a given caloric intake. Individuals, however, had distinct and consistent thermic responses to progressively greater caloric challenges. These unique thermic profiles to food ingestion were also independent of leanness or obesity. We conclude that the thermic effect of food increases linearly with caloric intake, and is independent of leanness and obesity.
Asunto(s)
Regulación de la Temperatura Corporal , Ingestión de Energía , Alimentos , Obesidad/metabolismo , Adulto , Composición Corporal , Peso Corporal , Calorimetría , Densitometría , Metabolismo Energético , Humanos , MasculinoRESUMEN
The resting metabolic rates (RMR) of 60 lean and obese men, aged 18-82 y and weighing 60-171 kg, were measured and body compositions were determined. Body compositional variables reflecting active protoplasmic tissue were all highly interrelated. Body weight alone gave prediction values for RMR that were comparable to those of other variables of active protoplasmic tissue mass. Regional distribution of fat had no influence on the RMR and the influence of age on RMR was trivial. The classic prediction equations and tables overestimate RMR of men. The 95%-confidence limits for both lean and obese men were broad. This conclusively demonstrates that metabolic efficiency is not necessarily or exclusively related to obesity. New regression equations for predicting the RMR based on weight and fat-free mass were developed: RMR = 879 + 10.2 WT kg and RMR = 290 + 22.3 FFMD kg, where FFMD is fat-free mass from densitometry measurements.