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1.
J Nutr ; 144(10): 1517-23, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24812072

RESUMEN

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068.


Asunto(s)
Biomarcadores/sangre , Peso Corporal/fisiología , Dieta Alta en Grasa , Grasas de la Dieta/administración & dosificación , Obesidad/metabolismo , Adulto , Glucemia , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Colesterol/sangre , Estudios Cruzados , Endotoxinas/sangre , Ingestión de Energía , Ayuno , Péptido 1 Similar al Glucagón/sangre , Humanos , Insulina/sangre , Interleucina-6/sangre , Masculino , Comidas , Persona de Mediana Edad , Periodo Posprandial , Suiza , Triglicéridos/sangre , Circunferencia de la Cintura
2.
Ther Umsch ; 70(2): 93-101, 2013 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-23385187

RESUMEN

The treatment of obesity is complex due to the multifactorial etiology. A modern therapy concept must therefore be tailored to the individual needs and problems and depends on various factors such as degree of obesity, the presence of physical complications, psychological co-morbidities, any treatment measures the patient underwent up to now as well as on motivational factors. Before deciding on a therapeutic measure a structured multidisciplinary cooperation is essential including psychosomatic medicine/psychiatry/psychotherapy, endocrinology, sports medicine, nutritional medicine and surgery as well. The treatment must be carried out in a multidisciplinary team and includes an adequate therapy of comorbidities and sometimes a psychopharmacological support. The success of a conservative treatment of obesity is remarkable and long-lasting and can be straightforwardly compared to bariatric surgery in financial as well as ethical terms, although for patients and their physicians the latter often carries the allure of quick success.


Asunto(s)
Algoritmos , Obesidad/diagnóstico , Obesidad/terapia , Grupo de Atención al Paciente , Humanos
3.
Br J Nutr ; 108(5): 762-8, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22943857

RESUMEN

Advances in food transformation have dramatically increased the diversity of products on the market and, consequently, exposed consumers to a complex spectrum of bioactive nutrients whose potential risks and benefits have mostly not been confidently demonstrated. Therefore, tools are needed to efficiently screen products for selected physiological properties before they enter the market. NutriChip is an interdisciplinary modular project funded by the Swiss programme Nano-Tera, which groups scientists from several areas of research with the aim of developing analytical strategies that will enable functional screening of foods. The project focuses on postprandial inflammatory stress, which potentially contributes to the development of chronic inflammatory diseases. The first module of the NutriChip project is composed of three in vitro biochemical steps that mimic the digestion process, intestinal absorption, and subsequent modulation of immune cells by the bioavailable nutrients. The second module is a miniaturised form of the first module (gut-on-a-chip) that integrates a microfluidic-based cell co-culture system and super-resolution imaging technologies to provide a physiologically relevant fluid flow environment and allows sensitive real-time analysis of the products screened in vitro. The third module aims at validating the in vitro screening model by assessing the nutritional properties of selected food products in humans. Because of the immunomodulatory properties of milk as well as its amenability to technological transformation, dairy products have been selected as model foods. The NutriChip project reflects the opening of food and nutrition sciences to state-of-the-art technologies, a key step in the translation of transdisciplinary knowledge into nutritional advice.


Asunto(s)
Microfluídica/instrumentación , Valor Nutritivo , Grasas de la Dieta/administración & dosificación , Digestión , Humanos , Inflamación/etiología , Periodo Posprandial , Suiza
4.
Ther Umsch ; 68(8): 421-33, 2011 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-21796592

RESUMEN

Compared to Europe's mean immigrant contingent of 7.3 to 8.6 % Switzerland holds the highest contingent of foreign population with 23.5 %. Therefore it is of utmost importance that physicians have a knowledge of the specific characteristics of immigrant patients. The influence of personality factors (experience, behavior) is not independent from the influence of culturally-related environmental factors (regional differences in diet, pollutants, meanings, etc.). In addition, different cultural groups rate their quality of life differently. Psychological reasons for recurrent abdominal pain are stress (life events), effects of self-medication (laxatives, cocaine) and sexual abuse but also rare infectious diseases are more common among immigrants (e.g. tuberculosis, histoplasmosis, etc.). Migration-specific characteristics are mainly to find in the semiotics of the symptoms: not every abdominal pain is real pain in the abdomen. Finally, it is crucial to make the distinction between organic, functional and psychological-related pain. This can, however, usually only be accomplished in the context of the entire situation of a patient and, depending on the situation, with the support of a colleague from the appropriate cultural group or an experienced interpreter. In this review we limit ourselves to the presentation of the working population of the migrants, because these represent the largest group of all migrants. The specific situation of asylum seekers will also be refrained to where appropriate.


Asunto(s)
Dolor Abdominal/psicología , Comparación Transcultural , Emigrantes e Inmigrantes/psicología , Trastornos Somatomorfos/psicología , Dolor Abdominal/etiología , Factores de Edad , Algoritmos , Barreras de Comunicación , Diagnóstico Diferencial , Humanos , Conducta de Enfermedad , Acontecimientos que Cambian la Vida , Calidad de Vida/psicología , Refugiados/psicología , Factores de Riesgo , Valores Sociales , Suiza
5.
Am J Drug Alcohol Abuse ; 36(1): 66-72, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20141400

RESUMEN

BACKGROUND: Cross-cultural comparisons may increase our understanding of different models of substance use treatment and help identify consistent associations between patients' characteristics, treatment conditions, and outcomes. OBJECTIVES: The aim of the study was to compare matched samples of substance use disorder (SUD) patients with personality disorders (PD) in Swiss and the United States (U.S.) residential SUD treatment programs and examine the relationship of program characteristics to 1-year outcomes. METHODS: A prospective, naturalistic design was used to compare 132 demographically matched Swiss and U.S. male patients drawn from a sample of 10 Swiss and 15 U.S. public treatment programs. Patients completed comparable inventories at admission, discharge, and 1-year follow-up. RESULTS: Compared to Swiss SUD-PD patients, U.S. SUD-PD patients had more severe substance use and psychosocial problems at admission and follow-up. More intensive treatment and a stronger emphasis on patients' involvement were related to better outcomes for both Swiss and U.S. SUD-PD patients. CONCLUSION: There may be some cross-cultural consistency in the associations between treatment characteristics and SUD-PD patients' outcomes. SCIENTIFIC SIGNIFICANCE: Treatment evaluation findings from representative programs in one country may apply elsewhere and contribute to our overall knowledge about how to improve SUD-PD patients' outcomes.


Asunto(s)
Comparación Transcultural , Trastornos de la Personalidad/psicología , Trastornos de la Personalidad/terapia , Centros de Tratamiento de Abuso de Sustancias/métodos , Trastornos Relacionados con Sustancias/psicología , Adulto , Diagnóstico Dual (Psiquiatría)/estadística & datos numéricos , Humanos , Masculino , Trastornos de la Personalidad/complicaciones , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Tratamiento Domiciliario/métodos , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/terapia , Suiza , Resultado del Tratamiento , Estados Unidos
6.
J Gastrointest Surg ; 23(2): 232-238, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30091038

RESUMEN

BACKGROUND: Mental health disorders are highly prevalent among bariatric surgery patients. Bariatric surgery induces weight loss with continuous health improvements. However, long-term follow-up data on weight loss and quality of life data of patients who have a mental illness after bariatric surgery are scarce, and it is not clear whether mental illness is associated with more pronounced weight regain. The aim was to investigate the impact of preoperative mental illness on the course of long-term weight changes after bariatric surgery. METHODS: Patients with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass surgery (RYGB) between 2005 and 2013 with a follow-up of at least 3 years were included. The study population was divided into two groups: patients with mental illness (MI) and patients without (No-MI). Weight loss outcomes over time were compared using mixed models up to 4 years after surgery. RESULTS: In total, 254 patients (RYGB 61.0%, SG 39%) were included. The distribution of baseline characteristics was similar between the MI (n = 108) and No-MI groups (n = 146). The most prevalent mental illness was depressive disorder (63.9%). In the MI group, the percent of total weight loss (%TWL) was significantly smaller over the study period. After 36 months, the predicted mean group-difference of %TWL was 4.6% (95% CI 1.9, 7.2; p = 0.001), and the predicted odds ratio for weight regain was 4.9 (95% CI 1.6, 15.1) for patients in the MI group. CONCLUSION: Preoperative mental illness leads to lower long-term weight loss and an increased risk of weight regain after bariatric surgery.


Asunto(s)
Cirugía Bariátrica , Trastornos Mentales/epidemiología , Obesidad Mórbida/cirugía , Calidad de Vida , Pérdida de Peso , Adulto , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Obesidad Mórbida/epidemiología , Obesidad Mórbida/fisiopatología , Estudios Retrospectivos , Suiza/epidemiología , Factores de Tiempo
7.
Neurosci Lett ; 375(3): 151-6, 2005 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-15694250

RESUMEN

In schizophrenic psychoses, structural and functional alterations of the amygdala have been demonstrated by several neuroimaging studies. However, postmortem examinations on the brains of schizophrenics did not confirm the volume changes reported by volumetric magnetic resonance imaging (MRI) studies. In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed a trimodal MRI design including high-resolution volumetry, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) in a sample of 14 schizophrenic patients and 14 matched controls. Three-dimensional MRI volumetry revealed a significant reduction of amygdala raw volumes in the patient group, while amygdala volumes normalized for intracranial volume did not differ between the two groups. The regional diffusional anisotropy of the amygdala, expressed as inter-voxel coherence (COH), showed a marked and significant reduction in schizophrenics. Assessment of qMTI parameters yielded significant group differences for the T2 time of the bound proton pool and the T1 time of the free proton pool, while the semi-quantitative magnetization transfer ratio (MTR) did not differ between the groups. The application of multimodal MRI protocols is diagnostically relevant for the differentiation between schizophrenic patients and controls and provides a new strategy for the detection and characterization of subtle structural alterations in defined regions of the living brain.


Asunto(s)
Amígdala del Cerebelo/patología , Imagen de Difusión por Resonancia Magnética/métodos , Imagenología Tridimensional/métodos , Esquizofrenia/patología , Adulto , Análisis de Varianza , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Lateralidad Funcional/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Esquizofrenia/fisiopatología
8.
Neuroreport ; 15(5): 867-71, 2004 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-15073533

RESUMEN

Previous MRI-volumetric studies in schizophrenic psychoses have demonstrated more or less pronounced volume reductions of the hippocampus in patients. Correspondingly, neuropathological examinations on the brains of schizophrenics showed diverse structural changes of the hippocampus. Employing a high-resolution 3D-MPRAGE sequence, we found volume reductions in most hippocampal subregions of schizophrenic patients, which, however, did not reach significant levels. An analysis of co-registered diffusion tensor imaging (DTI) data revealed significant alterations of the inter-voxel coherences in single hippocampal subdivisions of these patients, supporting the assumption of characteristic microstructural tissue changes relevant for the pathogenesis of schizophrenic psychoses. Our results argue for the usage of additional MRI modalities like DTI in order to detect subtle regional alterations of hippocampal structure in schizophrenics.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Hipocampo/patología , Esquizofrenia/patología , Adulto , Mapeo Encefálico , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Masculino , Esquizofrenia/fisiopatología
9.
Fertil Steril ; 79 Suppl 1: 815-20, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12620496

RESUMEN

OBJECTIVE: To investigate the presence of epithelial neutrophil-activating peptide 78 (ENA-78) in peritoneal fluid of women with and without endometriosis and to identify the cells that produce this inflammatory protein. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): Eighteen women with and 9 women without endometriosis. MAIN OUTCOME MEASURE(S): ENA-78 protein and mRNA levels were compared among women with and without endometriosis in samples of peritoneal fluid, samples of endometriotic lesions obtained by biopsy during laparoscopy, and peritoneal macrophages. Enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and in situ hybridization methods were used. Secretion of ENA-78 protein by interleukin-1beta-stimulated endometriotic stromal cells and in the media of lipopolysaccharide-stimulated peritoneal macrophages were compared to that in unstimulated cell cultures. RESULT(S): Peritoneal fluid concentrations of ENA-78 were significantly higher in affected women than in controls. Ectopic epithelial and stromal cells and peritoneal macrophages express ENA-78 messenger RNA. Interleukin-1beta stimulation of stromal cell cultures resulted in a 23-fold increase in ENA-78 concentration, and lipopolysaccharide stimulation of peritoneal macrophages increased concentrations by 8-fold. CONCLUSION(S): Levels of ENA-78 are elevated in the peritoneal fluid of women with endometriosis. Ectopic glandular cells, ectopic stromal cells, and peritoneal macrophages express this inflammatory chemokine. Epithelial neutrophil-activating peptide 78 may play an important role in the pathogenesis of endometriosis.


Asunto(s)
Líquido Ascítico/metabolismo , Quimiocinas CXC , Endometriosis/metabolismo , Interleucina-8/análogos & derivados , Interleucina-8/biosíntesis , Estudios de Casos y Controles , Quimiocina CXCL5 , Femenino , Humanos , Hibridación in Situ , Interleucina-1/farmacología , Interleucina-8/genética , Lipopolisacáridos/farmacología , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
10.
Psychiatry Res ; 219(3): 638-44, 2014 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-25011731

RESUMEN

Heart rate and breathing rate fluctuations represent interacting physiological oscillations. These interactions are commonly studied using respiratory sinus arrhythmia (RSA) of heart rate variability (HRV) or analyzing cardiorespiratory synchronization. Earlier work has focused on a third type of relationship, the temporal ratio of respiration rate and heart rate (HRR). Each method seems to reveal a specific aspect of cardiorespiratory interaction and may be suitable for assessing states of arousal and relaxation of the organism. We used HRR in a study with 87 healthy subjects to determine the ability to relax during 5 day-resting periods in comparison to deep sleep relaxation. The degree to which a person during waking state could relax was compared to somatic complaints, health-related quality of life, anxiety and depression. Our results show, that HRR is barely connected to balance (LF/HF) in HRV, but significantly correlates to the perception of general health and mental well-being as well as to depression. If relaxation, as expressed in HRR, during day-resting is near to deep sleep relaxation, the subjects felt healthier, indicated better mental well-being and less depressive moods.


Asunto(s)
Frecuencia Cardíaca/fisiología , Calidad de Vida , Respiración , Descanso/psicología , Sueño/fisiología , Adulto , Nivel de Alerta/fisiología , Arritmia Sinusal/fisiopatología , Femenino , Homeostasis , Humanos , Masculino , Descanso/fisiología
11.
J Stud Alcohol Drugs ; 70(5): 668-74, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19737490

RESUMEN

OBJECTIVE: Suicide attempts are common in patients being treated for alcohol-use disorders (AUDs). However, clinical assessment of suicide risk is difficult. In this Swiss multisite study, we propose a decision tree to facilitate identification of profiles of AUD patients at high risk for suicidal behavior. METHOD: In this retrospective study, we used a sample of 700 patients (243 female), attending 1 of 12 treatment programs for AUDs in the German-speaking part of Switzerland. Sixty-nine patients who reported a suicide attempt in the 3 months before the index treatment were compared using risk factors with 631 patients without a suicide attempt. Receiver operating characteristic (ROC) analyses were used to identify patients at risk of having had a suicide attempt in the previous 3 months. RESULTS: Consistent with previous empirical findings in AUD patients, a prior history of attempted suicide and severe symptoms of depression and aggression considerably increased the risk of a suicide attempt and, in combination, raised the likelihood of a prior suicide attempt to 52%. In addition, one third of AUD patients who had a history of suicide attempts and previous inpatient psychiatric treatment, or who were male and had previous inpatient psychiatric treatment, also reported a suicide attempt. CONCLUSIONS: The empirically supported decision tree helps to identify profiles of suicidal AUD patients in Switzerland and supplements clinicians' judgments in making triage decisions for suicide management.


Asunto(s)
Trastornos Relacionados con Alcohol/epidemiología , Trastornos Relacionados con Alcohol/psicología , Intento de Suicidio/psicología , Intento de Suicidio/estadística & datos numéricos , Adulto , Trastornos Relacionados con Alcohol/complicaciones , Árboles de Decisión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Suiza/epidemiología
12.
Alcohol Alcohol ; 42(4): 333-9, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17517820

RESUMEN

AIMS: In randomized controlled trials with high internal validity, pharmacotherapy using acamprosate, naltrexone, and, to a somewhat lesser extent, disulfiram has proved effective in preventing relapse in patients with alcohol use disorders (AUD). There remains, however, a paucity of studies with sufficient external validity in which the effectiveness of pharmacotherapy in clinical practice is investigated. This study aimed to make a contribution to close this gap in research. METHODS: In this naturalistic, prospective study, a comparison on indices of substance use, psychiatric symptoms, and treatment service utilization was carried out using samples of 92 patients who received pharmacotherapy and 323 patients who did not receive pharmacotherapy following discharge from 12 residential AUD programmes (index stay). RESULTS: Patients that received pharmacotherapy were more likely to use alcohol during the index stay and at the 1-year follow-up. Moreover, this patient group more readily utilized treatment services during a 2-year period prior to and a 1-year period following index stay than patients who were not given pharmacotherapy. Nevertheless, when pharmacotherapy was prescribed before first post-treatment alcohol use, it was associated with delay of alcohol use, fewer relapses, and a reduced need for inpatient treatment. In many cases, however, medication was not prescribed until alcohol use and relapse had occurred. The length of time to first alcohol use was longer, and the cumulative abstinence rate higher, for disulfiram than for acamprosate, the latter being generally prescribed for more severely alcohol-dependent patients. CONCLUSIONS: There is a need for further studies to probe the reasons why medication for relapse prevention is not prescribed upon discharge from residential treatment and for less severely alcohol-dependent patients.


Asunto(s)
Disuasivos de Alcohol/uso terapéutico , Alcoholismo/tratamiento farmacológico , Disulfiram/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Taurina/análogos & derivados , Acamprosato , Adulto , Factores de Edad , Alcoholismo/epidemiología , Alcoholismo/psicología , Femenino , Estudios de Seguimiento , Humanos , Pacientes Internos , Masculino , Trastornos Mentales/complicaciones , Trastornos Mentales/psicología , Persona de Mediana Edad , Pruebas Psicológicas , Prevención Secundaria , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Suiza/epidemiología , Taurina/uso terapéutico , Resultado del Tratamiento
13.
Biol Chem ; 388(3): 337-41, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17338642

RESUMEN

Epithelial cells in the human small intestine express meprin, an astacin-like metalloprotease, which accumulates normally at the brush border membrane and in the gut lumen. Therefore, meprin is targeted towards luminal components. In coeliac disease patients, peptides from ingested cereals trigger mucosal inflammation in the small intestine, disrupting epithelial cell differentiation and function. Using in situ hybridisation on duodenal tissue sections, we observed a marked shift of meprin mRNA expression from epithelial cells, the predominant expression site in normal mucosa, to lamina propria leukocytes in coeliac disease. Meprin thereby gains access to the substrate repertoire present beneath the epithelium.


Asunto(s)
Enfermedad Celíaca/metabolismo , Compartimento Celular/fisiología , Mucosa Intestinal/metabolismo , Membrana Mucosa/metabolismo , Tiopronina/metabolismo , Enfermedad Celíaca/patología , Expresión Génica , Humanos , Intestino Delgado/patología
14.
Neuroimage ; 30(3): 713-20, 2006 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-16337815

RESUMEN

Current treatments for Alzheimer's disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.


Asunto(s)
Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/fisiopatología , Demencia/diagnóstico , Demencia/fisiopatología , Imagen de Difusión por Resonancia Magnética , Corteza Entorrinal/fisiopatología , Hipocampo/fisiopatología , Sistema Límbico/fisiopatología , Vía Perforante/fisiopatología , Anciano , Femenino , Humanos , Masculino
15.
J Pathol ; 206(2): 178-85, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15880760

RESUMEN

Villous atrophy and increased numbers of intraepithelial T cells in duodenal biopsies represent a hallmark of coeliac disease. In the present study, an attempt has been made to define whether cytotoxic cell subsets are activated in situ in the affected mucosa of susceptible individuals early after ingestion of a gluten-containing diet. Duodenal biopsies from 11 patients with coeliac disease who repeatedly underwent endoscopic biopsy after ingestion of individually dosed amounts of gluten were used for immunohistochemistry and in situ hybridization. To identify the cell subsets expressing perforin mRNA and protein, in situ hybridization and FACS analyses were performed on cells isolated from fresh biopsies. Compared with normal mucosa, the number of intraepithelial lymphocytes containing perforin mRNA and protein increased significantly in tissue samples showing moderate or florid coeliac disease and closely paralleled the severity of morphological alteration, whereas the frequency of perforin-expressing lamina propria lymphocytes increased only moderately. Cells isolated from florid biopsies that expressed perforin mRNA and protein were preferentially T-cell receptor (TCR) alphabeta T cells. The increase in both the absolute number and the percentage of lymphocytes expressing perforin mRNA indicates in situ activation of lymphocytes within the epithelial compartment in florid coeliac disease upon ingestion of a gluten-containing diet in patients predisposed to coeliac disease.


Asunto(s)
Enfermedad Celíaca/inmunología , Duodeno/inmunología , Mucosa Intestinal/inmunología , Activación de Linfocitos/inmunología , Linfocitos T Citotóxicos/inmunología , Adulto , Biopsia , Complejo CD3/análisis , Proliferación Celular , Niño , Preescolar , Femenino , Expresión Génica , Glútenes/inmunología , Humanos , Inmunidad Mucosa , Masculino , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Perforina , Proteínas Citotóxicas Formadoras de Poros , ARN Mensajero/genética , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Subgrupos de Linfocitos T/inmunología
16.
J Pathol ; 204(2): 208-16, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15376263

RESUMEN

Chemokines regulate cellular trafficking to and from lymphoid follicles. Here, the distribution pattern of four CCL chemokines is defined by in situ hybridization in human lymphoid follicles from tonsils and lymph nodes (LNs) of newborns and adults. Cells expressing CCL11 (eotaxin) and CCL20 (Exodus) were preferentially located within follicles, while cells expressing CCL21 (secondary lymphoid-tissue chemokine) and CCL24 (eotaxin-2) mRNA were almost exclusively found in the perifollicular areas. Hence, the two CCR3-binding chemokines, CCL11 and CCL24, showed a mutually exclusive expression pattern in the intra- and extra-follicular areas, respectively. Chemokine gene expression paralleled follicular maturation: in tonsils, where approximately 80% of follicles are polarized, CCL11 and CCL20 mRNA-positive cells were detected more frequently than in lymph nodes from adults, where about half of follicles are non-polarized. No intrafollicular chemokine expression was detectable in the primary follicles from newborns. Extrafollicular cells expressing CCL21 and CCL24 were again more frequent in tonsils than in LNs from adults. The observed preferential presence of cells expressing CC chemokines in polarized human lymphoid follicles indicates that chemokines are not only instrumental in the induction of follicle formation, but may also be involved in their further differentiation.


Asunto(s)
Quimiocinas CC/análisis , Tejido Linfoide/química , Adulto , Inhibidores de la Angiogénesis/análisis , Inhibidores de la Angiogénesis/genética , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Movimiento Celular/genética , Movimiento Celular/fisiología , Quimiocina CCL11 , Quimiocina CCL20 , Quimiocina CCL21 , Quimiocina CCL24 , Quimiocinas CC/genética , Expresión Génica/genética , Humanos , Inmunohistoquímica/métodos , Hibridación in Situ/métodos , Recién Nacido , Ganglios Linfáticos/química , Proteínas Inflamatorias de Macrófagos/análisis , Proteínas Inflamatorias de Macrófagos/genética , Tonsila Palatina/química , ARN Mensajero/análisis
17.
Am J Pathol ; 162(4): 1183-90, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12651610

RESUMEN

Cathepsin D (Cath-D) expression in human primary breast cancer has been associated with a poor prognosis. In search of a better understanding of the Cath-D substrates possibly involved in cancer invasiveness and metastasis, we investigated the potential interactions between this protease and chemokines. Here we report that purified Cath-D, as well as culture supernatants from the human breast carcinoma cell lines MCF-7 and T47D, selectively degrade macrophage inflammatory protein (MIP)-1 alpha (CCL3), MIP-1 beta (CCL4), and SLC (CCL21). Proteolysis was totally blocked by the protease inhibitor pepstatin A, and specificity of Cath-D cleavage was demonstrated using a large chemokine panel. Whereas MIP-1 alpha and MIP-1 beta degradation was rapid and complete, cleavage of SLC was slow and not complete. Mass spectrometry analysis showed that Cath-D cleaves the Leu(58) to Trp(59) bond of SLC producing two functionally inactive fragments. Analysis of Cath-D proteolysis of a series of monocyte chemoattractant protein-3/MIP-1 beta hybrids indicated that processing of MIP-1 beta might start by cleaving off amino acids located in the C-terminal domain. In situ hybridization studies revealed MIP-1 alpha, MIP-1 beta, and Cath-D gene expression mainly in the stromal compartment of breast cancers whereas SLC transcripts were found in endothelial cells of capillaries and venules within the neoplastic tissues. Cath-D production in the breast carcinoma cell lines MCF-7 and T47D, as assessed by enzyme-linked immunosorbent assay of culture supernatants and cell lysates, was not affected by stimulation with chemokines such as interleukin-8 (CXCL8), SDF-1 (CXCL12), and SLC. These data suggest that inactivation of chemokines by Cath-D possibly influences regulatory mechanisms in the tumoral extracellular microenvironment that in turn may affect the generation of the antitumoral immune response, the migration of cancer cells, or both processes.


Asunto(s)
Neoplasias de la Mama/patología , Catepsina D/metabolismo , Quimiocinas CC/metabolismo , Proteínas Inflamatorias de Macrófagos/metabolismo , Secuencia de Aminoácidos , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Catepsina D/genética , Quimiocina CCL21 , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocinas CC/química , Quimiocinas CC/genética , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Cinética , Proteínas Inflamatorias de Macrófagos/química , Proteínas Inflamatorias de Macrófagos/genética , Datos de Secuencia Molecular , Especificidad por Sustrato , Células Tumorales Cultivadas
18.
Gastroenterology ; 127(3): 816-25, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15362037

RESUMEN

BACKGROUND & AIMS: Tumor necrosis factor (TNF) is cleaved proteolytically from a 26-kilodalton transmembrane precursor protein into secreted 17-kilodalton monomers. Transmembrane (tm) and secreted trimeric TNF are biologically active and may mediate distinct activities. We assessed the consequences of a complete inhibition of TNF processing on the course of colitis in recombination activating gene (RAG)2 -/- mice on transfer of CD4 CD45RB hi T cells. METHODS: TNF -/- mice, transgenic for a noncleavable mutant TNF gene, were used as donors of CD4 T cells, and, on a RAG2 -/- background, also as recipients. Kinetics of disease development were compared in the absence of TNF, in the absence of secreted TNF, and in the presence of secreted and tmTNF. The analysis at the end of the observation period included the histopathologic assessment of the intestine and the localization of TNF and interferon gamma (IFNgamma)-expressing cells. RESULTS: The complete prevention of TNF secretion in tmTNF transgenic RAG2 -/- mice neither prevented nor delayed disease induction by transferred transgenic for a noncleavable transmembrane mutant of mouse TNF (tmTNF tg) CD4 CD45RB hi T cells. tmTNF expression by transferred CD4 T cells, however, was not required for disease induction because severe colitis and weight loss also were observed in tmTNF RAG2 -/- recipients of TNF -/- CD4 CD45RB hi T cells. In the presence of tmTNF, the absence of secreted TNF did not affect frequency and distribution of TNF and interferon-gamma messenger RNA (mRNA)-expressing cells. CONCLUSIONS: These results indicate that specific inhibitors of TNF processing are not appropriate for modulating the pro-inflammatory and disease-inducing effects of TNF in chronic inflammatory disorders of the intestine.


Asunto(s)
Colitis/inmunología , Mucosa Intestinal/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Animales , Linfocitos T CD4-Positivos , Proteínas de Unión al ADN/genética , Técnicas de Transferencia de Gen , Antígenos Comunes de Leucocito/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Modelos Animales , Factor de Necrosis Tumoral alfa/genética
19.
Neuroimage ; 23(3): 1093-9, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15528109

RESUMEN

The hippocampal formation (HF) of healthy control subjects and schizophrenic patients was examined using an MRI experiment that implements sequences for relaxometry and magnetization transfer (MT) quantification. In addition to the semi-quantitative magnetization transfer ratio (MTR), all of the observable properties of the binary spin bath model were included. The study demonstrates that, in contrast to the MTR, quantitative MT parameters (especially the T2 relaxation time of restricted protons, T2b) are capable to differentiate functionally significant subregions within the HF. The MT methodology appears to be a promising new tool for the differential microstructural evaluation of the HF in neuropsychiatric disorders accompanied by memory disturbances.


Asunto(s)
Hipocampo/fisiopatología , Imagen por Resonancia Magnética/métodos , Esquizofrenia/fisiopatología , Adulto , Femenino , Lateralidad Funcional/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Trastornos de la Memoria/fisiopatología , Programas Informáticos
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