Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Mol Pain ; 17: 17448069211041853, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34505814

RESUMEN

Provoked vestibulodynia (PVD) is a chronic vulvar pain disorder characterized by hypersensitivity and severe pain with pressure localized to the vulvar vestibule. Knowledge regarding pathophysiological mechanisms contributing to the etiology and production of symptoms in PVD remains incomplete but is considered multifactorial. Using a cross-sectional observational study design, data from untargeted metabolomic profiling of vaginal fluid and plasma in women with PVD and healthy women was combined with pain testing and brain imaging in women with PVD to test the hypotheses that women with PVD compared to healthy women show differences in vaginal and plasma metabolites involved in steroid hormone biosynthesis. Steroid hormone metabolites showing group differences were correlated with vulvar vestibular pain and vaginal muscle tenderness and functional connectivity of brain regions involved in pain processing in women with PVD to provide insight into the functional mechanisms linked to the identified alterations. Sensitivity analyses were also performed to determine the impact of hormonal contraceptive use on the study findings. Women with PVD compared to healthy controls had significant reductions primarily in vaginal fluid concentrations of androgenic, pregnenolone and progestin metabolites involved in steroidogenesis, suggesting localized rather than systemic effects in vagina and vulvar vestibule. The observed reductions in androgenic metabolite levels showed large effect size associations with increased vulvar vestibular pain and vulvar muscle tenderness and decreases in androgenic and progestin metabolites were associated with decreased connectivity strength in primary sensorimotor cortices. Women with PVD showed symptom-associated reductions in vaginal fluid concentrations of metabolites involved in the biosynthesis of steroid hormones previously shown to affect the integrity of vulvar and vaginal tissue and nociceptive processing. Deficiency of certain steroids may be an important mechanism contributing to the pathophysiology of symptoms in PVD may provide potential diagnostic markers that could lead to new targets for therapeutic intervention.


Asunto(s)
Mialgia/fisiopatología , Corteza Sensoriomotora/fisiopatología , Vagina/fisiopatología , Vulvodinia/fisiopatología , Adulto , Estudios Transversales , Femenino , Humanos , Metabolómica/métodos , Persona de Mediana Edad , Mialgia/metabolismo , Dimensión del Dolor/métodos , Corteza Sensoriomotora/metabolismo , Vagina/metabolismo , Vulvodinia/metabolismo , Adulto Joven
2.
Psychosom Med ; 79(8): 880-887, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28570438

RESUMEN

OBJECTIVE: Weight loss surgery results in significant changes in the anatomy, function, and intraluminal environment of the gastrointestinal tract affecting the gut microbiome. Although bariatric surgery results in sustained weight loss, decreased appetite, and hedonic eating, it is unknown whether the surgery-induced alterations in gut microbiota play a role in the observed changes in hedonic eating. We explored the following hypotheses: (1) laparoscopic sleeve gastrectomy (LSG) results in changes in gut microbial composition; (2) alterations in gut microbiota are related to weight loss; (3) alterations in gut microbiome are associated with changes in appetite and hedonic eating. METHODS: Eight obese women underwent LSG. Their body mass index, body fat mass, food intake, hunger, hedonic eating scores, and stool samples were obtained at baseline and 1-month postsurgery. 16S ribosomal RNA gene sequencing was performed on stool samples. DESeq2 changes in microbial abundance. Multilevel-sparse partial least squares discriminant analysis was applied to genus-level abundance for discriminative microbial signatures. RESULTS: LSG resulted in significant reductions in body mass index, food intake, and hedonic eating. A microbial signature composed of five bacterial genera discriminated between pre- and postsurgery status. Several bacterial genera were significantly associated with weight loss (Bilophila, q = 3E-05; Faecalibacterium q = 4E-05), lower appetite (Enterococcus, q = 3E-05), and reduced hedonic eating (Akkermansia, q = .037) after surgery. CONCLUSIONS: In this preliminary analysis, changes in gut microbial abundance discriminated between pre- and postoperative status. Alterations in gut microbiome were significantly associated with weight loss and with reduced hedonic eating after surgery; however, a larger sample is needed to confirm these findings.


Asunto(s)
Apetito/fisiología , Cirugía Bariátrica/métodos , Conducta Alimentaria/fisiología , Microbioma Gastrointestinal/fisiología , Obesidad Mórbida/cirugía , Placer/fisiología , Pérdida de Peso/fisiología , Adulto , Femenino , Humanos , Persona de Mediana Edad
3.
J Neurosci ; 34(43): 14252-9, 2014 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-25339739

RESUMEN

Resting-state functional magnetic resonance imaging has been used to investigate intrinsic brain connectivity in healthy subjects and patients with chronic pain. Sex-related differences in the frequency power distribution within the human insula (INS), a brain region involved in the integration of interoceptive, affective, and cognitive influences, have been reported. Here we aimed to test sex and disease-related alterations in the intrinsic functional connectivity of the dorsal anterior INS. The anterior INS is engaged during goal-directed tasks and modulates the default mode and executive control networks. By comparing functional connectivity of the dorsal anterior INS in age-matched female and male healthy subjects and patients with irritable bowel syndrome (IBS), a common chronic abdominal pain condition, we show evidence for sex and disease-related alterations in the functional connectivity of this region: (1) male patients compared with female patients had increased positive connectivity of the dorsal anterior INS bilaterally with the medial prefrontal cortex (PFC) and dorsal posterior INS; (2) female patients compared with male patients had greater negative connectivity of the left dorsal anterior INS with the left precuneus; (3) disease-related differences in the connectivity between the bilateral dorsal anterior INS and the dorsal medial PFC were observed in female subjects; and (4) clinical characteristics were significantly correlated to the insular connectivity with the dorsal medial PFC in male IBS subjects and with the precuneus in female IBS subjects. These findings are consistent with the INS playing an important role in modulating the intrinsic functional connectivity of major networks in the resting brain and show that this role is influenced by sex and diagnosis.


Asunto(s)
Dolor Abdominal/fisiopatología , Corteza Cerebral/fisiopatología , Dolor Crónico/fisiopatología , Red Nerviosa/fisiopatología , Caracteres Sexuales , Dolor Abdominal/diagnóstico , Adulto , Dolor Crónico/diagnóstico , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
4.
Gastroenterology ; 146(5): 1212-21, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24480616

RESUMEN

BACKGROUND & AIMS: The study of intrinsic fluctuations in the blood oxygen level-dependent signal of functional magnetic resonance imaging can provide insight into the effect of physiologic states on brain processes. In an effort to better understand the brain-gut communication induced by the absorption and metabolism of nutrients in healthy lean and obese individuals, we investigated whether ingestion of nutritive and non-nutritive sweetened beverages differentially engages the hypothalamus and brainstem vagal pathways in lean and obese women. METHODS: In a 2-day, double-blind crossover study, 11 lean and 11 obese healthy women underwent functional magnetic resonance imaging scans after ingestion of 2 beverages of different sucrose content, but identical sweetness. During scans, subjects rested with eyes closed. RESULTS: Blood oxygen level-dependent fluctuations demonstrated significantly greater power in the highest frequency band (slow-3: 0.073-0.198 Hz) after ingestion of high-sucrose compared with low-sucrose beverages in the nucleus tractus solitarius for both groups. Obese women had greater connectivity between the right lateral hypothalamus and a reward-related brain region and weaker connectivity with homeostasis and gustatory-related brain regions than lean women. CONCLUSIONS: In a functional magnetic resonance imaging study, we observed sucrose-related changes in oscillatory dynamics of blood oxygen level-dependent fluctuations in brainstem and hypothalamus in lean and obese women. The observed frequency changes are consistent with a rapid vagally mediated mechanism due to nutrient absorption, rather than sweet taste receptor activation. These findings provide support for altered interaction between homeostatic and reward networks in obese individuals.


Asunto(s)
Tronco Encefálico/fisiopatología , Sacarosa en la Dieta/administración & dosificación , Hipotálamo/fisiopatología , Obesidad/fisiopatología , Delgadez/fisiopatología , Administración Oral , Adulto , Bebidas , Mapeo Encefálico/métodos , Tronco Encefálico/metabolismo , Estudios Cruzados , Sacarosa en la Dieta/metabolismo , Método Doble Ciego , Femenino , Homeostasis , Humanos , Hipotálamo/metabolismo , Imagen por Resonancia Magnética , Obesidad/metabolismo , Obesidad/psicología , Oscilometría , Oxígeno/sangre , Recompensa , Saciedad , Delgadez/metabolismo , Delgadez/psicología , Factores de Tiempo , Nervio Vago/fisiopatología , Adulto Joven
5.
J Neurosci ; 33(29): 11994-2002, 2013 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-23864686

RESUMEN

Abnormal responses of the brain to delivered and expected aversive gut stimuli have been implicated in the pathophysiology of irritable bowel syndrome (IBS), a visceral pain syndrome occurring more commonly in women. Task-free resting-state functional magnetic resonance imaging (fMRI) can provide information about the dynamics of brain activity that may be involved in altered processing and/or modulation of visceral afferent signals. Fractional amplitude of low-frequency fluctuation is a measure of the power spectrum intensity of spontaneous brain oscillations. This approach was used here to identify differences in the resting-state activity of the human brain in IBS subjects compared with healthy controls (HCs) and to identify the role of sex-related differences. We found that both the female HCs and female IBS subjects had a frequency power distribution skewed toward high frequency to a greater extent in the amygdala and hippocampus compared with male subjects. In addition, female IBS subjects had a frequency power distribution skewed toward high frequency in the insula and toward low frequency in the sensorimotor cortex to a greater extent than male IBS subjects. Correlations were observed between resting-state blood oxygen level-dependent signal dynamics and some clinical symptom measures (e.g., abdominal discomfort). These findings provide the first insight into sex-related differences in IBS subjects compared with HCs using resting-state fMRI.


Asunto(s)
Ondas Encefálicas/fisiología , Encéfalo/fisiopatología , Dolor Crónico/fisiopatología , Síndrome del Colon Irritable/fisiopatología , Caracteres Sexuales , Dolor Visceral/fisiopatología , Adulto , Mapeo Encefálico , Electroencefalografía , Femenino , Neuroimagen Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatología , Umbral del Dolor/fisiología , Estimulación Física , Factores Sexuales , Aferentes Viscerales/fisiopatología
6.
Gastroenterology ; 144(7): 1394-401, 1401.e1-4, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23474283

RESUMEN

BACKGROUND & AIMS: Changes in gut microbiota have been reported to alter signaling mechanisms, emotional behavior, and visceral nociceptive reflexes in rodents. However, alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans. We investigated whether consumption of a fermented milk product with probiotic (FMPP) for 4 weeks by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks. METHODS: Healthy women with no gastrointestinal or psychiatric symptoms were randomly assigned to groups given FMPP (n = 12), a nonfermented milk product (n = 11, controls), or no intervention (n = 13) twice daily for 4 weeks. The FMPP contained Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis. Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity. Multivariate and region of interest analyses were performed. RESULTS: FMPP intake was associated with reduced task-related response of a distributed functional network (49% cross-block covariance; P = .004) containing affective, viscerosensory, and somatosensory cortices. Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was associated with changes in midbrain connectivity, which could explain the observed differences in activity during the task. CONCLUSIONS: Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation.


Asunto(s)
Atención/fisiología , Encéfalo/fisiología , Productos Lácteos Cultivados , Probióticos , Adolescente , Adulto , Bifidobacterium , Femenino , Neuroimagen Funcional , Humanos , Lactobacillus , Lactococcus lactis , Imagen por Resonancia Magnética , Persona de Mediana Edad , Streptococcus thermophilus , Resultado del Tratamiento , Adulto Joven
7.
Gastroenterology ; 145(6): 1253-61.e1-3, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23954313

RESUMEN

BACKGROUND & AIMS: Alterations in central corticotropin-releasing factor signaling pathways have been implicated in the pathophysiology of anxiety disorders and irritable bowel syndrome (IBS). We aimed to characterize the effects of the corticotropin-releasing factor receptor 1 (CRF-R1) antagonist, GW876008, on brain and skin conductance responses during acquisition and extinction of conditioned fear to the threat of abdominal pain in subjects with IBS and healthy individuals (controls). METHODS: We performed a single-center, randomized, double-blind, 3-period crossover study of 11 women with IBS (35.50 ± 12.48 years old) and 15 healthy women (controls) given a single oral dose (20 mg or 200 mg) of the CRF-R1 antagonist or placebo. Blood-oxygen level-dependent responses were analyzed using functional magnetic resonance imaging in a tertiary care setting. RESULTS: Controls had greater skin conductance responses during acquisition than extinction, validating the fear-conditioning paradigm. In contrast, during extinction, women with IBS had greater skin conductance responses than controls-an effect normalized by administration of a CRF-R1 antagonist. Although the antagonist significantly reduced activity in the thalamus in patients with IBS and controls during acquisition, the drug produced greater suppression of blood-oxygen level-dependent activity in a wide range of brain regions in IBS patients during extinction, including the medial prefrontal cortex, pons, hippocampus, and anterior insula. CONCLUSIONS: Although CRF signaling via CRF-R1 is involved in fear acquisition and extinction learning related to expected abdominal pain in patients with IBS and controls, this system appears to be up-regulated in patients with IBS. This up-regulation might contribute to the previously reported abnormal brain responses to expected abdominal pain.


Asunto(s)
Trastornos de Ansiedad/fisiopatología , Hormona Liberadora de Corticotropina/fisiología , Extinción Psicológica/fisiología , Síndrome del Colon Irritable/fisiopatología , Receptores de Hormona Liberadora de Corticotropina/fisiología , Transducción de Señal/fisiología , Dolor Abdominal/fisiopatología , Dolor Abdominal/psicología , Adulto , Trastornos de Ansiedad/psicología , Encéfalo/fisiología , Mapeo Encefálico , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Miedo/fisiología , Miedo/psicología , Femenino , Respuesta Galvánica de la Piel/efectos de los fármacos , Respuesta Galvánica de la Piel/fisiología , Humanos , Persona de Mediana Edad , Pirazoles/farmacología , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Receptores de Hormona Liberadora de Corticotropina/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
8.
Sci Rep ; 13(1): 5488, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-37016129

RESUMEN

A growing body of preclinical and clinical literature suggests that brain-gut-microbiota interactions may contribute to obesity pathogenesis. In this study, we use a machine learning approach to leverage the enormous amount of microstructural neuroimaging and fecal metabolomic data to better understand key drivers of the obese compared to overweight phenotype. Our findings reveal that although gut-derived factors play a role in this distinction, it is primarily brain-directed changes that differentiate obese from overweight individuals. Of the key gut metabolites that emerged from our model, many are likely at least in part derived or influenced by the gut-microbiota, including some amino-acid derivatives. Remarkably, key regions outside of the central nervous system extended reward network emerged as important differentiators, suggesting a role for previously unexplored neural pathways in the pathogenesis of obesity.


Asunto(s)
Microbioma Gastrointestinal , Sobrepeso , Humanos , Sobrepeso/metabolismo , Obesidad/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Microbioma Gastrointestinal/genética , Metabolómica , Heces/química
9.
J Neurosci ; 31(35): 12491-500, 2011 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-21880911

RESUMEN

Alterations in corticotropin-releasing factor (CRF) signaling pathways have been implicated in irritable bowel syndrome (IBS) pathophysiology. We aimed to (1) determine the effect of the selective CRF receptor 1 antagonist (CRF(1)) GW876008 relative to placebo, on regional activation and effective connectivity of a stress-related emotional-arousal circuit during expectation of abdominal pain using functional magnetic resonance imaging in human subjects with a diagnosis of IBS and healthy controls (HCs), and (2) examine GW876008 effects on state-trait anxiety and hypothalamic-pituitary-adrenal (HPA) axis response. Although there were no drug-related effects on peripheral HPA activity, significant central effects were observed in brain regions associated with the stress response. Effective connectivity analysis showed drug-induced normalizations between key regions of the emotional-arousal circuit in patients. During pain expectation, orally administered GW876008 relative to placebo produced significant blood oxygen level-dependent (BOLD) signal reductions in the amygdala, hippocampus, insula, anterior cingulate, and orbitomedial prefrontal cortices across groups. Patients showed significantly greater BOLD responses in the left locus coeruleus and hypothalamus after placebo compared with HCs, and BOLD signal decreases in the left hypothalamus after drug. The inhibitory effects of GW876008 in the hypothalamus in patients were moderated by anxiety; patients having average and high levels of state anxiety showed drug-related BOLD decreases. GW876008 represents a novel tool for elucidating the neuronal mechanisms and circuitry underlying hyperactivation of CRF/CRF(1) signaling and its role in IBS pathophysiology. The unique state anxiety effects observed suggest a potential pathway for therapeutic benefit of CRF(1) receptor antagonism for patients with stress-sensitive disorders.


Asunto(s)
Dolor Abdominal , Mapeo Encefálico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Pirazoles/uso terapéutico , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/etiología , Dolor Abdominal/complicaciones , Dolor Abdominal/patología , Dolor Abdominal/psicología , Administración Oral , Adolescente , Hormona Adrenocorticotrópica/sangre , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Persona de Mediana Edad , Vías Nerviosas/irrigación sanguínea , Oxígeno/sangre , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Adulto Joven
10.
Neuroimage ; 63(4): 1854-63, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22917679

RESUMEN

BACKGROUND/AIMS: Alterations in noradrenergic (NE) signaling have been implicated in the pathophysiology of irritable bowel syndrome (IBS), and adrenergic receptors are potential treatment targets. METHODS: To characterize central NE signaling in IBS, 11 patients and 11 healthy controls (HCs) were studied 3 times during an auditory oddball vigilance task after double-blind ingestion of the α2-adrenoreceptor (α2AR) antagonist yohimbine (YOH), the α2AR agonist clonidine (CLO), or placebo (PLA). Regional cerebral glucose metabolism was measured with [¹8F] fluorodeoxyglucose (FDG) positron emission tomography (PET). Measures of anxiety, early-life trauma, plasma NE and blood pressure were acquired. RESULTS: Patients had higher plasma NE levels than HCs before and after ingestion of all drugs (all p<0.05). YOH increased plasma NE and more anxiety in patients than in HCs. After YOH, NE levels directly correlated with drug-induced increases in anxiety in IBS patients (r=0.61), but not in HCs. IBS patients showed less YOH-mediated reduction of activity in a central arousal circuit, consistent with fewer functional presynaptic α2AR. In HCs, but not in patients, activation of amygdala and subgenual anterior cingulate cortex (sgACC) was inversely correlated with activation of anterior mid cingulate cortex (aMCC), and state anxiety covaried directly with activity in limbic and right frontotemporal cortices, but indirectly with activity in the left frontotemporal cortex. YOH-mediated reduction of activity in brainstem and amygdala inversely correlated with early life trauma. CONCLUSIONS: IBS patients showed evidence for increased noradrenergic activity consistent with downregulation of presynaptic inhibitory α2ARs. Activity within central arousal circuits was biased toward greater excitability and reduced corticolimbic inhibition in IBS. Early life trauma may be one mediator of these abnormalities.


Asunto(s)
Sistema Nervioso Central/fisiopatología , Síndrome del Colon Irritable/fisiopatología , Norepinefrina/fisiología , Sistema Nervioso Simpático/fisiopatología , Adulto , Ansiedad/complicaciones , Ansiedad/psicología , Nivel de Alerta/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Sistema Nervioso Central/diagnóstico por imagen , Fatiga/psicología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Síndrome del Colon Irritable/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiología , Tomografía de Emisión de Positrones , Desempeño Psicomotor/fisiología , Receptores Adrenérgicos alfa 2/efectos de los fármacos , Receptores Adrenérgicos alfa 2/fisiología , Encuestas y Cuestionarios , Sistema Nervioso Simpático/diagnóstico por imagen , Simpaticolíticos , Heridas y Lesiones/psicología , Yohimbina , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA