RESUMEN
Cholecystokinin (CCK)-induced suppression of feeding is mediated by vagal sensory neurons that are destroyed by the neurotoxin capsaicin (CAP). Here we determined whether CAP-sensitive neurons mediate anorexic responses to intravenous infusions of gut hormones peptide YY-(3-36) [PYY-(3-36)] and glucagon-like peptide-1 (GLP-1). Rats received three intraperitoneal injections of CAP or vehicle (VEH) in 24 h. After recovery, non-food-deprived rats received at dark onset a 3-h intravenous infusion of CCK-8 (5, 17 pmol·kg⻹·min⻹), PYY-(3-36) (5, 17, 50 pmol·kg⻹·min⻹), or GLP-1 (17, 50 pmol·kg⻹·min⻹). CCK-8 was much less effective in reducing food intake in CAP vs. VEH rats. CCK-8 at 5 and 17 pmol·kg⻹·min⻹ reduced food intake during the 3-h infusion period by 39 and 71% in VEH rats and 7 and 18% in CAP rats. In contrast, PYY-(3-36) and GLP-1 were similarly effective in reducing food intake in VEH and CAP rats. PYY-(3-36) at 5, 17, and 50 pmol·kg⻹·min⻹ reduced food intake during the 3-h infusion period by 15, 33, and 70% in VEH rats and 13, 30, and 33% in CAP rats. GLP-1 at 17 and 50 pmol·kg⻹·min⻹ reduced food intake during the 3-h infusion period by 48 and 60% in VEH rats and 30 and 52% in CAP rats. These results suggest that anorexic responses to PYY-(3-36) and GLP-1 are not primarily mediated by the CAP-sensitive peripheral sensory neurons (presumably vagal) that mediate CCK-8-induced anorexia.
Asunto(s)
Anorexia/fisiopatología , Colecistoquinina/metabolismo , Modelos Animales de Enfermedad , Mucosa Intestinal/inervación , Intestino Delgado/inervación , Neuritis/fisiopatología , Neuronas Aferentes/metabolismo , Fragmentos de Péptidos/metabolismo , Animales , Anorexia/metabolismo , Anorexia/prevención & control , Conducta Animal/efectos de los fármacos , Capsaicina/administración & dosificación , Capsaicina/toxicidad , Colecistoquinina/administración & dosificación , Ingestión de Energía/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/metabolismo , Infusiones Intravenosas , Inyecciones Intraperitoneales , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiopatología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatología , Masculino , Neuritis/inducido químicamente , Neuritis/metabolismo , Neuronas Aferentes/efectos de los fármacos , Fragmentos de Péptidos/administración & dosificación , Péptido YY/administración & dosificación , Péptido YY/metabolismo , Ratas , Nervio Vago/efectos de los fármacos , Nervio Vago/metabolismo , Nervio Vago/fisiopatología , Enfermedades del Nervio Vago/inducido químicamente , Enfermedades del Nervio Vago/metabolismo , Enfermedades del Nervio Vago/fisiopatologíaRESUMEN
A 50-year-old man underwent repeat surgery for a benign vagal schwannoma in the middle mediastinum. He had undergone tumor enucleation at another hospital 4 months before presentation. The tumor (99 × 88 × 76 mm) was located in the aortopulmonary window and arose from the left vagus nerve. It had been enucleated, leaving its sheath behind to preserve the nerve. Imaging studies showed tumor regrowth without distant metastasis, and the tumor was extirpated along with the involved nerve during cardiopulmonary bypass. There was no nerve dysfunction, recurrence, or metastasis 6 months after the operation. A benign vagal schwannoma can be excised with nerve transection or enucleated without nerve transection. The present case suggests that a vagal mediastinal schwannoma should be extirpated along with the nerve because insufficient enucleation might lead to tumor regrowth.
Asunto(s)
Neoplasias de los Nervios Craneales/cirugía , Neoplasias del Mediastino/cirugía , Recurrencia Local de Neoplasia , Vagotomía , Enfermedades del Nervio Vago/cirugía , Nervio Vago/cirugía , Biomarcadores de Tumor/análisis , Biopsia , Neoplasias de los Nervios Craneales/química , Neoplasias de los Nervios Craneales/patología , Humanos , Inmunohistoquímica , Masculino , Neoplasias del Mediastino/química , Neoplasias del Mediastino/patología , Persona de Mediana Edad , Neoplasia Residual , Reoperación , Esternotomía , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Nervio Vago/química , Nervio Vago/patología , Enfermedades del Nervio Vago/metabolismo , Enfermedades del Nervio Vago/patologíaRESUMEN
Although recently the incidence of prehypertension has increased considerably, the pathophysiological mechanisms and the effects of gender in its causation have not yet been fully elucidated. Therefore, in this study body mass index (BMI), waist-hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP), and spectral indices of heart rate variability (HRV) were reordered and analyzed in normotensive and prehypertensive males and females. It was observed that low frequency-high frequency (LF-HF) ratio, the sensitive indicator of sympathovagal imbalance (SVI), is significantly more (P < .001) in male prehypertensives compared with female prehypertensives. Although SVI in prehypertensives was found to be due to both sympathetic activation and vagal inhibition, contribution of vagal withdrawal was prominent in males. The LF-HF ratio was significantly correlated with BMI, WHR, BHR, BP, and RPP, which was more prominent in male prehypertensives and the degree of correlation was more for WHR and diastolic pressure. It was concluded that vagal inhibition plays an important role in critical alteration of SVI in the genesis of prehypertension, especially in males, and WHR could be a better indicator of SVI in prehypertensives. It was suggested that prehypertensives should improve their vagal tone to restore the sympathovagal homeostasis.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Prehipertensión/fisiopatología , Caracteres Sexuales , Enfermedades del Nervio Vago/fisiopatología , Adulto , Enfermedades del Sistema Nervioso Autónomo/metabolismo , Presión Sanguínea/fisiología , Peso Corporal/fisiología , Metabolismo Energético/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Inhibición Neural/fisiología , Prehipertensión/metabolismo , Sistema Nervioso Simpático/fisiología , Nervio Vago/fisiología , Enfermedades del Nervio Vago/metabolismo , Relación Cintura-CaderaRESUMEN
Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.
Asunto(s)
Dieta/efectos adversos , Resistencia a Medicamentos , Leptina/metabolismo , Neuronas Aferentes/metabolismo , Obesidad/complicaciones , Obesidad/etiología , Nervio Vago/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Dieta Aterogénica , Grasas de la Dieta/farmacología , Resistencia a Medicamentos/efectos de los fármacos , Resistencia a Medicamentos/fisiología , Ingestión de Energía/efectos de los fármacos , Ingestión de Energía/fisiología , Leptina/farmacología , Lipopolisacáridos/farmacología , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/patología , Obesidad/metabolismo , Obesidad/patología , Ratas , Ratas Sprague-Dawley , Receptores de Leptina/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/fisiología , Nervio Vago/efectos de los fármacos , Nervio Vago/patología , Enfermedades del Nervio Vago/etiología , Enfermedades del Nervio Vago/metabolismoRESUMEN
A 40-year-old man was admitted to our department, because of sudden onset of dysphagia, hoarseness, left neck pain and headache. There were no skin lesions. On neurological examination, there were paralysis of the left soft palate and constrictor muscles of the pharynx, weakness of the left sternocleidomastoid and left upper trapezius. In cerebrospinal fluid (CSF) examination, cell count and protein concentration were elevated. Antibody titer to varicella zoster virus (VZV) was elevated in both the serum and CSF. And VZV-DNA was detected by PCR from CSF. Gd enhanced MRI showed the nodular lesion at the left jugular foramen. The diagnosis of Vernet's syndrome (VS) associated with VZV infection was made. The patient's symptoms were immediately improved with 30 mg of prednisone and 3 g of varaciclovir daily for 14 days. Only a few cases of VS due to VZV have been reported previously. Our case is the first case that detected VZV-DNA in CSF by PCR.
Asunto(s)
Encefalitis por Varicela Zóster/complicaciones , Enfermedades del Nervio Glosofaríngeo/etiología , Enfermedades del Nervio Vago/etiología , Adulto , Anticuerpos/sangre , Anticuerpos/líquido cefalorraquídeo , Encefalitis por Varicela Zóster/metabolismo , Encefalitis por Varicela Zóster/patología , Enfermedades del Nervio Glosofaríngeo/metabolismo , Enfermedades del Nervio Glosofaríngeo/patología , Enfermedades del Nervio Glosofaríngeo/virología , Herpesvirus Humano 3/inmunología , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades del Nervio Vago/metabolismo , Enfermedades del Nervio Vago/patología , Enfermedades del Nervio Vago/virologíaRESUMEN
Exposure to stressors that elicit fear and feelings of hopelessness can cause severe vagal activation leading to bradycardia, syncope, and sudden death. These phenomena though documented, are difficult to diagnose, treat clinically, and prevent. Therefore, an animal model incorporating these cardiovascular conditions could be useful. The present study examined 'sinking' during a 2-h swim stress, a phenomenon that occurs in 50% of rats during 25 degrees C water exposure. Concurrent measurements of body temperature, immobility, heart rate (HR), and PR interval (a measure of vagal activity) were made. Neither decreases in immobility nor variations in hypothermia during swim were correlated with sinking. Bradycardia was more severe in sinking rats (average minimum HR+/-SEM; 143+/-13 vs 247+/-14; p<0.01), and PR interval was elevated (p<0.0001). To examine potential modulation of vagal activity during stress, corticotropin-relasing factor (CRF) receptor antagonists (antalarmin, R121919 and astressin B), a glucocorticoid receptor antagonist (RU486), and a peripherally acting cholinergic antagonist (methylatropine nitrate) were administered. The centrally acting CRF antagonist, antalarmin (32 mg/kg), produced elongation of the PR interval (p<0.0001), robust bradycardia (135+/-18; p<0.001), and increased sinking (92%; p<0.05), and methylatropine nitrate (3.2 mg/kg) blocked these effects. Corroborating these data, two different CRF antagonists, R121919 (30 mg/kg) and astressin B (intracerebroventricular (i.c.v.), 0.03 mug/rat) increased sinking to 100%. RU486 (20 mg/kg) blocked HPA axis negative feedback and decreased percent sinking to 25%. From these studies, we concluded that sinking during a 2-h water exposure was a result of extreme vagal hyperactivity. Furthermore, stress-induced CRF release may serve to protect against elevated cardiac vagal activity.
Asunto(s)
Bradicardia/inducido químicamente , Bradicardia/fisiopatología , Tolerancia al Ejercicio/efectos de los fármacos , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Estrés Psicológico/complicaciones , Enfermedades del Nervio Vago/inducido químicamente , Animales , Bradicardia/metabolismo , Antagonistas Colinérgicos/farmacología , Hormona Liberadora de Corticotropina/metabolismo , Hormona Liberadora de Corticotropina/farmacología , Muerte Súbita Cardíaca , Modelos Animales de Enfermedad , Tolerancia al Ejercicio/fisiología , Fatiga/inducido químicamente , Fatiga/metabolismo , Fatiga/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Hipotermia Inducida , Masculino , Mifepristona/farmacología , Fragmentos de Péptidos/farmacología , Agitación Psicomotora/fisiopatología , Pirimidinas/farmacología , Pirroles/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Estrés Psicológico/fisiopatología , Natación/fisiología , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiopatología , Enfermedades del Nervio Vago/metabolismo , Enfermedades del Nervio Vago/fisiopatologíaRESUMEN
Facial nerve axotomy (FNA) is a well-established experimental model of motoneuron regeneration. After peripheral nerve axotomy, a sequence of events including glial activation and axonal regrowth leads to functional recovery of the afflicted pool of motoneurons. Using microarray analysis we identified an increase in the expression of 60 genes (at a false discovery rate of 0.1, genes were significant P < 0.004) within the facial nucleus as a consequence of nerve injury. In situ hybridization analysis validated the increased expression of many of these axotomy-induced genes. One specific gene, encoding a unique primary amino acid sequence, termed hemopoietic- and neurologic-expressed sequence-1 (Hn1), was evaluated more extensively using several additional nerve injury paradigms. Hn1 mRNA was upregulated in injured facial motoneurons in both rats and mice. Sustained upregulation of Hn1 mRNA was evident after nerve resection whereas levels of Hn1 mRNA returned to baseline in animals subjected to nerve crush or nerve transection. Hn1 was also increased in the dorsal motor nucleus and the nucleus ambiguous after vagus nerve axotomy, another regeneration model. No upregulation of Hn1 expression was observed, however, in two nonregeneration models: FNA in newborn rats and rubrospinal tractotomy. Hn1 mRNA was ubiquitous in the developing central nervous system whereas its expression in adult brain was confined to neurons of the hippocampus, cortex and cerebellum. These findings identify Hn1 as a gene associated with nervous system development and nerve regeneration.
Asunto(s)
Traumatismos del Nervio Facial/genética , Nervio Facial/metabolismo , Regeneración Nerviosa/genética , Proteínas del Tejido Nervioso/genética , Proteínas/genética , Activación Transcripcional/genética , Animales , Axotomía , Proteínas de Ciclo Celular , Nervio Facial/citología , Traumatismos del Nervio Facial/metabolismo , Regulación de la Expresión Génica/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Asociadas a Microtúbulos , Neuronas Motoras/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Rombencéfalo/citología , Rombencéfalo/metabolismo , Regulación hacia Arriba/fisiología , Nervio Vago/citología , Nervio Vago/metabolismo , Enfermedades del Nervio Vago/genética , Enfermedades del Nervio Vago/metabolismoRESUMEN
An unprecedented presentation of multicentric paraganglioma in a 48-year-old man is described. One of the paragangliomas, originally diagnosed as a carcinoid tumor, presented as a lung mass and was removed. Four years later, an intravagal paraganglioma was discovered. The lung and intravagal tumors had identical morphologic and immunoreactive characteristics. Both tumors consisted of chief cells (type 1) and sustentacular cells (type 2). The chief cells were immunoreactive with neuroendocrine markers (synaptophysin and chromogranin), but nonreactive with epithelial markers (CAM 5.2, high- and low-molecular-weight keratins, epithelial membrane antigen, and carcinoembryonic antigen). The sustentacular cells were positive for S100 protein. Although pulmonary carcinoids may mimic paragangliomas and occasionally contain sustentacular cells, the diagnosis was rejected because the tumor cells did not demonstrate reactivity with epithelial markers.