RESUMO
AIM: Repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex can induce analgesic effects in patients with chronic pain syndromes through its effect on central pain-modulatory systems. Our aim was to evaluate the effect of rTMS on rectal sensitivity in irritable bowel syndrome (IBS) patients. METHOD: In this randomized, sham-controlled, proof-of concept trial, 21 IBS patients (11 women and 10 men; mean age 44.0 ± 12.6 years) were randomized, using a double-blind crossover protocol, to active or sham rTMS for 5 days of treatment. The primary outcome was the increase in the pressure pain threshold after rTMS. Secondary outcomes were the changes in maximum tolerated rectal volume, rectal compliance and average pain intensity between baseline and the end of the treatments. RESULTS: There were no statistically significant differences between active and sham rTMS in terms of an increase in the pressure pain threshold, maximum tolerated volume and rectal compliance at the end of the treatments compared with baseline. However, in the subgroup of patients with the most marked rectal hypersensitivity, the volume threshold was significantly improved by active, but not by sham, rTMS (P = 0.03). Patients experienced a significant improvement in pain regardless of the type of stimulation. CONCLUSION: This pilot study failed to demonstrate any benefit of rTMS on our primary end-point. However, the effect of rTMS on rectal tolerated volume in the most hypersensitive patients was encouraging enough to plan more powered studies.
Assuntos
Síndrome do Intestino Irritável/terapia , Córtex Motor , Limiar da Dor/fisiologia , Pressão , Reto/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , Resultado do TratamentoRESUMO
Esophageal multichannel intraluminal pH-impedance recording (MII) is now a valid technique for determining the acidic, liquid, gas or mixed nature of gastroesophageal reflux episodes. However, some recordings may stop prematurely due to technical reasons or poor patient tolerance of the probe. Therefore, we questioned whether analysis of post-prandial 3-hour recording could predict the results obtained in ambulatory 24-hour recording. Fifty patients with symptoms of gastroesophageal reflux disease were investigated. For each patient, post-prandial 3-hour MII was recorded after a test meal, then followed by ambulatory 21-hour MII. Correlation between the total number of liquid reflux events in the 3-hour and 24-hour recordings was elevated (R=0.71; P<0.001), with better correlation for acid (R=0.80; P<0.001) and weak acid reflux (R=0.56; P<0.001) than non-acid reflux (R=0.44; P<0.01). Sensitivity and specificity of 3-hour recording in detecting elevated liquid reflux over 24 hours (id>75reflux/24 h) were 49% and 100%, respectively, for 8 or less liquid/mixed reflux events per 3 hours, and 78% and 88%, respectively for 15 or more liquid/mixed reflux events per 3 hours. The sensitivity and specificity of symptom association probability (SAP) calculated over 3 hours were 56% and 91%, respectively. In conclusion, we identified relevant indicators on the 3-hour post-prandial recording likely to give accurate prediction of absence or presence of gastroesophageal reflux disease from 24-hour MII recording.
Assuntos
Monitoramento do pH Esofágico , Refluxo Gastroesofágico/diagnóstico , Adulto , Idoso , Impedância Elétrica , Monitoramento do pH Esofágico/instrumentação , Feminino , Determinação da Acidez Gástrica/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de TempoRESUMO
AIM: The hypothesis was tested that evoked pressure curves (EPCs) after transcranial magnetic stimulation (TMS) would provide additional neuropathophysiological information on the descending pathways to the external anal sphincter (EAS) in patients with faecal incontinence (FI). METHOD: Twenty-five healthy subjects and 69 patients with FI were investigated. TMS was applied to the vertex, and EPCs were recorded with a probe placed through the EAS. TMS was performed with the EAS at rest and during contraction (facilitated responses). At least three responses were recorded for each modality. Clinical data and anorectal manometric, electrophysiological perineal and transanal ultrasound recordings were compared with respect to the EPC results. RESULTS: There was no statistically significant difference between the EPCs of healthy subjects and FI patients. Twenty-three per cent of the FI patients had abnormal EPC latencies, with significantly lower voluntary contraction amplitudes (P = 0.03) and significantly higher rectal sensation (P = 0.04) than the other group. We found no significant difference between FI patients with and without abnormal EPC latencies in terms of clinical characteristics and electrophysiological and endoanal ultrasound parameters. There was no difference in the identified causes of the FI between the two groups. CONCLUSION: As abnormal EPC latencies were found in 23% of FI patients with no known central neurological disease, abnormal EPC latencies might reveal undetected lesions of descending pathways in patients with FI.
Assuntos
Canal Anal/fisiopatologia , Potencial Evocado Motor/fisiologia , Incontinência Fecal/fisiopatologia , Contração Muscular/fisiologia , Músculo Estriado/fisiopatologia , Pressão , Estimulação Magnética Transcraniana/métodos , Adulto , Idoso , Canal Anal/fisiologia , Estudos de Casos e Controles , Eletromiografia , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Músculo Estriado/fisiologia , Adulto JovemRESUMO
OBJECTIVES: The objective of this study was to show that although transcutaneous electrical tibial nerve stimulation (TENS) is being increasingly used to treat fecal incontinence (FI), its efficacy has never been proved using controlled trials. METHODS: In this randomized, double-blind, sham-controlled trial, 144 patients aged 30-82 years from nine centers were randomly assigned to receive either active or sham stimulations for 3 months. The primary end point was the response to treatment based on the number of incontinence and urgency episodes. Secondary end points were severity scores, quality of life scores, delay to postpone defecation, patient self-assessment of treatment efficacy, physician assessment of TENS efficacy, anorectal manometry, and adverse events. RESULTS: No statistically significant difference was seen between active and sham TENS in terms of an improvement in the median number of FI/urgency episodes per week. Thirty-four patients (47%) who received the active TENS treatment exhibited a >30% decrease in the FI severity score compared with 19 patients (27%) who received the sham treatment (odds ratio 2.4, 95% confidence interval 1.1-5.1, P=0.02). No differences in delay to postpone defecation, patient self-assessment of treatment efficacy, or anorectal manometry were seen between the two groups. The evaluating physicians rated the active stimulations as more effective than the sham stimulations (P=0.01). One minor therapy-related adverse event was observed (1.5%) (see Supplementary Consort 1b). CONCLUSIONS: We failed to demonstrate any benefit of TENS on our primary end-point.
Assuntos
Incontinência Fecal/fisiopatologia , Incontinência Fecal/terapia , Nervo Tibial , Estimulação Elétrica Nervosa Transcutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/fisiopatologia , Defecação , Método Duplo-Cego , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Qualidade de Vida , Reto/fisiopatologia , Autorrelato , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo , Estimulação Elétrica Nervosa Transcutânea/efeitos adversos , Estimulação Elétrica Nervosa Transcutânea/métodos , Resultado do TratamentoRESUMO
AIM: Rectal hypercontractility can lead to faecal incontinence (FI). Botulinum toxin (BT) has been used successfully for the treatment of bladder overactivity. This study aimed to evaluate the therapeutic value of intrarectal injections of BT in inhibiting colorectal contractions and relieving FI in patients suffering from FI as a result of overactive rectal contractions. METHOD: A prospective open study was carried out in Rouen University Hospital. Six patients (four men and two women) with severe FI related to overactive rectal contractions underwent intrarectal submucosal injections of BT placed in three rows of 10, 1-ml injections (50 U/1 ml; Dysport(®)) starting 1 cm above the dentate line and repeated twice, at intervals of 5 cm proximally. The end-points included improvement in the FI score, in faecal incontinence quality of life (FIQL) and of manometric abnormality. RESULTS: All patients reported improvement in the FI score [18.2±1.1 at baseline vs 9.0±1.7 at 3 months (P=0.04)] and in FIQL. Rectal contractile activity was reduced. The frequency of contractions remained unaffected (28.1±6.6/h; P=0.46 vs baseline). High-amplitude contractions of >50 cmH(2)O were significantly decreased in all patients (16.6±3.9 vs 6.6±4.1/h; P=0.03). CONCLUSION: Patients with an 'overactive rectum' are a heterogeneous group, with varying causes of dysfunction. The dose of BT used was arbitrarily selected. Nevertheless, the study introduces a further therapeutic option in the treatment of FI caused by rectal overactivity.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Incontinência Fecal/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Reto/fisiopatologia , Adulto , Idoso , Incontinência Fecal/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Sigmoidoscopia , Resultado do TratamentoRESUMO
Gastroparesis is the most common gastric motility disorder. The cardinal symptoms are nausea, vomiting, gastric fullness, early satiety, or bloating, associated with slow gastric emptying in the absence of mechanical obstruction. Delayed gastric emptying is demonstrated by a gastric emptying scintigraphy or by a breath test. Gastroparesis can be idiopathic, post-operative, secondary to diabetes, iatrogenic, or post-infectious. Therapeutic care must be multidisciplinary including nutritional, medical, endoscopic and surgical modes. The complications of delayed gastric emptying must be sought and addressed, particularly malnutrition, in order to identify and correct vitamin deficiencies and fluid and electrolyte disturbances. An etiology should be identified and treated whenever possible. Improvement in symptoms can be treated by dietary regimes and pharmaceutical treatments, including prokinetics. If these are not effective, specialized endoscopic approaches such as endoscopic or surgical pyloromyotomy aim at relaxing the pyloric sphincter, while the implantation of an electrical stimulator of gastric muscle should be discussed in specialized centers.
Assuntos
Cirurgia Bariátrica , Terapia por Estimulação Elétrica , Gastroparesia , Piloromiotomia , Gastroparesia/diagnóstico , Gastroparesia/etiologia , Gastroparesia/cirurgia , Gastroparesia/terapia , Humanos , Piloro/cirurgiaRESUMO
AIM: Sacral nerve stimulation (SNS) reduces incontinence episodes and improves the quality of life of patients treated for faecal incontinence. However, the exact mechanism of action of this technique remains unclear. The present article reviews the pertinent neuroanatomy and neurophysiology related to SNS and provides explanations for potential mechanisms of action. METHOD: A systematic review of the literature was performed for studies of the potential mechanisms of action of SNS, using MEDLINE, PubMed, Embase and the Cochrane Library. Articles dealing with the technique, adverse events and economic evaluations of SNS, as well as literature reviews, were excluded, except for reviews dealing with the mechanisms of action of SNS. The following inclusion criteria were used to select articles: (i) articles in English, (ii) randomized, double-blinded, sham-controlled studies, and (iii) cohort studies. Case-control studies or retrospective studies were cited only when randomized or cohort studies could not be found. RESULTS: We propose three hypotheses to explain the mechanism of action of SNS: (i) a somato-visceral reflex, (ii) a modulation of the perception of afferent information, and (iii) an increase in external anal sphincter activity. CONCLUSION: The mechanism of action of SNS in patients with faecal incontinence almost certainly depends on the modulation of spinal and/or supraspinal afferent inputs. Further research on humans and animals will be required to gain a better understanding of the mechanisms of action of SNS.
Assuntos
Terapia por Estimulação Elétrica , Sistema Nervoso Entérico/fisiologia , Incontinência Fecal/fisiopatologia , Incontinência Fecal/terapia , Canal Anal/inervação , Colo/inervação , Defecação/fisiologia , Humanos , Plexo Lombossacral , Diafragma da Pelve/inervaçãoRESUMO
PURPOSE: Our aim was to evaluate medium-term results of transvaginal implantation of an artificial anal sphincter in a large series of patients. METHODS: Women undergoing treatment for severe fecal incontinence at Rouen University Hospital, Rouen, France, from January 2003 through December 2007 were eligible for the study if the fecal incontinence had lasted for 6 months and if they had attempted other therapies without success. All patients received implantation of an artificial anal sphincter via a transvaginal approach. Incontinence was assessed with the Cleveland Clinic Florida Fecal Incontinence Scale (Wexner score). RESULTS: A total of 32 women entered the study. Their median age was 63 (range, 26-79) years. At entry, 20 (63%) had severe destruction and scarring of the perineum, which was a contraindication for implantation via a perineal approach. Nine patients (28.1%) had previously undergone implantation of an AAS which had been removed because of complications, and 5 had had a Pickrell procedure for anal agenesia. No deaths occurred during the study. The device was removed in a total of 9 patients (28.1%): in 7 because of septic adverse events within the first 6 months after the operation, in 1 because of poor function, and in 1 for psychological reasons despite good functional results. Implantation was successful in 23 patients (71.9%), and the device remained activated for a mean follow-up of 41 (range, 18-75) months, with a mean decrease in Cleveland Clinic incontinence score from 18.4 to 6.8 (P < .0001). None of the patients complained of dyspareunia. CONCLUSIONS: The transvaginal approach for implantation of an artificial anal sphincter permits treatment of women with fecal incontinence who have severe damage and scarring of the anterior perineum. This route provides an alternative for patients whose only therapeutic option would previously have been a defunctioning stoma.
Assuntos
Canal Anal/cirurgia , Órgãos Artificiais , Incontinência Fecal/cirurgia , Hospitais Universitários , Adulto , Idoso , Defecação , Desenho de Equipamento , Incontinência Fecal/fisiopatologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , VaginaRESUMO
BACKGROUND AND AIMS: IBS patients have an impaired quality of life (QoL) and feel dissatisfaction with medical care. We aim to describe the expectations of members of the French Association of IBS patients (APSSII) concerning health care providers (HCPs) and a patients' organization. PATIENTS AND METHODS: From January to June 2013, APSSII members were asked to answer questionnaires on their expectations and experiences concerning IBS and HCP. RESULTS: 222/330 (67%) responded (women: 68.5%, 46.5±17.7 years, disease duration: 8.8±0.7 years, IBS-D 33.6%, IBS-C 26.7%, IBS-M 38.2%. IBS-SSS>300 in 53% and HAD score>19 in 45%). QoL impairment was correlated with disease severity and HAD score (r=-0.707 and r=-0.484, P<0.001 respectively), but not with IBS subtype. Expectations for IBS were "improved health", "better information on causes and treatments" (94%) and "better disease recognition" (86%). A significant gap was observed between expectations and experiences with HCPs. Better information, less isolation, recognition of the disease and a decrease in medical expenses were the main expectations for joining a patients' organization. CONCLUSIONS: French IBS patients have a severe disease with a significant psychological impact and impaired QoL in half of the patients, certain unsatisfied expectations concerning HCP and high expectations in joining a patients' organization.
Assuntos
Síndrome do Intestino Irritável/psicologia , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e QuestionáriosAssuntos
Colectomia , Neoplasias do Colo/cirurgia , Constipação Intestinal/cirurgia , Íleo/cirurgia , Reto/cirurgia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Some consider that patients with visceral hypersensitivity may represent a separate entity within the IBS population not only from a pathophysiological but also from a clinical perspective. The aim of this prospective exploratory study was to assess whether characteristics of abdominal pain in IBS patients could be suggestive of hypersensitivity. METHODS: This prospective study included consecutive IBS patients selected by Rome III criteria. Validated scores (IBS-SSS, Bristol stool scale, HADS) were used to phenotype patients who were also asked to describe the main location of their abdominal pain on a simple image (abdomen divided into 6 zones). Progressive isobaric rectal distensions were performed to demonstrate, with the ascending method of limits, allodynia (pain threshold lower than 24 mmHg). KEY RESULTS: Fifty patients (women: 72%), 42.6 ± 15.7 years old, were included. Sub-types were IBS-D, IBS-C and IBS-M in 58%, 22% and 20% of cases, respectively. Allodynia was present in 18% of cases. Neither IBS-SSS nor intensity of pain was predictive of hypersensitivity. In hypersensitive patients, pain was more often located in one of the two iliac fossa (P = 0.02) and located outside these areas in only 11% of cases. The sensitivity and the specificity of this pain location to differentiate hyper from normosensitive patients were 0.89 and 0.59, respectively. CONCLUSIONS & INFERENCES: The location of pain is different between hyper and normosensitive IBS patients. Pain located outside one of the two iliac fossa suggests that the patient is normosensitive.
Assuntos
Dor Abdominal/diagnóstico , Hiperalgesia/diagnóstico , Síndrome do Intestino Irritável/diagnóstico , Medição da Dor/métodos , Dor Visceral/diagnóstico , Dor Abdominal/fisiopatologia , Adulto , Feminino , Humanos , Hiperalgesia/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor/normas , Estudos Prospectivos , Dor Visceral/fisiopatologiaRESUMO
BACKGROUND: The functional lumen imaging probe (EndoFLIP® ) is a new technology that measures the distensibility of the anal canal represented by the anal distensibility index. The aims of this study were (i) to compare the anal distensibility index to anal pressure in a cohort of patients with fecal incontinence (FI) and (ii) to compare the diagnostic value of the EndoFLIP® to that of high-resolution anorectal manometry (HRAM) in the same cohort of patients. METHODS: Eighty-three consecutive patients with FI who underwent EndoFLIP® and HRAM assessments were enrolled. The diagnostic value of the EndoFLIP® was compared to that of HRAM and agreement between EndoFLIP® and HRAM data was assessed. KEY RESULTS: More than 70% of the patients diagnosed with anal deficiency at rest and/or during voluntary contractions by HRAM had the same diagnosis using the EndoFLIP® . Two patients with higher distensibility indexes at rest had normal anal resting pressures. Sixteen patients with a normal EndoFLIP® index (ie, normal distensibility index at rest and during voluntary contractions) had an abnormal HRAM result. Seven of these 16 patients (44%) had no sphincter lesion or neuropathic disorder that could explain an abnormal anal sphincter function. CONCLUSIONS & INFERENCES: We demonstrated that the anal distensibility index and HRAM results are largely in agreement. We did, however, identify several discrepancies between the two techniques, indicating that they may be complementary.
Assuntos
Canal Anal/fisiopatologia , Impedância Elétrica , Incontinência Fecal/diagnóstico , Incontinência Fecal/fisiopatologia , Manometria/métodos , Reto/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/patologia , Estudos de Coortes , Eletrodos , Feminino , Humanos , Masculino , Manometria/instrumentação , Pessoa de Meia-Idade , Estudos Prospectivos , Reto/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Anorexia nervosa, a restrictive eating disorder, is often associated with gastrointestinal disorders, particularly a delayed gastric emptying. However, the mechanisms remained poorly documented. Thus, we aimed to evaluate gastric emptying and antrum protein metabolism in the Activity-Based Anorexia model (ABA). METHODS: Females C57Bl/6 mice were randomized into 3 groups: Control, ABA, and Limited Food Access (LFA). Food access has been progressively limited from 6 h/day at day 6 to 3 h/day at day 9 and until day 17. ABA mice had free access to an activity wheel. Gastric emptying was assessed. On gastric extracts, a proteomic analysis was performed, as well as an evaluation of protein synthesis and protein oxidation. KEY RESULTS: Both LFA and ABA mice exhibited a delayed gastric emptying compared with Controls (P < .05). Proteomic approach revealed 15 proteins that were differentially expressed. Among these proteins, we identified 2 clusters of interest contributing to (i) the organization of muscle fiber with ACTA2, VCL, KRT19, KRT8, and DES proteins and (ii) "heat shock proteins" with STIP1, HSPD1, and HSPA8 proteins. ABA mice specifically exhibited an increased rate of gastric oxidized proteins. CONCLUSIONS AND INFERENCES: Delayed gastric emptying observed in anorectic conditions appears to be secondary to malnutrition. However, an oxidative stress is specifically present in the stomach of ABA mice. Its role remains to be further studied.
Assuntos
Anorexia/metabolismo , Esvaziamento Gástrico/fisiologia , Gastroparesia/metabolismo , Carbonilação Proteica/fisiologia , Antro Pilórico/metabolismo , Animais , Anorexia/complicações , Anorexia/fisiopatologia , Feminino , Gastroparesia/etiologia , Gastroparesia/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
Interactions between gastrointestinal signals are a part of integrated systems regulating food intake (FI). We investigated whether cholecystokinin (CCK)-8 and urocortin systems potentiate each other to inhibit FI and gastric emptying (GE) in fasted mice. Urocortin 1 and urocortin 2 (1 microg/kg) were injected ip alone or with CCK (3 microg/kg) in lean, diet-induced obese (DIO) or corticotropin-releasing factor receptor-2 (CRF(2))-deficient mice. Gastric vagal afferent activity was recorded from a rat stomach-vagus in vitro preparation. When injected separately, urocortin 1, urocortin 2, or CCK did not modify the 4-h cumulative FI in lean mice. However, CCK plus urocortin 1 or CCK plus urocortin 2 decreased significantly the 4-h FI by 39 and 27%, respectively, compared with the vehicle + vehicle group in lean mice but not in DIO mice. Likewise, CCK-urocortin-1 delayed GE in lean but not DIO mice, whereas either peptide injected alone at the same dose had no effect. CCK-urocortin 2 suppression of FI was observed in wild-type but not CRF(2)-deficient mice. Gastric vagal afferent activity was increased by intragastric artery injection of urocortin 2 after CCK at a subthreshold dose, and the response was reversed by devazepide. These data establish a peripheral synergistic interaction between CCK and urocortin 1 or urocortin 2 to suppress FI and GE through CRF(2) receptor in lean mice that may involve CCK modulation of gastric vagal afferent responsiveness to urocortin 2. Such synergy is lost in DIO mice, suggesting a resistance to the satiety signaling that may contribute to maintain obesity.
Assuntos
Colecistocinina/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Receptores de Hormônio Liberador da Corticotropina/fisiologia , Saciação/efeitos dos fármacos , Urocortinas/farmacologia , Animais , Colecistocinina/administração & dosagem , Sinergismo Farmacológico , Esvaziamento Gástrico/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Modelos Biológicos , Obesidade/fisiopatologia , Fragmentos de Peptídeos/administração & dosagem , Ratos , Receptores de Hormônio Liberador da Corticotropina/genética , Transdução de Sinais/efeitos dos fármacos , Estômago/efeitos dos fármacos , Estômago/inervação , Estômago/fisiologia , Urocortinas/administração & dosagem , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiologiaRESUMO
High-frequency/low-energy gastric electrical stimulation (GES) is an efficient therapy to treat gastric emptying-related disorders but its mechanism of action remains poorly understood. We aimed to assess the effects of high-frequency/low-energy GES on corticotropin-releasing factor (CRF)-producing neurons in the paraventricular nucleus of the hypothalamus (PVN), which are involved in gastric ileus induced by laparotomy. Two electrodes were implanted in the rat gastric antrum during laparotomy, then stimulation (amplitude: 2 mA; pulse duration 330 micros; frequency: 2 Hz; 1 min ON/2 min OFF) or sham stimulation (control group) were applied. Using immunohistochemistry, the number of c-Fos protein-expressing neurons (c-Fos protein-immunoreactive cells, Fos-IR) was quantified in the PVN after 1 h of stimulation. The number of neurons expressing simultaneously c-Fos protein and CRF mRNA was measured by means of immunocytochemistry combined with in situ hybridization. Finally, c-Fos and CRF mRNA levels in the hypothalamus were determined by in situ hybridization or quantitative reverse transcriptase-polymerase chain reaction. Fos-IR in the PVN was significantly decreased 1 h after GES (P<0.05) but was not affected by sub-diaphragmatic vagotomy. The number of neurons containing c-Fos protein and CRF mRNA was lower in the GES group compared with the control group (P<0.05). In addition, c-Fos and CRF mRNA levels in the PVN were significantly decreased by GES (PAssuntos
Hormônio Liberador da Corticotropina/metabolismo
, Terapia por Estimulação Elétrica
, Pseudo-Obstrução Intestinal/terapia
, Núcleo Hipotalâmico Paraventricular/metabolismo
, Complicações Pós-Operatórias/terapia
, Estômago/fisiopatologia
, Animais
, Contagem de Células
, Hormônio Liberador da Corticotropina/genética
, Modelos Animais de Doenças
, Regulação para Baixo/fisiologia
, Sistema Hipotálamo-Hipofisário/citologia
, Sistema Hipotálamo-Hipofisário/metabolismo
, Imuno-Histoquímica
, Pseudo-Obstrução Intestinal/metabolismo
, Pseudo-Obstrução Intestinal/fisiopatologia
, Masculino
, Complicações Pós-Operatórias/metabolismo
, Complicações Pós-Operatórias/fisiopatologia
, Proteínas Proto-Oncogênicas c-fos/genética
, Proteínas Proto-Oncogênicas c-fos/metabolismo
, RNA Mensageiro/metabolismo
, Ratos
, Ratos Wistar
, Estômago/inervação
, Vagotomia
RESUMO
Obestatin is a newly identified ghrelin-associated peptide (GAP) that is derived from post-translational processing of the prepro-ghrelin gene. Obestatin has been reported initially to be the endogenous ligand for the orphan receptor G protein-coupled receptor 39 (GPR39), and to reduce refeeding- and ghrelin-stimulated food intake and gastric transit in fasted mice, and body weight gain upon chronic peripheral injection. However, recent reports indicate that obestatin is unlikely to be the endogenous ligand for GPR39 based on the lack of specific binding on GRP39 receptor expressing cells and the absence of signal transduction pathway activation. In addition, a number of studies provided convergent evidence that ghrelin injected intracerebroventricularly or peripherally did not influence food intake, body weight gain, gastric transit, gastrointestinal motility, and gastric vagal afferent activity, as well as pituitary hormone secretions, in rats or mice. Similarly, obestatin did not alter ghrelin-induced stimulation of food intake or gastric transit. Therefore, the present state-of-knowledge on obestatin and GPR39 is leaving many unanswered questions that deserve further consideration. Those relate not only to redefining the biological action of obestatin that should be renamed GAP, but also the identification of the native ligand for GPR39.
Assuntos
Ingestão de Alimentos , Hormônios Peptídicos/química , Hormônios Peptídicos/fisiologia , Peptídeos/química , Terminologia como Assunto , Animais , Grelina , Humanos , Hormônios Peptídicos/genética , Processamento de Proteína Pós-Traducional , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Ghrelin is a gut peptide well established to induce prokinetic and appetite stimulatory actions. Obestatin is a novel 23-amino acid peptide derived from the processing of the ghrelin gene. The peptide name was in keeping with its initially reported actions to suppress food intake and digestive motility and to antagonize ghrelin's stimulatory effect through interaction with the orphan GPR-39 receptor. However, subsequently, these findings have been questioned because obestatin actions to reduce food intake and to inhibit gastrointestinal (GI) motility in vivo and in vitro have not been reproduced by several groups. Furthermore, while GPR-39 appears to be involved in gut motor functions, convergent reports showed that obestatin is not the cognate ligand for this receptor. In light of recent controversy over the effects of obestatin, the present findings from De Smet et al. provides additional evidence that obestatin does not influence food intake and GI motility in vivo and in vitro. Taken together, existing reports curtail the initial promise that obestatin is a new regulator of appetite and digestive motility. Therefore, it is proposed to rename obestatin as ghrelin-associated peptide.
Assuntos
Regulação do Apetite/fisiologia , Motilidade Gastrointestinal/fisiologia , Hormônios Peptídicos/fisiologia , Animais , Grelina , Humanos , Hormônios Peptídicos/genética , Hormônios Peptídicos/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
BACKGROUND: Sacral nerve stimulation (SNS) is a surgical treatment of fecal and urinary incontinence that consists of inserting a stimulating electrode into one of the s3 or s4 sacral holes. In addition to the benefit of SNS in the treatment of incontinence, recent studies showed that SNS is effective in the treatment of irritable bowel syndrome as well as bladder pain syndrome. The aim of this study was to evaluate the effect of SNS on visceral mechanosensitivity in a cross-organ sensitization rat model. METHODS: Hypersensitive model was obtained by instillation of acetic acid into the bladder of rats during 5 minutes, 30 minutes before the start of the experiments. Visceral sensitivity was assessed by monitoring the change in mean arterial pressure in response to graded isobaric colorectal distension series. To decipher the mechanisms underlying SNS effect, rats were administered intravenously either a nonselective opioid receptor antagonist (naloxone) or a nitric oxide synthesis antagonist (L-NAME). Neuronal activation in the dorsal horn of the sacral spinal cord was measured by counting c-fos immunoreactive cells in response to colorectal distension and NMS. KEY RESULTS: Intravesical acetic acid instillation increased mean arterial pressure variation in response to colorectal distension when compared to saline group. SNS reduced the variation in arterial pressure. Colorectal distension induced a rise in c-fos immunoreactive cells in the dorsal horn of the spinal cord. This effect was reduced by SNS. CONCLUSIONS & INFERENCES: SNS reduces visceral mechanosensitivity in a cross-organ sensitization model.
Assuntos
Colo/fisiologia , Mecanotransdução Celular/fisiologia , Reto/fisiologia , Sacro/fisiologia , Nervos Espinhais/fisiologia , Dor Visceral/fisiopatologia , Animais , Colo/efeitos dos fármacos , Colo/inervação , Estimulação Elétrica/métodos , Inibidores Enzimáticos/farmacologia , Masculino , Mecanotransdução Celular/efeitos dos fármacos , Antagonistas de Entorpecentes/farmacologia , Ratos , Ratos Sprague-Dawley , Reto/efeitos dos fármacos , Reto/inervação , Sacro/efeitos dos fármacos , Sacro/inervação , Dor Visceral/tratamento farmacológicoRESUMO
Pituitary adenylate cyclase-activating polypeptide (PACAP) and the proopiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone (alpha-MSH) both regulate multiple neuroendocrine functions and feeding behavior. Two subtypes of PACAP receptor mRNAs, pituitary adenylate cyclase-activating polypeptide-specific receptor (PAC1-R) and pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide mutual receptor (VPAC2-R), are actively expressed in the arcuate nucleus of the hypothalamus, where POMC cell bodies are located. This observation led us to investigate the possible regulatory action of PACAP on rat POMC neurons. Double-labeling in situ hybridization histochemistry revealed that approximately 50% of POMC-producing neurons express PAC1-R and/or VPAC2-R mRNAs. The proportion of POMC neurons that also contain PAC1-R mRNA was homogeneous along the rostro-caudal axis of the arcuate nucleus while POMC-positive cell bodies expressing the VPAC2-R subtype were more abundant in the rostral region. Incubation of mediobasal hypothalamic explants with PACAP (10(-7) M; 30 min) increased POMC mRNA expression, and this effect was blocked by PACAP6-38 (10(-6) M). In contrast, incubation with vasoactive intestinal polypeptide (10(-7) M) did not affect POMC mRNA level. Incubation of hypothalamic fragments with PACAP (10(-7) M) caused a significant increase in alpha-MSH content in the tissue and in the incubation medium. Altogether, the present results reveal that exogenous PACAP, acting probably through PAC1-R, regulates the activity of POMC neurons in the rat hypothalamus. These data suggest that the effects of PACAP on the gonadotropin-releasing hormone neuroendocrine axis and the regulation of feeding behavior may be mediated, at least in part, through modulation of POMC neurons.
Assuntos
Núcleo Arqueado do Hipotálamo/citologia , Expressão Gênica/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Pró-Opiomelanocortina/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hibridização In Situ/métodos , Técnicas In Vitro , Masculino , RNA Mensageiro/metabolismo , Radioimunoensaio/métodos , Ratos , Ratos Wistar , Receptores de Melanocortina/genética , Receptores de Melanocortina/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Receptores Tipo II de Peptídeo Intestinal Vasoativo/genética , Receptores Tipo II de Peptídeo Intestinal Vasoativo/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Estatísticas não Paramétricas , Fatores de TempoRESUMO
Obestatin is a new peptide for which anorexigenic effects were recently reported in mice. We investigate whether peripheral injection of obestatin or co-injection with cholecystokinin (CCK) can modulate food intake, gastric motor function (intragastric pressure and emptying) and gastric vagal afferent activity in rodents. Obestatin (30, 100 and 300 microg/kg, i.p.) did not influence cumulative food intake for the 2h post-injection in rats or mice nor gastric emptying in rats. In rats, obestatin (300 microg/kg) did not modify CCK (1 microg/kg, i.p.)-induced significant decrease in food intake (36.6%) and gastric emptying (31.0%). Furthermore, while rats injected with CCK (0.3 microg/kg, i.v.) displayed gastric relaxation, no change in gastric intraluminal pressure was elicited by obestatin (300 microg/kg, i.v.) pre- or post-CCK administration. In in vitro rat gastric vagal afferent preparations, 20 units that had non-significant changes in basal activity after obestatin at 30 microg responded to CCK at 10 ng by a 182% increase. These data show that obestatin neither influences cumulative food intake, gastric motility or vagal afferent activity nor CCK-induced satiety signaling.