RESUMO
Because of the devastating health effect of chronic burned tobacco inhalation, smoking cessation is a public health priority. After a short review of the validated pharmacological tools for smoking cessation we have analysed the clinical data obtained with the increasingly popular e-cigarette as an aid to help current smokers to quit. Although e-cigarette has not proved its effectiveness in smoking cessation yet, the public health authorities have usually adopted a pragmatic position. They recommend trying e-cigarette when validated pharmacological tools have failed in making patients abstinent, on the basis that e-cigarette is strongly assumed to be less toxic and may still help reducing the amount of smoked cigarettes.
Compte tenu des effets dévastateurs du tabagisme chronique sur la santé, le sevrage tabagique est un objectif prioritaire de santé publique. Après un bref rappel sur les méthodes validées d'aide au sevrage, nous abordons les données cliniques obtenues avec la cigarette électronique, dont l'utilisation chez nous devient de plus en plus populaire. Au vu de la littérature actuelle, il semble bien que si la cigarette électronique n'a pas encore démontré de façon univoque son efficacité dans l'aide au sevrage complet, néanmoins, les autorités officielles de santé ont généralement adopté une position compréhensive et pragmatique à son égard, au vu de son potentiel à réduire la consommation de cigarette classique chez les patients ayant échoué avec les aides au sevrage validées.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar/métodos , Bélgica , HumanosRESUMO
WHO, for the first time in its history, asked in 2003, all Member States to sign and enforce a Framework Convention on Tobacco Control (FCTC). Ten years later, it seems important to describe the achievements made in Belgium. The main legislative measures that are taken to control the major avoidable risk factor for health, are recalled. The present status of Belgium activity in this field is described, with an emphasis on the role of health professionals to help smokers quit. The difficult challenge of curing chronic tobacco dependence disease is underlined. Regarding the fight to render tobacco products less attractive, some breakthroughs are occurring in specific countries, and some are maybe coming soon in Europe.
Assuntos
Prevenção do Hábito de Fumar , Fumar/legislação & jurisprudência , Bélgica , Humanos , Saúde Pública , Abandono do Hábito de FumarRESUMO
Endoscopic submucosal dissection (ESD) was developed in Japan but has now also become permanently established in various centers in Europe. ESD is an endoscopic en bloc mucosal resection technique for the treatment of early cancers with a diameter >1 cm and also superficial precancerous lesions, which could only be removed unsatisfactorily in several fragments or with uncertain lateral safety margins using previous loop excision procedures. Using ESD a lesion is excised after circular marking and generous submucosal injection with a safety margin of approximately 5 mm and subsequently resected at the level of the submucosa with a 1-3 mm short diathermic knife. ESD requires high technical skills in interventional endoscopy and is more time-consuming than snare resection techniques. However, numerous studies have shown a clear superiority for ESD with respect to the R0 resection rate and the local recurrence rate. The present article gives a current review of the use of ESD in the upper and lower gastrointestinal tract and demonstrates perspectives of the procedure.
Assuntos
Dissecação/métodos , Endoscopia Gastrointestinal/métodos , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Mucosa/patologia , Mucosa/cirurgia , Dissecação/tendências , Endoscopia Gastrointestinal/tendências , HumanosRESUMO
PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.
Assuntos
Endoscopia por Cápsula/normas , Endoscopia por Cápsula/métodos , Catárticos/administração & dosagem , Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Contraindicações , Enema , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Prontuários Médicos/normas , Educação de Pacientes como AssuntoRESUMO
This review reports the highlights of the first International Conference on Capsule and Double-Balloon Endoscopy, held in Paris (27 - 28 August 2010), under the chairmanship of Professor G. Gay (Nancy, France). The conference was devoted to the technical issues and clinical experience related to capsule endoscopy and double-balloon endoscopy (DBE), techniques that have been developed over the past decade for the endoscopic investigation of intestinal diseases. The conference focused on the technical advances of new-generation endoscopes and capsules and the clinical experience gained with capsule endoscopy and DBE. Important advances in the knowledge of obscure gastrointestinal bleeding, inflammatory bowel diseases, and celiac disease were also discussed. The second part of the conference was mainly devoted to the investigation of the colon and discussed the technical issues and results of initial controlled studies of the colonic capsule vs. conventional colonoscopy. In addition, the clinical usefulness of double colonoscopy was demonstrated in patients with previously failed colonoscopy. Finally, the role of DBE was discussed with respect to the investigation and treatment of patients with surgically modified anatomy. The conference was attended by 750 delegates and presented a unique opportunity for an in-depth review of the current knowledge in the field and to ascertain/determine the main lines for the future developments of capsule endoscopy and DBE.
Assuntos
Endoscopia por Cápsula , Enteroscopia de Duplo Balão , Gastroenteropatias/diagnóstico , Colonoscopia , HumanosRESUMO
These recommendations on video capsule endoscopy, an emerging technology with an impact on the practice of endoscopy, were developed by the European Society of Gastrointestinal Endoscopy (ESGE) Guidelines Committee. The first draft of each section was prepared by one or two members of the writing team, who were selected as experts on the content of that section on the basis of their published work. They used evidence-based methodology, performing MEDLINE and PubMed literature searches to identify relevant clinical studies. Abstracts from scientific meetings were included only if there was no published full paper on a particular topic. If there was disagreement, the first author of the Guideline made the final decision. Recommendations were graded according to the strength of the supporting evidence. The draft guideline was critically reviewed by all authors and submitted to the ESGE councillors for their critical review before approval of the final document. The ESGE Guidelines Committee acknowledges that this document is based on a critical review of the data available at the time of preparation and that further studies may be needed to clarify some aspects. Moreover, this Guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. This document should be regarded as supplying recommendations only to gastroenterologists in providing care to their patients. It is not a set of rules and should not be construed as establishing a legal standard of care, or as encouraging, advocating, requiring, or discouraging any particular treatment. These recommendations must be interpreted according to the clinician's knowledge, expertise, and clinical judgment in the management of individual patients and, if necessary, a course of action that varies from recommendations must be undertaken.
Assuntos
Endoscopia por Cápsula , Gastroenteropatias/diagnóstico , Doenças do Colo/diagnóstico , Doenças do Esôfago/diagnóstico , Europa (Continente) , Humanos , Intestino Delgado/patologia , Sociedades MédicasRESUMO
Invasive intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas may be associated with pancreaticogastric fistulas as shown by case reports. We report the case of a benign IPMN associated with pancreaticogastric and pancreaticoduodenal fistulas. A 70-year-old woman was admitted with intestinal obstruction. Computed tomography and MRI showed a large dilatation of the main pancreatic duct (>1 cm) with intraductal nodules, and pancreaticogastric and pancreaticoduodenal fistulas. Several features in imaging were present to support a malignant IPMN, so that the patient underwent a pancreaticoduodenectomy. The histopathological examination of the surgical specimen showed a benign IPMN. This case proves that a benign IPMN can cause pancreaticogastric and pancreaticoduodenal fistulas, probably resulting from mechanical factors.
Assuntos
Adenocarcinoma Mucinoso/complicações , Carcinoma Ductal Pancreático/complicações , Carcinoma Papilar/complicações , Duodenopatias/etiologia , Fístula Gástrica/etiologia , Fístula Intestinal/etiologia , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/complicações , Adenocarcinoma Mucinoso/cirurgia , Idoso , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Papilar/cirurgia , Duodenopatias/cirurgia , Feminino , Fístula Gástrica/cirurgia , Humanos , Fístula Intestinal/cirurgia , Fístula Pancreática/cirurgia , Neoplasias Pancreáticas/cirurgia , PancreaticoduodenectomiaRESUMO
INTRODUCTION: Patients with interstitial lung diseases (ILD) can be suspected to be at risk of experiencing a rapid flare-up due to COVID-19. However, no specific data are currently available for these patients. METHODS: We retrospectively analyzed a cohort of 401 patients with ILD and determined the proportion of patients hospitalized for proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific symptoms of COVID-19. RESULTS: We found that 1% of patients (n = 4) were hospitalized (1 in ICU) for COVID-19. In total, 310 of the 401 patients answered the phone call. Only 33 patients (0.08%) experienced specific symptoms of SARS-CoV-2 infection. CONCLUSION: Our study did not demonstrate any increased occurrence of severe COVID-19 in ILD patients compared to the global population. Based on our findings, we could not make any conclusion on the incidence rate of SARS-CoV-2 infection in patients with ILDs, or on the overall outcome of immunocompromised patients affected by COVID-19.
Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for the investigation of functional bowel symptoms, and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of functional bowel symptoms was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: Much of the evidence for use of colonoscopy in evaluation of chronic abdominal pain, and/or constipation and/or abdominal bloating is modest. Major limitations include small numbers of patients and lack of adequate characterization of these patients. Large community-based follow-up studies are needed to enable better definition of the natural history of patients with functional bowel disorders. Guidelines stress that alarm features ("red flags"), such as rectal bleeding, anemia, weight loss, nocturnal symptoms, family history of colon cancer, age of onset > 50 years, and recent onset of symptoms should all lead to careful evaluation before a diagnosis of functional bowel disorder is made. EPAGE II assessed these symptoms by means of 12 clinical scenarios, rating colonoscopy as appropriate, uncertain and inappropriate in 42 % (5/12), 25 % (3/12), and 33 % (4/12) of these, respectively. CONCLUSIONS: Evidence to support the use of colonoscopy in the evaluation of patients with functional bowel disorders and no alarm features is lacking. These patients have no increased risk of colon cancer and thus advice on screening for this is not different from that for the general population. EPAGE II criteria, available online (http://www.epage.ch), consider colonoscopy appropriate in patients of > 50 years with chronic or new-onset bowel disturbances, but not in patients with isolated chronic abdominal pain.
Assuntos
Dor Abdominal/patologia , Colonoscopia , Enteropatias/patologia , Constipação Intestinal/patologia , Europa (Continente) , Guias como Assunto , Humanos , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Common bile duct lithiasis after Roux-en-Y gastric bypass (RYGB) or upper gastrointestinal stenosis has become a challenging problem nowadays, especially as obesity surgery is increasing. In this study, we assess the feasibility and performance of laparoscopy-assisted transgastric endoscopic retrograde cholangiopancreatography (LAERCP) and describe its technique. METHODS: A retrospective review of a prospectively collected database of consecutive patients undergoing a LAERCP between February 2014 and May 2015 was performed at a single institution. Indications were common bile duct lithiasis associated with acute or past episodes of cholangitis and pancreatitis. Endoscopic access to the gastric remnant was obtained laparoscopically. RESULTS: In total 5 cases were identified. Four of them had undergone a RYGB and one of them presented a benign esophageal peptic stenosis, not allowing peroral gastric access. Biliary cannulation using LAERCP associated with sphincterotomy and stone extraction was successfully achieved in all patients. Mean duration of the entire procedure was 134minutes (range: 66-200min). No early major complications were observed and the mean postoperative hospital stay was 4 days (range: 2-5 days). CONCLUSIONS: LAERCP is a safe and successful procedure for the treatment of common bile duct lithiasis when conventional biliary access is not feasible, notably after RYGB. Larger trials still need to be performed to evaluate efficacy, technical success, and complications related to this technique.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Cálculos Biliares/terapia , Laparoscopia , Esfinterotomia Endoscópica/métodos , Adulto , Feminino , Seguimentos , Cálculos Biliares/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND STUDY AIMS: The study aim was to compare the diagnostic yield of capsule endoscopy and esophagogastroduodenoscopy (EGD) in patients with suspected esophageal disease. Secondary aims were to assess interobserver variability of capsule endoscopy readings and safety. PATIENTS AND METHODS: In total, 98 patients (53 men, 53 +/- 13 years) with an indication for EGD were included. The patient population was artificially enriched to include two thirds of patients with abnormal esophageal findings at EGD, which was followed by capsule endoscopy. Capsule recordings were blindly read by three endoscopists, one from the center that recruited the patient and two from the other center. Study outcomes were the findings described on EGD and capsule endoscopy, agreement between EGD and capsule endoscopy for findings, quality of the capsule recording, and interobserver agreement for capsule endoscopy quality and findings. RESULTS: EGD was normal in 34 patients and showed esophageal findings in 62 (esophagitis 28, hiatus hernia 21, varices 21, Barrett's esophagus 11, others 7). Average esophageal transit time of the capsule was 361 +/- 393 seconds. Capsule endoscopy was normal in 36 patients but detected esophagitis in 23, hiatus hernia in 0, varices in 23, Barrett's esophagus in 18, and others in 4. The positive predictive value of capsule endoscopy was 80.0 % and the negative predictive value was 61.1 %. Overall agreement per patient was moderate between EGD and capsule endoscopy for the per-patient (kappa = 0.42) and per-findings (kappa = 0.40) analyses. Interobserver agreement between capsule endoscopy readings was moderate for findings (kappa = 0.39) and quality assessment (kappa = 0.24). No adverse event was observed after either EGD or capsule endoscopy. CONCLUSION: In this study, despite artificial prevalence enrichment, capsule endoscopy showed a moderate sensitivity and specificity in the detection of esophageal diseases.
Assuntos
Endoscopia por Cápsula/métodos , Endoscopia Gastrointestinal/métodos , Doenças do Esôfago/diagnóstico , Esofagoscopia/métodos , Adulto , Idoso , Análise de Variância , Método Duplo-Cego , Duodenoscopia/métodos , Neoplasias Esofágicas/diagnóstico , Varizes Esofágicas e Gástricas/diagnóstico , Feminino , Refluxo Gastroesofágico/diagnóstico , Gastroscopia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Probabilidade , Medição de Risco , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND STUDY AIMS: The endoscopes that were developed for double-balloon enteroscopy have been successfully used in cases of failed colonoscopy. This study was a pilot series in which a new colonoscope was tested that utilized this double-balloon principle. PATIENTS AND METHODS: A total of 29 patients (5 men, 24 women; mean age 54 years) in whom conventional colonoscopy had failed were included in this study. Both the failed colonoscopy and the double-balloon colonoscopy procedures were performed under general anesthesia, the usual practice in France. A prototype instrument (working length 152 cm, diameter 9.4 mm) designed to incorporate the principles of double-balloon enteroscopy was used. The completeness of colonoscopy was assessed according to conventional criteria by the achievement of a stable position in the cecum. The indicatons for the procedure, the time to reach the cecum, the need for fluoroscopic control, and adverse events were recorded. RESULTS: The previous colonoscopy failed due adhesions (n = 16), or to long or fixed loops (n = 13). Complete colonoscopy using the balloon method was achieved in 28/29 patients, taking an average time of 18 +/- 14 minutes; a long sigmoid loop limited the examination to the left flexure in one patient. Balloon colonoscopy using double-balloon methodology was used in 24 patients and the instrument was used without an overtube (i. e. using a single-balloon technique) in five patients. Fluoroscopy was used in 16 patients to monitor endoscope progression. No complications were reported. CONCLUSIONS: Double-balloon colonoscopy enables full colonic examination in almost all patients with a previous incomplete colonoscopy. The overtube should be used in most cases. The use of fluoroscopic assessment of scope progression could be reduced further with increasing experience.
Assuntos
Doenças do Colo/diagnóstico , Colonoscópios , Colonoscopia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Projetos Piloto , Falha de Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: Previous data from the literature reported blunted perception of airway obstruction in severe asthmatics with near fatal asthma. Approximately 25% of patients with asthma are current smokers. AIM: To determine whether there is an alteration in perception of airway obstruction during a non specific provocative challenge with methacholine in mild controlled asthmatics who smoke. METHODS: Enrolled in this study were 50 subjects, including 26 mild asthmatics and 24 healthy subjects, all of them current smokers. The first objective was the sensitivity of airway obstruction calculated by the regression slope linking the change in the visual analogic scale (VAS) assessed by the patient and the fall in FEV(1) during a methacholine challenge. RESULTS: Asthmatics who smoke had a blunted perception of airway obstruction during the bronchial challenge significantly different from that seen in healthy smokers (p=0.03). This impaired dyspnea perception was inversely related to baseline VAS (r=-0.29, p<0.05) and positively related to baseline FEV(1) (r=0.35, p<0.05). Perception of airway obstruction was not correlated with age, sex, atopy or with airway inflammation features such as exhaled NO or sputum eosinophils. CONCLUSION: Mild asthmatics who smoke display reduced dyspnea perception during a non-specific provocative challenge with methacholine. This altered perception of airway obstruction does not relate to airway inflammation.
Assuntos
Asma/complicações , Dispneia/psicologia , Percepção , Fumar/psicologia , Adulto , Asma/diagnóstico , Asma/fisiopatologia , Testes de Provocação Brônquica , Broncoconstrição , Broncoconstritores , Dispneia/etiologia , Dispneia/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Cloreto de Metacolina , Pessoa de Meia-Idade , Fumar/fisiopatologia , Capacidade VitalRESUMO
A case of collagenous colitis in a young man treated by isotretinoïn raises the hypothesis of an isotretinoïn inducedcess on the oossible account of atoov and auto-immunity in the family.
Assuntos
Colite Colagenosa/induzido quimicamente , Colite Colagenosa/patologia , Isotretinoína/efeitos adversos , Acne Vulgar/tratamento farmacológico , Adulto , Anticorpos Antinucleares/sangue , Autoimunidade , Colite Colagenosa/imunologia , Diagnóstico Diferencial , Diarreia/induzido quimicamente , Hipersensibilidade Alimentar/patologia , Humanos , MasculinoRESUMO
This review deals with the pharmacological and psychological means to help in smoking cessation and compares the efficacy of the different methods. Pharmacological support results in a smoking cessation rate reaching at best 20-25%. The efficacy of behavioural and cognitive therapy have been much less validated so far. Multidisciplinary specialized centres for helping smokers have been raised under the care of FARES in the French Community of Belgium.
Assuntos
Abandono do Hábito de Fumar/métodos , Tabagismo/terapia , Terapia Cognitivo-Comportamental , Humanos , Abandono do Hábito de Fumar/psicologia , Tabagismo/psicologia , Resultado do TratamentoRESUMO
Today the smoker carries a risk of mortality 70% higher compared to the nonsmoker. In Belgium active smoking is indisputably the most important cause of avoidable death. In 2004 it appears that 27% of the belgian population was smoking. This review describes the comorbidity associated with active tobacco consumption and defines the concepts of dependence and smoking cessation. It also identifies the three factors which determine the success of smoking cessation, i.e. the degree of nicotinic dependence, the presence of anxio-depressive disorders and the importance of the motivation to the stop.
Assuntos
Abandono do Hábito de Fumar , Tabagismo/terapia , Bélgica , Comorbidade , Humanos , Morbidade , Motivação , Avaliação das Necessidades , Saúde Pública , Tabagismo/complicaçõesRESUMO
PTH-related peptide (PTHrP), which shares 8 of 13 NH2-terminal residues with PTH, causes similar biological effects and interacts with the same receptor as PTH. In the gastrointestinal tract, human PTH and PTHrP-(1-34) relax rat fundic strips. However, the level of their action and the receptor involved in this effect are unknown. The aims of this study were 1) to determine the effects of human PTH-(1-34), human PTHrP-(1-34), -(1-16), and -(7-34) and vasoactive intestinal peptide (VIP) on circular isolated smooth muscle cells from guinea pig ileum; 2) to study the intracellular pathways involved in these effects; and 3) and to characterize the receptors involved by using specific antagonists. Smooth muscle cells were dispersed by enzymatic digestion. Contraction was assessed by measuring the length of 50 cells and expressed as the percent decrease in cell length from the control value. The relaxing effects of PTH, PTHrP and analogs, VIP, or antagonists were expressed as a percentage of the maximal effect observed in their absence. VIP, PTH-(1-34), and PTHrP-(1-34), -(1-16), and -(7-34) had no effect by themselves on these cells. However, when cells were contracted by the sulfated C-terminal octapeptide of cholecystokinin (10 nM), VIP, PTH-(1-34), and PTHrP(1-34) inhibited the sulfated C-terminal octapeptide of cholecystokinin-induced contraction in a concentration-dependent manner, whereas PTHrP-(1-16) and -(7-34) had no effect. The EC50 values of VIP, PTH-(1-34), and PTH-(1-34), and PTHrP-(1-34) were 7 nM, 20 pM, and 20 pM, respectively. The VIP antagonist ([D-P-Cl-Phe6,Leu17]VIP) inhibited VIP-, PTH-(1-34)-, and PTHrP(1-34)-induced relaxation, with IC50 values of 20, 500, and 400 pM, respectively. Likewise, the PTH/PTHrP antagonist [Tyr34-bovine PTH-(7-34)NH2] inhibited PTH-(1-34)-, PTHrP(1-34)-, and VIP-induced relaxation, with IC50 values of 1, 1, and 90 pM, respectively. Preincubation of cells with somatostatin, N-ethylmaleimide, and (R)-p-cyclic adenosine-3',5'-monophosphothioate inhibited the PTH-(1-34), PTHrP(1-34)-, and VIP-induced relaxation. In conclusion, human PTH and PTHrP induce a relaxation of intestinal smooth muscle by a direct myogenic effect. This effect requires the 1-34 amino acid sequence and is mediated by the activation of adenylate cyclase and protein kinase-A. Interactions among PTH, PTHrP, and VIP indicate that they may cross-react with their respective receptors.
Assuntos
Íleo/citologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/citologia , Músculo Liso/fisiologia , Hormônio Paratireóideo/farmacologia , Proteínas/farmacologia , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Acetilcolina/farmacologia , Animais , Colecistocinina/farmacologia , Interações Medicamentosas , Etilmaleimida/farmacologia , Galanina , Cobaias , Íleo/efeitos dos fármacos , Íleo/fisiologia , Masculino , Músculo Liso/efeitos dos fármacos , Hormônio Paratireóideo/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo , Fragmentos de Peptídeos/farmacologia , Peptídeos/farmacologia , Proteínas/metabolismo , Receptores de Peptídeo Intestinal Vasoativo/fisiologia , Somatostatina/farmacologia , Teriparatida , Peptídeo Intestinal Vasoativo/antagonistas & inibidores , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
1. A possible interaction between cyclic AMP and nitric oxide (NO) in mediating the relaxant effect of vasoactive intestinal polypeptide (VIP) on intestinal smooth muscle cells has been investigated. The effects of the inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME), have been studied on VIP-, forskolin-, and 8 bromo-cyclic AMP- induced relaxation of cells, dispersed by enzymatic digestion of muscle strips from the circular layer of guinea-pig ileum. 2. VIP alone did not modify the length of isolated muscle cells. By contrast, when the cells were contracted by cholecystokinin octapeptide, CCK8 (10 nM), VIP inhibited this contraction, inducing a concentration-dependent relaxation of the cells. Maximal relaxation was induced by 1 microM VIP (EC50 = 408.2 +/- 16.7 pM). 3. N-ethylmaleimide, inhibitors of adenylate cyclase or somatostatin, abolished the relaxing effect of VIP. (R)-p-cAMPs, an antagonist of cyclic AMP on protein kinase A also inhibited the VIP-induced relaxation by 92.1 +/- 6.3%. Inhibitors of nitric oxide synthase (NOS), L-NAME and L-NMMA, partially inhibited VIP-induced relaxation. The effect of L-NAME was reversed by L-arginine but not by D-arginine. 4. (R)-p-cAMPS and L-NAME also inhibited the cell relaxation induced either by forskolin which directly stimulates adenylate cyclase activity or 8-bromo-cyclic AMP, an analogue of cyclic AMP. 5. When cells were incubated for 30 min with dexamethasone 10 microM, a glucocorticoid known to decrease the synthesis of iNOS, the relaxing effect of a maximal concentration of VIP was decreased by 52 +/- 4% and L-NMMA had no further effect on this residual VIP-induced relaxation. Milrinone, a phosphodiesterase type III inhibitor, potentiated the relaxant effect of VIP. 6. These data demonstrate that the intracellular pathway mediating the relaxant effect of VIP in intestinal smooth muscle cells includes the sequential activation of adenylate cyclase, protein kinase A, activation of NOS and finally production of NO and cyclic GMP. NO could in turn regulate the cyclic AMP-dependent pathway of cell relaxation.
Assuntos
AMP Cíclico/farmacologia , Intestinos/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Óxido Nítrico/farmacologia , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Colforsina/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Cobaias , Masculino , NG-Nitroarginina Metil Éster/farmacologiaRESUMO
Fedotozine [(1R)-1-phenyl-1-[(3,4,5-trimethoxy)benzyloxymethyl]-N,N- dimethyl-n-propylamine, (2S,3S-tartrate] is derived from the arylacetamide series. As with other compounds of this series, fedotozine is more or less selective of kappa(1)-opioid receptors and particularly for the kappa(1a)-receptor subtype, where it acts as an agonist. Pharmacological studies have shown that fedotozine exerts a peripheral antinociceptive action, comparable with that of other kappa-agonists. Its main effects have been demonstrated at the level of the afferent nerve pathways originating from the gut. Fedotozine alters the processing of visceral sensations along these pathways and hence, the perception of gut stimuli at the brain level. It modifies reflexes induced in various pathological conditions, like experimental inflammation of the gut, chemically-induced peritonitis or post-operative ileus. Fedotozine also decreases the nociceptive reflexes triggered by noxious gut distension in animals. In humans, fedotozine decreases the perception of gut distension, both in physiological and pathological conditions. Clinical trials undertaken in patients with functional digestive disorders, non-ulcer dyspepsia and irritable bowel syndrome, have shown that fedotozine relieves abdominal pain in these patients in 6-week treatments. kappa-Opioid receptors remain an interesting area for future development of new treatments for abdominal pain in patients with functional digestive disorders.
Assuntos
Compostos de Benzil/farmacologia , Propilaminas/farmacologia , Receptores Opioides kappa/agonistas , Animais , Compostos de Benzil/farmacocinética , Compostos de Benzil/uso terapêutico , Doenças Funcionais do Colo/tratamento farmacológico , Dispepsia/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Dor/fisiopatologia , Propilaminas/farmacocinética , Propilaminas/uso terapêutico , Receptores Opioides kappa/efeitos dos fármacos , Receptores Opioides kappa/fisiologiaRESUMO
BACKGROUND: Visceral hypersensitivity plays a major role in the pathophysiology of irritable bowel syndrome, as shown by balloon distension studies. 5-HT3 receptors on afferent nerves may modulate visceral sensitivity and be the target of new treatments for irritable bowel syndrome. AIM: To evaluate the effects of alosetron, a potent and selective 5-HT3 antagonist, on the perception of colonic distension by patients with irritable bowel syndrome, and on the colonic compliance to distension with a barostat. METHODS: Twenty-five irritable bowel syndrome patients were included in a randomized double-blind parallel group trial; data were available for 22 (Rome criteria; 48 +/- 11 years: 13 men and nine women). Patients were treated for 7 days with placebo (n = 6), alosetron 0.25 mg b.d. (n = 8) or alosetron 4 mg b.d. (n = 8). On day 6, a barostat bag was placed in the left colon. On day 7, after an overnight fast, isobaric phasic distensions were performed (4 mmHg steps, 5 min) up to the step triggering a sensation of abdominal pain. RESULTS: Groups were comparable at inclusion (age, sex, symptoms, bowel habits). There were no differences between treatment groups in pressure recorded within the bag at the time of first sensation of abdominal pain. However, bag volumes were significantly increased. At the first sensation threshold, median volume differences of 61 mL and 90 mL (P = 0.028) were recorded with alosetron 0.25 mg b.d. and 4 mg b.d., respectively. At the threshold of abdominal pain, these differences were 71 mL (P = 0.039) and 84 mL (P = 0.017). Colonic compliance increased from 5.9 mL/mmHg on placebo to 7.6 mL/mmHg on alosetron 0.25 mg b.d. and to 9.8 mL/mmHg (P = 0.034) on alosetron 4 mg b.d. CONCLUSION: Alosetron increases the compliance of the colon to distension, and could thereby contribute to changes in perception of colonic distension and improvement in the symptoms of irritable bowel syndrome.