Intranasal administration of neuropeptide Y in man: systemic absorption and functional effects.

1. Exogenous neuropeptide Y (NPY, 10 nmol, 50 nmol and 100 nmol) and its vehicle (NaCl 0.9%) were administered in a double blind, randomized and controlled manner by intranasal spray in 7 healthy volunteers. Variations of plasma NPY concentration over time were measured during 120 min. Forty min after the administration of 50 nmol and 100 nmol of exogenous NPY, plasma NPY increased from 5.5 +/- 1.1 pM to 9.8 +/- 2.3 pM (P < 0.05) and from 9.06 +/- 5.1 pM to 20.8 +/- 6.16 pM (P < 0.001), respectively. There was no significant modification of the mean arterial blood pressure and no subjective discomfort was reported. 2. Nasal airway resistance (NAR) was measured by anterior rhinomanometry and was reduced by 25 +/- 3% and 32 +/- 5% after the spray of 50 nmol and 100 nmol, respectively, for about 90 min. 3. Double-blind, randomized, placebo-controlled and 3-way crossover design experiments were performed in 8 healthy volunteers to evaluate the influence of intranasal pretreatment with NPY (20 nmol) and the mixed alpha 1/alpha 2-adrenoceptor agonist oxymetazoline (20 nmol) on the functional effects of subsequent local irritation evoked by capsaicin (3.3 x 10(-4) mol). Subjective evaluation of NAR and local intensity of discomfort were evaluated by means of a visual analogue scale. Nasal secretions were collected and objective NAR was recorded by rhinomanometry. 4. Subjective NAR, nasal secretions and rhinomanometry recordings were not modified by intranasal application of saline, NPY or oxymetazoline. Subjective nasal obstruction, local discomfort, nasal secretions and NAR increase evoked by capsaicin were markedly reduced by NPY pretreatment (P < 0.05) when compared to saline or oxymetazoline. 5. It is concluded that intranasal application of exogenous NPY has very low systemic absorption but induced long lasting nasal vasoconstriction without cardiovascular effects. Pretreatment of the nasal mucosa with exogenous NPY reduces both secretagogue and vasodilator responses to subsequent application of capsaicin

Avaliação intra-operatória da pressão portal e resultados imediatos do tratamento cirúrgico da hipertensão portal em pacientes esquistossomóticos submetidos a desconexão ázigo-portal e esplenectomia Intra-operative evaluation of portal pressure and immediate results of surgical treatment of portal hypertension in schistosomotic patients submitted to esophagogastric devascularization with splenectomy

RACIONAL: No Brasil a principal causa de hipertensão portal é a esquistossomose mansônica na sua forma hepatoesplênica. Com relação ao seu tratamento, a preferência da maioria dos autores no Brasil recai sobre a desconexão ázigo-portal e esplenectomia geralmente associada à escleroterapia endoscópica pós-operatória para tratamento dessa enfermidade. No entanto, não estão bem estabelecidas as alterações hemodinâmicas portais decorrentes do tratamento cirúrgico da hipertensão portal e sua influência no resultado desse tratamento. OBJETIVOS: Avaliar o impacto imediato da desconexão ázigo-portal e esplenectomia na pressão portal e também os resultados do tratamento cirúrgico da hipertensão portal no que se refere à recidiva hemorrágica e ao calibre das varizes de esôfago. CASUÍSTICA E MÉTODO: Foram estudados 19 pacientes com esquistossomose hepatoesplênica e hipertensão portal, com história de hemorragia digestiva alta por ruptura de varizes esofágicas, com idade média de 37,9 anos. Estes pacientes não haviam sido submetidos a tratamento prévio e foram, eletivamente, tratados cirurgicamente com desconexão ázigo-portal e esplenectomia. Durante a cirurgia, foi avaliada a pressão portal, no início e no final do procedimento, através da cateterização da veia porta por cateter de polietileno introduzido por veia jejunal. Todos os pacientes foram submetidos a endoscopia no pré e no pós-operatório (em torno do 60&ordm; dia do pós-operatório) para avaliar, segundo classificação de Palmer, a variação do calibre das varizes esofagianas após a desconexão ázigo-portal e esplenectomia. RESULTADOS: Todos os pacientes apresentaram queda da pressão portal, sendo a média desta queda, após a desconexão ázigo-portal e esplenectomia, de 31,3%. Na avaliação pós-operatória (endoscopia após cerca de 60 dias) houve redução significativa do calibre das varizes esofagianas quando comparadas ao pré-operatório. CONCLUSÃO: A desconexão ázigo-portal e esplenectomia promoveram queda imediata na pressão portal, com conseqüente diminuição do calibre das varizes esofágicas. Observou-se ainda que não é insignificante o risco de mortalidade e complicações graves relacionados a essa técnica.<br>BACKGROUND: The main cause of portal hypertension in Brazil is the hepato-splenic form of mansonic schistosomiasis and the most employed technique for the surgical approach of this disease is the esophagogastric devascularization with splenectomy, generally associated to postoperative endoscopical esophageal varices sclerotherapy. The hemodynamic alterations after surgical treatment and its possible influence on the outcome are not well established. AIM: To evaluate the immediate impact of esophagogastric devascularization with splenectomy upon portal pressure as well as the results of the surgical treatment on digestive hemorrhage recurrence and on esophageal varices. METHODS: Nineteen patients with mean age of 37.9 years and portal hypertension and previous episodes of digestive hemorrhage caused by esophageal varices rupture due to hepato-splenic schistosomiasis were studied. None of the patients had received any treatment prior to the surgery and underwent to elective esophagogastric devascularization with splenectomy. Portal pressure was assessed at the beginning and at the end of esophagogastric devascularization with splenectomy through portal vein catheterization with a polyethylene catheter introduced through a jejunal branch vein. All patients were submitted to digestive endoscopy before and after the surgery, in order to classify the size of esophageal varices after esophagogastric devascularization with splenectomy according to Palmer’s classification. RESULTS: In all patients the portal pressure had diminished with a mean decrease of 31.3% after esophagogastric devascularization with splenectomy. In the postoperative endoscopic follow-up (1 month), the esophageal varices showed a statistically significant reduction in their size, when compared to the pre-surgical measurements. CONCLUSION: These results have demonstrated that the esophagogastric devascularization with splenectomy promotes immediate decrease in the portal pressure and a consequent reduction in the esophageal varices size. We also observed that the risk of mortality and severe complications related to this technique is not insignificant