RESUMEN
We report herein the case of a Belgian 76-year-old woman who developed a hepatic tumour suspected to be a breast cancer metastasis. Radiological imaging and guided biopsies were not contributive. The patient underwent an explorative laparoscopy with frozen sections that did not provide further diagnosis, and an open left bisegmentectomy was performed during the same anaesthesia. Histopathological examination of the hepatic mass showed Echinococcus multilocularis metacestodes, demonstrating alveolar echinococcosis. As our patient denied any travel in foreign countries and has undergone regular abdominal ultrasonographies since her mastectomy, it is highly likely that this alveolar echinococcosis had been contracted in Belgium. If some imported cases may be seldom managed in Belgium, to our knowledge, this case is the first occurrence of alveolar echinococcosis contracted in Belgium. This report, added to the demonstration of E. multilocaris infection of 50% of red foxes in Southern Belgium, and the potential infection of domestic cats and dogs, should attract attention of the medical community on the possible outbreak of endemic alveolar echinococcosis in Belgium, and on the related public health concerns.
Asunto(s)
Equinococosis Hepática/transmisión , Anciano , Animales , Bélgica/epidemiología , Gatos , Perros , Equinococosis Hepática/diagnóstico , Equinococosis Hepática/epidemiología , Femenino , HumanosRESUMEN
A reinvestigation of Strychnos icaja roots has resulted in the isolation of two tertiary quasi-symmetric bisindole alkaloids named strychnogucines A (1) and B (2). Their structures were identified by means of spectroscopic data interpretation. Compound 2 was highly active in vitro and compound 1 moderately active against four strains of Plasmodium falciparum. Strychnogucine B (2) was more active against a chloroquine-resistant strain than against a chloroquine-sensitive one (best CI(50), 80 nM against the W2 strain). In addition, this compound showed a selective antiplasmodial activity with 25-180 times greater toxicity toward P. falciparum, relative to cultured human cancer cells (KB) or human fibroblasts (WI38).
Asunto(s)
Alcaloides/farmacología , Antimaláricos/farmacología , Alcaloides/aislamiento & purificación , Animales , Antimaláricos/aislamiento & purificación , Células HeLa , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Plasmodium falciparum/efectos de los fármacos , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Estricnina/análogos & derivadosRESUMEN
Reinvestigation of Strychnos usambarensis Gilg resulted in the isolation of a tertiary phenolic bisindole alkaloid, 10'-hydroxyusambarensine (1), which was identified by detailed spectroscopic methods. Compound 1 was moderately active against two strains of Plasmodium falciparum in vitro.
Asunto(s)
Alcaloides/farmacología , Antimaláricos/farmacología , Indoles/farmacología , Plantas Medicinales/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Humanos , Técnicas In Vitro , Indoles/química , Indoles/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Raíces de Plantas/química , Plasmodium falciparum/efectos de los fármacos , Rwanda , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , TanzaníaRESUMEN
The development of new drugs requires increasingly the performance of large multinational clinical trials (MCT) with a common protocol. They must be planned when the demonstration of a hypothesis, which requires specific conditions (for example availability of patients with rare diseases, a particular infrastructure or expert knowledge in trial centers) has to be proven in an acceptable time. Our own experience has shown that such multinational trials are more time-consuming in their preparation and their analysis than multicenter trials which are run in one country. MCTs are associated with complex problems due to many differences in medical culture, treatment strategies, administrative guidelines, etc., between countries. When possible MCTs should be realized in countries and centers with relatively similar medical practices. A global coordination is necessary to control the progress of the trial in the different countries. The major requirements for the successful realisation of an MCT, from the writing of the first draft of the protocol until the publication of the results, are a well-coordinated multidisciplinary team and an effective project management.
Asunto(s)
Ensayos Clínicos como Asunto/métodos , Cooperación Internacional , Estudios Multicéntricos como Asunto/métodos , Ensayos Clínicos como Asunto/economía , Análisis Costo-Beneficio , Comparación Transcultural , Humanos , Estudios Multicéntricos como Asunto/economía , Grupo de Atención al Paciente/economía , Grupo de Atención al Paciente/organización & administración , Resultado del TratamientoRESUMEN
In developing countries, severe vitamin A deficiency is associated with increased child mortality. In Kivu, Zaïre, child mortality rate is approximately 50 per 1000 per year and protein calorie malnutrition is endemic. To evaluate vitamin A status in this population, we measured plasma retinol levels in 28 severely malnourished hospitalized children (plasma albumin level below 3 g/dl), and in 153 outpatients (mean plasma albumin level: 3.19 +/- 0.7 g/dl) as controls. Sixty percent of inpatients and 37 percent of out-patients had retinol levels below 10 micrograms/dl (P = 0.02) suggesting a high prevalence of severe vitamin A deficiency in this population. We found that plasma retinol levels were correlated with low retinol binding protein plasma levels (r = 0.77). We conclude that although vitamin A deficiency probably exists in this malnourished population, low retinol levels could at least partly be related to decreased levels of its carrier protein.
Asunto(s)
Países en Desarrollo , Desnutrición Proteico-Calórica/sangre , Deficiencia de Vitamina A/diagnóstico , Vitamina A/sangre , Biomarcadores/sangre , Niño , Preescolar , República Democrática del Congo , Femenino , Humanos , Lactante , Masculino , Desnutrición Proteico-Calórica/complicaciones , Sensibilidad y Especificidad , Deficiencia de Vitamina A/complicacionesRESUMEN
The review describes gastrointestinal receptors which are of therapeutic interest for the treatment of motility disorders. It updates the present knowledge on muscarinic, adrenergic, dopamine, opioid and dihydropyridine receptors, their subtypes, cellular sites and functional role as drug targets. On the basis of this pharmacological receptor concept, drugs like bethanechol, clonidine, lidamidine, metoclopramide, domperidone, cisapride, loperamide and nifedipine are evaluated in proven and potential indications. In view of the very complex regulation of motility, our understanding of receptors is still fragmentary and our tools to treat motility disorders do not fulfil all therapeutic requirements. This review tries to point out the areas of particular need for further basic research and the prospects of further drug development.
Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Antagonistas de Dopamina , Enfermedades Gastrointestinales/tratamiento farmacológico , Motilidad Gastrointestinal , Narcóticos/uso terapéutico , Parasimpatolíticos/uso terapéutico , Parasimpaticomiméticos/uso terapéutico , Receptores de Neurotransmisores/fisiología , Antagonistas de la Serotonina/uso terapéutico , Simpatomiméticos/uso terapéutico , Sistema Digestivo/inervación , Humanos , Receptores de Neurotransmisores/efectos de los fármacosRESUMEN
To investigate the effect of aclatonium napadisilate (Ac), a synthetic cholinergic compound, on human interdigestive gastrointestinal function, six healthy volunteers underwent gastrointestinal intubation for measurement of duodeno-jejunal motor activity and pancreatic enzyme secretion. Each subject was studied twice on two separate days and received either aclatonium (300 mg) or placebo intraduodenally in randomized order. Aclatonium significantly increased the overall length of the cycle of interdigestive motor complex (IMC) by a mean of 34% (p less than 0.05) without stimulating the phases of increased motor activity. Aclatonium slightly, but significantly increased output of lipase during phase II of the IMC (p less than 0.05), whereas outputs during phase I and III were not significantly changed. We conclude that aclatonium in a dose of 300 mg has only weak cholinergic effects on motility and exocrine pancreatic secretion in healthy humans during the interdigestive state.
Asunto(s)
Acetilcolina/análogos & derivados , Amilasas/metabolismo , Motilidad Gastrointestinal/efectos de los fármacos , Lipasa/metabolismo , Páncreas/enzimología , Parasimpaticomiméticos/farmacología , Acetilcolina/farmacología , Adulto , Duodeno/efectos de los fármacos , Duodeno/fisiología , Femenino , Humanos , Yeyuno/efectos de los fármacos , Yeyuno/fisiología , Masculino , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Páncreas/efectos de los fármacos , Distribución Aleatoria , Valores de ReferenciaRESUMEN
Numerous clinical studies have been performed to establish efficacy and safety of drugs in gastroenterological disorders. Only in a few if any of these studies, however, the rationale for the optimal dose and the dose regimens, respectively, have been addressed. Adequate and well-controlled dose finding studies play a key role in the clinical assessment of new drugs and in the evaluation of new indications. Hereby the range from the minimal effective dose to the maximal effective and well tolerated dose can be assessed and thus the optimal dose-range and dosage regimen be determined. Meaningful pharmacodynamic studies can be performed in the gastrointestinal tract also in healthy volunteers provided that a method with a high predictability for the desired therapeutic effect is available such as measurement of gastric acid secretion and its inhibition by a drug. Dose finding studies in gastroenterology can be carried out under two main aspects: First, to assess the pharmacodynamic and therapeutic effect of a compound on the gastrointestinal tract (e.g. anti-ulcer drug). Second, to evaluate the side effects of a drug on the gastrointestinal tract (e.g. gastric mucosal damage by non-steroidal anti-inflammatory drugs). For the evaluation of new drugs in gastrointestinal therapy a number of methods are available which yield accurate and reproducible data. While careful clinical-pharmacological dose-response studies using these methods have been carried out already more than a decade ago, it is surprising that therapeutic dose finding studies have become available only during the past few years. For scientific as well as for ethical reasons more trials which determine the optimal therapeutic dose are warranted.
Asunto(s)
Relación Dosis-Respuesta a Droga , Enfermedades Gastrointestinales/tratamiento farmacológico , Ensayos Clínicos como Asunto , Método Doble Ciego , HumanosRESUMEN
Nervous control of gastrointestinal motility is extremely complex, is regulated by the enteric system, the "brain of the gut", and modulated by extrinsic nerves. This system with its multiplicity of transmitters and receptors does not always allow a clear interpretation of experimental data, especially with compounds lacking specificity. In this review the complex situation is described particularly in relation to receptor populations (cholinergic, adrenergic, dopamine, histamine, 5-hydroxytryptamine, opioid, gamma-aminobutyric acid (GABA), prostanoid and dihydropyridine receptors), therapeutic aspects of drugs and their usefulness in children. Newer principles with known drugs and promising new compounds with a more appropriate kinetic or fewer side-effects, deriving from distinct pharmacological groups, as candidates for the treatment of gastrointestinal disorders are considered e.g. anticholinergics (prifinium or actilonium bromide), adrenergic alpha 2-agonists (clonidine, lidamidine) for diarrhoea in diabetic neuropathy, adrenergic beta-blockers for shortening postoperative ileus (propranolol), dopamine receptor antagonists (metoclopramide, domperidone, alizapride) and another prokinetic substance (cisapride) which may be useful for a number of applications as gastro-oesophageal reflux, gastro-paresis, intestinal pseudo-obstruction, cystic fibrosis and constipation, morphine derivatives (e.g. loperamide) for intractable diarrhoea and calcium antagonists (e.g. nifedipine) for achalasia. Increasing experience in digestive tract pharmacology and reliable clinical studies will furthermore be the basis for a more specific and better tolerated therapy of gastrointestinal motility disorders in adults and children.
Asunto(s)
Enfermedades Gastrointestinales/tratamiento farmacológico , Motilidad Gastrointestinal/efectos de los fármacos , Niño , Sistema Digestivo/efectos de los fármacos , Sistema Digestivo/inervación , Sistema Digestivo/fisiopatología , Fármacos Gastrointestinales/farmacología , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Gastrointestinales/fisiopatología , Humanos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Receptores de la Hormona Gastrointestinal/efectos de los fármacos , Receptores de la Hormona Gastrointestinal/fisiologíaRESUMEN
The study is of double-blind crossover design. In the first part of the study, rioprostil (300 micrograms and 600 micrograms) is given orally with a solid breakfast to 9 healthy male volunteers. Both doses of rioprostil delay and reduce the 3-h postprandial GIP release. They also reduce the maximal postprandial insulin concentration, but only rioprostil (600 micrograms) reduces the 3-h integrated release of insulin significantly (by approximately 20%). Neither dose modifies the postprandial glucose gastrin levels significantly. In another study two groups of 6 volunteers are studied in parallel; they are given either rioprostil (600 micrograms) or a placebo each evening for 14 days. On the mornings before and on days 13 and 14 of the study the volunteers take a solid breakfast and blood glucose is measured 1 h and 2 h postprandially. The results show that no differences in the basal and postprandial glucose levels are observed. In conclusion, rioprostil given with a meal can reduce the insulin release but it does not change the postprandial blood glucose levels when given as a single dose or repeatedly in an evening dose. This study shows that rioprostil can be given to patients with diabetes.
Asunto(s)
Antiulcerosos/farmacología , Glucemia/análisis , Polipéptido Inhibidor Gástrico/sangre , Gastrinas/sangre , Insulina/sangre , Prostaglandinas E/farmacología , Antiulcerosos/administración & dosificación , Método Doble Ciego , Alimentos , Humanos , Masculino , Prostaglandinas E/administración & dosificación , Prostaglandinas Sintéticas/farmacología , RioprostiloRESUMEN
The influence of rioprostil on the resting pressure of the lower oesophageal sphincter (LESP) and on the bolus-stimulated contraction wave amplitude of primary peristalsis is investigated in 9 healthy male volunteers receiving placebo or 300 micrograms and 600 micrograms of rioprostil orally in a randomized, double-blind, threefold crossover study. Manometry is performed using the low-compliance pneumohydraulic infusion system. The results show that: rioprostil, 600 micrograms, slightly increases LESP (ns) and contraction wave amplitudes, measured 10 cm above the lower oesophageal sphincter (LES) (p = 0.0039); rioprostil in both doses does not change the contraction wave amplitudes of the distal oesophagus, 5 cm above the LES; the duration of the peristaltic contractions is not altered. We conclude that rioprostil, in doses which effectively inhibit gastric acid and pepsin secretion and heal peptic ulcers, has no inhibitory effects on oesophageal motility. Studies are warranted, therefore, to establish the efficacy of rioprostil in the treatment of reflux oesophagitis.
Asunto(s)
Antiulcerosos/farmacología , Unión Esofagogástrica/fisiología , Esófago/fisiología , Prostaglandinas E/farmacología , Adulto , Método Doble Ciego , Humanos , Masculino , Peristaltismo/efectos de los fármacos , Presión , Prostaglandinas Sintéticas/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , RioprostiloRESUMEN
The aim of this study is a double-blind evaluation of the efficacy and safety of rioprostil, 300 micrograms, compared with ranitidine, 150 mg, when given twice a day for 4 or 8 weeks in patients with active, uncomplicated gastric ulcer disease. A total of 194 patients are entered into the study, of which 182 are statistically evaluated for efficacy. Eighty-seven receive rioprostil and 95 receive ranitidine. All patients receive two oral doses of study medication daily. After 4 weeks' treatment, 47.1% of the patients receiving rioprostil are endoscopically healed compared with 53.7% of those receiving ranitidine. After 8 weeks' treatment, the cumulative cure rates are 76.2% and 80.9% respectively. Side effects occur in 26% of the patients receiving rioprostil and in 15% of the patients receiving ranitidine. Gastrointestinal side effects are most common. Changes in stool consistency (i.e. soft stools or mild diarrhoea) are the most reported symptoms in patients receiving rioprostil. These effects are generally self-limiting. Three patients on rioprostil and one patient on ranitidine discontinue treatment due to side effects. No clinically significant changes in biochemical variables occur in either group throughout the treatment period. Rioprostil, 300 micrograms b.d., is a safe and effective treatment for gastric ulcer disease. Healing rates and alleviation of pain are comparable for both treatment groups. The change in stool consistency with rioprostil is of only minor clinical importance, that is, it occurs on about 2% of treatment days.
Asunto(s)
Antiulcerosos/uso terapéutico , Prostaglandinas E/uso terapéutico , Ranitidina/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Antiulcerosos/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Prostaglandinas E/administración & dosificación , Prostaglandinas Sintéticas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ranitidina/administración & dosificación , RioprostiloRESUMEN
This study is undertaken to evaluate the efficacy and safety of rioprostil, 300 micrograms, compared with ranitidine, 150 mg, when given twice daily for 4-6 weeks to patients with active, uncomplicated duodenal ulcer. The effects of each drug on ulcer healing are evaluated by endoscopy. Of a total of 355 patients who have entered this study, 319 are statistically evaluated for efficacy; 162 receive rioprostil and 157 receive ranitidine. After 4 weeks of treatment, 63% of the patients receiving rioprostil are endoscopically healed, compared with 72% of those receiving ranitidine. After 6 weeks of treatment, the cumulative healing rates are 86% and 93.5% respectively; this difference is statistically significant. Diarrhoea is the main adverse event, but is generally mild and self-limiting. These results indicate that rioprostil, 300 micrograms b.d., is a safe and effective treatment for duodenal ulcer, but is slightly less effective than ranitidine, 150 mg b.d.
Asunto(s)
Antiulcerosos/uso terapéutico , Úlcera Duodenal/tratamiento farmacológico , Prostaglandinas E/uso terapéutico , Ranitidina/uso terapéutico , Adulto , Anciano , Antiulcerosos/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Prostaglandinas E/administración & dosificación , Prostaglandinas Sintéticas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ranitidina/administración & dosificación , RioprostiloRESUMEN
When administered as 300 micrograms b.d. or as 600 micrograms once in the evening, the new prostaglandin E1 analogue, rioprostil, is capable of reducing nocturnal H+ activity (1200 h to 0800 h) by 52% and 74%, respectively (p less than 0.01). Diurnal acidity (0900 h to 1800 h), on the other hand, is only reduced by 33% and 15% (not significant). A single evening dose of rioprostil, 600 micrograms, is used successfully on 208 patients suffering from acute duodenal ulcer. After 2 weeks and 4 weeks of treatment, the healing rates are comparable to the high values obtained with ranitidine, 300 mg nocte (rioprostil, 600 micrograms nocte: 54.1% and 84.1%; ranitidine, 300 mg nocte: 54.4% and 89.9%). There are also no significant differences between the groups as regards symptomatic improvement. Severe diarrhoea and abdominal complaints do not occur with rioprostil, 600 micrograms nocte.
Asunto(s)
Antiulcerosos/administración & dosificación , Úlcera Duodenal/tratamiento farmacológico , Prostaglandinas E/administración & dosificación , Adulto , Antiulcerosos/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Prostaglandinas E/uso terapéutico , Prostaglandinas Sintéticas/administración & dosificación , Prostaglandinas Sintéticas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ranitidina/uso terapéutico , RioprostiloRESUMEN
Data from a large number of patients (1918) treated with rioprostil, H2-antagonists and placebo, are analysed to examine the safety profile of rioprostil in the treatment of active gastric ulcer or active duodenal ulcer. Rioprostil is administered to 1000 of those patients. Patients who dropped out of the studies and those with adverse drug reactions are classified and compared within different subgroups. The overall dropout rate for rioprostil patients is 8.8%: 2.3% of these because of adverse reactions. The incidence of adverse reactions during rioprostil treatment is 20.9%, with more than 60% of these having gastrointestinal symptoms, mainly appearing in the first week of therapy. Comparisons show a higher incidence of symptoms with rioprostil treatment than with ranitidine treatment because of the gastrointestinal symptoms. Possible differences are found between groups in sex, age, and drug dose. The analysis of laboratory variables does not show clinically important changes as a result of rioprostil treatment.
Asunto(s)
Antiulcerosos/efectos adversos , Úlcera Duodenal/tratamiento farmacológico , Prostaglandinas E/efectos adversos , Úlcera Gástrica/tratamiento farmacológico , Dolor Abdominal/inducido químicamente , Adulto , Antiulcerosos/uso terapéutico , Diarrea/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Prostaglandinas E/uso terapéutico , Prostaglandinas Sintéticas/efectos adversos , Prostaglandinas Sintéticas/uso terapéutico , RioprostiloRESUMEN
A single oral dose of rioprostil, a synthetic methyl-prostaglandin E1, together with or 2 h before ingestion of 0.8 mg beta-acetyldigoxin significantly delays the rate but does not change the extent of beta-acetyldigoxin absorption. However, repeated evening doses of rioprostil do not alter either the glycoside steady-state plasma levels or renal excretion.
Asunto(s)
Acetildigoxinas/farmacocinética , Antiulcerosos/farmacología , Digoxina/análogos & derivados , Prostaglandinas E/farmacología , Administración Oral , Adulto , Disponibilidad Biológica , Método Doble Ciego , Humanos , Absorción Intestinal/efectos de los fármacos , Masculino , Prostaglandinas Sintéticas/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , RioprostiloRESUMEN
The antisecretory effect of rioprostil on acid and pepsin secretion stimulated by pentagastrin or a meal, or on the 24-h intragastric acidity is tested in four different studies in 33 healthy male volunteers using a double-blind, crossover design. The oral doses of rioprostil used are 50 micrograms, 100 micrograms, 150 micrograms, 200 micrograms, 300 micrograms and 600 micrograms; these are the results obtained: Rioprostil reduces basal H+ and pepsin output by more than 50%. Rioprostil, 300 micrograms and 600 micrograms, significantly reduces the 3-h pentagastrin-stimulated acid output by 43.5% and 58.9%, respectively, and the 3-h stimulated pepsin output by 41.1% and 66.5%, respectively (p = 0.01). Depending on the method used for intragastric titration the following percentages of inhibition of acid secretion are observed, 40%, 65%, and 75% with 150 micrograms, 300 micrograms, and 600 micrograms rioprostil respectively, with one method and 32%, 34%, and 79% with 25 micrograms, 50 micrograms, and 200 micrograms rioprostil respectively, with a somewhat modified technique. The differences observed in % inhibition between these two studies can be explained by the use of a different intragastric titration technique. Rioprostil, 300 micrograms and 600 micrograms, significantly inhibits night-time acid secretion (AUC x h, 2400 h-0800 h) by 52% and 73.5% when compared with placebo (p = 0.03). The calculated ED50 for acid inhibition is 86.5 micrograms of rioprostil.
Asunto(s)
Antiulcerosos/farmacología , Ácido Gástrico/metabolismo , Pepsina A/metabolismo , Prostaglandinas E/farmacología , Adulto , Método Doble Ciego , Alimentos , Humanos , Masculino , Pentagastrina , Prostaglandinas Sintéticas/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , RioprostiloRESUMEN
The influence of rioprostil on the resting pressure of the lower esophageal sphincter (LESP) and on the bolus-stimulated contraction wave amplitude of primary peristalsis was investigated in 9 healthy male volunteers receiving placebo or 300 and 600 micrograms of rioprostil orally in a randomised, double-blind, threefold cross over study. Manometry was performed using the low-compliance pneumohydraulic infusion system. Rioprostil in a dose of 600 micrograms slightly increased LESP and contraction wave amplitudes measured 5 cm and 10 cm above LES. The duration of the peristaltic contractions was not altered. We conclude that rioprostil in doses which inhibit effectively gastric acid and pepsin secretion and heal peptic ulcers has no inhibitory effects on esophageal motility. Thus rioprostil may be a candidate to treat reflux esophagitis and studies are warranted to establish its efficacy.
Asunto(s)
Antiulcerosos/farmacología , Unión Esofagogástrica/efectos de los fármacos , Prostaglandinas E Sintéticas/farmacología , Prostaglandinas E/farmacología , Adulto , Ensayos Clínicos como Asunto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Masculino , Manometría , Peristaltismo/efectos de los fármacos , Distribución Aleatoria , RioprostiloRESUMEN
The effects of rioprostil (a newly developed synthetic prostaglandin E1 analogue) on meal-stimulated gastric acid secretion was evaluated in 8 healthy human volunteers. Gastric acid output was measured by intragastric titration on 4 different occasions. The following procedure was invariably employed: after a basal period of 45 min, 5 peptone meals (8%, 500 ml each) were given intragastrically in 45-min intervals and gastric acid output was measured continuously. 45 min after the first meal, either placebo or 150, 300 or 600 micrograms of rioprostil were given intragastrically in a randomized order and on different days. 15 min later, the second meal was given and intragastric titration continued. Rioprostil caused a dose-dependent inhibition of the 3-hour integrated gastric acid response to the peptone meals. The percentage of inhibition was 41, 68 and 79%, respectively, for 150, 300 and 600 micrograms of rioprostil. Whereas the inhibition by the two highest doses was statistically significant, this was not the case for the lowest dose of rioprostil. The integrated 3-hour plasma gastrin response to the peptone meals was not significantly changed by any of the doses of rioprostil. No significant adverse effects were observed with rioprostil.
Asunto(s)
Alimentos , Ácido Gástrico/metabolismo , Gastrinas/sangre , Prostaglandinas E/farmacología , Adolescente , Adulto , Humanos , Masculino , Prostaglandinas E/efectos adversos , Rioprostilo , Factores de TiempoRESUMEN
Calcitonin given in doses (0.2 and 1 MRC U/kg-1h-1) reproducing the levels observed in medullary carcinoma of the thyroid, induced the appearance of phase III type activity and reduced the duration of the IMC in the small intestine from 123 to 87 min with 0.2 MRC U kg-1h-1 and from 123 to 43 min with 1 MRC U kg-1h-1 but not in the stomach of young volunteers. This increase in phase III-like activity occurred despite a sharp reduction in motilin levels. Only the highest dose of calcitonin reduced significantly acid secretion (by more than 90%) while both doses reduced amylase secretion by respectively 65 and 71% when compared to the control levels. These changes in motility and secretion could partly explain the diarrhea observed in patients with the medullary carcinoma of the thyroid.