RESUMO
Lactulose is a nonabsorbable disaccharide commonly used in clinical practice to treat hepatic encephalopathy. However, its effects on neuropsychiatric disorders and motor behavior have not been fully elucidated. Male Wistar rats were bile-duct ligated, and 3 weeks after surgery, treated with lactulose administrated by gavage (1.43 or 3.57 g/kg), once a day for seven days. Plasma levels of ammonia, aspartate aminotransferase, total bilirubin, and creatinine were quantified and histopathological analysis of the livers was performed. Locomotor activity measurements were performed in an open field. The expression of water channel aquaporin-4 was investigated and the analysis of Fos protein immunoreactivity was used to evaluate the pattern of neural activation in brain areas related to motor behavior. Bile-duct ligated rats showed hyperammonemia, loss of liver integrity and function, impaired locomotor activity, reduced aquaporin-4 protein expression, and neuronal hyperactivity. Lactulose treatment was able to reduce ammonia plasma levels, despite not having an effect on biochemical parameters of liver function, such as aspartate aminotransferase activity and total bilirubin levels, or on the cirrhotic hepatic architecture. Lactulose was also able to reduce the locomotor activity impairments and to mitigate or reverse most changes in neuronal activation. Lactulose had no effect on reduced aquaporin-4 protein expression. Our findings confirm the effectiveness of lactulose in reducing hyperammonemia and neuronal hyperactivity in brain areas related to motor behavior, reinforcing the importance of its clinical use in the treatment of the symptoms of cirrhosis-associated encephalopathy.
Assuntos
Comportamento Animal/efeitos dos fármacos , Hiperamonemia/tratamento farmacológico , Lactulose/farmacologia , Fígado/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Amônia/sangue , Animais , Aquaporina 4/metabolismo , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Creatinina/sangue , Modelos Animais de Doenças , Hiperamonemia/metabolismo , Hiperamonemia/patologia , Lactulose/uso terapêutico , Fígado/metabolismo , Fígado/patologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos WistarRESUMO
Lactobacillus delbrueckii subsp. bulgaricus CIDCA 333 was dehydrated on desiccators containing silica gel in the presence of 20% w/w of two types of galacto-oligosaccharides (GOS Biotempo and GOS Cup Oligo H-70®) and lactulose, until no changes in water desorption were detected. After rehydration, bacterial growth was monitored at 37°C by determining: (a) the absorbance at 600 nm and (b) the near infrared spectra (NIR). Principal component analysis (PCA) was then performed on the NIR spectra of samples dehydrated in all conditions. A multiparametric flow cytometry assay was carried out using carboxyfluorescein diacetate and propidium iodide probes to determine the relative composition of damaged, viable, and dead bacteria throughout the growth kinetics. The absorbance at 600 nm and the position of the second derivative band at â¼1370 nm were plotted against the time of incubation. The efficiency of the protectants was GOS Biotempo > GOS Cup Oligo H-70® > lactulose. The better protectant capacity of GOS Biotempo was explained on the basis of the lower contribution of damaged cells immediately after rehydration (t = 0). PCA showed three groups along PC1, corresponding to the lag, exponential and stationary phases of growth, which explained 99% of the total variance. Along PC2, two groups were observed, corresponding to damaged or viable cells. The results obtained support the use of NIR to monitor the recovery of desiccated microorganisms in real time and without the need of chemical reagents. The use of GOS and lactulose as protectants in dehydration/rehydration processes was also supported.
Assuntos
Galactanos/farmacologia , Lactobacillus delbrueckii/efeitos dos fármacos , Lactulose/farmacologia , Substâncias Protetoras/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Desidratação , Citometria de Fluxo , Cinética , Lactobacillus delbrueckii/citologia , Lactobacillus delbrueckii/fisiologia , Reprodutibilidade dos Testes , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
OBJECTIVE: Crohn's disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. MATERIAL AND METHODS: Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. RESULTS: In volunteers, the lactulose/mannitol ratio was 0.005+/-0.0037, whereas this value was 0.021+/-0.01 in patients with CD (p=0.001). In the placebo group, there was an increase in lactulose/mannitol ratio by 0.004+/-0.010 (p=0.12) at the end of the third month. In the S. boulardii group, there was an improvement in intestinal permeability, with a decrease in the lactulose/mannitol ratio by 0.008+/-0.006 (p=0.0005) in the same period. CONCLUSIONS: Patients with CD in remission present alterations in the integrity of the intestinal mucosal barrier according to lactulose/mannitol ratio. S. boulardii added to baseline therapy improved intestinal permeability in these patients, even though complete normalization was not achieved.
Assuntos
Doença de Crohn/metabolismo , Mucosa Intestinal/metabolismo , Probióticos/uso terapêutico , Saccharomyces , Adulto , Doença de Crohn/terapia , Feminino , Humanos , Lactulose/farmacologia , Masculino , Manitol/farmacocinética , Pessoa de Meia-Idade , Permeabilidade , Indução de RemissãoRESUMO
Spontaneous bacterial peritonitis (SBP) is a major and serious complication of liver cirrhosis. Small intestinal bacterial overgrowth (SIBO) has been shown to occur with increased frequency in patients with cirrhosis. Studies have suggested that SIBO may contribute to the development of SBP. Aims: to assess the prevalence of SIBO and its relationship with the mortality in patients with cirrhosis. Patients and Methods: One hundred three cirrhotic patients, 62 male, mean age 56.6 (range 35-89) entered in the study in a four year period with a mean follow-up of 22.2 months (range 3-76). SIBO was evaluated by breath hydrogen test (BHT) with lactulose. A positive BHT was defined as an increase of 20 ppm during the first 60 min after lactulose ingestion. SBP was diagnosed by a polymorphonuclear leukocyte count greater than or equal to of 250 cells/mm3 in ascitic fluid. Results: A 50 percent of cirrhotic patients had SIBO at the beginning of follow-up period. The prevalence of SIBO was similar in patients with Child-Pugh class A, B, or C (48 percent 51 percent and 48 percent patients respectively). The presence of SBP was significantly higher in patients with SIBO (17/54 patients) than patients without SIBO (1/53 patients), p < 0.05. The mortality of cirrhotic patients was higher in the SIBO group than in the non-SIBO group (25/50 versus 16/35 patients. p < 0.05). Conclusions: The results of this study confirm that the presence of SIBO is a risk factor for SBP and mortality in patients with liver cirrhosis. SIBO should be investigated and treated during the follow-up in these patients.
La peritonitis bacteriana espontánea (PBE) es una complicación frecuente y grave en pacientes con cirrosis hepática. El sobrecrecimiento bacteriano intestinal (SBI) ha sido descrito con frecuencia en pacientes con cirrosis. Estudios han sugerido que el SBI puede ser un factor importante en el desarrollo de la PBE. Objetivos: Evaluar la prevalencia de SBI y su relación con la mortalidad en pacientes con cirrosis hepática. Pacientes y métodos: Ciento tres pacientes cirróticos, 67 hombres, edad promedio 58,6 (rango 35-89) entraron al estudio en un período de cuatro años con un seguimiento promedio de 22,2 meses (rango 3-76). El SBI fue evaluado por test de hidrógeno en aire espirado (THE) con lactulosa. Un examen era considerado positivo con un nivel mayor de 20 ppm después de la ingesta de lactulosa en los primeros 60 min. El diagnóstico de PBE se fundamentó en un recuento de polimorfonucleares mayor o igual que 250 células/mm3 en muestra de líquido ascítico. Resultados: El 50 por ciento de los pacientes cirróticos presentó SBI al comienzo de su seguimiento. La prevalencia de SBI fue similar en pacientes cirróticos Child-Pugh A, B, o C (48 por ciento, 50 por ciento y 50 por ciento respectivamente). La presencia de PBE fue significativamente mayor en pacientes con SBI (17/50 pacientes) que en pacientes sin SBI (1/53 pacientes). p < 0,05. La mortalidad de los pacientes cirróticos fue mayor en el grupo con SBI que en el grupo sin SBI (25/50 versus 16/53 pacientes, p < 0,05). Conclusiones: Los resultados de este estudio confirman que la presencia de SBI es un factor de riesgo de PBE y mortalidad en pacientes con cirrosis hepática. El SBI debería ser investigado y tratado durante el seguimiento de estos pacientes.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Cirrose Hepática/microbiologia , Cirrose Hepática/mortalidade , Intestino Delgado/microbiologia , Peritonite/microbiologia , Chile/epidemiologia , Cirrose Hepática/metabolismo , Estudos Prospectivos , Seguimentos , Fatores de Tempo , Hidrogênio/análise , Lactulose/farmacologia , Líquido Ascítico/química , Neutrófilos , Prevalência , Testes Respiratórios/métodos , Taxa de SobrevidaRESUMO
Realizamos 2000 colonoscopias ambulatoriais de dezembro de 1994 a maio de 1998. Na véspera, o preparo consistiu de dieta sem resíduos e quatro comprimidos de bisacodil às 19 horas. Para a manhä do dia do exame, orientamos o paciente diluir 120ml de lactulose em água ou suco de laranja coado até obter um litro de soluçäo e ingerí-la em uma hora, seis horas antes do início do procedimento endoscópico. Além disso, deveriam beber água ou chá à vontade até o momento do mesmo. As principais indicaçöes foram de dor abdominal, diarréia, enterorragia, obstipaçäo e pesquisa de tumores. Consideramos o resultado como Bom em 84, 85 por cento dos casos, Regular em 9,2 por cento e Ruim em 5,9 por cento. Ocorreu intolerância ao esquema em 3,35 por cento, quando os pacientes referiram vômitos. Queixas de cólicas abdominais, em 9,75 por cento dos casos, ocorreram principalmente durante a noite, sendo creditadas ao bisacodil. Mesmo os doentes com estenose näo complicaram com obstruçäo. Concluímos que o preparo de cólon para colonoscopia com lactose é eficaz, podendo ser feito a nível domiciliar, com boa aceitaçäo e maior conforto para o paciente
Assuntos
Humanos , Bisacodil/farmacologia , Colonoscopia , Colo/efeitos dos fármacos , Lactulose/farmacologiaRESUMO
El benzoato de sodio se ha utilizado en el tratamiento de la encefalopatía hepática hiperamonémica con buenos resultados. Con el objeto de investigar si la combinación de benzoato de sodio con un disacárido (lactosa, lactulosa) tiene un efecto aditivo sobre la disminución de amonio plasmático, se estudió el efecto de la combinación de benzoato de sodio con lactulosa en el modelo de anastomosis portocava en la rata, ya que éste es el modelo experimental que produce mayores elevaciones de amonio en sangre. Se utilizaron ratas Wistar de 250-300 g de peso en las que se practicó una anastomosis porto-cava terminolateral. Diez días después de la operación se inició tratamiento experimental por un periodo de siete días, dividiendo a los animales en cuatro grupos: a) solución salina, b) B.S. 500 mg/kg/día, c) lactulosa 4 g/kg/día, d) benzoato de sodio más lactulosa (dosis anotadas). También se incluyeron un grupo de ratas normales y un grupo con operación ficticia como controles. Se tomaron muestras de sangre arterial al final del periodo de estudio y se determinó amonio por el método enzimático. Resultados. El benzoato de sodio y la lactulosa disminuyeron significativamente las concentraciones de amonio plasmático (437ñ50, 433ñ85 ug/dl, respectivamente) en comparación con el grupo control (638 ñ 50 ug/dl, p = 0.05), tal como se esperaba. La combinación de benzoato de sodio con lactulosa produjo una disminución de amonio aún mayor (264 ñ 17 ug/dl, p<0.001), lo cual apoya la existencia de un efecto aditivo entre ambos fármacos. Estos hallazgos parecen reproducirse en la clínica de acuerdo a estudios clínicos preliminares en los que se ha utilizado la combinación de lactosa con benzoato de sodio. Estos resultados sugieren que puede haber un efecto aditivo entre el benzoato de sodio y disacáridos como la lactulosa, lo cual podría aumentar la eficiencia del tratamiento e incluso disminuir la dosis total de medicamentos y aumentar la tolerancia a cada uno de los fármacos. Finalmente, se plantea la posibilidad de emplear otros fármacos derivados del benzoato de sodio