RESUMO
OBJECTIVES: To evaluate intestinal barrier function in neonates undergoing cardiac surgery using lactulose/mannitol (L/M) ratio measurements, and to determine correlations with early breast milk feeding. STUDY DESIGN: This was a single-center, prospective, randomized pilot study of 27 term-born neonates (≥ 37 weeks gestation) requiring cardiac surgery who were randomized to 1 of 2 preoperative feeding groups: nil per os (NPO) or trophic (10 mL/kg/day) breast milk feeds. At 3 time points (preoperative [preop], postoperative [postop] day 7, and postop day 14), subjects were administered an oral L/M solution, after which urine L/M ratios were measured using gas chromatography, with higher ratios indicative of increased intestinal permeability. Trends over time in the mean urine L/M ratios for each group were estimated using a general linear mixed model. RESULTS: There were no adverse events related to preoperative trophic feeding. In the NPO group (n = 13), the mean urine L/M ratio was 0.06 at preop, 0.12 at postop day 7, and 0.17 at postop day 14. In the trophic breast milk feeds group (n = 14), the mean urine L/M ratio was 0.09 at preop, 0.19 at postop day 7, and 0.15 at postop day 14. In both groups, L/M ratios were significantly higher at postop day 7 and postop day 14 compared with preop (P < .05). CONCLUSION: Neonates have increased intestinal permeability after cardiac surgery extending to at least postop day 14. This pilot study was not powered to detect differences in benefit or adverse events comparing the NPO and trophic breast milk feeds groups. Further studies to identify mechanisms of intestinal injury and therapeutic interventions are warranted. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT01475357.
Assuntos
Fórmulas Infantis/administração & dosagem , Mucosa Intestinal/metabolismo , Lactulose/farmacocinética , Manitol/farmacocinética , Leite Humano , Biomarcadores/urina , Procedimentos Cirúrgicos Cardíacos , Nutrição Enteral , Enterocolite Necrosante/diagnóstico , Feminino , Humanos , Recém-Nascido , Lactulose/urina , Masculino , Manitol/urina , Permeabilidade , Projetos Piloto , Cuidados Pré-Operatórios , Estudos ProspectivosRESUMO
The gut barrier monitors and protects the gastrointestinal tract from challenges such as microorganisms, toxins and proteins that could act as antigens. There is evidence that gut barrier dysfunction may act as a primary disease mechanism in intestinal disorders. The aim of the present study was to evaluate the barrier function towards sugars after the appropriate treatment of celiac disease and Crohn's disease patients and compare the results with those obtained with healthy subjects. Fifteen healthy volunteers, 22 celiac disease patients after 1 year of a gluten-free diet, and 31 Crohn's disease patients in remission were submitted to an intestinal permeability test with 6.0 g lactulose and 3.0 g mannitol. Six-hour urinary lactulose excretion in Crohn's disease patients was significantly higher than in both celiac disease patients (0.42 vs 0.15 percent) and healthy controls (0.42 vs 0.07 percent). Urinary lactulose excretion was significantly higher in celiac disease patients than in healthy controls (0.15 vs 0.07 percent). Urinary mannitol excretion in Crohn's disease patients was the same as healthy controls (21 vs 21 percent) and these values were significantly higher than in celiac disease patients (10.9 percent). The lactulose/mannitol ratio was significantly higher in Crohn's disease patients in comparison to celiac disease patients (0.021 vs 0.013) and healthy controls (0.021 vs 0.003) and this ratio was also significantly higher in celiac disease patients compared to healthy controls (0.013 vs 0.003). In spite of treatment, differences in sugar permeability were observed in both disease groups. These differences in the behavior of the sugar probes probably reflect different mechanisms for the alterations of intestinal permeability.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Doença Celíaca/fisiopatologia , Doença de Crohn/fisiopatologia , Absorção Intestinal/fisiologia , Lactulose/farmacocinética , Manitol/farmacocinética , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Doença Celíaca/tratamento farmacológico , Doença Celíaca/metabolismo , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Lactulose/urina , Manitol/urina , Permeabilidade , Adulto JovemRESUMO
The gut barrier monitors and protects the gastrointestinal tract from challenges such as microorganisms, toxins and proteins that could act as antigens. There is evidence that gut barrier dysfunction may act as a primary disease mechanism in intestinal disorders. The aim of the present study was to evaluate the barrier function towards sugars after the appropriate treatment of celiac disease and Crohn's disease patients and compare the results with those obtained with healthy subjects. Fifteen healthy volunteers, 22 celiac disease patients after 1 year of a gluten-free diet, and 31 Crohn's disease patients in remission were submitted to an intestinal permeability test with 6.0 g lactulose and 3.0 g mannitol. Six-hour urinary lactulose excretion in Crohn's disease patients was significantly higher than in both celiac disease patients (0.42 vs 0.15%) and healthy controls (0.42 vs 0.07%). Urinary lactulose excretion was significantly higher in celiac disease patients than in healthy controls (0.15 vs 0.07%). Urinary mannitol excretion in Crohn's disease patients was the same as healthy controls (21 vs 21%) and these values were significantly higher than in celiac disease patients (10.9%). The lactulose/mannitol ratio was significantly higher in Crohn's disease patients in comparison to celiac disease patients (0.021 vs 0.013) and healthy controls (0.021 vs 0.003) and this ratio was also significantly higher in celiac disease patients compared to healthy controls (0.013 vs 0.003). In spite of treatment, differences in sugar permeability were observed in both disease groups. These differences in the behavior of the sugar probes probably reflect different mechanisms for the alterations of intestinal permeability.
Assuntos
Doença Celíaca/fisiopatologia , Doença de Crohn/fisiopatologia , Absorção Intestinal/fisiologia , Lactulose/farmacocinética , Manitol/farmacocinética , Adulto , Idoso , Estudos de Casos e Controles , Doença Celíaca/tratamento farmacológico , Doença Celíaca/metabolismo , Cromatografia Líquida de Alta Pressão , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Feminino , Humanos , Lactulose/urina , Masculino , Manitol/urina , Pessoa de Meia-Idade , Permeabilidade , Adulto JovemRESUMO
Low antimycobacterial drug concentrations have been observed in tuberculosis (TB) patients under treatment. The lactulose/mannitol urinary excretion test (L/M), normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R) and isoniazid (H) were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL) or H (3-6 mcg/mL) in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antituberculosos/farmacocinética , Absorção Intestinal , Isoniazida/farmacocinética , Rifampina/farmacocinética , Tuberculose Pulmonar/tratamento farmacológico , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Estudos Transversais , Isoniazida/uso terapêutico , Lactulose/farmacocinética , Lactulose/urina , Manitol/farmacocinética , Manitol/urina , Permeabilidade , Rifampina/uso terapêutico , Tuberculose Pulmonar/metabolismoRESUMO
Low antimycobacterial drug concentrations have been observed in tuberculosis (TB) patients under treatment. The lactulose/mannitol urinary excretion test (L/M), normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R) and isoniazid (H) were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL) or H (3-6 mcg/mL) in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.
Assuntos
Antituberculosos/farmacocinética , Absorção Intestinal , Isoniazida/farmacocinética , Rifampina/farmacocinética , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Estudos Transversais , Feminino , Humanos , Isoniazida/uso terapêutico , Lactulose/farmacocinética , Lactulose/urina , Masculino , Manitol/farmacocinética , Manitol/urina , Pessoa de Meia-Idade , Permeabilidade , Rifampina/uso terapêutico , Tuberculose Pulmonar/metabolismoRESUMO
We tested predictions that: (1) absorption of water-soluble probes decreases with increasing molecular size, consistent with movement through effective pores in epithelia, and (2) absorption of probes is enhanced when measured in the presence of luminal nutrients, as predicted for paracellular solvent drag. Probes (L-arabinose, L-rhamnose, perseitol, lactulose; MW 150.1-342.3 Da) were gavaged in nonanesthetized House sparrows ( Passer domesticus), or injected into the pectoralis, and serially measured in plasma. Bioavailability was calculated as F=AUC by gavage/AUC by injection, where AUC is the area under the curve of plasma probe concentration vs. time. Consistent with predictions, F declined with probe size by 75% from the smallest to the largest probe, and absorption of probes increased by 40% in the presence of luminal glucose or food compared to a mannitol control. Absorption of water-soluble probes by sparrows is much higher than in humans, which is much higher than in rats. These differences seem mainly attributable to differences in paracellular solvent flux and less to differences in effective paracellular pore size.
Assuntos
Arabinose/farmacocinética , Heptoses/farmacocinética , Mucosa Intestinal/metabolismo , Lactulose/farmacocinética , Ramnose/farmacocinética , Aves Canoras/metabolismo , Absorção , Fenômenos Fisiológicos da Nutrição Animal , Animais , Arabinose/administração & dosagem , Arabinose/química , Nutrição Enteral , Heptoses/administração & dosagem , Heptoses/química , Injeções Intramusculares , Lactulose/administração & dosagem , Lactulose/química , Peso Molecular , Ramnose/administração & dosagem , Ramnose/química , Solubilidade , ÁguaRESUMO
BACKGROUND AND AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage both in the upper and lower gastrointestinal tract. New anti-inflammatory drugs have been developed in an attempt to improve their gastrointestinal side effect profile. Our objective was to compare the effect on gastrointestinal permeability of acute equieffective doses of four different NSAIDs; three were designed to reduce gastrointestinal mucosal injury. MATERIALS: Healthy volunteers underwent sugar tests in a randomised fashion, 15 days apart, at: (1) baseline; (2) after two days of 75 mg slow release (microspheres) indomethacin; (3) after two days of 7.5 mg oral meloxicam which preferentially inhibits cyclooxygenase 2; and (4) after two days of 750 mg naproxen. A subgroup of subjects was tested after two days of 200 mg celecoxib. In each test, subjects ingested a solution containing sucrose, lactulose, and mannitol and sucralose, to evaluate gastroduodenal, intestinal, and colonic permeability, respectively. RESULTS: Gastric permeability was significantly affected by naproxen (p<0.05) but not by slow release indomethacin, meloxicam, or celecoxib. Intestinal permeability was significantly increased by the first three NSAIDs (p<0.05) but not by celecoxib. Abnormal lactulose/mannitol ratios were observed in 42% of meloxicam treatments, in 62% during indomethacin, and in 75% of subjects treated with naproxen. Finally, colonic permeability, as measured by sucralose, was not significantly increased by any of the four drugs. CONCLUSION: Our study provides evidence that the newly developed NSAIDs reduce gastric mucosal permeability significantly. However, most produced significant alteration of small intestinal permeability. In contrast, our results suggest that celecoxib seems to exhibit the most desirable gastrointestinal side effect profile.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Sacarose/análogos & derivados , Adulto , Celecoxib , Cromatografia Líquida de Alta Pressão , Intervalos de Confiança , Inibidores de Ciclo-Oxigenase/farmacologia , Preparações de Ação Retardada , Feminino , Mucosa Gástrica/metabolismo , Humanos , Indometacina/farmacologia , Mucosa Intestinal/metabolismo , Lactulose/farmacocinética , Masculino , Manitol/farmacocinética , Meloxicam , Pessoa de Meia-Idade , Naproxeno/farmacologia , Permeabilidade/efeitos dos fármacos , Pirazóis , Estatísticas não Paramétricas , Sacarose/farmacocinética , Sulfonamidas/farmacologia , Tiazinas/farmacologia , Tiazóis/farmacologiaRESUMO
Vitamin A (retinol) is required to maintain immunity and epithelial turnover and is a key micronutrient needed for combating infection. Vitamin A actions on the immune system are diverse and cannot be accounted for by a single effect or mechanism. The actions of retinol in maintaining gut integrity in humans and immunoglobulin levels in mice was investigated. For 30 children, performance on the lactulose/mannitol test, a test commonly used to assess intestinal barrier function, was inversely correlated (P=.012) with serum retinol concentrations. Thus, children with lower serum retinol, and presumably poorer vitamin A nutritional status, are more likely to have impaired intestinal integrity. Knockout mice that have impairments in plasma retinol transport have circulating immunoglobulin levels that are half those observed in matched wild type mice. No differences were observed in B and T cell populations present in spleen, thymus, and bone marrow.
Assuntos
Absorção Intestinal , Mucosa Intestinal/fisiologia , Proteínas de Ligação ao Retinol/metabolismo , Vitamina A/fisiologia , Animais , Brasil , Estudos de Coortes , Humanos , Recém-Nascido , Lactulose/farmacocinética , Estudos Longitudinais , Manitol/farmacocinética , Camundongos , Camundongos Knockout , Estado Nutricional , Análise de Regressão , Proteínas Plasmáticas de Ligação ao Retinol , Vitamina A/sangue , Vitamina A/farmacologiaRESUMO
BACKGROUND: The relationship between intestinal permeability and acute secretory diarrheal syndromes caused by rotavirus and Cryptosporidium parvum in infants less than 36 months of age was studied using the lactulose-mannitol excretion assay. METHODS: An oral solution containing 0.4 g/kg lactulose and 0.1 g/kg mannitol was administered to 15 infants with rotavirus, 7 with Cryptosporidium infection and a control group of 7 with secretory diarrhea admitted to the Oral Rehydration Unit of the National Children's Hospital in Lima, Peru. Urinary sugar excretion was measured using an enzymatic spectrophotometric method. The ratio of urinary excretion of lactulose to mannitol was used to measure intestinal mucosal permeability, with higher ratios indicative of increased intestinal permeability. Infants in all three groups were retested 20 days after the initial test. RESULTS: The (mean +/- SE) lactulose:mannitol (L:M) excretion ratios during the acute phase (day 1) of diarrhea in infants with rotavirus or Cryptosporidium and control infants were 0.67 +/- 0.1, 0.76 +/- 0.16, and 0.26 +/- 0.04, respectively. In the convalescent phase (day 20) the ratios were 0.19 +/- 0.02, 0.28 +/- 0.05, and 0.29 +/- 0.07, respectively. Significant reductions in L:M ratios were noted in rotavirus patients between days 1 and 20 (paired t-test; P < 0.01), Cryptosporidium patients between days 1 and 20 (paired t-test; P < 0.05), and between control subjects on day 1 and rotavirus patients on day 1 and Cryptosporidium patients on day 1 (unpaired t-tests; P < 0.05 for both). There were no significant differences in control subjects between days 1 and 20, control subjects and rotavirus patients on day 20, or control subjects and Cryptosporidium patients on day 20. CONCLUSIONS: The results indicate that increased intestinal permeability caused by rotavirus or cryptosporidium infections in Peruvian infants less than 36 months of age is a significant but reversible phenomenon. The temporal relationship observed in the current study and the contribution of such alterations in intestinal mucosal integrity to the burden of diarrheal disease and the development of malnutrition in developing countries is discussed.
Assuntos
Criptosporidiose/metabolismo , Cryptosporidium parvum , Diarreia/metabolismo , Mucosa Intestinal/metabolismo , Lactulose/farmacocinética , Manitol/farmacocinética , Infecções por Rotavirus/metabolismo , Animais , Pré-Escolar , Criptosporidiose/patologia , Diarreia/patologia , Fezes/química , Fezes/parasitologia , Fezes/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Absorção Intestinal/fisiologia , Mucosa Intestinal/patologia , Lactulose/administração & dosagem , Masculino , Manitol/administração & dosagem , Permeabilidade , Infecções por Rotavirus/patologia , Espectrofotometria , UrináliseRESUMO
BACKGROUND: Subclinical alterations of small intestinal function have been reported frequently in tropical countries. Studies of small intestinal permeability to lactulose and mannitol were therefore completed in Guatemalan infants from a low-income, periurban community to assess the prevalence of altered intestinal function and the factors associated with this condition. METHODS: Two hundred studies were successfully completed in 158 infants who had been free of diarrhea for at least 1 week before the day of study. Urinary concentrations of lactulose and mannitol during the 5-hour period after ingestion of 400 mg/kg body weight of lactulose and 100 mg/kg body weight of mannitol were measured by gas-liquid chromatography and compared by age group, feeding practices, anthropometric indexes, and serum iron and zinc concentrations. RESULTS: The overall prevalence of altered intestinal permeability (defined as a ratio of urinary recovery of lactulose to mannitol [L/M] > or =0.07) was 30%. The urinary L/M recovery ratio was positively associated with age; low weight for age; and, in infants less than 6 months of age, non-breast-feeding. Children with serum iron concentrations less than 7.16 microM/l (40 [microg/dl) had higher median L/M ratios (L/M = 0.068; 95% confidence interval [CI], 0.054, 0.085) than those with iron levels higher than this cutoff (L/M = 0.052; CI = 0.046, 0.058; p = 0.038). The median urinary L/M recovery ratio in 10 currently asymptomatic infants who had diarrhea during the week before testing (0.087; CI = 0.49, 0.154) was higher than that in children who had been free from diarrhea for at least 1 week (0.052; CI = 0.048, 0.056; p = 0.01). CONCLUSION: Age, feeding practices, low weight-for-age, low serum iron concentration, and recent diarrhea were all associated with altered intestinal function in this group of Guatemalan infants.