Effect of paracellular permeation enhancers on intestinal permeability of two peptide drugs, enalaprilat and hexarelin, in rats

Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat, a 349 Da peptide, but not hexarelin (887 Da). The primary aim of this paper was to investigate if paracellular permeability enhancers affected the intestinal permeation of the two peptides. This was investigated using the rat single-pass intestinal perfusion model with concomitant blood sampling. These luminal compositions included two paracellular permeation enhancers, chitosan (5 mg/mL) and ethylenediaminetetraacetate (EDTA, 1 and 5 mg/mL), as well as low luminal tonicity (100 mOsm) with or without lidocaine. Effects were evaluated by the change in lumen-to-blood permeability of hexarelin and enalaprilat, and the blood-to-lumen clearance of

Determination of volatile fatty acids clearance in intact ruminal digesta / Determinação do clearance de ácidos graxos voláteis na digesta ruminal intacta / Determinación del aclaramiento de ácidos grasos volátiles en digesta ruminal intacta

Abstract Cannulated cows were allocated to a cross-over design to evaluate the technique for determination of volatile fatty acid (VFA) clearance by infusion of marker solution into intact ruminal digesta, and verify the technique sensibility to the variation in the diet. Animals received diet of forage or forage plus concentrate and infusion of valeric acid and Cr-EDTA solution into intact or evacuated ruminal digesta. The total fractional rate of VFA clearance (FRVFAC) was estimated by the exponential decay of valerate over time. The passage FRVFAC to the omasum was assumed as the decay in ruminal Cr concentration and the absorption FRVFAC was estimated by the difference. The total FRVFAC and absorption did not differ between techniques. The passage FRVFAC, however, was lower when the marker solution was added into the evacuated digesta, probably reflecting the destabilization of the rumen environment during the evacuation and the largest volume of fluid observed in animals with evacuated digesta. In conclusion, the infusion of marker solution into intact digesta with homogenization performed by ruminal motility could be usable for the VFA ruminal clearance determination since it seems to cause lesser disturbance in the ruminal environment.

Resumo Bovinos canulados foram alocados em um delineamento cruzado para avaliar a técnica de determinação do clearance de ácidos graxos voláteis (VFA) por infusão de solução marcadora na digesta ruminal intacta, e verificado a sensibilidade da técnica à variação na dieta. Os animais receberam dieta de forragem ou forragem juntamente com concentrado e infusão de ácido valérico e solução de Cr-EDTA na digesta ruminal intacta ou evacuada. A taxa fracional total de depuração de AGV (FRVFAC) foi estimada pelo decaimento exponencial do valerato ao longo do tempo. A passagem FRVFAC para o omaso foi assumida como o decaimento na concentração ruminal de Cr e a absorção FRVFAC foi estimada pela diferença. A FRVFAC total e a absorção não diferiram entre as técnicas. A passagem FRVFAC, entretanto, foi menor quando a solução marcadora foi adicionada na digesta evacuada, provavelmente refletindo a desestabilização do ambiente ruminal durante a evacuação e o maior volume de líquido observado em animais com digesta evacuada. Em conclusão, a infusão da solução marcadora na digesta intacta com homogeneização realizada pela motilidade ruminal poderia ser utilizada para a determinação da depuração ruminal de VFA, uma vez que parece causar menor distúrbio no ambiente ruminal.

Resumen Los bovinos canulados fueron asignados en un delineamiento cruzado para evaluar la técnica de determinación del clearance de ácidos grasos volátiles (VFA) por infusión de solución marcadora en la digesta ruminal intacta, y verificado la sensibilidad de la técnica a la variación en la dieta. Los animales recibieron dieta de forraje o forraje junto con concentrado e infusión de ácido valérico y solución de Cr-EDTA en la digesta ruminal intacta o evacuada. La tasa fraccional total de depuración de AGV (FRVFAC) fue estimada por el decaimiento exponencial del valerato a lo largo del tiempo. El pasaje FRVFAC para el omaso fue asumido como el decaimiento en la concentración ruminal de Cr y la absorción FRVFAC fue estimada por la diferencia. La FRVFAC total y la absorción no difirieron entre las técnicas. El paso FRVFAC, sin embargo, fue menor cuando la solución marcadora fue agregada en la digestión evacuada, probablemente reflejando la desestabilización del ambiente ruminal durante la evacuación y el mayor volumen de líquido observado en animales con digestión evacuada. En conclusión, la infusión de la solución marcadora en la digesta intacta con homogeneización realizada por la motilidad ruminal podría ser utilizada para la determinación de la depuración ruminal de la VFA, ya que parece causar menor disturbio en el ambiente ruminal.

A Comparison of the Accuracy of Different Single Plasma Sample Methods for Measuring Glomerular Filtration Rate Using ⁵¹Cr-EDTA in Children / 대한핵의학회잡지

PURPOSE: Among the different methods of measuring glomerular filtration rate (GFR) using 51Cr-ethylenediaminetetraacetic acid clearance, the two-plasma-sample method (TPSM) is widely used, and highly accurate. The single-plasma-sample method (SPSM) is occasionally used for simplicity, at the expense of accuracy. Our aims were (1) to investigate the correlation and (2) to compare the accuracy of six known SPSMs in pediatric patients in reference to TPSM.METHODS: We retrospectively reviewed 122 pediatric cases (65 boys, age 7.3 ± 4.6 years) and analyzed 307 GFR measurements. SPSMs included Groth and Aasted at 120 min, Hamat 120 min, Christensen and Groth at 120 and 240 min, and Jacobsson at 120 and 240 min. Reference GFR (GFRref) was defined using TPSM GFR corrected by the Jodal and Brochner-Mortensen equation. GFRref < 30 mL min−1 1.73 m−2 were excluded. The standard error of the estimate (SEE) and the number of cases with differences > 10% (N10%) were used to evaluate accuracy.RESULTS: SPSMs generally correlated well with GFRref (r = 0.92~0.99) and were relatively accurate (SEE = 9.21~15.60). Groth and Aasted showed the smallest SEE, while Jacobsson at 240 min showed the smallest N10% for all GFRref ranges. As for the decreased GFRref, Ham was most accurate followed by Jacobsson at 240 min.CONCLUSIONS: Jacobsson at 240 min provided good accuracy in all GFRref ranges and was well correlated with TPSM. Jacobsson at 240 min might be the most appropriate method to substitute for TPSM in pediatric patients. Ham could be an alternative in patients with impaired renal function.

Funcionalidade do sulco do retículo em bovinos adultos e avaliação de técnicas alternativas para preparação, infusão e coleta de marcadores da fase fluida ruminal / Reticular groove functionality in adult cattle and evaluation of alternative techniques for preparation, infusion and sampling of ruminal fluid phase markers

Os objetivos deste trabalho foram determinar a funcionalidade do sulco do retículo em bovinos adultos e avaliar técnicas alternativas para preparação, infusão e coleta de marcadores da dinâmica ruminal. Quatro vacas com cânulas ruminais foram utilizadas em três ensaios experimentais. No ensaio 1 a porcentagem de água que passou diretamente ao omaso (27,39 por cento) tendeu a ser menor (P = 0,14) que a porcentagem de água que atingiu o ruminorretículo (72,61 por cento), indicando funcionamento ineficiente dessa estrutura em bovinos adultos. No ensaio 2, as taxas fracionais de passagem de fluido determinadas simultaneamente por Cr-EDTA (14,79 por cento h-1) e Co-EDTA preparado por técnica alternativa (14,76 por cento h-1) não diferiram (P = 0,96) e as regressões exponenciais tiveram alto coeficiente de determinação (r² = 0,90). A relação Co:Cr no fluido ruminal não diferiu ao longo das quatro horas de coleta de amostras (P = 0,68). Não houve variação entre a relação Co : Cr na urina e nas fezes. A técnica de fácil execução, proposta para preparação do Co-EDTA, mostrou-se efetiva. No ensaio 3, em que os marcadores foram infundidos à digesta sem homogeneização, a melhor plotagem (r² = 0,88; P < 0,001) da regressão exponencial foi obtida excluindo-se os cinco primeiros tempos de coleta (1,67 h após infusão) e dobrando-se os intervalos até as 5,33 h após infusão. Nesse padrão de coleta, os coeficientes de determinação das regressões exponenciais não diferiram (P = 0,17) de curvas padrões (r² = 1), quando comparados hipoteticamente. As técnicas alternativas propostas para infusão e amostragem são viáveis, mas requerem validação.

The objectives of this work were to determine the functionality of the reticular groove in adult cattle and to evaluate alternative techniques for preparation, infusion and collection of ruminal dynamics markers. Four cows with rumen cannulas were used in three experimental assays. In the first assay the water percentage that passed directly to the omasum (27.39 percent) tended to be lower (P = 0.14) than the water percentage that reached the reticulorumen (72.61 percent), indicating inefficient functioning of the reticular groove in adult bovines. In assay 2, the fractional rates estimated simultaneously by Cr-EDTA (14.79 percent h-1) and Co-EDTA prepared for an alternative technique (14.76 percent h-1) did not differ (P = 0.96). The exponential regressions had a high determination coefficient (r² = 0.90). The Co : Cr ratio in the ruminal fluid did not differ during the four hour sampling period (P = 0.68). There was no variation in the Co : Cr ratio in urine or feces. The simple technique proposed for the preparation of Co-EDTA, was effective. In assay 3, markers were infused into digesta without homogenization. The best plotting (r² = 0.88; P < 0.001) of the exponential regression was obtained by excluding the five initial collection times (1.67 h after infusion) and by doubling the sampling intervals until 5.33 h after infusion. Under this collection pattern, the exponential regression determination coefficients did not differ (P = 0.17) from the standard curves (r² = 1), when hypothetically compared. The alternative techniques proposed for infusion and sampling are viable, but require validation.

The changes of intestinal permeability in patients with mild acute pancreatitis / 대한내과학회지

BACKGROUND: Many studies in severe acute pancreatitis have demonstrated an increase in intestinal permeability, but not in mild acute pancreatitis. The current methods to measure intestinal permeability need much time and also laborious work. Therefore, we investigate the changes of intestinal permeability in patients with mild acute pancreatis and clinical predictive factor for the intestinal permeability in patients with acute pancreatitis. METHODS: The intestinal permeability were measured in 14 normal heathy controls, 41 patients with mild acute pancreatitis (alcoholic 14, biliary 12, idiopathic 15) by measuring 24 hour urine excretion of 51Cr-EDTA (51Cr-ethylenediaminetetraacetic acid) for evaluation of the gut barrier dysfunction. We compared the intestinal permeability with clinical characteristics of patients. RESULTS: The intestinal permeability was significantly increased in patients with mild acute pancreatitis (6.01+/-4.11%, p<0.001) versus control subjects (1.86+/-0.52%). There was no significant difference in the intestinal permeability among the patients with alcoholic, biliary and idiopathic pancreatitis. The correlation was not found between intestinal permeability and clinical characteristics in patients with mild acute pancreatitis. CONCLUSIONS: The intestinal permeability is increased in patients with mild acute pancreatitis regardless of etiology of pancreatitis. The predictive factor for gut barrier dysfunction is not detected in patients with mild acute pancreatitis.