RESUMEN
The purpose of the in vitro study was to compare the diffusive transport of creatinine, uric acid and glucose, directed from the interstitial (I) to the mesothelial (M) side of the peritoneum and in the opposite direction, before (15-60min) and after (75-120min) application of gentamicin and insulin. The experiments were undertaken on the rabbit parietal peritoneum in a modified Ussing chamber. A mathematical model was used to calculate a diffusive permeability coefficient P (in cm/s) and a diffusive mass transport coefficient KH (in mL/min). In the basic experimental series without drugs, the dynamics of peritoneal transport for examined solutes remained constant and there were no differences between transport directions (I--> M and M--> I). Mean values of P+/-SEM (KH+/-SEM) were 3.06+/-0.32 (321.1+/-33.5), 2.09+/-0.29 (219.2+/-30.7) and 2.73+/-0.47 (286.7+/-49.6) for creatinine, uric acid and glucose, respectively. The introduction of gentamicin decreased glucose transport directed from the mesothelial to the interstitial side of the membrane by about 12%. After insulin application we observed the increase of creatinine and glucose peritoneal transport rate. For creatinine, the above augmentation was by about 31% for I--> M and 83% for M--> I direction. In these conditions, the glucose transport directed from the interstitial to the mesothelial side of membrane increased by about 24%. Generally, in vitro gentamicin decreases, but insulin increases the diffusive permeability of the peritoneum for some small solutes. We suppose that these findings may be important for the efficiency of peritoneal dialysis.
Asunto(s)
Antibacterianos/farmacología , Gentamicinas/farmacología , Insulina/farmacología , Peritoneo/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Creatinina/metabolismo , Difusión , Glucosa/metabolismo , Técnicas In Vitro , Diálisis Peritoneal , Peritoneo/efectos de los fármacos , Permeabilidad , Conejos , Ácido Úrico/metabolismoRESUMEN
The effect of fluid mixing intensification, damage of mesothelial cells, gentamicin, and icodextrin on the diffusive glucose transport across the peritoneal membrane were evaluated in in vitro studies. A mathematical model of mass transport was used to calculate the diffusive permeability, expressed as a diffusive permeability coefficient (P). In the control conditions, the rate of glucose transfer from the interstitial to the mesothelial side of membrane (I-->M) and in the opposite direction (M-->I) remained constant, and the P value at mean was 2,731 +/- 1,493 x 10-4 (cm x s-1). The change of the stirring rate from 5.5 to 11 ml/min increased P values by about 74% for transport direction I-->M and 58% for M-->I, and the change from 11 to 22 ml/min enhanced P at mean by about 42% for both directions. The damage of the mesothelial layer, using sodium deoxycholate (2.5 mmol/L; 103.6 mg%), increased the glucose transfer from the interstitial to the mesothelial side of the peritoneum by 41% and to the opposite direction by 70%. Addition of icodextrin to the glucose solution increased glucose bidirectional transport at mean by about 14% for I-->M and 24% for M-->I. Furthermore, gentamicin did not change the I-->M transfer, but diminished M-->I transport by about 12%. In conclusion, the reduction of unstirred fluid layers at the mesothelium and the interstitium-fluid interfaces, removal of mesothelium, and addition of icodextrin increased the diffusive glucose transport in vitro; unstirred fluid layers restricted glucose transfer (I-->M) more than the mesothelium; and peritoneal glucose transport, directed from the mesothelial to the interstitial side of the peritoneum, decreased slightly after the addition of gentamicin.
Asunto(s)
Glucosa/farmacocinética , Peritoneo/metabolismo , Algoritmos , Análisis de Varianza , Animales , Antibacterianos/farmacología , Ácido Desoxicólico/farmacología , Detergentes/farmacología , Soluciones para Diálisis/farmacología , Difusión , Cámaras de Difusión de Cultivos , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Gentamicinas/farmacología , Glucanos/farmacología , Glucosa/farmacología , Icodextrina , Modelos Lineales , Modelos Biológicos , Peritoneo/efectos de los fármacos , Permeabilidad , ConejosRESUMEN
UNLABELLED: The effect of mixing fluid intensification, damage of mesothelial cells and gentamicin on the diffusive glucose transport across the peritoneal membrane were evaluated in the presented in vitro studies. A mathematical model of the mass transport was used to calculate the diffusive permeability, expressed as a diffusive permeability coefficient P [cm x s-1], for the investigated specimens. In the control conditions glucose transfer from the interstitial to the mesothelial side of membrane (I-->M) and in the opposite direction (M-->I) remained constant and P value at mean was 2.731 +/- 1.493 [cm x s-1 x 10(-4)]. The change of the stirring rate from 5.5 to 11 mL/min increased P values by about 74% for transport direction I-->M and 58% for M-->I, but change from 11 to 22 mL/min enhanced P at mean by about 42% for the both direction. The damage of the mesothelial layer, using of sodium deoxycholate (2.5 mmol/L; 103.6 mg%), increased the glucose transfer from the interstitial to the mesothelial side of the peritoneum by 41% and to the opposite direction by 57%. Furthermore, gentamicin did not change the I-->M transfer, but diminished M-->I transport by about 12%. IN CONCLUSION: 1. The reducing of unstirred fluid layer at the mesothelium and interstitium--fluid interface and the mesothelium damage increase the diffusive glucose transport in vitro; 2. The unstirred fluid layer restricts glucose transfer more than tissue barrier (mesothelium); 3. The peritoneal glucose transport, directed from the mesothelial to the interstitial side of the peritoneum (but not transfer to the opposite direction), decreases slightly after gentamicin introduction.
Asunto(s)
Glucosa/metabolismo , Modelos Biológicos , Peritoneo/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Ácido Desoxicólico/farmacología , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Espacio Extracelular/metabolismo , Gentamicinas/farmacología , Técnicas In Vitro , Permeabilidad/efectos de los fármacos , ConejosAsunto(s)
Soluciones para Diálisis/administración & dosificación , Glucanos/administración & dosificación , Glucosa/administración & dosificación , Diálisis Peritoneal , Soluciones para Diálisis/química , Soluciones para Diálisis/farmacocinética , Glucanos/química , Glucanos/farmacocinética , Glucosa/química , Glucosa/farmacocinética , Humanos , Icodextrina , Concentración Osmolar , Diálisis Peritoneal Ambulatoria Continua , UltrafiltraciónRESUMEN
The dynamics of bidirectional glucose transport across parietal peritoneum from anterior abdominal wall or diaphragm and small-bowel mesentery was analyzed. The mean transport values, expressed as transport coefficients, of intact peritoneum amounted 2.61; 0.18; 5.43 (10(-4) x cm x S-1), respectively. The chemical destruction of the mesothelium (2.5 mmol/l sodium deoxycholate) increased transperitoneal glucose transport across the investigated tissues. However, the intensification of transfer was different. Removal of the diaphragm pleural mesothelium caused greater increase of bidirectional glucose transport than the peritoneal mesothelium. Furthermore, the mean values of transport coefficient after peritoneal mesothelium damage were higher in relation to mesentery than to the peritoneum isolated from anterior abdominal wall and diaphragm. The obtained results suggest topographic heterogeneity of peritoneal membrane which refer to the mesothelium and submesothelial layers.
Asunto(s)
Glucosa/metabolismo , Peritoneo/metabolismo , Músculos Abdominales/metabolismo , Animales , Transporte Biológico/fisiología , Diafragma/metabolismo , Epitelio/metabolismo , Técnicas In Vitro , Mesenterio/metabolismo , Pleura/metabolismo , ConejosRESUMEN
The changes of peritoneal absorption and excretion of urea, uric acid and gentamicin caused by glucose or mannitol have been analysed. These modification were differentiated, depended on the type of transported molecule, used osmotic agent and time of its activity as well as transfer direction. For example, glucose caused the increase of uric acid absorption and the decrease of urea excretion by about 40%. In contrast, mannitol didn't change the uric acid transport, but lowered the bidirectional transfer of urea. The mean values of gentamicin transport diminished after application of glucose or mannitol. This lowering was smaller in comparison with isoosmolar conditions. The reasons of above modifications are complex. It supposes that in vitro the direct physical action of hyperosmolality, metabolic activity of glucose and membrane effect of gentamicin balanced the solvent drag process. Furthermore, the heterogenecity of glucose and mannitol influence on the transperitoneal compounds transport are related to the transport rates (mechanism) of the examined osmotic agents and/or their metabolic activity.
Asunto(s)
Glucosa/metabolismo , Manitol/metabolismo , Peritoneo/metabolismo , Absorción , Animales , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Gentamicinas/farmacocinética , Glucosa/farmacología , Técnicas In Vitro , Manitol/farmacología , Peritoneo/efectos de los fármacos , Conejos , Urea/farmacocinética , Ácido Úrico/farmacocinéticaRESUMEN
The changes of the transperitoneal molecules transport caused by glucose and dynamics of its transport have been determined in the case of undamaged tissue and the membrane with injured mesothelium in the in vitro studies. In the intact glucose induced increase of peritoneal uric acid absorption (40%) and lowering of urea and gentamicin excretion (25-40%). Glucose in the dialysis fluid lowered uric acid absorption and urea excretion (20-40%) in denuded animal peritoneum. The transperitoneal glucose transport remained constant at 2.61 x 10(-4) x cm x s-1. The mesothelium destruction caused an increase (32%) of mean values of absorption and excretion of this compound. The obtained results suggest that modifications of transport functions of the peritoneum caused by glucose depend rather on direct action of hypertonicity and metabolic effects of glucose than of the osmotic gradient. Furthermore, these changes may contribute to the rapid transperitoneal transport of glucose which increase after the destruction of the mesothelium.
Asunto(s)
Glucosa/metabolismo , Peritoneo/fisiología , Absorción , Animales , Transporte Biológico , Epitelio/metabolismo , Gentamicinas/farmacocinética , Técnicas In Vitro , Diálisis Peritoneal , Conejos , Urea/farmacocinética , Ácido Úrico/farmacocinéticaRESUMEN
It was shown elsewhere that in a peritoneally dialyzed woman with pulmonary tuberculosis, oral treatment with rifampicin and pyrazinamide (11 and 25 mg/kg/day, respectively) caused a decrease in the peritoneal transport of sodium, potassium, urea, uric acid, protein, and ultrafiltration rate by 48% to 75% compared to the pretreatment values. Pyrazinoic acid (PA), a metabolite of pyrazinamide, may account for these changes, because rifampicin was also previously used in this patient without peritoneal function impairment. Thus in the present study the influence of PA on the human peritoneum is examined using the modified Ussing-type chamber. PA (1 mg/dL) was introduced into the medium on the interstitial side of the membrane. After the introduction of PA, uric acid transfer from the interstitial to the mesothelial side decreased by about 50%. There were no significant changes in the urea and albumin transfer rates. In conclusion, PA induces changes in uric acid transfer acting directly on mesothelial cells, whereas a decrease in the peritoneal transfer of other solutes may be caused by a decrease in convective transfer rates due to impaired ultrafiltration.