Seminal plasma does not aid in the transport of phenolsulfonphthalein across the uterotubal junction in mares.

This study tested the hypothesis that the presence of prostaglandin E2 in seminal plasma would aid in the transport of phenolsulfonphthalein (PSP) across the uterotubal junction. Five mares in estrus were inseminated during estrus with PSP dissolved in phosphate-buffered saline and during the subsequent estrus with PSP added to a standard insemination dose. Serum and urine samples were obtained at hours 0, 1, 2, and 3 following treatment and examined for the presence of PSP. Phenolsulfonphthalein could not be detected in any of the urine samples collected from mares following either treatment. None of the serum samples collected following intrauterine installation of PSP in PBS contained PSP. Phenolsulfonphthalein was detected in serum samples from 1 mare following insemination with semen containing PSP. Components in seminal plasma such as PGE2 did not facilitate the transport of PSP across the uterotubal junction as had been hypothesized.

Le plasma séminal ne facilite pas le transport de la phénolsulfonphtaléine au travers de la jonction utéro-tubaire des juments. Cette étude a testé l'hypothèse voulant que la présence de la prostaglandine E2 dans le plasma séminal facilite le transport de la phénolsulfonphtaléine (PSP) au travers de la jonction utéro-tubaire. Cinq juments en oestrus ont été inséminées avec de la PSP dissoute dans une solution saline tamponnée au phosphate et, durant l'oestrus subséquent, avec de la PSP ajoutée à une dose d'insémination standard. Des prélèvements de sérum et d'urine ont été obtenus aux heures 0, 1, 2 et 3 ainsi qu'après le traitement et examinés pour déceler la présence de la PSP. La phénolsulfonphtaléine n'a pas pu être détectée dans aucun des échantillons d'urine prélevés auprès des juments après l'un ou l'autre des traitements. Aucun des échantillons de sérum prélevés après l'installation intra-utérine de la PSP dans PBS ne contenait de PSP. La phénolsulfonphtaléine a été détectée dans des échantillons de sérum provenant d'une jument après l'insémination avec du sperme contenant de la PSP. Des composants dans le plasma séminal comme le PGE2 n'ont pas facilité le transport de la PSP au travers de la jonction utéro-tubaire conformément à l'hypothèse émise.(Traduit par Isabelle Vallières).

Design, synthesis and performance evaluation of mPEG-PR: A novel non-absorbable marker.

The aim of the present study was to develop a new marker for correcting water flux in the in situ single-pass intestinal perfusion (SPIP) model. The new marker was designed and synthesized based on the application of both polyethylene glycol-4000 (PEG-4000) and phenol red as non-absorbable markers. The new marker mPEG-PR was obtained by combining phenol red with polyethylene glycol monomethyl ether-4000 (mPEG-4000) and verified by nuclear magnetic resonance (NMR), ultraviolet (UV) spectra, gel permeability chromatograph (GPC) and differential scanning calorimetry (DSC). mPEG-PR fully took the advantages of phenol red and PEG including the low permeability and the simple measuring method which were assessed by the in vitro and the in situ models. In the everted gut sac (EGS) studies, the permeability of mPEG-PR was significantly reduced by nearly 4 times compared with phenol red, and the absorptive percentage of mPEG-PR was <0.1% in 105 min. In addition, the solution with verapamil or without Ca2+ could help improve the absorption of phenol red but did not influence the absorption of mPEG-PR. The results of isosorbide dinitrate as a model drug in the in situ SPIP study showed that both the mPEG-PR marker and the gravimetric method were useful for correcting water flux, which had smaller coefficients of variation than the phenol red marker and the non-corrected method. In conclusion, mPEG-PR could potentially be applied as an accurate and convenient marker for correcting water volume in the intestinal perfusion study.

Human oral drugs absorption is correlated to their in vitro uptake by brush border membrane vesicles.

Brush border membrane vesicles (BBMV) were prepared from the rabbit small intestine for testing drug absorption potency through the enterocyte's apical membrane, which is an important compartment for drug oral absorption. Some modifications have been made to the traditional vesicle assay for adapting it to the 96-well plate format. The accumulation of 23 reference drugs was measured, and the data showed a good correlation with human oral absorption with a correlation coefficient R=0.853 (P<0.001), with the exception of a few false positive results. As the measured drug absorption may contain a membrane/protein binding component as well as drug uptake into vesicles, these two fractions can be discriminated by changing extravesicular osmolarity using different mannitol concentrations. This model can be applied for evaluating drug absorption rate/mechanisms, and helping drug selection in early drug research and development.

The molecular assembly of the ionic liquid/aliphatic carboxylic acid/aliphatic amine as effective and safety transdermal permeation enhancers.

In spite of numerous advantages, transdermal drug delivery systems are unfeasible for most drugs because of the barrier effect of the stratum corneum. Ionic liquids were recently used to enhance transdermal drug delivery by improving drug solubility. In the present study, safe and effective ionic liquids for transdermal absorption were obtained as salts generated by a neutralization reaction between highly biocompatible aliphatic carboxylic acids (octanoic acid or isostearic acid) and aliphatic amines (diisopropanolamine or triisopropanolamine) (Medrx Co., Ltd., 2009). The mechanism of skin permeability enhancement by ionic liquids was investigated by hydrophilic phenol red and hydrophobic tulobuterol. Further, the skin permeation enhancing effect was remarkably superior in the acid excess state rather than the neutralization state. Infrared absorption spectrum analysis confirmed that ionic liquids/aliphatic carboxylic acid/aliphatic amine are coexisting at all mixing states. In the acid excess state, ionic liquids interact with aliphatic carboxylic acids via hydrogen bonds. Thus, the skin permeation enhancing effect is not caused by the ionic liquid alone. The "liquid salt mixture," referred to as a complex of ingredients coexisting with ionic liquids, forms a molecular assembly incorporating hydrophilic drug. This molecular assembly was considered an effective and safety enhancer of transdermal drug permeation.

Characterization of secretory intestinal transport of phenolsulfonphthalein.

It is known that secretory transport limits the oral bioavailability of certain drugs. However, there is little information on the secretion of anionic compounds in the intestine. Phenolsulfonphthalein (PSP) and p-aminohippuric acid (PAH) have been used widely as substrates for organic anion transport systems. PAH is transported in the secretory direction in the intestine. It is possible that PSP and PAH share the same transport system at the mucosal membrane. The purpose of this study was to characterize the transport system for PSP in the intestine. In the jejunum, the serosal-to-mucosal permeation rate of PSP was significantly reduced in an ATP-depleted condition, whereas a significant difference was not observed in the ileum. Some multidrug resistance-associated protein 2 (Mrp2) inhibitors inhibited PSP permeation in the jejunum. However, pravastatin, a substrate of Mrp2, did not inhibit the PSP permeation. The jejunal secretory transport of pravastatin was significantly reduced in an ATP-depleted condition and by addition of probenecid, but PSP did not affect the jejunal permeation of pravastatin. These results suggest that PSP is secreted into the intestinal lumen by Mrp2-like transporter and that two Mrp2 substrates, PSP and pravastatin, are likely to be transported by different transport systems at the mucosal membrane.

Effect of intestinal atrophy and hepatic impairment induced by parenteral nutrition on drug absorption and disposition in rats.

BACKGROUND: Long-term parenteral nutrition (PN) has a high risk of hepatic dysfunction and intestinal atrophy. The present study investigated the effect of PN-induced intestinal atrophy and hepatic impairment on drug pharmacokinetics by using 2 contrasting compounds: phenolsulfonphthalein (PSP) and cyclosporin A (CyA). MATERIALS AND METHODS: PSP or CyA was administered to 7-day PN-fed Rats (PN rats) and sham operated rats (control rats) via intravenous (IV) or intraloop administration of the intestine. Pharmacokinetic parameters with 2-compartment analysis including area under the concentration vs time curve (AUC) and the permeability after in situ intraloop administration (P loop) were obtained from both concentration profiles after different administration routes. RESULTS: After IV administration of PSP to control and PN rats, there was no notable difference in any of the pharmacokinetic parameters. In contrast, after intraloop administration, AUC and P loop in PN rats were approximately 2.6- and 2.0-fold higher than that in control rats, respectively. On the other hand, after IV administration of CyA, the terminal half-life and total body clearance were prolonged and decreased in PN rats, respectively, resulting in 2.0-fold increase in AUC. After intraloop administration, the AUC of PN rats was increased to approximately 1.3-fold that of control rats, whereas no notable difference was observed in P loop. CONCLUSION: The intestinal permeability of PSP was enhanced by intestinal atrophy induced by PN, while the metabolism of CyA was diminished by hepatic impairment by PN. These results revealed the physicochemical property-based pharmacokinetic alterations during PN; for a more detailed understanding, however, further studies are needed.

pH-dependent cytotoxicity of contaminants of phenol red for MCF-7 breast cancer cells.

The pH indicator phenol red (phenolsulfonphthalein) is present in most tissue culture media. Contaminants of this indicator have shown substantial estrogenic activity for estrogen-dependent cells in culture, including the human breast cancer-derived MCF-7 cell line. In the course of other studies, we observed that brief (1- to 4-h) incubations of these cells at 37 C in serum-free medium (Hanks' or Earle's Balanced Salts Solution) could be toxic to MCF-7 cells when the pH was increased above 7.4, but only if phenol red (10 micrograms/ml) was present in the medium. Because damaged/killed cells detached from the substratum (greater than 98% of detached cells stained with trypan blue), we used DNA assay of the cells remaining after treatment and wash (98% of the remaining cells were dye excluding) to further assess cytotoxicity. The MCF-7 cells were more susceptible to the cytotoxicity at lower cell densities, so further characterization of phenol red cytotoxicity was performed at cell densities of 1-10 micrograms DNA/2-cm2 well, or approximately 40,000-400,000 cells/ml medium. In the pH range of 7.0-8.2, 50% cell death was observed in the presence of phenol red at pH as low as 7.6-7.7, with nearly 100% of the cells killed by pH 8.0. Little effect was seen in phenol red-free medium at any part of the tested pH range or in medium that contained phenol red at pH less than or equal to 7.4. In time-course studies of cytotoxicity at pH 8.0 (phenol red, 10 micrograms/ml), greater than 50% cell damage could be observed after less than 1 h, and little cell recovery was observed if the pH was restored to 7.4. For phenol red samples from two major commercial sources, the concentration for half-maximal cytotoxicity (TD50) in dose-responses after 4 h at pH 8.0 showed TD50 values of 2 and 6 micrograms/ml, while the estrogenic activities, as half-maximal stimulation of estrogen-dependent proliferation, were identical at 2 micrograms/ml. Both the cytotoxic and estrogenic activities could be removed from the phenol red by extraction with diethyl ether. A number of contaminants of the commercial phenol red were detected by reverse phase C18 HPLC. Cytotoxicity and estrogen bioassays of each of the HPLC fractions indicated that the pH-dependent cytotoxicity was separate from the estrogenic activity and confirmed that neither activity was associated with the phenol red itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Validation of gastric-emptying scintigraphy of solids and liquids in mice using dedicated animal pinhole scintigraphy.

UNLABELLED: Gastric emptying in small laboratory animals is a useful parameter to assess gastrointestinal motility for physiologic, pharmacologic, or other research purposes. In mice, phenol red recovery is considered the gold standard for determination of gastric emptying. However, this method requires sacrifice of the animal and yields data of gastric emptying at only 1 time point. Gastric-emptying scintigraphy, the gold standard technique in humans, allows sequential and serial measurements in the same subject. In this study, we developed and validated a novel method of gastric-emptying scintigraphy applied in mice, by comparing it with phenol red photospectrometry. METHODS: A dedicated animal pinhole gamma camera was equipped with a specially designed mouse application device. Gastric emptying was measured in unanesthetized mice using pinhole scintigraphy. First, gastric emptying determined with scintigraphy was compared with gastric phenol red recovery simultaneously within the same population. Subsequently, normal values for gastric emptying of solids and liquids in mice were established, and finally, the effects of handling stress and the late effects of frequently used anesthetics or sedatives on gastric emptying were assessed by scintigraphy. RESULTS: Gastric emptying of liquids measured by pinhole scintigraphy did not significantly differ from that measured by phenol red recovery. For the same information, 80% fewer animals were needed for the scintigraphic method. More stress-related delay in gastric emptying was induced by multiple handling of the mice, compared with the less frequent handling that was associated with taking measurements every 10 min or more (P < 0.05). The mean half-emptying time for solids measured by scintigraphy was significantly slower than that for liquid emptying (P < 0.01). Previous anesthesia did not significantly affect gastric emptying 6 h after induction. CONCLUSION: Dedicated small-animal pinhole gastric-emptying scintigraphy is a reliable tool to investigate gastrointestinal motility in mice, significantly reducing the number of laboratory animals needed for statistical power in trials. The technique enables sequential and serial measurement within 1 subject and is thus useful for follow-up investigations, which can be performed even after invasive procedures that require anesthesia.

Development of implant tablet for a week-long sustained release.

An implant tablet for a week-long sustained release was developed by the direct compression method using poly-DL-lactic acid (PLA) and poly(DL-lactic acid-co-glycolic acid) copolymer (PLGA) as a matrix and phenol red (PR) as a model drug. The in vitro release was affected by formulations, especially by drug content and polymer species. The release rate correlated with the rate of absorption of water. The implant tablet (30 mg) containing 1 mg of PR, prepared using PLGA (MW 10,000; lactic acid/glycolic acid=1:1, mol/mol) by compression at 50 kg/cm(2) for 10 s, was found to efficiently exhibit a week-long sustained release in vitro, and applied in vivo. The remaining amount or plasma concentration of PR after s.c. administration of the implant tablet to rats demonstrated that the implant tablet showed a week-long sustained release in vivo. The present implant tablet is suggested to be useful as a drug delivery system for supplying drugs for approximately 1 week.

Mucosal permeability regulates receptor binding of luminal epidermal growth factor in the adult rat intestine.

Epidermal growth factor (EGF) stimulates repair in the damaged intestine, but its role in the normal intestine is not clear. Because EGF receptors are found on the basolateral surface but not the luminal surface, we hypothesized that mucosal permeability regulates EGF binding. Adult male rats were divided into 3 groups, one that was fed normal chow (the control), one that was starved for 4 days, and one that was given methotrexate (MTX) intragastrically (10 mg/kg/day for 3 days). The rats were sacrificed and everted sacks of the jejunum were made and incubated in EGF solution. Western blot analysis of mucosal homogenates showed that the amount of phosphotyrosyl EGF receptor in the starved and MTX-treated groups was, respectively, about 1.5 times and 2 times that in the control group. The mucosal permeability in the starved and MTX treated groups also increased and varied directly with the amount of phosphotyrosyl EGF receptor. These results suggest that in the adult rat intestine, luminal EGF may play a role only under tissue damage, where enhanced permeability permits the EGF to pass through the mucosa and bind to its receptor on the basolateral membrane.

Effect of viscous additives on drug absorption from the liver surface in rats using phenol red as a model.

The purpose of this study is to obtain information that can be used to improve controlled release and residence time of drugs on the liver surface. Using carboxymethylcellulose sodium salt (CMC-Na) and polyvinyl alcohol (PVA), we examined the effect of viscous formulations on the absorption of phenol red as a model. In the presence of 3% CMC-Na or 15% PVA, the maximum plasma concentration of phenol red decreased after application to the rat liver surface using a cylindrical glass cell. The absorption ratios in 6 h calculated from the remaining amount of phenol red in the glass cell were 68.6, 60.5 and 48.7% (control: 73.1%) in the presence of 1 or 3% CMC-Na and 15% PVA, respectively. As a result of the reduction in the absorption ratio, the amount of phenol red excreted into the bile and urine in 6 h was decreased by the addition of the viscous additives. The decrease in absorption rate was characterized by a pharmacokinetic analysis of the plasma concentration profile. The change in absorption rate differed between the viscous additives, reflecting the result of the in vitro release experiment. Accordingly, the possibility that the drug absorption rate from the liver surface can be altered by viscous additives was suggested to have a promising prospect for therapeutic use.

Does paracellular permeability play a role in cholephilic dye-induced cholestasis?

Changes in hepatic paracellular permeability were investigated during the development of cholephilic dye-induced cholestasis in rats. For this purpose, four dyes with different cholestatic potency (phenol red, sulfobromophthalein, bromcresol green and rose bengal) were infused at a high, potentially damaging dose (280 nmol/min per 100 g body wt., i.v.), and changes in paracellular permeability were continuously monitored by measuring the access into bile of the permeability probe -14C-sucrose. The cholestatic potency of the different dyes was: rose bengal > bromcresol green > sulfobromophthalein > phenol red. All dyes increased [14C]sucrose bile-to-plasma ratio, producing a displacement towards curves of higher permeability. The capability of the dyes to increase biliary permeability followed the same order as their respective cholestatic potencies. The possible implications of the present results for cholephilic dye-induced cholestasis are discussed.

Validity of oral bioavailability estimates of phenolsulfonphthalein based on total urinary excretion from rats.

Urinary recovery of phenolsulfonphthalein from rats were determined after intracardial (0.075 mg) and oral (1.5 mg) doses. Although trace quantities of conjugated metabolites could be identified by TLC, the levels present did not introduce significant error into estimates of total phenolsulfonphthalein excretion if samples were assayed directly by colorimetric methods for only unchanged dye. The absolute availability of phenolsulfonphthalein based on urinary recovery under the present experimental conditions was estimated at 10.6%.

Effect of surfactants on absorption through membranes III: effects of dioctyl sodium sulfosuccinate and poloxalene on absorption of a poorly absorbable drug, phenolsulfonphthalein, in rats.

The influence of dioctyl sodium sulfosuccinate and poloxalene on the GI absorption of phenolsulfonphthalein in the rat was studied. Urinary excretion data after oral administration of the drug to intact rats and loss of the drug from the whole small intestine as a loop were both utilized to assess the effect of the surfactants on absorption. Dioctyl sodium sulfosuccinate markedly increased the absorption of the drug, and the extent was dependent on the surfactant concentration. Maximum effect was observed at the reported ED50 in rats, of the surfactant as a fecal softener. The mechanism responsible for absorption enhancement seems to be an alteration of the permeability of the intestinal membrane. Micellar complexation between the drug and the surfactant resulted in a lesser increase in absorption at the higher surfactant concentrations. Poloxalene did not increase drug absorption, but higher concentrations caused a decrease in absorption due to micellar entrapments of the drug molecules. The influence of dioctyl sodium sulfosuccinate on the peritoneal absorption of the drug was also investigated. Lower doses of the surfactant increased absorption of the drug by altering the membrane permeability. Higher doses decreased absorption due to unavailability of the drug molecules entrapped in the micelles.

Effect of application volume and area on the absorption of phenol red, as a model drug, from the liver surface in rats.

To determine the influence of the method of administration of a pharmaceutical formulation we have examined the importance of application volume and area in the absorption of phenol red, as a model drug, from the rat-liver surface. When 1 mg phenol red was applied to the rat-liver surface, in-vivo, in three volumes (0.1, 0.2 or 0.334 mL) using a cylindrical glass cell (i.d. 9 mm), the shape of the plasma concentration profile differed greatly, particularly the maximum concentration. These patterns were well fitted by a two-compartment model with first-order absorption, and the absorption-rate constant Ka obtained was inversely proportional to the application volume. The absorption ratio and biliary recovery of phenol red after 6 h increased with glass cell area (i.d. 6, 9 or 14 mm; area 0.28, 0.64 or 1.54 cm2). Furthermore, the permeability coefficient Papp derived from Ka did not depend on application area, indicating no difference in the absorption characteristics of the liver surface. This also implies transport of the drug by passive diffusion from the liver surface. After intraperitoneal administration to the rat-liver surface for clinical application, increasing the application volume resulted in the delayed disappearance of phenol red from the plasma. However, the difference was not as marked as that obtained by use of the glass cell. The assumption that the effective area relating to the absorption changed with the application volume enabled us to estimate Papp. Consequently, we speculate that absorbability can be estimated precisely by consideration of application volume and area.

Effect of instillation method on the absorption of phenolsulphonphthalein as a model drug from the liver and small intestinal serosal surface in rats.

We have examined the effect of the instillation method on the absorption of a drug from the liver and the small intestinal serosal surface in rats. We performed continuous microinstillation via an infusion pump and bolus instillation via a syringe, using phenolsulphonphthalein (phenol red) as the model drug. After continuous microinstillation of phenolsulphonphthalein 2.35 mg in 235 microL for 5 min on the liver and small intestinal serosal surface in rats, the AUC (area under the curve) of the plasma concentration profile up to 60 min was significantly higher compared with bolus instillation. A similar trend was observed after continuous microinstillation of phenolsulphonphthalein 2.35 mg in 117.5 microL for 2.5 min. The calculated absorption rate constants (Ka) after continuous microinstillation of phenolsulphonphthalein based on a two-compartment model with first-order absorption were higher than those after bolus instillation on the liver and small intestinal serosal surface at either instillation concentration. Moreover, Ka was increased after continuous microinstillation of 2.35 mg in 117.5 microL at either instillation site. Instillation of phenolsulphonphthalein on the liver surface resulted in a 1.2- to 2.3-fold higher Ka compared with the small intestinal serosal surface. This tendency was marked after continuous microinstillation of 2.35 mg in 117.5 microL. In conclusion, absorption could be enhanced by instilling a small amount of drug solution on the liver surface gradually and continuously, suggesting a promising approach for instillation site-selective drug delivery in the peritoneal cavity.

Absorption of phenol red and bromphenol blue as model drugs from the peritoneal cavity around the liver surface in rats.

The importance of the injection site on the pharmacokinetics of phenol red and bromphenol blue as model drugs after intraperitoneal administration into rat was examined. Their absorption rate from the peritoneal cavity was faster after intraperitoneal administration to the liver surface than that after intraperitoneal administration to the distal small intestine, as shown by the increase in maximum concentration and decrease in mean residence time in plasma. A similar tendency was observed in the biliary excretion pattern. The enhanced absorption rate was supported by the significantly smaller amount of both drugs remaining in the peritoneal cavity at 15 min after liver surface administration than that after small intestine administration. The liver concentration of the model drugs at 15 min after liver surface administration was 1.5-2.0 times that after small intestine administration. Accordingly, liver surface administration was shown to be effective with good absorption and efficient drug delivery to the liver.

Absorption of organic anions as model drugs following application to rat liver surface in-vivo.

Absorption of organic anions (phenol red, bromphenol blue and bromosulphonphthalein) has been studied after their application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0.64 cm2). Each drug appeared gradually in the blood with the peak level at about 1 h, after which its concentration declined slowly. Absorbed model drug was efficiently excreted into the bile. These observations appear to indicate the possibility of drug absorption from liver surface membrane. Absorption of model drugs was estimated to be more than 59% in 6 h. The biliary recovery and metabolism of phenol red did not change as compared with that after intravenous administration.

Mechanism for drug absorption from rat-liver surface membrane: effect of dose and transport inhibitors on the pharmacokinetics of phenol red.

We examined the effect of dose and transport inhibitors on the pharmacokinetics of phenol red as a model drug after application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0.64 cm2), to elucidate the mechanism for drug absorption from liver surface membrane. Absorption ratios of phenol red in 6 h were determined to be 91.1, 91.8 and 89.9% at a dose of 0.3, 1 and 3 mg, respectively. The AUC value for plasma concentration profile of phenol red was proportional to the dose. It is thus suggested that the absorption process of phenol red from rat liver surface does not approach saturability. The time course of the remaining amount of phenol red in the glass cell obeyed first-order kinetics at a dose of 0.3 mg, and its rate constant Ka was calculated to be 0.0069 min-1. Moreover, no significant difference was seen in the Ka value within the dose range of 0.3-3 mg, which was estimated by curve fitting of the plasma concentration profile of phenol red after application to rat liver surface in the two-compartment model with first-order absorption. 2,4-Dinitrophenol (0.3 mg) and probenecid (0.5 and 1 mg), inhibitors of metabolic energy and anion transport, respectively, had no significant effect on the pharmacokinetics of phenol red after application to rat liver surface. These data demonstrate that a specific transport mechanism such as active transport is not involved in phenol red absorption from rat liver surface membrane.

Assessing the permeability of the gastrointestinal mucosa after oral administration of phenolsulfonphthalein.

BACKGROUND/AIMS: In this study, the oral phenolsufonphthalein (PSP) absorption test as a simple and non-invasive method for the assessment of either the extent of the permeability of or damage to the gastrointestinal mucosa was evaluated. METHODOLOGY: The permeability of the gastrointestinal mucosa of patients with liver cirrhosis and those who underwent gastrointestinal surgery was assessed by the oral administration of 30 mg of PSP and the measurement of its urinary recovery rate. RESULTS: The urinary PSP excretion in patients with liver cirrhosis (n = 8; 28.8 +/- 6.0%) was significantly higher than that of patients who underwent vascular surgery (n = 8; 10.0 +/- 1.7%) (p < 0.01), which thus suggested an increased permeability of the gastrointestinal mucosa in patients with liver cirrhosis. The urinary PSP excretion rate in patients who underwent a total gastrectomy with Roux-en-Y reconstruction (n = 5) was 17.3 +/- 1.7% which was significantly higher than that observed in the control (p < 0.05), while the same rates in patients who underwent a partial gastrectomy (n = 10) or colectomy (n = 10) were 10.2 +/- 1.8% or 10.6 +/- 0.7%, respectively, which suggested that the intestinal mucosa is damaged by a total resection of the stomach. CONCLUSIONS: The oral PSP absorption test, which is non-invasive, simple and inexpensive, is thus considered to be useful for assessing the degree of damage to or the permeability of the gastrointestinal mucosa under various conditions.