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Intestinal permeability in cirrhotic patients with and without ascites.

OBJECTIVE: It has been suggested that increased intestinal permeability plays a pathogenic role in bacterial infections, such as spontaneous bacterial peritonitis, in patients with liver cirrhosis. The aim of this study was to assess whether intestinal permeability is altered in cirrhotic patients with and without ascites. MATERIAL AND METHODS: Intestinal permeability was assessed by a (51)Cr-EDTA permeability test in 20 cirrhotic patients (10 with and 10 without ascites) along with 20 age- and gender-matched healthy controls. In six patients with ascites, the test was performed before and after therapeutic paracentesis. RESULTS: The median (IQR) 24-h urinary excretion of (51)Cr-EDTA was higher in patients with cirrhosis (1.94% (1.21-2.70%)) compared with that in controls (1.40% (1.09-1.99%); p<0.05). Patients with (2.05% (1.50-3.46%); p<0.05) but not those without ascites (1.94% (1.13-2.53%); p>0.1) had significantly higher excretion values compared with those of controls. Only one patient without ascites and a total of four patients with ascites had increased intestinal permeability ((51)Cr-EDTA excretion > 95% confidence than that of controls; p>0.1). Paracentesis did not affect urinary (51)Cr-EDTA excretion significantly (1.69% (1.16-2.86%) versus 1.30% (1.08-1.79%) before and after, respectively; p>0.1). No significant correlation was found between clinical severity scores for liver disease and intestinal permeability. CONCLUSIONS: Only a small proportion of patients with liver cirrhosis have increased intestinal permeability and it is unlikely that this plays any major role in predisposing these patients to infections.

Adult↗

Middle cerebral artery occlusion increases cerebral capillary permeability.

One hour after middle cerebral artery occlusion, the regional blood to brain transfer coefficient of alpha-aminoisobutyric acid was determined in eight barbiturate anaesthetized rats. The transfer coefficient (microliter/min-1/g-1) was significantly higher in the ischaemic cortex (10.6 +/- 2.3) than in the contralateral cortex (6.5 +/- 1.0). Cerebral regional capillary surface area was determined in another group of twelve rats using an alkaline phosphatase stain for the total capillary bed and fluorescein isothiocyanate-dextran to visualize the perfused capillaries. Perfused capillary surface area (cm2/cm3) was lower in the ischaemic cortex (141 +/- 31) than in the contralateral cortex (426 +/- 32). Using these values for the transfer coefficient, surface area and our previously published data of regional cerebral blood flow after middle cerebral artery occlusion, we calculated the extraction fraction of alpha-aminoisobutyric acid, the permeability-surface area product and the permeability of cerebral regional capillary beds. Although, there are numerous reports of permeability-surface area product of brain capillaries, to our knowledge, the permeability has never been determined before. The calculated extraction fraction ratio for alpha-aminoisobutyric acid for ischaemic cortex/contralateral cortex was 3.1. Similar ratios for permeability-surface area product and capillary permeability were 1.6 and 4.4, respectively. Thus, there was a more than four fold increase in capillary permeability to small molecules in the ischaemic cortex one hour after middle cerebral artery occlusion.

Aminoisobutyric Acids↗

Nitric oxide and cyclic GMP attenuate sensitivity of the blood-tumor barrier permeability to bradykinin.

Intracarotid infusion of bradykinin and its analogue, RMP-7, selectively increase the permeability of brain tumor capillaries though the nitrix oxide (NO) and cyclic GMP pathway. Maximum blood-tumor barrier (BTB) permeability induced by bradykinin is observed at 15 min after intracarotid infusion and this effect is decreased even if the infusion continues. The mechanism for this decreased effect with long term infusion has not been clearly defined. This study sought to determine the involvement of the NO-cyclic GMP pathway in this event. Regional permeability was investigated in 44 Wistar rats with implanted RG2 gliomas, using quantitative autoradiography to determine the unidirectional transfer constant (Ki) of radiolabeled 14C-dextran. Tumor bearing rats were treated by intracarotid infusion of bradykinin (10 micrograms kg-1 min-1) with or without pretreatment with bradykinin, the NO donor s-nitrosoglutathione (10 nmol kg-1 min-1), or the cyclic GMP analogue, 8Br-cyclic GMP (200 micrograms kg-1 min-1). At 30 min of bradykinin infusion, BTB permeability was significantly lower compared to 15 min of bradykinin infusion (3.79 +/- 0.99 vs. 16.20 +/- 3.43 microliters g-1 min-1, p < 0.001). Pretreatment with an NO donor significantly decreased BTB permeability in bradykinin infused rats (5.09 +/- 2.61 vs. 13.51 +/- 4.19 microliters g-1 min-1, p < 0.001), as did pretreatment with a cyclic GMP analogue (4.48 +/- 0.95 vs. 12.31 +/- 3.90 microliters g-1 min-1, p < 0.001). There was no increased permeability in nontumor brain areas. Increased tumor permeability by bradykinin appears to be regulated by NO and cyclic GMP which are second messengers involved in the bradykinin B2 receptor mediated cascade.

Animals↗

Gastro-intestinal permeability is increased in patients with limited systemic sclerosis.

OBJECTIVE: to evaluate gastro-intestinal (GI) permeability in patients with limited systemic sclerosis (LSS) at baseline and after oral acetylsalicylic acid (ASA). METHODS: 13 patients with LSS and 10 controls were studied. Baseline GI permeability was assessed with orally administered sucrose, mannitol, and lactulose. Gastric lesions and Helicobacter status were investigated by endoscopy. In 5 patients and 6 controls (with normal baseline permeability) the GI permeability response was assessed after oral ASA. RESULTS: compared with controls, gastric (p<0.05) and intestinal (p<0.02) permeability was higher in LSS patients, at baseline. After oral ASA gastric permeability (sucrose) increased in both groups (controls: 186%, LSS: 265%), whereas the lactulose/mannitol ratio raised significantly only in LSS (+31% and +148%; p<0.05 vs controls). CONCLUSIONS: baseline permeability is altered in LSS; the exaggerated response of the small intestine to ASA may represent a genetically determined or a disease-related dysfunction of the mucosal barrier.

Adult↗

Intestinal permeability to mannitol and lactulose in children with type 1 diabetes with the HLA-DQB1*02 allele.

Food antigens and enteroviruses are possible triggers of type 1 diabetes. Because permeability of the intestinal epithelium may facilitate contact of these antigens with the mucosal immune system, we set out to study intestinal permeability in patients with type 1 diabetes. Children with type 1 diabetes (n = 26, mean age 12 years, mean duration of disease 4 years) and 24 healthy age-matched control children were given mannitol and lactulose orally, and their intestinal permeability was measured as a percentage of this dose recovered in urine. Patients with type 1 diabetes did not differ in their permeability to lactulose, nor was their lactulose/mannitol ratio any different from that of controls. However, patients with type 1 diabetes who had the HLA-DQB 1*02 allele and, therefore, a higher risk for celiac disease (CD) absorbed significantly more mannitol (mean + 95% CI): 17.7% (15.2-20.2) than did those negative for this allele: 12.3% (8.2-16.4), p = 0.04. Their lactulose permeability was also higher: 0.30 (0.16-0.44) and 0.09% (0-0.18), respectively, p = 0.02. Although the differences in permeability reach statistical significance, there was still much overlap between the two groups in terms of actual laboratory values. The higher permeability of patients with the HLA-DQB1*02 allele suggests that these patients may be more prone to develop abnormal immune responses to food antigens.

Adolescent↗

Cellular mechanisms of mainstream cigarette smoke-induced lung epithelial tight junction permeability changes in vitro.

Mainstream cigarette smoke increases the permeability of human airways; however, the mechanism for this increased permeability is poorly defined. Tight junctions between adjacent epithelial cells constitute the physiological barrier to fluid and macromolecules in epithelium. These structures are highly regulated by phosphorylation and their association with the cytoskeleton. The goal of these studies was to identify the signal transduction pathways that regulate smoke-induced permeability. Using a physiologically relevant air-liquid interface exposure system, electrically tight monolayers of the human bronchial epithelial cell-line Calu-3 were exposed to fresh, whole mainstream cigarette smoke. This exposure results in a regulated, dose-dependent loss of epithelial barrier function in the lung epithelial monolayers. With cigarette smoke exposure, transepithelial electrical resistance (TER) is decreased and albumin flux is increased, indicating a loss in barrier function to ions and macromolecules, respectively; however, both largely recover in 30 min. Smoke-induced losses of macromolecular barrier function are the result of multicellular junctional reorganization, resulting in increased leak volume rather than leak frequency. Inhibiting Rho kinase (ROCK) significantly reduces the smoke-induced permeability to both ions and macromolecules, while inhibiting protein tyrosine kinases (PTK) only reduces smoke-induced macromolecular permeability. Interestingly, inhibiting myosin light chain kinase (MLCK) exacerbates smoke-induced permeability, indicating that MLCK and ROCK have opposing regulatory roles. Our results demonstrate that the smoke-induced loss of epithelial barrier function in human bronchial epithelium is a regulated process rather than a cytotoxic response. Additionally, our results indicate that activation of PTK and ROCK and inactivation of MLCK contribute to the increased airway permeability caused by mainstream cigarette smoke.

Amides↗

Epithelial permeability and the transepithelial migration of human neutrophils.

Although polymorphonuclear leukocytes (PMN's) can migrate through every epithelium in the body regardless of its permeability, very little is known about the effect of epithelial permeability on PMN migration and the effect of emigrating PMN's on the permeability of the epithelium. In an in vitro model system of transepithelial migration, human PMN's were stimulated by 0.1 micrometer fMet-Leu-Phe to traverse confluent, polarized canine kidney epithelial monolayers of varying permeabilities. Epithelial permeability was determined by both conductance measurement and horseradish peroxidase (HRP) tracer studies. As epithelial permeability increased, the number of PMN invasion sites as well as the number of PMN's that traversed the monolayer increased. The effect of PMN migration on epithelial permeability was examined using the ultrastructural tracers HRP and lanthanum nitrate. PMN's traversing the monolayer made close cell-to-cell contacts with other invading PMNs and with adjacent epithelial cells. These close contacts appeared to prevent leakage of tracer across invasion sites. Following PMN emigration, epithelial junctional membranes reapproximated and were impermeable to the tracers. These results indicated that, in the absence of serum and connective tissue factors, (a) the number of PMN invasion sites and the number of PMN's that traversed an epithelium were a function of the conductance of the epithelium and (b) PMN's in the process of transepithelial migration maintained close cell-cell contacts and prevented the leakage of particles (greater than 5 nm in diameter) across the invasion site.

Animals↗

Junctional adhesion molecule-C regulates vascular endothelial permeability by modulating VE-cadherin-mediated cell-cell contacts.

We recently reported that junctional adhesion molecule (JAM)-C plays a role in leukocyte transendothelial migration. Here, the role of JAM-C in vascular permeability was investigated in vitro and in vivo. As opposed to macrovascular endothelial cells that constitutively expressed JAM-C in cell-cell contacts, in quiescent microvascular endothelial cells, JAM-C localized mainly intracellularly, and was recruited to junctions upon short-term stimulation with vascular endothelial growth factor (VEGF) or histamine. Strikingly, disruption of JAM-C function decreased basal permeability and prevented the VEGF- and histamine-induced increases in human dermal microvascular endothelial cell permeability in vitro and skin permeability in mice. Permeability increases are essential in angiogenesis, and JAM-C blockade reduced hyperpermeability and neovascularization in hypoxia-induced retinal angiogenesis in mice. The underlying mechanisms of the JAM-C-mediated increase in endothelial permeability were studied. JAM-C was essential for the regulation of endothelial actomyosin, as revealed by decreased F-actin, reduced myosin light chain phosphorylation, and actin stress fiber formation due to JAM-C knockdown. Moreover, the loss of JAM-C expression resulted in stabilization of VE-cadherin-mediated interendothelial adhesion in a manner dependent on the small GTPase Rap1. Together, through modulation of endothelial contractility and VE-cadherin-mediated adhesion, JAM-C helps to regulate vascular permeability and pathologic angiogenesis.

Animals↗

Permeability of wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels to polyatomic anions.

Permeability of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel to polyatomic anions of known dimensions was studied in stably transfected Chinese hamster ovary cells by using the patch clamp technique. Biionic reversal potentials measured with external polyatomic anions gave the permeability ratio (P/P) sequence NO > Cl > HCO > formate > acetate. The same selectivity sequence but somewhat higher permeability ratios were obtained when anions were tested from the cytoplasmic side. Pyruvate, propanoate, methane sulfonate, ethane sulfonate, and gluconate were not measurably permeant (P/P < 0.06) from either side of the membrane. The relationship between permeability ratios from the outside and ionic diameters suggests a minimum functional pore diameter of approximately 5.3 A. Permeability ratios also followed a lyotropic sequence, suggesting that permeability is dependent on ionic hydration energies. Site-directed mutagenesis of two adjacent threonines in TM6 to smaller, less polar alanines led to a significant (24%) increase in single channel conductance and elevated permeability to several large anions, suggesting that these residues do not strongly bind permeating anions, but may contribute to the narrowest part of the pore.

Amino Acid Sequence↗

Role of leaflet asymmetry in the permeability of model biological membranes to protons, solutes, and gases.

Bilayer asymmetry in the apical membrane may be important to the barrier function exhibited by epithelia in the stomach, kidney, and bladder. Previously, we showed that reduced fluidity of a single bilayer leaflet reduced water permeability of the bilayer, and in this study we examine the effect of bilayer asymmetry on permeation of nonelectrolytes, gases, and protons. Bilayer asymmetry was induced in dipalmitoylphosphatidylcholine liposomes by rigidifying the outer leaflet with the rare earth metal, praseodymium (Pr3+). Rigidification was demonstrated by fluorescence anisotropy over a range of temperatures from 24 to 50 degrees C. Pr3+-treatment reduced membrane fluidity at temperatures above 40 degrees C (the phase-transition temperature). Increased fluidity exhibited by dipalmitoylphosphatidylcholine liposomes at 40 degrees C occurred at temperatures 1-3 degrees C higher in Pr3+-treated liposomes, and for both control and Pr3+-treated liposomes permeability coefficients were approximately two orders of magnitude higher at 48 degrees than at 24 degrees C. Reduced fluidity of one leaflet correlated with significantly reduced permeabilities to urea, glycerol, formamide, acetamide, and NH3. Proton permeability of dipalmitoylphosphatidylcholine liposomes was only fourfold higher at 48 degrees than at 24 degrees C, indicating a weak dependence on membrane fluidity, and this increase was abolished by Pr3+. CO2 permeability was unaffected by temperature. We conclude: (a) that decreasing membrane fluidity in a single leaflet is sufficient to reduce overall membrane permeability to solutes and NH3, suggesting that leaflets in a bilayer offer independent resistances to permeation, (b) bilayer asymmetry is a mechanism by which barrier epithelia can reduce permeability, and (c) CO(2) permeation through membranes occurs by a mechanism that is not dependent on fluidity.

Acetamides↗

The permeability of endplate channels to monovalent and divalent metal cations.

The relative permeability of endplate channels to monovalent and divalent metal ions was determined from reversal potentials. Thallium is the most permeant ion with a permeability ratio relative to Na+ of 2.5. The selectivity among alkali metals is weak with a sequence, Cs+ greater than Rb+ greater than K+ greater than Na+ greater than Li+, and permeability ratios of 1.4, 1.3, 1.1, 1.0, and 0.9. The selectivity among divalent ions is also weak, with a sequence for alkaline earths of Mg++ greater than Ca++ greater than Ba++ greater than Sr++. The transition metal ions Mn++, Co++, Ni++, Zn++, and Cd++ are also permeant. Permeability ratios for divalent ions decreased as the concentration of divalent ion was increased in a manner consistent with the negative surface potential theory of Lewis (1979 J. Physiol. (Lond.). 286: 417--445). With 20 mM XCl2 and 85.5 mM glucosamine.HCl in the external solution, the apparent permeability ratios for the alkaline earth cations (X++) are in the range 0.18--0.25. Alkali metal ions see the endplate channel as a water-filled, neutral pore without high-field-strength sites inside. Their permeability sequence is the same as their aqueous mobility sequence. Divalent ions, however, have a permeability sequence almost opposite from their mobility sequence and must experience some interaction with groups in the channel. In addition, the concentrations of monovalent and divalent ions are increased near the channel mouth by a weak negative surface potential.

Animals↗

Ca2+-dependent changes in cyclic GMP levels are not correlated with opening and closing of the light-dependent permeability of toad photoreceptors.

We have measured the levels of 3',5'-guanosine monophosphate (cyclic GMP) in isolated retinas from toad to investigate their correlation to the opening and closing of the light-dependent permeability of photoreceptors. When Ca2+-induced changes in cyclic GMP concentration are compared with the Ca2+-induced changes in the permeability of photoreceptor light-dependent channel, four quantitative dissimilarities are noted. First, when extracellular Ca2+ ([Ca2+]o) is reduced from normal physiological levels to between 10(-6) and 10(-7) M, the light-dependent permeability is increased, but cyclic GMP levels are not significantly changed. Second, when [Ca2+]o is increased from 1.8 to 20 mM, the light-dependent permeability is suppressed, but cyclic GMP levels are decreased by only 10-15%, about one-quarter the decrease that can be obtained with bright illumination. Third, when [Ca2+]o is increased from 10(-8) M to 20 mM, the light-dependent permeability is closed rapidly, but the cyclic GMP decrease is slow. Fourth, when [Ca2+]o is lowered to 10(-8) M, the sensitivity of the light-dependent permeability to steady illumination is decreased by three to four orders of magnitude, but the sensitivity of the light-dependent decrease in cyclic GMP is not significantly affected. These observations indicate that there is no simple correlation between cyclic GMP levels and the permeability of the light-dependent channels and that Ca2+ can affect the conductance in the absence of changes in cyclic GMP content.

Animals↗

Calcium reduces the sodium permeability of luminal membrane vesicles from toad bladder. Studies using a fast-reaction apparatus.

Regulation of the sodium permeability of the luminal membrane is the major mechanism by which the net rate of sodium transport across tight epithelia is varied. Previous evidence has suggested that the permeability of the luminal membrane might be regulated by changes in intracellular sodium or calcium activities. To test this directly, we isolated a fraction of the plasma membrane from the toad urinary bladder, which contains a fast, amiloride-sensitive sodium flux with characteristics similar to those of the native luminal membrane. Using a flow-quench apparatus to measure the initial rate of sodium efflux from these vesicles in the millisecond time range, we have demonstrated that the isotope exchange permeability of these vesicles is very sensitive to calcium. Calcium reduces the sodium permeability, and the half-maximal inhibitory concentration is 0.5 microM, well within the range of calcium activity found in cells. Also, the permeability of the luminal membrane vesicles is little affected by the ambient sodium concentration. These results, when taken together with studies on whole tissue, suggest that cell calcium may be an important regulator of transepithelial sodium transport by its effect on luminal sodium permeability. The effect of cell sodium on permeability may be mediated by calcium rather than by sodium itself.

Amiloride↗

Tris+/Na+ permeability ratios of nicotinic acetylcholine receptors are reduced by mutations near the intracellular end of the M2 region.

Tris+/Na+ permeability ratios were measured from shifts in the biionic reversal potentials of the macroscopic ACh-induced currents for 3 wild-type (WT), 1 hybrid, 2 subunit-deficient, and 25 mutant nicotinic receptors expressed in Xenopus oocytes. At two positions near the putative intracellular end of M2, 2' (alpha Thr244, beta Gly255, gamma Thr253, delta Ser258) and -1', point mutations reduced the relative Tris+ permeability of the mouse receptor as much as threefold. Comparable mutations at several other positions had no effects on relative Tris+ permeability. Mutations in delta had a greater effect on relative Tris+ permeability than did comparable mutations in gamma; omission of the mouse delta subunit (delta 0 receptor) or replacement of mouse delta with Xenopus delta dramatically reduced relative Tris+ permeability. The WT mouse muscle receptor (alpha beta gamma delta) had a higher relative permeability to Tris+ than the wild-type Torpedo receptor. Analysis of the data show that (a) changes in the Tris+/Na+ permeability ratio produced by mutations correlate better with the hydrophobicity of the amino acid residues in M2 than with their volume; and (b) the mole-fraction dependence of the reversal potential in mixed Na+/Tris+ solutions is approximately consistent with the Goldman-Hodgkin-Katz voltage equation. The results suggest that the main ion selectivity filter for large monovalent cations in the ACh receptor channel is the region delimited by positions -1' and 2' near the intracellular end of the M2 helix.

Amino Acid Sequence↗

Corneal and scleral permeability of quinolones--a pharmacokinetics study.

PURPOSE: To investigate the corneal and scleral permeability of nalidixic acid and synthesized fluoroquinolones and their in vivo pharmacokinetics in rabbits. METHODS: The corneal and scleral permeability coefficients of ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were determined in rabbits using high performance liquid chromatography (HPLC). The aqueous humor levels of norfloxacin and ciprofloxacin were measured separately by topical instillation of 0.3% solutions of the two drugs onto rabbit eyes. RESULTS: Nalidixic acid had a higher corneal permeability coefficient (17.3 +/- 3.56 x 10(-6) cm/second) than all other drugs tested (p < 0.01). Corneal permeability coefficients in rabbits among ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were not significantly different (p > 0.1). Comparing the corneal and scleral permeability coefficients, only values for nalidixic acid were not significantly different (17.35 +/- 3.56 x l0(-6) cm/second versus 22.69 +/- 5.19 x 10(-6) cm/second, p > 0.05), while all other drugs had scleral permeability coefficients 8 to 10 times greater than corneal permeability coefficients. The mean aqueous humor concentration of norfloxacin and ciprofloxacin at 60 minutes to 180 minutes after instillation was around 0.3 microg/mL, a value higher than MIC90 of most bacteria.

Administration, Topical↗

Effects of Er:YAG and Nd:YAG lasers on dentin permeability in root surfaces: a preliminary in vitro study.

OBJECTIVE: This in vitro study evaluated the effects of Nd:YAG and Er:YAG lasers on reducing dentin permeability by sealing opened tubules. BACKGROUND DATA: According to hydrodynamic theory, dentine hypersensitivity occurs when dentin is exposed with tubules opened. Consequently, a painful sensation occurs due to an intensification of the dentinal permeability. Treatment, therefore, should be based on a decrease of this permeability, achieved by the obliteration of dentinal tubules. The Nd:YAG laser is known for its capacity to seal dentinal tubules; however, few studies concerning treatment with Er:YAG laser are available. METHODS: The Nd:YAG laser was used, based on two parameters: (A) 1.0 W, 10 Hz, and (B) 1.5 W, 15 Hz. The Er:YAG laser was used at 60 mJ, 2 Hz, four applications of 20 sec each, at 6 mm from the surface. After irradiation, all samples were immersed in 1% Rodamine B dye solution, in order to evaluate the penetration of the dye solution and observe the decrease/increase of dentinal permeability after the laser treatment. RESULTS: The laser conditions used in the present study decreased the permeability as follows: (a) when using the Er:YAG laser at 60 mJ, 2 Hz in 26.05%, and (b) when using the Nd:YAG laser at 1.5 W, 15 Hz in 19.03%--with no statistical difference between them. Additionally, the Nd:YAG laser at 1.0 W, 10 Hz, decreased permeability in 4.59%, with a smaller effect. CONCLUSIONS: According to the results of this in vitro study, the Er:YAG laser at 60 mJ, 2 Hz, and the Nd:YAG laser at 1.5 W, 15 Hz are useful for decreasing dentin permeability.

Analysis of Variance↗

Low aquaporin content and low osmotic water permeability of the plasma and vacuolar membranes of a CAM plant Graptopetalum paraguayense: comparison with radish.

Aquaporin facilitates the osmotic water transport across biomembranes and is involved in the transcellular and intracellular water flow in plants. We immunochemically quantified the aquaporin level in leaf plasma membranes (PM) and tonoplast of Graptopetalum paraguayense, a Crassulacean acid metabolism (CAM) plant. The aquaporin content in the Graptopetalum tonoplast was approximately 1% of that of radish. The content was calculated to be about 3 microg mg(-1) of tonoplast protein. The level of PM aquaporin in Graptopetalum was determined to be less than 20% of that of radish, in which an aquaporin was a major protein of the PM. The PM aquaporin was detected in the mesophyll tissue of Graptopetalum leaf by tissue print immunoblotting. The osmotic water permeability of PM and tonoplast vesicles prepared from both plants was determined with a stopped-flow spectrophotometer. The water permeability of PM was lower than that of the tonoplast in both plants. The Graptopetalum PM vesicles hardly showed water permeability, although the tonoplast showed a relatively high permeability. The water permeability changed depending on the assay temperature and was also partially inhibited by a sulfhydryl reagent. Furthermore, measurement of the rate of swelling and shrinking in different mannitol concentrations revealed that the protoplasts of Graptopetalum showed low water permeability. These results suggest that the low content of aquaporins in PM and tonoplast is one of the causes of the low water permeability of GRAPTOPETALUM: The relationship between the water-storage function of succulent leaves of CAM plants and the low aquaporin level is also discussed.

Amino Acid Sequence↗

Intestinal permeability in patients with ankylosing spondylitis and their healthy relatives.

Patients with AS were previously found to have increased intestinal permeability using the 51Cr-EDTA resorption test. In order to discover whether this alteration has taken place prior to, or as a consequence of the disease, we studied the intestinal permeability to 51Cr-EDTA in 20 patients with AS, 65 of their healthy relatives, and 25 normal volunteers. We also considered the HLA B27 antigen, the serum immunoglobulin A levels, the disease activity, the existence of peripheral arthritis, the ESR, the CRP values and the intake of drugs at the time of study. Gut permeability was found to have increased in the patients and their healthy relatives compared to the control group. No difference in gut permeability was found between patients and relatives regardless of whether they had the HLA B27 antigen or not. The increased intestinal permeability in the patients had no relation to the disease activity, to the presence of peripheral arthritis or to the intake of NSAIDs. Gut permeability was shown to bear no relation to IgA levels, ESR or CRP. Our findings suggest that the increase in gut permeability in AS patients and their relatives is a primary defect and may be an aetiologic factor in this disease.

Adolescent↗