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PubMed1998

Arachidonic acid increases cerebral microvascular permeability by free radicals in single pial microvessels of the anaesthetized rat.

1. We have investigated the permeability-increasing effect of arachidonic acid on pial venular capillaries in vivo using the single microvessel occlusion technique. 2. Permeability to Lucifer Yellow dye (476 Da) increased dose dependently when arachidonic acid was applied focally to the abluminal surface of the vessels. This was completely reversible at all but the highest dose. The permeability increase was 1.65 x 10(-6) +/- 0.247 x 10(-6) cm s-1 (mean +/- S.E.M.) at 0.25 mM, 3.53 x 10(-6) +/- 0.872 x 10(-6) cm s-1 at 0.5 mM, 12.61 x 10(-6) +/- 3.44 x 10(-6) cm s-1 at 1 mM and 18.46 x 10(-6) +/- 5.90 x 10(-6) cm s-1 at 2 mM arachidonic acid. There was a similar reversible dose-dependent permeability increase to eicosapentaenoic acid. 3. These permeability increases could be prevented by co-application of a mixture of the antioxidants superoxide dismutase and catalase (30 and 100 U ml-1), or by the iron chelator desferrioxamine (100 microM). 4. The permeability increases were also prevented by the cyclooxygenase and 5-lipoxygenase blockers indomethacin (100 microM) and nordihydroguariaretic acid (100 microM), respectively, when applied together, but not singly. 5. It was concluded that the permeability response to arachidonic acid depends on the formation of free radicals and subsequent lipid peroxidation.

Anesthesia↗
PubMed2006

Caspase-dependent alteration of the ADP/ATP translocator triggers the mitochondrial permeability transition which is not required for the low-potassium-dependent apoptosis of cerebellar granule cells.

We investigated ADP/ATP exchange mediated by the adenine nucleotide translocator and opening of the mitochondrial permeability transition pore in homogenates from cerebellar granule cells en route to apoptosis induced by low potassium. We showed that, in the first 3 h of apoptosis, when maximum cytochrome c release had already occurred, adenine nucleotide translocator function was impaired owing to the action of reactive oxygen species, but no permeability transition pore opening occurred. Over 3-8 h of apoptosis, the permeability transition pore progressively opened, owing to caspase action, and further ADP/ATP translocator impairment occurred. The kinetics of transport and permeability transition pore opening were inversely correlated, both in the absence and presence of inhibitors of antioxidant and proteolytic systems. We conclude that, en route to apoptosis, alteration of the adenine nucleotide translocator occurs, resulting in permeability transition pore opening. This process depends on the action of caspase on pore component(s) other than the ADP/ATP translocator, because no change in either amount or molecular weight of the latter protein was noted during apoptosis, as measured by western blotting. Cell death occurs via apoptosis in the presence of cyclosporin A, the permeability transition pore inhibitor, thus showing that permeability transition pore opening, not needed for cytochrome c release, is also unnecessary for apoptosis to occur.

Adenosine Diphosphate↗
PubMed1994

Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes.

1. The objectives of the present experiments were to assess the contribution of polymorphonuclear leucocytes (PMNLs), platelets and their products such as thromboxane A2 (TxA2), histamine and 5-hydroxytryptamine to platelet activating factor (PAF)-mediated protein extravasation in rat lungs. 2. Intravenous injection of PAF (1.0 and 5.0 micrograms kg-1) increased dose-dependently (up to 7.5 fold) the vascular permeability of the trachea, upper and lower bronchi to Evans blue dye (EB), a marker of albumin extravasation. The permeability of the pulmonary parenchyma was not affected significantly by PAF. 3. Thrombocytopenia induced by administration of the IgG fraction of goat anti-rat platelet serum (APS; 15 mg 100 g-1, i.p., 16-18 h) reduced by 55, 58 and 40% the effects of the lower dose of PAF (1.0 microgram kg-1) and by 31, 23 and 15% the effects of the higher dose of PAF (5.0 micrograms kg-1) on the permeability of the trachea, upper and lower bronchi respectively to albumin. 4. PMNL depletion induced by administration of rabbit anti-rat polymorphonuclear serum (ANS; 2 mg kg-1, i.v., 24 h) did not reduce significantly the effects of the lower dose of PAF (1.0 microgram kg-1) on the airways, however the effects of the higher dose of PAF (5.0 micrograms kg-1) on the permeability of the trachea, upper and lower bronchi to albumin were reduced by 43, 25 and 23% respectively. 5. The injection of both the anti-platelet and the anti-PMNL sera reduced by 61, 62 and 96% the effects of the lower dose of PAF (1.0 microg kg-1) and by 44, 39 and 47% the effects of the higher dose of PAF (5.0 microg kg-1) on the permeability of the trachea, upper and lower bronchi respectively.6. The combined injection of the TxA2-mimetic (U-44069; 5.0 microg kg-1) and PAF (1.0 and 5.0 microg kg-1)in thrombocytopenic rats overcame the vascular permeability decrease induced by APS treatment.7. Pretreatment of the animals with a combination of antagonists to histamine (mepyramine;3.0 mg kg-1) and 5-hydroxytryptamine (methysergide; 2.5 mg kg-1) did not cause a significant inhibition of the effect of PAF (1.0 and 5.0 microg kg-1) on EB extravasation in the airways.8. These data show that the effect of intravenous PAF on rat vascular permeability is partly modulated by polymorphonuclear leucocyte and platelet activation. Our results suggest that following its release,TxA2 could increase postcapillary hydrostatic pressure by inducing a venoconstriction and potentiate the extravasation elicited by PAF. These results do not suggest a major role for histamine and/or 5-hydroxytryptamine on PAF-induced albumin extravasation.

Animals↗
PubMed1975

The effect of Ca++, Mg++ and H+ on the capillary permeability of the rete mirabile of the eel, Anguilla vulgaris L.

The effects of EDTA, and of varying pH on the capillary permeability in the rete mirabile have been investigated: EDTA had to be added to the perfusate in excess to the total content of Ca++ and Mg++ in plasma in order to elicit changes in the permeability. When exposed to sufficient amounts of EDTA, the capillary permeability to hydrophilic molecules increased several fold whereas the permeability to THO and lipid-soluble molecules remained unchanged. The increase in the permeability to high-molecular dextrans was delayed. When the EDTA-effect was maximal the mutual relationship between the permeabilities of THO and the lipid-insoluble molecules became close to the ratio between the corresponding free diffusion coefficients in water. During exposure to EDTA the content of K+ and Na+ of the rete tissue (mostly endothelial cells) became very similar to that of plasma. Similar effects were obtained when the rete was perfused with plasma having a pH below 4 or above 9. The EDTA-effect was reversible during its initial stage. Perfusions with plasma in which Ca and Mg had been removed by dialysis at pH 3.5 were performed. When an EDTA-effect had been induced with this type of perfusates, it could be reversed by addition of equimolar amounts of either Ca++ or Mg++. This indicates Ca++ and Mg++ to be equally important in order to assure normal permeability properties of the capillary membrane.

Anguilla↗
PubMed1997

Permeability assessment of capsules for islet transplantation.

Despite considerable progress in the development of immunoisolation devices, the optimal permeability of such devices is not known. This limitation stems partly from deficits in knowledge about which molecules should be allowed to traverse the semipermeable membrane and which molecules should be excluded, and also partly from experimental obstacles that have prevented a systematic study of permeability. To determine the optimal permeability of immunoisolation devices, we have created a series of microcapsules (800 microM diameter) that span a broad range of molecular exclusion limits yet are identical in wall thickness and chemical composition. Capsule permeability was precisely defined by two complementary methods--size exclusion chromatography (SEC) and a newly developed methodology to assess permeability of biologically relevant proteins. The entry of interleukin-1 beta-125I was significantly delayed, but not prevented, when the capsule exclusion limit was decreased from 230 kD to 3.2 kD, as determined by SEC with dextran standards. The influx of IgG was as predicted, based on the viscosity radius R eta of IgG and the capsule exclusion limit defined by SEC. Glucose-stimulated insulin secretion by encapsulated pancreatic islets did not differ as capsule permeability was decreased from a molecular exclusion limit of 230 kD to 120 kD. These studies should assist in the design of immunoisolation devices by defining the permeability optimal for cell function and also should be applicable to any cell type or immunoisolation device.

Animals↗
PubMed1976

Permeability of individual human erythrocytes to thiourea.

The osmotic swelling to haemolysis of individual red blood cells by isosmotic thiourea has been studied using microcine photography. 2. Crenation occurs immediately upon addition of isosmotic thiourea. The cell becomes a crenated sphere without volume decrease. 3. Subsequently, the cell volume increases linearly with time with maximum swelling occurring at about 102 sec which is 81% of the total haemolysis time. 4. At maximum swelling, the cell volume is 92% greater than the initial cell volume. This volume increase is about double that measured with other permeating substances. 5. The much larger maximum volume implies that thiourea increases the area of the cell membrane. This increase varies from 0 to 75% for individual cells, with a mean of 22%. 6. Membrane expansion varies inversely as the initial cell membrane area and cell volume (r=0-790). 7. Using the increased surface area, increased maximum volume and the swelling time, the mean permeability is calculated to be 5-52 X 10(-7) cm/sec (S.D. of mean=+/-1-19 X 10(-7) cm/sec). The distribution of permeabilities represents a normal distribution. 8. The pre-lytic potassium loss ranged from 0 to 36% with a mean value of 16-5%. This is consistent with values reported in the literature for slow haemolysis. As with other permeants the distribution is skewed towards lower values. 9. Membrane permeability of individual cells varies with the amount of membrane expansion observed. Coefficient of correlation between permeability and expansion index is 0-674. 10. There is no correlation between permeability and the reciprocal of the haemolysis time (r=-0-035). The correlation between permeability and the reciprocal of the swelling time is also poor (r=0-303), probably owing to the variability in membrane expansion by thiourea in individual cells. 11. As has been shown previously for faster permeants, the permeability coefficient cannot be calculated from the haemolysis time. Because thiourea alters the membrane area and the haemolytic volume, the coefficient cannot be calculated from the swelling time unless the changes in the membrane area are also taken into account.

Cell Membrane↗
PubMed1977

Effect of anoxia and ATP depletion on the membrane potential and permeability of dog liver.

1. The mechanisms responsible for the depolarization of the hepatocytes secondary to anoxia have been studied in isolated perfused dog liver. It was attempted to elucidate the role of the inhibition of the sodium pump following exhaustion of the energy reserves and of the modifications of membrane permeability. Anoxia was compared to ouabain and to a reduction of the cellular ATP level. 2. Membrane potentials were measured with micro-electrodes. Potassium, sodium and chloride were determined in plasma samples and liver tissues. Extracellular space was measured with tritiated inulin or with an electrical impedance method. Adenine nucleotides were also measured in liver biopsies. 3. The fall in membrane potential produced by administration of ouabain (0-1 mM) is greater than the effect of the redistribution of sodium + potassium ions; this suggests that the sodium pump is functioning, at least partially, electrogenically. The administration of dinitrophenol (10 mM), which causes a 74% fall in the ATP level in 15 min, produces, as does ouabain, a depolarization which also corresponds to stopping an electrogenic pump. 4. A partial reduction in the level of ATP brought about by hypoxia, by an inhibitor of cellular respiration, antimycin (10 mM), or by fructose (20 mM) results in a hyperpolarization which may be attributed to an elevation of potassium permeability (PK) since it is concomitant to a loss of K from the liver. The change in membrane permeability could be related to a rise in the free calcium in the cells which has not been documented. Other possible hypothesis include a facilitated transport for potassium. 5. The administration of amobarbitone (10 mM) produces immediately a depolarization which is independent of the progressive reduction in the level of ATP. The depolarization has been attributed to a direct effect of amobarbitone on the membrane reducing the permeability for potassium ions. 6. The depolarization observed in ischaemic anoxia is greater than that produced by ouabain for the same variation in ions concentration. In addition to a likely inhibition of the electrogenic sodium pump, changes in membrane permeability inducing a rise in the PNa/PK ratio must also occur. 7. After ischaemic anoxia for 24 hr at 3 degrees C, the ratio of PNa/PK rises to 0-68 which indicates abolishment of the selective character of membrane permeability. The augmentation in cell volume produced by anoxia might result in an opening of membrane pores, which could entail the augmentation of sodium permeability; the latter would be responsible in part for the depolarization produced by anoxia. 8. According to the severity and length of oxygen deprivation an increase in PK, a cessation of the sodium pump activity and finally an increase in PNa will occur.

Adenosine Triphosphate↗
PubMed1979

Permeability of the fenestrated capillaries in the cat submandibular gland to lipid-insoluble molecules.

1. Permeability-surface area products for the fenestrated capillaries in the perfused cat submandibular gland have been measured for graded lipid-insoluble molecules using the single-passage, multiple-tracer dilution technique. 2. The permeability-surface area for [57Co]cyanocobalamin (mol. wt. 1353) increased as the perfusion flow was increased, but reached a constant value of 4.11 +/- 0.25 ml.min-1.g-1 (mean +/- S.E., n = 9) at flows above 8 ml. min-1.g-1. For [125I]insulin (approximate mol. wt. 6000) it was 1.80 +/- 0.13 ml.min-1.g-1 (mean +/- S.E., n = 9) and apparently diffusion-limited at all the high flow rates studied. A similar permeability-surface area product was measured for [14C]inulin (mol. wt. 5500): 1.76 +/- 0.10 (mean +/- S.E., n = 4). 3. Permeability-surface area values for cyanocobalamin and insulin in the salivary gland are respectively about 20 and 200 times larger than the estimates reported for the continuous capillaries of cardiac and skeletal muscle. 4. The permeability-surface area (PS) ratio [57Co]cyanocobalamin/[125I]insulin (2.33 +/- 0.15, mean +/- S.E., n = 9) was significantly greater than the apparent ratio of their free diffusion coefficients (1.76), suggesting restricted diffusion of insulin relative to cyanocobalamin across the capillary endothelium. 5. Permeability-surface area products for the smaller molecular weight tracers (22Na, 86Rb and 51Cr-EDTA (mol. wt. 357)) increased continuously with perfusion rate, indicating flow-limited solute exchange. The PS ratio of Rb/EDTA was close to unity whereas the corresponding free diffusion ratio is 3.85. 6. The high permeability-surface area values measured were thought to be associated with the fenestrae which appeared to act as high concentrations of 'small pores' rather than as 'large pores'.

Animals↗
PubMed1993

Non-electrolyte solute permeabilities of human placental microvillous and basal membranes.

1. Permeability to non-electrolytes of isolated microvillous and basal membranes from human term placenta was measured using stopped-flow light-scattering techniques. The studied solutes were urea, ethylene glycol, glycerol, creatinine, erythritol, arabitol and mannitol. 2. At 37 degrees C, permeability of the microvillous membrane to mannitol and urea was 0.30 +/- 0.02 x 10(-6) cm/s (mean +/- S.E.M.) and 3.2 +/- 0.2 x 10(-6) cm/s, respectively. The corresponding permeabilities for the basal membrane were 1.2 +/- 0.1 x 10(-6) cm/s (mannitol) and 4.4 +/- 0.3 x 10(-6) cm/s (urea). The basal membrane was substantially more permeable to hydrophilic solutes than the microvillous membrane. This is probably due to differences in lipid composition, as illustrated by membrane cholesterol content, which was found to be approximately 50% lower in the basal as compared to the microvillous membrane. 3. Similarities between permeabilities in placental membranes and lipid bilayers and the linear relationship noted between solute hydrophobicity and placental permeability suggested that solutes permeate both human syncytiotrophoblast membranes by a solubility/diffusion mechanism. In the microvillous membrane this was supported by data obtained for activation energies (> 10 kcal/mol) and reflection coefficients (close to 1). In the basal membrane, low activation energies for glycerol and urea and a low reflection coefficient for urea indicated that these solutes may, in part, share a common pathway with water. 4. It was estimated that the placental permeability to molecules with a molecular weight under 200 observed in vivo can, to a great extent, be accounted for by transcellular permeation.

Cell Membrane↗
PubMed2002

The role of guanylyl cyclases in the permeability response to inflammatory mediators in pial venular capillaries in the rat.

Inflammatory mediators have a role in the formation of cerebral oedema and there is evidence that cGMP is an important signal in vascular permeability increase. We have investigated the role and the source of cGMP in mediating the permeability response to acutely applied bradykinin and the histamine H(2) agonist dimaprit on single cerebral venular capillaries, by using the single vessel occlusion technique. We found that 8-bromo-cGMP applied acutely resulted in a small and reversible permeability increase with a log EC(50) -7.2 +/- 0.15 M. KT 5823, the inhibitor of cGMP-dependent protein kinase, abolished the permeability responses to both bradykinin and dimaprit, while zaprinast, an inhibitor of type 5 phosphodiesterase, potentiated the response to bradykinin. On the other hand, L-NMMA blocked the response to dimaprit, but not that to bradykinin. Inhibitors of soluble guanylyl cyclase, LY 85353 and methylene blue, also inhibited the permeability response to dimaprit, but not bradykinin. The permeability responses to the natriuretic peptides ANP and CNP were of similar magnitude to that of bradykinin with log EC(50) -10.0 +/- 0.33 M and -8.7 +/- 0.23 M, respectively. The natriuretic peptide receptor antagonist HS-142-1 blocked permeability responses to bradykinin as well as to ANP, and leukotriene D(4) blocked the responses to CNP and bradykinin, but not to dimaprit. In conclusion, the histamine H(2) receptor appears to signal via cGMP that is generated by a NO and soluble guanylyl cyclase, while bradykinin B(2) receptor also signals via cGMP but through particulate guanylyl cyclase.

Animals↗
PubMed2005

Ca2+ permeability of nicotinic acetylcholine receptors in rat hippocampal CA1 interneurones.

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely expressed in the brain where they are involved in a variety of physiological processes, including cognition and development. The nAChRs are ligand-gated cationic channels, and different subtypes are known to be differentially permeable to Ca2+; the alpha7-containing nAChRs are generally considered to be the most permeable. Ca2+ can activate and regulate a variety of signal transduction cascades, and the influx of Ca2+ through these receptors may have implications for synaptic plasticity. To determine the Ca2+ permeability of the nAChRs in rat hippocampal interneurones in the slice, which contain diverse subtypes of alpha7- and non-alpha7-containing nAChRs, we combined patch-clamp electrophysiology recordings with conventional fura-2 fluorescence imaging techniques. We estimated the relative Ca2+ permeability of the channels by determining the ratio of the increase in [Ca2+]i level (Delta[Ca2+]i) in the soma to the integrated transmembrane current (charge, Q) induced by the activation of the nAChRs, and compared this ratio to the highly Ca2+ permeable NMDA subtype of glutamate receptor channel. In all cells tested, the Delta[Ca2+]i/Q ratio was significantly larger (i.e. more than twice as big) for responses activated by NMDA than for alpha7-containing nAChRs in interneurones; the activation of the non-alpha7 nAChRs did not produce any significant increase in [Ca2+]i. Interestingly, the Ca2+ permeability of native alpha7 nAChRs in PC12 cells was significantly larger than in hippocampal interneurones, and not significantly different from NMDA receptors. Therefore, the alpha7-containing nAChRs in rat hippocampal interneurones are significantly less permeable to Ca2+ than not only NMDA receptors but also alpha7 nAChRs in PC12 cells.

Animals↗
PubMed2006

Both Ca2+-permeable and -impermeable AMPA receptors contribute to primary synaptic drive onto rat dorsal horn neurons.

Blockade of Ca2+-permeable AMPA receptors in the rat spinal cord diminishes the development of hyperalgesia and allodynia associated with peripheral injury. Cobalt uptake studies reveal that Ca2+-permeable AMPA receptors are expressed by some substance P receptor-expressing (NK1R+) neurons in lamina I, as well as other neurons throughout the superficial dorsal horn. Selective elimination of NK1R+ neurons in lamina I and lamina III/IV of the dorsal horn also suppresses development of hyperalgesia and allodynia. These observations raise the possibility that Ca2+-permeable AMPA receptors contribute to excitatory synaptic drive onto the NK1R+ neurons associated with allodynia and hyperalgesia. The first synapse in the pain pathway is the glutamatergic excitatory drive from the primary afferent fibres onto dorsal horn neurons. Therefore, we tested whether Ca2+-permeable AMPA receptors are located on lamina I and lamina III/IV NK1R+ neurons postsynaptic to primary afferent fibres, using inward rectification and polyamine toxins for receptor identification. We examined three different populations of dorsal horn neurons; lamina I NK1R+ neurons, including projection neurons, and non-NK1R+ (NK1R-) neurons including interneurons, and lamina III/IV NK1R+ neurons, believed to contribute to the low-threshold mechanosensory pathway. The majority of synapses in all three groups had rectification indices less than 1.0 and greater than 0.4, indicating that the AMPA receptors at these synapses are a mixture of Ca2+-permeable and -impermeable forms. Lamina III/IV NK1R+ neurons and lamina I NK1R- neurons have a significantly higher proportion of postsynaptic Ca2+-permeable AMPA receptors than lamina I NK1R+ neurons. Thus synaptically positioned Ca2+-permeable AMPA receptors directly contribute to low-threshold sensory afferent drive into the dorsal horn, and can mediate afferent input onto interneurons such as GABAergic neurons. These receptors also contribute to high-threshold primary afferent drive onto NK1R+ neurons in the superficial dorsal horn, but do so less consistently.

Animals↗
PubMedDate not supplied

Dependence of intertrabecular permeability on flow direction and anatomic site.

The structure-function relationships for the permeability of trabecular bone may have relevance for tissue engineering, total joint replacements, and whole bone mechanics. To investigate such relationships, we used a constant flow rate permeameter to determine the intrinsic permeability of trabecular bone specimens, oriented longitudinally or transversely to the principal trabecular orientation, from the human vertebral body (n=20), human proximal femur (n=12), and bovine proximal tibia (n=24). Overall, the intertrabecular permeability ranged from 2.68 x 10(-11) to 2.00 x 10(-8) m2. Significant negative nonlinear relations between intertrabecular permeability and volume fraction were found for each group except the longitudinal bovine proximal tibial specimens (r2=0.34-0.80). The average permeability ratio, a measure of the anisotropy, was 2.05, 6.60, and 23.3 for the human vertebral body, bovine tibia, and human femur, respectively. The permeability depended strongly on flow direction relative to the principal trabecular orientation (p<0.0001) and anatomic site (p <0.0001). In addition to providing a comprehensive description of intertrabecular permeability as a function of anatomic site and flow direction, these data provide substantial insight into the underlying structure-function relationships.

Animals↗
PubMed2002

Method for estimation of low outer membrane permeability to beta-lactam antibiotics.

The outer membrane of gram-negative bacteria plays a major role in beta-lactam resistance as it slows down antibiotic entry into the periplasm and therefore acts in synergy with beta-lactamases and efflux systems. Up to now, the quantitative estimation of low outer membrane permeability by the method of Zimmermann and Rosselet was difficult because of the secreted and cell surface-associated beta-lactamases. The method presented here uses the acylation of a highly sensitive periplasmic penicillin-binding protein (PBP) (BlaR-CTD) to assess the rate of beta-lactam penetration into the periplasm. The method is dedicated to measurement of low permeability and is only valid when the diffusion rate through the outer membrane is rate limiting. Cytoplasmic membrane associated PBPs do not interfere since they are acylated after the very sensitive BlaR-CTD. This method was used to measure the permeability of beta-lactamase-deficient strains of Enterobacter cloacae and Enterobacter aerogenes to benzylpenicillin, ampicillin, carbenicillin, cefotaxime, aztreonam, and cephacetrile. Except for that of cephacetrile, the permeability coefficients were equal to or below 10(-7) cm/s. For cephacetrile, carbenicillin, and benzylpenicillin, the outer membrane of E. cloacae was 20 to 60 times less permeable than that of Escherichia coli, whereas for cefotaxime, aztreonam, and ampicillin it was, respectively, 400, 1,000, and 700 times less permeable. The permeability coefficient for aztreonam is the lowest ever measured (P = 3.2 x 10(-9) cm/s). Using these values, the MICs for a beta-lactamase-overproducing strain of E. cloacae were successfully predicted, demonstrating the validity of the method.

Acylation↗
PubMed2001

Passive permeability and outward active transport of fluorescein across the blood-retinal barrier in early ARM.

AIM: To study the passive and active transport of fluorescein across the blood-retina barrier in early age related maculopathy (ARM) (soft drusen > 63 microm, hyperpigmentation and/or hypopigmentation in patients above 50 years of age). METHODS: 15 patients and 10 healthy subjects were included. Morphological changes were graded from 30 degrees fundus photographs using a simplified version of the epidemiological ARM study group classification system. Differential vitreous spectrofluorophotometry was used to assess the transport properties of the blood-retina barrier (that is, passive permeability and unidirectional permeability caused by outward active transport from the vitreous to the blood). RESULTS: The passive permeability of the patient group was not significantly different from that of the control group. Four patients with passive permeability more than 3 SD above the mean of the control group (mean 1.8 (SD 0.7) nm/s, range 1.0-3.0 nm/s, data normally distributed) all had centrally located drusen > 500 microm and superjacent pigment clumps of 63-500 microm in diameter. There was no significant difference between the unidirectional permeabilities for the patient group and for the control group (mean 47.4 (29.3) nm/s, range 12.7-91.1 nm/s). CONCLUSION: There was no significant difference in the passive permeability and in the unidirectional permeability of fluorescein. However, the study may indicate that the combination of very large drusen and superjacent pigment clumps in ARM may be associated with a deterioration of the blood-retina barrier.

Aged↗
PubMed1984

Cellobiose/mannitol sugar permeability test complements biopsy histopathology in clinical investigation of the jejunum.

Intestinal permeability to probe molecules has been shown to correlate closely with the presence or absence of villous atrophy in a jejunal biopsy. The purpose of this study was to establish if there exist groups of patients with functional derangement of intestinal permeability but normal histopathology of the small bowel mucosa. In 135 patients a cellobiose/mannitol permeability test was performed at the same time as jejunal biopsy. Diagnosis included coeliac disease, Crohn's disease, irritable bowel syndrome, idiopathic diarrhoea, self diagnosed food allergy, atopic eczema and postinfectious malabsorption. The value of the cellobiose/mannitol test in identifying patients with abnormal jejunal biopsy histopathology was confirmed. The permeability test was abnormal in all 28 patients with partial or subtotal villous atrophy, and also in all 10 in whom there was a high intraepithelial lymphocyte count despite normal villi and crypts. Functional abnormality of the small intestine has not previously been reported in patients with this jejunal biopsy abnormality. Abnormalities of permeability were also found in patients with idiopathic diarrhoea, folate deficiency, postinfectious or traveller's diarrhoea, small bowel Crohn's disease, and atopic eczema. These results show that sugar permeability tests have more potential in clinical investigation than merely serving as screening tests before jejunal biopsy. There are groups of patients without morphological changes in the small bowel in whom intestinal permeability is abnormal.

Adolescent↗
PubMed2001

Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs.

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.

Adult↗
PubMed1981

Membrane permeability to the molecular and ionic forms of DMO in barnacle muscle.

The time course of the intracellular pH (pHi) of barnacle muscle fibers was followed using microelectrodes while the fibers were exposed to 15 mM of the weak acid 5,5-dimethyloxazolidine-2,4-dione (DMO) at pH 6.5. The rapid initial fall in pHi was used to determine the membrane permeability to the DMO molecule, while the much slower fall during the subsequent plateau phase yielded the permeability to the DMO ion. This experimental approach and the mathematical treatment of the data can be used to obtain the membrane permeabilities to other weak acids or bases. We found values of 1.9 X 10(-4) cm/s for the permeability to the DMO molecule and 1.5 X 10(-7) cm/s for the permeability to the ion, assuming the fiber to be a cylinder. Thus the permeability of the neutral form is about 10(3) times that of the ionized form. At commonly encountered conditions of pHi = 7.3, outside pH = 7.5, and membrane potential = -52 mV, this permeability ratio introduces an error of only -0.01 to -0.02 into the determination of pHi based on the distribution of DMO.

Animals↗