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PubMed1998

Transient and prolonged increase in endothelial permeability induced by histamine and thrombin: role of protein kinases, calcium, and RhoA.

In the present study, we differentiated between short- and long-term effects of vasoactive compounds on human endothelial permeability in an in vitro model. Histamine induced a rapid and transient (<3 minutes) decrease in barrier function, as evidenced by a decreased transendothelial electrical resistance and an increased passage of 22Na ions. This increase in permeability was inhibited completely by chelation of intracellular calcium ions by BAPTA-AM and inhibition of calmodulin activity and myosin light chain (MLC) phosphorylation. The presence of serum factors prolonged the barrier dysfunction induced by histamine. Thrombin by itself induced a prolonged barrier dysfunction (>30 minutes) as evidenced by an increased passage of peroxidase and 40 kDa dextran. It was dependent only partially on calcium ions and calmodulin. The protein tyrosine kinase inhibitors genistein and herbimycin A, but not the inactive analogue daidzein, inhibited to a large extent the increase in permeability induced by thrombin. Genistein and BAPTA-AM inhibited the thrombin-induced permeability in an additive way, causing together an almost complete prevention of the thrombin-induced increase in permeability. Inhibition of protein tyrosine kinase was accompanied by a decrease in MLC phosphorylation and a reduction in the extent of F-actin fiber and focal attachment formation. Inhibition of RhoA by C3 transferase toxin reduced both the thrombin-induced barrier dysfunction and MLC phosphorylation. Genistein and C3 transferase toxin did not elevate the cellular cAMP levels. No evidence was found for a significant role of protein kinase C in the thrombin-induced increase in permeability or in the accompanying MLC phosphorylation. These data indicate that in endothelial cell monolayers that respond to histamine in a physiological way, thrombin induces a prolonged increase in permeability by "calcium sensitization," which involves protein tyrosine phosphorylation and RhoA activation.

Calcium↗
PubMed1997

Contrasting effects of hypochlorous acid and hydrogen peroxide on endothelial permeability: prevention with cAMP drugs.

Activated polymorphonuclear leukocytes generate a cascade of reduced oxygen metabolites. In addition to their antimicrobial role, hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) function as inflammatory mediators and increase the protein permeability of the vascular endothelium. The objectives of the present study were to compare the effects of H2O2 and HOCl with respect to relative potencies and the time course and magnitude of changes in cell shape and permeability of endothelial cell monolayers derived from bovine pulmonary artery, to determine if HOCl produced by conversion of H2O2 with myeloperoxidase and Cl- produces comparable results as the direct administration of HOCl, and to show that adenosine 3',5'-cyclic monophosphate (cAMP)-enhancing agents can prevent the increased endothelial permeability induced by HOCl and H2O2. HOCl given directly or produced by myeloperoxidase, H2O2, and Cl- caused faster and greater changes in cell shape (cell retraction), electrical resistance, and protein permeability (125I-labeled albumin clearance) of endothelial cell monolayers than induced by H2O2. HOCl (10 to 100 microM) induced these changes within 1 to 3 min, whereas H2O2 (50 to 400 microM) required approximately 30 min. 8-Bromo-cAMP prevented the increased endothelial protein permeability induced by HOCl or H2O2, but isoproterenol only prevented the H2O2 response. Thus, HOCl at a much lower concentration caused a faster and greater increase in endothelial permeability in vitro than H2O2, and an increased intracellular level of cAMP prevented the increased permeability induced by either oxidant.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2003

Water permeability of C-terminally truncated aquaporin 0 (AQP0 1-243) observed in the aging human lens.

PURPOSE: To first assess the distribution of posttranslationally truncated products of aquaporin 0 (AQP0) in dissected sections of a normal human lens and to determine the effect of backbone cleavage on the water permeability of AQP0. METHODS: A 27-year-old lens was concentrically dissected into six sections. Membrane protein was isolated from each section and cleaved with cyanogen bromide, and the peptides were separated and analyzed by reverse-phase (RP)-HPLC-mass spectrometry (MS). The sites of posttranslational AQP0 C-terminal truncation were determined by mass spectrometry. Truncated forms of AQP0 were expressed in a Xenopus laevis oocyte system, and the effect of truncation on AQP0 water permeability was assessed in an oocyte osmotic swelling assay. RESULTS: The extent of truncation at many sites within the C terminus increased with fiber cell age, and the effects of truncations after residues 234, 238, and 243 on AQP0 water permeability were examined. Truncation after residue 243 resulted in an approximate 15% decrease in permeability compared with the full-length protein, AQP0 1-263. However, rather than a direct effect on water transport, analysis of surface protein expression indicated that the decrease in permeability was a result of less efficient protein trafficking to the oocyte surface and that the permeabilities of full-length and 1-243 AQP0 were indistinguishable. Further, C-terminal truncation of AQP0 to 1-234 and 1-238, completely impaired trafficking into the plasma membrane, precluding the measurement of permeability. CONCLUSIONS: These data provide evidence that loss of 20 amino acids from the C terminus may not directly affect the ability of AQP0 to transport water.

Adult↗
PubMed2003

Mapping the blood vessels with paracellular permeability in the retinas of diabetic rats.

PURPOSE: Diabetic retinopathy increases the permeability of the blood-retinal barrier, but the specific vessels that become permeable have not been identified. Both transcellular and paracellular pathways of vascular solute flux have been proposed. This study was conducted to test the hypothesis that paracellular flux contributes to increased retinal vascular permeability after VEGF treatment or diabetes, and to map the types of vessels that became permeable. METHODS: Regions of paracellular flux were identified by perfusion with fluorescent concanavalin A (ConA). Rats were injected intravitreally with VEGF or made diabetic with streptozotocin (STZ). After specified times, the rats were perfused with fixative followed by ConA, which binds to the basement membrane but not the luminal surface of endothelial cells. With this approach, ConA labels only blood vessels with paracellular permeability. Retinas were also labeled by immunofluorescence for the tight junction proteins occludin and claudin-5 and examined by confocal microscopy. RESULTS: ConA labeling increased in the superficial arterioles and postcapillary venules, 2 weeks after the onset of diabetes. After 1 month, ConA labeling dramatically increased and extended to the capillaries of the outer plexiform layer. There was an inverse relationship between occludin immunoreactivity and ConA binding, but no change in claudin-5 immunoreactivity was detected. Injection of VEGF gave similar results. CONCLUSIONS: Diabetes and VEGF increase paracellular vascular permeability in the retina, associated with redistribution of occludin. This permeability begins in the superficial arterioles and postcapillary venules and progresses to the capillary bed.

Animals↗
PubMed2006

VEGF activation of protein kinase C stimulates occludin phosphorylation and contributes to endothelial permeability.

PURPOSE: VEGF is a potent permeabilizing factor that contributes to the pathogenesis of diabetic retinopathy and brain tumors. VEGF-induced vascular permeability in vivo and in cell culture requires PKC activity, but the mechanism by which PKC regulates barrier properties remains unknown. This study was conducted to examine how VEGF and diabetes alter occludin phosphorylation and endothelial cell permeability. METHODS: Chemical PKC inhibitors and activators were used to treat primary retinal endothelial cells in culture. In vitro kinase assays and Western blot analysis of two-dimensional (2D) and one-dimensional (1D) gel retardation assays were used to analyze occludin phosphorylation. Endothelial cell permeability was determined by measuring the flux of 70-kDa dextran through a cell monolayer in culture. Exogenous expression of a dominant negative PKCbetaII mutant (S217A) was used to assess the PKC dependence of VEGF-induced occludin phosphorylation and endothelial permeability. Occludin phosphorylation was also determined in retinas of streptozotocin-induced diabetic rats. RESULTS: VEGF stimulated the phosphorylation of occludin in primary retinal endothelial cells. Chemical inhibitors of PKC activity blocked the VEGF-induced increase in occludin phosphorylation, as assessed by 2D gel and gel retardation in Western blot analysis, and blocked part of the VEGF-induced monolayer permeability to 70-kDa dextran. Expression of a dominant negative PKCbetaII mutant blocked VEGF-induced occludin phosphorylation and endothelial permeability. Finally, elevated occludin phosphorylation was observed in the retina of diabetic animals. CONCLUSIONS: These results strongly suggest that VEGF-induced endothelial permeability requires PKC-dependent phosphorylation of occludin. Regulation of PKC activity and tight junction protein modifications may have therapeutic implications for treatment of diabetic retinopathy and brain tumors.

Animals↗
PubMed1977

Selective loss of calcium permeability on maturation of reticulocytes.

Calcium and sodium permeability of human reticulocytes have been studied and compared to mature erythrocytes. Mature erythrocytes had extremely low Ca2+ permeability which was less than 0.1% of values published for squid axon or HeLa cells. Calcium entry was markedly increased in reticulocyte-rich suspensions and the uptake was linearly related to the percentage of reticulocytes present. The data suggest that reticulocytes are 43-fold more permeable to Ca2+ than mature cells although their Ca2+ concentration is not increased. Sodium influx into reticulocyte-rich suspensions was also increased in direct proportion to the percent of reticulocytes present. Reticulocytes are sixfold more permeable to Na+ than mature cells so the ratio of Ca2+:Na+ permeability falls by sevenfold as the reticulocyte changes to an erythrocyte. [3H]Ouabain binding was increased in reticulocyte-rich cell suspensions and the correlation suggested a value of about 4,000 sites per reticulocyte compared with 362+/-69 per mature cell. Maturation of the human reticulocyte produces disproportionate changes in cation permeability and in particular a selective loss of Ca2+ permeability.

Anemia↗
PubMed1990

Hypertonic saline increases vascular permeability in the rat trachea by producing neurogenic inflammation.

In this study, we examined whether inhalation of hypertonic saline aerosols increases vascular permeability in the rat trachea, and we examined the role of neurogenic inflammation in this response. Stereological point counting was performed to measure the percent area occupied by Monastral blue-labeled blood vessels as a means of quantifying the increase in vascular permeability in tracheal whole mounts. Hypertonic saline aerosols (3.6-14.4% NaCl) increased vascular permeability in a dose-dependent fashion compared with 0.9% NaCl. Thus, the area density of Monastral blue-labeled vessels after inhalation of 3.6% NaCl was greater (21.2 +/- 3.5% mean +/- SEM, n = 5) than after 0.9% NaCl aerosol (3.3 +/- 0.9%, n = 5, P less than 0.5). The neutral endopeptidase inhibitor phosphoramidon (2.5 mg/kg, i.v.) significantly potentiated the increase of vascular permeability caused by 3.6% NaCl. Desensitization of sensory nerve endings by pretreatment with capsaicin markedly reduced the usual increase in vascular permeability caused by 3.6% NaCl, but the increase in vascular permeability induced by aerosolized substance P (10(-4) M) was unchanged. These findings suggest that hypertonic saline increases vascular permeability in the rat trachea by stimulating the release of neuropeptides from sensory nerves.

Animals↗
PubMed1990

Increased endothelial albumin permeability mediated by protein kinase C activation.

We examined the effects of activation of endothelial protein kinase C (PKC) of the endothelial barrier function. Exposure of confluent bovine pulmonary artery endothelial cell monolayers to phorbol 12-myristate 13-acetate (PMA) resulted in concentration-dependent (10(-8)-10(-6) M) increases in PKC activity and in the transendothelial flux of 125I-albumin. Exposure of the endothelium to 1-oleoyl 2-acetyl glycerol (OAG) also increased the transendothelial flux of 125I-albumin in a concentration-dependent manner. Neither 4 alpha-phorbol didecanoate nor 1-mono-oleoyl glycerol, which do not activate PKC, altered permeability. The increase in 125I-albumin permeability induced by PMA was inhibited by 25 microM H7 (a PKC inhibitor), but not by the control compound HA1004 (25 microM). After 16 h of exposure to PMA, 125I-albumin permeability returned to baseline and a significant reduction in cytosolic PKC activity was noted. Further challenge with PMA at this time resulted in no significant increase in PKC activity indicating downregulation of the enzyme; moreover, this PMA challenge did not increase endothelial permeability. Exposure of endothelial monolayers to phospholipase C (PLC), which increases membrane phosphatidylinositide turnover, or to alpha-thrombin also induced concentration-dependent activation of PKC and increases in 125I-albumin endothelial permeability. The thrombin- and PLC-induced permeability increases were inhibited by H7, but not by HA1004. The activation of endothelial PKC directly by PMA or OAG and by PLC and alpha-thrombin increases the transendothelial albumin permeability, indicating that PKC activation is an important signal transduction pathway by which extracellular mediators increase endothelial macromolecular transport.

Animals↗
PubMedDate not supplied

Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease.

BACKGROUND: Glutamine is a major fuel and an important nitrogen source for the small intestinal cell. It plays a key role in maintaining mucosal cell integrity and gut barrier function. Increased permeability may be a factor in the pathogenesis of Crohn's disease and may be an interesting parameter in the follow-up of the disease. Therefore, the aim of this study was to examine whether oral glutamine supplements are able to restore an increased intestinal permeability in patients with Crohn's disease. METHODS: The inclusion criteria for the study were Crohn's disease and a disturbed small intestinal permeability for 51Cr-EDTA. Of 38 patients screened, 18 had an increased permeability (6 hours urinary excretion >1.1% of label recovered in urine). Fourteen patients were included in the study and were randomized to receive either oral glutamine (7 g three times per day; n = 7) or placebo (7 g glycine three times per day; n = 7) in addition to their normal treatment during a 4-week period. The study was performed in a double-blind manner. RESULTS: Baseline permeability (mean +/- SD) was 2.32%+/-0.77% dose in the glutamine group and 2.29%+/-0.67% dose in the placebo group. Permeability did not change significantly after glutamine (3.26%+/-2.15% dose) or after placebo (2.27%+/-1.32% dose). There was no significant effect on plasma glutamine, plasma glutamate, plasma ammonium, Crohn's disease activity index, C-reactive protein, or nutritional status. CONCLUSIONS: Oral glutamine supplements, in the dose administered, do not seem to restore impaired permeability in patients with Crohn's disease.

Administration, Oral↗
PubMed2005

Linking solubility and permeability assays for maximum throughput and reproducibility.

Solubility and permeability are intimately linked in drug absorption processes. They have, however, been traditionally assayed separately. To support this linkage, a combined solubility/permeability assay was developed for determining absorption properties of chemical entities. First, solubility is determined at 4 pH values by comparing the concentration of a saturated compound solution to its dilute, known concentration. The filtered, saturated solution from the solubility assay is then used as input material for the membrane permeability determination. The permeability assay is a parallel artificial membrane technique whereby a membrane is created on a solid support parallel artificial membrane permeation assay (PAMPA). The 2 artificial membranes presented here model the gastrointestinal tract and the blood-brain barrier (BBB). Data are presented for control compounds, which are well documented in the literature and exemplify a range of solubility and membrane permeability. The advantages of the combination method are 1) reduction of sample usage and preparation time, 2) elimination of interference from compound precipitation in membrane permeability determination, 3) maximization of input concentration to permeability assay for improved reproducibility, and 4) optimization of sample tracking by streamlining data entry and calculations. BBB permeability ranking of compounds correlates well with literature CNS activity.

Blood-Brain Barrier↗
PubMed1998

Early feeding, antenatal glucocorticoids, and human milk decrease intestinal permeability in preterm infants.

To determine the effects of age, feeding regimen, and antenatal glucocorticoids on intestinal permeability, preterm infants (n = 132) were stratified by gestational age and by diet (mothers' own milk versus preterm formula), and assigned randomly to one of four feeding regimens: early-continuous, early-bolus, standard-continuous, and standard-bolus. At 10, 28, and 50 d of age permeability was determined by measuring the ratio of lactulose/ mannitol in the urine after the two sugars were administered enterally for 30 h. The mean (+/-SE) birth weight and gestational age of the infants were 1044 +/- 13 g and 27 +/- 0.1 wk, respectively. Permeability changed as a function of age (p = 0.003). Early feeding was associated with a reduction in permeability at 10 d of age (p = 0.01). Antenatal steroid administration was associated with decreased permeability at 28 d of age (p = 0.017). The feeding of human milk (versus formula) was associated with decreased permeability at 28 d of age (p = 0.02). Continuous versus bolus feeding did not affect permeability.

Aging↗
PubMed1999

Maturational changes in rabbit renal brush border membrane vesicle urea permeability.

Urea transport in the proximal tubule is thought to occur by passive diffusion through the lipid bilayers of the cell membranes. The lipid composition of cell membranes changes during maturation and may directly affect urea permeability of proximal tubule membranes. The present study examined the maturation of urea transport in rabbit renal brush border membrane vesicles (BBMV). BBMV from adult and neonatal (9- to 11-d-old) New Zealand white rabbits were loaded with 500 mM urea and mixed with an iso-osmotic mannitol solution using a stop-flow instrument. Vesicle shrinkage, due to efflux of urea, was followed with light scattering and urea permeability was calculated from an exponential fit of the data. Urea permeability was significantly lower in the neonatal BBMV than the adult at 25 degrees C (0.34+/-0.04 x 10(-6) versus 0.56+/-0.03 x 10(-6) cm/sec;p < 0.001, n=7) and 37 degrees C (0.45+/-0.04 x 10(-6) versus 0.66+/-0.03 x 10(-6) cm/sec; p=0.001, n=7). There was no effect of 250 microM phloretin on urea permeability in either adult or neonatal BBMV at either temperature. The activation energy for urea diffusion was higher in the neonatal than the adult BBMV. Because the maturational increase in urea permeability could potentially be due to a sodium-dependent urea transporter in the adult BBMV, the sodium dependence of urea uptake in adult BBMV was examined. There was no difference in urea permeability in the presence or absence of 20 mM NaCl. Permeability of the lipid-soluble molecule, glycerol, was also found to be the same in the neonatal and adult BBMV. Urea transport in the apical membrane of neonatal and adult proximal tubules is not phloretin sensitive, a finding consistent with diffusion of urea via the lipid bilayer. The rate of urea diffusion is lower in neonatal membranes and may be an important factor in overall urea excretion. This may also play a role in developing and maintaining a high medullary urea concentration and thus the ability to concentrate the urine during renal maturation.

Animals↗
PubMed2004

Fluorescein permeability and electrical resistance of human skin during low frequency ultrasound application.

Transdermal drug delivery offers an alternative to injections and oral medication but is limited by the low skin permeability of most drugs. The use of low-frequency ultrasound over long periods of time, typically over an hour, has been shown to enhance skin permeability, a phenomenon referred to as sonophoresis. In this study, we investigated the effects of short time sonication of human skin at 20 kHz and at variable intensities and duty cycles on the dynamics of fluorescein transport across the skin (permeability) as well as the changes in the skin's structural integrity (electrical resistance). We found that a short application of ultrasound enhanced the transport of fluorescein across human skin by a factor in the range of 2-9 for full thickness skin samples and by a factor in the range of 2-28 000 for heat-stripped stratum corneum samples (however, samples with very high (10(3)) enhancement were likely to have been damaged by ultrasound). The electrical resistance of the skin decreased by an average of 20% for full thickness samples and 58% for stratum corneum samples. Increasing the duty cycle from 10 to 60% caused a significant increase in permeability enhancement from 2.3 to 9.1, and an increase in intensity from 8 to 23 mW cm(-2) induced a significant increase in permeability enhancement from 2 to 7.4, indicating a clear dependence of the permeability on both duty cycle and intensity. The increase in solute flux upon ultrasound exposure was immediate, demonstrating for the first time the fast response dynamics of sonophoretic enhancement. In addition, a quantitative analysis of the thermal and convective dispersion effects associated with ultrasound application showed that each contributes significantly to the overall permeability enhancement observed.

Administration, Cutaneous↗
PubMed2001

Rho and Rac but not Cdc42 regulate endothelial cell permeability.

Endothelial permeability induced by thrombin and histamine is accompanied by actin stress fibre assembly and intercellular gap formation. Here, we investigate the roles of the Rho family GTPases Rho1, Rac1 and Cdc42 in regulating endothelial barrier function, and correlate this with their effects on F-actin organization and intercellular junctions. RhoA, Rac1 and Cdc42 proteins were expressed efficiently in human umbilical vein endothelial cells by adenovirus-mediated gene transfer. We show that inhibition of Rho prevents both thrombin- and histamine-induced increases in endothelial permeability and decreases in transendothelial resistance. Dominant-negative RhoA and a Rho kinase inhibitor, Y-27632, not only inhibit stress fibre assembly and contractility but also prevent thrombin- and histamine-induced disassembly of adherens and tight junctions in endothelial cells, providing an explanation for their effects on permeability. In contrast, dominant-negative Rac1 induces permeability in unstimulated cells and enhances thrombin-induced permeability, yet inhibits stress fibre assembly, indicating that increased stress fibre formation is not essential for endothelial permeability. Dominant-negative Cdc42 reduces thrombin-induced stress fibre formation and contractility but does not affect endothelial cell permeability or responses to histamine. These results demonstrate that Rho and Rac act in different ways to alter endothelial barrier function, whereas Cdc42 does not affect barrier function.

Actins↗
PubMed2004

The permeability of gap junction channels to probes of different size is dependent on connexin composition and permeant-pore affinities.

Gap junctions have traditionally been characterized as nonspecific pores between cells passing molecules up to 1 kDa in molecular mass. Nonetheless, it has become increasingly evident that different members of the connexin (Cx) family mediate quite distinct physiological processes and are often not interchangeable. Consistent with this observation, differences in permeability to natural metabolites have been reported for different connexins, although the physical basis for selectivity has not been established. Comparative studies of different members of the connexin family have provided evidence for ionic charge selectivity, but surprisingly little is known about how connexin composition affects the size of the pore. We have employed a series of Alexa dyes, which share similar structural characteristics but range in size from molecular weight 350 to 760, to probe the permeabilities and size limits of different connexin channels expressed in Xenopus oocytes. Correlated dye transfer and electrical measurements on each cell pair, in conjunction with a three-dimensional mathematical model of dye diffusion in the oocyte system, allowed us to obtain single channel permeabilities for all three dyes in six homotypic and four heterotypic channels. Cx43 and Cx32 channels passed all three dyes with similar efficiency, whereas Cx26, Cx40, and Cx45 channels showed a significant drop-off in permeability with the largest dye. Cx37 channels only showed significant permeability for the smaller two dyes, but at two- to sixfold lower levels than other connexins tested. In the heterotypic cases studied (Cx26/Cx32 and Cx43/Cx37), permeability characteristics were found to resemble the more restrictive parental homotypic channel. The most surprising finding of the study was that the absolute permeabilities calculated for all gap junctional channels in this study are, with one exception, at least 2 orders of magnitude greater than predicted purely on the basis of hindered pore diffusion. Consequently, affinity between the probes and the pore creating an energetically favorable in-pore environment, which would elevate permeant concentration within the pore and hence the flux, is strongly implicated.

Animals↗
PubMed1977

A new method for evaluating an increased general capillary permeability in patients.

The difference between total plasma volume determined with a substance which escapes from vascular beds in the presence of an increase of general capillary permeability and that determined with a substance which is confined to blood even in the presence of an increased capillary permeability may reflect the degree of an increase of general capillary permeability. The total plasma volume was determined by simultaneous injections of 131I-HSA and 51Cr tagged red cells. The capillary permeability was evaluated by calculating the difference (deltaTPV) between total plasma volume determined with 131I-HSA and that determined with 51Cr tagged red cell. deltaTPV in patients with systemic lupus erythematosus, idiopathic thrombocytopenic purpura, chronic active hepatitis, liver cirrhosis and subacute baterial endocarditis was larger than that of controls, averaging 204ml/m2, 178 ml/m2, 82 ml/m2, 131 ml/m2 and 179 ml/m2, respectively. The increase of deltaTPV was considered to indicate the increase of capillary permeability in these patients. A permeability increasing factor was present in serum of patients with an elevated deltaTPV. There was a significant correlation between deltaTPV and the titer of serum capillary permeability increasing factor in these patients.

Adult↗
PubMed1986

Deoxyribonuclease I sensitivity of DNA replicated in permeable mouse sarcoma cells.

To study chromatin structure at the sites of DNA replicated in permeable cells, deoxyribonuclease I (DNase I) sensitivity of newly replicated DNA in permeable mouse sarcoma cells was compared with that of newly replicated DNA in intact cells. About 35% of the DNA replicated in permeable cells was hypersensitive to DNase I, and the remaining DNA showed the same DNase I sensitivity as that of parental chromatin DNA. The sensitivity of DNA replicated in permeable cells was higher than that of DNA newly replicated in intact cells, and was close to that of DNA replicated in the presence of cycloheximide. The sensitivity of DNA pulse-labeled with [3H]deoxythymidine triphosphate by replication in permeable cells was reduced significantly by chasing with cold deoxythymidine triphosphate. The present results suggest that chromatin structure at the sites of DNA replicated in permeable cells is similar to that at the sites of DNA replicated in living cells in the absence of protein synthesis, and that some structural change (possibly toward the maturation) of newly replicated chromatin occurs after the DNA replication in permeable cells.

Animals↗
PubMed1986

Lysophosphatidylcholine potentiates the increase in mucosal permeability after small-intestinal ischaemia.

The influence of lysophosphatidylcholine (lysoPC), taurodeoxycholate (TDC), and taurochenodeoxycholate (TCDC) on the permeability properties of the ischaemic small-intestinal mucosa was investigated. We first studied the effect of ischaemia alone, then of lysoPC, TDC, or TCDC alone, and finally of ischaemia together with lysoPC, TDC, or TCDC on the permeability to sodium fluorescein in a ligated loop of the distal ileum in the rat. Longer periods of ischaemia alone (10 min or more) caused increased permeability, as did high concentrations (10 mM) of any of the agents. Low concentrations (1 mM) of lysoPC alone did not alter the gut permeability, but it significantly potentiated the increased permeability caused by 30 min of ischaemia. In contrast, 1 mM TDC or TCDC did not influence the permeability after 30 min of ischaemia. These findings imply that the ischaemic small intestine may be damaged by small amounts of lysoPC, with increased absorption of potentially pathogenic compounds as a possible consequence. They also point to the possibility that endogenously formed lysoPC may play a role in the mucosal damage and the increased permeability that occurs after small-intestinal ischaemia.

Animals↗