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The study of claudins in a model system of the proximal tubuleBorovac, Jelena Unknown Date
No description available.
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Lysine and Glycyl-L-Sarcosine Absorption Across Ovine Forestomach Epithelium In VitroMcCollum, Martha Quinn 20 August 1996 (has links)
Lysine absorption by ruminal and omasal epithelia was studied using parabiotic chambers that were sampled for 60-min. Lysine appearance in serosal buffers and the accumulation of lysine in tissues increased linearly (P < .001) with time. Lysine appearance in serosal buffers of ruminal tissue increased proportionally as the concentration of lysine increased in mucosal buffers. However, lysine appearance in serosal buffers of omasal tissue increased proportionally to a substrate concentration of 1.5 mM, then plateaued. Total absorption (tissue accumulation plus serosal appearance) increased linearly for ruminal tissue; however, for omasal tissue, total absorption increased linearly to 1.5 mM (P < .001), then plateaued. Using omasal epithelium, glycyl-L-sarcosine (Gly-Sar; .1 mM) absorption was studied during co-incubation with glycine and peptide substrates (each at 5 mM). Accumulation of Gly-Sar in omasal epithelium was greatest (P < .05) when Gly-Sar was present alone. Glycine inhibited (P < .05) Gly-Sar accumulation by 20%, whereas peptide substrates inhibited (P < .05) Gly-Sar accumulation by 60 to 85%. The absorption of Gly-Sar (.1 mM) alone or during co-incubation with either 10 mM butyric acid, or a mixture of VFA was also studied. Accumulation of Gly-Sar in tissue was greatest (P < .05) when Gly-Sar was present alone; butyric acid and VFA inhibited (P < .05) Gly-Sar accumulation by 50 to 84%. These results suggest absorption of amino acids and peptides by the omasum, and also suggest the mechanism involves mediated as well as possibly paracellular transport. / Master of Science
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Regulation of Intestinal Epithelial Barrier and Immune Function by Activated T CellsLe, Nga Thi Thanh 26 January 2021 (has links)
No description available.
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IMPACT OF NONIONIZABLE GLYCOL SOLUBILIZERS EXHIBITING DIFFERENT SURFACE ACTIVITIES ON INTESTINAL MEMBRANE PERMEABILITYTRISAL, PREETI 14 July 2005 (has links)
No description available.
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Synthetic peptides modulate epithelial junctionsYi, Sheng January 1900 (has links)
Master of Science / Department of Biochemistry / Bruce D. Schultz / John M. Tomich / Peptides based on the second transmembrane segment of the glycine receptor (M2GlyR) were made to provide a potential therapeutic treatment for cystic fibrosis (CF) and a latent absorption enhancer for drug delivery. For similarity of presentation, unique synthetic peptide sequences have been given alpha-numeric designations. Results are presented from studies focusing on four peptides.
In the first study, the contributions of synthetic peptides p1171, p1172 and p1173 to net transepithelial ion transport were measured as a first step toward the goal of testing whether pore length or electrostatics of pore lining residues will affect anion transport. Peptide p1130 exhibits many attributes that make it an ideal synthetic peptide for CF treatment, but has low permselectivity for anions. Therefore, it is used as a platform for modification. Peptide p1171 is doubly substituted with diaminopropionic acid at positions T13 and T17. Peptide p1172 and p1173 are separately one and two helical turn(s) inserted into the p1130 backbone. Apical exposure of MDCK monolayers to these peptides caused a rapid increase in short circuit current (Isc), an indicator of net ion transport. The increase in Isc caused by p1172 or p1173 was accompanied by increase in transepithelial electrical conductance (gte). The electrophysiological results suggested that these modified peptides can assemble in the apical membrane of epithelial cells to form functional ion-conducting pores.
Peptide NC-1059, which provides for ion transport across epithelial cells derived from many sources, was studied further to assess cellular changes that account for increased gte. NC-1059 increased Isc, gte and enhanced permeation of dextrans in a concentration dependent manner. Results from previous and current studies show that NC-1059 modulated the epithelial paracellular pathway by altering the distribution and abundance of junctional proteins. Immunoblotting and immunolabeling with confocal microscopy showed that NC-1059 induces reorganization of actin and causes a reduction in F-actin abundance in epithelial cells. The distributions were changed and cellular abundances were reduced of tight junction proteins occludin and ZO-1 and adherens junction proteins E-cadherin and β-catenin by NC-1059. These effects were largely reversed in 24 hr and fully recovered in 48 hr. Therefore, NC-1059 has the therapeutic potential to increase the efficiency of drug delivery across barrier membranes.
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Permeation of excised intestinal tissue by insulin released from Eudragit® L100/Trimethyl chitosan chloride microspheres /E.B. Marais.Marais, Etienne Barend January 2013 (has links)
The purpose of this research project was to develop and characterise matrix type microspheres prepared from Eudragit® L100, containing insulin as model peptide drug as well as an absorption enhancer, N-trimethyl chitosan chloride (TMC), to improve intestinal absorption via the paracellular route. Insulin loaded microspheres were prepared using a single water in oil emulsification/evaporation method in accordance with a fractional factorial design (23) and subsequently characterised in terms of morphology as well as internal structure. Also, insulin and TMC loading were determined using a high pressure liquid chromatography analysis (HPLC) and colorimetric assay, respectively.
Scanning electron microscopic characterisation revealed that most microsphere formulations showed a spherical shape and smooth surface with a sponge-like internal structure as well as relatively good homogeneity in terms of size distribution. Insulin loading ranged from 27.9 ± 14.25 – 52.4 ± 2.72% between the different formulations. TMC loading was lower than for insulin and ranged from 29.1 ± 3.3 - 37.7 ± 2.3% between the different formulations. The pronounced difference in insulin and TMC loading between the microsphere formulations is probably the result of the multitude parameters involved as well as the complex physicochemical processes which govern emulsification/solvent evaporation. Based on the microsphere characterisation results, two formulations were selected (i.e. B and F) for further characterisation (i.e. particle size distribution, dissolution behaviour, and enteric nature) and for in vitro evaluation of insulin transport across excised Fischer (FSR) rat intestinal tissue using a Sweetana-Grass diffusion chamber. Particle size analysis by means of laser light diffraction of the two selected microsphere formulations revealed that the mean particle size (based on volume) ranged from 135.7 ± 41.05 to 157.3 ± 31.74 m. Dissolution results for microsphere Formulations B and F revealed that both insulin and TMC were released from the microsphere formulations in an alkaline environment (pH 7.4). The mean dissolution time (MDT) for insulin ranged from 34.5 ± 4.01 to 42.6 ± 9.06 min, while the MDT for TMC ranged from 1.2 ± 1.73 to 6.8 ± 6.42 min. Statistical analysis revealed no significant differences in the MDT of either insulin or TMC (p-value > 0.05) between the two formulations, although the difference between insulin and TMC of each formulation was significant (p-value < 0.05). Microsphere formulations B and F released 36.92 and 48.21% of their total drug content over a period of 1 h in 0.1 M HCl.
Microsphere Formulation B showed 8.3 ± 0.52% and formulation F 8.9 ± 2.26% transport of the initial insulin dose after a period of 120 min across excised rat intestinal tissue. The increase in insulin transport by the microsphere formulations compared to that of the control group (i.e. insulin alone) correlated well with the decrease in transepithelial electrical resistance (TEER) caused by the microsphere formulations. The transport of insulin from Formulations B and F represented transport enhancement ratios of 10.67 and 9.68, respectively.
Insulin loaded EudragitL100 microspheres containing TMC were successfully prepared by emulsification/solvent evaporation that demonstrated promising potential to serve as oral drug delivery systems for insulin. The microspheres exhibited improved insulin permeability across intestinal epithelial tissue; however, its enteric properties should be improved and clinical effectiveness need to be confirmed by future in vivo studies. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.
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Permeation of excised intestinal tissue by insulin released from Eudragit® L100/Trimethyl chitosan chloride microspheres /E.B. Marais.Marais, Etienne Barend January 2013 (has links)
The purpose of this research project was to develop and characterise matrix type microspheres prepared from Eudragit® L100, containing insulin as model peptide drug as well as an absorption enhancer, N-trimethyl chitosan chloride (TMC), to improve intestinal absorption via the paracellular route. Insulin loaded microspheres were prepared using a single water in oil emulsification/evaporation method in accordance with a fractional factorial design (23) and subsequently characterised in terms of morphology as well as internal structure. Also, insulin and TMC loading were determined using a high pressure liquid chromatography analysis (HPLC) and colorimetric assay, respectively.
Scanning electron microscopic characterisation revealed that most microsphere formulations showed a spherical shape and smooth surface with a sponge-like internal structure as well as relatively good homogeneity in terms of size distribution. Insulin loading ranged from 27.9 ± 14.25 – 52.4 ± 2.72% between the different formulations. TMC loading was lower than for insulin and ranged from 29.1 ± 3.3 - 37.7 ± 2.3% between the different formulations. The pronounced difference in insulin and TMC loading between the microsphere formulations is probably the result of the multitude parameters involved as well as the complex physicochemical processes which govern emulsification/solvent evaporation. Based on the microsphere characterisation results, two formulations were selected (i.e. B and F) for further characterisation (i.e. particle size distribution, dissolution behaviour, and enteric nature) and for in vitro evaluation of insulin transport across excised Fischer (FSR) rat intestinal tissue using a Sweetana-Grass diffusion chamber. Particle size analysis by means of laser light diffraction of the two selected microsphere formulations revealed that the mean particle size (based on volume) ranged from 135.7 ± 41.05 to 157.3 ± 31.74 m. Dissolution results for microsphere Formulations B and F revealed that both insulin and TMC were released from the microsphere formulations in an alkaline environment (pH 7.4). The mean dissolution time (MDT) for insulin ranged from 34.5 ± 4.01 to 42.6 ± 9.06 min, while the MDT for TMC ranged from 1.2 ± 1.73 to 6.8 ± 6.42 min. Statistical analysis revealed no significant differences in the MDT of either insulin or TMC (p-value > 0.05) between the two formulations, although the difference between insulin and TMC of each formulation was significant (p-value < 0.05). Microsphere formulations B and F released 36.92 and 48.21% of their total drug content over a period of 1 h in 0.1 M HCl.
Microsphere Formulation B showed 8.3 ± 0.52% and formulation F 8.9 ± 2.26% transport of the initial insulin dose after a period of 120 min across excised rat intestinal tissue. The increase in insulin transport by the microsphere formulations compared to that of the control group (i.e. insulin alone) correlated well with the decrease in transepithelial electrical resistance (TEER) caused by the microsphere formulations. The transport of insulin from Formulations B and F represented transport enhancement ratios of 10.67 and 9.68, respectively.
Insulin loaded EudragitL100 microspheres containing TMC were successfully prepared by emulsification/solvent evaporation that demonstrated promising potential to serve as oral drug delivery systems for insulin. The microspheres exhibited improved insulin permeability across intestinal epithelial tissue; however, its enteric properties should be improved and clinical effectiveness need to be confirmed by future in vivo studies. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.
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NC-1059, a channel forming peptide, induces a reversible change in barrier function of epithelial monolayersSomasekharan, Suma January 1900 (has links)
Doctor of Philosophy / Department of Biochemistry / Bruce D. Schultz / John M. Tomich / NC-1059 is a synthetic channel-forming peptide that provides for ion transport across, and transiently reduces barrier integrity of, cultured epithelial monolayers derived from canine kidney (MDCK cells; Broughman, J. R. et al; Am J Physiol Cell Physiol 286: C1312-23). In this first study experiments were conducted to determine whether epithelial cells derived from other sources were similarly affected. Human (T84, Calu-3) and non-human (IPEC-J2, PVD9902) epithelial cells derived from intestinal (T84, IPEC-J2), airway (Calu-3), and genitourinary (PVD9902) tissues were grown on permeable supports. Ion transport and barrier function were assessed electrically in a modified Ussing chamber. Basal short circuit current (I[subscript sc]) was typically less than 3 [Mu]A cm[superscript-2]. Apical NC-1059 exposure caused, in all cell types, an increase in I[subscript sc] to >15 [Mu]A cm[superscript-2], indicative of net anion secretion or cation absorption that was followed by an increase in transepithelial conductance (g[subscript te] in mS cm[superscript-2]; T-84, 1.6 to 62; PVD9902, 0.2 to 51; IPEC-J2, 0.3 to 26; Calu-3, 2.2 to 13). NC-1059 induces a concentration dependent change in the I[subscript sc] and g[subscript te] across these epithelia. The results in all cases were consistent with both a transcellular and a paracellular effect of the peptide. NC-1059 enhanced permeation of dextrans ranging from 10 kDa to 70 kDa across all epithelia tested. These results document an effect of NC-1059 on the paracellular route of epithelial barriers. Immunolabeling, confocal microscopy and immunoblotting methods were used in a second study to assess the molecular changes associated with increased paracellular permeability. NC-1059 induced a substantial reorganization of actin within 60 minutes of exposure. Confocal microscopy revealed that the changes in actin organization were accompanied by a pronounced change in the abundance and distribution of tight junction proteins occludin and ZO-1. Immunoblotting results suggest a time and concentration dependent effect on cellular abundance of these tight junction proteins. The effects on g[subscript te] and junctional proteins are transient with > 85% of recovery in 24 hours post exposure and full recovery within 48 hours. The reversible modulation of the epithelial tight junctions has therapeutic potential to increase the efficiency of drug delivery across barrier membranes.
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Enhanced Intranasal Delivery of Gemcitabine to the Central Nervous SystemKrishan, Mansi January 2013 (has links)
No description available.
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Novel in vitro models for pathogen detection based on organic transistors integrated with living cells. / Integration de cellules avec des transistors organiques pour la detection rapide de pathogenes et toxinesTria, Scherrine 18 October 2013 (has links)
L’épithélium intestinal est un exemple de tissu qui a évolué pour former une barrière. Cette barrière limite le passage de produits toxiques d’agents pathogènes à partir de la lumière vers les tissus, tout en absorbant les nutriments, électrolytes et l'eau nécessaire à l'hôte. Les jonctions serrées sont des structures qui limitent le passage de la matière à travers l'espace intercellulaire. La capacité de mesurer le transport à travers cette barrière est d'une importance capitale car elle fournit des renseignements sur l’état de celle-ci, révélatrice de certains états pathologiques, puisque la perturbation ou dysfonctionnement des jonctions serrées est souvent due à ou est un indicatif de toxicité ou de maladie. En outre, le degré d'intégrité de la barrière est un indicateur clé de la pertinence d'un modèle in vitro particulier pour une utilisation en toxicologie et screening de médicaments. L'avènement de l'électronique organique a créé une occasion unique pour connecter les mondes de l'électronique et de la biologie, à l'aide des dispositifs tels que le transistor électrochimique organique (OECT), qui fournisse un moyen très sensible pour détecter des courants ioniques. Ces dispositifs ont une sensibilité sans précédent, dans un format qui peut être produit en masse à faible coût.Le but de cette étude était d'intégrer une couche de cellules représentative de la barrière gastro intestinale avec des OECTs, pour créer des dispositifs qui permettent de détecter les perturbations de cette barrière d’une manière rapide et sensible. Cette technique a était démontrée pour être au minimum aussi sensible mais d’une rapidité supérieure que les techniques actuelles sur le marché. / In biological systems, different tissues have evolved to form a barrier. An example is the intestinal epithelium, consisting of a single layer of cells lining the wall of the stomach and colon. It restricts the passage of harmful chemicals or pathogens from the light into the tissue, while selectively absorbing the most nutrients, electrolytes and water are necessary for the host. Tight junctions are structures which limit the passage of the material through the space between the cells. The ability to measure the paracellular and transcellular transport is of vital importance because it provides a wealth of information on the state of the barrier, indicative of certain disease states , since the disruption or malfunction of the structures involved in the transport through the tissue barrier is often caused or is indicative of toxicity or disease. In addition, the degree of integrity of the barrier is a key indicator of the relevance of a particular model in vitro for use in toxicology and drug screening. The advent of organic electronics has created a unique opportunity to connect the worlds of electronics and biology, using devices such as organic electrochemical transistor (OECT), which provides a very sensitive way to detect ionic currents. These devices have unprecedented sensitivity in a format that can be mass produced at low cost.The purpose of this study was to integrate a monolayer of cells representative of the gastro intestinal barrier with OECTs , to create devices that detect disruptions of the barrier in a timely and sensitive manner. This technique was demonstrated to be at least as sensitive, but a higher speed than current techniques on the market
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