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Georgi M.I.,Free University of Berlin | Rosendahl J.,Free University of Berlin | Ernst F.,Free University of Berlin | Gunzel D.,Institute of Clinical Physiology | And 3 more authors.
Pflugers Archiv European Journal of Physiology | Year: 2014

It has long been established that the absorption of short-chain fatty acids (SCFA) across epithelia stimulates sodium proton exchange. The apically released protons are not available as countercations for the basolateral efflux of SCFA anions and a suitable transport model is lacking. Patch clamp and microelectrode techniques were used to characterize an anion conductance expressed by cultured cells of the sheep and bovine rumen and the sheep omasum and to localize the conductance in the intact tissue. Cells were filled with a Na-gluconate solution and superfused with sodium salts of acetate, propionate, butyrate, or lactate. Reversal potential rose and whole cell current at +100 mV decreased with the size of the anion. Anion-induced currents could be blocked by diisothiocyanato-stilbene-2,2′-disulfonic acid (DIDS), NPPB (200μmol l-1), or pCMB (1 mmol l-1). In patches of bovine ruminal cells, single channels were observed with a conductance for chloride (327±11 pS), acetate (115±8 pS), propionate (102±10 pS), butyrate (81±2 pS), and gluconate (44±3 pS). Channels expressed by sheep rumen and omasum were similar. Microelectrode experiments suggest basolateral localization. In conclusion, forestomach epithelia express basolateral maxi-anion channels with a permeability sequence of chloride>acetate>propionate>butyrate. SCFA absorption may resemble functionally coupled transport of NaCl, with the Na+/K +-ATPase driving the basolateral efflux of the anion through a channel. Since protons are apically extruded, the model accurately predicts that influx of buffers with saliva is essential for the pH homeostasis of the ruminant forestomach. © 2013 Springer-Verlag.

Bruno R.M.,Institute of Clinical Physiology | Faconti L.,University of Pisa | Taddei S.,University of Pisa | Ghiadoni L.,University of Pisa
Current Opinion in Cardiology | Year: 2015

Purpose of review To provide an overview of available evidence of the relationship between birth weight and future hypertension development. Recent findings Fetal programming plays a significant role in future hypertension. Both low and high birth weight are able to influence weight gain during childhood, adult weight and blood pressure values during childhood and adulthood. To date, an increasing amount of evidence is available especially for the relationship between low birth weight and hypertension, supported also by pathophysiological studies. Summary In the era of personalized medicine, the possibility to reduce cardiovascular risk before or soon after birth and intervene on risk factors during childhood is appealing and promising for the future. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Scutaru A.M.,Free University of Berlin | Kruger M.,Free University of Berlin | Wenzel M.,Free University of Berlin | Richter J.,Institute of Clinical Physiology | And 2 more authors.
Bioconjugate Chemistry | Year: 2010

Fluorescent dyes (e.g., dansyl, fluoresceine isothiocyanate, or naphthalimide groups) are widely used as markers to study biological properties of drugs. In order to evaluate possible mediated cytotoxicity, we attached three molecules each to 1,3,5-tris(3-propylamino)benzene initially synthesized as core molecule for the design of dendrimers. Cytotoxic effects were only observed for the NO2-substituted naphthalimide conjugate. The intracellular distribution was visualized via confocal fluorescence microscopy and pointed to an accumulation in the endosome or nucleus, dependent on the cell line used. © 2010 American Chemical Society.

Schumann M.,Infectious Diseases and Rheumatology | Kamel S.,Infectious Diseases and Rheumatology | Pahlitzsch M.-L.,Infectious Diseases and Rheumatology | Lebenheim L.,Infectious Diseases and Rheumatology | And 6 more authors.
Annals of the New York Academy of Sciences | Year: 2012

In celiac disease, the gut-associated immune system is activated in response to the ingestion of gluten, causing an atrophy of the small intestinal mucosa. Although this condition is, in most cases, responsive to a gluten-free diet, celiac disease refractory to treatment occurs in a small percentage of celiacs. An epithelial barrier defect is known to be an integral part of celiac pathophysiology. However, the mucosa in refractory celiac disease underlies a constant inflammatory process. The epithelial barrier has not been addressed in this condition so far. Herein, the tight junction-associated barrier in refractory celiac disease is investigated functionally and structurally. Although normally expressed in celiac disease, claudin-4 is shown to be downregulated in refractory cases, presumably by two mechanisms, reduced protein expression and increased claudin endocytosis. Furthermore, the tightening claudin-5 is downregulated and the pore-forming claudin-2 is upregulated. © 2012 New York Academy of Sciences.

Juric M.,Hannover Medical School | Xiao F.,Tongji Hospital | Amasheh S.,Institute of Clinical Physiology | May O.,Hannover Medical School | And 5 more authors.
Inflammatory Bowel Diseases | Year: 2013

Background: Bicarbonate loss into the lumen occurs during intestinal inflammation in different species. However, candidate pathways like CFTR or DRA are inhibited in the inflamed gut. This study addressed the question whether and how inflammation-associated increased intestinal permeability may result in epithelial HCO- 3 loss. Methods: Murine proximal colon was studied because it does not express functional DRA but is inflamed in the tumor necrosis factor a overexpressing mouse model (TNFδARE). Luminal alkalization, 3H-mannitol fluxes, impedance spectroscopy, and dilution potentials were measured in Ussing chambers, whereas expression and localization of tight junction-associated proteins were analyzed by Western blots and immunohistochemistry. Results: Luminal alkalization rates and 3H-mannitol fluxes were increased in TNF+/δARE proximal colon, whereas forskolin-stimulated Isc was not altered. Epithelial resistance was reduced, but subepithelial resistance increased. The epithelial lining was intact, and enterocyte apoptosis rate was not increased despite massively increased Th1 cytokine levels and lymphoplasmacellular infiltration. Measurement of dilution potentials suggested a loss of cation selectivity with increased anion permeability. Western analysis revealed a downregulation of occludin expression and an upregulation of both claudin-2 and claudin-5, with no change in ZO-1, E-cadherin, claudin-4, and claudin-8. Immunohistochemistry suggested correct occludin localization but reduced tight junction density in TNF +/δARE surface epithelium. Conclusions: Inflammation during TNF-α overexpression leads to increased epithelial permeability in murine proximal colon, decreased tight junctional cation selectivity, and increased HCO- 3 loss into the lumen. Inflammation-associated colonic HCO- 3loss may occur through leaky tight junctions rather than through HCO23 secreting ion transporters. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.

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