HO Sensitivity of K Channels in Hypoxic Pulmonary Vasoconstriction: Experimental Conditions Matter.

Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange but, when impaired, can result in life-threatening hypoxemia. Moreover, under conditions of generalized alveolar hypoxia, HPV can result in pulmonary hypertension. Voltage-gated K channels (K channels) are key to HPV: a change in the intracellular hydrogen peroxide (HO) levels during acute hypoxia is assumed to modulate these channels' activity to trigger HPV.

Alteration of the microbiota with vancomycin and high-fiber diet affects short-chain fatty acid/free fatty acid receptor signaling in rat caecum.

Microbial short-chain fatty acids (SCFA) regulate intestinal functions via free-fatty acid (FFA) receptors type 2 and 3. Though the caecum is the most important fermentation chamber in many species, it is unknown whether this signaling system is modulated in dependence on the rate of fermentation within the lumen of this part of the large intestine. Thus, we asked the question whether alteration of the microbiota composition by antibiotic treatment or high-fiber diet affects the SCFA/FFA signaling using rat caecum as model system.

Purinergic control of apical ion conductance by luminal ATP in rat colonic epithelium.

ATP, released e.g. after cell damage or during inflammation, can alter ion transport across the intestinal mucosa via stimulation of purinergic receptors in the basolateral as well as in the apical membrane of epithelial cells.

Time-dependent effects of tumor necrosis factor α on Ca-dependent secretion in murine small intestinal organoids.

Background: Intestinal organoids are stem cell-derived, 3D "mini-guts" with similar functions as the native intestinal epithelium such as electrolyte transport or establishment of an epithelial barrier. During intestinal inflammation, epithelial functions are dysregulated by proinflammatory cytokines like tumor necrosis factor α (TNFα) and other messengers from the immune system resulting in a loss of electrolytes and water due to an impaired epithelial barrier and higher net secretion.

Methods: A murine small intestinal organoid model was established to study (long-term) effects of TNFα on the intestinal epithelium using live imaging, immunohistochemical staining and qPCR.

Gasotransmitters do not prevent changes in transepithelial ion transport induced by hypoxia followed by reoxygenation.

Objectives: How gaseous signalling molecules affect ion transport processes contributing to the physiological functions of the gastrointestinal tract under hypoxic conditions still needs to be clarified. The objective of the present study was to characterize the impact of gaseous signalling molecules on parameters of colonic ion transport during a hypoxia/reoxygenation cycle and the remaining secretory capacity of the epithelium after such a cycle.

Methods: Short-circuit current (I) and tissue conductance (G) recordings in Ussing chamber experiments were performed on rat colon samples using CORM-2 (putative CO donor; 35 and 350 µM), sodium nitroprusside (NO donor; 100 µM), NaHS (fast HS donor; 10 - 1,000 µM), GYY 4137 (slow HS donor; 50 µM) and Angeli's salt (HNO donor; 100 µM) as donors for gasotransmitters.

Atropine-functionalized gold nanoparticles binding to muscarinic receptors after passage across the intestinal epithelium.

Gold nanoparticles have a high potential to be a treatment of diseases by their specific drug delivery properties and multivalent receptor stimulation. For the present project, spherical gold nanoparticles were synthesized and functionalized with the muscarinic receptor antagonist atropine (Au-MUDA-AT NPs). The diameter of the gold core could precisely be controlled by using different synthetic methods and reducing agents resulting in functionalized gold nanoparticles with diameters ranging from 8 to 16 nm.

Multivalent stimulation of β-, but not β-receptors by adrenaline functionalised gold nanoparticles.

In this study, we present a strategy for the synthesis of catecholamine functionalised gold nanoparticles and investigated their multivalent interactions with adrenergic receptors in different biological systems. The catecholamines adrenaline and noradrenaline represent key examples of adrenergic agonists. We used gold nanoparticles as carriers and functionalised them on their surface with a variety of these neurotransmitter molecules.

Proteinase-activated receptors regulate intestinal functions in a segment-dependent manner in rats.

Proteinases released e.g. during inflammatory or allergic responses affect gastrointestinal functions via proteinase-activated receptors such as PAR1 and PAR2.

Ionotropic P2X4 and P2X7 receptors in the regulation of ion transport across rat colon.

Background And Purpose: ATP plays an important role as an extracellular messenger acting via different types of purinoceptors. Whereas most of the actions of ATP at intestinal epithelia are thought to be mediated by metabotropic P2Y receptors, the role of ionotropic P2X receptors remains unclear. Consequently, we investigated the role of P2X4 and P2X7 receptors on ion transport across rat colonic epithelia by using BzATP, a potent agonist at P2X7 (and weak agonist at P2X4).

Short-chain fatty acid receptors involved in epithelial acetylcholine release in rat caecum.

Short-chain fatty acids (SCFAs) produced by the microbial fermentation of carbohydrates are important energy substrates for mammals. Intestinal epithelia respond to these metabolites by stimulation of anion secretion via the release of epithelial acetylcholine. The present experiments were performed to discover which of the known receptors for SCFAs are expressed in rat caecum, the most important site of fermentation within the intestine of non-ruminant mammals.

Characterization of Cecal Smooth Muscle Contraction in Laying Hens.

The ceca play an important role in the physiology of the gastrointestinal tract in chickens. Nevertheless, there is a gap of knowledge regarding the functionality of the ceca in poultry, especially with respect to physiological cecal smooth muscle contraction. The aim of the current study is the ex vivo characterization of cecal smooth muscle contraction in laying hens.

The role of HCO in propionate-induced anion secretion across rat caecal epithelium.

Propionate, a metabolite from the microbial fermentation of carbohydrates, evokes a release of epithelial acetylcholine in rat caecum resulting in an increase of short-circuit current (I) in Ussing chamber experiments. The present experiments were performed in order to characterize the ionic mechanisms underlying this response which has been thought to be due to Cl secretion. As there are regional differences within the caecal epithelium, the experiments were conducted at oral and aboral rat corpus caeci.

Identifying classes of the pain, fatigue, and depression symptom cluster in long-term prostate cancer survivors-results from the multi-regional Prostate Cancer Survivorship Study in Switzerland (PROCAS).

Purpose: Aside from urological and sexual problems, long-term (≥5 years after initial diagnosis) prostate cancer (PC) survivors might suffer from pain, fatigue, and depression. These concurrent symptoms can form a cluster. In this study, we aimed to investigate classes of this symptom cluster in long-term PC survivors, to classify PC survivors accordingly, and to explore associations between classes of this cluster and health-related quality of life (HRQoL).

Health-related quality of life in long-term prostate cancer survivors after nerve-sparing and non-nerve-sparing radical prostatectomy-Results from the multiregional PROCAS study.

Background: Nerve-sparing (NS) surgery was developed to improve postoperative sexual and potentially urological outcomes after radical prostatectomy (RP). However, it is largely unknown how NSRP affects health-related quality of life (HRQoL) including urinary and sexual outcomes in prostate cancer (PC) survivors 5-10 years after diagnosis in comparison with Non-NSRP.

Methods: The study population included 382 stage pT2-T3N0M0 PC survivors 5-10 years post diagnosis, who were identified from the multiregional Prostate Cancer Survivorship in Switzerland (PROCAS) study.

The orphan solute carrier SLC10A7 is a novel negative regulator of intracellular calcium signaling.

SLC10A7 represents an orphan member of the Solute Carrier Family SLC10. Recently, mutations in the human SLC10A7 gene were associated with skeletal dysplasia, amelogenesis imperfecta, and decreased bone mineral density. However, the exact molecular function of SLC10A7 and the mechanisms underlying these pathologies are still unknown.

Interactions between rat submucosal neurons and mast cells are modified by cytokines and neurotransmitters.

The role of mast cells during inflammatory bowel diseases (IBD) is discussed controversially. Whereas several studies report an increase in mast cell density during IBD, others found a decrease. Recently, we observed a reduced response to mast cell degranulation induced by antigen contact in a colitis model.

Segmental differences in ion transport in rat cecum.

Ion-transport properties of the epithelium of the cecum, the biggest fermental chamber in non-ruminant species, are largely unknown. Recently, in Ussing chamber experiments, segmental differences in basal short-circuit current (I) in rat corpus ceci were observed. The oral segment usually exhibited a much lower or even negative basal I in comparison with the aboral segment.

Impact of Sensitization and Inflammation on the Interaction of Mast Cells With the Intestinal Epithelium in Rats.

The density of intestinal mast cells has been reported to increase during inflammatory bowel disease (IBD). As mast cell mediators are known to increase the permeability of epithelial tight junctions, we hypothesized that antigen responses in sensitized animals might be enhanced under inflammatory conditions. This would contribute to a vicious circle by further enhancing the entry of luminal antigens into the colonic wall and thereby continuing the inadequate immune response during IBD.

Evidence for metabotropic function of epithelial nicotinic cholinergic receptors in rat colon.

Background And Purpose: ACh exerts its actions via nicotinic (nAChR) and muscarinic receptors. In the peripheral nervous system, ionotropic nAChR mediate responses in excitable cells. However, recent studies demonstrate the expression of nAChR in the colonic epithelium, which are coupled to an induction of Cl secretion via activation of the Na -K -pump.

Efficacy of motivating short interventions for smokers in primary care (COSMOS trial): study protocol for a cluster-RCT.

Background: Tobacco abuse is a frequent issue in general practitioners' (GPs') offices, with doctors playing a key role in promoting smoking cessation to their patients. However, not all smokers are ready and willing to give up smoking. Thus, a GP focusing on smoking cessation alone might waste the opportunity to improve his patient's health by supporting a change in another harmful behaviour pattern.

Robustness of the non-neuronal cholinergic system in rat large intestine against luminal challenges.

Acetylcholine and atypical esters of choline such as propionyl- and butyrylcholine are produced by the colonic epithelium and are released when epithelial receptors for short-chain fatty acids (SCFA) are stimulated by propionate. It is assumed that the SCFA used by the choline acetyltransferase (ChAT), the central enzyme for the production of these choline esters, originate from the colonic lumen, where they are synthesized during the bacterial fermentation of carbohydrates. Therefore, it seemed to be of interest to study whether the non-neuronal cholinergic system in the colonic epithelium is affected by maneuvers intended to stimulate or to inhibit colonic fermentation by changing the intestinal microbiota.