Differential role of tachykinin NK3 receptors on cholinergic excitatory neurotransmission in the mouse stomach and small intestine.

Background And Purpose: Tachykinin NK(3) receptors are widely expressed in the mouse gastrointestinal tract but their functional role in enteric neuromuscular transmission remains unstudied in this species. We investigated the involvement of NK(3) receptors in cholinergic neurotransmission in the mouse stomach and small intestine.

Experimental Approach: Muscle strips of the mouse gastric fundus and ileum were mounted in organ baths for tension recordings.

Interaction between liquid water and hydroxide revealed by core-hole de-excitation.

The hydroxide ion plays an important role in many chemical and biochemical processes in aqueous solution. But our molecular-level understanding of its unusual and fast transport in water, and of the solvation patterns that allow fast transport, is far from complete. One proposal seeks to explain the properties and behaviour of the hydroxide ion by essentially regarding it as a water molecule that is missing a proton, and by inferring transport mechanisms and hydration structures from those of the excess proton.

TRPV1 receptors on unmyelinated C-fibres mediate colitis-induced sensitization of pelvic afferent nerve fibres in rats.

Patients with inflammatory bowel disease often suffer from gastrointestinal motility and sensitivity disorders. The aim of the current study was to investigate the role of transient receptor potential of the vanilloid type 1 (TRPV1) receptors in the pathophysiology of colitis-induced pelvic afferent nerve sensitization. Trinitrobenzene sulphate (TNBS) colitis (7.

Cation-specific interactions with carboxylate in amino acid and acetate aqueous solutions: X-ray absorption and ab initio calculations.

Relative interaction strengths between cations (X = Li (+), Na (+), K (+), NH 4 (+)) and anionic carboxylate groups of acetate and glycine in aqueous solution are determined. These model systems mimic ion pairing of biologically relevant cations with negatively charged groups at protein surfaces. With oxygen 1s X-ray absorption spectroscopy, we can distinguish between spectral contributions from H 2O and carboxylate, which allows us to probe the electronic structure changes of the atomic site of the carboxylate group being closest to the countercation.

Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase.

Folate deficiency and resultant increased homocysteine levels have been linked experimentally and epidemiologically with neurodegenerative conditions like stroke and dementia. Moreover, folate deficiency has been implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that the pathogenic mechanisms include uracil misincorporation and, therefore, analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase (Ung-/-) versus wild-type controls.

Unintentional failure to assess for experience in senior undergraduate OSCE scoring.

Context: One goal of undergraduate assessment is to test students' (future) performance. In the area of skills testing, the objective structured clinical examination (OSCE) has been of great value as a tool with which to test a number of skills in a limited time, with bias reduction and improved reliability. But can OSCEs measure undergraduate internship expertise in basic clinical skills?

Methods: Undergraduate students (n = 32) were given a questionnaire listing 182 basic clinical skills.

Regulation of the transcriptional activity of poised RNA polymerase II by the elongation factor ELL.

Many developmentally regulated genes contain a poised RNA polymerase II (Pol II) at their promoters under conditions where full-length transcripts are undetectable. It has been proposed that the transcriptional activity of such promoters is regulated at the elongation stage of Pol II transcription. In Drosophila, the heat-shock loci expressing the Hsp70 genes have been used as a model for the regulation of the transcriptional activity of poised Pol II.

Pseudoequivalent nitrogen atoms in aqueous imidazole distinguished by chemical shifts in photoelectron spectroscopy.

The photoelectron spectra of aqueous imidazole are presented, and the N 1s and C 1s binding energies are assigned aided by density functional theory calculations. The chemical equivalency of the two nitrogens of the cationic form is directly identified by the occurrence of a single N 1s photoelectron peak, which results from the delocalization of the positive charge over the molecule as a consequence of the Cv symmetry of the system. In contrast to NMR measurements, the photoemission process is faster than the rapid proton exchange in the aqueous environment, making the pseudoequivalent nitrogens of the neutral state clearly distinguishable with a N 1s binding energy shift of 1.

Worms and the treatment of inflammatory bowel disease: are molecules the answer?

The lack of exposure to helminth infections, as a result of improved living standards and medical conditions, may have contributed to the increased incidence of IBD in the developed world. Epidemiological, experimental, and clinical data sustain the idea that helminths could provide protection against IBD. Studies investigating the underlying mechanisms by which helminths might induce such protection have revealed the importance of regulatory pathways, for example, regulatory T-cells.

Ionization of aqueous cations: photoelectron spectroscopy and ab initio calculations of protonated imidazole.

Photoelectron spectroscopy and ab initio calculations employing a nonequilibrium polarizable continuum model were employed for determining the vertical ionization potential of aqueous protonated imidazole. The experimental value of 8.96 eV is in in excellent agreement with calculations, which also perform quantitatively for ionization of aqueous alkali cations as benchmark species.

Electron dynamics in charge-transfer-to-solvent states of aqueous chloride revealed by Cl- 2p resonant Auger-electron spectroscopy.

Charge-transfer-to-solvent (CTTS) excited states of aqueous chloride are studied by a novel experimental approach based on resonant inner-shell photoexcitation, Cl(-)aq 2p --> e(i), i = 1-4, which denotes a series of excitations to lowest and higher CTTS states. These states are clearly identified through the occurrence of characteristic spectator Auger decays to double Cl 3p valence-hole states, where the CTTS states can be more stabilized as compared to single Cl(-)aq 2p core excitations and optical valence excitations. Furthermore, we have found for the first time that the CTTS electron e(i) bound by a single Cl 2p hole not only behaves as a spectator e(i) --> e'(i), bound by a double valence-hole state before relaxation of the excited electron (i) itself, but also shows electron dynamics to the relaxed lowest state, e(i) --> e'(1*).

Effect of cannabidiol on sepsis-induced motility disturbances in mice: involvement of CB receptors and fatty acid amide hydrolase.

Sepsis is an inflammatory condition that is associated with reduced propulsive gastrointestinal motility (ileus). A therapeutic option to treat sepsis is to promote intestinal propulsion preventing bacterial stasis, overgrowth and translocation. Recent evidence suggests that anti-oxidants improve sepsis-induced ileus.

Ionization of imidazole in the gas phase, microhydrated environments, and in aqueous solution.

Hydration of neutral and cationic imidazole is studied by means of ab initio and molecular dynamics calculations, and by photoelectron spectroscopy of the neutral species in a liquid microjet. The calculations show the importance of long range solvent polarization and of the difference between the structure of water molecules in the first shell around the neutral vs cationic species for determining vertical and adiabatic ionization potentials. The vertical ionization potential of neutral imidazole of 8.

[Use of a gelatine-thrombin matrix for closure of the access tract without a nephrostomy tube in minimally invasive percutaneous nephrolitholapaxy].

Background: The spectrum of percutaneous stone treatment was significantly widened following the introduction of the miniaturized percutaneous nephrolitholapaxy. At the end of the procedure usually a nephrostomy tube was placed to avoid urine paravasation and prolonged bleeding. In this work the tube-less mini-PCNL with direct closure of the access tract was compared to traditional mini-PCNL with placement of the nephrostomy tube.

Review article: gastrointestinal sensory and motor disturbances in inflammatory bowel disease - clinical relevance and pathophysiological mechanisms.

Background: It is well known that inflammation has a profound impact on the neuromuscular apparatus of the gastrointestinal tract during the inflammatory insult and in periods of remission, at the site of inflammation and at distance from this site. The importance of this interaction is illustrated by the higher prevalence of functional gut disorders in patients with inflammatory bowel disease.

Aims: To document the epidemiological and clinical significance of functional alterations of gut motility and sensitivity in patients with inflammatory bowel disease and to formulate potential pathophysiological mechanisms.

Functional study on TRPV1-mediated signalling in the mouse small intestine: involvement of tachykinin receptors.

Afferent nerves in the gut not only signal to the central nervous system but also provide a local efferent-like effect. This effect can modulate intestinal motility and secretion and is postulated to involve the transient receptor potential of the vanilloid type 1 (TRPV1). By using selective TRPV1 agonist and antagonists, we studied the efferent-like effect of afferent nerves in the isolated mouse jejunum.

Clinical skills training in a skills lab compared with skills training in internships: comparison of skills development curricula.

Context: The necessity of learning skills through "integrated skills training" at an undergraduate level has been supported by several studies. The University of Antwerp implemented undergraduate skills training in its renewed curriculum in 1998, after it was demonstrated that Flemish students did not master their medical skills as well as Dutch students who received "integrated skills training" as part of their undergraduate medical course.

Aim: The aim of this study was to compare the skill outcome levels of two different student populations: students who had been trained in basic clinical skills mainly through clinical internships in year 7 with students who had learned these skills through an integrated longitudinal programme in a special learning environment in years 1-5 prior to their internship experience.

Drosophila UTX is a histone H3 Lys27 demethylase that colocalizes with the elongating form of RNA polymerase II.

Histone H3 methylation at Lys27 (H3K27 methylation) is a hallmark of silent chromatin, while H3K4 methylation is associated with active chromatin regions. Here we report that a Drosophila JmjC family member, dUTX, specifically demethylates di- and trimethylated but not monomethylated H3K27. dUTX localization on chromatin correlates with the elongating form of RNA polymerase II (Pol II), and dUTX can associate with Pol II.

Ions at aqueous interfaces: from water surface to hydrated proteins.

The surfaces of aqueous solutions are traditionally viewed as devoid of inorganic ions. Molecular simulations and surface-selective spectroscopic techniques show, however, that large polarizable anions and hydronium cations can be found (and even enhanced) at the surface and are involved in chemistry at the air/water interface. Here, we review recent studies of ions at the air/water interface and compare from this perspective water with other polar solvents.

TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats.

Rats with experimental colitis suffer from impaired gastric emptying (GE). We previously showed that this phenomenon involves afferent neurons within the pelvic nerve. In this study, we aimed to identify the mediators involved in this afferent hyperactivation.

pH-induced protonation of lysine in aqueous solution causes chemical shifts in X-ray photoelectron spectroscopy.

We demonstrate the applicability of X-ray photoelectron spectroscopy to obtain charge- and site-specific electronic structural information of biomolecules in aqueous solution. Changing the pH of an aqueous solution of lysine from basic to acidic results in nitrogen 1s and carbon 1s chemical shifts to higher binding energies. These shifts are associated with the sequential protonation of the two amino groups, which affects both charge state and hydrogen bonding to the surrounding water molecules.

Experimental pancreatitis disturbs gastrointestinal and colonic motility in mice: effect of the prokinetic agent tegaserod.

Acute pancreatitis remains a potentially life-threatening disease associated with gastrointestinal motility disturbances. Prokinetic agents may be useful to overcome these motility disturbances. In this study, we investigated the effect of acute necrotizing pancreatitis (ANP) on gastrointestinal motility in female mice and evaluated the effect of tegaserod, a prokinetic 5-hydroxytryptamine-4 (5HT4) receptor agonist.

Hydrogen bonding in liquid water probed by resonant Auger-electron spectroscopy.

We have measured resonant and off-resonant Auger-electron spectra of liquid water. Continuumlike transitions near and above the O1s vertical ionization energy are identified by the characteristic normal Auger-electron spectra. On the contrary, well-resolved spectator shifts of the main Auger-electron peak are observed at the liquid-water O1s absorption main edge and near the absorption pre-edge.

Pharmacokinetics of mycophenolate mofetil in hematopoietic stem cell transplant recipients.

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is increasingly used in the prophylaxis of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HCT). Few pharmacokinetic data are available about the use of MMF for this indication. This case series aimed at analyzing the pharmacokinetics of MMF in a population of HCT recipients representative for everyday practice.