Allein mit Medikamenten kommt man dem Reizdarmsyndrom (RDS) in der Regel nicht bei. Einen guten Effekt erzielt einer Studie zufolge die darmbezogene Hypnotherapie — auch in Gruppenanwendung.
Funktionelle Dyspepsie, also Reizmagenbeschwerden ohne strukturelle Erkrankung, ist häufig — doch gibt es keine Therapie-Leitlinie. Nun wurde ein Behandlungsschema auf Basis eines Studien-Reviews ...vorgelegt.
Background
In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract. Today, our knowledge of the ingredients of the Cannabis ...plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors. After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS. Cannabinoid receptors and their endogenous ligands, the endocannabinoids, participate in the regulation of GI motility, secretion, and the maintenance of the epithelial barrier integrity. In addition, other receptors, such as the transient receptor potential cation channel subfamily V member 1 (TRPV1), the peroxisome proliferator‐activated receptor alpha (PPARα) and the G‐protein coupled receptor 55 (GPR55), are important participants in the actions of CBs in the gut and critically determine the course of bowel inflammation and colon cancer.
Purpose
The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.
The review summarizes important and recent findings on the role of cannabinoid receptors and their ligands in the gastrointestinal tract. It emphasizes the role of the endocannabinoid system in disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.
Viele Medikamente zur Behandlung des Reizdarmsyndroms (RDS) erreichen nicht den deutschen Markt. Eine neue Studie zeigt aber wieder, dass auch Yoga und eine FODMAP-reduzierte Diät wirksam sind.
Background
Diarrhea‐predominant irritable bowel syndrome (IBS‐D) is a functional gastrointestinal (GI) disorder, which occurs more frequently in women than men. The aim of our study was to determine ...the role of activation of classical estrogen receptors (ER) and novel membrane receptor, G protein‐coupled estrogen receptor (GPER) in human and mouse tissue and to assess the possible cross talk between these receptors in the GI tract.
Methods
Immunohistochemistry was used to determine the expression of GPER in human and mouse intestines. The effect of G‐1, a GPER selective agonist, and estradiol, a non‐selective ER agonist, on muscle contractility was characterized in isolated preparations of the human and mouse colon. To characterize the effect of G‐1 and estradiol in vivo, colonic bead expulsion test was performed. G‐1 and estradiol activity on the visceral pain signaling was assessed in the mustard oil‐induced abdominal pain model.
Key Results
GPER is expressed in the human colon and in the mouse colon and ileum. G‐1 and estradiol inhibited muscle contractility in vitro in human and mouse colon. G‐1 or estradiol administered intravenously at the dose of 20 mg/kg significantly prolonged the time to bead expulsion in females. Moreover, G‐1 prolonged the time to bead expulsion and inhibited GI hypermotility in both genders. The injection of G‐1 or estradiol resulted in a significant reduction in the number of pain‐induced behaviors in mice.
Conclusions and Inferences
GPER and ER receptors are involved in the regulation of GI motility and visceral pain. Both may thus constitute an important pharmacological target in the IBS‐D therapy.
Estrogen receptors (ER) and G protein‐coupled estrogen receptors are involved in colonic motility and visceral pain. GPER is expressed in the human colon. G‐1, a selective GPER agonist, and estradiol, a non‐selective ER agonist, inhibited muscle contractility in vitro in human colon.
Background
G protein‐coupled receptor 55 (GPR55) is a lysophospholipid receptor responsive to certain cannabinoids. The role of GPR55 in inflammatory processes of the gut is largely unknown. Using ...the recently characterized GPR55 inhibitor CID16020046, we determined the role of GPR55 in experimental intestinal inflammation and explored possible mechanisms of action.
Methods
Colitis was induced by either 2.5% dextran sulfate sodium (DSS) supplemented in the drinking water of C57BL/6 mice or by a single intrarectal application of trinitrobenzene sulfonic acid (TNBS).
Key Results
Daily application of CID16020046 (20 mg/kg) significantly reduced inflammation scores and myeloperoxidase (MPO) activity. In the DSS colitis model, levels of tumor necrosis factor alpha (TNF‐α) and interleukin 1 beta (IL‐1β), and the expression of cyclooxygenase (Cox)‐2 and signal transducer and activator of transcription 3 (STAT‐3) were reduced in colon tissues while in TNBS‐induced colitis, levels of Cox‐2, IL‐1β and IL‐6 were significantly lowered. Evaluation of leukocyte recruitment by flow cytometry indicated reduced presence of lymphocytes and macrophages in the colon following GPR55 inhibition in DSS‐induced colitis. In J774A.1 mouse macrophages, inhibition of GPR55 revealed reduced migration of macrophages and decreased CD11b expression, suggesting that direct effects of CID16020046 on macrophages may have contributed to the improvement of colitis. GPR55−/− knockout mice showed reduced inflammation scores as compared to wild type mice in the DSS model suggesting a pro‐inflammatory role in intestinal inflammation.
Conclusions & Inferences
Pharmacological blockade of GPR55 reduces experimental intestinal inflammation by reducing leukocyte migration and activation, in particular that of macrophages. Therefore, CID16020046 represents a possible drug for the treatment of bowel inflammation.
The unknown role of the atypical cannabinoid receptor GPR55 was investigated in intestinal inflammation using a novel GPR55 antagonist and GPR55−/− knockout mice. The GPR55 antagonist improved intestinal inflammation macroscopically, decreased levels of pro‐inflammatory cytokines and reduced leukocyte recruitment to the colon. The GPR55−/− knockout mice were less susceptible to intestinal inflammation than their wild type littermates suggesting that GPR55 may be an important target for future cannabinoid‐based treatment of bowel inflammation.
View the podcast on this paper at the following sites:iTunes: https://itunes.apple.com/dk/podcast/neurogastroenterology-motility/id1030702548Youtube: https://www.youtube.com/watch?v=0lsPgWalBv8&feature=em-upload_owner#action=share
Recent reports suggested that the activation of Transient Receptor Potential Vanilloid 4 (TRPV4) receptors in the gastrointestinal tract has pro‐inflammatory effects. In this study, we demonstrated ...for the first time that TRPV4 mRNA expression is up‐regulated in patients with inflammatory bowel diseases (IBD). Furthermore, selective blockade of TRPV4 in the 2,4,6‐trinitrobenzenesulfonic acid animal model alleviates colitis and pain associated with the intestinal inflammation. Our study indicates that TRPV4 may play a role in mechanisms of defense in intestinal inflammation and that TRPV4 may be an attractive target for future systemic or topic anti‐inflammatory treatment in patients with IBD.
Hydride ion formation in stoichiometric UO2 Flitcroft, J. M; Molinari, M; Brincat, N. A ...
Chemical communications (Cambridge, England),
2015-Nov-21, Letnik:
51, Številka:
9
Journal Article
Recenzirano
We investigated atomic hydrogen solubility in UO
2
using DFT. We predict that hydrogen energetically prefers to exist as a hydride ion rather than form a hydroxyl group by 0.27 eV, and that on ...diffusion hydrogen's charge state will change. The activation energy for conversion of hydride to hydroxyl is 0.94 eV.
We investigated hydrogen solubility in UO
2
using DFT and predicted that hydrogen species energetically prefers to exist as a hydride ion rather than a proton in a hydroxyl group and on diffusion hydrogen's charge state will change.
Kaffeekonsum ist dosisabhängig mit einem niedrigeren Risiko für die Entwicklung von Gallensteinen assoziiert. Das hat eine Metaanalyse von fünf prospektiven Studien ergeben.
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