Targeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal

Irritable bowel syndrome is a group of functional gastrointestinal disorders with not yet fully clarified etiology. Recent evidence suggesting that mast cells may play a central role in the pathogenesis of irritable bowel syndrome paves the way for agents targeting histamine receptors as a potential therapeutic option in clinical treatment. In this review, the role of histamine and histamine receptors is debated. Moreover, the clinical evidence of anti-histamine therapeutics in irritable bowel syndrome is discussed

Usefulness of Contrast-Enhanced Ultrasound in the Differentiation between Hepatocellular Carcinoma and Benign Liver Lesions

A differentiation between hepatocellular carcinoma (HCC) and benign liver lesions is required. The aim of the study was to perform an analysis of the time of enhancement of focal liver lesions in a contrast-enhanced ultrasound (CEUS) examination. The curves of enhancement and the homogeneity of the tumor enhancement were assessed. The study included 52 patients with diagnoses of hepatocellular adenoma (18), focal nodular hyperplasia (11) and HCC (28). The study included magnetic resonance imaging or computed tomography and a comparison of the obtained information with CEUS. In the benign lesions groups after 20–30 s, the enhancement was similar to the liver parenchyma. In the HCC group, the enhancement was slightly less intense compared to the liver parenchyma and the benign lesions. The difference of the enhancement in the arterial phase (benign lesions vs. HCC) was p = 0.0452, and the difference of enhancement in the late venous phase (benign lesions vs. HCC) was p = 0.000003. The homogeneity of the enhancement (benign lesions vs. HCC), respectively, was p = 0.001 in the arterial phase, p = 0.0003 in the portal venous phase and p = 0.00000007 in the late venous phase. Liver tumors can be classified as benign when they are homogenous in the arterial phase and don’t present washout. HCC in the arterial phase is inhomogeneous and washout is observed in the venous phases. When radiological symptoms suggest malignant lesion, CEUS can be used to select the best biopsy access

A Crosstalk between the Cannabinoid Receptors and Nociceptin Receptors in Colitis—Clinical Implications

Inflammatory bowel diseases (IBD) refer to a group of gastrointestinal (GI) disorders with complex pathogenesis characterized by chronic intestinal inflammation with a variety of symptoms. Cannabinoid and nociceptin opioid receptors (NOPs) and their ligands are widely distributed in the GI tract. The nociceptin opioid receptor is a newly discovered member of the opioid receptor family with unique characteristics. Both cannabinoid and NOP systems exhibit antinociceptive and anti-inflammatory activity and contribute to maintaining proper motility, secretion and absorption in the GI tract. Furthermore, they influence high and low voltage calcium channels, which play a crucial role in the processing of pain, and share at least two kinases mediating their action. Among them there is NF-κB, a key factor in the regulation of inflammatory processes. Therefore, based on functional similarities between cannabinoid and nociceptin receptors and the anti-inflammatory effects exerted by their ligands, there is a high likelihood that there is an interaction between cannabinoid receptors 1 and 2 and the nociceptin receptor in colitis. In this review, we discuss potential overlaps between these two systems on a molecular and functional level in intestinal inflammation to create the basis for novel treatments of IBD

Use of Satellite Data in Monitoring of Hydrophysical Parameters of the Baltic Sea Environment

Intensive development of infrastructure for fast processing of outsized amount of space-borne data enables now to use the satellite data for operational controlling the state of its environment. In our presentation we show some examples of analysis of processes in marine environment which are possible due to satellite data and algorithms of its processing developed in SatBaltic Project. It concerns supporting of modelling of solar energy inflow to the sea with space-borne input data, identification and analysis of sea ice cover, supporting of oil spill detection, and identification of phenomena which modify spatial distribution of the sea surface temperature

Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment

Although development of biologics has importantly improved the effectiveness in inducing and maintaining remission in inflammatory bowel disease (IBD), biologic therapies still have several limitations. Effective, low-cost drug therapy with good safety profile and compliance is therefore a substantial unmet medical need. A promising target for IBD treatment strategies are Janus kinase (JAK) inhibitors, which are small molecules that interact with cytokines implicated in pathogenesis of IBD. In contrast to monoclonal antibodies, which are able to block a single cytokine, JAK inhibitors have the potential to affect multiple cytokine-dependent immune pathways, which may improve the therapeutic response in some IBD patients. Tofacitinib, inhibiting signaling via different types of JAKs, has been already approved for ulcerative colitis, and several other small-molecule are still under investigation. However, one of the main concerns about using JAK inhibitors is the risk of thromboembolic events. Moreover, patients with COVID-19 appear to have an increased susceptibility for immunothrombosis. Therefore, thrombotic complications may become a serious limitation in the use of JAK inhibitors in the SARS-CoV-2 pandemic. As many questions about safety and efficacy of small molecules still remain unclear, in our review we present the current data regarding approved JAK inhibitors, as well as those in clinical development for the treatment of IBD

Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis

Background: Recent studies suggest that lipids, including free fatty acids (FFAs), are necessary for proper μ opioid receptor (MOR) binding and that activation of opioid receptors (ORs) improves intestinal inflammation. The objective of the study was to investigate a possible interaction between the ORs and FFA receptors (FFARs) ligands in the colitis. Methods: The potential synergistic effect of ORs and FFARs ligands was evaluated using mouse model of acute colitis induced by dextran sulfate sodium (DSS, 4%). Compounds were injected intraperitoneally (i.p.) once or twice daily at the doses of 0.01 or 0.02 mg/kg body weight (BW) (DAMGO—an MOR agonist), 0.3 mg/kg BW (DPDPE—a δ OR (DOR) agonist) and 1 mg/kg BW (naloxone—a non-selective OR antagonist, GLPG 0974—a FFAR2 antagonist, GSK 137647—a FFAR4 agonist and AH 7614—a FFAR4 antagonist) for 4 days. Results: Myeloperoxidase (MPO) activity was significantly decreased after DAMGO (0.02 mg/kg BW) and GSK 137647 (1 mg/kg BW) administration and co-administration as compared to DSS group. Conclusions: Treatment with ligands of ORs and FFARs may affect the immune cells in the inflammation; however, no significant influence on the severity of colitis and no synergistic effect were observed