Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.
Im Rahmen des Forschungsprojektes “Hydrophobierende und/oder porenverschließende Injektionsmittel“ (gefördert durch die FFG Forschungsförderungsgesellschaft) wurden die Wirksamkeit und die Anwendungsgrenzen von hydrophobierenden und/oder porenverschließenden Injektionsmitteln zur nachträglichen Horizontalabdichtung von Bruchsteinmauerwerk unter besonderer Berücksichtigung der Einbringungsart untersucht. In Abhängigkeit des Durchfeuchtungsgrades (gering, mittel, hoch) und der Einbringungsart (Hohldochtverfahren, Infusionsschlauchverfahren, Injektionscremeverfahren, Druckverfahren) wurde die Wirksamkeit von sieben Injektionsmitteln an vier unterschiedlichen in der Wiener Bausubstanz häufig vorkommenden Gesteinstypen (St. Margarethener Kalksandstein, Leithakalk, Rohrbacher Konglomerat, Quarzsandstein aus der Flyschzone) im Labor, an Versuchspfeilern und an zwei Objekten untersucht. Die Untersuchungen haben hinsichtlich des Einsatzes von hydrophobierenden und/oder porenverschließenden Injektionsmitteln zur nachträglichen Horizontalabdichtung von Bruchsteinmauerwerk sehr unterschiedliche Ergebnisse gebracht, wodurch an jedem Objekt vor Durchführung der Injektionsarbeiten im Rahmen der Bauwerksdiagnostik eine Gesteinserkundung hinsichtlich der physikalischen Eigenschaften zur Auswahl objektspezifisch geeigneter Injektionsmittel erforderlich ist. Post‐construction horizontal waterproofing of quarry stone masonry by means of injection technology. In the context of the research project Hydrophobic and/or capillary‐obstructing injection materials, subsidised by the Austrian Research Promotion Agency (FFG), hydrophobic and/or capillary‐obstructing injection materials for post‐construction horizontal waterproofing of quarry stone masonry were tested with regard to effectiveness and limitations of application, in consideration of the way in which the injection material is introduced. The effectiveness of seven injection materials was tested on four different types of stone that are typical of masonry in Vienna (St. Margarethen sandy limestone, Leitha limestone, Rohrbach conglomerate, and quartz sandstone from the Flysch zone), for different degrees of dampness (low, medium, high) and different ways of introducing the sealing material (cardboard tube, flexible plastic tube, paste injection, pressure injection). The tests were carried out in the laboratory, on test pillars built for this purpose and two buildings. Regarding the effects of hydrophobic and/or capillary‐obstructing injection materials for post‐construction horizontal waterproofing of quarry stone masonry, the tests performed have shown highly diverse results: therefore, before injections are applied, it is necessary in each case to analyse the physical properties of the masonry in question in the context of building diagnostics in order to be able to select an injection material that is suitable for this object.
The effect of HD‐03, a herbal formulation was investigated on the hepatocellular antioxidant defence system in CCl4 treated rats. Three doses of CCl4 were administered orally with liquid paraffin (1:1) to induce hepatic damage. Twenty four hours after the last dose, blood was collected by decapitation for the estimation of serum ALT and AST. The levels of antioxidant enzymes, lipid peroxidation and glycogen in the liver were estimated. Nineteen days pretreatment with HD‐03 (750 mg/kg) significantly reversed CCl4‐induced changes in serum ALT and AST levels. HD‐03 pretreatment also significantly reversed the CCl4‐induced changes in the different components of the cellular antioxidant system and lipid peroxidation. Pretreatment with HD‐03 significantly restored the hepatic glycogen levels which were depleted in CCl4 intoxicated rats. The observed reversal produced by HD‐03 in the serum AST and ALT may be due to the membrane stabilizing potential which helps in preventing the leakage of intracellular enzymes into the systemic circulation. The increase in the hepatic glycogen levels in HD‐03 pretreated rats, indicates its preventive effect on subcellular injury caused by CCl4, which leads to glycogenolysis, as a result of disturbance in the intracellular Ca+2 pool. The inhibition of lipid peroxidation and enhancement in the activity of antioxidant enzymes by HD‐03 may be due to the direct free radical scavenging activity and reactivation of these enzymes in the liver. Thus the antioxidant potential and inhibitory effect onlipid peroxidation may play an important role in the antihepatotoxic activity of HD‐03. © 1998 John Wiley & Sons, Ltd.
BackgroundThe role of G protein-coupled receptor (GPR40), which is highly expressed in pancreatic beta cells, has been studied extensively in the amelioration of beta cell dysfunction in T2D using rat and mouse islets, beta cell lines and in animal models of diabetes. But its potential as a therapeutic target has not been fully explored. This aim of the study is to evaluate the therapeutic potential of CNX-011-67, a highly selective, potent and orally bioavailable GPR40 agonist, in controlling diabetes and other metabolic parameters.MethodsSeven week old male ZDF rats were treated with either vehicle or CNX-011-67, 5 mg/kg twice daily, for seven weeks. The animals were subjected to oral glucose tolerance and insulin tolerance tests. Plasma glucose, insulin, triglyceride, HbA1c, fructosamine and free fatty acids were measured at selected time points. Pancreas from control and treated animals were subjected to insulin and pancreatic and duodenal homeobox 1 (PDX1) immunohistochemistry and were also evaluated by electron microscopy. Also the potential impact of CNX-011-67 on islet insulin secretion, content, ATP levels and markers of both glucose oxidation, beta cell health in rat islets under chronic glucolipotoxic conditions was evaluated.ResultsTreatment of male ZDF rats with CNX-011-67 for 7 weeks significantly enhanced insulin secretion in response to oral glucose load, delayed the onset of fasting hyperglycemia by 3 weeks, reduced nonfasting glucose excursions, fasting free fatty acids and triglyceride levels. A significant increase in PDX1 expression and insulin content and reduction in plasma fructosamine, HOMA-IR, and beta cell apoptosis were observed. CNX-011-67 improves glucose mediated insulin secretion, insulin gene transcription and islet insulin content in cultured rat islets under chronic glucolipotoxic condition. Also enhanced glucose oxidation in the form of increased islet ATP content and overall improvement in beta cell health in the form of reduced expression of stress markers (TXNIP and CHOP mRNA) were observed.ConclusionsThese findings, suggest that long-term oral therapy with CNX-011-67 could be of clinical value to provide good glycemic control and improve islet beta cell function.
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