Intestinal anti-inflammatory activity of coumarin and 4-hydroxycoumarin in the trinitrobenzenesulphonic acid model of rat colitis. (17/71)

Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation.  (+info)

Comparison of the effect of 4-hydroxycoumarin and umbelliferone on the phase transition of dipalmitoylphosphatidylcholine (DPPC) bilayers. (18/71)

The study compares the effect of the addition of two coumarins: 4-hydroxycoumarin (4-HC) and 7-hydroxycoumarin (umbelliferone; UMB) on dipalmitoylphosphatidylcholine (DPPC) membranes. The study was based on microcalorimetric and fluorescence measurements. The examinations have shown that 4-HC changes parameters of phase transition of DPPC membranes to a greater degree than UMB. It is associated with different location of each coumarin in the lipid membrane, which is caused by different orientation of polarity of coumarin molecules. 4-HC molecules that are amphiphilic "along" incorporate inside the membrane interacting with lipid carbohydrate chains. UMB molecules amphiphilic "across" the molecule are not incorporated inside the membrane and do not interact with acyl chains.  (+info)

Clinical signs, laboratory changes and toxicokinetics of brodifacoum in the horse. (19/71)

Six horses gavaged with a commercial brodifacoum (BDF)-containing bait (Talone) at a dosage of 0.125 mg of BDF/kg of body weight showed weight loss, severe hypocoagulability and hemogram alterations. Four of the horses became depressed and anorectic; one required vitamin K1 therapy. Increases in clotting times were observed at 24 h in the partial thromboplastin time (PTT) followed by the thrombotest (TBT) and one-stage prothrombin time (PT) at 48 h. Elevated mean PTT, PT and TBT were observed from days 4 to 8 (p less than 0.05) with levels returning to pretreatment levels by day 12. Maximum prolongation was a fourfold increase in PTT (day 4), a 2.5-fold increase in TBT (day 6) and a twofold increase in PT (day 6). Thrombin clotting times remained unchanged. In two horses prolongation in clotting time did not normalize until day 23. The mean hematocrit (0.38 +/- 0.01 L/L) was decreased (p less than 0.05) from day 8 (0.33 +/- 0.02 L/L) to day 14 (0.33 +/- 0.01 L/L). The hemoglobin concentration and erythrocyte numbers were decreased (p less than 0.05) from day 6 (20.1%, 17.6% respectively) to day 14 (22%, 20% respectively). Platelet counts decreased on day 6 (17.2%) to nine (14.6%). No other significant changes were observed in routine hematological and serum biochemical parameters. Peak plasma concentrations of BDF occurred 2 to 3 h after oral administration; two horses had detectable levels of BDF at nine days. Pharmacokinetic evaluation indicated that BDF has a half-life of 1.22 +/- 0.22 days, a body clearance of 1073.1 +/- 53.21 mL/kg/day, a volume of distribution of 1853.7 +/- 26.41 ng-day/mL and closely approximates a one-compartment model in the elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS)  (+info)

Electrochemical synthesis of 4-(dihydroxyphenylthio)-2H-chromen-2-one derivatives. (20/71)

The 4-(dihydroxyphenylthio)-2H-chromen-2-one derivatives have been synthesized by direct electrochemical oxidation of catechols in the presence of 4-mercaptocoumarin as a nucleophile in water/acetonitrile (50/50) solution, in a one-pot process, at carbon rod electrode, in an undivided cell and in constant current conditions, through an EC mechanism. The products are characterized by spectra data. Besides, the difference in electrochemical oxidation of catechol in the presence of 4-hydroxycoumarin and 4-mercaptocoumarin explained by computational structure, natural bond orbital (NBO) analysis and density functional theory (DFT: B3LYP/6-31G*//B3LYP/6-31G*) based methods, using the GAUSSIAN 98 package of programs.  (+info)

Thymic cystic degeneration, pseudoepitheliomatous hyperplasia, and hemorrhage in a dog with brodifacoum toxicosis. (21/71)


Investigating unexpected INRs: in search of the culprit--adherence, interactions, genetics, and superwarfarin. (22/71)

Treatment with coumarin derivatives is highly individualised due to high intra- and inter-individual variation in dose response and risks of severe bleeding or thromboembolic complications. Treatment focuses on reaching and maintaining a stable target international normalised ratio (INR). However, unexpected INRs that are not explained by noncompliance or vitamin K intake may occur. Here we describe seven cases of unexpected INRs, and provide clues that clarify the underlying mechanism.  (+info)

Pseudo-cyclic face-to-face rigid structure caused by the intramolecular ion pair effect. (23/71)


Consequences of the Y139F Vkorc1 mutation on resistance to AVKs: in-vivo investigation in a 7th generation of congenic Y139F strain of rats. (24/71)