Investigation of solubility properties of nifluminic acid containing cyclodextrins and polyvidone

One of the most important task of the pharmaceutical technology is to reach a possible high gastrointestinal absorbtion of the active ingredient. Therefore, it is necessary to have a good solubility in the gastric/intestinal medium. In this way the applied drug quantity and unwanted side effects can be reduced with solubility increasing. The water-insoluble drug's solubility and bioavailability can be increased by the alteration of their physicochemical properties. Nifluminic acid is a frequently used anti-inflammatory drug with low aqueous solubility. Inclusion complexation with cyclodextrins is an efficacious method to improve the solubility, stability and bioavailability. Ternary systems were prepared and investigated to use nifluminic acid, hydoxypropyl-beta-cyclodextrin and polyvidone. The aims of the study were to investigate the solubility rate, the in vitro diffusion ability, to determine the n-octanol/water partition coefficient, and to study the thermoanalitycal properties of products. The results suggested that complexation with cyclodextrin and the use of polyvidone is better method than to prepare binary systems. Inclusion complexation was presumed in the event of the ternary composition to improve the bioavailability of nifluminic acid.     

Impact of a novel cardioprotective agent on the ischaemia-reperfusion-induced Akt kinase activation

Cardioprotective effect of a free radical-scavenging compound (HO-3073) was examined during ischaemia-reperfusion (IR) in isolated heart perfusion system and its influence on the pro-survival Akt signalling pathway was addressed. Rat hearts were perfused according to the Langendorff method and subjected to a global 25-min ischaemia and 15, 45 and 90-min reperfusion either untreated or treated with HO-3073 (2, 5 and 10 microM) and/or wortmannin (100 nM, inhibitor of phosphatidylinositol-3-kinase). HO-3073 facilitated the recovery of myocardial energy metabolism as assessed by 31P NMR spectroscopy (creatine phosphate recovery in reperfusion was 76+/-5%, while in untreated hearts 32+/-4%). Functional performance of the hearts followed by a left ventricular balloon manometer was also markedly improved by HO-3073 administration (recovery of rate-pressure product related to normoxia was 47+/-3%, while in untreated hearts 12+/-3%). HO-3073 diminished the infarct size measured by TTC staining (29+/-6% as opposed to 64+/-7% in untreated ischaemia-reperfusion). HO-3073 also significantly attenuated lipid peroxidation (thiobarbituric acid reactive substances) and protein oxidation (protein carbonyl content) compared to untreated hearts. HO-3073 enhanced the ischaemia-reperfusion-triggered phosphorylation of Akt-1 (activation) and glycogen synthase kinase-3 beta (inactivation) as evidenced by Western blot analysis. Wortmannin co-administration neutralised the beneficial effects of HO-3073 on cardiac energetics, contractile function, infarct size, as well as Akt signalling. Our results first display that a radical-scavenging molecule possesses the ability to intensify the pro-survival functioning of phosphatidylinositol-3-kinase/Akt pathway, which is presumed to play an additive role in the cardioprotective properties of HO-3073.     

The role of the tissue adhesive fibrin seal (FS) in esophageal anastomoses

Following Surgical Removal Of Esophageal Tumors, Leakage And Medistinitis Is A Frequent And Often Fatal Complication. A New Method Has Been Developed To Seal Suture Lines In The Esophagus With Preparations Containing Fibrinogen, Cold Insoluble Globulin, Factor Xiii, Antiplasmin, Platelet Growth Factor, Thrombin, And Calcium Chloride. In Experimental Animals Operated On By Standard Methods, Esophageal Leakage Developed In 50% Of The Animals And Death In 40%. By Contrast, In Treated Animals, Esophageal Leak And Death Developed In Only 20%. More Adhesions Were Found In Treated Animals Than In Control Animals.     

The application of tissue adhesives in small bowel anastomoses

One layer everted end-to-end anastomosis was performed on the small bowel of mongrel dogs. Cultures of Serratia marcescens were injected into the lumen. Twenty-four hours later the animals were reexplored, and peritoneal cultures were observed. In animals where Fibrin Seal (consisting of fibrinogen, cold insoluble globulin, factor XIII, platelet growth factor, antiplasmin, thrombin, and calcium chloride) was applied to the suture line, negative cultures were found except for two experiments in which dehiscence or contamination from the Serratia injection site occurred.