Therapy trials with bacterial compounds in irritable bowel syndrome (IBS) have produced conflicting results. This study was performed in 1988 and 1989, and was re-analysed according to current IBS standards. Two hundred ninety-seven patients with lower abdominal symptoms diagnosed as IBS were treated for 8 weeks by the compound ProSymbioflor((R)) (Symbiopharm GmbH, Herborn, Germany), an autolysate of cells and cell fragments of Enterococcus faecalis and Escherichia coli, or placebo in a double-blinded, randomized fashion. Patients were seen weekly by the physician, who assessed the presence of core IBS symptoms. Responders had at least a 50% decrease in global symptom score (GSS) and in abdominal pain score (APS) reports at >/=1 visit during treatment. The responder rate in GSS to the drug was 102/149 (68.5%) in comparison to placebo with 56/148 (37.8%) (P < 0.001), the improvement in APS was 108/149 (72.5%) and 66/148 (44.6%) respectively (P = 0.001). The number-needed-to-treat was 3.27 for GSS and 3.59 for the APS report. Kaplan-Meier analysis revealed a mean response time of 4-5 weeks for active treatment and more than 8 weeks for placebo (P < 0.0001). Treatment of IBS with the bacterial lysate ProSymbioflor is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners.

Treatment of IBS with the probiotic Symbioflor-2 is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners and by gastroenterologists.

AimsThe study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN " 50 mg enteric coated tablets. MethodsDiclofenac (48 mg) was administered topically three times daily for 3 days onto a defined area of the thigh of 12 healthy males. After a 14-day wash out period, subjects were orally treated with 50 mg diclofenac three times daily for 3 days. In vivo microdialysis in subcutaneous and muscle tissues was per formed immediately after the final doses from both treatments on day 4, and 48 h later. Plasma samples were taken simultaneously. ResultsThe relative bioavailability of diclofenac in subcutaneous adipose and skeletal muscle tissue was substantially higher after topical compared with oral dosing (324% and 209%, respectively) whereas relative plasma bioavailability was 50-fold lower. Plasma C max values were approximately 250-fold lower after topical compared with oral drug administration (i.e. median values = 4.89 ng mL -1 ; 95% CI: 3.37-7.68 and 1240 ng mL -1 ; 95% CI: 787-1389 ng mL -1 ). Both treatments were well tolerated. ConclusionsOwing to its favourable penetration characteristics and low systemic availability, MIKA Diclofenac Spray Gel 4% is a rational alternative to oral diclofenac formulations for the treatment of inflammatory soft tissue conditions.

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The rate of transition from an unstable to a stable complex and the dependence of this on the number of fatty acid ligands present was determined for the binding of warfarin on human serum albumin. When oleate or palmitate was added in amounts up to 2:1 excess to human serum albumin Solutions the measured rate constant for the transition (k 2) was increased in comparison with fatty acid free albumin. When the fatty acid concentration is further increased, k 2 decreases. When the fatty acid level is 2 to 3 mol per mol albumin, the affinity constant (K A) is higher than for fatty acid free Solutions. With higher ratios the value for K A is reduced. According to the observed changes in kinetic parameters, the binding of warfarin is apparently affected allosterically. A reduced plasma protein binding of coumarins should be expected when fatty acid levels are raised over a prolonged period. Einfluß von Palmitat und Oleat auf die Bindung von Warfarin an menschliches Serumalbumin: Stopped-Flow Untersuchungen Zusammenfassung: Bei der Bindung von Warfarin an Humanserumalbumin wird die Geschwindigkeit der Umlagerung vom instabilen in den stabilen Warfarin-Humanserumalbuminkomplex von der Anzahl der Fettsäureliganden bestimmt. Wird Oleat oder Palmitat zu einer Lösung von Humanserumalbumin gegeben, werden bis zum Überschuß Von 2:1 höhere Werte für die Geschwindigkeitskonstante der Umlagerung (k 2) als bei fettsäurefreiem Humanserumalbumin gemessen. Bei weiterer Erhöhung der Fettsäufekonzentration | nimmt k 2 ab. Auch die Bindüngskönstante (K A) ist abhängig vom Grad der Komplexierung des Humanserum-J albumins mit den freien Fettsäuren. Bei 2 bis 3 mol Fettsäure pro mol Albumin werden höhere Affmitätskon-' • • stanten gefunden als in fettsäurefreien Albuminlösungen; bei einem höherem Verhältnis sind die Werte für K A erniedrigt. Entsprechend den Änderungen der kinetischen Kenngrößen wird die Warfarinbindung offensichtlich alloste-' risch beeinflußt. Bei längerfristig erhöhter Fettsäurekonzentration im menschlichen Plasma ist daher eine verminderte Eiweißbindung für Cumafine anzunehmen.