174. Die Therapie des candida-induzierten perforierten Ulcus duodeni

Zusammenfassung In 7 Fällen unter 98 Patienten mit perforierten Duodenalulcera konnte mikrobiologisch und histologisch bewiesen werden, daß an der Perforation Candidamykosen beteiligt waren. Alle Patienten hatten Risikofaktoren wie Diabetes mellitus, Mangelernährung, Tumorleiden, oder sie hatten zuvor ein Antibioticum oder ein Antacidum erhalten. Nach Diagnosestellung wurde die postoperative Behandlung auf Antimycotica umgestellt. Bei einer Patientin wurde die Candidainfektion nicht rechtzeitig erkannt. Sie verstarb an einer Candidasepsis. Die anderen Patienten überlebten.     

Kunststoffnetze aus Polypropylen beeinflussen das Wachstum humaner Zellen in vitro Eine experimentelle Studie Eine experimentelle Studie

Hintergrund. Ziel der Untersuchung war es, den Einfluss von Kunststoffnetzen aus Polypropylen auf die Proliferation und die Apoptose (programmierter Zelltod) von Zellen in vitro zu testen.     

Improvement in the healing of colonic anastomoses by vitamin B5 and C supplements. Experimental study in the rabbit

To study the effects of vitamins B5 and C on the healing process of colonic anastomoses, 3 groups of 20 rabbits were given daily either placebo (group A), or vitamin B5 (100 mg/kg: group B) or vitamin C (100 mg/kg: group C). After 8 days of supplementation, via a midline incision and under general anaesthesia, 2 colonic segments were removed, and the continuity was restored. On the 3rd post-operative day, the rabbits were killed and the anastomoses were removed. Mechanical properties of both normal colon and anastomoses were determined by using bursting pressure tests, number of burst anastomoses, fibroblast count, hydroxyproline concentration and determination by microanalysis of trace element content: Mg, P, S, Ca, Fe, Cu, Zn and Mn. Vitamin B5 (p = 0.03) and vitamin C (p less than 0.01) both decreased the number of burst anastomoses. Furthermore the required bursting pressure values were higher with vitamin C (p = 0.01) than in controls. Both vitamins restored normal Zn levels at the anastomotic site, whereas these levels decreased on the 3rd post-operative day during the normal healing process of colonic anastomosis. Moreover, vitamins B5 and C increased Fe, Cu and Mn levels, which are intimately all involved in collagen synthesis. Vitamins B5 and C enhance the colonic wound healing process in the rabbit, acting together in synergy in vivo as well as in vitro, as previously demonstrated.     

Cell‐free supernatants of Escherichia coli Nissle 1917 modulate human colonic motility: evidence from an in vitro organ bath study

Abstract Clinical studies have shown that probiotics influence gastrointestinal motility, e.g. Escherichia coli Nissle 1917 (EcN) (Mutaflor^®) proved to be at least as efficacious as lactulose and more potent than placebo in constipated patients. As the underlying mechanisms are not clarified, the effects of EcN culture supernatants on human colonic motility were assessed in vitro. Human colonic circular smooth muscle strips (n = 94, 17 patients) were isometrically examined in an organ bath and exposed to different concentrations of EcN supernatants. Contractility responses were recorded under (i) native conditions, (ii) electrical field stimulation (EFS), (iii) non‐adrenergic non‐cholinergic conditions, and (iv) enteric nerve blockade by tetrodotoxin (TTX). As concentrations of acetic acid were increased in EcN supernatants, contractility responses to acetic acid were additionally tested. EcN supernatants significantly increased the maximal tension forces both at low and high concentrations. Neither blockade of both adrenergic and cholinergic nerves nor application of TTX abolished these effects. EFS‐induced contractility responses were not altered after exposure to EcN supernatants. Acetic acid elicited effects comparable to EcN supernatants only under TTX conditions. EcN supernatants modulate in vitro contractility of the human colon. As neither partial nor TTX blockade of enteric nerves abolished these effects, EcN supernatants appear to enhance colonic contractility by direct stimulation of smooth muscle cells. Active metabolites may include other substances than acetic acid, as acetic acid only partially resembled the effects elicited by EcN supernatants. The data provide a rationale for therapeutical application of probiotics in gastrointestinal motility disorders.     

Prostaglandin ethanolamides (prostamides): in vitro pharmacology and metabolism

We investigated whether prostaglandin ethanolamides (prostamides) E(2), F(2alpha), and D(2) exert some of their effects by 1) activating prostanoid receptors either per se or after conversion into the corresponding prostaglandins; 2) interacting with proteins for the inactivation of the endocannabinoid N-arachidonoylethanolamide (AEA), for example fatty acid amide hydrolase (FAAH), thereby enhancing AEA endogenous levels; or 3) activating the vanilloid receptor type-1 (TRPV1). Prostamides potently stimulated cat iris contraction with potency approaching that of the corresponding prostaglandins. However, prostamides D(2), E(2), and F(2alpha) exhibited no meaningful interaction with the cat recombinant FP receptor, nor with human recombinant DP, EP(1-4), FP, IP, and TP prostanoid receptors. Prostamide F(2alpha) was also very weak or inactive in a panel of bioassays specific for the various prostanoid receptors. None of the prostamides inhibited AEA enzymatic hydrolysis by FAAH in cell homogenates, or AEA cellular uptake in intact cells. Furthermore, less than 3% of the compounds were hydrolyzed to the corresponding prostaglandins when incubated for 4 h with homogenates of rat brain, lung, or liver, and cat iris or ciliary body. Very little temperature-dependent uptake of prostamides was observed after incubation with rat brain synaptosomes or RBL-2H3 cells. We suggest that prostamides' most prominent pharmacological actions are not due to transformation into prostaglandins, activation of prostanoid receptors, enhancement of AEA levels, or gating of TRPV1 receptors, but possibly to interaction with novel receptors that seem to be functional in the cat iris.     

The effect of ionic and nonionic contrast media (amidotrizoate, iopromide) on cardiac function (contractility, relaxation, perfusion)

In 30 patients the influence of ionic (Amidotrizoate) and non-ionic (Iopromide) contrast agents on the heart parameters contractility, relaxation, perfusion and the rate of extrasystoles was investigated. They were significantly less influenced by Iopromide than by Amidotrizoate. A negative inotropic action was detectable only for Amidotrizoate. It is concluded that non-ionic contrast media should be used especially for critical patients.     

Pharmacological characterization of a novel antiglaucoma agent,Bimatoprost (AGN 192024)

Replacement of the carboxylic acid group of prostaglandin (PG) F(2alpha) with a nonacidic moiety, such as hydroxyl, methoxy, or amido, results in compounds with unique pharmacology. Bimatoprost (AGN 192024) is also a pharmacologically novel PGF(2alpha) analog, where the carboxylic acid is replaced by a neutral ethylamide substituent. Bimatoprost potently contracted the feline lung parenchymal preparation (EC(50) value of 35-55 nM) but exhibited no meaningful activity in a variety of PG-sensitive tissue and cell preparations. Its activity seemed unrelated to FP receptor stimulation according to the following evidence. 1) Bimatoprost exhibited no meaningful activity in tissues and cells containing functional FP receptors. 2) Bimatoprost activity in the cat lung parenchyma is not species-specific because its potent activity in this preparation could not be reproduced in cells stably expressing the feline FP receptor. 3) Radioligand binding studies using feline and human recombinant FP receptors exhibited minimal competition versus [(3)H]17-phenyl PGF(2a) for Bimatoprost. 4) Bimatoprost pretreatment did not attenuate PGF(2alpha)-induced Ca(2+) signals in Swiss 3T3 cells. 5) Regional differences were apparent for Bimatoprost but not FP agonist effects in the cat lung. Bimatoprost reduced intraocular pressure in ocular normotensive and hypertensive monkeys over a 0.001 to 0.1% dose range. A single-dose and multiple-dose ocular distribution/metabolism studies using [(3)H]Bimatoprost (0.1%) were performed. Within the globe, bimatoprost concentrations were 10- to 100-fold higher in anterior segment tissues compared with the aqueous humor. Bimatoprost was overwhelmingly the predominant molecular species identified at all time points in ocular tissues, indicating that the intact molecule reduces intraocular pressure.     

Doppler tissue analysis of mitral annular velocities: evidence for systolic abnormalities in patients with diastolic heart failure.

BACKGROUND: The presence of signs and symptoms of heart failure (HF), abnormal diastolic function and an ejection fraction > 45%, have been defined as diastolic HF (DHF). However, a cut-off value of 45% for ejection fraction seems arbitrary as mild systolic dysfunction may be overlooked. It was the goal of this study to assess the additive information derived from Doppler tissue imaging for patients with DHF. METHODS: As a measure of left ventricular (LV) long-axis function, systolic and diastolic velocities of the mitral annulus (peak, peak early, and peak late) derived from pulsed Doppler tissue imaging were assessed in 36 asymptomatic control subjects, 36 patients with DHF, and 35 patients with systolic HF (SHF). As a measure of overall LV performance, the Tei index (isovolumic contraction time and isovolumic relaxation time divided by ejection time) was assessed. RESULTS: In the DHF group, peak systolic annular velocity was reduced (7.1 +/- 1.2 cm/s) as compared with the control group (9.0 +/- 1.2 cm/s, P <.05), and was even lower in the SHF group (5.0 +/- 0.7 cm/s, P <.01 SHF group vs DHF/control groups). The Tei index was increased in the DHF group (0.53 +/- 0.14) in comparison with the control group (0.39 +/- 0.07, P <.05), and was highest in the SHF group (0.94 +/- 0.43, P <.01 SHF group vs control/DHF groups). Using peak systolic annular velocity < 7.95 cm/s as a cut-off value (derived from receiver operating characteristic curve analysis), patients with DHF were separated from control subjects with a sensitivity of 83% and a specificity of 83%. A Tei index > 0.43 separated patients with DHF and control subjects with a sensitivity of 79% and a specificity of 72%. CONCLUSION: Systolic long-axis LV function is also impaired in patients with DHF, resulting in feasible diagnosis of DHF by Doppler tissue imaging analysis of LV long-axis function and overall LV function with the Tei index.