Search results for "TYR"
showing 10 items of 2017 documents
Butyrate, a postbiotic of intestinal bacteria, affects pancreatic cancer and gemcitabine response in in vitro and in vivo models
2022
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer. The characteristic excessive stromatogenesis accompanying the growth of this tumor is believed to contribute to chemoresistance which, together with drug toxicity, results in poor clinical outcome. An increasing number of studies are showing that gut microbiota and their metabolites are implicated in cancer pathogenesis, progression and response to therapies. In this study we tested butyrate, a product of dietary fibers' bacterial fermentation, whose anticancer and anti-inflammatory functions are known. We provided in vitro evidence that, beside slowing proliferation, butyrate enhanced gemcitabine effectiveness against two hum…
GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation
2015
Although an extensive body of literature confirmed γ-aminobutyric acid (GABA) as mediator within the enteric nervous system (ENS) controlling gastrointestinal (GI) function, the true significance of GABAergic signalling in the gut is still a matter of debate. GABAergic cells in the bowel include neuronal and endocrine-like cells, suggesting GABA as modulator of both motor and secretory GI activity. GABA effects in the GI tract depend on the activation of ionotropic GABAA and GABAC receptors and metabotropic GABAB receptors, resulting in a potential noteworthy regulation of both the excitatory and inhibitory signalling in the ENS. However, the preservation of GABAergic signalling in the gut …
�ber das Verhalten und Reaktionsverm�gen von glatter Muskulatur und Herzmuskulatur in chloridfreiem Medium (Methylsulfat-Tyrode-L�sung)
1961
Um die Bedeutung der Chlorid-Ionen fur die Funktion von glatter Muskulatur und Herzgewebe zu untersuchen, wurden die Chlorid-Ionen der Tyrodelosung durch die einwertigen, nicht permeierenden und indifferenten Methylsulfat-Ionen ersetzt. Die Versuche wurden am Meerschweinchen-Ileum, Kaninchen-Duodenum, Ratten-Uterus, spontan schlagenden Vorhof des Meerschweinchens und am Froschherz nach Straub durchgefuhrt. Keines der genannten Organe reagierte beim Uberfuhren in chloridfreies Medium oder bei stundenlangem Aufenthalt in Methylsulfat-Tyrodelosung mit einer wesentlichen Funktionsanderung. Wahrend die Herzmuskulatur in chloridfreiem Milieu unverandert auf positiv oder negativ inotrop wirksame S…
Efecto in vitro de la adición de resinas de intercambio iónico sobre la biodisponibilidad de electrolitos en fórmulas de nutrición enteral artificial
2008
The in vitro effect of the addition of ion exchange resins on the bioavailability of electrolytes in artificial enteral feeding formulas Objective: To determine in vitro free ion concentration in three standard artificial enteral feeding formulas following the addition of ion exchange resins. Method: Three standard types of AEF were chosen: Osmolite HN®, Nutrison Standard® and Isosource Standard®. The ion exchange resins used were: Sodium Polystyrene Sulfonate and Calcium Polystyrene Sulfonate. 100 ml of AEF were mixed in a beaker with 1.5 g or 3 g of ion exchange resins for 48 hours at 37oC. Subsequently, the samples were precipitated and the supernatant obtained was used for determining t…
Impact of nutritional status on the pharmacokinetics of erlotinib in rats
2015
Malnourishment is a complex condition in which physiopathological changes take place in multiple systems as a result of energy, protein and nutrient deficiency. The purpose of this study was to evaluate, using an experimental animal model, the impact of nutritional status on the pharmacokinetic profile of erlotinib, a reversible, highly selective, human epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. Two groups of rats -WN (well-nourished) and UN (undernourished) - were fed with different diets for 23-26 days. Rats were assigned randomly to one of three erlotinib treatments (n = 42) consisting of a single dose administered intravenously (i.v.), via oral solution or v…
Synthesis of 2H-Imidazo[2',1':2,3] [1,3]thiazolo[4,5-e]isoindol-8-yl-phenylureas with promising therapeutic features for the treatment of acute myelo…
2022
Despite progressive advances in understanding the molecular biology of acute myeloid leukemia (AML), the conventional therapeutic approach has not changed substantially, and the outcome for most patients is poor. Thus, continuous efforts on the discovery of new compounds with improved features are required. Following a multistep sequence, we have identified a new tetracyclic ring system with strong antiproliferative activity towards several haematological cell lines. The new compounds possess structural properties typical of inactive-state-binding kinase inhibitors and are structurally related to quizartinib which is known as type-II tyrosine kinase inhibitor. In particular, the high activi…
Entwicklung von Tyrosinkinase-Inhibitoren bei hämatologischen Neoplasien. FLT3 und JAK2 als therapeutischeTargets
2008
Tyrosinkinase-Inhibitoren stellen einen wichtigen Beitrag zur Weiterentwicklung und Verbesserung der Therapie von hamatologischen Neoplasien dar. Zahlreiche Inhibitoren befinden sich bereits in fortgeschrittener klinischer Testung. Wahrend bei einem Teil der Erkrankungen (CML) die Inhibitor-Therapie bereits als Standard etabliert ist, befinden sich die “small molecules” bei Akuter Myeloischer Leukamie und chronisch-myeloproliferativen Syndromen noch in der Etablierungsphase. Die Entwicklung von neuen zielgerichteten Substanzen zahlt zu den grosen praklinischen und klinischen Herausforderungen der nachsten Jahre.
Über die Wirkung von Prostaglandin E1 auf den Ca-Haushalt isolierter Meerschweinchenherzen
1967
The stimulatory effect of PGE1 on different functions of isolated guinea-pig hearts (Langendorff method, Tyrode solution) was coupled with an increase in the rate of45Ca uptake from the perfusion medium. The total myocardial Ca content and the amount of exchangeable cellular Ca were not affected. This action of PGE1 on the myocardial Ca metabolism seems to be related to the positive inotropic action of PGE1 and can most probably be explained by an increase in the membrane permeability to Ca ions (similar to the action of epinephrine).
Experiments on the metyrapone reducing microsomal enzyme system.
1970
The formation of reduced metyrapone [2-methyl-1.2-bis-(3-pyridyl)-1-propanol] from metyrapone [2-methyl-1.2-bis-(3-pyridyl)-1-propanone] in the liver has been studied. Reduced metyrapone appeared as the main metabolite of metyrapone in the isolated perfused rat liver. Experiments on the intracellular distribution of the metyrapone reducing activity revealed that metyrapone reductase is mainly localized in the microsomal fraction. In the 105,000 × g supernatant only a little activity was found.
�ber die Wirkung von Metyrapon auf den mikrosomalen Arzneimittelabbau
1967
The inhibitor of adrenal steroid-11-β-hydroxylation, Metyrapone (SU 4885), also decreases the rate of drug hydroxylation reactions, both in vitro and in vivo. The follwing oxidative microsomal reactions were studied: O-demethylation of p-nitroanisole, N-demethylation of amidopyrine, and ring hydroxylation of acetanilide. In all three cases Metyrapone inhibits the formation of the reaction products. The inhibitor concentrations required for reduction of the initial reaction rates to one half are 7.5 · 10−4 M, 5 · 10−4m and 20 · 10−4 M, respectively. Steroid C-11-β-hydroxylation is reduced to one half by 2.5 · 10−4 M Metyrapone.