• Publikační typ
• abstrakt z konference MeSH

• MeSH
• veterinární lékařství MeSH

• Konspekt
• Veterinární lékařství
• NLK Obory
• veterinární lékařství
• NLK Publikační typ
• elektronické časopisy

Two trials were carried out to determine: (a) if there is a positive relation between the frequency of aggressive interactions among female pampas deer and their position within the hierarchy (HI), (b) if short-term removal of the male triggers an increase in the frequency of aggression, and (c) if the magnitude of this increase is related to the individual rank position of the female. Each of 19 breeding groups comprised one adult male and from four to six adult females. The HI was determined for each female and all aggressive interactions were recorded. These were recorded while the male was present (i.e., all of Trial 1 and the "with male" period in Trial 2) and after removal of the male (i.e., the "without male" period in Trial 2). The individual percentage change in the frequency of aggressive interactions after male removal was calculated. In Trial 1 the HI, the frequency of different types of aggressive interaction and the total of aggressive interactions were positively related (all: p < .001; General Linear Mixed Model [GLMM]). In Trial 2, the frequency of total aggressive interactions increased after male removal (F(1, 27) = 3.5; p < .001; GLMM). The individual percentage changes in aggressive interaction between periods were positively related to HI (F(6, 24) = 2.56; p = .05; GLMM). For female pampas deer maintained in breeding groups, we conclude that the frequency of aggressive interactions increases within the hierarchy. Aggression also increases after the short-term removal of the male, mainly among females of higher social status.

• MeSH
• agrese * MeSH
• sociální dominance MeSH
• sociální prostředí MeSH
• vysoká zvěř * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• CD-ROM MeSH
• ultrasonografie dopplerovská barevná MeSH
• Publikační typ
• atlasy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• chemie, klinická chemie
• NLK Publikační typ
• CD-ROM

BACKGROUND: In recent years the number of natural products used as pharmaceuticals, components of dietary supplements and cosmetics has increased tremendously requiring more extensive evaluation of their pharmacokinetic properties. PURPOSE: This study aims at combining in vitro and in silico methods to evaluate the gastrointestinal absorption (GIA) of natural flavonolignans from milk thistle (Silybum marianum (L.) Gaertn.) and their derivatives. METHODS: A parallel artificial membrane permeability assay (PAMPA) was used to evaluate the transcellular permeability of the plant main components. A dataset of 269 compounds with measured PAMPA values and specialized software tools for calculating molecular descriptors were utilized to develop a quantitative structure-activity relationship (QSAR) model to predict PAMPA permeability. RESULTS: The PAMPA permeabilities of 7 compounds constituting the main components of the milk thistle were measured and their GIA was evaluated. A freely-available and easy to use QSAR model predicting PAMPA permeability from calculated physico-chemical molecular descriptors was derived and validated on an external dataset of 783 compounds with known GIA. The predicted permeability values correlated well with obtained in vitro results. The QSAR model was further applied to predict the GIA of 31 experimentally untested flavonolignans. CONCLUSIONS: According to both in vitro and in silico results most flavonolignans are highly permeable in the gastrointestinal tract, which is a prerequisite for sufficient bioavailability and use as lead structures in drug development. The combined in vitro/in silico approach can be used for the preliminary evaluation of GIA and to guide further laboratory experiments on pharmacokinetic characterization of bioactive compounds, including natural products.

• MeSH
• flavonoidy chemie   farmakokinetika   MeSH
• flavonolignany farmakokinetika   MeSH
• intestinální absorpce účinky léků   MeSH
• kvantitativní vztahy mezi strukturou a aktivitou * MeSH
• lidé MeSH
• membrány umělé MeSH
• ostropestřec mariánský chemie   MeSH
• permeabilita buněčné membrány účinky léků   MeSH
• počítačová simulace MeSH
• potravní doplňky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Profiling blood-brain barrier permeability of bioactive molecule is an important issue in early drug development, being a part of the optimization process of a compound's physicochemical properties, and hence pharmacokinetic profile. The study aimed to develop and optimize a new in vitro method for assessment of the compound's brain penetration. The tool is proposed as an alternative to the PAMPA-BBB (Parallel Artificial Membrane Permeability Assay for Blood-Brain Barrier) and based on a capillary electrochromatography (CEC) technique. It utilizes liposomes as structural substitutes of biological membranes, which are used as a capillary inner wall coating material. Following optimization of analysis conditions, migration times for a set of 25 reference drugs (mainly non-ionized in pH 7.4) were examined in a liposome coated capillary. On that basis, the retention factor (log k) was determined for each reference drug. Obtained log k values and experimentally received reference permeability parameters: log BB (in vivo data) and log Pe (PAMPA-BBB data) were compared with one another. Correlation coefficients were calculated, giving comparable results for CEC log k/log BB and analogical PAMPA-BBB log Pe/log BB analyses. Approximate ranges of log k for the central nervous system (CNS) permeable (CNS(+)) and non-permeable (CNS(-)) drugs were established.

• MeSH
• elektroforéza kapilární MeSH
• hematoencefalická bariéra chemie   MeSH
• léčivé přípravky analýza   MeSH
• lidé MeSH
• liposomy chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

This study is focused on in vitro permeation of the original Czech compound, a skin/mucosa tissue regeneration promoter, known under the international nonproprietary name "alaptide," in micronized and nanonized forms. Alaptide showed a great potential for local applications for treatment and/or regeneration of the injured skin. The above mentioned technological modifications influence the permeation of alaptide through artificial or biological membranes, such as PAMPA or skin. The permeation of micronized and nanonized form of alaptide formulated to various semisolid pharmaceutical compositions through full-thickness pig ear skin using a Franz cell has been investigated in detail. In general, it can be concluded that the nanonized alaptide permeated through the skin less than the micronized form; different observations were made for permeation through the PAMPA system, where the micronized form showed lower permeation than the nanonized alaptide.

• MeSH
• cyklické peptidy * chemie   farmakologie   MeSH
• kůže * MeSH
• membrány umělé * MeSH
• nanočástice chemie   MeSH
• neuropeptidy * chemie   farmakologie   MeSH
• permeabilita MeSH
• prasata MeSH
• umělá kůže * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In recent studies, several alkaloids acting as cholinesterase inhibitors were isolated from Corydalis cava (Papaveraceae). Inhibitory activities of (+)-thalictricavine (1) and (+)-canadine (2) on human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) were evaluated with the Ellman's spectrophotometric method. Molecular modeling was used to inspect the binding mode of compounds into the active site pocket of hAChE. The possible permeability of 1 and 2 through the blood⁻brain barrier (BBB) was predicted by the parallel artificial permeation assay (PAMPA) and logBB calculation. In vitro, 1 and 2 were found to be selective hAChE inhibitors with IC50 values of 0.38 ± 0.05 µM and 0.70 ± 0.07 µM, respectively, but against hBChE were considered inactive (IC50 values > 100 µM). Furthermore, both alkaloids demonstrated a competitive-type pattern of hAChE inhibition and bind, most probably, in the same AChE sub-site as its substrate. In silico docking experiments allowed us to confirm their binding poses into the active center of hAChE. Based on the PAMPA and logBB calculation, 2 is potentially centrally active, but for 1 BBB crossing is limited. In conclusion, 1 and 2 appear as potential lead compounds for the treatment of Alzheimer's disease.

• MeSH
• acetylcholinesterasa chemie   účinky léků   MeSH
• alkaloidy chemie   farmakologie   MeSH
• Alzheimerova nemoc farmakoterapie   enzymologie   MeSH
• berberin analogy a deriváty   chemie   farmakologie   MeSH
• biologický transport účinky léků   MeSH
• butyrylcholinesterasa chemie   účinky léků   MeSH
• cholinesterasové inhibitory chemie   farmakologie   MeSH
• Corydalis chemie   MeSH
• disacharidy chemie   farmakologie   MeSH
• dusíkaté sloučeniny chemie   farmakologie   MeSH
• hematoencefalická bariéra účinky léků   MeSH
• lidé MeSH
• molekulární modely MeSH
• počítačová simulace MeSH
• vazba proteinů účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Herein we report an efficient two step synthesis and biological assessment of 12 racemic tetrahydropyranodiquinolin-8-amines derivatives as antioxidant, cholinesterase inhibitors and non-hepatotoxic agents. Based on the results of the primary screening, we identified 7-(3-methoxyphenyl)-9,10,11,12-tetrahydro-7H-pyrano[2,3-b:5,6-h']diquinolin-8-amine (2h) as a particularly interesting non-hepatotoxic compound that shows moderate antioxidant activity (1.83 equiv Trolox in the ORAC assay), a non competitive inhibition of hAChE (IC50 = 0.75 ± 0.01 μM), and brain permeable as determined by the PAMPA-Blood Brain Barrier assay.

• MeSH
• acetylcholinesterasa MeSH
• Alzheimerova nemoc farmakoterapie   MeSH
• aminochinoliny chemická syntéza   farmakologie   MeSH
• antioxidancia chemie   farmakologie   MeSH
• cholinesterasové inhibitory chemie   farmakologie   MeSH
• GPI-vázané proteiny antagonisté a inhibitory   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• lékové postižení jater MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Alzheimer's disease is the most common cause of dementia. Currently, acetylcholinesterase (AChE) inhibition is the most widely used therapeutic treatment. A large number of naturally occurring compounds have been found to inhibit AChE. In this report the mechanism of AChE inhibition of two Amaryllidaceae alkaloids, 8-O-demethylmaritidine (1) and undulatine (2), and their possible penetration across the blood-brain barrier have been studied. Both compounds act via a mixed inhibition mechanism. Based on the parallel artificial permeation assay (PAMPA) for the prediction of blood-brain barrier (BBB) penetration, only 2 should be able to cross the BBB by passive permeation.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• alkaloidy amarylkovitých farmakologie   MeSH
• Alzheimerova nemoc farmakoterapie   MeSH
• biologický transport účinky léků   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• hematoencefalická bariéra účinky léků   MeSH
• lidé MeSH
• molekulární struktura MeSH
• techniky in vitro MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH