New studies have shown the great potential of the combination of in situ enzymatically cross-linked hydrogels based on tyramine derivative of hyaluronic acid (HA-TA) with platelet-rich plasma (PRP) and platelet lysate in regenerative medicine. This study describes how the presence of PRP and platelet lysate affects the kinetics of gelation, viscoelastic properties, swelling ratio, and the network structure of HA-TA hydrogels and how the encapsulation of PRP in hydrogels affects the bioactivity of released PRP determined as the ability to induce cell proliferation. The properties of hydrogels were tuned by a degree of substitution and concentration of HA-TA derivatives. The addition of platelet derivatives to the reaction mixture slowed down the cross-linking reaction and reduced elastic modulus (G') and thus cross-linking efficiency. However, low-swellable hydrogels (7-190%) suitable for soft tissue engineering with G' 200-1800 Pa were prepared with a gelation time within 1 min. It was confirmed that tested cross-linking reaction conditions are suitable for PRP incorporation because the total bioactivity level of PRP released from HA-TA hydrogels was ≥87% and HA-TA content in the hydrogels and thus mesh size (285-482 nm) has no significant effect on the bioactivity level of released PRP.
Sympathomimetic agents are a group of chemical compounds that are able to activate the sympathetic nervous system either directly via adrenergic receptors or indirectly by increasing endogenous catecholamine levels or mimicking their intracellular signaling pathways. Compounds from this group, both used therapeutically or abused, comprise endogenous catecholamines (such as adrenaline and noradrenaline), synthetic amines (e.g., isoproterenol and dobutamine), trace amines (e.g., tyramine, tryptamine, histamine and octopamine), illicit drugs (e.g., ephedrine, cathinone, and cocaine), or even caffeine and synephrine. In addition to the effects triggered by stimulation of the sympathetic system, the discovery of trace amine associated receptors (TAARs) in humans brought new insights about their sympathomimetic pharmacology and toxicology. Although synthetic sympathomimetic agents are mostly seen as toxic, natural sympathomimetic agents are considered more complacently in the terms of safety in the vision of the lay public. Here, we aim to discuss the pharmacological and mainly toxicological aspects related to sympathomimetic natural agents, in particular of trace amines, compounds derived from plants like ephedra and khat, and finally cocaine. The main purpose of this review is to give a scientific and updated view of those agents and serve as a reminder on the safety issues of natural sympathomimetic agents most used in the community.
- MeSH
- aminy MeSH
- kokain * farmakologie MeSH
- lidé MeSH
- noradrenalin MeSH
- sympatomimetika * farmakologie MeSH
- tyramin farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the world. OA is often associated with the loss of viscoelastic and tribological properties of synovial fluid (SF) due to degradation of hyaluronic acid (HA) by reactive oxygen species (ROS) and hyaluronidases. Viscosupplementation is one of the ways how to effectively restore SF functions. However, current viscosupplementation products provide only temporal therapeutic effect because of short biological half-life. In this article we describe a novel device for viscosupplementation (NV) based on the cross-linked tyramine derivative of HA, chondroitin sulfate (CS), and high molecular weight HA by online determination of viscoelastic properties loss during degradation by ROS and hyaluronidase. Rheological and tribological properties of developed viscosupplement were compared with HA solutions with different molecular weights in the range 500-2000 kDa, which are currently commonly used as medical devices for viscosupplementation treatment. Moreover, based on clinical practice and scientific literature all samples were also diluted by model OA SF in the ratio 1:1 (vol/vol) to better predict final properties after injection to the joint. The observed results confirmed that NV exhibits appropriate rheological properties (viscosity, elastic, and viscous moduli) comparable with healthy SF and maintain them during degradation for a significantly longer time than HA solutions with molecular weight in the range 500-2000 kDa and cross-linked material without CS.
- MeSH
- artróza kolenních kloubů * MeSH
- chondroitinsulfáty farmakologie MeSH
- hyaluronoglukosaminidasa terapeutické užití MeSH
- injekce intraartikulární MeSH
- kyselina hyaluronová farmakologie MeSH
- lidé MeSH
- osteoartróza * farmakoterapie MeSH
- reaktivní formy kyslíku MeSH
- tyramin terapeutické užití MeSH
- viskosuplementace * metody MeSH
- viskosuplementy terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population.
- MeSH
- 4-hydroxykumariny chemická syntéza chemie farmakologie MeSH
- difrakce rentgenového záření MeSH
- HCT116 buňky MeSH
- HeLa buňky MeSH
- karboanhydrasy chemie metabolismus MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie enzymologie MeSH
- neurotransmiterové látky chemie MeSH
- oktopamin chemie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- simulace molekulární dynamiky MeSH
- simulace molekulového dockingu MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Alzheimer's disease (AD) is a multifactorial neurodegenerative condition of the central nervous system (CNS) that is currently treated by cholinesterase inhibitors and the N-methyl-d-aspartate receptor antagonist, memantine. Emerging evidence strongly supports the relevance of targeting butyrylcholinesterase (BuChE) in the more advanced stages of AD. Within this study, we have generated a pilot series of compounds (1-20) structurally inspired from belladine-type Amaryllidaceae alkaloids, namely carltonine A and B, and evaluated their acetylcholinesterase (AChE) and BuChE inhibition properties. Some of the compounds exhibited intriguing inhibition activity for human BuChE (hBuChE), with a preference for BuChE over AChE. Seven compounds were found to possess a hBuChE inhibition profile, with IC50 values below 1 μM. The most potent one, compound 6, showed nanomolar range activity with an IC50 value of 72 nM and an excellent selectivity pattern over AChE, reaching a selectivity index of almost 1400. Compound 6 was further studied by enzyme kinetics, along with in-silico techniques, to reveal the mode of inhibition. The prediction of CNS availability estimates that all the compounds in this survey can pass through the blood-brain barrier (BBB), as disclosed by the BBB score.
- MeSH
- acetylcholinesterasa chemie MeSH
- alkaloidy amarylkovitých chemie MeSH
- butyrylcholinesterasa chemie MeSH
- cholinesterasové inhibitory chemie farmakologie MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- neuroblastom farmakoterapie patologie MeSH
- počítačová simulace MeSH
- proliferace buněk MeSH
- simulace molekulového dockingu * MeSH
- tyramin analogy a deriváty chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
Tyramine is one of the most toxic biogenic amines and it is produced commonly by lactic acid bacteria in fermented food products. In present study, we investigated the influence of selected nisin-producing Lactococcus lactis subsp. lactis strains and their cell-free supernatants (CFSs) on tyramine production by four Lactobacillus and two Lactiplantibacillus strains isolated from cheese and beer. Firstly, we examined the antimicrobial effect of the CFSs from twelve Lactococcus strains against tested tyramine producers by agar-well diffusion assay. Six Lactococcus strains whose CFSs showed the highest antimicrobial effect on tyramine producers were further studied. Secondly, we investigated the influence of the selected six Lactococcus strains and their respective CFSs on tyramine production by tested Lactobacillus and Lactiplantibacillus strains in MRS broth supplemented with 2 g.L-1 of l-tyrosine. Tyramine production was monitored by HPLC-UV. The tyramine formation of all tested Lactobacillus and Lactiplantibacillus strains was not detected in the presence of Lc. lactis subsp. lactis CCDM 71 and CCDM 702, and their CFSs. Moreover, the remainder of the investigated Lactococcus strains (CCDM 670, CCDM 686, CCDM 689 and CCDM 731) and their CFSs decreased tyramine production significantly (P < 0.05) - even suppressing it completely in some cases - in four of the six tested tyramine producing strains.
- MeSH
- antibakteriální látky analýza metabolismus farmakologie MeSH
- kultivační média chemie metabolismus farmakologie MeSH
- Lactobacillaceae účinky léků růst a vývoj izolace a purifikace MeSH
- Lactobacillus účinky léků růst a vývoj izolace a purifikace MeSH
- Lactococcus lactis chemie metabolismus MeSH
- pivo mikrobiologie MeSH
- sýr mikrobiologie MeSH
- tyramin analýza metabolismus farmakologie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- histamin škodlivé účinky MeSH
- lidé MeSH
- potravinová alergie * MeSH
- potravinová intolerance MeSH
- tyramin škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Enterococci are widespread bacteria forming the third largest genus among lactic acid bacteria. Some possess probiotic properties or they can produce beneficial proteinaceous antimicrobial substances called enterocins. On the other hand, some enterococci produce biogenic amines (BAs), so this study is focused on the sensitivity to enterocins of biogenic amine-producing faecal enterococci from ostriches and pheasants. Altogether, 60 enterococci isolated from faeces of ostriches and pheasants were tested for production of BAs. This target of the identified enterococci involved 46 strains selected from 140 ostriches and 17 from 60 pheasants involving the species Enterococcus hirae, E. faecium, E. faecalis, and E. mundtii. Although BAs histamine, cadaverine, putrescine, and tryptamine were not detected in the enterococci tested, in general high BA production by the tested enterococci was noted. The species E. hirae formed the majority of the enterococcal strains from ostrichs faeces (34 strains). High production of tyramine (TYM) was measured with an average amount of 958.16 ± 28.18 mg/ml. Among the enterococci from pheasants, the highest was production of TYM compared to phenylethylamine, spermidine, and spermine. Enterococci featured high BA production; however, they were sensitive to seven enterocins with inhibition activity ranging from 100 up to 25,600 AU/ml.
- MeSH
- biogenní aminy biosyntéza MeSH
- Enterococcus klasifikace izolace a purifikace MeSH
- feces chemie mikrobiologie MeSH
- fenethylaminy metabolismus MeSH
- Galliformes mikrobiologie MeSH
- přemostěné cyklické sloučeniny metabolismus MeSH
- spermidin biosyntéza MeSH
- spermin biosyntéza MeSH
- Struthioniformes mikrobiologie MeSH
- tyramin biosyntéza MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS: The goal of our study was to reveal the important mechanism(s) responsible for the enhanced contractility of isolated arteries from animals suffering genetic hypertension. MAIN METHODS: Contractile force of endothelium-denuded arteries, modulated by various interventions, was measured by wire myography. KEY FINDINGS: Spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) arteries were stimulated by norepinephrine, increased extracellular K(+) or tyramine. Strain difference was not observed in the contraction elicited by exogenous norepinephrine but SHR arteries responded more to tyramine (causing endogenous norepinephrine release from neuronal varicosities). K(+)-induced contraction was enhanced in SHR arteries, with no involvement of endogenous catecholamines. The α-adrenoceptor blockade lowered tyramine-induced contraction more in SHR arteries; similar effect was achieved by guanethidine-induced sympathectomy. Partial depolarization of WKY arteries by 20mM K(+) enhanced its contraction to SHR level. The blockade of β-adrenoceptors by propranolol or selective β2-antagonist ICI-118,551 induced contraction of SHR endothelium-denuded arteries but was without significant effects on WKY arteries unless they were stimulated with K(+). Both tyramine-induced and propranolol-induced contractions were attenuated by flupirtine and abolished by nifedipine. SIGNIFICANCE: The differences of SHR and WKY arteries were not related to vascular expression of α- and β-adrenoceptors or G-proteins. Enhanced contractility of SHR arteries is related to both increased presence of endogenous norepinephrine in vascular wall and also to altered vascular smooth muscle membrane potential.
- MeSH
- arterie fyziologie MeSH
- draslík metabolismus MeSH
- hypertenze MeSH
- membránové potenciály MeSH
- noradrenalin metabolismus MeSH
- potkani inbrední SHR fyziologie MeSH
- potkani inbrední WKY MeSH
- svalová kontrakce MeSH
- svaly hladké cévní fyziologie MeSH
- tyramin metabolismus MeSH
- vazokonstrikce * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Tau protein in cerebrospinal fluid (CSF) is an important biomarker of Alzheimer's disease and some other brain diseases. Enzyme-linked immunosorbent assays (ELISAs) have been mostly used for quantification of tau and other biomarkers in CSF. However, these assays do not have sufficient sensitivity and dynamic range. In this study we tested the suitability of gold nanoparticles functionalized with tau-specific monoclonal antibody and oligonucleotide template for immuno-polymerase chain reaction (Nano-iPCR) quantification of tau protein in human CSF samples and compared it with ELISA, either commercial or newly developed with tyramide signal amplification. Our data indicate that Nano-iPCR is superior in sensitivity and detection range to ELISA in tau protein detection.
- MeSH
- Alzheimerova nemoc diagnóza MeSH
- biologické markery MeSH
- ELISA * MeSH
- kovové nanočástice * MeSH
- lidé MeSH
- monoklonální protilátky imunologie MeSH
- polymerázová řetězová reakce metody MeSH
- proteiny tau MeSH
- senzitivita a specificita MeSH
- tyramin metabolismus MeSH
- zlato * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
