The effect of selected plasticizers (triethyl citrate, ethyl pyruvate, methyl and ethyl salicylate, triacetin, tributyrin) on thermal and rheological properties of the oligoesters of DL-lactic and glycolic acids crosslinked with mannitol was studied. Plasticization of the oligoesters was performed by their fusion at 80 °C and subsequent mixing with a plasticizer in the concentration 20 %. All plasticizers in this concentration were miscible with the oligoesters and the blends did not tend to phase separation. The efficiency of plasticizers was evaluated by lowering the glass transition temperature of the non-plasticized oligoester. All the tested plasticizers proved to be effective. The plasticizers also induced a decrease in dynamic viscosity of the oligoester, which is necessary for the manufacture of oligoesters as drug delivery carriers applied by injection or topically as sprays. Ethyl pyruvate was the most effective plasticizer of the DL-lactic and glycolic oligoesters crosslinked with mannitol.
Three oligoesters with different molar mass and degree of branching, intended as drug carriers, were synthesized and their thermal, rheological, adhesive, and drug release properties were studied. Triethyl citrate, ethyl pyruvate, ethyl salicylate, methyl salicylate, triacetin and tributyrin at a concentration of 20% were tested as plasticizers to improve drug incorporation, and application of the polymeric system. All of the tested plasticizers significantly depressed the Tg by at least 25.5°C. Plasticized oligoesters possessed remarkable adhesive properties on mucin in vitro, the adhesion is at least twofold bigger than it is for gels of cellulose derivatives. It was demonstrated that adhesivity increased with decreasing viscosity of oligoester matrices. In vitro dissolution tests of the flat matrices showed the prolongation of fluconazole release up to over 3 days for the oligoester carrier with the highest molar weight and degree of branching. Depending on the matrix hydrophilization, plasticizing led to an acceleration of the fluconazole release, the 3-h burst effect increased three times.
- MeSH
- Adhesives chemistry MeSH
- Esters chemistry MeSH
- Fluconazole chemistry MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Molecular Weight MeSH
- Drug Carriers chemistry MeSH
- Polymers chemistry MeSH
- Rheology methods MeSH
- Viscosity MeSH
- Plasticizers chemistry MeSH
- Publication type
- Journal Article MeSH
Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug-polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00 s(-1) at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at Tg depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters.
- MeSH
- Acyclovir administration & dosage chemistry MeSH
- Biocompatible Materials chemistry MeSH
- Time Factors MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Lactic Acid chemistry MeSH
- Polyglycolic Acid chemistry MeSH
- Delayed-Action Preparations MeSH
- Surface Properties MeSH
- Drug Liberation MeSH
- Particle Size MeSH
- Plasticizers administration & dosage chemistry MeSH
- Publication type
- Journal Article MeSH
Phthalates and the substitute plasticizer DINCH belong to the first group of priority substances investigated by the European Human Biomonitoring Initiative (HBM4EU) to answer policy-relevant questions and safeguard an efficient science-to-policy transfer of results. Human internal exposure levels were assessed using two data sets from all European regions and Israel. The first collated existing human biomonitoring (HBM) data (2005-2019). The second consisted of new data generated in the harmonized "HBM4EU Aligned Studies" (2014-2021) on children and teenagers for the ten most relevant phthalates and DINCH, accompanied by a quality assurance/quality control (QA/QC) program for 17 urinary exposure biomarkers. Exposures differed between countries, European regions, age groups and educational levels. Toxicologically derived Human biomonitoring guidance values (HBM-GVs) were exceeded in up to 5% of the participants of the HBM4EU Aligned Studies. A mixture risk assessment (MRA) including five reprotoxic phthalates (DEHP, DnBP, DiBP, BBzP, DiNP) revealed that for about 17% of the children and teenagers, health risks cannot be excluded. Concern about male reproductive health emphasized the need to include other anti-androgenic substances for MRA. Contaminated food and the use of personal care products were identified as relevant exposure determinants paving the way for new regulatory measures. Time trend analyses verified the efficacy of regulations: especially for the highly regulated phthalates exposure dropped significantly, while levels of the substitutes DINCH and DEHTP increased. The HBM4EU e-waste study, however, suggests that workers involved in e-waste management may be exposed to higher levels of restricted phthalates. Exposure-effect association studies indicated the relevance of a range of endpoints. A set of HBM indicators was derived to facilitate and accelerate science-to-policy transfer. Result indicators allow different groups and regions to be easily compared. Impact indicators allow health risks to be directly interpreted. The presented results enable successful science-to-policy transfer and support timely and targeted policy measures.
- MeSH
- Biological Monitoring * MeSH
- Child MeSH
- Adult MeSH
- Risk Assessment MeSH
- Phthalic Acids * urine MeSH
- Environmental Pollutants * urine MeSH
- Humans MeSH
- Adolescent MeSH
- Environmental Monitoring methods MeSH
- Environmental Exposure analysis MeSH
- Plasticizers * analysis MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Geographicals
- Europe MeSH
Plasticita je specifická vlastnost nervového systému se vyvíjet, reagovat na změny vnitřního a zevního prostředí, případně se jim přizpůsobit, a to za fyziologických i patologických situací. Existují důkazy o dynamičnosti nervového systému, která je charakterizována rovnováhou mezi rigiditou a plasticitou, přičemž plastické změny neuronálních systémů využívají obecných společných mechanizmů. Výsledkem plasticity mohou být příznivé, ale i nepříznivé změny za vývoje (plasticita evoluční), při krátkodobé expozici (plasticita reaktivní), při dlouhodobé nebo opakované zátěži (plasticita adaptační) nebo při funkční, případně morfologické obnově poškozených neuronálních okruhů (plasticita reparační). Projevy plasticity mají obdobný základ bez ohledu na příčinu, která je vyvolala, a na oddíl CNS, ve kterém probíhají. Přitom nezralá nervová tkáň se jeví jako zvlášť plastická.
Plasticity is a specific endowment of the nervous system to develop, to react or to adjust to the internal and external environmental changes, both in the physiological and pathological conditions. Cumulative evidence has revealed the dynamism of the nervous system, based on the balance between the rigidity and plasticity. Different aspects of neuroplasticity can employ common general cellular mechanism. Effects of plasticity can be either positive or negative changes during the development (evolutional plasticity), after the short-term exposition (reactive plasticity), after the long-term or permanent stimuli (adaptational plasticity), and during functional or structural recovery of the damaged neuronal circuits (reparation plasticity). Manifestations of plasticity have probably the same basis, irrespective of a cause, which triggered them, or the brain region where they were accomplished. Activity of neuroplastic processes appears to be especially high in the immature nervous tissue.
- MeSH
- Classification MeSH
- Neuronal Plasticity MeSH
- Synapses MeSH
- Developmental Biology MeSH
- Publication type
- Review MeSH
Vývojový aspekt přináší informace o faktorech růstu a modulace a o základních mechanismech zapojování nervových funkcí. Na druhé straně je ontogenetický výzkum ztížen trvalou proměnlivostí a mimořádnou dynamičností vývoje nervového systému. Přitom při činnosti nervového systému hraje důležitou úlohu jeho plasticita, kterou definujeme jako specifickou schopnost nervového systému se vyvíjet, reagovat na změny zevního a vnitřního prostředí, popř. se jim přizpůsobit a to za fyziologických i patologických situací.
The developmental aspect brings information on factors of growth and modulation, and about the basic mechanisms of the onset of functions. Contrary to it, ontogenetical research is complicated by factors of variability and large dynamism in the development of the nervous system.At the same time, in the activity of the nervous systeman important role plays plasticity, which is defined as a specific feature of the nervous system to develop or to respond to changes of the external and internal environment or to adjust to them both under physiological and pathological conditions.
Fused deposition modelling (FDM) is a process of additive manufacturing allowing creating of highly precise complex three-dimensional objects for a large range of applications. The principle of FDM is an extrusion of the molten filament and gradual deposition of layers and their solidification. Potential applications in pharmaceutical and medical fields require the development of biodegradable and biocompatible thermoplastics for the processing of filaments. In this work, the potential of production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) filaments for FDM was investigated in respect to its thermal stability. Copolymer P(3HB-co-4HB) was biosynthesised by Cupriavidus malaysiensis. Rheological and mechanical properties of the copolymer were modified by the addition of plasticizers or blending with poly(lactic acid). Thermal stability of mixtures was studied employing thermogravimetric analysis and rheological analyses by monitoring the time-dependent changes in the complex viscosity of melt samples. The plasticization of P(3HB-co-4HB) slightly hindered its thermal degradation but the best stabilization effect was found in case of the copolymer blended with poly(lactic acid). Overall, rheological, thermal and mechanical properties demonstrated that the plasticized P(3HB-co-4HB) is a potential candidate of biodegradable polymer for FDM processes.
Neuroplastické děje mohou být založeny na modulaci přenosu signálu na synapsích (např. výdeje transmiteru, aktivity receptorů na postsynaptické membráně, změn účinnosti přenosu v postsynaptickém oddílu) nebo mohou být podmíněny změnami vztahů mezi neurony (např. změnami počtu a druhu synapsí, smyslu zapojení jednotlivých prvků neuronálních okruhů). Výsledné změny se pak mohou nacházet v komunikaci mezi jednotlivými neurony (synaptická úroveň), v činnosti místních neuronálních okruhů (úroveň lokálních okruhů), nebo ve vztazích jednotlivých funkčních mozkových celků (multimodulární úroveň). Podstatou neuroplasticity mohou být změny stavby, prokazatelné morfologickými metodami, což se uplatňuje zejména za vývoje a v reakci na poškození (vznik a zánik neuronů, růst jejich výběžků a trnů, přebudování, případně vytváření nových synapsí). Jemnější metody však prokazují, že změny mohou být i na úrovni molekulární (aktivita enzymů, zejména aktivace proteosyntézy a změny ve tvorbě a výdeji mediátorů a modulátorů, aktivace receptorů, úprava aktivity iontových kanálů). Obě úrovně neuroplastických dějů se promítají do změn funkčních parametrů synaptického přenosu. Projevy plasticity mají proto obdobný základ, bez ohledu na příčinu, která je vyvolala, a na oddíl CNS, ve které probíhají.
Neuroplastic mechanisms are based on a modulation of the signal transmission over synapses (e.g., the transmitter release, activity of postsynaptic receptors, efficiency changes in the transmission in the postsynaptic segment). They can be related to the interneuronal relations changes (e.g., number of certain types of synapses, significance of the wiring of different elements of the neuronal circuits). Resulting changes may occur in the communication between neurons (synaptic level), in the activity of the local neuronal circuits (level of local circuits) or in the relations between individual functional brain systems (multimodular level). Neuroplasticity might be based on structural changes, which can be revealed by morphological methods. Such forms of plasticity are more frequent during the development or as a reaction to injury (proliferation and decease of neurons, formation of their processes and spines, remodeling or formation of synapses). More specific methods have determined that these changes are located at the molecular level (enzyme activity, production and release of transmitters or modulators, receptor activation, modulation of ion channels). Both levels of neuroplastic mechanisms bring about changes of functional parameters of the synaptic transmission. Manifestations of plasticity have probably the same basis, irrespectively of a cause, which triggered them, or the brain region where they were accomplished.
