Temperature preferences
Dotaz
Zobrazit nápovědu
Psilocybin, a naturally occurring psychedelic compound in magic mushrooms, shows promise as a novel intervention with a single administration inducing rapid and long-lasting antidepressant effects. However, there are limited studies on the optimal dosing required for the beneficial effects of psilocybin given its side effects. To address this gap, we investigated in Wistar rats whether a single psilocybin administration (0.1, 0.32, 1.0, and 3.2 mg/kg) had antidepressant-like effects in the forced swim test (FST), a pro-social effect in the social interaction test (SIT), and the ability to alter pleasure using the sucrose preference test (SPT). We also examined the dose-response relationships of psilocybin on the head-twitch response (HTR), locomotor activity, body temperature, and weight gain. Furthermore, we explored whether the brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex (PFC) paralleled the behavioral changes observed after psilocybin. In the FST, psilocybin induced dose-dependent inverted-U-shaped responses with only the intermediate dose of 0.32 mg/kg producing short and long-term antidepressant-like effects. A similar pattern was observed for the SIT, the SPT, and the HTR. In contrast, the high doses of psilocybin (1.0 and 3.2 mg/kg), while deprived of anti-depressant-like activity, significantly reduced body temperature, locomotor activity, and body weight gain. BDNF levels in the hippocampus and PFC increased dose-dependently after psilocybin, but linearly suggesting a dissociation between high BDNF levels and the observed antidepressant-like behaviors. Our results indicated that there is a narrow window for the therapeutic potential of psilocybin, with 0.32 mg/kg effectively producing antidepressant-like effects without the accompanying adverse effects observed only at higher doses.
- MeSH
- antidepresiva * farmakologie terapeutické užití MeSH
- halucinogeny * farmakologie MeSH
- hipokampus účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- plavání psychologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- prefrontální mozková kůra účinky léků metabolismus MeSH
- psilocybin * farmakologie terapeutické užití MeSH
- tělesná teplota účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract. METHODS: Hard gelatin capsules and DRcapsTMcapsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms. RESULTS: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcapsTM capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields. CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.
- MeSH
- bakteriální polysacharidy chemie MeSH
- biokompatibilní materiály chemie MeSH
- celulosa * chemie analogy a deriváty MeSH
- deriváty hypromelózy chemie MeSH
- hydrofobní a hydrofilní interakce * MeSH
- hydrogely chemie MeSH
- kofein chemie aplikace a dávkování MeSH
- kolon * metabolismus MeSH
- kyseliny polymethakrylové chemie MeSH
- lékové transportní systémy * metody MeSH
- léky s prodlouženým účinkem chemie MeSH
- polymery chemie MeSH
- polyvinyly chemie MeSH
- tobolky * MeSH
- uvolňování léčiv * MeSH
- želatina * chemie MeSH
- železité sloučeniny chemie aplikace a dávkování MeSH
- Publikační typ
- časopisecké články MeSH
The lipids in the mammalian stratum corneum (SC) adopt an unusually rigid arrangement to form a vital barrier preventing water loss and harmful environmental impacts. Just above the physiological temperature, a subset of barrier lipids undergoes a phase transition from a very tight orthorhombic to a looser hexagonal arrangement and vice versa. The purpose of this lipid transition in skin physiology is unknown. Permeability experiments on isolated human SC indicated that the transition affects the activation energy for a model compound that prefers lateral movement along lipid layers but not for water or a large polymer that would cross the SC through the pore pathway. The orthorhombic phase content of SC lipids, as determined by infrared spectroscopy, was also modulated by (de)hydration. Spontaneous rearrangement of human SC lipid monolayers into 10 nm higher multilamellar islets at 32-37 °C but not at room temperature was revealed by atomic force microscopy. Our findings add to our knowledge of fundamental skin physiology suggesting a fine temperature- and hydration-controlled switch from fluid lipids (required for lipid barrier assembly) to rigid and tightly packed lipids in the mature SC (necessary for the water and permeability barriers).
Structured catalytic membranes with high porosity and a low pressure drop are particularly suitable for industrial processes carried out at high space velocities. One of these processes is the catalytic total oxidation of volatile organic compounds, which is an economically feasible and environmentally friendly way of emission abatement. Noble metal catalysts are typically preferred due to high activity and stability. In this paper, the preparation of a thermally stable polybenzimidazole electrospun membrane, which can be used as a support for a platinum catalyst applicable in the total oxidation of volatile organic compounds, is reported for the first time. In contrast to commercial pelletized catalysts, high porosity of the membrane allowed for easy accessibility of the platinum active sites to the reactants and the catalytic bed exhibited a low pressure drop. We have shown that the preparation conditions can be tuned in order to obtain catalysts with a desired platinum particle size. In the gas-phase oxidation of ethanol, acetone, and toluene, the catalysts with Pt particle sizes 2.1 nm and 26 nm exhibited a lower catalytic activity than that with a Pt particle size of 12 nm. Catalysts with a Pt particle size of 2.1 nm and 12 nm were prepared by equilibrium adsorption, and the higher catalytic activity of the latter catalyst was ascribed to more reactive adsorbed oxygen species on larger Pt nanoparticles. On the other hand, the catalyst with a Pt particle size of 26 nm was prepared by a solvent evaporation method and contained less active polycrystalline platinum. Last but not least, the catalyst containing only 0.08 wt.% of platinum achieved high conversion (90%) of all the model volatile organic compounds at moderate temperatures (lower than 335 °C), which is important for reducing the costs of the abatement technology.
- Publikační typ
- časopisecké články MeSH
Several clinical trials have proved the efficacy and safety of T-cells chimeric antigen receptor (CAR-T cells) in treatment of malignant lymphoma and the first products were registered in the European Union in 2018. The shelf-life of CAR-T cell products in the liquid state is short, so cryopreservation offers a significant benefit for logistics in manufacturing and patient management. Direct shipment of the cryopreserved CAR-T cell therapy products to the clinical department is feasible, nevertheless, intermediate storage in the hospital cryostorage facility gives significant advantage in planning of their administration to patients. Moreover, some manufacturers prefer transport of the starting material cryopreserved at the collection site. The cryopreservation protocol used for starting material by the authors is based on combining dimethyl sulphoxide (DMSO) with hydroxyethyl starch (HES) and slow controlled cooling in cryobags housed in metal cassettes. This achieves the mononuclear cell post-thaw viability of 98.8 ± 0.5 % and recovery of 72.8, ± 10.2 %. Transport of the starting material to the manufactures and return transport of the CAR-T therapy product is performed by authorized courier companies. Intermediate cryostorage of the final CAR-T cell therapy product is performed in a separate dry-storage liquid nitrogen container. On the day of infusion, the cryopreserved products are transported to the clinical department in a dry shipper. On the wards the product is removed from the cassette, inserted into a sterile plastic bag, thawed in a 37 degree C water bath followed by immediate intravenous administration. The authors discuss the adherence of the used technology to good manufacturing practice (GMP) principles and genetic safety assurance rules. Doi: 10.54680/fr23310110112.
- MeSH
- chimerické antigenní receptory * genetika MeSH
- imunoterapie adoptivní metody MeSH
- kryoprezervace metody MeSH
- lidé MeSH
- nízká teplota MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The short oligodeoxynucleotide (ODN) probes are suitable for good discrimination of point mutations. However, the probes suffer from low melting temperatures. In this work, the strategy of using acridine-4-carboxamide intercalators to improve thermal stabilisation is investigated. The study of large series of acridines revealed that optimal stabilisation is achieved upon decoration of acridine by secondary carboxamide carrying sterically not demanding basic function bound through a two-carbon linker. Two highly active intercalators were attached to short probes (13 or 18 bases; designed as a part of HFE gene) by click chemistry into positions 7 and/or 13 and proved to increase the melting temperate (Tm) of the duplex by almost 8°C for the best combination. The acridines interact with both single- and double-stranded DNAs with substantially preferred interaction for the latter. The study of interaction suggested higher affinity of the acridines toward the GC- than AT-rich sequences. Good discrimination of two point mutations was shown in practical application with HFE gene (wild type, H63D C > G and S65C A > C mutations). Acridine itself can also serve as a fluorophore and also allows discrimination of the fully matched sequences from those with point mutations in probes labelled only with acridine.
The influence of experimental conditions on chromatographic behaviour of promising oligodeoxynucleotide double-labelled molecular probes containing an azaphthalocyanine macrocycle as a perspective dark quencher was studied. A recently introduced new stationary phase based on styrene-divinylbenzene copolymer was tested. The planar and hydrophobic structure of the azaphthalocyanine is considerably different from those of currently used fluorophores and quenchers. Thus, the most challenging issue was the separation of the double-labelled probe from its main impurity represented by a mono-labelled probe, containing only the azaphthalocyanine macrocycle. The absorbance measurement cannot simply determine this impurity, and its presence fundamentally compromises the biological assay. The commonly used gradient elution was not suitable and isocratic conditions seemed to be more appropriate. The azaphthalocyanine moiety influences the properties of the modified oligodeoxynucleotides substantially, and thus their chromatographic behaviour was determined predominantly by this quencher. Acetonitrile was the preferred organic solvent for the analysis of probes containing the azaphthalocyanine quencher and the effect of ion-pairing reagents was dependent on the probe structure. The temperature seemed to be an effective parameter for fine-tuning of the separation and mass transfer improvement. Generally, our findings could be helpful in method development for purity evaluation of double-labelled oligodeoxynucleotide probes and semipreparative methods.
- MeSH
- acetonitrily chemie MeSH
- aza sloučeniny * analýza chemie MeSH
- fluorescenční barviva * analýza chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- molekulární sondy * analýza chemie MeSH
- oligodeoxyribonukleotidy * analýza chemie MeSH
- rozpouštědla MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Publikační typ
- časopisecké články MeSH
Campylobacter jejuni is the most frequent cause of bacterial gastrointestinal food-borne infection worldwide. The transmission of Campylobacter and Arcobacter-like species is often made possible by their ability to adhere to various abiotic surfaces. This study is focused on monitoring the biofilm ability of 69 strains of Campylobacter spp. and lesser described species of the Arcobacteraceae family isolated from food, water, and clinical samples within the Czech Republic. Biofilm formation was monitored and evaluated under an aerobic/microaerophilic atmosphere after cultivation for 24 or 72 h depending on the surface material. An overall higher adhesion ability was observed in arcobacters. A chi-squared test showed no association between the origin of the strains and biofilm activity (p > 0.05). Arcobacter-like species are able to form biofilms under microaerophilic and aerobic conditions; however, they prefer microaerophilic environments. Biofilm formation has already been demonstrated at refrigerator temperatures (5 °C). Arcobacters also showed higher biofilm formation ability at the temperature of 30 °C. This is in contrast to Campylobacter jejuni NP 2896, which showed higher biofilm formation ability at temperatures of 5-30 °C. Overall, the results demonstrated the biofilm formation ability of many strains, which poses a considerable risk to the food industry, medical practice, and human health.
- Publikační typ
- časopisecké články MeSH
House dust mites inhabit bed mattresses contaminating them with allergens. A strong temperature/moisture gradient exists in mattresses when it is used by humans daily. Here, we studied migration patterns of the mite Dermatophagoides farinae in continuous and time-discontinuous temperature gradients consisting of five sectors with 19-23, 23-28, 28-32, 32-36 and 36-41 °C, containing dye-labeled diets as an indicator of mite presence and feeding. The mites migrated through the sectors and fed on the labeled diets or stayed unfed. The numbers of mites with the same coloration in their guts and the numbers of unfed mites in the sectors were recorded. Unfed mites provided information on short-term temperature preferences. Apart from a control trial, two experiments were performed: (i) a constant 19-41 °C gradient for 24 h, and (ii) alternating cycles of the same temperature gradient (19-41 °C, 8 h) and room temperature (16 h) for 5 days to model the typical daily occupancy of bed by humans. In both experiments, fed mites preferred a sector with 32-36 °C, suggesting that in mattresses, house dust mites prefer to stay as close as possible to the resting human, thus maximizing allergen exposure. However, the number of unfed mites decreased with increased temperatures in the gradient. Experiment (ii) showed that the fed mites remained at the same optimal distance from the heat source, suggesting that they stay at the upper surface of the regularly used mattress, even when human was temporarily absent during the day. Unfed mites apparently hide deeper in mattresses as suggested by their avoidance of increased temperatures.
BACKGROUND: Sand flies are principal vectors of the protozoan parasites Leishmania spp. and are widely distributed in all warmer regions of the world, including the Mediterranean parts of Europe. In Central European countries, the sand fly fauna is still under investigation. Phlebotomus mascittii, a suspected but unproven vector of Leishmania infantum, is regarded as the most widely distributed species in Europe. However, many aspects of its biology and ecology remain poorly known. The aim of this study was to provide new data on the biology and ecology of Ph. mascittii in Austria to better understand its current distribution and potential dispersal. METHODS: Sand flies were collected by CDC light traps at four localities in Austria for 11 (2018) and 15 weeks (2019) during the active sand fly season. Climatic parameters (temperature, relative humidity, barometric pressure and wind speed) were retrospectively obtained for the trapping periods. Sand flies were identified by a combined approach (morphology, DNA barcoding, MALDI-TOF protein profiling), and blood meals of engorged females were analysed by DNA sequencing and MALDI-TOF mass spectrometry. RESULTS: In total, 450 individuals of Ph. mascittii were caught. Activity was observed to start at the beginning of June and end at the end of August with peaks in mid-July at three locations and early August at one location. Increased activity was associated with relatively high temperatures and humidity. Also, more individuals were caught on nights with low barometric pressure. Analysis of five identified blood meals revealed chicken (Gallus gallus) and equine (Equus spp.) hosts. Sand fly abundance was generally associated with availability of hosts. CONCLUSION: This study reports unexpectedly high numbers of Ph. mascittii at selected Austrian localities and provides the first detailed analysis of its ecology to date. Temperature and humidity were shown to be good predictors for sand fly activity. Blood meal analyses support the assumption that Ph. mascittii feeds on mammals as well as birds. The study significantly contributes to understanding the ecology of this sand fly species in Central Europe and facilitates prospective entomological surveys.
- MeSH
- ekologie * MeSH
- hmyz - vektory * parazitologie MeSH
- koně MeSH
- kur domácí MeSH
- Leishmania infantum MeSH
- Phlebotomus * genetika MeSH
- Psychodidae MeSH
- retrospektivní studie MeSH
- roční období * MeSH
- sekvenční analýza DNA MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Rakousko MeSH
