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Astrocytes actively participate in neurotransmitter homeostasis by bidirectional communication with neuronal cells, a concept named the tripartite synapse, yet their role in dopamine (DA) homeostasis remains understudied. In the present study, we investigated the kinetic and molecular mechanisms of DA transport in cultured striatal astrocytes of adult rats. Kinetic uptake experiments were performed using radiolabeled [3H]-DA, whereas mRNA expression of the dopamine, norepinephrine, organic cation and plasma membrane monoamine transporters (DAT, NET, OCTs and PMAT) and DA receptors D1 and D2 was determined by qPCR. Additionally, astrocyte cultures were subjected to a 24 h treatment with the DA receptor agonist apomorphine, the DA receptor antagonist haloperidol and the DA precursor L-DOPA. [3H]-DA uptake exhibited temperature, concentration and sodium dependence, with potent inhibition by desipramine, nortriptyline and decynium-22, suggesting the involvement of multiple transporters. qPCR revealed prominent mRNA expression of the NET, the PMAT and OCT1, alongside lower levels of mRNA for OCT2, OCT3 and the DAT. Notably, apomorphine significantly altered NET, PMAT and D1 mRNA expression, while haloperidol and L-DOPA had a modest impact. Our findings demonstrate that striatal astrocytes aid in DA clearance by multiple transporters, which are influenced by dopaminergic drugs. Our study enhances the understanding of regional DA uptake, paving the way for targeted therapeutic interventions in dopaminergic disorders.

Abstract Water-soluble poly(vinyl alcohol) (PVOH) is widely used in the textile and paper industries and in households as detergent pods. In addition to conventional microplastics, water-soluble PVOH poses an environmental threat because it is usually washed down the drain unnoticed and unobstructed. If not treated during wastewater treatment, it enters the aquatic ecosystem in estimated quantities of several thousand tons annually. The present study aims to address the degradation of PVOH on a laboratory scale by acoustic and hydrodynamic cavitation, assisted or not with an oxidative agent. A hydrodynamic cavitation generator, designed with consideration for real-life application, presents an innovative technology adapted for wastewater treatment. The effects of temperature, addition of external oxidant, and methanol as a hydroxyl radical (•OH) scavenger to PVOH solutions were systematically studied. At optimal operating conditions, PVOH molar mass averages significantly decreased (from weight average molar mass of 124 to 1.6 kg mol−1 in case of 60 min treatment with hydrodynamic cavitation and addition of external oxidant) with concomitant narrowing of molar mass distribution. The SEC/MALS, FTIR, and 1H NMR results show that mechanical degradation of PVOH chains predominates in acoustic cavitation, while chemical effects also play an important role in hydrodynamic cavitation. Findings from this study could serve as model research for the degradation of other carbon-backbone polymers and provide a route to improved ultimate (bio)degradation of functionalized polymers in the environment.

Astrocytes are crucial in the regulation of neurotransmitter homeostasis, and while their involvement in the dopamine (DA) tripartite synapse is acknowledged, it necessitates a more comprehensive investigation. In the present study, experiments were conducted on primary astrocyte cultures from the striatum and cortex of neonatal rats. The pharmacological intricacies of DA uptake, including dependence on time, temperature, and concentration, were investigated using radiolabelled [3H]-DA. The mRNA expression of transporters DAT, NET, PMAT, and OCTs was evaluated by qPCR. Notably, astrocytes from both brain regions exhibited prominent mRNA expression of NET and PMAT, with comparatively lower expression of DAT and OCTs. The inhibition of DA uptake by the DAT inhibitor, GBR12909, and NET inhibitors, desipramine and nortriptyline, impeded DA uptake in striatal astrocytes more than in cortical astrocytes. The mRNA expression of NET and PMAT was significantly upregulated in cortical astrocytes in response to the DA receptor agonist apomorphine, while only the mRNA expression of NET exhibited changes in striatal astrocytes. Haloperidol, a DA receptor antagonist, and L-DOPA, a DA precursor, did not induce significant alterations in transporter mRNA expression. These findings underscore the intricate and region-specific mechanisms governing DA uptake in astrocytes, emphasizing the need for continued exploration to unravel the nuanced dynamics of astrocytic involvement in the DA tripartite synapse.

IntroductionData are lacking on the pharmacokinetic profile and safety of levobupivacaine (LB) used for regional anesthesia of the maxilla and mandibles in dogs.MethodsInfraorbital block (n = 10), inferior alveolar block (n = 10) or both infraorbital and inferior alveolar blocks (n = 10) were administered to dogs undergoing dental surgery under isoflurane anesthesia. The dose of LB was calculated as 0.11 ml/kg2/3 for the infraorbital block and 0.18 ml/kg2/3 for the inferior alveolar block. Blood samples were collected before and immediately after administration of the oral blocks, and 3, 4, 7, 12, 17, 32, 47, 62, 92, and 122 min thereafter. Quantification of LB in plasma was performed by LC-MS/MS.Results and discussionThe results are presented as median and interquartile range. In dogs in which all four quadrants of the oral cavity were desensitized with LB, the Cmax was 1,335 (1,030–1,929) ng/ml, the Tmax was 7 (4–9.5) min, and the AUC(0 → 120) was 57,976 (44,954–96,224) ng min/ml. Plasma concentrations of LB were several times lower than the reported toxic concentrations, and no signs of cardiovascular depression or neurotoxicity were observed in any of the dogs, suggesting that the occurrence of severe adverse effects after administration of LB at the doses used in this study is unlikely.

To increase the sustainability of prefabricated timber buildings and constructions, composite timber beams with “box” cross-sections were developed in collaboration with an industry partner. They were constructed from a solid timber frame and from webs made of residual waste wood-particle boards from prefabricated timber buildings production. The developed beams’ design concepts presented in this paper were governed by architectural features of prefabricated timber buildings, geometrical limitations, available production technology, and structural demand related to various possible applications. The paper presents the results of experimental bending tests of six variations of the developed composite timber beams constructed by mechanical fasteners only. The developed design concept of composite timber beams without adhesives is beneficial compared to glued beams in terms of design for deconstruction and lower VOC emissions. The tests were conducted to study the influence of the following parameters on the beams’ mechanical behavior: (i) web material (oriented strand boards (OSBs) vs. cement-particle boards); (ii) the influence of beam timber frame design (flanges and web stiffeners vs. flanges, web stiffeners, and compressive diagonals), and (iii) the influence of stiffener–flange joint design. Besides the beams’ load-bearing capacities, their linear and non-linear stiffness characteristics were the main research interest. While adding compressive timber diagonals did not prove to significantly increase the stiffness of the beams in the case of cement-particle board webs, it increased their load-bearing capacity by enabling the failure of flanges instead of prior webs and stiffener–flange joints failure. For beams with OSB webs, failure of the bottom flange was achieved already with the “basic” timber frame design, but timber diagonals proved beneficial to increase the stiffness characteristics. Finally, mechanical characteristics of the developed beams needed in structural design for their application are provided together with further development guidelines.

Astrocytes, glial cells in the central nervous system, perform a multitude of homeostatic functions and are in constant bidirectional communication with neuronal cells, a concept named the tripartite synapse; however, their role in the dopamine homeostasis remains unexplored. The aim of this study was to clarify the pharmacological and molecular characteristics of dopamine transport in cultured cortical astrocytes of adult rats. In addition, we were interested in the expression of mRNA of dopamine transporters as well as dopamine receptors D1 and D2 and in the effect of dopaminergic drugs on the expression of these transporters and receptors. We have found that astrocytes possess both Na+‐dependent and Na+‐independent transporters. Uptake of radiolabelled dopamine was time‐, temperature‐ and concentration‐dependent and was inhibited by decynium‐22, a plasma membrane monoamine transporter inhibitor, tricyclic antidepressants desipramine and nortriptyline, both inhibitors of the norepinephrine transporter. Results of transporter mRNA expression indicate that the main transporters involved in cortical astrocyte dopamine uptake are the norepinephrine transporter and plasma membrane monoamine transporter. Both dopamine receptor subtypes were identified in cortical astrocyte cultures. Twenty‐four‐hour treatment of astrocyte cultures with apomorphine, a D1/D2 agonist, induced upregulation of D1 receptor, norepinephrine transporter and plasma membrane monoamine transporter, whereas the latter was downregulated by haloperidol and L‐DOPA. Astrocytes take up dopamine by multiple transporters and express dopamine receptors, which are sensitive to dopaminergic drugs. The findings of this study could open a promising area of research for the fine‐tuning of existing therapeutic strategies. [ABSTRACT FROM AUTHOR]

This study investigated the cardiopulmonary effects and pharmacokinetics of dexmedetomidine (DEX) used as an adjunctive analgesic for regional anesthesia of the oral cavity with levobupivacaine in anesthetized dogs. Forty dogs were randomly assigned to four groups of 10 dogs. All dogs received levobupivacaine (4 blocks) with DEX IO (infraorbital block, n = 10) or IA (inferior alveolar block, n = 10) or placebo (PLC; n = 10) or DEX (n = 10) was injected intravenously (IV) after administration of levobupivacaine. The dose of DEX was always 0.5 µg/kg. Cardiopulmonary parameters were recorded, and blood was drawn for the quantification of DEX in plasma using LC-MS/MS. Heart rate was lower in all LB + DEX groups, while mean arterial pressure (MAP) was higher in the LB + DEX IV and LB + DEX IA groups compared to the LB + PLC IV group. Compared to DEX IV, IO and IA administration resulted in lower MAP up to 2 min after application. Absorption of DEX was faster at IO administration (Cmax and Tmax were 0.47 ± 0.08 ng/mL and 7.22 ± 1.28 min and 0.76 ± 0.09 ng/mL and 7.50 ± 1.63 min for the IO and IA block, respectively). The IA administration resulted in better bioavailability and faster elimination (t1/2 was 63.44 ± 24.15 min and 23.78 ± 3.78 min for the IO and IA block, respectively). Perineural administration of DEX may be preferable because of the less pronounced cardiovascular response compared to IV administration.

An experimental study on the effects of electroporation on pancreatic tissue was performed in pigs, and the fentanyl transdermal patch (FTP) was used postoperatively as part of multimodal pain management. Ingestion of an FTP, which resulted in fentanyl intoxication, was suspected 5 days after placement in one of the experimental pigs. The pig was first dysphoric, running in the stall, panting and vocalizing until it finally became depressed and it remained lying on the floor. Ingestion of an FTP was not observed but the fentanyl plasma concentration on the day of intoxication was 20.7 ng/ml, while at its peak after FTP administration it was only 0.492 ng/ml. The intoxication was successfully treated with a single intramuscular naloxone injection.

Composites of polylactide (PLA) or poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and ZnO nanoparticles (nZnO) were prepared by melt processing. During extrusion and moulding nano ZnO formed aggregates with sizes between 0.5 and 5 μm in PLA and between 0.5 and 15 μm in PHBV. Nano ZnO acted as a disruptor of PLA crystallization process and shifted the polymer glass transition temperature to lower temperatures. This was explained by degradation of PLA polymer chains during melt processing. SEC, FTIR and 1H NMR confirmed that PLA degradation was correlated to nZnO concentration. The effect of nZnO on crystallization of PHBV matrix was much less intense which was shown by TGA. On the other hand, PHBV showed significantly lower thermal stability than PLA. ZnO participated as a reactant and an accelerator in the degradation reaction of PLA and at a smaller extent with PHBV. The results of this study revealed that addition of pure nZnO in concentrations higher than 0.1 wt.% is not recommended for the preparation of PLA/nZnO composites by melt processing while in the case of PHBV the nZnO concentration may be higher but it should not exceed 1.0 wt.%. The exposure time of these materials to high temperatures during melt processing should also be minimized.

Astrocytes are crucial in the regulation of neurotransmitter homeostasis, and while their involvement in the dopamine (DA) tripartite synapse is acknowledged, it necessitates a more comprehensive investigation. In the present study, experiments were conducted on primary astrocyte cultures from the striatum and cortex of neonatal rats. The pharmacological intricacies of DA uptake, including dependence on time, temperature, and concentration, were investigated using radiolabelled [3H]-DA. The mRNA expression of transporters DAT, NET, PMAT, and OCTs was evaluated by qPCR. Notably, astrocytes from both brain regions exhibited prominent mRNA expression of NET and PMAT, with comparatively lower expression of DAT and OCTs. The inhibition of DA uptake by the DAT inhibitor, GBR12909, and NET inhibitors, desipramine and nortriptyline, impeded DA uptake in striatal astrocytes more than in cortical astrocytes. The mRNA expression of NET and PMAT was significantly upregulated in cortical astrocytes in response to the DA receptor agonist apomorphine, while only the mRNA expression of NET exhibited changes in striatal astrocytes. Haloperidol, a DA receptor antagonist, and L-DOPA, a DA precursor, did not induce significant alterations in transporter mRNA expression. These findings underscore the intricate and region-specific mechanisms governing DA uptake in astrocytes, emphasizing the need for continued exploration to unravel the nuanced dynamics of astrocytic involvement in the DA tripartite synapse. [ABSTRACT FROM AUTHOR]

Differential scanning calorimetry provides unique signatures of blood plasma samples. Plasma samples from diseased individuals yield specific thermograms, which differ from each other and from plasma samples of healthy individuals. Thermograms from individuals suffering from chronic lymphocytic leukemia, multiple myeloma and acute myeloid leukemia were measured with DSC. To obtain additional information about thermal behaviour of plasma proteins immunoaffinity chromatography was introduced. An immunoextraction of HSA using a chromatographic column with immobilized anti-HSA was carried out in order to enrich less abundant plasma proteins, which could provide a further insight into disease development. Efficiency of HSA depletion and protein composition of fractionated plasma was validated by SDS-PAGE.

We used a combination of density functional theory (DFT) calculations and the implicit quantization of the acidic N−H and O−H bonds to assess the effect of deuteration on the binding of agonists (2-methylhistamine and 4-methylhistamine) and antagonists (cimetidine and famotidine) to the histamine H2 receptor. The results show that deuteration significantly increases the affinity for 4-methylhistamine and reduces it for 2-methylhistamine, while leaving it unchanged for both antagonists, which is found in excellent agreement with experiments. The revealed trends are interpreted in the light of the altered strength of the hydrogen bonding upon deuteration, known as the Ubbelohde effect, which affects ligand interactions with both active sites residues and solvent molecules preceding the binding, thus providing strong evidence for the relevance of hydrogen bonding for this process. In addition, computations further underline an important role of the Tyr250 residue for the binding. The obtained insight is relevant for the therapy in the context of (per)deuterated drugs that are expected to enter therapeutic practice in the near future, while this approach may contribute towards understanding receptor activation and its discrimination between agonists and antagonists.