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1.
Eur J Neurosci ; 59(7): 1558-1566, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38308520

RESUMEN

The excitation-inhibition imbalance manifesting as epileptic activities in Alzheimer's disease is gaining more and more attention, and several potentially involved cellular and molecular pathways are currently under investigation. Based on in vitro studies, dopamine D1-type receptors in the anterior cingulate cortex and the hippocampus have been proposed to participate in this peculiar co-morbidity in mouse models of amyloidosis. Here, we tested the implication of dopaminergic transmission in vivo in the Tg2576 mouse model of Alzheimer's disease by monitoring epileptic activities via intracranial EEG before and after treatment with dopamine antagonists. Our results show that neither the D1-like dopamine receptor antagonist SCH23390 nor the D2-like dopamine receptor antagonist haloperidol reduces the frequency of epileptic activities. While requiring further investigation, our results indicate that on a systemic level, dopamine receptors are not significantly contributing to epilepsy observed in vivo in this mouse model of Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Epilepsia , Ratones , Animales , Antagonistas de Dopamina/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Receptores de Dopamina D2/metabolismo , Benzazepinas/farmacología , Benzazepinas/uso terapéutico , Receptores de Dopamina D1/metabolismo , Epilepsia/tratamiento farmacológico , Modelos Animales de Enfermedad , Amiloidosis/tratamiento farmacológico
2.
Biomacromolecules ; 25(5): 2863-2874, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38564884

RESUMEN

With the rapid increase of the number of patients with gastrointestinal diseases in modern society, the need for the development of physiologically relevant in vitro intestinal models is key to improve the understanding of intestinal dysfunctions. This involves the development of a scaffold material exhibiting physiological stiffness and anatomical mimicry of the intestinal architecture. The current work focuses on evaluating the scaffold micromorphology of gelatin-methacryloyl-aminoethyl-methacrylate-based nonporous and porous intestinal 3D, intestine-like constructs, fabricated via digital light processing, on the cellular response. To this end, Caco-2 intestinal cells were utilized in combination with the constructs. Both porous and nonporous constructs promoted cell growth and differentiation toward enterocyte-like cells (VIL1, ALPI, SI, and OCLD expression showed via qPCR, ZO-1 via immunostaining). The porous constructs outperformed the nonporous ones regarding cell seeding efficiency and growth rate, confirmed by MTS assay, live/dead staining, and TEER measurements, due to the presence of surface roughness.


Asunto(s)
Hidrogeles , Andamios del Tejido , Humanos , Porosidad , Hidrogeles/química , Células CACO-2 , Andamios del Tejido/química , Proliferación Celular , Gelatina/química , Intestinos/citología , Metacrilatos/química , Ingeniería de Tejidos/métodos , Diferenciación Celular
3.
J Cell Mol Med ; 25(11): 5113-5123, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33942485

RESUMEN

Albeit previous experiments suggest potential anti-inflammatory effect of exogenous methane (CH4 ) in various organs, the mechanism of its bioactivity is not entirely understood. We aimed to investigate the potential mitochondrial effects and the underlying mechanisms of CH4 in rat cardiomyocytes and mitochondria under simulated ischaemia/reperfusion (sI/R) conditions. Three-day-old cultured cardiomyocytes were treated with 2.2% CH4 -artificial air mixture during 2-hour-long reoxygenation following 4-hour-long anoxia (sI/R and sI/R + CH4 , n = 6-6), with normoxic groups serving as controls (SH and SH + CH4 ; n = 6-6). Mitochondrial functions were investigated with high-resolution respirometry, and mitochondrial membrane injury was detected by cytochrome c release and apoptotic characteristics by using TUNEL staining. CH4 admixture had no effect on complex II (CII)-linked respiration under normoxia but significantly decreased the complex I (CI)-linked oxygen consumption. Nevertheless, addition of CH4 in the sI/R + CH4 group significantly reduced the respiratory activity of CII in contrast to CI and the CH4 treatment diminished mitochondrial H2 O2 production. Substrate-induced changes to membrane potential were partially preserved by CH4 , and additionally, cytochrome c release and apoptosis of cardiomyocytes were reduced in the CH4 -treated group. In conclusion, the addition of CH4 decreases mitochondrial ROS generation via blockade of electron transport at CI and reduces anoxia-reoxygenation-induced mitochondrial dysfunction and cardiomyocyte injury in vitro.


Asunto(s)
Hipoxia/fisiopatología , Metano/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Isquemia Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Oxígeno/metabolismo , Animales , Animales Recién Nacidos , Potencial de la Membrana Mitocondrial , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Isquemia Miocárdica/etiología , Isquemia Miocárdica/patología , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno
4.
Molecules ; 26(19)2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34641462

RESUMEN

In this work core/shell composite polymer/TiO2 nanofibers and from those TiO2 nanotubes were prepared. First, poly(vinyl alcohol) (PVA) and poly(vinylpyrrolidone) (PVP) fibers were synthetized by electrospinning. They were covered with a 100 nm thick amorphous TiO2 layer by atomic layer deposition at 50 °C. Later the polymer core was removed by two different methods: dissolution and annealing. In the case of dissolution in water, the as-prepared TiO2 nanotubes remained amorphous, while when annealing was used to remove the polymers, the TiO2 crystallized in anatase form. Due to this, the properties of amorphous and crystalline TiO2 nanotubes with exactly the same structure and morphology could be compared. The samples were investigated by SEM-EDX, ATR-IR, UV-Vis, XRD and TG/DTA-MS. Finally, the photocatalytic properties of the TiO2 nanotubes were studied by decomposing methyl-orange dye under UV light. According to the results, crystalline anatase TiO2 nanotubes reached the photocatalytic performance of P25, while amorphous TiO2 nanotubes had observable photocatalytic activity.

5.
Crit Care Med ; 47(5): e403-e411, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30985462

RESUMEN

OBJECTIVES: Methane (CH4) breath test is an established diagnostic method for gastrointestinal functional disorders. Our aim was to explore the possible link between splanchnic circulatory changes and exhaled CH4 in an attempt to recognize intestinal perfusion failure. DESIGN: Randomized, controlled in vivo animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized, ventilated Sprague-Dawley rats (280 ± 30 g) and Vietnamese minipigs (31 ± 7 kg). INTERVENTIONS: In the first series, CH4 was administered intraluminally into the ileum before 45 minutes mesenteric ischemia or before reperfusion in non-CH4 producer rats to test the appearance of the gas in the exhaled air. In the porcine experiments, the superior mesenteric artery was gradually obstructed during consecutive, 30-minute flow reductions and 30-minute reperfusions achieving complete occlusion after four cycles (n = 6), or nonocclusive mesenteric ischemia was induced by pericardial tamponade (n = 12), which decreased superior mesenteric artery flow from 351 ± 55 to 182 ± 67 mL/min and mean arterial pressure from 96.7 ± 18.2 to 41.5 ± 4.6 mm Hg for 60 minutes. MEASUREMENTS AND MAIN RESULTS: Macrohemodynamics were monitored continuously; RBC velocity of the ileal serosa or mucosa was recorded by intravital videomicroscopy. The concentration of exhaled CH4 was measured online simultaneously with high-sensitivity photoacoustic spectroscopy. The intestinal flow changes during the occlusion-reperfusion phases were accompanied by parallel changes in breath CH4 output. Also in cardiac tamponade-induced nonocclusive intestinal ischemia, the superior mesenteric artery flow and RBC velocity correlated significantly with parallel changes in CH4 concentration in the exhaled air (Pearson's r = 0.669 or r = 0.632, respectively). CONCLUSIONS: we report a combination of in vivo experimental data on a close association of an exhaled endogenous gas with acute mesenteric macro- and microvascular flow changes. Breath CH4 analysis may offer a noninvasive approach to follow the status of the splanchnic circulation.


Asunto(s)
Isquemia Mesentérica , Metano , Daño por Reperfusión , Animales , Masculino , Ratas , Pruebas Respiratorias , Modelos Animales de Enfermedad , Hemodinámica/efectos de los fármacos , Isquemia Mesentérica/fisiopatología , Metano/farmacología , Ratas Sprague-Dawley , Flujo Sanguíneo Regional , Daño por Reperfusión/fisiopatología , Porcinos
6.
Ann Bot ; 119(2): 301-309, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-28025290

RESUMEN

BACKGROUND AND AIMS: Dolines are small- to large-sized bowl-shaped depressions of karst surfaces. They may constitute important microrefugia, as thermal inversion often maintains cooler conditions within them. This study aimed to identify the effects of large- (macroclimate) and small-scale (slope aspect and vegetation type) environmental factors on cool-adapted plants in karst dolines of East-Central Europe. We also evaluated the potential of these dolines to be microrefugia that mitigate the effects of climate change on cool-adapted plants in both forest and grassland ecosystems. METHODS: We compared surveys of plant species composition that were made between 2007 and 2015 in 21 dolines distributed across four mountain ranges (sites) in Hungary and Romania. We examined the effects of environmental factors on the distribution and number of cool-adapted plants on three scales: (1) regional (all sites); (2) within sites and; (3) within dolines. Generalized linear models and non-parametric tests were used for the analyses. KEY RESULTS: Macroclimate, vegetation type and aspect were all significant predictors of the diversity of cool-adapted plants. More cool-adapted plants were recorded in the coolest site, with only few found in the warmest site. At the warmest site, the distribution of cool-adapted plants was restricted to the deepest parts of dolines. Within sites of intermediate temperature and humidity, the effect of vegetation type and aspect on the diversity of cool-adapted plants was often significant, with more taxa being found in grasslands (versus forests) and on north-facing slopes (versus south-facing slopes). CONCLUSIONS: There is large variation in the number and spatial distribution of cool-adapted plants in karst dolines, which is related to large- and small-scale environmental factors. Both macro- and microrefugia are therefore likely to play important roles in facilitating the persistence of cool-adapted plants under global warming.


Asunto(s)
Ecosistema , Fenómenos Fisiológicos de las Plantas , Cambio Climático , Frío , Refugio de Fauna
7.
Sleep ; 47(1)2024 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-37889222

RESUMEN

Sleep scoring plays a pivotal role both in sleep research and in clinical practice. Traditionally, this process has relied on manual scoring by human experts, but it is marred by time constraints, and inconsistencies between different scorers. Consequently, the quest for more efficient and reliable approaches has sparked a great interest in the realm of automatic sleep-scoring methods. In this article, we provide an exploration of the merits and drawbacks of automatic sleep scoring, alongside the pressing challenges and critical considerations that demand attention in this evolving field.


Asunto(s)
Fases del Sueño , Sueño , Humanos , Polisomnografía , Atención , Proyectos de Investigación , Electroencefalografía
8.
3D Print Addit Manuf ; 11(1): 1-9, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38389696

RESUMEN

Foam 3D printing in construction is a promising manufacturing approach that aims to reduce the amount of material, hazardous labor, and costs in producing lightweight and insulating building parts that can reduce the operational energy in buildings. Research using cement-free mineral foams derived from industrial waste showed great potential in previous studies that reduced the amount of concrete needed in composite structures. This article collates the latest developments in this line of work. It presents the material system with its principal components and the advanced robotic 3D printing setup with a climate-controlled fabrication chamber. Print path schemes and hybrid fabrication methods combining 3D printing and casting are evaluated. Furthermore, the article discusses the effect of different print path schemes on the thermal insulation and compressive strength performance of printed parts. A full-scale final prototype synthesizes these findings and demonstrates the fabrication of modular, lightweight, and insulating construction elements that can be assembled into monolithic wall structures. The advantages and challenges of this novel approach are elaborated on in the conclusions. Finally, the article presents future advancements required to leverage this research as a scalable construction method that can help address the biggest challenges in building low-carbon and energy-efficient structures.

9.
Materials (Basel) ; 17(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38930365

RESUMEN

Gelatin-based photo-crosslinkable hydrogels are promising scaffold materials to serve regenerative medicine. They are widely applicable in additive manufacturing, which allows for the production of various scaffold microarchitectures in line with the anatomical requirements of the organ to be replaced or tissue defect to be treated. Upon their in vivo utilization, the main bottleneck is to monitor cell colonization along with their degradation (rate). In order to enable non-invasive visualization, labeling with MRI-active components like N-(2,2-difluoroethyl)acrylamide (DFEA) provides a promising approach. Herein, we report on the development of a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink in combination with DFEA, applicable in digital light processing-based additive manufacturing towards bone tissue regeneration. The fabricated hydrogel constructs show excellent shape fidelity in line with the printing resolution, as DFEA acts as a small molecular crosslinker in the system. The constructs exhibit high stiffness (E = 36.9 ± 4.1 kPa, evaluated via oscillatory rheology), suitable to serve bone regeneration and excellent MRI visualization capacity. Moreover, in combination with adipose tissue-derived stem cells (ASCs), the 3D-printed constructs show biocompatibility, and upon 4 weeks of culture, the ASCs express the osteogenic differentiation marker Ca2+.

10.
Drug Deliv ; 31(1): 2305818, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38424728

RESUMEN

Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly(ε-caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization (1H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin.


AUP-PCL MN arrays provide long-term transdermal drug delivery of hydrocortisoneAUP-PCL-based MN arrays provide superior drug release profiles compared to PCL MNsEffective skin penetration AUP-PCL-based MNs on skin was achieved.


Asunto(s)
Cicatriz Hipertrófica , Poliésteres , Humanos , Administración Cutánea , Preparaciones Farmacéuticas/metabolismo , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/metabolismo , Liberación de Fármacos , Piel/metabolismo , Sistemas de Liberación de Medicamentos , Polímeros/metabolismo , Agujas
11.
Biodivers Data J ; 12: e119539, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841134

RESUMEN

Background: Biological invasions pose an increasing risk to nature, social security and the economy, being ranked amongst the top five threats to biodiversity. Managing alien and invasive species is a priority for the European Union, as outlined in the EU Biodiversity Strategy for 2030 and the Kunming-Montreal Global Biodiversity Framework. Alien plant species are acknowledged to impact the economy and biodiversity; thus, analysing the distribution of such species provides valuable inputs for the management and decision-making processes. The database presented in the current study is the first consolidated checklist of alien plant species that are present in Romania, both of European Union concern and of national interest. This database complements a prior published distribution, based only on records from literature, bringing new information regarding the occurrence of alien plants in Romania, as revealed by a nationwide field survey. We consider this database a valuable instrument for managing biological invasions at both national and regional levels, as it can be utilised in further research studies and in drafting management and action plans, assisting stakeholders in making informed decisions and implementing management actions. New information: We present the results of the first nationwide survey of alien plant species in Romania, conducted between 2019 and 2022, in the framework of a national project coordinated by the Ministry of Environment, Waters and Forests and the University of Bucharest. The present database complements and updates the database published by Sirbu et. al (2022), which included occurrence records published until 2019. The new database includes 98323 occurrence records for 396 alien plant species in 77 families, with most species belonging to the Asteraceae family. One alien plant species in our database, the black locust Robiniapseudoacacia L., had more than 10,000 occurrence records. The distribution database also includes information on newly-reported invasive alien plant species of European Union concern in Romania (i.e. the floating primrose-willow Ludwigiapeploides (Kunth) P.H.Raven) and documents the presence of plants in 44 additional families compared to Sirbu et al. (2022). Each entry includes information on species taxonomy, location, year, person who recorded and identified the alien plant, geographical coordinates and taxon rank.

12.
Am J Physiol Cell Physiol ; 304(2): C207-14, 2013 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-23174561

RESUMEN

Previous studies demonstrated methane generation in aerobic cells. Our aims were to investigate the methanogenic features of sodium azide (NaN(3))-induced chemical hypoxia in the whole animal and to study the effects of l-α-glycerylphosphorylcholine (GPC) on endogenous methane production and inflammatory events as indicators of a NaN(3)-elicited mitochondrial dysfunction. Group 1 of Sprague-Dawley rats served as the sham-operated control; in group 2, the animals were treated with NaN(3) (14 mg·kg(-1)·day(-1) sc) for 8 days. In group 3, the chronic NaN(3) administration was supplemented with daily oral GPC treatment. Group 4 served as an oral antibiotic-treated control (rifaximin, 10 mg·kg(-1)·day(-1)) targeting the intestinal bacterial flora, while group 5 received this antibiotic in parallel with NaN(3) treatment. The whole body methane production of the rats was measured by means of a newly developed method based on photoacoustic spectroscopy, the microcirculation of the liver was observed by intravital videomicroscopy, and structural changes were assessed via in vivo fluorescent confocal laser-scanning microscopy. NaN(3) administration induced a significant inflammatory reaction and methane generation independently of the methanogenic flora. After 8 days, the hepatic microcirculation was disturbed and the ATP content was decreased, without major structural damage. Methane generation, the hepatic microcirculatory changes, and the increased tissue myeloperoxidase and xanthine oxidoreductase activities were reduced by GPC treatment. In conclusion, the results suggest that methane production in mammals is connected with hypoxic events associated with a mitochondrial dysfunction. GPC is protective against the inflammatory consequences of a hypoxic reaction that might involve cellular or mitochondrial methane generation.


Asunto(s)
Inhibidores Enzimáticos/efectos adversos , Metano/biosíntesis , Azida Sódica/efectos adversos , Adenosina Trifosfato/análisis , Animales , Hipoxia de la Célula , Fármacos Gastrointestinales/farmacología , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/microbiología , Glicerilfosforilcolina/farmacología , Inflamación/inducido químicamente , Inflamación/metabolismo , Circulación Hepática/efectos de los fármacos , Masculino , Microcirculación/efectos de los fármacos , Microscopía Confocal/métodos , Microscopía por Video/métodos , Peroxidasa/análisis , Técnicas Fotoacústicas/métodos , Ratas , Ratas Sprague-Dawley , Rifamicinas/farmacología , Rifaximina , Xantina Deshidrogenasa/análisis
13.
Orv Hetil ; 154(7): 257-61, 2013 Feb 17.
Artículo en Húngaro | MEDLINE | ID: mdl-23395789

RESUMEN

INTRODUCTION: Since May 2011, protease inhibitor/ribavirin/peginterferon combination has become the standard treatment for both treatment-naive and treatment-experienced patients infected with hepatitis C virus genotype 1. In Hungary, due to limited resources, the therapy of treatment-experienced patients might only be financed in the near future. AIM: The aim of this retrospective study was to find out characteristics of the patient group waiting for new triple combination in a single hepatology centre in Hungary, and to estimate the possible rate of their sustained virologic response. METHOD: Between January 2004 and September 2012, 269 patients with chronic hepatitis C virus infection were treated with peginterferon/ribavirin therapy. 142 patients failed to achieve sustained virologic response, but out of them, 93 individuals are the possible candidates for the triple antiviral treatment. In the latter group, the previous virologic response to dual therapy was determined. To register fibrosis scores, findings of liver biopsy and/or fibroelastography were also collected. Interleukin28B genotypes of 49 patients were determined. RESULTS: Among the 93 treatment-experienced patients, 25 relapsed, 26 responded partially , 6 broke through, and 36 null-responders were found. 29% of patients had mild or moderate fibrosis and 71% of those already had severe fibrosis. Of the 49 patients with known interleukin28B genotype only 8 patients had the CC genotype. CONCLUSIONS: About half of the patients (mostly relapsers, and some partial responders as well) have a good chance of achieving sustained virologic response, which may be influenced by the fibrosis score.


Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Adulto , Anciano , Antivirales/administración & dosificación , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Hepatitis C Crónica/virología , Humanos , Hungría , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Cirrosis Hepática/prevención & control , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Recurrencia , Retratamiento , Estudios Retrospectivos , Ribavirina/uso terapéutico , Resultado del Tratamiento , Listas de Espera
14.
Photoacoustics ; 30: 100469, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36911594

RESUMEN

High temporal resolution concentration measurements in rapid gas flows pose a serious challenge for most analytical instruments. The interaction of such flows with solid surfaces can generate excessive aero-acoustic noise making the application of the photoacoustic detection method seemingly impossible. Yet, the fully open photoacoustic cell (OC) has proven to be operable even when the measured gas flows through it at a velocity of several m/s. The OC is a slightly modified version of a previously introduced OC based on the excitation of a combined acoustic mode of a cylindrical resonator. The noise characteristics and analytical performance of the OC are tested in an anechoic room and under field conditions. Here we present the first successful application of a sampling-free OC for water vapor flux measurements.

15.
Neurobiol Aging ; 123: 35-48, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36634385

RESUMEN

The link between Alzheimer's disease (AD) and network hypersynchrony - manifesting as epileptic activities - received considerable attention in the past decade. However, several questions remain unanswered as to its mechanistic underpinnings. Therefore, our objectives were (1) to better characterise epileptic events in the Tg2576 mouse model throughout the sleep-wake cycle and disease progression via electrophysiological recordings and (2) to explore the involvement of noradrenergic transmission in this pathological hypersynchrony. Over and above confirming the previously described early presence and predominance of epileptic events during rapid-eye-movement (REM) sleep, we also show that these events do not worsen with age and are highly phase-locked to the section of the theta cycle during REM sleep where hippocampal pyramidal cells reach their highest firing probability. Finally, we reveal an antiepileptic mechanism of noradrenergic transmission via α1-adrenoreceptors that could explain the intriguing distribution of epileptic events over the sleep-wake cycle in this model, with potential therapeutic implications in the treatment of the epileptic events occurring in many AD patients.


Asunto(s)
Enfermedad de Alzheimer , Epilepsia , Ratones , Animales , Enfermedad de Alzheimer/patología , Ratones Transgénicos , Sueño/fisiología , Modelos Animales de Enfermedad , Sueño REM
16.
J Burn Care Res ; 44(1): 158-169, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36318807

RESUMEN

Hypertrophic scarring (HTS) is frequently observed after deep dermal and full-thickness skin defects. Local drug delivery in HTS has been shown more effective compared to other (minimally) invasive treatments. Disadvantages being operator-dependency and non-uniform drug distribution. Moreover, injections are painful and difficult when confronted with extensive scars or HTS in children. Corticoid-embedded dissolving microneedles (CEDMN) were developed that provide painless skin penetration and direct dermal drug delivery. Hyaluronic acid-based DMN and CEDMN patches were utilized. Structural analysis was performed via nuclear magnetic resonance (NMR) spectroscopy while gel permeation chromatography (GPC) was applied to determine chain length (molar mass) and dispersity of hyaluronic acid. Mechanical properties were evaluated by compression testing. Five burn victims with HTS were included. For each individual, three comparable scars were chosen. One control scar was left untreated. Two scars were treated with either 600 or 800 µm CEDMN patches. Patients were treated monthly for 4 months. Treatment with 800 µm CEDMN was initiated after 8 weeks. Assessor-blinded POSAS was registered. Hydration, evaporation, color and elasticity were recorded. The physico-chemical characterization suggests that the mechanical properties enable skin penetration and adequate drug delivery. Patients experienced the therapy as painless. According to the POSAS, all scars improved over time. However, the scars that were treated with CEDMN patches improved faster and with increased increment. The 800 µm CEDMN ensured the fastest POSAS-decrease. Hyaluronic acid-based CEDMN patches are valuable alternatives to intracicatrical injections, as they offer a painless and effective method for administering corticosteroids in HTS.


Asunto(s)
Quemaduras , Cicatriz Hipertrófica , Niño , Humanos , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/patología , Ácido Hialurónico/uso terapéutico , Quemaduras/complicaciones , Quemaduras/terapia , Quemaduras/patología , Piel/patología , Corticoesteroides/uso terapéutico , Resultado del Tratamiento
17.
Macromol Biosci ; 23(10): e2300016, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37243584

RESUMEN

To provide prominent accessibility of fishmeal to the European population, the currently available, time- and cost-extensive feeding trials, which evaluate fish feed, should be replaced. The current paper reports on the development of a novel 3D culture platform, mimicking the microenvironment of the intestinal mucosa in vitro. The key requirements of the model include sufficient permeability for nutrients and medium-size marker molecules (equilibrium within 24 h), suitable mechanical properties (G' < 10 kPa), and close morphological similarity to the intestinal architecture. To enable processability with light-based 3D printing, a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink is developed and combined with Tween 20 as porogen to ensure sufficient permeability. To assess the permeability properties of the hydrogels, a static diffusion setup is utilized, indicating that the hydrogel constructs are permeable for a medium size marker molecule (FITC-dextran 4 kg mol-1 ). Moreover, the mechanical evaluation through rheology evidence a physiologically relevant scaffold stiffness (G' = 4.83 ± 0.78 kPa). Digital light processing-based 3D printing of porogen-containing hydrogels results in the creation of constructs exhibiting a physiologically relevant microarchitecture as evidenced through cryo-scanning electron microscopy. Finally, the combination of the scaffolds with a novel rainbow trout (Oncorhynchus mykiss) intestinal epithelial cell line (RTdi-MI) evidence scaffold biocompatibility.

18.
Front Neurol ; 13: 836292, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35481265

RESUMEN

The observation that a pathophysiological link might exist between Alzheimer's disease (AD) and epilepsy dates back to the identification of the first cases of the pathology itself and is now strongly supported by an ever-increasing mountain of literature. An overwhelming majority of data suggests not only a higher prevalence of epilepsy in Alzheimer's disease compared to healthy aging, but also that AD patients with a comorbid epileptic syndrome, even subclinical, have a steeper cognitive decline. Moreover, clinical and preclinical investigations have revealed a marked sleep-related increase in the frequency of epileptic activities. This characteristic might provide clues to the pathophysiological pathways underlying this comorbidity. Furthermore, the preferential sleep-related occurrence of epileptic events opens up the possibility that they might hasten cognitive decline by interfering with the delicately orchestrated synchrony of oscillatory activities implicated in sleep-related memory consolidation. Therefore, we scrutinized the literature for mechanisms that might promote sleep-related epileptic activity in AD and, possibly dementia onset in epilepsy, and we also aimed to determine to what degree and through which processes such events might alter the progression of AD. Finally, we discuss the implications for patient care and try to identify a common basis for methodological considerations for future research and clinical practice.

19.
Materials (Basel) ; 15(5)2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35268885

RESUMEN

Using an ideal biomaterial to treat injured bones can accelerate the healing process and simultaneously exhibit antibacterial properties; thus protecting the patient from bacterial infections. Therefore, the aim of this work was to synthesize composites containing silicate-based bioactive glasses and different types of noble metal structures (i.e., AgI pyramids, AgIAu composites, Au nanocages, Au nanocages with added AgI). Bioactive glass was used as an osteoconductive bone substitute and Ag was used for its antibacterial character, while Au was included to accelerate the formation of new bone. To investigate the synergistic effects in these composites, two syntheses were carried out in two ways: AgIAu composites were added in either one step or AgI pyramids and Au nanocages were added separately. All composites showed good in vitro bioactivity. Transformation of AgI in bioactive glasses into Ag nanoparticles and other silver species resulted in good antibacterial behavior. It was observed that the Ag nanoparticles remained in the Au nanocages, which was also beneficial in terms of antibacterial properties. The presence of Au nanoparticles contributed to the composites achieving high cell viability. The most outstanding result was obtained by the consecutive addition of noble metals into the bioactive glasses, resulting in both a high antibacterial effect and good cell viability.

20.
J Nanosci Nanotechnol ; 21(4): 2388-2393, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33500055

RESUMEN

The synthesis and investigation of vertically aligned carbon nanotube (VACNT) based materials are gaining more-and-more interest among scientists due to their specific properties (e.g., electrical, optical, mechanical). Therefore, our interest for the present research has focused on synthesis of WO3/VACNT based nanostructures (using carbon nanotube forests obtained by catalytic chemical vapor deposition-CCVD method on aluminum substrate) using different synthesis pathways and WO3 precursors. The obtained composites were investigated by scanning electron microscopy (SEM), Raman spectroscopy, while the obtained crystal structures were characterized by X-ray diffraction (XRD). Results have shown that depending on the synthesis method, and using as template the carbonaceous structure, we can successfully obtain non-stochiometric tungsten oxide (W18O49) or WO3 composites.

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