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Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets

World Journal of Psychiatry 2021年第7期11卷 277-296页

作者： MatejĽupták Danica Michaličková zdeněk fišar Eva kitzlerová Jana Hroudová Institute of Pharmacology First Faculty of MedicineCharles University and General University Hospital in PraguePrague 12800Czech Republic Department of Psychiatry First Faculty of MedicineCharles University and General University Hospital in PraguePrague 12000Czech Republic

Schizophrenia is a severe psychiatric disorder characterized by emotional,behavioral and cognitive disturbances, and the treatment of schizophrenia is oftencomplicated by noncompliance and pharmacoresistance. The search for thepathophysiological mechanisms underlying schizophrenia has resulted in theproposal of several hypotheses to explain the impacts of environmental, genetic,neurodevelopmental, immune and inflammatory factors on disease onset andprogression. This review discusses the newest insights into the pathophysiologyof and risk factors for schizophrenia and notes novel approaches in antipsychotictreatment and potential diagnostic and theranostic biomarkers. The currenthypotheses focusing on neuromediators (dopamine, glutamate, and serotonin),neuroinflammation, the cannabinoid hypothesis, the gut-brain axis model, andoxidative stress are summarized. key genetic features, including small nucleotidepolymorphisms, copy number variations, microdeletions, mutations andepigenetic changes, are highlighted. Current pharmacotherapy of schizophreniarelies mostly on dopaminergic and serotonergic antagonists/partial agonists, butnew findings in the pathophysiology of schizophrenia have allowed theexpansion of novel approaches in pharmacotherapy and the establishment ofmore reliable biomarkers. Substances with promising results in preclinical andclinical studies include lumateperone, pimavanserin, xanomeline, roluperidone,agonists of trace amine-associated receptor 1, inhibitors of glycine transporters,AMPA allosteric modulators, mGLUR2-3 agonists, D-amino acid oxidase inhibitorsand cannabidiol. The use of anti-inflammatory agents as an add-on therapy ismentioned.

关键词： Schizophrenia Immune system Inflammation Genetics Novel antipsychotics Add-on therapy

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Control mechanisms in mitochondrial oxidative phosphorylation

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Neural Regeneration Research 2013年第4期8卷 363-375页

作者： Jana Hroudová zdeněk fisar Department of Psychiatry First Faculty of MedicineCharles University in Prague and General University Hospital in PraguePragueCzech Republic

Distribution and activity of mitochondda are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5＇- triphosphate production is regulated by many control mechanism-firstly by oxygen, substrate level, adenosine-5＇-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by ＂second control mechanisms,＂ such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, aUosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5＇-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria similarly, decline of antioxidative enzyme activities （e.g. in the elderly） enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.

关键词： neural regeneration reviews mitochondria metabolic pathway membrane potential oxidative phosphorylation electron transport chain complex reactive oxygen species respiratory state calcium uncoupling protein fatty acid neuroregeneration

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Up and down the spectrum:upconversion nanocrystal and semiconductor material fused into a single nanocomposite

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Light(Science & Applications) 2022年第7期11卷 1331-1333页

作者： Hans H.Gorris zdeněk Farka Department of Biochemistry Masaryk University62500 BrnoCzech Republic

A nanocomposite consisting of a cubic EuSe semiconductor material grown on a hexagonal upconversion nanoparticle has overcome the crystal lattice mismatch that typically prevents the epitaxial growth of such heterogeneous ***^(3+)at the interface layer shows its characteristic red emission band both under UV excitation light due to energy transfer from the semiconductor and under NIR excitation light due to energy transfer after *** storage and security applications are suggested for this new nanocomposite.

关键词： excitation fused overcome

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Effect of unburned carbon content in fly ash on the retention of 12 elements out of coal-combustion flue gas

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Journal of Environmental Sciences 2012年第9期24卷 1624-1629页

作者： Lucie Bartonov Bohumír ech Lucie Ruppenthalov Vendula Majvelderov Dagmar Juchelkov zdeněk klika Faculty of Metallurgy and Material Engineering VSB-Technical University of OstravaTr.17.listopadu 15708 33 Ostrava-PorubaCzech Republic

The aim of this study was to evaluate whether unburned carbon particles present in fly ash can help in the retention of S, Cl, Br, As, Se, Cu, Ni, Zn, Ga, Ge, Rb, and Pb out of flue gas during the coal combustion at fluidised-bed power station where the coal was combusted along with limestone. The competitive influence of 10%-25% CaO in fly ashes on the distribution of studied elements was studied as well to be clear which factor governs behaviour of studied elements. Except of S （with significant association with CaO） and Rb and Pb （with major affinity to A1203） the statistically significant and positive correlation coefficients were calculated for the relations between unburned carbon content and Br （0.959）, Cl （0.957）, Cu （0.916）, Se （0.898）, Ni （0.866）, As （0.861）, Zn （0.742）, Ge （0.717）, and Ga （0.588） content. The results suggest that the unburned carbon is promising material in terms of flue gas cleaning even if contained in highly calcareous fly ashes.

关键词： unburned carbon coal combustion fluidised bed trace elements emissions retention

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Clinical and economic consequences of pancreatic fistula after elective pancreatic resection

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Hepatobiliary & Pancreatic Diseases International 2013年第5期12卷 533-539页

作者： filip Ceka Bohumil Jon zdeněk ubrt Alexander Ferko Department of Surgery Faculty of Medicine and University Hospital Hradec Králové Department of field Surgery Military Health Science FacultyHradec KrálovéDefence University Brno

BACkGROUND:Postoperative pancreatic fistula is the main cause of morbidity after pancreatic *** study aimed to quantify the clinical and economic consequences of pancreatic fistula in a medium-volume pancreatic surgery ***:Hospital records from patients who had undergone elective pancreatic resection in our department were *** fistula was defined according to the International Study Group on Pancreatic fistula(ISGPF).The consequences of pancreatic fistula were determined by treatment cost,hospital stay,and out-patient follow-up until the pancreatic fistula was completely *** costs of the treatment are calculated in *** cost increase index was calculated for pancreatic fistula of grades A,B,and C as multiples of the total cost for the no fistula ***:In 54 months,102 patients underwent elective pancreatic *** patients(39.2%) developed pancreatic fistula,and 54 patients(52.9%) had one or more *** median length of hospital stay for the no fistula,grades A,B,and C fistula groups was 12.5,14,20,and 59 days,*** hospital stay of patients with fistula of grades B and C was significantly longer than that of patients with no fistula(Pfistula,grades A,B,and C fistula groups,***:The grading recommended by the ISGPF is useful for comparing the clinical severity of fistula and for analyzing the clinical and economic consequences of pancreatic *** fistula prolongs the hospital stay and increases the cost of treatment in proportion to the severity of the fistula.

关键词： pancreatic resection pancreatic fistula cost analysis

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Friction Sensitivity of Nitramines. Part Ⅳ:Links to Surface Electrostatic Potentials

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含能材料 2011年第6期19卷 613-615页

作者： zdeněk Friedl Marcela Jungová Svatopluk Zeman Adéla Husarová Faculty of Chemistry Brno University of TechnologyCZ-612 00 BrnoThe Czech Republic Institute of Energetic Materials Faculty of Chemical TechnologyUniversity of PardubiceCZ-532 10 PardubiceThe Czech Republic

The friction sensitivity(FS) of five aliphatic linear and eight cyclic nitramines has been determined and correlated with DFT B3LYP/6-31-G(d,p) // 6-311+G(d,p) positive(VS,max) and negative(VS,min) extremes of molecular surface electrostatic potentials VS(r).While there is an ambiguous relationship between the VS,max values and FS values,the decrease of FS is connected(more or less) with increase in VS,min values.

关键词： physical chemistry electrostatic potential friction nitramines sensitivity

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Comparing the removal of polycyclic aromatic hydrocarbons in soil after different bioremediation approaches in relation to the extracellular enzyme activities

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Journal of Environmental Sciences 2019年第2期31卷 249-258页

作者： zdeněk ko?ná? Tereza ?ástková Lucie Wiesnerová Luká? Praus Ivan Jablonsky Martin koudela Pavel Tlusto? Department of Agroenvironmental Chemistry and Plant Nutrition Faculty of AgrobiologyFood and Natural ResourcesCzech University of Life Sciences Prague Department of Horticulture Faculty of AgrobiologyFood and Natural ResourcesCzech University of Life Sciences Prague

A 120-day experiment was conducted to compare the removal of polycyclic aromatic hydrocarbons(PAHs) from agricultural soil after natural attenuation(NA), phytoremediation(P), mycoremediation(M), and plant-assisted mycoremediation(PAM) approaches in relation to the extracellular enzyme activities in soil. The NA treatment removed the total soil PAH content negligibly. The P treatment using maize(Zea mays) enhanced only the removal of low and medium molecular PAHs. The Pleurotus ostreatus cultivated on 30–50 mm wood chip substrate used in M treatment was the most successful in the removal of majority PAHs. Therefore,significantly(p kg dw(dry weight)(36%) from all tested M treatments was observed. When using the same fungal substrate together with maize in PAM treatment, the total PAH removal was not statistically different from the previous M treatment. However, the maize-assisted mycoremediation treatment significantly boosted fungal biomass, microbial and manganese peroxidase activity in soil which strongly correlated with the removal of total PAHs. The higher PAH removal in that PAM treatment could be reflected in the following post-harvest time. Our suggested M and PAM approaches could be promising in situ bioremediation strategies for PAH-contaminated soils.

关键词： PAHs Biodegradation White-rot fungi Ligninolytic enzymes Microbial activity

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Identification of altitude profiles in 3D geovisualizations:the role of interaction and spatial abilities

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International Journal of Digital Earth 2019年第2期12卷 156-172页

作者： Petr kubíček Čeněk Šašinka zdeněk Stachoň Lukáš Herman Vojtěch Juřík Tomáš Urbánek Jiří Chmelík Department of Geography Faculty of ScienceMasaryk UniversityBrnoCzech Republic HUME Lab Faculty of ArtsMasaryk UniversityBrnoCzech Republic Department of Psychology Faculty of ArtsMasaryk UniversityBrnoCzech Republic Department of Computer Graphics and Design Faculty of InformaticsMasaryk UniversityBrnoCzech Republic

Three-dimensional geovisualizations are currently pushed both by technological development and by the demands of experts in various applied *** the presented empirical study,we compared the features of real 3D(stereoscopic)versus pseudo 3D(monoscopic)geovisualizations in static and interactive digital elevation *** tested 39 high-school students in their ability to identify the correct terrain profile from digital elevation ***’performance was recorded and further analysed with respect to their spatial abilities,which were measured by a psychological mental rotation test and think aloud *** results of the study indicated that the influence of the type of 3D visualization(monoscopic/stereoscopic)on the performance of the users is not clear,the level of navigational interactivity has significant influence on the usability of a particular 3D visualization,and finally no influences of the spatial abilities on the performance of the user within the 3D environment were identified.

关键词： 3D geovisualizations stereoscopic and monoscopic 3D vision spatial abilities level of navigational interactivity

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Pancreatic Castleman disease treated with laparoscopic distal pancreatectomy

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Hepatobiliary & Pancreatic Diseases International 2013年第3期12卷 332-334页

作者： filip ecka Alexander Ferko Bohumil Jon zdeněk ubrt Petra kaparová Rudolf Repák Department of Surgery Faculty of Medicine and University Hospital Hradec Králové Department of field Surgery Military Health Science Faculty Hradec Králové Defence University Brno fingerland Department of Pathology Faculty of Medicine and University Hospital Hradec Králové Second Department of Internal Medicine Faculty of Medicine and University Hospital Hradec Králové

BACkGROUND: Castleman disease is an uncommon lympho-proliferative disorder most frequently occurring in the mediastinum. Abdominal forms are less frequent, with pancreatic localization of the disease in particular being extremely rare. Only seventeen cases have been described in the world literature. METHOD: This report describes an interesting and unusual case of pancreatic Castleman disease treated with laparoscopic resection. RESULTS: A 48-year-old woman presented with epigastric pain. CT scan showed a well-encapsulated mass on the ventral border of the pancreas. Endosonography with fine needle aspiration biopsy was performed. Biopsy showed lymphoid elements and structures of a normal lymph node. The patient was treated with laparoscopic distal pancreatectomy. The pancreas was transected with a Ligasure device and the pancreatic stump was secured with a manual suture. One year after surgery the patient was complaint-free and showed no signs of recurrence of the disease. CONCLUSIONS: Laparoscopic distal pancreatectomy is a feasible and safe method for the treatment of lesions in the body and tail of the pancreas. Transection of the pancreas with a Ligasure device offers the advantages of low bleeding and low risk of pancreatic fistula.

关键词： Castleman disease pancreas laparoscopic distal pancreatectomy Ligasure

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Molecular rotor based on an oxidized resorcinarene

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Organic Chemistry Frontiers 2022年第1期9卷 39-50页

作者： Daniel T.Payne Jan Labuta zdeněk Futera Václav Březina Lenka Hanyková Mandeep k.Chahal Jonathan P.Hill International Center for Materials Nanoarchitectonics National Institute for Materials ScienceNamiki 1-1TsukubaIbaraki 305-0044Japan bInternational Center for Young Scientists National Institute for Materials ScienceNamiki 1-1TsukubaIbaraki 305-0044Japan Institute of Physics Faculty of ScienceUniversity of South BohemiaBranišovská1760ČeskéBudějovice 37005Czech Republic Faculty of Mathematics and Physics Charles UniversityV Holešovičkách 218000 Prague 8Czech Republic

Molecular rotors are an important class of dynamic molecules which have been studied not only for their possible uses as components of molecular machines but also because of potential applications as probes of local viscosity in biological media,especially self-assembled *** the former,factors affecting rotational motility are critical while for the latter the rotor activity must be complexed with an output signal(often fluorescence)for reporting of local *** single stator-double rotor activity of an oxidized resorcinarene(fuchsonarene)macrocycle containing unsaturated hemiquinonoid groups at its meso positions was *** contain two hemiquinonoid substituents at diagonally-opposed meso-positions with two electron rich phenol groups at the remaining meso-positions between the hemiquinonoid *** meso-substituents are in proximity at one side of the resorcinarene macrocycle(so-called rccc-type isomer)with rotational activity of the phenol *** rates of the phenol moieties can be controlled by varying temperature,solvent polarity and acidity of the medium of study with rotation being thermally activated in neutral and acidic media and tunable in the range from 2 s^(−1) to 20000 s^(−1).Experimental and computational data indicate that rotation of the mobile phenol meso-substituents is remotely affected by interactions with acidic solvents at the carbonyl CvO groups of macrocyclic acetyloxy groups,which occurs with the emergence of a lower energy electronic absorption band whose intensity is correlated with both the acidity of the medium and the rotation rate of the phenol ***-dependent DFT calculations suggest that the low energy band is due to a molecular conformational adjustment affecting electronic conjugation caused by strong interaction of macrocyclic acetyloxy carbonyl groups with the acid *** work presents a molecular mechanical model for estimating solution acidity a

关键词： substituent rotation oxidized

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