The influence of immune system dysregulation and latent toxoplasmosis on brain morphology in schizophrenia: animal models and a prospective volumetric study in patients

Co-operating institution – 3rd Faculty of Medicine, Charles University Prague
Provider – Ministry of Health, Czech Republic

Grant number – NT 13843
Time period – 2012–2015

The project is based on a translational approach that combines two animal models of early and late immune activation and longitudinal volumetric analysis of the brain in schizophrenia. The animal section includes i) a model of early immune stimulation by administration of lipopolysaccharide (LPS) on 5–9 postnatal day (PD) and ii) a model of latent toxoplasmosis. In both models, Th1/Th2 cytokines will be determined and behavioral testing will be performed, followed by volumometric evaluation, determination of enzymes and kynurenine pathway metabolites, dopaminergic and glutamatergic activity and evaluation of neurodegeneration and activation of microglia. The human part consists of a prospective evaluation of brain morphometry and the determination of plasma levels of Th1/Th2 cytokines and T. gondii serology in a group of 80 patients with schizophrenia in early stages of the disease and 80 control subjects. On the entry into the study and after one year, the effect of immune parameters on the volume of gray matter and the progression of its reduction will be evaluated using voxel-based morphometry.

Molecular mechanisms of subclinical inflammation in adipose tissue and its role in the etiopathogenesis of type 2 diabetes mellitus

Co-operating institutions – 1st Faculty of Medicine (Charles University Prague) and the Institute of Microbiology (Academy of Sciences of the Czech Republic)
Provider – Ministry of Health, Czech Republic

Grant number – NT 13299
Time period – 2012–2015

The aim of the project is to clarify the importance of the subtypes of immunocompetent cells (macrophages, lymphocytes, etc.) in the creation and development of subclinical inflammation in adipose tissue in obesity and type 2 diabetes mellitus. The project also aims to identify the factors involved in the interaction between immunocompetent cells and their precursors circulating in the blood and other components of adipose tissue (adipocytes). The project is based on detailed metabolic, hormonal and immunological characterization of the patients before and after weight reduction using a low-calorie diet or bariatric surgery. Modern cytometric and molecular biological methods will be used for the determination of the cellular content of subcutaneous and visceral adipose tissue and peripheral blood and gene expression of selected chemotactic factors. With the use of metabolomic analysis of adipose tissue and plasma samples, new signaling molecules involved in the communication between immunocompetent cells (especially during metabolically useful weight reduction will be identified).

Research of new cytostatics based on platinum complexes

Co-operating institution – VUAB Pharma a.s.
Provider – Technology Agency of the Czech Republic

Grant number – TA02010781
Time period – 2012–2014

The aim of the project is to develop a new platinum-based drug (Pt(IV) complex) for the treatment of tumors with improved therapeutic efficacy and the possibility of oral administration of the drug in order to improve the life quality of patients. The project strategy is based on targeted optimization of the structure of Pt (IV) complex in comparison to the "satraplatin" and / or "LA-12". Analytical methods of quality control and basic clinical data of new platinum drugs for clinical drug trials are a part of the solution.

Research and development of rapid generation gas decontaminated medium system based on the hydrogen peroxide vapor (VPHP) and study of decontamination medium operation mechanism in form of aerosol or gas

Co-operating institutions – BLOCK a.s. and the Institute of Microbiology (Academy of Sciences of the Czech Republic)
Provider – Technology Agency of the Czech Republic

Grant number – TA02011185
Time period – 2012–2015

The technology using hydrogen peroxide vapors (Vapor Phase Hydrogen Peroxide - VPHP) is a progressive method of sterilization and decontamination, which is limited mainly by the speed of onset of the desired concentration of peroxide in the target area. The project will deal with the optimization and efficiency improvement to achieve desired concentrations of the peroxide. This optimization is important for efficient use of equipment generating VPHP and mainly for economical use of sterilized areas such as isolator boxes.

Asymmetric transfer hydrogenation of C=X bond: novel chiral auxiliaries, mechanistic studies and green catalyst heterogenization

Co-operating institution – Institute of Microbiology (Academy of Sciences of the Czech Republic)
Provider - Czech Science Foundation

Grant number – P106/12/1276
Time period – 2012–2015

Transfer hydrogenation, whereby an organic molecule serves as a hydrogen donor, is widely recognized as a potentially lucrative niche technology, particularly significant and attractive whenever standard hydrogenation (using gaseous H2) is not applicable or practical. Naturally, asymmetric transfer hydrogenation (ATH) emerged in this field and quickly became the ultimate technique for the production of fine chemicals. The proposed project will be focused on novel chiral diamine ligands efficient in the ATH of C=X bond, which will be investigated in silico by means of molecular modelling and further synthesized and organized to a ligand library, which will serve in a systematical testing. Furthermore, the mechanism of ketone or imine hydrogenation will be studied by molecular modelling and NMR spectroscopy. For the practical application of catalysts, a simple procedure will be optimized for their immobilization upon cheap polymeric supports.

What is the role of mesolimbic reward circuit in the long-term effect of prenatal methamphetamine exposure in rats?

Co-operating institution – 3rd Faculty of Medicine, Charles University Prague
Provider – Czech Science Foundation

Grant number – GAP303/10/0580
Time period – 2010–2014

Drug addiction is a still an acute problem of nowadays. Dopaminergic mesolimbic reward system seems to play a major role in the development of drug addiction. Previously we demonstrated that prenatal methamphetamine (MA) exposure impairs postnatal development of rat pups, their cognitive functions in adulthood, and affects pain sensitivity and seizure threshold. Our most recent microdialysis work demonstrates that prenatal MA exposure has long-term effects on motor behaviour and dopamine metabolism of adult rats. We demonstrated that prenatal MA exposure increases the dopamine level and its metabolites in nucleus accumbens (NAc) after challenge dose of MA (1 mg/kg) in adulthood. It was suggested that a shift of activation prefrontal cortex (PFC) and striatum and there from ventral striatum (NAc) and dorsal striatum (caudate/putamen) is responsible for the change from the first taste of drug and the compulsive behaviour (addiction). The present study will, therefore, investigate the dopamine system also in PFC, dorsal striatum and other parts of mesolimbic reward circuit. Seven specific aims will test our hypotheses by pharmacological, behavioral, electrophysiological and molecular methods. The results will have an importance in the research of drug abuse and in designing future educational and prevention strategies to minimize these side effects in the progeny.

Research and development of modular system for built-in cleanrooms in health care units with increased resistance against decontamination agent

Co-operating institution – BLOCK a.s.
Provider – Ministry of Industry and Trade of the Czech Republic

Grant number – FR-TI2/594
Time period – 2010–2013

Built-in clean rooms in health care units (surgery, ICU, sterile surgical room etc.) require a high degree of sterility, surface resistance, simple adjustability and soundproof properties. The problem of such rooms rests in the materials used for the construction of different elements of built-in premises This project is oriented on the research and development of new suitable materials for a built-in clean room modular system with increased resistance against modern decontamination agents. We will develop a simple dismountable connection between the elements under hermetical premises maintenance, which ensures dismantling of the system. The development will be also focused on soundproofing of the system. The research and development will lead to the design of a suitable modular system for built-in clean rooms in health care units.

Study of modern aspects of asymmetric hydrogenation of imines

Cooperating institution – Institute of Microbiology (Academy of Sciences of the Czech Republic)
Provider – Czech Science Foundation

Grant number – 104/09/1497
Time period – 2009–2012

There is a rising interest in an efficient synthesis of enantiopure compounds. Enantioseparations are very uneconomical and lack environmental friendliness. Therefore, there is a growing interest in asymmetric reactions. From the industrial point of view, hydrogenation represents one of the most important processes and likewise, the interest in enantioselective hydrogenation is also increasing. The asymmetric hydrogenation of the C=N bond represents both scientifically and industrially a very interesting task, but still not completely solved. This project is focused on the asymmetric transfer hydrogenation of imines, which is a very attractive alternative to classical hydrogenation by hydrogen. In this process, compounds like 2-propanol or formic acid are used as a hydrogen source, and thus the manipulation with dangerous hydrogen is avoided. Relationship between structure of the catalyst, substrate, and of course of asymmetric hydrogenation will be studied. Main attention will be focused on ruthenium and rhodium complexes and modification of their structure to get high enantioselectivity and activity.