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    Wyświetlanie 1-11 z 11
    Tytuł:
    Comparison of binding interactions of dibromoflavonoids with transthyretin.
    Autorzy:
    Muzioł, Tadeusz
    Cody, Vivian
    Wojtczak, Andrzej
    Powiązania:
    https://bibliotekanauki.pl/articles/1044031.pdf
    Data publikacji:
    2001
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    dibromoflavone complex
    crystal structure
    transthyretin
    Opis:
    The crystal structure of rat transthyretin (rTTR) complex with the dibromoflavone EMD21388 was determined to 2.3 Å resolution and refined to R = 0.203 and Rfree = 0.288. Two different orientations of EMD21388, which differ in the channel penetration by 1.6 Å, were found in the A/C binding site of rTTR. The single ligand position observed in the B/D site is intermediate between the two positions found in the A/C site. The position of the dibromoflavone in the B/D site is similar to that reported for dibromoaurone in human TTR. The bromine atoms of EMD21388 form strong interactions in the P3 and P3' pockets of rTTR. Due to the different molecular architectures of both ligands, dibromoflavone forms only one interaction with Lys-15 near the channel entrance, while direct interactions with the pair of Lys-15 were reported for dibromoaurone. The C3* methyl group of EMD21388 mediates the bridging interactions between two TTR subunits in the P2 pockets. The interactions of the O2* hydroxyl group of dibromoaurone with the Thr-119 side chain in the P3 pockets are not matched by similar interactions in EMD21388. Both these alternative interactions can explain the competitive binding of 3',5'-dibromoflavonoids to transthyretin.
    Źródło:
    Acta Biochimica Polonica; 2001, 48, 4; 885-892
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Complex of rat transthyretin with tetraiodothyroacetic acid refined at 2.1 and 1.8 Å resolution.
    Autorzy:
    Muzioł, Tadeusz
    Cody, Vivian
    Luft, Joseph
    Pangborn, Walter
    Wojtczak, Andrzej
    Powiązania:
    https://bibliotekanauki.pl/articles/1044030.pdf
    Data publikacji:
    2001
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    rat transthyretin
    tetraiodothyroacetic acid complex
    multiple binding modes
    crystal structure
    Opis:
    The crystal structure of rat transthyretin (rTTR) complex with 3,5,3' ,5' -tetraiodothyroacetic acid (T4Ac) was determined at 1.8 Å resolution with low temperature synchrotron data collected at CHESS. The structure was refined to R = 0.207 and Rfree= 0.24 with the use of 8-1.8 Å data. The additional 8000 reflections from the incomplete 2.1-1.8 data shell, included in the refinement, reduced the Rfree index by 1.3%. Structure comparison with the model refined against the complete 8-2.1 Å data revealed no differences in the ligand orientation and the conformation of the polypeptide chain in the core regions. However, the high-resolution data included in the refinement improved the model in the flexible regions poorly defined with the lower resolution data. Also additional sixteen water molecules were found in the difference map calculated with the extended data. The structure revealed both forward and reverse binding of tetraiodothyroacetic acid in one binding site and two modes of forward ligand binding in the second site, with the phenolic iodine atoms occupying different sets of the halogen binding pockets.
    Źródło:
    Acta Biochimica Polonica; 2001, 48, 4; 877-884
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Computer modeling studies of the structural role of NADPH binding to active site mutants of human dihydrofolate reductase in complex with piritrexim.
    Autorzy:
    Nowak, Wiesław
    Cody, Vivian
    Wojtczak, Andrzej
    Powiązania:
    https://bibliotekanauki.pl/articles/1044034.pdf
    Data publikacji:
    2001
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    ESFF forcefield
    NADPH
    dihydrofolate reductase
    enzyme structure
    chemotherapy
    piritrexim
    computer modeling
    Opis:
    Dihydrofolate reductase (DHFR, EC 1.5.1.3) is one of the enzymes active in the folate cycle which plays an important role in DNA synthesis. Inhibition of DHFR is a key element in the treatment of many diseases, including cancer and AIDS related infections. A search for new selective inhibitors is motivated by the resistance to common drugs observed in the course of treatment. In this paper, results of a detailed computer analysis of human DHFR interactions with the lipophilic inhibitor piritrexim (PTX) are presented. It was found that the NADPH cofactor contributes 30% of the total PTX-enzyme interaction energy. Substitution of the highly conserved Glu30 with alanine does not lead to the release of the inhibitor from the hDHFR pocket. The important L22F point mutation does affect PTX orientation but does not change the binding energy. Simulations of the dynamics of binary hDHFR-TX complexes were performed with the use of Extensible Systematic Force Field (ESFF) and the results indicate structural changes in the enzyme induced by NADPH binding.
    Źródło:
    Acta Biochimica Polonica; 2001, 48, 4; 903-916
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Health inequities as a challenge to the social policies of European governments
    Autorzy:
    Wojtczak, Andrzej
    Powiązania:
    https://bibliotekanauki.pl/articles/2188035.pdf
    Data publikacji:
    2019-05-06
    Wydawca:
    Uniwersytet Jagielloński. Wydawnictwo Uniwersytetu Jagiellońskiego
    Tematy:
    nierówności w zdrowiu
    polityka zdrowotna
    polityka społeczna
    Unia Europejska
    health inequities
    health determinants
    health policy
    social policy
    European Union
    Opis:
    Health inequities are defined as systematic differences in health that can be avoided by appropriate policy intervention, and for this reason are considered unfair and unjust. Health inequities are not solely related to access to health care services; they are caused by the unequal distribution of these determinants of health, including power, income, goods and services, poor and unequal living conditions, and the differences in healthdamaging behaviours that these wider determinants produce. They are defined as systematic differences in health that can be avoided by appropriate policy intervention and that are therefore deemed to be unfair and unjust. To be able to devise effective action, we first need to understand the causes of these inequities in health. Health inequities are not solely related to access to health care services; there are many determinants related to living and working conditions, as well as the overall macro-policies prevailing in a country or region. The differences in social and economic development are reflected in health inequities that can be seen both between and within countries. Furthermore, evidence shows that even in the more affluent countries health inequities are seen in all parts of Europe. In the WHO European Region the gap in life expectancy between countries is 17 years for men and 12 years for women. Inequities in health are caused by the unequal distribution of these determinants of health, including power, income, goods and services, poor and unequal living conditions, and the differences in health-damaging behaviours that these wider determinants produce. The experiences of various countries indicates that in order to narrow the health inequities countries have to improve living conditions including the provision of comprehensive welfare systems, and high-quality education and health services. The Strategy Health 2020 developed and approved by the WHO European Region countries is focusing on reducing inequities in health, which are key strategic objectives of endorsed by the 53 Member States. It emphasizes the need to strengthen population-based prevention on the social determinants of health. Also, in 2009 the European Commission developed European Union (EU) Health Strategy Programme titled “Solidarity in health: reducing health inequalities in the European Union”.
    Źródło:
    Zdrowie Publiczne i Zarządzanie; 2019, 17, 1; 9-15
    2084-2627
    Pojawia się w:
    Zdrowie Publiczne i Zarządzanie
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Modeling studies of potato nucleoside triphosphate diphosphohydrolase NTPDase1: an insight into the catalytic mechanism
    Autorzy:
    Kozakiewicz, Anna
    Neumann, Piotr
    Banach, Mariusz
    Komoszyński, Michał
    Wojtczak, Andrzej
    Powiązania:
    https://bibliotekanauki.pl/articles/1040830.pdf
    Data publikacji:
    2008
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    potato apyrase
    NTPDase1
    enzymatic mechanism
    homology modeling
    Opis:
    Nucleoside triphosphate diphosphohydrolase - NTPDase1 (apyrase, EC 3.6.1.5) was modeled based on sequence homology. The single polypeptide chain of apyrase is folded into two domains. The putative catalytic site with the apyrase conserved regions (ACR 1-5) is located between these two domains. Modeling confirmed that apyrase belongs to the actin superfamily of proteins. The amino acids interacting with the nucleoside triphosphate substrate and probably involved in the catalyzed hydrolysis were identified. The proposed two-step catalytic mechanism of hydrolysis involves Thr127 and Thr55 as potential nucleophilic factors responsible for the cleavage of the Pγ and Pβ anhydride bonds, respectively. Their action seems to be assisted by Glu170 and Glu78 residues, respectively. The presence of two nucleophiles in the active site of apyrase explains the differences in the hydrolytic activity between apyrases and other enzymes belonging to the NTPDase family.
    Źródło:
    Acta Biochimica Polonica; 2008, 55, 1; 141-150
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Ochrona zdrowia w Polsce dziś i w perspektywie następnej dekady
    Health care in Poland today and in the next decade
    Autorzy:
    Wojtczak, Andrzej
    Powiązania:
    https://bibliotekanauki.pl/articles/40494636.pdf
    Data publikacji:
    2015-12-01
    Wydawca:
    Akademia Humanistyczno-Ekonomiczna w Łodzi
    Tematy:
    ochrona zdrowia
    prognozy
    Polska
    healthcare
    forecasts
    Polska
    Opis:
    Prognozy trendów demograficznych i zdrowotnych wskazują na wolniejsze tempo wzrostu liczby ludności globu w nadchodzących dekadach. W krajach przemysłowo rozwiniętych miarą poprawy stanu zdrowia ludzi jest wzrost średniej długości życia. W Polsce w przypadku mężczyzn wynosi ona ponad 73, a w przypadku kobiet ponad 82 lata. Wzrost ten kompensowany jest obniżającym się wskaźnikiem dzietności, który w krajach Europy wynosi poniżej 1.6. W Europie do roku 2030 odsetek osób powyżej 65 r. ż. wzrośnie do 23,8%, a w Polsce liczba osób w wieku ponad 65 lat przekroczy 8 milionów. W nadchodzącej dekadzie hierarchia problemów zdrowotnych Polaków będzie podobna do obecnej. Niemal połowa zgonów powodowana jest chorobami układu krążenia, głównie zawałami serca i udarami mózgu. Choroby nowotworowe są i pozostaną drugą przyczyną zgonów wśród mężczyzn, a pierwszą wśród kobiet. Wypadki komunikacyjne i urazy stanowić będą coraz większy problem tak zdrowotny jak i ekonomiczny. Poprawa zdrowia psychicznego jest sprawa pilną, a grupą szczególnie wymagającą pomocy jest młodzież. Priorytetem jest zapobieganie szybko zwiększającej się, szczególnie u dzieci, epidemii nadwagi i otyłości. W następnej dekadzie będą pojawiać się stałe doskonalone metody diagnostyczne i lecznicze. Coraz częściej leki dostarczane będą bezpośrednio do zmienionych patologicznie narządów Zwiększać się będą możliwości chirurgicznych zabiegów nieinwazyjnych, które szczególną rolę będą miały w operacjach naczyniowych mózgu. Pomimo postępów w mapowaniu ludzkiego genomu i poznawaniu roli różnych genów w określonych chorobach, nie należy oczekiwać, że w następnej dekadzie terapia genowa będzie dostępną metoda leczniczą. Poznanie mechanizmów działania mózgu powinno pozwolić na zachowanie sprawności intelektualnej przez długie lata a także na przywracanie utraconej pamięci oraz na dalsze postępy w leczeniu chorób psychicznych. Możliwe będzie przywracanie osłabionego słuchu, wzroku oraz zdolności umysłowych i pamięci. Wyzwaniem będzie zapewnienie świadczeń dla szybko wzrastającej liczby coraz starszych osób i nadganianie zaniedbań wynikających z braku dobrze funkcjonujących programów zapobiegania chorób i umacnianie zdrowia – warunku utrzymania większej liczby seniorów w grupie aktywnych zawodowo. Dużym wyzwaniem jest brak dbałości naszych współziomków o własne zdrowie - unikanie nałogów i przestrzeganie zasad zdrowego stylu życia. Uchwalona ostatnio Ustawa o Zdrowiu Publicznym powinna dać nowy impuls i stworzyć platformę działań poprawiających i umacniających zdrowie Polaków.
    Projections of demographic and health trends indicate a slower pace of global population growth in the coming decades. In industrialized countries, the improvement in people's health is measured by an increase in average life expectancy. In Poland, the life expectancy for men is over 73 years, and for women, it is over 82 years. This increase is offset by a declining fertility rate, which in European countries is below 1.6. By 2030, the proportion of people over 65 in Europe will rise to 23.8%, and in Poland, the number of people over 65 will exceed 8 million. In the coming decade, the hierarchy of health problems for Poles will be similar to the current one. Nearly half of deaths are caused by cardiovascular diseases, mainly heart attacks and strokes. Cancer is and will remain the second leading cause of death among men and the first among women. Traffic accidents and injuries will become an increasing health and economic problem. Improving mental health is urgent, with young people being a particularly vulnerable group in need of help. A priority is to prevent the rapidly increasing epidemic of overweight and obesity, especially among children. In the next decade, continuously improved diagnostic and therapeutic methods will emerge. Increasingly, drugs will be delivered directly to pathologically altered organs. The possibilities for non-invasive surgical procedures will expand, playing a significant role in vascular surgeries of the brain. Despite advances in mapping the human genome and understanding the role of various genes in specific diseases, gene therapy is not expected to become a widely available treatment method in the next decade. Understanding the mechanisms of brain function should allow for the maintenance of intellectual fitness for many years, the restoration of lost memory, and further progress in treating mental illnesses. It will be possible to restore impaired hearing, vision, and cognitive abilities. Ensuring services for the rapidly growing number of increasingly elderly people will be a challenge, as will addressing the shortcomings resulting from the lack of well-functioning disease prevention and health promotion programs – a condition for keeping more seniors in the active workforce. A significant challenge is the lack of care among our compatriots for their health – avoiding addictions and following healthy lifestyle principles. The recently enacted Public Health Act should give a new impetus and create a platform for actions to improve and strengthen the health of Poles.
    Źródło:
    Civitas Hominibus. Rocznik filozoficzno-społeczny; 2015, 10; 57-66
    1896-1819
    2391-5145
    Pojawia się w:
    Civitas Hominibus. Rocznik filozoficzno-społeczny
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Relationship between the induction of inflammatory processes and infectious diseases in patients with ischemic stroke
    Autorzy:
    Cieślak, Marek
    Wojtczak, Andrzej
    Cieślak, Michał
    Powiązania:
    https://bibliotekanauki.pl/articles/1039529.pdf
    Data publikacji:
    2013
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    cytokines
    interleukin-1 receptor
    ischemic stroke
    Opis:
    Pro-inflammatory cytokines participate in the induction of ischemic stroke. So far, their participation in the cerebral ischemia was proven for the tumor necrosis factor TNF-α, interleukin-1 (IL-1), and interleukin-6 (IL-6). The release of the pro-inflammatory cytokines into the extracellular space causes the enlargement of the brain damage region, and consequently increases the neurological deficit and negatively affects the survival rate prognoses. That is confirmed by the increased concentration of pro-inflammatory cytokines in blood and the cerebrospinal fluid of patients with brain stroke, as well as by the research on the induced/experimental cerebral ischemia in animals. The pro-inflammatory cytokines participate in the migration of the reactive T lymphocytes to the regions of brain ischemia where they enhance the nerve tissue damage by down-regulation of microcirculation, induce the pro-thrombotic processes and release other neurotoxic cytokines. Also, in the early stage of cerebral ischemia, cytokines activate the axis hypothalamus-pituitary gland-adrenal cortex and increase the cortisol concentration in blood, what results in the decreased resistance to infectious diseases. Administration of the inhibitor of the interleukin-1 receptor (IL-1Ra) inhibits the inflammatory processes in the region of brain ischemia, and subsequently improves the prognosis for the size of the neurological deficit and the survival rate, as well as resistance to infectious diseases.
    Źródło:
    Acta Biochimica Polonica; 2013, 60, 3; 345-349
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Role of pro-inflammatory cytokines of pancreatic islets and prospects of elaboration of new methods for the diabetes treatment
    Autorzy:
    Cieślak, Marek
    Wojtczak, Andrzej
    Cieślak, Michał
    Powiązania:
    https://bibliotekanauki.pl/articles/1039121.pdf
    Data publikacji:
    2015
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    interleukin 1β
    interleukin-6
    tumor necrosis factor-α
    pancreatic derived factor
    insulin resistance
    Opis:
    Several relations between cytokines and pathogenesis of diabetes are reviewed. In type 1 and type 2 diabetes an increased synthesis is observed and as well as the release of pro-inflammatory cytokines, which cause the damage of pancreatic islet cells and, in type 2 diabetes, the development of the insulin resistance. That process results in the disturbed balance between pro-inflammatory and protective cytokines. Pro-inflammatory cytokines such as interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as recently discovered pancreatic derived factor PANDER are involved in the apoptosis of pancreatic β-cells. Inside β-cells, cytokines activate different metabolic pathways leading to the cell death. IL-1β activates the mitogen-activated protein kinases (MAPK), affects the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activates the inducible nitric oxide synthase (iNOS). TNF-α and IFN-γ in a synergic way activate calcium channels, what leads to the mitochondrial dysfunction and activation of caspases. Neutralization of pro-inflammatory cytokines, especially interleukin 1β with the IL-1 receptor antagonist (IL-1Ra) and/or IL-1β antibodies might cause the extinction of the inflammatory process of pancreatic islets, and consequently normalize concentration of glucose in blood and decrease the insulin resistance. In type 1 diabetes interleukin-6 participates in regulation of balance between Th17 and regulatory T cells. In type 2 diabetes and obesity, the long-duration increase of IL-6 concentration in blood above 5 pg/ml leads to the chronic and permanent increase in expression of SOCS3, contributing to the increase in the insulin resistance in cells of the skeletal muscles, liver and adipose tissue.
    Źródło:
    Acta Biochimica Polonica; 2015, 62, 1; 15-21
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Structural basis of negative cooperativity in transthyretin
    Autorzy:
    Neumann, Piotr
    Cody, Vivian
    Wojtczak, Andrzej
    Powiązania:
    https://bibliotekanauki.pl/articles/1044029.pdf
    Data publikacji:
    2001
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    negative cooperativity
    transthyretin
    Opis:
    A comparison of the AC and BD binding sites of transthyretin (TTR) was made in terms of the interatomic distances between the Cα atoms of equivalent amino acids, measured across the tetramer channel in each binding site. The comparison of the channel diameter for apo TTR from different sources revealed that in the unliganded transthyretin tetramers the distances between the A, D and H β-strands are consistently larger, while the distances between the G β-strands are smaller in one site than in the other. These differences might be described to have a 'wave' character. An analogous analysis performed for transthyretin complexes reveals that the shape of the plot is similar, although the amplitudes of the changes are smaller. The analysis leads us to a model of the changes in the binding sites caused by ligand binding. The sequence of events includes ligand binding in the first site, followed by a slight collapse of this site and concomitant opening of the second site, binding of the second molecule and collapse of the second site. The following opening of the first, already occupied site upon ligand binding in the second site is smaller because of the bridging interactions already formed by the first ligand. This explains the negative cooperativity (NC) effect observed for many ligands in transthyretin.
    Źródło:
    Acta Biochimica Polonica; 2001, 48, 4; 867-875
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
      Wyświetlanie 1-11 z 11

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