asymmetric synthesis Dotaz Zobrazit nápovědu
The main pathological condition in patients with impaired wound healing is diabetes mellitus. These patients have significantly low circulating nitric oxide (NO) levels because the stimulatory action of insulin on NO synthesis is absent. Additionally, asymmetric dimethylarginine (ADMA), an inhibitor of NO synthase, is increased owing to the generation of oxidative stress. NO was thought to contribute to wound healing. Hyperbaric oxygen (HBO) treatment is generally used in order to accelerate the healing of wounds. The aim of this study was to determine the changes in plasma procollagen type I and III N-terminal peptides (PINP and PIIINP), total nitrite/nitrate (NOx) and ADMA levels; and to evaluate their relation to healing during the HBO treatment of foot ulcers. Data obtained from 18 diabetic patients before and after the HBO therapy were compared statistically by the Wilcoxon test. NOx was increased in 11 and ADMA was decreased in 12 patients following HBO treatment. Both PINP (32.6±29.4 µg/l vs 44.3±33.4 µg/l) and PIIINP (6.97±3.01 µg/l vs 7.92±2.49 µg/l) were significantly increased (p<0.05). Progressive reductions were observed in wound areas, as assessed by the digital wound imaging. In 12 patients, wounds healed by 50 % or higher; whereas only two subjects had minimal improvements (15 % or less healing). The duration of diabetes correlated negatively with wound healing (r = -498, p<0.05). This study suggests that increased collagen synthesis is associated with wound healing during hyperbaric oxygen therapy. Nitric oxide generation may also contribute to the healing process.
- MeSH
- arginin analogy a deriváty krev MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- diabetická noha metabolismus patologie terapie MeSH
- financování organizované MeSH
- hojení ran MeSH
- hyperbarická oxygenace MeSH
- kolagen biosyntéza MeSH
- lidé středního věku MeSH
- lidé MeSH
- oxid dusnatý krev MeSH
- peptidové fragmenty krev MeSH
- prokolagen krev MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
At present, asymmetric hydrogenation is an attractive method for the synthesis of enantioenriched chiral compounds, such as drugs, agrochemicals or fragrances. This review is focused on the asymmetric transfer hydrogenation (ATH) of imines, in particular 3,4-dihydroisoquinolines. Mechanistic aspects of ATH are discussed and analytical methods for the monitoring of ATH as developed in our group are presented. The effect of structural changes of the catalyst and substrate on the course of ATH is also described. The influence of temperature, reactant concentrations and other reaction parameters as well as the utilizability of ATH in chemical industry are discussed.
Climatic changes are altering Earth's hydrological cycle, resulting in altered precipitation amounts, increased interannual variability of precipitation, and more frequent extreme precipitation events. These trends will likely continue into the future, having substantial impacts on net primary productivity (NPP) and associated ecosystem services such as food production and carbon sequestration. Frequently, experimental manipulations of precipitation have linked altered precipitation regimes to changes in NPP. Yet, findings have been diverse and substantial uncertainty still surrounds generalities describing patterns of ecosystem sensitivity to altered precipitation. Additionally, we do not know whether previously observed correlations between NPP and precipitation remain accurate when precipitation changes become extreme. We synthesized results from 83 case studies of experimental precipitation manipulations in grasslands worldwide. We used meta-analytical techniques to search for generalities and asymmetries of aboveground NPP (ANPP) and belowground NPP (BNPP) responses to both the direction and magnitude of precipitation change. Sensitivity (i.e., productivity response standardized by the amount of precipitation change) of BNPP was similar under precipitation additions and reductions, but ANPP was more sensitive to precipitation additions than reductions; this was especially evident in drier ecosystems. Additionally, overall relationships between the magnitude of productivity responses and the magnitude of precipitation change were saturating in form. The saturating form of this relationship was likely driven by ANPP responses to very extreme precipitation increases, although there were limited studies imposing extreme precipitation change, and there was considerable variation among experiments. This highlights the importance of incorporating gradients of manipulations, ranging from extreme drought to extreme precipitation increases into future climate change experiments. Additionally, policy and land management decisions related to global change scenarios should consider how ANPP and BNPP responses may differ, and that ecosystem responses to extreme events might not be predicted from relationships found under moderate environmental changes.
Acyclic nucleoside bisphosphonates (ANbPs) have previously been shown to be good inhibitors of human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and Plasmodium falciparum (Pf) hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPRT). On the basis of this scaffold, a new series of ANbPs was synthesized. One of these new ANbPs, [3-(guanine-9-yl)-2-((2-phosphonoethoxy)methyl)propoxy]methylphosphonic acid, exhibited Ki values of 6 and 70 nM for human HGPRT and Pf HGXPRT, respectively. These low Ki values were achieved by inserting an extra carbon atom in the linker connecting the N(9) atom of guanine to one of the phosphonate groups. The crystal structure of this ANbP in complex with human HGPRT was determined at 2.0 Å resolution and shows that it fills three key pockets in the active site. The most potent phosphoramidate prodrugs of these compounds have IC50 values in the low micromolar range in Pf lines and low toxicity in human A549 cells, demonstrating that these ANbPs are excellent antimalarial drug leads.
- MeSH
- antimalarika chemie farmakologie MeSH
- bisfosfonáty chemie farmakologie MeSH
- lidé MeSH
- nukleosidy chemie farmakologie MeSH
- pentosyltransferasy antagonisté a inhibitory metabolismus MeSH
- Plasmodium falciparum účinky léků enzymologie metabolismus MeSH
- simulace molekulového dockingu MeSH
- tropická malárie farmakoterapie enzymologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
