Mao, Y*
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Diabetes je závažná nemoc, kterou však lze zvládnout! Za pouhých 12 týdnů získáte opět zdraví a duševní rovnováhu!Pokud patříte k těm, kdo jsou postiženi diabetem, je načase s tím něco udělat. Tato kniha vám nabízí jednoduchý, ale průkopnický program, který pomáhá zvládnout diabetes 1. a 2. typu. Jde o zcela přirozený postup, založený na nezbytném alkalickém vnitřním prostředí organismu, jenž pomáhá zpomalit, zastavit nebo dokonce zvrátit nemoc a poškození, jež často způsobuje. A to bez vysokých dávek léků, které většina diabetiků užívá. Dozvíte se - Jaké potraviny jíst, jakých se vyvarovat a které jsou nejlepší pro snížení cukru v krvi - Spoustu skvělých pokrmů, které vyrovnávají pH organismu - Jak nahradit jídla, která zvyšují hladinu cukru v krvi, zdravými potravinami - Návod jak se zbavit stresu a cvičit bez rizika - Že přístup k fyzické kondici ve stylu „bez práce nejsou koláče“ vede k překyselení a zvýšenému množství cukru v krvi - Proč je pročištění organismu – neboli tzv. tekutinové hody – nejúčinnějším začátkem pH stravování a obnovy energie … a mnohem víc.
OBJECTIVES: Since the city of Xi'an has been extremely concerned with the serious problem of taxi involved crashes, injuries and fatalities, the primary purpose of this study is to identify the risk factors associated with the magnitude and nature of the problem and provide possible measures for enhancing the overall safety performance of taxi industry. METHODS: Using 726 crash samples from the original of 7,183 observations in Xi'an over the period from 2006 to 2012, comparative statistics and systematic analysis were employed to describe the distribution of taxi crashes by driver characteristics, roadway contributors and environmental factors and then determine the significant factors contributing to crash injuries and fatalities. RESULTS: The trend and pattern of taxi involved crashes vary significantly. Middle aged (77.27%) male (91.60%) drivers with limited education (68.59%) and less driving (31.27%) and job (82.50%) experience were much more likely to be involved in such a crash. Additionally, it is found that a large majority of taxi crashes occurred with the most frequent type of rear end collisions (30.72%), on six-lane segments without median (16.94%) or four legged intersections (15.29%), under adverse weather conditions (31.82%), at weekends (34.99%), and during winter days (34.72%), but fatal and serious crashes were more likely to happen at night (30.72%) or under wet road surface conditions (16.94%), due to driver's overspeeding, unbelted, disregarding signs or signals, or other types of risk driving behaviour. CONCLUSIONS: The risk of taxi related crashes varies by drivers, roadways and environment. To reduce the risk of potential crashes for taxi drivers, we recommend the targeted legislation and enforcement, stronger night and trip restrictions, awareness of risk behaviour, and periodical training requirement. Such proposals and measures are expected to help mitigate taxi crashes and promote road safety in China.
- MeSH
- bezpečnost MeSH
- chování MeSH
- doprava * MeSH
- dopravní nehody prevence a kontrola trendy MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- rizikové faktory MeSH
- statistika jako téma MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Čína MeSH
Spiramycin is a 16-membered macrolide antibiotic produced by Streptomyces ambofaciens and used in human medicine for the treatment of various respiratory tract and genital infections. Several impurities were detected in spiramycin-fermentation broth, especially impurities D and F, which decreased the separation-extraction yield and increased production cost. Dextrins, as the main carbon source, influence the accumulation of spiramycin and impurities. In this work, two types of dextrin from vendor Y and Z were compared to study their influences on spiramycin production. Our results showed that final spiramycin production with dextrin Z was enhanced twofold as compared with dextrin Y; however, the content of impurities F and D were higher with dextrin Z relative to dextrin Y. Several parameters (adenosine triphosphate, total sugar, reducing sugar, and reducing sugar to total sugar) were analyzed to reveal differences in the fermentation process. In vitro dextrin hydrolysis by amylase revealed structural differences in the two types of dextrin, and real-time quantitative polymerase chain reaction analyses showed that the transcription of srm7 and srm21 (involved in forosaminyl methylation) was enhanced and potentially related to the reduced formation of impurity F with dextrin Y. Furthermore, the srm20/srm33 ratio, representing flux balance of forosaminyl and mycarosyl, was ~ 1, implying that forosaminyl and mycarosyl biosynthesis were well balanced, resulting in reduced production of impurity D with dextrin Y.
Oxyceroides gen. nov., including three new species, O. gracilis sp. nov., O. sinica sp. nov. and O. tangi sp. nov. from South China in the Oriental region are described and illustrated. Related genera from other biogeographical realms are briefly discussed. Identification keys to the known Oriental Oxycerini and to the three new species of Oxyceroides are given.
- MeSH
- anatomické struktury zvířat anatomie a histologie růst a vývoj MeSH
- Diptera anatomie a histologie klasifikace růst a vývoj MeSH
- rozšíření zvířat MeSH
- velikost orgánu MeSH
- velikost těla MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Čína MeSH
Guanine-rich oligonucleotides can form a unique G-quadruplex (GQ) structure with stacking units of four guanine bases organized in a plane through Hoogsteen bonding. GQ structures have been detected in vivo and shown to exert their roles in maintaining genome integrity and regulating gene expression. Understanding GQ conformation is important for understanding its inherent biological role and for devising strategies to control and manipulate functions based on targeting GQ. Although a number of biophysical methods have been used to investigate structure and dynamics of GQs, our understanding is far from complete. As such, this work explores the use of the site-directed spin labeling technique, complemented by molecular dynamics simulations, for investigating GQ conformations. A nucleotide-independent nitroxide label (R5), which has been previously applied for probing conformations of noncoding RNA and DNA duplexes, is attached to multiple sites in a 22-nucleotide DNA strand derived from the human telomeric sequence (hTel-22) that is known to form GQ. The R5 labels are shown to minimally impact GQ folding, and inter-R5 distances measured using double electron-electron resonance spectroscopy are shown to adequately distinguish the different topological conformations of hTel-22 and report variations in their occupancies in response to changes of the environment variables such as salt, crowding agent, and small molecule ligand. The work demonstrates that the R5 label is able to probe GQ conformation and establishes the base for using R5 to study more complex sequences, such as those that may potentially form multimeric GQs in long telomeric repeats.
- MeSH
- G-kvadruplexy * MeSH
- konformace nukleové kyseliny MeSH
- konformace proteinů MeSH
- lidé MeSH
- oligonukleotidy chemie MeSH
- oxid dusný chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
ETHNOPHARMACOLOGICAL RELEVANCE: The development of selective inhibitors of monoamine oxidase B (MAO-B) has been essential in treating Parkinson's disease. However, the apparent hepatotoxicity and drug-drug interactions of current inhibitors accentuate the need for the development of novel pharmacotherapies. Crossyne guttata (L.) D. & U. Müll-Doblies is used frequently by Rastafarian bush doctors to treat alcoholism, a disorder which is also accentuated by MAO. OBJECTIVE: The study sought to isolate, identify and characterise the biologically active constituents of C. guttata based on their ability to inhibit the MAO enzymes. MATERIALS AND METHODS: Column chromatography was used to isolate the biologically active alkaloids of C. guttata. The ability of the alkaloids to inhibit the biotransformation of 4-aminoantipyrine by the MAO enzymes was evaluated in vitro. In silico docking was conducted using AutoDock Vina server while the pharmacokinetic properties of the compounds were evaluated using SwissADME. RESULTS: Chromatographic separation of an ethanolic fraction of C. guttata yielded the alkaloids crinamine 1 and epibuphanisine 2. 1 and 2 along with structurally related alkaloids haemanthamine 3 and haemanthidine 4 were evaluated for their ability to inhibit the action of isozymes of MAO in vitro. Alkaloids effected submicromolar IC50 values against MAO-B, the most potent of which being crinamine 1 (0.014 μM) > haemanthidine 4 (0.017 μM) > epibuphanisine 2 (0.039 μM) > haemanthamine 3 (0.112 μM). Binding energies of the alkaloids correlated well with their inhibitory potential with crinamine displaying the best binding efficacy and binding energy score with MAO-B. DISCUSSION AND CONCLUSION: Crinamine and epibuphanisine exhibited potent and selective inhibitory activity towards MAO-B. After comprehensive in silico investigations encompassing robust molecular docking analysis, the drug-like attributes and safety of the alkaloids suggest the crinamine is a potentially safe drug for human application.
- MeSH
- alkaloidy amarylkovitých chemie farmakokinetika farmakologie toxicita MeSH
- bezpečnost pacientů MeSH
- biologické modely * MeSH
- Cercopithecus aethiops MeSH
- hodnocení rizik MeSH
- inhibitory MAO chemie farmakokinetika farmakologie toxicita MeSH
- konformace proteinů MeSH
- lidé MeSH
- monoaminoxidasa chemie metabolismus MeSH
- mutace MeSH
- Salmonella typhimurium účinky léků genetika MeSH
- simulace molekulového dockingu * MeSH
- Vero buňky MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Alzheimer's disease (AD) is a complex disease with an unknown etiology. Available treatments, limited to cholinesterase inhibitors and N-methyl-d-aspartate receptor (NMDAR) antagonists, provide symptomatic relief only. As single-target therapies have not proven effective, rational specific-targeted combination into a single molecule represents a more promising approach for treating AD, and is expected to yield greater benefits in alleviating symptoms and slowing disease progression. In the present study, we designed, synthesized, and biologically evaluated 24 novel N-methylpropargylamino-quinazoline derivatives. Initially, compounds were thoroughly inspected by in silico techniques determining their oral and CNS availabilities. We tested, in vitro, the compounds' effects on cholinesterases and monoamine oxidase A/B (MAO-A/B), as well as their impacts on NMDAR antagonism, dehydrogenase activity, and glutathione levels. In addition, we inspected selected compounds for their cytotoxicity on undifferentiated and differentiated neuroblastoma SH-SY5Y cells. We collectively highlighted II-6h as the best candidate endowed with a selective MAO-B inhibition profile, NMDAR antagonism, an acceptable cytotoxicity profile, and the potential to permeate through BBB. The structure-guided drug design strategy applied in this study imposed a novel concept for rational drug discovery and enhances our understanding on the development of novel therapeutic agents for treating AD.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Alzheimerova nemoc * farmakoterapie MeSH
- cholinesterasové inhibitory terapeutické užití MeSH
- inhibitory MAO terapeutické užití MeSH
- lidé MeSH
- monoaminoxidasa metabolismus MeSH
- neuroblastom * farmakoterapie MeSH
- racionální návrh léčiv MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Human behavior is influenced by both genetic and environmental factors. Monoamine oxidase A (MAOA) is among the most investigated genetic determinants of violent behaviors, while the monoamine oxidase B (MAOB) is explored in Parkinson's disease. We collected twenty-four post-mortem brain tissue datasets of 3871 and 1820 non-demented males and females, respectively, who died from causes not attributable to neurodegenerative diseases. The gene expressions of MAOA and MAOB (MAO genes) were analyzed in these subjects, who were further stratified according to age into eleven groups ranging from late Infancy (5-9 months) to centenarians (>100 years). MAO genes were differently expressed in brains during the entire life span. In particular, maximal and minimal expression levels were found in early life and around the teen years. Females tended to have higher MAO gene levels throughout their lives than those found in age-matched males, even when expressions were separately measured in different brain regions. We demonstrated the existence of age- and sex- related variations in the MAO transcript levels in defined brain regions. More in-depth protein studies are needed to confirm our preliminary results obtained only on messenger RNAs in order to establish the role played by MAO genes in human development.
- MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- monoaminoxidasa biosyntéza MeSH
- mozek enzymologie MeSH
- novorozenec MeSH
- pohlavní dimorfismus * MeSH
- předškolní dítě MeSH
- regulace genové exprese enzymů * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stárnutí metabolismus MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters, has an important role in the brain development and function, and MAO inhibitors have a range of potential therapeutic uses. We investigated systematically in vitro effects of pharmacologically different antidepressants and mood stabilizers on MAO activity. Methods: Effects of drugs on the activity of MAO were measured in crude mitochondrial fraction isolated from cortex of pig brain, when radiolabeled serotonin (for MAO-A) or phenylethylamine (for MAO-B) was used as substrate. The several antidepressants and mood stabilizers were compared with effects of well known MAO inhibitors such as moclobemide, iproniazid, pargyline, and clorgyline. Results: In general, the effect of tested drugs was found to be inhibitory. The half maximal inhibitory concentration, parameters of enzyme kinetic, and mechanism of inhibition were determined. MAO-A was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > desipramine > amitriptyline > imipramine > citalopram > venlafaxine > reboxetine > olanzapine > mirtazapine > tianeptine > moclobemide, cocaine > lithium, valproate. MAO-B was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > venlafaxine > amitriptyline > olanzapine > citalopram > desipramine > reboxetine > imipramine > tianeptine > mirtazapine, cocaine > moclobemide, lithium, valproate. The mechanism of inhibition of MAOs by several antidepressants was found various. Conclusions: It was concluded that MAO activity is acutely affected by pharmacologically different antidepressants at relatively high drug concentrations; this effect is inhibitory. There are differences both in inhibitory potency and in mechanism of inhibition between both several drugs and the two MAO isoforms. While MAO inhibition is not primary biochemical effect related to their therapeutic action, it can be supposed that decrease of MAO activity may be concerned in some effects of these drugs on serotonergic, noradrenergic, and dopaminergic neurotransmission.
- MeSH
- afekt účinky léků MeSH
- amitriptylin farmakologie MeSH
- antidepresiva farmakologie MeSH
- antimanika farmakologie MeSH
- benzodiazepiny farmakologie MeSH
- citalopram farmakologie MeSH
- cyklohexanoly farmakologie MeSH
- desipramin farmakologie MeSH
- fluoxetin farmakologie MeSH
- imipramin farmakologie MeSH
- inhibitory MAO farmakologie MeSH
- iproniazid farmakologie MeSH
- klorgylin farmakologie MeSH
- kokain farmakologie MeSH
- kyselina valproová farmakologie MeSH
- lithium farmakologie MeSH
- mianserin analogy a deriváty farmakologie MeSH
- mitochondrie účinky léků enzymologie MeSH
- moklobemid farmakologie MeSH
- monoaminoxidasa účinky léků metabolismus MeSH
- morfoliny farmakologie MeSH
- mozková kůra cytologie MeSH
- pargylin farmakologie MeSH
- prasata MeSH
- techniky in vitro MeSH
- thiazepiny farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer's disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC50 = 11.90 ± 0.05 nM), moderate hAChE (IC50 = 1.73 ± 0.34 μM), hMAO A (IC50 = 2.78 ± 0.12 μM), and MAO B (IC50 = 21.29 ± 3.85 μM) inhibition, while keeping a strong antioxidant power (3.04 TE, ORAC test). Consequently, the results reported here support the development of new multitarget Donepezil + Chromone + Melatonin hybrids, such as compound 14n, as a potential drug for AD patients cure.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- chromony chemie farmakologie MeSH
- donepezil chemie farmakologie MeSH
- inhibitory MAO chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- melatonin chemie farmakologie MeSH
- molekulární struktura MeSH
- monoaminoxidasa metabolismus MeSH
- simulace molekulového dockingu MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
