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71.
M.G.M. De Ruyter R. Cronnelly N. Castagnoli 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1980,183(2):193-201
A reversed-phase, ion-pair liquid chromatographic method for the quantitative determination of quaternary acetylcholinesterase inhibitors is described. The method uses an ion-pair extraction to isolate the drugs from biological material prior to liquid chromatographic separation and online UV detection at 214 nm. Quantitation down to 5 ng/ml and within-day precision with coefficient of variation (C.V.) of 1.5% (n=10, = 100 ng/ml) for neostigmine, C.V., 1.7% (n=10, = 80 ng/ml) for pyridostigmine and C.V., 1.5% (n=10, = 100 ng/ml) for edrophonium have been achieved. The assay was designed for pharmacokinetic studies of these drugs in anesthetized patients. 相似文献
72.
Shrinidh Joshi Hannah Wollenzien Estelle Leclerc Yagna PR Jarajapu 《Journal of cellular physiology》2019,234(11):20420-20431
CD34+ hematopoietic stem/progenitor cells (HSPCs) are vasculogenic and hypoxia is a strong stimulus for the vasoreparative functions of these cells. Angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1–7)/Mas receptor (MasR) pathway stimulates vasoprotective functions of CD34+ cells. This study tested if ACE2 and MasR are involved in the hypoxic stimulation of CD34+ cells. Cells were isolated from circulating mononuclear cells derived from healthy subjects (n = 46) and were exposed to normoxia (20% O2) or hypoxia (1% O2). Luciferase reporter assays were carried out in cells transduced with lentivirus carrying ACE2- or MasR- or a scramble-3′-untranslated region gene with a firefly luciferase reporter. Expressions or activities of ACE, angiotensin receptor Type 1 (AT1R), ACE2, and MasR were determined. In vitro observations were verified in HSPCs derived from mice undergoing hindlimb ischemia (HLI). In vitro exposure to hypoxia-increased proliferation and migration of CD34+ cells in basal conditions or in response to vascular endothelial growth factor (VEGF) or stromal-derived factor 1α (SDF) compared with normoxia. Expression of ACE2 or MasR was increased relative to normoxia while ACE or AT1R expressions were unaltered. Luciferase activity was increased by hypoxia in cells transfected with the luciferase reporter plasmids coding for the ACE2- or MasR promoters relatively to the control. The effects of hypoxia were mimicked by VEGF or SDF under normoxia. Hypoxia-induced ADAM17-dependent shedding of functional ACE2 fragments. In mice undergoing HLI, increased expression/activity of ACE2 and MasR were observed in the circulating HSPCs. This study provides compelling evidence for the hypoxic upregulation of ACE2 and MasR in CD34+ cells, which likely contributes to vascular repair. 相似文献
73.
Active uptake of MPP+, a metabolite of MPTP, by brain synaptosomes 总被引:20,自引:0,他引:20
K Chiba A J Trevor N Castagnoli 《Biochemical and biophysical research communications》1985,128(3):1228-1232
Mouse brain synaptosomal preparations were used to study uptake of N-methyl-4-phenylpyridine (MPP+), a metabolite of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). The uptake of [3H]-MPP+ by striatal synaptosomes was approximately 25 X greater than that of [3H]-MPTP, with a KM of 0.48 microM and a Vmax of 5.3 nmoles/g tissue/min. Uptake was Na+ dependent and inhibited by ouabain, cocaine and dopamine (Ki 0.12 microM). Synaptosomes prepared from the corpus striatum accumulated [3H]-MPP+ at a rate 5-10 times higher than preparations from other brain regions. This selective uptake of MPP+ may contribute to the specificity of the toxic effects of MPTP on nigrostriatal dopaminergic neurons. 相似文献
74.
Role of 14-3-3 proteins in the regulation of neutral trehalase in the yeast Saccharomyces cerevisiae
In higher eukaryotes, 14-3-3 proteins participate in numerous cellular processes, and carry out their function through a variety of different molecular mechanisms, including regulation of protein localization and enzyme activation. Here, it is shown that the two yeast 14-3-3 homologues, Bmh1p and Bmh2p, form a complex with neutral trehalase (Nth1p), an enzyme that is responsible for trehalose degradation and is required in a variety of stress conditions. In a purified in vitro system, either one of the two 14-3-3 yeast isoforms are necessary for complete activation of neutral trehalase (Nth1p) after phosphorylation by PKA. It is further demonstrated that Bmh1p and Bmh2p bind to the amino-terminal region of phosphorylated trehalase, thereby modulating its enzymatic activity. This work represents the first demonstration of enzyme activation mediated by 14-3-3 binding in yeast. 相似文献
75.
Sonja Melman Ellen NC Schoorel Carmen Dirksen Anneke Kwee Luc Smits Froukje de Boer Madelaine Jonkers Mallory D Woiski Ben Willem J Mol Johannes PR Doornbos Harry Visser Anjoke JM Huisjes Martina M Porath Friso MC Delemarre Simone MI Kuppens Robert Aardenburg Ivo MA Van Dooren Francis PJM Vrouenraets Frans TH Lim Gunilla Kleiverda Paulien CM van der Salm Karin de Boer Marko J Sikkema Jan G Nijhuis Rosella PMG Hermens Hubertina CJ Scheepers 《Implementation science : IS》2013,8(1):1-8
Background
Caesarean section (CS) rates are rising worldwide. In the Netherlands, the most significant rise is observed in healthy women with a singleton in vertex position between 37 and 42 weeks gestation, whereas it is doubtful whether an improved outcome for the mother or her child was obtained. It can be hypothesized that evidence-based guidelines on CS are not implemented sufficiently. Therefore, the present study has the following objectives: to develop quality indicators on the decision to perform a CS based on key recommendations from national and international guidelines; to use the quality indicators in order to gain insight into actual adherence of Dutch gynaecologists to guideline recommendations on the performance of a CS; to explore barriers and facilitators that have a direct effect on guideline application regarding CS; and to develop, execute, and evaluate a strategy in order to reduce the CS incidence for a similar neonatal outcome (based on the information gathered in the second and third objectives).Methods
An independent expert panel of Dutch gynaecologists and midwives will develop a set of quality indicators on the decision to perform a CS. These indicators will be used to measure current care in 20 hospitals with a population of 1,000 women who delivered by CS, and a random selection of 1,000 women who delivered vaginally in the same period. Furthermore, by interviewing healthcare professionals and patients, the barriers and facilitators that may influence the decision to perform a CS will be measured. Based on the results, a tailor-made implementation strategy will be developed and tested in a controlled before-and-after study in 12 hospitals (six intervention, six control hospitals) with regard to effectiveness, experiences, and costs.Discussion
This study will offer insight into the current CS care and into the hindering and facilitating factors influencing obstetrical policy on CS. Furthermore, it will allow definition of patient categories or situations in which a tailor-made implementation strategy will most likely be meaningful and cost effective, without negatively affecting the outcome for mother and child.Trial registration
http://www.clinicaltrials.gov: NCT01261676 相似文献76.
Molecular evolution in the gnd locus of Salmonella enterica 总被引:3,自引:0,他引:3
The gnd gene, the structural gene for 6-phosphogluconate dehydrogenase, was
sequenced and analyzed in 34 isolates from different serovars of the seven
subspecies of Salmonella enterica to provide comparative information on the
evolution in this gene, which has been studied extensively in Escherichia
coli. The gene tree obtained by the neighbor- joining method in general
gave separate branches for each subspecies, with the few exceptions readily
explained by recombination. There is evidence of recombination involving
transfer of long (more than 400 bp) and short (30-150 bp) segments of DNA.
Four of the six long-segment transfers detected are at the 5' end of the
gene, and in all four cases a variant of the chi sequence is located close
to the recombination junction and appears to have mediated the
recombination events. We suggest that in these four cases and in a fifth
case with intersubspecies transfer of the whole gnd gene, the adjacent rfb
(O antigen) locus may have been transferred in the same event. The
estimates of the number of synonymous substitutions per synonymous site,
KS, and the number of nonsynonymous substitutions per nonsynonymous site,
KA, within the E. coli and S. enterica gnd genes, and also between the two
species show an interesting distribution, with KS being lower toward the
ends of the gene and KA in particular being lower in the first than in the
second domain. In S. enterica, synonymous sites also seem to be subjected
to negative selection. The ratio of KA to KS was higher within S. enterica
and E. coli than between them, which may indicate that intraspecies
variation is essentially between clones and that mildly deleterious
mutations can be fixed within clones, which would thus raise KA within
species.
相似文献
77.
78.
Expression of the selective nigrostriatal neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP] requires its bioactivation by MAO B which leads to the formation of potentially reactive metabolites including the 2-electron oxidation product, 1-methyl-4-phenyl-2,3-dihydropyridinium species [MPDP+] and the 4-electron oxidation product, the 1-methyl-4-phenyl pyridinium species [MPP+]. The latter metabolite accumulates in brain striatal tissues, is a substrate for dopaminergic active uptake systems and is an inhibitor of mitochondrial NADH dehydrogenase, a respiratory chain enzyme located in the inner mitochondrial membrane. In intact mitochondria this inhibition of respiration may be facilitated by active uptake of MPP+, a process dependent on the membrane electrical gradient. In considering possible mechanisms involved in the biochemical effects of MPP+, its redox cycling potential appears to be much lower than its chemical congener paraquat, based on attempted radical formation by chemical or enzymic reduction. Theoretically, a carbon-centered radical intermediate could be formed by 1-electron reduction of MPP+, or by 1-electron oxidation of 1-methyl-4-phenyl-1,2-dihydropyridine, the free base form of MPDP+. The 1-electron reduction of such a radical could form 1-methyl-4-phenyl-1,4-dihydropyridine [DHP]. Synthetic DHP is neurotoxic in C57B mice, and its administration leads to the formation of MPP+ in the brain, presumably through rapid auto-oxidation. The hydrolysis of DHP would yield 3-phenylglutaraldehyde and methylamine. Recent studies demonstrating the formation of methylamine in brain mitochondrial preparations containing MPTP support our suggestion that DHP may be a brain metabolite of MPTP. 相似文献
79.
Characterization of arachidonic acid metabolic profiles in animal tissues by high-resolution gas chromatography-mass spectrometry 总被引:1,自引:0,他引:1
C Chiabrando A Noseda M Novella Castagnoli M Salmona R Fanelli 《Biochimica et biophysica acta》1984,794(2):292-297
A standardized, highly specific routine method was developed for the quantitative profiling of cyclooxygenase metabolites of arachidonic acid in animal tissues. Whole homogenates were used to assess the potential capacity of tissues to metabolize endogenous arachidonic acid. Samples were analyzed by high-resolution gas chromatography-mass spectrometry in the selected ion monitoring mode. The screening of several rat tissues by this method revealed marked tissue-specificity in both the synthesis capacity and prostaglandin profile. The major products detected were: 6-ketoprostaglandin F1alpha for lung, stomach, muscle and heart; prostaglandin D2 for spleen, brain and liver; prostaglandin F2alpha for kidney and prostaglandin E2 for seminal vesicles. Marked species differences were found when guinea pig tissues were analyzed. 相似文献
80.