The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.
Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.
Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.
Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low Km value was relatively comparable to that for marmoset livers.
These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.
IntroductionThis study assessed the cleaning, shaping, and disinfection abilities of 2 instrumentation systems in molar root canals using a novel correlative analytical approach.MethodsThe root canals from extracted mandibular and maxillary molars with apical periodontitis were pair matched according to anatomic similarities as determined by micro–computed tomographic analysis and prepared with either XP-endo Shaper (FKG Dentaire, La Chaux-de-Fonds, Switzerland) (n = 16) or Reciproc Blue (VDW, Munich, Germany) (n = 16) instruments and 2.5% sodium hypochlorite irrigation. Pre- and postpreparation micro–computed tomographic scans were used to identify and calculate the unprepared surface areas (shaping), which were histobacteriologically evaluated for the presence of residual bacteria (disinfection) and pulp tissue remnants (cleaning) in each canal third.ResultsUnprepared canal surface areas for XP-endo Shaper and Reciproc Blue in the full canal length were approximately 26% and 19% (P < .05), respectively (30% and 23% in the apical part of the canal, P > .05). Preparation with Reciproc Blue resulted in 37.5% canals free of bacteria in all sections examined and 56% in the apical sections only. XP-endo Shaper resulted in 44% canals free of bacteria in all sections, and 56% in the apical part of the canal only. Pulp tissue remnants were not observed in 31% (all canal sections) and 50% (apical canal sections) of specimens from both instrument systems. No significant differences were observed between instruments when comparing the amount of pulp tissue remnants and the number of cases negative for bacteria and tissue remnants (P > .05).ConclusionsAlthough the Reciproc Blue instrument had superior shaping ability in comparison with XP-endo Shaper, both systems performed similarly in cleaning and disinfecting root canals. Irregular canals and difficult-to-reach areas were not thoroughly cleaned and disinfected by any of the tested systems. 相似文献
Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.
Methods
In eighteen consecutive AMI patients (mean age 56.78?±?12.4 years, mean left ventricle ejection fraction – LVEF: 41.9?±?9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice – on admission and after 19.2?±?5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.
Results
AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p?=?0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p?=?0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p?=?0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p?=?0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p?=?0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p?=?0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines ? IL-6 and TNF-α.
Conclusions
These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium. 相似文献
The reaction route (RR) graph approach recently developed by us for complex, non-linear kinetic mechanisms is applied to the hydrogen oxidation and evolution reactions. A corresponding RR graph is constructed and translated into an equivalent electrical circuit network by associating each elementary step with a characteristic resistance for the steady-state case and considering the overall reaction as a power source. It is further shown that the steady-state kinetics of the reaction can be investigated employing the conventional methods of the electrical network theory. Using a set of rate constants for the hydrogen evolution reaction (her) in alkaline solutions from the literature, the dominant RRs are identified and simplified mechanisms and kinetics derived. 相似文献
The aim of this study was to examine the effects of dietary fenofibrate (0.05% in the diet) on ketone body production and lipid secretion in isolated perfused rat liver. Feeding with fenofibrate for 7–9 days caused an increased liver weight. Ketone body production was significantly greater in the livers perfused with oleic acid than in those perfused without fatty acid, with the elevation of the ratio ofβ-hydroxybutyrate:acetoacetate indicating an increased redox potential in mitochondrial compartments by exogenous fatty acid. On the other hand, fenofibrate feeding caused a further stimulation of ketone body production from both endogenous and exogenous fatty acid substrates, respectively, with a decreased ratio ofβ-hydroxybutyrate:acetoacetate as compared to respective control livers, indicating a decreased redox potential. Hepatic secretion of triglyceride, but not of cholesterol, was decreased markedly in the fenofibrate-fed rats, especially when oleate was provided, suggesting an inverse relationship between rates of ketogenesis and triglyceride secretion. These results suggest that the altered hepatic metabolism of long-chain fatty acids between oxidation and esterification caused by fenofibrate may thus be a factor responsible for the decreased secretion of triglyceride, hence leading to hypotriglyceridaemiain vivo. 相似文献
Aerobic exercise and beta-blocking drugs are regularly prescribed as treatment for hypertension and as a prophylactic for patients at risk from coronary heart disease and for those recovering from an infarct. Some beta blockers, particularly non-beta1-selective drugs, may make exercise more difficult, possibly by interfering with substrate metabolism during exercise. This study examined the effects of low and high doses of a beta1-selective blocker, metoprolol, and a nonselective beta blocker, propranolol, on exercise metabolism. The study involved 20 healthy subjects (10 men, 10 women) who walked on a treadmill at 50% of their maximal oxygen uptake for 1 h on five occasions, separated by 7 days. On each of the five occasions they received one of the following treatments, given in random order: placebo, metoprolol 50 mg, metoprolol 100 mg, propranolol 40 mg, or propranolol 80 mg, all taken twice daily. Fat oxidation, expressed as a percentage of total energy expenditure, was significantly lower than with placebo for all of the active treatments except metoprolol 50 mg (placebo: 42.7 ± 11.6%; metoprolol 50 mg: 38.7 ± 14.1%, p = NS; metoprolol 100 mg: 36.3 ± 13.7%, p = 0.05; propranolol 40 mg: 31.2 ± 9.3%, p = 0.01; propranolol 80 mg: 29.5 ± 10.9%, p = 0.01); and significantly lower with propranolol than with metoprolol (propranolol 40 mg: p = 0.0036; propranolol 80 mg: p = 0.01). Plasma ammonia concentration was significantly higher than with placebo with propranolol 40 mg, propranolol 80 mg, and metoprolol 100 mg (p = 0.01 for all); with metoprolol 50 mg, there was no difference from placebo (p = NS). Both beta blockers in this study reduced fat metabolism and increased perceived exertion to some degree. Additional inhibition of fat oxidation occurred with the nonselective drug, probably in intramuscular rather than adipose lipolysis, and was probably beta2 mediated. The results of this study suggest that a selective beta blocker has less of an adverse effect on substrate metabolism than does a nonselective beta blocker. Beta1-selective drugs may offer advantages in patients who undertake regular aerobic exercise. 相似文献
INTRODUCTION The phenomenon of anaerobic ammonium oxidation was originally discovered in a denitrifying fluidized-bed reactor treating effluent from a methanogenic reactor in the 1990s[1]. Anaerobic ammonium oxidation (ANAMMOX) process is a strictly anaerobic denitrification process, in which ANAMMOX autotrophic bacteria directly oxidize ammonium to dinitrogen gas using nitrite as electron acceptor. In recent years, the anammox process has received great attention and lots of researc… 相似文献