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.
BackgroundIsolated local recurrent or persistent esophageal cancer (EC) after curative intended definitive (dCRT) or neoadjuvant chemoradiotherapy (nCRT) with initially omitted surgery, is a potential indication for salvage surgery. We aimed to evaluate safety and efficacy of salvage surgery in these patients.Material and methodsA systematic literature search following PRISMA guidelines was performed using databases of PubMed/Medline. All included studies were performed in patients with persistent or recurrent EC after initial treatment with dCRT or nCRT, between 2007 and 2017. Survival analysis was performed with an inverse-variance weighting method.ResultsOf the 278 identified studies, 28 were eligible, including a total of 1076 patients. Postoperative complications after salvage esophagectomy were significantly more common among patients with isolated persistent than in those with locoregional recurrent EC, including respiratory (36.6% versus 22.7%; difference in proportion 10.9 with 95% confidence interval (CI) [3.1; 18.7]) and cardiovascular complications (10.4% versus 4.5%; difference in proportion 5.9 with 95% CI [1.5; 10.2]). The pooled estimated 30- and 90-day mortality was 2.6% [1.6; 3.6] and 8.0% [6.3; 9.8], respectively. The pooled estimated 3-year and 5-year overall survival (OS) were 39.0% (95% CI: [35.8; 42.2]) and 19.4% [95% CI:16.5; 22.4], respectively. Patients with isolated persistent or recurrent EC after initial CRT had similar 5-year OS (14.0% versus 19.7%, difference in proportion −5.7, 95% CI [-13.7; 2.3]).ConclusionsSalvage surgery is a potentially curative procedure in patients with locally recurrent or persistent esophageal cancer and can be performed safely after definitive or neoadjuvant chemoradiotherapy when surgery was initially omitted. 相似文献
PurposeTo evaluate tumor and ablation zone morphology and densitometry related to tumor recurrence in participants with Stage IA non–small cell lung cancer undergoing radiofrequency ablation in a prospective, multicenter trial.Materials and MethodsForty-five participants (median 76 years old; 25 women; 20 men) from 16 sites were followed for 2 years (December 2006 to November 2010) with computed tomography (CT) densitometry. Imaging findings before and after ablation were recorded, including maximum CT attenuation (in Hounsfield units) at precontrast and 45-, 90-, 180-, and 300-s postcontrast.ResultsEvery 1-cm increase in the largest axial diameter of the ablation zone at 3-months’ follow-up compared to the index tumor reduced the odds of 2-year recurrence by 52% (P = .02). A 1-cm difference performed the best (sensitivity, 0.56; specificity, 0.93; positive likelihood ratio of 8). CT densitometry precontrast and at 45 seconds showed significantly different enhancement patterns in a comparison among pretreated lung cancer (delta = +61.2 HU), tumor recurrence (delta = +57 HU), and treated tumor/ablation zone (delta [change in attenuation] = +16.9 HU), (P < .0001). Densitometry from 45 to 300 s was also different among pretreated tumor (delta = −6.8 HU), recurrence (delta = −11.2 HU), and treated tumor (delta = +12.1 HU; P = .01). Untreated and residual tumor demonstrated washout, whereas treated tumor demonstrated increased attenuation.ConclusionsAn ablation zone ≥1 cm larger than the initial tumor, based on 3-month follow-up imaging, is recommended to decrease odds of recurrence. CT densitometry can delineate tumor versus treatment zones. 相似文献
Breast pseudoaneurysms after a core needle biopsy are a rare complication with a low incidence. However, it is important to be aware of the possibility of complications that require treatment. 相似文献
Inappropriate use of acetaminophen (APAP) can lead to morbidity and mortality secondary to hepatic necrosis. Ginsenoside Rg1 is a major active ingredient in processed Panax ginseng, which is proved to elicit biological effects. We hypothesized the beneficial effect of Rg1 on APAP-mediated hepatotoxicity was through Nrf2/ARE pathway. The study was conducted in cells and mice, comparing the actions of Rg1. Rg1 significantly improved cell survival rates and promoted the expression of antioxidant proteins. Meanwhile, Rg1 reduced the excessive ROS and the occurrence of cell apoptosis, which were related to Nrf2/ARE pathway. Expression of Nrf2 has a certain cell specificity.
Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.
Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.
Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.
Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.