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51.
《Yao wu shi pin fen xi = Journal of food and drug analysis.》2019,27(2):585-594
Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer and has been suggested to be a subchronic toxicant in rats. DPHP has been approved to be used in food containers and handling by the U.S. Food and Drug Administration. The use of DPHP is still increasing, and the risk of human exposure to DPHP via food may be high. Exposure markers measured in human samples are commonly used to monitor human exposure levels. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and a rat model were used to discover tentative DPHP exposure markers. DPHP and mono-(2-propylheptyl) phthalate (MPHP) were used as the precursors for calculating metabolite candidates using biotransformation mass changes of known enzymatic reactions. A rat model was designed to validate these metabolite candidates as tentative exposure markers. A total of 28 signals show dose–response relationships and these signals contain a few isomers. The chemical structures of 15 tentative exposure marker signals were speculated based on the product ion mass spectra from MS/MS analysis. These 15 signals included 7 chemical structures and some of them may be isomers. The different arrangement of the atoms in space of these isomers should be validated by standard compounds in the future studies. Among the 7 speculated chemical structures, 2 structures were novel tentative DPHP metabolites, and 5 structures have been previously reported in the literature. The results indicate that using UPLC-MS and a rat model can be used to identify tentative toxicant exposure markers. 相似文献
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53.
《Drug metabolism and pharmacokinetics》2019,34(1):87-94
The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with Ki values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with Km values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CLR) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CLR (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CLR of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates. 相似文献
54.
Mengdie Jiang Bihan Wu Yongbing Sun Yanhuai Ding Yixi Xie 《Toxicology mechanisms and methods》2019,29(4):291-299
In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA. 相似文献
55.
目的 观察高通量血液透析(HFHD)与低通量血液透析(LFHD)的不同模式运用到老年患者维持性血液透析(MHD)中对其血压的影响。方法 选择2015年2月—2017年10月本院治疗的MHD老年患者74例,先为其施LFHD 3个月,再为其辅以3个月的HFHD,3次/周,4 h/次,对比不同透析模式对患者血压的影响。结果 实施HFHD后患者的平均动脉压(MAP)有所降低,在第3 h与第4 h透析后,血压把控优于LFHD(P<0.05)。结论 对于MHD老年患者来说,实施HFHD是优良的透析方法。 相似文献
56.
Ewelina Kazimierczyk Andrzej Eljaszewicz Paula Zembko Ewa Tarasiuk Malgorzata Rusak Agnieszka Kulczynska-Przybik Marta Lukaszewicz-Zajac Karol Kaminski Barbara Mroczko Maciej Szmitkowski Milena Dabrowska Bozena Sobkowicz Marcin Moniuszko Agnieszka Tycinska 《Pharmacological reports : PR》2019,71(1):73-81
Background
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57.
Su Jeong Seong Jin Pyo Hong Bong-Jin Hahm Hong Jin Jeon Jee Hoon Sohn Jun Young Lee Maeng Je Cho 《Journal of Korean medical science》2015,30(11):1675-1681
While decreasing trend in gender differences in alcohol use disorders was reported in Western countries, the change in Asian countries is unknown. This study aims to explore the shifts in gender difference in alcohol abuse (AA) and dependence (AD) in Korea. We compared the data from two nation-wide community surveys to evaluate gender differences in lifetime AA and AD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Face-to-face interviews using the Composite International Diagnostic Interview (CIDI) were applied to all subjects in 2001 (n=6,220) and 2011 (n=6,022). Male-to-female ratio of odds was decreased from 6.41 (95% CI, 4.81-8.54) to 4.37 (95% CI, 3.35-5.71) for AA and from 3.75 (95% CI, 2.96-4.75) to 2.40 (95% CI, 1.80-3.19) for AD. Among those aged 18-29, gender gap even became statistically insignificant for AA (OR, 1.59; 95% CI, 0.97-2.63) and AD (OR, 1.18; 95% CI, 0.80-2.41) in 2011. Men generally showed decreased odds for AD (0.55; 95% CI, 0.45-0.67) and women aged 30-39 showed increased odds for AA (2.13; 95% CI 1.18-3.84) in 2011 compared to 2001. Decreased AD in men and increased AA in women seem to contribute to the decrease of gender gap. Increased risk for AA in young women suggests needs for interventions. 相似文献
58.
59.
ABSTRACT
Introduction
Immune checkpoint inhibitors (ICIs) have proved to be groundbreaking in the field of oncology. However, immune system overactivation from ICIs has introduced a novel medical entity known as immune-related adverse events (irAEs), that can affect any organ or tissue. ICI-induced inflammatory arthritis (ICI-IIA) is the most common musculoskeletal irAE and can lead to significant morbidity and limitation in anti-cancer therapy. 相似文献60.
Hila Emmert Melina Fonfara Elke Rodriguez Stephan Weidinger 《Experimental dermatology》2020,29(8):749-758
Emerging evidence suggests oxidative stress plays a role in the pathophysiology of both atopic dermatitis (AD) and psoriasis (PSO). We established in vitro models of AD and PSO skin, and characterized these models in regard to their oxidative stress state. Both AD and PSO model keratinocytes exhibited elevated reactive oxygen species (ROS) levels and accumulated more DNA damage than control cells after oxidative stress induced by 250 µmol/L H2O2. Elevated ROS levels and DNA damage accumulation could be inhibited by the NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI). Further, immunofluorescence analysis revealed the presence of both NOX1 and NOX4 in keratinocytes. By inhibiting NOX1, stress-related signalling cascades and elevated ROS levels could be abrogated, and survival of AD and PSO cells improved. Taken together, this study reveals that inhibition of NOX inhibition could abrogate elevated oxidative stress in a 2D model of AD and PSO. 相似文献