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1.
Drug Dev Ind Pharm ; : 1-11, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646854

RESUMO

OBJECTIVE: The choline derivative (CD) and polyethylene-glycol (PEG) dually modified artemether (ARM) nanostructured lipid carriers (CD-PEG-ARM-NLC) have been designed to prolong the circulation of ARM in blood, as well as to develop targeting for new permeability pathways (NPPs) and erythrocyte choline carriers (ECCs) that are expressed on the Plasmodium-infected erythrocyte membrane. SIGNIFICANCE: The CD-PEG-ARM-NLC constructed in this study was found to be able to target endoerythrocytic Plasmodium by increasing the drug concentration and residence time in the infected erythrocytic microenvironment and minimizing toxicity and side effects. METHODS: CD-PEG-ARM-NLC was prepared using high-pressure homogenization followed by physicochemical characterization. The targeting ability of CD-PEG-NLC to infected erythrocytes probed by coumarin-6 was investigated by using fluorescence microscopy imaging. The SYBR Green I assay for parasite nucleic acid was adapted in order to assess the efficacy of inhibition against parasite growth in vitro. The antimalarial activity of ARM-loaded NLCs was evaluated by a Pearson four-day suppressive test in Pyy265BY-bearing mice. RESULTS: In vitro imaging indicated that the intracellular delivery of CD-PEG-ARM-NLC was efficiently taken up by the infected erythrocytes via ECCs and NPPs, which could be inhibited by addition of furosemide (an inhibitor of NPPs) and excessive choline (native substrate of ECCs). Moreover, in vitro and in vivo studies that evaluated antimalarial activity suggested that CD-PEG-ARM-NLC exhibited higher antimalarial activity in comparison to ARM-NLC and PEG-ARM-NLC. CONCLUSION: These findings suggested that choline and PEG dually modified NLC could be promising preparations for the production of hydrophobic antimalarial drugs, particularly for ARM.

2.
J Craniofac Surg ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33587520

RESUMO

BACKGROUND: Z-epicanthoplasty is a popular method of correcting mild to moderate epicanthal folds. However, it has some limitations, such as, under correction, recurrence, and leaving of a visible scar. This study aimed to modify the traditional Z-epicanthoplasty to optimize its application in correcting severe cases of epicanthal fold. METHODS: A total of 117 Asian female patients received the modified Z-epicanthoplasty between January 2018 and April 2018. The type and severity of epicanthal fold were evaluated preoperatively, whereas the intercanthal distance, interpupillary distance, and scar visibility and cosmetic results were evaluated preoperatively and one-year postsurgery. RESULTS: A total of 142 eyes had epicanthus tarsalis, whereas 92 eyes had epicanthus palpebralis. Of these, 29 were mild, 95 were moderate, and 119 were severe. After the operation, the intercanthal distance ratio was decreased from 0.615 (range, 0.548-0.685) preoperatively to 0.564 (range, 0.500-0.632). The mean reduction was 5.1% (range, 1.2%-10.1%; P < 0.001, Wilcoxon signed-rank test). Also, 195 eyes (83.3%) had no apparent scar and 36 (15.4%) had visible scar only under close inspection. Three eyes (1.32%) had visible scar without the need for revision. No reoccurrence was observed. And the cosmetic outcomes were scored as either excellent or good. CONCLUSIONS: The modified Z-epicanthoplasty which released the medial canthus activity sufficiently and corrected epicanthal fold at its maximum displacement is an effective method for the treatment of all degrees of epicanthus tarsalis and epicanthus palpebralis in Asian females.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33405153

RESUMO

Mount of embodied carbon emissions flow along industrial chains and form a complex network. In order to reveal the structure and evolution characteristics of embodied carbon emission flow network among China's industrial sectors, this study applies a complex network theory to construct six embodied carbon emission flow networks with 30 sectors on the basis of China's input-output tables from 2002 to 2015. Through the analysis of complex network technology indicators, the overall structural characteristics of the network, the key sectors, and the key flow paths are analyzed. Main results show that six embodied carbon emission flow networks all have the small-world characteristics; there is an industrial cluster phenomenon in the network. During the study period, construction, manufacturing, and service-related industry community are the absorption sites for embodied carbon emissions. Coal- and petroleum-related industry communities are the divergent sites for embodied carbon emissions; moreover, electric and heat power and fuel processing are the important "suppliers" of embodied carbon emissions; construction and other service are the important "consumers" of embodied carbon emissions. Non-metallic products are the important "transmitters" of embodied carbon emissions. Metal smelting and chemical industry are at the core of the network because of their high weighted degree and betweenness centrality. The central effect of key sectors continues to increase over time; furthermore, the distribution of embodied carbon emission flows in the six networks all have long-tail characteristics, and this characteristic became more prominent over time. There are key edge-weights in the networks. About 11 to 15% of the edges carry 80% of the embodied carbon emissions. Further based on edge-weight analysis, this study identifies the key paths of embodied carbon emission flow in the six networks, and most key paths pass through construction. Thus, such key sectors and key flow paths should receive more attention when making carbon emission reduction policies.

6.
Food Chem ; 347: 128980, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33465693

RESUMO

In order to achieve accurate detection and evaluation of the freshness of fish samples, high sensitivity and selectivity of histamine sensors based on solution-gated graphene transistors (SGGT) have been successfully developed. By using graphene (Gra), multi-walled carbon nanotubes (MWNT) and gold nanoparticles (AuNP) to functionalize the gate electrode, the electrocatalytic performance of the device can be significantly improved. We have found that graphene, MWNT and AuNP modified SGGT sensors exhibit an ultra-low detection limit of 100 nM for histamine, a linear range of 3 µM-100 µM. We have also demonstrated that the SGGT-based histamine sensor has a high recovery rate and is capable of assessing the histamine content of actual fish samples in a fast and accurate manner. Considering the superior performance of the SGGT-based histamine sensor, it can be readily extended to histamine determination in many other real food samples for their freshness assessment.

7.
Environ Sci Technol ; 55(4): 2597-2607, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33502168

RESUMO

Defect engineering in an electrocatalyst, such as doping, has the potential to significantly enhance its catalytic activity and stability. Herein, we report the use of a defect engineering strategy to enhance the electrochemical reactivity of Ti4O7 through Ce3+ doping (1-3 at. %), resulting in the significantly accelerated interfacial charge transfer and yielding a 37-129% increase in the anodic production of the hydroxyl radical (OH•). The Ce3+-doped Ti4O7 electrodes, [(Ti1-xCex)4O7], also exhibited a more stable electrocatalytic activity than the pristine Ti4O7 electrode so as to facilitate the long-term operation. Furthermore, (Ti1-xCex)4O7 electrodes were also shown to effectively mineralize perfluorooctanesulfonate (PFOS) in electrooxidation processes in both a trace-concentration river water sample and a simulated preconcentration waste stream sample. A 3 at. % dopant amount of Ce3+ resulted in a PFOS oxidation rate 2.4× greater than that of the pristine Ti4O7 electrode. X-ray photoelectron spectroscopy results suggest that Ce3+ doping created surficial oxygen vacancies that may be responsible for the enhanced electrochemical reactivity and stability of the (Ti1-xCex)4O7 electrodes. Results of this study provide insights into the defect engineering strategy for boosting the electrochemical performance of the Ti4O7 electrode with a robust reactivity and stability.

8.
Neurobiol Dis ; 151: 105257, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33434616

RESUMO

TGFß-activated kinase 1 (TAK1) is a master regulator that drives multiple cell death and proinflammatory signaling pathways, making it a promising therapeutic target to treat ischemic stroke. However, whether targeting TAK1 could improve stroke outcomes has never been tested in female subjects, hindering its potential translation into clinical use. Here we examined the therapeutic effect of 5Z-7-Oxozeaenol (OZ), a selective TAK1 inhibitor, in ovariectomized female mice after middle cerebral artery occlusion (MCAO). OZ significantly reduced neuronal cell death and axonal injury at the acute stage and mitigated neuroinflammation at the subacute stage after MCAO in ovariectomized female mice. Consistent with RNA sequencing analysis that TAK1 activation contributed to microglia/macrophage-mediated inflammatory responses in the post-stroke brain, inhibition of TAK1 with OZ caused phenotypic shift of microglia/macrophages toward an inflammation-resolving state. Furthermore, microglia/macrophage-specific TAK1 knockout (TAK1 mKO) reproduced OZ's effects, causally confirming the role of TAK1 in determining proinflammatory microglial/macrophage responses in post-stroke females. Post-stroke treatment with OZ for 5 days effectively promoted long-term neurological recovery and the integrity of both gray matter and white matter in female mice. Together, the TAK1 inhibitor OZ elicits long-lasting improvement of stroke outcomes in female mice, at least partially through enhancing beneficial microglial/macrophage responses and inflammation resolution. Given its therapeutic efficacy on both male and female rodents, TAK1 inhibitor is worth further investigation as a valid treatment to ischemic stroke.

9.
Sci Total Environ ; 767: 144485, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33429275

RESUMO

PM2.5 is recognized as an atmospheric pollutant that seriously jeopardizes human health. Emerging evidence indicates that PM2.5 exposure is associated with metabolic disorders. Existing epidemiology and toxicology studies on the health effects of PM2.5 usually focused on its different components and doses, the effects on susceptible populations, or the effects of indoor and outdoor pollution. The underlying mechanisms of exposure time are poorly understood. Liver, as the central organ involved in various metabolisms, has special signaling pathways non-existed in lung and cardiovascular systems. Exacerbation in liver by the prolonged exposure of PM2.5 leads to hepatic function disorder. It is therefore essential to elucidate the mechanism underlying hepatotoxicity after PM2.5 exposure from the perspective of time-response relationship. In this study, targeted metabolomics was utilized to explore the hepatic injury in mice after PM2.5 exposure. Our results showed that prolonged exposure of PM2.5 would aggravate liver metabolic disorders. The metabolic process was divided into three phases. In phase I, it was found that PM2.5 exposure disturbed the hepatic urea synthesis. In phase II, oxidative damages and inflammations obviously occurred in liver, which would further cause neurobehavioral disorders and fat deposits. In phase III, the changes of metabolites and metabolic pathways indicated that the liver has been severely damaged, with the accelerated biosynthesis and fat metabolism. Finally, using ROC analysis coupled with their biological functions, 4 potential biomarkers were screened out, with which we established a method to classify and diagnose the progress of liver damage in mice after PM2.5 exposure. In this paper, we not only established the time-response relationship of PM2.5, but also provided new insights for the classification and prediction of the toxic injury stages in mice liver, which provides a ground work for the future drug intervention to prevent oxidative damage of PM2.5.

10.
J Agric Food Chem ; 69(4): 1398-1404, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33433214

RESUMO

As one of the most toxic forms of arsenic, inorganic As(III) is easy to accumulate in rice, leading to severe public health problems. Effective control of As(III) requires the development of fast analytical methods for its detection with high sensitivity and specificity. Toward this end, in this work, we report the fabrication of an As(III) electrochemical sensor based on a solution-gated graphene transistor (SGGT) platform with a novel sensing mechanism. The gold gate electrode of the SGGT was modified with DNA probes and then blocked with bovine serum albumin (BSA). The specific interaction between As(III) and gold disrupted the adsorption states of DNA probes, redistributing surface charges on the gate electrode, further leading to potential drop changes at the interfaces of the gate electrode and graphene active layer. This new mechanism based on DNA-charge-redistribution-induced SGGT current responses (denoted as "DNA-SGGT") was found to greatly improve the selectivity of the sensor: the response of DNA-SGGT to As(III) was effectively enhanced fourfold, while to other interfering cations, it was significantly reduced. The optimized sensor showed a detection limit as low as 5 nM with superior selectivity to As(III). The as-prepared DNA-SGGT-based sensor has also been successfully applied to the detection of As(III) in practical rice samples with a high recovery rate, showing great potential for heavy metal detection in many types of food samples.

11.
Res Social Adm Pharm ; 17(1): 1853-1858, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33317764

RESUMO

BACKGROUND: The practical experiences of active pharmacists involved in managing critically ill patients with coronavirus disease 2019 (COVID-19) have been rarely reported. OBJECTIVE: This work aimed to share professional experiences on medication optimization and provide a feasible reference for the pharmaceutical care of critically ill patients with COVID-19. METHODS: This study was conducted in a COVID-19-designated hospital in China. A group of dedicated clinical pharmacists participated in multidisciplinary rounds to optimize the treatments for critically ill patients with COVID-19. Consensus on medication recommendations was reached by a multidisciplinary team through bi-daily discussion. Related drug, classification, cause, and adjustment content for recommendations were recorded and reviewed. RESULTS: A total of 111 medication recommendations were supplied for 22 out of 33 (56.7%) critically ill patients from 1 February 2020 to 18 March 2020, and 106 (95.5%) of these were accepted. Among these recommendations, 64 (67.7%), 32 (28.8%), and 15 (13.5%) were related to antibiotics and antifungals, antiviral agents, and other drugs, respectively. Recommendation types significantly differed for different anti-infectives (p < 0.05). For antibiotics and antifungals, treatment effectiveness accounted for 60.9% of recommendation types, with 15 (38.5%) cases related to untreated infections. For antiviral agents, adverse drug events were the most common recommendation types (84.4%), with 20 (74.1%) cases related to liver function dysfunction. Discontinuation of suspected antiviral agents (66.7%) was usually recommended after the occurrence of adverse events that may progress and bring poor outcomes. CONCLUSION: Forceful and extensive on-ward participation is recommended for clinical pharmacists in managing critically ill patients. Our experiences highlight the need for special attention toward untreated infections and adverse events related to antiviral agents.


Assuntos
/terapia , Unidades de Terapia Intensiva , Farmacêuticos/organização & administração , Serviço de Farmácia Hospitalar/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Antivirais/efeitos adversos , China , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/organização & administração , Papel Profissional , Estudos Retrospectivos
12.
Physiother Res Int ; : e1887, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33305872

RESUMO

OBJECTIVE: The aim of the present study was to develop a cross-cultural adaptation and to evaluate the validity and reliability of a Chinese version of the LiSat-11 test. METHODS: LiSat-11 was translated into Chinese according to standardized procedures. A cross-sectional descriptive study was conducted to examine its reliability and validity, in accordance to COnsensus-based Standards for the election of health Measurements Instruments guidelines, among persons with stroke approximately 3 years after their discharge from rehabilitation. Participants completed the LiSat-11, 36-Item Short-Form Health Survey (SF-36), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI) and Hospital Anxiety and Depression Scale (HADS). To examine the test-retest reliability, thirty of these participants completed LiSat-11 again after 2 weeks. RESULTS: In total, 60 persons with stroke were recruited. The Chinese version of LiSat-11 demonstrated good internal consistency with Cronbach's alphas at 0.82. Ceiling effects were found in five of the eleven items of LiSat-11, and there was a floor effect in one item. LiSat-11 had moderate to high correlations with SF-36 with Spearman's correlation coefficient (rho) ranging from 0.44 to 0.73 (p < 0.01) in a concurrent validity test, and high correlations were also found between LiSat-11 and HADS-A/D in a convergent validity test with rho = -0.63/-0.67 (p < 0.01). Low correlations with NIHSS, BI and mRS were found in a divergent validity test, rho = -0.25, 0.17 and -0.26, respectively. CONCLUSION: The current study verified that the translated Chinese version of the Life Satisfaction Checklist-11 is a reliable and valid tool for measuring the life satisfaction of persons with chronic stroke.

13.
Curr Pharm Des ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334280

RESUMO

BACKGROUND: Type 1 diabetes is a chronic autoimmune disease featured by insulin deprivation caused by pancreatic ß-cell loss, followed by hyperglycaemia. OBJECTIVE: Currently, there is no cure for this disease in clinical treatment, and patients have to accept a lifelong injection of insulin. The exploration of potential diagnosis biomarkers through analysis of mass data by bioinformatic tools and machine learning is important for Type 1 diabetes. METHODS: We collected two mRNA expression datasets of Type 1 diabetes peripheral blood samples from GEO, screened out differentially expressed genes (DEGs) by R software, conducted GO and KEGG pathway enrichment using the DEGs. And the STRING database and Cytoscape were used to build PPI network and predict hub genes. We constructed a Logistic regression model by using the hub genes to assess sample type. RESULTS: Bioinformatic analysis of GEO dataset revealed 92 and 75 DEGs in GSE50098 and GSE9006 datasets, separately, and 10 overlapping DEGs. PPI network of these 10 DEGs showed 7 hub genes, namely EGR1, LTF, CXCL1, TNFAIP6, PGLYRP1, CHI3L1 and CAMP. We built a Logistic regression basing on these hub genes and optimized the model to 3 genes (LTF, CAMP and PGLYRP1) based Logistic model. The values of area under curve (AUC) of training set GSE50098 and testing set GSE9006 were 0.8452 and 0.8083, indicating the efficacy of this model. CONCLUSION: Integrated bioinformatic analysis of gene expression in Type 1 diabetes and the effective Logistic regression model built in our study may provide promising diagnostic methods for Type 1 diabetes.

14.
Huan Jing Ke Xue ; 41(12): 5617-5627, 2020 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-33374079

RESUMO

In recent years, the health risks of cooking oil fumes have been widely concerning. Since formaldehyde is one of the major pollutants emitted from cooking oil fumes, the degradation of formaldehyde should be investigated. Due to the advances and innovations in the degradation of pollutants, biodegradation was evaluated in this research. In this study, we screened out the strain of XF-1, which can degrade formaldehyde from cooking oil fume condensates. The strain of XF-1 was identified as Bacillus amyloliquefaciens sp. by a sequence analysis combing morphology, physiological, and biochemical experiments. The degrading characteristics of the strain were further studied. In the medium with a formaldehyde concentration of 100 mg·L-1, the efficiency of XF-1 for degrading formaldehyde was 95.80% within 34 h. When the initial concentration of formaldehyde was <300 mg·L-1, the XF-1 strain could completely degrade the formaldehyde within 120 h. When the formaldehyde concentration was 800 mg·L-1, the degradation rate of the XF-1 strain reached 73.01% at 96 h. The maximum tolerated concentration of formaldehyde was 1500 mg·L-1. According to a single factor experiment (pH, inoculation amount, formaldehyde concentration, and temperature), the influence of each factor on the degradation of formaldehyde was studied. The optimal growth condition of the strain was 30℃ at pH 6 with an inoculum amount of 10%. The degradation specificity of formaldehyde was studied by comparing it with that of other bacillus species. The results showed that XF-1 strain was specific with regard to the function of degrading formaldehyde and was able to withstand a high oil environment. The maximum tolerable oil concentration of XF-1 was 900 g·L-1. By analyzing the extracellular metabolites, it was determined that the metabolic pathway of formaldehyde degradation was the RuMP assimilation pathway. In this paper, a strain of formaldehyde degrading bacteria that was also resistant to oil was screened out and its metabolic mechanism was studied. The results indicated that the bacteria had broad application prospects in the treatment of formaldehyde emitted from cooking oil fumes.


Assuntos
Bactérias , Poluentes Ambientais , Biodegradação Ambiental , Poluentes Ambientais/toxicidade , Formaldeído , RNA Ribossômico 16S , Temperatura
16.
Oncol Lett ; 20(6): 355, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33154765

RESUMO

Gastric cancer (GC) remains a threat to the health of the global population. The present study investigated the effects and mechanisms of the long non-coding RNA myocardial infarction associated transcript (MIAT) on the proliferation, apoptosis and metastasis of GC (HGC-27 and AGS) cells. The expression levels of MIAT, micoRNA (miR)-331-3p and RAB5B mRNA were analyzed using reverse transcription-quantitative PCR analysis. Cell growth, apoptosis, migration and invasion were measured using 5-ethynyl-2'-deoxyuridine, flow cytometry, wound healing and Transwell assays, respectively. A luciferase assay was used to determine whether miR-331-3p targeted MIAT and RAB5B. The results indicated that MIAT levels were significantly upregulated in GC tissues and cells, correlated with RAB5B levels and inversely associated with miR-331-3p levels. MIAT overexpression promoted proliferation and metastasis, and inhibited the apoptosis of GC cells. MIAT knockdown had the opposite effect on GC cells. The rescue experiments revealed that the effects of MIAT knockdown on the biological behaviour of GC cells were attenuated by RAB5B overexpression. These data suggest that MIAT promotes GC progression via modulating miR-331-3p/RAB5B pathway.

17.
J Food Biochem ; 44(10): e13431, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33090543

RESUMO

The biochemical properties and thermal inactivation of polyphenol oxidase (PPO) from three main planted lily cultivars in China, namely, Lilium lancifolium Thunb, Lilium brownie var. viridulum, and Lilium davidii var. unicolor cotton were evaluated. Data indicate that the PPO from three cultivars showed two optimum pH levels of 4.0 and 6.5-7.0 and temperature of 15°C and exhibited the highest affinity toward 4-methylcatechol. However, this enzyme did not exhibit monophenolase activity. Thiourea and L-cysteine were more effective than other inhibitors. The enzymatic activity of L. lancifolium Thunb PPO crude extract was higher than that of L. brownie var. viridulum and L. davidii var. unicolor cotton. For thermal inactivation, L. davidii var. unicolor cotton PPO showed the best thermal resistance at 65-75°C, and L. lancifolium Thunb showed stability at 45°C. The deactivation of the three types of PPO followed the first-order reaction kinetics, and the activation energy (Ea) was 144.28, 138.00, and 107.12 kJ/mol for L. lancifolium Thunb PPO, L. brownie var. viridulum PPO, and L. davidii var. unicolor cotton PPO, respectively. PRACTICAL APPLICATIONS: Lilium is an ornamental and edible plant typically used for food and traditional Chinese medicine. Its flowers are used for decoration, and its underground bulbs are rich in various bioactive substances. Fresh lily bulbs easily turn brown and lose economic value during storage and processing. Polyphenol oxidase (PPO) is a crucial molecule involved in the enzymatic browning of fruit and vegetables. In this study, PPO was extracted from three main planted lily cultivars in China. Namely, Lilium lancifolium Thunb, Lilium brownie var. viridulum, Lilium davidii var. unicolor cotton and was partially characterized. The results are of considerable importance to further understand the PPO of lily bulbs and provide guidance for the inactivation of enzymes and the processing of lily bulb juice.

19.
Front Pharmacol ; 11: 1252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973503

RESUMO

Objective: High variabilities in tacrolimus (TAC) exposure are still problems that confuse physicians. TAC trough levels (TAC Cmin) fluctuated considerably after endoscopic retrograde cholangiopancreatography (ERCP) treatment in several liver transplant (LT) patients. We aimed to investigate the variation regularity of TAC Cmin post-ERCP and related factors. Methods: This study was a retrospective, observational study conducted at the First Affiliated Hospital of Zhejiang University in China. From October 2017 to January 2019, 26 LT patients that received ERCP were included (73 TAC Cmin measures). The absolute difference and the variation extent in TAC Cmin pre- and post-ERCP were analyzed. Patients were divided into mild and obvious variation groups, and the differences were compared. Results: The TAC Cmin in LT patients significantly increased in the first three days post-ERCP (p<0.05) and increased by more than 20% in 18 out of 26 (69.2%) patients. The mean extent of variation in TAC Cmin was 45.1% (95% confidence interval [CI]: 28.3-81.3%) and 31.4% (95% CI: 9.7-53.1%) on days 1 and 3 post-ERCP, respectively. The increasing TAC Cmin gradually returned to baseline within a week (p>0.05). The daily TAC dose and total bile acid (TBA) level were significantly higher (p<0.05) in patients with obvious variation in TAC Cmin. The differences in other demographics, clinical characteristics, variation in laboratory data, and serum amylase levels between the two groups were not significant. Conclusion: The TAC Cmin significantly increased in LT patients during the first three days after ERCP, and the level returned to baseline within a week. The daily TAC dose and TBA levels may be related to this increase. Frequent drug concentration monitoring should be executed in the early phase post-ERCP, especially in patients with related factors.

20.
J Pharm Sci ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32976901

RESUMO

Artemisinin (ART) drugs showed declining plasma concentrations after repeated oral dosing, known as time-dependent pharmacokinetics (PK). ART and dihydroartemisinin (DHA) were adopted as representatives to evaluate the roles of first-pass effects and systemic metabolism in time-dependent PK by comparison of oral versus intravenous administration and 1 dose versus 5 consecutive doses PK in rats and dogs, respectively. The hepatic extraction ratio (ERh) and the intestinal elimination changes were further investigated in rats to distinguish the roles of hepatic first-pass effect or intestinal first-pass effect. The induction capacities of ARTs to cytochrome P450 (CYP450) in rats and human cells were evaluated as well. For ART, only the oral groups showed time-dependent PK. A fairly high ERh that obtained for ART was not sensitive to multiple oral doses. An increased elimination and CYP450 expression have also been found in the intestine. For DHA, though a significant CYP450 induction was observed, neither time-dependent PK nor changes in the first-pass effects was found. In conclusion, time-dependent PK of ART was mainly caused by the increased intestinal first-pass effect rather than hepatic first-pass effect or systemic metabolism. DHA was not involved in auto-induction elimination, thus showing no time-dependent PK.

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