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  • MDPI AG  (6)
  • Choi, Min Sun  (6)
  • 1
    In: Cancers, MDPI AG, Vol. 13, No. 22 ( 2021-11-21), p. 5842-
    Abstract: The lymph node ratio (LNR) has been investigated as a prognostic factor in many different types of cancers, including differentiated thyroid cancer; however, reports regarding medullary thyroid cancer (MTC) are limited. Therefore, this study aims to evaluate LNR as a risk factor for structural recurrence in patients with MTC. Medical records of patients treated for MTC in a single tertiary center between 1995 and 2017 were retrospectively reviewed. LNR is defined as the number of metastatic lymph nodes or lymph node metastases (LNM) divided by the number of retrieved lymph nodes or lymph node yield (LNY). In the survival analysis, recurrence-free survival was defined as the time from the date of total thyroidectomy to recurrence or last follow-up. To identify risk factors influencing structural recurrence, univariable and multivariable Cox proportional hazard models were used. A total of 132 patients were enrolled. The mean age of study participants was 49.7 years, and 86 patients (65%) were women. Structural recurrence was identified in 39 patients at the end of the study period, and the median follow-up period was 8.7 years. In univariable analyses, gross extra thyroidal extension, N stage, postoperative serum calcitonin and carcinoembryonic antigen (CEA) levels, and LNR were significant (p 〈 0.05) predictors of structural recurrence. In multivariable analysis, postoperative serum calcitonin, postoperative serum CEA, and LNR were identified as a predictor of disease-free survival (p 〈 0.05). LNR can potentially predict structural recurrence as a quantitative evaluation tool for lymph node metastasis in patients with MTC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 2
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  Pharmaceutics Vol. 14, No. 4 ( 2022-03-30), p. 746-
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 4 ( 2022-03-30), p. 746-
    Abstract: The absorption of orally administered aspirin into the blood was affected by gastrointestinal environmental factors such as gut pH, digestive enzymes, and microbiota. The intake of coffee affects the pharmacological effects of aspirin. Therefore, we examined the gut microbiota-mediated effect of coffee bean extract (CBE) intake on the pharmacokinetics of aspirin in mice. The intake of CBE modified the gut microbiota composition and their α- and β-diversities: It decreased the Proteobacteria, Helicobacteriaceae, and Bacteroidaceae populations in the fecal microbiota composition, while the S24-7_f (Muribaculaceae) and Lactobacillaceae populations increased. The fecal aspirin-hydrolyzing activities of humans and mice to salicylic acid were 0.045 ± 0.036 μmole/h/g and 0.032 ± 0.003 μmole/h/g, respectively. However, CBE treatment significantly suppressed the aspirin-hydrolyzing activity in mice. Furthermore, the area under the serum concentration–time curves (AUCs) of aspirin and salicylic acid were 0.265 ± 0.050 µg·h/mL and 16.224 ± 5.578 µg·h/mL in CBE-treated mice, respectively, and 0.248 ± 0.042 µg·h/mL and 10.756 ± 2.071 µg·h/mL in control mice, respectively. Moreover, CBE treatment suppressed the multidrug resistance protein 4 (Mrp4) expression in the intestines of mice, while the P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) expression was not affected. Furthermore, the CBE-treated mouse fecal lysate suppressed Mrp4 expression in Caco-2 cells compared to that of vehicle-treated mice, while CBE treatment did not affect Mrp4 expression. Oral gavage of caffeine also suppressed the Mrp4 expression in the intestines of mice. These findings suggest that intake of coffee can increase the absorption of aspirin by modifying the gut microbiome.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 3
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    Online Resource
    MDPI AG ; 2019
    In:  Metabolites Vol. 9, No. 7 ( 2019-07-05), p. 132-
    In: Metabolites, MDPI AG, Vol. 9, No. 7 ( 2019-07-05), p. 132-
    Abstract: Ginkgo leaf extract (GLE) is a popular herbal medicine and dietary supplement for the treatment of various diseases, including cardiovascular disease. GLE contains a variety of secondary plant metabolites, such as flavonoids and terpenoids, as active components. Some of these phytochemicals have been known to be metabolized by gut microbial enzymes. The aim of this study was to investigate the effects of the gut microbiota on the pharmacokinetics of the main constituents of GLE using antibacterial-treated mice. The bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, isorhamnetin, kaempferol, and quercetin pharmacokinetic profiles of orally administered GLE (600 mg/kg), with or without ciprofloxacin pretreatment (150 mg/kg/day for 3 days), were determined. In the antibacterial-treated mice, the maximum plasma concentration (Cmax) and area under the curve (AUC) of isorhamnetin were significantly (p 〈 0.05) increased when compared with the control group. The Cmax and AUC of kaempferol and quercetin (other flavonol glycosides) were slightly higher than those of the control group, but the difference was not statistically significant, while both parameters for terpenoids of GLE showed no significant difference between the antibacterial-treated and control groups. These results showed that antibacterial consumption may increase the bioavailability of isorhamnetin by suppressing gut microbial metabolic activities.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662251-8
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  • 4
    In: Pharmaceutics, MDPI AG, Vol. 12, No. 2 ( 2020-02-03), p. 127-
    Abstract: HSG4112, a racemic drug, is a new anti-obesity agent. In this study, the stereoselective pharmacokinetics of HSG4112 were investigated in rats and dogs, and the underlying mechanism was investigated. The plasma concentrations of HSG4112(S) and HSG4112(R) were quantitated in plasma from rats and beagle dogs after IV and/or oral administration of racemic HSG4112. The concentration of HSG4112(S) was significantly higher than that of HSG4112(R) in rat plasma. Contrarily, the concentration of HSG4112(R) was significantly higher than HSG4112(S) in dog plasma. A metabolic stability test with liver microsomes showed that HSG4112(S) was more stable than HSG4112(R) in rat liver microsomes, but the difference between stereoisomers did not appear in dog liver microsomes. However, the stereoselectivity was observed in dog liver and intestinal microsomes after uridine 5’-diphospho-glucuronic acid was added. Thus, stereoselective metabolism by uridine 5’-diphospho-glucuronosyltransferases is mainly responsible for the stereoselective pharmacokinetics in dogs. These results suggest that the species difference in the stereoselective plasma pharmacokinetics of HSG4112 is due to the stereoselective metabolism.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 5
    In: Pharmaceutics, MDPI AG, Vol. 11, No. 4 ( 2019-04-03), p. 162-
    Abstract: Acetyl triethyl citrate (ATEC) is a water-soluble plasticizer used in pharmaceutical plasticized polymers. In this study, the pharmacokinetics and metabolism of ATEC were investigated using liquid chromatography–tandem mass spectrometry (LC–MS/MS) in rats. Plasma protein precipitation with methanol was used for sample preparation. For chromatographic separation, a C18 column was used. The mobile phases consisted of 0.1% formic acid and 90% acetonitrile, and gradient elution was used. The following precursor-product ion pairs were selected for reaction monitoring analysis: 319.1 m/z → 157 m/z for ATEC and 361.2 m/z → 185.1 m/z for tributyl citrate (internal standard) in positive ion mode. The LC–MS/MS method was fully validated and successfully applied to a pharmacokinetic study of ATEC in rats. The pharmacokinetic study showed that the volume of distribution and mean residence time of ATEC were higher after oral administration than after intravenous administration, pointing to extensive first-pass metabolism and distribution in tissue. In addition, the plasma concentration profile of the postulated metabolites of ATEC was investigated in plasma, urine, and feces. The resulting data indicated that ATEC was extensively metabolized and excreted mainly as metabolites rather than as the parent form. The developed analytical method and the data on the pharmacokinetics and metabolism of ATEC may be useful for understanding the safety and toxicity of ATEC.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 6
    In: Nutrients, MDPI AG, Vol. 11, No. 8 ( 2019-08-19), p. 1947-
    Abstract: Caffeine is commonly taken via the daily dietary consumption of caffeine-containing foods. The absorbed caffeine is metabolized to yield various metabolites by drug-metabolizing enzymes, and measuring the levels of each caffeine metabolite can provide useful information for evaluating the phenotypes of those enzymes. In this study, the urinary concentrations of caffeine and its 13 metabolites were determined, and the phenotypes of drug metabolic enzymes were investigated based on the caffeine metabolite ratios. Human urine samples were pretreated using solid phase extraction, and caffeine and its metabolites were analyzed using liquid chromatography-tandem mass spectrometry. Based on the urinary caffeine metabolite concentrations, the caffeine metabolite ratios were calculated for six human subjects at specified time points after caffeine intake. Variations in urinary metabolite levels among individuals and time points were reported. In addition, the resultant enzyme activities showed different patterns, depending on the metabolite ratio equations applied. However, some data presented a constant metabolite ratio range, irrespective of time points, even at pre-dose. This suggests the possibility of urinary caffeine metabolite analysis for routine clinical examination. These findings show that urinary caffeine and the metabolite analysis would be useful in evaluating metabolic phenotypes for personalized medicine.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2518386-2
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