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1.
BMC Infect Dis ; 20(1): 166, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087700

RESUMO

BACKGROUND: In this study, we evaluated the genetic relatedness of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KPN) isolates from an outbreak in a neonatal intensive care unit (NICU) in August 2017, We implemented an active countermeasure to control this outbreak successfully. METHODS: The incidence of healthcare-associated ESBL-KPN bacteremia was evaluated before and after initiating enhanced infection control (IC) practices in January 2018. Surveillance cultures were set up and monitored for neonates, medical personnel, and NICU environments. Molecular analyses, including pulse-field gel electrophoresis (PFGE), sequence typing, and ESBL genotyping, were performed for the isolated KPN strains. RESULTS: After implementing the enhanced IC procedures, the healthcare-associated bacteremia rate decreased from 6.0 to 0.0 per 1000 patient-days. Samples from neonates (n = 11/15, 73.3%), medical personnel (n = 1/41, 2.4%), and medical devices and the environments (6/181, 3.3%) tested positive for ESBL-KPN in the surveillance cultures in December 2017. Active surveillance cultures revealed that 23 of 72 neonates who were screened (31.9%) were colonized with ESBL-KPN between January and March 2018. All the isolates demonstrated closely related PFGE patterns and were identified as ST307 strain carrying the CTX-M-15 gene. CONCLUSIONS: Contaminated NICU environments and medical devices, as well as transmission by medical personnel, appeared to be the source of the outbreak of ESBL-KPN infection. We employed an enhanced IC strategy during January-March 2018 and successfully controlled the clonal outbreak of CTX-M-15-positive KPN. ST307 has emerged as an important bacteremia-causing pathogen in the NICU and should be carefully monitored.

2.
Int J Infect Dis ; 90: 197-200, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605810

RESUMO

BACKGROUND: Hand hygiene (HH) is crucial to prevent healthcare-associated infections and the spread of multidrug-resistant organisms. The monitoring of HH compliance may be affected by observer expertise. A sufficient duration of HH is necessary to remove microorganisms. The aim of this study was to measure compliance with both the World Health Organization (WHO) checklist and optimal HH as reported by unit-based observers and infection control nurses (ICN). METHODS: Optimal HH was defined as adhering to the exact duration and following a six-step procedure. The disparity in compliance with the WHO checklist and optimal HH was analyzed among each profession, unit, and indication, covering a period of 3 years. RESULTS: There was a statistically significant difference in WHO checklist compliance (94.4% vs. 87.0%, p<0.01) and optimal HH rate (86.3% vs. 42.4%, p<0.01) between unit-based observers and ICN. The optimal HH rate was especially lower for doctors (30.1%), in the intensive care units (39.4%), and before clean and aseptic procedures (37.0%) as observed by ICN. CONCLUSIONS: Although the overall WHO checklist HH rate was reported to be higher than 90%, optimal HH was only half this rate. More education and awareness of the significance of HH, as well as adherence to the optimal HH procedures, are needed to prevent hospital-acquired infections.

3.
Xenobiotica ; 50(4): 380-388, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31233374

RESUMO

1. Glycyrol is a coumestan derivative that is isolated from roots of Glycyrrhiza uralensis. Glycyrol exhibits several biological effects, including anti-oxidative and anti-inflammatory effects.2. Herein, we characterized glycyrol metabolism by cytochrome P450 enzymes (CYPs) and UDP-glucuronosyltransferases (UGTs) using human liver microsomes (HLM), human liver cytosol, human intestinal microsomes, or human recombinant cDNA-expressed CYPs and UGTs. The analysis was conducted using high resolution mass spectroscopy (HR-MS) on a Q ExactiveTM HF Hybride Quadrupole-Orbitrap mass spectrometer.3. NADPH-supplemented HLM generated six glycyrol metabolites (M1-M6) via hydroxylation, oxidation, and hydration; both NADPH- and UDPGA-supplemented liver microsomes generated three glucuronides (M7-M9). Reaction phenotyping revealed that CYP1A2 is the primary enzyme responsible for phase I metabolism, with minor involvement of the CYP3A4/5, CYP2D6, and CYP2E1 enzymes. Glucuronidation of glycyrol was primarily mediated by UGT1A1, UGT1A3, UGT1A9, and UGT2B7.4. In conclusion, glycyrol undergoes the efficient metabolic hydroxylation and glucuronidation reactions in human liver microsomes, which are predominantly catalyzed by CYP1A2, UGT1A1/3/9, and UGT2B7.

4.
Nature ; 574(7779): 575-580, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31645732

RESUMO

The Warburg effect, which originally described increased production of lactate in cancer, is associated with diverse cellular processes such as angiogenesis, hypoxia, polarization of macrophages and activation of T cells. This phenomenon is intimately linked to several diseases including neoplasia, sepsis and autoimmune diseases1,2. Lactate, which is converted from pyruvate in tumour cells, is widely known as an energy source and metabolic by-product. However, its non-metabolic functions in physiology and disease remain unknown. Here we show that lactate-derived lactylation of histone lysine residues serves as an epigenetic modification that directly stimulates gene transcription from chromatin. We identify 28 lactylation sites on core histones in human and mouse cells. Hypoxia and bacterial challenges induce the production of lactate by glycolysis, and this acts as a precursor that stimulates histone lactylation. Using M1 macrophages that have been exposed to bacteria as a model system, we show that histone lactylation has different temporal dynamics from acetylation. In the late phase of M1 macrophage polarization, increased histone lactylation induces homeostatic genes that are involved in wound healing, including Arg1. Collectively, our results suggest that an endogenous 'lactate clock' in bacterially challenged M1 macrophages turns on gene expression to promote homeostasis. Histone lactylation thus represents an opportunity to improve our understanding of the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer.


Assuntos
Epigênese Genética , Glicólise/genética , Histonas/química , Histonas/metabolismo , Ácido Láctico/metabolismo , Acetilação , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , Homeostase , Humanos , Hipóxia/metabolismo , Lisina/química , Lisina/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Transcrição Genética
5.
Molecules ; 24(16)2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430908

RESUMO

APINACA (known as AKB48, N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide), an indazole carboxamide synthetic cannabinoid, has been used worldwide as a new psychoactive substance. Drug abusers take various drugs concomitantly, and therefore, it is necessary to characterize the potential of APINACA-induced drug-drug interactions due to the modulation of drug-metabolizing enzymes and transporters. In this study, the inhibitory effects of APINACA on eight major human cytochrome P450s (CYPs) and six uridine 5'-diphospho-glucuronosyltransferases (UGTs) in human liver microsomes, as well as on the transport activities of six solute carrier transporters and two efflux transporters in transporter-overexpressed cells, were investigated. APINACA exhibited time-dependent inhibition of CYP3A4-mediated midazolam 1'-hydroxylation (Ki, 4.5 µM; kinact, 0.04686 min-1) and noncompetitive inhibition of UGT1A9-mediated mycophenolic acid glucuronidation (Ki, 5.9 µM). APINACA did not significantly inhibit the CYPs 1A2, 2A6, 2B6, 2C8/9/19, or 2D6 or the UGTs 1A1, 1A3, 1A4, 1A6, or 2B7 at concentrations up to 100 µM. APINACA did not significantly inhibit the transport activities of organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic cation transporter (OCT)1, OCT2, P-glycoprotein, or breast cancer resistance protein at concentrations up to 250 µM. These data suggest that APINACA can cause drug interactions in the clinic via the inhibition of CYP3A4 or UGT1A9 activities.


Assuntos
Transporte Biológico/efeitos dos fármacos , Canabinoides/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Glucuronosiltransferase/antagonistas & inibidores , Linhagem Celular , Interações de Medicamentos , Células HEK293 , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Transportadores de Ânions Orgânicos/metabolismo
6.
Pharmaceutics ; 11(7)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336576

RESUMO

Catalposide, an active component of Veronica species such as Catalpa ovata and Pseudolysimachion lingifolium, exhibits anti-inflammatory, antinociceptic, anti-oxidant, hepatoprotective, and cytostatic activities. We characterized the in vitro metabolic pathways of catalposide to predict its pharmacokinetics. Catalposide was metabolized to catalposide sulfate (M1), 4-hydroxybenzoic acid (M2), 4-hydroxybenzoic acid glucuronide (M3), and catalposide glucuronide (M4) by human hepatocytes, liver S9 fractions, and intestinal microsomes. M1 formation from catalposide was catalyzed by sulfotransferases (SULTs) 1C4, SULT1A1*1, SULT1A1*2, and SULT1E1. Catalposide glucuronidation to M4 was catalyzed by gastrointestine-specific UDP-glucuronosyltransferases (UGTs) 1A8 and UGT1A10; M4 was not detected after incubation of catalposide with human liver preparations. Hydrolysis of catalposide to M2 was catalyzed by carboxylesterases (CESs) 1 and 2, and M2 was further metabolized to M3 by UGT1A6 and UGT1A9 enzymes. Catalposide was also metabolized in extrahepatic tissues; genetic polymorphisms of the carboxylesterase (CES), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes responsible for catalposide metabolism may cause inter-individual variability in terms of catalposide pharmacokinetics.

7.
Ann Lab Med ; 39(6): 537-544, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31240881

RESUMO

BACKGROUND: Several factors contribute to differences in Streptococcus pneumoniae serotype distribution. We investigated the serotype distribution and antimicrobial resistance of S. pneumoniae isolated between 2014 and 2016 in Korea. METHODS: We collected a total of 1,855 S. pneumoniae isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR. We investigated the distribution of each serotype by patient age, source of the clinical specimen, and antimicrobial resistance pattern. RESULTS: The most common serotypes were 11A (10.1%), followed by 19A (8.8%), 3 (8.5%), 34 (8.1%), 23A (7.3%), and 35B (6.2%). The major invasive serotypes were 3 (12.6%), 19A (7.8%), 34 (7.8%), 10A (6.8%), and 11A (6.8%). Serotypes 10A, 15B, 19A, and 12F were more common in patients ≤5 years old, while serotype 3 was more common in patients ≥65 years old compared with the other age groups. The coverage rates of pneumococcal conjugate vaccine (PCV)7, PCV10, PCV13, and pneumococcal polysaccharide vaccine 23 were 11.8%, 12.12%, 33.3%, and 53.6%, respectively. Of the 1,855 isolates, 857 (46.2%) were multi-drug resistant (MDR), with serotypes 11A and 19A predominant among the MDR strains. The resistance rates against penicillin, cefotaxime, and levofloxacin were 22.8%, 12.5%, and 9.4%, respectively. CONCLUSIONS: There were significant changes in the major S. pneumoniae serotypes in the community. Non-PCV13 serotypes increased in patients ≤5 years old following the introduction of national immunization programs with the 10- and 13-polyvalent vaccines.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Streptococcus pneumoniae/genética , Adolescente , Adulto , Idoso , Criança , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , República da Coreia , Sorogrupo , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Adulto Jovem
9.
Cancer Genomics Proteomics ; 16(4): 273-286, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31243108

RESUMO

BACKGROUND/AIM: Prostate cancer (PCa) is the most frequent cancer found in males worldwide. The aim of this study was to identify new biomarkers using mutated peptides for the prognosis and prediction of advanced PCa, based on proteogenomics. MATERIALS AND METHODS: The tryptic peptides were analyzed by tandem mass tag-based quantitative proteomics. Proteogenomics were used to identify mutant peptides as novel biomarkers in advanced PCa. RESULTS: Using a human database, increased levels of INTS7 and decreased levels of SH3BGRL were found to be associated with the aggressiveness of PCa. Using proteogenomics and a cancer mutation database, 70 mutant peptides were identified in PCa cell lines. Using parallel reaction monitoring, the expression of seven mutant peptides was found to be altered in tumors, amongst which CAPN2 D22E was the most significantly up-regulated mutant peptide in PCa tissues. CONCLUSION: Altered mutant peptides present in PCa tissue could be used as new biomarkers in advanced PCa.


Assuntos
Neoplasias da Próstata/genética , Proteogenômica/métodos , Espectrometria de Massas em Tandem/métodos , Humanos , Masculino , Metástase Neoplásica , Neoplasias da Próstata/patologia , Proteoma/metabolismo
10.
J Med Microbiol ; 68(7): 1053-1058, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31169483

RESUMO

BACKGROUND: Streptococcus pyogenes is the most common cause of bacterial pharyngitis. Genotyping of emm is useful for molecular epidemiological survey of S. pyogenes. Antibiotic resistance data are needed for empirical treatments. METHODS: In total, 358 children in Changwon, Korea who had pharyngitis symptoms were subjected to throat cultures to isolate S. pyogenes in 2017. emm genotyping was performed by direct sequencing. An antibiotic susceptibility test was performed using the disk diffusion method for erythromycin (ERY), clindamycin (CLI), tetracycline (TET) and ofloxacin (OFX). Screening for macrolide resistance phenotype and its determinants was performed for the ERY-resistant strains. RESULTS: A total of 190 strains (53.1 %) of S. pyogenes were isolated from 358 children. The most frequent emm genotype was emm4 (53.2 %), followed by emm89 (12.6 %), emm28 (11.6 %) and emm1 (10 %). Antibiotic resistance rates to ERY, CLI, TET and OFX were 3.2 %, 2.6 %, 1.1 % and 2.6%, respectively. There were five isolates of the cMLSB phenotype having the ermB gene and one M phenotype harbouring the mefA gene. CONCLUSIONS: The distribution of emm genotypes was quite different from those previously reported in Korea. emm4 accounted for more than 50  % of the genotypes. Macrolide resistance rates remained very low, but five of six ERY-resistant strains displayed the cMLSB phenotype.


Assuntos
Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Transporte/genética , Farmacorresistência Bacteriana/genética , Faringite/epidemiologia , Faringite/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/genética , Adolescente , Antibacterianos/farmacologia , Criança , Pré-Escolar , Genótipo , Humanos , República da Coreia/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/efeitos dos fármacos
11.
Molecules ; 24(4)2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30823561

RESUMO

25B-NBF, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-fluorobenzyl)ethanamine, is a new psychoactive substance classified as a phenethylamine. It is a potent agonist of the 5-hydroxytryptamine receptor, but little is known about its metabolism and elimination properties since it was discovered. To aid 25B-NBF abuse screening, the metabolic characteristics of 25B-NBF were investigated in human hepatocytes and human cDNA-expressed cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes using liquid chromatography⁻high resolution mass spectrometry. At a hepatic extraction ratio of 0.80, 25B-NBF was extensively metabolized into 33 metabolites via hydroxylation, O-demethylation, bis-O-demethylation, N-debenzylation, glucuronidation, sulfation, and acetylation after incubation with pooled human hepatocytes. The metabolism of 25B-NBF was catalyzed by CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, and UGT2B7 enzymes. Based on these results, it is necessary to develop a bioanalytical method for the determination of not only 25B-NBF but also its metabolites in biological samples for the screening of 25B-NBF abuse.


Assuntos
Compostos de Benzil/química , Compostos de Benzil/metabolismo , Etilaminas/química , Etilaminas/metabolismo , Hepatócitos/metabolismo , Fenetilaminas/metabolismo , Antagonistas da Serotonina/metabolismo , Biocatálise , Cromatografia Líquida , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Humanos , Estrutura Molecular , Receptores de Serotonina/metabolismo , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem
12.
Artigo em Inglês | MEDLINE | ID: mdl-30718251

RESUMO

The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization has raised concerns about the emergence of resistance to these agents. However, the clinical significance of MRSA positive for the qacA and qacB chlorhexidine tolerance genes has not been established. We investigated the clinical features and predictive factors of MRSA bloodstream infection (BSI) isolates, caused by qacA- and qacB-positive MRSA, from 2010 to 2016 at a tertiary hospital in South Korea. A total of 246 MRSA BSI isolates were included; 71 (28.9%) isolates carried qacA/B The annual frequency of qacA- and qacB-positive MRSA bacteremia did not change significantly over the study period. Patients infected with qacA- and qacB-positive MRSA had common risk factors for health care-associated infections, including prior antibiotic use, central venous catheterization in situ, intensive care unit-acquired bacteremia, and nosocomial infection. The qacA- and qacB-positive isolates were also associated with an increasing chlorhexidine MIC and resistance to non-ß-lactam antibiotics. The qacA- and qacB-positive isolates were more likely to belong to sequence type 5 (ST5), which is a common health care-associated MRSA strain in South Korea. In multivariable analyses, qacA- and qacB-positive MRSA isolates were found to be associated with agr dysfunction (adjusted odds ratio [aOR], 6.45; 95% confidence interval [CI], 2.59 to 16.10), ST5 MRSA strain (aOR, 4.96; 95% CI, 1.85 to 13.26), nosocomial infection (aOR, 4.88; 95% CI, 2.20 to 10.83), and antibiotic use within the previous 3 months (aOR, 2.59; 95% CI, 1.20 to 5.59). These findings suggest that the microbiological features of qacA and qacB carriage provide a selective advantage for specific MRSA strains in hospital environments.

13.
Proteomics ; 19(7): e1800284, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30724459

RESUMO

Diverse metabolic pathways, such as the tricarboxylic acid cycle, pyruvate metabolism, and oxidative phosphorylation, regulate the differentiation of induced pluripotent stem cells (iPSCs) to cells of specific lineages and organs. Here, the protein dynamics during cardiac differentiation of human iPSCs into cardiomyocytes (CMs) are characterized. The differentiation is induced by N-(6-methyl-2-benzothiazolyl)-2-[(3,4,6,7-tetrahydro-4-oxo-3-phenylthieno[3,2-d]pyrimidin-2-yl)thio]-acetamide, a Wnt signaling inhibitor, and confirmed by the mRNA and protein expression of cTnT and MLC2A in CMs. For comparative proteomics, cells from three stages, namely, hiPSCs, cardiac progenitor cells, and CMs, are prepared using the three-plex tandem mass tag labeling approach. In total, 3970 proteins in triplicate analysis are identified. As the result, the upregulation of proteins associated with branched chain amino acid degradation and ketogenesis by the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis are observed. The levels of 3-hydroxymethyl-3-methylglutaryl-CoA lyase, 3-hydroxymethyl-3-methylglutaryl-CoA synthase 2, and 3-hydroxybutyrate dehydrogenase 1, involved in ketone body metabolism, are determined using western blotting, and the level of acetoacetate, the final product of ketogenesis, is higher in CMs. Taken together, these observations indicate that proteins required for the production of diverse energy sources are naturally self-expressed during cardiomyogenic differentiation. Furthermore, acetoacetate concentration might act as a regulator of this differentiation.

14.
Ann Lab Med ; 39(3): 278-283, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30623614

RESUMO

BACKGROUND: BacT/Alert Virtuo (BioMérieux, Durham, NC, USA) is a recently developed blood culture system that includes functions of automatic registration, loading, and unloading of the blood culture bottles, as well as measurement of blood volume. We compared the performances between the BacT/Alert Virtuo and 3D (BioMérieux) blood culture systems. METHODS: A total of 952 patients (1,904 sets) visiting an university-affiliated hospital in Korea for blood cultures were enrolled. Five milliliters of blood was added into each of the two aerobic (FA Plus) and two anaerobic (FN Plus) bottles of the Virtuo and 3D systems for a single set. Positive rate and time to detection (TTD) were compared between the two systems. RESULTS: The positive rates were 8.3% and 8.4% in FA Plus bottles and 7.8% and 8.3% in FN Plus bottles, in the Virtuo and 3D systems, respectively (P>0.05). Median TTDs were shorter in the Virtuo than in the 3D system for all isolates (11.5 hours [N=305] vs 11.8 hours [N=318], P<0.001), Staphylococcus aureus (N=38; 14.3 hours vs 16.0 hours, P=0.021), and Escherichia coli (N=117; 10.4 hours vs 11.0 hours, P<0.001). CONCLUSIONS: The Virtuo has the potential to detect pathogens early in all bottle types. This might improve the prognosis of sepsis by allowing for implementation of expeditious management.


Assuntos
Hemocultura/métodos , Técnicas Bacteriológicas/instrumentação , Técnicas Bacteriológicas/métodos , Hemocultura/instrumentação , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Reprodutibilidade dos Testes , República da Coreia , Sepse/diagnóstico , Sepse/microbiologia
15.
Dig Dis Sci ; 64(1): 144-151, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30054843

RESUMO

BACKGROUND AND STUDY AIM: Although propofol is widely used for sedation for endoscopic procedures, concerns remain regarding cardiopulmonary adverse events. Etomidate has little effect on the cardiovascular and respiratory systems, but patient satisfaction analysis is lacking. We compared the efficacy and safety of balanced propofol and etomidate sedation during advanced endoscopic procedures. METHODS: As a randomized noninferiority trial, balanced endoscopic sedation was achieved using midazolam and fentanyl, and patients were randomly assigned to receive propofol (BPS) or etomidate (BES) as add-on drug. The main outcomes were sedation efficacy measured on a 10-point visual analog scale (VAS) and safety. RESULTS: In total, 186 patients (94 in the BPS group and 92 in the BES group) were evaluated. BES did not show noninferiority in terms of overall patient satisfaction, with a difference in VAS score of -0.35 (97.5 % confidence interval -1.03 to ∞, p = 0.03). Among endoscopists and nurses, BES showed noninferiority to BPS, with differences in VAS scores of 0.06 and 0.08, respectively. Incidence of cardiopulmonary adverse events was lower in the BES group (27.7 versus 14.1 %, p = 0.023). Hypoxia occurred in 5.3 and 1.1 % of patients in the BPS and BES group (p = 0.211). Myoclonus occurred in 12.1 % (11/92) in the BES group. BES had lower risk of overall cardiopulmonary adverse events (odds ratio 0.401, p = 0.018). CONCLUSIONS: BES was not noninferior to BPS in terms of patient satisfaction. However, BES showed better safety outcomes in terms of cardiopulmonary adverse events.


Assuntos
Sedação Consciente/métodos , Estado de Consciência/efeitos dos fármacos , Endoscopia do Sistema Digestório/métodos , Etomidato/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Propofol/administração & dosagem , Idoso , Colangiopancreatografia Retrógrada Endoscópica , Colonoscopia , Sedação Consciente/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Ressecção Endoscópica de Mucosa/efeitos adversos , Endoscopia do Sistema Digestório/efeitos adversos , Etomidato/efeitos adversos , Feminino , Fentanila/administração & dosagem , Gastroscopia , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Satisfação do Paciente , Propofol/efeitos adversos , República da Coreia , Resultado do Tratamento
16.
Ann Lab Med ; 39(1): 31-35, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30215227

RESUMO

BACKGROUND: The SD Bioline Strep A Ultra (SD, Yongin, Korea) is a recently developed rapid antigen detection test (RADT) for diagnosing bacterial pharyngitis caused by Group A Streptococcus, We evaluated the performance of SD Bioline Strep A Ultra, using the number of colony forming units and color intensity. METHODS: Three throat swabs each were taken from 343 children with pharyngitis who visited pediatric clinics. We evaluated the performance of SD Bioline Strep A Ultra and compared its positive rate with the number of colony forming units, using the Fisher exact test. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value (95% confidence interval) were 97.4% (94.0-99.1%), 90.8% (85.0-94.9%), 93.0% (88.5-96.1%), and 96.5% (92.0-98.9%), respectively. Positive rate significantly differed by number of colony forming units (P=0.021). ROC plot for color intensity showed 0.938 of AUC (area under curve). CONCLUSIONS: SD Bioline Strep A Ultra showed excellent performance, and its positive rate differed by the number of colony counts. This RADT could be used as a sensitive and semi-quantitative method detecting bacterial pharyngitis.


Assuntos
Infecções Estreptocócicas/diagnóstico , Streptococcus pyogenes/crescimento & desenvolvimento , Adolescente , Antígenos de Bactérias/análise , Área Sob a Curva , Criança , Pré-Escolar , Cor , Feminino , Humanos , Lactente , Masculino , Faringe/microbiologia , Curva ROC , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/isolamento & purificação , Streptococcus pyogenes/metabolismo
17.
Arch Pharm Res ; 42(4): 380, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30426386

RESUMO

The author would like to change conflict of interest statement of the online published article.

18.
J Bone Metab ; 25(4): 235-241, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30574468

RESUMO

Background: Procollagen type I N-terminal propeptide (PINP) is one of the most clinically useful bone formation biomarkers. Therefore, the purpose of this study was to independently evaluate the performance of automated total PINP assay and established age- and gender-specific reference intervals for PINP in healthy Korean population. Methods: The imprecision, linearity, and detection capability of Elecsys total PINP assay was determined and reference interval was established using 599 serums from Korean population with normal bone mineral densities based on bone densitometry. Age groups were divided into 20s, 30s, 40s, 50s, 60s and over. Results: Elecsys total PINP had excellent performance in imprecision, linearity, and detection capability. When partitioning age groups in Korean male and female populations, there was significant difference in total PINP between different age groups. In male populations, PINP level was decreased with increasing age, then it remained steady after middle-age. In female populations, there was a decreasing tendency similar to that in the male population with a sharp increase in the 50 to 59 age group. Conclusions: Elecsys total PINP assay showed precise and reliable performance in our study. We established age-related PINP reference intervals for Korean male and female population with normal bone mineral densities.

19.
Arch Pharm Res ; 41(4): 450-458, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29550976

RESUMO

Cocktail substrates are useful in investigating drug-drug interactions (DDI) that can rapidly identify the cytochrome P450 (CYP) isoforms that interact with test drugs. In this study, we developed and validated five probe drugs for CYP1A, CYP2B, CYP2C, CYP2D, and CYP3A using LC-MS/MS to determine CYP activities in mice. The five probe substrates were caffeine (2 mg/kg), bupropion (30 mg/kg), omeprazole (4 mg/kg), dextromethorphan (40 mg/kg), and midazolam (2 mg/kg) for CYP1A, CYP2B, CYP2C, CYP2D, and CYP3A, respectively. The cocktail substrates were orally administered to male 5-week-old ICR mice over 0-240 min. The analytical method was validated; it showed high selectivity, linearity, and acceptable accuracy. We confirmed the lack of interaction of this cocktail in the control state (no effect of CYP inducer or inhibitor) and suggested AUCratio (metabolite/substrate) as a unit to evaluate DDI in vivo. In addition, the cocktail assay was applied for the determination of pharmacokinetic parameters against phenobarbital as a selective CYP2B inducer and ketoconazole as a strong CYP3A inhibitor. The concentration of cocktail substrates and the LC-MS/MS method were optimized. In conclusion, we developed a simultaneous and comprehensive analysis system for predicting potential DDI in mice.


Assuntos
Inibidores do Citocromo P-450 CYP3A/metabolismo , Indutores das Enzimas do Citocromo P-450/metabolismo , Interações de Medicamentos/fisiologia , Espectrometria de Massas em Tandem/métodos , Animais , Cafeína/administração & dosagem , Cafeína/análise , Cafeína/metabolismo , Cromatografia Líquida/métodos , Cromatografia Líquida/tendências , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/análise , Indutores das Enzimas do Citocromo P-450/administração & dosagem , Indutores das Enzimas do Citocromo P-450/análise , Dextrometorfano/administração & dosagem , Dextrometorfano/análise , Dextrometorfano/metabolismo , Previsões , Masculino , Camundongos , Camundongos Endogâmicos ICR , Midazolam/administração & dosagem , Midazolam/análise , Midazolam/metabolismo , Espectrometria de Massas em Tandem/tendências
20.
Ann Lab Med ; 38(3): 212-219, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29401555

RESUMO

BACKGROUND: The molecular characterization of Streptococcus dysgalactiae subsp. equisimilis (SDSE) has not yet been performed in Korea. This study aimed to find the differences or similarities in the clinical features, molecular epidemiological findings, and antimicrobial resistance patterns of SDSE from two countries (Korea and Japan). METHODS: SDSE isolates were collected from Korea (N=69) from 2012-2016 and Japan (N=71) from 2014-2016. Clinical characteristics, emm genotypes, and sequence types (STs) were compared. Microdilution tests were performed using different antimicrobials, and their resistance determinants were screened. RESULTS: Median ages were 69 years in Korea and 76 years in Japan. The most common underlying diseases were diabetes and malignancy. Blood-derived isolates comprised 36.2% and 50.7% of Korean and Japanese isolates, respectively; mortality was not different between the two groups (5.8% vs 9.9%, P=0.53). Among Korean isolates with 20 different combined ST-emm types, ST127-stG245 (N=16), ST128-stG485 (N=10), and ST138-stG652 (N=8) were prevalent. Among Japanese isolates with 29 different combined types, ST17-stG6792 (N=11), ST29-stG485 (N=7), and ST205-stG6792 (N=6) were prevalent. Resistance rates to erythromycin, clindamycin, and minocycline were 34.8%, 17.4%, and 30.4% in Korea and 28.2%, 14.1%, and 21.4% in Japan, respectively. CONCLUSIONS: SDSE infections commonly occurred in elderly persons with underlying diseases. There was a significant difference in the distribution of ST-emm types between the two countries. Antimicrobial resistance rates were comparable with different frequencies of resistance determinants in each country.


Assuntos
Antibacterianos/farmacologia , Infecções Estreptocócicas/patologia , Streptococcus/efeitos dos fármacos , Idoso , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana , Eritromicina/farmacologia , Genótipo , Humanos , Japão , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , República da Coreia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/mortalidade , Streptococcus/genética , Streptococcus/isolamento & purificação
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