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The increasing emergence of multidrug-resistant (MDR) bacteria has been recognized as a public health threat worldwide. Hospitalized patients and outpatients are commonly infected by non-fermenting Gram-negative bacilli (NFGNB), particularly the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB) and Pseudomonas aeruginosa. Antimicrobial agents are critical for treating the nosocomial infections caused by NFGNB. The aim of this study was to assess antimicrobial resistance and the use of antimicrobial agents. The bacterial isolates of 638,152 specimens from both inpatients and outpatients, retrieved from 2001 to 2008 at a medical center in central Taiwan, were examined for their susceptibility to various antimicrobial agents, including cefepime, imipenem, ciprofloxacin, gentamicin, amikacin, meropenem, and levofloxacin. Administrated prescriptions of the monitored antibiotics were analyzed using the Taiwan National Health Insurance Research Database (NHIRD). Our results show that the defined daily doses (DDDs) for cefepime, imipenem, and ciprofloxacin increased with time, and a trend toward reduced antimicrobial sensitivities of both ACB and P. aeruginosa was noticeable. In conclusion, the antimicrobial sensitivities of ACB and P. aeruginosa were reduced with the increased use of antibiotics. Continuous surveillance of antibiotic prescriptions and the prevalence of emerging resistance in nosocomial infections is warranted.
RESUMEN
RATIONALE: Cardiac fibrosis plays a critical role in the pathogenesis of heart failure. Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited, and there is a clear need to identify novel mediators of cardiac fibrosis to facilitate the development of better therapeutics. Exploiting coexpression gene network analysis on RNA sequencing data from failing human heart, we identified TXNDC5 (thioredoxin domain containing 5), a cardiac fibroblast (CF)-enriched endoplasmic reticulum protein, as a potential novel mediator of cardiac fibrosis, and we completed experiments to test this hypothesis directly. OBJECTIVE: The objective of this study was to determine the functional role of TXNDC5 in the pathogenesis of cardiac fibrosis. METHODS AND RESULTS: RNA sequencing and Western blot analyses revealed that TXNDC5 mRNA and protein were highly upregulated in failing human left ventricles and in hypertrophied/failing mouse left ventricle. In addition, cardiac TXNDC5 mRNA expression levels were positively correlated with those of transcripts encoding transforming growth factor ß1 and ECM proteins in vivo. TXNDC5 mRNA and protein were increased in human CF (hCF) under transforming growth factor ß1 stimulation in vitro. Knockdown of TXNDC5 attenuated transforming growth factor ß1-induced hCF activation and ECM protein upregulation independent of SMAD3 (SMAD family member 3), whereas increasing expression of TXNDC5 triggered hCF activation and proliferation and increased ECM protein production. Further experiments showed that TXNDC5, a protein disulfide isomerase, facilitated ECM protein folding and that depletion of TXNDC5 led to ECM protein misfolding and degradation in CF. In addition, TXNDC5 promotes hCF activation and proliferation by enhancing c-Jun N-terminal kinase activity via increased reactive oxygen species, derived from NAD(P)H oxidase 4. Transforming growth factor ß1-induced TXNDC5 upregulation in hCF was dependent on endoplasmic reticulum stress and activating transcription factor 6-mediated transcriptional control. Targeted disruption of Txndc5 in mice (Txndc5-/-) revealed protective effects against isoproterenol-induced cardiac hypertrophy, reduced fibrosis (by ≈70%), and markedly improved left ventricle function; post-isoproterenol left ventricular ejection fraction was 59.1±1.5 versus 40.1±2.5 (P<0.001) in Txndc5-/- versus wild-type mice, respectively. CONCLUSIONS: The endoplasmic reticulum protein TXNDC5 promotes cardiac fibrosis by facilitating ECM protein folding and CF activation via redox-sensitive c-Jun N-terminal kinase signaling. Loss of TXNDC5 protects against ß agonist-induced cardiac fibrosis and contractile dysfunction. Targeting TXNDC5, therefore, could be a powerful new therapeutic approach to mitigate excessive cardiac fibrosis, thereby improving cardiac function and outcomes in patients with heart failure.
Asunto(s)
Cardiomiopatía Hipertrófica/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Insuficiencia Cardíaca/metabolismo , Miocardio/patología , Proteína Disulfuro Isomerasas/fisiología , Pliegue de Proteína , Tiorredoxinas/fisiología , Factor de Transcripción Activador 6/biosíntesis , Factor de Transcripción Activador 6/genética , Animales , Cardiomiopatía Hipertrófica/patología , Células Cultivadas , Fibroblastos/patología , Fibrosis/metabolismo , Regulación de la Expresión Génica , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/patología , Humanos , Isoproterenol/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocardio/metabolismo , NADPH Oxidasa 4/biosíntesis , NADPH Oxidasa 4/genética , Células 3T3 NIH , Oxidación-Reducción , Proteína Disulfuro Isomerasas/antagonistas & inhibidores , Proteína Disulfuro Isomerasas/genética , Interferencia de ARN , ARN Interferente Pequeño/farmacología , Tiorredoxinas/antagonistas & inhibidores , Tiorredoxinas/genéticaRESUMEN
OBJECTIVE: The purpose of this study was to verify the antibacterial performance and cell proliferation activity of zirconium (Zr)-carbon (C)-nitride (N) coatings on commercially pure titanium (Ti) with different C contents. MATERIALS AND METHODS: Reactive nitrogen gas (N(2)) with and without acetylene (C(2)H(2)) was activated by Zr plasma in a cathodic-arc evaporation system to deposit either a zirconium nitride (ZrN) or a Zr-C-N coating onto Ti plates. The bacterial activity of the coatings was evaluated against Staphylococcus aureus with the aid of SYTO9 nucleic acid staining and scanning electron microscopy (SEM). Cell compatibility, mRNA expression, and morphology related to human gingival fibroblasts (HGFs) on the coated samples were also determined by using the MTT assay, reverse transcriptase-polymerase chain reaction, and SEM. RESULTS: The Zr-C-N coating with the highest C content (21.7 at%) exhibited the lowest bacterial preservation (P<0.001). Biological responses including proliferation, gene expression, and attachment of HGF cells to ZrN and Zr-C-N coatings were comparable to those of the uncoated Ti plate. CONCLUSIONS: High-C-content Zr-C-N coatings not only provide short-term antibacterial activity against S. aureus but are also biocompatible with HGF cells.
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Antibacterianos/farmacología , Materiales Biocompatibles Revestidos/farmacología , Compuestos Organometálicos/farmacología , Titanio/química , Circonio/química , Carbono/química , Adhesión Celular/efectos de los fármacos , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Expresión Génica/efectos de los fármacos , Encía/citología , Humanos , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Compuestos de Nitrógeno/química , Staphylococcus aureus/efectos de los fármacos , Propiedades de SuperficieRESUMEN
Fructus gardeniae has long been used by traditional Chinese medical practitioners for its anti-inflammatory, anti-oxidant, anti-tumor and anti-hyperlipidemic characteristics. Here we describe our finding that F. gardeniae greatly reduces anti-enterovirus 71 (EV71) activity, resulting in significant decreases in EV71 virus yields, EV71 infections, and internal ribosome entry site activity. We also found that geniposide, a primary F. gardeniae component, inhibited both EV71 replication and viral IRES activity. Our data suggest the presence of a mechanism that blocks viral protein translation. According to our findings, F. gardeniae and geniposide deserve a closer look as potential chemopreventive agents against EV71 infections.
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Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Enterovirus Humano A/efectos de los fármacos , Infecciones por Enterovirus/tratamiento farmacológico , Gardenia/química , Iridoides/farmacología , Medicina Tradicional China , ARN Viral/genética , Ribosomas/metabolismo , Antivirales/química , Línea Celular Tumoral , Medicamentos Herbarios Chinos/química , Infecciones por Enterovirus/virología , Humanos , Iridoides/química , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Biosíntesis de Proteínas/efectos de los fármacos , Biosíntesis de Proteínas/genética , ARN Viral/metabolismo , Replicación Viral/efectos de los fármacosRESUMEN
3,4-Ethylenedioxythiophene and bis[2-(2-methoxyethoxy)ethoxy]thiophene bridged donor-acceptor molecules for dye-sensitized solar cells have been synthesized, one of which achieved a solar-to-energy conversion efficiency of 7.3%, compared to 7.7% optimized for N719 dye.
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The purpose of this study was to evaluate the effectiveness of acupressure on gastrointestinal (GI) motility in women after trans-abdominal hysterectomy (TAH). Patients were randomly assigned into two groups of 21 and 20 patients each. The experimental group received acupressure for 3 minutes at each of three meridian points: Neiguan (PC-6), Zusanli (ST-36) and Sanyinjiao (SP-6). The control group received 3 minutes of acupressure on sham points. Acupressure was performed twice a day. A questionnaire was used to determine patients' satisfaction prior to and after afternoon acupressure. GI contractions were measured with a multifunctional stethoscope before and after acupressure. Acupressure of these three meridian points significantly (p < 0.05) increased GI motility in the experimental group, but there was little change in the control group (p > 0.05). Our conclusions are that non-invasive acupressure of these meridian points can significantly improve GI motility and can be incorporated into the technical curriculum and clinical education program of nursing schools. Patients and their family members can be taught to continue this procedure at home to enhance GI motility in patients who have undergone TAH.