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1.
BMC Med Educ ; 23(1): 560, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559039

RESUMO

BACKGROUND: An effective test mechanism to evaluate clinical knowledge and skills of the entry-level healthcare professionals is important for providing clinical competency and improving patient care. This study aimed to develop novel, innovative computer-based test (Inno-CBT) item types for application in the national examination of Korean healthcare professionals. METHODS: This exploratory study was conducted from May 2021 to March 2022 by a team of faculty members from pharmacy schools in South Korea. A literature search using PubMed, Google Scholar, RISS, Web of Science, and KoreaMed was performed. Forum presentations, media articles, and previous reports by the Korea Health Personnel Licensing Examination Institute (KHPLEI) were included. Workshops were held, information and ideas were collected and conceptualized, and item types were designed, drafted, and refined. By repeating this process, the Inno-CBT item types were finalized. RESULTS: Forty-one Inno-CBT item types with 28 subtypes were developed. New digital technologies, such as a reactive responsive media interface, an animation insertion, multimedia embedding, and network surfing, were utilized in these novel types. It was anticipated that these Inno-CBT item types would effectively measure abilities in healthcare knowledge, problem-solving skills, and professional behaviors. Some potential barriers to implementing the Inno-CBT item types include item difficulty, operational unfamiliarity, complexity in scoring protocols, and network security. CONCLUSIONS: A variety of styles of novel Inno-CBT item types were developed to evaluate the multifaceted and in-depth professional abilities required for healthcare professionals. Prior to implementing these item types in the national examination, item validation and technical support should be conducted.


Assuntos
Pessoal de Saúde , Licenciamento , Humanos , República da Coreia , Docentes , Computadores
2.
BMC Med Educ ; 23(1): 231, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37041575

RESUMO

BACKGROUND: The assessment of pharmacy students' readiness to begin the education of an advanced pharmacy practice experience (APPE) in clinical pharmacy settings continues to gain increasing attention. This study aimed to develop an objective structured clinical examination (OSCE) in the core domains acquired through an introductory pharmacy practice experience (IPPE), for evaluating its appropriateness as a tool of assessing clinical pharmacist competency for APPEs in Korean pharmacy students throughout a pilot study. METHODS: OSCE's core competency domains and case scenarios were developed through a literature review, ideation by researchers, and external experts' consensus by a Delphi method. A prospective single-arm pilot test was conducted to implement the OSCE for Korean pharmacy students who completed a 60-h course of in-class simulation IPPE. Their competencies were assessed by four assessors in each OSCE station with a pass-fail grading system accompanied by a scoring rubric. RESULTS: OSCE competency areas including patient counseling, provision of drug information, over-the-counter (OTC) counseling, and pharmaceutical care services were developed with four interactive and one non-interactive cases. Twenty pharmacy students participated in the OSCE pilot test, and their competencies were evaluated by 20 assessors. The performance rate was the lowest in the area of patient counseling for a respiratory inhaler (32.1%) and the highest (79.7%) in OTC counseling for constipation. The students had an average performance rate of 60.4% in their communication skills. Most participants agreed on the appropriateness, necessity, and effectiveness of the OSCE in evaluating pharmacy students' clinical performance and communication skills. CONCLUSIONS: The OSCE model can be used to assess pharmacy students' readiness for off-campus clinical pharmacy practice experience. Our pilot study suggests the necessity of conducting an OSCE domain-based adjustment of difficulty levels, and strengthening simulation-based IPPE education.


Assuntos
Serviço de Farmácia Hospitalar , Farmácia , Estudantes de Farmácia , Humanos , Projetos Piloto , Estudos Prospectivos , Avaliação Educacional/métodos
3.
Am J Physiol Heart Circ Physiol ; 322(3): H406-H416, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35060752

RESUMO

Amniotic products are potent immunomodulators used clinically to repair tissue injury. Little information exists regarding the potential of cell-free human amniotic fluid (hAF) to treat cardiovascular disease. Herein, we sought to determine the influence and efficacy of acellular hAF on myocardial ischemia-reperfusion injury. Processed hAF was obtained from volunteer donors at the time of elective caesarean section and manufactured using proprietary methods. Left anterior descending coronary artery ligation was performed on rats for 60 min. Thirty minutes after release and reperfusion, either saline or hAF was injected intramyocardially. Serial echocardiography revealed that compared with saline-injected rats, hAF animals maintained their ejection fraction and did not adversely remodel through the 4-wk period. This preserved ventricular function correlated with decreased infarct size, less fibrosis, and reduced expression of cytokines and infiltrating inflammatory cells. Comparative arrays of different donor hAF lots confirmed the presence of a wide array of immunomodulatory and host-defense proteins. The observed functional cardioprotection was furthermore evident when given intravenously and across multiple hAF donors. In conclusion, our data demonstrate, for the first time, the cardioprotective effect of acellular hAF on myocardial injury. These observations spanned across diverse donors and likely result from the mixture of a plethora of naturally produced cytokines, chemokines, and immune-modulating proteins rather than a single, defined mechanistic culprit. The ubiquitous availability of hAF as a cell-free solution further suggests its potential for widespread adoption as a therapy for myocardial ischemia-reperfusion injury.NEW & NOTEWORTHY Rather than targeting a single pathway implicated in myocardial reperfusion injury, cell-free human amniotic fluid-a naturally derived cocktail composed of thousands of proteins involved with innate immunity and anti-inflammation-markedly reduces injury and preserves cardiac function in a model of rodent myocardial ischemia-reperfusion. With its ubiquitous availability as well as its anti-inflammatory and nonimmunogenic properties, human cell-free amniotic fluid offers potential for use as a cardioprotective adjunct.


Assuntos
Líquido Amniótico/química , Cardiotônicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Cardiotônicos/análise , Citocinas/genética , Citocinas/metabolismo , Feminino , Humanos , Fatores Imunológicos/análise , Masculino , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Função Ventricular
4.
Ann Thorac Surg ; 114(1): 98-107, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34419440

RESUMO

BACKGROUND: Recent clinical trials have suggested that blockade of interleukin-1 (IL-1) can have a favorable impact on patients with myocardial infarction and heart failure. However, the mechanism of antagonism of this specific cytokine in mediating cardiac disease remains unclear. Hence, we sought to determine the influence of IL-1 blockade on acute hypertensive remodeling. METHODS: Transverse aortic constriction was performed in C57BL mice with or without intraperitoneal administration of interleukin 1 receptor antagonism (IL-1Ra). Function, structure, and molecular diagnostics were subsequently performed and analyzed. RESULTS: Six weeks after transverse aortic constriction, a progressive decline of ejection fraction and increases in left ventricle mass and dimensions were effectively mitigated with IL-1Ra. Transverse aortic constriction resulted in an expected profile of hypertrophic markers including myosin heavy chain, atrial natriuretic peptide, and skeletal muscle actin, which were all significantly lower in IL-1Ra treated mice. Although trichrome staining 2 weeks after transverse aortic constriction demonstrated similar levels of fibrosis, IL-1ra-reduced expression of collagen-1, tissue inhibitor of metallopeptidase 1, and periostin. Investigating the angiogenic response to pressure overload, similar levels of vascular endothelial growth factor were observed, but IL-1Ra was associated with more stromal cell-derived factor-1. Immune cell infiltration (macrophages and lymphocytes) was also decreased in IL-1Ra treated mice. Similarly, cytokine concentrations of IL-1, IL-18, and IL-6 were all reduced in IL-1Ra-treated animals. CONCLUSIONS: Interleukin-1Ra prevents the progression toward heart failure associated with acute pressure overload. This functional response was associated with reductions in mediators of fibrosis, cellular infiltration, and cytokine production. These results provide mechanistic insight into recent clinical trials and could springboard future investigations in patients with pressure-overload-based cardiomyopathies.


Assuntos
Insuficiência Cardíaca , Proteína Antagonista do Receptor de Interleucina 1 , Animais , Citocinas , Modelos Animais de Doenças , Fibrose , Insuficiência Cardíaca/etiologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-1 , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Interleucina-1 , Fator A de Crescimento do Endotélio Vascular , Remodelação Ventricular
5.
Int Clin Psychopharmacol ; 34(1): 9-17, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30096056

RESUMO

It has been reported that selective serotonin reuptake inhibitors (SSRIs) might induce major adverse cardiovascular events (MACE), but the association between the use of SSRIs and MACE has not been elucidated as yet. Therefore, the aim of this study was to evaluate the association between the use of SSRIs and MACE in depressed patients with previous cardiovascular events. Two researchers independently selected randomized-controlled studies (RCTs) according to the predefined inclusion criteria and evaluated the quality of articles. A quantitative analysis was carried out to estimate pooled risk ratios (RRs) for the association between the use of SSRIs and MACE. Ten RCTs were selected in the final analysis. The use of SSRIs in depressed patients with previous cardiovascular events significantly decreased the risk of MACE [RR: 0.74; 95% confidence interval (CI): 0.55-0.99]. The risk of myocardial infarction was also reduced significantly (RR: 0.59, 95% CI: 0.37-0.93), associations with stroke and all-cause-death (cardiac or other causes): risk of stroke (RR: 0.88, 95% CI: 0.35-2.25) or all-cause death (RR: 0.83; 95% CI: 0.66-1.05). This meta-analysis suggests that the use of SSRIs decreased the risk of MACE by significantly reducing the risk of myocardial infraction in patients with depression and previous cardiovascular events.


Assuntos
Doenças Cardiovasculares/epidemiologia , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/epidemiologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Humanos , Infarto do Miocárdio/epidemiologia , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia
6.
Sci Rep ; 7(1): 11643, 2017 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-28912479

RESUMO

Jarid2 is a component of the Polycomb Repressor complex 2 (PRC2), which is responsible for genome-wide H3K27me3 deposition, in embryonic stem cells. However, Jarid2 has also been shown to exert pleiotropic PRC2-independent actions during embryogenesis. Here, we have investigated the role of Jarid2 during pancreas development. Conditional ablation of Jarid2 in pancreatic progenitors results in reduced endocrine cell area at birth due to impaired endocrine cell differentiation and reduced prenatal proliferation. Inactivation of Jarid2 in endocrine progenitors demonstrates that Jarid2 functions after endocrine specification. Furthermore, genome-wide expression analysis reveals that Jarid2 is required for the complete activation of the insulin-producing ß-cell differentiation program. Jarid2-deficient pancreases exhibit impaired deposition of RNAPII-Ser5P, the initiating form of RNAPII, but no changes in H3K27me3, at the promoters of affected endocrine genes. Thus, our study identifies Jarid2 as a fine-tuner of gene expression during late stages of pancreatic endocrine cell development. These findings are relevant for generation of transplantable stem cell-derived ß-cells.


Assuntos
Diferenciação Celular/genética , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Complexo Repressor Polycomb 2/genética , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proliferação de Células , Células Endócrinas/citologia , Células Endócrinas/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Histonas/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , RNA Polimerase II/metabolismo , Transcrição Gênica , Transcriptoma
7.
Artigo em Inglês | MEDLINE | ID: mdl-28352065

RESUMO

PURPOSE: The survey aimed to obtain opinions about a proposed implementation of pharmacy skills assessment in Korean pharmacist licensure examination (KPLE). METHODS: A 16-question survey was distributed electronically to 2,738 people including 570 pharmacy professors of 35 pharmacy schools, 550 preceptors from 865 practice sites and 1,618 students who graduated in 2015. The survey solicited responses concerning the adequacy of the current KPLE in assessing pharmacy knowledge/skills/attitudes, deficiencies of pharmacy skills testing in assessing the professional competencies necessary for pharmacists, plans for pharmacy skills tests in the current KPLE, and subject areas of pharmacy practice. RESULTS: A total of 466 surveys were returned. The current exam is not adequate for assessing skills and attitudes according to 42%-48% of respondents. Sixty percent felt that skills test is necessary to assess qualifications and professional competencies. Almost two-thirds of participants stated that testing should be implemented within 5 years. More than 60% agreed that candidates should be graduates and that written and skills test scores can be combined for pass-fail decisions. About 70% of respondents felt that the test should be less than 2 hours in duration. Over half of the respondents thought that the assessor should be a pharmacy faculty member with at least 5 years of clinical experience. Up to 70% stated that activities related to patient care were appropriate and practical for the scope of skills test. CONCLUSION: Pharmacy skills assessment was supported by the majority of respondents.


Assuntos
Competência Clínica/estatística & dados numéricos , Educação em Farmácia/métodos , Licenciamento em Farmácia , Farmacêuticos/psicologia , Estudantes de Farmácia/psicologia , Adulto , Atitude do Pessoal de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Serviço de Farmácia Hospitalar , Preceptoria , República da Coreia , Inquéritos e Questionários , Adulto Jovem
8.
Int J Nurs Pract ; 22(6): 625-632, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27653752

RESUMO

This study was designed to construct and test the structural equation modelling on nurses' turnover intention including emotional labour, job stress, emotional intelligence and burnout in order to identify the mediating effect of emotional intelligence between those variables. Emotional labour, job stress and burnout increase turnover intention of nurses. However, emotional intelligence is negatively correlated with emotional labour and reduces job stress, burnout and turnover intention. Structural equation modelling was used to analyse the goodness of fit of the hypothetical model of nurses' turnover intention. Research data were collected via questionnaires from 4 to 22 August 2014 and analysed using SPSS version 18.0 and AMOS version 20.0. The model fit indices for the hypothetical model were suitable for recommended. Emotional intelligence has decreasing effect on turnover intention through burnout, although its direct effect on turnover intention is not significant. Emotional intelligence has mediation effect between emotional labour and burnout. This study's results suggest that increasing emotional intelligence might critically decrease nurses' turnover intention by reducing the effect of emotional labour on burnout.


Assuntos
Esgotamento Profissional , Inteligência Emocional , Emprego/psicologia , Enfermeiras e Enfermeiros/psicologia , Estresse Psicológico , Humanos , Reorganização de Recursos Humanos
9.
Biomaterials ; 97: 164-75, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27174688

RESUMO

In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM.


Assuntos
Dendrímeros/química , Expressão Gênica , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Relaxina/genética , Remodelação Ventricular , Animais , Morte Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Matriz Extracelular/metabolismo , Hemodinâmica , Humanos , Imageamento Tridimensional , Masculino , Camundongos , Infarto do Miocárdio/patologia , Células NIH 3T3 , Ratos Sprague-Dawley , Sístole , Transfecção
10.
J Exp Bot ; 67(6): 2007-22, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26884603

RESUMO

Plant cell growth is restricted by the cell wall, and cell wall dynamics act as signals for the cytoplasmic and nuclear events of cell growth. Among various receptor kinases, ROOT HAIR SPECIFIC 10 (RHS10) belongs to a poorly known receptor kinase subfamily with a proline-rich extracellular domain. Here, we report that RHS10 defines the root hair length of Arabidopsis thaliana by negatively regulating hair growth. RHS10 modulates the duration of root hair growth rather than the growth rate. As poplar and rice RHS10 orthologs also showed a root hair-inhibitory function, this receptor kinase-mediated function appears to be conserved in angiosperms. RHS10 showed a strong association with the cell wall, most probably through its extracellular proline-rich domain (ECD). Deletion analysis of the ECD demonstrated that a minimal extracellular part, which includes a few proline residues, is required for RHS10-mediated root hair inhibition. RHS10 suppressed the accumulation of reactive oxygen species (ROS) in the root, which are necessary for root hair growth. A yeast two-hybrid screening identified an RNase (RNS2) as a putative downstream target of RHS10. Accordingly, RHS10 overexpression decreased and RHS10 loss increased RNA levels in the hair-growing root region. Our results suggest that RHS10 mediates cell wall-associated signals to maintain proper root hair length, at least in part by regulating RNA catabolism and ROS accumulation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Parede Celular/enzimologia , Raízes de Plantas/enzimologia , Raízes de Plantas/crescimento & desenvolvimento , Prolina/metabolismo , Proteínas Quinases/metabolismo , Sequência de Aminoácidos , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Sequência de Bases , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Parede Celular/efeitos dos fármacos , Sequência Conservada , Epistasia Genética/efeitos dos fármacos , Etilenos/farmacologia , Genes de Plantas , Ácidos Indolacéticos/farmacologia , Modelos Biológicos , Raízes de Plantas/citologia , Raízes de Plantas/efeitos dos fármacos , Domínios Proteicos , Proteínas Quinases/química , Proteínas Quinases/genética , Transporte Proteico/efeitos dos fármacos , RNA de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Deleção de Sequência , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo
11.
Mol Ther ; 24(4): 805-11, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26782638

RESUMO

Ways for extending the longevity of stem cells are imperative to attain diverse expected therapeutic effects. Here, we constructed a three-dimentional (3D) scaffold system for human mesenchymal stem cell (hMSC) delivery. Intramyocardial injections of porous PEI1.8k blended with poly(lactic-co-glycolic acid) (PLGA) (PLGA/PEI1.8k) (PPP) microparticles by physical electrostatic conjugation and structural entrapment of hMSCs demonstrated enhanced functional and geometric improvements on post-infarct cardiac remodeling in rats. In the hMSC-loaded PPP delivery, increases of coronary artery blood flow rate and in vivo engraftment rate as well as time-dependent functional, geometric, and pathologic findings reversing post-infarct cardiac remodeling account for improved left ventricular (LV) systolic function up to the level of sham thoracotomy group. This study expands our understanding by proving that increase of coronary artery blood flow augmented functional recovery of hMSC-loaded PPP delivery system after myocardial infarction (MI).


Assuntos
Circulação Coronária , Iminas/química , Ácido Láctico/química , Células-Tronco Mesenquimais/citologia , Infarto do Miocárdio/terapia , Polietilenos/química , Ácido Poliglicólico/química , Remodelação Ventricular , Animais , Diferenciação Celular , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Alicerces Teciduais , Função Ventricular Esquerda
12.
J Control Release ; 219: 181-191, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26453806

RESUMO

Oncolytic adenovirus (Ad) vectors present a promising modality to treat cancer. Many clinical trials have been done with either naked oncolytic Ad or combination with chemotherapies. However, the systemic injection of oncolytic Ad in clinical applications is restricted due to significant liver toxicity and immunogenicity. To overcome these issues, Ad has been engineered physically or chemically with numerous polymers for shielding the Ad surface, accomplishing extended blood circulation time and reduced immunogenicity as well as hepatotoxicity. In this review, we describe and classify the characteristics of polymer modified oncolytic Ad following each strategy for cancer treatment. Furthermore, this review concludes with the highlights of various polymer-coated Ads and their prospects, and directions for future research.


Assuntos
Adenoviridae , Terapia Genética , Neoplasias/terapia , Vírus Oncolíticos , Polímeros , Adenoviridae/química , Animais , Vetores Genéticos , Humanos , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/química , Polímeros/química , Eletricidade Estática , Microambiente Tumoral
13.
Biomacromolecules ; 16(7): 2132-43, 2015 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-26096567

RESUMO

Recently, adenovirus (Ad) has been utilized as a viral vector for efficient gene delivery. However, substantial immunogenicity and toxicity have obstructed oncolytic Ad's transition into clinical studies. The goal of this study is to generate an adenoviral vector complexed with multidegradable bioreducible core-cross-linked polyethylenimine (rPEI) polymer that has low immunogenicity and toxicity while having higher transduction efficacy and stability. We have synthesized different molecular weight rPEIs and complexed with Ad at varying molar ratios to optimize delivery of the Ad/polymer complex. The size and surface charge of Ad/rPEIs were characterized. Of note, Ad/rPEIs showed significantly enhanced transduction efficiency compared to either naked Ad or Ad/25 kDa PEI in both coxsackievirus and adenovirus receptor (CAR) positive and negative cancer cells. The cellular uptake result demonstrated that the relatively small size of Ad/16 kDa rPEIs (below 200 nm) was more critical to the complex's internalization than its surface charge. Cancer cell killing effect and viral production were significantly increased when oncolytic Ad (RdB/shMet, or oAd) was complexed with 16 kDa rPEI in comparison to naked oAd-, oAd/25 kDa PEI-, or oAd/32 kDa rPEI-treated cells. This increased anticancer cytotoxicity was more readily apparent in CAR-negative MCF7 cells, implying that it can be used to treat a broad range of cancer cells. Furthermore, A549 and HT1080 cancer cells treated with oAd/16 kDa rPEI had significantly decreased Met and VEGF expression compared to either naked oAd or oAd/25 kDa PEI. Overall, these results demonstrate that shMet expressing oncolytic Ad complexed with multidegradable bioreducible core-cross-linked PEI could be used as efficient and safe cancer gene therapy.


Assuntos
Adenoviridae/genética , Vetores Genéticos/farmacologia , Vírus Oncolíticos/genética , Polietilenoimina/química , Adenoviridae/química , Apoptose , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Terapia Genética/métodos , Vetores Genéticos/síntese química , Células HEK293 , Humanos , Células MCF-7 , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/química , Transdução Genética
14.
J Control Release ; 205: 128-33, 2015 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-25575866

RESUMO

Multipotent mesenchymal stem cells (MSCs) promise a therapeutic alternative for many debilitating and incurable diseases. However, one of the major limitations for the therapeutic application of human MSC (hMSC) is the lengthy ex vivo expansion time for preparing a sufficient amount of cells due to the low engraftment rate after transplantation. To solve this conundrum, a porous biodegradable polymeric microsphere was investigated as a potential scaffold for the delivery of MSCs. The modified water/oil/water (W1/O/W2) double emulsion solvent evaporation method was used for the construction of porous microspheres. PEI1.8k was blended with poly(lactic-co-glycolic acid) (PLGA) to enhance electrostatic cellular attachment to the microspheres. The porous PLGA/PEI1.8k (PPP) particles demonstrated an average particle size of 290µm and an average pore size of 14.3µm, providing a micro-carrier for the MSC delivery. PPP particles allowed for better attachment of rMSCs than non-porous PLGA/PEI1.8k (NPP) particles and non-porous (NP) and porous PLGA (PP) microspheres. rMSC successfully grew on the PPP particles for 2weeks in vitro. Next, PPP particles loaded with 3 different amounts of hMSC showed increased in vivo engraftment rates and maintained the stemness characteristics of hMSC compared with hMSCs-alone group in rats 2weeks after intramyocardial administration. These customized PPP particles for MSC delivery are a biodegradable and injectable scaffold that can be used for clinical applications.


Assuntos
Iminas/química , Ácido Láctico/química , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Infarto do Miocárdio/cirurgia , Miocárdio/patologia , Polietilenos/química , Ácido Poliglicólico/química , Regeneração , Alicerces Teciduais , Animais , Adesão Celular , Diferenciação Celular , Linhagem da Célula , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Sobrevivência de Enxerto , Humanos , Injeções Intralesionais , Masculino , Microesferas , Infarto do Miocárdio/patologia , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Ratos Sprague-Dawley , Fatores de Tempo
15.
J Control Release ; 190: 424-39, 2014 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-24746626

RESUMO

Most currently available cationic polymers have significant acute toxicity concerns such as cellular toxicity, aggregation of erythrocytes, and entrapment in the lung capillary bed, largely due to their poor biocompatibility and non-degradability under physiological conditions. To develop more intelligent polymers, disulfide bonds are introduced in the design of biodegradable polymers. Herein, the sustained innovations of biomimetic nano-sized constructs with bioreducible poly(disulfide amine)s demonstrate a viable clinical tool for the treatment of cardiovascular disease, anemia, diabetes, and cancer.


Assuntos
Doenças Cardiovasculares/terapia , Diabetes Mellitus Tipo 2/terapia , Técnicas de Transferência de Genes , Terapia Genética , Neoplasias/terapia , Polímeros/química , Adenoviridae , Materiais Biocompatíveis , Vetores Genéticos , Humanos , Nanopartículas , Plasmídeos , RNA Interferente Pequeno
16.
Arch Pharm Res ; 37(10): 1295-300, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24452665

RESUMO

The health insurance review and assessment services, responsible for the assessment of quality and quantity of healthcare providers' services, implemented a public disclosure policy for antibiotic prescribing rate in February 2006. The aim of this study was to investigate changes of overall antibiotic consumption following the policy by analysing national healthcare utilization data from 2005 to 2009. Prescription information of systemic antibiotics excluding antifungals and topical antibiotics was retrospectively collected from the population-based health insurance claims sample data for the five years from 2005 to 2009. Those data were analysed using the standardised anatomical therapeutic chemical/defined daily dose method. Antibiotic consumption was standardised by the defined daily dose per 1,000 inhabitants per day (DID). Descriptive statistics was used to present consumption figures for every year. Secondary comparison to other OECD countries based on published reports was added to weigh the antibiotic consumption level of South Korea in a global perspective. Overall antibiotic consumption decreased in 2006 (23.8 DID, 3.6 % decrease from 24.7 DID in 2005) and 2007 (21.5 DID, 9.7 % decrease from 2006), but rebounded in 2008 (24.3 DID, 13 % increase from 2007) and 2009 (25.2 DID, 3.7 % increase from 2008). Temporal decreases in 2006 and 2007 were attributed to fewer prescriptions of penicillins (J01C group), among which the decrease in amoxicillin consumption was almost equal to that of overall antibiotic consumption. A similar fluctuation trend in overall antibiotic consumption occurred in the out-patient setting rather than the in-patient setting. Amoxicillin decreased since 2007, while amoxicillin/clavulanic acid, cefaclor and clarithromycin increased without dropping. The estimated antibiotic consumption level in this study was higher than the average of OECD countries, and the yearly fluctuation shown during the five years was a country specific pattern observed only in South Korea. Overall antibiotic consumption was temporarily decreased in 2006 and 2007. But this result might not signify an effect of government policy of antibiotic prescribing rate disclosure to the public. The results presented in DID unit, a more objective index than prescribing rates, suggest the need for further strategies to reduce antibiotic use nationwide.


Assuntos
Antibacterianos/uso terapêutico , Revelação , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/tendências , Política de Saúde , Programas Nacionais de Saúde/estatística & dados numéricos , Humanos , República da Coreia , Estudos Retrospectivos
17.
Int J Clin Pharmacol Ther ; 51(7): 585-92, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23611570

RESUMO

This study was conducted to investigate overall systemic antibiotic consumption levels and specific patterns using standardized Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology. National Health Insurance claims data during 2008 and 2009 was used. Antibiotic prescription data was classified using the ATC system and converted into DDD. Consumption figures were presented as the number of DDD per 1,000 inhabitants per day (DID). Detailed information on indications and seasonal variations, age and institutional determinants on antibiotic consumption were also explored. Total consumption was slightly increased from 24.3 to 25.2 DID in 2009 compared to 2008. The most frequently prescribed antibiotic was amoxicillin/clavulanic acid (5.1 and 5.2 DID, in 2008 and 2009, respectively), followed by cefaclor (3.0 and 3.3 DID) and amoxicillin (3.3 and 3.2 DID). Respiratory system diseases were the main causes of antimicrobial prescription (47.3%) and acute forms of bronchitis, tonsillitis and sinusitis were the most common diseases. There were typical seasonal fluctuations with heightened winter peaks. Consumption figures under 5 years of age (41.6 and 43.3 DID) were even higher than figures in aged 65 - 80 (36.2 and 39.1 DID). Antibiotic consumption in South Korea remained high compared with other OECD countries. Efforts to increase prudent antibiotic use, especially for upper respiratory system infections and for younger children, should be made to decrease antibiotic use.


Assuntos
Antibacterianos/uso terapêutico , Povo Asiático/estatística & dados numéricos , Infecções Bacterianas/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Infecções Bacterianas/etnologia , Criança , Pré-Escolar , Vias de Administração de Medicamentos , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Revisão de Uso de Medicamentos , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Recém-Nascido , Seguro de Serviços Farmacêuticos/estatística & dados numéricos , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estações do Ano , Fatores de Tempo , Adulto Jovem
18.
Cell Mol Neurobiol ; 33(2): 223-32, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23180003

RESUMO

The maintenance of water homeostasis under pathological conditions is mediated by the aquaporin-4 (AQP4) channel in astrocytes. To clarify the transcriptional regulation for AQP4 under conditions of astrocytic swelling, we examined the role of nuclear factor of activated T cells 5 (NFAT5). We evaluated NFAT5 expression patterns after the induction of brain edema and following excitotoxic neuronal death by kainic acid injection. In injured hippocampi, NFAT5 expression increased in astrocytes from 12 h to 3 days post-injection. AQP4 was redistributed from perivascular to whole-cell processes in astrocytes. NFAT5 and AQP4 expression increased under astrocytic swelling induced by ammonia treatment, and NFAT5-targeted silencing significantly reduced AQP4 expression. The promoter region required for NFAT5 transcriptional activation was located between -49 and -38 bp of rat AQP4. The amount of NFAT5 bound to the promoter of AQP4 was increased in response to ammonia. Our data demonstrate that NFAT5 is necessary for the transcriptional regulation of AQP4 expression and for local astrocyte swelling with accompanying restriction of the neuropil extracellular space in vivo.


Assuntos
Aquaporina 4/metabolismo , Astrócitos/metabolismo , Fatores de Transcrição/metabolismo , Animais , Aquaporina 4/genética , Astrócitos/efeitos dos fármacos , Sequência de Bases , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Imunofluorescência , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Caínico/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Dados de Sequência Molecular , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neurotoxinas/toxicidade , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
19.
J Korean Acad Nurs ; 42(3): 369-76, 2012 Jun.
Artigo em Coreano | MEDLINE | ID: mdl-22854549

RESUMO

PURPOSE: The purpose of this study was to identify the effects of a Yoga-focused prenatal program on the stress, anxiety, self confidence and labor pain of pregnant women who had in vitro fertilization (IVF) treatment. METHODS: A quasi experimental study with a non-equivalent control group pretest-posttest design was used. The data collection period and meditation program were between January 9 and August 31, 2009. Forty-six women who were pregnant following IVF, and were between 12-20 weeks gestation, participated in the study (23 experimental group, 23 control group). Data were analyzed using Chi-square test, Mann-Whitney U Test, ANCOVA, and Cronbach's alpha coefficients with the SPSS 12.0 for Windows Program. RESULTS: Although the sample size was limited, women who participated in the program showed statistically significant improvements in stress, anxiety, labor pain, and labor confidence for women pregnant after IVF. CONCLUSION: The result indicate that this 12-week Yoga-focused educational program can be utilized for women pregnant following IVF to reduce their stress, anxiety, and labor pain, and to increase delivery confidence. It is suggested that the Yoga-focused educational program be offered to every pregnant woman.


Assuntos
Ansiedade/prevenção & controle , Dor do Parto/terapia , Gestantes/psicologia , Autoimagem , Yoga , Adulto , Feminino , Fertilização in vitro , Humanos , Gravidez , Desenvolvimento de Programas , Estresse Psicológico
20.
J Biochem Mol Toxicol ; 26(6): 213-23, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22711419

RESUMO

Ethane dimethanesulfonate (EDS), a well-known alkylating agent, selectively destroys Leydig cells. To clarify the molecular pathways underlying EDS action on Leydig cells, we analyzed gene expression profiles of an EDS-treated TM3 Leydig cell line. In this study, we analyzed the representative canonical pathways and toxicity pathways/gene lists using the Ingenuity Pathways Analysis program. In TM3 cells, 677 and 6756 genes were identified as being up- or downregulated after 3 and 24 h EDS treatments, respectively, (>1.3-fold changes, p < 0.05). Toxicological pathway analysis revealed that expression of genes related to Nrf2-mediated oxidative stress response showed remarkable changes in early or later stage of EDS-treated TM3 cells. Several genes related to steroidogenesis and apoptosis were also differentially expressed at 24 h in EDS-treated TM3 cells. Overall, toxicological pathway analysis using gene expression profiling showed that oxidative stress might be an important factor in cell death in TM3 cells affected by EDS treatment.


Assuntos
Perfilação da Expressão Gênica , Células Intersticiais do Testículo/efeitos dos fármacos , Mesilatos/toxicidade , Animais , Apoptose/genética , Linhagem Celular , Células Intersticiais do Testículo/metabolismo , Masculino , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Estresse Oxidativo , Esteroides/biossíntese
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