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1.
Nurs Open ; 9(2): 1105-1113, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34914200

RESUMO

AIM: This study aims to compare the early development of professional value between the students in the traditional programme (BSN) and those in the accelerated BSN (ABSN) programmes. DESIGN: A longitudinal design was conducted. METHODS: Data were collected from three schools of nursing during one academic year. A total of 117 BSN students and 101 ABSN students completed the survey of demographic information and the Nurses' Professional Values Scale-Revised questionnaires. All data were analysed by IBM SPSS-Statistics 22. RESULTS: Results showed that, in the beginning of the first professional nursing course, both students in the BSN and the ABSN programmes reported similar level of professional values. However, after one academic year, the changes in the professional value varied both between these two programmes and among the three different nursing schools. The increased professional value in school A represented the possibility for students to improve during their first-year professional nursing programme. As educators, we should redesign our teaching strategies according to the different conditions of students in each programme.


Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Bacharelado em Enfermagem/métodos , Humanos , Estudos Longitudinais , Escolas de Enfermagem , Inquéritos e Questionários
2.
Artigo em Inglês | MEDLINE | ID: mdl-34067371

RESUMO

The quality of nurses' work has a direct effect on patient health, and poor sleep has been positively associated with nurses' medical errors. The aim of this study was to investigate the relationship between quality of sleep and heart rate variability (HRV) among female nurses. A descriptive cross-sectional correlational study design was used in January 2014 to study female nurses (n = 393) employed in a medical center in Taiwan. Data were obtained from several questionnaires. HRV was analyzed with five-minute recordings of heart rate signals obtained using a Heart Rater SA-3000P. Approximately 96% of the participants self-reported a poor quality of sleep. Compared to non-shift nurses, significant decreases were found in total power (TP) and low-frequency HRV among shift-work nurses. However, negative correlations were found between sleep quality and HRV, including total power, low frequency, and the low frequency/high frequency ratio (r = -0.425, p < 0.05; r = -0.269, -0.266, p < 0.05). In a stepwise multiple regression analysis, 23.1% of variance in quality of sleep can be explained by TP and heart rate. The sleep quality of female nurses was poor and this affected their autonomic nervous system, which can contribute unfavorable consequences for their health.


Assuntos
Enfermeiras e Enfermeiros , Sono , Estudos Transversais , Feminino , Frequência Cardíaca , Humanos , Taiwan
3.
Healthcare (Basel) ; 9(5)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33924759

RESUMO

(1) Background: Healthcare workplace violence has been a focused issue in the whole world. The rate of the occurrence is pretty high in every country. The emergency room is a high risk and high frequency place for violence to occur. Under the medical service demands from people, it is quite easy to bring about conflicts. This leads to serious physical and mental harm to nurses. When suffering from physical and mental injuries, resilience is a protective factor away from negative influence. It is rare to explore and study how the nurses' resilience ability, workplace violence and turnover intention are related. Thus, the aim of this study is to understand resilience as a mediator effect in emergency nurses toward the workplace violence. (2) Methods: A cross-sectional survey study was used to collect information from emergency room nurses of a medical center in northern Taiwan. There were 132 samples in total. Three research instruments were included as follows: Hospital Workplace Violence Prevention Questionnaire, Connor-Davidson Resilience Scale, and Turnover Intention Scale. Statistical analysis using t-test, ANOVA, Correlation, as well as Sobel test were used in this study. (3) Results: The results revealed that the average age was 29.5 ± 5.6. Almost 58% of nurses experienced workplace violence. Twelve percent of nurse had experienced physical violence and 53.8% had experienced mental violence. There was significant relationship between shift personnel and religious believers. To the people who suffered physical violence, there was a significant relationship between emergency room working years and the total working years. There was significant difference between those who had suffered mental violence and religious believers. Female nurses suffered mental violence to a much higher extent than male nurses. There was a significant relationship between nurses' working years, the total working years, resilience, and turnover intention. Resilience was not the mediator for workplace violence toward turnover intention in this study. (4) Conclusions: The outcome of this study suggested that on an individual level, nurses can enhance self-protection and communication skills to decrease workplace violence. For emergency environment settings, designing a good working environment, visitors' restriction, avoiding working alone, and enhancing supervising alarm system are recommended. As for hospital administrators, fitness for work and to set up a project team is necessary. These can be references in planning prevention on workplace violence and promoting quality of workplace and patient safety in the future.

4.
Complement Ther Clin Pract ; 43: 101358, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33711748

RESUMO

The purpose of this study was to explore the effectiveness of an essential oil massage on the sleep quality of the critical care nurses. A randomized controlled trial with single blind was conducted. A total of 112 critical care nurses were recruited. Participants were randomly allocated to either the experimental or control group. Only the experimental group received four sessions consisting of a lavender essential oil massage. The results of this study revealed that the overall subjective sleep quality and objective sleep parameters did not reach a significant difference between the two groups before and after the intervention, but a progressive the subjective sleep quality score reduction was observed in the experimental group. The findings of this study might provide information to critical care nurses who are under high pressure to find the optional alternative way of managing their self-sleep health by employing safe and convenient alternatives through aromatherapy.


Assuntos
Aromaterapia , Óleos Voláteis , Cuidados Críticos , Humanos , Massagem , Método Simples-Cego , Sono
5.
Artigo em Inglês | MEDLINE | ID: mdl-33488750

RESUMO

BACKGROUND: Occupational stress is a common issue faced by workers in every discipline. Complementary and alternative medicine (CAM) therapies, such as aromatherapy massage or massage, have antistress effects in the literature. The purpose of this randomized clinical trial with triple blinds is to evaluate the immediate effects of lavender aromatherapy massage for improving work stress, burnout, and HRV parameters of female employees in a university. METHODS: A total of 53 subjects in experimental group whereas 57 subjects in control group completed interventions and measurement and led to power of 0.98. Inferential statistics, as independent t-test, paired t-test, and Chi-Square test, were performed to verify the expected relationships. RESULTS: The present study found that subjects in experimental group reported a lower role stress and less inclined to type A personality trait after aromatherapy massage with lavender. For control group, only less inclined to type A personality trait was reported after receiving massage. For burnout, a significant lower personal burnout and work-related burnout were reported after aromatherapy massage whereas only increased client-related burnout was reported in control group. For HRV, both the experimental and control groups reported higher SDNN and RMSSD in time domain after intervention. Contradictory HRT and PSI in time domain were significantly lower after intervention. In frequency domain of HRV, both groups reported significantly higher value in VLF and HF. In addition, the experimental group reported significantly higher value in TP and LF after intervention. CONCLUSIONS: Both the lavender aromatherapy massage and massage did show immediate effect on different dimensions of work stress, burnout, and HRV. These two interventions can be applied as routine leisure activities by personal preference to reduce stresses occurring in work environment.

6.
BMC Med Educ ; 19(1): 68, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832632

RESUMO

BACKGROUND: Pain assessment and treatment are key factors affecting the quality and safety of care for patients and capabilities related to them are crucial for new nursing staff. Consequently, we developed a multimedia-assisted teaching program for nursing newcomers' pain assessment learning to facilitate their practical pain assessment ability. The goal of this study was to evaluate a multimedia instructional program to boost new nurses' ability to conduct pain assessment and treatment, through simulated scenario instruction. METHODS: A quasi-experimental, pretest-posttest design with purposive sampling was used in this study. Eighty-six nurses were enrolled (control group, n = 39; experimental group, n = 47). Both groups underwent traditional pain assessment training in the classroom. The control group received lectures using PowerPoint files; while the experimental group undertook pain assessment training with the same content but delivered via multimedia-assisted instruction based on the ADDIE model. Pre- and post-instruction questionnaires relating to pain knowledge were completed. Participants' competence in performing pain assessment was subsequently evaluated one-month post instruction. RESULTS: The experimental group had significantly higher satisfaction scores (27.67 ± 3.76 vs. 31.36 ± 3.42, p < .01, respectively), and demonstrated greater knowledge of pain assessment (7.73 ± 0.67 vs. 7.08 ± 0.90, p < .05, respectively) than did the control group. Additionally, when evaluated at the one month follow-up, newcomers in the experimental group had better communication ability to perform pain assessment (26.58 ± 3.01 vs. 25.08 ± 3.32, p < .05, respectively). CONCLUSIONS: The program can improve nurses' pain assessment knowledge and competence. Newcomers were able to better respond to patients in pain, which is essential for pain assessment. This pilot study thus suggests a new, multimedia program for training nursing newcomers in pain assessment.


Assuntos
Competência Clínica/normas , Instrução por Computador , Educação Continuada em Enfermagem , Multimídia , Medição da Dor/normas , Avaliação Educacional , Feminino , Humanos , Masculino , Pesquisa em Educação em Enfermagem , Medição da Dor/enfermagem , Segurança do Paciente , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Qualidade da Assistência à Saúde , Adulto Jovem
7.
Hu Li Za Zhi ; 63(2): 26-32, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27026554

RESUMO

Clinical practice guidelines (CPGs), representing the current best-practice guidelines and recommendations for care, are supported by systematic review and evidence-based research. CPGs provide an effective and efficient approach to caring for patients and improving quality of care. Recently, the National Health Insurance Administration and National Institutes of Health developed CPGs for major diseases in Taiwan. This paper introduces the process that was used to develop one of these CPGs, the Taiwan Chronic Kidney Disease Clinical Guidelines, which was published in 2015. Further, we introduce the general development of published nursing guidelines in Taiwan. These CPGs are expected to initiate various renal-care guidelines and to promote the quality of renal care in the country.


Assuntos
Guias de Prática Clínica como Assunto , Insuficiência Renal Crônica/terapia , Humanos , Qualidade da Assistência à Saúde , Taiwan
8.
Hu Li Za Zhi ; 62(6): 48-56, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26645444

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is a potentially lethal respiratory sleep disorder. However, few studies have studied OSA women. PURPOSE: The purpose of the current study was to explore the life experiences of women with OSA. METHODS: A qualitative study using the grounded theory method was used to establish a descriptive theory. RESULTS: The results were expressed in terms of three stages with related categories. Stage 1: No interest days due to poor sleep, including "uncontrollable sleep", "perceived health deteriorates", and "poor female image harmed by snoring"; Stage 2: Indecision and disappointments during treatment seeking, including "doctor shopping", "being urged by others to seek medical help", and "being shocked by the severity of disease"; and Stage 3: Accepting a new lifestyle with a continuous positive pressure respirator, including "adaptation of the new sleep", "adequate sleep", and "secret worry of being an OSA woman". CONCLUSIONS: Based on the findings of the present study, medical knowledge and treatments related to OSA should be widely promoted with appropriate professional education and counseling services in order to enhance the awareness of patients and to facilitate their acceptance of the healing process using a continuous positive airway pressure respirator.


Assuntos
Apneia Obstrutiva do Sono/terapia , Adulto , Idoso , Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Feminino , Humanos , Pessoa de Meia-Idade , Pesquisa Qualitativa , Sono , Ventiladores Mecânicos
9.
PLoS One ; 8(12): e82821, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24376586

RESUMO

BACKGROUND: STAT3 activation is frequently detected in breast cancer and this pathway has emerged as an attractive molecular target for cancer treatment. Recent experimental evidence suggests ALDH-positive (ALDH(+)), or cell surface molecule CD44-positive (CD44(+)) but CD24-negative (CD24(-)) breast cancer cells have cancer stem cell properties. However, the role of STAT3 signaling in ALDH(+) and ALDH(+)/CD44(+)/CD24(-) subpopulations of breast cancer cells is unknown. METHODS AND RESULTS: We examined STAT3 activation in ALDH(+) and ALDH(+)/CD44(+)/CD24(-) subpopulations of breast cancer cells by sorting with flow cytometer. We observed ALDH-positive (ALDH(+)) cells expressed higher levels of phosphorylated STAT3 compared to ALDH-negative (ALDH(-)) cells. There was a significant correlation between the nuclear staining of phosphorylated STAT3 and the expression of ALDH1 in breast cancer tissues. These results suggest that STAT3 is activated in ALDH(+) subpopulations of breast cancer cells. STAT3 inhibitors Stattic and LLL12 inhibited STAT3 phosphorylation, reduced the ALDH(+) subpopulation, inhibited breast cancer stem-like cell viability, and retarded tumorisphere-forming capacity in vitro. Similar inhibition of STAT3 phosphorylation, and breast cancer stem cell viability were observed using STAT3 ShRNA. In addition, LLL12 inhibited STAT3 downstream target gene expression and induced apoptosis in ALDH(+) subpopulations of breast cancer cells. Furthermore, LLL12 inhibited STAT3 phosphorylation and tumor cell proliferation, induced apoptosis, and suppressed tumor growth in xenograft and mammary fat pad mouse models from ALDH(+) breast cancer cells. Similar in vitro and tumor growth in vivo results were obtained when ALDH(+) cells were further selected for the stem cell markers CD44(+) and CD24(-). CONCLUSION: These studies demonstrate an important role for STAT3 signaling in ALDH(+) and ALDH(+)/CD44(+)/CD24(-) subpopulations of breast cancer cells which may have cancer stem cell properties and suggest that pharmacologic inhibition of STAT3 represents an effective strategy to selectively target the cancer stem cell-like subpopulation.


Assuntos
Neoplasias da Mama/metabolismo , Antígeno CD24/metabolismo , Receptores de Hialuronatos/metabolismo , Isoenzimas/metabolismo , Retinal Desidrogenase/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Família Aldeído Desidrogenase 1 , Animais , Antraquinonas/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Óxidos S-Cíclicos/farmacologia , Feminino , Citometria de Fluxo , Humanos , Camundongos SCID , Fosforilação , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Sulfonamidas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
ACS Chem Neurosci ; 4(6): 930-9, 2013 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-23472668

RESUMO

The molecular chaperone, heat shock protein 70 (Hsp70), is an emerging drug target for treating neurodegenerative tauopathies. We recently found that one promising Hsp70 inhibitor, MKT-077, reduces tau levels in cellular models. However, MKT-077 does not penetrate the blood-brain barrier (BBB), limiting its use as either a clinical candidate or probe for exploring Hsp70 as a drug target in the central nervous system (CNS). We hypothesized that replacing the cationic pyridinium moiety in MKT-077 with a neutral pyridine might improve its clogP and enhance its BBB penetrance. To test this idea, we designed and synthesized YM-08, a neutral analogue of MKT-077. Like the parent compound, YM-08 bound to Hsp70 in vitro and reduced phosphorylated tau levels in cultured brain slices. Pharmacokinetic evaluation in CD1 mice showed that YM-08 crossed the BBB and maintained a brain/plasma (B/P) value of ∼0.25 for at least 18 h. Together, these studies suggest that YM-08 is a promising scaffold for the development of Hsp70 inhibitors suitable for use in the CNS.


Assuntos
Benzotiazóis/síntese química , Benzotiazóis/metabolismo , Barreira Hematoencefálica/metabolismo , Permeabilidade Capilar/fisiologia , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Proteínas de Choque Térmico HSP70/metabolismo , Piridinas/metabolismo , Tiazóis/metabolismo , Tiazolidinas/síntese química , Tiazolidinas/metabolismo , Proteínas tau/antagonistas & inibidores , Animais , Benzotiazóis/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Proteínas de Choque Térmico HSP70/química , Humanos , Células MCF-7 , Camundongos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Piridinas/química , Piridinas/farmacologia , Tiazóis/química , Tiazóis/farmacologia , Tiazolidinas/farmacologia , Proteínas tau/química , Proteínas tau/metabolismo
11.
Cancer Res ; 72(17): 4551-61, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22751135

RESUMO

Cancer stem cells (CSC; also called tumor-initiating cells) comprise tumor cell subpopulations that preserve the properties of quiescence, self-renewal, and differentiation of normal stem cells. In addition, CSCs are therapeutically important because of their key contributions toward drug resistance. The hypoxia-inducible transcription factor HIF1α is critical for CSC maintenance in mouse lymphoma. In this study, we showed that low concentrations of the HSP90 inhibitor 17-AAG eliminate lymphoma CSCs in vitro and in vivo by disrupting the transcriptional function of HIF1α, a client protein of HSP90. 17-AAG preferentially induced apoptosis and eliminated the colony formation capacity of mouse lymphoma CSCs and human acute myeloid leukemia (AML) CSCs. However, low concentrations of 17-AAG failed to eliminate highly proliferative lymphoma and AML cells (non-CSCs), in which the AKT-GSK3 signaling pathway is constitutively active. The heat shock transcription factor HSF1 is highly expressed in non-CSCs, but it was weakly expressed in lymphoma CSCs. However, siRNA-mediated attenuation of HSF1 abrogated the colony formation ability of both lymphoma and AML CSCs. This study supports the use of 17-AAG as a CSC targeting agent and, in addition, shows that HSF1 is an important target for elimination of both CSCs and non-CSCs in cancer.


Assuntos
Benzoquinonas/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Lactamas Macrocíclicas/farmacologia , Linfoma/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Inativação Gênica , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Fatores de Transcrição de Choque Térmico , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Leucemia Mieloide Aguda/metabolismo , Linfoma/genética , Camundongos , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
12.
J Nurs Scholarsh ; 44(1): 2-10, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22171781

RESUMO

PURPOSE: The purpose of this study was to compare the time needed to reach a specified temperature and the efficiency of two warming methods-warm cotton blankets and a radiant warmer-for hypothermia patients in a postanesthetic care unit (PACU) after spinal surgery. DESIGN: This study was conducted according to a quasi-experimental design. Data were collected from a medical referral center in northern Taiwan. A total of 130 post-spinal surgery patients with hypothermia were recruited in the study. METHODS: Of the 130 patients in the PACU, 65 were warmed by the radiant warmer (group R); whereas the other 65 patients were warmed by warm cotton blankets (group B). Tympanic temperature was measured for each patient every 10 min until it reached 36 °C in the PACU. Analysis of covariance and generalized estimating equation regression analysis were performed to compare the time needed to reach a specified temperature and the efficiency of the two warming methods, respectively. FINDINGS: Both groups were similar in their baseline characteristics. After adjusting for temperature upon arrival at the PACU, group R needed a significantly shorter time for rewarming to 36 °C than group B (F [1, 125]= 58.17, p < .001). The results of the generalized estimating equation also showed that the radiant warmer was more efficient than warm cotton blankets in increasing patients' body temperatures to 36 °C (χ2 = 37.44, p < .001). None of the patients appeared to have wound infections, and there were no differences in the length of hospital stay or medical costs for current hospitalization in both groups. CONCLUSIONS: Using the radiant warmer may be a more efficient method than providing warm cotton blankets for warming post-spinal surgery hypothermia patients in the PACU. CLINICAL RELEVANCE: For hospitals that are unable to use forced-air warming to warm postsurgical hypothermia patients in the PACU, the radiant warmer is a more efficient device to rewarm patients.


Assuntos
Hipotermia/terapia , Cuidados Pós-Operatórios/métodos , Sala de Recuperação , Reaquecimento/métodos , Coluna Vertebral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Roupas de Cama, Mesa e Banho , Equipamentos e Provisões Hospitalares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
13.
Eur J Oncol Nurs ; 14(4): 310-5, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20554475

RESUMO

PURPOSE OF THE RESEARCH: Oral cancer is a common malignant disease in Taiwan. The purpose of this prospective follow-up study was to identify the changes in quality of life for newly diagnosed oral cancer patients during the acute stage. METHODS AND SAMPLE: Subjects were recruited from the outpatient department (OPD) in a medical center located in the northern part of Taiwan. 22 subjects completed both the EORTC QLQ-C30 and the EORTC QLQ-H&N35 at diagnosis, postoperative discharge, and the first postoperative follow-up. In addition, 91% of the subjects received surgery only as their main treatment. KEY RESULTS: During the three assessments, as measured by the EORTC QLQ-C30, subjects reported that their physical function was much better at diagnosis than at both postoperative discharge and first postoperative follow-up. Their role functioning was much better at diagnosis than at postoperative discharge. Nevertheless, subjects reported better emotional functioning at the first postoperative follow-up than at the other two points of assessment. Only less financial difficulty was reported in the first postoperative follow-up than at diagnosis and postoperative discharge. For QLQ-H&N35, subjects reported that several symptoms (i.e., swallowing) were more severe at postoperative discharge than at diagnosis. Usage of nutritional supplements at first postoperative follow-up was higher than that at diagnosis. CONCLUSION: Newly diagnosed oral cancer patients reported significant changes in certain domains of both the EORTC QLQ-C30 and QLQ-H&N35. Health professionals need to identify the pattern of changes and to provide supportive care to these new oral cancer patients throughout the treatment process, especially during the planning of discharge.


Assuntos
Adaptação Psicológica , Atitude Frente a Saúde , Neoplasias Bucais/psicologia , Qualidade de Vida/psicologia , Atividades Cotidianas/psicologia , Doença Aguda , Adulto , Emoções , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/complicações , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/terapia , Pesquisa Metodológica em Enfermagem , Alta do Paciente , Estudos Prospectivos , Papel (figurativo) , Estatísticas não Paramétricas , Inquéritos e Questionários , Taiwan
14.
Clin Cancer Res ; 16(9): 2580-90, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-20388854

RESUMO

PURPOSE: The existence of cancer stem cells (CSCs) in breast cancer has profound implications for cancer prevention. In this study, we evaluated sulforaphane, a natural compound derived from broccoli/broccoli sprouts, for its efficacy to inhibit breast CSCs and its potential mechanism. EXPERIMENTAL DESIGN: Aldefluor assay and mammosphere formation assay were used to evaluate the effect of sulforaphane on breast CSCs in vitro. A nonobese diabetic/severe combined immunodeficient xenograft model was used to determine whether sulforaphane could target breast CSCs in vivo, as assessed by Aldefluor assay, and tumor growth upon cell reimplantation in secondary mice. The potential mechanism was investigated using Western blotting analysis and beta-catenin reporter assay. RESULTS: Sulforaphane (1-5 micromol/L) decreased aldehyde dehydrogenase-positive cell population by 65% to 80% in human breast cancer cells (P < 0.01) and reduced the size and number of primary mammospheres by 8- to 125-fold and 45% to 75% (P < 0.01), respectively. Daily injection with 50 mg/kg sulforaphane for 2 weeks reduced aldehyde dehydrogenase-positive cells by >50% in nonobese diabetic/severe combined immunodeficient xenograft tumors (P = 0.003). Sulforaphane eliminated breast CSCs in vivo, thereby abrogating tumor growth after the reimplantation of primary tumor cells into the secondary mice (P < 0.01). Western blotting analysis and beta-catenin reporter assay showed that sulforaphane downregulated the Wnt/beta-catenin self-renewal pathway. CONCLUSIONS: Sulforaphane inhibits breast CSCs and downregulates the Wnt/beta-catenin self-renewal pathway. These findings support the use of sulforaphane for the chemoprevention of breast cancer stem cells and warrant further clinical evaluation.


Assuntos
Brassica/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Plântula/química , Tiocianatos/farmacologia , Aldeído Desidrogenase/metabolismo , Família Aldeído Desidrogenase 1 , Animais , Anticarcinógenos/administração & dosagem , Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Feminino , Humanos , Isoenzimas/metabolismo , Isotiocianatos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Retinal Desidrogenase , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Sulfóxidos , Tiocianatos/administração & dosagem , Proteínas Wnt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
15.
Mol Pharm ; 6(4): 1152-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19438225

RESUMO

(-)-Epigallocatechin-3-gallate [(-)-EGCG], the most abundant polyphenolic catechin in green tea, showed chemoprevention and anticancer activities. (-)-EGCG was reported to bind to the C-terminal domain of heat shock protein 90 (Hsp90). The purpose of this study is to investigate (-)-EGCG as a novel Hsp90 inhibitor to impair Hsp90 superchaperone complex for simultaneous downregulation of oncogenic proteins in pancreatic cancer cells. MTS assay showed that (-)-EGCG exhibited antiproliferative activity against pancreatic cancer cell line Mia Paca-2 in vitro with IC50 below 50 muM. (-)-EGCG increased caspase-3 activity up to 3-fold in a time- and concentration-dependent manner. Western blotting analysis demonstrated that (-)-EGCG induced downregulation of oncogenic Hsp90 client proteins by approximately 70-95%, including Akt, Cdk4, Raf-1, Her-2, and pERK. Co-immunoprecipitation showed that (-)-EGCG decreased the association of cochaperones p23 and Hsc70 with Hsp90 by more than 50%, while it had little effect on the ATP binding to Hsp90. Proteolytic fingerprinting assay confirmed direct binding between (-)-EGCG and the Hsp90 C-terminal domain. These data suggest that the binding of (-)-EGCG to Hsp90 impairs the association of Hsp90 with its cochaperones, thereby inducing degradation of Hsp90 client proteins, resulting antiproliferating effects in pancreatic cancer cells.


Assuntos
Anticarcinógenos/farmacologia , Catequina/análogos & derivados , Proteínas de Choque Térmico HSC70/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias Pancreáticas/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Western Blotting , Catequina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas de Choque Térmico HSC70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Imunoprecipitação , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia
16.
Hu Li Za Zhi ; 55(5): 56-63, 2008 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-18836975

RESUMO

About 8,000 people die every year in Taiwan as a result of nosocomial infection. Clinically, there is a high possibility for patients to contract nosocomial infection if medical equipment is not completely sterilized. In order to provide care and safety to patients in the operating room, increase management effectiveness and efficiency, and to reduce equipment operating costs, a project was developed to improve operating room management through data collection and analysis. A computerized barcode operational system for packages of surgical instruments was developed and executed throughout an entire operating room. The results showed that average time spent searching for surgical instruments decreased by 2,872 minutes (47.8hrs/month), 150% of the target figure; computerized monitoring of equipment expiration dates reduced total cost by 29.2% abnormal recognition of equipment tags was reduced to 0%. This project is the first one of its kind in the world.


Assuntos
Processamento Eletrônico de Dados/métodos , Salas Cirúrgicas/organização & administração , Instrumentos Cirúrgicos , Salas Cirúrgicas/economia , Fatores de Tempo
17.
ACS Chem Biol ; 3(10): 635-44, 2008 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-18831589

RESUMO

High-throughput screening of National Cancer Institute libraries of synthetic and natural compounds identified the vinylogous ureas 2-amino-5,6,7,8-tetrahydro-4 H-cyclohepta[ b]thiophene-3-carboxamide (NSC727447) and N-[3-(aminocarbonyl)-4,5-dimethyl-2-thienyl]-2-furancarboxamide (NSC727448) as inhibitors of the ribonuclease H (RNase H) activity of HIV-1 and HIV-2 reverse transcriptase (RT). A Yonetani-Theorell analysis demonstrated that NSC727447, and the active-site hydroxytropolone RNase H inhibitor beta-thujaplicinol were mutually exclusive in their interaction with the RNase H domain. Mass spectrometric protein footprinting of the NSC727447 binding site indicated that residues Cys280 and Lys281 in helix I of the thumb subdomain of p51 were affected by ligand binding. Although DNA polymerase and pyrophosphorolysis activities of HIV-1 RT were less sensitive to inhibition by NSC727447, protein footprinting indicated that NSC727447 occupied the equivalent region of the p66 thumb. Site-directed mutagenesis using reconstituted p66/p51 heterodimers substituted with natural or non-natural amino acids indicates that altering the p66 RNase H primer grip significantly affects inhibitor sensitivity. NSC727447 thus represents a novel class of RNase H antagonists with a mechanism of action differing from active site, divalent metal-chelating inhibitors that have been reported.


Assuntos
Furanos/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , Inibidores da Transcriptase Reversa/farmacologia , Ribonuclease H do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Tiofenos/farmacologia , Ureia/análogos & derivados , Sítios de Ligação , Técnicas de Química Combinatória , Furanos/química , Transcriptase Reversa do HIV/química , Humanos , Inibidores da Transcriptase Reversa/química , Ribonuclease H do Vírus da Imunodeficiência Humana/química , Tiofenos/química
18.
Nucleic Acids Res ; 34(18): 5157-65, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16998183

RESUMO

Indolicidin is a host defense tridecapeptide that inhibits the catalytic activity of HIV-1 integrase in vitro. Here we have elucidated its mechanism of integrase inhibition. Using crosslinking and mass spectrometric footprinting approaches, we found that indolicidin interferes with formation of the catalytic integrase-DNA complex by directly binding DNA. Further characterization revealed that the peptide forms covalent links with abasic sites. Indolicidin crosslinks single- or double-stranded DNAs and various positions of the viral cDNA with comparable efficiency. Using truncated and chemically modified peptides, we show that abasic site crosslinking is independent of the PWWP motif but involves the indolicidin unique lysine residue and the N- and C- terminal NH2 groups. Because indolicidin can also inhibit topoisomerase I, we believe that multiple actions at the level of DNA might be a common property of antimicrobial peptides.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , DNA/química , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Sítios de Ligação , DNA/metabolismo , DNA Topoisomerases Tipo I/metabolismo , DNA de Cadeia Simples/química , DNA de Cadeia Simples/metabolismo , Integrase de HIV/metabolismo , Lisina/química , Ligação Proteica , Bases de Schiff/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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