Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 72
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-38575735

RESUMO

This paper describes the successful implementation of Measurement-Based Care (MBC) within a Partial Hospitalization Program (PHP) for children and adolescents. Measurement-based care (MBC), the practice of using patient-reported measures routinely to inform decision-making, is associated with improved clinical outcomes for behavioral health patients (Jong et al., Clinical Psychology Review 85, 2021; Fortney & Sladek, 2015). MBC holds great promise in partial hospital programs (PHP) to improve outcomes, yet implementation strategies are as complex as the setting itself. This paper provides a case study example of MBC implementation in a PHP for youth. Over the course of 18 months, an interdisciplinary staff of approximately 20 behavioral health professionals provided partial hospitalization level of care to 633 (39% in-person, 61% telehealth) youth from ages 5 to 18 years old. MBC in this setting incorporated daily patient self-report and weekly caregiver-reported measurements. This descriptive reconstruction, which includes examples of the data that were used during the implementation project, illustrates specific barriers and facilitators in a successful implementation in the local PHP setting. Implementation strategies to address workflow integration, leadership and supervision, and coaching are described, including evolution of these strategies over the course of implementation. Practical considerations for implementing MBC in youth PHP settings are discussed. Finally, the authors explore the potential relationships between the data-driven MBC model of decision making and the development of resilient organizations.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38662178

RESUMO

Measurement-based care (MBC) research and practice, including clinical workflows and systems to support MBC, are grounded in adult-serving mental health systems. MBC research evidence is building in child and adolescent services, but MBC practice is inherently more complex due to identified client age, the family system and the need to involve multiple reporters. This paper seeks to address a gap in the literature by providing practical guidance for youth-serving clinicians implementing MBC with children and their families. We focus on MBC as a data-informed, client-centered communication process, and present three key strategies to enhance usual care child and adolescent psychotherapy via developmentally-appropriate MBC. These strategies include (1) go beyond standardized measures; (2) lean into discrepancies; and (3) get curious together. Case-based examples drawn from various child-serving settings illustrate these key strategies of MBC in child psychotherapy.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38733413

RESUMO

We face increasing demand for greater access to effective routine mental health services, including telehealth. However, treatment outcomes in routine clinical practice are only about half the size of those reported in controlled trials. Progress feedback, defined as the ongoing monitoring of patients' treatment response with standardized measures, is an evidence-based practice that continues to be under-utilized in routine care. The aim of the current review is to provide a summary of the current evidence base for the use of progress feedback, its mechanisms of action and considerations for successful implementation. We reviewed ten available meta-analyses, which report small to medium overall effect sizes. The results suggest that adding feedback to a wide range of psychological and psychiatric interventions (ranging from primary care to hospitalization and crisis care) tends to enhance the effectiveness of these interventions. The strongest evidence is for patients with common mental health problems compared to those with very severe disorders. Effect sizes for not-on-track cases, a subgroup of cases that are not progressing well, are found to be somewhat stronger, especially when clinical support tools are added to the feedback. Systematic reviews and recent studies suggest potential mechanisms of action for progress feedback include focusing the clinician's attention, altering clinician expectations, providing new information, and enhancing patient-centered communication. Promising approaches to strengthen progress feedback interventions include advanced systems with signaling technology, clinical problem-solving tools, and a broader spectrum of outcome and progress measures. An overview of methodological and implementation challenges is provided, as well as suggestions for addressing these issues in future studies. We conclude that while feedback has modest effects, it is a small and affordable intervention that can potentially improve outcomes in psychological interventions. Further research into mechanisms of action and effective implementation strategies is needed.

4.
Artigo em Inglês | MEDLINE | ID: mdl-37768486

RESUMO

Intended for researchers and clinical leaders, this article suggests that embedded program evaluation is a good fit with the desired features of practice-oriented research. The systematic nature of evaluation that is built into the operational workflow of a practice setting may increase the diversity of methods available to explore processes and outcomes of interest. We propose a novel conceptual framework that uses a human-centered systems lens to foster such embedded evaluation in clinical routine. This approach emphasizes the evaluator-practitioner partnership to build confidence in the bi-directional learning of practice-based evidence with evidence-based practice. The iterative cycles inherent to design thinking are aimed at developing better evaluation questions. The attention to structure and context inherent to systems thinking is intended to support meaningful perspectives in the naturally complex world of health care. Importantly, the combined human-centered systems lens can create greater awareness of the influence of individual and systemic biases that exist in any endeavor or institution that involves people. Recommended tools and strategies include systems mapping, program theory development, and visual facilitation using a logic model to represent the complexity of mental health treatment for communication, shared understanding, and connection to the broader evidence base. To illustrate elements of the proposed conceptual framework, two case examples are drawn from routine outcome monitoring (ROM) and progress feedback. We conclude with questions for future collaboration and research that may strengthen the partnership of evaluators and practitioners as a community of learners in service of local and system-level improvement.

5.
Artigo em Inglês | MEDLINE | ID: mdl-37646966

RESUMO

Implementation science is the scientific study of methods to promote the uptake of research findings and other evidence-based practices in routine care, with the goal of improving the quality and effectiveness of health services (Bauer et al., 2015). In addition to this common goal, practice-oriented psychotherapy research (and researchers) and implementation science (and scientists) share a common focus on the people and the places where treatment happens. Thus, there exists strong potential for combining these two approaches. In this article, we provide a primer on implementation science for psychotherapy researchers and highlight important areas and examples of convergence and complementarity between implementation science and practice-oriented psychotherapy research. Specifically, we (a) define and describe the core features of implementation science; (b) discuss similarities and areas of complementarity between implementation science and practice-oriented psychotherapy research; (c) discuss a case example that exemplifies the integration of implementation science and practice-oriented research; and (d) propose directions for future research and collaborations that leverage both implementation science and practice-oriented research.

6.
Artigo em Inglês | MEDLINE | ID: mdl-37917313

RESUMO

BACKGROUND: Progress feedback, also known as measurement-based care (MBC), is the routine collection of patient-reported measures to monitor treatment progress and inform clinical decision-making. Although a key ingredient to improving mental health care, sustained use of progress feedback is poor. Integration into everyday workflow is challenging, impacted by a complex interrelated set of factors across patient, clinician, organizational, and health system levels. This study describes the development of a qualitative coding scheme for progress feedback implementation that accounts for the dynamic nature of barriers and facilitators across multiple levels of use in mental health settings. Such a coding scheme may help promote a common language for researchers and implementers to better identify barriers that need to be addressed, as well as facilitators that could be supported in different settings and contexts. METHODS: Clinical staff, managers, and leaders from two Dutch, three Norwegian, and four mental health organizations in the USA participated in semi-structured interviews on how intra- and extra-organizational characteristics interact to influence the use of progress feedback in clinical practice, supervision, and program improvement. Interviews were conducted in the local language, then translated to English prior to qualitative coding. RESULTS: A team-based consensus coding approach was used to refine an a priori expert-informed and literature-based qualitative scheme to incorporate new understandings and constructs as they emerged. First, this hermeneutic approach resulted in a multi-level coding scheme with nine superordinate categories and 30 subcategories. Second-order axial coding established contextually sensitive categories for barriers and facilitators. CONCLUSIONS: The primary outcome is an empirically derived multi-level qualitative coding scheme that can be used in progress feedback implementation research and development. It can be applied across contexts and settings, with expectations for ongoing refinement. Suggestions for future research and application in practice settings are provided. Supplementary materials include the coding scheme and a detailed playbook.

7.
J Clin Child Adolesc Psychol ; 51(4): 375-388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35263198

RESUMO

Mental health organizations that serve youth are under pressure to adopt measurement-based care (MBC), defined as the continuous collection of client-report data used to support clinical decision-making as part of standard care. However, few frameworks exist to help leadership ascertain how to select an MBC approach for a clinical setting. This paper seeks to define how an MBC approach can display clinical utility to provide such a framework. Broadly, we define clinical utility as evidence that an MBC approach assists stakeholders in fulfilling clinical goals related to care quality (i.e., improve client-clinician alliance and clinical outcomes) at the client (i.e., youth and caregiver), clinician, supervisor, and administrator levels. More specifically, our definition of clinical utility is divided into two categories relevant to the usability and usefulness of an MBC approach for a specific setting: (a) implementability (i.e., evidence indicating ease of use in a clinical setting) and (b) usefulness in aiding clinical activities (i.e., evidence indicating the potential to improve communication and make clinical activities related to care quality easier or more effective). These categories provide valuable information about how easy an MBC approach is to use and the potential benefits that the MBC data will confer. To detail how we arrived at this definition, we review prior definitions of clinical utility, discuss how previous definitions inform our definition of clinical utility for MBC, and provide examples of how the concept of clinical utility can be applied to MBC. We finish with a discussion of future research directions.


Assuntos
Serviços de Saúde Mental , Adolescente , Comunicação , Humanos
8.
Adm Policy Ment Health ; 48(2): 250-265, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32656631

RESUMO

Mental health clinicians and administrators are increasingly asked to collect and report treatment outcome data despite numerous challenges to select and use instruments in routine practice. Measurement-based care (MBC) is an evidence-based practice for improving patient care. We propose that data collected from MBC processes with patients can be strategically leveraged by agencies to also support clinicians and respond to accountability requirements. MBC data elements are outlined using the Precision Mental Health Framework (Bickman et al. in Adm Policy Mental Health Mental Health Serv Res 43:271-276, 2016), practical guidance is provided for agency administrators, and conceptual examples illustrate strategic applications of one or more instruments to meet various needs throughout the organization.


Assuntos
Serviços de Saúde Mental , Saúde Mental , Humanos , Objetivos Organizacionais , Assistência ao Paciente
9.
Adm Policy Ment Health ; 47(5): 788-794, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32323215

RESUMO

With a career spanning more than half a century, Leonard Bickman has contributed to improving children's mental health through research on innovative interventions, such as measurement-based care, and service-level initiatives, including systems of care. Len's highly productive career in children's mental health services research is founded in his influence on the science of program evaluation, particularly in the area of program theory. This article provides an abridged and combined version of a video interview with Len dated April 16, 2019 and written responses to a series of questions posed to Len in advance of the festschrift held in his honor at Johns Hopkins Bloomberg School of Public Health on May 11, 2018.


Assuntos
Pesquisa sobre Serviços de Saúde/organização & administração , Serviços de Saúde Mental/organização & administração , Adolescente , Criança , Humanos
10.
Adm Policy Ment Health ; 47(5): 649-654, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32715428

RESUMO

This introductory article describes the genesis of the Festschrift for Leonard Bickman and of this Festschrift special issue entitled, The Future of Children's Mental Health Services. The special issue includes a collection of 11 original children's mental health services research articles, broadly organized in accordance with three themes (i.e., Improving Precision and Use of Service Data to Guide Policy and Practice, Implementation and Dissemination, and Preparing for Innovation), followed by an interview-style article with Bickman. Then follows a featured manuscript by Bickman himself, three invited commentaries, and a compilation of letters and notes in which colleagues reflect on his career and on their experiences of him. The introduction concludes with a few thoughts about the future of children's mental health services portended by the extraordinary scholarly contributions of Bickman and those who have been inspired by him.


Assuntos
Saúde da Criança , Transtornos Mentais/terapia , Serviços de Saúde Mental/organização & administração , Big Data , Necessidades e Demandas de Serviços de Saúde/organização & administração , Humanos , Aprendizado de Máquina , Políticas
12.
Adm Policy Ment Health ; 43(3): 286-91, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25344848

RESUMO

Measurement feedback systems (MFSs) are increasingly recognized as evidence-based treatments for improving mental health outcomes, in addition to being a useful administrative tool for service planning and reporting. Promising research findings have driven practice administrators and policymakers to emphasize the incorporation of outcomes monitoring into electronic health systems. To promote MFS integrity and protect against potentially negative outcomes, it is vital that adoption and implementation be guided by scientifically rigorous yet practical principles. In this point of view, the authors discuss and provide examples of three user-centered and theory-based principles: emphasizing integration with clinical values and workflow, promoting administrative leadership with the 'golden thread' of data-informed decision-making, and facilitating sustainability by encouraging innovation. In our experience, enacting these principles serves to promote sustainable implementation of MFSs in the community while also allowing innovation to occur, which can inform improvements to guide future MFS research.


Assuntos
Tomada de Decisões , Avaliação de Resultados em Cuidados de Saúde/métodos , Melhoria de Qualidade , Tomada de Decisão Clínica , Retroalimentação , Humanos , Serviços de Saúde Mental/organização & administração , Serviços de Saúde Mental/normas , Inovação Organizacional , Avaliação de Resultados em Cuidados de Saúde/organização & administração , Avaliação de Programas e Projetos de Saúde , Fluxo de Trabalho
13.
Adm Policy Ment Health ; 43(3): 426-40, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25735619

RESUMO

Measurement feedback systems (MFSs) have been proposed as a means of improving practice. The present study examined the implementation of a MFS, the Contextualized Feedback System (CFS), in two community-based clinic sites. Significant implementation differences across sites provided a basis for examining factors that influenced clinician uptake of CFS. Following the theoretical implementation framework of Aarons et al. (Adm Policy Mental Health Mental Health Serv Res 38(1):4-23, 2011), we coded qualitative data collected from eighteen clinicians (13 from Clinic U and 5 from Clinic R) who participated in semi-structured interviews about their experience with CFS implementation. Results suggest that clinicians at both clinics perceived more barriers than facilitators to CFS implementation. Interestingly, clinicians at the higher implementing clinic reported a higher proportion of barriers to facilitators (3:1 vs. 2:1); however, these clinicians also reported a significantly higher level of organizational and leadership supports for CFS implementation. Implications of these findings are discussed.


Assuntos
Atitude do Pessoal de Saúde , Retroalimentação , Serviços de Saúde Mental , Avaliação de Resultados em Cuidados de Saúde , Adulto , Feminino , Humanos , Liderança , Masculino , Inovação Organizacional , Pesquisa Qualitativa
14.
Adm Policy Ment Health ; 43(3): 410-25, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25876736

RESUMO

A randomized experiment was conducted in two outpatient clinics evaluating a measurement feedback system called contextualized feedback systems. The clinicians of 257 Youth 11-18 received feedback on progress in mental health symptoms and functioning either every 6 months or as soon as the youth's, clinician's or caregiver's data were entered into the system. The ITT analysis showed that only one of the two participating clinics (Clinic R) had an enhanced outcome because of feedback, and only for the clinicians' ratings of youth symptom severity on the SFSS. A dose-response effect was found only for Clinic R for both the client and clinician ratings. Implementation analyses showed that Clinic R had better implementation of the feedback intervention. Clinicians' questionnaire completion rate and feedback viewing at Clinic R were 50 % higher than clinicians at Clinic U. The discussion focused on the differences in implementation at each site and how these differences may have contributed to the different outcomes of the experiment.


Assuntos
Retroalimentação , Transtornos Mentais/terapia , Serviços de Saúde Mental , Avaliação de Resultados em Cuidados de Saúde , Adolescente , Criança , Feminino , Humanos , Masculino , Avaliação de Processos em Cuidados de Saúde , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Psychother Res ; 25(6): 678-93, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26337327

RESUMO

OBJECTIVE: This study explored how clinician-reported content addressed in treatment sessions was predicted by clinician feedback group and multi-informant cumulative problem alerts that appeared in computerized feedback reports for 299 clients aged 11-18 years receiving home-based community mental health treatment. METHOD: Measures included a clinician report of content addressed in sessions and additional measures of treatment progress and process (e.g., therapeutic alliance) completed by clinicians, clients, and their caregivers. Item responses in the top 25th percentile in severity from these measures appeared as "problem alerts" on corresponding computerized feedback reports. Clinicians randomized to the feedback group received feedback weekly while the control group did not. Analyses were conducted using the Cox proportional hazards regression for recurrent events. RESULTS: For all content domains, the results of the survival analyses indicated a robust effect of the feedback group on addressing specific content in sessions, with feedback associated with shorter duration to first occurrence and increased likelihood of addressing or focusing on a topic compared to the non-feedback group. CONCLUSION: There appears to be an important relationship between feedback and cumulative problem alerts reported by multiple informants as they influence session content.


Assuntos
Serviços Comunitários de Saúde Mental/métodos , Retroalimentação , Avaliação de Processos e Resultados em Cuidados de Saúde/métodos , Psicoterapia/métodos , Adolescente , Cuidadores , Criança , Serviços Comunitários de Saúde Mental/normas , Pesquisa sobre Serviços de Saúde , Serviços de Assistência Domiciliar/normas , Humanos , Avaliação de Processos e Resultados em Cuidados de Saúde/normas , Psicoterapia/normas
16.
Psychotherapy (Chic) ; 60(1): 1-16, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35771518

RESUMO

Professional practice guidelines (PPGs) are intended to promote a high level of professional practice and serve as an educational resource, providing pragmatic guidance in a clinical area for psychologists. Measurement-based care (MBC) is an evidence-based psychological practice with accumulating empirical support and alignment with patient-centered care. In connection with the American Psychological Association's Advisory Committee for Measurement-based Care and the Mental and Behavioral Health Registry, this article outlines various lines of support for the development and implementation of an MBC PPG. In addition to research evidence, we address the demonstrated need of this guideline across three domains: public benefit, professional guidance, and legal and regulatory issues. Consistent with the aspirational spirit of a PPG, this article proposes a draft PPG statement and highlights how an MBC PPG would improve service delivery, facilitate implementation of an evidence-based practice associated with symptom reduction, improved retention, and greater patient satisfaction, as well as create a framework that will better align changes in reimbursement models with patients' and providers' treatment goals. We also identify key future directions and critical gaps in MBC science and implementation that require attention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Prática Clínica Baseada em Evidências , Satisfação do Paciente , Humanos , Estados Unidos , Prática Profissional , Sociedades Científicas
17.
JAMA Netw Open ; 6(9): e2336023, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37755828

RESUMO

Importance: Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice. Objective: To assess the reporting of observational studies that explicitly aimed to emulate a target trial. Evidence Review: We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation. Findings: A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation. Conclusion and Relevance: In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.


Assuntos
Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Hypertens Res ; 45(10): 1643-1652, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35882996

RESUMO

Randomized clinical trials attempt to reduce bias and create similar groups at baseline to infer causal effects. In meta-analyses, baseline imbalance may threaten the validity of the treatment effects. This meta-epidemiological study examined baseline imbalance in comparisons of exercise and antihypertensive medicines. Baseline data for systolic blood pressure, diastolic blood pressure, and age were extracted from a network meta-analysis of 391 randomized trials comparing exercise types and antihypertensive medicines. Fixed-effect meta-analyses were used to determine the presence of baseline imbalance and/or inconsistency. Meta-regression analyses were conducted on sample size, the risk of bias for allocation concealment, and whether data for all randomized participants were presented at baseline. In one exercise comparison, the resistance group was 0.3 years younger than the control group (95% confidence interval 0.6 to 0.1). Substantial inconsistency was observed in other exercise comparisons. Less data were available for medicines, but there were no occurrences of baseline imbalance and only a few instances of inconsistency. Several moderator analyses identified significant associations. We identified baseline imbalance as well as substantial inconsistency in exercise comparisons. Researchers should consider conducting meta-analyses of key prognostic variables at baseline to ensure balance across trials.


Assuntos
Anti-Hipertensivos , Exercício Físico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Breast Cancer Res ; 13(5): R102, 2011 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-22023734

RESUMO

INTRODUCTION: Cationic antimicrobial peptides (CAPs) defend against microbial pathogens; however, certain CAPs also exhibit anticancer activity. The purpose of this investigation was to determine the effect of the pleurocidin-family CAPs, NRC-03 and NRC-07, on breast cancer cells. METHODS: MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) and acid phosphatase cell-viability assays were used to assess NRC-03- and NRC-07-mediated killing of breast carcinoma cells. Erythrocyte lysis was determined with hemolysis assay. NRC-03 and NRC-07 binding to breast cancer cells and normal fibroblasts was assessed with fluorescence microscopy by using biotinylated-NRC-03 and -NRC-07. Lactate dehydrogenase-release assays and scanning electron microscopy were used to evaluate the effect of NRC-03 and NRC-07 on the cell membrane. Flow-cytometric analysis of 3,3'-dihexyloxacarbocyanine iodide- and dihydroethidium-stained breast cancer cells was used to evaluate the effects of NRC-03 and NRC-07 on mitochondrial membrane integrity and reactive oxygen species (ROS) production, respectively. Tumoricidal activity of NRC-03 and NRC-07 was evaluated in NOD SCID mice bearing breast cancer xenografts. RESULTS: NRC-03 and NRC-07 killed breast cancer cells, including drug-resistant variants, and human mammary epithelial cells but showed little or no lysis of human dermal fibroblasts, umbilical vein endothelial cells, or erythrocytes. Sublethal doses of NRC-03 and, to a lesser extent, NRC-07 significantly reduced the median effective concentration (EC50) of cisplatin for breast cancer cells. NRC-03 and NRC-07 bound to breast cancer cells but not fibroblasts, suggesting that killing required peptide binding to target cells. NRC-03- and NRC-07-mediated killing of breast cancer cells correlated with expression of several different anionic cell-surface molecules, suggesting that NRC-03 and NRC-07 bind to a variety of negatively-charged cell-surface molecules. NRC-03 and NRC-07 also caused significant and irreversible cell-membrane damage in breast cancer cells but not in fibroblasts. NRC-03- and NRC-07-mediated cell death involved, but did not require, mitochondrial membrane damage and ROS production. Importantly, intratumoral administration of NRC-03 and NRC-07 killed breast cancer cells grown as xenografts in NOD SCID mice. CONCLUSIONS: These findings warrant the development of stable and targeted forms of NRC-03 and/or NRC-07 that might be used alone or in combination with conventional chemotherapeutic drugs for the treatment of breast cancer.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proteínas de Peixes/farmacologia , Sequência de Aminoácidos , Animais , Neoplasias da Mama/patologia , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Membrana Celular/efeitos dos fármacos , Células Cultivadas , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Camundongos , Camundongos SCID , Membranas Mitocondriais/efeitos dos fármacos , Dados de Sequência Molecular , Espécies Reativas de Oxigênio/metabolismo , Veias Umbilicais/citologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Antimicrob Agents Chemother ; 55(11): 5205-13, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21844316

RESUMO

In this study, we constructed and evaluated a target-specific, salt-resistant antimicrobial peptide (AMP) that selectively targeted Streptococcus mutans, a leading cariogenic pathogen. The rationale for creating such a peptide was based on the addition of a targeting domain of S. mutans ComC signaling peptide pheromone (CSP) to a killing domain consisting of a portion of the marine-derived, broad-spectrum AMP pleurocidin to generate a target-specific AMP. Here, we report the results of our assessment of such fusion peptides against S. mutans and two closely related species. The results showed that nearly 95% of S. mutans cells lost viability following exposure to fusion peptide IMB-2 (5.65 µM) for 15 min. In contrast, only 20% of S. sanguinis or S. gordonii cells were killed following the same exposure. Similar results were also observed in dual-species mixed cultures of S. mutans with S. sanguinis or S. gordonii. The peptide-guided killing was further confirmed in S. mutans biofilms and was shown to be dose dependent. An S. mutans mutant defective in the CSP receptor retained 60% survival following exposure to IMB-2, suggesting that the targeted peptide predominantly bound to the CSP receptor to mediate killing in the wild-type strain. Our work confirmed that IMB-2 retained its activity in the presence of physiological or higher salt concentrations. In particular, the fusion peptide showed a synergistic killing effect on S. mutans with a preventive dose of NaF. In addition, IMB-2 was relatively stable in the presence of saliva containing 1 mM EDTA and did not cause any hemolysis. We also found that replacement of serine-14 by histidine improved its activity at lower pH. Because of its effectiveness, salt resistance, and minimal toxicity to host cells, this novel target-specific peptide shows promise for future development as an anticaries agent.


Assuntos
Anti-Infecciosos/farmacologia , Peptídeos/farmacologia , Streptococcus mutans/efeitos dos fármacos , Anti-Infecciosos/química , Ácido Edético/química , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Peptídeos/química , Cloreto de Sódio/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA