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1.
J Clin Nurs ; 30(1-2): 136-144, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33090623

RESUMO

BACKGROUND: Agitation in older people is commonly associated with cognitive decline, complex medical diagnoses and polypharmacy. Impaired communication and comprehension within a dementia trajectory adds complexity to assessment and management. Despite high prevalence, agitated behaviours remain challenging to manage in residential aged care settings. AIM: To explore staff perceptions of agitation in residents of aged care facilities, including the influence of dementia, when selecting management strategies to reduce agitated behaviour. DESIGN: Qualitative descriptive. METHODS: Semi-structured interviews with 11 aged care staff were conducted at two aged care sites. Transcripts were examined using content analysis to identify common issues and categories. The study complied with COREQ guidelines (see. Appendix S1). RESULTS: Participants reported managing resident agitation at least once per shift; most frequently manifesting as wandering, restlessness or aggression. Management strategies included distraction, providing space, knowing the resident, identifying causative factors, spending individual time and if necessary medication administration. Agitation management was more challenging for residents with dementia due to impaired communication or comprehension of instruction. CONCLUSIONS: While participants strived to deliver individualized person-centred care, this was difficult given time and resource constraints. Contemporary management of agitation therefore remains variable in everyday practice, with resident preference used when causative factors were known. Conversely, for residents with impaired communication and/or comprehension, distraction and chemical restraint were commonly used. Nuanced education for assessment and management is recommended to better address this unmet need for some residents. RELEVANCE TO CLINICAL PRACTICE: For optimal care, appropriate allocation of time and resources is necessary to identify causative and contextual factors for individual residents. Recommendations are for additional staff training in communication and attitude, and collaborating with frontline staff to develop a practical guide for management of agitation in aged care. These simple initiatives may help to improve consistency of care delivery and resident outcomes.


Assuntos
Demência , Casas de Saúde , Idoso , Idoso de 80 Anos ou mais , Demência/terapia , Humanos , Percepção , Agitação Psicomotora/terapia , Pesquisa Qualitativa
2.
Gerontol Geriatr Educ ; 42(3): 399-422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33252017

RESUMO

Appropriately skilled staff are required to meet the health and care needs of aging populations yet, shared competencies for the workforce are lacking. This study aimed to develop multidisciplinary core competencies for health and aged care workers in Australia through a scoping review and Delphi survey. The scoping review identified 28 records which were synthesized through thematic analysis into draft domains and measurable competencies. Consensus was sought from experts over two Delphi rounds (n = 111 invited; n = 59 round one; n = 42 round two). Ten domains with 66 core competencies, to be interpreted and applied according to the worker's scope of practice were finalized. Consensus on multidisciplinary core competencies which are inclusive of a broad range of registered health professionals and unregistered aged care workers was achieved. Shared knowledge, attitudes, and skills across the workforce may improve the standard and coordination of person-centered, integrated care for older Australians from diverse backgrounds.


Assuntos
Geriatria , Idoso , Envelhecimento , Austrália , Competência Clínica , Técnica Delphi , Geriatria/educação , Humanos , Recursos Humanos
3.
Aust Health Rev ; 37(1): 112-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23257197

RESUMO

As well as providing primary health care services, Aboriginal and Torres Strait Islander health workers are known to significantly contribute to the overall acceptability, access and use of health services through their role of cultural brokerage in the communities within which they work. As such they are uniquely positioned to positively influence health improvements for this vulnerable population. This study sought to identify key areas that both Aboriginal and Torres Strait Islander and non-Indigenous health professionals working within Indigenous communities felt were important in providing support for their roles. This group of workers require support within their roles particularly in relation to cultural awareness and capability, resource provision, educational opportunities, collaboration with colleagues and peers, and professional mentorship.


Assuntos
Atitude do Pessoal de Saúde , Serviços de Saúde da Criança/normas , Competência Cultural , Pessoal de Saúde/psicologia , Serviços de Saúde do Indígena/normas , Centros de Saúde Materno-Infantil/normas , Adolescente , Adulto , Feminino , Grupos Focais , Pessoal de Saúde/normas , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico , Queensland , Apoio Social , Recursos Humanos , Adulto Jovem
4.
Expert Rev Clin Pharmacol ; 16(3): 195-205, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36787628

RESUMO

INTRODUCTION: There is a need for resources to guide informal carers in medication management for people with dementia. Availability of resources on medication management guidance has yet to be explored. AREAS COVERED: A systematic search of MEDLINE, Embase, CINAHL and PsycINFO was performed in May 2022 to identify and evaluate resources for carers of people with dementia that provide guidance in medication management. Google and known repositories were also searched. Readability of text-based resources was examined using the Flesch-Kincaid reading level, the Flesch reading ease and the Gunning-Fog index. Resources were further evaluated using the Patient Education Material Assessment Tool (PEMAT or PEMAT-A/V). EXPERT OPINION: Fifteen resources were identified, which largely focused on medication administration with limited discussion of shared decision-making. Current resources do not appear to have included people living with dementia or their carers in their development and did not address high-risk care settings. Codesign of resources with carers and people with dementia would ensure that resources are comprehensive and target their needs. Future research should therefore focus on development of readily available and understandable resources that provide medication management guidance for carers across different health settings, to comprehensively address the multi-faceted nature of dementia.


Assuntos
Cuidadores , Demência , Humanos , Conduta do Tratamento Medicamentoso
5.
J Am Med Dir Assoc ; 24(4): 548-554, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36933568

RESUMO

OBJECTIVE: To examine the effectiveness of acupressure on cognition and quality of life (QoL) among older adults with cognitive disorders residing in long-term care (LTC) settings. DESIGN: A clustered, randomized, assessor-blinded, controlled trial with a repeated measures design. SETTING AND PARTICIPANTS: Participants were recruited from residential care facilities in Taiwan from August 2020 to February 2021. Ninety-two older residents in 18 facilities were randomized to either the intervention arm (9 facilities, n = 46) or the control arm (9 facilities, n = 46). METHODS: Acupressure was performed at Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), Fengchi (GB20), Shuigou (GV26), Neiguan (PC6), Shenmen (HT7), and Zusanli (ST36). The duration for pressing each acupoint was 3 minutes. The acupressure force was maintained at 3 kg. Acupressure was performed once a day 5 times a week for 12 weeks. The primary outcome measure was the Cognitive Abilities Screening Instrument (CASI). Secondary outcomes included the digit span backward test, the Wisconsin Card Sorting Test (perseverative responses, perseverative errors, and categories completed), semantic fluency tests of categories of animals, fruits, and vegetables, and the Quality of Life-Alzheimer's Disease (QoL-AD). Data were collected at preintervention and postintervention. Three-level mixed effects models were performed. This study complied with the CONSORT checklist. RESULTS: After adjusting for covariates, there was a significant increase in CASI scores, the digit span backward test, perseverative responses, perseverative errors, categories completed, semantic fluency tests of categories, and QoL-AD scores in the intervention versus control arm at 3 months. CONCLUSIONS AND IMPLICATIONS: This study provides support for the use of acupressure to improve cognition and QoL during care among older residents with cognitive disorders in LTC settings. Acupressure can be integrated into aged care practice to improve cognition and QoL of older residents with cognitive disorders in LTC settings.


Assuntos
Acupressão , Doença de Alzheimer , Disfunção Cognitiva , Humanos , Assistência de Longa Duração , Qualidade de Vida , Disfunção Cognitiva/terapia , Cognição
6.
Breastfeed Rev ; 20(1): 7-15, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22724308

RESUMO

Abundant evidence recognises breastfeeding as being associated with significant short and long-term health benefits for both infant and mother. Until recently, the role of breastfeeding as an independent factor in reducing risk for sudden unexpected infant death remained unclear. In October 2010, SIDS and Kids Australia held a consensus forum with international researchers and key stakeholders to review current evidence relating to safe infant sleeping recommendations. Following this forum and the publication of key reviews, the SIDS and Kids National Scientific Advisory Group has supported the decision that a critical threshold had been reached within the evidence that is supportive of breastfeeding as a specific risk reduction measure for sudden unexpected death in infancy. A sixth recommendation, Breastfeed baby if you can, will be included in the 2012 SIDS and Kids Safe Sleeping national public health campaign.


Assuntos
Aleitamento Materno/estatística & dados numéricos , Promoção da Saúde/métodos , Bem-Estar do Lactente/estatística & dados numéricos , Comportamento de Redução do Risco , Morte Súbita do Lactente/prevenção & controle , Austrália , Medicina Baseada em Evidências , Feminino , Humanos , Lactente , Mães/educação , Guias de Prática Clínica como Assunto , Saúde Pública
7.
J Law Med Ethics ; 50(1): 52-59, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35243999

RESUMO

We propose that marketing of unhealthy foods and beverages to Black and Latino consumers results from the intersection of a business model in which profits come primarily from marketing an unhealthy mix of products, standard targeted marketing strategies, and societal forces of structural racism, and contributes to health disparities.


Assuntos
Bebidas , Alimentos , Comércio , Humanos , Marketing
8.
Australas J Ageing ; 41(2): 309-313, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34821448

RESUMO

OBJECTIVE: Research involving people with dementia is vital to appropriately inform policy and practice decisions affecting this population. As dementia-care researchers, we frequently advocate to Human Research Ethics Committees for the right of people with dementia to choose whether to participate in research. This brief report provides some considerations for researchers and ethics committees. METHOD: Descriptive summary of principles that argue for inclusion of people with dementia in research studies. RESULTS: Specifically excluding people living with dementia from research because of perceived cognitive impairment is inappropriate in light of human rights principles and the right to contribute to evidence-based care. CONCLUSIONS: There is a difference between capacity to provide informed consent and ability to provide perspectives that are valid for each individual. Providing the opportunity for a person with dementia to participate in research and offering support to do this is a matter of human rights.


Assuntos
Disfunção Cognitiva , Demência , Demência/diagnóstico , Demência/psicologia , Demência/terapia , Comitês de Ética em Pesquisa , Humanos , Consentimento Livre e Esclarecido/psicologia , Pesquisadores
9.
Antimicrob Agents Chemother ; 55(4): 1650-60, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21245437

RESUMO

Pyrimidinediones, a novel class of compounds, have previously been shown to possess antiviral activity at nanomolar concentrations. One member of this class of compounds, IQP-0528, was selected as the lead molecule for formulation development owing to its stability at physiologically relevant conditions, wide therapeutic window, and antiviral activity in the nanomolar range. Here, we report the development of two vaginal gels--3.0% hydroxyethyl cellulose (HEC) formulation and a 0.65% Carbopol formulation--for the sustained delivery of IQP-0528. Stability studies under accelerated conditions confirmed the chemical stability of IQP-0528 and mechanical stability of the gel formulation for 3 months. In vitro release studies revealed that diffusion-controlled release of IQP-0528 occurred over 6 h, with an initial lag time of approximately 1 h. Based on the drug release profile, the 3.0% HEC gel was selected as the lead formulation for safety and activity evaluations. The in vitro and ex vivo safety evaluations showed no significant loss in cell viability or significant inflammatory response after treatment with a 3.0% HEC gel containing 0.25% IQP-0528. In an in vitro HIV-1 entry inhibition assay, the lead formulation showed an 50% effective concentration of 0.14 µg/ml for gel in culture media, which corresponds to ∼0.001 µM IQP-0528. The antiviral activity was further confirmed by using polarized cervical explants, in which the formulation showed complete protection against HIV infection. In summary, these results are encouraging and warrant further evaluation of IQP-0528 gel formulations in in vivo models, as well as the development of alternative formulations for the delivery of IQP-0528 as a microbicide.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacologia , Pirimidinonas/administração & dosagem , Pirimidinonas/farmacologia , Cremes, Espumas e Géis Vaginais/administração & dosagem , Animais , Fármacos Anti-HIV/química , Feminino , HIV-1/efeitos dos fármacos , Humanos , Técnicas In Vitro , Pirimidinonas/química , Suínos , Vagina/metabolismo , Cremes, Espumas e Géis Vaginais/química
10.
Antimicrob Agents Chemother ; 54(3): 1343-6, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20086159

RESUMO

To identify novel anti-HIV-1 peptides based on the antimicrobial peptide database (APD; http://aps.unmc.edu/AP/main.php), we have screened 30 candidates and found 11 peptides with 50% effective concentrations (EC(50)) of <10 microM and therapeutic indices (TI) of up to 17. Furthermore, among the eight peptides (with identical amino acid compositions but different sequences) generated by shuffling the sequence of an aurein 1.2 analog, two had a TI twice that of the original sequence. Because antiviral peptides in the database have an arginine/lysine (R/K) ratio of >1, increases in the Arg contents of amphibian maximin H5 and dermaseptin S9 peptides and the database-derived GLK-19 peptide improved the TIs. These examples demonstrate that the APD is a rich resource and a useful tool for developing novel HIV-1-inhibitory peptides.


Assuntos
Fármacos Anti-HIV , Peptídeos Catiônicos Antimicrobianos , HIV-1/efeitos dos fármacos , Sequência de Aminoácidos , Proteínas de Anfíbios/química , Proteínas de Anfíbios/genética , Proteínas de Anfíbios/farmacologia , Animais , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bases de Dados de Proteínas , Desenho de Fármacos , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Relação Estrutura-Atividade
11.
Antimicrob Agents Chemother ; 54(4): 1512-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20086149

RESUMO

Triciribine (TCN) is a tricyclic nucleoside that inhibits human immunodeficiency virus type 1 (HIV-1) replication by a unique mechanism not involving the inhibition of enzymes directly involved in viral replication. This activity requires the phosphorylation of TCN to its 5' monophosphate by intracellular adenosine kinase. New testing with a panel of HIV and simian immunodeficiency virus isolates, including low-passage-number clinical isolates and selected subgroups of HIV-1, multidrug resistant HIV-1, and HIV-2, has demonstrated that TCN has broad antiretroviral activity. It was active in cell lines chronically infected with HIV-1 in which the provirus was integrated into chromosomal DNA, thereby indicating that TCN inhibits a late process in virus replication. The selection of TCN-resistant HIV-1 isolates resulted in up to a 750-fold increase in the level of resistance to the drug. DNA sequence analysis of highly resistant isolate HIV-1(H10) found five point mutations in the HIV-1 gene nef, resulting in five different amino acid changes. DNA sequencing of the other TCN-resistant isolates identified at least one and up to three of the same mutations observed in isolate HIV-1(H10). Transfer of the mutations from TCN-resistant isolate HIV-1(H10) to wild-type virus and subsequent viral growth experiments with increasing concentrations of TCN demonstrated resistance to the drug. We conclude that TCN is a late-phase inhibitor of HIV-1 replication and that mutations in nef are necessary and sufficient for TCN resistance.


Assuntos
Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Ribonucleosídeos/farmacologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana/fisiologia , Linhagem Celular , Farmacorresistência Viral/genética , Genes nef , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/genética , HIV-2/efeitos dos fármacos , Humanos , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Mutação Puntual , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Montagem de Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética , Replicação Viral/fisiologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética
12.
Nurse Educ Today ; 84: 104252, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31698289

RESUMO

BACKGROUND: The international literature highlights patient safety as a critical issue in contemporary health care. Poor interpersonal relationships and ineffective health care team communication are identified as dominant human factors contributing to clinical errors and adverse events. Of concern is that some students appear to lack the skills to speak up for themselves, their patients and others when witnessing unsafe practice on clinical placement. STUDY AIMS: To elicit student and staff perspectives on the quality, effectiveness and appropriateness of an assertiveness-based communication activity prior to clinical placement. DESIGN: The study used a qualitative design. A communication module was offered in the second week of the practice laboratory and involved the use of two graded assertiveness frameworks. SETTING: School of Nursing, Midwifery and Paramedicine, at a regional university in South East Queensland, Australia. PARTICIPANTS: Of the 535 first year undergraduate nursing students enrolled in the laboratory courses, 73 (13.6%) completed an anonymous online survey. Individual interviews were conducted with a university student wellbeing coordinator and student mentor to gain their perspectives of the data. METHODS: An evaluation survey with seven qualitative questions and individual semi-structured interviews were employed. Data was analysed using a thematic approach. RESULTS: Five major themes emerged from the survey data: vicarious learning, establishing boundaries, support in practice, advocacy awareness and practice utility. Three themes emerged from the interviews: empowerment and confidence; support and preparation for advocacy; and authentic learning. CONCLUSIONS: Findings indicate that teaching assertiveness skills and establishing a preparatory framework for 'speaking up for safety' early in a nursing students tertiary education can have important psychosocial implications for their confidence, empowerment and success. The activity provided an authentic learning experience with perceived practical application to the workplace and, has the potential to enhance first year curricula by improving communication tools used for students preparing for practice.


Assuntos
Assertividade , Docentes de Enfermagem/psicologia , Tocologia/educação , Enfermagem Obstétrica/educação , Segurança do Paciente , Estudantes de Enfermagem/psicologia , Currículo , Bacharelado em Enfermagem , Feminino , Humanos , Entrevistas como Assunto , Masculino , Queensland , Inquéritos e Questionários , Adulto Jovem
13.
J Adv Nurs ; 65(6): 1293-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19374672

RESUMO

AIM: This paper is a report of a study conducted to explore the impact of preidentified contextual themes (related to work environment and socialization) on nursing medication practice. BACKGROUND: Medication administration is a complex aspect of paediatric nursing and an important component of day-to-day nursing practice. Many attempts are being made to improve patient safety, but many errors remain. Identifying and understanding factors that influence medication administration errors are of utmost importance. METHOD: A cross-sectional survey was conducted with a sample of 278 paediatric nurses from the emergency department, intensive care unit and medical and surgical wards of an Australian tertiary paediatric hospital in 2004. The response rate was 67%. RESULT: Contextual influences were important in determining how closely medication policy was followed. Completed questionnaires were returned by 185 nurses (67%). Younger nurses aged <34 years thought that their medication administration practice could be influenced by the person with whom they checked the drugs (P = 0.001), and that there were daily circumstances when it was acceptable not to adhere strictly to medication policy (P < 0.001), including choosing between following policy and acting in the best interests of the child (P = 0.002). Senior nurses agreed that senior staff dictate acceptable levels of medication policy adherence through role modelling (P = 0.01). Less experienced nurses reported greater confidence with computer literacy (P < 0.001). CONCLUSIONS: Organizations need to employ multidisciplinary education programmes to promote universal understanding of, and adherence to, medication policies. Skill mix should be closely monitored to ensure adequate support for new and junior staff.


Assuntos
Alfabetização Digital , Fidelidade a Diretrizes/normas , Sistemas de Medicação no Hospital/normas , Recursos Humanos de Enfermagem Hospitalar/psicologia , Enfermagem Pediátrica/normas , Adulto , Fatores Etários , Atitude do Pessoal de Saúde , Criança , Estudos Transversais , Humanos , Erros de Medicação/prevenção & controle , Preparações Farmacêuticas/administração & dosagem , Fatores de Tempo
14.
Complement Ther Med ; 42: 366-373, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30670268

RESUMO

OBJECTIVE: Lavender and Lemon Balm essential oils are popular in the management of older person agitation due to their ease of application, minimal side effects and low interaction with concurrent medications. This study addressed limitations in the literature to evaluate and compare effectiveness of Lavender and Lemon Balm essential oils on the agitated behaviour of older people with and without dementia living in residential aged care facilities [RACFs]. METHODS: Forty-nine nursing home residents with dementia (n=39) and without dementia (n=10) exhibiting agitation participated in this study. Participants were randomised to a counterbalanced, repeated measures design experiment that tests the treatments Lavender, Lemon Balm, and Placebo (Sunflower oil). Treatments were administered once daily for two-weeks followed by a two-week washout period before commencing the subsequent treatment. All participants trialed all three treatments over a 10-week period. Data were collected on the Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory (CMAI). RESULTS: A significant difference was shown when essential oils effect were compared between the cognitive groups. Post hoc analysis reports Lemon Balm more effective in reducing NPI agitation (p = .04) and CMAI physical non-aggressive behaviour (PNAB) (p = .02) in residents without dementia. Lemon Balm less effective in reducing NPI irritability (p = 0.01) and Lavender more effective in reducing CMAI PNAB (p = 0.04) in dementia. CONCLUSION: The findings support an opposing effect of Lemon Balm and Lavender in reducing agitated behaviour between the participant cognitive groups. There was no reduction in agitation with treatments when compared to placebo independent of cognitive groups.


Assuntos
Aromaterapia , Demência , Lavandula/química , Melissa/química , Óleos Voláteis/uso terapêutico , Extratos Vegetais/uso terapêutico , Agitação Psicomotora/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ansiedade/complicações , Demência/complicações , Depressão/complicações , Feminino , Instituição de Longa Permanência para Idosos , Humanos , Masculino , Casas de Saúde , Óleos de Plantas/uso terapêutico , Agitação Psicomotora/etiologia
15.
Women Birth ; 32(5): 460-465, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31303540

RESUMO

BACKGROUND: Approaches to health promotion that are collaborative, support strengths inherent in Aboriginal and Torres Strait Islander culture, and demonstrate respect and understanding for individual communities, have achieved the most positive outcomes to date. AIM: To illustrate how the implementation and evaluation of a safe infant sleep health promotion strategy was facilitated by embedding recognised best practice principles for the conduct of research with Aboriginal and Torres Strait Islander peoples and communities. METHODS: The Pepi-Pod® Program was introduced across rural, remote and metropolitan locations in Queensland between 2013 and 2017. This case study discusses the partnership between the Pepi-Pod® Program and one community-controlled maternal and child health service that employed an Aboriginal Health Worker led model of maternal and child health care for remote regions of Queensland. FINDINGS: Best practice principles were embedded within the program design and adaptation, and in the approach to community consultation prior to program implementation. Collaborative partnerships based on trust, which established stakeholder expectations through transparent communication processes, together with effective engagement in achieving program goals, led to the implementation of this evidence-based health promotion initiative as intended. Consideration for locally relevant and culturally competent program delivery was key to success. The integrity of the program was maintained and embedded into ongoing service delivery. CONCLUSIONS: Through adherence to best practice principles for research with Aboriginal and Torres Strait Islander communities, implementation and evaluation of health promotion programs can be conducted in mutually acceptable, feasible and sustainable ways that develop capacity within participating health services.


Assuntos
Pesquisa Participativa Baseada na Comunidade/métodos , Assistência à Saúde Culturalmente Competente , Medicina Baseada em Evidências , Promoção da Saúde/métodos , Serviços de Saúde Materno-Infantil , Havaiano Nativo ou Outro Ilhéu do Pacífico , Austrália , Pesquisa Participativa Baseada na Comunidade/ética , Feminino , Serviços de Saúde do Indígena , Humanos , Lactente , Queensland
16.
Antimicrob Agents Chemother ; 52(8): 2787-96, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18559653

RESUMO

In the absence of a fully effective human immunodeficiency virus (HIV) vaccine, topical microbicides represent an important strategy for preventing the transmission of HIV through sexual intercourse, the predominant mode of HIV transmission worldwide. Although a comprehensive understanding of HIV transmission has not yet emerged in the microbicide field, it is likely the result of rapid infection of monocyte-derived cells in the vaginal mucosa by CCR5-tropic viruses. Inhibition of HIV transmission requires agents that prevent entry, fusion, reverse transcription, or other preintegrative replication events or agents which directly inactivate HIV or modulate the target cells to render them uninfectible. In vitro assays typically used to evaluate the ability of a microbicide to prevent virus transmission use epithelial or human osteosarcoma-derived cells or immune cells more relevant to the development of anti-HIV therapeutic agents and quantify virus production at short time intervals following infection. We have developed a microbicide transmission and sterilization assay (MTSA) to more sensitively and quantitatively evaluate virus transmission in cell culture in the presence of microbicidal compounds. Results obtained with the MTSA demonstrate that the inhibitory capacity of microbicides is often overestimated in short-term transmission inhibition assays, while some compounds yield equivalent inhibitory results, indicating a biological relevance for the MTSA-based evaluations to identify superior potent microbicides. The MTSA defines the concentration of the microbicide required to totally suppress the transmission of virus in cell culture and may thus help define the effective concentration of the microbicide required in a formulated microbicide product.


Assuntos
Fármacos Anti-HIV/farmacologia , Anti-Infecciosos/farmacologia , HIV/efeitos dos fármacos , Pirimidinonas/farmacologia , Fármacos Anti-HIV/química , Anti-Infecciosos/química , Linhagem Celular , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Pirimidinonas/química
17.
Antimicrob Agents Chemother ; 52(9): 3438-40, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18591279

RESUMO

From among 15 human cathelicidin LL-37-derived peptides, FK-13 was identified as the smallest peptide active against human immunodeficiency virus (HIV) and GI-20 had the highest therapeutic index, which was twice that of LL-37. BMAP-18, which is derived from bovine cathelicidin BMAP-27, possessed a therapeutic index similar to that of GI-20. Peptide sequence order, helical structures, and aromatic residues are important in HIV inhibition.


Assuntos
Fármacos Anti-HIV , Peptídeos Catiônicos Antimicrobianos/química , HIV-1/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bovinos , Infecções por HIV/virologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Relação Estrutura-Atividade , Catelicidinas
18.
Antimicrob Agents Chemother ; 52(5): 1768-81, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18316528

RESUMO

Topical microbicides are self-administered, prophylactic products for protection against sexually transmitted pathogens. A large number of compounds with known anti-human immunodeficiency virus type 1 (HIV-1) inhibitory activity have been proposed as candidate topical microbicides. To identify potential leads, an in vitro screening algorithm was developed to evaluate candidate microbicides in assays that assess inhibition of cell-associated and cell-free HIV-1 transmission, entry, and fusion. The algorithm advances compounds by evaluation in a series of defined assays that generate measurements of relative antiviral potency to determine advancement or failure. Initial testing consists of a dual determination of inhibitory activity in the CD4-dependent CCR5-tropic cell-associated transmission inhibition assay and in the CD4/CCR5-mediated HIV-1 entry assay. The activity is confirmed by repeat testing, and identified actives are advanced to secondary screens to determine their effect on transmission of CXCR4-tropic viruses in the presence or absence of CD4 and their ability to inhibit CXCR4- and CCR5-tropic envelope-mediated cell-to-cell fusion. In addition, confirmed active compounds are also evaluated in the presence of human seminal plasma, in assays incorporating a pH 4 to 7 transition, and for growth inhibition of relevant strains of lactobacilli. Leads may then be advanced for specialized testing, including determinations in human cervical explants and in peripheral blood mononuclear cells against primary HIV subtypes, combination testing with other inhibitors, and additional cytotoxicity assays. PRO 2000 and SPL7013 (the active component of VivaGel), two microbicide products currently being evaluated in human clinical trials, were tested in this in vitro algorithm and were shown to be highly active against CCR5- and CXCR4-tropic HIV-1 infection.


Assuntos
Algoritmos , Fármacos Anti-HIV/farmacologia , Anti-Infecciosos Locais/farmacologia , HIV-1/efeitos dos fármacos , Amidas/farmacologia , Anilidas/farmacologia , Antagonistas dos Receptores CCR5 , Antígenos CD4/imunologia , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Furanos/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Naftalenossulfonatos/farmacologia , Polímeros/farmacologia , Compostos de Amônio Quaternário/farmacologia , Receptores CXCR4/antagonistas & inibidores , Tioamidas
19.
Bioorg Med Chem Lett ; 18(2): 469-73, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-18083556

RESUMO

During studies on the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), analogues were discovered that exhibit low micromolar and submicromolar cytotoxicities. Since the ADAMs are structurally related to the tubulin polymerization inhibitor CC-5079, a set of 14 ADAMs were tested for inhibition of tubulin polymerization in an attempt to identify the biological target responsible for their cytotoxicity. The results indicate that, overall, the ADAMs are poor inhibitors of tubulin polymerization. However, the two most cytotoxic compounds, 15 and 16, are in fact active as inhibitors of tubulin assembly with IC(50) values of 3.7+/-0.3 and 2.8+/-0.2 microM, respectively, and they both inhibit the binding of colchicine to tubulin. Both compounds were investigated for anticancer activity in the National Cancer Institute's panel of 60 human cancer cell lines, and both compounds consistently displayed submicromolar cytotoxicities with mean-graph midpoint (MGM) values of 0.31+/-0.08 and 0.47+/-0.09 microM, respectively.


Assuntos
Biopolímeros/química , Metano/análogos & derivados , Tubulina (Proteína)/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Transcriptase Reversa do HIV/antagonistas & inibidores , Humanos , Metano/farmacologia , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/farmacologia
20.
Bioorg Med Chem Lett ; 18(4): 1530-3, 2008 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-18222088

RESUMO

The alkenyldiarylmethanes (ADAMs) are currently being investigated as non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) of potential value in the treatment of HIV infection and AIDS. During the course of these studies, a number of ADAM analogues have been identified that protect HIV-infected cells from the cytopathic effects of the virus by an unknown, HIV-1 RT-independent mechanism. Since the phosphodiesterase 4 family is required for HIV infection, the effect of various ADAMs on the activity of PDE4B2 was investigated in an effort to determine if the ADAMs could possibly be targeting phosphodiesterases. Six compounds representative of the ADAM class were tested for inhibition of cAMP hydrolysis by PDE4B2 enzymatic activity. Four ADAMs were found to be weak inhibitors of PDE4B2 and two of them were inactive. The experimental results are consistent with an antiviral mechanism that does not include inhibition of PDE4 isoforms.


Assuntos
Alcenos/farmacologia , Metano/análogos & derivados , Inibidores da Fosfodiesterase 4 , Inibidores de Fosfodiesterase/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Alcenos/síntese química , Alcenos/química , Linhagem Celular Tumoral , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Transcriptase Reversa do HIV/antagonistas & inibidores , Humanos , Concentração Inibidora 50 , Oxazóis/síntese química , Oxazóis/química , Oxazóis/farmacologia , Inibidores de Fosfodiesterase/síntese química , Inibidores de Fosfodiesterase/química , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/química , Relação Estrutura-Atividade
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