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1.
Digit Health ; 9: 20552076231211118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38033518

RESUMO

Background: Despite positive findings around the use of eHealth in dementia care, it is rarely translated into routine practice. This can be facilitated by early involvement of end-users in the development of an implementation plan. This study aimed to co-design strategies to implement an eHealth intervention, the EMBED-Care Framework, to support assessment and decision-making for people with dementia in care homes. Methods: A qualitative co-design method was applied through a series of workshops. Participants included family carers and health and social care practitioners. People with dementia were included through a series of stakeholder engagement meetings. The workshops focused on co-developing strategies in response to identified determinants of implementation. A codebook thematic analytic approach was taken, guided by the Normalisation Process Theory (NPT). Results: Three workshops were conducted from July 2021 to November 2021, attended by 39 participants. Three overarching phases of implementation were identified which aligned with the constructs of the NPT: (a) incentivising adoption of the Framework, which requires promotion of its benefits and alignment with recommendations for good quality dementia care to engage stakeholders, relating to 'coherence' and 'cognitive participation' constructs; (b) enabling its operation, which requires ensuring compatibility with care home processes, provision of training and support from 'champions', relating to 'collective action'; (c) sustaining use of the Framework, which requires monitoring of implementation and appraisal of its effects, relating to 'reflexive monitoring'. Conclusions: We have developed a multi-strategy, theoretically driven plan to implement eHealth to support assessment and decision-making for people with dementia in care homes. Successful implementation requires incentivisation to adopt, ability to operate and motivation to sustain use of eHealth. The plan is strengthened through collaborating with end-users to increase its value, credibility and real-world relevance. The theoretically informed strategies target mechanisms of the NPT, demonstrated to shape the implementation process and outcomes, ready for testing.

2.
MethodsX ; 9: 101807, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034521

RESUMO

The characterisation technologies have advanced rapidly in the last decade. From a qualitative observation of minerals with optical microscopy, more quantitative techniques have emerged. Examples are the SEM-based technologies that focus on mineralogical identification at the microscale and the X-ray microtomography systems that allow identifying rock features in three dimensions. Features such as rock texture and mineralogy have a degree of control on how the rock behaves in the processing plant and thus can affect the project's economic feasibility. None of the available measurement devices is currently capable of identifying all the aspects of rock characteristics that are of interest in linking mineralogy and texture to process response in a single measurement. However, through the integrated use of the techniques in a complementary approach is possible to generate the required suite of information about the mineralogical composition and mineral grain size and shape in a given sample. A multisource method for rock characterisation has been developed in this work. This method includes: • A multistage imaging process that uses 2D and 3D microscopes • An object-segmentation technique to separate mineral grains in the photomicrographs for the quantification of mineralogical and textural properties. • A segmentation technique was developed to create particles of different sizes from a larger image.

3.
J Med Internet Res ; 24(2): e29837, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35113029

RESUMO

BACKGROUND: As dementia progresses, symptoms and concerns increase, causing considerable distress for the person and their caregiver. The integration of care between care homes and health care services is vital to meet increasing care needs and maintain quality of life. However, care home access to high-quality health care is inequitable. eHealth can facilitate this by supporting remote specialist input on care processes, such as clinical assessment and decision-making, and streamlining care on site. How to best implement eHealth in the care home setting is unclear. OBJECTIVE: The aim of this review was to identify the key factors that influence the implementation of eHealth for people living with dementia in long-term care. METHODS: A systematic search of Embase, PsycINFO, MEDLINE, and CINAHL was conducted to identify studies published between 2000 and 2020. Studies were eligible if they focused on eHealth interventions to improve treatment and care assessment or decision-making for residents with dementia in care homes. Data were thematically analyzed and deductively mapped onto the 6 constructs of the adapted Consolidated Framework for Implementation Research (CFIR). The results are presented as a narrative synthesis. RESULTS: A total of 29 studies were included, focusing on a variety of eHealth interventions, including remote video consultations and clinical decision support tools. Key factors that influenced eHealth implementation were identified across all 6 constructs of the CFIR. Most concerned the inner setting construct on requirements for implementation in the care home, such as providing a conducive learning climate, engaged leadership, and sufficient training and resources. A total of 4 novel subconstructs were identified to inform the implementation requirements to meet resident needs and engage end users. CONCLUSIONS: Implementing eHealth in care homes for people with dementia is multifactorial and complex, involving interaction between residents, staff, and organizations. It requires an emphasis on the needs of residents and the engagement of end users in the implementation process. A novel conceptual model of the key factors was developed and translated into 18 practical recommendations on the implementation of eHealth in long-term care to guide implementers or innovators in care homes. Successful implementation of eHealth is required to maximize uptake and drive improvements in integrated health and social care.


Assuntos
Demência , Telemedicina , Cuidadores , Demência/terapia , Humanos , Assistência de Longa Duração , Qualidade de Vida
4.
J Cardiovasc Nurs ; 37(2): 134-145, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33394624

RESUMO

BACKGROUND: Depression is prevalent among adults with chronic heart failure (CHF) and is associated with higher rates of morbidity and mortality and higher healthcare costs. OBJECTIVES: The aim of this study was to explore the efficacy of psychological interventions in reducing depression and improving quality of life and clinical outcomes (mortality, hospitalization) among adults with CHF. METHODS: This study performed a systematic review involving searches of 6 databases (MEDLINE, CINAHL, EMBASE, PsycINFO, ASSIA, and SSCI), the Cochrane library, and gray literature, completed in January 2020. Experimental and nonexperimental quantitative studies of psychological interventions for adults with CHF were included. Each study was quality appraised, and key data were extracted and tabled. Overall findings are presented as a narrative synthesis. RESULTS: Nine studies met eligibility. Study authors sampled 757 participants and evaluated 4 psychological interventions: cognitive behavioral therapy alone or combined with exercise, mindfulness-based psychoeducation, coping skills training, and innovative holistic meditation. Cognitive behavioral therapy was significantly associated with improved depression and quality of life, and reduced hospitalization risk. Mindfulness-based psychoeducation, holistic meditation, and coping skills training positively impacted depression and quality of life. Coping skills training also reduced hospitalization and mortality risks. CONCLUSION: Although this review indicates that psychological interventions can be beneficial to adults with CHF who have depression, the overall weight of evidence contains a number of biases. Larger, higher-powered studies are needed to confirm or refute these findings and to better understand how specific intervention and sample characteristics relate to outcomes.


Assuntos
Terapia Cognitivo-Comportamental , Insuficiência Cardíaca , Adulto , Depressão/terapia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Humanos , Intervenção Psicossocial , Qualidade de Vida/psicologia
5.
Palliat Med ; 35(10): 1961-1974, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34423701

RESUMO

BACKGROUND: Palliative care is advocated for older people with frailty and multimorbidity in the community. However, how to best deliver it is unclear. AIM: To develop and model an intervention of short-term specialized palliative care that is initiated timely based on complex care needs and integrated with primary care for older people with frailty and their family, detailing the intervention components, outcomes and preconditions needed for implementation, using a novel theoretical approach. DESIGN: Observational study informed by the UK MRC guidance for complex interventions integrated with a Theory of Change (i.e. hypothetical causal pathway to impact) approach. We synthesized evidence from a systematic review, semi-structured interviews, group discussions and Theory of Change workshops. SETTING: Primary care in Flanders, Belgium. RESULTS: We identified patient and family carer-related long-term outcomes and preconditions to achieve them for example, service providers are willing and able to deliver the intervention. The intervention components included implementation components, for example, training for service providers, and a core component, that is, provision of timely short-term specialized palliative care by a specialized palliative home care nurse. The latter includes: short-term service delivery; collaborative and integrative working within primary care; delivery of holistic needs- and capacity-based care; person-centred and family-focussed; and goal-oriented pro-active care. CONCLUSIONS: The Theory of Change approach allowed us to identify multiple intervention components targeting different stakeholders to achieve the desired outcomes. It also facilitated a detailed description of the intervention which aims to increase replicability and effective comparisons with other interventions.


Assuntos
Cuidadores , Fragilidade , Idoso , Bélgica , Humanos , Estudos Observacionais como Assunto , Cuidados Paliativos , Atenção Primária à Saúde
6.
Cochrane Database Syst Rev ; 9: CD012780, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32996586

RESUMO

BACKGROUND: Serious illness is often characterised by physical/psychological problems, family support needs, and high healthcare resource use. Hospital-based specialist palliative care (HSPC) has developed to assist in better meeting the needs of patients and their families and potentially reducing hospital care expenditure. There is a need for clarity on the effectiveness and optimal models of HSPC, given that most people still die in hospital and also to allocate scarce resources judiciously. OBJECTIVES: To assess the effectiveness and cost-effectiveness of HSPC compared to usual care for adults with advanced illness (hereafter patients) and their unpaid caregivers/families. SEARCH METHODS: We searched CENTRAL, CDSR, DARE and HTA database via the Cochrane Library; MEDLINE; Embase; CINAHL; PsycINFO; CareSearch; National Health Service Economic Evaluation Database (NHS EED) and two trial registers to August 2019, together with checking of reference lists and relevant systematic reviews, citation searching and contact with experts to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the impact of HSPC on outcomes for patients or their unpaid caregivers/families, or both. HSPC was defined as specialist palliative care delivered by a palliative care team that is based in a hospital providing holistic care, co-ordination by a multidisciplinary team, and collaboration between HSPC providers and generalists. HSPC was provided to patients while they were admitted as inpatients to acute care hospitals, outpatients or patients receiving care from hospital outreach teams at home. The comparator was usual care, defined as inpatient or outpatient hospital care without specialist palliative care input at the point of entry into the study, community care or hospice care provided outside of the hospital setting. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed risk of bias and extracted data. To account for use of different scales across studies, we calculated standardised mean differences (SMDs) with 95% confidence intervals (CIs) for continuous data. We used an inverse variance random-effects model. For binary data, we calculated odds ratio (ORs) with 95% CIs. We assessed the evidence using GRADE and created a 'Summary of findings' table. Our primary outcomes were patient health-related quality of life (HRQoL) and symptom burden (a collection of two or more symptoms). Key secondary outcomes were pain, depression, satisfaction with care, achieving preferred place of death, mortality/survival, unpaid caregiver burden, and cost-effectiveness. Qualitative data was analysed where available. MAIN RESULTS: We identified 42 RCTs involving 7779 participants (6678 patients and 1101 caregivers/family members). Twenty-one studies were with cancer populations, 14 were with non-cancer populations (of which six were with heart failure patients), and seven with mixed cancer and non-cancer populations (mixed diagnoses). HSPC was offered in different ways and included the following models: ward-based, inpatient consult, outpatient, hospital-at-home or hospital outreach, and service provision across multiple settings which included hospital. For our main analyses, we pooled data from studies reporting adjusted endpoint values. Forty studies had a high risk of bias in at least one domain. Compared with usual care, HSPC improved patient HRQoL with a small effect size of 0.26 SMD over usual care (95% CI 0.15 to 0.37; I2 = 3%, 10 studies, 1344 participants, low-quality evidence, higher scores indicate better patient HRQoL). HSPC also improved other person-centred outcomes. It reduced patient symptom burden with a small effect size of -0.26 SMD over usual care (95% CI -0.41 to -0.12; I2 = 0%, 6 studies, 761 participants, very low-quality evidence, lower scores indicate lower symptom burden). HSPC improved patient satisfaction with care with a small effect size of 0.36 SMD over usual care (95% CI 0.41 to 0.57; I2 = 0%, 2 studies, 337 participants, low-quality evidence, higher scores indicate better patient satisfaction with care). Using home death as a proxy measure for achieving patient's preferred place of death, patients were more likely to die at home with HSPC compared to usual care (OR 1.63, 95% CI 1.23 to 2.16; I2 = 0%, 7 studies, 861 participants, low-quality evidence). Data on pain (4 studies, 525 participants) showed no evidence of a difference between HSPC and usual care (SMD -0.16, 95% CI -0.33 to 0.01; I2 = 0%, very low-quality evidence). Eight studies (N = 1252 participants) reported on adverse events and very low-quality evidence did not demonstrate an effect of HSPC on serious harms. Two studies (170 participants) presented data on caregiver burden and both found no evidence of effect of HSPC (very low-quality evidence). We included 13 economic studies (2103 participants). Overall, the evidence on cost-effectiveness of HSPC compared to usual care was inconsistent among the four full economic studies. Other studies that used only partial economic analysis and those that presented more limited resource use and cost information also had inconsistent results (very low-quality evidence). Quality of the evidence The quality of the evidence assessed using GRADE was very low to low, downgraded due to a high risk of bias, inconsistency and imprecision. AUTHORS' CONCLUSIONS: Very low- to low-quality evidence suggests that when compared to usual care, HSPC may offer small benefits for several person-centred outcomes including patient HRQoL, symptom burden and patient satisfaction with care, while also increasing the chances of patients dying in their preferred place (measured by home death). While we found no evidence that HSPC causes serious harms, the evidence was insufficient to draw strong conclusions. Although these are only small effect sizes, they may be clinically relevant at an advanced stage of disease with limited prognosis, and are person-centred outcomes important to many patients and families. More well conducted studies are needed to study populations with non-malignant diseases and mixed diagnoses, ward-based models of HSPC, 24 hours access (out-of-hours care) as part of HSPC, pain, achieving patient preferred place of care, patient satisfaction with care, caregiver outcomes (satisfaction with care, burden, depression, anxiety, grief, quality of life), and cost-effectiveness of HSPC. In addition, research is needed to provide validated person-centred outcomes to be used across studies and populations.


Assuntos
Cuidadores/estatística & dados numéricos , Serviços Hospitalares de Assistência Domiciliar/economia , Cuidados Paliativos/economia , Cuidados Paliativos/métodos , Assistência Terminal/economia , Assistência Terminal/métodos , Assistência Ambulatorial/economia , Viés , Cuidadores/psicologia , Análise Custo-Benefício , Família , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Hospitalização/economia , Humanos , Neoplasias/mortalidade , Neoplasias/terapia , Manejo da Dor/estatística & dados numéricos , Satisfação do Paciente , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Avaliação de Sintomas/estatística & dados numéricos
7.
PLoS One ; 13(7): e0200240, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29995932

RESUMO

BACKGROUND: Assessment of people with dementia is challenging; with undetected and under treated symptoms and concerns resulting in avoidable distress, and few evidence-based interventions to support this. We aimed to understand the mechanisms of action of a measure to support comprehensive assessment of people with dementia in care homes; and its acceptability, feasibility, and implementation requirements. METHODS: A qualitative study with an embedded quantitative component in three residential care homes, underpinned by an initial theoretical model of mechanisms of action. The measure, the Integrated Palliative care Outcome Scale for Dementia (IPOS-Dem), was introduced into the care of residents with dementia for 12 weeks. Qualitative data comprised focus groups and semi-structured interviews with family, care home staff, general practitioners and district nurses; and non-participant observations. Quantitative data comprised IPOS-Dem data. Directed content analysis for qualitative data, and descriptive statistics were used for quantitative data. FINDINGS: Key mechanisms of action were: improved observation and awareness of residents, collaborative assessment, comprehensive 'picture of the person', systematic record keeping, improved review and monitoring, care planning and changes to care provision, and facilitated multi-agency communication. Potential benefit included improved symptom management, improved comprehensive care, and increased family empowerment and engagement. IPOS-Dem was found to be acceptable and feasible. It was perceived as quick and easy to use, with proportion of overall missing data decreasing from 2.1% to 1.1% from baseline to final time points. 'Trust' in the measure was important; and leadership essential to ensure integration into care processes. CONCLUSIONS: In a population with complex care needs, with challenges to assessment and barriers to multi-agency working, a measure introduced into routine care is feasible and acceptable, and supports assessment and management of symptoms and concerns. A refined theoretical model demonstrating the likely mechanisms of action was developed. Further evaluation is required to test its effectiveness.


Assuntos
Demência/diagnóstico , Demência/enfermagem , Casas de Saúde , Cuidados Paliativos , Qualidade de Vida , Humanos , Avaliação de Processos em Cuidados de Saúde , Pesquisa Qualitativa
8.
Trials ; 19(1): 401, 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30053891

RESUMO

BACKGROUND: UK deaths due to chronic liver diseases such as cirrhosis have quadrupled over the last 40 years, making this condition now the third most common cause of premature death. Most patients with advanced cirrhosis (end-stage liver disease [ESLD]) develop ascites. This is often managed with diuretics, but if refractory, then the fluid is drained from the peritoneal cavity every 10-14 days by large volume paracentesis (LVP), a procedure requiring hospital admissions. As the life expectancy of patients with ESLD and refractory ascites (if ineligible for liver transplantation) is on average ≤ 6 months, frequent hospital visits are inappropriate from a palliative perspective. One alternative is long-term abdominal drains (LTADs), used successfully in patients whose ascites is due to malignancy. Although inserted in hospital, these drains allow ascites management outside of a hospital setting. LTADs have not been formally evaluated in patients with refractory ascites due to ESLD. METHODS/DESIGN: Due to uncertainty about appropriate outcome measures and whether patients with ESLD would wish or be able to participate in a study, a feasibility randomised controlled trial (RCT) was designed. Patients were consulted on trial design. We plan to recruit 48 patients with refractory ascites and randomise them (1:1) to either (1) LTAD or (2) current standard of care (LVP) for 12 weeks. Outcomes of interest include acceptability of the LTAD to patients, carers and healthcare professionals as well as recruitment and retention rates. The Integrated Palliative care Outcome Scale, the Short Form Liver Disease Quality of Life questionnaire, the EuroQol 5 dimensions instrument and carer-reported (Zarit Burden Interview) outcomes will also be assessed. Preliminary data on cost-effectiveness will be collected, and patients and healthcare professionals will be interviewed about their experience of the trial with a view to identifying barriers to recruitment. DISCUSSION: LTADs could potentially improve end-of-life care in patients with refractory ascites due to ESLD by improving symptom control, reducing hospital visits and enabling some self-management. Our trial is designed to see if such patients can be recruited, as well as to inform the design of a subsequent definitive trial. TRIAL REGISTRATION: ISRCTN, ISRCTN30697116 . Registered on 7 October 2015.


Assuntos
Ascite/terapia , Drenagem/instrumentação , Drenagem/métodos , Doença Hepática Terminal/terapia , Cirrose Hepática/terapia , Cuidados Paliativos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/diagnóstico , Ascite/etiologia , Drenagem/efeitos adversos , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/etiologia , Inglaterra , Estudos de Viabilidade , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
BMJ Support Palliat Care ; 8(1): 41-44, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28774963

RESUMO

OBJECTIVES: Evaluations of new services for palliative care in non-cancer conditions are few. OPTCARE Neuro is a multicentre trial evaluating the effectiveness of short-term integrated palliative care (SIPC) for progressive long-term neurological conditions. Here, we present survey results describing the current levels of collaboration between neurology and palliative care services and exploring the views of professionals towards the new SIPC service. METHODS: Neurology and palliative care teams from six UK trial sites (London, Nottingham, Liverpool, Cardiff, Brighton and Chertsey) were approached via email to complete an online survey. The survey was launched in July 2015 and consisted of multiple choice or open comment questions with responses collected using online forms. RESULTS: 33 neurology and 26 palliative care professionals responded. Collaborations between the two specialties were reported as being 'good/excellent' by 36% of neurology and by 58% of palliative care professionals. However, nearly half (45%) of neurology compared with only 12% of palliative care professionals rated current levels as being 'poor/none'. Both professional groups felt that the new SIPC service would influence future collaborations for the better. However, they identified a number of barriers for the new SIPC service such as resources and clinician awareness. CONCLUSIONS: Our results demonstrate the opportunity to increase collaboration between neurology and palliative care services for people with progressive neurological conditions, and the acceptability of SIPC as a model to support this. TRIAL REGISTRATION NUMBER: ISRCTN18337380; Pre-results.


Assuntos
Atitude do Pessoal de Saúde , Medicina Integrativa/organização & administração , Neurologia/organização & administração , Cuidados Paliativos/organização & administração , Humanos , Colaboração Intersetorial , Inquéritos e Questionários
10.
Age Ageing ; 45(6): 863-873, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27586857

RESUMO

BACKGROUND: understanding how best to provide palliative care for frail older people with non-malignant conditions is an international priority. We aimed to develop a community-based episodic model of short-term integrated palliative and supportive care (SIPS) based on the views of service users and other key stakeholders in the United Kingdom. METHOD: transparent expert consultations with health professionals, voluntary sector and carer representatives including a consensus survey; and focus groups with older people and carers were used to generate recommendations for the SIPS model. Discussions focused on three key components of the model: potential benefit of SIPS, timing of delivery and processes of integrated working between specialist palliative care and generalist practitioners. Content and descriptive analysis was employed and findings were integrated across the data sources. FINDINGS: we conducted two expert consultations (n = 63), a consensus survey (n = 42) and three focus groups (n = 17). Potential benefits of SIPS included holistic assessment, opportunity for end of life discussion, symptom management and carer reassurance. Older people and carers advocated early access to SIPS, while other stakeholders proposed delivery based on complex symptom burden. A priority for integrated working was the assignment of a key worker to co-ordinate care, but the assignment criteria remain uncertain. INTERPRETATION: key stakeholders agree that a model of SIPS for frail older people with non-malignant conditions has potential benefits within community settings, but differ in opinion on the optimal timing and indications for this service. Our findings highlight the importance of consulting all key stakeholders in model development prior to feasibility evaluation.


Assuntos
Atitude do Pessoal de Saúde , Cuidadores/psicologia , Serviços de Saúde Comunitária/organização & administração , Prestação Integrada de Cuidados de Saúde/organização & administração , Idoso Fragilizado/psicologia , Fragilidade/terapia , Conhecimentos, Atitudes e Prática em Saúde , Serviços de Saúde para Idosos/organização & administração , Cuidados Paliativos/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Avaliação de Processos em Cuidados de Saúde/organização & administração , Fatores Etários , Idoso , Envelhecimento/psicologia , Consenso , Inglaterra , Grupos Focais , Fragilidade/diagnóstico , Fragilidade/psicologia , Humanos , Modelos Organizacionais , Atenção Primária à Saúde/organização & administração , Pesquisa Qualitativa , Participação dos Interessados , Inquéritos e Questionários , Resultado do Tratamento
11.
Free Radic Res ; 39(9): 1005-16, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16087482

RESUMO

There is increasing interest in the ability of diets rich in polyphenols to modulate age-related diseases and promote healthy ageing. We have conducted a pilot experiment with eight tomato varieties to correlate the total antioxidant capacity of the tomato variants with the specific constituent flavonoids present. A strong correlation was observed with the flavonol rhamnoglucoside rutin but not with other flavonoids, such as naringenin chalcone, or hydroxycinnamates, such as chlorogenic, which are also present in the tomato. To test the rigor of this correlation a second study was undertaken with a further 37 tomato varieties selected for low, medium and high rutin levels. We show that the flavonol rutin contributes to the greatest extent to the antioxidant capacity of tomatoes and suggest that this flavonoid may be a useful target for up-regulation in tomatoes in order to improve their antioxidant status.


Assuntos
Antioxidantes/farmacologia , Rutina/farmacologia , Solanum lycopersicum , Cromatografia Líquida de Alta Pressão , Solanum lycopersicum/química , Solanum lycopersicum/genética , Espectrometria de Massas/métodos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Rutina/genética , Rutina/isolamento & purificação , Transdução de Sinais
12.
Neurosci Lett ; 371(2-3): 106-10, 2004 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-15519738

RESUMO

The levels of zinc in the brain are directly affected by dietary zinc and deficiency has been associated with alcohol withdrawal seizures, excitotoxicity, impaired learning and memory and an accelerated rate of dysfunction in aged brain. Although zinc is essential for a healthy nervous system, high concentrations of zinc are neurotoxic, thus it is important to identify the most effective forms of zinc for treatment of conditions of the central nervous system. Accumulating evidence suggests that zinc-histidine complex (Zn(His)(2)) has greater biological potency and enhanced bioavailability compared with other zinc salts and also has antioxidant potential. Therefore, in this study we investigated the ability of zinc-histidine to protect cultured cortical neurons against hydrogen peroxide-induced damage. Pre-treating neurons for 18 h with subtoxic concentrations of zinc-histidine (5-25 microM) improved neuronal viability and strongly inhibited hydrogen peroxide-induced (75 microM, 30 min) cell damage as assessed by MTT turnover and morphological analysis 24h later. Low concentrations of zinc-histidine were more neuroprotective than zinc chloride. There was evidence of an anti-apoptotic mechanism of action as zinc-histidine inhibited hydrogen peroxide-induced caspase-3 activation and c-jun-N-terminal kinase phosphorylation. In summary, zinc supplementation with zinc-histidine protects cultured neurons against oxidative insults and inhibits apoptosis which suggests that zinc-histidine may be beneficial in the treatment of diseases of the CNS associated with zinc deficiency.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Histidina/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Compostos Organometálicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Células Cultivadas , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , Camundongos , Neurônios/metabolismo , Estresse Oxidativo/fisiologia
13.
Org Lett ; 4(25): 4391-3, 2002 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-12465895

RESUMO

[reaction: see text] Computer-aided design protocols to identify new chiral ligands for reactions proceeding through well-defined transition states are outlined. Ligand families are discovered via computational screening of large structural databases such as the Cambridge Structural Database. Using this method, a novel cis-decalin ligand has been identified as a chiral auxiliary for the allylboration of aldehydes. Synthesis, resolution, and evaluation revealed that this new auxiliary provided the aldehyde facial approach upon which the design was predicated.


Assuntos
Desenho Assistido por Computador , Desenho de Fármacos , Bases de Dados Factuais , Avaliação Pré-Clínica de Medicamentos , Ligantes , Estrutura Molecular , Software , Estereoisomerismo
15.
Free Radic Res ; 36(2): 157-62, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11999383

RESUMO

Oxidative damage to DNA has often been used as a biomarker for oxidative stress and more specifically for cancer risk. Indeed, the measurement of oxidative damage to DNA, particularly of 8-hydroxyguanine (8OHG) and 8-hydroxy-2'-deoxyguanosine (8OHdG), has been adopted as a method for establishing the effects of antioxidant supplementation towards protection from certain cancers, cardiovascular and neuro-degenerative diseases, both in patients and healthy individuals. However, reported levels of 8OHdG or 8OHG vary considerably, possibly due to the different methodologies used, and only few data are available for the non-smoking and the female population. In this paper, steady-state levels of oxidative damage to DNA measured in a group of 20 males and 19 females are reported. Significant gender differences in levels of modified DNA bases such as 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FAPy guanine), 8-hydroxyadenine (8OHA) and 5-hydroxycytosine (5OHC), measured by gas chromatography-mass spectrometry (GC/MS), were observed. The results are discussed in relation to the Vitamin C and iron status of the subjects and to the existing, yet limited, literature data. The role of gender in predisposition to oxidative damage to DNA needs to be addressed in future studies.


Assuntos
Adenina/análogos & derivados , Citosina/análogos & derivados , Dano ao DNA , DNA/análise , DNA/metabolismo , Estresse Oxidativo , Caracteres Sexuais , Adenina/sangue , Adenina/metabolismo , Adulto , Ácido Ascórbico/metabolismo , Citosina/sangue , Citosina/metabolismo , DNA/genética , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Pirimidinas/sangue , Pirimidinas/metabolismo
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