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1.
Artigo em Inglês | MEDLINE | ID: mdl-35805477

RESUMO

Globally, there is an urgent need for solutions that can support our aging populations to live well and reduce the associated economic, social and health burdens. Implementing smart technologies within homes and communities may assist people to live well and 'age in place'. To date, there has been little consultation with older Australians addressing either the perceived benefits, or the potential social and ethical challenges associated with smart technology use. To address this, we conducted five World Cafés in two Australian states, aiming to capture citizen knowledge about the possibilities and challenges of smart technologies. The participants (n = 84) were aged 55 years and over, English-speaking, and living independently. Grounding our analysis in values-based social science and biomedical ethical principles, we identified the themes reflecting the participants' understanding, resistance, and acceptance of smart technologies, and the ethical principles, including beneficence, non-maleficence, autonomy, privacy, confidentiality, and justice. Similar to other studies, many of the participants demonstrated cautious and conditional acceptance of smart technologies, while identifying concerns about social isolation, breaches of privacy and confidentiality, surveillance, and stigmatization. Attention to understanding and incorporating the values of older citizens will be important for the acceptance and effectiveness of smart technologies for supporting independent and full lives for older citizens.


Assuntos
Serviços de Assistência Domiciliar , Idoso , Envelhecimento , Austrália , Humanos , Privacidade , Tecnologia
2.
Health Promot J Austr ; 33(3): 566-575, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34529305

RESUMO

ISSUE ADDRESSED: Aboriginal and Torres Strait Islander peoples face challenges in accessing aged care and are less likely to use some services than their non-Indigenous counterparts. Culturally safe care is increasingly recognised as an enabler to improve access and quality of care. This study explored older Aboriginal peoples' perceptions and experience of culturally safe aged care. METHODS: We conducted semi-structured interviews with sixty-three older Aboriginal people, purposively sampled from three rural and remote geographic locations in South Australia, between April and October 2018, with participants who were both receiving and not receiving aged care services. We asked participants how organisations do or could meet their aged care needs. We analysed interview data inductively into themes. These themes were incorporated into six principles of culturally safe aged care which were subsequently endorsed by participants and study stakeholders. RESULTS: Participants described culturally safe aged care services as those which facilitated or maintained connection to participants' culture, traditional lands and community. Five themes were identified: maintaining cultural identity, culturally informed service delivery, culturally competent workforce, culturally supportive environments and partnerships and collaboration within the aged care service system. CONCLUSION: Addressing cultural safety in aged care will require organisations to adapt their policies, service delivery, environments and work practices to meet the needs of older Aboriginal peoples. SO WHAT? Identifying culturally safe aged care from the perspectives of older Aboriginal and Torres Strait Islander peoples provides timely insight to how services may be better designed and implemented to promote quality of life.


Assuntos
Serviços de Saúde do Indígena , Idoso , Austrália , Humanos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Qualidade de Vida , População Rural
3.
Arch Gerontol Geriatr ; 92: 104257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32979550

RESUMO

OBJECTIVES: The aim of this study was to investigate whether perceptions of the neighbourhood environment (NE) and objective measures of the NE were associated with frailty in older adults. METHODS: A cross-sectional study in Adelaide, Australia, recruited a sample of 115 community-dwelling adults aged ≥60 years. Respondents' perceptions of their NEs were assessed using the Neighbourhood Environment Walkability Scale (NEWS). An objective assessment of these NEWS survey questions was conducted using seven variables: residential density, land use mix diversity, street connectivity, accessibility, seasonal persistent green cover, road crash density and crime rate. Frailty was evaluated using the FRAIL (fatigue, resistance, ambulation, illnesses and loss of weight) scale. Multivariable linear regression analyses were employed to assess the associations between NEWS and frailty, and to assess the associations between objective neighbourhood variables and frailty. RESULTS: Frail and pre-frail older adults were more likely to live in areas with lower residential density, lower density of road crashes, and higher accessibility than robust participants. Additionally, a poorer perception of the overall environment, worse land-use mix and accessibility and worse crime safety were associated with frailty and pre-frailty after adjustment of covariates and objective GIS variables. DISCUSSION: Neighbourhood characteristics, both objective and perceived, are associated with frailty levels in older adults, and that strategies to tackle frailty must consider the impact of the neighbourhood environment.


Assuntos
Fragilidade , Idoso , Austrália , Estudos Transversais , Fragilidade/epidemiologia , Humanos , Características de Residência , Caminhada
4.
J Appl Gerontol ; 40(6): 609-619, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32368955

RESUMO

Neighborhood physical characteristics have been consistently associated with the health of older adults. This article investigates links between frailty and perceptions of the neighborhood environment. Using a cross-sectional analysis of 370 community-dwelling older adults from Nagoya, Japan, neighborhood perceptions were assessed using the Neighborhood Environmental Walkability Scale (NEWS) in addition to frailty, using a frailty index. Frailty was associated with the NEWS composite index, land use mix diversity, land use mix access, street connectivity, walking infrastructure, aesthetics, and crime safety, after adjustment for covariates. Older adults with increasing frailty have poorer perceptions of their neighborhoods, which could lead to further constriction of the life-space, less social and physical engagement, and worsening of frailty status.


Assuntos
Ambiente Construído , Fragilidade , Idoso , Estudos Transversais , Planejamento Ambiental , Fragilidade/epidemiologia , Humanos , Estudos Longitudinais , Percepção , Características de Residência , Caminhada
5.
HERD ; 14(1): 141-163, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32452231

RESUMO

BACKGROUND: The public areas of the hospital built environment have hardly been investigated for their age-friendliness. OBJECTIVE: This exploratory, multidisciplinary pilot study investigates the relationship between the physical environment and design of hospital spaces and older people's outpatient experience. METHODS: Sixteen participants were recruited from a geriatric Outpatient Clinic at a metropolitan public hospital in Australia. Participants were engaged in a concurrent mixed-method approach, comprising a comprehensive geriatric survey, walking observation, semi-structured interview and an independent architectural audit. RESULTS: Several elements arising from the hospital environment were identified as facilitators and barriers for its utilization and intrinsically related to participants' physical capacity. DISCUSSION: Age-friendly hospital design needs to consider strategies to remove barriers for older adults of different capacities, thus promoting healthy aging.


Assuntos
Meio Ambiente , Caminhada , Idoso , Austrália , Hospitais , Humanos , Projetos Piloto
6.
Australas J Ageing ; 39(3): e472-e477, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32124560

RESUMO

OBJECTIVE: To assess the changes in fifth-year medical students' perceptions of the importance of frailty and competence in assessing, diagnosing and managing frailty after a 4.5-week geriatric medicine course. METHODS: Students' perceived importance and competence was assessed before and after the course using a 26-item Likert scale questionnaire with scores ranging from 1 to 6. RESULTS: Students' perceptions of the importance of defining frailty (P = .01), explaining what frailty is (P = .03), advising on nutritional needs (P = .001) and exercise (P = .001) and prescribing an exercise program (P < .001) significantly improved after the course. Medical students' perceived competence in assessing, diagnosing and managing frailty was low to moderate precourse and increased significantly postcourse (2.3 [1.2] 4.9 [2.9], mean [IQR], P < .001) across all items. CONCLUSION: An appropriate curriculum focusing on geriatric health conditions such as frailty can improve senior medical students' perceived importance and competence in assessing, diagnosing and managing frailty.


Assuntos
Educação de Graduação em Medicina , Fragilidade , Geriatria , Estudantes de Medicina , Idoso , Competência Clínica , Currículo , Fragilidade/diagnóstico , Fragilidade/terapia , Geriatria/educação , Humanos , Percepção , Inquéritos e Questionários
7.
Healthcare (Basel) ; 7(4)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683757

RESUMO

Outdoor and indoor environments impact older people's mobility, independence, quality of life, and ability to "age in place". Considerable evidence suggests that not only the amount, but also the quality, of public green spaces in the living environment is important. The quality of public green spaces is mostly measured through expert assessments by planners, designers and developers. A disadvantage of this expert-determined approach is that it often does not consider the appraisals or perceptions of residents. Daily experience, often over long periods of time, means older residents have acquired insider knowledge of their neighbourhood, and thus, may be more qualified to assess these spaces, including measuring what makes a valued or quality public green space. The aim of this Australian pilot study on public green spaces for ageing well was to test an innovative citizen science approach to data collection using smart phones. "Senior" citizen scientists trialed the smart phone audit tool over a three-month period, recording and auditing public green spaces in their neighbourhoods. Data collected included geocoded location data, photographs, and qualitative comments along with survey data. While citizen science research is already well established in the natural sciences, it remains underutilised in the social sciences. This paper focuses on the use of citizen science with older participants highlighting the potential for this methodology in the fields of environmental gerontology, urban planning and landscape architecture.

8.
Healthcare (Basel) ; 7(4)2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31684164

RESUMO

Taking an international perspective of healthy ageing, people are living longer and are generally in better health than previous generations [...].

10.
JMIR Res Protoc ; 8(7): e12632, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31368445

RESUMO

BACKGROUND: Young people with refugee experiences are widely acknowledged as encountering multiple disadvantages that affect their school completion and retention, university entry, and subsequent employment. This paper discusses the rationale for and protocol of a mixed methods investigation focusing on improving education and employment outcomes among refugee background youth aged 15 to 24 years from three focus regions: the Middle East (Afghanistan, Iran, Iraq, Syria), South Asia (Nepal, Bhutan, Myanmar/Burma, Pakistan) and Africa (Sudan, South Sudan, Liberia, Ethiopia, Somalia, DR Congo). OBJECTIVE: The rationale of the project is to identify the facilitators and barriers to successful transition from school to further education and employment; investigate participant awareness of support systems available when faced with education and employment difficulties; redress the disadvantages encountered by refugee background youth; and bridge the gap between research, policy, and practice in relation to social inclusion and participation. METHODS: The study involves collecting survey data from 600 youth followed by individual interviews with a subset of 60 youth, their parents/primary caregivers, and their teachers. A cross-sectional survey will assess facilitators and barriers to successful transition from school to further education and employment. Individual interviews will provide context-rich data on key issues relevant to education and employment outcomes. RESULTS: The study began in 2016 and is due for completion by the end of 2019. The quantitative survey has been conducted with 635 participants and was closed in March 2019. The qualitative interview stage is ongoing, and the current total in April 2019 is 93 participants including educators, youth, and family members of the youth. Analysis and presentation of results will be available in 2020. Some preliminary findings will be available during the late half of 2019. CONCLUSIONS: This project will contribute new and unique insights to knowledge in relation to key factors influencing education and employment outcomes among refugee youth. This research will enable effective planning for the needs of some of Australia's most disadvantaged and marginalized young people, leading to a sustainable improvement in the education and employability of young refugees. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12632.

11.
Arch Gerontol Geriatr ; 84: 103908, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31319367

RESUMO

Frailty prevalence defined by the deficit accumulation model (Frailty Index) has limited exploration in a Japanese population. The objective of this paper is to investigate the prevalence of frailty by Frailty Index among a cohort of healthy Japanese older adults, define risk factors associated with pre-frailty and frailty status and evaluate Frailty Index's agreement with Frailty Phenotype and Kihon checklist. METHODS: Data from 673 participants of the 2014 wave of the Nagoya Longitudinal Study - Healthy Elderly were used. Annual assessments include investigation of mood, memory, health status, nutrition, physical performance and oral health. The Frailty Index was compared to Frailty Phenotype and Kihon Checklist, and factors associated to Frailty Index were investigated through univariate and multivariate logistic regression. RESULTS: Frailty prevalence was 13.5% (n = 91) by Frailty Index, 1.5% (n = 10) by Frailty Phenotype and 4% (n = 27) by Kihon Checklist. Although the correlations between the three scales were moderate to high, the agreement between the scales was poor. In terms of risk factors, age, polypharmacy and physical activity level were associated with being pre-frail and frail. Having a higher waist circumference was associated with being pre-frail, and lower handgrip strength and lower walking speed were associated with being frail. CONCLUSIONS: The Frailty Index showed similar metrics and agreement comparable to findings of previous studies, and was able to identify a higher number of individuals who were pre-frail and frail. Age, polypharmacy, physical activity, waking speed and waist circumference were associated with pre-frailty and frailty by frailty index.


Assuntos
Fragilidade/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , Idoso Fragilizado , Avaliação Geriátrica , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência
12.
World J Gastroenterol ; 18(15): 1732-44, 2012 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-22553397

RESUMO

AIM: To investigate the influence of macrophages on hepatocyte phenotype and function. METHODS: Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophage-conditioned medium on HepG2 mRNA and protein expression determined. The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus (HCV) infection. RESULTS: Conditioned media from macrophages, but not monocytes, induced a transient morphological change in hepatocytes associated with upregulation of vimentin (7.8 ± 2.5-fold, P = 0.045) and transforming growth factor (TGF)-ß1 (2.6 ± 0.2-fold, P < 0.001) and downregulation of epithelial cadherin (1.7 ± 0.02-fold, P = 0.017) mRNA expression. Microarray analysis revealed significant upregulation of lipocalin-2 (17-fold, P < 0.001) and pathways associated with inflammation, and substantial downregulation of pathways related to hepatocyte function. In patients with chronic HCV, real-time polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA (F0 1.0 ± 0.3, F1 2.2 ± 0.2, F2 3.0 ± 9.3, F3/4 4.0 ± 0.8, P = 0.003) and protein expression (F1 1.0 ± 0.5, F2 1.3 ± 0.4, F3/4 3.6 ± 0.4, P = 0.014) with increasing liver injury. High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase (MMP)-9 in macrophage-conditioned medium, and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-ß1 (2.9 ± 0.2 vs 1.04 ± 0.1, P < 0.001) in macrophage-conditioned media treated HepG2 cells. In patients with chronic HCV infection, hepatic mRNA expression of CD163 (F0 1.0 ± 0.2, F1/2 2.8 ± 0.3, F3/4 5.3 ± 1.0, P = 0.001) and MMP-9 (F0 1.0 ± 0.4, F1/2 2.8 ± 0.3, F3/4 4.1 ± 0.8, P = 0.011) was significantly associated with increasing stage of fibrosis. CONCLUSION: Secreted macrophage products alter the phenotype and function of hepatocytes, with increased expression of inflammatory mediators, suggesting that hepatocytes actively participate in liver injury.


Assuntos
Hepatócitos/fisiologia , Mediadores da Inflamação/metabolismo , Macrófagos/fisiologia , Proteínas de Fase Aguda/fisiologia , Antígenos CD/fisiologia , Antígenos de Diferenciação Mielomonocítica/fisiologia , Perfilação da Expressão Gênica , Células Hep G2 , Humanos , Lipocalina-2 , Lipocalinas/fisiologia , Cirrose Hepática/metabolismo , Metaloproteinase 9 da Matriz/fisiologia , Fenótipo , Proteínas Proto-Oncogênicas/fisiologia , RNA Mensageiro/análise , Receptores de Superfície Celular/fisiologia
13.
Hepatology ; 53(6): 1819-29, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21381070

RESUMO

UNLABELLED: Interleukin 32 (IL-32) is a recently described proinflammatory cytokine that activates p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), thereby inducing proinflammatory cytokines such as IL-1ß and tumor necrosis factor alpha (TNF-α). We investigated the role of IL-32 in patients with chronic hepatitis C virus (HCV) infection. Steady-state hepatic messenger RNA (mRNA) levels of IL-32 were determined in a cohort of 90 subjects; anti-IL-32 staining was used in a second cohort of 132 consecutive untreated chronic HCV patients. Correlations with histological features of steatosis, inflammation, and fibrosis were made. In vitro, endogenous IL-32 in monocytes and in the human hepatoma cell line Huh-7.5 were examined. The effects of IL-32-overexpression and IL-32-silencing on HCV replication were studied using HCV luciferase reporter viruses. There were highly significant positive associations between hepatic IL-32 mRNA expression and liver steatosis, inflammation, fibrosis, smooth muscle actin (SMA) area, and serum alanine aminotransferase (ALT) levels. IL-32 protein expression was positively associated with portal inflammation, SMA area, and ALT. In vitro, IL-1ß and TNF-α significantly induced IL-32 expression in human Huh-7.5 cells. Alone, stimulation with interferon alpha (IFN-α) did not induce IL-32 expression in Huh-7.5. However, IFN-α exerted a significant additive effect on TNF-α-induced but not IL-1ß-induced IL-32 expression, particularly in CD14+ monocytes. This effect was dependent both on NF-κB and Jak/STAT signaling. Viral infection of Huh-7.5 cells resulted in a significant (11-fold) induction of IL-32 mRNA expression. However, modulation of IL-32 in Huh-7.5 cells by overexpression or silencing did not influence HCV virus replication as determined by luciferase assays. CONCLUSION: IL-32 is a novel proinflammatory cytokine involved in HCV-associated liver inflammation/fibrosis. IL-32 is expressed by human hepatocytes and hepatoma cells and its expression is regulated by proinflammatory stimuli.


Assuntos
Hepatite C Crônica/metabolismo , Hepatite C Crônica/patologia , Interleucinas/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Adulto , Biópsia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hepacivirus/fisiologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Interferon-alfa/farmacologia , Interleucina-1beta/farmacologia , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator de Necrose Tumoral alfa/farmacologia , Replicação Viral/fisiologia
14.
J Gastroenterol Hepatol ; 26(2): 319-27, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21261722

RESUMO

BACKGROUND AND AIM: Hepatitis C virus (HCV) proteins activate the unfolded protein response (UPR) in experimental models. The role of the UPR in the pathogenesis of HCV-induced liver injury has not been determined. Our aim was to investigate the role of the UPR in the pathogenesis of chronic HCV. METHODS: Liver biopsy samples from 124 patients with chronic HCV and 24 HCV/HBV-negative subjects with histologically normal liver (NDL) were assessed. The hepatic mRNA expression of components of the UPR was measured by semi-quantitative real-time polymerase chain reaction. Glucose regulated protein (GRP) 78 protein expression was assessed by immunohistochemistry. RESULTS: The expression of GRP78 mRNA and growth arrest and damage inducible protein 34 (GADD34) mRNA was significantly lower in subjects with HCV than NDL (P = 0.007 and P < 0.001, respectively). There was no significant difference in the expression of GRP94 mRNA, spliced X box binding protein 1 (sXBP1) mRNA, C/EBP homologous protein mRNA (CHOP) and ER degradation enhancing α-mannosidase-like protein (EDEM) mRNA and GRP78 protein between patients with HCV and NDL. There were no relationships between elements of the UPR and inflammation or fibrosis in patients with HCV. CONCLUSION: Downstream components of UPR were not activated in patients with chronic HCV. Therefore, the UPR may not play a prominent role in liver injury in patients with chronic HCV infection.


Assuntos
Hepatite C Crônica/metabolismo , Fígado/metabolismo , Resposta a Proteínas não Dobradas , Fator 6 Ativador da Transcrição/metabolismo , Adulto , Antígenos de Diferenciação/genética , Biópsia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Distribuição de Qui-Quadrado , Proteínas de Ligação a DNA/genética , Chaperona BiP do Retículo Endoplasmático , Endorribonucleases/metabolismo , Feminino , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Hepatite C Crônica/genética , Hepatite C Crônica/patologia , Humanos , Imuno-Histoquímica , Fígado/patologia , Fígado/virologia , Masculino , Proteína Fosfatase 1 , Proteínas Serina-Treonina Quinases/metabolismo , Queensland , RNA Mensageiro/metabolismo , Fatores de Transcrição de Fator Regulador X , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição CHOP/genética , Fatores de Transcrição/genética , Resposta a Proteínas não Dobradas/genética , eIF-2 Quinase/metabolismo
15.
J Hepatol ; 49(6): 1046-54, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18752865

RESUMO

BACKGROUND/AIMS: Increased expression of sterol regulatory element binding protein (SREBP)-1c, a transcription factor regulating lipogenesis, has been reported in HCV core protein-transfected hepatocytes. Our aim was to investigate the role of SREBP-1c in the pathogenesis of HCV-related steatosis. METHODS: One hundred and twenty-four patients with HCV and 13 subjects with histologically normal liver (NDL) were studied. The mRNA expression of SREBP-1c, fatty acid synthase (FAS), glycerol-3-phosphate acyltransferase (GPAT) and microsomal triglyceride transfer protein (MTP) was measured by qPCR, and SREBP-1 protein quantitated by immunohistochemistry. RESULTS: There was no significant difference in the hepatic expression of SREBP-1c mRNA between subjects with HCV and NDL. In patients with HCV, a significant negative relationship was seen between hepatic SREBP-1c mRNA expression and grade of steatosis (r(s)=-0.28, p=0.002), stage of fibrosis (r(s)=-0.375, p<0.001) and severity of inflammation (r(s)=-0.313, p<0.001). These relationships were observed for patients infected with either viral genotype 1 or 3. Following multivariate logistic regression analysis, hepatic SREBP-1c expression remained independently associated with fibrosis (p=0.008) and hepatic inflammation (p=0.005). HCV-infected patients with HOMA>2 had significantly higher expression of FAS mRNA than HCV-infected subjects with HOMA2 (p=0.006) and NDL (p=0.016). CONCLUSIONS: SREBP-1c may not play a prominent role in the pathogenesis of HCV-related steatosis.


Assuntos
Fígado Gorduroso , Hepatite C Crônica/genética , Lipogênese/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Adulto , Proteínas de Transporte/genética , Ácido Graxo Sintases/genética , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/virologia , Feminino , Expressão Gênica , Glicerol-3-Fosfato O-Aciltransferase/genética , Hepatite C Crônica/patologia , Humanos , Imuno-Histoquímica , Resistência à Insulina/genética , Masculino , RNA Mensageiro/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
16.
Hepatology ; 48(1): 80-7, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18571785

RESUMO

UNLABELLED: Obesity and fatty liver are commonly observed among patients with chronic hepatitis C virus (HCV) and are risk factors for increased hepatic fibrosis. Obesity is accompanied by a low-grade, chronic inflammatory response that may contribute to pathogenesis of obesity-related comorbidities. To assess whether obesity and steatosis potentiate expression of inflammatory markers in chronic HCV, serum protein and hepatic messenger RNA (mRNA) levels of c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured in 171 patients with chronic HCV. The relationships of body mass index, steatosis, histological features of inflammation and fibrosis with serum and hepatic levels of these factors were determined. In comparison with lean patients, overweight and obese subjects had increased circulating (P < 0.001) and hepatic (P = 0.003) CRP, and there was a significant correlation between serum protein and hepatic CRP mRNA levels (r(s)= 0.51, P < 0.001). Obesity (P = 0.001) and steatosis (P < 0.001) were associated with increased circulating but not hepatic IL-6, and a weak correlation was seen between serum protein and hepatic IL-6 mRNA levels (r(s)= 0.29, P = 0.003). An independent relationship was seen between hepatic TNF-alpha mRNA levels and higher total inflammatory score (P < 0.001) and stage of fibrosis (P = 0.037). Subjects with HCV genotype 3 had lower hepatic TNF-alpha mRNA levels compared with subjects with genotype 1 (P = 0.017), but there was no relationship between serum TNF-alpha protein and hepatic TNF-alpha mRNA levels. CONCLUSION: In patients with chronic HCV, obesity and steatosis are associated with increased expression of selected inflammatory markers; however, circulating levels of IL-6 and TNF-alpha do not reflect hepatic expression. Hepatic TNF-alpha was associated with both increased inflammatory activity and hepatic fibrosis, providing support for the key role of this pro-inflammatory cytokine in liver injury in chronic HCV.


Assuntos
Biomarcadores/sangue , Fígado Gorduroso/complicações , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Obesidade/complicações , Adulto , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Feminino , Fibrose , Hepatite C Crônica/metabolismo , Hepatite C Crônica/patologia , Humanos , Interleucina-6/sangue , Interleucina-6/genética , Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
Electrophoresis ; 23(19): 3310-20, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12373758

RESUMO

To obviate the need for multilocus sequencing, a method using denaturing gradient gel electrophoresis (DGGE) was developed for the multilocus sequence typing (MLST) of Staphylococcus aureus isolates. Sequence types (STs) were obtained on the basis of sequences of polymerase chain reaction (PCR) products from seven housekeeping genes and compared to the reference MLST database. The melt curves, sequences and DGGE profiles were compared for 100 STs (i) to determine PCR conditions with 40-mer GC-clamps attached to the forward and reverse primers; (ii) to choose single restriction enzyme sites for digestion of PCR products into two fragments each with a GC-clamp attached and (iii) to optimize DGGE conditions. When the DGGE types (DT) were analyzed, the majority of DTs (76/100) were accurately classified into one ST (95% of nucleotide changes were detected), 10 DTs were classified into one of two STs corresponding to a single nucleotide ambiguity and 14 DTs were classified into 3 or 4 STs corresponding to 4 or 5 nucleotide ambiguities. A combination of STs and DTs were used to obtain septuplet sets of STs (7-ST) for 25 S. aureus isolates. When compared to the reference MLST database, one methicillin-resistant S. aureus (MRSA) isolate had the same genotype as the first MRSA clone. The DGGE-MLST method can be used as a rapid, accurate and 20-fold less expensive method than DNA sequencing for the detection of all sequence types. This combined laboratory and in silico approach could have wide applicability not only to MLST methods for other bacteria but to the screening of multilocus nucleotide differences deposited in other mutation databases.


Assuntos
DNA Bacteriano/genética , Análise de Sequência de DNA/métodos , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Alelos , Sequência de Bases , Eletroforese em Gel de Ágar , Genes Bacterianos/genética , Desnaturação de Ácido Nucleico , Filogenia
18.
Microbiology (Reading) ; 141 ( Pt 5): 1255-1265, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7773419

RESUMO

To develop a rapid and accurate method of typing large numbers of clinical isolates of Staphylococcus aureus, the spacer region C of the rRNA operon [1391-507 (16S-23S)] was enzymically amplified from 322 strains. When the products were separated by denaturing PAGE, 15 variable-length rrn alleles were demonstrated, ranging in size from 906 to 1223 bp. The variable-length HpaII-digested region C [(region E; 1446-196 (16S-23S)] amplification products were cloned into M13mp18RF to sequence separate variable-length alleles. A total of 17 region E inserts were sequenced, aligned and divided into nine alleles by length (938-1174) and sequence properties. The 16S-23S spacer rDNA varied in length (303-551 bp) and in properties; three alleles contained a tRNAIle gene alone, two alleles contained a tRNAIle and a tRNAAla gene, and four alleles lacked tRNA genes. The sequences of two alleles showed less than 1% variation when isolated from two or three S. aureus strains. The 48 penicillin- and methicillin-sensitive strains were divided into 26 ribotypes; in contrast, the 274 methicillin-resistant S. aureus (MRSA) strains were divided into nine ribotypes (A-I) with 97% typing as either ribotype A or B (rrnL was missing in B). The sequence conservation of the rrn operons argues for the use of the 16S-23S spacer region as a stable and direct indicator of the evolutionary divergence of S. aureus strains.


Assuntos
DNA Ribossômico/genética , Filogenia , Reação em Cadeia da Polimerase/métodos , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Alelos , Sequência de Bases , Primers do DNA , DNA Ribossômico/química , Genes Bacterianos , Humanos , Resistência a Meticilina/genética , Dados de Sequência Molecular , Resistência às Penicilinas/genética , RNA Ribossômico 16S/genética , RNA Ribossômico 23S/genética , RNA de Transferência de Fenilalanina/genética , Reprodutibilidade dos Testes , Mapeamento por Restrição , Homologia de Sequência do Ácido Nucleico , Staphylococcus aureus/isolamento & purificação
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