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1.
JAMA ; 321(17): 1702-1715, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063572

RESUMO

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main Outcomes and Measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). Conclusions and Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.


Assuntos
Índice de Massa Corporal , Ganho de Peso na Gestação , Complicações na Gravidez , Resultado da Gravidez , Adulto , Peso ao Nascer , Cesárea/estatística & dados numéricos , Diabetes Gestacional , Feminino , Humanos , Hipertensão Induzida pela Gravidez , Recém-Nascido , Obesidade , Gravidez , Nascimento Prematuro
2.
PLoS Med ; 16(2): e1002744, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742624

RESUMO

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.


Assuntos
Índice de Massa Corporal , Análise de Dados , Ganho de Peso na Gestação/fisiologia , Obesidade Pediátrica/epidemiologia , Austrália/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , América do Norte/epidemiologia , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Obesidade Pediátrica/diagnóstico , Gravidez , Fatores de Risco
3.
BMC Med ; 16(1): 201, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30396358

RESUMO

BACKGROUND: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. METHODS: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. RESULTS: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. CONCLUSIONS: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

4.
Appetite ; 130: 190-198, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30118787

RESUMO

This exploratory article examines the novel term food sense and informal learning in the context of home cooking. Its theory draws from Dewey's work and from his notions of reflexive thought and action. The data consist of a transcribed audio recording of an in-depth, video-based, stimulated-recall (SR) interview. The auto-ethnographic videos were used to stimulate conversation during the interview and were previously collected as part of a broader research project on home cooking in a Finnish family context. Based on the theory and the data, the definition of food sense was refined into a model consisting of three levels: 'Understanding' as the ability to define and interpret emerging ruptures in activity; 'Applying' as the competence to plan and execute solutions that function in context; and 'Re-defining' as the reformulation of activities to enable new ways of doing. In reference to the empirical examples, two of the three episodes represented 'Understanding' and 'Applying'; whereas the third example included also the potential for re-defining habitual ways of action. However, despite possession of relevant knowledge and initial motivation, the emergence of negative emotions of the person in charge of the cooking process prevented reformulating existing cooking habits. By providing novel insights into the social, cultural, and situated nature of home cooking, the article complements the more individual-focused and/or knowledge-based approaches used by other recent studies of cooking skills and learning.

5.
Clin Nutr ; 2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-30017243

RESUMO

BACKGROUND & AIMS: Human milk (HM) contains a wide array of non-nutritive bioactive elements, including glucocorticoid hormones (glucocorticoid; cortisol and cortisone). The relationship between milk-borne glucocorticoids, measures of maternal health and patterns of breast-feeding is not yet established. This study was conducted to determine the influence of maternal and infant related biological and socio-demographic factors on the levels of glucocorticoids hormones in HM. METHODS: Samples were obtained from lactating mothers (n = 656) participating in the Finnish cohort the STEPS study (Steps to the Healthy Development and Well-being of Children) when the infants were 11.29 (±2.6) weeks of age. Glucocorticoids (both cortisol and cortisone) concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Maternal demographics, biological and social factors were obtained using hospital records and self-reported diaries and questionnaires. RESULTS: The majority of women reported that they were exclusively breastfeeding at the time of sample donation (51.2%). For all collected samples, cortisone (9.55 ± 3.44 ng/ml) was the predominant hormone and cortisol (7.39 ± 5.97 ng/ml) was present in all samples. Strong and positive correlation was found between cortisol and cortisone (r = 0.60, p=<0.0001). Cortisone was statistically different between overweight, normal and underweight women (p = 0.01) for cortisol no difference was seen (p = 0.96). Whilst, preterm birth (born before 37 week gestation) was positively associated with both cortisol (p = 0.04) and cortisone (p = 0.01). There was also a significant but weaker negative relationship between mothers educational status and cortisol (p = 0.05) and no effect was seen for cortisone (p = 0.82). Interestingly, no significant differences was found in glucocorticoid concentrations between exclusive and partial breastfeeding women. CONCLUSION: HM contains glucocorticoids hormones. The concentrations are influenced by the varying maternal factors including maternal weight, preterm birth and maternal educational status, suggesting the possible role of maternal biological and social influences on milk hormonal composition. Interestingly, there was no influence of feeding patterns on HM glucocorticoids. Further analysis is required to fully explore the relationship with measures of maternal stress, including mother's glucocorticoid status.

6.
Acta Oncol ; 56(10): 1272-1276, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28562152

RESUMO

BACKGROUND: Recent trends in the end-of-life (EOL) cancer care have suggested that the levels of treatment are becoming more aggressive. The aim of this single-center study was to evaluate the time from the last intravenous (IV) chemotherapy treatment to death and identify factors correlating with treatment closer to death. MATERIAL AND METHODS: The study included all patients diagnosed with cancer at Turku University Central Hospital between the years 2005 and 2013 (N = 38,982) who received IV chemotherapy during the last year of life (N = 3285). The cohort of patients and their respective clinical information were identified from electronic medical records. Statistical analysis was performed to assess and compare the treatment strategies, taking into account the patient's age, the year they were treated, and the type of cancer they were diagnosed with. RESULTS: A total of 11,250 cancer patients died during the observation time and one-third (N = 3285, 29.2%) of them had received IV chemotherapy during the last year of life. The time from the last IV chemotherapy regimen to death remained consistent across the follow-up time. During the last month of life, every third patient under the age of 50 years and only one-tenth of patients over the age of 80 years received IV chemotherapy. Hematological malignancies and lymphomas were treated closer to death when compared to other diagnostic groups. CONCLUSIONS: During the period of 9 years, the pattern of EOL IV chemotherapy treatment remained stable. Every third patient died at tertiary care. Only 7.2% of patients who received IV chemotherapy during the last year of life were treated 14 days before death, which is in line with international recommendations. However, significant variation in EOL treatment strategies between different diagnosis and age groups were identified.


Assuntos
Neoplasias/tratamento farmacológico , Assistência Terminal , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Finlândia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Circ Cardiovasc Genet ; 10(3)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28620069

RESUMO

BACKGROUND: Obesity is a known risk factor for cardiovascular disease. Early prediction of obesity is essential for prevention. The aim of this study is to assess the use of childhood clinical factors and the genetic risk factors in predicting adulthood obesity using machine learning methods. METHODS AND RESULTS: A total of 2262 participants from the Cardiovascular Risk in YFS (Young Finns Study) were followed up from childhood (age 3-18 years) to adulthood for 31 years. The data were divided into training (n=1625) and validation (n=637) set. The effect of known genetic risk factors (97 single-nucleotide polymorphisms) was investigated as a weighted genetic risk score of all 97 single-nucleotide polymorphisms (WGRS97) or a subset of 19 most significant single-nucleotide polymorphisms (WGRS19) using boosting machine learning technique. WGRS97 and WGRS19 were validated using external data (n=369) from BHS (Bogalusa Heart Study). WGRS19 improved the accuracy of predicting adulthood obesity in training (area under the curve [AUC=0.787 versus AUC=0.744, P<0.0001) and validation data (AUC=0.769 versus AUC=0.747, P=0.026). WGRS97 improved the accuracy in training (AUC=0.782 versus AUC=0.744, P<0.0001) but not in validation data (AUC=0.749 versus AUC=0.747, P=0.785). Higher WGRS19 associated with higher body mass index at 9 years and WGRS97 at 6 years. Replication in BHS confirmed our findings that WGRS19 and WGRS97 are associated with body mass index. CONCLUSIONS: WGRS19 improves prediction of adulthood obesity. Predictive accuracy is highest among young children (3-6 years), whereas among older children (9-18 years) the risk can be identified using childhood clinical factors. The model is helpful in screening children with high risk of developing obesity.


Assuntos
Obesidade/etiologia , Adolescente , Adulto , Área Sob a Curva , Índice de Massa Corporal , Proteína C-Reativa/análise , Proteínas de Transporte/genética , Criança , Pré-Escolar , Feminino , Finlândia , Seguimentos , Humanos , Modelos Logísticos , MAP Quinase Quinase 5/genética , Aprendizado de Máquina , Masculino , Obesidade/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único , Curva ROC , Fatores de Risco , Fator de Transcrição AP-2/genética
8.
Appetite ; 116: 157-163, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28457982

RESUMO

Maintaining normal weight in the current obesogenic environment is a challenge. However, some people can do it. More insight is needed to understand how and why some people succeed in long-term weight maintenance. This study uses a rare, qualitative approach by describing the thoughts of successful weight management and self-perceived requirements for success in weight maintenance. We interviewed 39 individuals who have maintained normal weight for their entire lives (men and women). The content analysis revealed a main theme: flexible, permissive and conscious self-regulation, which was divided into two subthemes (eating-related behavior and weight-related behavior). The informants reported certain routines that supported their weight management: regular eating, sufficient meal sizes, eating in response to hunger, healthy and vegetable-rich diet along with moderate feasting and flexible eating restriction. Flexibility in routines allowed freedom in their eating behavior. In addition, informants regarded themselves as physically active, and they enjoyed regular exercise. Regular weighing was generally considered unnecessary. Normal weight was regarded as a valuable and worthwhile issue, and most of the informants worked to keep their weight stable. Although the perceived workload varied among informants, the weight management strategies were similar. It was crucial to be conscious of the balance between eating and energy consumption. Further, flexibility characterized their behavior and was the basis of successful weight management. Women were more aware of weight control practices and knowledge than men, but otherwise, women and men reported similar weight management methods and attitudes. In conclusion, the interviewees who have maintained the normal weight had created a personal weight-management support environment where weight management was a lifestyle.


Assuntos
Adaptação Psicológica , Manutenção do Peso Corporal , Exercício , Estilo de Vida Saudável , Modelos Psicológicos , Cooperação do Paciente , Adulto , Idoso , Regulação do Apetite , Índice de Massa Corporal , Exercício/psicologia , Comportamento Alimentar/psicologia , Feminino , Finlândia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Cooperação do Paciente/psicologia , Pesquisa Qualitativa , Autorrelato , Autocontrole/psicologia , Fatores Sexuais
9.
Acta Oncol ; 56(10): 1265-1271, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28503990

RESUMO

BACKGROUND: Palliative radiotherapy can improve quality of life for cancer patients during the last months of life. However, very short life expectancy may devastate the benefit of the treatment. This single center study assesses the utilization of radiotherapy during the last weeks of life. MATERIAL AND METHODS: All cancer patients (N = 38,982) treated with radiotherapy (N = 11,395) in Turku University Central Hospital during 2005-2013 were identified in the database consisting of electronic patient records. One fourth (N = 2904, 25.5%) of the radiotherapy treatments were given during the last year of life. The last radiotherapy treatments and the time from the last radiotherapy treatment to death were assessed in regards to patients' age, cancer diagnosis, domicile, place of death and the treatment year. Treatments given during the last two weeks of life were also assessed regarding the goal of treatment and the reason for possible discontinuation. RESULTS: The median time from the last fraction of radiotherapy to death was 84 d. During the last two weeks before death (N = 340), pain (29.4%) was the most common indication for radiotherapy. Treatment was discontinued in 40.6% of the patients during the last two weeks of life, and worsening of general condition was the most common reason for discontinuity (70.3%). The patients receiving radiotherapy during the last weeks of life were more likely to die in tertiary care unit. During the last year of life single-fraction treatment was used only in 7% of all therapy courses. There was a statistically significant (p < .05) decrease in the median number of fractions in the last radiotherapy treatment between 2005-2007 (8 fractions) and 2011-2013 (6 fractions). CONCLUSIONS: Up to 70% of the treatments during the last two weeks of life were not delivered to alleviate pain and utilization of single fraction radiotherapy during the last year of life was infrequent. These observations suggest that practice of radiotherapy during the last weeks of life should be revisited.


Assuntos
Neoplasias/radioterapia , Assistência Terminal , Finlândia , Humanos , Estudos Retrospectivos
10.
Appetite ; 105: 274-82, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27245571

RESUMO

The study analysed public debates on the association of milk fats, vegetable oils and cardiovascular diseases (CVDs) between 1978 and 2013 in Finland, a country with a decades-long history of public health initiatives targeting fat consumption. The main agendas, conflicts and participants were analysed. The data were collected from the newspaper Helsingin Sanomat and consisted of 52 threads and 250 texts. We identified four themes around which there were repeated, often overlapping conflicts: the health risks of saturated fats, expertise of the risks of fat consumption, the adequate evidence of the risks of fat consumption, and framing the fat question. During the research period, the main arguments of the effects of consumption of fats have remained the same. References to epidemiological and intervention studies and framing of the fat question as a public health issue, have been ongoing, as has the definition of what constitutes genuine expertise. Yet, we also found discontinuities. In the early 2000s new emphases began to emerge: personal experiences were increasingly presented as evidence of the effects of dietary choices on human health, and the question of fat consumption was framed either as one of enjoyment or of a consumers' right to choose rather than only being a public health question. Moreover, new professional groups such as chefs and creative professionals now joined the discussion.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Gorduras na Dieta/uso terapêutico , Medicina Baseada em Evidências , Glicolipídeos/efeitos adversos , Glicoproteínas/efeitos adversos , Dieta Saudável , Ciências da Nutrição/história , Óleos Vegetais/uso terapêutico , Animais , Manteiga/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/etiologia , Comportamento do Consumidor , Culinária , Gorduras na Dieta/efeitos adversos , Finlândia/epidemiologia , Preferências Alimentares/etnologia , Dieta Saudável/etnologia , Dieta Saudável/tendências , História do Século XX , História do Século XXI , Humanos , Leite/efeitos adversos , Jornais como Assunto , Ciências da Nutrição/tendências , Óleos Vegetais/efeitos adversos , Prazer , Competência Profissional , Risco , Paladar , Recursos Humanos
11.
Appetite ; 103: 358-368, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27131417

RESUMO

How have eating patterns changed in modern life? In public and academic debate concern has been expressed that the social function of eating may be challenged by de-structuration and the dissolution of traditions. We analyzed changes in the social context and conduct of eating in four Nordic countries over the period 1997-2012. We focused on three interlinked processes often claimed to be distinctive of modern eating: delocalization of eating from private households to commercial settings, individualization in the form of more eating alone, and informalization, implying more casual codes of conduct. We based the analysis on data from two surveys conducted in Denmark, Finland, Norway and Sweden in 1997 and 2012. The surveys reported in detail one day of eating in representative samples of adult populations in the four countries (N = 4823 and N = 8242). We compared data regarding where, with whom, and for how long people ate, and whether parallel activities took place while eating. While Nordic people's primary location for eating remained the home and the workplace, the practices of eating in haste, and while watching television increased and using tablets, computers and smartphones while eating was frequent in 2012. Propensity to eat alone increased slightly in Denmark and Norway, and decreased slightly in Sweden. While such practices vary with socio-economic background, regression analysis showed several changes were common across the Nordic populations. However, the new practice of using tablets, computers, and smartphones while eating was strongly associated with young age. Further, each of the practices appeared to be related to different types of meal. We conclude that while the changes in the social organization of eating were not dramatic, signs of individualization and informalization could be detected.


Assuntos
Ingestão de Alimentos/psicologia , Comportamento Alimentar/psicologia , Adolescente , Adulto , Idoso , Atitude Frente aos Computadores , Estudos Transversais , Dinamarca , Feminino , Finlândia , Humanos , Masculino , Refeições/psicologia , Pessoa de Meia-Idade , Noruega , Restaurantes , Meio Social , Isolamento Social/psicologia , Fatores Socioeconômicos , Inquéritos e Questionários , Suécia
13.
Eur J Neurosci ; 43(5): 626-39, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26741810

RESUMO

Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator involved in the regulation of mitochondrial biogenesis and cell defense. The functions of PGC-1α in physiology of brain mitochondria are, however, not fully understood. To address this we have studied wild-type and transgenic mice with a two-fold overexpression of PGC-1α in brain neurons. Data showed that the relative number and basal respiration of brain mitochondria were increased in PGC-1α transgenic mice compared with wild-type mitochondria. These changes occurred concomitantly with altered levels of proteins involved in oxidative phosphorylation (OXPHOS) as studied by proteomic analyses and immunoblottings. Cultured hippocampal neurons from PGC-1α transgenic mice were more resistant to cell degeneration induced by the glutamate receptor agonist kainic acid. In vivo kainic acid induced excitotoxic cell death in the hippocampus at 48 h in wild-type mice but significantly less so in PGC-1α transgenic mice. However, at later time points cell degeneration was also evident in the transgenic mouse hippocampus, indicating that PGC-1α overexpression can induce a delay in cell death. Immunoblotting showed that X-linked inhibitor of apoptosis protein (XIAP) was increased in PGC-1α transgenic hippocampus with no significant changes in Bcl-2 or Bcl-X. Collectively, these results show that PGC-1α overexpression contributes to enhanced neuronal viability by stimulating mitochondria number and respiration and increasing levels of OXPHOS proteins and the anti-apoptotic protein XIAP.


Assuntos
Lesões Encefálicas/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Animais , Lesões Encefálicas/etiologia , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/metabolismo , Morte Celular , Células Cultivadas , Proteínas Inibidoras de Apoptose/genética , Ácido Caínico/toxicidade , Camundongos , Fosforilação Oxidativa , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
14.
Cell Transplant ; 25(1): 55-69, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26021843

RESUMO

Therapeutic effects of skeletal myoblast transplantation into the myocardium are mediated via paracrine factors. We investigated the ability of myoblast-derived soluble mediators to protect cardiomyocytes from oxidative stress. Fetal rat cardiac cells were treated with conditioned medium from cultures of myoblasts or cardiac fibroblasts, and oxidative stress was induced with H2O2. Myoblast-derived factors effectively prevented oxidative stress-induced cardiac cell death and loss of mitochondrial membrane potential. This protective effect was mediated via epidermal growth factor (EGF) receptor and c-Met signaling, and mimicked by neuregulin 1 but not EGF. Microarray analysis of cardiac cells treated with myoblast versus cardiac fibroblast-derived mediators revealed differential regulation of genes associated with antioxidative effects: cystathionine-γ-lyase (cst), xanthine oxidase, and thioredoxin-interacting protein as well as tribbles homolog 3 (trib3). Cardiac cell pretreatment with tunicamycin, an inducer of trib3, also protected them against H2O2-induced cell death. Epicardial transplantation of myoblast sheets in a rat model of acute myocardial infarction was used to evaluate the expression of CST and trib3 as markers of myoblasts' paracrine effect in vivo. Myoblast sheets induced expression of the CST as well as trib3 in infarcted myocardium. CST localized around blood vessels, suggesting smooth muscle cell localization. Our results provide a deeper molecular insight into the therapeutic mechanisms of myoblast-derived paracrine signaling in cardiac cells and suggest that myoblast transplantation therapy may prevent oxidative stress-induced cardiac deterioration and progression of heart failure.


Assuntos
Cardiotônicos/metabolismo , Cistationina gama-Liase/metabolismo , Receptores ErbB/metabolismo , Mioblastos Esqueléticos/metabolismo , Estresse Oxidativo , Comunicação Parácrina , Receptor ErbB-4/metabolismo , Resposta a Proteínas não Dobradas , Fator 4 Ativador da Transcrição/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Meios de Cultivo Condicionados/farmacologia , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/transplante , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Comunicação Parácrina/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Tunicamicina/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos
15.
Neuropharmacology ; 102: 266-75, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26631533

RESUMO

Mitochondrial dysfunction has been linked to several neurodegenerative diseases such as Parkinson's disease (PD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master gene for mitochondrial biogenesis and has been shown to be neuroprotective in models of PD. In this work we have studied the mechanisms by which peroxisome proliferator-activated receptor-γ (PPARγ) selective agonist N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino)ethyl]-l-tyrosine hydrate (GW1929) acts on human dopaminergic neurons in culture. Data showed that GW1929 increased the viability of human dopaminergic neurons and protected them against oxidative stress induced by H2O2 and the mitochondrial toxin Rotenone. The enhanced resilience of the neurons was attributed to increased levels of mitochondrial antioxidants and of PGC-1α. GW1929 treatment further increased cell respiration, mitochondrial biogenesis and sirtuin-1 (SIRT1) expression in the human dopaminergic neurons. Phosphorylation of cAMP responsive element-binding protein (CREB) was also robustly increased in GW1929-treated cells. Together these results show that the PPARγ agonist GW1929 influences CREB signaling and PGC-1α activities in the human dopaminergic neurons contributing to an increased cell viability. This supports the view that drugs acting on the PPARγ-PGC-1α signaling in neurons may have beneficial effects in PD and possible also in other brain disorders.


Assuntos
Benzofenonas/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , PPAR gama/agonistas , Fatores de Transcrição/metabolismo , Tirosina/análogos & derivados , Linhagem Celular , Neurônios Dopaminérgicos/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fosforilação/efeitos dos fármacos , Sirtuína 1/metabolismo , Tirosina/farmacologia
16.
Cell Mol Life Sci ; 73(7): 1365-79, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26616211

RESUMO

Parkinson's disease (PD is a progressive neurological disorder characterized by the degeneration and death of midbrain dopamine and non-dopamine neurons in the brain leading to motor dysfunctions and other symptoms, which seriously influence the quality of life of PD patients. The drug L-dopa can alleviate the motor symptoms in PD, but so far there are no rational therapies targeting the underlying neurodegenerative processes. Despite intensive research, the molecular mechanisms causing neuronal loss are not fully understood which has hampered the development of new drugs and disease-modifying therapies. Neurotrophic factors are by virtue of their survival promoting activities attract candidates to counteract and possibly halt cell degeneration in PD. In particular, studies employing glial cell line-derived neurotrophic factor (GDNF) and its family member neurturin (NRTN), as well as the recently described cerebral dopamine neurotrophic factor (CDNF) and the mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown positive results in protecting and repairing dopaminergic neurons in various models of PD. Other substances with trophic actions in dopaminergic neurons include neuropeptides and small compounds that target different pathways impaired in PD, such as increased cell stress, protein handling defects, dysfunctional mitochondria and neuroinflammation. In this review, we will highlight the recent developments in this field with a focus on trophic factors and substances having the potential to beneficially influence the viability and functions of dopaminergic neurons as shown in preclinical or in animal models of PD.


Assuntos
Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Neurônios Dopaminérgicos/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Neurturina/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/uso terapêutico , Resposta a Proteínas não Dobradas , alfa-Sinucleína/imunologia , alfa-Sinucleína/farmacologia , alfa-Sinucleína/uso terapêutico
17.
Springerplus ; 3: 2, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25932355

RESUMO

Mitochondrial dysfunctions accompany several neurodegenerative disorders and contribute to disease pathogenesis among others in Parkinson's disease (PD). Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a major regulator of mitochondrial functions and biogenesis, and was suggested as a therapeutic target in PD. PGC-1α is regulated by both transcriptional and posttranslational events involving also the action of growth factors. Fibroblast growth factor-21 (FGF21) is a regulator of glucose and fatty acid metabolism in the body but little is known about its action in the brain. We show here that FGF21 increased the levels and activity of PGC-1α and elevated mitochondrial antioxidants in human dopaminergic cells in culture. The activation of PGC-1α by FGF21 occurred via the NAD(+)-dependent deacetylase Sirtuin-1 (SIRT1) subsequent to an increase in the enzyme, nicotinamide phosphoribosyltransferase (Nampt). FGF21 also enhanced mitochondrial respiratory capacity in human dopaminergic neurons as shown in real-time analyses of living cells. FGF21 is present in the brain including midbrain and is expressed by glial cells in culture. These results show that FGF21 activates PGC-1α and increases mitochondrial efficacy in human dopaminergic neurons suggesting that FGF21 could potentially play a role in dopaminergic neuron viability and in PD.

18.
Food Chem ; 146: 583-90, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24176384

RESUMO

The composition and structures of TAGs in the human milk from mothers with different food choices and prepregnancy body mass index were determined with two tandem mass spectrometric methods (negative APCI-MS/MS and positive UHPLC/ESI-MS/MS) at the infant's age of three months. The normal weight mothers with recommended food choices had more 18:3n-3 and less 18:0 in their milk than normal weight mothers with non-recommended food choices. A significant difference between the normal weight mothers on the non-recommended food choices and the other groups was seen in acyl carbon number: number of double bond (ACN:DB)-groups 54:6, 54:5, 54:3 and 54:2. In ACN:DB 52:7 and 52:6 the two recommended food choices-groups differed significantly from the two non-recommended food choices-groups. The regioisomerism of TAGs varied little despite differences in mother's weight and diet with sn-18:1-16:0-18:1 as the most prevalent regioisomer in the milk (13.8±2.7%). The results of this study highlight the importance of structure specific human milk substitutes and the careful selection of the MS/MS methods for analysis of mixtures of several isobaric TAGs.


Assuntos
Leite Humano/química , Sobrepeso/metabolismo , Triglicerídeos/química , Adulto , Estudos de Coortes , Dieta , Feminino , Humanos , Leite Humano/metabolismo , Mães , Espectrometria de Massas em Tandem , Triglicerídeos/metabolismo
19.
Int J Environ Res Public Health ; 10(10): 4925-43, 2013 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-24157513

RESUMO

This study focused on the heterogeneity of consumer reactions, measured through poultry meat purchase intentions, when facing three cases of risk. The heterogeneity was analysed by latent class logistic regression that included all three risk cases. Approximately 60% of the respondents belonged to the group of production risk avoiders, in which the intention to purchase risk food was significantly lower than in the second group of risk neutrals. In addition to socio-demographic variables, the purchase intentions were statistically associated with several attitude-based variables. We highlighted some policy implications of the heterogeneity. Overall, the study demonstrated that risk matters to consumers, not all risk is equal, and consumer types react somewhat differently to different types of risk.


Assuntos
Comportamento do Consumidor , Microbiologia de Alimentos , Inocuidade dos Alimentos , Carne/economia , Adolescente , Adulto , Idoso , Animais , Antecipação Psicológica , Comportamento de Escolha , Coleta de Dados , Feminino , Finlândia , Preferências Alimentares , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Aves Domésticas , Fatores de Risco , Adulto Jovem
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