RESUMO
BACKGROUND: Increasing proportions of geriatric patients pose tremendous challenges for our society. Developments in assistive technologies have the potential to support older and frail people in aging and care. To reach a sustainable adoption of these technologies, the perceptions and wishes of future users must be understood. In particular, the relationships between individual health-related factors, and the perceptions of aging and using assistive technologies in severe health situations must be empirically examined. METHODS: Addressing this research gap, our quantitative study (N = 570) investigates the impact of diverse future users' age and health status on their a) perceptions of aging, b) perceptions and acceptance of using assistive technologies in aging and care, as well as c) end-of-life decisions regarding technology usage. For this, four groups were segmented for the comparison of younger (< 50 years) healthy, younger chronically ill, older (50 + years) healthy, and older chronically ill participants. RESULTS: The results revealed that health status is more decisive for age-related perceptions compared to age. The technology-related perceptions were slightly impacted by either chronological age or health status. The end-of-life decisions showed the most striking differences in the willingness to use assistive technologies, revealing older chronically ill participants to have more restrained attitudes towards technology usage than older healthy as well as all younger participants. CONCLUSIONS: The findings suggest that the benefits of assistive technologies in private or professional care contexts should be communicated and implemented tailored to the respective user group's needs. Moreover, the results allow us to derive practical implications within the geriatric care context.
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Envelhecimento , Tecnologia Assistiva , Idoso , Humanos , Atitude Frente a Saúde , Doença Crônica , Morte , Nível de Saúde , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Depression in old age is associated with an increased fall risk. Especially in cognitively challenging situations, fall-promoting gait deviations could appear due to depression- and age-related cognitive deficits. AIM: This study investigates (i) whether there are differences in gait performance between depressed older patients and healthy controls and (ii) if gait patterns aggravate when performing a cognitive task whilst walking. METHODS: 16 depressed older patients (mean age: 73.1 ± 5.8 years) and 19 healthy controls (mean age: 73.3 ± 6.1 years) were included in the study. Spatiotemporal gait parameters (speed, stride length, swing time) and minimum toe clearance were recorded using a three-dimensional motion-capture system under a single- and a dual-task condition (counting backwards). RESULTS: After Bonferroni correction, depressed older patients showed significantly slower walking speed, shorter strides and smaller minimum toe clearance, as well as greater variability in stride length than healthy controls. Under the dual-task, gait performance deteriorated compared with single-task, with slower gait speed, shorter strides, and longer swing time. DISCUSSION: Slower walking speed and shorter steps of depressed patients may be a strategy to counteract their fall risk. Increased variability suggests a less stable gait pattern in patients, which could be a reason for their increased fall risk. CONCLUSIONS: Depression in old age has a strong effect on gait performance. Possible interventions that might prevent falls in this vulnerable group are discussed. The study was registered at Open Science Framework on May 18, 2021 (publicly accessible May 30, 2023).
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Depressão , Análise e Desempenho de Tarefas , Humanos , Idoso , Fenômenos Biomecânicos , Marcha , CaminhadaRESUMO
Assistive robotics as a gerontological geriatric field of research so far seem to be perceived more as "recalcitrant". Predominant is a reserved attitude as to whether this should be considered a research topic to be taken seriously. The reliability of research results and the scientific half-life period are questioned as digital technique generations change exceedingly rapidly and also only a few sustainable standards and guidelines are established. In this context there is a danger that essential developments will be missed in gerontology and geriatrics, then the momentum is active right now and can now be shaped. In the scientific gerontology and geriatrics these developments should not be missed out on but must be grasped with pioneering spirit and proactively co-created. This can be achieved by further research endeavors, public activities and the utilization of knowledge from clinical and nursing practice with each having feedback into development and research.
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Geriatria , Robótica , Idoso , Idoso de 80 Anos ou mais , Humanos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Meningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. METHODS: In vivo, we studied the effects of vitamin D3 on survival and the host's immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured. RESULTS: Mice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation. CONCLUSION: Our observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.
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Colecalciferol/deficiência , Infecções por Escherichia coli/complicações , Escherichia coli/patogenicidade , Meningoencefalite/etiologia , Meningoencefalite/mortalidade , Deficiência de Vitamina D , Análise de Variância , Animais , Carga Bacteriana/métodos , Peso Corporal , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/microbiologia , Sistema Nervoso Central/patologia , Colecalciferol/administração & dosagem , Colecalciferol/sangue , Citocinas/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Meningoencefalite/patologia , Camundongos , Camundongos Endogâmicos C57BL , Baço/metabolismo , Baço/microbiologia , Baço/patologia , Fatores de TempoRESUMO
An age-dependent decline in skeletal muscle mass, strength, and endurance during the aging process is a physiological development, but several factors may exacerbate this process, leading to the threatening state of sarcopenia, frailty, and eventually higher mortality rates. Obesity appears to be such a promoting factor and has been linked in several studies to sarcopenia. The reason for this causal association remains poorly understood. Notwithstanding the fact that a higher body mass might simply lead to diminished physical activity and therefore contribute to a decline in skeletal muscle, several molecular mechanisms have been hypothesized. There could be an obesity derived intracellular lipotoxicity (i.e., elevated intramuscular levels of lipids and their derivatives), which induces apoptosis by means of an elevated oxidative stress. Paracrine mechanisms and inflammatory cytokines, such as CRP and IL-6 could be confounders of the actual underlying pathological mechanism. Due to a cross-talk of the hypothalamo-pituitary axis with nutritional status, obese subjects are more in a catabolic state of metabolism, with a higher susceptibility to muscle wasting under energy restriction. Obesity induces insulin resistance in the skeletal muscle, which consequently leads to perturbed metabolism, and misrouted signaling in the muscle cells. In obesity, muscle progenitor cells could differentiate to an adipocyte-like phenotype as a result of paracrine signals from (adipo)cytokines leading to a reduced muscular renewal capacity. The present review outlines current knowledge concerning possible pathways, which might be involved in the molecular pathogenesis of sarcopenic obesity.
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Envelhecimento/fisiologia , Obesidade/etiologia , Sarcopenia/etiologia , Humanos , Resistência à Insulina/fisiologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Obesidade/fisiopatologia , Sarcopenia/fisiopatologia , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: The immune system undergoes several alterations of innate and adaptive immunity during ageing. The main features of the aged immune system are a reduced diversity of T cell receptors and a reduced activity of innate immune cells with subsequent changes in adaptive immunity resulting in a less effective, less specific, and dys-regulated immune response and in an increased susceptibility towards infection, malignancy, and autoimmunity. The process is referred to as immunosenescence and is also modulated by environmental modifiers, such as dietary factors. High fat diet (HFD), via direct modulation of immune cell function by fatty acids and/or increased body fat mass, influences immune function. However, it is not clear whether HFD is beneficial or detrimental for the functioning of the ageing immune system. METHODS: Male Wistar rats fed with either a high fat diet (HFD 43 en% of fat) or control diet (SD, 25 en% of fat) over up to 24 month and were analyzed for plasma IL-1ß, IL-6, TNF, IgM, IgG1, IgA, IgG2a, IgG2b, IgG2c, light chains lambda and kappa, testosterone, prolactin and percentage of splenic B cells and apoptosis rate, respectively. RESULTS: In general, all analyzed immunoglobuline isotypes increased with age, except for IgA. This increase was attenuated by HFD. In HFD and SD rats the percentage of B cells in the spleen and also their apoptotic rate was lower in aged as compared to young animals with no additional diet-induced effect. Testosterone and prolactin levels were lower in old animals, as expected. There was a statistical trend towards an increased prolactin/testosterone ratio in middle aged (6-12 monthsnth) HFD rats as compared to SD. IL-6 was neither affected by HFD nor age. On the other hand, HFD rats showed a decrease in IL-1ß as compared to SD, which correlated with the above-mentioned suppressive effect on immunoglobulin isotypes, especially IgM. CONCLUSION: In Wistar rats, HFD reveals an immunosuppressive effect in ageing animals by decreasing immunoglobulins, especially IgM, and IL-1ß when compared to SD.
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BACKGROUND: Knowledge about the molecular pathomechanisms of sarcopenia is still sparse, especially with regard to nutritional risk factors and the subtype of sarcopenic obesity. OBJECTIVE: The aim of this study was to characterize diet-induced and age-related changes on the quality and quantity of the quadriceps muscle in a rat model of sarcopenia by different magnetic resonance (MR) techniques. METHODS: A total of 36 6-month-old male Sprague-Dawley rats were randomly subdivided into 2 groups and received either a high-fat diet (HFD) or a control diet (CD). At the age of 16 months, 15 HFD and 18 CD rats underwent MR at 1.5 T. T1-weighted images as well as T2 relaxation time maps were acquired perpendicular to the long axis of the quadriceps muscles. Maximum cross-sectional area (CSA) of the quadriceps muscle was measured on T1-weighted images, and T2 relaxation times of muscle were assessed in a region without visible intramuscular fat (T2lean muscle) and across the complete CSA (T2muscle). Furthermore, (1)H-MR spectroscopy was performed to evaluate the relative lipid content of the quadriceps muscles. These measurements were repeated 5 months later in the surviving 8 HFD and 14 CD rats. RESULTS: HFD rats revealed significantly decreased CSA and CSA per body weight (BW) as well as prolonged T2 relaxation times of muscle. A higher weight gain (upper tertile during the first 6 months of diet in CD rats) resulted in a significant change of T2muscle, but had no relevant impact on CSA. Advancing age up to 21 months led to significantly decreased BW, CSA and CSA/BW, significantly prolonged T2muscle and T2lean muscle and enlarged lipid content in the quadriceps muscle. CONCLUSIONS: In an experimental setting a chronically fat-enriched diet was shown to have a relevant and age-associated influence on both muscle quantity and quality. By translational means the employed MR techniques give rise to the possibility of an early detection and noninvasive quantification of sarcopenia in humans, which is highly relevant for the field of geriatrics.
Assuntos
Envelhecimento/fisiologia , Dieta Hiperlipídica , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologia , Sarcopenia/metabolismo , Sarcopenia/patologia , Envelhecimento/patologia , Animais , Modelos Animais de Doenças , Metabolismo dos Lipídeos/fisiologia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Gait initiation is challenging for older individuals with poor physical function, particularly for those with frailty. Frailty is a geriatric syndrome associated with increased risk of illness, falls, and functional decline. This study examines whether spatial and temporal parameters of gait initiation differ between groups of older adults with different levels of frailty, and whether fear of falling, and balance ability are correlated with the height of lifting the food during gait initiation. METHODS: Sixty-one individuals aged > 65 years, classified by Fried frailty phenotype, performed five self-paced gait initiation trials. Data was collected using a three-dimensional passive optical motion capture system, consisting of 10 cameras with the ability to perceive reflective markers, and two force plates. The total duration of gait initiation and the duration of its four sub-phases, the first step length, and the maximum foot clearance during the first step were derived, and compared statistically between groups. Additionally, an association analysis was conducted between foot clearance and fear of falling, and confidence in balance in older individuals. RESULTS: Frail individuals had significantly longer unloading durations, and total durations of gait initiation compared to non-frail older adults. Additionally, they had shorter first step lengths compared to non-frail older adults. Pre-frail older adults also showed shorter steps compared to the non-frail group. However, there were no significant differences between groups for the maximum foot clearance during the first step. Nevertheless, the maximum foot clearance of older individuals correlated significantly with their fear of falling and confidence in balance. CONCLUSION: Older adults with reduced physical function and signs of frailty mainly display longer duration of gait initiation and decreased first step length compared to non-frail older adults. The release phase is decreased as the double support phase is prolonged in frail patients. This information can guide the development of specialized exercise programs to improve mobility in this challenging motion between static and dynamic balance.
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Obesity has been suggested as a risk factor for sarcopenia. However, the underlying pathogenic concept of sarcopenic obesity is mainly based on phenotypical data from clinical observation. The present pilot study describes a rodent animal model which opens up prospects to carry out translational research of sarcopenic obesity in an experimental setting. Starting with 2 months, male Wistar rats were fed with a diet containing either 25 en % (control diet, CD) versus 45 en % (high fat diet, HFD) of neutral fat. At the age of 20 and 23 months quadriceps muscles were examined in vivo by magnetic resonance techniques which revealed a positive correlation between muscular fat and body weight (r = 0.639) and a negative correlation between muscular fat content and muscle volume (r = -0.742). Expression and phosphorylation status of proteins within the PKB/Akt and AMPK-dependent signaling pathway were examined in muscles of the 24 month-old animals which significantly showed a 50 percent upregulation of Ser(473)P-PKB/Akt and a 90 % constitutive downregulation of S6K1 in the HFD rats. Notably, S6K1 is a key mediator for muscular protein biosynthesis with additional negative feedback on PKB/Akt. Furthermore, muscular expression of the mitochondrial key regulator PGC-1α in the aged HFD rats was only 25 % of that concurrent controls (p = 0.029). These explorative findings in the aging high-fat fed rat might serve as a firm starting point for controlled longitudinal observations in a larger animal cohort of both sexes studying the natural history of sarcopenic obesity.
Assuntos
Envelhecimento/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/metabolismo , Obesidade , Músculo Quadríceps , Sarcopenia , Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Quinases Proteína-Quinases Ativadas por AMP , Animais , Peso Corporal , Modelos Animais de Doenças , Humanos , Imageamento por Ressonância Magnética , Masculino , Obesidade/complicações , Obesidade/metabolismo , Tamanho do Órgão , Fosforilação , Projetos Piloto , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologia , Ratos , Ratos Wistar , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Sarcopenia/metabolismo , Transdução de Sinais , Pesquisa Translacional BiomédicaRESUMO
Gait behavior is considered an important indicator for the assessment of the general health status and provides a diagnostic observation for neuro-degenerative and musculo-skeletal diseases. Individual changes in gait behavior often reflect a deterioration of the current health status in a general sense and therefore provide significant information for clinicians and care-givers. In this work, we have used an unobtrusive sensor setup comprising three inertial measurement units (IMUs) located at the wrist, the chest and the thigh to obtain an objective measure of the human locomotion. We conducted a clinical trial in a movement laboratory environment to obtain a database of gait data at different walking speeds and conditions. The aging-simulation suit GERT was used to deteriorate the individual gait behavior during the experiments. Treadmill walking trials were used to train different classifiers to discriminate normal walking from GERT-affected walking patterns. Level-ground walking trials were used to validate the previously generated classifiers. A five-fold cross validation during the training process yielded overall F1-scores between 0.965 and 0.986. The validation tests showed promising results with prediction accuracies of more than 80%. Clinical relevance- The clinical relevance of this contri-bution can be considered two-fold. First we demonstrate the possibility of an unobtrusive monitoring system to iden-tify individual deterioration of gait behavior. Second we also validate the use of aging-simulation suits to introduce individual changes of gait patterns in healthy subjects to create a database of simulated yet realistic gait impairments associated with aging.
Assuntos
Marcha , Caminhada , Teste de Esforço , Humanos , Locomoção , Velocidade de CaminhadaRESUMO
The ongoing demographic change forces different stakeholders to cope with increasing needs in nursing care and the economic costs. Consequences arising from the population aging can be supported by assistive technologies to maintain older individuals' autonomy. However, older adults' opinions on the assistance of health-related technologies and their attitudes toward aging and care largely remain underexplored. This paper provides a geriatric and socio-technical perspective, investigating individual perceptions of (a) aging, (b) nursing care, and (c) the adoption of assistive technologies in a cross-national subject group. For this purpose, N = 384 individuals (60+ years) participated in an online survey. Findings indicate that most older adults are open to assistive technologies and that individual care preferences contribute to a successful adoption of these technologies. Among individual factors, health status, and gender affect respondents' opinions the most. Our findings help to understand older adults' acceptance of assistive technologies and contribute to the research on the nursing care in private and professional environments.
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Envelhecimento , Tecnologia Assistiva , Adulto , Idoso , Atitude , Tecnologia Biomédica , Humanos , Inquéritos e QuestionáriosRESUMO
Acute and chronic critical conditions are associated with reduced serum levels of free triiodothyronine (FT(3)), free thyroxine FT(4), and thyrotropin, known as nonthyroidal illness syndrome (NTIS). It is still controversial whether these changes reflect a protective mechanism or a maladaptive process during prolonged illness. However, larger studies to determine the prevalence of the NTIS and its association with outcome in medical intensive care units (ICUs) are missing. Complete thyroid hormone levels from 247 of 743 patients admitted to our ICU between October 2002 and February 2004 were retrospectively evaluated. From these patients, Acute Physiology and Chronic Health II scores, ICU mortality, length of stay, mechanical ventilation, and concomitant medication were recorded. Ninety-seven patients (44.1%) had low FT(3) levels indicating an NTIS, either with normal (23.6%) or reduced (20.5%) serum thyrotropin levels. Of 97 patients with NTIS, 24 (23.3%) also showed reduced serum FT(4) levels. The NTIS was significantly associated with Acute Physiology and Chronic Health II scores, mortality, length of stay, and mechanical ventilation. In a multivariate Cox regression analysis, the combination of low FT(3) and low FT(4) was an independent risk factor for survival. Nonthyroidal illness syndrome is frequent at a medical ICU. A reduction of FT(4) together with FT(3) is associated with an increase in mortality and might reflect a maladaptive process, thereby worsening the disease.
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Síndromes do Eutireóideo Doente/epidemiologia , Síndromes do Eutireóideo Doente/terapia , APACHE , Cuidados Críticos , Síndromes do Eutireóideo Doente/diagnóstico , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Síndrome , Hormônios Tireóideos/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
BACKGROUND: Pancreatitis and exocrine pancreatitic insufficiency have been described as extraintestinal manifestations of inflammatory bowel disease. In this study, we investigated whether the endocrine pancreatic function is also disturbed in patients with inflammatory bowel disease. METHODS: Seventeen patients with Crohn's disease and 13 healthy volunteers participated in the study. We analyzed the plasma insulin response in a 75-g oral glucose tolerance test. Glucose and insulin levels were determined at time 0 (fasting levels) and 30, 60, 90, 120, 180, 240, and 300 min after glucose uptake. Insulin resistance and beta cell function (BCF) were analyzed by calculating respective indices. RESULTS: Fasting and oral glucose-tolerance test glucose levels appeared to be similar in patients with Crohn's disease and in the controls. Impaired fasting glucose, impaired glucose tolerance, and/or overt diabetes mellitus were not observed in the volunteers. Insulin as well as the index for BCF were significantly increased in patients with Crohn's disease. In addition, insulin resistance was shown to be significantly elevated in Crohn's disease. CONCLUSIONS: Patients with Crohn's disease reveal an increased insulin secretion caused by an enhanced BCF, which may be induced by an up-regulated enteropancreatic axis. This hypersecretion may override the insulin resistance given by the chronic inflammatory state.
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Doença de Crohn/metabolismo , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Adulto , Glicemia/análise , Peptídeo C/sangue , Feminino , Teste de Tolerância a Glucose , Homeostase/fisiologia , Humanos , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
Based on a 15-year old hypothesis, it is believed that an adequate ingestion of folate vitamins decreases, whereas a nutritional depletion of folate increases the risk of colorectal cancer. The present article reviews the efforts to provide biochemical and epidemiological evidence for folate as a chemopreventive agent against colorectal carcinogenesis. BIOLOGICAL EVIDENCE: Tetrahydrofolates govern the intracellular one-carbon metabolism and account for proper DNA biosynthesis and macromolecular modification. Numerous experimental studies traced different molecular pathways and tried to link folate depletion with DNA instability and/or mutagenesis. However, none of the proposed underlying molecular mechanisms appear clearly defined. EPIDEMIOLOGICAL EVIDENCE: Numerous case-control and prospective studies have been conducted on folate and colorectal cancer, which all together miss a clinical bottom line. The recommendation of folate intake to prevent colorectal cancer is therefore not evidence-based.
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Neoplasias Colorretais/prevenção & controle , Ácido Fólico/uso terapêutico , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Medicina Baseada em Evidências , Ácido Fólico/química , Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/complicações , Humanos , Resultado do TratamentoRESUMO
Glitazones are known to modulate fatty acid-induced effects on insulin secretion in the pancreatic beta-cell. The present study focused on combined effects of troglitazone and oleate on preproinsulin (PPI) biosynthesis. Insulin-producing INS-1 cells were incubated for 4 hr at 11.2mM glucose in the presence (O(+)) or absence (O(-)) of 200 microM oleate with (T(+)) or without (T(-)) 10 microM troglitazone. After cell lysis, cytoplasmic RNA was extracted and employed for Northern blotting and corresponding in vitro translation. Compared with untreated controls (CTRL=O(-)/T(-)), the cellular content of PPI-mRNA from cells which had been simultaneously treated by troglitazone and oleate (O(+)/T(+)) was significantly diminished (O(+)/T(+)=75+/-10% x CTRL; P=0.015). The PPI-mRNA content from those cells which had been exclusively exposed either to oleate (O(+)/T(-)) or troglitazone (O(-)/T(+)) did not significantly differ from that of the untreated controls. In spite of that decreased PPI-mRNA content, in vitro translation revealed the highest yield of newly synthesized PPI in RNA samples from those cells which had been simultaneously exposed to oleate and troglitazone before (O(+)/T(+)=1.6+/-0.3 x CTRL; P=0.01). It is concluded that troglitazone and oleate synergistically affect the translational rate at the level of the PPI-mRNA molecule.
Assuntos
Cromanos/farmacologia , Ácido Oleico/farmacologia , Proinsulina/genética , Biossíntese de Proteínas/efeitos dos fármacos , Precursores de Proteínas/genética , Tiazóis/farmacologia , Tiazolidinedionas , Animais , Linhagem Celular , Sinergismo Farmacológico , Insulina/imunologia , Insulina/metabolismo , Secreção de Insulina , Proinsulina/efeitos dos fármacos , Proinsulina/metabolismo , Precursores de Proteínas/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Ratos , Receptores Citoplasmáticos e Nucleares/biossíntese , Fatores de Transcrição/biossíntese , TroglitazonaRESUMO
OBJECTIVE: Free fatty acids (FFAs) deplete the intracellular insulin stores of pancreatic beta-cells. It has been suggested that this results from a lipotoxic dysregulation of both insulin secretion and insulin synthesis. In the present study, this hypothesis was tested within a 12-h time-course by directly relating the FFA-induced loss of intracellular insulin to corresponding parameters of insulin secretion and de novo biosynthesis. Palmitate, cis-monoenic oleate and the trans-monoenic elaidate were employed as model FFAs to elucidate potentially different effects due to chain length and configuration. METHODS: INS-1 cells were incubated for 1, 4 or 12 h with 11.2 mmol/l glucose with 200 micromol/l palmitate, oleate or elaidate and compared with non-FFA-exposed controls with respect to content and secretion of immunoreactive insulin (IRI). Biosynthesis of insulin was monitored by pulse-labeling experiments and by Northern blot analysis. RESULTS: IRI content dropped by 50-60% after a short-term exposure with all FFAs employed (P< or =0.001). It tended to recover after 12 h of treatment with oleate and elaidate but not with palmitate. FFA treatment increased insulin secretion by 25% (P< or =0.05) which could not account quantitatively for the intracellular loss. FFA-induced changes in insulin biosynthesis did not correlate clearly with the FFA-induced intracellular loss. CONCLUSIONS: The FFA-induced loss of IRI is an acute effect independent of the FFA employed. It cannot be sufficiently explained by FFA-induced perturbances of IRI secretion and biosynthesis. We therefore postulate an additional FFA-triggered mechanism, e.g. intracellular IRI degradation.
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Insulina/biossíntese , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ácido Oleico/farmacologia , Ácido Palmítico/farmacologia , Animais , Northern Blotting , Glucose/farmacologia , Insulina/análise , Insulina/metabolismo , Secreção de Insulina , Insulinoma , Ilhotas Pancreáticas/química , Ácidos Oleicos , Neoplasias Pancreáticas , Proinsulina/biossíntese , Proinsulina/genética , Precursores de Proteínas/biossíntese , Precursores de Proteínas/genética , RNA Mensageiro/análise , Ratos , Células Tumorais CultivadasRESUMO
While free fatty acids (FFA) are well known as insulin secretagogues, their effects on pancreatic alpha cells have been mostly neglected. In the present study we therefore systematically analyzed the glucagon metabolism of rat pancreatic islets under the influence of FFA. Primary islets were incubated in the presence or absence of 200 micromol/L albumin-complexed palmitate or oleate at 2.8 mmol/L versus 16.7 mmol/L glucose and glucagon secretion was monitored over 8 hours. In addition to these time-course experiments, dose dependency of palmitate-induced effects was tested by a 2-hour incubation with 50 to 300 micromol/L albumin-complexed palmitate at 2.8 mmol/L and 5.6 mmol/L glucose. Apart from glucagon secretion, intracellular immunoreactive glucagon and cellular preproglucagon-mRNA (PPG-mRNA) content were determined from the remaining cell lysates. FFA, especially palmitate, induced a significant and dose-dependent increase of glucagon secretion (in average 2-fold above control) during the first 120 minutes of incubation at low to normal glucose (2.8 and 5.6 mmol/L). There was no significant glucagonotropic effect of FFA at concomitant 16.7 mmol/L glucose. Intracellular glucagon as well as cellular PPG-mRNA content were found to be dose-dependently diminished by palmitate when compared with untreated controls at 5.6 mmol/L glucose. The present analysis therefore points to a new role for FFA as a nutritient secretagogue and a modulator of alpha-cellular glucagon metabolism.
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Glicemia/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Glucagon/metabolismo , Ilhotas Pancreáticas/metabolismo , Precursores de Proteínas/metabolismo , Albuminas/metabolismo , Animais , Relação Dose-Resposta a Droga , Ácidos Graxos não Esterificados/farmacologia , Glucagon/genética , Técnicas In Vitro , Ilhotas Pancreáticas/efeitos dos fármacos , Masculino , Ácido Oleico/metabolismo , Ácido Palmítico/metabolismo , Proglucagon , Precursores de Proteínas/genética , RNA Mensageiro/análise , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: Genetic hemochromatosis leads to iron overload in many tissues and may lead to liver cirrhosis and hepatocellular carcinoma. Early diagnosis and therapy are crucial. Since 80-100% of hemochromatosis patients of European origin are homozygous for a cysteine to tyrosine exchange in the HFE gene at codon 282, genetic screening might be useful. Representative population studies are needed to evaluate the phenotype of people heterozygous and homozygous for the C282Y mutation. OBJECTIVE: To determine the correlation between parameters of iron metabolism and the hemochromatosis genotype in a large population-based study. METHODS: A representative population-based survey, the Diabetomobil study, analyzed 5,083 German probands. Serum transferrin saturation and ferritin levels were determined, and the C282Y mutation of the HFE gene was analyzed by restriction fragment length polymorphism-polymerase chain reaction analysis. RESULTS: Nine of 373 probands with a transferrin saturation > 55% (2.4%) and none of 264 randomly selected probands with a transferrin saturation < or = 55% (0%) were homozygous for the C282Y mutation. Three of the nine homozygous probands had ferritin values less than 250 micrograms/L. The frequency of the heterozygous genotype was 8.8%, and the percentage of heterozygous probands increased with increasing levels of transferrin saturation. CONCLUSION: We propose a population screening strategy with an initial transferrin saturation test, followed by genotyping for the C282Y mutation if the transferrin saturation is above 55%, regardless of the ferritin level. Heterozygous individuals with higher transferrin saturation values may be protected against iron loss but may also be more susceptible for certain liver diseases, depending on the simultaneous prevalence of other diseases.
Assuntos
Hemocromatose/genética , Hemocromatose/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Ferro/metabolismo , Proteínas de Membrana/genética , Mutação/genética , Adulto , Idoso , Feminino , Ferritinas/sangue , Frequência do Gene , Testes Genéticos , Genótipo , Alemanha/epidemiologia , Hemocromatose/complicações , Hemocromatose/epidemiologia , Proteína da Hemocromatose , Heterozigoto , Homozigoto , Humanos , Sobrecarga de Ferro/genética , Sobrecarga de Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Penetrância , Fenótipo , Polimorfismo de Fragmento de Restrição , Vigilância da População , Prevalência , Transferrina/metabolismoRESUMO
RESEARCH METHODS AND PROCEDURES: High-fat (HF) diet feeding can induce obesity and metabolic disorders in rodents that resemble the human metabolic syndrome. However, this dietary intervention is not standardized, and the HF-induced phenotype varies distinctly among different studies. The question which HF diet type is best to model the metabolic deterioration seen in human obesity remains unclear. Therefore, in this review, metabolic data obtained with different HF diet approaches are compiled. Both whole-body and organ-specific diet effects are analyzed. RESULTS: On the basis of these results, we conclude that animal fats and omega-6/omega-9-containing plant oils can be used to generate an obese and insulin-resistant phenotype in rodents, whereas fish oil-fed animals do not develop these disorders. DISCUSSION: Looking at the present data, it does not seem possible to define an ideal HF diet, and an exact definition of diet composition and a thorough metabolic characterization of the HF diet effects in a researcher's specific laboratory setting remains essential for metabolic studies with this model.