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1.
Viruses ; 12(11)2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33198291

RESUMO

Studies of virus-host interactions in vitro may be hindered by biological characteristics of conventional monolayer cell cultures that differ from in vivo infection. Three-dimensional (3D) cell cultures show more in vivo-like characteristics and may represent a promising alternative for characterisation of infections. In this study, we established easy-to-handle cell culture platforms based on bioprinted 3D matrices for virus detection and characterisation. Different cell types were cultivated on these matrices and characterised for tissue-like growth characteristics regarding cell morphology and polarisation. Cells developed an in vivo-like morphology and long-term cultivation was possible on the matrices. Cell cultures were infected with viruses which differed in host range, tissue tropism, cytopathogenicity, and genomic organisation and virus morphology. Infections were characterised on molecular and imaging level. The transparent matrix substance allowed easy optical monitoring of cells and infection even via live-cell microscopy. In conclusion, we established an enhanced, standardised, easy-to-handle bioprinted 3D-cell culture system. The infection models are suitable for sensitive monitoring and characterisation of virus-host interactions and replication of different viruses under physiologically relevant conditions. Individual cell culture models can further be combined to a multicellular array. This generates a potent diagnostic tool for propagation and characterisation of viruses from diagnostic samples.

2.
PLoS Biol ; 17(10): e3000463, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31613875

RESUMO

The Animal Study Registry (ASR; www.animalstudyregistry.org) was launched in January 2019 for preregistration of animal studies in order to increase transparency and reproducibility of bioscience research and to promote animal welfare. The registry is free of charge and is designed for exploratory and confirmatory studies within applied science as well as basic and preclinical research. The registration form helps scientists plan their study thoroughly by asking detailed questions concerning study design, methods, and statistics. With registration, the study automatically receives a digital object identifier (DOI) that marks it as intellectual property of the researcher. To accommodate the researchers concerns about theft of ideas, users can restrict the visibility of their registered studies for up to 5 years. The full content of the study becomes publicly accessible at the end of the embargo period. Because the platform is embedded in the infrastructure of the German Federal Government, continuity and data security are provided. By registering a study in the ASR, researchers can show their commitment to transparency and data quality to reviewers and editors, to third-party donors, and to the general public.


Assuntos
Experimentação Animal/legislação & jurisprudência , Bem-Estar do Animal/legislação & jurisprudência , Sistema de Registros , Projetos de Pesquisa/legislação & jurisprudência , Experimentação Animal/ética , Bem-Estar do Animal/ética , Segurança Computacional , Confiabilidade dos Dados , Alemanha , Regulamentação Governamental , Humanos , Propriedade Intelectual
3.
Environ Sci Technol ; 53(21): 12725-12733, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31536708

RESUMO

A key challenge of mixture toxicity testing is that a multitude of substances with even more combinations need to be tested in a broad dose range. Consequently testing in rodent bioassays, the current gold standard of toxicity testing, is hardly feasible. High-throughput compatible cell culture systems, however, suffer from limitations with respect to toxicokinetics, tissue interactions, and compensatory mechanisms. Therefore, simple organisms like the nematode Caenorhabditis elegans, combining relevant advantages of complex in vivo and fast in vitro assays might prove highly valuable within a testing strategy for mixtures. To investigate the comparability between results obtained with C. elegans and traditional rodent assays, we used five azole fungicides as well investigated model substances. Our findings suggest that azoles act additively in C. elegans which is in line with previous results in rats. Additionally, we show that toxicokinetics are one important factor for the differences in the relative toxicity of the azoles in both species. Importantly, we also demonstrate that in contrast to most rodent in vivo studies, C. elegans assays provide well-defined concentration-response relationships which are a very good basis for the prediction of mixture effects. We conclude that C. elegans may be an appropriate model for mixture toxicity testing at least within a first step to identify and prioritize relevant mixtures for further testing.


Assuntos
Fungicidas Industriais , Nematoides , Animais , Azóis , Caenorhabditis elegans , Ratos , Testes de Toxicidade
4.
Stem Cell Res ; 38: 101474, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31176917

RESUMO

Von Hippel-Lindau (VHL) syndrome is a familial cancer syndrome caused by mutations in the tumor suppressor gene VHL. We generated human iPSC lines from primary dermal fibroblasts of three VHL syndrome patients carrying distinct VHL germ line mutations (c.194C>G, c.194C>T and nt440delTCT, respectively). Characterization of the iPSC lines confirmed expression of pluripotency markers, trilineage differentiation potential and absence of exogenous vector expression. The three hiPSC lines were genetically stable and retained the VHL mutation of each donor. These iPSC lines, the first derived from VHL syndrome patients, offer a useful resource to study disease pathophysiology and for anti-cancer drug development.


Assuntos
Mutação em Linhagem Germinativa , Células-Tronco Pluripotentes Induzidas , Proteína Supressora de Tumor Von Hippel-Lindau , Doença de von Hippel-Lindau , Linhagem Celular , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/metabolismo , Doença de von Hippel-Lindau/patologia
5.
Cancers (Basel) ; 11(5)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052565

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most commonly diagnosed cancer worldwide. Despite advances in the treatment management, locally advanced disease has a poor prognosis, with a 5-year survival rate of approximately 50%. The growth of HNSCC is maintained by a population of cancer stem cells (CSCs) which possess unlimited self-renewal potential and induce tumor regrowth if not completely eliminated by therapy. The population of CSCs is not only a promising target for tumor treatment, but also an important biomarker to identify the patients at risk for therapeutic failure and disease progression. This review aims to provide an overview of the recent pre-clinical and clinical studies on the biology and potential therapeutic implications of HNSCC stem cells.

6.
Am J Hum Genet ; 103(6): 1045-1052, 2018 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-30526862

RESUMO

We describe six persons from three families with three homozygous protein truncating variants in PUS7: c.89_90del (p.Thr30Lysfs∗20), c.1348C>T (p.Arg450∗), and a deletion of the penultimate exon 15. All these individuals have intellectual disability with speech delay, short stature, microcephaly, and aggressive behavior. PUS7 encodes the RNA-independent pseudouridylate synthase 7. Pseudouridylation is the most abundant post-transcriptional modification in RNA, which is primarily thought to stabilize secondary structures of RNA. We show that the disease-related variants lead to abolishment of PUS7 activity on both tRNA and mRNA substrates. Moreover, pus7 knockout in Drosophila melanogaster results in a number of behavioral defects, including increased activity, disorientation, and aggressiveness supporting that neurological defects are caused by PUS7 variants. Our findings demonstrate that RNA pseudouridylation by PUS7 is essential for proper neuronal development and function.


Assuntos
Agressão/fisiologia , Nanismo/genética , Variação Genética/genética , Deficiência Intelectual/genética , Transtornos do Desenvolvimento da Linguagem/genética , Microcefalia/genética , Adolescente , Animais , Criança , Drosophila melanogaster/genética , Éxons/genética , Feminino , Técnicas de Inativação de Genes/métodos , Homozigoto , Humanos , Masculino , Linhagem , Fenótipo , RNA Mensageiro/genética , RNA de Transferência/genética
7.
PLoS One ; 13(9): e0202762, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30208060

RESUMO

We developed a new probabilistic model to assess the impact of recommendations rectifying the reproducibility crisis (by publishing both positive and 'negative' results and increasing statistical power) on competing objectives, such as discovering causal relationships, avoiding publishing false positive results, and reducing resource consumption. In contrast to recent publications our model quantifies the impact of each single suggestion not only for an individual study but especially their relation and consequences for the overall scientific process. We can prove that higher-powered experiments can save resources in the overall research process without generating excess false positives. The better the quality of the pre-study information and its exploitation, the more likely this beneficial effect is to occur. Additionally, we quantify the adverse effects of both neglecting good practices in the design and conduct of hypotheses-based research, and the omission of the publication of 'negative' findings. Our contribution is a plea for adherence to or reinforcement of the good scientific practice and publication of 'negative' findings.


Assuntos
Pesquisa Biomédica , Modelos Teóricos , Editoração , Reprodutibilidade dos Testes
8.
Horm Metab Res ; 50(8): 602-608, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30081408

RESUMO

Circulating tumor cells (CTCs) have been shown to be a valuable prognostic marker for different solid cancers. Within the present study we quantified CTCs in thyroid cancer (TC) patients. Special focus was given to disease-free PTC patients with undetectable serum thyroglobulin (Tg) levels. Altogether, 67 TC patients (33 papillary, 20 follicular, 14 medullary) were included in the study. CTC numbers, which were normalized to 3.3×105 peripheral blood mononuclear cells, were correlated with clinical outcome. TC patients had significantly higher CTC numbers compared to controls. The number of CTCs correlated to the initial tumor stage. Importantly, in comparison to controls, differentiated TC patients with serum Tg levels<0.3 ng/ml (no evidence of tumor recurrence) revealed a significantly higher amount of CTCs, also associated to their former tumor stage. Regarding the tumor-free papillary TC (PTC) patients the number of CTCs additionally correlated to the time point of radioiodine (RI) therapy: PTC patients with RI therapies>8 years before CTC measurement had significantly higher CTC numbers compared to those with RI therapy<8 years ago. We found a clear correlation between the number of CTCs and the tumor stage. Importantly, PTC patients who are in remission may still have increased numbers of CTCs. Follow-up analyses in these patients will reveal whether these data will have a clinical impact.


Assuntos
Células Neoplásicas Circulantes/patologia , Neoplasias da Glândula Tireoide/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/sangue , Carcinoma Papilar/patologia , Contagem de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia
9.
Genes (Basel) ; 9(5)2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29748516

RESUMO

Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells and an extracellular matrix that is mechanically stable, yet flexible at the same time. Unlike most tissues, bone is under constant renewal facilitated by a coordinated interaction of bone-forming and bone-resorbing cells. It is thus challenging to recreate bone in its complexity in vitro and most current models rather focus on certain aspects of bone biology that are of relevance for the research question addressed. In addition, animal models are still regarded as the gold-standard in the context of bone biology and pathology, especially for the development of novel treatment strategies. However, species-specific differences impede the translation of findings from animal models to humans. The current review summarizes and discusses the latest developments in bone tissue engineering and organoid culture including suitable cell sources, extracellular matrices and microfluidic bioreactor systems. With available technology in mind, a best possible bone model will be hypothesized. Furthermore, the future need and application of such a complex model will be discussed.

10.
PLoS One ; 12(3): e0173197, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28257453

RESUMO

OBJECTIVE: Betatrophin has been identified as a marker linking liver with beta cell function and lipid metabolism in murine models. Until now, the regulation of circulating betatrophin in humans is not entirely clear. We here analyzed the relation of betatrophin levels to phenotypes of the metabolic syndrome and speculated that renal function might influence circulating betatrophin levels and explain age-dependent changes of betatrophin. SUBJECTS: We analyzed blood samples from 535 individuals participating in the Metabolic Syndrome Berlin Potsdam study. RESULTS: In a crude analysis we found a positive correlation between betatrophin levels and HbA1c (r = 0.24; p < 0.001), fasting glucose (r = 0.20; p < 0.001) and triglycerides (r = 0.12; p = 0.007). Furthermore betatrophin was positively correlated with age (r = 0.47; p <0.001), systolic blood pressure (r = 0.17; p < 0.001), intima media thickness (r = 0.26; p < 0.001) and negatively correlated with CKD-EPI eGFR (r = -0.33; p < 0.001) as an estimate of renal function. Notably, eGFR remained highly associated with betatrophin after adjustment for age, waist circumference, gender, HbA1c and lipid parameters in a multivariate linear regression model (ß = -0.197, p< 0.001). CONCLUSIONS: Our data suggest that circulating levels of betatrophin depend on age, gender, waist circumference, total/HDL cholesterol ratio and renal function. Especially the association to eGFR highlights the importance for future studies to address renal function as possible influence on betatrophin regulation and consider eGFR as potential confounder when analyzing the role of betatrophin in humans.


Assuntos
Rim/metabolismo , Metabolismo dos Lipídeos , Síndrome Metabólica/sangue , Hormônios Peptídicos/sangue , Adulto , Idoso , Proteínas Semelhantes a Angiopoietina , Glicemia , Pressão Sanguínea , Espessura Intima-Media Carotídea , Receptores ErbB/sangue , Feminino , Teste de Tolerância a Glucose , Hemoglobina A Glicada/metabolismo , Humanos , Rim/fisiopatologia , Masculino , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Triglicerídeos/sangue
11.
Aging (Albany NY) ; 7(8): 553-67, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26318988

RESUMO

Reducing the expression of the Indy (Acronym for 'I'm Not Dead, Yet') gene in lower organisms promotes longevity and leads to a phenotype that resembles various aspects of caloric restriction. In C. elegans, the available data on life span extension is controversial. Therefore, the aim of this study was to determine the role of the C. elegans INDY homolog CeNAC2 in life span regulation and to delineate possible molecular mechanisms. siRNA against Indy/CeNAC2 was used to reduce expression of Indy/CeNAC2. Mean life span was assessed in four independent experiments, as well as whole body fat content and AMPK activation. Moreover, the effect of Indy/CeNAC2 knockdown in C. elegans with inactivating variants of AMPK (TG38) was studied. Knockdown of Indy/CeNAC2 increased life span by 22±3 % compared to control siRNA treated C. elegans, together with a decrease in whole body fat content by ~50%. Indy/CeNAC2 reduction also increased the activation of the intracellular energy sensor AMPK/aak2. In worms without functional AMPK/aak2, life span was not extended when Indy/CeNAC2 was reduced. Inhibition of glycolysis with deoxyglucose, an intervention known to increase AMPK/aak2 activity and life span, did not promote longevity when Indy/CeNAC2 was knocked down. Together, these data indicate that reducing the expression of Indy/CeNAC2 increases life span in C. elegans, an effect mediated at least in part by AMPK/aak2.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/enzimologia , Longevidade , Transportadores de Ânions Orgânicos/genética , Proteínas Serina-Treonina Quinases/metabolismo , Tecido Adiposo , Animais , Caenorhabditis elegans/genética , Restrição Calórica , Ativação Enzimática , Técnicas de Silenciamento de Genes , Glucose
12.
J Cell Commun Signal ; 9(2): 143-50, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25663268

RESUMO

IGFBP-2 affects growth and metabolism and is thought to impact on energy homeostasis and the accretion of body fat via its heparin binding domains (HBD). In order to assess the function of the HBD present in the linker domain (HBD1) we have generated transgenic mice overexpressing mutant human IGFBP-2 lacking the PKKLRP sequence and carrying a PNNLAP sequence instead. Transgenic mice expressed high amounts of human IGFBP-2, while endogenous IGFBP-2 or IGF-I serum concentrations were not affected. In both genders we performed a longitudinal analysis of growth and metabolism including at least 4 separate time points between the age of 10 and 52 weeks. Body composition was assessed by nuclear magnetic resonance (NMR) analysis. Food intake was recorded by an automated online-monitoring. We describe negative effects of mutant human IGFBP-2 on body weight, longitudinal growth and lean body mass (p < 0.05). Very clearly, negative effects of mutant IGFBP-2 were not observed for fat mass accretion throughout life. Instead, relative fat mass was increased in transgenic mice of both genders (p < 0.05). In male mice transgene expression significantly increased absolute mass of total body fat over all age groups (p < 0.05). Food intake was increased in female but decreased in male transgenic mice at an age of 11 weeks. Thus our study clearly provides gender- and time-specific effects of HBD1-deficient hIGFBP-2 (H1d-BP-2) on fat mass accretion and food intake. While our data are in principal agreement with current knowledge on the role of HB-domains for fat accretion we now may also speculate on a role of HBD1 for the control of eating behavior.

13.
Clin Endocrinol (Oxf) ; 82(6): 838-43, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25640450

RESUMO

OBJECTIVE: Insulin resistance and subclinical inflammation are characteristics in the development of type 2 diabetes mellitus (T2DM). The adipokine chemerin has been associated with both factors. The aim of this study was to analyse whether chemerin predicts T2DM. DESIGN: Blood samples of 440 participants of the Metabolic-Syndrome Berlin-Potsdam (MesyBepo) follow-up study without diabetes at baseline were available for chemerin measurement. Mean follow-up of participants was 5·3 years. Glucose metabolism was analysed using oral glucose tolerance test including insulin measurements. Chemerin was measured using a commercially available ELISA. RESULTS: Thirty-five individuals developed T2DM during follow-up. Chemerin predicted incident T2DM (Chemerin 1. Tertile: reference, 2. Tertile: OR 2·33 [0·68-7·95]; Chemerin 3. Tertile: OR 3·42 [1·01-11·58] after adjustment for age, sex, BMI, follow-up time, HbA1c, HOMA-IR and WHR). In a secondary analysis, chemerin also predicted worsening of fasting glucose and HbA1c (adjusted for age, sex, BMI, time of follow-up, WHR, HDL cholesterol and triglycerides). CONCLUSIONS: Our data suggest that chemerin is a weak predictor of T2DM.


Assuntos
Quimiocinas/sangue , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Alemanha , Teste de Tolerância a Glucose/métodos , Hemoglobina A Glicada/análise , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
14.
Diabetes Care ; 36(1): 145-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22933429

RESUMO

OBJECTIVE: The incidence of the metabolic syndrome and type 2 diabetes mellitus (T2DM) is rising worldwide. Liver-derived fibroblast growth factor (FGF)-21 affects glucose and lipid metabolism. The aim of this study was to analyze the predictive value of FGF-21 on the incidence of T2DM and the metabolic syndrome. RESEARCH DESIGN AND METHODS: The Metabolic Syndrome Berlin Potsdam (MeSyBePo) recall study includes 440 individuals. Glucose metabolism was analyzed using an oral glucose tolerance test, including insulin measurements. FGF-21 was measured using enzyme-linked immunosorbent assay. Primary study outcome was diabetes and the metabolic syndrome incidence and change of glucose subtraits. RESULTS: During a mean follow-up of 5.30 ± 0.1 years, 54 individuals developed the metabolic syndrome, 35 developed T2DM, and 69 with normal glucose tolerance at baseline progressed to impaired glucose metabolism, defined as impaired fasting glucose, impaired glucose tolerance, or T2DM. FGF-21 predicted incident metabolic syndrome (lnFGF-21 odds ratio [OR] 2.6 [95% CI 1.5 - 4.5]; P = 0.001), T2DM (2.4 [1.2-4.7]; P = 0.01), and progression to impaired glucose metabolism (2.2 [1.3 - 3.6]; P = 0.002) after adjustment for age, sex, BMI, and follow-up time. Additional adjustment for waist-to-hip ratio, systolic blood pressure, HDL cholesterol, triglycerides, and fasting glucose did not substantially modify the predictive value of FGF-21. CONCLUSIONS: FGF-21 is an independent predictor of the metabolic syndrome and T2DM in apparently healthy Caucasians. These results may indicate FGF-21 resistance precedes the onset of the metabolic syndrome and T2DM.


Assuntos
Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Fatores de Crescimento de Fibroblastos/sangue , Síndrome Metabólica/sangue , Adolescente , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
J Clin Bioinforma ; 2: 3, 2012 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-22300499

RESUMO

BACKGROUND: High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called 'omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. METHODS: We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. RESULTS: We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. CONCLUSIONS: We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods.

16.
Metabolism ; 60(2): 306-11, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20362303

RESUMO

Fibroblast growth factor-21 (FGF-21) has been proposed as a novel metabolic regulator, and animal experiments suggested that FGF-21 may affect energy balance. In humans, FGF-21 was correlated with obesity. Until now, no data exist regarding the relationship of FGF-21 and weight reduction in humans. We therefore investigated whether FGF-21 is modified by a moderate intended weight loss in a human trial. Thirty obese individuals (24 female, 6 male) participated in a weight reduction program for 6 months. In addition to several anthropometric and metabolic parameters, FGF-21 was measured before and after weight loss. Baseline serum FGF-21 was independently associated with markers of lipid metabolism and waist circumference. The multimodal intervention induced a moderate weight loss (97.4 ± 3.1 vs 92.2 ± 3.1 kg, P < .001), which was accompanied by a significant improvement of lipid and glucose metabolism. However, FGF-21 levels were not modified by moderate weight reduction; and FGF-21 levels at baseline were not a predictive marker for subsequent weight loss. The results presented here confirmed that FGF-21 levels are associated with markers of lipid metabolism and an estimate of abdominal adiposity. The finding that moderate weight loss did not induce changes of FGF-21 levels in humans suggests that FGF-21 is not directly regulated by fat mass under those conditions.


Assuntos
Adiposidade , Fatores de Crescimento de Fibroblastos/metabolismo , Metabolismo dos Lipídeos , Perda de Peso , Gordura Abdominal/metabolismo , Índice de Massa Corporal , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Glucose/metabolismo , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Circunferência da Cintura/fisiologia
17.
Atherosclerosis ; 213(2): 549-51, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20832065

RESUMO

OBJECTIVE: Retinol is transported in a complex with retinol-binding protein 4 (RBP4) and transthyretin (TTR) in the circulation. While retinol is associated with various cardiovascular risk factors, the relation between retinol, RBP4, TTR and carotid intima media thickness (IMT) has not been analysed yet. METHODS: Retinol, RBP4 and TTR were measured in 96 individuals and their relation to mean and maximal IMT was determined. RESULTS: Mean IMT correlated with RBP4 (r=0.335, p<0.001), retinol (r=-0.241, p=0.043), RBP/TTR ratio (r=0.254, p=0.025) and retinol/RBP4 ratio (r=-0.549, p<0.001). Adjustment for age, sex, BMI, blood pressure, HDL/total cholesterol ratio, triglyceride, diabetes and smoking revealed that the retinol/RBP4 ratio was strongly and independently associated with mean IMT. Similar results were found for maximal IMT, which included the measurement of plaques. CONCLUSION: The data support that the transport complex of vitamin A is associated with the IMT, an established parameter of atherosclerosis. Changes in RBP4 saturation with retinol may link renal dysfunction and insulin resistance to atherosclerosis.


Assuntos
Artéria Carótida Primitiva/patologia , Pré-Albumina/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Túnica Íntima/patologia , Túnica Média/patologia , Vitamina A/sangue , Artéria Carótida Primitiva/diagnóstico por imagem , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Ultrassonografia
18.
Int J Food Microbiol ; 88(2-3): 325-9, 2003 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-14597005

RESUMO

Plasmid pRE25 from Enterococcus faecalis transfers resistances against kanamycin, neomycin, streptomycin, clindamycin, lincomycin, azithromycin, clarithromycin, erythromycin, roxithromycin, tylosin, chloramphenicol, and nourseothricin sulfate by conjugation in vitro to E. faecalis JH2-2, Lactococcus lactis Bu2, and Listeria innocua L19. Its nucleotide sequence of 50237 base pairs represents the largest, fully sequenced conjugative multiresistance plasmid of enterococci (Plasmid 46 (2001) 170). The gene for chloramphenicol resistance (cat) was identified as an acetyltransferase identical to the one of plasmid pIP501 of Streptococcus agalactiae. Erythromycin resistance is due to a 23S ribosomal RNA methyl transferase, again as found in pIP501 (ermB). The aminoglycoside resistance genes are packed in tandem as in transposon Tn5405 of Staphylococcus aureus: an aminoglycoside 6-adenyltransferase, a streptothricin acetyl transferase, and an aminoglycoside phosphotransferase.). Identical resistance genes are known from pathogens like Streptococcus pyogenes, S. agalactiae, S. aureus, Campylobacter coli, Clostridium perfringens, and Clostridium difficile. pRE25 is composed of a 30.5-kbp segment almost identical to pIP501. Of the 15 genes involved in conjugative transfer, 10 codes for putative transmembrane proteins (e.g. trsB, traC, trsF, trsJ, and trsL). The enterococcal part is joined into the pIP501 part by insertion elements IS1216V of E. faecium Tn1545 (three copies), and homologs of IS1062 (E. faecalis) and IS1485 (E. faecium). pRE25 demonstrates that enterococci from fermented food do participate in the molecular communication between Gram-positive and Gram-negative bacteria of the human and animal microflora.


Assuntos
Conjugação Genética , Farmacorresistência Bacteriana Múltipla/genética , Enterococcus faecalis/genética , Produtos da Carne/microbiologia , Fatores R/genética , Animais , DNA Bacteriano/genética , Enterococcus faecalis/efeitos dos fármacos , Evolução Molecular , Fermentação , Microbiologia de Alimentos , Humanos , Suínos
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