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1.
Int J Mol Sci ; 20(22)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717287

RESUMO

Sodium/phosphate co-transporters are considered to be important mediators of phosphorus (P) homeostasis. The expression of specific sodium/phosphate co-transporters is routinely used as an immediate response to dietary interventions in different species. However, a general understanding of their tissue-specificity is required to elucidate their particular contribution to P homeostasis. In this study, the tissue-wide gene expression status of all currently annotated sodium/phosphate co-transporters were investigated in two pig trials focusing on a standard commercial diet (trial 1) or divergent P-containing diets (trial 2). A wide range of tissues including the gastrointestinal tract (stomach, duodenum, jejunum, ileum, caecum, and colon), kidney, liver, bone, muscle, lung, and aorta were analyzed. Both trials showed consistent patterns in the overall tissue-specific expression of P transporters. While SLC34A2 was considered as the most important intestinal P transporter in other species including humans, SLC34A3 appeared to be the most prominent intestinal P transporter in pigs. In addition, the P transporters of the SLC17 family showed basal expression in the pig intestine and might have a contribution to P homeostasis. The expression patterns observed in the distal colon provide evidence that the large intestine may also be relevant for intestinal P absorption. A low dietary P supply induced higher expressions of SLC20A1, SLC20A2, SLC34A1, and SLC34A3 in the kidney cortex. The results suggest that the expression of genes encoding transcellular P transporters is tissue-specific and responsive to dietary P supply, while underlying regulatory mechanisms require further analyses.

2.
Nutrients ; 11(2)2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30791512

RESUMO

Phosphorus (P) is an important element of various metabolic and signalling processes, including bone metabolism and immune function. To elucidate the routes of P homeostasis and utilization, a five-week feeding study was conducted with weaned piglets receiving a diet with recommended amounts of P and Ca (M), or a diet with lower (L) or higher (H) P values and a constant Ca:P ratio. Routes of P utilization were deduced via bone characteristics (MicroCT), genome-wide transcriptomic profiles of peripheral blood mononuclear cells (PBMCs), and serum mineral levels. MicroCT revealed significantly lower bone mineral density, trabecular number, and mechanical fracture load in (L). Gene expression analyses showed transcripts of 276 and 115 annotated genes with higher or lower abundance in (H) than (L) that were related to basic cellular and metabolic processes as well as response to stimuli, developmental processes and immune system processes. This study shows the many molecular routes involved in P homeostasis that should be considered to improve endogenous mechanisms of P utilization.


Assuntos
Cálcio na Dieta/metabolismo , Dieta/métodos , Homeostase/fisiologia , Fósforo na Dieta/metabolismo , Transcriptoma/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Osso e Ossos/metabolismo , Cálcio na Dieta/administração & dosagem , Leucócitos Mononucleares/metabolismo , Fósforo na Dieta/administração & dosagem , Suínos
3.
Clin Epigenetics ; 10(1): 161, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30587240

RESUMO

BACKGROUND: Most research into myocardial infarctions (MIs) have focused on preventative efforts. For survivors, the occurrence of an MI represents a major clinical event that can have long-lasting consequences. There has been little to no research into the molecular changes that can occur as a result of an incident MI. Here, we use three cohorts to identify epigenetic changes that are indicative of an incident MI and their association with gene expression and metabolomics. RESULTS: Using paired samples from the KORA cohort, we screened for DNA methylation loci (CpGs) whose change in methylation is potentially indicative of the occurrence of an incident MI between the baseline and follow-up exams. We used paired samples from the NAS cohort to identify 11 CpGs which were predictive in an independent cohort. After removing two CpGs associated with medication usage, we were left with an "epigenetic fingerprint" of MI composed of nine CpGs. We tested this fingerprint in the InCHIANTI cohort where it moderately discriminated incident MI occurrence (AUC = 0.61, P = 6.5 × 10-3). Returning to KORA, we associated the epigenetic fingerprint loci with cis-gene expression and integrated it into a gene expression-metabolomic network, which revealed links between the epigenetic fingerprint CpGs and branched chain amino acid (BCAA) metabolism. CONCLUSIONS: There are significant changes in DNA methylation after an incident MI. Nine of these CpGs show consistent changes in multiple cohorts, significantly discriminate MI in independent cohorts, and were independent of medication usage. Integration with gene expression and metabolomics data indicates a link between MI-associated epigenetic changes and BCAA metabolism.


Assuntos
Metilação de DNA , Perfilação da Expressão Gênica/métodos , Estudo de Associação Genômica Ampla/métodos , Leucócitos/química , Infarto do Miocárdio/genética , Idoso , Ilhas de CpG , Epigênese Genética , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Fatores de Risco
4.
Blood ; 132(17): 1842-1850, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30042098

RESUMO

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry-specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10-5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.

5.
BMC Genomics ; 19(1): 207, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29554878

RESUMO

BACKGROUND: In monogastric animals, phosphorus (P) homeostasis is maintained by regulating intestinal absorption, bone mobilization, and renal excretion. Since P is a non-renewable resource, a shortage is imminent due to widespread over-usage in the farming and animal husbandry industries. As a consequence, P efficiency should be improved in pig production. We sought to characterize the transcriptional response in re-/absorbing and excreting tissues in pigs to diets varying in calcium: phosphorus ratios. Weaned piglets were assigned to one of three groups fed diets varying in digestible P content for a period of five weeks. Gene expression profiles were analyzed in jejunum, colon, and kidney. RESULTS: Transcriptome analysis revealed that reduced dietary P intake affects gene expression in jejunum and kidney, but not in colon. The regulation of mineral homeostasis was reflected via altered mRNA abundances of CYP24A1, CYP27A1, TRPM6, SPP1, and VDR in jejunum and kidney. Moreover, lowered abundances of transcripts associated with the classical complement system pathway were observed in the jejunum. In kidney, shifted transcripts were involved in phospholipase C, calcium signaling, and NFAT signaling, which may have immunomodulatory implications. CONCLUSIONS: Our results revealed local transcriptional consequences of variable P intake in intestinal and renal tissues. The adaptive responses are the result of organismal efforts to maintain systemic mineral homeostasis while modulating immune features at local tissue sites. Therefore, the deviation from the currently recommended dietary P supply must be carefully considered, as the endogenous mechanisms that respond to low P diets may impact important adaptive immune responses.


Assuntos
Homeostase , Mucosa Intestinal/metabolismo , Rim/metabolismo , Fósforo na Dieta/administração & dosagem , Desmame , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Colo/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Jejuno/metabolismo , Minerais/metabolismo , Suínos
6.
Res Vet Sci ; 118: 295-303, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29547728

RESUMO

Postprandial alterations of plasma amino acid (PAA) levels partly reflect a temporal contribution of the feed. How cereal grains affect PAA levels is not known. We hypothesized that a meal of cereal grains causes a temporal increase of PAA, affected by grain species, grain genotype and meal size. Six mares were used in three consecutive trials, receiving four oats, barley and maize genotypes, respectively. Individual grain genotypes were provided as 3 meal sizes corresponding to 1.0, 1.5 or 2.0 g starch/kg body weight. Meadow hay (1.5 kg/100 kg body weight) was offered daily. At the test days, 1 kg hay was fed 60 min prior to the grain meal. Blood samples were taken before grain feeding (0 min) and 30, 60, 90, 120, 180, 240 and 300 min thereafter. Subsequently, the remaining hay was offered. The genotype × starch quantity (i.e., meal size) interaction had a major effect on postprandial PAA concentrations (P < 0.05). Availability of amino acids (AA), ingested from different grain genotypes, apparently differed at both the digestive and post-digestive level. Thus, AA supply from grain feeding can better be assessed on the genotype level. The concentrations of most PAA increased rapidly with a postprandial maximum at around 30 min. Hay feeding might have an underrated capability for AA provision because increases of PAA levels were initialized already by ingestion of a 1 kg hay. It remains unclear which portion of the PAA kinetics response originates from hay feeding and which one from the cereal grain meal.

7.
Ambio ; 47(Suppl 1): 20-29, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29159450

RESUMO

Dietary phosphorus frequently exceeds age-specific requirements and pig manure often contains high phosphorus load which causes environmental burden at regional scales. Therefore, feeding strategies towards improved phosphorus efficiency and reduced environmental phosphorus load have to be developed. A 5-week feeding trial was conducted: piglets received medium, lower (-25%), or higher (+25%) amounts of phosphorus and calcium. Dietary responses were reflected by performance parameters, bone characteristics, and molecular data retrieved from serum, intestinal mucosa, and kidney cortex (p < 0.05). Transcripts associated with vitamin D hydroxylation (Cyp24A1, Cyp27A1, Cyp27B1) were regulated by diet at local tissue sites. Low-fed animals showed attempts to maintain mineral homoeostasis via intrinsic mechanisms, whereas the high-fed animals adapted at the expense of growth and development. Results suggest that a diet containing low phosphorus and calcium levels might be useful to improve resource efficiency and to reduce phosphorus losses along the agricultural value chain.


Assuntos
Bem-Estar do Animal , Fósforo na Dieta , Suínos , Animais , Cálcio na Dieta , Dieta , Fósforo
8.
Hypertension ; 70(4): 743-750, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28784648

RESUMO

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of protein levels encoded by candidate genes for subsequent cardiovascular disease was investigated. Eight transcripts (CRIP1, MYADM, TIPARP, TSC22D3, CEBPA, F12, LMNA, and TPPP3) were identified jointly accounting for up to 13% (95% confidence interval, 8.7-16.2) of BP variability. Changes in CRIP1, MYADM, TIPARP, LMNA, TSC22D3, CEBPA, and TPPP3 expression associated with BP changes-among these, CRIP1 gene expression was additionally correlated to measures of cardiac hypertrophy. Assessment of circulating CRIP1 (cystein-rich protein 1) levels as biomarkers showed a strong association with increased risk for incident stroke (hazard ratio, 1.06; 95% confidence interval, 1.03-1.09; P=5.0×10-5). Our comprehensive analysis of global gene expression highlights 8 novel transcripts significantly associated with BP, providing a link between gene expression and BP. Translational approaches further established evidence for the potential use of CRIP1 as emerging disease-related biomarker.


Assuntos
Proteínas de Transporte/genética , Hipertensão , Proteínas com Domínio LIM/genética , Acidente Vascular Cerebral , Adulto , Pressão Sanguínea/genética , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Proteínas Estimuladoras de Ligação a CCAAT/genética , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/diagnóstico , Hipertensão/genética , Masculino , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/genética , Poli(ADP-Ribose) Polimerases/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores de Transcrição/genética
9.
J Immunol Res ; 2017: 8394593, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28638837

RESUMO

Helicobacter pylori infection shows a worldwide prevalence of around 50%. However, only a minority of infected individuals develop clinical symptoms or diseases. The presence of H. pylori virulence factors, such as CagA and VacA, has been associated with disease development, but assessment of virulence factor presence requires gastric biopsies. Here, we evaluate the H. pylori recomLine test for risk stratification of infected patients by comparing the test score and immune recognition of type I or type II strains defined by the virulence factors CagA, VacA, GroEL, UreA, HcpC, and gGT with patient's disease status according to histology. Moreover, the immune responses of eradicated individuals from two different populations were analysed. Their immune response frequencies and intensities against all antigens except CagA declined below the detection limit. CagA was particularly long lasting in both independent populations. An isolated CagA band often represents past eradication with a likelihood of 88.7%. In addition, a high recomLine score was significantly associated with high-grade gastritis, atrophy, intestinal metaplasia, and gastric cancer. Thus, the recomLine is a sensitive and specific noninvasive test for detecting serum responses against H. pylori in actively infected and eradicated individuals. Moreover, it allows stratifying patients according to their disease state.


Assuntos
Gastrite/imunologia , Gastrite/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Imunoensaio/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/isolamento & purificação , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/isolamento & purificação , Biópsia , Feminino , Gastrite/sangue , Gastrite/diagnóstico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/classificação , Helicobacter pylori/imunologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Fatores de Virulência/sangue , Adulto Jovem
10.
PLoS One ; 11(11): e0166015, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27824951

RESUMO

BACKGROUND: Elevated levels of C-reactive protein (CRP, determined by a high-sensitivity assay) indicate low-grade inflammation which is implicated in many age-related disorders. Epigenetic studies on CRP might discover molecular mechanisms underlying CRP regulation. We aimed to identify DNA methylation sites related to CRP concentrations in cells and tissues regulating low-grade inflammation. RESULTS: Genome-wide DNA methylation was measured in peripheral blood in 1,741 participants of the KORA F4 study using Illumina HumanMethylation450 BeadChip arrays. Four CpG sites (located at BCL3, AQP3, SOCS3, and cg19821297 intergenic at chromosome 19p13.2, P ≤ 1.01E-07) were significantly hypomethylated at high CRP concentrations independent of various confounders including age, sex, BMI, smoking, and white blood cell composition. Findings were not sex-specific. CRP-related top genes were enriched in JAK/STAT pathways (Benjamini-Hochberg corrected P < 0.05). Results were followed-up in three studies using DNA from peripheral blood (EPICOR, n = 503) and adipose tissue (TwinsUK, n = 368) measured as described above and from liver tissue (LMU liver cohort, n = 286) measured by MALDI-TOF mass spectrometry using EpiTYPER. CpG sites at the AQP3 locus (significant p-values in peripheral blood = 1.72E-03 and liver tissue = 1.51E-03) and the SOCS3 locus (p-values in liver < 2.82E-05) were associated with CRP in the validation panels. CONCLUSIONS: Epigenetic modifications seem to engage in low-grade inflammation, possibly via JAK/STAT mediated pathways. Results suggest a shared relevance across different tissues at the AQP3 locus and highlight a role of DNA methylation for CRP regulation at the SOCS3 locus.


Assuntos
Aquaporina 3/fisiologia , Epigênese Genética/fisiologia , Inflamação/genética , Proteína 3 Supressora da Sinalização de Citocinas/fisiologia , Tecido Adiposo/fisiopatologia , Aquaporina 3/genética , Proteína C-Reativa/fisiologia , Metilação de DNA/fisiologia , Epigênese Genética/genética , Feminino , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Estudo de Associação Genômica Ampla , Humanos , Inflamação/fisiopatologia , Janus Quinases/fisiologia , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Transcrição STAT/fisiologia , Transdução de Sinais/fisiologia , Proteína 3 Supressora da Sinalização de Citocinas/genética
11.
N Biotechnol ; 33(6): 842-851, 2016 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-27501906

RESUMO

Cyanophycin (CP) is a proteinogenic polymer that can be substituted for petroleum in the production of plastic compounds and can also serve as a source of valuable dietary supplements. However, because there is no economically feasible system for large-scale industrial production, its application is limited. In order to develop a low-input system, CP-synthesis was established in the two commercial Nicotiana tabacum (N. tabacum) cultivars 'Badischer Geudertheimer' (BG) and 'Virginia Golta' (VG), by introducing the cyanophycin-synthetase gene from Thermosynecchococcus elongatus BP-1 (CphATe) either via crossbreeding with transgenic N. tabacum cv. Petit Havana SR1 (PH) T2 individual 51-3-2 or by agrobacterium-mediated transformation. Both in F1 hybrids (max. 9.4% CP/DW) and T0 transformants (max. 8.8% CP/DW), a substantial increase in CP content was achieved in leaf tissue, compared to a maximum of 1.7% CP/DW in PH T0 transformants of Hühns et al. (2008). In BG CP, yields were homogenous and there was no substantial difference in the variation of the CP content between primary transformants (T0), clones of T0 individuals, T1 siblings and F1 siblings of hybrids. Therefore, BG meets the requirements for establishing a master seed bank for continuous and reliable CP-production. In addition, it was shown that the polymer is not only stable in planta but also during silage, which simplifies storage of the harvest prior to isolation of CP.


Assuntos
Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Tabaco/genética , Tabaco/metabolismo , Proteínas de Bactérias/metabolismo , Biomassa , Biotecnologia , Cianobactérias/enzimologia , Cianobactérias/genética , Fermentação , Hibridização Genética , Peptídeo Sintases/genética , Peptídeo Sintases/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Estabilidade Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Tabaco/crescimento & desenvolvimento , Transformação Genética
12.
J Anim Sci Technol ; 58: 24, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27413536

RESUMO

BACKGROUND: Clinoptilolite is a natural zeolite with high adsorption capacity for polar mycotoxins such as aflatoxins. The efficacy of clinoptilolite in ameliorating the toxic effects of aflatoxicosis has been proven in monogastric animals, but there is no such evidence for ruminants. The aim of this study was to evaluate, under field conditions, whether the dietary administration of clinoptilolite in dairy cows could reduce the concentration of aflatoxin M1 (AFM1) in bulk-tank milk, in farms with higher than or close to 0.05 µg/kg of milk (European maximum allowed residual level). An objective of the present study was also to investigate the effect of particle size of clinoptilolite on aflatoxin binding. METHODS: Fifteen commercial Greek dairy herds with AFM1 concentrations in bulk tank milk ≥0.05 µg/kg were selected. Bulk tank milk AFM1 was determined prior to the onset and on day 7 of the experiment. Clinoptilolite was added in the total mixed rations of all farms at the rate of 200 g per animal per day, throughout this period. Two different particle sizes of clinoptilolite were used; less than 0.15 mm in 9 farms (LC group) and less than 0.8 mm in 6 farms (HC group). RESULTS: Clinoptilolite administration significantly reduced AFM1 concentrations in milk in all farms tested at an average rate of 56.2 % (SD: 15.11). The mean milk AFM1 concentration recorded on Day 7 was significantly (P < 0.001) lower compared to that of Day 0 (0.036 ± 0.0061 vs. 0.078 ± 0.0074 µg/kg). In LC group farms the reduction of milk AFM1 concentration was significantly higher than HC group farms (0.046 ± 0.0074 vs. 0.036 ± 0.0061 µg/kg, P = 0.002). As indicated by the Pearson correlation, there was a significant and strong linear correlation among the milk AFM1 concentrations on Days 0 and 7 (R = 0.95, P < 0.001). CONCLUSIONS: Dietary administration of clinoptilolite, especially of smallest particle size, at the rate of 200 g per cow per day can effectively reduce milk AFM1 concentration in dairy cattle and can be used as a preventive measure for the amelioration of the risks associated with the presence of aflatoxins in the milk of dairy cows.

13.
Food Nutr Res ; 60: 30298, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27343205

RESUMO

BACKGROUND: For the increasing development of type 2 diabetes dietary habits play an important role. In this regard, dietary supplements are of growing interest to influence the progression of this disease. OBJECTIVE: The aim of this study was to investigate the effect of a cascade-fermented dietary supplement based on fruits, nuts, and vegetables fortified with chromium and zinc on metabolic control in patients with type 2 diabetes mellitus. METHODS: This was a randomized, placebo-controlled, double-blind, intervention study under free-living conditions using a cross-over design. Thirty-six patients with type 2 diabetes mellitus were enrolled and randomized either to receive a cascade-fermented dietary supplement enriched with chromium (100 µg/d) and zinc (15 mg/d) or a placebo similar in taste but without supplements, over a period of 12 weeks. After a wash-out period of 12 weeks, the patients received the other test product. The main outcome variable was the levels of glycated hemoglobin (HbA1c). Other outcome variables were fasting blood glucose, fructosamine, and lipid parameters. RESULTS: Thirty-one patients completed the study. HbA1c showed no relevant changes during both treatment periods, nor was there a relevant difference between the two treatments (HbA1c: p=0.48). The same results were found for fructosamine and fasting glucose (fructosamine: p=0.9; fasting glucose: p=0.31). In addition, there was no effect on lipid metabolism. CONCLUSION: This intervention study does not provide evidence that a cascade-fermented plant-based dietary supplement enriched with a combination of chromium and zinc improves glucose metabolism in patients with type 2 diabetes mellitus under free-living conditions.

14.
Am J Physiol Regul Integr Comp Physiol ; 310(10): R917-25, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26962023

RESUMO

Phosphorus (P) is of vital importance for many aspects of metabolism, including bone mineralization, blood buffering, and energy utilization. In order to identify molecular routes affecting intrinsic P utilization, we address processes covering P intake, uptake, metabolism, and excretion. In particular, the interrelation of bone tissue and immune features is of interest to approximate P intake to animal's physiology and health status. German Landrace piglets received different levels of digestible phosphorus: recommended, higher, or lower amounts. At multiple time points, relevant serum parameters were analyzed and radiologic studies on bone characteristics were performed. Peripheral blood mononuclear cells were collected to assess differential gene expression. Dietary differences were reflected by serum phosphorus, calcium, parathyroid hormone, and vitamin D. Bone reorganization was persistently affected as shown by microstructural parameters, cathepsin K levels, and transcripts associated with bone formation. Moreover, blood expression patterns revealed a link to immune response, highlighting bidirectional loops comprising bone formation and immune features, where the receptor-activator of NF-κB ligand/receptor-activator of NF-κB kinase system may play a prominent role. The modulated P supplementation provoked considerable organismal plasticity. Genes found to be differentially expressed due to variable P supply are involved in pathways relevant to P utilization and are potential candidate genes for improved P efficiency.


Assuntos
Ração Animal/análise , Osso e Ossos/metabolismo , Fósforo na Dieta/administração & dosagem , Fósforo/metabolismo , Suínos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Densidade Óssea , Dieta/veterinária , Relação Dose-Resposta a Droga , Transcriptoma
15.
Brain ; 139(Pt 2): 346-54, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26626369

RESUMO

Thioredoxin 2 (TXN2; also known as Trx2) is a small mitochondrial redox protein essential for the control of mitochondrial reactive oxygen species homeostasis, apoptosis regulation and cell viability. Exome sequencing in a 16-year-old adolescent suffering from an infantile-onset neurodegenerative disorder with severe cerebellar atrophy, epilepsy, dystonia, optic atrophy, and peripheral neuropathy, uncovered a homozygous stop mutation in TXN2. Analysis of patient-derived fibroblasts demonstrated absence of TXN2 protein, increased reactive oxygen species levels, impaired oxidative stress defence and oxidative phosphorylation dysfunction. Reconstitution of TXN2 expression restored all these parameters, indicating the causal role of TXN2 mutation in disease development. Supplementation with antioxidants effectively suppressed cellular reactive oxygen species production, improved cell viability and mitigated clinical symptoms during short-term follow-up. In conclusion, our report on a patient with TXN2 deficiency suggests an important role of reactive oxygen species homeostasis for human neuronal maintenance and energy metabolism.


Assuntos
Homeostase/fisiologia , Mitocôndrias/metabolismo , Proteínas Mitocondriais/deficiência , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/metabolismo , Criança , Humanos , Masculino , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Doenças Neurodegenerativas/genética , Oxirredução , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/genética
16.
Surg Today ; 46(5): 603-12, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26212215

RESUMO

PURPOSE: Secondary peritonitis remains challenging to manage and some recent evidence suggests that on-demand relaparotomy is more appropriate than planned relaparotomy. This study was designed to validate the predictive power of postoperative procalcitonin (PCT) changes in relation to elimination of the septic abdominal focus. METHODS: In this prospective trial, postoperative PCT serum levels were monitored in 234 surgical patients with secondary peritonitis. The PCT ratio on postoperative days (PODs) 1 and 2 (focus index; FI) was calculated and correlated with the success of the operation. RESULTS: A cutoff value of 1.1 was calculated for the FI. Values below 1.1 indicated insufficient elimination of the focus and values above 1.1 correlated with effective treatment. The optimal time for first PCT sampling was found to be 12-24 h after the index operation. After the respective data cleanup, successful elimination of the intraabdominal focus could be confirmed, with a sensitivity of 93 % and a specificity of 71 %. CONCLUSIONS: The FI is a single parameter-based reliable predictor of successful surgical eradication and strengthens the on-demand relaparotomy concept as the method of choice to treat secondary peritonitis.


Assuntos
Calcitonina/sangue , Laparotomia/métodos , Peritonite/diagnóstico , Peritonite/cirurgia , Reoperação , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Humanos , Pessoa de Meia-Idade , Monitorização Fisiológica , Período Pós-Operatório , Estudos Prospectivos
17.
Artigo em Inglês | MEDLINE | ID: mdl-26500701

RESUMO

BACKGROUND: Disease risk and incidence between males and females reveal differences, and sex is an important component of any investigation of the determinants of phenotypes or disease etiology. Further striking differences between men and women are known, for instance, at the metabolic level. The extent to which men and women vary at the level of the epigenome, however, is not well documented. DNA methylation is the best known epigenetic mechanism to date. RESULTS: In order to shed light on epigenetic differences, we compared autosomal DNA methylation levels between men and women in blood in a large prospective European cohort of 1799 subjects, and replicated our findings in three independent European cohorts. We identified and validated 1184 CpG sites to be differentially methylated between men and women and observed that these CpG sites were distributed across all autosomes. We showed that some of the differentially methylated loci also exhibit differential gene expression between men and women. Finally, we found that the differentially methylated loci are enriched among imprinted genes, and that their genomic location in the genome is concentrated in CpG island shores. CONCLUSION: Our epigenome-wide association study indicates that differences between men and women are so substantial that they should be considered in design and analyses of future studies.

18.
World J Gastroenterol ; 21(2): 525-32, 2015 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-25593468

RESUMO

AIM: To investigate the relation of patient characteristics and procedural parameters to the endoscopic detection rate of colonic adenomas. Further to study, which factors may be capable to predict the localization of adenomatous lesions. METHODS: We used the data base of a prospective randomized colonoscopy study (The ColoCap trial) to identify patients being diagnosed with colon adenoma. Logistic regression analysis was conducted to reveal predictors for adenoma detection in the entire colon and also with respect to the proximal and distal part. Covariates including age, gender, duration of colonoscopy and comorbidities were defined to determine association between predictors and adenoma detection. RESULTS: Equal numbers of adenomas were detected in the proximal and distal side of the splenic flexure [126 (57%) vs 94 (43%), P = 0.104]. Simultaneous occurrence of adenomas in both sides of the colon was rare. The appearance of both proximal and distal adenoma was associated with increasing age (P = 0.008 and P = 0.024) and increasing duration of colonoscopy (P < 0.001 and P = 0.001). Male gender was a predictor for adenoma detection in the proximal colon (P = 0.008) but statistical significance was slightly missed with respect to the distal colon (P = 0.089). Alcohol abuse was found to be a predictor for the detection of distal adenoma (P = 0.041). CONCLUSION: Increasing age and longer duration of colonoscopy are factors with a strong impact on adenoma detection both in the proximal and distal colon. Since proximal adenomas occurred in absence of distal adenomas, complete colonoscopy should be performed for screening.


Assuntos
Adenoma/diagnóstico , Colo/patologia , Neoplasias do Colo/diagnóstico , Colonoscopia , Adenoma/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
19.
Int Orthop ; 39(5): 865-70, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25294307

RESUMO

PURPOSE: Anterior cruciate ligament (ACL) injury represents one of the most common diagnoses in orthopaedic sports medicine. In the past, anatomic knowledge about the different bundles within the cruciate ligaments triggered new treatment concepts, such as double-bundle ACL reconstruction. Recently, besides complete tearing, partial ACL ruptures and bundle augmentation became a focus. However, only little is known regarding rotational stability of the knee with an isolated torn postero-lateral (PL) bundle. Therefore, the aim of the present study was the torsiometric analysis of tibio-femoral restraint patterns of the PL-insufficient knee joint. METHODS: Fresh human whole body cadavers were enrolled. After diagnostic arthroscopy to ensure the structural integrity of the cruciate ligaments, knee joints underwent torsiometry at 0°, 30°, and 90° degree flexion. Then stepwise the PL bundle and the anteromedial (AM) bundle were arthroscopically resected, while torsiometry of the PL- as well as of the ACL-deficient knee joints was repeated. An area under the curve (AUC) was calculated. All statistical analyses were conducted using a p-value of 0.05 as level of significance. RESULTS: The comparison of charged and equilibrated curves during internal rotation revealed significant results at low flexion (30° flexion) angles between the ACL intact versus PL absent conditions (p = 0.04). In addition, charged and equilibrated curves during external rotation at 90° flexion, thus high angles, resulted in a significant difference when comparing the ACL-intact with the PL-deficient condition (p = 0.01). CONCLUSIONS: In the present cadaver study using the Torsiometer tool we found a distinct destabilization of the rotational restraints in full knee extension only after total ACL resection. In contrast, no significant findings resulted after an isolated dissection of the PL bundle during internal deflection. Nevertheless, a significant loss of stability was found during unstressed external deflection after isolated PL bundle dissection. Therefore patients, undergoing PL augmentation might benefit regarding rotational instability patterns.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho/cirurgia , Articulação do Joelho/fisiopatologia , Adulto , Reconstrução do Ligamento Cruzado Anterior , Cadáver , Feminino , Fêmur/fisiologia , Humanos , Instabilidade Articular/cirurgia , Traumatismos do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Rotação , Ruptura , Tíbia/fisiologia , Torção Mecânica
20.
Spine J ; 15(3): 467-76, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25315133

RESUMO

BACKGROUND CONTEXT: During the past decade, a disproportionate increase of spinal fusion procedures has been observed. Along with this trend, image-guided spine surgery has been experiencing a renaissance in the recent years. A wide range of different navigation systems are available on the market today. However, only few published studies assess the learning curves concerning these new spinal navigation techniques. So far, a study on the learning curve for intraoperative three-dimensional fluoroscopy (3DFL)-navigated pedicle screw (PS) placement is still lacking. PURPOSE: The purpose of the study was to analyze the learning curve for 3DFL-navigated thoracolumbar PS placement. STUDY DESIGN/SETTING: The study design included a prospective case series. PATIENT SAMPLE: A cohort of 145 patients were recruited from January 2011 to June 2012. OUTCOME MEASURES: The outcome measures were duration of intraoperative 3D scans, PS placement, PS accuracy on postoperative computed tomography (CT) scans, and PS-related revisions and complications. METHODS: From the introduction of spinal navigation to our department in January 2011 until June 2012, the learning curve for the duration of intraoperative 3D scan acquisition (navigation or control scan) and placement time per screw, intraoperative screw revisions, screw-related complications, revision surgeries, and PS accuracy on postoperative CT scans were assessed in 145 patients undergoing dorsal navigated instrumentation for 928 PS (736 lumbosacral and 192 thoracic). The observed time span was divided into four intervals. Results of the second, third, and last periods were compared with the first (reference) period, respectively. RESULTS: The mean navigation 3D scan time decreased (first and fourth periods) from 15.4±7.8 (range, 4-40) to 8.4±3.3 (3-15) minutes (p<.001). The mean control 3D scan time (after PS placement) decreased from 11.2±4.8 (5-25) to 6.6±3.0 (3-15) minutes (p<.001). The mean PS insertion time decreased from 5.3±2.5 (1-15) to 3.2±2.3 (1-17) minutes (p<.001). The mean proportion of correctly positioned PS (all 928) according to the Gertzbein and Robbins classification grades A and B increased initially from 83.1% (first period) to 95.1% (second period, p=.001), 96.4% (third period, p=.002), and 92.4% (fourth period, p=.049). No learning effect was found with respect to intraoperative screw revisions. There was one revision surgery. CONCLUSIONS: We could demonstrate significant learning effects for 3DFL-navigated PS placement with regard to intraoperative 3D scan acquisition, PS placement time, and PS accuracy.


Assuntos
Fluoroscopia , Curva de Aprendizado , Vértebras Lombares/cirurgia , Parafusos Pediculares , Fusão Vertebral , Vértebras Torácicas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Imagem Tridimensional , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/métodos , Implantação de Prótese/normas , Fusão Vertebral/educação , Fusão Vertebral/normas , Cirurgia Assistida por Computador
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