30 resultados para GHI
Resumo:
Kanzerogene polyaromatische Kohlenwasserstoffe (PAKs), wie Benzo[a]pyren, besitzen eine Bay-Region mit ortho-kondensiertem Benzoring. Dadurch ist die enzymatische Bildung von Bay-Region-Dihydrodiolepoxiden (Oxiranylring in der sterisch abgeschirmten Molekülbucht) möglich, die als ultimal kanzerogene Metaboliten der PAKs gelten. Diese lösen durch DNA-Modifikation Primärläsionen aus, die, sofern sie nicht enzymatisch repariert werden, bei der DNA-Replikation Fehler verursachen (Mu-tationen). Der Mehrstufenprozeß der Kanzerogenese (Promotion und Progression) führt schließlich zur neoplastischen Entartung der Zelle. Benzo[ghi]perylen (BghiP) repräsentiert eine Gruppe von PAKs, die keine „klassische“ Bay-Region besitzen und daher keine vicinalen Dihydrodiolepoxiden bilden können. Trotzdem ist BghiP mutagen, z. B. in den Stämmen TA98 und TA100 von Salmonella typhimurium (1,3- bzw. 4,3 his+-Revertanten/nmol) nach metabolischer Aktivierung mit der postmitochondrialen Fraktion von Ratten nach Behandlung mit 3-Methylcholanthren. Hemmung der mikrosomalen Epoxidhydrolase (mEH) mit 1,1,1-Trichlor-2-propenoxid (TCPO) steigert die bakterielle Mutagenität von BghiP im Stamm TA98 um das 4-fache, was Arenoxide als ultimale Mutagene wahrscheinlich macht. Dieses Ergebnis wird au-ßerdem durch Untersuchung der DNA-Bindung mit dem Verfahren des 32P-Postlabelings bestätigt (Dr. Fickler, Institut für Toxikologie, Universität Mainz). Danach bildete mikrosomal aktiviertes BghiP drei Addukte (ein Hauptaddukt, zwei Nebenaddukte), die durch Hemmung der mEH mit TCPO verstärkt wurden (das Hauptaddukt um 29%). Um den für die bakterielle Mutagenität von BghiP verantwortlichen Metaboliten zu identifizieren, wurde die mikrosomale Biotransformaton von BghiP aufgeklärt. Umsetzung von BghiP mit Lebermikrosomen von Ratten nach Behandlung mit Aroclor 1254 lieferte 17 mit Ethylacetat extrahierbare Metaboliten. Zwölf dieser Metaboliten konnten durch eine Kombination von chromatographischen, spektroskopi-schen und biochemischen Methoden identifiziert werden. Daraus ergeben sich zwei Biotransformati-onswege: Weg I beginnt mit einem Angriff von Cytochrom P450-abhängigen Monooxygenasen an Position 7 und der Bildung des 7-Phenols. Dieses wird dann in das 7,8- bzw. 7,10-Diphenol überführt, die schließlich zu den mehrkernigen Chinonen an der 7,8- bzw. 7,10-Position oxidiert werden. Im Bio-transformationsweg II werden die K-Regionen von BghiP durch Cytochrom P450 funktionalisiert. Zu-nächst entstehen das auf indirektem Weg identifizierte 3,4-Oxid und das 3,4,11,12-Bisoxid, die in mikrosomalen Umsetzungen von BghiP nur nach Hemmung der mEH gebildet werden. Enzymatische Hydrolyse des 3,4-Oxides ergibt das trans-3,4-Dihydrodiol, das zum 3,4-Chinon oxidiert wird. Ebenso entsteht aus dem 3,4,11,12-Bisoxid das trans-3,4-trans-11,12-Bisdihydrodiol, aus dem durch Oxidati-on das trans-3,4-Dihydrodiol-11,12-Chinon hervorgeht. Untersuchung der stereoselektiven enzymati-schen Bildung der K-Region-trans-Di¬hydrodiole ergaben eine präferentielle Entstehung der 3R,4R- bzw. 3R,4R,11R,12R-Enantiomere. Untersuchungen der bakteriellen Mutagenität der Hauptmetaboliten 3,4-Dihydrodiol und dem 7-Phenol machte deutlich, dass beide Biotransformationswege I und II von BghiP zur bakteriellen Mutagenität beitragen. Das 7-Phenol aus Weg I ist ein proximales Mutagen, was auch von Phenolen anderer PAKs bekannt ist. Das 3,4-Dihydrodiol aus Weg II wird so schwach zu Mutagenen aktiviert, dass dem vermutlich gebildete 3,4-Dihydrodiol-11,12-oxid keine große Bedeutung als ultimales Mutagen von BghiP zukommt. Die Bestimmung der direkten mutagenen Aktivität (ohne metabolische Aktivierung) der mutmaßlich ultimal mutagenen Arenoxide von BghiP ergab, dass die des 3,4,11,12-Bisarenoxides sehr gering war (1,3 his+-Revertanten/nmol im Stamm TA98). Das 3,4-Oxid hingegen bewirkte einen deutlichen gentoxischen Effekt in den Stämmen TA98 und TA100 (5,5 bzw. 10 his+-Revertanten/nmol). Dies wurde durch die Bestimmung der DNA-Bindung mit dem 32P-Postlabeling, in dem das 3,4-Oxid für das Hauptaddukt von BghiP verantwortlich gemacht werden konnte, bestätigt. Daher kommt dem 3,4-Oxid als ultimales Mutagen die größte Bedeutung für die Gentoxizität von BghiP zu. Die Ergebnisse dieser Arbeit lassen bei PAKs ohne Bay-Region auf Arenoxide schließen, die eine notwendige Voraussetzung für DNA-Bindung und Mutagenität sind.
Resumo:
Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5×10-8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6×10-8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98-1.14; p=0.17), displaying high degree of heterogeneity (I2=57%; Qhet p=0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.
Resumo:
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Resumo:
大范围、实时、准确地监测典型草原地区草场退化或健康状况对于草原生态系统的保育、农牧业的可持续性发展具有非常重要的意义。比起传统的群落学研究方法,遥感技术对于监测大尺度的植被状况具有无可争议的优越性,并且已经被广泛引入监测植被覆盖变化的研究中。本项研究系统地分析、综述了过去用非遥感手段对放牧和草场退化的关注和研究,介绍了遥感技术应用于植被研究的理论基础、主要途径(植被指数)、有关领域的研究进展。特别是本文提出草场退化状况或整体健康状况可以由基干相互独立的层面表示,而过去监测植被变化主要依赖的NDVI等植被指数只能监测草原植被的个别层面(总量层)。 本文以草场放牧退化比较典型的内蒙古锡林河流域为研究对象,在进行了大量的野外样方调查的基础上,提出一种结合群落样方调查和遥感技术的监测草场健康状况的新方法。本文引入主成份分析方法(PCA),从包含12个反映群落各方面信息的变量中提取出3个有特定生态学意义的主成份,并进一步对其进行分析组合,得出一个能比较敏感、全面反映群落健康状况的新指标-草场健康指数(GHI)。 从6波段的植被光谱反射数据中比较理想地提取出2个主成份:可见光因子和红外光因子。表征群落总量、放牧退化的主成份和GHI与样方光谱反射值有相当的相关性,由此得到GHI与可光、红外光因子的回归模型。 应用此模型到卫星遥感数据(TM),得到GHI影像,并与同一数据的NDVI影像作对比研究,发现GHI在反映放牧等人为干扰对草原植被的影响效应方面比NDVI有明显的优点。此外,GHI影像对植被分布格局,特别是斑块结构有更好的显示效果。应用GHI到历史TM数据,对所研究地域的植被覆盖变化、农牧业的变迁模式等进行了定性研究。研究还发现有较长放牧史的过度放牧区的植被类型没有沿牧压梯度的规律性分布,而是呈随机斑块分布模式。
Resumo:
The use of portion control practices has rarely been quantified. The present study aimed to: (1) explore which portion control practices are actually used by the general population and their association with cognitive restraint, demographic background and general health interest (GHI), and (2) examine how the usage of portion control practices predicts the estimated consumption of an energy dense food (i.e. pizza). Twenty-two portion control practices were rated in terms of their frequency of use from 'never' to 'very often' by a representative sample of 1012 consumers from the island of Ireland. Three factors were extracted and named: measurement-strategy scale, eating-strategy scale, and purchasing-strategy scale. The eating-strategy scale score was the highest, while the measurement-strategy scale carried the lowest frequency score. For each strategy scale score, the strongest predictor was GHI, followed by gender. Having higher GHI and being female were independently associated with more frequent portion control. Both the eating-strategy scale score and the purchasing-strategy scale score were negatively associated with pizza portion size consumption estimates. In conclusion, while this study demonstrates that the reported use of portion control practices is low, the findings provide preliminary evidence for their validity. Further studies are needed to explore how portion control practices are used in different kinds of portion size decisions and what their contribution is to the intake of food over an extended period of time.
Resumo:
Purpose:
This study explored how meal-related variables, socio-demographics and psychological predispositions affect the portion
size and perceived fillingness of an evening meal in Danish and Irish households.
Methods:
Using survey data collected in 2115 respondents from Denmark (DK) and the Island of Ireland (IOI), we compared four
sets of predictors of the portion size chosen for four evening meals (i.e. pizza/soup/chicken salad/pork meal): Biological
variables (hunger, thirst), socio-demographic variables (gender, age, BMI); psychological predispositions (cognitive
restraint, uncontrolled eating, emotional eating, general health interest) and meal-related variables (expected fillingness,
perceived healthiness, liking, frequency of consumption). We also compared five sets of predictors (the previous
four plus portion size) of perceived portion fillingness.
Results:
Portion size selections were associated mainly with demographic variables (gender, BMI) and psychological predispositions
(cognitive restraint, uncontrolled eating). In addition, only liking and sometimes expected healthiness (mealrelated
variables) appeared as drivers. Conversely, perceived portion fillingness was mostly influenced by the selected
portion size as well as expected fillingness and liking. There were some differences between meals; e.g. GHI not a
predictor for Pizza but a predictor for Chicken salad. Also some country differences were observed; emotional eating
predicted portion selection in the IOI but not DK.
Conclusions:
When making portion size selections at home, psychological predispositions, restrained and uncontrolled eating as well
as meal-related variables, liking and healthiness explained the decisions. However, surprisingly, individuals’ expected
fillingness of a food did not influence their portion size selection but was a driver of fillingness of the selected portion.
Resumo:
The purpose of this study was to test a comprehensive model of meal portion size determinants consisting of sociodemographic, psychological and food-related variables, whilst controlling for hunger and thirst.
Using cross-sectional nationally representative data collected in 2075 participants from the Island of Ireland (IoI) and Denmark (DK), eight separate hierarchical multiple regression analyses were conducted to examine the association between food-related variables and meal portion size (i.e. pizza, vegetable soup, chicken salad and a pork meal) within each country. Stepwise regressions were run with physiological control measures (hunger and thirst) entered in the first step, sociodemographic variables (sex, age, body mass index (BMI)) in the second step; psychological variables (cognitive restraint, uncontrolled eating, emotional eating, general health interest (GHI)) in the third step and food-related variables (expected fillingness, liking, expected healthfulness, food familiarity) in the fourth step.
Sociodemographic variables accounted for 2-19% of the variance in meal portion sizes; psychological variables explained an additional 3-8%; and food-related variables explained an additional 2-12%. When all four variable groups were included in the regression models, liking and sometimes expected healthfulness was positively associated with meal portion size. The strongest association was for liking, which was statistically significant in both countries for all meal types. Whilst expected healthfulness was not associated with pizza portion size in either country, it was positively associated with meals that have a healthier image (vegetable soup; chicken salad and in IoI, the pork meal).
In conclusion, after considering sociodemographic and psychological variables, and the food-related variables of liking and expected healthfulness, there may be little merit in manipulating the satiating power, at least of these type of meals, to maintain or promote weight loss.
Keywords: Meal portion size; psychological variables; expected fillingness; expected healthfulness; food liking; food familiarity.
Resumo:
Context: Inherited GH insensitivity (GHI) is usually caused by mutations in the GH receptor (GHR). Patients present with short stature associated with high GH and low IGF-I levels and may have midfacial hypoplasia ( typical Laron syndrome facial features). We previously described four mildly affected GHI patients with an intronic mutation in the GHR gene (A.(1) -> G.(1) substitution in intron 6), resulting in the activation of a pseudoexon (6 Psi) and inclusion of 36 amino acids. Objective: The study aimed to analyze the clinical and genetic characteristics of additional GHI patients with the pseudoexon (6 Psi) mutation. Design/Patients: Auxological, biochemical, genetic, and haplotype data from seven patients with severe short stature and biochemical evidence of GHI were assessed. Main Outcome Measures: We assessed genotype-phenotype relationship. Results: One patient belongs to the same extended family, previously reported. She has normal facial features, and her IGF-I levels are in the low-normal range for age. The six unrelated patients, four of whom have typical Laron syndrome facial features, have heights ranging from -3.3 to -6.0 SD and IGF-I levels that vary from normal to undetectable. We hypothesize that the marked difference in biochemical and clinical phenotypes might be caused by variations in the splicing efficiency of the pseudoexon. Conclusions: Activation of the pseudoexon in the GHR gene can lead to a variety of GHI phenotypes. Therefore, screening for the presence of this mutation should be performed in all GHI patients without mutations in the coding exons.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Resumo:
A intensidade da cor verde da folha pode ser alternativa para estimar a concentração de N na planta, devido à relação entre o teor de clorofila e o de N no tecido foliar. Objetivou-se neste trabalho avaliar índices da cor verde da grama esmeralda obtidos da análise da imagem digital e pelo uso do clorofilômetro para predizer o estado nutricional em N fornecido pelo lodo de esgoto. O experimento foi instalado e desenvolvido em uma propriedade comercial de grama esmeralda, localizada na cidade de Itapetininga (SP). O delineamento experimental foi em blocos casualizados, com quatro repetições e cinco doses de lodo de esgoto: 0, 10, 20, 30 e 40 Mg ha-1, base seca. As doses de lodo aplicadas correspondem a 100, 200, 300 e 400 kg ha-1 de nitrogênio disponível. Foram avaliadas as concentrações de N e a intensidade de coloração verde da folha pelo uso do clorofilômetro (ICV) e por meio da análise da imagem digital (G, H e ICVE) aos 45, 105 e 165 dias após a aplicação do lodo. Os valores de intensidade obtidos foram correlacionados com a concentração de N na lâmina foliar e com a taxa de cobertura do solo determinada nas mesmas épocas. A aplicação de doses de lodo de esgoto proporcionou aumento dos índices de cor verde e da concentração de N nas folhas da grama esmeralda. A concentração de N na lâmina foliar pode auxiliar a adubação nitrogenada em cobertura, pois proporcionou altas correlações com a taxa de cobertura do solo. O matiz (H) obtido com a imagem digital e a intensidade de cor verde da folha (ICV) obtida com o clorofilômetro correlacionaram-se com a concentração de N e com a taxa de cobertura do solo e, dessa forma, podem servir como índices na recomendação da adubação nitrogenada.
Resumo:
Several evidences point for beneficial effects of growth hormone (GH) in heart failure (HF). Taking into account that HF is related with changes in myocardial oxidative stress and in energy generation from metabolic pathways, it is important to clarify whether GH increase or decrease myocardial oxidative stress and what is its effect on energetic metabolism in HF condition. Thus, this study investigated the effects of two different doses of GH on energetic metabolism and oxidative stress in myocardium of rats with HF. Male Wistar rats (n = 25) were submitted to aortic stenosis (AS). The HF was evidenced by tachypnea and echocardiographic criteria around 28 weeks of AS. The rats were then randomly divided into three groups: (HF) with HF, treated with saline (0.9% NaCl); (HF-GHI), treated with 1 mk/kg/day recombinant human growth hormone (rhGH), and (HF-GH2) treated with 2 mg/kg/day rhGH. GH was injected, subcutaneously, daily for 2 weeks. A control group (sham; n = 12), with the same age of the others rats was evaluated to confirm data for AS. HF had lower IGF-I (insulin-like growth factor-I) than sham-operated rats, and both GH treatments normalized IGF-I level. HF-GH1 animals had lower lipid hydroperoxide (LH), LH/total antioxidant substances (TAS) and glutathione-reductase than HF. Glutathione peroxidase (GSH-Px), hydroxyacyl coenzyme-A dehydrogenase, lactate dehydrogenase(LDH) were higher in HF-GH1 than in HF. HF-GH2 compared with HF, had increased LH/TAS ratio, as well as decreased oxidized glutathione and LDH activity. Comparing the two GH doses, GSH-Px, superoxide dismutase and LDH were lower in HF-GH2 than in HF-GHI. In conclusion, GH effects were dose-dependent and both tested doses did not aggravate the heart dysfunction. The higher GH dose, 2 mg/kg exerted detrimental effects related to energy metabolism and oxidative stress. The lower dose, 1 mg/kg GH exerted beneficial effects enhancing antioxidant defences, reducing oxidative stress and improving energy generation in myocardium of rats with heart failure. (c) 2007 Elsevier Ltd. All rights reserved.
Resumo:
Microparticles found in the air may be associated with organic matter that contains several compounds, such as Polycyclic Aromatic Hydrocarbons (PAHs) and nitro-PAHs, and may pose a significant risk to human health, possibly leading to DNA mutations and cancers. This study associated genotoxicity assays for evaluating human exposure with the atmospheric air of two urban areas in southern Brazil, that received different atmospheric contributions. Site 1 was under urban-industrial influence and the other was a non-industrial reference, Site 2. Organic extracts from the airborne particulate matter were tested for mutagenicity via the Salmonella/microsome assay and analyzed for PAH composition. Cells samples of people residing in these two cities were evaluated using the comet and micronucleus assay (MN).Concentrations of the individual PAHs ranged from 0.01ng/m3 (benzo[a]anthracene) to 5.08ng/m3 (benzo[ghi]perylene). As to mutagenicity analysis of airborne, Site 1 presented all the mutagenic responses, which varied from 3.2±1.22rev/m3 (TA98 no S9) to 32.6±2.05rev/m3 (TA98, S9), while Site 2 ranged from negative to minimal responses. Site 1 presented a high quantity of nitro and amino derivatives of PAHs, and peaked at 56.0±3.68rev/μg (YG1024 strain). The two groups presented very low DNA damage levels without intergroup difference. Although Site 1 presented high mutagenic responses in the air samples, high PAH levels, healthy people exposed to this environment did not show significative damage in their genetic material. However, the evaluation of different environmental and genetic damage in such population is necessary to monitor possible damages. © 2013 Elsevier Inc.
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In understanding that the efforts made in improving global health affects the health of U.S. citizens, a policy analysis of President Barak Obama's Global Health Initiative was conducted. Using materials gathered from experts in the field of health and their findings and recommendations, paired with the current policies of other G8 countries that pledged to support the efforts of improving global health, the analysis was conducted using four specifically defined criteria. The set criteria determine the appropriateness, responsiveness, effectiveness and equity of Obama's GHI in comparison to other G8 country health policies and overall global health priorities. G8 countries without a specific global health policy, or with a policy that was not in English were excluded from this study and Switzerland, headquarters of the World Health Organization, was added due to its membership in the OECD, and the fact that it has a specific foreign health policy. In evaluating the U.S. Global Health Initiative it is clear that in terms of implementing foreign policy specific to health, the United States is on the forefront alongside the United Kingdom and Switzerland. Other G8 Countries have pledged monies and in order to Millennium Development Health Goals by 2015. The U.S. Global Health Policy does not address issues necessary to meet Millennium Development Goals in Health. Instead the Global Health Initiative is focused narrowly on Fighting and rolling back the HIV/Aids Epidemic based on President Bush's PEPFAR policy. Policy recommendations for a more effective and efficient Global Health Initiative include building upon the PEPFAR policy foundation in order to strengthen health systems worldwide, allowing individuals and communities to combat unnecessary death and disease through research, education, and other preventative methods.^
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Pockmarks are geological features that are found on the bottom of lakes and oceans all over the globe. Some are active, seeping oil or methane, while others are inactive. Active pockmarks are well studied since they harbor specialized microbial communities that proliferate on the seeping compounds. Such communities are not found in inactive pockmarks. Interestingly, inactive pockmarks are known to have different macrofaunal communities compared to the surrounding sediments. It is undetermined what the microbial composition of inactive pockmarks is and if it shows a similar pattern as the macrofauna. The Norwegian Oslo Fjord contains many inactive pockmarks and they are well suited to study the influence of these geological features on the microbial community in the sediment. Here we present a detailed analysis of the microbial communities found in three inactive pockmarks and two control samples at two core depth intervals. The communities were analyzed using high-throughput amplicon sequencing of the 16S rRNA V3 region. Microbial communities of surface pockmark sediments were indistinguishable from communities found in the surrounding seabed. In contrast, pockmark communities at 40 cm sediment depth had a significantly different community structure from normal sediments at the same depth. Statistical analysis of chemical variables indicated significant differences in the concentrations of total carbon and non-particulate organic carbon between 40 cm pockmark and reference sample sediments. We discuss these results in comparison with the taxonomic classification of the OTUs identified in our samples. Our results indicate that microbial surface sediment communities are affect by the water column, while the 40 cm communities are affect by local conditions within the sediment.