Protective effect of N-acetylcysteine on the toxicity of silver nanoparticles:Bioavailability and toxicokinetics in Enchytraeus crypticus

We previously demonstrated that N-acetylcysteine (NAC) could reduce the toxicity of silver (Ag) materials (nanoparticles (NPs) and Ag nitrate) to the soil invertebrate Enchytraeus crypticus (Oligochaeta). It remains however, unclear whether the antitoxic mechanism of NAC was caused by NAC-Ag binding in the soil or inside the organisms. This study aimed at determining the bioavailability of Ag in the soil in a 21-day toxicity test as well as the Ag uptake and elimination kinetics in E. crypticus exposed to AgNPs in LUFA 2.2 standard soil amended with low (100 mg/kg dry soil) and high (600 mg/kg dry soil) NAC concentrations. The addition of NAC to the soil alleviated the toxicity of AgNPs by decreasing the internal Ag concentration of E. crypticus in a dose-dependent manner. Indeed, NAC reduced the binding of Ag to the soil, which probably was due to the formation of soluble but biologically unavailable Ag-cysteine complexes. The reduced Ag uptake in the enchytraeids was explained from an increased elimination at high NAC levels. These findings reinforce the view that metal complexing-compounds like NAC play a key role in the modulation of AgNP toxicity and bioavailability in terrestrial environments. Further, it may inform on the potential of NAC as a remediation solution for Ag or other metal-contaminated soils

Hyperhomocysteinemia in Renal Transplantation: Preliminary Results

Cardiovascular disease (CVD) is a major cause of morbidity and mortality after renal transplantation (RT).[1] and [2] The excess risk of CVD in RT is due in part to a higher prevalence of established atherosclerotic risk factors, including hypertension, dyslipidemia, diabetes, obesity, and physical inactivity.[1] and [2] However, some renal-related risk factors like immunosuppressive medication and residual renal insufficiency also contribute to this excess CVD risk and may complicate the management of dyslipidemia and hypertension in this population.[1] and [2] Accordingly, there is a compelling need to identify and safely manage other putative CVD risk factors among RT patients. Elevated plasma homocysteine is emerging as an important risk factor for cardiovascular disease in general populations.[3] and 4 R Clarke, L Daly and K Robinson et al., N Engl J Med 324 (1991), p. 1149. View Record in Scopus | Cited By in Scopus (1372)[4] Some studies have demonstrated that hyperhomocysteinemia is present in patients with impaired renal function and is associated with CVD.[5], [6] and [7] Only a small number of studies are available on the prevalence and determinants of hyperhomocysteinemia in renal transplant recipients.[8], [9], [10], [11], [12], [13], [14] and [15] We undertook this study to 1. estimate the prevalence of hyperhomocysteinemia in renal transplant recipients; 2. examine the relationships between plasma total homocysteine (tHcy) and its metabolic determinants vitamin B6, vitamin B12, and folic acid; and 3. identify other determinants of tHcy

Recuperação da vegetação de caatinga após impacto em Assaré - CE

Recuperação da vegetação de caatinga apósimpacto em Assaré - C

Fitofiosionomia de uma caatinga no município de Milagres, CE

Fitofiosionomia de uma caatinga nomunicípio de Milagres, C

Prevalence of diabetes-associated gene variants and its association with blood glucose levels in the Algarve population, Portugal

The global rise in incidence of type 2 (T2D) has been called a pandemic, constituting a major public health concern. Although environmental factors play a substantial role in the etiology of T2D, genetic susceptibility has been established as a key component in T2D risk. Given the absence of studies regarding the prevalence of T2D associated variants in the Portuguese population, our aim was to determine the prevalence of disease-associated variants and determine its relative contribution to this phenotype. For this purpose, we have recruited 221 individuals (93 males and 128 females), between 26-91 years old (mean age 57.1), who were enrolled in the Health Centre of S. Brás de Alportel (Algarve). For each participant, we have measured total glucose levels and collected DNA. In addition, each participant has answered an exhaustive questionnaire including socio-demographic information, health history and lifestyle. We have selected and analysed three of the most significant loci previously reported to be associated with T2D in Caucasian populations (TCF7L2 rs7903146, PARPG rs1801282 and FTO rs9939609) and performed an association analysis between glucose levels in this population and the selected gene variants. The mean total population glucose level was 103.85±35.3 g/dl. We found a significant difference in the mean glucose levels between males (mean = 111.5±51.3 g/dl) and females (mean = 98.4±17.6 g/dl) (Mann-Whitney test P < 0.001). The relative allele frequencies of the genotyped variants have been established. Genotype distribution for all investigated SNPs was in Hardy-Weinberg equilibrium. We found a marginal association between glucose levels and genotypes at the TCF7L2 locus (Mann-Whitney test P = 0.045) in females but not in males, with carriers of the T allele displaying higher levels of blood glucose than homozygous for the A allele. This difference is also observed in males, although not reaching significance. No association was found between glucose levels and the other genotyped variants. These results suggest that the pathophysiology of the disease may be different between males and females, or that environmental factors are influencing this trait in males. We are currently investigating the later hypothesis by increasing our sample size and by analysing lifestyle information provided by the participants in order to evaluate gene-environment interactions influencing glucose levels in the Portuguese population.The pilot study of the Portuguese Component of the European Health Examination Survey (EHES) project has received funding from the European Commission/DG Sanco (Agreement number: 20092301 – EHES JA – EAHC). This study has also received funding from the Portuguese Foundation for Science and Technology (FCT) (Project Reference: PTDC/SAU-ESA/101743/2008)

Prevalence of alpha-1 antitrypsin deficiency and hereditary hemochromatosis gene mutations in Algarve, Portugal

Alpha-1 antitrypsin (AAT) deficiency and hereditary hemochromatosis (HH) are two of the most fatal genetic disorders in adult life, affecting million individuals worldwide. They are often under-diagnosed conditions and diagnosis is only made when the patient is already in the advanced stages of damage. AAT deficiency results from mutations in one highly pleiomorphic gene located on chromosome 14, SERPINA 1, being Z and S mutations the most relevant clinically. These mutations will lead to an AAT deficit that compromises the lungs protection, originating emphysema, chronic bronchitis, asthma or even chronic obstructive pulmonary disease (COPD) and it is also strongly associated with various liver diseases. On the other hand, C282Y and H63D mutations in the HFE gene, located on chromosome 6, are reported to be mostly responsible for the iron accumulation in HH disorder, leading to severe damage in different organs. Disease manifestations include cirrhosis, hepatic fibrosis, diabetes mellitus, arthropathy and hepatocarcinoma. Given the insufficient population-based information about the prevalence of these gene variants in the Portuguese population, the aim of this study was to assess their frequency in a representative sample from São Brás de Alportel, in the South of Portugal. To achieve our goal, we have genotyped a total of 208 adult subjects, including 118 females and 90 males (mean age: 58 years, range: 26-91). Regarding AAT deficiency, we found 4,3% MZ, 0,5% SS and 15,4% MS genotypes. The calculated frequency for the Z allele was 2,2% (95% CI: 0-11,7%) and for the S allele was 8,2% (95% CI: 0-17,4%). About HH, we found 1,4% C282Y/H63D, 2,4% H63D/H63D, 5,8% C282Y/N and 23,6% H63D/N genotypes. Frequencies of C282Y and H63D alleles were 3,6% (95% CI: 0-13%) and 14,9% (95% CI: 6-23,8%), respectively. The observed allele frequencies were in Hardy-Weinberg Equilibrium and no association was found with related diseases likely due to the smaller sample available. Our findings show the highest prevalence of Z allele from SERPINA1 gene found, when compared to other populations. The remaining findings are in agreement with previously published studies. Future studies involving a larger sample size will be necessary to evaluate the penetrance of the studied gene mutations and to assess gene-environment interactions that influence disease risk, contributing to reduce the burden of these diseases which can have a great public health impact.The pilot study of the Portuguese Component of the European Health Examination Survey (EHES) project has received funding from the European Commission/DG Sanco (Agreement number: 20092301 – EHES JA – EAHC). This study has also received funding from the Portuguese Foundation for Science and Technology (FCT) (Project Reference: PTDC/SAU-ESA/101743/2008)

Genetic variation at the CY2C19 gene associated with Metabolic Syndrome susceptibility in a South Portuguese population

Metabolic syndrome (MetS) is a cluster of conditions — increased blood pressure, high blood glucose level, excess body fat around the waist and abnormal cholesterol levels — that occur together, increasing the risk of heart disease, stroke and diabetes. In Portugal, the MetS prevalence is estimated to be 27,5% with regional variations, being highest in the Alentejo (30,99%) and lowest in the Algarve (24,42%), constituting a public health problem. Although for clinical settings, a binary definition of MetS enabling a yes or no diagnosis is useful, it is clear that dichotomizing a continuous outcome variable reduces the statistical power of the MetS association studies. Therefore, the aim of the present study is to identify genetic risk factors involved in MetS etiology, using a continuous MetS score. To achieve our goal, a principal component analysis was performed to compute a score using the six normalized risk factors for MetS (waist circumference, diastolic and systolic blood pressure, glucose, triglycerides and HDL blood levels), with a higher MetS score indicating a less favorable MetS profile. After calculating this score, an association study was performed using 37 SNPs in candidate genes involved in MetS related diseases. A total of 206 subjects, including 119 women and 87 men (mean age: 56,31± 16,37 years, range: 26-91 years) were included in this analysis. We found 4 SNPs significantly associated with higher MetS scores (rs4244285 (CYP2C19), rs279871 (GABRA2), rs1647 (NPY) and rs1142345(TPMT)). P-values are 4,36x10-4, 1,3x10-2, 1,7x10-2 and 9,76x10-3 respectively. After correcting for multiple testing only rs4244285 (CYP2C19) remains significant (p=0,016). In addition, we have performed a multiple regression analysis considering the CYP2C19 genotype as the independent variable, adjusted for age. The resulting model explains 17% of the MetS score variance. After adding the remaining SNP genotypes that do not survive the multiple testing correction, the same model is able to explain 23,1% of the score. Our findings support the evidence of an association between CYP2C19 rs4244285 gene polymorphism and the MetS score, emphasizing the importance of lipid metabolism, thought cytochrome P450 enzymes, in the MetS etiology. However, further studies will be necessary to replicate these findings in different populations as well as functional studies to clarify the role of this variant in the etiology of MetS.The pilot study of the Portuguese Component of the European Health Examination Survey (EHES) project has received funding from the European Commission/DG Sanco (Agreement number: 20092301 – EHES JA – EAHC). This study has also received funding from the Portuguese Foundation for Science and Technology (FCT) (Project Reference: PTDC/SAU-ESA/101743/2008)

End-to-End Adversarial Retinal Image Synthesis.

In medical image analysis applications, the availability of the large amounts of annotated data is becoming increasingly critical. However, annotated medical data is often scarce and costly to obtain. In this paper, we address the problem of synthesizing retinal color images by applying recent techniques based on adversarial learning. In this setting, a generative model is trained to maximize a loss function provided by a second model attempting to classify its output into real or synthetic. In particular, we propose to implement an adversarial autoencoder for the task of retinal vessel network synthesis. We use the generated vessel trees as an intermediate stage for the generation of color retinal images, which is accomplished with a generative adversarial network. Both models require the optimization of almost everywhere differentiable loss functions, which allows us to train them jointly. The resulting model offers an end-to-end retinal image synthesis system capable of generating as many retinal images as the user requires, with their corresponding vessel networks, by sampling from a simple probability distribution that we impose to the associated latent space. We show that the learned latent space contains a well-defined semantic structure, implying that we can perform calculations in the space of retinal images, e.g., smoothly interpolating new data points between two retinal images. Visual and quantitative results demonstrate that the synthesized images are substantially different from those in the training set, while being also anatomically consistent and displaying a reasonable visual quality

Evaluation of MTHFR C677T gene polymorphism and homocysteine level in coronary atherosclerotic disease

OBJECTIVE: The aim of this study is to determine the prevalence of C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism and correlate it with plasma homocysteine levels in coronary artery disease (CAD). METHODS: Ninety-three patients with documented CAD from Hospital Universitário Oswaldo Cruz (Recife, PE, Brazil) and 108 healthy controls were evaluated. Homocysteine and folate levels were determined by HPLC and chemoluminescence, respectively, and lipid profile was considered. Genotyping was done by RFLP/PCR. RESULTS: The groups were homogeneous for the C677T polymorphisms. The homocysteine level in cases (11.7 µmol/L) was statistically different from that observed in controls (8.84 µmol/L, p< 0.05). It was also observed that 72% of the patients had homocysteine values above12 µmol/L while the control group presented only 32% in this range. There was no relationship between homozigosity for the C677T polymorphism and the homocysteine level (p= 0.634). We noticed statistical differences between folate levels from patients and controls (6.22 and 7.69 ng/dL, p< 0.05, respectively). However, there was no correlation between homocysteine and folate concentrations in the entire group (r= -0.202). Comparing cases and controls, the odds ratio (OR) when homocysteine is high and folate is low was OR= 11.9; CI 95%= 4.16-34.42, p< 0.01. CONCLUSION: A lack of correlation between C677T mutation and homocysteine level suggests that environmental factors and others genetic factors seem to exert more influence on homocysteine level in this population.OBJETIVO: O objetivo deste trabalho é determinar a prevalência do polimorfismo C677T do gene metilenotetraidrofolato redutase (MTHFR) e associá-la com a concentração plasmática de homocisteína plasmática na doença arterial coronariana (DAC). MÉTODOS: Foram avaliados 93 pacientes com DAC documentada, atendidos no Hospital Universitário Oswaldo Cruz (Recife, PE, Brasil), e 108 controles sem a doença. Foram determinados os perfis lipídicos de pacientes e controles. As concentrações plasmáticas de homocisteína e folato foram determinadas por HPLC e quimioluminescência, respectivamente. A genotipagem foi realizada por RFLP/PCR. RESULTADOS: Os grupos de pacientes e controles foram homogêneos quanto aos perfis genéticos do polimorfismo investigado. Nos pacientes, as concentrações plasmáticas médias de homocisteina (11,7 ± 4,4 µmol/L) e de folato (6,22 ± 3,0 ng/dL) foram estatisticamente diferentes daquelas observadas nos controles (8,84 ± 3,2 µmol/L e 7,69 ± 3,1 ng/dL, respectivamente), ao nível de significância de 0,05. Entretanto, não houve correlação entre concentração plasmática de homocisteína e folato nos pacientes (r= -0,202). Não foi observada associação entre a homozigosidade 677TT para MTHFR e a concentração plasmática de homocisteína sérica (p= 0,634). A comparação dos casos e controles que apresentaram simultaneamente alta concentração plasmática de homocisteína e baixa concentração de folato, resultou numa razão de chance superior à de cada variável analisada independentemente (RC= 11,9; IC 95%= 4,16-34,42, p< 0,01). CONCLUSÕES: A mutação C677T não parece ser um fator genético importante capaz de explicar a hiperhomocisteinemia moderada observada nos pacientes com DAC. Outros fatores, ambientais e genéticos, devem ser investigados.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Departamento de Pediatria Laboratório de Erros Inatos de MetabolismoUniversidade de Pernambuco ICB Departamento de Ciências FisiológicasUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Hospital das ClínicasUNIFESP, Depto. de Pediatria Laboratório de Erros Inatos de MetabolismoSciEL

Nonlinear coupled Alfv\'{e}n and gravitational waves

In this paper we consider nonlinear interaction between gravitational and electromagnetic waves in a strongly magnetized plasma. More specifically, we investigate the propagation of gravitational waves with the direction of propagation perpendicular to a background magnetic field, and the coupling to compressional Alfv\'{e}n waves. The gravitational waves are considered in the high frequency limit and the plasma is modelled by a multifluid description. We make a self-consistent, weakly nonlinear analysis of the Einstein-Maxwell system and derive a wave equation for the coupled gravitational and electromagnetic wave modes. A WKB-approximation is then applied and as a result we obtain the nonlinear Schr\"{o}dinger equation for the slowly varying wave amplitudes. The analysis is extended to 3D wave pulses, and we discuss the applications to radiation generated from pulsar binary mergers. It turns out that the electromagnetic radiation from a binary merger should experience a focusing effect, that in principle could be detected.Comment: 20 pages, revtex4, accepted in PR