Acute exercise in treated phenylketonuria patients:Physical activity and biochemical response

Background: In phenylketonuria, dietary treatment prevents most of the severe brain disease. However, patients have to follow a diet restricted in several natural components, what may cause decreased bone density and obesity. Exercise is known to improve both mental functioning and bone density also avoiding obesity, and could optimize aspects of central and peripheral outcome, regardless changes in phenylalanine (Phe) levels. However, the acute effects of exercise on metabolic parameters in phenylketonuria patients are unknown and thereby long-term adaptations are unclear. Therefore, this study aimed to evaluate patients' basal metabolic rate (BMR), and their acute response to an aerobic exercise session on plasma concentrations of Phe, tyrosine (Tyr), and branched-chain amino acids (BCAA), as well as metabolic and hormonal responses. Methods: Five early- and four late diagnosed phenylketonuria patients aged 21 ± 4 years and 17 sex-, age-, and BMI-matched controls were evaluated for BMR, peak oxygen consumption (VO2peak) and plasma amino acid, glucose, lipid profile and hormonal levels. At least one week later, participants performed a 30-min aerobic exercise session (intensities individually calculated using the VO2peak results). Blood samples were collected in fasted state (moment 1, M1) and immediately after a small breakfast, which included the metabolic formula for patients but not for controls, and the exercise session (moment 2, M2). Results: Phenylketonuria patients and controls showed similar BMR and physical capacities. At M1, patients presented higher Phe concentration and Phe/Tyr ratio; and lower levels of BCAA and total cholesterol than controls. Besides that, poorly controlled patients tended to stay slightly below the prescribed VO2 during exercise. Both patients and controls showed increased levels of total cholesterol and LDL at M2 compared with M1. Only controls showed increased levels of Tyr, lactate, and HDL; and decreased Phe/Tyr ratio and glucose levels at M2 compared to values at M1. Conclusions: Acute aerobic exercise followed by a Phe-restricted breakfast did not change Phe concentrations in treated phenylketonuria patients, but it was associated with decreased Phe/Tyr only in controls. Further studies are necessary to confirm our results in a higher number of patients

A CORE DESIGN APPROACH AIMED AT THE SUSTAINABILITY AND INTRINSIC SAFETY OF THE EUROPEAN LEAD-COOLED FAST REACTOR

Among the Generation-IV fast reactor technologies, a Lead-cooled Fast Reactor concept is currently under development in Europe as a potential candidate for the deployment, to meet long-term objectives of European energy policies. Within the Lead-cooled European Advanced DEmonstration Reactor (LEADER) project, co-financed by the European Union within the 7th EURATOM Framework Programme, the conceptual design of the reference Generation-IV European LFR (ELFR) industrial plant was developed, benefiting from and further optimizing the concept put forward during the ELSY 6th EURATOM Framework Programme project. In order to embed in the design the safety and sustainability goals in the most effective way, an innovative, dedicated design approach was developed and applied to the design of the ELFR fuel pins, fuel assemblies and core. This new approach, together with the main analysis results supporting the design of the reference ELFR configuration, are presented and discussed in detail.JRC.F.5-Nuclear Reactor Safety Assessmen

Journal of Inherited Metabolic Disease

Trabalho completo: acesso retrito, p. 732–738The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16–57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for noncarriers; there was, however, an overlap between carriers 'and non-carriers' values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations

Journal of Medical Ethics

Texto completo: acesso restrito. p. 233-239Background/Aims Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disorder treated with bone marrow transplantation or enzyme replacement therapy with laronidase, a high-cost orphan drug. Laronidase was approved by the US Food and Drug Administration and the European Medicines Agency in 2003 and by the Brazilian National Health Surveillance Agency in 2005. Many Brazilian MPS I patients have been receiving laronidase despite the absence of a governmental policy regulating access to the drug. Epidemiological and treatment data concerning MPS I are scarce. This study aims to present a demographic profile of Brazilian patients with MPS I, describe the routes of access to laronidase in Brazil, and discuss associated ethical issues relating to public funding of orphan drugs. Methods In this cross-sectional observational study, data were collected nationwide between January and September 2008 from physicians, public institutions and non-governmental organisations involved with diagnosis and treatment of MPS I, using two data collection instruments specifically designed for this purpose. Results The minimum prevalence of MPS I in Brazil was estimated at 1/2 700 000. Most patients (69.8%) were younger than 15 years; 60 (88.2%) received laronidase. The most common route of access to the drug was through lawsuits (86.6%). Conclusions In Brazil, MPS I is predominantly a paediatric illness. Even though the cost of laronidase treatment is not officially covered by the Brazilian government, most MPS I patients receive the drug, usually through litigation. This gives rise to major ethical conflicts concerning drug access in a low-resource context. The Brazilian health policy framework lacks evidence-based clinical protocols for the distribution of orphan drugs

Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing.

Submitted by Nuzia Santos ([email protected]) on 2017-04-12T19:01:34Z No. of bitstreams: 1 ve_Oliveira_Felipe_Phenylketonuria_CPqRR_2016.pdf: 5478745 bytes, checksum: 1d0d9580be46c56f2b8a9c16a83097e5 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2017-04-12T19:10:17Z (GMT) No. of bitstreams: 1 ve_Oliveira_Felipe_Phenylketonuria_CPqRR_2016.pdf: 5478745 bytes, checksum: 1d0d9580be46c56f2b8a9c16a83097e5 (MD5)Made available in DSpace on 2017-04-12T19:10:17Z (GMT). No. of bitstreams: 1 ve_Oliveira_Felipe_Phenylketonuria_CPqRR_2016.pdf: 5478745 bytes, checksum: 1d0d9580be46c56f2b8a9c16a83097e5 (MD5) Previous issue date: 2016Universidade Federal do Rio Grande do Sul. Programa de Pós-Graduação em Genética e Biologia Molecular. Porto Alegre, RS, Brazil/Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório Basic Research and Advanced Investigations in Neurosciences. Porto Alegre, RS, BrazilUniversidade Federal do Rio Grande do Sul. Programa de Pós-Graduação em Genética e Biologia Molecular. Porto Alegre, RS, Brazil/Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório Basic Research and Advanced Investigations in Neurosciences. Porto Alegre, RS, BrazilUniversidade Federal do Pampa. Centro Interdisciplinar de Pesquisas em Biotecnologia–CIP-Biotec. São Gabriel, RS, BrazilUniversity of Florida. Emerging Pathogens Institute. College of Public Health and Health Professions and College of Medicine. Department of Epidemiology. Gainesville, FL, United States of AmericaOswaldo Cruz Fundation. René Rachou Research Centre. Genomics and Computational Biology Group. Belo Horizonte, MG, BrazilUniversity of Florida. Emerging Pathogens Institute. College of Public Health and Health Professions and College of Medicine. Department of Epidemiology. Gainesville, FL, United States of AmericaHospital de Clínicas de Porto Alegre. Serviço de Genética Médica. Porto Alegre, RS, BrazilHospital de Clínicas de Porto Alegre. Serviço de Genética Médica. Porto Alegre, RS, BrazilUniversidade Federal do Pampa. Centro Interdisciplinar de Pesquisas em Biotecnologia–CIP-Biotec. São Gabriel, RS, BrazilUniversidade Federal do Rio Grande do Sul. Programa de Pós-Graduação em Genética e Biologia Molecular. Porto Alegre, RS, Brazil/Hospital de Clínicas de Porto Alegre. Centro de Pesquisa Experimental. Laboratório de Pesquisas Básicas e Aplicadas em Neurociencias. Porto Alegre, RS, BrazilPhenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear

Behavioural Responses of Western Flower Thrips, Frankliniella occidentalis (Pergande), to Volatiles from Three Aromatic Plants

The behavioural responses of adult female western flower thrips, Frankliniella occidentalis (Pergande) to volatiles from meadow-sweet (Filipendula ulmaria), bay laurel (Laurus nobilis) and sage (Salvia officinalis) were investigated in laboratory bioassays. Volatiles collected by entrainment of a solvent extract of F. ulmaria were more attractive than was the original extract. Frankliniella occidentalis was also significantly attracted to volatiles from L. nobilis and S. officinalis. Analysis by gas chromatography and mass spectrometry identified 1,8-cineole (eucalyptol) as one of the main volatile components of all three plant species. In coupled gas chromatography-electroantennography studies with F. ulmaria, both 1,8-cineole and methyl salicylate elicited responses from F. occidentalis. Eucarvone was identified as the major component of F. ulmaria volatiles, but showed no electrophysiological activity. Behavioural responses of thrips to a range of concentrations of 1,8-cineole and methyl salicylate were tested using a modified Pettersson 'star' olfactometer. 1,8-cineole showed some attractant activity for the thrips at 0.01 mg, but methyl salicylate was repellent at all the concentrations tested. RÉSUMÉ La réponse comportementale de femelles adultes de thrips (Frankliniella occidentalis) aux émissions volatiles de trois plantes aromatiques, la filipendule (Filipendula ulmaria), le laurier-sauce (Laurus nobilis) et la sauge (Salvia officinalis), a été étudiée dans des essais au laboratoire. Les produits volatils obtenus par collecte d'effluves d'un extrait par solvant de F. ulmaria se sont montrés plus attractifs que l'extrait original. Frankliniella occidentalis a aussi été attiré significativement par les émissions volatiles de L. nobilis et S. officinalis. Des analyses par chromatographie en phase gazeuse et spectrométrie de masse ont permis d'identifier le 1,8-cineole (eucalyptol) comme l'un des composés volatils majeurs des trois espèces végétales. Dans des études par couplage chromatographie en phase gazeuse-électroantennographie, avec un extrait de F. ulmaria, le 1,8-cineole et le methyl salicylate ont tous deux induit des réponses chez F. occidentalis. L'eucarvone a été identifié comme le composé majoritaire des émissions volatiles de F. ulmaria, mais n'a induit aucune activité électrophysiologique. Les réponses comportementales des thrips à une gamme de concentrations de 1,8-cineole et de methyl salicylate ont été évaluées dans un olfactomètre de Pettersson modifé. Le 1,8-cineole a induit une certaine attraction chez les thrips à la concentration de 0,01 mg, mais le methyl salicylate a été répulsif à toutes les concentrations testées