SUICÍDIO ASSISTIDO: A NORMATIZAÇÃO DO SUICÍDIO ASSISTIDO E A APLICAÇÃO DO PRINCÍPIO DA PROPORCIONALIDADE COMO ALTERNATIVA À MORTE DIGNA

O suicídio assistido é uma técnica de autoextermínio, que ocorre mediante a utilização de medicamentos letais, devidamente prescritos pelo médico ou por meio do desligamento dos aparelhos responsáveis pela manutenção da vida do indivíduo. O próprio paciente é quem aciona os mecanismos que determinam sua morte, administrando as drogas letais prescritas pelo médico ou desligando os aparelhos que o mantêm vivo. Teve-se, com o presente trabalho, por objetivo delimitar a existência do suicídio assistido, seu contexto histórico, conceituando a morte, a longevidade, o suicídio e, finalmente, o suicídio assistido e sua incidência no direito brasileiro, tendo como paradigma o direito estrangeiro. Os princípios e direitos constitucionais diretamente relacionados ao suicídio assistido também serão objeto de estudo, quais sejam, o direito à vida, à dignidade e, principalmente, à autonomia da vontade. A busca pela normatização do suicídio assistido contará com a análise da aplicação do princípio da proporcionalidade como forma de permitir ao paciente uma morte com dignidade. A pesquisa teve aporte doutrinário, análise de legislação vigente e relato dos casos reais de suicídio assistido.Palavras-chave: Suicídio assistido. Direito à vida. Direito à dignidade humana. Princípio da proporcionalidade

TESTAMENTO VITAL: A NORMATIZAÇÃO DO TESTAMENTO VITAL COMO ALTERNATIVA À MORTE DIGNA

 Nas últimas décadas a expectativa de vida das pessoas tem aumentado consideravelmente. O avanço das pesquisas de tratamentos de doenças terminais e incuráveis tem sido fator relevante ao prolongamento de vida do ser humano, gerando dilemas éticos e também jurídicos. O objetivo da pesquisa é analisar o alcance das diretivas antecipadas de vontade em face do princípio constitucional da dignidade humana, contemplando, também, questões que envolvem os princípios constitucionais preconizados no direito à saúde, à vida e à intimidade e à vida privada. Como resultado parcial da pesquisa, pode-se inferir que, mediante aplicação do ordenamento jurídico brasileiro vigente na atualidade, nenhum ser humano pode ser submetido a determinadas técnicas médicas que prolongam sua vida a qualquer custo, mesmo contra a sua vontade. Assim, o testamento vital é um importante instrumento para transparecer esse desejo. Trata-se de uma exigência decorrente da interpretação-aplicação sistemática do princípio constitucional da dignidade humana e das demais normas existente sobre a matéria. A análise da experiência estrangeira sobre o tema conduziu à conclusão de que, para que se tenha maior segurança jurídica sobre o tema, é necessário que ele seja tratado por lei e não apenas por ato administrativo do Conselho Federal de Medicina. A metodologia empregada na pesquisa utilizou fontes bibliográficas e documentais.Palavras-chave: Testamento vital. Dignidade humana. Direitos fundamentais.

Nota dei curatori. Prospettive diverse per obiettivi comuni

Proarch 4 Webinar Meeting. Tavoli Tematic

DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function

Parkinson's disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons and by accumulation of alpha-synuclein (aS) aggregates in the surviving neurons. The dopamine catabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is a highly reactive and toxic molecule that leads to aS oligomerization by covalent modifications to lysine residues. Here we show that DOPAL-induced aS oligomer formation in neurons is associated with damage of synaptic vesicles, and with alterations in the synaptic vesicles pools. To investigate the molecular mechanism that leads to synaptic impairment, we first aimed to characterize the biochemical and biophysical properties of the aS-DOPAL oligomers; heterogeneous ensembles of macromolecules able to permeabilise cholesterol-containing lipid membranes. aS-DOPAL oligomers can induce dopamine leak in an in vitro model of synaptic vesicles and in cellular models. The dopamine released, after conversion to DOPAL in the cytoplasm, could trigger a noxious cycle that further fuels the formation of aS-DOPAL oligomers, inducing neurodegeneration

Assessment of lower limbs edema in healthy workers who are exposed to long-term gravity

The aim of this study is to establish changes in leg volumes in healthy subjects (HS) after prolonged standing and prolonged lying. The study was carried out on two HS groups: the group A (20 subjects) included physicians and nurses who underwent a water plethysmography test, before and after eight hours of standing still in the operating room. The group B (20 subjects) included volunteers who were assessed before and after 10 h of supine resting. Group A: baseline leg volume was 1857.5 mL±196.9 on the right and 1850 mL±194.7 on the left limb. After eight hours of hydrostatic pressure action the two lower limbs volume was significantly increased to 1945 mL±209.6, and to 1940 mL±216.2, respectively (P<0.0001). The increased volume is significantly correlated with time (R2=0.95, P<0.0001). Group B: baseline leg volume was 1875 mL±175.1 on the right, and 1862.5 mL±166.9 on the left limb. After ten hours of resting supine the volume was 1770 mL±195.6, and to 1757.5 mL±194.2, respectively (P<0.0001). The decreased volume is significantly but inverted correlated with time (R2=−0.98, P<0.0001). This study demonstrates how the hydrostatic pressure is a main determinant for fluid accumulation in the lower extremity. To counteract the gravitational gradient becomes the mandatory prophylactic approach for healthy individuals who are exposed to an increased chronic venous disease risk

Conformational equilibria in monomeric alpha-synuclein at the single molecule level

Natively unstructured proteins defy the classical "one sequence-one structure" paradigm of protein science. Monomers of these proteins in pathological conditions can aggregate in the cell, a process that underlies socially relevant neurodegenerative diseases such as Alzheimer and Parkinson. A full comprehension of the formation and structure of the so-called misfolded intermediates from which the aggregated states ensue is still lacking. We characterized the folding and the conformational diversity of alpha-synuclein (aSyn), a natively unstructured protein involved in Parkinson disease, by mechanically stretching single molecules of this protein and recording their mechanical properties. These experiments permitted us to directly observe directly and quantify three main classes of conformations that, under in vitro physiological conditions, exist simultaneously in the aSyn sample, including disordered and "beta-like" structures. We found that this class of "beta-like" structures is directly related to aSyn aggregation. In fact, their relative abundance increases drastically in three different conditions known to promote the formation of aSyn fibrils: the presence of Cu2+, the occurrence of the pathogenic A30P mutation, and high ionic strength. We expect that a critical concentration of aSyn with a "beta-like" structure must be reached to trigger fibril formation. This critical concentration is therefore controlled by a chemical equilibrium. Novel pharmacological strategies can now be tailored to act upstream, before the aggregation process ensues, by targeting this equilibrium. To this end, Single Molecule Force Spectroscopy can be an effective tool to tailor and test new pharmacological agents.Comment: 37 pages, 9 figures (including supplementary material

Thermodynamics and NMR studies on Duck, Heron and Human HBV encapsidation signals

Hepatitis B virus (HBV) replication is initiated by binding of its reverse transcriptase (P) to the apical stem-loop (AL) and primer loop (PL) of epsilon, a highly conserved RNA element at the 5′-end of the RNA pregenome. Mutation studies on duck/heron and human in vitro systems have shown similarities but also differences between their P–epsilon interaction. Here, NMR and UV thermodynamic data on AL (and PL) from these three species are presented. The stabilities of the duck and heron ALs were found to be similar, and much lower than that of human. NMR data show that this low stability stems from an 11-nt internal bulge destabilizing the stem of heron AL. In duck, although structured at low temperature, this region also forms a weak point as its imino resonances broaden to disappearance between 30 and 35°C well below the overall AL melting temperature. Surprisingly, the duck- and heron ALs were both found to be capped by a stable well-structured UGUU tetraloop. All avian ALs are expected to adhere to this because of their conserved sequence. Duck PL is stable and structured and, in view of sequence similarities, the same is expected for heron - and human PL

Preparation of selective and segmentally labeled single-stranded DNA for NMR by self-primed PCR and asymmetrical endonuclease double digestion

We demonstrate a new, efficient and easy-to-use method for enzymatic synthesis of (stereo-)specific and segmental 13C/15N/2H isotope-labeled single-stranded DNA in amounts sufficient for NMR, based on the highly efficient self-primed PCR. To achieve this, new approaches are introduced and combined. (i) Asymmetric endonuclease double digestion of tandem-repeated PCR product. (ii) T4 DNA ligase mediated ligation of two ssDNA segments. (iii) In vitro dNTP synthesis, consisting of in vitro rNTP synthesis followed by enzymatic stereo-selective reduction of the C2′ of the rNTP, and a one-pot add-up synthesis of dTTP from dUTP. The method is demonstrated on two ssDNAs: (i) a 36-nt three-way junction, selectively 13C9/15N3/2H(1′,2″,3′,4′,5′,5″)-dC labeled and (ii) a 39-nt triple-repeat three-way junction, selectively 13C9/15N3/2H(1′,2″,3′,4′,5′,5″)-dC and 13C9/15N2/2H(1′,2″,3′,4′,5′,5″)-dT labeled in segment C20-C39. Their NMR spectra show the spectral simplification, while the stereo-selective 2H-labeling in the deoxyribose of the dC-residues, straightforwardly provided assignment of their C1′–H2′ and C2′–H2′ resonances. The labeling protocols can be extended to larger ssDNA molecules and to more than two segments