Relevância da Infecção VHC em Coagulopatias Congénitas

Introdução: A infecção pelo vírus da hepatite C (VHC) em doentes com coagulopatias congénitas (CC), como consequência da terapêutica empregue entre os anos 70 e 80 com transfusão de derivados de plasma humano, constitui um problema de saúde substancial e relevante. Objectivos: Análise e avaliação da relevância representada pela infecção VHC e suas complicações no tratamento duma população de doentes com CC. Métodos: Análise retrospectiva duma série de 161 doentes com CC tratados no Serviço de Imunohemoterapia do Centro Hospitalar de Lisboa Central (Lisboa, Portugal). Revisão sistemática de processos clínicos. Elaboração duma base de dados compreendendo a informação reunida e estudo estatístico das suas variáveis: idade, género, tipo e gravidade da coagulopatia e modalidade de tratamento. Relativamente à infecção por VHC: genotipo, tipo e duração do tratamento, frequência de resposta mantida ao tratamento e recidiva, co-infecções e complicações major e minor. Resultados: Dos 161 doentes 65 (40%) estão infectados pelo VHC. Dos doentes com hemofilia A: 36% são grave e 62% dos quais estão infectados pelo VHC; 9% moderada com 57%; 25% ligeira com 20%. No grupo da hemofilia B: 8% são grave com 23% infectados e 6% moderada ou ligeira com 10%. Relativamente ao grupo com doença de von Willebrand: 12% são tipo 2 com 16% infectados e 4% tipo 3 com 86%. Uma coorte de 26 doentes foi submetida a terapêutica para a infecção pelo VHC, com o primeiro doente a receber tratamento em 1993. Destes, 5 eram seropositivos para o VIH. O tratamento variou de monoterapia com interferão a terapêutica combinada de interferão ou interferão-peguilado com ribavirina. Conclusões: A infecção pelo VHC representa uma complicação significativa do tratamento empregue no passado na população em estudo. Considerando que a maioria destes doentes foi infectada nos finais dos anos 70 e início dos anos 80 assim como a evolução natural da infecção pelo VHC em doentes sem CC, prevê-se que a prevalência de complicações major deverá aumentar significativamente nos próximos anos. É de suma importância a implementação de medidas profilácticas na revisão e adaptação dos protocolos de seguimento de forma a prevenir a progressão da patologia hepática nestes doentes

Critical evaluation of proteomic protocols for passion fruit (Passiflora edulis Sims) leaves, a crop with juice market benefits

Passion fruit grows practically all over Brazilian territory; its production is largely destined to juice industry and expanding to overseas markets. The suitability of four protein extraction protocols for plant proteome was  investigated to determine the best choice for studies concerning passion fruit leaf proteins. Trichloroacetic acid (TCA)/acetone extraction; isoelectric  focusing (IEF) buffer extraction; phenol (Phe) extraction and Phe-SDS extraction were tested. The Phe method produced the best results, showing higher reproducibility of resolved protein spots and clearer 2D gel  background staining. In comparison, the Phe-SDS method presented fewer spots and lower reproducibility. The TCA/acetone method produced the fewest identifiable spots and the IEF buffer produced the poorest results,displaying fewer reproducibly detected spots, more vertical streaks and darker 2D staining. Selected spots, obtained with Phe method, were identified by spectrometric analysis (MALDI-TOF-TOF) to exemplify the viability to perform more comprehensive proteomic studies with passion fruit leaves and, therefore increase information about stress-related and developmental responses in this fruit crop.Key words: Passion fruit, proteomic, protein extraction, juice industry

Endoscopic study of the intranasal ostium in external dacryocystorhinostomy postoperative. Influence of saline solution and 5-fluorouracil

PURPOSE: To study, through endoscopy, the postoperative structural changes of the intranasal ostium following external dacryocystorhinostomy and to evaluate the influence of saline solution and 5-fluorouracil. METHODS: Fifty patients were distributed into the following groups: Group SS-dacryocystorhinostomy and an injection of saline solution during surgery (13 patients); Group 5-FUI-dacryocystorhinostomy and an injection of 5 fluorouracil during surgery (17 patients); Group C-dacryocystorhinostomy only (11 patients); Group 5-FU3-dacryocystorhinostomy and 3 injections, 1 during surgery and 1 on the third and fifth postsurgical days (9 patients). RESULTS: Pair-wise group comparisons using the nonparametric Mann-Whitney test revealed that there was a significant reduction of the ostium area only in Group 5-FU1 vs. Group SS on the 60(th) postoperative day (P < .01); however, a comparative study among the 4 groups using the Kruskal-Wallis test showed no significant changes in the ostium area on the 60(th) postoperative day. The ostium area within groups at the 30(th) vs 60(th) postoperative day was significantly reduced for Group C (P < .05; Mann-Whitney test); no significant changes were found for the other groups. DISCUSSION: These results suggest that the use of 5-fluorouracil in external dacryocystorhinostomy does not significantly influence the final size of the surgical fistula as determined 2 months postsurgery.621414

Election turnout statistics in many countries: similarities, differences, and a diffusive field model for decision-making

We study in details the turnout rate statistics for 77 elections in 11 different countries. We show that the empirical results established in a previous paper for French elections appear to hold much more generally. We find in particular that the spatial correlation of turnout rates decay logarithmically with distance in all cases. This result is quantitatively reproduced by a decision model that assumes that each voter makes his mind as a result of three influence terms: one totally idiosyncratic component, one city-specific term with short-ranged fluctuations in space, and one long-ranged correlated field which propagates diffusively in space. A detailed analysis reveals several interesting features: for example, different countries have different degrees of local heterogeneities and seem to be characterized by a different propensity for individuals to conform to the cultural norm. We furthermore find clear signs of herding (i.e. strongly correlated decisions at the individual level) in some countries, but not in others.Comment: 15 pages, 9 figures, 7 table

Vasorelaxant Activity of AP39, a Mitochondria-Targeted H2S Donor, on Mouse Mesenteric Artery Rings In Vitro

This is the final version. Available from MDPI via the DOI in this record. The data presented in this study are available on request from the corresponding author.Mitochondria-targeted hydrogen sulfide (H2S) donor compounds, such as compound AP39, supply H2S into the mitochondrial environment and have shown several beneficial in vitro and in vivo effects in cardiovascular conditions such as diabetes and hypertension. However, the study of their direct vascular effects has not been addressed to date. Thus, the objective of the present study was to analyze the effects and describe the mechanisms of action of AP39 on the in vitro vascular reactivity of mouse mesenteric artery. Protein and gene expressions of the H2S-producing enzymes (CBS, CSE, and 3MPST) were respectively analyzed by Western blot and qualitative RT-PCR, as well the in vitro production of H2S by mesenteric artery homogenates. Gene expression of CSE and 3MPST in the vessels has been evidenced by RT-PCR experiments, whereas the protein expression of all the three enzymes was demonstrated by Western blotting experiments. Nonselective inhibition of H2S-producing enzymes by AOAA abolished H2S production, whereas it was partially inhibited by PAG (a CSE selective inhibitor). Vasorelaxation promoted by AP39 and its H2S-releasing moiety (ADT-OH) were significantly reduced after endothelium removal, specifically dependent on NO-cGMP signaling and SKCa channel opening. Endogenous H2S seems to participate in the mechanism of action of AP39, and glibenclamide-induced KATP blockade did not affect the vasorelaxant response. Considering the results of the present study and the previously demonstrated antioxidant and bioenergetic effects of AP39, we conclude that mitochondria-targeted H2S donors may offer a new promising perspective in cardiovascular disease therapeutics.The Royal SocietySao Paulo Research Foundation (FAPESP)Sao Paulo Research Foundation (FAPESP)Brazilian National Council for Scientific and Technological Development (CNPq)Brazilian National Council for Scientific and Technological Development (CNPq)Coordination for the Improvement of Higher Education Personnel (CAPES

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice.

Published onlineJournal ArticleThis is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The recently described 'gasomediator' hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slow-releasing (GYY4137) and spontaneous H2S donors (Na2S and Lawesson's reagent, LR) were evaluated in histamine and compound 48/80 (C48/80)-dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.) injected with C48/80 (3μg/site) or histamine (1μmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3-100nmol range). The involvement of endogenous H2S and KATP channel-dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected (125)I-albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80-induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis exacerbated C48/80-induced responses, whereas the blockade of KATP channels by glibenclamide did not. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) revealed that Na2S and LR, but not GYY4137, significantly attenuated C48/80-induced histamine release from rat peritoneal mast cell in vitro. We provide first evidences that H2S exerted protective effect against acute pruritus mediated via histaminergic pathways in murine skin, thus making of H2S donors a potential alternative/complementary therapy for treatment of acute pruritus.Sao Paulo Research Foundation (Fapesp grant numbers: 2013/04.151-3, 2014/15.576-8, 2014/24.518-1) and CNPq (grant number: 163278/2012-1). GDN, MNM and SKPC are recipients of fellowships from the National Council for Scientific and Technological Development (CNPq). We thank Irene M Gouvea, Flávia B de Lira and Mauro Sucupira for their techinical support

The Ecm11-Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast

During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation