Effect of oral sirolimus therapy on inflammatory biomarkers following coronary stenting

We studied the effect of oral sirolimus, administered to prevent and treat in-stent restenosis (ISR), on the variation of serum levels of inflammatory markers following coronary stenting with bare metal stents. The mean age of the patients was 56 ± 13 years, 65% were males and all had clinically manifested ischemia. Serum levels of high sensitivity C-reactive protein (hs-CRP) concentration were determined by chemiluminescence and serum levels of all other biomarkers by ELISA. One group of patients at high risk for ISR received a loading oral dose of 15 mg sirolimus and 5 mg daily thereafter for 28 days after stenting (SIR-G). A control group (CONT-G) was submitted to stenting without sirolimus therapy. The increase in hs-CRP concentration was highest at 24 h after stenting in both groups. A significant difference between SIR-G and CONT-G was observed at 4 weeks (-1.50 ± 5.0 vs -0.19 ± 0.4, P = 0.008) and lost significance 1 month after sirolimus discontinuation (-1.73 ± 4.3 vs -0.01 ± 0.7, P = 0.0975). A continuous fall in MMP-9 concentration was observed in SIR-G, with the greatest reduction at 4 weeks (-352.9 ± 455 vs +395.2 ± 377, P = 0.0004), while a positive variation was noted 4 weeks after sirolimus discontinuation (227 ± 708 vs 406.2 ± 472.1, P = 0.0958). SIR-G exhibited a higher increase in P-selectin after sirolimus discontinuation at week 8 (46.1 ± 67.9 vs 5.8 ± 23.7, P = 0.0025). These findings suggest that the anti-restenotic actions of systemic sirolimus include anti-proliferative effects and modulation of the inflammatory response with inhibition of adhesion molecule expression.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Hospital São Paulo and Hospital do Rim e Hipertensão Disciplinas de Cardiologia e NefrologiaUniversidade Federal do Espírito Santo Hospital Universitário Cassiano Antonio de Morais Disciplina de CardiologiaUNIFESP, Hospital São Paulo and Hospital do Rim e Hipertensão Disciplinas de Cardiologia e NefrologiaFAPESP: 03/02946-7SciEL

Free Non-vascularized Toe Phalangeal Transfers in Symbrachydactyly: Outcome Analysis

Free nonvascularized toe phalangeal transfer is an established surgical option for the reconstruction of hypoplastic digits. The purpose of the present study was to evaluate our experience with this procedure and to assess bone growth and digit function as well foot morbidity. Material and Methods We retrospectively evaluated the clinical records for all children with symbrachydactyly submitted to free nonvascularized toe phalangeal transfer between 2002 and 2017. A total of 8 patients were included. We summoned the patients to na appointment to clinically assess the range ofmotion, the stability, and the alignment of the neo-joint. We radiographically measured the final length and the expected percentage of growth of the transferred phalanx. We also evaluated the foot for comorbidities. Results The mean age at the time of the first surgery was 19 months (range: 8–42 months). A total of 20 phalanges were harvested: 16 total proximal phalanges, 2 middle phalanges, 1 subtotal proximal phalanx, and 1 accessory thumb phalanx. The distal part of one proximal phalanx was trimmed because the skin pocket was too tight. Two patients underwent a secondary procedure to release the syndactyly. One transfer required revision surgery due to distal tip necrosis and exposition of the transferred phalanx. In the present series, the overall clinical and radiographic outcomes were compatible to those reported in other studies. Discussion The main limitation of the nonvascularized toe phalanx transfer is the preexisting soft tissue envelope of the finger and the limited growth potential of the transferred bone. Conclusion Irrespective of the amount of growth achieved in the transferred phalanx, the actual transfer and growth attained should not be viewed as the end result, but rather as a means of providing a stable and functional joint.La transferência no vascularizada y libre de la falange del pie es una opción quirúrgica establecida para la reconstrucción de dedos hipoplásicos. El objetivo de este estudio fue analizar nuestra experiencia con este procedimiento y evaluar el crecimiento óseo y la función digital, así como la morbilidad del pie. Material y Métodos Analizamos retrospectivamente el proceso clínico de los niños (n ¼ 8) con simbraquidactilia que se sometieron a una transferencia no vascularizada y libre de la falange del pie entre 2002 y 2017. Hicimos una consulta para evaluar clínicamente el rango de movilidad, la estabilidad, y la alineación de la nueva articulación. Medimos la longitud final y el porcentaje de crecimiento esperado de la falange transferida. Evaluamos el pie para la comorbilidad. Resultados La edad media al momento de la cirugía fue de 19 meses (rango: 8–42 meses). Se recogieron un total de 20 falanges: 16 falanges proximales totales, 2 falanges medianas, 1 falange proximal subtotal, y 1 falange accesoria del pulgar. La parte distal de una falange proximal se sacrificó porque la envoltura de la piel estaba demasiado apretada. Dos pacientes se sometieron a un procedimiento secundario por la liberación de sindactilia. Una transferencia requirió revisión debido a la necrosis de la porción distal y la exposición de la falange transferida. En la presente serie, los resultados clínicos y radiográficos generales fueron compatibles con los descritos por otros estudios. Discusión Las principales limitaciones de la transferencia no vascularizada y libre de las falanges del pie son la envoltura preexistente de tejidos blandos y el potencial de crecimiento limitado del hueso transferido. Conclusión Independientemente del crecimiento obtenido con la transferencia de la falange, esto no debe verse como el resultado final, sino como un medio paramejorar la estabilidad y la funcionalidad de la nueva articulación.info:eu-repo/semantics/publishedVersio

The lipodistrofy in patients living with HIV / AIDS

Objective: To discuss the relationship between the presence of lipodystrophy in patients with HIV / AIDS and outline actions that optimize quality of life better. Method: This is a research type of qualitative literature. Data collection was conducted during the months of July and August 2011, through the database of the Electronic Library of Brazilian Scientific Journals (SciELO Brazil) and pubmed. We use the following keywords for search: HIV / AIDS and Lipodystrophy. Results: Based on reading the articles grouped the main changes related to lipodystrophy in three categories: 1) psychosocial changes, 2) bodily changes, and 3) metabolic disorders. Conclusion: Given the complexity of the effects caused by lipodystrophy, highlights the importance of multidisciplinary team with these clients and their families seeking comprehensive care and promote quality of life

Inteligência emocional dos professores: relevância para as práticas inclusivas

The main aim of this work is to evaluate the emotional intelligence and the inclusive practices of special education teachers, who work with handicapped children and teenagers in public elementary and secondary schools, so as to understand which variables can influence emotional intelligence of view of special education teachers. This way we can understand the importance of developing this concept in self-managing emotions in building inter and intra personal relationships, leading to these professionals having greater effectiveness within the school. In our empirical research, we apply the “EQ-map” scale, which allowed us to evaluate the Emotional Quotient of a group of special education teachers specializing in mental and motor areas as well as visual and auditory disabilities. We also conducted interviews with the aim of realizing the special education teachers’ perceptions regarding emotional intelligence. The results are in line with those found through the questionnaire. In this sense, our main results show that in our sample emotional intelligence is located mostly in vulnerability levels and need for attention, which varies inversely with Life occurrences and general health and positively with the Quality of Life and Satisfaction, Relationship Quotient and Optimal Performance. This is a descriptive epidemiological, cross-sectional and correlational study.O trabalho que desenvolvemos tem como principal objectivo avaliar a Inteligência Emocional de Professores de Educação Especial que trabalham com crianças e jovens portadoras de deficiência em Escolas públicas e privadas do Ensino Básico e Secundário e a sua relevancia para a inclusão. Nesta perspectiva, pretende-se perceber quais as variáveis que podem influenciar a Inteligência Emocional no contexto dos docentes de Educação Especial, para que deste modo possamos compreender a importância do desenvolvimento deste conceito na auto gestão das emoções e na construção de relações inter e intra pessoais, que levem a uma maior eficácia das práticas inclusivas destes profissionais. Aplicamos uma Escala, o “EQ-map”, que nos permitiu avaliar o Quociente Emocional de um grupo de professores de Educação Especial especializados, nas áreas mental-motora, visual e auditiva. Fizemos também entrevistas com o objectivo de perceber quais as percepções que os Professores de Educação Especial têm sobre a Inteligência Emocional e os resultados vão ao encontro dos encontrados pelo questionário. Neste sentido, os nossos principais resultados revelam que a Inteligência Emocional da nossa amostra se situa maioritariamente em níveis de vulnerabilidade e a necessitar de atenção e que varia negativamente com a Ocorrências de Vida e Saúde em Geral e positivamente com a Qualidade de vida, Satisfação de Vida, Quociente de Relacionamento e Desempenho Óptimo Trata-se de um estudo epidemiológico, transversal correlacional e descritivo

Proteomic atlas of organ vasculopathies triggered by Staphylococcus aureus sepsis

Sepsis is a life-threatening condition triggered by a dysregulated host response to microbial infection resulting in vascular dysfunction, organ failure and death. Here we provide a semi-quantitative atlas of the murine vascular cell-surface proteome at the organ level, and how it changes during sepsis. Using in vivo chemical labeling and high-resolution mass spectrometry, we demonstrate the presence of a vascular proteome that is perfusable and shared across multiple organs. This proteome is enriched in membrane-anchored proteins, including multiple regulators of endothelial barrier functions and innate immunity. Further, we automated our workflows and applied them to a murine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis to unravel changes during systemic inflammatory responses. We provide an organ-specific atlas of both systemic and local changes of the vascular proteome triggered by sepsis. Collectively, the data indicates that MRSA-sepsis triggers extensive proteome remodeling of the vascular cell surfaces, in a tissue-specific manner.Fil: Gómez Toledo, Alejandro. University of California; Estados UnidosFil: Golden, Gregory. University of California; Estados UnidosFil: Rosa Campos, Alexandre. Sanford-Burnham-Prebys Medical Discovery Institute; Estados UnidosFil: Cuello, Héctor Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Sorrentino, James. University of California at San Diego; Estados UnidosFil: Lewis, Nathan. University of California at San Diego; Estados UnidosFil: Varki, Nissi. University of California at San Diego; Estados UnidosFil: Nizet, Victor. University of California at San Diego; Estados UnidosFil: Smith, Jeffrey W.. Sanford-Burnham-Prebys Medical Discovery Institute; Estados UnidosFil: Esko, Jeffrey D.. University of California; Estados Unido

Cross Talk between eIF2α and eEF2 Phosphorylation Pathways Optimizes Translational Arrest in Response to Oxidative Stress

Summary(#br)The cellular stress response triggers a cascade of events leading to transcriptional reprogramming and a transient inhibition of global protein synthesis, which is thought to be mediated by phosphorylation of eukaryotic initiation factor-2α (eIF2α). Using mouse embryonic fibroblasts (MEFs) and the fission yeast S. pombe, we report that rapid translational arrest and cell survival in response to hydrogen peroxide-induced oxidative stress do not rely on eIF2α kinases and eIF2α phosphorylation. Rather H 2 O 2 induces a block in elongation through phosphorylation of eukaryotic elongation factor 2 (eEF2). Kinetic and dose-response analyses uncovered crosstalk between the eIF2α and eEF2 phosphorylation pathways, indicating that, in MEFs, eEF2 phosphorylation initiates the acute shutdown in translation, which is maintained by eIF2α phosphorylation. Our results challenge the common conception that eIF2α phosphorylation is the primary trigger of translational arrest in response to oxidative stress and point to integrated control that may facilitate the survival of cancer cells

Organogênese in vitro como método eficiente para a propagação de Dalbergia nigra

The objective of this work was to establish an efficient protocol for the in vitro organogenesis of Dalbergia nigra. For this purpose, 30-day-old seedlings were sectioned at their cotyledonary nodes and nodal segments. These materials were cultivated in a medium with different combinations of the 6-benzylaminopurine and thidiazuron cytokinins. After 60 days in a growth chamber set at 27°C and a 16-hour photoperiod, growth characteristics were analyzed. Explants from the cotyledonary nodes show a greater morphogenetic potential, regardless of the addition of cytokinins. Cotyledonary nodes in the medium supplemented with 2.22 µmol L-1 BAP show the best combination for the in vitro propagation of D. nigra.O objetivo deste trabalho foi estabelecer um protocolo eficiente para a organogênese in vitro de Dalbergia nigra. Para isso, plântulas com 30 dias de idade foram seccionadas em seus nós cotiledonares e segmentos nodais. Esses materiais foram cultivados em meio com diferentes combinações das citocininas 6-benzilaminopurina e tidiazuron. Após 60 dias em sala de crescimento mantida a 27°C e submetida a fotoperíodo de 16 horas, foram analisadas as características de crescimento. Explantes dos nós cotiledonares apresentam maior potencial morfogenético, independentemente da adição de citocininas. Nós cotiledonares em meio suplementado com 2.22 µmol L-1 de BAP são a melhor combinação para a propagação in vitro de D. nigra

Sustainable strategies based on glycine–betaine analogue ionic liquids for the recovery of monoclonal antibodies from cell culture supernatants

Monoclonal antibodies (mAbs) are of crucial interest for therapeutic purposes, particularly in vaccination and immunization, and in the treatment of life-threatening diseases. However, their downstream processing from the complex cell culture media in which they are produced still requires multiple steps, making mAbs extremely high-cost products. Therefore, the development of cost-effective, sustainable and biocompatible purification strategies for mAbs is in high demand to decrease the associated economic, environmental and health burdens. Herein, novel aqueous biphasic systems (ABS) composed of glycine–betaine analogue ionic liquids (AGB-ILs) and K2HPO4/KH2PO4 at pH 7.0, the respective three-phase partitioning (TPP) systems, and hybrid processes combined with ultrafiltration were investigated and compared in terms of performance as alternative strategies for the purification and recovery of anti-human interleukin-8 (anti-IL-8) mAbs, which are specific therapeutics in the treatment of inflammatory diseases, from Chinese Hamster Ovary (CHO) cell culture supernatants. With the studied ABS, mAbs preferentially partition to the IL-rich phase, with recovery yields up to 100% and purification factors up to 1.6. The best systems were optimized in what concerns the IL concentration, allowing to take advantage of IL-based three-phase partitioning approaches where a precipitate enriched in mAbs is obtained at the ABS interface, yielding 41.0% of IgG with a purification factor of 2.7 (purity of 60.9%). Hybrid processes combining the two previous techniques and an ultrafiltration step were finally applied, allowing the recovery of mAbs from the different fractions in an appropriate buffer solution for further biopharmaceutical formulations, while allowing the simultaneous IL removal and reuse. The best results were obtained with the hybrid process combining TPP and ultrafiltration, allowing to obtain mAbs with a purity higher than 60%. The recyclability of the IL was additionally demonstrated, revealing no losses in the purification and recovery performance of these systems for mAbs. The biological activity of anti-IL-8 mAbs is maintained after the several purification and recovery steps, indicating that the novel ABS, three-phase partitioning and hybrid processes comprising AGB-ILs are promising and sustainable strategies in mAbs downstream processing.publishe

Decreased PGC1-α levels and increased apoptotic protein signaling are associated with the maladaptive cardiac hypertrophy in hyperthyroidism

Hyperthyroidism can lead to the activation of proteins which are associated with inflammation, apoptosis, hypertrophy, and heart failure. This study aimed to explore the inflammatory and apoptotic proteins involved in the hyperthyroidism-induced cardiac hypertrophy establishment. Male Wistar rats were divided into control and hyperthyroid (12 mg/L L-thyroxine, in drinking water for 28 days) groups. The expression of inflammatory and apoptotic signaling proteins was quantified in the left ventricle by Western blot. Hyperthyroidism was confirmed by evaluation of T3 and T4 levels, as well as cardiac hypertrophy development. There was no change in the expression of HSP70, HIF1-a, TNF-a, MyD88, p-NFjB, NFjB, p-p38, and p38. Reduced expression of p53 and PGC1-a was associated with increased TLR4 and decreased IL-10 expression. Decreased Bcl-2 expression and increased Bax/Bcl-2 ratio were also observed. The results suggest that reduced PGC1-a and IL-10, and elevated TLR4 proteins expression could be involved with the diminished mitochondrial biogenesis and anti-inflammatory response, as well as cell death signaling, in the establishment of hyperthyroidism-induced maladaptive cardiac hypertrophy

RNA Editing of Microtubule-Associated Protein Tau Circular RNAs Promotes Their Translation and Tau Tangle Formation

Aggregation of the microtubule-associated protein tau characterizes tauopathies, including Alzheimer’s disease and frontotemporal lobar degeneration (FTLD-Tau). Gene expression regulation of tau is complex and incompletely understood. Here we report that the human tau gene (MAPT) generates two circular RNAs (circRNAs) through backsplicing of exon 12 to either exon 7 (12→7 circRNA) or exon 10 (12→10 circRNA). Both circRNAs lack stop codons. The 12→7 circRNA contains one start codon and is translated in a rolling circle, generating a protein consisting of multimers of the microtubule-binding repeats R1–R4. For the 12→10 circRNA, a start codon can be introduced by two FTLD-Tau mutations, generating a protein consisting of multimers of the microtubule-binding repeats R2–R4, suggesting that mutations causing FTLD may act in part through tau circRNAs. Adenosine to inosine RNA editing dramatically increases translation of circRNAs and, in the 12→10 circRNA, RNA editing generates a translational start codon by changing AUA to AUI. Circular tau proteins self-aggregate and promote aggregation of linear tau proteins. Our data indicate that adenosine to inosine RNA editing initiates translation of human circular tau RNAs, which may contribute to tauopathies