RESUMO
Since human angiotensin-converting enzyme 2 (ACE2) serves as a primary receptor for SARS-CoV-2, characterizing ACE2 regions that allow SARS-CoV-2 to enter human cells is essential for designing peptide-based antiviral blockers and elucidating the pathogenesis of the virus. We identified and synthesized a 25-mer mimetic peptide (encompassing positions 22-46 of the ACE2 alpha-helix α1) implicated in the S1 receptor-binding domain (RBD)-ACE2 interface. The mimetic (wild-type, WT) ACE2 peptide significantly inhibited SARS-CoV-2 infection of human pulmonary Calu-3 cells in vitro. In silico protein modeling predicted that residues F28, K31, F32, F40, and Y41 of the ACE2 alpha-helix α1 are critical for the original, Delta, and Omicron strains of SARS-CoV-2 to establish the Spike RBD-ACE2 interface. Substituting these residues with alanine (A) or aspartic acid (D) abrogated the antiviral protective effect of the peptides, indicating that these positions are critical for viral entry into pulmonary cells. WT ACE2 peptide, but not the A or D mutated peptides, exhibited significant interaction with the SARS-CoV-2 S1 RBD, as shown through molecular dynamics simulations. Through identifying the critical amino acid residues of the ACE2 alpha-helix α1, which is necessary for the Spike RBD-ACE2 interface and mobilized during the in vitro viral infection of cells, we demonstrated that the WT ACE2 peptide protects susceptible K18-hACE2 mice against in vivo SARS-CoV-2 infection and is effective for the treatment of COVID-19.
Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Peptídeos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Humanos , Animais , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Camundongos , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/uso terapêutico , Tratamento Farmacológico da COVID-19 , Antivirais/farmacologia , Antivirais/química , Linhagem Celular , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Pneumonia/prevenção & controle , Pulmão/virologia , Pulmão/patologia , FemininoRESUMO
BACKGROUND: The autoimmune regulator (Aire) gene is critical for the appropriate establishment of central immune tolerance. As one of the main controllers of promiscuous gene expression in the thymus, Aire promotes the expression of thousands of downstream tissue-restricted antigen (TRA) genes, cell adhesion genes and transcription factor genes in medullary thymic epithelial cells (mTECs). Despite the increasing knowledge about the role of Aire as an upstream transcriptional controller, little is known about the mechanisms by which this gene could be regulated. RESULTS: Here, we assessed the posttranscriptional control of Aire by miRNAs. The in silico miRNA-mRNA interaction analysis predicted thermodynamically stable hybridization between the 3'UTR of Aire mRNA and miR-155, which was confirmed to occur within the cellular milieu through a luciferase reporter assay. This finding enabled us to hypothesize that miR-155 might play a role as an intracellular posttranscriptional regulator of Aire mRNA. To test this hypothesis, we transfected a murine mTEC cell line with a miR-155 mimic in vitro, which reduced the mRNA and protein levels of Aire. Moreover, large-scale transcriptome analysis showed the modulation of 311 downstream mRNAs, which included 58 TRA mRNAs. Moreover, miR-155 mimic-transfected cells exhibited a decrease in their chemotaxis property compared with control thymocytes. CONCLUSION: Overall, the results indicate that miR-155 may posttranscriptionally control Aire mRNA, reducing the respective Aire protein levels; consequently, the levels of mRNAs encode tissue-restricted antigens were affected. In addition, miR-155 regulated a crucial process by which mTECs allow thymocytes' migration through chemotaxis.
Assuntos
MicroRNAs , Fatores de Transcrição , Animais , Células Epiteliais/metabolismo , Camundongos , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Proteína AIRERESUMO
The autoimmune regulator (Aire) gene in medullary thymic epithelial cells (mTECs) encodes the AIRE protein, which interacts with its partners within the nucleus. This "Aire complex" induces stalled RNA Pol II on chromatin to proceed with transcription elongation of a large set of messenger RNAs and microRNAs. Considering that RNA Pol II also transcribes long noncoding RNAs (lncRNAs), we hypothesized that Aire might be implicated in the upstream control of this RNA species. To test this, we employed a loss-of-function approach in which Aire knockout mTECs were compared to Aire wild-type mTECs for lncRNA transcriptional profiling both in vitro and in vivo model systems. RNA sequencing enables the differential expression profiling of lncRNAs when these cells adhere in vitro to thymocytes or do not adhere to them as a way to test the effect of cell adhesion. Sets of lncRNAs that are unique and that are shared in vitro and in vivo were identified. Among these, we found the Aire-dependent lncRNAs as for example, Platr28, Ifi30, Morrbid, Malat1, and Xist. This finding represents the first evidence that Aire mediates the transcription of lncRNAs in mTECs. Microarray hybridizations enabled us to observe that temporal thymocyte adhesion modulates the expression levels of such lncRNAs as Morrbid, Xist, and Fbxl12o after 36 h of adhesion. This finding shows the existence of a synergistic mechanism involving a link between thymocyte adhesion, Aire, and lncRNAs in mTECs that might be important for immune self-representation.
Assuntos
Células Epiteliais/metabolismo , RNA Longo não Codificante/metabolismo , Timócitos/citologia , Timo/citologia , Fatores de Transcrição/metabolismo , Animais , Adesão Celular , Linhagem Celular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , Fases de Leitura Aberta/genética , RNA Longo não Codificante/genética , Fatores de Tempo , Transcrição Gênica , Proteína AIRERESUMO
In 2017, the Brazilian Society of Anesthesiology (SBA) and the National Medical Residency Committee (CNRM) presented a joint competence matrix to train and evaluate physicians specializing in Anesthesiology, which was enforced in 2019. The competency-based curriculum aims to train residents in relation to certain results, in that residents are considered capable when they are able to act in an appropriate and effective manner within certain standards of performance. Canada and the United States (US) also use competency-based curriculum to train their professionals. In Canada, the format is the basis for using an evaluation method known as Entrustable Professional Activities (EPA), in which the mentor assesses residents' capacity to perform certain tasks, classified in 5 levels. The US, in turn, uses Milestones as evaluation, in which competencies and sub-competencies are assessed according to residents' progress during training. The present article aims to describe and compare the different competency-based curriculum and the evaluation methods used in the three countries, and proposes a reflection on future paths for medical education in Anesthesiology in Brazil.
Assuntos
Anestesiologia , Internato e Residência , Anestesiologia/educação , Brasil , Canadá , Competência Clínica , Educação Baseada em Competências , Humanos , Estados UnidosRESUMO
In this work, we demonstrate that adhesion between medullary thymic epithelial cells (mTECs) and thymocytes is controlled by miRNAs. Adhesion between mTECs and developing thymocytes is essential for triggering negative selection (NS) of autoreactive thymocytes that occurs in the thymus. Immune recognition is mediated by the MHC / TCR receptor, whereas adhesion molecules hold cell-cell interaction stability. Indeed, these processes must be finely controlled, if it is not, it may lead to aggressive autoimmunity. Conversely, the precise molecular genetic control of mTEC-thymocyte adhesion is largely unclear. Here, we asked whether miRNAs would be controlling this process through the posttranscriptional regulation of mRNAs that encode adhesion molecules. For this, we used small interfering RNA to knockdown (KD) Dicer mRNA in vitro in a murine mTEC line. A functional assay with fresh murine thymocytes co-cultured with mTECs showed that single-positive (SP) CD4 and CD8 thymocyte adhesion was increased after Dicer KD and most adherent subtype was CD8 SP cells. Analysis of broad mTEC transcriptional expression showed that Dicer KD led to the modulation of 114 miRNAs and 422 mRNAs, including those encoding cell adhesion or extracellular matrix proteins, such as Lgals9, Lgals3pb, Tnc and Cd47. Analysis of miRNA-mRNA networks followed by miRNA mimic transfection showed that these mRNAs are under the control of miR-181b-5p and miR-30b*, which may ultimately control mTEC-thymocyte adhesion. The expression of CD80 surface marker in mTECs was increased after Dicer KD following thymocyte adhesion. This indicates the existence of new mechanisms in mTECs that involve the synergistic action of thymocyte adhesion and regulatory miRNAs.
Assuntos
Adesão Celular/imunologia , Células Epiteliais/imunologia , MicroRNAs/imunologia , Timócitos/imunologia , Timo/imunologia , Animais , Antígeno B7-1/imunologia , Biomarcadores/sangue , Diferenciação Celular/imunologia , Feminino , Regulação da Expressão Gênica/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Antígenos de Linfócitos T/imunologia , Tolerância a Antígenos Próprios/imunologia , Fatores de Transcrição/imunologiaRESUMO
PURPOSE:: To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage. METHODS:: Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed. RESULTS:: Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups. CONCLUSION:: The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.
Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Volume Sanguíneo/efeitos dos fármacos , Dobutamina/administração & dosagem , Hemorragia/fisiopatologia , Norepinefrina/administração & dosagem , Cloreto de Sódio/administração & dosagem , Vasoconstritores/administração & dosagem , Animais , Combinação de Medicamentos , Hematócrito , Infusões Intravenosas , Rim/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Coelhos , Distribuição Aleatória , Fatores de TempoRESUMO
ABSTRACT PURPOSE: To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage. METHODS: Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed. RESULTS: Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups. CONCLUSION: The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.
Assuntos
Animais , Coelhos , Volume Sanguíneo/efeitos dos fármacos , Cloreto de Sódio/administração & dosagem , Norepinefrina/administração & dosagem , Agonistas Adrenérgicos beta/administração & dosagem , Dobutamina/administração & dosagem , Hemorragia/fisiopatologia , Fatores de Tempo , Infusões Intravenosas , Distribuição Aleatória , Combinação de Medicamentos , Hematócrito , Rim/efeitos dos fármacos , Pulmão/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage. METHODS: Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed. RESULTS: Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups. CONCLUSION: The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.(AU)
Assuntos
Animais , Coelhos , Norepinefrina/análise , Dobutamina/análise , Volume Plasmático/veterinária , Catecolaminas , Hemorragia/prevenção & controle , Hemorragia/veterinária , Hipovolemia/prevenção & controleAssuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estenose das Carótidas/cirurgia , Transtornos Cognitivos/etiologia , Endarterectomia das Carótidas/efeitos adversos , Artéria Cerebral Posterior/anatomia & histologia , Artéria Carótida Interna/patologia , Artéria Carótida Interna/cirurgiaRESUMO
JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi comparar as pontuações da equipe de internos pelas avaliações da "qualidade geral do ensino" durante um rodízio em anestesia para ortopedia nos primeiros seis meses (11 residentes receberam o currículo impresso em uma pasta) e nos últimos seis meses (9 residentes receberam o mesmo currículo em um computador tablet [iPad®, Apple Inc., Cupertino, Ca]). MÉTODOS: No início do rodízio de duas semanas, o residente recebeu um iPad contendo: um programa de estudo com exercícios diários de leitura; os objetivos do rodízio em relação às competências essenciais do Accreditation Council for Graduate Medical Education (ACGME); e artigos de periódicos. Antes do estudo, esses materiais curriculares foram distribuídos em um fichário impresso. O iPad também forneceu sites revisados por pares e acesso online direto a livros referentes à matéria, mas não estava conectado ao prontuário eletrônico. No final do rodízio, os residentes responderam às perguntas de forma anônima para avaliar o mesmo em uma escala ordinal de 1 (insuficiente) a 5 (excelente). Os residentes não sabiam que os dados seriam analisados retrospectivamente para este estudo. RESULTADOS: A pontuação média global do rodízio, avaliada pela "qualidade geral do ensino desse rodízio" aumentou de 4,09 (N = 11 avaliações antes da intervenção, DP 0,83, mediana de 4, variação de 3-5) para 4,89 (N = 9 avaliações após a intervenção, DP 0,33, mediana 5, variação de 4-5) p = 0,04. CONCLUSÕES: Os residentes responderam favoravelmente à introdução de um currículo inovador via iPad para o rodízio em anestesia ortopédica. São necessários mais estudos para mostrar como tais tecnologias de computação móvel podem melhorar a aprendizagem, especialmente porque os residentes trabalham em vários locais, têm limites de horas de trabalho e precisam documentar o aprendizado da residência em seis competências essenciais do ACGME.
BACKGROUND AND OBJECTIVES: The goal of this study was to compare scores on house staff evaluations of "overall teaching quality" during a rotation in anesthesia for orthopedics in the first six months (n = 11 residents were provided with curriculum in a printed binder) and in the final six months (n = 9 residents were provided with the same curriculum in a tablet computer (iPad, Apple®, Inc, Cupertino, Ca)). METHODS: At the beginning of the two-week rotation, the resident was given an iPad containing: a syllabus with daily reading assignments, rotation objectives according to the ACGME core competencies, and journal articles. Prior to the study, these curriculum materials had been distributed in a printed binder. The iPad also provided peer reviewed internet sites and direct access to online textbooks, but was not linked to the electronic medical record. At the end of the rotation, residents anonymously answered questions to evaluate the rotation on an ordinal scale from 1 (unsatisfactory) to 5 (outstanding). All residents were unaware that the data would be analyzed retrospectively for this study. RESULTS: The mean global rating of the rotation as assessed by "overall teaching quality of this rotation" increased from 4.09 (N = 11 evaluations before intervention, SD 0.83, median 4, range 3-5) to 4.89 (N = 9 evaluations after intervention, SD 0.33, median 5, range 4-5) p = 0.04. CONCLUSIONS: Residents responded favorably to the introduction of an innovative iPad based curriculum for the orthopedic anesthesia rotation. More studies are needed to show how such mobile computing technologies can enhance learning, especially since residents work at multiple locations, have duty hour limits, and the need to document resident learning in six ACGME core competencies.
JUSTIFICATIVA Y OBJETIVOS: El objetivo de este estudio, fue comparar las puntuaciones del equipo de internos de las evaluaciones de la "calidad general de la enseñanza", durante una rotación en Anestesia para ortopedia, seis meses antes de la introducción del currículo vía iPad, cuando 11 residentes recibieron el currículo en una carpeta impresa; y seis meses después de la introducción de ese currículo, cuando nueve residentes recibieron el mismo currículo en un computador tablet [iPad®, Apple Inc., Cupertino, Ca]. MÉTODOS: Al comienzo de la rotación de dos semanas, el residente recibió un iPad que contenía: un programa de estudio con ejercicios diarios de lectura; los objetivos de la rotación con relación a las competencias esenciales del Accreditation Council for Graduate Medical Education (ACGME); y artículos de periódicos. Antes del estudio, esos materiales curriculares se distribuyeron en un archivo impreso. El iPad también suministró Paginas Web revisadas por pares en la Internet y el acceso directo a libros online referentes a la materia, pero no estaba conectado a la historia clínica electrónica. Al final de la rotación, los residentes respondieron a las preguntas de forma anónima para evaluar la rotación en una escala ordinal desde 1 (insuficiente), hasta 5 (excelente). Los residentes no sabían que los datos serían analizados retrospectivamente para este estudio. RESULTADOS: La puntuación promedio global de la rotación, evaluada por la "calidad general de la enseñanza de esa rotación" aumentó de 4,09 (N = 11 evaluaciones antes de la intervención, DE 0,83, mediana de 4, variación de 3-5) para 4,89 (N = 9 evaluaciones después de la intervención, DE 0,33, mediana 5, variación 4-5) p = 0,04. CONCLUSIONES: Los residentes respondieron favorablemente a la introducción de un currículo innovador vía iPad para la rotación en Anestesia ortopédica. Pero son necesarios más estudios para mostrar cómo esas tecnologías de computación móvil pueden mejorar el aprendizaje, especialmente porque los residentes trabajan en varios locales, tienen límites de horas de trabajo y necesitan documentar el aprendizaje de la residencia en seis competencias esenciales del ACGME.
Assuntos
Recursos Audiovisuais , Anestesiologia/educação , Computadores de Mão , Educação de Pós-Graduação em Medicina/métodos , Ortopedia/educação , Estudos RetrospectivosRESUMO
JUSTIFICATIVA E OBJETIVOS: A duração do efeito dos anestésicos locais (AL) pode ser ampliada pela sua incorporação aos sistemas de liberação prolongada como microesferas. No entanto, a possibilidade de que os sistemas de liberação prolongada de AL sejam neurotóxicos não tem recebido a devida atenção na literatura. Este estudo teve o objetivo de investigar os efeitos de microesferas de ácido poliláctico-co-glicólico puras, preenchidas com bupivacaína em excesso enantiomérico de 50 por cento ou com bupivacaína (BP), assim como os efeitos da bupivacaína em excesso enantiomérico de 50 por cento em nervo ciático de ratos Wistar. MÉTODO: Os ratos foram alocados em quatro grupos de acordo com o tempo de avaliação (dois, quatro, seis e oito dias) e denominados conforme a solução injetada sobre o nervo ciático: microsferas com bupivacaína em excesso enantiomérico de 50 por cento (MBE), microesferas com bupivacaína (MB); microesferas puras (MP) e bupivacaína em excesso enantiomérico de 50 por cento (BE). RESULTADOS: Nos cortes histológicos semifinos observou-se distribuição regular homogênea nas fibras de colágeno no endoneuro e nenhuma alteração degenerativa dos axônios ou das bainhas de mielina foi constatada. Nos cortes ultrafinos foram observados axônios mielinizados e fibras de Remak de aspecto normal com axoplasma apresentando distribuição homogênea de neurofilamentos e microtúbulos. A análise histomorfométrica dos axônios não revelou diferença significativa entre os diâmetros dos axônios dos grupos estudados.
BACKGROUND AND OBJECTIVES: The duration of Local Anesthetic (LA) effects can be expanded by its incorporation into systems of sustained release microspheres. However, the possibility that LA sustained release systems are neurotoxic has not received due attention in literature. The objective of this study was to investigate the effects of pure microspheres of poly(lactic-co-glycolic acid), filled with 50 percent enantiomeric excess bupivacaine or bupivacaine (BP), as well as the effects of 50 percent enantiomeric excess bupivacaine in the sciatic nerve of Wistar rats. METHODS: The rats were allocated into four groups according to the evaluation time (two, four, six, and eight days) and nominated according to the injected solution on the sciatic nerve: Microspheres with 50 percent Enantiomeric excess Bupivacaine (MEB), Microspheres with Bupivacaine (MB), Pure Microspheres (PM), and 50 percent Enantiomeric excess Bupivacaine (EB). RESULTS: In semi-fine histologic sections, no regular homogeneous distribution of collagen fibers in the endoneurium or degenerative changes of axons and myelin sheaths were observed. In ultrathin sections, we found myelinated axons and normal Remak fibers with axoplasm showing homogeneous distribution of neurofilaments and microtubules. Histomorphometric analysis of axons revealed no significant difference between the axon diameters of the studied groups.
JUSTIFICATIVA Y OBJETIVOS: La duración del efecto de los anestésicos locales (AL), puede ser ampliada por su incorporación a los sistemas de liberación prolongada como microesferas. Sin embargo, la posibilidad de que los sistemas de liberación prolongada de AL sean neurotóxicos, no ha recibido la debida atención en la literatura. Este estudio tuvo el objetivo de investigar los efectos de microesferas de ácido poliláctico-co-glicólico puras, rellenados con bupivacaína en exceso enantiomérico de 50 por ciento o con bupivacaína (BP), como también los efectos de la bupivacaína en exceso enantiomérico de 50 por ciento en nervio ciático de ratones Wistar. MÉTODO: Los ratones se dividieron en cuatro grupos de acuerdo con el tiempo de evaluación (dos, cuatro, seis y ocho días), y fueron denominados conforme a la solución inyectada sobre el nervio ciático: microesferas con bupivacaína en exceso enantiomérico de 50 por ciento (MBE), microesferas con bupivacaína (MB); microesferas puras (MP) y bupivacaína en exceso enantiomérico de 50 por ciento (BE). RESULTADOS: En los cortes semifinos se observó la distribución regular homogénea en las fibras de colágeno en el endoneuro y no se comprobó ninguna alteración degenerativa de los axones o de las vainas de mielina. En los cortes ultrafinos fueron observados axones mielinizados y fibras de Remak de aspecto normal con axoplasma presentando una distribución homogénea de neurofilamentos y microtúbulos. El análisis histomorfométrico de los axones no reveló diferencias significativas entre los diámetros de los axones de los grupos estudiados.
Assuntos
Animais , Masculino , Ratos , Anestésicos Locais/farmacologia , Bupivacaína/farmacologia , Microesferas , Nervo Isquiático/efeitos dos fármacos , Testes de Toxicidade Aguda , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Ratos Wistar , Nervo Isquiático/patologiaRESUMO
BACKGROUND AND OBJECTIVES: The goal of this study was to compare scores on house staff evaluations of "overall teaching quality" during a rotation in anesthesia for orthopedics in the first six months (n=11 residents were provided with curriculum in a printed binder) and in the final six months (n=9 residents were provided with the same curriculum in a tablet computer (iPad, Apple®, Inc, Cupertino, Ca)). METHODS: At the beginning of the two-week rotation, the resident was given an iPad containing: a syllabus with daily reading assignments, rotation objectives according to the ACGME core competencies, and journal articles. Prior to the study, these curriculum materials had been distributed in a printed binder. The iPad also provided peer reviewed internet sites and direct access to online textbooks, but was not linked to the electronic medical record. At the end of the rotation, residents anonymously answered questions to evaluate the rotation on an ordinal scale from 1 (unsatisfactory) to 5 (outstanding). All residents were unaware that the data would be analyzed retrospectively for this study. RESULTS: The mean global rating of the rotation as assessed by "overall teaching quality of this rotation" increased from 4.09 (N=11 evaluations before intervention, SD 0.83, median 4, range 3-5) to 4.89 (N=9 evaluations after intervention, SD 0.33, median 5, range 4-5) p=0.04. CONCLUSIONS: Residents responded favorably to the introduction of an innovative iPad based curriculum for the orthopedic anesthesia rotation. More studies are needed to show how such mobile computing technologies can enhance learning, especially since residents work at multiple locations, have duty hour limits, and the need to document resident learning in six ACGME core competencies.
Assuntos
Anestesiologia/educação , Recursos Audiovisuais , Computadores de Mão , Educação de Pós-Graduação em Medicina/métodos , Ortopedia/educação , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: The duration of Local Anesthetic (LA) effects can be expanded by its incorporation into systems of sustained release microspheres. However, the possibility that LA sustained release systems are neurotoxic has not received due attention in literature. The objective of this study was to investigate the effects of pure microspheres of poly(lactic-co-glycolic acid), filled with 50% enantiomeric excess bupivacaine or bupivacaine (BP), as well as the effects of 50% enantiomeric excess bupivacaine in the sciatic nerve of Wistar rats. METHODS: The rats were allocated into four groups according to the evaluation time (two, four, six, and eight days) and nominated according to the injected solution on the sciatic nerve: Microspheres with 50% Enantiomeric excess Bupivacaine (MEB), Microspheres with Bupivacaine (MB), Pure Microspheres (PM), and 50% Enantiomeric excess Bupivacaine (EB). RESULTS: In semi-fine histologic sections, no regular homogeneous distribution of collagen fibers in the endoneurium or degenerative changes of axons and myelin sheaths were observed. In ultrathin sections, we found myelinated axons and normal Remak fibers with axoplasm showing homogeneous distribution of neurofilaments and microtubules. Histomorphometric analysis of axons revealed no significant difference between the axon diameters of the studied groups.
Assuntos
Anestésicos Locais/farmacologia , Bupivacaína/farmacologia , Microesferas , Nervo Isquiático/efeitos dos fármacos , Testes de Toxicidade Aguda , Anestésicos Locais/administração & dosagem , Animais , Bupivacaína/administração & dosagem , Masculino , Ratos , Ratos Wistar , Nervo Isquiático/patologiaRESUMO
JUSTIFICATIVA E OBJETIVOS: Operações no abdome superior e tórax provocam intensa dor. Entre as principais complicações da dor pós-operatória estão as complicações cardiocirculatórias. O objetivo deste trabalho foi testar a hipótese de que a analgesia pós-operatória com o emprego de anestésicos locais mais opioides espinhais pode reduzir a incidência de complicações cardiovasculares no pós-operatório de pacientes nessas condições, comparando-se a métodos clássicos de analgesia pós-operatória, opioides e AINES, administrados segundo demanda do paciente. MÉTODO: Oitenta pacientes adultos ASA I e II, sem alterações ECG, alocados em dois grupos de 40: Grupo A, sob anestesia geral com propofol, cisatracúrio e isoflurano, associado à anestesia peridural, com cateter e controle da analgesia pós-operatória com bupivacaína e morfina peridural; e Grupo B, sob anestesia geral com as mesmas drogas e doses que o Grupo A, mais analgesia pós-operatória realizada com AINES e morfina endovenosa no final da operação e em intervalos regulares. Em ambos foi aplicado Holter por 24 horas. A avaliação da dor foi realizada pela escala analógica visual. RESULTADOS: Na avaliação da dor observou-se no Grupo A evidente predomínio do escore 0 (p < 0,001) e também houve redução dos níveis de pressão arterial no pós-operatório de forma mais acentuada. As disritmias ventriculares e supraventriculares foram cinco vezes mais frequentes no Grupo B (p = 0,00001), em que também detectou-se tendência a maior frequência de extrassístoles ventriculares em idade > 50 anos (22,2 por cento versus 0,0 por cento. p = 0,26). Não se observou diferença significativa da frequência cardíaca entre os grupos (p > 0,05). CONCLUSÕES: A melhor qualidade da analgesia no pós-operatório, realizada nos pacientes do Grupo A, reduziu a incidência de complicações cardiovasculares.
BACKGROUND AND OBJECTIVES: Upper abdomen and thorax surgeries cause intense pain. Some of postoperative pain main complications are cardiocirculatory complications. The objective of this study was to test the hypothesis that postoperative analgesia with employment of local anesthetics plus spinal opioids may reduce the incidence of cardiovascular complications in postoperative period of patients in these conditions, comparing with classical methods of postoperative analgesia, opioids and NSAIDs, administered upon patient's demand. METHOD: Eighty adult patients, ASA I and II, without ECG alterations, were allocated into two groups of 40: Group A, patients under general anesthesia with propofol, cisatracurium and isoflurane, associated with epidural anesthesia with catheter and control of postoperative analgesia with bupivacaine and epidural morphine; and Group B, patients under general anesthesia with the same drugs and doses of A, plus postoperative analgesia carried out with NSAIDs and intravenous morphine at the end of surgery and in regular intervals. In both groups Holter was applied for 24 hours. Pain evaluation was carried out through visual analog scale. RESULTS: In pain evaluation, an evident predominance of 0 score (p < 0.001) was observed in Group A and there was also reduction of blood pressure levels in postoperative period in a more accentuated way. Ventricular and supraventricular dysrhythmias were five times more frequent in Group B (p = 0.00001), in which a tendency to a higher frequency of ventricular extrasystoles in age > 50 years (22.2 percent versus 0.0 percent. p = 0.26) was also detected. No significative difference of heart rate among groups (p > 0.05) was observed. CONCLUSIONS: The best quality of analgesia in postoperative period, carried out in Group A, reduced the incidence of cardiovascular complications.
JUSTIFICATIVA Y OBJETIVOS: Las operaciones en el abdomen superior y el tórax provocan un intenso dolor. Entre las principales complicaciones del dolor postoperatorio están las complicaciones cardiocirculatorias. El objetivo de este trabajo, fue comprobar la hipótesis de que la analgesia postoperatoria con el uso de los anestésicos locales y de los opioides espinales, puede reducir la aparición de complicaciones cardiovasculares en el postoperatorio de los pacientes que están en esas condiciones, comparando los métodos clásicos de analgesia postoperatoria, opioides y AINES, administrados según la demanda del paciente. MÉTODO: Ochenta pacientes adultos ASA I, II, sin alteraciones de ECG, fueron divididos en dos grupos de 40 cada uno: Grupo A, bajo anestesia general con propofol, cisatracurio e isoflurano, asociado a la anestesia epidural, con catéter y control de la analgesia postoperatoria con bupivacaína y morfina epidural; y Grupo B, bajo anestesia general con los mismos fármacos y dosis que el Grupo A, y con analgesia postoperatoria realizada con AINES y morfina ev al final de la operación, y en intervalos regulares. En ambos grupos se aplicó Holter por 24 horas. La evaluación del dolor fue realizada por la escala analógica visual. RESULTADOS: En la evaluación del dolor, se observó en el Grupo A un evidente predominio de la puntuación 0 (p < 0,001) y también hubo una reducción de los niveles de presión arterial en el postoperatorio de una forma más acentuada. Las arritmias ventriculares y supraventriculares fueron cinco veces más frecuentes en el Grupo B (p = 0,00001), donde también se detectó una tendencia para una mayor frecuencia de extrasístoles ventriculares en la edad > 50 años (22,2 por ciento versus 0,0 por ciento. P = 0,26). No se observó diferencia significativa de la frecuencia cardíaca entre los grupos (p > 0,05). CONCLUSIONES: La mejor calidad de la analgesia en el postoperatorio, realizada en el Grupo A...
Assuntos
Humanos , Analgesia/métodos , Arritmias Cardíacas/epidemiologia , Dor Pós-Operatória/complicações , Dor Pós-Operatória/tratamento farmacológico , Medição da Dor , Procedimentos Cirúrgicos TorácicosRESUMO
BACKGROUND AND OBJECTIVES: Upper abdomen and thorax surgeries cause intense pain. Some of postoperative pain main complications are cardiocirculatory complications. The objective of this study was to test the hypothesis that postoperative analgesia with employment of local anesthetics plus spinal opioids may reduce the incidence of cardiovascular complications in postoperative period of patients in these conditions, comparing with classical methods of postoperative analgesia, opioids and NSAIDs, administered upon patient's demand. METHOD: Eighty adult patients, ASA I and II, without ECG alterations, were allocated into two groups of 40: Group A, patients under general anesthesia with propofol, cisatracurium and isoflurane, associated with epidural anesthesia with catheter and control of postoperative analgesia with bupivacaine and epidural morphine; and Group B, patients under general anesthesia with the same drugs and doses of A, plus postoperative analgesia carried out with NSAIDs and intravenous morphine at the end of surgery and in regular intervals. In both groups Holter was applied for 24 hours. Pain evaluation was carried out through visual analog scale. RESULTS: In pain evaluation, an evident predominance of 0 score (p<0.001) was observed in Group A and there was also reduction of blood pressure levels in postoperative period in a more accentuated way. Ventricular and supraventricular dysrhythmias were five times more frequent in Group B (p=0.00001), in which a tendency to a higher frequency of ventricular extrasystoles in age>50 years (22.2% versus 0.0%. p=0.26) was also detected. No significative difference of heart rate among groups (p>0.05) was observed. CONCLUSIONS: The best quality of analgesia in postoperative period, carried out in Group A, reduced the incidence of cardiovascular complications.
Assuntos
Abdome/cirurgia , Analgesia Epidural , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Dor Pós-Operatória/complicações , Dor Pós-Operatória/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Cirurgia Torácica , Arritmias Cardíacas/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologiaRESUMO
JUSTIFICATIVA E OBJETIVOS: Alcançar melhores benefícios terapêuticos dos anestésicos locais no controle da dor pós-operatória, através de carreadores de liberação controlada. Este estudo teve por objetivo a comparação das características dos bloqueios sensitivo e motor entre microesferas sem anestésico local; microesferas com bupivacaína racêmica encapsulada; microesferas com bupivacaína em excesso enantiomérico 50 por cento e bupivacaína em excesso enantiomérico 50 por cento sem as microesferas. MÉTODO: Ratos (Wistar), alocados em quatro grupos: A (Microesfera); B (Microesfera de bupivacaína S50-R50); C (Microesfera de Bupivacaína em excesso enantiomérico de 50 por cento); D (Bupivacaína em excesso enantiomérico de 50 por cento). A anestesia inalatória, realizada previamente ao bloqueio do nervo ciático (halotano a 2 por cento e O2 a 100 por cento). O bloqueio sensorial foi medido pelo tempo exigido para cada rato retirar a pata de uma placa quente a 56ºC (positivo > 4 s). O bloqueio motor foi medido pelo tempo entre a injeção do medicamento até a recuperação do escore 2 de critério estabelecido. RESULTADOS: Nos grupos B, C e D a resposta sensitiva foi significativamente mais frequente do que no Grupo A (p < 0,001). Entre os Grupos B, C e D não se observam diferenças estatisticamente significativas de resposta positiva ao teste sensitivo (p > 0,05). Nos Grupos B, C e D, a resposta ao teste motor também foi significativamente mais frequente do que no grupo A (p = 0,02). Nos Grupos B e D, observou-se tendência de maior positividade ao teste motor que no Grupo C (p = 0,10). CONCLUSÕES: A liberação controlada de microesfera de bupivacaína em excesso enantiomérico de 50 por cento apresentou resultado semelhante em relação à analgesia quando comparado às outras formulações anestésicas e menor bloqueio motor.
BACKGROUND AND OBJECTIVES: To achieve better therapeutic benefits of local anesthetics in the control of postoperative pain through controlled-release carrier. The objective of this study was to compare the characteristics of sensory and motor blockade between microspheres without local anesthetic: racemic bupivacaine-loaded microspheres; 50 percent enantiomeric excess bupivacaine-loaded microspheres; and free 50 percent enantiomeric excess bupivacaine. METHODS: Wistar rats were distributed into four groups: A (Microsphere); B (S50-R50 bupivacaine-loaded microsphere); C (50 percent enantiomeric excess bupivacaine-loaded microsphere); and D (50 percent enantiomeric excess bupivacaine). Inhalation anesthesia was performed before the sciatic nerve block (2 percent halothane and 100 percent O2). Sensorial blockade was measured by the time required for each rat to withdraw its paw from a hot plate at 56ºC (positive > 4 sec). Motor blockade was measured by the time between drug injection until recovery of a motor score of 2 on the established criterion. RESULTS: The sensory response was significantly more frequent in groups B, C, and D than in group A (p < 0.001). There were no statistically significant differences in the response to the sensory test in groups B, C, and D (p > 0.05). The response to the motor test was also significantly more frequent in groups B, C, and D than in group A (p = 0.02). A tendency to greater positivity in the motor test was more frequently found in groups B and D than in group C (p = 0.10). CONCLUSIONS: Controlled-release of 50 percent enantiomeric excess bupivacaine-loaded microspheres showed similar results regarding analgesia and less motor blockade when compared to other anesthetic formulations.
JUSTIFICATIVA Y OBJETIVOS: Alcanzar mejores beneficios terapéuticos de los anestésicos locales en el control del dolor postoperatorio a través de portadores de liberación controlada. Este estudio quiso establecer la comparación de las características de los bloqueos sensitivo y motor entre las microesferas sin anestésico local; microesferas con bupivacaína racémica encapsulada; microesferas con bupivacaína en exceso enantiomérico al 50 por ciento y bupivacaína en exceso enantiomérico al 50 por ciento sin las microesferas. MÉTODO: Se usaron ratones (Wistar) divididos en cuatro grupos: A (Microesfera); B (Microesfera de bupivacaína S50-R50); C (Microesfera de Bupivacaína en exceso enantiomérico de 50 por ciento); D (Bupivacaína en exceso enantiomérico de 50 por ciento). La anestesia inhalatoria fue realizada previamente al bloqueo del nervio ciático (halotano al 2 por ciento y O2 al 100 por ciento). El bloqueo sensorial se midió por el tiempo exigido para que cada ratón retirase la pata de una placa caliente a 56ºC (positivo > 4 s). El bloqueo motor fue medido por el tiempo entre la inyección del medicamento hasta la recuperación de la puntuación 2 de criterio establecido. RESULTADOS: En los grupos B, C y D la respuesta sensitiva fue significativamente más frecuente que en el Grupo A (p < 0,001). Entre los Grupos B, C y D no se observaron diferencias estadísticamente significativas de respuesta positiva al test sensitivo (p > 0,05). En los Grupos B, C y D, la respuesta al test motor también fue significativamente más frecuente que en el grupo A (p = 0,02). En los Grupos B y D, se observó una tendencia a una mayor positividad para el test motor que en el Grupo C (p = 0,10). CONCLUSIONES: La liberación controlada de microesfera de bupivacaína en exceso enantiomérico de 50 por ciento, presentó un resultado similar con relación a la analgesia cuando se le comparó con las otras formulaciones anestésicas y un menor bloqueo motor.