RESUMO
INTRODUCCIÓN: Un nuevo brote de coronavirus surgió en 2019 en Wuhan, China, causando conmoción en el sistema sanitario de todo el mundo; el Comité Internacional de Taxonomía de Virus lo denominó SARS-CoV-2, agente causante de la enfermedad COVID-19.El espectro de gravedad de la enfermedad es muy amplio: la mayoría de los pacientes no presentan gravedad, pero otros pueden desarrollar neumonías, y la insuficiencia respiratoria aguda es la causa más frecuente de mortalidad. Objetivo: analizar y desarrollar las distintas alternativas terapéuticas aportadas por la Biotecnología para tratar los síntomas de aquellos pacientes con COVID-19. Metodología: se realizó una revisión de la bibliografía disponible, a partir de enero de 2020 en PubMed, acerca de los tratamientos que se encuentran aún en ensayos clínicos y aquellos que cuentan con aprobación bajo uso de emergencia para la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a políticas de salud establecidas para la terapéutica durante dicha pandemia. Resultados: este trabajo aborda las nuevas alternativas terapéuticas para COVID-19 derivadas de la Biotecnología, que se encuentran tanto en uso como en etapas de ensayos clínicos comprendidos dentro del segmento de los biofármacos y las bioterapias. Se incluye un breve resumen del estatus regulatorio de entidades de salud, el mecanismo de acción de dichas terapias y características generales de cada uno. Se incluyen novedosas bioterapias que se empezaron a implementar para afrontar la pandemia. Conclusiones: la pandemia de coronavirus está poniendo a prueba el sistema sanitario internacional, para brindar soluciones tanto desde el diagnóstico y prevención como para el tratamiento de la población a fin de disminuir la mortalidad. Esto incluyó, obviamente también, al área de la Biotecnología aplicada a la salud, que ha aportado en los tres aspectos mencionados; el presente trabajo se centra en las respuestas de tipo terapéutico que ha brindado y que están comercializadas o en fases clínicas. (AU)
INTRODUCTION: A new coronavirus outbreak emerged in 2019 in Wuhan, China, causing a shock to the healthcare system around the world; the International Committee on Taxonomy of Viruses named it SARS-CoV- 2, the infectious agent of the COVID-19 disease. The spectrum of severity of the disease is very wide, most patients are not serious, but others can develop pneumonia, with acute respiratory failure being the most frequent cause of mortality. Objective: to analyze and develop the different therapeutic alternatives provided by Biotechnology dedicated to Health, to treat the symptoms of those COVID-19 patients who require it, and thus reduce mortality.Methodology: a review of the available literature from January 2020 in PubMed of the treatments that are still in clinical trials and those that have been approved under emergency use for the disease COVID-19 was performed. Searches were also carried out through Google and Google Scholar for publications of Health organizations in reference to health policies established for therapeutics during the mentioned pandemic. Results: this work addresses the new therapeutic alternatives derived from Biotechnology, which are both in use and in stages of clinical trials, to treat patients who developed COVID-19 included within the segment of biopharmaceuticals and biotherapies. A brief summary of the regulatory status of health entities, the mechanism of action of said therapies and general characteristics of each one is included. Innovative biotherapies that began to be implemented to face the pandemic are included. Conclusions: The coronavirus pandemic has driven the international health system to the test, to provide solutions both from the diagnosis, prevention and treatment of the population to reduce the mortality of patients. This obviously also included the area of Biotechnology applied to health, which has contributed in the three aspects mentioned. The present work focuses on the therapeutic responses that it has provided and that are commercialized or in clinical phases. (AU)
Assuntos
Humanos , Animais , Produtos Biológicos/uso terapêutico , Terapia Biológica/métodos , Corticosteroides/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , COVID-19/tratamento farmacológico , Antivirais/uso terapêutico , Antivirais/farmacologia , Terapia Biológica/classificação , Terapia Biológica/normas , Biotecnologia , Ensaios Clínicos como Assunto , Peptidil Dipeptidase A/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/efeitos dos fármacos , Agentes de Imunomodulação/uso terapêutico , Soroterapia para COVID-19 , Cavalos , Soros Imunes/biossíntese , Anticorpos Monoclonais/uso terapêuticoRESUMO
BACKGROUND: Bacterial-mediated cancer immunotherapy (BCI) elicits a more robust initial immune response than conventional immunotherapy, but does not prevent tumor recurrence and metastasis. BCI is associated with recruitment of tumor-infiltrating neutrophils, which could suppress the therapeutic efficacy of this modality. Development endothelial locus 1 (Del-1), a potent inhibitor of neutrophil recruitment, antagonizes lymphocyte function-associated antigen-1 on the vascular endothelium. Here, we aimed to determine the effect of Del-1-secreting S.tâ³ppGpp on anti-tumor activity and tumor-infiltrating neutrophil recruitment in a mouse model of colon cancer. METHODS: We investigated the anti-cancer activity of Del-1-secreting engineered Salmonella (â³ppGpp S. Typhimurium) in the mice colon cancer models. RESULTS: In the present study, we identified that Del-1-secreting engineered Salmonella had more potent anti-cancer activity compared with normal S.tâ³ppGpp without Del-1 secretion. We postulated that Del-1 expression increased M1 macrophage recruitment to tumors by decreasing tumor-infiltrating neutrophils. This approach could enhance the anti-cancer effects of S.tâ³ppGpp. CONCLUSIONS: Collectively, the approach of using engineered bacteria that deliver Del-1 to block tumor-infiltrating neutrophil recruitment is a potential therapeutic approach.
Assuntos
Terapia Biológica/métodos , Proteínas de Ligação ao Cálcio/fisiologia , Moléculas de Adesão Celular/fisiologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/terapia , Infiltração de Neutrófilos , Salmonella typhimurium , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Resultado do TratamentoRESUMO
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Introduction: The development of recommendations for the treatment of rheumatoid arthritis (RA) in the Cuban context may be one of the ways to achieve better control of this disease. Objective: To reach a consensus and update relevant aspects of conventional and biological RA modifier therapy in Cuba. Methods: 18 specialists from 8 Cuban provinces, experts in RA care, were summoned, according to the years of dedication to the specialty, the conferences on this topic and their publications. The first meeting took place in March 2016 in the provincial hospital of Villa Clara, Cuba, with the participation of all the experts. A review of the literature on conventional and biological therapy previously collected by the participants was developed, and two teams were formed: the first would address everything related to conventional therapy in RA (HRCT) and the other, biological therapy in RA (TBAR). Three questionnaires related to the use of corticosteroids, HRCT and TBAR, were prepared, answered by the participants via email. In a second meeting, held in October 2016 in Havana, the analysis of all the responses provided was carried out. Questions with a response of 90% or more votes were considered as recommendations. Results: The questionnaires were answered by 95% of the participants. 9 recommendations and 1 algorithm were established. The recommendations are as follows: methotrexate is the drug of choice in the treatment of RA after diagnosis; The administration of another conventional drug (DMARDc) (azathioprine, salazosulfapyridine, antimalarials and leflunomide) is recommended in patients with a diagnosis of active RA in whom methotrexate is contraindicated or there is a failure in response - consider the administration of low doses of prednisone or equivalent (<7.5 mg/d) associated with DMARDc in patients with active moderate to severe RA, for the shortest possible time; perform serological control including tests for hepatitis B and C viruses and screening for HIV in all patients diagnosed with RA before starting treatment with DMARDc and biologics; in patients in remission or, at least, with a DAS-28 below 3.2, consideration should be given to withdrawing one of the DMARDs or reducing, to the minimum possible expression, the dose of both disease modifiers; if methotrexate fails, tocilizumab in combination with methotrexate or as monotherapy will be indicated. Conclusions: Aspects related to conventional therapy with methotrexate, azathioprine, salazosulfapyridine, antimalarials and leflunomide were agreed. The value of early diagnosis and immediate initiation of DMARDc therapy and the use of glucocorticoids was analyzed. Treatment with tocilizumab, the only biological available in Cuba against RA, will be administered when there is a failure in the response to conventional therapy and combinations between these drugs. It is recommended to hold educational conferences through the mass media aimed at patientshttp(AU)
Assuntos
Humanos , Artrite Reumatoide/tratamento farmacológico , Terapia Biológica/métodos , Antimaláricos/uso terapêutico , Artrite Reumatoide/terapiaRESUMO
Introducción: El proceso de colonización del microbioma intestinal en los primeros 1000 días de vida tiene repercusión en la salud y enfermedades del niño dependientes de factores de riesgo. Objetivos: Revisar evidencias importantes sobre el significado de la relación entre la microbiota Intestinal y los primeros 1000 días de vida, y repercusión de los principales factores de riesgo. Métodos: Se revisaron publicaciones en idiomas español e inglés en PubMed, Google Scholar y SciELO: enero 2005-febrero 2020 usando los términos microbiota intestinal, microbiomas, primeros 1000 días de vida, factores de riesgo, enterocolitis necrosante, probióticos y prebióticos. Análisis e integración de la información: Hay demostrados argumentos que vinculan la microbiota intestinal y primeros 1000 días de vida del niño, según modo de parto, tiempo de gestación y lactancia. Se examina los beneficios del parto vaginal, lactancia materna y la aparición de enfermedades a mediano y largo plazo, relacionadas con factores de riesgo, como cesárea, prematuridad, lactancia artificial y exposición antibiótica prenatal y posnatal. Se describe resultados favorables con el uso de bioterapia con probióticos y prebióticos en la enterocolitis necrosante. Conclusiones: Se expone el valor de la microbiota intestinal en los primeros 1000 días de vida para la salud del niño, influenciada por condiciones de normalidad como el parto vaginal y la lactancia materna e implicaciones clínicas relacionadas con factores de riesgo mencionado. Es importante el tratamiento con probióticos multicepas y prebióticos para la recuperación de la microbiota en el niño en enfermedades como la enterocolitis necrosante y estados de sepsis grave(AU)
Introduction: The process of colonizing the gut microbiome in the first 1000 days of life has an impact on the health and diseases dependent on risk factors of the child. Objectives: Review important evidence on the meaning of the relation between the gut microbiota and the first 1000 days of life and the impact of the main risk factors. Methods: Spanish and English language publications were reviewed on PubMed, Google Scholar and SciELO, from January 2005 to February 2020 using the terms: gut microbiota, microbiomes, first 1000 days of life, risk factors, necrotizing enterocolitis, probiotics and prebiotics. Analysis and information integration: Arguments linking the gut microbiota and the child's first 1000 days of life are demonstrated, depending on the child's mode of delivery, gestation time and lactation. It is conducted an assessment of benefits of vaginal delivery, breastfeeding and the onset of medium- and long-term diseases related to risk factors, such as C-section, prematurity, artificial lactation, and prenatal and postnatal antibiotic exposure. Favorable results with the use of biotherapy with probiotics and prebiotics in necrotizing enterocolitis are described. Conclusions: It is presented the value of the gut microbiota in the first 1000 days of life for the health of the child, influenced by normal conditions such as vaginal delivery and breastfeeding, and clinical implications related to the mentioned risk factors. Treatment with multi-strain probiotics and prebiotics for microbiota recovery in the child is important in diseases such as necrotizing enterocolitis and states of severe sepsis(AU)
Assuntos
Humanos , Recém-Nascido , Lactente , Terapia Biológica/métodos , Saúde da Criança , Fatores de Risco , Microbioma Gastrointestinal , Publicações , Literatura de Revisão como Assunto , Probióticos/efeitos adversos , Enterocolite NecrosanteRESUMO
Leishmaniasis is a neglected tropical disease that affects millions of people around the world. Larval excretion/secretion (ES) of the larvae of flies of the Calliphoridae family has microbicidal activity against Gram-positive and Gram-negative bacteria, in addition to some species of Leishmania. Our study aimed at assessing the in vitro efficacy of Lucilia cuprina larval ES against the promastigote and amastigote forms of Leishmania amazonensis, elucidating possible microbicidal mechanisms and routes of death involved. Larval ES was able to inhibit the viability of L. amazonensis at all concentrations, induce morphological and ultrastructural changes in the parasite, retraction of the cell body, roughness of the cytoplasmic membrane, leakage of intracellular content, ROS production increase, induction of membrane depolarization and mitochondrial swelling, the formation of cytoplasmic lipid droplets and phosphatidylserine exposure, thus indicating the possibility of apoptosis-like death. To verify the efficacy of larval ES on amastigote forms, we performed a phagocytic assay, measurement of total ROS and NO. Treatment using larval ES reduced the percentage of infection and the number of amastigotes per macrophage of lineage J774A.1 at all concentrations, increasing the production of ROS and TNF-α, thus indicating possible pro-inflammatory immunomodulation and oxidative damage. Therefore, treatment using larval ES is effective at inducing the death of promastigotes and amastigotes of L. amazonensis even at low concentrations.
Assuntos
Antiprotozoários/farmacologia , Calliphoridae/química , Larva/química , Leishmania/efeitos dos fármacos , Leishmaniose/terapia , Animais , Terapia Biológica/métodos , Secreções Corporais/química , Morte Celular/efeitos dos fármacos , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Humanos , Leishmania/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células VeroRESUMO
CONTEXTE: Le présent document ainsi que les constats qu'il énonce ont été rédigés en réponse à une interpellation du ministère de la Santé et des Services sociaux dans le contexte de la crise sanitaire liée à la maladie à coronavirus (COVID-19) au Québec. L'objectif est de réaliser une recension des données publiées et de mobiliser les savoirs clés afin d'informer les décideurs publics et les professionnels de la santé et des services sociaux. Bien que les constats reposent sur un repérage exhaustif des données scientifiques publiées, sur l'évaluation de la qualité méthodologique des études et sur une appréciation du niveau de preuve scientifique par paramètre clinique d'intérêt ainsi que sur la consultation de cliniciens avec différentes spécialités et expertises, le processus ne repose pas entièrement sur les normes habituelles à l'INESSS. Dans les circonstances d'une telle crise de santé publique, l'INESSS reste à l'affût de toutes nouvelles données, qu'elles soient de nature scientifique ou contextuelle, susceptibles de lui faire modifier cette réponse. PRÉSENTATION DE LA DEMAND:E La COVID-19 est une maladie causée par le virus SRAS-CoV-2 qui infecte préférentiellement les cellules qui expriment à leu
Assuntos
Humanos , Terapia Biológica/métodos , Interleucinas/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , COVID-19/tratamento farmacológico , Avaliação em Saúde , Análise Custo-BenefícioRESUMO
Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013.A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed.These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.
Assuntos
Terapia Biológica/normas , Reumatologia/normas , Sociedades Médicas/normas , Espondilartrite , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Terapia Biológica/métodos , Brasil , Exercício Físico , Terapia por Exercício , Glucocorticoides/uso terapêutico , Antígeno HLA-B27/sangue , Humanos , Imageamento por Ressonância Magnética , Educação de Pacientes como Assunto , Prognóstico , Reprodutibilidade dos Testes , Articulação Sacroilíaca , Sacroileíte/diagnóstico , Coluna Vertebral/diagnóstico por imagem , Espondilartrite/classificação , Espondilartrite/diagnóstico por imagem , Espondilartrite/terapiaRESUMO
BACKGROUND: The anecdotic evidence of the benefits from biologic agents for psoriasis is extensive. However, data on the efficacy of biologic agents for pustular psoriasis are limited. METHODS: To update the data on the efficacy and safety of biologic agents for the management of pustular psoriasis. A systematic review of published data regarding biologic therapies on PubMED database, used in the management of pustular psoriasis from 2012 was undertaken. RESULTS: A total of 209 articles were identified, and 43 articles were selected for inclusion. TNF-α inhibitors were used in 205 patients, and 86 patients received ustekinumab, secukinumab, brodalumab, ixekizumab and IL-1 inhibitors. Overall response was favorable for most modalities. No serious adverse events were reported. Inconsistent measures of treatment response and study variability limited the overall evaluation of data. CONCLUSIONS: Infliximab and ustekinumab have the most evidence of efficacy and safety for the treatment of pustular psoriasis. Recent evidence supports the use of IL-17 antagonists. Prospective controlled and comparative trials are needed to further explore the efficacy and safety of biologic agents in order to establish objective recommendations for the management of this challenging condition.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Terapia Biológica/métodos , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , HumanosRESUMO
Background: Biological therapies have a significant economic and clinical burden but, in general, lose their effectiveness over time. This study evaluated the medication persistence and costs associated to use of anti-TNF agents for psoriatic arthritis (PsA) treatment. Methods: A historical cohort composed of individuals in Brazil with PsA diagnosis was developed during the period between 2010 and 2015. The difference among the anti-TNF agents was verified by the log-rank test. The predictors of medication non-persistence were identified by Cox regression. The costs were compared by variance analysis with Bonferroni correction. Results: 11,008 patients were analyzed. Adalimumab (51%) was the most used anti-TNF agent. Individuals using adalimumab presented higher medication persistence as compared to etanercept and infliximab. The costs with anti-TNF agents corresponded to 90% of the total costs and were similar among anti-TNF agents. The non-persistence predictors were female sex, younger patients, to live in the Northeastern and Northern regions of Brazil, to use infliximab and etanercept, and have more comorbidities. Conclusion: The direct costs with anti-TNF agents were the main component of total costs. Outpatient and inpatient costs increase when medication persistence decreases. A considerable price reduction of anti-TNF agents has been observed over the years.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Terapia Biológica/métodos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adulto , Antirreumáticos/economia , Artrite Psoriásica/economia , Artrite Psoriásica/epidemiologia , Terapia Biológica/economia , Brasil/epidemiologia , Estudos de Coortes , Custos e Análise de Custo , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE OF REVIEW: An update on new therapies currently approved or potentially useful in the future for the management of patients suffering moderate-to-severe atopic dermatitis. RECENT FINDINGS: New pathogenic mechanisms involved in atopic dermatitis have permitted to propose novel therapeutic approaches devised to control the inflammatory process observed in involved cutaneous tissues by neutralizing mediators, cytokines, and their receptors. Recent research findings have disclosed important and previously unrecognized pathogenic mechanisms that have resulted in innovative targeted therapies, such as dupilumab, and potentially other biologicals and small molecules. Further studies should permit the sub-classification of patients according to the relevance of different mediators and inflammatory cells. It can be concluded that the treatment of atopic dermatitis has entered into the era of personalized/precision medicine.