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Mesenchymal stem cell-and extracellular vesicle-based therapies for Alzheimer's disease:progress,advantages,and challenges

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Neural Regeneration Research 2023年第8期18卷 1645-1651页

作者： Renata Guedes de Jesus Gonçalves Juliana Ferreira Vasques Almir Jordão da Silva-Junior Fernanda Gubert Rosalia Mendez-Otero Instituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Instituto Nacional de Ciência e Tecnologia em medicina Regenerativa Rio de JaneiroBrazil Plataformas Inovadoras em Terapias Avançadas Departamento de Ciência e Tecnologia-Ministério da Saúde(DECIT-MS)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Brazil Programa Redes de Pesquisa em Saúde no Estado do Rio de Janeiro Rio de JaneiroBrazil Instituto de Ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Programa Redes de Pesquisa em Nanotecnologia no Estado do Rio de Janeiro Rio de JaneiroBrazil

Alzheimer's disease is a severe, highly disabling neurodegenerative disease, clinically characterized by a progressive decline in cognitive functions, and is the most common form of dementia in the elderly. For decades, the search for disease-modifying therapies has focused on the two main Alzheimer's disease histopathological hallmarks, seeking to prevent, mitigate, or clear the formation of extracellular aggregates of β-amyloid peptide and intracellular neurofibrillary tangles of tau protein, although without clinical success. Mesenchymal stem cell-based therapy has emerged as a promising alternative for the treatment of Alzheimer's disease, especially because it also targets other crucial players in the pathogenesis of the disease, such as neuroinflammation, synaptic dysfunction/loss, oxidative stress, and impaired neurogenesis. Herein, we review current knowledge of the therapeutic potential of mesenchymal stem cells and their extracellular vesicles for Alzheimer's disease, discussing the most recent findings in both preclinical and clinical trials as well as how advanced technologies have helped to overcome some limitations and contributed to stimulate the development of more effective treatments.

关键词： Alzheimer's disease amyloid-β cell therapy cell transplantation exosomes extracellular vesicles mesenchymal stem cell micro vesicles neuroinflammation tau protein

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Clinical and pathological characterization of epstein-barr virus-associated gastric carcinomas in portugal

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World Journal of Gastroenterology 2017年第40期23卷 7292-7302页

作者： Joana Ribeiro Andreia Oliveira Mariana Malta Claudia Oliveira Fernanda Silva Ana Galaghar Luís Pedro Afonso Maria Cassiano Neves Rui Medeiros Pedro Pimentel-Nunes Hugo Sousa Molecular Oncology and Viral Pathology Group Portuguese Oncology Institute of Porto Faculty of Medicine of Porto University department of Pathology Portuguese Oncology Institute of Porto Medical Oncology department Portuguese Oncology Institute of Porto Instituto CUF de Oncologia Virology Service Portuguese Oncology Institute of Porto Research department-Portuguese League Against Cancer(Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte) Gastroenterology Service Portuguese Oncology Institute of Porto CINTESIS-Center for Health Technology and Services Research(Centro de Investigacao Médica Faculdade de Medicina da Universidade do Porto)

AIM To determine the prevalence of epstein-barr virus(eb V)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer(GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. eb V was detected by in situ hybridization for the detection of eb V-encoded small RNAs(ebe Rs) and eb V latent proteins(LMP1 and LMP2 A) were detected by *** The analysis showed that eb V-associated gastric carcinomas(eb Va GC) represents 8.4%(15/179) of all GC cases, with a significant differential distribution among histological types(P denosquamous carcinoma, 8.7%(8/92) of tubular adenocarcinomas, 8.0%(2/25) of mixed carcinomas and 2%(1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of eb Va GC in the upper third and middle(cardia, fundus and body) of the stomach(P = 0.041), a significant lower number of regional lymph nodes invasion(P = 0.025) and a tendency for better prognosis(P = 0.222). eb V latent protein expression revealed that all eb Va GC cases were LMP1-negative, nevertheless 6 cases(40%) expressed LPM2 A, which reveals that these cases show a distinct eb V-Latency profile(latency II-like).CONCLUSION eb Va GC represents 8.4% of all GC in the North Region of Portugal. The eb V-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.

关键词： Gastric cancer Epstein-barr virus Prevalencel Epstein-barr virus-associated gastric carcinomas

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Neuroinflammation and oxidative stress act in concert to promote neurodegeneration in the diabetic retina and optic nerve:galectin-3 participation

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Neural Regeneration Research 2020年第4期15卷 625-635页

作者： Henrique Rocha Mendonca Raul Carpi-Santos Karin da Costa Calaza Ana Maria Blanco Martinez Laboratorio de Neurodegeneracao e Reparo Departamento de PatologiaPrograma de Pos-graduacao em Anatomia PatologicaFaculdade de MedicinaHospital Universitrio Clementino Fraga FilhoFederal University of Rio de JaneiroRio de JaneiroBrazil Polo Universitario Macae Unidade Integrada de Pesquisa em Produtos Bioativos e BiocienciasFederal University of Rio de JaneiroMacaeBrazil Laboratorio Integrado de Morfologia Instituto de Biodiversidade e SustentabilidadeNucleo de Pesquisas Ecologicas de MacaeFederal University of Rio de JaneiroMacaeBrazil Laboratorio de Neurobiologia Celular Instituto de Ciencias BiomedicasCentro de Ciencias da SaudeFederal University of Rio de JaneiroRio de JaneiroBrazil Laboratorio de Neurobiologia da Retina Departamento de NeurobiologiaPrograma de Pos-Graduacao em NeurocienciasFluminense Federal UniversityNiteroiBrazil

Diabetes is a lifelong disease characterized by glucose metabolic imbalance,in which low insulin levels or impaired insulin signaling lead to hyperglycemic *** 20 years of diabetes progression,95%of patients will have diabetic retinopathy,the leading cause of visual defects in working-age people *** diabetes is considered a microvascular disease,recent studies have shown that neurodegeneration precedes vascular changes within the diabetic visual system,albeit its mechanisms are still under *** and oxidative stress are intrinsically related phenomena,since macrophage/microglia and astrocytes are the main sources of reactive oxygen species during central nervous system chronic degenerative diseases,and both pathological processes are increased in the visual system during *** present review will focus on recent findings of the contribution of oxidative stress derived from neuroinflammation in the early neurodegenerative aspects of the diabetic visual system and their relationship with galectin-3.

关键词： diabetes diabetic retinopathy galectin-3 neurodegeneration neuroinflammation optic nerve oxidative stress retina

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The balance between efficient anti-inflammatory treatment and neuronal regeneration in the olfactory epithelium

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Neural Regeneration Research 2018年第10期13卷 1711-1714页

作者： Seo Young Chang Isaias Glezer department of Biochemistry Escola Paulista de MedicinaUniversidade Federal de SAo Paulo

The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that constitute the olfactory epithelium（OE）. Importantly, the OE is a highly active site of adult neurogenesis where short-lived neurons are efficiently replenished, even after massive neuronal cell loss. It is suggested that the degree of olfactory function recovery after OE injury may depend on the nature of the lesion（traumatic, chemical, infectious or inflammatory）, as well on the velocity of cellular regeneration. Topical steroidal anti-inflammatory drugs, such as glucocorticoids, are routinely prescribed for treating upper airway inflammatory conditions, such as chronic rhinosinusitis. While the therapeutic strategy aims to minimize the inflammatory damage and dysfunction to nasal air conduction, new evidences raise concerns if such drugs may impair neuronal regeneration in the OE. In consequence, new directions are necessary in terms of drug development or prescription, in order to preserve olfactory function through lifelong repeated episodes of chronic inflammation in the upper respiratory tract. Here we discuss mechanisms involved in glucocorticoid deleterious effects to OE regeneration and possible therapeutic alternatives considering relevant side effects.

关键词： anti-inflammatory drugs corticosteroids hyposmia inflammation rhinosinusitis olfactory epithelium sensory neurons cell proliferation

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Expression of Multidrug Resistance ATP-Binding Cassette(abc)Transporters in Canine Mammary Tumors

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Advances in Breast Cancer Research 2015年第3期4卷 77-85页

作者： Breno S.Salgado Suely Nonogaki Luisa M.Soares Angela Akamatsu Cristiano R.N.da Silva Thiago P.Anacleto Rodolfo Malagó Rafael M.Rocha Fátima Gartner Noeme S.Rocha departamento de Patologia Faculdade de Medicina de BotucatuUniversidade Estadual PaulistaCampus de BotucatuBotucatuBrazil Instituto de Ciências Biomédicas Abel Salazar Universidade do Porto(Intitute of Biomedical Sciences Abel Salazar of University of Porto)OportoPortugal fundacao Antonio Prudente Hospital A.C.CamargoSao PauloBrazil departamento de Clínica Veterinária Faculdade de Medicina Veterinária e ZootecniaUniversidade Estadual PaulistaUNESP.BotucatuBrazil Hospital Escola de medicina Veterinária Fundacao de Ensino e Pesquisa de Itajubá—FEPIItajubáBrazil

Mammary neoplasms are the most common tumors in female dogs. They are usually treated using solely surgical mastectomy—which is recognized as unsatisfactory in many cases. Given this, the benefits of chemotherapy in dogs with mammary cancer need to be further explored. Some drugs that can be used for treating canines with mammary tumors may be substrates of uptake and/or efflux transporters such as the ATP-binding cassette (abc) transporters. Unfortunately, very little is known regarding the pathobiology of such proteins in canine tumors, including mammary cancer. Accordingly, this study was designed to characterize the expression of abc transporters P-glycoprotein, MRP1, and MRP2 and their relation with clinicopathologic factors in order to allow a better understanding of their influence in canine mammary cancer. P-glycoprotein was expressed in tumors from 55.8% of patients, while MRP1 and MRP2 were expressed in 37.2% and 39.5% of tumors, respectively. P-glycoprotein expression showed to be related with regional lymph node spread (P = 0.0038), as well as with tumor grade (P = 0.0353) and with a shorter survival (P = 0.0245). MRP1 revealed a strong association with a higher histological grade (P determined as prognostic indicator independent of lymph node status using Cox proportional-hazards regression multivariate analysis (P = 0.0216). No relations between MRP2 and clinicopathologic features were observed. We have found that P-glycoprotein and MRP1 are expressed in highly aggressive canine mammary tumors and are related with poor prognosis. Our results suggest that they may play a significant role in the course of canine mammary cancer progression and be promising candidate markers for a validation study on therapy outcome.

关键词： MDR1 P-Gp MRP1 MRP2 abcC2 Mammary Neoplasms Prognosis dog

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Dietary approach in the treatment of nonalcoholic fatty liver disease

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World Journal of Hepatology 2015年第24期7卷 2522-2534页

作者： Silvia Marinho Ferolla Luciana Costa Silva Maria de Lourdes Abreu Ferrari Aloísio Sales da Cunha Flaviano dos Santos Martins Cláudia Alves Couto Teresa Cristina Abreu Ferrari departamento de Clínica Médica Centro de Pós-GraduacaoFaculdade de MedicinaUniversidade Federal de Minas GeraisBelo Horizonte 30130-100Minas GeraisBrazil departamento de Propedêutica Complementar Faculdade de MedicinaUniversidade Federal de Minas GeraisBelo Horizonte 30130-100Minas GeraisBrazil departamento de Microbiologia Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo Horizonte 31270-901Minas GeraisBrazil

Nonalcoholic fatty liver disease(NAFLD) has been identified as one of the most prevalent chronic liver disease in adults and children populations. NAFLD is usually associated with the metabolic syndrome(MS), which is chiefly related to insulin resistance and its consequences. Insulin resistance has a crucial role in the pathogenesis of hepatic steatosis and potentially nonalcoholic steatohepatitis(NASH). Because of the contemporary epidemics of MS and obesity, the burden of NAFLD is also expected to rise. Unhealthy diets, such as the so-called western diet, are enriched in fructose, trans-fatty acids and saturated fat and seem to be associated with the development of NAFLD. In human studies, certain dietary sugars, particularly fructose, are used as a substrate for lipogenesis leading to hepatic fatty infiltration, inflammation, and possibly fibrosis. Other investigations have shown that fat consumption especially cholesterol and trans/saturated fatty acids are also steatogenic and seem to increase visceral adiposity. The identification of specific dietary components that favor the development of NASH could be important for the management of this disorder. This review focuses on the effects of different dietary approaches to prevent and treat NAFLD emphasizing the macronutrients and energy composition.

关键词： Fatty liver Dietary carbohydrates Dietary fats Die

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Effects of voluntary imipramine intake via food and water in paradigms of anxiety and depression in naive mice

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Translational Neuroscience and Clinics 2016年第3期2卷 172-182,149页

作者： Joao Pedro Costa-Nunes Anastassia Bakhmet Margarida Araújo-Correia Andreia Barbosa Valenca Tatyana Strekalova Harry W.M.Steinbusch School for Mental Health and Neuroscience Maastricht University Center for Neuroscience and Cell Biology Universidade de CoimbraFaculdade de MedicinaRua Larga Centro de Biologia Ambiental Faculdade de Ciências da Universidade de Lisboa department of Human Anatomy Moscow State Medical University Centro de Estudos de doencas Crónicas(CEdoC) Edifício CEDOCⅡRua Camara Pestana Centro Interdisciplinar de Investigacao em Saúde Animal(CIISA) Faculdade de Medicina VeterináriaAlameda da Universidade Técnica

Objective: We sought to investigate the efficacy of oral dosing in mice with imipramine(7mg/kg/day) via water or in food pellets, and to compare its effects in the paradigms of learned helplessness, locomotion, hedonic state, and anxiety. Methods: Water and food consumption were measured to determine daily imipramine dosage in C57BL/6N mice. Next, baseline scores for O-maze, dark/light box, and sucrose tests were measured. Mice were then subjected to a 4-week treatment of voluntary ingestion of drinking water or food pellets containing imipramine. Lastly, all groups were subjected to novel cage, open field, O-maze, dark/light box, sucrose test, and forced swim test to assess the effects of the treatment. Results: In na?ve mice, imipramine delivered via food, induced a reduction of total floating and increased latency in the forced swim test, i.e., antidepressant-like effects. No other significant effects were found. dosing with water did not change behavior in the forced swim, sucrose preference test, anxiety, or locomotor paradigms, but increased exploration in the novel cage. Conclusions: Voluntary ingestion is an effective method of chronic dosing with imipramine in na?ve mice. delivery of imipramine with food pellets elicits antidepressant-like effects in the forced swim test, with no effects on anxiety, locomotion, or preference behaviors. In contrast, no such effects were observed with treatment via drinking water, suggesting that a higher dose may be required. Our work argues for a broader use of oral delivery using food-treated pellets, in small rodent models of pre-clinical depression. It may substantially improve animal welfare and overcome potential confounds in translational research, which are frequently associated with adverse chronic invasive pharmacotherapies.

关键词： pre-clinical models depression anxiety oral dosing animal welfare

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Prevalence of sarcopenia using different methods in patients with non-alcoholic fatty liver disease

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World Journal of Hepatology 2022年第8期14卷 1643-1651页

作者： Naiade Silveira Almeida Raquel Rocha Claudineia Almeida de Souza Ana Carolina Sirelli da Cruz Bruna dos Reis Ribeiro Luiza Valois Vieira Carla daltro Rafael Silva Manoel Sarno Helma Pinchemel Cotrim Programa de Pós-Graduação em medicina e Saúde Universidade Federal da BahiaSalvador 40110-060BABrazil departamento de Ciência da Nutrição Escola de NutriçãoUniversidade Federal da BahiaSalvador 40110-060Brazil Caliper Clínica e Escola de Imagem Salvador 41810-012Brazil

BACKGROUND Sarcopenia is a clinical condition associated with several liver diseases and it includes non-alcoholic fatty liver disease(NAFLD)in its broad spectrum as steatosis,steatohepatitis and ***,the criteria to define sarcopenia are diverse,and even those established in consensus have been discussed regarding their performance in making an accurate *** To evaluate the prevalence of sarcopenia,using different methods,in patients with NAFLD,and its association with clinical-anthropometric *** This was an observational study of outpatients with *** was defined by the European Working Group Consensus on Sarcopenia in Older People of 2010(EWGSOP1)and 2018(EWGSOP2).The skeletal muscle index was used to estimate muscle mass,handgrip strength was assessed using the dynamometer and physical performance by walking a distance of four meters at usual walking *** non-invasive fibrosis scores,fibrosis-4(FIB-4)index and Aspartate aminotransferase to platelet ratio index(APRI),were used to assess the absence and presence of *** Fifty-seven individuals with NAFLD were evaluated,the mean age(SD)was 52.7(11.3)years and 75.4%were *** assessed by FIB-4 and APRI was observed in 3.7%and 16.6%of patients with NAFLD,*** diagnosis of sarcopenia was identified only by EWGSOP1 in 3.5%of NAFLD patients,and the prevalence of probable/pre-sarcopenia was higher using the EWGSOP2 consensus at 26.3%,when compared to 1.8%with *** defined by EWGSOP1,was associated with grade I steatosis,but without overweight(P0.05).EWGSOP2 showed a greater number of patients with probable sarcopenia,and who were overweight(12(80.0%)),with a higher degree of steatosis[11(73.3%)and presence of fibrosis(1(6.7%),FIB-4 and 3(20.0%),APRI]compared to EWGSOP1[1(100%),0(0.0%),0(0.0%),FIB-4 and 0(0.0%),APRI,respectively].CONCLUSION The presen

关键词： Non-alcoholic fatty liver disease Sarcopenia Muscle strength Physical performance Liver fibrosis

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Safety of Transcranial Direct Current Electrical Stimulation in dermatomyositis: A Case Report

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Open Journal of Rheumatology and Autoimmune Diseases 2020年第2期10卷 88-93页

作者： Rafael Giovani Missé Luiz Felipe Adsuara de Sousa Lucas de Macedo dos Santos Abrahão Fontes Baptista Clarice Tanaka Julia Maria D’Andréa Greve Samuel Katsuyuki Shinjo Division of Rheumatology Faculdade de Medicina FMUSPUniversidade de Sao PauloSao PauloSPBrazil(BR) department of Physical Therapy Speech Therapy and Occupational TherapyHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSao PauloSPBrazil(BR) Center for Mathematics Computing and CognitionUniversidade Federal de ABCSPBrazil(BR) Laboratory of Movement Studies Institute of Orthopedics and TraumatologyHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloBrazil(BR)

Transcranial direct current stimulation (tDCS) has emerged as a nonpharmacological tool in physical rehabilitation. There have currently no studies that evaluated the safety and efficacy of tDCS in patients with dermatomyositis. Case-report: Three adult women with dermatomyositis were allocated randomly to intervention (i-tDCS, one patient) or not (sham-tDCS, two patients) of three consecutive days of tDCS and evaluated in four periods: before-tDCS (PRE), 15 minutes after-tDCS (0th POST), 15 days after-tDCS (15th POST), and 30 days after-tDCS (30th POST). The tDCS was safe throughout the protocol, without disease relapsing or adverse effects related to tDCS. Furthermore, the tDCS increased the muscle torque and total work of dominant and non-dominant elbow flexors in the patient with i-tDCS, when compared to two patients with sham-tDCS. Conclusions: The tDCS was safe and appeared to influence long-term strength in the limb of the patient with stable dermatomyo-sitis.

关键词： dermatomyositis Neuromodulation Safety Systemic Autoimmune Myopathies

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Resolutive Results with Oral Corticosteroids for Patients with COVID-19 in Pulmonary Inflammatory Phase. Successful Outpatient Experience during the Collapse of Belem do Para Health System—Brazil

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Health 2021年第8期13卷 830-838页

作者： Roberto S. Zeballos Luciana N. L. Cruz Vânia C. R. Brilhante Adriana V. Lima Carlliane L. L. P. Martins Karla N. A. Lima Michele C. G. L. Leão Belinete L. Cruz Alessandra B. Dysarz Paulo C. B. Lobato Erika S. Almeida Rute A. P. Costa Klevison C. Araújo Augusto C. C. Almeida Leônidas B. D. Junior Kathia O. Harada Rita H. V. S. Araújo Elaine X. Prestes Ivete M. S. Souza Avany M. P. Pereira Antônio B. M. A. Rocha Iracema A. Estevão Fagnei I. C. Carvalho Paulo M. P. Melo Clinical Care Sao Paulo Brazil Instituto de Ciencias da Saude Faculdade de Medicina Universidade Federal do Para Belem Brazil fundacao Publica Estadual Hospital de Clinicas Gaspar Vianna Belem Brazil Hospital da Policia Militar do Para Belem Brazil Imunoclinic Belem Brazil Universidade Estadual do Para Fundacao Santa Casa de Misericordia do Para Belem Brazil Clinica Barros Cirurgia Plastica Belem Brazil Secretaria de Estado de Saude Publica Castanhal Brazil Centro de Tratamento Oncologico Belem Brazil Sociedade Brasileira de Valorizaç ã o das Sociedades Medicas—SOBEMED S&#227 o Paulo Brazil Clinica de Nutrologia Sao Luiz Brazil Hospital Nipo Brasileiro de Olhos Belem Brazil Centro de Ciencias Biologicas e da Saude Universidade do Estado do Para Belem Brazil Hospital Regional do Baixo Amazonas Santarem Brazil Clinica Vallinoto Secretaria de Saude de Barcarena Barcarena Brazil Estrategia Saude da Familia Secretaria Municipal de Saude de Ananindeua Centro Universitario do Estado do Para Belem Brazil A. M. P. Endocrinologia Belem Brazil Instituto Avertano Rocha Belem Brazil departamento de Neurocirurgia Hospital Militar de Area De Sao Paulo Sao Paulo Brazil

In the face of new diseases, medicine needs to reinvent itself in order to contain and control epidemics, such as the one we have recently faced, COVID-19, a disease with a wide spectrum of clinical severity. A new moment has been established, since the application of well-known, effective and safe medications for other diseases, has shown high success rates in the treatment of COVID-19. Thereunto, studies with early intervention are needed, which can change the unfavorable outcome of patients. In this article, we report the successful experience using an oral strategy during the collapse of Belem (Para, Brazil) Health System. Two hundred and ten patients were diagnosed with respiratory failure due to COVID-19, with no option of hospital treatment due to lack of beds and resources. These patients were then started on therapeutic regimen consisting of 40 mg prednisolone, 40 mg enoxaparin and macrolides (500 mg clarithromycin, 500 mg axetylcefuroxime) associated and followed in outpatient facilities. Two hundred and eight patients had an excellent therapeutic response and there were only two fatalities. These results push research boundaries, valuing outpatient treatment with early use of prednisolone in the initial pulmonary phase, preventing severe COVID-19 pneumonitis. Adoption of the proposed treatment intends to reduce the need for hospitalization, as well as lethality, with social robust benefits and incalculable economic savings since involves the use of accessible, safe and not expensive medications.

关键词： COVID-19 Corticosteroids Pulmonary Inflammatory Phase Collapse Brazil

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