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Fibromyalgia is a debilitating and chronic pain processing disorder, in which the proportion of patients who achieve good results with pharmacotherapy is small. However, choosing the best available evidence on pharmacotherapy can optimize patient clinical outcomes. Objective: This overview aimed to identify in systematic reviews the effects of pharmacotherapy on fibromyalgia, considering the quality of the reviews and the efficacy of the outcomes. Methods: This search was performed in seven databases: PubMed, Web of Science, COCHRANE, Lilacs, Embase, Scopus and IPA. The methodological quality was evaluated using A MeaSurement Tool to Assess Systematic Reviews 2. The protocol was registered in the PROSPERO database (CRD42018095943). Results: A total of 63 systematic reviews were selected after reading full texts, but only 8 of them were of moderate to high quality and were included in this overview. All included reviews were published in English, between 2012 and 2018, performed meta-analysis, used the American College of Rheumatology (1990) diagnostic criteria for fibromyalgia, and jointly assessed pain improvement, adverse reactions, and withdrawal. Most reviews included only randomized controlled trials. Of the fourteen drugs addressed in systematic reviews evaluated, duloxetine, milnacipran, and pregabalin showed evidence of improvement in pain (Moderate: ≤30%) and other fibromyalgia symptoms, as depression and fatigue. However, these medications presented significant withdrawals due to adverse reactions (mainly nausea, headache, dizziness and constipation). The rate of treatment withdrawal reached 36%. Conclusion: Few studies have high quality and sufficient evidence on the effect of medicines on fibromyalgia, resulting in a lack of support for prescribers to choose drugs that meet criteria for need, effectiveness, safety and compliance.
Fibromialgia é um distúrbio de processamento da dor debilitante e crônico, em que a proporção de pacientes que obtêm bons resultados com a farmacoterapia é pequena. No entanto, escolher a melhor evidência disponível sobre a farmacoterapia pode otimizar os resultados clínicos do paciente. Objetivo: Esta overview teve como objetivo identificar em revisões sistemáticas os efeitos da farmacoterapia na fibromialgia, considerando a qualidade das revisões e a eficácia dos resultados. Métodos: Esta busca foi realizada em sete bases de dados: PubMed, Web of Science, COCHRANE, Lilacs, Embase, Scopus e IPA. A qualidade metodológica foi avaliada usando A MeaSurement Tool to Assess Systematic Reviews 2. O protocolo foi registrado no PROSPERO (CRD42018095943). Resultados: Um total de 63 revisões sistemáticas foram selecionadas após a leitura de textos completos, mas apenas 8 delas eram de qualidade moderada a alta e foram incluídas nesta overview. Todas as revisões incluídas foram publicadas em inglês, entre 2012 e 2018, realizaram meta-análises, utilizaram os critérios de diagnósticos do American College of Rheumatology (1990) para fibromialgia e avaliaram conjuntamente a melhora da dor, reações adversas e retiradas. A maioria das revisões incluiu apenas ensaios clínicos randomizados. Dos quatorze medicamentos abordados nas revisões sistemáticas avaliadas, duloxetina, milnaciprano e pregabalina mostraram evidências de melhora da dor (moderada: ≤30%) e de outros sintomas da fibromialgia como depressão e fadiga. No entanto, esses medicamentos apresentaram retiradas significativas devido a reações adversas (principalmente náusea, cefaleia, tontura e constipação). A taxa de abandono ao tratamento chegou a 36%. Conclusão: Poucos estudos apresentam evidências suficientes e de alta qualidade sobre o efeito dos medicamentos na fibromialgia, resultando na falta de apoio para os prescritores escolherem medicamentos que atendam aos critérios de necessidade, eficácia, segurança e adesão.
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Zebrafish are increasingly being utilized as a model to investigate infectious diseases and to advance the understanding of pathogen-host interactions. Here, we take advantage of the zebrafish to recapitulate congenital ZIKV infection and, for the first time, demonstrate that it can be used to model infection and reinfection and monitor anti-viral and inflammatory immune responses, as well as brain growth and eye abnormalities during embryonic development. By injecting a Brazilian strain of ZIKV into the yolk sac of one-cell stage embryos, we confirmed that, after 72 h, ZIKV successfully infected larvae, and the physical condition of the virus-infected hosts included gross morphological changes in surviving embryos (84%), with a reduction in larval head size and retinal damage characterized by increased thickness of the lens and inner nuclear layer. Changes in locomotor activity and the inability to perceive visual stimuli are a result of changes in retinal morphology caused by ZIKV. Furthermore, we demonstrated the ability of ZIKV to replicate in zebrafish larvae and infect new healthy larvae, impairing their visual and neurological functions. These data reinforce the deleterious activity of ZIKV in the brain and visual structures and establish the zebrafish as a model to study the molecular mechanisms involved in the pathology of the virus.
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Traumatismos Oculares , Doenças Retinianas , Infecção por Zika virus , Zika virus , Animais , Larva , Peixe-Zebra , Zika virus/fisiologiaRESUMO
BACKGROUND: It is often unclear whether systematic reviews and primary studies are de-signed to elucidate the efficacy or effectiveness of interventions. This may compromise the use of the information in clinical or policy decisions. OBJECTIVE: This overview aimed to evaluate the methodological profiles of studies on fibromyalgia pharmacotherapy in terms of the quality and nature of the interventions (efficacy versus effective-ness). METHODS: The protocol was registered in the International Prospective Register of Systematic Re-views database. Seven databases were searched for relevant publications. Systematic reviews inves-tigating the effectiveness or efficacy of fibromyalgia pharmacotherapy were included. Methodolog-ical quality was investigated using A MeaSurement Tool to Assess Systematic Reviews (AM-STAR), and efficacy andeffectiveness were evaluated using Rating of Included Trials on the Effica-cy-effectiveness Spectrum (RITES). RESULTS: In this overview, 4,107 studies were initially identified. 8 systematic reviews and 34 prima-ry studies remained after overlaps were removed. Of the eight systematic reviews, 4.76% (n=3) and 7.93% (n=5) were of moderate and high quality, respectively. An analysis of systematic reviews clearly showed the criteria "participants characteristics" and "trial setting" with the most frequent answers as scales 1 and 2 (strong emphasis on efficacy or rather strong emphasis on efficacy), re-spectively. RITES analysis revealed that the most frequent response was "strong emphasis on effi-cacy" in 68% (92/136) of primary studies. CONCLUSION: This analysis showed, in both systematic reviews and primary studies, a predominantly strong emphasis on efficacy, suggesting the need for methodological quality improvement in future studies, especially those designed to provide evidence related to effectiveness. The protocol for this overview has been registered in the International Prospective Register of Sys-tematic Reviews (PROSPERO; CRD42018095943).
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Fibromialgia , Humanos , Fibromialgia/tratamento farmacológico , Revisões Sistemáticas como AssuntoRESUMO
Zebrafish are increasingly being utilized as a model to investigate infectious diseases and to advance the understanding of pathogen–host interactions. Here, we take advantage of the zebrafish to recapitulate congenital ZIKV infection and, for the first time, demonstrate that it can be used to model infection and reinfection and monitor anti-viral and inflammatory immune responses, as well as brain growth and eye abnormalities during embryonic development. By injecting a Brazilian strain of ZIKV into the yolk sac of one-cell stage embryos, we confirmed that, after 72 h, ZIKV successfully infected larvae, and the physical condition of the virus-infected hosts included gross morphological changes in surviving embryos (84%), with a reduction in larval head size and retinal damage characterized by increased thickness of the lens and inner nuclear layer. Changes in locomotor activity and the inability to perceive visual stimuli are a result of changes in retinal morphology caused by ZIKV. Furthermore, we demonstrated the ability of ZIKV to replicate in zebrafish larvae and infect new healthy larvae, impairing their visual and neurological functions. These data reinforce the deleterious activity of ZIKV in the brain and visual structures and establish the zebrafish as a model to study the molecular mechanisms involved in the pathology of the virus.
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PURPOSE: The last two decades have seen the emergence of several viral outbreaks. Some of them are the severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome 2 (SARS-CoV2) - the cause of the coronavirus disease 2019 (COVID-19). Ever, vaccines for emergency use have been authorized for the control and prevention of COVID-19. Currently, there is an urgent need to develop a vaccine for prophylaxis of COVID-19 and for other future epidemics. METHODS: This review describes patented vaccines for SARS and MERS-CoV and vaccines developed and approved for emergency use against the new coronavirus (COVID-19). The European Patent Office and the World Intellectual Property Organization were the patent databases used using specific terms. In addition, another search was carried out in the Clinical Trials in search of ongoing clinical studies focused on the COVID-19 vaccine. RESULTS: The patent search showed that most vaccines are based on viral vector platforms, nucleic acids, or protein subunits. The review also includes an overview of completed and ongoing clinical trials for SARS-CoV-2 in several countries. CONCLUSION: The information provided here lists vaccines for other types of coronavirus that have been used in the development of vaccines for COVID-19.
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COVID-19 , Vacinas , Vacinas contra COVID-19 , Humanos , RNA Viral , SARS-CoV-2RESUMO
Since January 2020, the World Health Organization announces COVID-19 outbreak a case of public health emergency of international interest, and declaring it a pandemic on March. Due to the high transmission of this disease, rate precautions have been implemented, such as the use of masks by the population, personal protective equipment (PPE), and safety protocols, mainly to health workers. Thus, we performed a patent review to evaluate the current patents related to the protective mask. The review was carried out in the patent database in the period of May 2019 to May 2020. After the process of screening and eligibility, 563 patents were selected for our analysis according to the aim of the study which used masks such as a PPE against dust particles and pathogens, mostly when it is about airborne transmission, such as viruses and bacteria. Here, an overview of the main materials used in the mask manufacturing and their efficiency was described. The results of the review showed that most of the masks used cotton, nylon, silver fiber fabrics, among others as fabrics to develop the masks. It also makes an analysis of masks composed of nanotechnology which provide high filtration efficiency. Moreover, the review also brought possibilities of masking the population, which already have been done in countries such as China and Korea and ways of sterilization for reuse of PPE during COVID-19 outbreak. Thus, this review can further researchers in the developing of masks to decrease the spread of a pandemic disease. Graphical abstract.
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COVID-19 , Máscaras , Pandemias , Pacientes , Equipamento de Proteção Individual , Bases de Dados Factuais , HumanosRESUMO
Our recent data show the valuable potential of TnP for the development of a new and safe anti-inflammatory drug due to its ability to control the traffic and activation of leukocytes in response to inflammation. Although there is considerable knowledge surrounding the cellular mechanisms of TnP, less is known about the mechanistic molecular role of TnP underlying its immunomodulatory functions. Here, we conducted investigations to identify whether miRNAs could be one of the molecular bases of the therapeutic effect of TnP. Using a zebrafish model of neutrophilic inflammation with a combination of genetic gain- and loss-of-function approaches, we showed that TnP treatment was followed by up-regulation of only four known miRNAs, and mature dre-miR-26a-1, herein referred just as miR-26a was the first most highly expressed. The knockdown of miR-26a ubiquitously resulted in a significant reduction of miR-26a in embryos, accompanied by impaired TnP immunomodulatory function observed by the loss of the control of the removal of neutrophils in response to inflammation, while the overexpression increased the inhibition of neutrophilic inflammation promoted by TnP. The striking importance of miR-26a was confirmed when rescue strategies were used (morpholino and mimic combination). Our results identified miR-26a as an essential molecular regulator of the therapeutic action of TnP, and suggest that miR-26a or its targets could be used as promising therapeutic candidates for enhancing the resolution of inflammation.
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INTRODUCTION: Coronavirus has been responsible for several virus outbreaks since 2003, caused by SARS-CoV-1, MERS-CoV, and currently SARS-CoV-2 (COVID-19), the causative agent of coronavirus disease in 2019. COVID-19 has become a global public health emergency because of its high virulence and mortality capacity. This patent review aims to provide an overview of the patents that present possible treatments for SARS-CoV-1, SARS-CoV-2 and MERS-CoV. AREAS COVERED: To treat SARS, MERS and SARS-CoV-2, researchers have filed patents for a number of therapeutic agents. Most of the treatments found were protease inhibitors aimed at proteases such as PLpro, 3 CLpro, RNA helicase, and Spike protein, or used monoclonal antibodies and interferons. In addition, the use of Chinese folk medicine and its multitude of medicinal plants with strong antiviral properties was reinforced. Thus, these therapies used in previous epidemics can serve as an aid in the new pandemic by SARS-CoV-2 and be a starting point for new treatments. EXPERT OPINION: The various antiviral alternatives presented in this review offer therapeutic options to fight coronavirus infections. If shown to be effective, these drugs may be extremely important in the current pandemic.
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Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Patentes como Assunto , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Animais , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Desenvolvimento de Medicamentos , Descoberta de Drogas , Interações Hospedeiro-Patógeno , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/virologia , Resultado do Tratamento , Tratamento Farmacológico da COVID-19RESUMO
Anxiety disorders appear to involve distinct neurobiological mechanisms and several medications are available against this mental health problem. However, pharmacological therapeutic approaches display undesirable side effects for patients, particularly when long-term therapy is required. Some evidences have suggested that Coriandrum sativum extract (CSE) provide sedative and anxiolytic effects. We investigate if CSE could attenuate anxiety-like behaviors induced by novelty and alarm substance exposures in zebrafish. Adult zebrafish were injected with vehicle, clonazepam, or CSE (25, 50 or 100 mg/kg) and submitted to novel tank test. At the end, saline or alarm substance was added and anxiety-like responses were recorded. Twenty-four hours after, fish were submitted to the light/dark test. Novelty associated with alarm substance exposure decreased distance traveled and total time mobile in novel tank, and CSE (at 50 and 100 mg/kg) prevented these alterations similarly to clonazepam. Alarm substance reduced the time spent in white compartment (p = 0.0193 as compared with vehicle group). Clonazepam and CSE prevented this anxiogenic effect of alarm substance. CSE presents anxiolytic effects against alarm substance-induced locomotor and anxiogenic responses similarly to clonazepam. These data corroborate with the use of this plant in traditional medicine and provides a putative new pharmacological intervention for anxiety disorders.
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Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Coriandrum/química , Medo/efeitos dos fármacos , Peixe-Zebra/fisiologia , Animais , Ansiolíticos/química , Transtornos de Ansiedade/tratamento farmacológico , Comportamento Animal , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/químicaRESUMO
Allergic inflammation is a response of the body against pathogens by cytokine release and leucocyte recruitment. Recently, there was an increase in morbimortality associated with allergic inflammation, especially asthma. The treatment has many adverse effects, requiring the search for new therapies. Monoterpenes are natural products with anti-inflammatory activity demonstrated in several studies and can be an option to inflammation management. Thus, we investigated the effects of citronellol, α-terpineol and carvacrol on allergic inflammation. The model of asthma was established by OVA induction in male Swiss mice. The monoterpenes were administered (25, 50 or 100 mg/kg, i.p.) 1 h before induction. After 24hs, the animals were sacrificed to leucocytes and TNF-α quantification. Monoterpenes significantly decrease leucocyte migration and TNF-α levels, possibly by modulation of COX, PGE2 and H1 receptor, as demonstrated by molecular docking. These findings indicate that alcoholic monoterpenes can be an alternative for treatment of allergic inflammation and asthma.