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O artigo é uma revisão sobre os aspectos relacionados ao envelhecimento masculino e necessidades de tratamentos, com ênfase no hipogonadismo tardio, baixa produção de testosterona e possível desenvolvimento do Distúrbio Androgênico do Envelhecimento Masculino (DAEM). O objetivo foi apresentar o DAEM e suas implicações sobre a qualidade de vida do paciente para promover e validar o tratamento, quando realmente for apropriado, para esse quadro clínico. Utilizou-se como a fonte de pesquisa Google Acadêmico, banco de dados Biblioteca Virtual em Saúde e do PubMed foram obtidos artigos com as aplicações dos seguintes filtros: 2010-2023 e descritores em saúde (andropausa, reposição hormonal, testosterona, DAEM, hipogonadismo e síndromes metabólicas). Os critérios de inclusão utilizados foram a disponibilidade integral dos artigos, ter os idiomas inglês e português, e abordar o tema da Doença Androgênica do Envelhecimento, todas as suas repercussões sobre a qualidade de vida do homem e, sobretudo, o seu tratamento. Para excluir artigos encontrados na busca, foram observadas obras que apenas tangenciam o tema e tinham enfoque em outros aspectos, como: estética e esporte. Após a aplicação do método, 14 trabalhos foram selecionados por estabelecerem grande relação com o tema. Esse distúrbio acarreta para o indivíduo um conjunto de sinais e sintomas capazes de comprometer sua qualidade de vida: disfunção erétil, baixa libido, obesidade, redução de massa magra ou sarcopenia, osteoporose e distúrbios do humor. O diagnóstico é feito clinicamente e através de exames laboratoriais de dosagem sérica de testosterona. Perante a confirmação diagnóstica e sem patologizar processos fisiológicos do envelhecimento, o tratamento indicado é a reposição de testosterona que tende a normalizar o quadro do idoso por amenizar ou finalizar os sinais e sintomas desse paciente, proporcionando-o uma terceira idade com qualidade de vida. Vale destacar que as disposições de formulações de testosterona são inúmeras: orais, transdérmicas, intramusculares ou injetáveis. A via de administração depende da situação individual de cada paciente e cada tipo de medicamento tem seus benefícios se comparado aos outros, seja por comparação entre efeitos colaterais, estabilidade de níveis séricos hormonais, custo e acesso. O DAEM precisa ser identificado e diagnosticado naqueles pacientes que necessitam de um tratamento por apresentar sinais e sintomas prejudiciais ao bem-estar. Para isso, a indústria farmacêutica disponibiliza uma gama de formas de administração de testosterona. Entretanto, é preciso ter clareza sobre a real necessidade de medicar um paciente.
The article is a review of aspects related to male aging and treatment needs, with an emphasis on late-onset hypogonadism, low testosterone production and the possible development of Androgenic Male Aging Disorder (AMAD). The aim was to present the AMAD and its implications for the patient's quality of life in order to promote and validate treatment, where appropriate, for this clinical condition. The search source used was Google Scholar, the Virtual Health Library database and PubMed, where articles were obtained using the following filters: 2010-2023 and health descriptors (andropause, hormone replacement, testosterone, AMAD, hypogonadism and metabolic syndromes). The inclusion criteria used were that the articles were available in full, that they were in English and Portuguese, and that they dealt with the subject of Androgenic Ageing Disorder, all its repercussions on men's quality of life and, above all, its treatment. To exclude articles found in the search, we looked at works that only touched on the subject and focused on other aspects, such as aesthetics and sport. After applying the method, 14 articles were selected because they were closely related to the topic. This disorder leads to a set of signs and symptoms that can compromise the individual's quality of life: erectile dysfunction, low libido, obesity, reduced lean mass or sarcopenia, osteoporosis and mood disorders. The diagnosis is made clinically and through laboratory tests of serum testosterone levels. Once the diagnosis has been confirmed and without pathologizing the physiological processes of ageing, the treatment indicated is testosterone replacement, which tends to normalize the condition of the elderly by easing or ending the signs and symptoms of the patient, providing them with a quality old age. It's worth noting that there are many different formulations of testosterone: oral, transdermal, intramuscular or injectable. The route of administration depends on the individual situation of each patient and each type of medication has its benefits compared to the others, whether it's a comparison of side effects, stability of serum hormone levels, cost and accessibility. AMAD needs to be identified and diagnosed in those patients who need treatment because they have signs and symptoms that are detrimental to their well-being. To this end, the pharmaceutical industry offers a range of forms of testosterone administration. However, it is necessary to be clear about the real need to medicate a patient.
El artículo es una revisión de los aspectos relacionados con el envejecimiento masculino y las necesidades de tratamiento, con énfasis en el hipogonadismo de inicio tardío, la baja producción de testosterona y el posible desarrollo del Trastorno Androgénico del Envejecimiento Masculino (TAME). El objetivo fue presentar el TAME y sus implicaciones en la calidad de vida del paciente, con el fin de promover y validar el tratamiento de esta condición clínica, cuando sea apropiado. La fuente de búsqueda utilizada fue Google Scholar, la base de datos de la Biblioteca Virtual de Salud y PubMed, donde se obtuvieron artículos utilizando los siguientes filtros: 2010-2023 y descriptores de salud (andropausia, reemplazo hormonal, testosterona, TAME, hipogonadismo y síndromes metabólicos). Los criterios de inclusión utilizados fueron que los artículos estuvieran disponibles en su totalidad, en inglés y portugués, y que abordaran el tema del Trastorno Androgénico del Envejecimiento, todas sus repercusiones en la calidad de vida de los hombres y, sobre todo, su tratamiento. Para excluir los artículos encontrados en la búsqueda, se consideraron los trabajos que sólo tocaban el tema y se centraban en otros aspectos, como la estética y el deporte. Tras aplicar el método, se seleccionaron 14 artículos por estar estrechamente relacionados con el tema. Este trastorno conlleva un conjunto de signos y síntomas que pueden comprometer la calidad de vida del individuo: disfunción eréctil, libido baja, obesidad, reducción de la masa magra o sarcopenia, osteoporosis y trastornos del estado de ánimo. El diagnóstico se realiza clínicamente y mediante pruebas de laboratorio de los niveles séricos de testosterona. Una vez confirmado el diagnóstico y sin patologizar los procesos fisiológicos del envejecimiento, el tratamiento indicado es el reemplazo de testosterona, que tiende a normalizar la condición del anciano, aliviando o terminando con sus signos y síntomas, proporcionándole una vejez con calidad de vida. Cabe destacar que existen diversas formulaciones de testosterona: oral, transdérmica, intramuscular o inyectable. La vía de administración depende de la situación individual de cada paciente y cada tipo de medicación tiene sus ventajas frente a las demás, ya sea en comparación con los efectos secundarios, la estabilidad de los niveles séricos de la hormona, el coste y la accesibilidad. Es necesario identificar y diagnosticar el TAME en aquellos pacientes que necesitan tratamiento porque presentan signos y síntomas perjudiciales para su bienestar. Para ello, la industria farmacéutica ofrece diversas formas de administración de testosterona. Sin embargo, es necesario tener clara la necesidad real de medicar a un paciente.
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Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low-grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID-19 pandemic, as these formulations helped to limit SARS-CoV-2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses.
Assuntos
Infecções Respiratórias , Vacinas de mRNA , Humanos , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/virologia , Infecções Respiratórias/imunologia , Desenvolvimento de Vacinas , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Animais , Vacinas contra COVID-19/imunologia , RNA Mensageiro/genética , RNA Mensageiro/imunologiaRESUMO
Focal Epithelial Hyperplasia or Multifocal Epithelial Hyperplasia (MEH), also known as Heck's disease, is considered a rare pathology of the oral mucosa associated with human papillomavirus types 13 and 32. For reasons not fully understood, MEH disproportionally affects specific populations of indigenous groups around the world. After the first reports in Native Americans, the epidemiology of the disease has been described in different geographical regions mainly related to particular indigenous populations, the majority of the studies are clinical case reports, but the biological determinants are still unknown. Some suggested risk factors include chronic irritation caused by smoking, a galvanic current, vitamin A deficiency, and/or a familial-genetic predisposition; however, the scientific evidence is not solid due the scarcity of case-control studies or longitudinal cohorts. In light of the evidence, further study of the pathology of MEH should be considered and proper clinical trials for effective treatments should be designed. The disease warrants further study as it is considered as neglected by research and it affects rural/remote population groups usually living in adverse socioeconomic conditions.
Assuntos
Hiperplasia Epitelial Focal , Mucosa Bucal , Infecções por Papillomavirus , Humanos , Hiperplasia Epitelial Focal/patologia , Mucosa Bucal/patologia , Fatores de Risco , Infecções por Papillomavirus/complicações , Etnicidade , Papillomaviridae/genética , Papillomaviridae/patogenicidadeRESUMO
The novel Equine Parvovirus-Hepatitis (EqPV-H) was first identified in the serum and liver of a horse that died of equine serum hepatitis, also known as Theiler's disease. Several reports in recent years strongly suggest that EqPV-H is the etiologic agent of Theiler's disease. Brazil is the only South American country where infection with this virus has been reported. This study investigated the presence of EqPV-H DNA in horse serum pools (n=51), commercial horse serum batches (n=5) and individual serum samples from donor horses (n=175) from Argentina. All serum samples were analyzed by quantitative polymerase chain reaction (qPCR) and samples with positive or indeterminate results were further analyzed by NS1 nested-PCR for phylogenetic studies. None of the serum pools was positive by qPCR but 9/51 pools were indeterminate (one or both test sample's Ct values were higher than the limit of detection). The NS1 nested-PCR detected the EqPV-H DNA in 8 of these indeterminate samples (15.7â¯% of serum pools). Three of the commercial horse serum batches (60â¯%) contained EqPV-H DNA, detected either by qPCR and/or nested-PCR. From the 175 individual horse serum samples, three (1.71â¯%) were positive for EqPV-H by both techniques. The genetic analysis of the 12 partial NS1 sequences obtained showed that the local isolates were similar to EqPV-H sequences from Germany and China. This study provides the first evidence of the presence of EqPV-H in horses and in horse sera commercially available in Argentina and emphasizes the importance of controlling the biosecurity of commercial equine sera as well as any other blood-derived biological products of equine origin. DATA AVAILABILITY: Viral sequences generated in this study were uploaded to the NCBI nucleotide database and are available with the accession numbers PP408676-PP408687.
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Hepatite Viral Animal , Doenças dos Cavalos , Infecções por Parvoviridae , Parvovirus , Filogenia , Animais , Cavalos , Argentina/epidemiologia , Doenças dos Cavalos/virologia , Doenças dos Cavalos/epidemiologia , Infecções por Parvoviridae/veterinária , Infecções por Parvoviridae/virologia , Infecções por Parvoviridae/epidemiologia , Hepatite Viral Animal/virologia , Hepatite Viral Animal/epidemiologia , Parvovirus/genética , Parvovirus/isolamento & purificação , Parvovirus/classificação , DNA ViralRESUMO
OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. METHODS: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DISCUSSION: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.
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Neoplasias , Infecções Respiratórias , Viroses , Humanos , Masculino , Feminino , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/virologia , Criança , Pré-Escolar , Estudos Prospectivos , Viroses/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Chile , Neutropenia Febril/tratamento farmacológico , Lactente , Suspensão de Tratamento , Febre/tratamento farmacológico , Resultado do Tratamento , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Hospitalização , AdolescenteRESUMO
Glomeruli can be damaged in several conditions after kidney transplantation, with a potential impact on the graft function and survival. Primary glomerulonephritis, a group of glomerular immunological damage that results in variable histological patterns and clinical phenotypes, can occur in kidney transplant recipients as a recurrent or de novo condition. Specific immunologic conditions associated with kidney transplantation, such as acute rejection episodes, can act as an additional trigger after transplantation, impacting the incidence of these glomerulopathies. The post-transplant GN recurrence ranges from 3% to 15%, varying according to the GN subtype and post-transplant time, mainly occurring after 3-5 years of kidney transplantation. Advances in the knowledge of glomerulonephritis pathophysiology have provided new approaches to pre-transplant risk evaluation and post-transplant monitoring. Glomeruli can be affected by several systemic viral infections, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), cytomegalovirus (CMV), and BK virus. The diagnosis of these infections, as well as the identification of possible complications associated with them, are important to minimize the negative impacts of these conditions on kidney transplant recipients' outcomes.
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Odontogenic keratocyst (OK) is a benign intraosseous cystic lesion characterized by a parakeratinized stratified squamous epithelial lining with palisade basal cells. It represents 10-12% of odontogenic cysts. The changes in its classification as a tumor or cyst have increased interest in its pathogenesis. OBJECTIVE: Identify key genes in the pathogenesis of sporadic OK through in silico analysis. MATERIALS AND METHODS: The GSE38494 technical sheet on OK was analyzed using GEOR2. Their functional and canonical signaling pathways were enriched in the NIH-DAVID bioinformatic platform. The protein-protein interaction network was constructed by STRING and analyzed with Cytoscape-MCODE software v 3.8.2 (score > 4). Post-enrichment analysis was performed by Cytoscape-ClueGO. RESULTS: A total of 768 differentially expressed genes (DEG) with a fold change (FC) greater than 2 and 469 DEG with an FC less than 2 were identified. In the post-enrichment analysis of upregulated genes, significance was observed in criteria related to the organization of the extracellular matrix, collagen fibers, and endodermal differentiation, while the downregulated genes were related to defensive response mechanisms against viruses and interferon-gamma activation. CONCLUSIONS: Our in silico analysis showed a significant relationship with mechanisms of extracellular matrix organization, interferon-gamma activation, and response to viral infections, which must be validated through molecular assays.
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Cistos Odontogênicos , Tumores Odontogênicos , Humanos , Interferon gama , Cistos Odontogênicos/genética , Cistos Odontogênicos/patologia , Tumores Odontogênicos/patologia , Mapas de Interação de Proteínas/genéticaRESUMO
It is well known that as part of their response to infectious agents such as viruses, microglia transition from a quiescent state to an activated state that includes proinflammatory and anti-inflammatory phases; this behavior has been described through in vitro studies. However, recent in vivo studies on the function of microglia have questioned the two-phase paradigm; therefore, a change in the frequency of in vitro studies is expected. A systematic review was carried out to identify the microglial cytokine profile against viral infection that has been further evaluated through in vitro studies (pro-inflammatory or anti-inflammatory), along with analysis of its publication frequency over the years. For this review, 531 articles published in the English language were collected from PubMed, Web of Science, EBSCO and ResearchGate. Only 27 papers met the inclusion criteria for this systematic review. In total, 19 cytokines were evaluated in these studies, most of which are proinflammatory; the most common are IL-6, followed by TNF-α and IL-1ß. It should be pointed out that half of the studies were published between 2015 and 2022 (raw data available in https://github.com/dadriba05/SystematicReview.git ). In this review, we identified that evaluation of pro-inflammatory cytokines released by microglia against viral infections has been performed more frequently than that of anti-inflammatory cytokines; additionally, a higher frequency of evaluation of the response of microglia cells to viral infection through in vitro studies from 2015 and beyond was noted.
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Citocinas , Viroses , Humanos , Microglia , Fator de Necrose Tumoral alfa , Anti-InflamatóriosRESUMO
BACKGROUND: Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. RESULTS: Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-ß, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. CONCLUSIONS: Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.
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COVID-19 , Interferon Tipo I , SARS-CoV-2 , alfa-Sinucleína , Células Endoteliais , Humanos , Linhagem Celular , Replicação ViralRESUMO
Knowledge regarding the profile of eligible blood donors presenting positive results in laboratory screening is essential for reducing transfusion-transmitted human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Our study aimed to evaluate the prevalence, incidence, predictor variables and residual risk (RR) of HIV/HBV/HCV in blood bags donated in Minas Gerais, Brazil. This study analysed data retrieved from the records of a large blood bank relating to donations collected at multiple centres within the period 2012-2018, during which 1 991 120 blood bags were screened using immunoassays and nucleic acid tests (NATs). Multilevel modelling was used to investigate the association between sex, civil status and age group with HIV/HBV/HCV. RR was estimated from the incidence values (restricted to negative and positive tests within the study period) and window periods for infections. The prevalence in first time donors, incidence and RR of HCV (223.73 cases per 100 000; 54.84 per 100 000 persons-year and 1.6527 per 100 000, respectively) were higher than those of HIV (172.65 cases per 100 000; 28.25 per 100 000 persons-year and 0.8514 per 100 000) and HBV (168.17 cases per 100 000; 18.54 per 100 000 persons-year and 0.5588 per 100 000). The odds of acquiring infection were greater in male, single and older donors. Sixteen donors were identified as seronegative and NATs+ during the 7-year span of the study. Our study has clarified some spatiotemporal trends regarding HIV/HBV/HCV infections in donated blood in Brazil. The results will contribute to the formulation of directives addressed to high-risk donors.
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Infecções por HIV , Hepatite B , Hepatite C , Masculino , Humanos , Feminino , Incidência , Hepatite B/epidemiologia , Brasil/epidemiologia , Doadores de Sangue , Prevalência , Fatores de Risco , Hepatite C/epidemiologia , Vírus da Hepatite B , Infecções por HIV/epidemiologia , HepacivirusRESUMO
Extracellular vesicles (EVs) are lipid bilayer envelopes that encapsulate cell-specific cargo, rendering them promising biomarkers for diverse diseases. Chagas disease, caused by the parasite Trypanosoma cruzi, poses a significant global health burden, transcending its initial epicenter in Latin America to affect individuals in Europe, Asia, and North America. In this study, we aimed to characterize circulating EVs derived from patients with chronic Chagas disease (CCD) experiencing a reactivation of acute symptoms. Blood samples collected in EDTA were processed to isolate plasma and subsequently subjected to ultracentrifugation for particle isolation and purification. The EVs were characterized using a nanoparticle tracking analysis and enzyme-linked immunosorbent assay (ELISA). Our findings revealed distinctive differences in the size, concentration, and composition of EVs between immunosuppressed patients and those with CCD. Importantly, these EVs play a critical role in the pathophysiology of Chagas disease and demonstrate significant potential as biomarkers in the chronic phase of the disease. Overall, our findings support the potential utility of the CL-ELISA assay as a specific sensitive tool for detecting circulating EVs in chronic Chagasic patients, particularly those with recurrent infection following an immunosuppressive treatment or with concurrent HIV and Chagas disease. Further investigations are warranted to identify and validate the specific antigens or biomarkers responsible for the observed reactivity in these patient groups, which may have implications for diagnosis, the monitoring of treatment, and prognosis.
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This work aimed to assess the Sf9 cell metabolism during growth, and infection steps with recombinant baculovirus bearing rabies virus proteins, to finally obtain rabies VLP in two culture systems: Schott flask (SF) and stirred tank reactor (STR). Eight assays were performed in SF and STR (four assays in each system) using serum-free SF900 III culture medium. Two non-infection growth kinetics assays and six recombinant baculovirus infection assays. The infection runs were carried out at 0.1 pfu/cell multiplicity of infection (MOI) for single baculovirus bearing rabies glycoprotein (BVG) and matrix protein (BVM) and a coinfection with both baculoviruses at MOI of 3 and 2 pfu/cell for BVG and BVM, respectively. The SF assays were done in triplicate. The glucose, glutamine, glutamate, lactate, and ammonium uptake or release specific rates were quantified over the exponential growth phase and infection stage. The highest uptake specific rate was observed for glucose (42.5 × 10-12 mmol cell/h) in SF and for glutamine (30.8 × 10-12 mmol/cell/h) in STR, in the exponential growth phases. A wave pattern was observed for assessed analytes throughout the infection phase and the glucose had the highest wave amplitude within the 10-10 mmol cell/h order. This alternative uptake and release behavior is in harmony with the lytic cycle of baculovirus in insect cells. The virus propagation and VLP generation were not limited by glucose, glutamine, and glutamate, neither by the toxicity of lactate nor ammonium under the conditions appraised in this work. The findings from this work can be useful to set baculovirus infection processes at high cell density to improve rabies VLP yield, purity, and productivity.
Assuntos
Compostos de Amônio , Vírus da Raiva , Raiva , Animais , Células Sf9 , Vírus da Raiva/genética , Glutamina , Baculoviridae/genética , Proteínas Recombinantes/genética , Meios de Cultura Livres de Soro , Ácido Glutâmico , Lactatos , Glucose , SpodopteraRESUMO
BACKGROUND: Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. RESULTS: Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-ß, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. CONCLUSIONS: Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.
Assuntos
Humanos , Interferon Tipo I , alfa-Sinucleína , SARS-CoV-2 , COVID-19 , Replicação Viral , Linhagem Celular , Células EndoteliaisRESUMO
Rabies is a fatal zoonotic disease that affects several mammals. Hematophagous bats are recognized hosts of the rabies virus, and their main food source is the blood of other mammals, particularly cattle. During feeding, bats transmit the virus to cattle, which are victims of the disease, contributing to economic losses and increasing the risk of infection for humans. Based on this affinity in the rabies cycle between bats and cattle, the objective of this study was to analyze the phylogenetic relationships of rabies virus samples in cattle and bats. The G gene of the rabies virus was chosen for this study because it is directly related to the infection process. Nucleotide sequences of the viral G gene were selected from GenBank for samples obtained from infected cattle and bats. Maximum parsimony analyses were conducted using the Molecular Evolutionary Genetics Analysis software. The Maxima Parsimony tree indicated a phylogenetic relationship between the G genes of both hosts, indicating that the virus evolved from bats to cattle. Analysis of parsimoniously informative sites revealed that the viral G gene carried specific mutations in each host. Knowledge of the evolutionary relationships between the rabies virus and its hosts is critical for identifying potential new hosts and the possible routes of infection for humans.
A Raiva é uma zoonose fatal que infecta várias espécies de mamíferos. Os morcegos hematófagos são reconhecidos como hospedeiros do vírus da Raiva e sua principal fonte de alimento é o sangue de outros mamíferos, especialmente os bovinos. Quando se alimentam, os morcegos transmitem o vírus para o bovino os quais são vítimas da doença, contribuindo para perdas econômicas e riscos de infecção para humanos. Baseado nesta afinidade do ciclo da Raiva entre morcegos e bovinos, o objetivo deste estudo foi analisar as relações filogenéticas de amostras do vírus da Raiva em ambos os hospedeiros, bovinos e morcegos. O gene G do vírus da Raiva foi escolhido para esta pesquisa porque ele está diretamente relacionado ao processo de infecção. Sequências de nucleotídeos do gene G viral foram selecionadas no GenBank a partir de amostras obtidas de bovinos e morcegos infectados. Análises de Máxima Parcimônia foram conduzidas utilizando o software Molecular Evolutionary Genetics Analysis. A árvore de Máxima Parcimônia indicou uma relação filogenética entre o gene G de ambos os hospedeiros, indicando que o vírus evoluiu dos morcegos para os bovinos. A análise dos sítios parcimoniosamente informativos revelou que o gene G viral apresentou mutações específicas em cada hospedeiro. O conhecimento sobre as relações evolutivas do vírus da Raiva e seus hospedeiros é crucial para identificar nos hospedeiros potenciais e novas rotas possíveis de infecção para humanos.
La rabia es una zoonosis fatal que infecta a varias especies de mamíferos. Los murciélagos hematófagos son reconocidos como huéspedes del virus de la rabia y su principal fuente de alimentación es la sangre de otros mamíferos, especialmente del ganado. Al alimentarse, los murciélagos transmiten el virus al ganado que es víctima de la enfermedad, contribuyendo a pérdidas económicas y riesgos de infección para los humanos. Basado en esta afinidad del ciclo de la rabia entre murciélagos y ganado, el objetivo de este estudio fue analizar las relaciones filogenéticas de las muestras de virus de la rabia tanto en huéspedes, ganado y murciélagos. El gen G del virus de la rabia fue elegido para esta investigación porque está directamente relacionado con el proceso de infección. Las secuencias de nucleótidos del gen G viral se seleccionaron en GenBank a partir de muestras obtenidas de bovinos y murciélagos infectados. Los análisis de parsimonia máxima se realizaron utilizando el software Molecular Evolutionary Genetics Analysis. El árbol de Máxima Parsimônia indicó una relación filogenética entre el gen G de ambos huéspedes, indicando que el virus evolucionó de murciélagos a bovinos. El análisis de los sitios parsimoniosamente informativos reveló que el gen G viral presentaba mutaciones específicas en cada huésped. El conocimiento sobre las relaciones evolutivas del virus de la rabia y sus huéspedes es crucial para identificar huéspedes potenciales y nuevas posibles rutas de infección para humanos.
Assuntos
Animais , Filogenia , Vírus da Raiva/genética , Viroses/veterinária , Quirópteros/virologiaRESUMO
Resumen Dentro de los síntomas que presentaron los pacientes que cursaron COVID-19 se documentó una importante incidencia de anosmia, asociada muchas veces a alteraciones en el gusto, sin una base fisiopatológica concluyente. La resonancia magnética proporciona datos estructurales morfológicos sobre el nervio olfatorio, el bulbo olfatorio y las cortezas primarias y secundarias. En esta serie de pacientes con anosmia posterior a COVID-19 se identificaron alteraciones estructurales de los bulbos olfatorios principalmente con elevación de la señal en secuencias T2, y en menor medida aumento de su volumen. Dichas características fueron interpretadas en probable relación con edema e inflamación posterior a la infección viral, observando en ciertos casos, además, asimetría de los bulbos olfatorios.
Abstract Anosmia, a frequent symptom among patients affected by COVID-19 and often associated with alterations in taste, does not have a clear pathophysiological basis in this context. Magnetic resonance imaging enables the structural assessment of the olfactory nerve, olfactory bulb, and primary and secondary cortices. In this group of patients with post-COVID anosmia, were identified structural abnormalities at the level of the olfactory bulb mainly depicted as elevation of the signal in T2-weighted sequences, and to a lesser extent as an increase in their volume. These characteristics were interpreted in probable relation to edema and inflammation after the viral infection, showing in certain cases asymmetry of the olfactory bulbs.
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ABSTRACT BACKGROUND: Acute kidney failure is a serious consequence of coronavirus disease 2019 (COVID-19). OBJECTIVES: To identify the prevalence of COVID-19, kidney failure, frequency of death, and associated factors in patients receiving intensive care. DESIGN AND SETTING: Analytical cross-sectional study conducted in the intensive care unit (ICU) of a medium-sized philanthropic general hospital in center-west Minas Gerais. METHODS: Adults and older individuals who underwent real-time polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were evaluated by the nephrology team. RESULTS: Among the 176 patients, the prevalence of COVID-19 and acute kidney injury (AKI) were 103 (58.5%) and 132 (75%), respectively, and 44 (25%) had chronic kidney disease (CKD) and 16 (15,5%) were positive for SARS-CoV-2. In the Charlson index classification, which estimates the risk of death, a statistically significant difference was identified in the percentages of groups with and without COVID-19 for indices 0, 1, and 2. There was a significant association between kidney disease and ICU mortality (P < 0.05). Patients with CKD had fewer fatal outcomes (13/97, 13.4%) than those with AKI (85/97, 87.6%). CONCLUSIONS: COVID-19 rates remained high long after diagnosis and prevention of SARS-CoV-2 infection. In addition, a higher death rate among patients who developed AKI, whose prevalence was also greater than that in the national literature, regardless of the presence of COVID-19, revealed a worrying scenario and corroborated the need for early and judicious approaches to preserve the lives of patients with AKI admitted to intensive care units.
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Purinergic signaling has been associated with immune defenses against pathogens such as bacteria, protozoa, fungi, and viruses, acting as a sentinel system that signals to the cells when a threat is present. This review focuses on the roles of purinergic signaling and its therapeutic potential for viral infections. In this context, the purinergic system may play potent antiviral roles by boosting interferon signaling. In other cases, though, it can contribute to a hyperinflammatory response and disease severity, resulting in poor outcomes, such as during flu and potentially COVID-19. Lastly, a third situation may occur since viruses are obligatory intracellular parasites that hijack the host cell machinery for their infection and replication. Viruses such as HIV-1 use the purinergic system to favor their infection and persistence within the host cell. Therefore, understanding the particular nuances of purinergic signaling in each viral infection may contribute to designing proper therapeutic strategies to treat viral diseases.
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Beak deformation, known as avian keratin disorder (AKD), can impair feeding and preening of birds, reducing their survival. This disorder is apparently caused by Poecivirus infection, although to date, the viral origin has been corroborated in only a few North American bird species. Considering that fruit-eating birds can track spatiotemporal variations in fruit abundance and that AKD may have a viral origin, the incidence of this disease can be expected to increase with flocking by birds. Therefore, we evaluated if austral thrushes (Turdus falcklandii) were attracted to urban areas when exotic plants offered fruits and if flocking of thrushes in urban areas increased the spread of AKD in this species in a Patagonian town. We fitted GPS loggers on some individuals with normal beaks in rural areas and found that they visit the town in fall. Through point count censuses, we recorded greater abundances of thrushes with normal and deformed beaks during fall-winter in urban sites than in rural sites. However, the abundance of birds with AKD declined more (78-87%) than that of individuals with normal beaks (44-52%) during the transition from fall-winter to spring-summer. In urban zones in our study area, fruits of exotic species ripen during fall, attracting austral thrushes from rural sites. Nevertheless, such an attraction for food resources may be an ecological trap for this species, as the increase in incidence of AKD in urban areas may drastically reduce the survival of birds during the most unfavorable period of the year.
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While SARS-CoV-2 infection causes a mild disease in most children, SARS-CoV-2 infection may be lethal in a few of them. In the defense against SARS-CoV-2, type I interferons are key players, and several studies have identified a defective or neutralized interferon response as the cause of overwhelming viral infection. However, inappropriate, untimely, or excessive interferon production may also be detrimental to the host. Here, we describe two patients with STAT1 gain-of-function (GOF), a known type I interferonopathy, who died of COVID-19. Whole-exome sequencing and interferon-gamma-activated sequence (GAS) and interferon-sensitive responsive element (ISRE) reporter assay were performed to identify and characterize STAT1 variants. Patient 1 developed hemophagocytic lymphohistiocytosis (HLH) in the context of COVID-19 infection and died in less than a week at the age of 4 years. Patient 2 developed a high fever, cough, and hypoxemia and succumbed to COVID-19 pneumonia at the age of 5 years. Two heterozygous missense variants, p.E563Q and p.K344E, in STAT1 were identified. Functional validation by reporter assay and immunoblot confirmed that both variants are gain-of-function (GOF). GOF variants transiently expressing cells exhibited enhanced upregulation of downstream genes, including ISG15, MX1, and OAS1, in response to IFN-α stimulation. A catastrophic course with HLH or acute respiratory failure is thought to be associated with inappropriate immunoregulatory mechanisms to handle SARS-CoV-2 in STAT1 GOF. While most patients with inborn errors of immunity who developed COVID-19 seem to handle it well, these cases suggest that patients with STAT1-GOF might be at risk of developing fatal complications due to SARS-CoV-2.