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A low-grade and persistent inflammation, which is the hallmark of obesity, requires the participation of NLRP3 and cell death. During Mycobacterium tuberculosis infection, NLRP3 signaling is important for bacterial killing by macrophages in vitro but was shown to be dispensable for host protection in vivo. We hypothesized that during obesity-tuberculosis (TB) comorbidity, NLRP3 signaling might play a detrimental role by inducing excessive inflammation. We employed a model of high-fat-diet-induced obesity, followed by M. tuberculosis infection in C57BL/6 mice. Obese mice presented increased susceptibility to infection and pulmonary immunopathology compared to lean mice. Using treatment with NLRP3 antagonist and Nlrp3-/- mice, we showed that NLRP3 signaling promoted cell death, with no effect in bacterial loads. The levels of palmitate were higher in the lungs of obese infected mice compared to lean counterparts, and we observed that this lipid increased M. tuberculosis-induced macrophage death in vitro, which was dependent on NLRP3 and caspase-1. At the chronic phase, although lungs of obese Nlrp3-/- mice showed an indication of granuloma formation compared to obese wild-type mice, there was no difference in the bacterial load. Our findings indicate that NLRP3 may be a potential target for host-directed therapy to reduce initial and severe inflammation-mediated disease and to treat comorbidity-associated TB. © 2022 The Pathological Society of Great Britain and Ireland.
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Mycobacterium tuberculosis , Tuberculosis , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Palmitatos/metabolismo , Ratones Endogámicos C57BL , Tuberculosis/patología , Pulmón/patología , Inflamación/patología , Obesidad/metabolismo , Muerte Celular , ComorbilidadRESUMEN
There is evidence that IL-22 and IL-17 participate in the pathogenesis of allergic asthma. To investigate the role of IL-22, we used IL-22 deficient mice (IL-22 KO) sensitized and challenged with ovalbumin (OVA) and compared with wild type (WT) animals exposed to OVA. IL-22 KO animals exposed to OVA showed a decreased number and frequency of eosinophils, IL-5 and IL-13 in the airways, reduced mucus production and pulmonary inflammation. In addition, IL-22 KO animals exhibited a decreased percentage and number of lung CD11c+CD11b+ cells and increased apoptosis of eosinophils. Th17 cell transfer generated from IL-22 KO to animals previously sensitized and challenged with OVA caused a reduction in eosinophil frequency and number in the airways compared to animals transferred with Th17 cells generated from WT mice. Therefore, IL-22 is deleterious with concomitant secretion of IL-17. Our findings show a pro-inflammatory role for IL-22, confirmed in a model of allergen-free and allergen-specific immunotherapy. Moreover, during the comorbidity asthma and pneumonia that induces neutrophil inflammation, IL-22 was not detrimental. Our results show that targeting IL-22 would negatively affect the survival of eosinophils, reduce the expansion or migration of CD11c+CD11b+ cells, and negatively regulate allergic asthma.
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Asma , Neumonía , Ratones , Animales , Interleucina-17/genética , Asma/patología , Pulmón/patología , Eosinófilos , Neumonía/patología , Alérgenos , Comorbilidad , Ovalbúmina , Modelos Animales de Enfermedad , Líquido del Lavado Bronquioalveolar , Ratones Endogámicos BALB CRESUMEN
Numerous studies have associated alterations in the gut microbiota composition with almost every known inflammatory disease. However, proving the biological relevance of distinct microbial signatures and linking specific microorganisms to host phenotypes, remains a considerable challenge. Correspondingly, increased abundance of members of Prevotella genus within microbial communities colonizing distinct mucosal surfaces has been found in individuals diagnosed with rheumatoid arthritis, periodontitis, metabolic disorders, and intestinal and vaginal dysbiosis. Still, the role of Prevotella spp. in the incidence of these diseases continues to be debated. For many years, poor understanding of Prevotella biology could be in large part attributed to the lack of experimental tools. However, in the recent years significant advances have been made towards overcoming these limitations, including increased number of isolates and improved understanding of genetic diversity. Besides discussing the most relevant associations between Prevotella spp. and inflammatory disorders, in the present review we examine the recent efforts to expand the Prevotella experimental "toolbox" and we highlight remaining experimental challenges that should advance future research and our understanding of Prevotella-host interplay.
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Disbiosis , Microbioma Gastrointestinal , Interacciones Microbiota-Huesped , Inflamación/microbiología , Prevotella/metabolismo , Tracto Gastrointestinal , Humanos , IntestinosRESUMEN
BACKGROUND: The mediators produced by CD4+ T lymphocytes are involved in the pathogenesis of aneurysmal lesions in abdominal aortic aneurysm (AAA) patients. The aim of this study was to identify and characterize the CD4+ T cell subsets involved in human AAA. METHODS: The CD4+ T cell subsets in 30 human aneurysmal lesions were determined using flow cytometry (FC) and immunohistochemistry (IHC). The peripheral blood mononuclear cells (PBMCs) from patients with AAA were also analyzed by FC and compared with control subjects. RESULTS: Human aneurysmal lesions contained IFN-γ, IL-12p35, IL-4, IL-23p19, IL-17R, and IL-22 positive cells. PBMCs from AAA patients had higher expression levels of IFN-γ, TNF-α, IL-4, and IL-22 when compared to controls. CONCLUSIONS: Our results show the presence of TH1, TH2, TH17, and TH22 subsets in aneurysmal lesions of AAA patients and suggest that these cells may be mainly activated in situ, where they can induce tissue degradation and contribute to the pathogenesis of AAA.
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Aneurisma de la Aorta Abdominal/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Subgrupos de Linfocitos T/metabolismo , Anciano , Aneurisma de la Aorta Abdominal/inmunología , Linfocitos T CD4-Positivos/inmunología , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Subunidad p35 de la Interleucina-12/metabolismo , Subunidad p19 de la Interleucina-23/metabolismo , Interleucina-4/metabolismo , Interleucinas/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Interleucina-22RESUMEN
Besides their role in fighting viral infection and tumor resistance, recent studies have shown that NK cells also participate in the immune response against other infectious diseases. The aim of this study was to characterize the possible role of NK cells in the immune response against Paracoccidioides brasiliensis. Purified NK cells from paracoccidioidomycosis patients and healthy individuals were incubated with P. brasiliensis yeast cells or P. brasiliensis-infected monocytes, with or without the addition of recombinant IL-15. We found that NK cells from paracoccidioidomycosis patients exhibit a lower cytotoxic response compared with healthy individuals. NK cells are able directly to recognize and kill P. brasiliensis yeast cells, and this activity seems to be granule-dependent but perforin-independent, whereas the cytotoxicity against P. brasiliensis-infected monocytes is perforin-dependent. These results indicate that NK cells participate actively in the immune response against the P. brasiliensis infection either by directly destroying yeast cells or by recognizing and killing infected cells. Granulysin is the possible mediator of the cytotoxic effect, as the reduced cytotoxic activity against the yeast cells detected in patients with paracoccidioidomycosis is accompanied by a significantly lower frequency of CD56(+)granulysin(+) cells compared with that in healthy controls. Furthermore, we show that NK cells released granulysin in cultures after being stimulated by P. brasiliensis, and this molecule is able to kill the yeast cells in a dose-dependent manner. Another important finding is that stimulated NK cells are able to produce proinflammatory cytokines (IFN-γ and TNF-α) supporting their immunomodulatory role in the infection.
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Citotoxicidad Inmunológica/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Paracoccidioides/inmunología , Paracoccidioidomicosis/inmunología , Paracoccidioidomicosis/patología , Antifúngicos/farmacología , Antígenos de Diferenciación de Linfocitos T/fisiología , Movimiento Celular/inmunología , Células Cultivadas , Técnicas de Cocultivo , Humanos , Inmunofenotipificación/métodos , Mediadores de Inflamación/fisiología , Interferón gamma/biosíntesis , Células K562 , Células Asesinas Naturales/microbiología , Activación de Linfocitos/inmunología , Paracoccidioides/patogenicidad , Paracoccidioidomicosis/terapia , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
The human gut microbiota is influenced by various factors, including health status and environmental conditions, yet considerable inter-individual differences remain unexplained. Previous studies identified that the gut microbiota of men who have sex with men (MSM) is distinct from that of non-MSM. Here, we reveal through species-level microbiota analysis using shotgun metagenomics that the gut microbiota of many MSM with Western origin resembles gut microbial communities of non-Westernized populations. Specifically, MSM gut microbiomes are frequently dominated by members of the Prevotellaceae family, including co-colonization of species from the Segatella copri complex and unknown Prevotellaceae members. Questionnaire-based analysis exploring inter-individual differences in MSM links specific sexual practices to microbiota composition. Moreover, machine learning identifies microbial features associated with sexual activities in MSM. Together, this study shows associations of sexual activities with gut microbiome alterations in MSM, which may have a large impact on population-based microbiota studies.
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Microbioma Gastrointestinal , Microbiota , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Conducta SexualRESUMEN
Risk factors for atherosclerosis may contribute to chronic low-grade inflammation. A highly cytotoxic and inflammatory CD4(+) cell subset (CD4(+)CD28(null) cells) has been associated with inflammatory diseases, including acute coronary syndromes (ACS). The aim of this study was to quantify and characterize CD4(+)CD28(null) cells in individuals with risk factors for atherosclerosis and patients with coronary artery disease (CAD). In order to achieve this goal, peripheral blood mononuclear cells (PBMCs) from individuals with risk factors for atherosclerosis and patients with CAD were analyzed using flow cytometry to detect cytotoxic molecules and evaluate the expression of homing receptors and inflammatory cytokines in CD4(+) cell subsets. The cells were evaluated ex vivo and after stimulation in culture. We found no differences in the proportions of CD4(+)CD28(null) cells among the groups. Compared with the CD4(+)CD28(+) population, the ex vivo CD4(+)CD28(null) subset from all groups expressed higher levels of granzymes A and B, perforin, granulysin and interferon-γ (IFN-γ). Individuals with risk factors and patients with ACS showed the highest levels of cytotoxic molecules. After stimulation, tumor necrosis factor-α (TNF-α) expression in the CD4(+)CD28(null) subset from these groups increased more than in the other groups. Stimulation with LPS decreased the expression of cytotoxic molecules by CD4(+)CD28(null) cells in all groups. In conclusion, our results show that risk factors for atherosclerosis may alter the CD4(+)CD28(null) cells phenotype, increasing their cytotoxic potential. Our findings also suggest that CD4(+)CD28(null) cells may participate in the early phases of atherosclerosis.
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Aterosclerosis/inmunología , Antígenos CD28/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Enfermedad de la Arteria Coronaria/inmunología , Subgrupos de Linfocitos T/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Diferenciación de Linfocitos T/biosíntesis , Linfocitos T CD4-Positivos/inmunología , Femenino , Granzimas/biosíntesis , Humanos , Interferón gamma/biosíntesis , Leucocitos Mononucleares/metabolismo , Lipopolisacáridos/farmacología , Masculino , Persona de Mediana Edad , Perforina/biosíntesis , Receptores CCR7/metabolismo , Receptores CXCR3/metabolismo , Factores de Riesgo , Subgrupos de Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
There are several methods of laboratory diagnosis of filarids, the most used are the thick smear and the Knott method. Both are quick to perform, have a low cost and allow observing the presence, quantifying and analyzing the morphological characteristics of microfilariae. Knowing the morphological viability of fixed microfilariae is of practical importance, as it allows the transport of samples to a laboratory, facilitates epidemiological studies , and allows the storage of samples for didactic. Thus, the aim of this study was to evaluate the morphological viability of microfilariae fixed in the refrigerated modified knott test using 2% formalin. To perform the modified Knott technique, 10 samples of microfilaremic dogs aged over 6 months were used. To evaluate the morphological viability time of the microfilariae in the modified Knott concentrate, the evaluations were repeated after intervals of 0, 1, 7, 30, 60, 120, 180, 240, and 304 days. In the present study, we did not verify any difference in the morphology of the microfilariae in any of the analyzed intervals from day 0 to 304 days, and it is possible to conclude that the use of 2% formalin in the modified Knott technique allows the microfilariae to be identified in a period of 304 days. days after processing the sample without changes in its morphology.
Existem diversos métodos de diagnóstico laboratorial de filarídeos, os mais utilizados são a gota espessa e o método do Knott. Ambos são de rápida execução, possui baixo custo e permitem observar a presença, quantificar e analisar as características morfológicas das microfilárias. Conhecer a viabilidade morfológica das microfilárias fixadas tem importância prática, pois permite o transporte de amostras para um laboratório, facilita estudos epidemiológicos, e permite o armazenamento de amostras para fins didáticos. Desta maneira, o objetivo do trabalho foi avaliar a viabilidade morfológica das microfilárias fixadas em teste do knott modificado refrigerado utilizando formalina a 2%. Para realização da técnica de knott modificado foram utilizadas 10 amostras de cães microfilarêmicos, com idade superior a 6 meses. Para avaliar o tempo de viabilidade morfológica das microfilárias no concentrado de Knott modificado, foram repedidas as avaliações após intervalos de 0,1,7, 30, 60, 120, 180, 240 e 304 dias. No presente estudo não verificamos diferença na morfologia das microfilárias em nenhum dos intervalos analisados deste do dia 0 até 304 dias, sendo possível concluir que a utilização da formalina a 2% na técnica de Knott modificada permite que as microfilárias possam ser identificadas em período de 304 dias após o processamento da amostra sem que ocorram alterações na sua morfologia.
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Background and Objective: Pancreatic adenocarcinoma remains a dismal disease and is expected to become an even greater burden in the near future. This review focuses on the different surgical aspects for pancreaticoduodenectomy (PD), distal and total pancreatectomy (TP), incorporating lessons from both the western and eastern visions in treating pancreatic cancer. Methods: We conducted an extensive literature review through PubMed, prioritizing papers published in the last 5 years, but older emblematic papers were also included. We included articles that explored the treatment of pancreatic adenocarcinoma, with focus on the surgical aspect and strategies to improve outcomes. References of selected articles were also reviewed to identify any missed studies. Only papers in English were included. Key Content and Findings: As evidence continues to build, it is clear that both systemic and surgical therapies have a fundamental and complementary role. State of art surgical treatment encompasses complete mesopancreas excision for radical lymphadenectomy. Preoperative planning of dissection planes, extensive knowledge of vascular anatomic variations, oncological principles and expertise for vascular resections are mandatory to perform a more radical operation, in pursuit of improved outcomes. Conclusions: Based on current data, patient selection remains key and a more radical surgical approach brings more accomplishing results bringing as to believe that more is better.
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INTRODUCTION: Fungal infections of the central nervous system present a variety of clinical syndromes, such as meningitis, encephalitis, raised intracranial pressure with a nonspecific presentation, and, in the last two decades, have increased the incidence of these fungal infections. Fungal meningoencephalitis is frequently associated with Cryptococcus, but this report stands out for presenting one species of Penicillium genus. OBJECTIVES: Here, we present the first case of meningoencephalitis associated with brain injury caused by Penicillium chrysogenum, in a patient who is immunocompetent and was admitted to Hospital Naval Marcílio Dias, Rio de Janeiro, Brazil. METHODS: To identify the fungal species, we performed phenotypic and genotypic methodologies, from the culture to the sequencing of internal transcribed spacer region, and ß-tubulin gene, a rare fungus in cerebrospinal fluid cultures, belonging to the genus Penicillium, was identified. CONCLUSION: We highlight the importance of the first report of meningoencephalitis caused by P. chrysogenum in a patient who is immunocompetent, registered in Brazil. We also emphasize the need for further studies to determine an effective treatment with the least possible side effects for patients infected by fungi that are rarely related to the most severe forms of invasive infections.
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Meningitis , Meningoencefalitis , Micosis , Penicillium chrysogenum , Penicillium , Humanos , Penicillium chrysogenum/genética , Brasil/epidemiología , Meningoencefalitis/diagnóstico , Meningoencefalitis/tratamiento farmacológico , Penicillium/genéticaRESUMEN
Introduction: Everyday, gas station attendants ate exposed to numerous toxic substances found in fuels. Benzene stands out among these toxic chemical agents; depending on its concentration, it can cause mucosal irritation or even pulmonary edema. A considerable number of gas station attendants is aware of the risks associated with benzene poisoning, but they are not aware of the risks associated with other automotive pollutants. Objectives: To evaluate and understand the risk perception of automotive fuel poisoning among gas station attendants in the Sorocaba region, state of São Paulo. Methods: Sixty gas station attendants were evaluated in the Sorocaba region. Data were collected between October 2019 and September 2020 using a semi-structured, individual, closed-ended questionnaire whose questions identified the participants' perception and aimed to analyze: the general profile of the studied population; practices for handling fuels and knowledge on their toxic effects, use and instructions of personal protective equipment, symptoms possibly associated with fuel exposure, the participants' perception of poisoning risks, and their participation in occupational medicine programs. Results: The obtained results demonstrated that most gas station attendants wore at least basic personal protective equipment, and some of them reported symptoms linked with benzene exposure. Still, a considerable number of employers does not provide adequate training to gas station attendants, which is possibly associated with inadequate use of personal protective equipment. Conclusions: Our data showed indications of non-compliance by gas station attendants as to the use of personal protective equipment at the workplace, and by employers as to the provision of adequate training.
Introdução: Todos os dias, trabalhadores frentistas são expostos a inúmeras substâncias tóxicas presentes nos combustíveis. Entre os agentes químicos tóxicos, destaca-se o benzeno que, dependendo da concentração, pode causar irritabilidade de mucosas e até edema pulmonar. Um número considerável de frentistas conhece os riscos associados à intoxicação por benzeno, porém desconhece os riscos causados pelos demais poluentes automotivos. Objetivos: Avaliar e compreender a percepção de risco de intoxicações por combustíveis automotivos em frentistas da região de Sorocaba, São Paulo. Métodos: Foram 60 frentistas avaliados na região de Sorocaba. A coleta de dados foi realizada de outubro de 2019 a setembro de 2020, a partir de um questionário semiestruturado, individual e fechado, cujas questões identificaram a percepção dos sujeitos envolvidos, buscando analisar: perfil geral da população estudada; práticas que envolvem o manuseio de combustíveis e o conhecimento sobre efeitos tóxicos; uso e instruções quanto aos equipamentos de proteção individual; sintomas possivelmente associados com exposição a combustíveis; percepção dos sujeitos quanto ao risco de intoxicações; participação em programas de medicina ocupacional. Resultados: Os resultados obtidos demonstraram que boa parte dos frentistas utiliza ao menos equipamentos de proteção individual básicos, e que alguns reportam sintomas ligados à exposição ao benzeno. Ainda, um número considerável de empregadores não fornece treinamento adequado aos frentistas, o que possivelmente se associa com uso inadequado de equipamentos de proteção individual. Conclusões: Os dados apresentados mostram que existe indícios de inobservância por parte dos frentistas quanto ao uso de equipamentos de proteção individual no local de trabalho e por parte de empregadores quanto à disponibilização de treinamento adequado.
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OBJECTIVE: The aim of this study was to identify which types of skin reactions are associated with slime toys and which of their ingredients are most frequently involved in cases of poisoning. DATA SOURCE: Between January and July 2021, articles were selected using PubMed, SciELO, and LILACS databases. The following descriptors were used: (dermatitis OR rash OR eczema OR inflammation) AND slime. Inclusion criteria were articles available in full, in either Portuguese, English, or Spanish, published between January 2000 and July 31, 2021, and articles reporting cases of contact dermatitis or eczema potentially or directly attributed to slime toys. Articles not meeting these criteria and duplicate texts in the databases were excluded. DATA SYNTHESIS: In total, 65 publications were identified, of which 16 were included in this review. This resulted in a total of 22 children (2 males, 20 females), aged between 4 and 13 years, who were reportedly intoxicated by slime toys, most of these being linked to homemade preparations. Studies reported the occurrence of contact or allergic dermatitis on hands, fingers, nails, forearms, and cheeks. The most allergenic and/or irritant ingredients included liquid detergent and soap. Additionally, patch tests identified positive reactions to methylisothiazolinone and methylchloroisothiazolinone, the preservatives used by chemical industries on preparation of glue, soap, detergents, etc. CONCLUSIONS: Although slime toys might be important for improving motor development and parental relationships, homemade slime toy recipes include several allergenic and irritant ingredients which might be exposed to vulnerable children and cause intoxications. Therefore, homemade slime toys preparations should be used cautiously and under the supervision of adults.
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Dermatitis Alérgica por Contacto , Eccema , Niño , Masculino , Adulto , Femenino , Adolescente , Humanos , Preescolar , Dermatitis Alérgica por Contacto/epidemiología , Dermatitis Alérgica por Contacto/etiología , Irritantes , Jabones , Pruebas del Parche/efectos adversos , Eccema/complicaciones , AlérgenosRESUMEN
BACKGROUND: Diffusion tensor imaging has emerged as a promising tool for quantitative analysis of neuronal damage in Parkinson disease, with potential value for diagnostic and prognostic evaluation. PURPOSE: The aim of this study was to examine Parkinson disease-associated alterations in specific brain regions revealed by diffusion tensor imaging and how such alterations correlate with clinical variables. MATERIAL AND METHODS: Diffusion tensor imaging was performed on 42 Parkinson disease patients and 20 healthy controls with a 1.5-T scanner. Manual fractional anisotropy measurements were performed for the ventral, intermediate, and dorsal portions of the substantia nigra, as well as for the cerebral peduncles, putamen, thalamus, and supplementary motor area. The correlation analysis between these measurements and the clinical variables was performed using χ2 variance and multiple linear regression. RESULTS: Compared to healthy controls, Parkinson disease patients had significantly reduced fractional anisotropy values in the substantia nigra (P < .05). Some fractional anisotropy measurements in the substantia nigra correlated inversely with duration of Parkinson disease and Parkinson disease severity scores. Reduced fractional anisotropy values in the substantia nigra were also correlated inversely with age variable. fractional anisotropy values obtained for the right and left putamen varied significantly between males and females in both groups. CONCLUSION: Manual fractional anisotropy measurements in the substantia nigra were confirmed to be feasible with a 1.5-T scanner. Diffusion tensor imaging data can be used as a reliable biomarker of Parkinson disease that can be used to support diagnosis, prognosis, and progression/treatment monitoring.
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The intestinal microbiota modulates IL-22 production in the intestine, including the induction of IL-22-producing CD4+ T helper cells. Which specific bacteria are responsible for the induction of these cells is less well understood. Here, we demonstrate through the use of novel gnotobiotic knock-in reporter mice that segmented filamentous bacteria (SFB), which are known for their ability to induce Th17 cells, also induce distinct IL-17A negative CD4+ T cell populations in the intestine. A subset of these cells instead produces IL-22 upon restimulation ex vivo and also during enteric infections. Furthermore, they produce a distinct set of cytokines compared to Th17 cells including the differential expression of IL-17F and IFN-γ. Importantly, genetic models demonstrate that these cells, presumably Th22 cells, develop independently of intestinal Th17 cells. Together, our data identifies that besides Th17, SFB also induces CD4+ T cell populations, which serve as immediate source of IL-22 during intestinal inflammation.
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Linfocitos T CD4-Positivos/inmunología , Microbioma Gastrointestinal/inmunología , Interleucinas/inmunología , Células Th17/inmunología , Animales , Linfocitos T CD4-Positivos/metabolismo , Interleucinas/biosíntesis , Mucosa Intestinal/microbiología , Ratones , Ratones Endogámicos C57BL , Salmonella typhi , Células Th17/metabolismo , Fiebre Tifoidea/inmunología , Fiebre Tifoidea/microbiología , Interleucina-22RESUMEN
Although vaccination against Coronavirus disease-2019 (COVID-19) is still occurring, several adverse effects temporally related to these vaccines are already being reported, even if through isolated case reports. In the present study, we describe the lesions seen on magnetic resonance imaging (MRI) of three patients who developed neurological symptoms after receiving the ChAdOX1 nCoV-19 vaccine (Oxford/AstraZeneca). The first patient presented with an ischemic stroke in the posterior limb of the left internal capsule, two days after vaccination. The second patient presented with a left facial nerve palsy, seven days after vaccination. The third patient presented with myelitis, eight days after receiving the vaccine. All patients presented the symptoms after the first dose of the vaccine and did not have a history of previous COVID-19. The real incidence of these types of complications is not known yet, but it is important to consider the possibility of COVID-19 vaccine complications, in patients with a recent history of vaccination and recent development of neurological symptoms, even though this association is only casual. Longitudinal studies are necessary to further analyze the incidence of the adverse effects of each vaccine against SARS-CoV-2.
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COVID-19 , Vacunas , Vacunas contra la COVID-19 , ChAdOx1 nCoV-19 , Humanos , Neuroimagen , SARS-CoV-2 , Vacunas/efectos adversosRESUMEN
The microbiota of the gut-lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17- cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut-lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.
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Disbiosis/etiología , Disbiosis/microbiología , Interferón gamma/biosíntesis , Obesidad/complicaciones , Obesidad/microbiología , Neumonía/microbiología , Tuberculosis/complicaciones , Inmunidad Adaptativa , Animales , Carga Bacteriana , Susceptibilidad a Enfermedades , Disbiosis/inmunología , Trasplante de Microbiota Fecal , Heces/microbiología , Femenino , Leucocitos/metabolismo , Pulmón/inmunología , Pulmón/microbiología , Pulmón/patología , Ratones Endogámicos C57BL , Microbiota , Obesidad/inmunología , Neumonía/inmunología , Tuberculosis/inmunologíaRESUMEN
Patients with paracoccidioidomycosis (PCM) exhibit a suppression of the cellular immune response characterized by negative delayed-type hypersensitivity (DTH) to Paracoccidioides brasiliensis antigens, the apoptosis of lymphocytes, and high levels of expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), interleukin-10 (IL-10), and transforming growth factor ß (TGF-ß). The aim of this study was to investigate whether and how regulatory T cells (Treg cells) are involved in this immunosuppression by analyzing the number, phenotype, and activity of these cells in patients with active disease (AD group) and patients who had received treatment (TD group). Our results showed that the AD patients had more Treg cells than the TD patients or controls (C group) and also had elevated levels of expression of regulatory markers (glucocorticoid-induced tumor necrosis factor [TNF] receptor-related protein [GITR], CTLA-4, CD95L, LAP-1, and CD38). An analysis of regulatory activity showed that Treg cells from the AD group had greater activity than did cells from the other groups and that cell-cell contact is mandatory for this activity in the C group but was only partially involved in the regulatory activity of cells from AD patients. The addition of anti-IL-10 and anti-TGF-ß neutralizing antibodies to the cultures showed that the production of cytokines may be another mechanism used by Treg cells. In conclusion, the elevated numbers of these cells with an increased regulatory phenotype and strong suppressive activity suggest a potential role for them in the immunosuppression characteristic of paracoccidioidomycosis. In addition, our results indicate that while Treg cells act by cell-cell contact, cytokine production also plays an important role.
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Huésped Inmunocomprometido , Paracoccidioidomicosis/inmunología , Linfocitos T Reguladores/fisiología , Antifúngicos/uso terapéutico , Técnicas de Cocultivo , Citocinas/genética , Citocinas/metabolismo , Regulación de la Expresión Génica/inmunología , Humanos , Inmunidad Celular , Paracoccidioidomicosis/tratamiento farmacológico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Subgrupos de Linfocitos T/citologíaRESUMEN
BACKGROUND: Patients with diabetes mellitus who undergo coronary stenting are at increased risk of restenosis. It is known that inflammation plays a crucial role in restenosis. OBJECTIVE: We assessed the inflammatory response to elective coronary stent implantation (CSI) in stable diabetic and nondiabetic patients. METHODS: C-reactive protein (CRP), soluble (s) P-selectin, and soluble intercellular adhesion molecule (sICAM)-1 plasma levels were determined in diabetic (n = 51) and nondiabetic (n = 56) patients before and 48 hours and 4 weeks after bare metal stenting (BMS). RESULTS: Diabetic patients presented significantly higher inflammatory marker levels before and after CSI. Nonetheless, diabetic and nondiabetic patients had postintervention peak of markers attained within 48 hours. At baseline, diabetic and nondiabetic patients presented CRP levels of 5.0 +/- 20.1 (P < or = 0.04) and 3.8 +/- 9.4 microg/ml and, at 48 hours postintervention, 22.0 +/- 20.2 (P = 0.001; P = 0.002) and 12.6 +/- 11.3 (P < or = 0.0001) microg/ml. Regarding sP-selectin, diabetic and nondiabetic patients obtained levels of, at baseline, 182 +/- 118 (P < or = 0.04) and 105 +/- 48 ng/ml and, at 48 hours, 455 +/- 290 (P = 0.001; P < or = 0.01) and 215 +/- 120 (P < or = 0.04) ng/ml. For diabetic and nondiabetic patients, sICAM-1 levels were, at baseline, 248 +/- 98 (P < or = 0.04) and 199 +/- 94 ng/ml and, at 48 hours, 601 +/- 201 (P = 0.001; P < or = 0.01) and 283 +/- 220 (P = 0.001) ng/ml. At 4 weeks, for all patients, markers returned to preprocedural levels: versus before PCI: *P = 0.001, (section sign)P < or = 0.0001; versus nondiabetic patients: (#)P < or = 0.04, (paragraph sign)P = 0.002, (Upsilon)P < or = 0.01. CONCLUSIONS: Diabetic and nondiabetic patients exhibited a temporal inflammatory response after an elective BMS. However, diabetic patients present higher preprocedural levels of CRP, sP-selectin, and sICAM-1 and reveal a further exacerbated inflammatory response after intervention. The differences in inflammatory response may have implications in restenosis within these two sets of patients.
Asunto(s)
Proteína C-Reactiva/análisis , Diabetes Mellitus/sangre , Inflamación/sangre , Molécula 1 de Adhesión Intercelular/sangre , Selectina-P/sangre , Stents/efectos adversos , Anciano , Angina de Pecho/terapia , Constricción Patológica , Femenino , Estudios de Seguimiento , Humanos , Inflamación/etiología , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Abstract Objective: The aim of this study was to identify which types of skin reactions are associated with slime toys and which of their ingredients are most frequently involved in cases of poisoning. Data source: Between January and July 2021, articles were selected using PubMed, SciELO, and LILACS databases. The following descriptors were used: (dermatitis OR rash OR eczema OR inflammation) AND slime. Inclusion criteria were articles available in full, in either Portuguese, English, or Spanish, published between January 2000 and July 31, 2021, and articles reporting cases of contact dermatitis or eczema potentially or directly attributed to slime toys. Articles not meeting these criteria and duplicate texts in the databases were excluded. Data synthesis: In total, 65 publications were identified, of which 16 were included in this review. This resulted in a total of 22 children (2 males, 20 females), aged between 4 and 13 years, who were reportedly intoxicated by slime toys, most of these being linked to homemade preparations. Studies reported the occurrence of contact or allergic dermatitis on hands, fingers, nails, forearms, and cheeks. The most allergenic and/or irritant ingredients included liquid detergent and soap. Additionally, patch tests identified positive reactions to methylisothiazolinone and methylchloroisothiazolinone, the preservatives used by chemical industries on preparation of glue, soap, detergents, etc. Conclusions: Although slime toys might be important for improving motor development and parental relationships, homemade slime toy recipes include several allergenic and irritant ingredients which might be exposed to vulnerable children and cause intoxications. Therefore, homemade slime toys preparations should be used cautiously and under the supervision of adults.
Resumo Objetivo: Identificar quais tipos de reações de pele e ingredientes do brinquedo slime estão frequentemente envolvidos em relatos de intoxicação. Fontes de dados: Entre janeiro e julho de 2021, ocorreu a seleção dos artigos, utilizando-se as bases de dados: United States National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). Foram utilizados os seguintes descritores: (dermatitis OR rash OR eczema OR inflammation) AND slime. Incluíram-se artigos disponíveis na íntegra, em português, inglês ou espanhol, publicados entre janeiro de 2000 e 31 julho de 2021, que relatassem casos de crianças e adolescentes que apresentaram reação cutânea após a manipulação do brinquedo slime. Foram excluídos artigos sem aderência ao tema e textos duplicados nas bases de dados. Síntese dos dados: Identificaram-se 65 publicações, sendo 16 utilizadas para a elaboração desta revisão. Isso resultou no total de 22 crianças (duas do sexo masculino, 20 do feminino), com idades entre quatro e 13 anos, que teriam sido intoxicadas por slime, a maioria dos casos ligado a preparações caseiras. Estudos relataram a ocorrência de dermatite de contato ou alérgica nas mãos, dedos, unhas, antebraços e bochechas. Os ingredientes mais alergênicos e/ou irritantes foram detergentes líquidos e sabão. Ademais, o patch test identificou reações positivas para metilisotiazolinona e metilcloroisotiazolinona, que são conservantes utilizados em produtos como cola, sabão, detergente, etc. Conclusões: Ainda que o brinquedo slime seja importante para o desenvolvimento motor e das relações parentais, receitas caseiras incluem vários ingredientes alergênicos e irritantes, que podem ser expostos a crianças vulneráveis e causar intoxicações. Sendo assim, as preparações do slime devem ser feitas com cautela e sob supervisão de adultos.
RESUMEN
Parkinson's disease is one of the most common neurodegenerative diseases. Clinically, it is characterized by motor symptoms. Parkinson's disease should be differentiated from atypical parkinsonism conditions. Conventional magnetic resonance imaging is the primary imaging method employed in order to facilitate the differential diagnosis, and its role has grown after the development of advanced techniques such as diffusion-weighted imaging. The purpose of this article was to review the role of magnetic resonance imaging in Parkinson's disease and in the differential diagnosis with atypical parkinsonism, emphasizing the diffusion technique.
A doença de Parkinson é uma das doenças neurodegenerativas mais comuns. Clinicamente, é caracterizada por sintomas motores, devendo ser diferenciada com outras doenças que cursam com parkinsonismo, definidas como parkinsonismo atípico. A ressonância magnética convencional é o principal método de imagem para auxiliar este diagnóstico diferencial e, atualmente, seu papel tem crescido com as técnicas avançadas, como a difusão. O objetivo deste artigo é revisar o papel da ressonância magnética na doença de Parkinson e no diagnóstico diferencial com parkinsonismo atípico, com ênfase na técnica de difusão.