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Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Histopathologically, AD presents two pathognomonic hallmarks: (1) neurofibrillary tangles, characterized by intracellular deposits of hyperphosphorylated tau protein, and (2) extracellular amyloid deposits (amyloid plaques) in the brain vasculature (cerebral amyloid angiopathy; CAA). It has been proposed that vascular amyloid deposits could trigger neurovascular unit (NVU) dysfunction in AD. The NVU is composed primarily of astrocytic feet, endothelial cells, pericytes, and basement membrane. Although physical exercise is hypothesized to have beneficial effects against AD, it is unknown whether its positive effects extend to ameliorating CAA and improving the physiology of the NVU. We used the triple transgenic animal model for AD (3xTg-AD) at 13 months old and analyzed through behavioral and histological assays, the effect of voluntary physical exercise on cognitive functions, amyloid angiopathy, and the NVU. Our results show that 3xTg-AD mice develop vascular amyloid deposits which correlate with cognitive deficits and NVU alteration. Interestingly, the physical exercise regimen decreases amyloid angiopathy and correlates with an improvement in cognitive function as well as in the underlying integrity of the NVU components. Physical exercise could represent a key therapeutic approach in cerebral amyloid angiopathy and NVU stability in AD patients.
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Doença de Alzheimer , Angiopatia Amiloide Cerebral , Camundongos , Animais , Doença de Alzheimer/metabolismo , Placa Amiloide/metabolismo , Células Endoteliais/metabolismo , Camundongos Transgênicos , Angiopatia Amiloide Cerebral/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Peptídeos beta-Amiloides/metabolismoRESUMO
Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1-5% of the total number of cases. It is categorized as early onset (EOAD; <65 years of age) and presents genetic mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or the Amyloid precursor protein (APP). Sporadic AD represents 95% of the cases and is categorized as late-onset (LOAD), occurring in patients older than 65 years of age. Several risk factors have been identified in sporadic AD; aging is the main one. Nonetheless, multiple genes have been associated with the different neuropathological events involved in LOAD, such as the pathological processing of Amyloid beta (Aß) peptide and Tau protein, as well as synaptic and mitochondrial dysfunctions, neurovascular alterations, oxidative stress, and neuroinflammation, among others. Interestingly, using genome-wide association study (GWAS) technology, many polymorphisms associated with LOAD have been identified. This review aims to analyze the new genetic findings that are closely related to the pathophysiology of AD. Likewise, it analyzes the multiple mutations identified to date through GWAS that are associated with a high or low risk of developing this neurodegeneration. Understanding genetic variability will allow for the identification of early biomarkers and opportune therapeutic targets for AD.
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Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/metabolismo , Estudo de Associação Genômica Ampla , Mutação , Doenças Neurodegenerativas/genética , Presenilina-1/genética , Presenilina-2/genéticaRESUMO
Central nervous system (CNS) infections including meningitis and encephalitis, resulting from the blood-borne spread of specific microorganisms, provoke nervous tissue damage due to the inflammatory process. Moreover, different pathologies such as sepsis can generate systemic inflammation. Bacterial lipopolysaccharide (LPS) induces the release of inflammatory mediators and damage molecules, which are then released into the bloodstream and can interact with structures such as the CNS, thus modifying the blood-brain barrier's (BBB´s) and blood-cerebrospinal fluid barrier´s (BCSFB´s) function and inducing aseptic neuroinflammation. During neuroinflammation, the participation of glial cells (astrocytes, microglia, and oligodendrocytes) plays an important role. They release cytokines, chemokines, reactive oxygen species, nitrogen species, peptides, and even excitatory amino acids that lead to neuronal damage. The neurons undergo morphological and functional changes that could initiate functional alterations to neurodegenerative processes. The present work aims to explain these processes and the pathophysiological interactions involved in CNS damage in the absence of microbes or inflammatory cells.
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Encefalite , Doenças Neuroinflamatórias , Humanos , Inflamação/metabolismo , Encefalite/patologia , Microglia/metabolismo , Neurônios/metabolismoRESUMO
Tuberculosis (TB) of the central nervous system (CNS) presents high mortality due to brain damage and inflammation events. The formation and deposition of immune complexes (ICs) in the brain microvasculature during Mycobacterium tuberculosis (Mtb) infection are crucial for its pathobiology. The relevance of ICs to Mtb antigens in the pathogenesis of CNS-TB has been poorly explored. Here, we aimed to establish a murine experimental model of ICs-mediated brain vasculitis induced by cell wall antigens of Mtb. We administered a cell wall extract of the prototype pathogenic Mtb strain H37Rv to male BALB/c mice by subcutaneous and intravenous routes. Serum concentration and deposition of ICs onto blood vessels were determined by polyethylene glycol precipitation, ELISA, and immunofluorescence. Histopathological changes in the brain, lung, spleen, liver, and kidney were evaluated by hematoxylin and eosin staining. Our results evidenced that vasculitis developed in the studied tissues. High serum levels of ICs and vascular deposition were evident in the brain, lung, and kidneys early after the last cell wall antigen administration. Cell wall Mtb antigens induce strong type III hypersensitivity reactions and the development of systemic vasculitis with brain vascular changes and meningitis, supporting a role for ICs in the pathogenesis of TB.
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Mycobacterium tuberculosis , Tuberculose , Vasculite , Masculino , Animais , Camundongos , Complexo Antígeno-Anticorpo , Modelos Animais de Doenças , Tuberculose/microbiologia , Antígenos de Bactérias , Parede CelularRESUMO
Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by Mycobacterium tuberculosis. The mechanisms by which M. tuberculosis bacilli enter the CNS are still unclear. However, the BBB and the BCSFB have been proposed as possible routes of access into the brain. We previously reported that certain strains of M. tuberculosis possess an enhanced ability to cause secondary CNS infection in a mouse model of progressive pulmonary tuberculosis. Here, we evaluated the morphostructural and molecular integrity of CNS barriers. For this purpose, we analyzed through transmission electron microscopy the ultrastructure of brain parenchymal microvessels and choroid plexus epithelium from animals infected with two mycobacterial strains. Additionally, we determined the expression of junctional proteins and cytokines by immunological techniques. The results showed that the presence of M. tuberculosis induced disruption of the BCSFB but no disruption of the BBB, and that the severity of such damage was related to the strain used, suggesting that variations in the ability to cause CNS disease among distinct strains of bacteria may also be linked to their capacity to cause direct or indirect disruption of these barriers. Understanding the pathophysiological mechanisms involved in CNS tuberculosis may facilitate the establishment of new biomarkers and therapeutic targets.
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Doenças do Sistema Nervoso Central , Tuberculose Meníngea , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo , Doenças do Sistema Nervoso Central/metabolismo , Epitélio , CamundongosRESUMO
The α-synucleinopathies constitute a subset of neurodegenerative disorders, of which Parkinson's disease (PD) is the most common worldwide, characterized by the accumulation of misfolded α-synuclein in the cytoplasm of neurons, which spreads in a prion-like manner to anatomically interconnected brain areas. However, it is not clear how α-synucleinopathy triggers neurodegeneration. We recently developed a rat model through a single intranigral administration of the neurotoxic ß-sitosterol ß-D-glucoside (BSSG), which produces α-synucleinopathy. In this model, we aimed to evaluate the temporal pattern of levels in oxidative and nitrosative stress and mitochondrial complex I (CI) dysfunction and how these biochemical parameters are associated with neurodegeneration in different brain areas with α-synucleinopathy (Substantia nigra pars compacta, the striatum, in the hippocampus and the olfactory bulb, where α-syn aggregation spreads). Interestingly, an increase in oxidative stress and mitochondrial CI dysfunction accompanied neurodegeneration in those brain regions. Furthermore, in silico analysis suggests a high-affinity binding site for BSSG with peroxisome proliferator-activated receptors (PPAR) alpha (PPAR-α) and gamma (PPAR-γ). These findings will contribute to elucidating the pathophysiological mechanisms associated with α-synucleinopathies and lead to the identification of new early biomarkers and therapeutic targets.
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Encéfalo , Complexo I de Transporte de Elétrons , Mitocôndrias , Estresse Oxidativo , Sinucleinopatias , alfa-Sinucleína , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Complexo I de Transporte de Elétrons/metabolismo , Mitocôndrias/metabolismo , Estresse Nitrosativo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Ratos , Sinucleinopatias/metabolismo , Sinucleinopatias/fisiopatologia , alfa-Sinucleína/química , alfa-Sinucleína/metabolismoRESUMO
Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.
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INTRODUCTION: Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB due to its high mortality and functional sequelae. There are several differential diagnoses for TB; and, it can also cause secondary conditions, such as vasculitis. METHODOLOGY: 155 biopsies, corresponding to 155 different patients out of 5,386 registered biopsies from 2008-2013, met the criteria of unknown etiology vasculitis and evidence of cerebral vascular disease. These were analyzed to assess the presence of central nervous system TB. The selected cases were assessed with Suzaan Marais (SM) criteria for clinical tuberculosis. After that, Ziehl-Neelsen (ZN) staining and polymerase chain reaction (PCR) were performed to amplify a fragment of the insertion sequence IS6110 of M. tuberculosis. 21 patients met the criteria for definitive tuberculosis by ZN staining and PCR, and 2 met the criteria for possible tuberculosis. Tumor necrosis factor (TNF)-α, TNF-R1, and TNF-R2 were determined by immunohistochemistry in histological sections from formalin-fixed paraffin-embedded (FF-PE) tissues in the 23 selected patients. RESULTS: Granulomatous TB was present in almost half of the cases. TNF-R1 and TNF-R2 were expressed mainly in blood vessels, histiocytes, and macrophages. TNF-R2 expression was higher than the other markers, which suggests an anti-inflammatory response against M. tuberculosis. CONCLUSIONS: The histopathological presentation of TB is not always limited to granulomas, abscesses, or meningitis; there are also clinical presentations characterized only with chronic inflammation of nervous and vascular tissue.
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Mycobacterium tuberculosis , Tuberculose , Vasculite , Humanos , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral , Tuberculose/diagnóstico , Fator de Necrose Tumoral alfa , Vasculite/complicaçõesRESUMO
Osteosarcopenic obesity (OSO) is characterized by bone density, mass, and muscle strength loss, in conjunction with adipose tissue increase. OSO impairs physical activity and mobility, provoking autonomy loss; also, it is known that augmenting body fat in the elderly decreases life expectancy. The main factors influencing this health deterioration are the inflammatory environment induced by adipose tissue and its infiltration into muscle tissue, which leads to oxidative stress generation. Currently, there are several treatments to delay OSO, among which exercise training stands out because it improves muscle fiber quality and quantity and decreases adipose tissue. We have recently demonstrated that the combined treatment between moderate exercise and metformin slows sarcopenia's onset by a mechanism that includes adipose reduction and REDOX regulation. On the other hand, tert-butylhydroquinone (tBHQ) is a well-known antioxidant that counteracts oxidative stress. Therefore, to slow down obesity's harmful effects on muscle mass and bone mineral density, we performed different interventions, including combining a Fartlek-type exercise routine with metformin and tBHQ administration, in a model of middle-aged female Wistar rats with obesity induced with a hypercaloric diet. Our results showed that the combined exercise-metformin-tBHQ treatment increased muscle mass and strength, decreased body weight, body mass index, and fat percentage, and improved redox status, thus increasing animal survival.
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Doenças Ósseas Metabólicas/prevenção & controle , Hidroquinonas/farmacologia , Metformina/farmacologia , Obesidade/terapia , Condicionamento Físico Animal , Sarcopenia/prevenção & controle , Animais , Doenças Ósseas Metabólicas/etiologia , Feminino , Obesidade/complicações , Ratos , Sarcopenia/etiologiaRESUMO
BACKGROUND: Cholesteatomas are benign tumors mainly composed of cholesterol crystals that rarely arise within the orbit. However, orbital cholesteatomas require a complete surgical resection due to their recidivating potential. Transcranial approaches offering a broad surgical exposure of the orbital cavity have been scarcely used for the management of these tumors. Here, we provide evidence of the benefits of the pterional craniotomy for the surgical resection of orbital tumors by sharing our experience in the surgical management of a cholesteatoma of the superotemporal orbital wall. CASE PRESENTATION: A 45-year-old Hispanic man with a 2-year history of progressive proptosis of the left eye attended to our center complaining of diplopia and migraine. At his arrival, physical examination revealed ptosis, palpebral edema, and exophthalmos of the left eye, as well as the abolishment of the ipsilateral photomotor and consensual responses. Fundoscopy showed mild optic atrophy, whereas a T2-weighted magnetic resonance imaging (MRI) of the head showed a hyperintense mass arising at the superotemporal wall of the orbit that was displacing the eyeball. The tumor was resected using a pterional craniotomy without postoperative complications. The histopathological analysis of the tumor revealed a cholesteatoma. The patient recovered the functionality of the left eye with no visual sensitive deficits nor tumor recurrence 1 year after the surgery. CONCLUSIONS: Our results support the use of the pterional craniotomy as a safe procedure for the surgical resection of cholesteatomas arising at the superotemporal walls of the orbit, with low postoperative morbidity.
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Colesteatoma , Exoftalmia , Craniotomia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Órbita/diagnóstico por imagem , Órbita/cirurgiaRESUMO
Our work evaluated cardiac function and mitochondrial bioenergetics parameters in hearts from male Wistar rats subjected to the UUO model during 28 days of progression. We measured markers of kidney damage and inflammation in plasma and renal fibrosis by histological analysis and Western blot. Cardiac function was evaluated by echocardiography and proteins involved in cardiac damage by Western blot. Oxygen consumption and transmembrane potential were monitored in cardiac mitochondria using high-resolution respirometry. We also determined the activity of ATP synthase and antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and catalase. Our results show that, although renal dysfunction is established in animals subjected to ureteral obstruction, cardiac function is maintained along with mitochondrial function and antioxidant enzymes activity after 28 days of injury evolution. Our results suggest that renocardiac syndrome might develop but belatedly in obstruction-induced renal damage, opening the opportunity for treatment to prevent this condition.
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The mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the establishment of adaptive immunity. Hence, several innate immune mechanisms may participate in the containment of Mtb infection and prevent extrapulmonary disease manifestations. Natural killer (NK) cells participate in defensive processes that distinguish latent TB infection (LTBI) from active pulmonary TB (PTB). However, their role in TBM is unknown. Here, we performed a cross-sectional analysis of circulating NK cellCID="C008" value="s" phenotype in a prospective cohort of TBM patients (n = 10) using flow cytometry. Also, we addressed the responses of memory-like NK cell subpopulations to the contact with Mtb antigens in vitro. Finally, we determined plasma levels of soluble NKG2D receptor ligands in our cohort of TBM patients by enzyme-linked immunosorbent assay (ELISA). Our comparative groups consisted of individuals with LTBI (n = 11) and PTB (n = 27) patients. We found that NK cells from TBM patients showed lower absolute frequencies, higher CD69 expression, and poor expansion of the CD45RO+ memory-like subpopulation upon Mtb exposure in vitro compared to LTBI individuals. In addition, a reduction in the frequency of CD56brightCD16- NK cells characterized TBM patients but not LTBI or PTB subjects. Our study expands on earlier reports about the role of NK cells in TBM showing a reduced frequency of cytokine-producing cells compared to LTBI and PTB.
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Células Matadoras Naturais/imunologia , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Meníngea/imunologia , Tuberculose Pulmonar/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata , Imunofenotipagem , Células Matadoras Naturais/metabolismo , Tuberculose Latente/sangue , Tuberculose Latente/microbiologia , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Tuberculose Meníngea/sangue , Tuberculose Meníngea/microbiologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1ß, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.
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COVID-19 , Citocinas , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Metaloproteinase 1 da Matriz , Metaloproteinase 3 da Matriz , Receptores Imunológicos , Adulto , Idoso , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Citocinas/sangue , Citocinas/imunologia , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/metabolismo , Influenza Humana/sangue , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Masculino , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 1 da Matriz/imunologia , Metaloproteinase 3 da Matriz/sangue , Metaloproteinase 3 da Matriz/imunologia , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores Imunológicos/sangue , Receptores Imunológicos/imunologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
[This corrects the article DOI: 10.3389/fimmu.2021.633297.].
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The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.
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Biomarcadores/metabolismo , Quimiocinas CXC/metabolismo , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/diagnóstico , Pulmão/metabolismo , Mycobacterium tuberculosis/fisiologia , SARS-CoV-2/fisiologia , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/mortalidade , Quimiocinas CXC/genética , Quimiocinas CXC/imunologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Influenza Humana/mortalidade , Pulmão/patologia , Masculino , México , Pessoa de Meia-Idade , Pandemias , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Análise de Sobrevida , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/mortalidade , Adulto JovemRESUMO
INTRODUCTION: Intestinal and extraintestinal infections by Aeromonas spp., remain controversial, due to the existence of healthy carriers of Aeromonas spp. In children under five years old, the diarrhea of infectious origin constitutes the second cause of mortality and remains a major concern for public health. The aim of this work was to detect the pheno/genotype of ß-lactamases and class 1 integrons in Aeromonas spp., strains isolated from pediatric patients in a tertiary referral hospital in Mexico. METHODOLOGY: Sixty-six strains of Aeromonas spp., were isolated from clinical samples of pediatric origin and were identified by RFLP-PCR 16S rRNA. Resistance phenotype according to CLSI, genetic and phenotypic detection of extended-spectrum ß-lactamases (ESBL) and metallo-b-lactamases (MBL) was performed. Finally, characterization of class 1 integrons was performed. RESULTS: Aeromonas spp., strains of diarrheic origin were more predominant. A wide heterogeneity was detected, where A. caviae was the predominant specie. Second-generation cephalosporins, fluoroquinolones, and nitrofurans had best antimicrobial activity; moreover, antibiotics of the ß-lactamic and lincosamides families showed lower inhibitory activity. Phenotypically, prevalences of 4.55% and 3.03% were detected for MBL (intestinal origin) and ESBL (extraintestinal origin), respectively. blaIMIS-cphA and blaTEM-1 genes, and nineteen class 1 integrons carrying two variants of cassettes corresponding to adenylyl transferases (aadA), and dihydrofolate reductases (dfrA). Monogenic array with aadA1 cassette was predominantly. CONCLUSIONS: ESBL and class 1 integrons, in Aeromonas collected from pediatric patients, determines a major detection challenge for the clinical microbiology laboratory and represents a remarkable epidemiological risk of nosocomial spread of multidrug-resistant determinants.
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Aeromonas/efeitos dos fármacos , Aeromonas/genética , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Fenótipo , Adolescente , Aeromonas/enzimologia , Criança , Pré-Escolar , Diarreia/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Lactente , Recém-Nascido , Integrons/genética , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S/genética , Centros de Atenção Terciária/estatística & dados numéricos , beta-Lactamases/genéticaRESUMO
Amoebae of the genus Acanthamoeba are etiological agents of granulomatous amoebic encephalitis (GAE). Recently, through an in vivo GAE model, Acanthamoeba trophozoites were immunolocalized in contact with the peripheral nervous system (PNS) cells-Schwann cells (SC). In this study, we analyzed in greater detail the in vitro early morphological events (1, 2, 3, and 4 h) during the interaction of A. culbertsoni trophozoites (ATCC 30171) with SC from Rattus norvegicus (ATCC CRL-2941). Samples were processed for scanning and transmission electron microscopy as well as confocal microscopy. After 1 h of interaction, amoebae were observed to be adhered to the SC cultures, emitting sucker-like structures associated with micro-phagocytic channels. In addition, evidence of necrosis was identified since edematous organelles as well as multivesicular and multilamellar bodies characteristics of autophagy were detected. At 2 h, trophozoites migrated beneath the SC culture in which necrosis and autophagy persisted. By 3 and 4 h, extensive lytic zones were observed. SC necrosis was confirmed by confocal microscopy. We reported for the first time the induction of autophagic and necrotic processes in PNS cells, associated in part with the contact-dependent pathogenic mechanisms of A. culbertsoni trophozoites.
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Spinal cord teratomas are rare. There are few reports of teratomas affecting the cervical spine and their association with spondylotic radiculopathy has not been described. A 59-year-old woman with history of fecal incontinence attended with cervical radicular pain radiating to upper limbs. Physical examination showed distal muscle hypotrophy and abolishment of bicipital, tricipital, and brachioradialis reflexes of the right arm, preserving proximal strength. Also, hiporreflexia and loss of proprioception in the right lower limb was observed. Magnetic resonance imaging showed an intramedullary mass at C7-T1, accompanied by intervertebral disk protrusions and dural sac compressions at the same level. One-stage posterior-anterior operative approach for tumor resection, decompression of the radiculopathy and replacement of intervertebral discs was performed. The histopathological diagnosis was for a mature teratoma. We described the first case of an intramedullary cervical teratoma associated with radiculopathy in an adult, providing evidence of rare long-lasting teratomas affecting the cervical spine.
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Radiculopatia/etiologia , Neoplasias da Medula Espinal/cirurgia , Espondilose/complicações , Teratoma/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Descompressão Cirúrgica , Diagnóstico Tardio , Discotomia , Incontinência Fecal/etiologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Hipestesia/etiologia , Fixadores Internos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/etiologia , Laminectomia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Cervicalgia/etiologia , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/diagnóstico por imagem , Fusão Vertebral , Espondilose/diagnóstico por imagem , Teratoma/complicações , Teratoma/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagemRESUMO
Animal models are and will remain valuable tools in medical research because their use enables a deeper understanding of disease development, thus generating important knowledge for developing disease control strategies. Central nervous system tuberculosis (CNS TB) is the most devastating disease in humans. Moreover, as the variability of signs and symptoms delay a timely diagnosis, patients usually arrive at the hospital suffering from late stage disease. Therefore, it is impossible to obtain fresh human tissue for research before an autopsy. Because of these reasons, studies on human CNS TB are limited to case series, pharmacological response reports, and post mortem histopathological studies. Here, we review the contribution of the different animal models to understand the immunopathology of the disease and the host-parasitic relationship, as well as in the development of new strategies of vaccination and to test new drugs for the treatment of CNS TB.