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Parkinson's Disease is a synucleinopathy that primarily affects the dopaminergic cells of the central nervous system, leading to motor and gastrointestinal disturbances. However, intestinal peripheral neurons undergo a similar neurodegeneration process, marked by α-synuclein (αSyn) accumulation and loss of mitochondrial homeostasis. We investigated the metabolic alterations in different biometrics that compose the gut-brain axis (blood, brain, large intestine, and feces) in an MPTP-induced mouse model of sporadic Parkinson's Disease. Animals received escalating administration of MPTP. Tissues and fecal pellets were collected, and the metabolites were identified through the untargeted Nuclear Magnetic Resonance spectroscopic (1H NMR) technique. We found differences in many metabolites from all the tissues evaluated. The differential expression of metabolites in these samples mainly reflects inflammatory aspects, cytotoxicity, and mitochondrial impairment (oxidative stress and energy metabolism) in the animal model used. The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. This data reinforces previous studies showing that Parkinson's disease is associated with metabolic perturbation not only in brain-related tissues, but also in periphery structures such as the gut. In addition, the evaluation of the microbiome and metabolites from gut and feces emerge as promising sources of information for understanding the evolution and progression of sporadic Parkinson's Disease.
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Microbioma Gastrointestinal , Intoxicación por MPTP , Enfermedad de Parkinson , Trastornos Parkinsonianos , Ratones , Animales , Enfermedad de Parkinson/metabolismo , Eje Cerebro-Intestino , Microbioma Gastrointestinal/fisiología , Espectroscopía de Resonancia Magnética , Modelos Animales de EnfermedadRESUMEN
Gut microbiota influences neurodevelopment, behavior and contributes to neurodegenerative disorders. One possible mechanism is the direct modulation of calcium (Ca2+) signaling and protein homeostasis in enteroendocrine cells (EECs), a component of the gut epithelium. Here, we present a protocol to isolate fractions of conditioned media (CM) from the anaerobic bacteria Akkermansia muciniphila and the utilization of this CM to monitor Ca2+ fluctuation in EECs by imaging. This protocol can be adapted and applied to various bacterial cultures and cell types. For complete details on the use and execution of this protocol, please refer to Amorim Neto et al. (2022).
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Bacterias Anaerobias , Señalización del Calcio , Anaerobiosis , Medios de Cultivo Condicionados/farmacología , Células EnteroendocrinasRESUMEN
Therapeutic strategies based on immunomodulation have improved cancer therapy. Most approaches target co-stimulatory pathways or the inhibition of immunosuppressive mechanisms, to enhance immune response and overcome the immune tolerance of tumors. Here, we propose a novel platform to deliver targeted immunomodulatory signaling, enhancing antitumor response. The platform is based on virus-like particles derived from lentiviral capsids. These particles may be engineered to harbor multifunctional ligands on the surface that drive tropism to the tumor site and deliver immunomodulatory signaling, boosting the antitumor response. We generated virus-like particles harboring a PSMA-ligand, TNFSF co-stimulatory ligands 4-1BBL or OX40L, and a membrane-anchored GM-CSF cytokine. The virus-like particles are driven to PSMA-expressing tumors and deliver immunomodulatory signaling from the TNFSF surface ligands and the anchored GM-CSF, inducing T cell proliferation, inhibition of regulatory T cells, and potentiating elimination of tumor cells. The PSMA-targeted particles harboring immunomodulators enhanced antitumor activity in immunocompetent challenged mice and may be explored as a potential tool for cancer immunotherapy.
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The gut microbiota influence neurodevelopment, modulate behavior, and contribute to neurodegenerative disorders. Several studies have consistently reported a greater abundance of Akkermansia muciniphila in Parkinson disease (PD) fecal samples. Therefore, we investigated whether A.muciniphila-conditioned medium (CM) could initiate α-synuclein (αSyn) misfolding in enteroendocrine cells (EEC) - a component of the gut epithelium featuring neuron-like properties. We found that A. muciniphila CM composition is influenced by the ability of the strain to degrade mucin. Our in vitro experiments showed that the protein-enriched fraction of mucin-free CM induces RyR-mediated Ca2+ release and increased mitochondrial Ca2+ uptake leading to ROS generation and αSyn aggregation. Oral administration of A. muciniphila cultivated in the absence of mucin to mice led to αSyn aggregation in cholecystokinin (CCK)-positive EECs but no motor deficits were observed. Noteworthy, buffering mitochondrial Ca2+ reverted the damaging effects observed. These molecular insights offer evidence that bacterial proteins can induce αSyn aggregation in EECs.
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Parkinson's disease (PD) is a neurodegenerative condition featured by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (αSyn) aggregates. Growing evidence suggests that PD diagnosis happens late in the disease progression and that the pathology may originate much earlier in the enteric nervous system (ENS) before advancing to the brain, via autonomic fibers. It was recently described that a specific cell type from the gut epithelium named enteroendocrine cells (EECs) possess many neuron-like properties including αSyn expression. By facing the gut lumen and being directly connected with αSyn-containing enteric neurons in a synaptic manner, EECs form a neural circuit between the gastrointestinal tract and the ENS, thereby being a possible key player in the outcome of PD in the gut. We have characterized the progression and the cellular mechanisms involved in αSyn pre-formed fibrils (PFFs) transfer from EECs to neuronal cells. We show that brain organoids efficiently internalize αSyn PFF seeds which triggers the formation of larger intracellular inclusions. In addition, in the enteroendocrine cell line STC-1 and in the neuronal cell line SH-SY5Y, αSyn PFFs induced intracellular calcium (Ca2+) oscillations on an extracellular Ca2+ source-dependent manner and triggered αSyn fibrils internalization by endocytosis. We characterized the spread of αSyn PFFs from enteroendocrine to neuronal cells and showed that this process is dependent on physical cell-to-cell contact and on Rab35 GTPase. Lastly, inhibition of Rab35 increases the clearance of αSyn fibrils by redirecting them to the lysosomal compartment. Therefore, our results reveal mechanisms that contribute to the understanding of how seeded αSyn fibrils promote the progression of αSyn pathology from EECs to neuronal cells shifting the focus of PD etiology to the ENS.
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Enfermedad de Parkinson , Sinucleinopatías , alfa-Sinucleína , Proteínas de Unión al GTP rab , Encéfalo/metabolismo , Neuronas Dopaminérgicas/metabolismo , Humanos , Enfermedad de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Proteínas de Unión al GTP rab/metabolismoRESUMEN
Current studies estimate that 1-3% of females with unexplained intellectual disability (ID) present de novo splice site, nonsense, frameshift, or missense mutations in the DDX3X protein (DEAD-Box Helicase 3 X-Linked). However, the cellular and molecular mechanisms by which DDX3X mutations impair brain development are not fully comprehended. Here, we show that the ID-linked missense mutation L556S renders DDX3X prone to aggregation. By using a combination of biophysical assays and imaging approaches, we demonstrate that this mutant assembles solid-like condensates and amyloid-like fibrils. Although we observed greatly reduced expression of the mutant allele in a patient who exhibits skewed X inactivation, this appears to be enough to sequestrate healthy proteins into solid-like ectopic granules, compromising cell function. Therefore, our data suggest ID-linked DDX3X L556S mutation as a disorder arising from protein misfolding and aggregation.
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Plant species from Annonaceae are commonly used in traditional medicine to treat various cancer types. This study aimed to investigate the antiproliferative potential of an alkaloid and acetogenin-rich fraction from the fruit peel of Annona crassiflora in HepG2 cells. A liquid-liquid fractionation was carried out on the ethanol extract of A. crassiflora fruit peel in order to obtain an alkaloid and acetogenin-rich fraction (AF-Ac). Cytotoxicity, proliferation and migration were evaluated in the HepG2 cells, as well as the proliferating cell nuclear antigen (PCNA), vinculin and epidermal growth factor receptor (EGFR) expression. In addition, intracellular Ca2+ was determined using Fluo4-AM and fluorescence microscopy. First, 9 aporphine alkaloids and 4 acetogenins that had not yet been identified in the fruit peel of A. crassiflora were found in AF-Ac. The treatment with 50 µg/mL AF-Ac reduced HepG2 cell viability, proliferation and migration (p < 0.001), which is in accordance with the reduced expression of PCNA and EGFR levels (p < 0.05). Furthermore, AF-Ac increased intracellular Ca2+ in the HepG2 cells, mobilizing intracellular calcium stores, which might be involved in the anti-migration and anti-proliferation capacities of AF-Ac. Our results support the growth-inhibitory potential of AF-Ac on HepG2 cells and suggest that this effect is triggered, at least in part, by PCNA and EGFR modulation and mobilization of intracellular Ca2+. This study showed biological activities not yet described for A. crassiflora fruit peel, which provide new possibilities for further in vivo studies to assess the antitumoral potential of A. crassiflora, especially its fruit peel.
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Acetogeninas/análisis , Alcaloides/análisis , Annona/química , Frutas/química , Neoplasias Hepáticas/patología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Hep G2 , HumanosRESUMEN
The assessment of three-dimensional (3D) brain cytoarchitecture at a cellular resolution remains a great challenge in the field of neuroscience and constant development of imaging techniques has become crucial, particularly when it comes to offering direct and clear obtention of data from macro to nano scales. Magnetic resonance imaging (MRI) and electron or optical microscopy, although valuable, still face some issues such as the lack of contrast and extensive sample preparation protocols. In this context, x-ray microtomography (µCT) has become a promising non-destructive tool for imaging a broad range of samples, from dense materials to soft biological specimens. It is a new supplemental method to be explored for deciphering the cytoarchitecture and connectivity of the brain. This review aims to bring together published works using x-ray µCT in neurobiology in order to discuss the achievements made so far and the future of this technique for neuroscience.
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There is a lack of information correlating low adiposity with hypertension experienced by Spontaneous Hypertensive Rats (SHR) or overweight and normotension in Wistar-Kyoto (WKY). We aimed to investigate this lipodystrophy phenomenon by measuring fluorescence lifetime (FLIM), optical redox ratio (ORR), serum levels of hypothalamic-pituitary-adrenal (HPA) and/or hypothalamic-pituitary-thyroid (HPT) hormones axes between Wistar, WKY and SHR before and after establishment of hypertension. Under high blood pressure, we evaluated serum adipokines. Brown adipose tissue was characterized as lower ORR and shorter FLIM compared to white adipose tissue. HPT axis showed a crucial role in the SHR adipose tissue configuration by attenuating whitening. The increased adiposity in WKY may act as a preventive agent for hypertension, since SHR, with low adiposity, establishes the disease. The hypertensive environment can highlight key adipokines that may result in new therapeutic approaches to the treatment of adiposity dysfunctions and hypertension.
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Tejido Adiposo Pardo/fisiología , Tejido Adiposo/fisiología , Hipertensión , Lipodistrofia , Adipoquinas/sangre , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/metabolismo , Tejido Adiposo Pardo/diagnóstico por imagen , Animales , Presión Sanguínea/fisiología , Hipertensión/complicaciones , Hipertensión/diagnóstico por imagen , Hipertensión/metabolismo , Hipertensión/fisiopatología , Sistema Hipotálamo-Hipofisario/diagnóstico por imagen , Sistema Hipotálamo-Hipofisario/fisiología , Lipodistrofia/diagnóstico por imagen , Lipodistrofia/etiología , Lipodistrofia/fisiopatología , Masculino , Microscopía Fluorescente/métodos , Oxidación-Reducción , Sistema Hipófiso-Suprarrenal/diagnóstico por imagen , Sistema Hipófiso-Suprarrenal/fisiología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/fisiologíaRESUMEN
BACKGROUND: Interaction of nuclear-distribution element-like 1 with disrupted-in-schizophrenia 1 protein is crucial for neurite outgrowth/neuronal migration, and this interaction competitively inhibits nuclear-distribution element-like 1 peptidase activity. Nuclear-distribution element-like 1 activity is reduced in antipsychotic-naïve first-episode psychosis and in medicated chronic schizophrenia, with even lower activity in treatment-resistant schizophrenia. AIMS: The purpose of this study was to investigate in a rat model overexpressing human non-mutant disrupted-in-schizophrenia 1, with consequent dysfunctional disrupted-in-schizophrenia 1 signaling, the relation of nuclear-distribution element-like 1 activity with neurodevelopment and dopamine-related phenotypes. METHODS: We measured cell distribution in striatum and cortex by histology and microtomography, and quantified the basal and amphetamine-stimulated locomotion and nuclear-distribution element-like 1 activity (in blood and brain) of transgenic disrupted-in-schizophrenia 1 rat vs wild-type littermate controls. RESULTS: 3D assessment of neuronal cell body number and spatial organization of mercury-impregnated neurons showed defective neuronal positioning, characteristic of impaired cell migration, in striatum/nucleus accumbens, and prefrontal cortex of transgenic disrupted-in-schizophrenia 1 compared to wild-type brains. Basal nuclear-distribution element-like 1 activity was lower in the blood and also in several brain regions of transgenic disrupted-in-schizophrenia 1 compared to wild-type. Locomotion and nuclear-distribution element-like 1 activity were both significantly increased by amphetamine in transgenic disrupted-in-schizophrenia 1, but not in wild-type. CONCLUSIONS: Our findings in the transgenic disrupted-in-schizophrenia 1 rat allow us to state that decreased nuclear-distribution element-like 1 activity reflects both a trait (neurodevelopmental phenotype) and a state (amphetamine-induced dopamine release). We thus define here a role for decreased nuclear-distribution element-like 1 peptidase activity both for the developing brain (the neurodevelopmental phenotype) and for the adult (interaction with dopaminergic responses), and present nuclear-distribution element-like 1 activity in a novel way, as unifying neurodevelopmental with dysfunctional dopamine response phenotypes.
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Anfetamina/farmacología , Núcleo Celular/enzimología , Estimulantes del Sistema Nervioso Central/farmacología , Cisteína Endopeptidasas/metabolismo , Proteínas del Tejido Nervioso/genética , Trastornos del Neurodesarrollo/genética , Esquizofrenia/genética , Animales , Animales Modificados Genéticamente , Encéfalo/diagnóstico por imagen , Recuento de Células , Modelos Animales de Enfermedad , Actividad Motora , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Esquizofrenia/diagnóstico por imagenRESUMEN
Este texto tem objetivo descritivo e exploratório sobre a relação entre o adolescente ofensor sexual e sua mãe, visto que o funcionamento familiar tem grande importância no comportamento ofensivo e deve ser foco de avaliação e intervenção. A partir do referencial teórico sistêmico, foi realizado um estudo de caso qualitativo por meio de análise documental, tendo como base os registros e materiais produzidos em um atendimento terapêutico familiar. Foram observadas dinâmicas familiares transgeracionais, vinculação afetiva distante e de rejeição entre a mãe e filho, inexistência da figura paterna, experiências traumáticas vividas pelo adolescente e uma estrutura familiar rígida e desmembrada. Os resultados apresentaram relação com a produção científica e corroboram a necessidade de intervenção tanto com o adolescente que comete abuso sexual, como com sua família.
This text has a descriptive and exploratory objective on the relationship between the adolescent sexual offender and his mother, since the familiar functioning is very important in the offensive behavior and should be focus of evaluation and intervention. From the systemic theoretical framework, a qualitative case study was carried out based on the records and materials produced in a family therapy service. Transgenerational family dynamics, distant affective attachment and rejection between mother and child, lack of paternal figure, traumatic experiences experienced by the adolescent and a rigid and dismembered family structure were observed. The results show the relationship with the scientific production and corroborate the need for intervention both with the adolescent who commits sexual abuse, and with his family.
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The spread of microtomography as a tool for visualization of soft tissues has had a significant impact on a better understanding of complex biological systems. This technique allows a detailed three-dimensional quantitative view of the specimen to be obtained, correlating its morphological organization with its function, providing valuable insights on the functionality of the tissue. Regularly overlooked, but of great importance, proper sample mounting and preparation are fundamental for achieving the highest possible image quality even for the high-resolution imaging systems currently under development. Here, a quantitative analysis compares some of the most common sample-mounting strategies used for synchrotron-based X-ray microtomography of soft tissues: alcoholic-immersion, paraffin-embedding and critical-point drying. These three distinct sample-mounting strategies were performed on the same specimen in order to investigate their impact on sample morphology regardless of individual sample variation. In that sense, the alcoholic-immersion strategy, although causing less shrinkage to the tissue, proved to be the most unsuitable approach for a high-throughput high-resolution imaging experiment due to sample drifting. Also, critical-point drying may present some interesting advantages regarding image quality but is also incompatible with a high-throughput experiment. Lastly, paraffin-embedding is shown to be the most suitable strategy for current soft tissue microtomography experiments. Such detailed analysis of biological sample-mounting strategies for synchrotron-based X-ray microtomography are expected to offer valuable insights on the best approach for using this technique for 3D imaging of soft tissues and following morphometric analysis.
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INTRODUCTION: Reduced expression of the vesicular acetylcholine transporter (VAChT) leads to changes in the distribution and shape of synaptic vesicles (SVs) at neuromuscular junctions (NMJs), suggesting vesicular acetylcholine (ACh) as a key component of synaptic structure and function. It is poorly understood how long-term changes in cholinergic transmission contribute to age- and disease-related degeneration in the motor system. METHODS: In this study we performed confocal imaging, electrophysiology, electron microscopy, and analyses of respiratory mechanics of the diaphragm NMJ components in 12-month-old wild-type (WT) and VAChTKDHOM mice. RESULTS: Diaphragms of NMJs of the VAChTKDHOM mice were similar to those in WT mice in number, colocalization, and fragmentation of pre-/postsynaptic components. However, they had increased spontaneous SV exocytosis, miniature endplate potential frequency, and diminished MEPP amplitude. No impairment in respiratory mechanics at rest was observed, probably due to the large neurotransmission safety factor of the diaphragm. DISCUSSION: The present findings help us to understand the consequences of reduced ACh release at the NMJs during aging.
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Envejecimiento/patología , Diafragma/ultraestructura , Síndromes Miasténicos Congénitos/patología , Unión Neuromuscular/ultraestructura , Vesículas Sinápticas/ultraestructura , Acetilcolina/metabolismo , Envejecimiento/metabolismo , Animales , Diafragma/metabolismo , Diafragma/fisiopatología , Modelos Animales de Enfermedad , Endocitosis , Potenciales Postsinápticos Excitadores/fisiología , Exocitosis , Técnicas de Silenciamiento del Gen , Ratones , Microscopía Confocal , Microscopía Electrónica de Transmisión , Placa Motora , Síndromes Miasténicos Congénitos/genética , Síndromes Miasténicos Congénitos/metabolismo , Síndromes Miasténicos Congénitos/fisiopatología , Unión Neuromuscular/metabolismo , Unión Neuromuscular/fisiopatología , Mecánica Respiratoria/fisiología , Transmisión Sináptica , Vesículas Sinápticas/metabolismo , Proteínas de Transporte Vesicular de Acetilcolina/genéticaRESUMEN
Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2). Nrf2 regulates expression of proteins that protect against oxidative stress and inflammation caused by alcohol overconsumption. Here, we assessed genetic variants of NFE2L2 for association with ALD. Specimens from patients diagnosed with cirrhosis caused by ALD were genotyped for three NFE2L2 single nucleotide polymorphisms (SNP) (SNPs: rs35652124, rs4893819, and rs6721961). Hematoxylin & eosin and immunohistochemistry were performed to determine the inflammatory score and Nrf2 expression, respectively. SNPs rs4893819 and rs6721961 were not specifically associated with ALD, but analysis of SNP rs35652124 suggested that this polymorphism predisposes to ALD. Furthermore, SNP rs35652124 was associated with a lower level of Nrf2 expression. Moreover, liver samples from ALD patients with this polymorphism displayed more severe inflammatory activity. Together, these findings provide evidence that the SNP rs35652124 variation in the Nrf2-encoding gene NFE2L2 is a potential genetic marker for susceptibility to ALD.
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Predisposición Genética a la Enfermedad , Cirrosis Hepática Alcohólica/genética , Factor 2 Relacionado con NF-E2/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Adulto , Estudios de Casos y Controles , Etanol/farmacología , Femenino , Expresión Génica , Hepacivirus/crecimiento & desarrollo , Hepacivirus/patogenicidad , Hepatitis C/patología , Hepatitis C/virología , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Alcohólica/metabolismo , Cirrosis Hepática Alcohólica/patología , Cirrosis Hepática Alcohólica/cirugía , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Estrés OxidativoRESUMEN
O presente texto trata de uma pesquisa qualitativa realizada no contexto de um programa de atendimento psicossocial grupal ao autor adulto de violência sexual. O objeto está centrado no estudo exploratório da avaliação de risco de reincidência do ato violento por meio da aplicação de um instrumento atuarial complementar ao instrumento da entrevista. O método de pesquisa foi a análise documental. O instrumento SVR-2.0 é um checklist composto por 20 questões relacionadas aos fatores de risco para a prática de violência sexual ou de sua reincidência e é preenchido pelos profissionais responsáveis pelos atendimentos ao autor de violência. A avaliação de risco de reincidência do comportamento violento sexual no exemplo estudado foi considerada como alto. Apontam-se ainda os cuidados e as limitações no uso do checklist devido à condição de pouca experiência do uso desse instrumento no país.
This paper describes a qualitative research developed in the context of a group psychosocial program to adult sexual offenders. An exploratory study on recidivism risk assessment of violent offenses was made through the administration of an actuarial instrument, in addition to an interview instrument. The research method was the document analysis. The instrument SVR-2.0 is a checklist consisting of 20 questions related to the risk factors of sexual violence or its recurrence. It is filled by the professionals responsible for the adult sexual offenders' treatments. The recidivism risk assessment of violent sexual behavior in the case study was considered high. The cautions and limitations in the use of the checklist are also pointed out due to the little experience of its use in Brazil.
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Delitos Sexuales , Abuso Sexual Infantil , Violación , ReincidenciaRESUMEN
O nematódeo Spirocerca lupi, causador da espirocercose, é um parasito que acometeprincipalmente cães e canídeos silvestres. Seu ciclo biológico envolve hospedeirosintermediários, os besouros coprófagos e pequenas aves, répteis e roedores que servem como hospedeiros paratênicos. A doença é de ocorrência cosmopolita, com maior prevalência em países tropicais e subtropicais, sendo endêmica na África do Sul. Também já foi relatada em alguns países da América do Sul, incluindo o Brasil, sendo mais prevalente em cães de caça e cães errantes. Os vermes adultos parasitam esôfago, estômago e artéria aorta dos hospedeiros definitivos, provocando nódulos, granulomas e diversas lesões. A sintomatologia da espirocercose varia de acordo com o processo migratório do parasito no organismo do animal, os órgãos afetados, bem como a evolução da doença. Sintomas como a regurgitação, a emese, a disfagia e a perda de peso, são as principais manifestações clínicas observadas em cães parasitados. O diagnóstico se baseia nos achados clínicos, exames de imagem, parasitológico de fezes ou das secreções daregugitação, emese e achados de necropsia. O tratamento pode ser clínico, ainda poucoviável, ou cirúrgico para remoção dos nódulos contendo os parasitos. Como medidas preventivas a literatura cita evitar o acesso de cães aos hospedeiros paratênicos e, além disso, eles não devem ser alimentados com vísceras cruas de outros animais domésticos e silvestres.
The nematode Spirocerca lupi, which causes spirocercosis, is a parasite that mainly affects dogs and wild canids. Its biological cycle involves intermediate hosts, the coprophagous beetles and small birds, reptiles and rodents that serve as paratenic hosts. The disease is of cosmopolitan occurrence with a higher prevalence in tropical and subtropical countries, being endemic in South Africa. It has also been reported in some South American countries, including Brazil, being more prevalent in hunting dogs and stray dogs. The adult worms parasite the esophagus, stomach and aorta artery of the definitive hosts, causing nodules, granulomas and several lesions. The symptoms of spirocercosis varies according to the migratory process of the parasite in the animal organism, the affected organs, as well as the evolution of the disease. Symptoms such regurgitation, dysphagia and weight loss are the main clinical manifestations observed in parasitized dogs. The diagnosis is based on clinical findings, imaging, parasitological examination of feces or secretions of the regurgitation, emese and necropsy findings. The treatment can be clinical, still little viable, or surgical for removal of the nodules containing the parasites. As preventive measures theliterature cites avoiding access of dogs to paratenic hosts and, in addition, they should not be fed with raw viscera of other domestic and wild animals.
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Animales , Perros , Infecciones por Spirurida/veterinaria , ThelazioideaRESUMEN
O nematódeo Spirocerca lupi, causador da espirocercose, é um parasito que acometeprincipalmente cães e canídeos silvestres. Seu ciclo biológico envolve hospedeirosintermediários, os besouros coprófagos e pequenas aves, répteis e roedores que servem como hospedeiros paratênicos. A doença é de ocorrência cosmopolita, com maior prevalência em países tropicais e subtropicais, sendo endêmica na África do Sul. Também já foi relatada em alguns países da América do Sul, incluindo o Brasil, sendo mais prevalente em cães de caça e cães errantes. Os vermes adultos parasitam esôfago, estômago e artéria aorta dos hospedeiros definitivos, provocando nódulos, granulomas e diversas lesões. A sintomatologia da espirocercose varia de acordo com o processo migratório do parasito no organismo do animal, os órgãos afetados, bem como a evolução da doença. Sintomas como a regurgitação, a emese, a disfagia e a perda de peso, são as principais manifestações clínicas observadas em cães parasitados. O diagnóstico se baseia nos achados clínicos, exames de imagem, parasitológico de fezes ou das secreções daregugitação, emese e achados de necropsia. O tratamento pode ser clínico, ainda poucoviável, ou cirúrgico para remoção dos nódulos contendo os parasitos. Como medidas preventivas a literatura cita evitar o acesso de cães aos hospedeiros paratênicos e, além disso, eles não devem ser alimentados com vísceras cruas de outros animais domésticos e silvestres.(AU)
The nematode Spirocerca lupi, which causes spirocercosis, is a parasite that mainly affects dogs and wild canids. Its biological cycle involves intermediate hosts, the coprophagous beetles and small birds, reptiles and rodents that serve as paratenic hosts. The disease is of cosmopolitan occurrence with a higher prevalence in tropical and subtropical countries, being endemic in South Africa. It has also been reported in some South American countries, including Brazil, being more prevalent in hunting dogs and stray dogs. The adult worms parasite the esophagus, stomach and aorta artery of the definitive hosts, causing nodules, granulomas and several lesions. The symptoms of spirocercosis varies according to the migratory process of the parasite in the animal organism, the affected organs, as well as the evolution of the disease. Symptoms such regurgitation, dysphagia and weight loss are the main clinical manifestations observed in parasitized dogs. The diagnosis is based on clinical findings, imaging, parasitological examination of feces or secretions of the regurgitation, emese and necropsy findings. The treatment can be clinical, still little viable, or surgical for removal of the nodules containing the parasites. As preventive measures theliterature cites avoiding access of dogs to paratenic hosts and, in addition, they should not be fed with raw viscera of other domestic and wild animals.(AU)
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Animales , Perros , Thelazioidea , Infecciones por Spirurida/veterinariaRESUMEN
In chronic schistosomiasis, liver fibrosis is linked to portal hypertension, which is a condition associated with high mortality and morbidity. High mobility group box 1 (HMGB1) was originally described as a nuclear protein that functions as a structural co-factor in transcriptional regulation. However, HMGB1 can also be secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 acts as a multifunctional cytokine that contributes to infection, injury, inflammation, and immune responses by binding to specific cell-surface receptors. HMGB1 is involved in fibrotic diseases. From a clinical perspective, HMGB1 inhibition may represent a promising therapeutic approach for treating tissue fibrosis. In this study, we demonstrate elevated levels of HMGB1 in the sera in experimental mice or in patients with schistosomiasis. Using immunohistochemistry, we demonstrated that HMGB1 trafficking in the hepatocytes of mice suffering from acute schistosomiasis was inhibited by Glycyrrhizin, a well-known HMGB1 direct inhibitor, as well as by DIC, a novel and potential anti-HMGB1 compound. HMGB1 inhibition led to significant downregulation of IL-6, IL4, IL-5, IL-13, IL-17A, which are involved in the exacerbation of the immune response and liver fibrogenesis. Importantly, infected mice that were treated with DIC or GZR to inhibit HMGB1 pro-inflammatory activity showed a significant increase in survival and a reduction of over 50% in the area of liver fibrosis. Taken together, our findings indicate that HMGB1 is a key mediator of schistosomotic granuloma formation and liver fibrosis and may represent an outstanding target for the treatment of schistosomiasis.
Asunto(s)
Granuloma , Proteína HMGB1/inmunología , Cirrosis Hepática , Hígado , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni , Animales , Citocinas/inmunología , Femenino , Granuloma/inmunología , Granuloma/parasitología , Granuloma/patología , Humanos , Hígado/inmunología , Hígado/parasitología , Hígado/patología , Cirrosis Hepática/inmunología , Cirrosis Hepática/parasitología , Cirrosis Hepática/patología , Masculino , Ratones Endogámicos BALB C , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/patologíaRESUMEN
The assessment of neuronal number, spatial organization and connectivity is fundamental for a complete understanding of brain function. However, the evaluation of the three-dimensional (3D) brain cytoarchitecture at cellular resolution persists as a great challenge in the field of neuroscience. In this context, X-ray microtomography has shown to be a valuable non-destructive tool for imaging a broad range of samples, from dense materials to soft biological specimens, arisen as a new method for deciphering the cytoarchitecture and connectivity of the brain. In this work we present a method for imaging whole neurons in the brain, combining synchrotron-based X-ray microtomography with the Golgi-Cox mercury-based impregnation protocol. In contrast to optical 3D techniques, the approach shown here does neither require tissue slicing or clearing, and allows the investigation of several cells within a 3D region of the brain.