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1.
Toxicon ; 240: 107630, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342412

RESUMO

The pathophysiology of recurrent pregnancy loss (RPL) involves deficiencies in the proliferation and migration capacities of endometrial stromal cells (hESCs), which impair embryo implantation and development. Since animal venoms are rich source of bioactive molecules, we aimed to characterize the cytoprotective effects of Lonomia obliqua venom on hESCs. hESCs were isolated from endometrial biopsies and the mechanisms of L. obliqua venomous secretions on cell viability, proliferation and migration were characterized. Venom components were identified by chromatography and proteomic analyses. L. obliqua venom induced hESC proliferation, viability and migration in a dose-dependent manner, both in the presence and absence of serum. By ion-exchange chromatography, one fraction enriched in cytoprotective components and devoid of hemotoxins was obtained. Venom proteome identified at least six protein classes with potential cytoprotective properties (hemolins, lipocalins, hemocyannins, antiviral proteins, antimicrobial peptides, and protease inhibitors). L. obliqua venom protected hESCs from oxidative insult. Cytoprotection was also related to nitric oxide and PKC-ERK-activation and down-regulation of cAMP-PKA-dependent pathways that control cell proliferation. L. obliqua venom-induced hESC viability, proliferation and migration occurs mainly by protecting against oxidative damage and activating ERK. Thus, L. obliqua venom components are promising pharmacological tools to understand the underlying mechanisms of hESC deficiency in RPL.


Assuntos
Venenos de Artrópodes , Animais , Humanos , Venenos de Artrópodes/química , Proteômica , Células Epiteliais
2.
Rev. Baiana Saúde Pública (Online) ; 47(4): 223-237, 20240131.
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1537817

RESUMO

O sono é um estado essencial para sobrevivência humana, ele exerce função biológica, restauradora e de conservação energética do organismo, promovendo equilíbrio físico e mental. Alta prevalência da má qualidade de sono e sonolência diurna excessiva (SDE) têm sido relatadas por estudantes universitários de diversos cursos, ocasionando prejuízos na concentração e queda dos rendimentos acadêmicos. O objetivo deste trabalho foi avaliar a qualidade de sono, a SDE e suas possíveis associações com sintomas depressivos em estudantes de odontologia. Foi realizado um estudo transversal e descritivo com 251 alunos do curso de odontologia da Faculdade de Farmácia, Odontologia e Enfermagem da Universidade Federal do Ceará. Os instrumentos utilizados foram o Índice de Qualidade de Sono de Pittsburgh (IQSP), Escala de Sonolência de Epworth (ESE) e Inventário de Depressão de Beck (IDB). Verificou-se uma alta prevalência de má qualidade de sono (53,4%) e SDE (35,1%) entre os estudantes, sem diferença significante em relação ao sexo para ambas. Foi encontrada correlação positiva entre IDB com IQSP e ESE (r = 0,478; p = 0,000 e r = 0,202; p = 0,000, respectivamente). Os resultados mostraram uma alta prevalência de má qualidade de sono e SDE e ambos os achados apresentaram associação com sintomas depressivos.


Sleep is an essential state for human survival. It has a biological, restorative and energy conservation function for the organism, promoting physical and mental balance. A high prevalence of poor sleep quality and excessive daytime sleepiness (EDS) has been reported among university students from different courses, causing impaired concentration and a drop in academic performance. This study evaluates sleep quality, EDS and their possible associations with depressive symptoms in dentistry students. A cross-sectional descriptive research was conducted with 251 students from the Dentistry Course at the School of Pharmacy, Dentistry and Nursing, Federal University of Ceará. Variables of interest were assessed by Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Beck Depression Inventory (BDI). Results show a high prevalence of poor sleep quality (53.4%) and EDS (35.1%) among students, with no significant difference regarding gender. BDI had a positive correlation with PSQI and ESS (r= 0.478, p= 0.000; and r= 0.202, p =0.000, respectively). Both findings were associated with depressive symptoms.


El sueño es un estado esencial para la supervivencia humana, tiene una función biológica, reparadora y de conservación de energía para el organismo, favoreciendo el equilibrio físico y mental. Se ha reportado una alta prevalencia de mala calidad del sueño y somnolencia diurna excesiva (SDE) en estudiantes universitarios de diferentes carreras que provoca alteración de la concentración y caída del rendimiento académico. El objetivo de este trabajo fue evaluar la calidad del sueño, la SDE y sus posibles asociaciones con síntomas depresivos en estudiantes de odontología. Se realizó un estudio descriptivo transversal con 251 estudiantes de la carrera de Odontología de la Facultad de Farmacia, Odontología y Enfermería de la Universidad Federal de Ceará. Los instrumentos utilizados fueron el Índice de Calidad del Sueño de Pittsburgh (PSQI), la Escala de Somnolencia de Epworth (ESS) y el Inventario de Depresión de Beck (BDI). Hubo una alta prevalencia de mala calidad del sueño (53,4%) y SDE (35,1%) entre los estudiantes, sin diferencia significativa en relación con el género para ambos. Se encontró una correlación positiva entre BDI con PSQI y ESS (r= 0,478; p= 0,000 y r= 0,202; p = 0,000, respectivamente). Los resultados mostraron una alta prevalencia de mala calidad del sueño y SDE, y ambos hallazgos se asociaron con síntomas depresivos.

3.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1511723

RESUMO

Introduction: traumatic brain injury is a global public health problem due to its severity and high rates of morbimortality worldwide. Identifying predictors associated with increased mortality and unfavorable functional outcomes after the traumatic brain injury event is crucial for minimizing morbidity and mortality rates. Therefore, this study aims to establish a protocol to investigate the predictors of mortality and functional recovery after severe traumatic brain injury in Brazil.Methods: The study will include all patients admitted for severe traumatic brain injury (Glasgow Coma Scale ≤ 8) at the State Hospital of Urgency and Emergency, which is the referral trauma hospital of Espirito Santo. The outcomes of interest are hospital mortality and functional recovery 24 months after hospital discharge. Subjects will be followed up at seventy-two hours, three months, six months, twelve months, and twenty-four months after the trauma. Morbidity will be determined by assessing: 1) the level of motor and cognitive disability, 2) functional impairment and quality of life, and 3) aspects of rehabilitation treatment. Additionally, the traumatic brain injury load, estimated by the years of life lost, will be calculated. Discussion: the results of this study will help identify variables that can predict morbidity and mortality, as well as diagnostic and therapeutic targets for patients with severe traumatic brain injury. Furthermore, the findings will have practical implications for: 1) the development of public policies, 2) investments in hospital infrastructure 3) understanding the socioeconomic impact of functional loss in the individuals.Study registration: the study received approval from the Ethics Committee of the Federal University of Espirito Santo under protocol number 4.222.002 on August 18, 2020.


Introdução: traumatismo cranioencefálico é um problema global de saúde pública devido à sua gravidade e altas taxas de morbimortalidade em todo o mundo. Identificar preditores associados ao aumento da mortalidade e desfechos funcionais desfavoráveis após o evento do traumatismo craniencefálico é primordial para minimizar as taxas de morbidade e mortalidade. Portanto, este estudo tem como objetivo estabelecer um protocolo para investigar os preditores de mortalidade e recuperação funcional após traumatismo cranioencefálico grave no Brasil. Métodos: este estudo tem como objetivo investigar os preditores de mortalidade e recuperação funcional em pacientes com traumatismo cranioencefálico, além de fornecer uma visão geral do traumatismo cranioencefálico no estado do Espírito Santo. O estudo abrangerá todos os pacientes internados por traumatismo cranioencefálico grave (Escala de Coma de Glasgow ≤ 8) no Hospital Estadual de Urgência e Emergência, o hospital de referência para traumas no Espírito Santo. Os desfechos de interesse incluem mortalidade hospitalar e recuperação funcional após 24 meses da alta hospitalar. Os participantes serão acompanhados em setenta e duas horas, três meses, seis meses, doze meses e vinte e quatro meses após o trauma. A morbidade será determinada pela avaliação de: 1) nível de incapacidade motora e cognitiva, 2) comprometimento funcional e qualidade de vida, e 3) aspectos do tratamento e reabilitação. Além disso, a carga de traumatismo cranioencefálico, estimada em anos de vida perdidos, será calculada. Discussão: os resultados deste estudo ajudarão a identificar variáveis que podem predizer a morbidade e a mortalidade após traumatismo cranioencefálico grave. Além disso, as descobertas terão implicações práticas para: 1) o desenvolvimento de políticas públicas, 2) investimentos em infraestrutura hospitalar e 3) compreensão do impacto socioeconômico da perda funcional nesses indivíduos. Registro do estudo: o estudo recebeu aprovação do Comitê de Ética da Universidade Federal do Espírito Santo sob o número de protocolo 4.222.002 em 18 de agosto de 2020

4.
Parasitol Res ; 122(8): 1915-1921, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37272976

RESUMO

Hydatigera taeniaeformis is a cestode that uses felines and rodents as definitive and intermediate hosts, respectively. Its larval stage, or metacestode, infects a wide variety of rodent species and develops in the liver parenchyma into a cyst. The aim of this study was to evaluate the occurrence of H. taeniaeformis metacestode in various species of wild rodents from Peru. For this, the livers of 356 rodents were macroscopically examined for any parasitic form compatible with metacestodes. Metacestodes were identified by measuring characteristic morphological parameters, and the diagnosis was confirmed by molecular analysis of a fragment of the cytochrome c oxidase subunit 1 gene (cox1). Five rodents: two small-eared pygmy rice rats (Oligoryzomys microtis), two white-naped squirrels (Simosciurus nebouxii), and one pygmy rice rat (Oligoryzomys sp.) were infected with H. taeniaeformis metacestodes. The cox1 sequences from our metacestodes showed up to 100% identity with previous H. taeniaeformis sequences from the GenBank. These results demonstrated the occurrence of H. taeniaeformis in new intermediate hosts, as well as the first molecular contribution for H. taeniaeformis from Peru.


Assuntos
Cestoides , Taenia , Ratos , Gatos , Animais , Peru/epidemiologia , Taenia/genética , Cestoides/genética , Cestoides/anatomia & histologia , Sciuridae , Larva , Sigmodontinae
5.
Epilepsy Behav ; 143: 109245, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37182500

RESUMO

PURPOSE: This multicenter study aimed to evaluate the efficacy and tolerability of add-on cannabidiol (CBD) in treatment-resistant patients with epilepsy with myoclonic-atonic seizures (EMAtS) (n = 22) and Sturge Weber syndrome (SWS) with myoclonic-atonic seizures (n = 4). METHODS: Patients who met the diagnostic criteria of treatment-resistant EMAtS or SWS with myoclonic-atonic seizures were included. Cannabidiol was added in doses ranging from 8 to 40 mg/kg/day. Efficacy was assessed by comparing seizure frequency before and after initiating CBD therapy. Neurologic examinations, brain magnetic resonance imaging, repeated prolonged electroencephalography (EEG) and/or video-EEG recordings, and neurometabolic studies were performed in all patients, and genetic investigations in 15. RESULTS: After a mean follow-up of 19 months, 15/26 patients (57.7%) who received add-on CBD had a >50% seizure decrease; three (11.5%) became seizure-free. The remaining 11 patients (42.3%) had a 25-50% seizure reduction. Drop attacks, including myoclonic-atonic seizures and generalized tonic-clonic seizures, as well as atypical absences and nonconvulsive status epilepticus responded well to CBD. In SWS patients, focal motor seizures without consciousness impairment and focal non-motor seizures with consciousness impairment were recognized in two each; in three a 30% reduction of focal seizures was observed. Side effects were mild and did not lead to CBD discontinuation. CONCLUSION: This study evaluating the use of add-on CBD in children with EMAtS or SWS with myoclonic-atonic seizures found that 15/26 (57.7%) had a >50% seizure reduction with good tolerability; three (11.5%) became seizure-free.


Assuntos
Canabidiol , Epilepsias Mioclônicas , Epilepsia Generalizada , Humanos , Criança , Canabidiol/uso terapêutico , Epilepsias Mioclônicas/complicações , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/diagnóstico , Convulsões/complicações , Convulsões/tratamento farmacológico , Convulsões/diagnóstico , Epilepsia Generalizada/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Eletroencefalografia
6.
Int J Mol Sci ; 23(24)2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36555275

RESUMO

Gastrointestinal diseases, such as peptic ulcers, are caused by a damage in the gastric mucosa provoked by several factors. This stomach injury is regulated by many inflammatory mediators and is commonly treated with proton-pump inhibitors, histamine H2 receptor blockers and antacids. However, various medicinal plants have demonstrated positive effects on gastric ulcer treatment, including plants of the Ceiba genus. The aim of this study was to evaluate the antiulcer and anti-inflammatory activities of the stem bark ethanolic extract of Ceiba speciosa (A. St.-Hil.) Ravenna. We performed a preliminary quantification of phenolic compounds by high-performance liquid chromatography-diode array detection (HPLC-DAD), followed by the prospection of other chemical groups through nuclear magnetic resonance (NMR) spectroscopy. A set of in vitro assays was used to evaluate the extract potential regarding its antioxidant activity (DPPH: 19.83 ± 0.34 µg/mL; TPC: 307.20 ± 6.20 mg GAE/g of extract), effects on cell viability and on the release of TNF-α in whole human blood. Additionally, in vivo assays were performed to evaluate the leukocyte accumulation and total protein quantification in carrageenan-induced air pouch, as well as the antiulcerogenic effect of the extract on an ethanol-induced ulcer in rats. The extract contains flavonoids and phenolic compounds, as well as sugars and quinic acid derivatives exhibiting potent antioxidant activity and low toxicity. The extract reduced the release of TNF-α in human blood and inhibited the activity of p38α (1.66 µg/mL), JAK3 (5.25 µg/mL), and JNK3 (8.34 µg/mL). Moreover, it reduced the leukocyte recruitment on the pouch exudate and the formation of edema, reverting the effects caused by carrageenan. The extract presented a significant prevention of ulcer formation and a higher reduction than the reference drug, Omeprazole. Therefore, C. speciosa extract has demonstrated relevant therapeutic potential for the treatment of gastric diseases, deserving the continuation of further studies to unveil the mechanisms of action of plant bioactive ingredients.


Assuntos
Antiulcerosos , Ceiba , Extratos Vegetais , Úlcera Gástrica , Animais , Humanos , Ratos , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Carragenina/efeitos adversos , Ceiba/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Úlcera
7.
J Cell Biochem ; 123(9): 1495-1505, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35892149

RESUMO

Following health agencies warning, the use of animal origin supplements should be avoided in biological products proposed as therapy in humans. Platelet lysate and several other growth factors sources are alternatives to replace fetal calf serum, the current gold standard in clinical-grade cell culture. However, the platelet supplement's content lacks data due to different production methods. The principle behind these products relays on the lysis of platelets that release several proteins, some of which are contained in heterogeneous granules and coordinate biological functions. This study aims to analyze the composition and reproducibility of a platelet lysate produced with a standardized method, by describing several batches' protein and particle content using proteomics and dynamic light scattering. Proteomics data revealed a diversified protein content, with some related to essential cellular processes such as proliferation, morphogenesis, differentiation, biosynthesis, adhesion, and metabolism. It also detected proteins responsible for activation and binding of transforming growth factor beta, hepatocyte growth factor, and insulin-like growth factor. Total protein, biochemical, and growth factors quantitative data showed consistent and reproducible values across batches. Novel data on two major particle populations is presented, with high dispersion level at 231 ± 96 d.nm and at 30 ± 8 d.nm, possibly being an important way of protein trafficking through the cellular microenvironment. This experimental and descriptive analysis aims to support the content definition and quality criteria of a cell supplement for clinical applications.


Assuntos
Produtos Biológicos , Células-Tronco Mesenquimais , Somatomedinas , Animais , Plaquetas/metabolismo , Diferenciação Celular , Proliferação de Células , Terapia Baseada em Transplante de Células e Tecidos , Células Cultivadas , Meios de Cultura/química , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Proteômica , Reprodutibilidade dos Testes , Soroalbumina Bovina/análise , Soroalbumina Bovina/metabolismo , Somatomedinas/análise , Somatomedinas/metabolismo , Fator de Crescimento Transformador beta/metabolismo
8.
Rev Soc Bras Med Trop ; 55: e00632022, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35613221

RESUMO

Mass vaccination campaigns are essential to control the ongoing novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic. The Covishield vaccine consists of the replication-deficient simian adenovirus vector ChAdOx1, which contains the full-length structural spike protein of SARS-CoV-2. Occasionally, it can lead to cutaneous reactions that contribute to fear of vaccination, hesitancy, and incomplete vaccination schedules. We report a case of facial angioedema following the first dose of Covishield in a 63-year-old woman with no previous history of allergies or hypersensitivity to drugs or vaccines. No rebound of angioedema was recorded after the second homologous and third heterologous doses.


Assuntos
Angioedema , COVID-19 , ChAdOx1 nCoV-19 , Adenoviridae , Angioedema/induzido quimicamente , Anticorpos Antivirais , COVID-19/prevenção & controle , ChAdOx1 nCoV-19/efeitos adversos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinação/efeitos adversos
9.
Rev. Soc. Bras. Med. Trop ; 55: e0063, 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1376358

RESUMO

ABSTRACT Mass vaccination campaigns are essential to control the ongoing novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic. The Covishield vaccine consists of the replication-deficient simian adenovirus vector ChAdOx1, which contains the full-length structural spike protein of SARS-CoV-2. Occasionally, it can lead to cutaneous reactions that contribute to fear of vaccination, hesitancy, and incomplete vaccination schedules. We report a case of facial angioedema following the first dose of Covishield in a 63-year-old woman with no previous history of allergies or hypersensitivity to drugs or vaccines. No rebound of angioedema was recorded after the second homologous and third heterologous doses.

10.
ACS Appl Nano Mater ; 4(1): 211-219, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-34142014

RESUMO

Onion-like carbon nanoparticles were synthesized from diamond nanoparticles to be used as the precursor for graphene oxide quantum dots. Onion-like carbon nanoparticles were exfoliated to produce two types of nanoparticles, graphene oxide quantum dots that showed size-dependent fluorescence and highly stable inner cores. Multicolor fluorescent quantum dots were obtained and characterized using different techniques. Polyacrylamide gel electrophoresis showed a range of emission wavelengths spanning from red to blue with the highest intensity shown by green fluorescence. Using high-resolution transmission electron microscopy, we calculated a unit cell size of 2.47 Å in a highly oxidized and defected structure of graphene oxide. A diameter of ca. 4 nm and radius of gyration of ca. 11 Å were calculated using small-angle X-ray scattering. Finally, the change in fluorescence of the quantum dots was studied when single-stranded DNA that is recognized by telomerase was attached to the quantum dots. Their interaction with the telomerase present in cancer cells was observed and a change was seen after six days, providing an important application of these modified graphene oxide quantum dots for cancer sensing.

11.
Toxicol Lett ; 341: 11-22, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33472085

RESUMO

AIMS: Accidental contact with the Lonomia obliqua caterpillar is a common event in southern Brazil. Envenomed victims present consumption coagulopathy, which can evolve to acute kidney injury (AKI). In the present study, we searched for AKI biomarkers and changes in molecular pathway signatures through urine proteomic analysis. METHODOLOGY: Male Wistar rats were injected with L. obliqua venom (1.5 mg/kg, via s.c.) or 0.9 % NaCl and distributed into metabolic cages. After 24 h, urine was obtained, and the set of differentially regulated proteins was analyzed by MudPIT technology in an OrbiTRAP mass spectrometer. RESULTS: L. obliqua venom leads to an increase in urine output and water and electrolyte excretion and to an increase in the albumin to creatine ratio in urine. The proteomic analysis revealed an up-regulation of tubular injury biomarkers, such as neutrophil-gelatinase associated lipocalin (NGAL) and cystatin C, in urine from envenomed rats. Several components related to the heme scavenging system were up-regulated or exclusively identified in urine from envenomed animals. There was an increase in urinary heme levels and hemoglobin subunits, hemopexin, haptoglobin, and biliverdin reductase. Similarly, kinin- and angiotensin-generating/degrading peptidases, such as kallikreins, neprilysin, plasmin, dipeptidyl peptidase IV, cathepsin D, kininogen, and neutral, basic, glutamyl, and acidic aminopeptidases, were also up-regulated in urine. CONCLUSIONS: L. obliqua envenomation induced tubular and glomerular injury, probably involving heme/hemoglobin toxicity and an imbalance in the kinin/angiotensin generating/degrading system.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Aminopeptidases/metabolismo , Venenos de Artrópodes/toxicidade , Hemoglobinúria , Lepidópteros , Proteômica , Aminopeptidases/química , Animais , Heme , Hemoglobinas , Larva/fisiologia , Masculino , Ratos , Ratos Wistar , Urinálise , Urina/química
12.
Sci Rep ; 10(1): 21604, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303883

RESUMO

Zika virus (ZIKV) infection during pregnancy was associated with microcephaly in neonates, but clinical and experimental evidence indicate that ZIKV also causes neurological complications in adults. However, the changes in neuron-glial communication, which is essential for brain homeostasis, are still unknown. Here, we report that hippocampal slices from adult rats exposed acutely to ZIKV showed significant cellular alterations regarding to redox homeostasis, inflammatory process, neurotrophic functions and molecular signalling pathways associated with neurons and glial cells. Our findings support the hypothesis that ZIKV is highly neurotropic and its infection readily induces an inflammatory response, characterized by an increased expression and/or release of pro-inflammatory cytokines. We also observed changes in neural parameters, such as adenosine receptor A2a expression, as well as in the release of brain-derived neurotrophic factor and neuron-specific enolase, indicating plasticity synaptic impairment/neuronal damage. In addition, ZIKV induced a glial commitment, with alterations in specific and functional parameters such as aquaporin 4 expression, S100B secretion and glutathione synthesis. ZIKV also induced p21 senescence-associated gene expression, indicating that ZIKV may induce early senescence. Taken together, our results indicate that ZIKV-induced neuroinflammation, involving nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NFκB) pathways, affects important aspects of neuron-glia communication. Therefore, although ZIKV infection is transient, long-term consequences might be associated with neurological and/or neurodegenerative diseases.


Assuntos
Comunicação Celular , Hipocampo/patologia , Neuroglia/patologia , Neurônios/patologia , Infecção por Zika virus/patologia , Zika virus/patogenicidade , Animais , Feminino , Masculino , Gravidez , Ratos , Ratos Wistar
13.
Mol Reprod Dev ; 87(9): 952-965, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32749760

RESUMO

Male infertility or subfertility is frequently associated with disruption of the hypothalamic-pituitary-testis axis events, like secondary hypogonadism. However, little is known how this condition affects the proteomic composition of the epididymal fluid. In the present study, we evaluated the proteomic changes in the cauda epididymal fluid (CEF) in a swine model of secondary hypogonadism induced by anti-GnRH immunization using multidimensional protein identification technology. Seven hundred and eighteen proteins were identified in both GnRH-immunized and control groups. GnRH immunization doubled the number of proteins in the CEF, with 417 proteins being found exclusively in samples from GnRH-immunized boars. CEF from GnRH-immunized boars presented an increase in the number of proteins related to cellular and metabolic processes, with affinity to organic cyclic compounds, small molecules, and heterocyclic compounds, as well changed the enzymatic profile of the CEF. Also, a significant increase in the number of proteins associated to the ubiquitin-proteasome system was identified in CEF from GnRH-immunized animals. These results bring strong evidence of the impact of secondary hypogonadism on the epididymal environment, which is responsible for sperm maturation and storage prior ejaculation. Finally, the differently expressed proteins in the CEF are putative seminal biomarkers for testicular and epididymal disorders caused by secondary hypogonadism.


Assuntos
Líquidos Corporais/metabolismo , Epididimo/metabolismo , Hipogonadismo/metabolismo , Infertilidade Masculina/metabolismo , Proteoma/metabolismo , Animais , Anticorpos/farmacologia , Líquidos Corporais/química , Líquidos Corporais/efeitos dos fármacos , Anticoncepção Imunológica/métodos , Anticoncepção Imunológica/veterinária , Epididimo/química , Epididimo/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/imunologia , Hormônio Liberador de Gonadotropina/metabolismo , Hipogonadismo/etiologia , Hipogonadismo/imunologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Infertilidade Masculina/etiologia , Infertilidade Masculina/imunologia , Infertilidade Masculina/veterinária , Masculino , Modelos Animais , Proteoma/análise , Proteoma/efeitos dos fármacos , Proteômica , Transdução de Sinais/efeitos dos fármacos , Suínos/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
14.
Rev. Soc. Bras. Med. Trop ; 53: e20190516, 2020. graf
Artigo em Inglês | Sec. Est. Saúde SP, Coleciona SUS, LILACS | ID: biblio-1136894

RESUMO

Abstract The differential diagnosis of optic neuritis is broad and varied. We report the case of a 24-year-old Brazilian man who presented with five-week history of fever, malaise, myalgia, severe fatigue, tender right preauricular lymphadenopathy, and acute vision blurring associated with right optic disc swelling and exudates in a macular star pattern. His illness developed soon after an infestation of fleas broke out among his cats. Diagnosis of ocular bartonellosis was confirmed by serological and molecular analyses targeting amplification of Bartonella spp. htrA gene. Signs and symptoms only improved after initiation of antimicrobial therapy.


Assuntos
Humanos , Animais , Masculino , Gatos , Adulto Jovem , Retinite/microbiologia , Bartonella henselae/isolamento & purificação , Retinite/diagnóstico , Retinite/tratamento farmacológico , Doxiciclina/uso terapêutico , Antibacterianos/uso terapêutico
15.
J Proteome Res ; 18(11): 3885-3895, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31502459

RESUMO

Cryptococcus gattii is the causative agent of cryptococcosis infection that can lead to pneumonia and meningitis in immunocompetent individuals. The molecular basis of the pathogenic process and impact on the host biochemistry are poorly understood and remain largely unknown. In this context, a comparative proteomic analysis was performed to investigate the response of the host during an infection caused by C. gattii. Lungs of experimentally infected rats were analyzed by shotgun proteomics to identify differentially expressed proteins induced by C. gattii clinical strain. The proteomic results were characterized using bioinformatic tools, and subsequently, the molecular findings were validated in cell culture and lungs of infected animals. A dramatic change was observed in protein expression triggered by C. gattii infection, especially related to energy metabolism. The main pathways affected include aerobic glycolysis cycle, TCA cycle, and pyrimidine and purine metabolism. Analyses in human lung fibroblast cells confirmed the altered metabolic status found in infected lungs. Thus, it is clear that C. gattii infection triggers important changes in energy metabolism leading to the activation of glycolysis and lactate accumulation in lung cells, culminating in a cancerlike metabolic status known as the Warburg effect. The results presented here provide important insights to better understand C. gattii molecular pathogenesis.


Assuntos
Criptococose/metabolismo , Metabolismo Energético/fisiologia , Glicólise/fisiologia , Pulmão/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Animais , Linhagem Celular , Criptococose/microbiologia , Cryptococcus gattii/fisiologia , Modelos Animais de Doenças , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Pulmão/microbiologia , Masculino , Ratos Wistar
16.
Rev. bras. oftalmol ; 78(2): 91-97, mar.-abr. 2019. tab
Artigo em Português | LILACS | ID: biblio-1003568

RESUMO

Resumo Objetivos: Identificar e descrever as alterações oculares em idosos com HIV ou aids através de exame oftalmológico. Avaliar a associação entre as alterações oculares encontradas e o nível de linfócitos T CD4, tempo da terapia antirretroviral, características demográficas e faixa etária. Métodos: Série de 40 casos de pacientes idosos com HIV examinados nos serviços de oftalmologia e imunologia do Hospital Universitário Gaffrée e Guinle (HUGG) de janeiro de 2017 a junho de 2018. Foi realizado o seguinte exame oftalmológico: anamnese, acuidade visual, motilidade ocular, reflexo pupilar, biomicroscopia, tonometria de aplanação e fundoscopia. As análises estatísticas foram realizadas pelo SPSS 20.0. Resultados: A média de idade dos 40 pacientes foi 64,7 anos (dp: 5,1) e o diagnóstico de infeção pelo HIV foi em média há 16.6 anos (dp:7). A maioria dos pacientes examinados possui visão normal (n=22; 55%) e pressão intraocular normal (entre 11 e 21 mmHg). As principais queixas dos pacientes durante a anamnese foram: embaçamento visual (50%), redução da acuidade visual (47.5%), prurido ocular (27.5%), lacrimejamento (25%) e ardência (25%). As alterações biomicroscópicas mais frequentes foram catarata (92.5%), seguida de olho seco (32.5%). Na fundoscopia encontrou-se 43,8 % de alterações da vascularização retiniana, 43.8 % de alterações relacionadas ao nervo óptico e 31,3% relacionadas ao pólo posterior da retina. Conclusão: Alterações oculares foram comuns e podem ser justificadas pela: senilidade, estado inflamatório gerado pela infecção crônica do HIV, efeitos adversos da Terapia antirretroviral prolongada e senescência biológica precoce associada a infecção do HIV.


Abstract Objectives: Identify and describe ocular changes in elderly with HIV or aids through ophthalmological examination. Evaluate the association between ocular alterations and the level of TCD4 lymphocytes, time of antiretroviral therapy, demographic characteristics and age range. Methods: Case series of 40 elderly patients with HIV infection. The study was carried out at the ophthalmology and immunology outpatient clinics of the Gaffrée and Guinle University Hospital (HUGG) from january 2017 to june 2018. The patients were attended at the ophthalmology clinic and underwent a ophthalmological exam including: anamnesis, visual acuity, ocular motility, pupillary reflex, biomicroscopy, aplanation tonometry and fundoscopy. Statistical analyses were performed using SPSS 20.0. Results: The average of the 40 patients was 64.7 years (sd: 5.1), aged between 60 and 78 years, and the average time of HIV infection was 16.6 years (sd: 7 years). Most of the patients examined had normal vision (55%) and normal intraocular pressure (between 11 and 21 mmHg). The main complaints of patients during anamnesis were visual blurring (50%), visual acuity reduction (47.5%), ocular itchiness (27.5%), tearing (25%) and burning (25%).The most frequent changes in biomicroscopy were: cataract (92.5%) and dry eye (32.5%). Funduscopy found 43.8% of retinal vascularization alterations, 43.8% of alterations related to the optic nerve and 31.3% related to retinal posterior pole. Conclusion: Ocular changes were common and can be explained by senility, inflamatory changes caused by chronic HIV infection, adverse effects of antiretroviral therapy and early biological ageing associated to HIV infection.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Infecções por HIV/complicações , Oftalmopatias/etiologia , Fatores de Tempo , Linfócitos T CD4-Positivos , Infecções por HIV/tratamento farmacológico , Fatores Etários , Contagem de Linfócito CD4 , Fármacos Anti-HIV , Terapia Antirretroviral de Alta Atividade , Técnicas de Diagnóstico Oftalmológico , Oftalmopatias/diagnóstico
17.
N Biotechnol ; 49: 71-76, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30223040

RESUMO

Feather hydrolysates were obtained through submerged cultivation of 50 g/L feathers with Chryseobacterium sp. kr6. Culture supernatants, displaying antioxidant properties, as evaluated by the 2,2'-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radical scavenging method, were partially purified by gel-filtration chromatography. Fractions showing scavenging activity were pooled, lyophilized and tested at different concentrations (0.1-1.0 mg/mL) by the total reactive antioxidant potential (TRAP) method, showing promising antioxidant capacities. Antioxidant activities of the partially purified feather hydrolysate (PPFH; 24.5 µg) were demonstrated by its ability to scavenge hydroxyl radicals and to inhibit lipid peroxidation. In addition, PPFH (0.24-24.5 µg) was found to reduce ferric ion (Fe3+), but did not display Fe2+-chelating activity. Thus, the main antioxidant activities could be related to the donation of hydrogen atoms, electron transfer and scavenging of hydroxyl radicals. PPFH was analyzed by mass spectrometry and five peptides were identified and chemically synthesized. The antioxidant activity of one peptide LPGPILSSFPQ was confirmed by ABTS and TRAP. The structure of this keratin-derived bioactive peptide has not been previously described.


Assuntos
Antioxidantes/química , Plumas/química , Queratinas/química , Peptídeos/química , Hidrolisados de Proteína/química , Sequência de Aminoácidos , Animais , Galinhas , Sequestradores de Radicais Livres/química , Radical Hidroxila/química , Peroxidação de Lipídeos
18.
Mol Neurobiol ; 56(7): 4708-4717, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30377986

RESUMO

The recent microcephaly outbreak in Brazil has been associated with Zika virus (ZIKV) infection. The current understanding of damage caused by ZIKV infection is still unclear, since it has been implicated in other neurodegenerative and developmental complications. Here, the differential proteome analysis of human mesenchymal stem cells (hMSC) infected with a Brazilian strain of ZIKV was identified by shotgun proteomics (MudPIT). Our results indicate that ZIKV induces a potential reprogramming of the metabolic machinery in nucleotide metabolism, changes in the energy production via glycolysis and other metabolic pathways, and potentially inhibits autophagy, neurogenesis, and immune response by downregulation of signaling pathways. In addition, proteins previously described in several brain pathologies, such as Alzheimer's disease, autism spectrum disorder, amyotrophic lateral sclerosis, and Parkinson's disease, were found with altered expression due to ZIKV infection in hMSC. This potential link between ZIKV and several neuropathologies beyond microcephaly is being described here for the first time and can be used to guide specific follow-up studies concerning these specific diseases and ZIKV infection.


Assuntos
Células-Tronco Mesenquimais/metabolismo , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/virologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologia , Zika virus/fisiologia , Adulto , Feminino , Humanos , Proteoma/metabolismo
19.
Eur J Med Genet ; 62(11): 103571, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30414531

RESUMO

Malformations of cortical development are a frequent cause of drug-resistant Epilepsy and developmental delay. Hemimegalencephaly is a Malformation of cortical development characterized by enlargement of all or a part of one cerebral hemisphere. Germline and somatic mutation in genes belonging to the Mammalian Target of Rapamycin (mTOR) pathway has been identified in patients suffering from epilepsy secondary to Hemimegalencephaly and focal cortical dysplasia. We present here a patient suffering from severe neonatal Epilepsy since 3 h of life secondary to Hemimegalencephaly, requiring an anatomic hemispherectomy surgical procedure for seizure control, where by means of next-generation sequencing at an ultra-high depth coverage, we were able to identify a novel somatic mutation in the RHEB gene (NM_005614: c.119A > T: p. Glu40Val). The histopathological diagnosis was Cortical Dysplasia type IIB determined by the presence of dysmorphic neurons of variable size with nuclear alteration and balloon cells in the context of Hemimegalencephaly, which are similar to that have been demonstrated in hyperactivating RHEB models. This is the first report of a somatic mutation in RHEB gene in a patient suffering from Epilepsy secondary to Hemimegalencephaly. It highlights different current topics in the fields of genetics of Malformations of cortical development: a-somatic mosaicism is not uncommon in these neurodevelopmental disorders; b-the molecular diagnostic approach should involve the use of state-of-the-art methods and the sampling of different tissues; c-new findings might facilitate therapeutics discoveries while providing an improved understanding of normal brain development.


Assuntos
Epilepsia Resistente a Medicamentos/genética , Hemimegalencefalia/genética , Malformações do Desenvolvimento Cortical/genética , Proteína Enriquecida em Homólogo de Ras do Encéfalo/genética , Epilepsia Resistente a Medicamentos/patologia , Feminino , Hemimegalencefalia/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Recém-Nascido , Malformações do Desenvolvimento Cortical/patologia , Mutação , Serina-Treonina Quinases TOR/genética
20.
IDCases ; 10: 71-74, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28966914

RESUMO

Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis or P. lutzii. It is a neglected tropical infectious disease that poses a major public health burden in endemic areas of Latin America. Mucosae of the upper digestive and respiratory tracts are commonly involved and many patients have disease at multiple mucosal sites, with or without lung involvement. Mucosal PCM presenting as solitary true vocal fold disease is relatively rare. We present the case of a 67-year-old Brazilian forest guard who presented with a 6-month history of hoarseness and globus pharyngeus due to a solitary left true vocal fold infiltration and vegetation diagnosed as PCM. Silent pulmonary disease was also present. A laryngoscopy video is offered as supplemental material to this report. He completely remitted after surgical removal and amphotericin B deoxycholate treatment.

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