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1.
Biochem Pharmacol ; 178: 114050, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32446887

RESUMO

Efavirenz (EFV) is used for antiretroviral treatment of HIV infection, and successfully inhibits viral replication and mother-to-child transmission of HIV during pregnancy and childbirth. Unfortunately, the drug induces neuropsychiatric symptoms such as anxiety and depressed mood and potentially affects cognitive performance. EFV acts on, among others, the serotonin transporter and serotonin receptors that are expressed in the developing brain. Yet, how perinatal EFV exposure affects brain cytoarchitecture remains unclear. Here, we exposed pregnant and lactating rats to EFV, and examined in the medial prefrontal cortex (mPFC) of their adult offspring the effects of the maternal EFV exposure on cortical architecture. We observed a significant decrease in the number of cells, mainly mature neurons, in the infra/prelimbic and cingulate cortices of adult offspring. Next, we found an altered cortical cytoarchitecture characterized by a significant reduction in deep- and superficial-layer cells. This was accompanied by a sharp increase in programmed cell death, as we identified a significantly higher number of cleaved Caspase-3-positive cells. Finally, the serotonergic and dopaminergic innervation of the mPFC subdomains was increased. Thus, the perinatal exposure to EFV provoked in the mPFC of adult offspring cell death, significant changes in cytoarchitecture, and disturbances in serotonergic and dopaminergic innervation. Our results are important in the light of EFV treatment of HIV-positive pregnant women, and its effect on brain development and cognitive behavior.


Assuntos
Alcinos/toxicidade , Benzoxazinas/toxicidade , Ciclopropanos/toxicidade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Inibidores da Transcriptase Reversa/toxicidade , Animais , Animais Recém-Nascidos , Fármacos Anti-HIV/toxicidade , Feminino , Masculino , Córtex Pré-Frontal/crescimento & desenvolvimento , Gravidez , Ratos , Ratos Wistar
2.
Lupus ; 28(13): 1549-1557, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619143

RESUMO

OBJECTIVE: This study aimed to analyze the expression of the high mobility group box-1 (HMGB1) protein in neutrophil extracellular traps (NETs) of patients with lupus nephritis (LN) and its association with clinical and histopathological features of the disease. METHODS: Twenty-three patients with biopsy-confirmed LN and 14 systemic lupus erythematosus (SLE) patients with active disease (SLE Disease Activity Index (SLEDAI) score ≥ 6) and no evidence of LN were included. Clinical and laboratory features were recorded. NETs and the expression of HMGB1 were assessed by confocal microscopy, and serum HMGB1 levels were measured by ELISA. RESULTS: In comparison to patients without kidney disease, patients with LN had a higher expression of HMGB1 in spontaneous (57 vs. 30.4; p = 0.027) and lipopolysaccharide (LPS)-induced (55.8 vs. 24.9; p = 0.005) NETs. We found a positive correlation between serum HMGB1 and the expression of HMGB1 in LPS-induced NETs (r = 0.447, p = 0.017). The expression of HMGB1 in spontaneous NETs correlated with SLEDAI score (r = 0.514, p = 0.001), anti-dsDNA antibodies (r = 0.467, p = 0.004), the rate of glomerular filtration descent (r = 0.543, p = 0.001), and diverse histopathological components of active nephritis in the kidney biopsy, such as the activity index (r = 0.581, p = 0.004), fibrinoid necrosis (r = 0.603, p = 0.002), and cellular crescents (r = 0.486, p = 0.019). CONCLUSIONS: In patients with SLE, NETs are a source of extracellular HMGB1. The expression of HMGB1 in NETs is higher among patients with LN, which correlates with clinical and histopathological features of active nephritis and suggest a possible role of this alarmin in the pathophysiology of kidney damage in SLE.


Assuntos
Armadilhas Extracelulares/metabolismo , Proteína HMGB1/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Proteína HMGB1/sangue , Humanos , Nefrite Lúpica/sangue , Masculino , Índice de Gravidade de Doença , Adulto Jovem
3.
Cell Tissue Bank ; 16(2): 287-94, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25098349

RESUMO

The neuropathological examination of postmortem human brain tissue is an essential resource for the definitive diagnosis and research on neurodegenerative diseases. Due to the growing need of donated brains to supply the Brain Banks, the understanding of the factors associated with the consent for the donation in our context is an important aspect of the process of brain donation. The verbal answers and the donation consent rate were evaluated in three groups: 30 relatives of patients who underwent verification of the cause of death, 14 patients assisted at a neurology ambulatory outpatient clinic, and 18 patients' relatives. The donation consent rates were of 46.6, 92.8 and 88.8 %, respectively. The main reasons for refusal were the disagreement with the autopsy, philosophical and religious issues, objections from other family members, and the consideration of the wishes of the deceased. The consent was specially motivated by the interest in the advances of scientific knowledge, altruistic reasons and the personal experiences with the disease. Factors as the emotional fragility at the moment of death, the beliefs, family matters, and the lack of knowledge are key elements in the donation process. Future goals include the establishment of a brain donor program with the support of academic institutions, hospitals, scientists, community, patient's associations and autopsy assistants. Approaching patients and relatives in specialized ambulatories clinic during assistance is probably the most efficient mean of obtaining brains for research.


Assuntos
Encéfalo/cirurgia , Família/etnologia , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Autopsia/métodos , Encéfalo/patologia , Brasil , Tomada de Decisões/fisiologia , Família/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Doadores de Tecidos/psicologia
4.
Rev Cubana Med Trop ; 53(2): 111-7, 2001.
Artigo em Espanhol | MEDLINE | ID: mdl-15844299

RESUMO

Toxoplasmposis is one of the zoonotic diseases which is widely spread all over the world. It is caused by Toxoplasma gondii. In this paper we made a chronological synthesis of some of the numerous investigations that have been made in the world and in Cuba.


Assuntos
Pesquisa Biomédica/história , Toxoplasmose/história , Animais , História do Século XX , Humanos
5.
J Clin Microbiol ; 27(12): 2684-6, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2687317

RESUMO

One hundred fifty-five biopsy specimens from the gastric mucosa of 81 patients undergoing routine endoscopy procedures were tested for the presence of Campylobacter pylori by three methods: Gram stain, culture, and modified Minitek, a rapid urea disk test (BBL Microbiology Systems, Cockeysville, Md.). Twenty-nine patients were infected with C. pylori. Sensitivities and specificities of detection were 100 and 94% with the Minitek test and 93 and 100% with Gram stain, respectively. Rapid testing by the urea disk is a simple, cost-effective, and accurate method for detecting the presence of C. pylori in gastric biopsy specimens.


Assuntos
Campylobacter/isolamento & purificação , Mucosa Gástrica/microbiologia , Ureia/metabolismo , Urease/análise , Técnicas Bacteriológicas , Biópsia , Campylobacter/enzimologia , Gastrite/microbiologia , Gastroscopia , Humanos , Valor Preditivo dos Testes
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