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1.
J Perinat Med ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38943320

RESUMO

OBJECTIVES: This case series aims to evaluate the long-term outcomes of congenital cytomegalovirus (CMV) infection in a population treated with valaciclovir during pregnancy. The study focuses on assessing the prevalence of long-term sequelae in infants with confirmed CMV fetal infection. METHODS: A retrospective analysis was conducted on 33 pregnancies corresponding to 34 fetus with confirmed CMV congenital infection. They were followed from November 2004 to December 2020. Valaciclovir treatment was initiated after confirmation of fetal infection, and fetal outcomes were monitored through serial ultrasounds, neurosonography, and fetal magnetic resonance imaging (MRI). Postnatal assessments included: PCR confirmation, symptoms evaluation at birth, and long-term follow-up protocols for visual, auditory, and neurodevelopmental assessment. RESULTS: Therapy was started at a median gestational age of 24 weeks. Of the 34 newborns 79.4 % were asymptomatic at birth. Median follow-up time was 6 years and 32.35 % developed long-term sequelae. Neurosensorial hearing loss (SNHL) was the predominant sequelae. In the cases which developed sequelae 54.5 % had imaging findings, and all with major findings developed long-term sequelae. CONCLUSIONS: In our treated population we had a higher asymptomatic rate at birth comparing with a non-treated population, similar to those found in previous studies. We had a long-term sequelae rate of 32.35 %, similar to recent studies on non-treated population, although we registered a slightly lower rate of SNHL. A larger multicenter studies with a longer follow-up time, where treatment is started in the first trimester, is of the utmost importance, so we can truly understand the correlation between these imaging findings, therapy and long-term sequelae.

2.
Commun Biol ; 7(1): 179, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351154

RESUMO

The translocated intimin receptor (Tir) is an essential type III secretion system (T3SS) effector of attaching and effacing pathogens contributing to the global foodborne disease burden. Tir acts as a cell-surface receptor in host cells, rewiring intracellular processes by targeting multiple host proteins. We investigated the molecular basis for Tir's binding diversity in signalling, finding that Tir is a disordered protein with host-like binding motifs. Unexpectedly, also are several other T3SS effectors. By an integrative approach, we reveal that Tir dimerises via an antiparallel OB-fold within a highly disordered N-terminal cytosolic domain. Also, it has a long disordered C-terminal cytosolic domain partially structured at host-like motifs that bind lipids. Membrane affinity depends on lipid composition and phosphorylation, highlighting a previously unrecognised host interaction impacting Tir-induced actin polymerisation and cell death. Furthermore, multi-site tyrosine phosphorylation enables Tir to engage host SH2 domains in a multivalent fuzzy complex, consistent with Tir's scaffolding role and binding promiscuity. Our findings provide insights into the intracellular Tir domains, highlighting the ability of T3SS effectors to exploit host-like protein disorder as a strategy for host evasion.


Assuntos
Proteínas de Escherichia coli , Proteínas de Escherichia coli/metabolismo , Proteínas de Transporte , Receptores de Superfície Celular/metabolismo
3.
Brain Res Mol Brain Res ; 99(1): 17-25, 2002 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-11869804

RESUMO

The activity and expression of nitric oxide synthase (NOS) isoforms and protein nitrotyrosine (NT) residues were investigated in whole encephalic mass (WEM) homogenates during the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. EAE stages (0-III) were daily defined by clinical evaluation, and in the end of each stage, WEMs were removed for analysis of NOS activity, protein NT residues and mRNA for the different NOS isoforms. In the presence of NADPH, WEMs from EAE-III rats showed lower Ca2+-dependent NOS activity than those from control group. These differences disappeared in the presence of exogenous calmodulin, flavin adenine dinucleotide (FAD), tetrahydrobiopterin (BH4) and NADPH. Of all the cofactors, just the omission of FAD caused comparable decrease of Ca2+-dependent NOS activity from both groups. Ca2+-independent NOS activity from EAE-III animals was insensitive to the omission of any of the cofactors, while in control animals this activity was significantly inhibited by the omission of either FAD or BH4. Increased levels of both iNOS mRNA and protein NT expression were observed in animals with EAE, which also showed lower levels of a thermolabile NOS inhibitor in WEM homogenates and sera than controls. In conclusion, during late EAE stages, constitutive Ca2+-dependent NOS activity decreases concomitantly with iNOS upregulation, which could be responsible for the high protein NT levels. The differential dependence of iNOS activity on cofactors and the absence of an endogenous thermolabile NOS inhibitor in animals with EAE could reflect additional control mechanisms of NOS activity in this model of multiple sclerosis.


Assuntos
Biopterinas/análogos & derivados , Encéfalo/enzimologia , Encefalomielite Autoimune Experimental/enzimologia , Neurônios/enzimologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Animais , Biopterinas/metabolismo , Encéfalo/fisiopatologia , Cálcio/metabolismo , Calmodulina/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Encefalomielite Autoimune Experimental/fisiopatologia , Feminino , Flavina-Adenina Dinucleotídeo/metabolismo , Masculino , NADP/metabolismo , Óxido Nítrico Sintase/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Frações Subcelulares/metabolismo
4.
Rev. SPAGESP ; 3(3): 232-236, 2002.
Artigo em Português | Index Psicologia - Periódicos | ID: psi-28475

RESUMO

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