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1.
Clin Neurol Neurosurg ; 241: 108305, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38713964

RESUMO

OBJECTIVE: Establish the evolution of the connectome before and after resection of motor area glioma using a comparison of connectome maps and high-definition differential tractography (DifT). METHODS: DifT was done using normalized quantitative anisotropy (NQA) with DSI Studio. The quantitative analysis involved obtaining mean NQA and fractional anisotropy (FA) values for the disrupted pathways tracing the corticospinal tract (CST), and white fiber network changes over time. RESULTS: We described the baseline tractography, DifT, and white matter network changes from two patients who underwent resection of an oligodendroglioma (Case 1) and an IDH mutant astrocytoma, grade 4 (Case 2). CASE 1: There was a slight decrease in the diffusion signal of the compromised CST in the immediate postop. The NQA and FA values increased at the 1-year follow-up (0.18 vs. 0.32 and 0.35 vs. 0.44, respectively). CASE 2: There was an important decrease in the immediate postop, followed by an increase in the follow-up. In the 1-year follow-up, the patient presented with radiation necrosis and tumor recurrence, increasing NQA from 0.18 in the preop to 0.29. Fiber network analysis: whole-brain connectome comparison demonstrated no significant changes in the immediate postop. However, in the 1-year follow up there was a notorious reorganization of the fibers in both cases, showing the decreased density of connections. CONCLUSIONS: Connectome studies and DifT constitute new potential tools to predict early reorganization changes in a patient's networks, showing the brain plasticity capacity, and helping to establish timelines for the progression of the tumor and treatment-induced changes.


Assuntos
Neoplasias Encefálicas , Conectoma , Imagem de Tensor de Difusão , Estudos de Viabilidade , Glioma , Humanos , Imagem de Tensor de Difusão/métodos , Conectoma/métodos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/cirurgia , Glioma/diagnóstico por imagem , Glioma/patologia , Masculino , Pessoa de Meia-Idade , Adulto , Córtex Motor/diagnóstico por imagem , Córtex Motor/cirurgia , Córtex Motor/fisiopatologia , Tratos Piramidais/diagnóstico por imagem , Feminino , Oligodendroglioma/cirurgia , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/patologia , Astrocitoma/cirurgia , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia
2.
Curr Opin Insect Sci ; 63: 101194, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38522648

RESUMO

Mosquitoes are vectors for arboviruses, such as dengue, Zika, and Chikungunya. Symbiotic interactions can affect the intrinsic ability of mosquitoes to acquire and transmit arboviruses, referred to as vector competence. Insect-specific viruses (ISVs) are commonly found in symbiotic associations with mosquitoes in the wild and can affect many aspects of mosquito biology. Here, we review current knowledge on the effects of symbiotic ISV-mosquito interactions on vector competence. We discuss potential mechanisms underlying these interactions and their implications for shaping new biological control strategies. Finally, we highlight the need for field data analyzing the circulation of ISVs in mosquitoes associated with mechanistic studies in the laboratory.

3.
World Neurosurg ; 181: e620-e627, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37898264

RESUMO

INTRODUCTION: Skull-base chordomas are aggressive tumors with a propensity for recurrence/progression. Even with standard of care (SoC), 5-year recurrence rates are variable (19%-54%). This high recurrence/progression rate correlates with increased morbidity and mortality. We sought to analyze a multicenter cohort of skull base chordomas to identify predictors of progression in patients receiving SoC. METHODS: The [Blinded]-Neurosurgery data registry was queried for skull base chordomas treated from 2008-2020. Patients with the histopathologic diagnosis of chordoma were included. The cohort was composed of patients with preoperative and postoperative magnetic resonance imaging. Tumor volume and radiologic characteristics were obtained from axial T2 sequences using a Digital Imaging and Communications in Medicine viewer. Survival analysis was performed using Kaplan-Meier method, and time-to-event multivariate regression was performed to identify independent predictors of progression. RESULTS: The cohort included 195 patients, of which 66 patients met inclusion criteria; median age was 44, and 28 (42%) were females. Fifty-four (82%) received SoC, 7 (11%) resection only, and 5 (8%) radiotherapy only. Median preoperative and postoperative tumor volumes were 11.55 cm3 (0.33-54.89) and 0.34 cm3 (0-42.52), respectively. Recurrence rate with SoC was 37%. Postoperative tumor volume (P = 0.010) correlated with progression. A postoperative volume of >4.9 cm3 (P = 0.044), ≤81.3% of tumor resection (P = 0.02), and lower-clivus location (P < 0.005) correlated with decreased time to progression. CONCLUSIONS: Skull base chordomas can be challenging to resect. Even though maximal resection and radiotherapy improve rate of tumor progression, many of these lesions eventually recur. We have identified a postoperative tumor volume of ≥4.9 cm3 and extent of resection of ≤81.3% in this cohort as predictors of progression in patients receiving SoC.


Assuntos
Cordoma , Neoplasias da Base do Crânio , Feminino , Humanos , Masculino , Cordoma/diagnóstico por imagem , Cordoma/cirurgia , Cordoma/patologia , Seguimentos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Base do Crânio/patologia , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/cirurgia , Neoplasias da Base do Crânio/patologia , Análise de Sobrevida , Resultado do Tratamento , Adulto
4.
Front Neurol ; 14: 1228285, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37528861

RESUMO

Gross-total resection of foramen magnum meningiomas remains the gold standard of treatment and should be performed whenever possible. The transcondylar approach (and its variations) represents the most used approach for meningiomas located in the lateral or anterior borders of the foramen magnum. Endoscopic transclivus approaches represent a useful option in selected cases of anterior midline foramen magnum meningiomas, to be performed in centers with advanced experience in endoscopic skull base surgery, with the caveats of increased risk of postoperative cerebrospinal fluid leak. Alternatively, radiosurgery remains an option for well-selected cases, especially for the management of asymptomatic patients with small enlarging tumors. Advances in molecular profiling, as well as genetic analysis, may guide adjuvant treatment.

5.
Virus Evol ; 9(2): vead041, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37636319

RESUMO

The Asian bush mosquito Aedes japonicus is rapidly invading North America and Europe. Due to its potential to transmit multiple pathogenic arthropod-borne (arbo)viruses including Zika virus, West Nile virus, and chikungunya virus, it is important to understand the biology of this vector mosquito in more detail. In addition to arboviruses, mosquitoes can also carry insect-specific viruses that are receiving increasing attention due to their potential effects on host physiology and arbovirus transmission. In this study, we characterized the collection of viruses, referred to as the virome, circulating in Ae. japonicus populations in the Netherlands and France. Applying a small RNA-based metagenomic approach to Ae. japonicus, we uncovered a distinct group of viruses present in samples from both the Netherlands and France. These included one known virus, Ae. japonicus narnavirus 1 (AejapNV1), and three new virus species that we named Ae. japonicus totivirus 1 (AejapTV1), Ae. japonicus anphevirus 1 (AejapAV1) and Ae. japonicus bunyavirus 1 (AejapBV1). We also discovered sequences that were presumably derived from two additional novel viruses: Ae. japonicus bunyavirus 2 (AejapBV2) and Ae. japonicus rhabdovirus 1 (AejapRV1). All six viruses induced strong RNA interference responses, including the production of twenty-one nucleotide-sized small interfering RNAs, a signature of active replication in the host. Notably, AejapBV1 and AejapBV2 belong to different viral families; however, no RNA-dependent RNA polymerase sequence has been found for AejapBV2. Intriguingly, our small RNA-based approach identified an ∼1-kb long ambigrammatic RNA that is associated with AejapNV1 as a secondary segment but showed no similarity to any sequence in public databases. We confirmed the presence of AejapNV1 primary and secondary segments, AejapTV1, AejapAV1, and AejapBV1 by reverse transcriptase polymerase chain reaction (PCR) in wild-caught Ae. japonicus mosquitoes. AejapNV1 and AejapTV1 were found at high prevalence (87-100 per cent) in adult females, adult males, and larvae. Using a small RNA-based, sequence-independent metagenomic strategy, we uncovered a conserved and prevalent virome among Ae. japonicus mosquito populations. The high prevalence of AejapNV1 and AejapTV1 across all tested mosquito life stages suggests that these viruses are intimately associated with Ae. japonicus.

6.
mSystems ; 8(2): e0081622, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-36912639

RESUMO

The scale of post-transcriptional regulation and the implications of its interplay with other forms of regulation in environmental acclimation are underexplored for organisms of the domain Archaea. Here, we have investigated the scale of post-transcriptional regulation in the extremely halophilic archaeon Halobacterium salinarum NRC-1 by integrating the transcriptome-wide locations of transcript processing sites (TPSs) and SmAP1 binding, the genome-wide locations of antisense RNAs (asRNAs), and the consequences of RNase_2099C knockout on the differential expression of all genes. This integrated analysis has discovered that 54% of all protein-coding genes in the genome of this haloarchaeon are likely targeted by multiple mechanisms for putative post-transcriptional processing and regulation, with about 20% of genes likely being regulated by combinatorial schemes involving SmAP1, asRNAs, and RNase_2099C. Comparative analysis of mRNA levels (transcriptome sequencing [RNA-Seq]) and protein levels (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry [SWATH-MS]) for 2,579 genes over four phases of batch culture growth in complex medium generated additional evidence for the conditional post-transcriptional regulation of 7% of all protein-coding genes. We demonstrate that post-transcriptional regulation may act to fine-tune specialized and rapid acclimation to stressful environments, e.g., as a switch to turn on gas vesicle biogenesis to promote vertical relocation under anoxic conditions and modulate the frequency of transposition by insertion sequence (IS) elements of the IS200/IS605, IS4, and ISH3 families. Findings from this study are provided as an atlas in a public Web resource (https://halodata.systemsbiology.net). IMPORTANCE While the transcriptional regulation landscape of archaea has been extensively investigated, we currently have limited knowledge about post-transcriptional regulation and its driving mechanisms in this domain of life. In this study, we collected and integrated omics data from multiple sources and technologies to infer post-transcriptionally regulated genes and the putative mechanisms modulating their expression at the protein level in Halobacterium salinarum NRC-1. The results suggest that post-transcriptional regulation may drive environmental acclimation by regulating hallmark biological processes. To foster discoveries by other research groups interested in the topic, we extended our integrated data to the public in the form of an interactive atlas (https://halodata.systemsbiology.net).


Assuntos
Archaea , Transcriptoma , Humanos , Archaea/genética , Transcriptoma/genética , Genoma , RNA Antissenso/genética , Ribonucleases/genética
7.
J Neurooncol ; 158(3): 497-506, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35699848

RESUMO

PURPOSE: The presence of necrosis or microvascular proliferation was previously the hallmark for glioblastoma (GBM) diagnosis. The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/-10 copy changes. We hypothesize that these tumors are early histological GBM and will eventually develop the classic histological features. METHODS: Medical records from 65 consecutive patients diagnosed with molGBM at three tertiary-care centers from our institution were retrospectively reviewed from November 2017-October 2021. Only patients who underwent reoperation for tumor recurrence and whose tissue at initial diagnosis and recurrence was available were included in this study. The detailed clinical, histopathological, and radiographic scenarios are presented. RESULTS: Five patients were included in our final cohort. Three (60%) patients underwent reoperation for recurrence in the primary site and 2 (40%) underwent reoperation for distal recurrence. Microvascular proliferation and pseudopalisading necrosis were absent at initial diagnosis but present at recurrence in 4 (80%) patients. Radiographically, all tumors showed contrast enhancement, however none of them showed the classic radiographic features of GBM at initial diagnosis. CONCLUSIONS: In this manuscript we present preliminary data for a hypothesis that molGBMs are early histological GBMs diagnosed early in their natural history of disease and will eventually develop necrosis and microvascular proliferation. Further correlative studies are needed in support of this hypothesis.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioblastoma/cirurgia , Humanos , Isocitrato Desidrogenase/genética , Mutação , Necrose , Estudos Retrospectivos
8.
Pituitary ; 25(3): 540-549, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35508745

RESUMO

PURPOSE: Transsphenoidal surgery (TSS) is the first-line treatment for patients with Cushing's Disease (CD). Recurrence rates after a first TSS range between 3 and 22% within 3 years. Management of recurrent or persistent CD may include repeat TSS or stereotactic radiosurgery (SRS). We performed a meta-analysis to explore the overall efficacy of TSS and SRS for patients with CD after an initial surgical intervention. METHODS: EMBASE, PubMed, SCOPUS, and Cochrane databases were searched from their dates-of-inception up to December 2021. Inclusion criteria were comprised of patients with an established diagnosis of CD who presented with persistent or biochemically recurrent disease after a first TSS for tumor resection and were treated with a second TSS or SRS. RESULTS: Search criteria yielded 2,116 studies of which 37 articles from 15 countries were included for analysis. Mean age ranged between 29.9 and 47.9 years, and mean follow-up was 11-104 months. TSS was used in 669 (67.7%) patients, while SRS was used in 320 (32.4%) patients, and remission rates for CD were 59% (95%CI 0.49-0.68) and 74% (95%CI 0.54-0.88), respectively. There was no statistically significant difference in the remission rate between TSS and SRS (P = 0.15). The remission rate of patients with recurrent CD undergoing TSS was 53% (95%CI 0.32-0.73), and for persistent CD was 41% (95%CI 0.28-0.56) (P = 0.36). CONCLUSION: Both TSS and SRS are possible approaches for the treatment of recurrent or persistent CD after a first TSS. Our data show that either TSS or SRS represent viable treatment options to achieve remission for this subset of patients.


Assuntos
Hipersecreção Hipofisária de ACTH , Radiocirurgia , Pré-Escolar , Humanos , Hipersecreção Hipofisária de ACTH/patologia , Hipersecreção Hipofisária de ACTH/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
9.
J Neurooncol ; 157(1): 177-185, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35175545

RESUMO

PURPOSE: Histological diagnosis of glioblastoma (GBM) was determined by the presence of necrosis or microvascular proliferation (histGBM). The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM, WHO grade 4) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/- 10 copy changes. The objective of this study was to explore and compare the survival outcomes between histGBM and molGBM. METHODS: Medical records for patients diagnosed with GBM at the three tertiary care academic centers of our institution from November 2017 to October 2021. Only patients who underwent adjuvant chemoradiation were included. Patients without molecular feature testing or with an IDH mutation were excluded. Univariable and multivariable analyses were performed to evaluate progression-free (PFS) and overall- survival (OS). RESULTS: 708 consecutive patients were included; 643 with histGBM and 65 with molGBM. Median PFS was 8 months (histGBM) and 13 months (molGBM) (p = 0.0237) and median OS was 21 months (histGBM) versus 26 months (molGBM) (p = 0.435). Multivariable analysis on the molGBM sub-group showed a worse PFS if there was contrast enhancement on MRI (HR 6.224 [CI 95% 2.187-17.714], p < 0.001) and a superior PFS on patients with MGMT methylation (HR 0.026 [CI 95% 0.065-0.655], p = 0.007). CONCLUSIONS: molGBM has a similar OS but significantly longer PFS when compared to histGBM. The presence of contrast enhancement and MGMT methylation seem to affect the clinical behavior of this subset of tumors.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Astrocitoma/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Isocitrato Desidrogenase/genética , Mutação , Prognóstico
11.
J Infect ; 82(3): 399-406, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33589297

RESUMO

BACKGROUND: There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term. METHODS: Observational case series and case-control studies reporting 33 cases of recurrent, symptomatic, qRT-PCR positive COVID-19. Recurrent disease was defined as symptomatic recurrence after symptom-free clinical recovery, with release from isolation >14 days from the beginning of symptoms confirmed by qRT-PCR. The case control study-design compared this group of patients with a control group of 62 patients randomly selected from the same COVID-19 database. RESULTS: Of 33 recurrent COVID-19 patients, 26 were female and 30 were HCW. Mean time to recurrence was 50.5 days which was associated with being a HCW (OR 36.4 (p <0.0001)), and blood type A (OR 4.8 (p = 0.002)). SARS-CoV-2 antibodies were signifcantly lower in recurrent patients after initial COVID-19  (2.4 ±â€¯0.610; p<0.0001) and after recurrence (6.4 ±â€¯11.34; p = 0.007).  Virus genome sequencing identified reinfection by a different isolate in one patient. CONCLUSIONS: This is the first detailed case series showing COVID-19 recurrence with qRT-PCR positivity. For one individual detection of phylogenetically distinct genomic sequences in the first and second episodes confirmed bona fide renfection, but in most cases the data do not formally distinguish between reinfection and re-emergence of a chronic infection reservoir. These episodes were significantly associated with reduced Ab response during initial disease and argue the need for ongoing vigilance without an assumption of protection after a first episode.


Assuntos
COVID-19 , Pessoal de Saúde , Reinfecção , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , SARS-CoV-2 , Índice de Gravidade de Doença
12.
J Neurosurg Sci ; 65(2): 151-159, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33491347

RESUMO

The development of extended endoscopic endonasal approaches (EEA) to the anterior skull base has allowed successful resection of selected extradural and intradural skull base tumors through an endonasal corridor, minimizing brain and cranial nerve manipulation. However, as the complexity of the approaches has increased, so has the need for more robust and reliable reconstructive options to minimize morbidity. Reconstructive decision-making after extended EEA for anterior skull base tumors must take into consideration multiple factors including patient characteristics (Body Mass Index, previous surgeries, and radiation), location and the size of the skull base defect. A multilayered reconstruction which includes a combination of free grafts and a vascularized flap is the standard approach to anterior skull base defects after EEA and should be applied in a stepwise manner tailored to each patient. The techniques and materials used to accomplish skull base repair are discussed, the outcomes in the literature are reviewed, and our reconstructive paradigm presented.


Assuntos
Procedimentos de Cirurgia Plástica , Neoplasias da Base do Crânio , Encéfalo , Endoscopia , Humanos , Base do Crânio/cirurgia , Neoplasias da Base do Crânio/cirurgia
13.
J Neurosurg Sci ; 65(2): 103-117, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33245220

RESUMO

Endoscopic endonasal approaches (EEA) to the skull base have significantly impacted the management of lesions located in the cranial base. Specifically, lesions arising from the anterior cranial fossa, such as pituitary macroadenomas, craniopharyngiomas meningiomas and craniofacial malignancies have benefited from the development of such approaches. Understanding of the anatomy of the anterior fossa is of utmost importance for the successful selection of the approach and application of surgical techniques in EEA. In the current manuscript, we review the most relevant points of surgical anatomy and nuances of the surgical technique of EEA to the anterior fossa. Anatomical landmarks for the transtuberculum transplanum and transcribriform approaches are discussed and a step-by-step description for those approaches is presented. We reinforce that safe and effective application of such techniques follow the same principles of other skull base surgery techniques: mastering of surgical anatomy, adequate case selection, correct instrumentation and surgical experience.


Assuntos
Neoplasias Meníngeas , Neoplasias da Base do Crânio , Fossa Craniana Anterior/cirurgia , Humanos , Neoplasias Meníngeas/cirurgia , Procedimentos Neurocirúrgicos , Base do Crânio/cirurgia , Neoplasias da Base do Crânio/cirurgia
14.
Viruses ; 12(7)2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32708079

RESUMO

Arboviruses, including the Zika virus, have recently emerged as one of the most important threats to human health. The use of metagenomics-based approaches has already proven valuable to aid surveillance of arboviral infections, and the ability to reconstruct complete viral genomes from metatranscriptomics data is key to the development of new control strategies for these diseases. Herein, we used RNA-based metatranscriptomics associated with Ion Torrent deep sequencing to allow for the high-quality reconstitution of an outbreak-related Zika virus (ZIKV) genome (10,739 nt), with extended 5'-UTR and 3'-UTR regions, using a newly-implemented bioinformatics approach. Besides allowing for the assembly of one of the largest complete ZIKV genomes to date, our strategy also yielded high-quality complete genomes of two arthropod-infecting viruses co-infecting C6/36 cell lines, namely: Alphamesonivirus 1 strain Salvador (20,194 nt) and Aedes albopictus totivirus-like (4618 nt); the latter likely represents a new viral species. Altogether, our results demonstrate that our bioinformatics approach associated with Ion Torrent sequencing allows for the high-quality reconstruction of known and unknown viral genomes, overcoming the main limitation of RNA deep sequencing for virus identification.


Assuntos
Arbovírus/genética , Surtos de Doenças , Perfilação da Expressão Gênica/métodos , Genoma Viral/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Nidovirales/genética , Infecção por Zika virus/virologia , Zika virus/genética , Humanos , Mosquitos Vetores/virologia , Filogenia , Reação em Cadeia da Polimerase , Infecção por Zika virus/epidemiologia
15.
J Virol Methods ; 282: 113888, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32445875

RESUMO

Herein, we describe the detection of a SARS-CoV-2 genome through metatranscriptome next-generation sequencing directly from the nasopharyngeal swab of a suspected case of local transmission of Covid-19, in Brazil. Depletion of human ribosomal RNA and use of an optimized in-house developed bioinformatics strategy contributed to successful detection of the virus.

16.
Mol Pharmacol ; 97(4): 295-303, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32102968

RESUMO

The main objective of this study was to clarify the topical mechanisms underlying diclofenac-induced gastric toxicity by considering for the first time both ionization states of this nonsteroidal anti-inflammatory drug. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes were the model system chosen to mimic the protective phospholipid layers of the gastric mucosa and to describe the interactions with diclofenac, considering the pH gradient found in the gastric mucosa (3 < pH < 7.4). Complementary experimental techniques were combined to evaluate the drug's affinity for DMPC bilayers, as well as to assess the drug's effects on the structural properties of the phospholipid bilayer. The diclofenac-DMPC interactions were clearly dependent on the drug's ionization state. Neutral diclofenac displayed greater affinity for DMPC bilayers than anionic diclofenac. Moreover, the protonated/neutral form of the drug induced more pronounced and/or distinct alterations in the structure of the DMPC bilayer than the deprotonated/ionized form, considering similar membrane concentrations. Therefore, neutral diclofenac-induced changes in the structural properties of the external phospholipid layers of the gastric mucosa may constitute an additional toxicity mechanism of this worldwide-used drug, which shall be considered for the development of safer therapeutic strategies. SIGNIFICANCE STATEMENT: Neutral or anionic diclofenac exerted distinct alterations in phosphatidylcholine bilayers, which are used in this work as models for the protective phospholipid layers of the gastric mucosa. Remarkable changes were induced by neutral diclofenac in the structural properties of the phospholipid bilayer, suggesting that both ionized and neutral states of nonsteroidal anti-inflammatory drugs must be considered to clarify their mechanisms of toxicity and to ultimately develop safer anti-inflammatory drugs.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Diclofenaco/toxicidade , Dimiristoilfosfatidilcolina/química , Mucosa Gástrica/efeitos dos fármacos , Bicamadas Lipídicas/química , Mucosa Gástrica/química , Concentração de Íons de Hidrogênio , Lipossomos/química , Estrutura Molecular , Espalhamento a Baixo Ângulo , Difração de Raios X
17.
World Neurosurg ; 127: 336-345, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004861

RESUMO

BACKGROUND: Adult sellar atypical teratoid/rhabdoid tumor (ATRT) is a rare diagnosis that has recently been shown to be a clinicopathologically and genetically distinct variant of ATRT occurring almost exclusively in middle-aged women. Although up to one third of pediatric ATRT is caused by a familial syndrome, no previous cases of a familial adult sellar ATRT have been reported. We present the first case report of a familial germline mutation causing adult sellar ATRT and a literature review of 29 previously reported cases of sporadic adult sellar ATRT. CASE DESCRIPTION: A 51-year-old woman with a family history of brain tumors spanning 3 generations presented with visual decline and was diagnosed with an adult sellar ATRT. Genetic studies showed a heterozygous splice-site loss-of-function mutation of the INI1 gene in exon 7. Treatment included endoscopic endonasal biopsy, craniospinal irradiation, and focal tumor boost, followed by adjuvant chemotherapy. CONCLUSIONS: This is the first case report of a familial germline mutation causing adult sellar ATRT. This article highlights the importance of a thorough family history and genetic testing in these individuals and reviews the current genetics, histopathology, and multidisciplinary treatment approach in this rare condition.


Assuntos
Neoplasias Encefálicas/genética , Mutação em Linhagem Germinativa/genética , Tumor Rabdoide/genética , Proteína SMARCB1/genética , Teratoma/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia
18.
J Neurosurg Sci ; 63(1): 88-95, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26603533

RESUMO

Endoscopic skull base surgery is one of the most recent fields of neurosurgery. Successive innovations were developed throughout history so that the current concepts that rule this surgical field could be reached. The current paper presents the evolution of endoscopic surgery and its current results on the treatment of skull base tumor, based on a review of meta-analysis and clinical series. A PubMed search for articles published between January 1990 and January 2014 about "endoscopic skull base surgery", "endoscopic transsphenoidal approach", "endoscopic treatment of parasellar tumors" and "suprasellar lesions" was performed. According to the current data, endoscopic surgery seems to be superior to open and transsphenoidal microscopic removal of giant pituitary adenomas. Endoscopy is at least as successful as transsphenoidal microsurgery for the removal of pituitary adenomas and craniopharyngiomas. Transcranial open approaches, in the context of anterior midline skull base meningiomas, present higher rates of gross total resection, fewer complications and better clinical results than endoscopy approaches. The rate of postoperative CSF leakage has been significantly reduced with the introduction of new techniques such as the Hadad-Bassagasteguy flap but still represent one of the most important complications of this technique. Currently, selected tumors located at the anterior, middle and posterior fossa can be adequately assessed using the endoscope with low rates of postoperative CSF leaks. Endoscopic surgery has substantially evolved in the last decades through the collaboration of different teams around the world. The endoscope is now an essential tool in the neurosurgery armamentarium with great potential for new applications in the nearby future.


Assuntos
Neuroendoscopia/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Neoplasias Hipofisárias/cirurgia , Neoplasias da Base do Crânio/cirurgia , História do Século XX , História do Século XXI , Humanos , Neuroendoscopia/efeitos adversos , Neuroendoscopia/história
19.
Sci Rep ; 7(1): 175, 2017 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-28282967

RESUMO

Gregarines (Apicomplexa) are a diverse group of protozoan parasites, which infects gut and other body cavities of invertebrate hosts. In reproductive system of insects, gregarine has been reported only in the accessory glands and spermathecae of females; therefore, this is the first report of a gregarine species in seminal vesicles of insects. Different developmental stages, including sporozoytes, oocysts and trophozoites were described from morphological descriptions using light and electron transmission microscopy. The parasites were described in seminal vesicles of the beetle Tribolium castaneum a model organism and an important insect pest. DNA sequence analysis suggests that the protozoan parasite was an Ascogregarina sp.


Assuntos
Apicomplexa/classificação , Apicomplexa/crescimento & desenvolvimento , Besouros/parasitologia , Análise de Sequência de DNA/métodos , Animais , Apicomplexa/genética , Apicomplexa/ultraestrutura , DNA de Protozoário/genética , Feminino , Masculino , Microscopia Eletrônica de Transmissão , Filogenia , Glândulas Seminais/parasitologia
20.
J Neurosurg Sci ; 60(1): 27-43, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26657135

RESUMO

Comprehensive understanding of the vascular anatomy, including anatomic variations, anatomy of the perforators, and areas of irrigation for each specific vascular trunk is relevant for the treatment of intracranial aneurysms. Understanding the microanatomy of the cerebral vessels helps surgeons to select the most appropriate microsurgical approach for each case. Anterior circulation aneurysms may be originated from the internal carotid artery and its branches, anterior cerebral artery, middle cerebral artery and anterior communicating artery. Although presenting different surgical nuances, we favor the use of the pterional approach for most anterior circulation aneurysms. In some instances, extensions of the pterional approach improve the surgical exposure and may be selected. In its turn, posterior fossa aneurysms remain a challenge to the neurosurgeon. The exquisite eloquence and complexity of posterior fossa contents require a through knowledge of microsurgical anatomy of this region. Such anatomic background guides the surgeon to the most appropriate approach, which may vary dependind on the size, position of the aneuryms and its relatonship to the surrounding structures.


Assuntos
Encéfalo/irrigação sanguínea , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/cirurgia , Humanos , Microcirurgia , Procedimentos Neurocirúrgicos
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