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1.
Brain Spine ; 4: 102829, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812880

RESUMO

Introduction: Surgical training traditionally adheres to the apprenticeship paradigm, potentially exposing trainees to an increased risk of complications stemming from their limited experience. To mitigate this risk, augmented and virtual reality have been considered, though their effectiveness is difficult to assess. Research question: The PASSION study seeks to investigate the improvement of manual dexterity following intensive training with neurosurgical simulators and to discern how surgeons' psychometric characteristics may influence their learning process and surgical performance. Material and methods: Seventy-two residents were randomized into the simulation group (SG) and control group (CG). The course spanned five days, commencing with assessment of technical skills in basic procedures within a wet-lab setting on day 1. Over the subsequent core days, the SG engaged in simulated procedures, while the CG carried out routine activities in an OR. On day 5, all residents' technical competencies were evaluated. Psychometric measures of all participants were subjected to analysis. Results: The SG demonstrated superior performance (p < 0.0001) in the brain tumour removal compared to the CG. Positive learning curves were evident in the SG across the three days of simulator-based training for all tumour removal tasks (all p-values <0.05). No significant differences were noted in other tasks, and no meaningful correlations were observed between performance and any psychometric parameters. Discussion and conclusion: A brief and intensive training regimen utilizing 3D virtual reality simulators enhances residents' microsurgical proficiency in brain tumour removal models. Simulators emerge as a viable tool to expedite the learning curve of in-training neurosurgeons.

2.
Cancers (Basel) ; 16(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38254896

RESUMO

The lack of early detection and a high rate of recurrence/progression after surgery are defined as the most common causes of a very poor prognosis of Gliomas. The developments of quantification systems with special regards to artificial intelligence (AI) on medical images (CT, MRI, PET) are under evaluation in the clinical and research context in view of several applications providing different information related to the reconstruction of imaging, the segmentation of tissues acquired, the selection of features, and the proper data analyses. Different approaches of AI have been proposed as the machine and deep learning, which utilize artificial neural networks inspired by neuronal architectures. In addition, new systems have been developed using AI techniques to offer suggestions or make decisions in medical diagnosis, emulating the judgment of radiologist experts. The potential clinical role of AI focuses on the prediction of disease progression in more aggressive forms in gliomas, differential diagnosis (pseudoprogression vs. proper progression), and the follow-up of aggressive gliomas. This narrative Review will focus on the available applications of AI in brain tumor diagnosis, mainly related to malignant gliomas, with particular attention to the postoperative application of MRI and PET imaging, considering the current state of technical approach and the evaluation after treatment (including surgery, radiotherapy/chemotherapy, and prognostic stratification).

3.
FEBS J ; 291(4): 722-743, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37947039

RESUMO

Physiologically, renal medullary cells are surrounded by a hyperosmolar interstitium. However, different pathological situations can induce abrupt changes in environmental osmolality, causing cell stress. Therefore, renal cells must adapt to survive in this new condition. We previously demonstrated that, among the mechanisms involved in osmoprotection, renal cells upregulate triglyceride biosynthesis (which helps preserve glycerophospholipid synthesis and membrane homeostasis) and cyclooxygenase-2 (which generates prostaglandins from arachidonic acid) to maintain lipid metabolism in renal tissue. Herein, we evaluated whether hyperosmolality modulates phospholipase A2 (PLA2 ) activity, leading to arachidonic acid release from membrane glycerophospholipid, and investigated its possible role in hyperosmolality-induced triglyceride synthesis and accumulation. We found that hyperosmolality induced PLA2 expression and activity in Madin-Darby canine kidney cells. Cytosolic PLA2 (cPLA2) inhibition, but not secreted or calcium-independent PLA2 (sPLA2 or iPLA2 , respectively), prevented triglyceride synthesis and reduced cell survival. Inhibition of prostaglandin synthesis with indomethacin not only failed to prevent hyperosmolality-induced triglyceride synthesis but also exacerbated it. Similar results were observed with the peroxisomal proliferator activated receptor gamma (PPARγ) agonist rosiglitazone. Furthermore, hyperosmolality increased free intracellular arachidonic acid levels, which were even higher when prostaglandin synthesis was inhibited by indomethacin. Blocking PPARγ with GW-9662 prevented the effects of both indomethacin and rosiglitazone on triglyceride synthesis and even reduced hyperosmolality-induced triglyceride synthesis, suggesting that arachidonic acid may stimulate triglyceride synthesis through PPARγ activation. These results highlight the role of cPLA2 in osmoprotection, since it is essential to provide arachidonic acid, which is involved in PPARγ-regulated triglyceride synthesis, thus guaranteeing cell survival.


Assuntos
PPAR gama , Prostaglandinas , Animais , Cães , PPAR gama/genética , Ácido Araquidônico/metabolismo , Rosiglitazona , Pressão Osmótica , Fosfolipases A2 , Indometacina , Homeostase , Glicerofosfolipídeos , Triglicerídeos
4.
Environ Toxicol Pharmacol ; 101: 104192, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37348771

RESUMO

The effects of the exposure of proliferating MDCK cells to thallium [Tl(I) or Tl(III)] on cell viability and proliferation were investigated. Although Tl stopped cell proliferation, the viability was > 95%. After 3 h, two autophagy markers (SQSTM-1 expression and LC3ß localization) were altered, and at 48 h increased expression of SQSTM-1 (60%) and beclin-1 (50-100%) were found. At 24 h, the expression of endoplasmic reticulum (ER) stress markers ATF-6 and IRE-1 were increased in 100% and 150%, respectively, accompanied by XBP-1 splicing and nuclear translocation. At 48 h, major ultrastructure abnormalities were found, including ER enlargement and cytoplasmic vacuolation which was not prevented by protein synthesis inhibition. Increased PHB (85% and 40% for Tl(I) and Tl(III), respectively) and decreased ß-tubulin (45%) expression were found which may be related to the promotion of paraptosis. In summary, Tl(I) and Tl(III) promoted ER stress and probably paraptosis in MDCK cells, impairing their proliferation.


Assuntos
Apoptose , Tálio , Animais , Cães , Tálio/farmacologia , Células Madin Darby de Rim Canino , Estresse do Retículo Endoplasmático , Proliferação de Células , Autofagia
5.
Life Sci ; 319: 121544, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36871933

RESUMO

AIMS: Calcium oxalate (Oxa), constituent of most common kidney stones, damages renal tubular epithelial cells leading to kidney disease. Most in vitro studies designed to evaluate how Oxa exerts its harmful effects were performed in proliferative or confluent non-differentiated renal epithelial cultures; none of them considered physiological hyperosmolarity of renal medullary interstitium. Cyclooxygenase 2 (COX2) has been associated to Oxa deleterious actions; however, up to now, it is not clear how COX2 acts. In this work, we proposed an in vitro experimental system resembling renal differentiated-epithelial cells that compose medullary tubular structures which were grown and maintained in a physiological hyperosmolar environment and evaluated whether COX2 â†’ PGE2 axis (COX2 considered a cytoprotective protein for renal cells) induces Oxa damage or epithelial restitution. MAIN METHODS: MDCK cells were differentiated with NaCl hyperosmolar medium for 72 h where cells acquired the typical apical and basolateral membrane domains and a primary cilium. Then, cultures were treated with 1.5 mM Oxa for 24, 48, and 72 h to evaluate epithelial monolayer restitution dynamics and COX2-PGE2 effect. KEY FINDINGS: Oxa completely turned the differentiated phenotype into mesenchymal one (epithelial-mesenchymal transition). Such effect was partially and totally reverted after 48 and 72 h, respectively. Oxa damage was even deeper when COX2 was blocked by NS398. PGE2 addition restituted the differentiated-epithelial phenotype in a time and concentration dependence. SIGNIFICANCE: This work presents an experimental system that approaches in vitro to in vivo renal epithelial studies and, more important, warns about NSAIDS use in patients suffering from kidney stones.


Assuntos
Oxalato de Cálcio , Cálculos Renais , Oxalato de Cálcio/química , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Células Epiteliais/metabolismo , Cálculos Renais/química , Células Madin Darby de Rim Canino , Animais , Cães
7.
Mol Diagn Ther ; 27(1): 5-13, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36401787

RESUMO

BACKGROUND: Data on molecular alterations harbored by melanoma brain metastases (MBMs) are limited, and this has hampered the development of more effective therapeutic strategies. We conducted a systematic review and meta-analysis of all the studies reporting DNA sequencing data of MBMs, in order to identify recurrently mutated genes and molecular pathways significantly enriched for genetic alterations. METHODS: We searched PubMed, Embase and Scopus for articles published from the inception of each database to June 30, 2021. We included in the analysis all the studies that reported individual patient data on DNA sequencing of MBMs, assessing single nucleotide variants (SNVs) and/or gene copy number variations (CNVs) in at least five tumor samples. Meta-analysis was performed for genes evaluated for SNVs and/or CNVs in at least two studies. Pooled proportions of samples with SNVs and/or CNVs was calculated by applying random-effect models based on the DerSimonian-Laird method. Gene-set enrichment analysis (GSEA) was performed to identify molecular pathways significantly enriched for mutated genes. RESULTS: Ten studies fulfilled the inclusion criteria and were included in the analysis, for a total of 531 samples of MBMs evaluated. Twenty-seven genes were found recurrently mutated with a meta-analytic rate of SNVs higher than 5%. GSEA conducted on the list of these 27 recurrently mutated genes revealed vascular endothelial growth factor-activated receptor activity and transmembrane receptor protein tyrosine kinase activity to be among the top 10 gene ontology (GO) molecular functions significantly enriched for mutated genes, while regulation of apoptosis and cell proliferation were among the top 10 significantly enriched GO biological processes. Notably, a high meta-analytic rate of SNVs was found in several actionable cancer-associated genes, such as all the vascular endothelial growth factor (VEGF) receptor isoforms (i.e., Flt1 and Flt2 genes, for both SNV rate: 0.22, 95% CI 0.04-0.49; KDR gene, SNV rate: 0.1, 95% CI 0.05-0.16). Finally, two tumor suppressor genes were characterized by a high meta-analytic rate of CNVs: CDKN2A/B (CNV rate: 0.59, 95% CI 0.23-0.90) and PTEN (CNV rate: 0.31, 95% CI 0.02-0.95). CONCLUSION: MBMs harbored actionable molecular alterations that could be exploited as therapeutic targets to improve the poor prognosis of patients.


Assuntos
Neoplasias Encefálicas , Melanoma , Humanos , Variações do Número de Cópias de DNA , Fator A de Crescimento do Endotélio Vascular/genética , Melanoma/patologia , Mutação , Neoplasias Encefálicas/genética
8.
World Neurosurg ; 168: 165-172, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36202344

RESUMO

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive ablative technique with specific indications for neuro-oncology, especially in the case of lesions in eloquent areas. Even being performed through a small catheter under stereotactic conditions, the risk of damaging vital structures such as white matter tracts or cortical eloquent areas is not negligible. The mechanism of damage can be related to catheter insertion or to excessive laser ablation. An accurate preoperative workup, aimed at locating the eloquent structures, can be combined with a real-time intraoperative neurophysiologic monitoring to reduce surgical morbidity while maximizing the efficacy of LITT. METHODS: We developed a synergistic approach for neurophysiology-guided LITT based on state-of-the-art technologies, namely, magnetoencephalography, diffusion tensor imaging, and intraoperative neurophysiologic monitoring. RESULTS: As a result, we improved the planning phase thanks to a more precise representation of functional structures that allows the simulation of different trajectories and the identification of the most suitable trajectory to treat the lesion while respecting the functional boundaries. Catheter insertion is conducted under continuous neurophysiologic feedback and the ablation phase is modeled on the functional boundaries identified by stimulation, allowing it to be extremely accurate. CONCLUSIONS: An integrated approached guided by neurophysiology is able to reduce the surgical morbidity even in a relatively accurate technique such as LITT. To the best of our knowledge, this represents the first report on this synergistic approach which could really impact the treatment of tumors in eloquent areas. Future studies are needed in the effort to implement this approach in functional or epilepsy neurosurgery as well.


Assuntos
Neoplasias Encefálicas , Terapia a Laser , Humanos , Imagem de Tensor de Difusão , Neurofisiologia , Terapia a Laser/métodos , Procedimentos Neurocirúrgicos , Lasers , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/cirurgia
9.
Methods Mol Biol ; 2378: 169-187, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34985700

RESUMO

The unfolded protein response (UPR) is a complex network of intracellular pathways that transmits signals from ER lumen and/or ER bilayer to the nuclear compartment in order to activate gene transcription. UPR is activated by the loss of ER capacities, known as ER stress, and occurs to restore ER properties. In this regard, glycerolipid (GL) synthesis activation contributes to ER membrane homeostasis and IRE1α-XBP1, one UPR pathway, has a main role in lipogenic genes transcription. Herein, we describe the strategy and methodology used to evaluate whether IRE1α-XBP1 pathway regulates lipid metabolism in renal epithelial cells subjected to hyperosmolar environment. XBP1s activity was hindered by blocking IRE1α RNAse activity and by impeding its expression; under these conditions, we determined GL synthesis and lipogenic enzymes expression.


Assuntos
Endorribonucleases , Proteínas Serina-Treonina Quinases , Estresse do Retículo Endoplasmático/genética , Endorribonucleases/genética , Endorribonucleases/metabolismo , Lipídeos , Proteínas Serina-Treonina Quinases/genética , Resposta a Proteínas não Dobradas , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
10.
Acta Neurochir (Wien) ; 163(12): 3465-3471, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34148147

RESUMO

BACKGROUND: Laser-interstitial thermal therapy (LITT) is an ablative treatment based on a surgically implanted laser-emitting catheter to induce a focal ablation of the pathological tissue. The main indications in neurosurgery are primary brain tumors, metastases, radiation necrosis, and pediatric brain tumors. Several approaches have been proposed to implant the laser-emitting catheter, both in frameless and frame-based conditions. METHODS: We report our approach for Robot assisted laser-interstitial thermal therapy of brain lesions with iSYS1 and Visualase (Medtronic). CONCLUSIONS: iSYS1 represents a significant adjunct to LITT procedures and may be safely implemented in routine laser-catheter positioning.


Assuntos
Neoplasias Encefálicas , Terapia a Laser , Robótica , Neoplasias Encefálicas/cirurgia , Criança , Humanos , Lasers , Imageamento por Ressonância Magnética
11.
World Neurosurg ; 154: e19-e28, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34157459

RESUMO

BACKGROUND: Skull base meningiomas represent a challenge for neurosurgeons, and the procedures are typically performed by experienced neurosurgeons, thus limiting resident training. A new simulation and rehearsal device can be used as an aid for senior surgeons during these operations and serve as a training tool for junior surgeons. METHODS: Forty patients harboring an anterior/middle fossa meningioma were recruited. Surgical Theater, a rehearsal/simulation platform, was used for preoperative planning and intraoperative 3D navigation on 20 patients (CT-MADE group), while the remaining (control group) underwent a traditional navigation. Qualitative comparisons between the 2 groups were made with regard to surgical procedure and patient outcome. Satisfaction questionnaires were completed by expert neurosurgeons and residents to assess the overall usefulness of the platform. Furthermore, the surface of the simulated craniotomy performed during the planning was compared with the one actually performed during surgery in order to evaluate the reliability of the planning. RESULTS: No differences between the 2 groups were found (surgery duration: P = 0.4; visual impairment: P = 0.56). Both residents and senior neurosurgeons enjoyed using the platform for intraoperative navigation and planning; simulated craniotomies were significantly smaller as compared with the real ones (P = 0.009), probably because it was not intuitive to depict the exact margins of the operculum with the platform. CONCLUSION: Surgical Theater helped residents to improve their anatomic and procedural comprehension and was deemed as a useful aid to safely perform some demanding neurosurgical procedures, by both senior and junior surgeons.


Assuntos
Meningioma/cirurgia , Neuronavegação/métodos , Neurocirurgia/educação , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Base do Crânio/cirurgia , Adulto , Idoso , Simulação por Computador , Craniotomia , Feminino , Humanos , Internato e Residência , Masculino , Pessoa de Meia-Idade , Neurocirurgiões/educação , Cirurgia Assistida por Computador , Inquéritos e Questionários , Tomografia Computadorizada por Raios X
12.
Liver Int ; 41(7): 1677-1693, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33641248

RESUMO

BACKGROUND AND AIMS: Non-alcoholic fatty liver (NAFLD) and its more serious form non-alcoholic steatohepatitis increase risk of hepatocellular carcinoma (HCC). Lipid metabolic alterations and its role in HCC development remain unclear. SPARC (Secreted Protein, Acidic and Rich in Cysteine) is involved in lipid metabolism, NAFLD and diabetes, but the effects on hepatic lipid metabolism and HCC development is unknown. The aim of this study was to evaluate the role of SPARC in HCC development in the context of NAFLD. METHODS: Primary hepatocyte cultures from knockout (SPARC-/- ) or wild-type (SPARC+/+ ) mice, and HepG2 cells were used to assess the effects of free fatty acids on lipid accumulation, expression of lipogenic genes and de novo triglyceride (TG) synthesis. A NAFLD-HCC model was stabilized on SPARC-/- or SPARC+/+ mice. Correlations among SPARC, lipid metabolism-related gene expression patterns and clinical prognosis were studied using HCC gene expression dataset. RESULTS: SPARC-/- mice increases hepatic lipid deposits over time. Hepatocytes from SPARC-/- mice or inhibition of SPARC by an antisense adenovirus in HepG2 cells resulted in increased TG deposit, expression of lipid-related genes and nuclear translocation of SREBP1c. Human HCC database analysis revealed that SPARC negatively correlated with genes involved in lipid metabolism, and with poor survival. In NAFLD-HCC murine model, the absence of SPARC accelerates HCC development. RNA-seq study revealed that pathways related to lipid metabolism, cellular detoxification and proliferation were upregulated in SPARC-/- tumour-bearing mice. CONCLUSIONS: The absence of SPARC is associated with an altered hepatic lipid metabolism, and an accelerated NAFLD-related HCC development.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Animais , Carcinoma Hepatocelular/metabolismo , Metabolismo dos Lipídeos , Lipídeos , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Osteonectina/genética , Osteonectina/metabolismo
13.
Heliyon ; 6(11): e05396, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33294652

RESUMO

The functional renal epithelium is composed of differentiated and polarized tubular cells with a strong actin cortex and specialized cell-cell junctions. If, under pathological conditions, these cells have to resist higher kidney osmolarity, they need to activate diverse mechanisms to survive external nephrotoxic agents such as inflammation and oxidative stress. Wine pomace polyphenols exert protective effects on renal cells. In this study, two wine-pomace products and their protective effects upon promotion and preservation of normal cell differentiation and attenuation of oxalate-induced type II epithelial mesenchymal transition (EMT) are evaluated. Treatment with gastrointestinal and colonic bioavailable fractions from red (rWPP) and white (wWPP) wine pomaces, both in the presence and the absence of oxalate, showed similar cell numbers and nuclear size than the non-treated differentiated MDCK cells. Immunofluorescence analysis showed the reduction of morphological changes and the preservation of cellular junctions for the rWPP and wWPP pre-treatment of cells exposed to oxalate injury. Hence, both rWPP and wWPP attenuated oxalate type II EMT in MDCK cells that conserved their epithelial morphology and cellular junctions through the antioxidant activities of grape pomace polyphenols.

14.
Heliyon ; 6(10): e05149, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33072916

RESUMO

Our previous reports showed that 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) has antiproliferative actions in endothelial cells stably expressing viral G protein-coupled receptor (vGPCR) associated with the pathogenesis of Kaposi's sarcoma. It has been reported that COX-2 enzyme, involved in the tumorigenesis of many types of cancers, is induced by vGPCR. Therefore, we investigated whether COX-2 down-regulation is part of the growth inhibitory effects of 1α,25(OH)2D3. Proliferation was measured in presence of COX-2 inhibitor Celecoxib (10-20 µM) revealing a decreased in vGPCR cell number, displaying typically apoptotic features in a dose dependent manner similarly to 1α,25(OH)2D3. In addition, the reduced cell viability observed with 20 µM Celecoxib was enhanced in presence of 1α,25(OH)2D3. Remarkably, although COX-2 mRNA and protein levels were up-regulated after 1α,25(OH)2D3 treatment, COX-2 enzymatic activity was reduced in a VDR-dependent manner. Furthermore, an interaction between COX-2 and VDR was revealed through GST pull-down and computational analysis. Additionally, high-affinity prostanoid receptors (EP3 and EP4) were found down-regulated by 1α,25(OH)2D3. Altogether, these results suggest a down-regulation of COX-2 activity and of prostanoid receptors as part of the antineoplastic mechanism of 1α,25(OH)2D3 in endothelial cells transformed by vGPCR.

15.
Handb Clin Neurol ; 170: 101-106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32586481

RESUMO

Falcine meningiomas (FMs) are defined as meningiomas arising from the falx, covered by the overlying brain parenchyma, and not involving the superior sagittal sinus (SSS). FMs together with parasagittal meningiomas represent the second most common location of intracranial meningioma. Clinical presentation depends on the dimensions and location of the FM. Surgery for FM removal deserves several considerations related to bridging veins, anterior cerebral artery branches, arterial feeders, SSS involvement, FM locations, and FM dimensions. In this chapter the principal aspects influencing surgical strategy are analyzed together with approaches and management.


Assuntos
Dura-Máter/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Cavidades Cranianas/cirurgia , Dura-Máter/patologia , Humanos , Neoplasias Meníngeas/patologia , Meningioma/patologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-31927142

RESUMO

In renal cells, hyperosmolarity can induce cellular stress or differentiation. Both processes require active endoplasmic reticulum (ER)-associated protein synthesis. Lipid biosynthesis also occurs at ER surface. We showed that hyperosmolarity upregulates glycerophospholipid (GP) and triacylglycerol (GL-TG) de novo synthesis. Considering that massive synthesis of proteins and/or lipids may drive to ER stress, herein we evaluated whether hyperosmolar environment induces ER stress and the participation of inositol-requiring enzyme 1α (IRE1α)-XBP1 in hyperosmotic-induced lipid synthesis. Treatment of Madin-Darby canine kidney (MDCK) cells with hyperosmolar medium triggered ER stress-associated unfolded protein response (UPR). Hyperosmolarity significantly increased xbp1 mRNA and protein as function of time; 24 h of treatment raised the spliced form of XBP1 protein (XBP1s) and induced its translocation to nuclear compartment where it can act as a transcription factor. XBP1 silencing or IRE1α ribonuclease (RNAse) inhibition impeded the expression of lipin1, lipin2 and diacylglycerol acyl transferase-1 (DGAT1) enzymes which yielded decreased GL-TG synthesis. The lack of XBP1s also decreased sterol regulatory element binding protein (SREBP) 1 and 2. Together our data demonstrate that hyperosmolarity induces IRE1α â†’ XBP1s activation; XBP1s drives the expression of SREBP1 and SREBP2 which in turn regulates the expression of the lipogenic enzymes lipin1 (LPIN1) and 2 (LPIN2) and DGAT1. We also demonstrated for the first time that tonicity-responsive enhancer binding protein (TonEBP), the master regulator of osmoprotective response, regulates XBP1 expression. Thus, XBP1 acts as an osmoprotective protein since it is activated by high osmolarity and upregulates lipid metabolism, membranes generation and the restoration of ER homeostasis.


Assuntos
Rim/metabolismo , Lipogênese , Osmorregulação , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Cães , Estresse do Retículo Endoplasmático , Rim/citologia , Células Madin Darby de Rim Canino , Pressão Osmótica , RNA Mensageiro/genética , Regulação para Cima , Proteína 1 de Ligação a X-Box/genética
17.
Biochim Biophys Acta Biomembr ; 1861(10): 182993, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132336

RESUMO

Mutations in the ATP13A2 gene (PARK9, CLN12, OMIM 610513) were initially associated with a form of Parkinson's Disease (PD) known as Kufor Rakeb Syndrome (KRS). However, the genetic spectrum of ATP13A2-associated disorders was expanded in the last years, because it has been found to underlay variants of neuronal ceroid-lipofuscinoses (NCLs) and hereditary spastic paraplegia. As ATP13A2 seems to be a key component of the endo-lysosome pathway, the fact that these pathologies are commonly characterized by endo-lysosomal dysfunction is not surprising. Here we report that increasing the level of functional ATP13A2 in a stable SH-SY5Y cell line disrupts lipid homeostasis. ATP13A2 overexpression increases the fluorescence intensity of the fluorescent analog phosphatidylethanolamine (NBD-PE) and the formation of multilamellar bodies, resembling the so-called "drug-induced phospholipidosis". We also found that expression of ATP13A2 reduces the ceramide-fluorescence intensity and the content of bis(monoacylglyceryl)phosphate (BMP). BMP is required for lipid degradation and exosome biogenesis inside acidic compartments, so this result suggests that ATP13A2 may be modifying the lipid digestion capacity and/or the redistribution of lipids in these subcellular organelles. In addition, ATP13A2-overexpression decreased the total content of triglycerides (TGs), cholesterol and lipid droplets. As TGs are necessary for the synthesis of new membranes, this observation suggests that increasing the function of ATP13A2 switches the endo-lysosomal system towards vesicle secretion.


Assuntos
Fosfolipídeos/metabolismo , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/metabolismo , Linhagem Celular Tumoral , Colesterol/metabolismo , Endossomos/metabolismo , Homeostase , Humanos , Metabolismo dos Lipídeos , Lisossomos/metabolismo , Monoglicerídeos/metabolismo , Mutação , Lipofuscinoses Ceroides Neuronais/genética , Lipofuscinoses Ceroides Neuronais/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/metabolismo , Fosfatidiletanolaminas/metabolismo , Triglicerídeos/metabolismo
18.
Oper Neurosurg (Hagerstown) ; 17(4): 403-412, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690491

RESUMO

BACKGROUND: Robotic technologies have been used in the neurosurgical operating rooms for the last 30 yr. They have been adopted for several stereotactic applications and, particularly, image-guided biopsy of intracranial lesions which are not amenable for open surgical resection. OBJECTIVE: To assess feasibility, safety, accuracy, and diagnostic yield of robot-assisted frameless stereotactic brain biopsy with a recently introduced miniaturized device (iSYS1; Interventional Systems Medizintechnik GmbH, Kitzbühel, Austria), fixed to the Mayfield headholder by a jointed arm. METHODS: Clinical and surgical data of all patients undergoing frameless stereotactic biopsies using the iSYS1 robotized system from October 2016 to December 2017 have been prospectively collected and analyzed. Facial surface registration has been adopted for optical neuronavigation. RESULTS: Thirty-nine patients were included in the study. Neither mortality nor morbidity related to the surgical procedure performed with the robot was recorded. Diagnostic tissue samples were obtained in 38 out of 39 procedures (diagnostic yield per procedure was 97.4%). All patients received a definitive histological diagnosis. Mean target error was 1.06 mm (median 1 mm, range 0.1-4 mm). CONCLUSION: The frameless robotic iSYS1-assisted biopsy technique was determined to be feasible, safe, and accurate procedure; moreover, the diagnostic yield was high. The surface matching registration method with computed tomography as the reference image set did not negatively affect the accuracy of the procedure.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Biópsia Guiada por Imagem/métodos , Linfoma/patologia , Neuronavegação/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Astrocitoma/patologia , Abscesso Encefálico/patologia , Ependimoma/patologia , Estudos de Viabilidade , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oligodendroglioma/patologia , Projetos Piloto , Técnicas Estereotáxicas , Tomografia Computadorizada por Raios X
19.
Oper Neurosurg (Hagerstown) ; 16(3): E95-E100, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29873789

RESUMO

BACKGROUND AND IMPORTANCE: Mesencephalic tectal gliomas represent a subset of midbrain tumors, which are more frequent in children than in adults. They usually become symptomatic when causing hydrocephalus by occluding the aqueduct. Because of their slow progression, due to their benign histology, they are characterized by a relatively good prognosis, although hydrocephalus might jeopardize patients' prognosis. Treatment is usually represented by cerebrospinal fluid diversion associated or not with biopsy. CLINICAL PRESENTATION: We report 2 illustrative cases of tectal gliomas in adults where endoscopic third ventriculostomy (ETV) and simultaneous endoscopic biopsy were obtained during the same operation by means of a single burr hole with a flexible endoscope. CONCLUSION: We recommend using this overlooked neurosurgical tool for such cases, since it allows the surgeon to safely perform an ETV, then judge whether biopsy can be done or not, without harming the patient, and possibly achieving an important piece of information (histopathological diagnosis) to manage this subset of oncological patients.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Hidrocefalia/cirurgia , Neuroendoscopia/métodos , Teto do Mesencéfalo , Ventriculostomia/métodos , Adulto , Amaurose Fugaz/etiologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Glioma/complicações , Glioma/patologia , Cefaleia/etiologia , Humanos , Hidrocefalia/etiologia , Masculino , Terceiro Ventrículo , Adulto Jovem
20.
World Neurosurg ; 122: e1398-e1404, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30458322

RESUMO

OBJECTIVE: Piezoelectric surgery represents an innovative technique to perform safe and effective osteotomies and is an alternative to traditional bony tissue management using rotating or perforating instruments. We evaluated the safety and feasibility of craniotomies using an ultrasonic device that allows the selective cut of mineralized structures, avoiding damages to the vascular, dural, and parenchymal structures. METHODS: We analyzed a series of 300 patients (age range, 1-81 years; SD ± 15.2) who underwent elective cranial surgery for brain tumors, in which the craniotomy was performed using a piezoelectric device. Pre- and postoperative imaging, clinical notes, and intraoperative details were collected. RESULTS: There were 197 patients (66%) who underwent surgery for supratentorial tumors; the remaining 103 patients (34%) underwent surgery for infratentorial ones. Tumors involved the skull base in 125 cases. Meningiomas, gliomas, and schwannomas represented the most common histotypes. Duraplasty for dural damages was not necessary in all cases; no venous sinuses or parenchymal injuries were reported during bone work. We noted in 13 cases (4.3%) a minor dural tear, requiring only direct sutures. Bone flaps were always intact after craniotomy. No subgaleal cerebrospinal fluid (CSF) collection or CSF leak was recorded. Because of the minimal bone gap, we always achieved correct bone flap ossification. No reabsorption or mobilization of bone flap was noted. CONCLUSIONS: We illustrate the feasibility and safety of a piezosurgical cutter to perform craniotomies. This alternative technique appears to be safe, with excellent cosmetic effects, adding another tool to the neurosurgical armamentarium.


Assuntos
Craniotomia/métodos , Neoplasias Infratentoriais/cirurgia , Piezocirurgia/métodos , Neoplasias Supratentoriais/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cisto Epidérmico/patologia , Cisto Epidérmico/cirurgia , Estudos de Viabilidade , Feminino , Glioma/patologia , Glioma/cirurgia , Humanos , Lactente , Neoplasias Infratentoriais/patologia , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/patologia , Meningioma/cirurgia , Pessoa de Meia-Idade , Imagem Multimodal , Neurilemoma/patologia , Neurilemoma/cirurgia , Estudos Retrospectivos , Neoplasias da Base do Crânio/patologia , Neoplasias da Base do Crânio/cirurgia , Neoplasias Supratentoriais/patologia , Tomografia Computadorizada por Raios X , Adulto Jovem
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