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PURPOSE: Awake surgery is the standard treatment to preserve motor and language functions. This longitudinal study aimed to evaluate the resection rate and preservation of neurocognitive functions in patients with right frontal lobe glioma who underwent awake surgery. METHODS: Thirty-three patients (mean age, 48.0 years) with right frontal lobe glioma who underwent awake surgery at our hospital between 2013 and 2019 were included. Fourteen, thirteen, and six cases had WHO classification grades of II, III, and IV, respectively. We evaluated visuospatial cognition (VSC) and spatial working memory (SWM) before and three months after surgery. Relevant brain areas for VSC and SWM were intraoperatively mapped, whenever the task was successfully accomplished. Therefore, patients were divided into an intraoperative evaluation group and a non-evaluation group for each function, and the resection rate and functional outcomes were compared. RESULTS: The removal rate in the evaluation group for VSC and SWM were similar to that in the non-evaluation group. Chronic impairment rate of VSC was significantly lower in the evaluation than in the non-evaluation group (5.6% vs. 33.3%, p = 0.034). No patient showed postoperative SWM impairment in the evaluation group as opposed to the non-evaluation group (16.7%, p = 0.049). The probability of resection of the deeper posterior part of the middle frontal gyrus, the relevant area of VSC, was higher in the non-evaluation group than in the evaluation group. CONCLUSIONS: We statistically verified that awake surgery for right frontal lobe glioma results in successful preservation of VSC and SWM with satisfying resection rates.
Assuntos
Neoplasias Encefálicas/cirurgia , Cognição/fisiologia , Lobo Frontal/cirurgia , Glioma/cirurgia , Memória de Curto Prazo/fisiologia , Procedimentos Neurocirúrgicos/métodos , Vigília , Adulto , Mapeamento Encefálico , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Lobo Frontal/patologia , Glioma/patologia , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: P2Y purinergic receptors (P2YR) are G protein-coupled receptors that are stimulated by extracellular nucleotides. They mediate cellular effects by regulating cAMP production, protein kinase C activation, inositol trisphosphate generation, and Ca2+ release from intracellular stores. The P2Y6 receptor of this family is selectively stimulated by UDP, and selectively inhibited by MRS2578. In the present study, we examined the effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in human basophils. METHODS: Basophils were purified from human peripheral blood. The mRNA expression of genes encoding P2YR and ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase) was measured by RT-PCR. Intracellular Ca2+ influx via UDP/P2Y6 receptor signaling in basophils was detected using a calcium probe. The effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in basophils was confirmed by measuring CD63 expression by flow cytometry. Autocrine secretion of nucleotides was detected by HPLC analysis. RESULTS: We showed that purified basophils express P2Y6 mRNA and that UDP increased intracellular Ca2+, which was reduced by MRS2578 treatment. UDP promoted IgE-dependent degranulation. Furthermore, MRS2578 inhibited IgE-dependent degranulation in basophils. HPLC analysis indicated that basophils spontaneously secrete UTP. In addition, basophils expressed the extracellular nucleotide hydrolases ENTPDase2, ENTPDase3, and ENTPDase8. CONCLUSIONS: This study showed that UDP/P2Y6 receptor signaling is involved in the regulation of IgE-dependent degranulation in basophils, which might stimulate the P2Y6 receptor via the autocrine secretion of UTP. Thus, this receptor represents a potential target to regulate IgE-dependent degranulation in basophils during allergic diseases.
Assuntos
Basófilos/imunologia , Basófilos/metabolismo , Degranulação Celular/imunologia , Imunoglobulina E/imunologia , Receptores Purinérgicos P2/metabolismo , Transdução de Sinais , Difosfato de Uridina/metabolismo , Adulto , Basófilos/efeitos dos fármacos , Cálcio/metabolismo , Degranulação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Expressão Gênica , Voluntários Saudáveis , Humanos , Imunoglobulina E/sangue , Isotiocianatos/farmacologia , Pirofosfatases/genética , Pirofosfatases/metabolismo , Receptores Purinérgicos P2/genética , Tioureia/análogos & derivados , Tioureia/farmacologia , Uridina Trifosfato/metabolismo , Adulto JovemRESUMO
Intraoperative motor-evoked potentials (MEPs) are measured for assessing motor function during surgery. MEP monitoring is often performed in thoracoabdominal aortic aneurysm (TAAA) surgery, but false positives are common and amplification methods are needed to obtain waveforms under severe conditions to assess proper spinal cord function. One method of amplitude amplification in transcranial-stimulated MEP monitoring is multitrain stimulation. There are few reports on multitrain-stimulated MEP monitoring for this surgery. A 57-year-old woman underwent open repair of the thoracoabdominal aorta due to a dissecting aortic aneurysm. After opening the chest, the aneurysm was incised proximally, and anastomosis with an artificial vessel was initiated. The lumbar artery leading to the Adam-Kiewicz artery was reconstructed at a body temperature of 25 °C. However, the single-train stimulation did not produce MEPs. When the measurement was switched to multitrain stimulation, MEPs were elicited in the lower extremity muscle groups and the waveforms were maintained until the end of the measurement. This case illustrates that MEP monitoring using multitrain stimulation during descending thoracic aortic aneurysm surgery can effectively elicit MEPs under challenging conditions, in which conventional single-train stimulation may be insufficient.
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Gliomas, particularly glioblastomas (GBMs), pose significant challenges due to their aggressiveness and poor prognosis. Early detection through biomarkers is critical for improving outcomes. This study aimed to identify novel biomarkers for gliomas, particularly GBMs, using chiral amino acid profiling. We used chiral amino acid analysis to measure amino acid L- and D-isomer levels in resected tissues (tumor and non-tumor), blood, and urine from 33 patients with primary gliomas and 24 healthy volunteers. The levels of D-amino acid oxidase (DAO), a D-amino acid-degrading enzyme, were evaluated to investigate the D-amino acid metabolism in brain tissue. The GBM mouse model was created by transplanting GBM cells into the brain to confirm whether gliomas affect blood and urine chiral amino acid profiles. We also assessed whether D-amino acids produced by GBM cells are involved in cell proliferation. D-asparagine (D-Asn) levels were higher and DAO expression was lower in glioma than in non-glioma tissues. Blood and urinary D-Asn levels were lower in patients with GBM than in healthy volunteers (p < 0.001), increasing after GBM removal (p < 0.05). Urinary D-Asn levels differentiated between healthy volunteers and patients with GBM (area under the curve: 0.93, sensitivity: 0.88, specificity: 0.92). GBM mouse model validated the decrease of urinary D-Asn in GBM. GBM cells used D-Asn for cell proliferation. Gliomas induce alterations in chiral amino acid profiles, affecting blood and urine levels. Urinary D-Asn emerges as a promising diagnostic biomarker for gliomas, reflecting tumor presence and severity.
Assuntos
Asparagina , Neoplasias Encefálicas , D-Aminoácido Oxidase , Glioblastoma , Humanos , Glioblastoma/metabolismo , Glioblastoma/urina , Glioblastoma/patologia , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/urina , Neoplasias Encefálicas/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Asparagina/urina , Asparagina/metabolismo , Adulto , D-Aminoácido Oxidase/metabolismo , D-Aminoácido Oxidase/genética , Camundongos , Idoso , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Proliferação de CélulasRESUMO
INTRODUCTION: Heme oxygenase-1 (HO-1) is the rate limiting enzyme that catalyzes the conversion of heme into biliverdin, free iron, and carbon monoxide (CO). The first human case of HO-1 deficiency showed abnormalities in blood coagulation and the fibrinolytic system. Thus, HO-1 or HO-1 products, such as CO, might regulate coagulation and the fibrinolytic system. This study examined whether tricarbonyldichlororuthenium (II) dimer (CORM-2), which liberates CO, modulates the expression of tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1) in human umbilical vein endothelial cells (HUVECs), and TF expression in peripheral blood mononuclear cells (PBMCs). Additionally, we examined the mechanism by which CO exerts its effects. MATERIALS AND METHODS: HUVECs were pretreated with 50 µM CORM-2 for 3 hours, and stimulated with tumor necrosis factor-α (TNF-α, 10 ng/ml) for an additional 0-5 hours. PBMCs were pretreated with 50-100 µM CORM-2 for 1 hour followed by stimulating with lipopolysaccharid (LPS, 10 ng/ml) for additional 0-9 hours. The mRNA and protein levels were determined by RT-PCR and western blotting, respectively. RESULTS: Pretreatment with CORM-2 significantly inhibited TNF-α-induced TF and PAI-1 up-regulation in HUVECs, and LPS-induced TF expression in PBMCs. CORM-2 inhibited TNF-α-induced activation of p38 MAPK, ERK1/2, JNK, and NF-κB signaling pathways in HUVECs. CONCLUSIONS: CORM-2 suppresses TNF-α-induced TF and PAI-1 up-regulation, and MAPKs and NF-κB signaling pathways activation by TNF-α in HUVECs. CORM-2 suppresses LPS-induced TF up-regulation in PBMCs. Therefore, we envision that the antithrombotic activity of CORM-2 might be used as a pharmaceutical agent for the treatment of various inflammatory conditions.