RESUMO
The number of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) is increasing annually. The prognostic nutritional index (PNI) is used as a novel and valuable prognostic marker for various neoplastic diseases and other critical illnesses. This study aimed to identify the short-term prognostic value of preoperative PNI in elderly patients who underwent neurosurgical clipping for aSAH. This retrospective study included elderly patients with aSAH who underwent neurosurgical clipping from January 2018 to December 2020. Clinical variables and 6-month outcomes were collected and compared. Epidemiological data and effect factors of prognosis were evaluated. Multivariate logistic regression and receiver operating characteristics (ROC) curve analyses were used to evaluate the predictive value of preoperative PNI. Multiple logistic regression was performed to establish a nomogram. A total of 124 elderly patients were enrolled. Multivariate logistic regression analysis showed that preoperative PNI (odds ratio (OR), 0.779; 95% confidence interval (CI), 0.689-0.881; P < 0.001), Hunt-Hess grade (OR, 3.291; 95%CI, 1.816-5.966; P < 0.001), and hydrocephalus (OR, 9.423; 95%CI, 2.696-32.935; P < 0.001) were significant predictors. The area under the ROC curve of PNI was 0.829 (95% CI, 0.755-0.903; P < 0.001) with a sensitivity and specificity of 68.4% and 83.3%, respectively, and the cutoff value was 46.36. Patients with preoperative PNI of < 46.36 had a significantly unfavorable 6-months prognosis (F = 40.768, P < 0.001). Preoperative PNI is independently correlated with the 6-month prognosis in elderly patients who undergo neurosurgical clipping for aSAH.
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Hemorragia Subaracnóidea , Humanos , Idoso , Prognóstico , Hemorragia Subaracnóidea/cirurgia , Avaliação Nutricional , Estudos Retrospectivos , NomogramasRESUMO
Macrophage migration inhibitory factor (MIF) is a pluripotent pro-inflammatory cytokine and is related to acute and chronic inflammatory responses, immune disorders, tumors, and other diseases. In this study, an integrated virtual screening strategy and bioassays were used to search for potent MIF inhibitors. Twelve compounds with better bioactivity than the prototypical MIF-inhibitor ISO-1 (IC50 = 14.41 µM) were identified by an in vitro enzymatic activity assay. Structural analysis revealed that these inhibitors have novel structural scaffolds. Compound 11 was then chosen for further characterization in vitro, and it exhibited marked anti-inflammatory efficacy in LPS-activated BV-2 microglial cells by suppressing the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs). Our findings suggest that MIF may be involved in the regulation of microglial inflammatory activation and that small-molecule MIF inhibitors may serve as promising therapeutic agents for neuroinflammatory diseases.
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Fatores Inibidores da Migração de Macrófagos , Anti-Inflamatórios/química , Bioensaio , Fatores Inibidores da Migração de Macrófagos/metabolismo , Microglia/metabolismo , NF-kappa B/metabolismoRESUMO
This qualitative study describes the psychological experience of patients hospitalized with COVID-19. These patients went through 3 psychological stages: extremely uncertainties during the initial diagnostic stage, complicated feelings of negativity during the treatment stage, and positive growth in the recovery stage. It is important for nurses to provide holistic care.
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COVID-19 , Emoções , Humanos , Pesquisa Qualitativa , SARS-CoV-2RESUMO
BACKGROUND Rupture of intracranial aneurysms (IA) is associated with high rates of mortality around the world. Use of intestinal probiotics can regulate the pathophysiology of aneurysms, but the details of the mechanism involved have been unclear. MATERIAL AND METHODS The GEO2R analysis website was used to detect the DEGs between IAs, AAAs, samples after supplementation with probiotics, and normal samples. The online tool DAVID provides functional classification and annotation analyses of associated genes, including GO and KEGG pathway. PPI of these DEGs was analyzed based on the STRING database, followed by analysis using Cytoscape software. RESULTS We found 170 intersecting DEGs (contained in GSE75240 and more than 2 of the 4 aneurysms datasets), 5 intersecting DEGs (contained in all datasets) and 1 intersecting DEG (contained in GSE75240 and all IAs datasets). GO analysis results suggested that the DEGs primarily participate in signal transduction, cell adhesion, immune response, response to drug, extracellular matrix organization, cell-cell signaling, and inflammatory response in the BP terms, and the KEGG pathways are mainly enriched in focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor interaction, amoebiasis, chemokine signaling pathway, proteoglycans, and PI3K-Akt signaling pathway in cancer pathways. Through PPI network analysis, we confirmed 2 candidates for further study: CAV1 and MYH11. These downregulated DEGs are associated with the formation of aneurysms, and the change of these DEGs is the opposite in probiotics-treated animals. CONCLUSIONS Our study suggests that MYH11 and CAV1 are potential target genes for prevention of aneurysms. Further experiments are needed to verify these findings.
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Biologia Computacional , Aneurisma Intracraniano/genética , Probióticos , Caveolina 1/genética , Regulação para Baixo , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Cadeias Pesadas de Miosina/genética , SoftwareRESUMO
OBJECTIVE: to investigate the impact of craniotomy on oxidative stress and its effect on levels of plasma L-carnitine (LC). METHODS: plasma levels of reactive oxygen species, superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), catalase (CAT), total antioxidative capacity (T-AOC), and thiobarbituric acid reactive substances (TBARS) were measured in 34 patients (26 males and 8 females, mean age 47.7 ± 6.7 years) before and after craniotomy. Plasma levels of LC, acetyl-L-carnitine (ALC), and propionyl-L-carnitine (PLC) were also measured before and after the craniotomy. RESULTS: the plasma concentrations of SOD, GSH-Px, CAT, and T-AOC within the first 4 h after craniotomy were lower than their baseline values (P < 0.05). There were no statistically significant differences in the mean plasma levels of SOD, GSH-Px, CAT, or T-AOC between the baseline and 24 h post-operative values. The level of TBARS at 4 h after the craniotomy was lower than the pre-operative level (P < 0.05), but the 24 h post-operative value was similar to the baseline concentration (P > 0.05). Plasma levels of LC, ALC, and PLC were lower after the craniotomy (P < 0.05), but these levels returned to the baseline levels 24 h after the operation. CONCLUSIONS: craniotomy and the associated procedures for surgery/anesthesia temporarily reduce antioxidant activity and plasma levels of L-carnitine.
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Carnitina/sangue , Craniotomia/efeitos adversos , Estresse Oxidativo , Adulto , Antioxidantes/metabolismo , Proteínas Sanguíneas/metabolismo , Feminino , Humanos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/sangueRESUMO
The increasing evidence of microplastic (MP) contamination influence on aquatic organisms has been extensively reported globally. However, the discussions of extracting MPs from oily food samples are limited, highlighting the pressing need for effective and standardized analytical methods to extract MPs from oily food. Previous methods, such as using acid, alkali or oxidizing solutions as digestion reagents, usually take a long time to digest oily food, increasing the possibility of procedural contamination of MPs in food over time. The objective of this study was to develop a rapid, efficient, economical and simple analytical method to extract MPs from oily food samples. This innovative protocol combines the use of 4 : 1 HNO3 : H2O2 as a digestion reagent to accelerate the digestion within 1 h at 50 °C and hexane as a washing solution to remove the oil adsorbed on the surface of MPs and membranes. Four common types of MPs, namely, polyethylene terephthalate, polyethylene, polystyrene and polypropylene of different sizes were added to oily flours to demonstrate this method. The mean recovery of MPs was 95% ± 2% (range: 93-98%), and no significant changes in color, particle size, surface area and spectrum features were found for all recovered polymers except for PS with minor changes in color and surface. The method was confirmed to be effective on rice, noodles, bean products and various meat samples. All in all, the present method can facilitate the observation and identification of characteristics of MPs, providing an innovative combination method for quantitative and qualitative analyses of MPs in oily food samples.
Assuntos
Microplásticos , Poluentes Químicos da Água , Álcalis , Hexanos , Peróxido de Hidrogênio , Plásticos/análise , Polietileno , Polietilenotereftalatos , Polipropilenos , Poliestirenos/análise , Poluentes Químicos da Água/análiseRESUMO
The aim of the study was to investigate the effects of baicalin on blood glucose, insulin and cytokine levels. Rat diabetes was induced by intraperitoneal (i.p.) injection of nicotinamide and streptozotocin. Diabetic rats were dosed with i.p. baicalin or oral metformin daily for 8 days. Blood glucose, insulin and hepatic glycogen were determined using conventional methods. The activity of hepatic hexokinase was determined using a coupled assay with glucose-6-phosphate dehydrogenase. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and adiponectin were measured by enzyme-linked immunosorbent assay. Administration of baicalin at 50 or 100 mg/kg significantly decreased plasma glucose levels in a dose dependent manner. The serum insulin level was not increased by baicalin treatment. Administration of baicalin at a high dose (100 mg/kg) resulted in a significant increase of liver glycogen content and a reduction of serum TNF-α. The activity of hepatic hexokinase was significantly increased after dosing baicalin at 25, 50 or 10 mg/kg. Administration of baicalin (50 or 10 mg/kg) or metformin (10 mg/kg) significantly alleviated the morphological injury to the pancreas caused by STZ. The possible mechanisms contributing to the hypoglycemic effect include increasing the hepatic glycogen content and glycolysis, and reducing the serum levels of TNF-α.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Adiponectina/sangue , Animais , Glicemia/efeitos dos fármacos , Glicogênio/análise , Hexoquinase/metabolismo , Insulina/sangue , Interleucina-6/sangue , Fígado/metabolismo , Masculino , Metformina/farmacologia , Niacinamida , Pâncreas/patologia , Ratos , Ratos Wistar , Estreptozocina , Fator de Necrose Tumoral alfa/sangueRESUMO
Drug resistance is the major cause of the failure of cancer chemotherapy, so one of the most important features in developing effective cancer therapeutic strategies is to overcome drug resistance. Quinoline moiety has become one of the most privileged structural motifs in anticancer agent discovery since its derivatives possess potent activity against various cancers including drug-resistant cancers. Several quinoline-based compounds which are represented by Anlotinib, Bosutinib, Lenvatinib, and Neratinib have already been applied in clinical practice to fight against cancers, so quinoline-based compounds are potential anticancer agents. The present short review article provides an overview of the recent advances of quinoline-based compounds with potential activity against drug-resistant cancers. The structure-activity relationship and mechanisms of action are also discussed.
Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Quinolinas/uso terapêutico , Desenho de Fármacos , Humanos , Quinolinas/química , Quinolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
Traditional herbal medicine (THM) is an important part of the traditional Chinese medicine culture. Due to its high medicinal potential, it should not only serve for the Chinese people's medical use, but also contribute to the world medicine, THM for the international market must be standardized and large-scale, and produced according to the "Good Agriculture Practice" (GAP). The quality of THM directly affects the patient's treatment status and safety of use. Therefore, the quality assurance of THM runs through the entire process of research and development, production and clinical practice. The standardized production and cultivation of THM is the starting point of the THM industry chain and plays a decisive role in the economic development of the THM industry. This article summarizes the development history, limitations and future development of GAP, and clarifies the opportunities for THM in the rapid development of the international and domestic Chinese medicine industry. In addition, analyzing the deficiencies that were existing in the former GAP implementation process and by suggesting science-based quality measures, it is hoped to stipulate improved GAP guidelines in the future and to lay the foundation for a modern THM international trade.
RESUMO
OBJECTIVE: To investigate the effects of early intensive rehabilitation management on the recovery of motor function and activities of daily living in patients with moderate traumatic brain injury. METHODS: Eighty-seven patients (age range, 18-65 years) with traumatic brain injury that met the enrollment criteria were randomly divided into 2 groups. Group 1 received early and high-intensity rehabilitation management (from 7 days after injury, 7 d/wk, 4 times/d, 1 h/session) for 4 weeks; group 2 received ordinary rehabilitation (from 14 days after injury, 5 d/wk, 2 times/d, 1 h/session) for 4 weeks. The Fugl-Meyer Assessment (FMA, motor function) and Barthel Index (BI) were used to assess the daily living functional state before treatment, 3 months after injury, and 6 months after injury. The Glasgow Coma Scale (GCS) was used to assess outcomes 6 months after injury. RESULTS: Three months after rehabilitation, the FMA (motor function) score was significantly higher in the early intensive intervention group versus the control group (59.83 ± 11.87 vs. 44.56 ± 8.32, respectively; P < 0.05); no significant between-group differences were found in the GCS score or BI score (P > 0.05). Six months after rehabilitation, the FMA score and BI score were significantly higher in the early intensive intervention group versus the control group (FMA: 73.18 ± 16.55 vs. 57.86 ± 10.67, P < 0.01; BI: 87.17 ± 13.85 vs. 60.68 ± 11.98, P < 0.01, respectively). The GCS score was higher in the early intensive intervention group versus the control group (4.24 ± 0.91 vs. 3.43 ± 0.88, P < 0.05, respectively) 6 months after injury. CONCLUSIONS: Early intensive rehabilitation management might be more beneficial for neurologic function and activities of daily living in patients with moderate traumatic brain injury.
Assuntos
Atividades Cotidianas , Lesões Encefálicas Traumáticas/reabilitação , Reabilitação Neurológica/métodos , Recuperação de Função Fisiológica , Adulto , Lesões Encefálicas Traumáticas/fisiopatologia , Intervenção Médica Precoce/métodos , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos ProspectivosRESUMO
Neuroinflammation is a secondary response following ischemia stroke. Arginine is a non-essential amino acid that has been shown to inhibit acute inflammatory reaction. In this study we show that arginine treatment decreases neuronal death after rat cerebral ischemia/reperfusion (I/R) injury and improves functional recovery of stroke animals. We also show that arginine suppresses inflammatory response in the ischemic brain tissue and in the cultured microglia after OGD insult. We further provide evidence that the levels of HIF-1α and LDHA are increased after rat I/R injury and that arginine treatment prevents the elevation of HIF-1α and LDHA after I/R injury. Arginine inhibits inflammatory response through suppression of HIF-1α and LDHA in the rat ischemic brain tissue and in the cultured microglia following OGD insult, and protects against ischemic neuron death after rat I/R injury by attenuating HIF-1α/LDHA-mediated inflammatory response. Together, these results indicate a possibility that arginine-induced neuroprotective effect may be through the suppression of HIF-1α/LDHA-mediated inflammatory response in microglia after cerebral ischemia injury.
Assuntos
Arginina/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/patologia , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Arginina/farmacologia , Morte Celular , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , L-Lactato Desidrogenase/metabolismo , Masculino , Microglia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais/efeitos dos fármacosRESUMO
l-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how l-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intracerebral hemorrhage (ICH) in vivo. We demonstrate that l-lysine treatment promotes M2 microglial polarization and reduces inflammatory response both in vitro and in vivo, suggesting that l-lysine may play a neuroprotective role in ICH injury. Indeed, we show that l-lysine treatment reduces cortical neuronal death after hemin insult in vitro and decrease the number of degenerating neurons after ICH in vivo. l-lysine also improves the functional recovery of ICH animals in neurobehavioral tests. Consistent with the role of PTEN in regulating inflammatory response, we find that PTEN inhibition promotes M2 microglial polarization and suppresses pro-inflammatory response in mouse ICH injury, which contribute to the neuroprotective effect of l-lysine. Moreover, our results reveal that microRNA-575 directly suppressed PTEN to promote M2 microglial polarization and mediate the neuroprotective effect of l-lysine in ICH injury. Together, our results suggest that l-lysine confers neuroprotection after ICH injury through enhancing M2 microglial polarization and reducing inflammatory response, which is mediated by microRNA-575 upregulation and subsequent PTEN downregulation.
Assuntos
Hemorragia Cerebral/metabolismo , Inflamação/tratamento farmacológico , Lisina/farmacologia , MicroRNAs/metabolismo , Fármacos Neuroprotetores/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Polaridade Celular/efeitos dos fármacos , Hemorragia Cerebral/complicações , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Inflamação/etiologia , Inflamação/metabolismo , Lisina/uso terapêutico , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Regulação para Cima/efeitos dos fármacosRESUMO
In certain surgical procedures, sacrificing the superior petrosal vein (SPV) is required. Previous studies have reported transient cerebellar edema, venous infarction, or hemorrhage that might occur after sectioning of the SPV. The present study investigated the pathophysiological changes in cerebellum and brain stem after SPV sacrifice. Rabbits were divided into the operation group where the SPV was sacrificed and the control group where the SPV remained intact. Each group was further subdivided into 4, 8, 12, 24, 48, and 72 h groups which represented the time period from sacrificing of the SPV to killing of the rabbits. The water content (WC), Na+ content, K+ content, and pathophysiological changes in cerebellum and brain stem tissue were measured. In comparison with the control, the WC and Na+ content of cerebellar tissue were increased in the 4, 8, 12, and 24 h operation subgroups (P<0.05), but only increased in the 4-h subgroup of the brain stem tissue (P<0.05). The K+ content of the cerebellar tissue decreased in the 4, 8, 12, and 24 h operation subgroups (P<0.05) but only decreased in the 4-h subgroup of brain stem tissue (P<0.05). Nissl staining and TEM demonstrated that cerebellar edema occurred in the 4, 8, 12, and 24 h operation subgroups but not in the 48- and 72-h subgroups. Brain stem edema occurred in the 4-h operation subgroup. In summary, cerebellum and brain stem edema can be observed at different time points after sacrificing of the SPV in the rabbit model.
Assuntos
Edema Encefálico/fisiopatologia , Tronco Encefálico/fisiopatologia , Cerebelo/fisiopatologia , Veias Cerebrais/fisiopatologia , Animais , Edema Encefálico/metabolismo , Tronco Encefálico/irrigação sanguínea , Tronco Encefálico/metabolismo , Cerebelo/irrigação sanguínea , Cerebelo/metabolismo , Veias Cerebrais/metabolismo , Modelos Animais de Doenças , Humanos , Corpos de Nissl/metabolismo , Corpos de Nissl/patologia , CoelhosRESUMO
MicroRNA (miR)24 has been reported to associate with various diseases by acting on different signaling pathways. The present study aimed to elucidate the association between miR24 expression levels and vasospasm following subarachnoid hemorrhage (SAH), and its underlying mechanism. An miR online database was searched, identifying endothelial nitric oxide synthase (NOS3) as a potential target gene of miR24. A luciferase reporter assay performed to investigate the regulatory association between miR24 and NOS3 revealed that miR24 bound to the NOS3 3' untranslated region and inhibited NOS3 expression. Reverse transcriptionquantitative polymerase chain reaction and western blot analysis were performed to investigate the miR24 and NOS3 expression levels in samples from patients with SAH, and demonstrated a negative correlation between the two. In addition, miR24 expression levels were increased in SAH patients with vasospasm compared with those without, whereas the opposite results were observed for NOS3. Vascular smooth muscle cells (VSMCs) transfected with an miR24 inhibitor exhibited increased expression levels of NOS3, whereas those transfected with an miR24 mimic or NOS3 small interfering RNA exhibited reduced expression levels of NOS3, compared with the control. These results indicated a negative regulatory association between miR24 and NOS3. Downregulation of NOS3 may induce vasospasm following SAH, which may be due to the upregualtion of miR24 in VSMCs.
Assuntos
Regulação Enzimológica da Expressão Gênica , MicroRNAs/biossíntese , Óxido Nítrico Sintase Tipo III/biossíntese , Hemorragia Subaracnóidea/metabolismo , Regulação para Cima , Vasoespasmo Intracraniano/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/patologia , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/patologiaRESUMO
Several studies investigated the prognostic role of copeptin in stroke. The aim of this study is to assess copeptin levels in serum, and investigate their associations with risk of recurrent stroke in a 1-year follow-up study in patients with ischemic stroke. In this post hoc analysis, serum levels of copeptin and NIH stroke scale (NIHSS) were measured at the time of admission in a cohort of 316 patients with ischemic stroke. The end point was stroke recurrence after 1-year follow-up. We used logistic regression model to assess the relationship between copeptin levels and risk recurrent stroke. Logistic regression analysis considering traditional risk factors showed a relationship between serum copeptin levels and moderate-to-high clinical severity when serum copeptin was used as a continuous variable (OR, 1.05; 95% CI, 1.03-1.09). In the follow-up, 54 patients (17.1%) had a stroke recurrence. The stroke recurrence events distribution across the copeptin quartiles ranged between 5.1% (first quartile) to 23.1% (fourth quartile). In multivariate models comparing the third (OR = 2.78; 95% CI 1.85-3.53) and fourth quartiles (OR = 4.00; 95% CI 2.86-6.50) against the first quartile of the copeptin, levels of copeptin were associated with stroke recurrence events. A higher serum copeptin level is a predictor of both severity at admission and stroke recurrence at 1-year in stroke patients.
Assuntos
Isquemia Encefálica/sangue , Glicopeptídeos/sangue , Acidente Vascular Cerebral/sangue , Idoso , Área Sob a Curva , Biomarcadores/sangue , Isquemia Encefálica/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Recidiva , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/epidemiologia , Fatores de TempoRESUMO
OBJECTIVE Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF165 and SDF-1 in a rat model of cerebral infarction. METHODS An adenoviral vector expressing VEGF165 and SDF-1 connected via an internal ribosome entry site was constructed (Ad- VEGF165-SDF-1). A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad- VEGF165-SDF-1 or control adenovirus Ad- LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO. Coexpression and distribution of VEGF165 and SDF-1 were examined by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence. The neurological severity score of each rat was measured on Days 3, 7, 14, 21, and 28 after MCAO. Angiogenesis and vascular remodeling were evaluated via bromodeoxyuridine and CD34 immunofluorescence labeling. Relative cerebral infarction volumes were determined by T2-weighted MRI and triphenyltetrazolium chloride staining. Cerebral blood flow, relative cerebral blood volume, and relative mean transmit time were assessed using perfusion-weighted MRI. RESULTS The Ad- VEGF165-SDF-1 vector mediated coexpression of VEGF165 and SDF-1 in multiple sites around the ischemic core, including the cortex, corpus striatum, and hippocampal granular layer. Coexpression of VEGF165 and SDF-1 improved neural function, reduced cerebral infarction volume, increased microvascular density and promoted angiogenesis in the ischemic penumbra, and improved cerebral blood flow and perfusion. CONCLUSIONS Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral infarction.
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Isquemia Encefálica/genética , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Quimiocina CXCL12/genética , Terapia Genética/métodos , Fator A de Crescimento do Endotélio Vascular/genética , Remodelação Vascular/genética , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Surgical accesses to lesions of the posterolateral pontomesencephalic junction (PMJ) region and the posterolateral tentorial gap remain a challenge in the field of neurosurgery. Since the first report of application of the extreme lateral supracerebellar infratentorial (ELSI) approach in resecting the PMJ lesions in 2000, a few articles concerning the ELSI approach have been published. The present review mainly provided an intimate introduction of the ELSI approach, and evaluated it in facets of patient position, skin incision, craniectomy, draining veins, retraction against the cerebellum, exposure limits, patient healing, as well as advantages and limitations compared with other approaches. The ELSI approach is proposed to be a very young and promising approach to access the lesions of posterolateral PMJ region and the posterolateral tentorial gap. Besides, it has several advantages such as having a shorter surgical pathway, causing less surgical complications, labor-saving, etc. Still, more studies are needed to improve this approach.
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Craniotomia/métodos , Mesencéfalo/patologia , Mesencéfalo/cirurgia , Ponte/patologia , Ponte/cirurgia , Cerebelo , Humanos , Procedimentos Neurocirúrgicos/métodos , Resultado do TratamentoAssuntos
Dura-Máter/cirurgia , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Angiografia Digital , Artéria Carótida Interna/cirurgia , Dissecação da Artéria Carótida Interna/patologia , Dissecação da Artéria Carótida Interna/cirurgia , Angiografia Cerebral , Feminino , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Humanos , Complicações Intraoperatórias/cirurgia , Masculino , Hemorragia Subaracnóidea/cirurgia , Tomografia Computadorizada por Raios XRESUMO
The urine excretion of L-carnitine (LC), acetyl-L-carnitine (ALC) and propionyl-Lcarnitine (PLC) and their relations with the antioxidant activities are presently unknown. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Urine concentrations of LC, ALC and PLC were detected by HPLC. Superoxide dismutase (SOD), total antioxidative capacity (T-AOC), malondialdehyde (MDA) and nitrogen monoxidum (NO) activities were measured by spectrophotometric methods. The 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excretion of LC was 53.13±31.36 µmol, 166.93±76.87 µmol, 219.92±76.30 µmol, 100.48±23.89 µmol, 72.07±25.77 µmol, respectively. The excretion of ALC was 29.70±14.43 µmol, 80.59±32.70 µmol, 109.85±49.21 µmol, 58.65±18.55 µmol, and 80.43±35.44 µmol, respectively. The urine concentration of PLC was 6.63±4.50 µmol, 15.33±12.59 µmol, 15.46±6.26 µmol, 13.41±11.66 µmol and 9.67±7.92 µmol, respectively. The accumulated excretion rate of LC was 6.1% within 24h after its administration. There was also an increase in urine concentrations of SOD and T-AOC, and a decrease in NO and MDA. A positive correlation was found between urine concentrations of LC and SOD (r = 0.8277) or T-AOC (r = 0.9547), and a negative correlation was found between urine LC excretions and NO (r = -0.8575) or MDA (r = 0.7085). In conclusion, a single oral LC administration let to a gradual increase in urine L-carnitine excretion which was associated with an increase in urine antioxidant enzymes and the total antioxidant capacities. These data may be useful in designing therapeutic regimens of LC or its analogues in the future.
A excreção urinária de L-carnitina (LC), acetil-L-carnitina (ALC) e propionil-L-carnitine (PLC) e as suas relações com as atividades antioxidantes são presentemente desconhecidos. Líquido de L-carnitina (2,0 g) foi administrada por via oral como uma dose única em 12 indivíduos saudáveis. As concentrações urinárias de LC, PLC e ALC foram detectados por HPLC. Atividades superóxido dismutase (SOD), a capacidade antioxidante total (T-AOC), malondialdeído (MDA) e óxido nítrico (NO) foram medidas por métodos espectrofotométricos. O 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excreção de LC foi 53,13±31.36 µmol, 166,93±76.87 µmol, 219,92±76.30 µmol, 100,48±23.89 µmol, 72,07±25.77 µmol, respectivamente. A excreηão de ALC foi 29,70±14.43 µmol, 80,59±32.70 µmol, 109,85±49.21 µmol, 58,65±18.55 µmol, e 80,43±35.44 µmol, respectivamente. A concentraηão de urina de PLC foi 6,63±4.50 µmol, 15,33±12.59 µmol, 15,46±6.26 µmol, 13,41±11.66 µmol e 9,67±7.92 µmol, respectivamente. A taxa de excreηão acumulada de LC foi de 6,1% 24 horas após sua administração. Houve também um aumento nas concentrações de urina de SOD e T-COA e diminuição de NO e de MDA. Correlação positiva foi encontrada entre as concentrações de urina de LC e SOD (r = 0,8277) ou T-AOC (r = 0,9547) e correlação negativa entre a excreção de LC e NO (r = -0,8575) ou MDA (r = 0,7085). Em conclusão, a administração oral única de LC leva ao aumento gradual na excreção urinária de L-carnitina, que foi associada com o aumento das enzimas antioxidantes na urina e as capacidades antioxidantes totais. Estes dados podem ser úteis no futuro para o planejamento de esquemas terapêuticos de LC ou os seus análogos, no futuro.