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1.
Neurosci Lett ; 740: 135461, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33115643

RESUMO

BACKGROUND: Elderly patients receive propofol at regular intervals for sedation during gastrointestinal endoscopy. However, the link between cognition and intermittent propofol exposure remains unclear. Thus, we used aged rats to investigate the effect of propofol on cognition. METHODS: The study included two parts. In the first part, aged (18-20 months old) male Sprague-Dawley rats underwent intermittent intraperitoneal injection of propofol (200 mg/kg) or intralipid, every 9 days or once a day. In the second part, some aged rats received intraperitoneal injection of Bay 11-7082 (1 mg/kg), a specific inhibitor of NF-κB, 30 min before propofol injection. Memory tests were performed to evaluate cognition 24 h after the entire treatment. The hippocampal neuronal damage was assessed by TUNEL staining. The hippocampal levels of p-NF-κB p65, NLRP3, caspase-1 p20, and cleaved caspase-3 were detected by western blotting. The hippocampal and serum levels of IL-1ß, IL-6, and TNF-α were evaluated using ELISA. RESULTS: There were no differences in the behavioral tests, hippocampal neuronal damage, and neuroinflammation between groups given intralipid and propofol treatment every 9 days. However, repeated propofol treatment once a day promoted activation of NF-κB and the NLRP3 inflammasome, inducing cognitive impairment and neuroinflammation. Interestingly, pretreatment with Bay-11-7082 not only inhibited NF-κB/NLRP3 inflammasome activation, but also attenuated neuronal damage and cognitive dysfunction in aged rats exposed to daily propofol treatment. CONCLUSIONS: Intermittent propofol treatment every 9 days may be safe for aged rats. However, propofol treatment once a day could impair the cognition of aged rats, partly through the activation of the NF-κB pathway and NLRP3 inflammasome, which may be a potential targets for the treatment of cognitive impairment in elderly patients.

2.
Anal Bioanal Chem ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106945

RESUMO

Propofol is a widely used intravenous anesthetic agent in sedation and general anesthesia. To improve the safety and maintain the depth of anesthesia, it is important to develop a rapid, sensitive, and reliable method to monitor the concentration of propofol in blood during anesthesia continuously. Here, we present a novel strategy based on paper spray ionization-mass spectrometry (PSI-MS) to detect propofol. Samples (in 10 µL) were mixed with methanol as protein precipitation solvent and 2,6-dimethylphenol as internal standard. Protein micro-precipitation was achieved with methanol by vortexing and centrifuging for 5 s each, and propofol was extracted to the supernatant. PSI-MS was performed in negative ionization mode, and MS signal lasted for 1 min. The analysis of a single sample was completed within 2 min. The area ratios of propofol to internal standard were calculated for quantification. Limit of detection of 5.5 ng mL-1 and limit of quantification of 18.2 ng mL-1 were achieved for propofol in whole blood. Calibration curve was linear in the range of 0.02-10 µg mL-1. The developed method was used successfully in monitoring the propofol concentration in 3 patients' whole blood during anesthesia, showing its further application in controlling and feeding-back target concentration infusion. Graphical abstract.

3.
Medicine (Baltimore) ; 99(36): e21691, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899001

RESUMO

This retrospective study explored the efficacy and safety of dexmedetomidine in treating early postoperative cognitive dysfunction (EPPNCD) after video-assisted thoracoscopic lobectomy (VATL) in elderly male patients with lung cancer (LC).This study included a total of 80 elderly male patients with LC who received VATL. All of them were equally assigned to a treatment group and a control group, with 40 patients each group. The primary outcome included cognitive dysfunction, as evaluated by mini-mental state examination scale. The secondary outcomes consisted of incidence of EPPNCD, lung function (as measured by forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow, and maximal voluntary ventilation), and adverse events. All outcome data were analyzed before and 3 days after surgery.After surgery, all patients in the treatment group exerted better efficacy in mini-mental state examination scale (P < .01) and incidence of EPPNCD (P = .03), than patients in the control group. However, no significant differences were detected in forced vital capacity (P = .65), forced expiratory volume in 1 second (P = .50), peak expiratory flow (P = .73), and maximal voluntary ventilation (P = .27) between 2 groups. In addition, there is similar safety profile between 2 groups.The findings of this study showed that dexmedetomidine may benefit EPPNCD after VATL in elderly male patients with LC. Future studies are needed to warrant the present conclusions.


Assuntos
Analgésicos não Entorpecentes/administração & dosagem , Dexmedetomidina/administração & dosagem , Neoplasias Pulmonares/cirurgia , Complicações Cognitivas Pós-Operatórias/tratamento farmacológico , Cirurgia Torácica Vídeoassistida/efeitos adversos , Idoso , Analgésicos não Entorpecentes/efeitos adversos , Estudos Controlados Antes e Depois , Dexmedetomidina/efeitos adversos , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Brain Behav ; 10(4): e01592, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32157827

RESUMO

INTRODUCTION: The mechanisms underlying sleep deprivation-induced memory impairments and relevant compensatory signaling pathways remain elusive. We tested the hypothesis that increased brain-derived neurotrophic factor (BDNF) expression in the basal forebrain following acute sleep deprivation was a compensatory mechanism to maintain fear memory performance. METHODS: Adult male Wistar rats were deprived of 6-hr total sleep from the beginning of the light cycle. The effects of sleep deprivation on BDNF protein expression and activation of downstream tropomyosin receptor kinase B (TrkB)/phospholipase C-γ1 (PLCγ1) signaling in the basal forebrain and fear memory consolidation were examined. BDNF or selective downstream TrkB receptor antagonist ANA-12 was further injected into the basal forebrain bilaterally to observe the changes in fear memory consolidation in response to modulation of the BDNF/TrkB signaling. RESULTS: Six hours of sleep deprivation-induced both short- and long-term fear memory impairments. Increased BDNF protein expression and TrkB and PLCγ1 phosphorylation in the basal forebrain were observed after sleep deprivation. Microinjection of BDNF into the basal forebrain partly reversed fear memory deficits caused by sleep deprivation, which were accompanied by increased BDNF protein levels and TrkB/PLCγ1 activation. After ANA-12 microinjection, sleep deprivation-induced activation of the BDNF/TrkB pathway was inhibited and impairments of fear memory consolidation were further aggravated. CONCLUSIONS: Acute sleep deprivation induces compensatory increase of BDNF expression in the basal forebrain. Microinjection of BDNF into the basal forebrain mitigates the fear memory impairments caused by sleep deprivation by activating TrkB/PLCγ1 signaling.

5.
J Cell Biochem ; 121(1): 371-384, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31218737

RESUMO

BACKGROUND: Postoperative cognitive dysfunction (POCD) is one of the common postoperative complications, which is more common in aged patients. POCD mainly manifests as cognitive function changes after surgery, such as memory decline and inattention. In some severe cases, patients may suffer from personality changes and (or) social behavior decline. The aim of the current study is to confirm the effect and elucidate the mechanism of bone marrow mesenchymal stem cells (BMSCs) in postoperative central inflammatory mice. METHODS: Mice were randomly assigned to four groups: sham, sham+BMSCs, model, and BMSCs group. In the model group, mice were intraperitoneally injected 8 mg/kg per day lipopolysaccharide for 5 days. In sham+BMSCs and BMSCs group, BMSCs (1 × 10 7 ) in 100 µL saline were injected into sham mice and model mice, respectively. RESULTS: In the model group, transforming growth factor ß (TGF-ß) protein expression was significantly increased, compared with that in the sham group. BMSCs were treated into postoperative central inflammatory mice, which resulted in a decreased of TGF-ß protein expression. TGF-ß and smad2 protein expression were suppressed, and apoptosis rate and inflammation were inhibited in coculture with BMSCs. The suppression of TGF-ß inhibited the effects of BMSCs on apoptosis rate and inflammation in postoperative central inflammatory through a smad2 signaling pathway. The promotion of TGF-ß reduced the effects of BMSCs on apoptosis rate and inflammation in postoperative central inflammatory through a smad2 signaling pathway. CONCLUSION: The present study demonstrates that BMSCs regulates TGF-ß to adjust neuroinflammation in postoperative central inflammatory mice.

6.
Front Pharmacol ; 9: 1364, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532709

RESUMO

The translocator protein (18 kDa) (TSPO) recently attracted increasing attention in the pathogenesis of post-traumatic stress disorder (PTSD). This study is testing the hypothesis that the overexpression of TSPO in hippocampus dentate gyrus (DG) could alleviate the anxiogenic-like response in the mice model of PTSD induced by foot-shock. In this study, hippocampal DG overexpression of TSPO significantly reversed the increase of the contextual freezing response, the decrease of the percentage of both entries into and time spent in the open arms in elevated plus maze test and the decrease of the account of crossings from the dark to light compartments in light-dark transition test induced by electric foot-shocks procedure. It was further showed that the behavioral effects of TSPO overexpression were blocked by PK11195, a selective TSPO antagonist. In addition, the expression of TSPO and level of allopregnanolone (Allo) decreased in the mouse model of PTSD, which was blocked by overexpression of TSPO in hippocampal dentate gyrus. The difference of neurogenesis among groups was consistent with the changes of TSPO and Allo, as evidenced by bromodeoxyuridine (BrdU)- positive cells in the hippocampal dentate gyrus. These results firstly suggested that TSPO in hippocampal dentate gyrus could exert a great effect on the occurrence and recovery of PTSD in this animal model, and the anti-PTSD-like effect of hippocampal TSPO over-expression could be at least partially mediated by up-regulation of Allo and subsequent stimulation of the adult hippocampal neurogenesis.

7.
Int Immunopharmacol ; 65: 438-447, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30388518

RESUMO

Neuroinflammation is believed to be one of the primary causes of cognitive impairment. Previous studies showed that the antioxidant vitamin C (Vit C) performs many beneficial functions such as immunostimulant and anti-inflammatory actions, but its role in inflammatory cognitive impairment is unclear. In the current study, we investigated the effect and possible mechanism of action of Vit C in lipopolysaccharide (LPS)-induced cognitive impairment. Intracerebroventricular LPS-induced memory impairment was used as the model for neuroinflammatory cognitive dysfunction. Vit C was administered by intracerebroventricular microinjection 30 min prior to LPS exposure. It was found that Vit C significantly protected animals from LPS-induced memory impairment as evidenced by improved performance in the Morris water maze and novel object recognition tests without changes in spontaneous locomotor activity. Vit C pretreatment inhibited the activation of microglia and the production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Furthermore, Vit C pretreatment markedly decreased the malondialdehyde (MDA) level, increased superoxide dismutase (SOD) activity, and modulated the Bax/Bcl-2 ratio and p-p38 MAPK activation in the hippocampus of LPS-treated mice. Together, these results suggest that vitamin C pretreatment could protect mice from LPS-induced cognitive impairment, possibly through the modulation of oxidative stress and inflammatory responses.


Assuntos
Anti-Inflamatórios/uso terapêutico , Ácido Ascórbico/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Inflamação Neurogênica/tratamento farmacológico , Animais , Disfunção Cognitiva/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Lipopolissacarídeos/imunologia , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto , Transtornos da Memória/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Inflamação Neurogênica/imunologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Neural Regen Res ; 13(11): 1937-1944, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30233067

RESUMO

Translocator protein has received attention for its involvement in the pathogenesis of depression. This study assessed the effects of the new translocator protein ligand, YL-IPA08, on alleviating inflammation-induced depression-like behavior in mice and investigated its mechanism of action. Mice were intracerebroventricularly injected with 1, 10, 100 or 1000 ng lipopolysaccharide. The tail-suspension test and the forced swimming test confirmed that 100 ng lipopolysaccharide induced depression-like behavior. A mouse model was then established by intraventricular injection of 100 ng lipopolysaccharide. On days 16-24 after model establishment, mice were intragastrically administered 3 mg/kg YL-IPA08 daily. Immunohistochemistry was used to determine BrdU and NeuN expression in the hippocampus. YL-IPA08 effectively reversed the depression-like behavior of lipopolysaccharide-treated mice, restored body mass, increased the number of BrdU-positive cells, and the number and proportion of BrdU and NeuN double-positive cells. These findings indicate that YL-IPA08 can attenuate lipopolysaccharide-induced depression-like behavior in mice by promoting the formation of hippocampal neurons.

9.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(2): 135-140, 2018 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-29502050

RESUMO

OBJECTIVE: To compare the medium- and long-term effect of pneumatic ballistic extracorporeal shock wave versus ultrasound-guided hormone injection in the treatment of plantar fasciitis. METHODS: The clinical data were collected from patients with plantar fasciitis admitted to PLA General Hospital pain department from September, 2015 to February, 2017. The patients were randomly divided into ultrasound-guided drug injection group and shock wave group. The therapeutic parameters including the numerical rating scale (NRS) scores in the first step pain in the morning, American Orthopedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Scale, and thickness of the plantar fascia were monitored before and at 1 week, 1 month, 3 months, and 6 months after the treatment. The recurrence rate, effectiveness, and patient satisfaction were compared between the two groups at 6 months after the treatment. RESULTS: Thirty-nine patients were enrolled in shock wave group and 38 patients in ultrasound group. The NRS scores in the first step pain in the morning were lowered after treatment in both groups (P<0.05), and the scores were significantly lower in ultrasound group than in shock wave group at 1 week and 1 month (P<0.01), but significantly higher in ultrasound group than in shock wave group at 3 and 6 months after treatment (P<0.05). The AOFAS functional scores were increased in both groups (P<0.05) at 6 months after treatment, was significantly lower in ultrasound group than in shock wave group than group B (90.44∓13.27 vs 75.76∓21.40; P<0.05). The effective rates in shock wave group and ultrasound group were 92.31% and 76.32%, respectively (P<0.05). Recurrence was found in 1 patient (2.56%) in shock wave group and in 8 (21.05%) in ultrasound group (P<0.05). The patient satisfaction scores were significantly higher in shock wave group than in ultrasound group (8.13∓2.67 vs 6.63∓3.75, P=0.048). CONCLUSION: Pneumatic ballistic extracorporeal shock achieves better medium- and long-term outcomes than ultrasound-guided hormone injection in the treatment of plantar fasciitis.


Assuntos
Fasciíte Plantar/terapia , Ondas de Choque de Alta Energia/uso terapêutico , Hormônios/uso terapêutico , Terapia por Ultrassom , Hormônios/administração & dosagem , Humanos , Injeções , Medição da Dor , Prognóstico , Resultado do Tratamento
10.
Mol Med Rep ; 17(3): 4573-4580, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29328382

RESUMO

Propofol postconditioning (P­PostC) offers cardioprotection in mice, and the upregulation of autophagy protects cardiac cells against ischemia/reperfusion injury. The present study aimed to examine the effects of P­PostC on the induction of autophagy and its potential roles in hypoxia/reoxygenation (H/R) injury. Rat heart­derived H9c2 cells were exposed to H/R, comprising 6 h of hypoxia followed by 4 h of reoxygenation, as well as postconditioning with various concentrations of propofol at the onset of reperfusion. Lactate dehydrogenase (LDH) activity and the rate of cell apoptosis were measured to evaluate the degree of cardiomyocyte H/R injury. The induction of autophagy in myocytes subjected to H/R injury and P­PostC was detected by western blotting and immunofluorescence. Furthermore, the activation of c­Jun N­terminal kinase (JNK) in cells treated with P­PostC with or without co­treatment with SP600125, an inhibitor of JNK, was also determined by western blotting. P­PostC reduced the activity of LDH in the culture medium and the percentage of apoptotic cells compared with cells in the untreated H/R group. In addition, P­PostC induced autophagy and promoted survival signaling in H9c2 cardiac myoblast cells. The inhibition of autophagy by 3­methyladenine treatment diminished the cardioprotective effects of P­PostC. These results indicated that propofol postconditioning promoted cell survival through the induction of autophagy in H9c2 cardiac cells, and that the stress­activated protein kinase/JNK survival pathway may be partly involved in P­PostC­induced autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Hipóxia Celular , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Propofol/farmacologia , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Antracenos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , L-Lactato Desidrogenase/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Oxigênio/farmacologia , Fosforilação/efeitos dos fármacos , Ratos , Proteína Sequestossoma-1/metabolismo
11.
Brain Res Bull ; 130: 274-282, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28235598

RESUMO

Postoperative cognitive dysfunction (POCD) is characterized by cognitive impairments in patients after surgery. Hippocampal neuroinflammation induced by surgery is highly associated with POCD. Phosphodiesterase-4 (PDE4) is an enzyme that specifically hydrolyses cyclic adenosine monophosphate (cAMP), which plays an important role during neuroinflammation and the process of learning and memory. However, the role of PDE4 in the development of POCD remains unclear. Male 14-month-old C57BL/6 mice received carotid artery exposure to mimic POCD. First, we evaluated cognitive performance by a Morris water maze (MWM) and fear conditioning system (FCS) test after surgery. The expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were investigated. Then, we used rolipram, a PDE4 inhibitor, to block the effects of PDE4. The cognitive performance of the mice and the expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were examined again. Mice displayed learning and memory impairment, overexpression of PDE4B and PDE4D, elevation of pro-inflammatory cytokines, and reduction in the expression of p-CREB, PSD95 and cAMP levels after surgery. The expression of PDE4B and PDE4D in the hippocampus decreased following blocking of PDE4 by rolipram. Meanwhile, rolipram attenuated the cognitive impairment and the elevation of pro-inflammatory cytokines induced by surgery. Moreover, rolipram reversed the reduction of p-CREB and PSD95. These results indicate that PDE4 subtype overexpression may be involved in the development of surgery-induced cognitive dysfunction in mice.


Assuntos
Disfunção Cognitiva/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Encefalite/metabolismo , Complicações Pós-Operatórias/metabolismo , Animais , Comportamento Animal , Disfunção Cognitiva/etiologia , Citocinas/metabolismo , Encefalite/complicações , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora , Plasticidade Neuronal
12.
J Neuroinflammation ; 14(1): 17, 2017 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-28109286

RESUMO

BACKGROUND: Considerable evidence has shown that neuroinflammation and oxidative stress play an important role in the pathophysiology of postoperative cognitive dysfunction (POCD) and other progressive neurodegenerative disorders. Increasing evidence suggests that acetaminophen (APAP) has unappreciated antioxidant and anti-inflammatory properties. However, the impact of APAP on the cognitive sequelae of inflammatory and oxidative stress is unknown. The objective of this study is to explore whether APAP could have neuroprotective effects on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: A mouse model of LPS-induced cognitive impairment was established to evaluate the neuroprotective effects of APAP against LPS-induced cognitive impairment. Adult C57BL/6 mice were treated with APAP half an hour prior to intracerebroventricular microinjection of LPS and every day thereafter, until the end of the study period. The Morris water maze was used to assess cognitive function from postinjection days 1 to 3. Animal behavioural tests as well as pathological and biochemical assays were performed to evaluate LPS-induced hippocampal damage and the neuroprotective effect of APAP. RESULTS: Mice treated with LPS exhibited impaired performance in the Morris water maze without changing spontaneous locomotor activity, which was ameliorated by treatment with APAP. APAP suppressed the accumulation of pro-inflammatory cytokines and microglial activation induced by LPS in the hippocampus. In addition, APAP increased SOD activity, reduced MDA levels, modulated glycogen synthase kinase 3ß (GSK3ß) activity and elevated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Moreover, APAP significantly decreased the Bax/Bcl-2 ratio and neuron apoptosis in the hippocampus of LPS-treated mice. CONCLUSIONS: Our results suggest that APAP may possess a neuroprotective effect against LPS-induced cognitive impairment and inflammatory and oxidative stress via mechanisms involving its antioxidant and anti-inflammatory properties, as well as its ability to inhibit the mitochondrial permeability transition (MPT) pore and the subsequent apoptotic pathway.


Assuntos
Acetaminofen/farmacologia , Antioxidantes/farmacologia , Disfunção Cognitiva , Hipocampo/efeitos dos fármacos , Animais , Disfunção Cognitiva/induzido quimicamente , Lipopolissacarídeos/toxicidade , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia
13.
BMC Anesthesiol ; 16: 75, 2016 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-27609188

RESUMO

BACKGROUND: The settings of mechanical ventilation, like tidal volume (VT), occasionally need to be adjusted in the process of anesthesia for some special reasons. The aim of this study was therefore to assess the relationship between pulse pressure variations (PPVs) in different settings of VT in anesthetized healthy patients under mechanical ventilation. METHODS: Sixty nine ASA I-II patients scheduled for gastrointestinal surgery under general anesthesia were included in this prospective study. All the patients were ventilated at a VT of 6, 8 or 10 ml/kg (predicted body weight) with no positive end expiratory pressure (PEEP) in a random order after intubation. PPV, mean arterial blood pressure, and other hemodynamic and respiratory parameters were recorded in each VT setting respectively after Partial Pressure of End-Tidal Expiration Carbon Dioxide (PetCO2) maintained between 30 mmHg and 40 mmHg by changing Respiratory Rate (RR) before incision. RESULTS: The values of PPV at different settings of VT showed a tight correlation between each other (6 vs. 8 ml/kg: r = 0.97, P < 0.0001; 6 vs.10 ml/kg: r = 0.95, P < 0.0001; 8 vs. 10 ml/kg: r = 0.98, P < 0.0001, respectively). CONCLUSION: There is a direct linear correlation between PPVs at different tidal volumes in anesthetized ASA I-II patients. PPV in any of the 3 VT settings (6, 8 or 10 ml/kg) can deduce that in any other 2 settings. Further studies are needed to explore the effect of intraoperative confounders for this knowledge to be clinically applied. TRIAL REGISTRATION: NCT01950949 , www.clinicaltrials.gov , July 26, 2013.


Assuntos
Anestesia Geral , Pressão Sanguínea/fisiologia , Pulso Arterial , Volume de Ventilação Pulmonar/fisiologia , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial , Estatística como Assunto , Adulto Jovem
14.
Neurochem Res ; 41(7): 1587-603, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27038931

RESUMO

Stromal cell-derived factor 1 (SDF-1)/chemokine CXC motif ligand 12 (CXCL12), a chemokine that is upregulated in dorsal root ganglion (DRG) during chronic pain models, has recently been found to play a central role in pain hypersensitivity. The purpose of present study is to investigate the functional impact of SDF-1 and its receptor, chemokine CXC motif receptor 4 (CXCR4), on two TTXR sodium channels in rat DRG using electrophysiological techniques. Preincubation with SDF-1 caused a concentration-dependent increase of Nav1.8 and Nav1.9 currents amplitudes in acutely isolated small diameter DRG neurons in short-term culture. As to Nav1.9, changes in current density and kinetic properties of Nav1.9 current evoked by SDF-1(50 ng/ml) was eliminated by CXCR4 antagonist AMD3100 and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. The increase in Nav1.9 current was also blocked by pertussis toxin (PTX) but not cholera toxin (CTX), showing involvement of Gi/o but not Gs subunits. As to Nav1.8, inhibitors (AMD3100, PTX, CTX, LY294002) used in present study didn't inhibit the increased amplitude of Nav1.8 current and shifted activation curve of Nav1.8 in a hyperpolarizing direction in the presence of SDF-1 (50 ng/ml). In conclusion, our data demonstrated that SDF-1 may excite primary nociceptive sensory neurons by acting on the biophysical properties of Nav1.8 and Nav1.9 currents but via different mechanisms.


Assuntos
Quimiocina CXCL12/farmacologia , Gânglios Espinais/fisiologia , Canal de Sódio Disparado por Voltagem NAV1.8/fisiologia , Canal de Sódio Disparado por Voltagem NAV1.9/fisiologia , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Gânglios Espinais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
15.
Brain Res Bull ; 121: 192-200, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26851069

RESUMO

Translocator protein 18 kDa (TSPO) is now an attractive drug target for controlling neuroinflammation. Studies applying TSPO ligands to neurodegenerative diseases, especially Alzheimer's disease (AD), were rare. Our study was aimed to evaluate the effect of PK11195, a specific TSPO ligand, in an animal model of neuroinflammation caused by systemic LPS administration. C57/BL6 mice were treated with lipopolysaccharide (LPS, 500 µg/kg, i.p.) three days after PK11195 administration (3mg/kg, i.p.). The drugs were not discontinued until the mice were sacrificed. Cognitive function was assessed by Morris water maze (MWM) seven days after LPS injection. Chronic LPS-injection in mice was characterized by cognitive dysfunction, increased expression of cyclooxygenase (COX)-2 and TSPO, elevated Aß content with increased expression of ß-site APP cleaving enzyme-1 (BACE-1) and insulin-degrading enzyme (IDE) as well as decreased brain progesterone and brain-derived neurophic factor (BDNF) level. PK11195 pretreatment protected cognitive function in LPS-injected animals and normalized the inflammatory proteins. Moreover, PK11195 pre-administration decreased elevated hippocampal Aßx-42 levels and increased brain levels of progesterone, allopregnanolone. However, LPS-induced BDNF decrease was not reversed by PK11195 administration. Our data demonstrated that PK11195 could protect cognitive deficits induced by chronic LPS administration. The underling mechanism may involve alleviated neuroinflammation, increased synthesis of neurosteroid and decreased Aß accumulation accompanied by down-regulation of BACE-1.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Anti-Inflamatórios/uso terapêutico , Encefalite/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Isoquinolinas/uso terapêutico , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Encefalite/induzido quimicamente , Encefalite/metabolismo , Encefalite/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Pregnanolona/metabolismo , Progesterona/metabolismo , Receptores de GABA/metabolismo
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 37(2): 179-84, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25936706

RESUMO

OBJECTIVE: To investigate the effects of different positive end expiratory pressures (PEEP) on functional hemodynamic parameters in patients lying in prone position during operation under general anesthesia. METHODS: Totally 60 patients undergoing cervical vertebra operation or lumbar vertebra operation were studied. All patients were also monitored with Vigileo/FloTrac system. The functional hemodynamic parameters including stroke volume variation (SVV), pulse pressure variation (PPV), and pleth variability index (PVI) under PEEP levels of 0 mmHg, 5 mmHg, 10 mmHg, and 15 mmHg were recorded before and after volume expansion (hydroxyethyl starch 6%,7 ml/kg). Fluid responsiveness was defined as an increase in stroke volume index (SVI) ≥ 15%(△SVI ≥ 15%). Responders were defined as patients demonstrating an increase in SVI ≥ 15% after intravascular volume expansion and non-responders as patients whose SVI changed <15%. Receiver operating characteristic (ROC) curves were generated for SVV, PPV, and PVI under different PEEP levels to determine their diagnosis accuracies and thresholds and their potential correlations. RESULTS: In the prone position, SVV, PPV, and PVI were significantly higher compared to those in the supine position (P<0.05) and the mean arterial pressure significantly decreased (P<0.05); however, the changes of heart rate, stroke volume, SVI, cardiac output, and cardiac index showed no significant difference (P>0.05). In the prone position, along with the elevation of PEEP (0 mmHg, 5 mmHg, 10 mmHg, and 15 mmHg), the areas under the ROC curves of SVV were 0.864, 0.759, 0.718, and 0.521, the area under the ROC of PPV were 0.873, 0.792,0.705, and 0.505, and the area under the ROC of PVI were 0.851, 0.765 ,0.709, and 0.512. Under PEEP=0 mmHg, the diagnostic thresholds of SVV, PPV, and PVI were 10.5, 11.5, and 13.5. Under PEEP=5 mmHg, the diagnostic thresholds of SVV,PPV, and PVI were 11.5,13.5, and 14.5.Under PEEP=10 mmHg,the diagnostic thresholds of SVV, PPV, and PVI were 13.5,14.5, and 16.5.In the prone position,there was a significant correlation between SVV,PPV,PVI,and PEEP. CONCLUSIONS: SVV,PPV and PVI can predict fluid responsiveness similarly under the PEEP levels of 0,5, and 10 mmHg. Their diagnostic thresholds increases with the PEEP and the diagnostic accuracies decrease with the PEEP. However, under the PEEP level of 15 mmHg, SVV, PPV, and PVI can not predict fluid responsiveness accurately.


Assuntos
Decúbito Ventral , Acidente Vascular Cerebral , Anestesia Geral , Pressão Sanguínea , Débito Cardíaco , Hemodinâmica , Humanos , Respiração com Pressão Positiva , Curva ROC , Volume Sistólico
17.
Clin Exp Pharmacol Physiol ; 42(8): 828-36, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26016707

RESUMO

This study examined the effects of perioperative dexmedetomidine treatment on physiological modulators of surgical stress response. The quality of the included studies was assessed prior to performing meta-analyses of the weighted mean differences in the changes from baseline of stress hormones and interpreted in the light of statistical heterogeneity between the studies. Nineteen studies (844 surgical subjects) data were used for this meta-analysis. Dexmedetomidine administration significantly decreased blood cortisol levels (µg/dL) postoperatively (mean difference with 95% confidence interval (CI) from controls: -18.78 (-28.45, -9.10); P < 0.05). In the subgroup analysis, the mean difference between dexmedetomidine-treated and saline-treated subjects in the changes from baseline of the cortisol levels was -20.10 (-30.96, -9.25; P < 0.05) but, between dexmedetomidine- and comparator-treated subjects, it was not statistically significantly different (-15.13 (-49.78, 19.52); P < 0.05). Compared with controls, dexmedetomidine treatment also decreased adrenaline and noradrenaline levels significantly (mean difference in the percent changes from baseline: -90.41 (-145.79, -35.03)%; P < 0.05 and -62.82 (-85.47, -0.40.17)%; P < 0.05, respectively). Dexmedetomidine also decreased prolactin levels with a mean difference of -19.42 (-39.37, 0.52) µg/L (P = 0.06). In conclusion, perioperative use of dexmedetomidine reduces serum catecholamine and cortisol levels but the decrease in cortisol levels was not statistically different from the comparator anaesthetics. More data will be required to assess the effects of dexmedetomidine on corticotropin, prolactin, and growth hormone.


Assuntos
Dexmedetomidina/farmacologia , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/fisiologia , Período Perioperatório , Estresse Fisiológico/efeitos dos fármacos , Animais , Humanos
18.
J Neuroinflammation ; 12: 20, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25644393

RESUMO

BACKGROUND: Neuroinflammation often results in enduring cognitive impairment and is a risk factor for postoperative cognitive dysfunction. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that the iron chelator deferoxamine (DFO) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of DFO on the cognitive sequelae of neuroinflammation is unknown. METHODS: A mouse model of lipopolysaccharide (LPS)-induced cognitive impairment was established to evaluate the neuroprotective effects of DFO against LPS-induced memory deficits and neuroinflammation. Adult C57BL/6 mice were treated with 0.5 µg of DFO 3 days prior to intracerebroventricular microinjection of 2 µg of LPS. Cognitive function was assessed using a Morris water maze from post-injection days 1 to 3. Animal behavioral tests, as well as pathological and biochemical assays were performed to evaluate the LPS-induced hippocampal damage and the neuroprotective effect of DFO. RESULTS: Treatment of mice with LPS resulted in deficits in cognitive performance in the Morris water maze without changing locomotor activity, which were ameliorated by pretreatment with DFO. DFO prevented LPS-induced microglial activation and elevations of IL-1ß and TNF-α levels in the hippocampus. Moreover, DFO attenuated elevated expression of caspase-3, modulated GSK3ß activity, and prevented LPS-induced increases of MDA and SOD levels in the hippocampus. DFO also significantly blocked LPS-induced iron accumulation and altered expression of proteins related to iron metabolism in the hippocampus. CONCLUSIONS: Our results suggest that DFO may possess a neuroprotective effect against LPS-induced neuroinflammation and cognitive deficits via mechanisms involving maintenance of less brain iron, prevention of neuroinflammation, and alleviation of oxidative stress and apoptosis.


Assuntos
Desferroxamina/uso terapêutico , Encefalite/tratamento farmacológico , Transtornos da Memória/prevenção & controle , Sideróforos/uso terapêutico , Animais , Caspase 3/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Encefalite/induzido quimicamente , Encefalite/complicações , Comportamento Exploratório/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Interleucina-1beta/metabolismo , Ferro/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Tempo de Reação/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Curr Med Res Opin ; 30(11): 2279-89, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25050590

RESUMO

BACKGROUND: In epidural analgesia, synthetic opioids increase the potency of amide local anesthetics by modifying their analgesic properties. The purpose of this systematic review and meta-analysis is to compare the efficacy and safety of bupivacaine with ropivacaine and levobupivacaine in combination with sufentanil (BUPI-, ROPI-, and LBUPI-SUF respectively) in epidural analgesia for labor. METHODS: A literature search was made in multiple electronic databases for original research papers published between 1995 and 2014. Meta-analyses were based on mean differences between the groups as well as odds ratios where appropriate. Both the fixed effects and random effects models were utilized and heterogeneity was tested with the I(2) index. RESULTS: Analgesia duration was significantly longer in ROPI-SUF and LBUPI-SUF than in BUPI-SUF administered women with a mean difference (95% CI) of 16.12 (2.56, 29.68); P < 0.03 and 18.02 (9.09, 26.96); P < 0.0001 respectively under a random effects model (REM). Effective analgesia achievement was significantly earlier in the BUPI-SUF than in either the ROPI-SUF (2.61 [1.87, 3.36]; P < 0.00001) or the LBUPI-SUF groups (4.53 [3.66, 5.40]; P < 0.00001) under a fixed effects model (FEM) but not under a REM (I(2 )= 85%). Motor blockade incidence was higher in BUPI-SUF anesthetized patients, although the difference was not statistically significant. A higher incidence of instrumental deliveries was evident in the ROPI-SUF (FEM: 1.68 [1.13, 2.50]; P < 0.02/REM: 1.76 [1.00, 3.11]; P = 0.05) and LBUPI-SUF (FEM: 2.03 [1.07, 3.86]; P < 0.04/REM: 2.03 [1.07, 3.86]; P < 0.04) groups than in the BUPI-SUF group of patients. Inconsistencies in the availability of parametric data and use of slightly varying anesthetic dosages in included studies were important limitations. CONCLUSION: Whereas significantly longer labor analgesia can be achieved with ROPI-SUF and LBUPI-SUF and ropivacaine is associated with comparatively less motor blockade, labor duration after epidural analgesia has been found to be shorter in BUPI-SUF and there is a low incidence of instrumental delivery.


Assuntos
Amidas/administração & dosagem , Analgésicos Opioides/administração & dosagem , Anestesia Epidural , Anestésicos Locais/administração & dosagem , Bupivacaína/análogos & derivados , Dor do Parto/tratamento farmacológico , Sufentanil/administração & dosagem , Bupivacaína/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Levobupivacaína , Gravidez , Ropivacaina
20.
Vasc Endovascular Surg ; 48(5-6): 372-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24951292

RESUMO

Therapeutic angiogenesis using gene therapy is a novel strategy for the treatment of critical limb ischemia (CLI). We conducted a meta-analysis to evaluate the efficacy and safety of gene therapy for the treatment of CLI with no option of revascularization. Randomized placebo controlled trials of gene therapy on CLI were identified by searching PubMed (from 1990 to October 2013) and EMBASE (from 1990 to October 2013). Five eligible studies were selected for the meta-analysis. Among these studies, a total of 425 patients received gene therapy of either fibroblast growth factor 1 or hepatocyte growth factor, and 365 patients were given placebo. No statistical differences were observed between the 2 groups in major amputation or death at 1 year (risk ratio [RR], 0.83; 95% confidence interval [CI], 0.51-1.39; P = .48) and wound healing at 6 months (RR, 1.55; 95% CI, 0.73-3.28; P = .25). Gene therapy had similar occurrence of serious adverse events as control (RR, 1.05; 95% CI, 0.97-1.14; P = .23).


Assuntos
Proteínas Angiogênicas/biossíntese , Extremidades/irrigação sanguínea , Terapia Genética , Isquemia/terapia , Neovascularização Fisiológica/genética , Amputação , Proteínas Angiogênicas/genética , Distribuição de Qui-Quadrado , Estado Terminal , Medicina Baseada em Evidências , Fator 1 de Crescimento de Fibroblastos/biossíntese , Fator 1 de Crescimento de Fibroblastos/genética , Terapia Genética/efeitos adversos , Terapia Genética/mortalidade , Fator de Crescimento de Hepatócito/biossíntese , Fator de Crescimento de Hepatócito/genética , Humanos , Isquemia/diagnóstico , Isquemia/genética , Isquemia/metabolismo , Isquemia/mortalidade , Isquemia/fisiopatologia , Salvamento de Membro , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Cicatrização
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