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1.
Mol Neurobiol ; 56(10): 7085-7096, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30976982

RESUMO

Fibroblast growth factor-inducible-14 (Fn14), a receptor for tumor necrosis-like weak inducer of apoptosis, is expressed in the neurons of dorsal root ganglion (DRG). Its mRNA is increased in the injured DRG following peripheral nerve injury. Whether this increase contributes to neuropathic pain is unknown. We reported here that peripheral nerve injury caused by spinal nerve ligation (SNL) increased the expression of Fn14 at both protein and mRNA levels in the injured DRG. Blocking this increase attenuated the development of SNL-induced mechanical, thermal, and cold pain hypersensitivities. Conversely, mimicking this increase produced the increases in the levels of phosphorylated extracellular signal-regulated kinase ½ and glial fibrillary acidic protein in ipsilateral dorsal horn and the enhanced responses to mechanical, thermal, and cold stimuli in the absence of SNL. Mechanistically, the increased Fn14 activated the NF-κB pathway through promoting the translocation of p65 into the nucleus of the injured DRG neurons. Our findings suggest that Fn14 may be a potential target for the therapeutic treatment of peripheral neuropathic pain.


Assuntos
NF-kappa B/metabolismo , Neuralgia/metabolismo , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais , Receptor de TWEAK/metabolismo , Animais , Células Cultivadas , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Ligadura , Masculino , Camundongos , Microinjeções , Neuralgia/patologia , Limiar da Dor , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Nervos Espinhais/metabolismo , Nervos Espinhais/patologia
2.
Mediators Inflamm ; 2016: 1045657, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26924896

RESUMO

Sepsis-associated encephalopathy (SAE) is characterized as brain dysfunction associated with sepsis. In this study we sought to investigate the effects of resveratrol in mice with SAE, as well as its effects in NLRP3 inflammasome and IL-1ß, which were critical in the pathogenesis of SAE. SAE was induced in mice via cecal ligation and puncture (CLP), and resveratrol was administered at two doses after surgery. Spatial learning memory functions were evaluated by Morris water maze testing. Apoptosis in the hippocampus was quantified using TUNEL assay. Inflammation in the hippocampus was quantified by measuring the levels of microglial activation, NLRP3, and IL-1ß. CLP mice treated with resveratrol demonstrated a better spatial memory during water maze training. The TUNEL assay demonstrated significantly attenuated rates of apoptosis, in resveratrol treated mice, while decreasing the number of iba-1 positive microglia in the hippocampus region. NLRP3 expression and IL-1ß cleavage were well inhibited by resveratrol dose-dependently. The in vitro results showed that in the BV2 cell lines resveratrol prevents ATP induced NLRP3 activation and IL-1ß cleavage, which were reversed by the sirtuin 1 inhibitor, nicotinamide. In conclusion, resveratrol improves the spatial memory in mice with SAE and inhibits the NLRP3/IL-1ß axis in the microglia.


Assuntos
Interleucina-1beta/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Encefalopatia Associada a Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/metabolismo , Estilbenos/uso terapêutico , Animais , Linhagem Celular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resveratrol
3.
Med Sci Monit ; 22: 206-10, 2016 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-26787637

RESUMO

BACKGROUND: Propofol is widely used in sedation for colonoscopy, but its adverse effects on cardiovascular and respiratory systems are still concerning. The present study investigated whether target controlled infusion (TCI) of propofol could provide a better sedation quality than manually controlled infusion (MCI) in training inexperienced anesthesiology residents. MATERIAL/METHODS: Eighteen training residents were allocated into 2 groups receiving TCI and MCI training in their first month in the endoscopy center, while receiving MCI and TCI training instead in their second month. The last 2 patients at the end of each month were included to analyze the sedation quality of TCI and MCI techniques by comparing satisfaction of endoscopist and patients based on the visual analogue scale (VAS). Heart rate (HR), mean blood pressure (MAP), SpO2, and recovery time were also compared as the secondary outcomes. RESULTS: The demographic data were similarly distributed among the TCI and MCI patients. Endoscopist's satisfaction score in the TCI group was significantly higher than in the MCI group, 81.3±7.2 versus 74.2±9.5 (P=0.003), but the patients' satisfaction score was similar between the 2 groups. More stable hemodynamic status was obtained in the TCI group, manifested as higher lowest MAP and lower highest MAP than in the MCI group. Lowest SpO2 in the TCI group was significantly higher than in the MCI group. Patients in the TCI group recovered earlier than in the MCI group. CONCLUSIONS: TCI is a more effective and safer technique for anesthesiology residents in sedation for colonoscopy.


Assuntos
Anestesiologia/educação , Colonoscopia/educação , Internato e Residência , Propofol/administração & dosagem , Propofol/farmacologia , Adulto , Estudos Cross-Over , Demografia , Feminino , Humanos , Infusões Intravenosas , Masculino , Estudos Prospectivos
4.
J Neurosurg Anesthesiol ; 28(4): 303-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26368663

RESUMO

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease affecting the quality of life in the elderly. We speculated that PD patients might have abnormal pharmacodynamics due to the degenerative neural system, and the present study was performed to investigate the pharmacodynamics of remifentanil in PD patients. MATERIALS AND METHODS: Two arms of patients were recruited, including 31 PD patients undergoing pulse generator placement after deep brain stimulator implantation and 31 pair-controlled patients undergoing intracranial surgery without PD (NPD). Patients were anesthetized with target-controlled infusion of propofol and remifentanil. The effective concentration of remifentanil to inhibit responses to intubation and skin incision in 50% and 95% patients (EC50 and EC95) was determined by the up and down method. RESULTS: Demographic data, bispectral index, and hemodynamic values were similar between the PD and the NPD groups. The average remifentanil concentration used in the PD group for tracheal intubation is significantly lower than in the NPD group (P<0.001). The EC50 for inhibiting the response to tracheal intubation were 1.86 ng/mL (95% confidential interval [CI], 1.77-1.96 ng/mL) in the PD group and 3.20 ng/mL (95% CI, 3.13-3.27 ng/mL) in the NPD group. The average remifentanil concentration used in the PD group for skin incision is significantly lower than in the NPD group (P<0.001). EC50 for inhibiting the response to skin incision were 2.17 ng/mL (95% CI, 2.09-2.25 ng/mL) in the PD group and 3.09 ng/mL (95% CI, 3.02-3.17 ng/mL) in the NPD group. CONCLUSIONS: The remifentanil concentrations required for inhibiting responses to tracheal intubation and skin incision are reduced markedly in PD patients undergoing pulse generator placement (NCT01992692).


Assuntos
Anestésicos Intravenosos/farmacologia , Estimulação Encefálica Profunda/instrumentação , Intubação Intratraqueal , Doença de Parkinson/cirurgia , Piperidinas/farmacologia , Ferida Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Remifentanil , Pele
6.
BMC Anesthesiol ; 15: 161, 2015 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-26547293

RESUMO

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) is an effective therapeutic method used to treat patients with pancreatic stones. However, the anesthesia for this procedure has been underappreciated, with minimal reports of these procedures in certain case series with general or epidural anesthesia. METHODS: A cohort of 60 patients who elected to undergo ESWL in order to treat pancreatic stones for the first time were randomly selected and divided into two groups. One group of patients received target controlled infusion (TCI) of remifentanil, while the other group of patients received TCI of remifentanil plus a bolus of flurbiprofen axetil (a cyclooxygenase inhibitor) (Rem group and Rem + Flu group, n = 30 for each group). The Dixon's up-and-down method was used to calculate the half maximum effective concentration (EC50) of remifentanil. Visual analogue scales of pain, Ramsay sedation scale, hemodynamic changes, and adverse events were also recorded. RESULTS: The EC50 of remifentanil was calculated to be 4.0 ng/ml (95 % confidential interval: 3.84 ng/ml, 4.16 ng/ml) and 2.76 ng/ml (95 % confidential interval: 2.63 ng/ml, 2.89 ng/ml) in the Rem group and Rem + Flu group respectively (p < 0.001). Pain score was comparable between the two groups, while the Ramsay sedation scale was higher in the Rem group. Hemodynamic data showed that patients in the Rem group experienced higher mean arterial pressures and higher heart rates across the procedures. Patients in Rem group demonstrated a lower respiratory rate (p < 0.001) and a lower SpO2 (p = 0.001). Less adverse events occurred in Rem + Flu group, including a reduced respiratory depression requiring wake-up as well as reduced postoperative nausea and vomiting. CONCLUSION: Remifentanil plus flurbiprofen axetil provided satisfactory analgesia and sedation for ESWL of pancreatic stones with less adverse events. (Clinicaltrial.gov: NCT01998217 ; registered on November 19, 2013).


Assuntos
Cálculos/terapia , Flurbiprofeno/análogos & derivados , Litotripsia/métodos , Piperidinas/administração & dosagem , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Pressão Arterial/efeitos dos fármacos , Cálculos/patologia , Quimioterapia Combinada , Feminino , Flurbiprofeno/administração & dosagem , Flurbiprofeno/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Pancreatopatias/patologia , Pancreatopatias/terapia , Piperidinas/efeitos adversos , Náusea e Vômito Pós-Operatórios/epidemiologia , Estudos Prospectivos , Remifentanil , Taxa Respiratória/efeitos dos fármacos
7.
Biomed Res Int ; 2015: 953729, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26495319

RESUMO

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, but whether the neurodegenerative process influences the pharmacodynamics of propofol remains unclear. We aimed to evaluate the effect of PD on pharmacodynamics of propofol. A total of 31 PD patients undergoing surgical treatment (PD group) and 31 pair-controlled non-PD patients undergoing intracranial surgery (NPD group) were recruited to investigate the propofol requirement for unconsciousness induction. Unconsciousness was induced in all patients with target-controlled infusion of propofol. The propofol concentration at which unconsciousness was induced was compared between the two groups. EC50 and EC95 were calculated as well. Demographic data, bispectral index, and hemodynamic values were comparable between PD and NPD groups. The mean target concentration of propofol when unconsciousness was achieved was 2.32 ± 0.38 µg/mL in PD group, which was significantly lower than that in NPD group (2.90 ± 0.35 µg/mL). The EC50 was 2.05 µg/mL (95% CI: 1.85-2.19 µg/mL) in PD group, much lower than the 2.72 µg/mL (95% CI: 2.53-2.88 µg/mL) in NPD group. In conclusion, the effective propofol concentration needed for induction of unconsciousness in 50% of patients is reduced in PD patients. (This trial is registered with NCT01998204.).


Assuntos
Estado de Consciência/efeitos dos fármacos , Esquema de Medicação , Propofol/administração & dosagem , Anestésicos Gerais/administração & dosagem , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Resultado do Tratamento
8.
J Surg Res ; 193(2): 902-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25439504

RESUMO

BACKGROUND: The controversial results from different studies suggested that leukocyte recruitment mediated by leukotriene B4 (LTB4) and its receptor might improve pathogen clearance, but might also aggravate organ injury during sepsis. The present study was performed to compare the effect of BLT1 ligand LTB4 and its antagonist U-75302 on the development of sepsis. METHODS: Sepsis in mice was induced by cecal ligation and puncture (CLP). The mice were allocated into sham group, CLP group, U-75302 group, and LTB4 group. In the latter three groups, CLP mice were treated by intraperitoneal saline, U-75302, and LTB4, respectively. Their effect on the progression of sepsis were compared by histopathologic tests, level of systemic cytokines, counts of immune cells and bacterial clearance, and survival rate. RESULTS: The histopathologic tests showed that U-75302 attenuated lung injury, whereas LTB4 aggravated liver injury. LTB4 increased the plasma levels of interleukin-6, tumor necrosis factor-α, and U-75302 increased the level of plasma interleukin-10. LTB4 increased whereas U-75302 reduced the neutrophil numbers in the peritoneal lavage fluid. LTB4 also increased the number of peritoneal and splenic CD4(+) and CD8(+) T cells. Bacterial clearance in blood and peritoneal lavage fluid was significantly enhanced in the LTB4 group. Both U-75302 and LTB4 did not change the survival rate significantly compared with vehicle, but mortality in the LTB4 group was significantly higher than in the U-75302 group. Dose response analyses were also performed to compare the effect of U-75302 and LTB4 at different doses. Different doses of both agents did not influence the survival rate of CLP mice. CONCLUSIONS: U-75302 attenuates sepsis-induced organ injury, whereas LTB4 increases the leukocyte recruitment toward infection site, but LTB4 showed a more lethal effect than U-75302 during polymicrobial sepsis.


Assuntos
Álcoois Graxos/toxicidade , Glicóis/toxicidade , Leucotrieno B4/toxicidade , Receptores do Leucotrieno B4/metabolismo , Sepse/metabolismo , Animais , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Receptores do Leucotrieno B4/agonistas , Receptores do Leucotrieno B4/antagonistas & inibidores
9.
Anesthesiology ; 122(4): 852-63, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25437496

RESUMO

BACKGROUND: Recent studies have shown that neutrophils may display an antigen-presenting function and inhibit lymphocyte proliferation by expressing programmed cell death 1 ligand 1 (PD-L1). The current study was performed to investigate the effect of neutrophils and their pathophysiological significance during sepsis. METHODS: Neutrophil PD-L1 expression was determined in both septic mice (n = 6) and patients (n = 41). Neutrophils from septic mice were subtyped into PD-L1 and PD-L1 populations to determine their phenotypes and functions. Septic neutrophils were cocultured with lymphocytes to observe the effect of septic neutrophils on lymphocyte apoptosis. RESULTS: The PD-L1 level on neutrophils from septic mice was significantly up-regulated (21.41 ± 4.76%). This level increased with the progression of sepsis and the migration of neutrophils from the bone marrow to the blood and peritoneal cavity. The percentages of CD11a, CD62L, and C-C chemokine receptor type 2 were lower, whereas the percentages of CD16 and CD64 were higher on PD-L1 neutrophils than on PD-L1 neutrophils. The migratory capacity of PD-L1 neutrophils was compromised. Septic neutrophils induced lymphocyte apoptosis via a contact mechanism, and this process could be reversed by anti-PD-L1 antibody. PD-L1 was also up-regulated on neutrophils from patients with severe sepsis (14.6% [3.75%, 42.1%]). The levels were negatively correlated with the monocyte human leukocyte antigen-DR level and positively correlated with the severity of septic patients. Neutrophil PD-L1 was a predictor for the prognosis of severe sepsis, with an area of 0.74 under the receiver operating curve. CONCLUSIONS: PD-L1 is up-regulated on neutrophils during sepsis, which may be related to sepsis-induced immunosuppression.


Assuntos
Antígeno B7-H1/biossíntese , Tolerância Imunológica/fisiologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Sepse/imunologia , Sepse/metabolismo , Idoso , Animais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Estudos Prospectivos , Regulação para Cima/fisiologia
10.
Mediators Inflamm ; 2014: 195290, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24891762

RESUMO

Intercellular adhesion molecule-1 (ICAM-1) is a key adhesion molecule mediating neutrophil migration and infiltration during sepsis. But its role in the outcome of sepsis remains contradictory. The current study was performed to investigate the role of anti-ICAM-1 antibody in the outcome of polymicrobial sepsis and sepsis-induced immune disturbance. Effect of anti-ICAM-1 antibody on outcome of sepsis induced by cecal ligation and puncture (CLP) was evaluated by the survival analysis, bacterial clearance, and lung injury. Its influence on neutrophil migration and infiltration, as well as lymphocyte status, in thymus and spleen was also investigated. The results demonstrated that ICAM-1 mRNA was upregulated in lung, thymus, and spleen of CLP mice. Anti-ICAM-1 antibody improved survival and bacterial clearance in CLP mice and attenuated lung injury. Migration of neutrophils to peritoneal cavity was enhanced while their infiltration into lung, thymus, and spleen was hampered by ICAM-1 blockade. Anti-ICAM-1 antibody also prevented sepsis-induced apoptosis in thymus and spleen. Positive costimulatory molecules including CD28, CD80, and CD86 were upregulated, while negative costimulatory molecules including PD-1 and PD-L1 were downregulated following anti-ICAM-1 antibody administration. In conclusion, ICAM-1 blockade may improve outcome of sepsis. The rationale may include the modulated neutrophil migration and the reversed immunosuppression.


Assuntos
Molécula 1 de Adesão Intercelular/imunologia , Neutrófilos/citologia , Sepse/imunologia , Animais , Anticorpos/imunologia , Apoptose , Ceco/lesões , Ceco/patologia , Adesão Celular , Movimento Celular , Imunossupressão , Pulmão/metabolismo , Lesão Pulmonar/patologia , Linfócitos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Sepse/microbiologia , Baço/metabolismo , Timo/metabolismo
12.
Clin Exp Med ; 12(1): 31-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21607877

RESUMO

Upon CNS injury, adenosine-5'-triphosphate is released and acts on P2X7 receptors, which might influence many cytokines secretion from glial cells and, in turn, affects the survival of neurons. Propofol, an intravenous anesthetic, has been shown to provide neuroprotective effect. However, the effect of propofol on astrocyte-associated processes remains to be clarified. In this study, we investigated the effects of propofol on P2X7 activity in astrocytes and tumor necrosis factor-α (TNF-α) secretion from these cells and thereby to infer the possible role(s) of glial P2X7 receptors in propofol neural protective effects. Whole-cell patch clamp results showed that in clinically relevant concentrations (3.3, 10 or 33 µM), propofol increased the P2X7 current amplitudes significantly and propofol in 10 µM extended the inactivation times of P2X7 receptors. Enzyme-linked immunosorbent assay showed that propofol increased the secretion of TNF-α from astrocytes in high concentration (300 µM), while inhibited in clinically relevant concentration (10 µM). Both of these effects were not influenced by Brilliant blue G. These results suggest that in clinically relevant concentrations, propofol increases the activity of P2X7 receptors in activated astrocytes, but this does not contribute to the downregulation of the secretion of TNF-α.


Assuntos
Astrócitos/efeitos dos fármacos , Propofol/farmacologia , Agonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Astrócitos/metabolismo , Células Cultivadas , Fenômenos Eletrofisiológicos , Ensaio de Imunoadsorção Enzimática , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Técnicas de Patch-Clamp , Ratos , Receptores Purinérgicos P2X7/metabolismo , Corantes de Rosanilina/metabolismo , Corantes de Rosanilina/farmacologia , Fatores de Tempo
13.
World J Gastroenterol ; 17(30): 3538-43, 2011 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-21941422

RESUMO

AIM: To investigate the efficacy and safety of propofol sedation for endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Databases including PubMed, Embase, and the Cochrane Central Register of Controlled Trials updated as of October 2010 were searched. Main outcome measures were ERCP procedure duration, recovery time, incidence of hypotension and hypoxia. RESULTS: Six trials with a total of 663 patients were included. The pooled mean difference in ERCP procedure duration between the propofol and traditional sedative agents was -8.05 (95% CI: -16.74 to 0.63), with no significant difference between the groups. The pooled mean difference in the recovery time was -18.69 (95% CI: -25.44 to -11.93), which showed a significant reduction with use of propofol sedation. Compared with traditional sedative agents, the pooled OR with propofol sedation for ERCP causing hypotension or hypoxia was 1.69 (95% CI: 0.82-3.50) and 0.90 (95% CI: 0.55-1.49), respectively, which indicated no significant difference between the groups. CONCLUSION: Propofol sedation during ERCP leads to shorter recovery time without an increase of cardiopulmonary side effects. Propofol sedation can provide adequate sedation during ERCP.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Hipnóticos e Sedativos , Propofol , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Humanos
14.
J Surg Res ; 167(2): e339-44, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21392793

RESUMO

BACKGROUND: Recently it has been demonstrated that hydrogen, as a novel antioxidant, can selectively reduce hydroxyl radicals (·OH) and peroxynitrite anion (ONOO-) in vitro and exert therapeutic antioxidant activity in many diseases. This study was designed to investigate the effect of hydrogen-rich saline on renal ischemia/reperfusion (I/R) injury in rats. METHODS: A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. Physiologic saline, hydrogen-rich saline, or nitrogen-rich saline (8 mL/kg) were administered intraperitoneally at 5 min before reperfusion, respectively. RESULTS: After I/R injury, serum blood urea nitrogen (BUN), creatinine (Cr), tissue malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OhdG), TNF-α, IL-1ß, IL-6 levels, and myeloperoxidase (MPO) activity were all increased significantly, while tissue superoxide dismutase (SOD) and catalase (CAT) activities were all decreased significantly. Hydrogen-rich saline reversed these changes and relieved morphological renal injury and I/R-induced apoptosis, while no significant changes were observed in the nitrogen-rich saline-treated group compared with physiologic saline-treated group. CONCLUSIONS: Hydrogen-rich saline is able to attenuate the renal I/R injury, which is possibly by reduction of oxidative stress and inflammation.


Assuntos
Hidrogênio/uso terapêutico , Rim/irrigação sanguínea , Rim/fisiopatologia , Traumatismo por Reperfusão/prevenção & controle , Cloreto de Sódio/uso terapêutico , Animais , Citocinas/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animais de Doenças , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/fisiopatologia
15.
NMR Biomed ; 22(6): 601-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19322815

RESUMO

This study proposes an NMR-based metabonomic approach to early prognostic evaluation of sepsis. Forty septic rats receiving cecal ligation and puncture (CLP) were divided into the surviving group and nonsurviving group on day 6, while 20 sham-operated rats served as the control group. Serum samples were collected from septic and sham-operated rats at 12 h after surgery and analyzed using (1)H NMR spectroscopy. Orthogonal partial least squares (OPLS) were applied and showed clustering according to predefined groups, indicating that NMR-based metabolic profiling could reveal pathologic characteristics in the serum of sham-operated, surviving, and nonsurviving septic rats. In addition, six characteristic metabolites including lactate, alanine, acetate, acetoacetate, hydroxybutyrate, and formate, which are mainly involved in energy metabolism, changed markedly in septic rats, especially in the nonsurvivors. Using these metabolites, a predictive model for prognostic evaluation of sepsis was constructed using a radial basis function neural network (RBFNN) with a prediction accuracy of about 87% by test samples. The results indicated that the NMR-based metabonomic approach is a potential technique for the early prognostic evaluation of sepsis.


Assuntos
Metabolômica/métodos , Ressonância Magnética Nuclear Biomolecular , Sepse , Animais , Humanos , Masculino , Prognóstico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Sepse/diagnóstico , Sepse/metabolismo , Sepse/fisiopatologia , Soro/química , Soro/metabolismo , Taxa de Sobrevida
16.
Zhong Xi Yi Jie He Xue Bao ; 7(2): 130-4, 2009 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-19216855

RESUMO

OBJECTIVE: To study the effects of salidroside-pretreatment on changes of neuroethology in rats with global cerebral ischemia-reperfusion injury so as to investigate its probable mechanism. METHODS: Sixty SD male rats were randomly divided into sham-operated group, untreated group and salidroside-pretreated group. The rats in salidroside-pretreated group were intraperitoneally administered with salidroside for seven days. The dose of salidroside was 12 mg/(kg.d). Thirty minutes after the last administration, the acute global cerebral ischemia-reperfusion in rats of the untreated group and the salidroside-pretreated group was induced by using the modified Pulsinelli's 4-vessel occlusion method. Five rats in each group were killed to obtain their brains 24 hours after reperfusion. The water content in the right brain was measured by calculating the ratio of dry weight to wet weight of the right brain. Activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in hippocampus of the rats were measured. Then neurological severity scores (NSSs) of the other 15 rats in each group were observed respectively before and 6, 12, 24, 48 and 96 h after reperfusion. At the fifth day after reperfusion, the test of Morris water maze was carried out to examine the memories and learning abilities of the rats. RESULTS: The content of MDA, the activity of SOD, the NSS, the mean incubation period and the ratio of time in the second quadrant in the untreated group were significant different from those in the sham-operated group (P<0.05). Compared with the untreated group, the brain water content, the content of MDA and the NSS degraded, and the mean incubation period shortened in salidroside-pretreated group. The activity of SOD and the ratio of residence time in the second quadrant increased in salidroside-pretreated group as compared with the untreated group (P<0.05). CONCLUSION: Salidroside can reduce the degree of cerebral edema of rats with global cerebral ischemia-reperfusion injury, relieve the metabolism abnormity of free radical and improve the function of cognition.


Assuntos
Isquemia Encefálica/patologia , Glucosídeos/uso terapêutico , Precondicionamento Isquêmico/métodos , Aprendizagem em Labirinto/efeitos dos fármacos , Fenóis/uso terapêutico , Traumatismo por Reperfusão/patologia , Animais , Encéfalo/metabolismo , Isquemia Encefálica/psicologia , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/psicologia , Superóxido Dismutase/metabolismo
17.
Sheng Li Xue Bao ; 61(1): 72-8, 2009 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-19224057

RESUMO

The purpose of this study was to establish a model of trigeminal neuralgia (TN) through an approach from lower edge of cheekbone and to observe the functional changes in the voltage-gated potassium currents in the cultured trigeminal ganglion (TG) neurons. Thirty Sprague-Dawley male rats were divided into two groups, the sham-operated (sham) group and the operated group. The TN model was carried out by using a chronic constriction injury of the infraorbital nerve (ION-CCI) from lower edge of cheekbone. Peripheral pain threshold test and whole-cell patch clamp recording were used to determine the difference between sham and ION-CCI rats. The withdrawal threshold of whisker pad in operated side of ION-CCI rat was decreased significantly from 6 d after operation and then maintained until 21 d, with the lowest on the 15th day. The threshold of whisker pad in non-operated side of operated rats was also decreased significantly compared with that in the sham group. Delayed rectifier potassium current (I(K)) in cultured ION-CCI TG neurons was decreased significantly compared with that in the sham group. Transient outward potassium currents (I(A)) in both operated and non-operated sides of TG neurons from ION-CCI rats were also reduced significantly compared with that in the sham group. The present study provided a new method of ION-CCI. In this model, the decrease of I(A) and I(K) might contribute, at least in part, to the decrease in mechanical pain threshold of whisker pad and the subsequent hyperalgia.


Assuntos
Canais de Potássio/metabolismo , Gânglio Trigeminal/metabolismo , Neuralgia do Trigêmeo/fisiopatologia , Animais , Células Cultivadas , Constrição , Modelos Animais de Doenças , Hiperalgesia , Masculino , Limiar da Dor , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Vibrissas
18.
J Infect ; 56(6): 474-81, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18471887

RESUMO

OBJECTIVES: Early prognostic evaluation of sepsis is an attractive strategy to decrease the mortality of septic patients, but presently there are no satisfactory approaches. Our goal is to establish an early, rapid and efficient approach for prognostic evaluation of sepsis. METHODS: Forty-five septic rats, induced by cecal ligation and puncture, were divided into surviving (n=23) and nonsurviving group (n=22) on day 6. Serum samples were obtained from septic and sham-operated rats (n=25) at 12h after surgery. HPLC/MS assays were performed to acquire serum metabolic profiles, and radial basis function neural network (RBFNN) was employed to build predictive model for prognostic evaluation of sepsis. RESULTS: Principle component analysis allows a clear discrimination of the pathologic characteristics among rats from surviving, nonsurviving and sham-operated groups. Six metabolites related to the outcome of septic rats were then structurally identified, which included linolenic acid, linoleic acid, oleic acid, stearic acid, docosahexaenoic acid and docosapentaenoic acid. A RBFNN model was built upon the metabolic profile data from rat serum, and a high predictive accuracy over 94% was achieved. CONCLUSIONS: HPLC/MS-based metabonomic approach combined with pattern recognition permits accurate outcome prediction of septic rats in the early stage. The proposed approach has advantages of rapid, low-cost and efficiency, and is expected to be applied in clinical prognostic evaluation of septic patients.


Assuntos
Metabolismo/fisiologia , Sepse/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Espectrometria de Massas , Análise de Componente Principal , Prognóstico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sepse/sangue , Organismos Livres de Patógenos Específicos
20.
Chin J Traumatol ; 10(4): 200-5, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17651588

RESUMO

OBJECTIVE: To assess the incidence, etiology, physiological and clinical features, mortality, and predictors of acute respiratory distress syndrome (ARDS) in intensive care unit (ICU). METHODS: A retrospective analysis of 5 314 patients admitted to the ICU of our hospital from April 1994 to December 2003 was performed in this study. The ARDS patients were identified with the criteria of the American-European Consensus Conference (AECC). Acute physiology and chronic health evaluation III (APACHE III), multiple organ dysfunction syndrome score (MODS score), and lung injury score (LIS) were determined on the onset day of ARDS for all the patients. Other recorded variables included age, sex, biochemical indicators, blood gas analysis, length of stay in ICU, length of ventilation, presence or absence of tracheostomy, ventilation variables, elective operation or emergency operation. RESULTS: Totally, 131 patients (2.5%) developed ARDS, among whom, 12 patients were excluded from this study because they died within 24 hours and other 4 patients were also excluded for their incomplete information. Therefore, there were only 115 cases (62 males and 53 females, aged 22-75 years, 58 years on average) left, accounting for 2.2% of the total admitted patients. Their average ICU stay was (11.27+/-7.24) days and APACHE III score was 17.23+/-7.21. Pneumonia and sepsis were the main cause of ARDS. The non-survivors were obviously older and showed significant difference in the ICU length of stay and length of ventilation as compared with the survivors. On admission, the non-survivors had significantly higher MODS and lower BE (base excess). The hospital mortality was 55.7%. The main cause of death was multiple organ failure. Predictors of death at the onset of ARDS were advanced age, MODS > or = to 8, and LIS > or = 2.76. CONCLUSIONS: ARDS is a frequent syndrome in this cohort. Sepsis and pneumonia are the most common risk factors. The main cause of death is multiple organ failure. The mortality is high but similar to most recent series including severe comorbidities. Based on this patient population, advanced age, MODS score, and LIS may be the important prognostic indicators for ARDS.


Assuntos
Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Estudos Retrospectivos
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