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1.
Medicine (Baltimore) ; 98(51): e18311, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860981

RESUMO

BACKGROUND: Studies have shown the efficacy of norepinephrine in the treatment of maternal hypotension during cesarean section by comparing it to treatment with phenylephrine. However, few studies have compared the efficacy of norepinephrine to ephedrine. METHODS: Ninety-seven women undergoing elective cesarean section were administered norepinephrine at 4 µg/minute (group N; n = 48) or ephedrine at 4 mg/minute (group E; n = 49) immediately postspinal anesthesia, with an on-off titration to maintain systolic blood pressure (SBP) at 80% to 120% of baseline. A rescue bolus of 8 µg norepinephrine was given whenever SBP reached the predefined lower limit. Our primary outcome was the incidence of tachycardia. Secondary outcomes included the incidence of bradycardia, hypertension, hypotension, severe hypotension, hypotensive episodes, number of rescue top-ups, hemodynamic performance error including median performance error (MDPE), and median absolute performance error (MDAPE). Neonatal Apgar scores and umbilical arterial (UA) blood gas data were also collected. RESULTS: Women in group N experienced fewer cases of tachycardia (4.2% vs 30.6%, P = .002, odds ratio: 0.11 [95% confidence interval, CI: 0.02-0.47]), a lower standardized heart rate (HR) (70.3 ±â€Š11 vs 75 ±â€Š11, P = .04, difference: 4.7 ±â€Š2.2 [95% CI: 0.24-9.1]), and a lower MDPE for HR (1.3 ±â€Š9.6 vs 8.4 ±â€Š13.5 bpm, P = .003, difference: 3.1 ±â€Š1.8 [95% CI: -0.6-6.7]). In addition, the lowest or the highest HR was lower in group N compared to group E (both P < .05). Meanwhile, the standardized SBP in group N was lower than that in group E (P = .04). For neonates, the UA blood gas showed a higher base excess (BE) and a lower lactate level in group N compared to E (both P < .001). Other hemodynamic variables, maternal, and neonatal outcomes were similar. CONCLUSION: Infusion of 4 µg/minute norepinephrine presented fewer cases of tachycardia, less fluctuation and a lower HR compared to baseline values, as well as a less stressed fetal status compared to ephedrine infusion at 4 mg/minute. In addition, norepinephrine infusion presented a lower standardized SBP compared to ephedrine.


Assuntos
Raquianestesia/métodos , Cesárea/efeitos adversos , Efedrina/uso terapêutico , Hipotensão/prevenção & controle , Norepinefrina/uso terapêutico , Adulto , Raquianestesia/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Cesárea/métodos , Método Duplo-Cego , Efedrina/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipotensão/etiologia , Infusões Intravenosas , Norepinefrina/administração & dosagem , Gravidez
2.
Psychopharmacology (Berl) ; 236(7): 1999-2014, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30798405

RESUMO

Patients suffering from neuropathic pain have a higher incidence of depression and cognitive decline. Although environment enrichment (EE) may be effective in the treatment of neuropathic pain, the precise mechanisms underlying its actions remain determined. The aim of the study was to examine the molecular mechanisms underlying the EE's beneficial effects in mice with neuropathic pain. EE attenuated the pain threshold reduction, depression-like phenotype, and memory deficit in mice after chronic constriction injury (CCI). Furthermore, EE attenuated decreased neurogenesis and increased inflammation in the hippocampus of mice with neuropathic pain after CCI. Moreover, the suppression of adult hippocampal neurogenesis by temozolomide antagonized the beneficial effects of EE on depression-like phenotype and cognitive deficit in the mice with neuropathic pain. In addition, lipopolysaccharide-induced increase in tumor necrosis factor-α (TNF-α) in the hippocampus antagonized the beneficial effects of EE for these behavioral abnormalities in mice with neuropathic pain. Knock-down of NPAS4 (neuronal PAS domain protein 4) in the hippocampus by lentivirus targeting NPAS4 blocked these beneficial effects of EE in the mice with neuropathic pain. These all findings suggest that hippocampal NPAS4 plays a key role in the beneficial effects of EE on the pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain. Therefore, it is likely that NPAS4 would be a new therapeutic target for perceptional, affective, and cognitive dimensions in patients with chronic pain.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Depressão/metabolismo , Meio Ambiente , Transtornos da Memória/metabolismo , Neuralgia/metabolismo , Limiar da Dor/fisiologia , Animais , Depressão/psicologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/psicologia , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Limiar da Dor/psicologia , Fenótipo , Temozolomida/farmacologia
3.
Neurosci Lett ; 694: 93-98, 2019 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-30496785

RESUMO

Nerve injury can induce memory impairment in mice. The aim of this research is to study the effect of environmental enrichment (EE) on long-term memory impairment in nerve-injured mice and the underlying mechanisms. Adult male C57BL/6 mice were received sham or chronic constriction injury (CCI) operation and reared in a standard environment (SE) or EE for 4 weeks after the operation. The pain threshold, long-term memory, expression of brain-derived neurotrophic factor (BDNF) and synaptic plasticity in hippocampus were determined. The results showed that CCI can induce the reduction in the mechanical and thermal pain thresholds, which were accompanied by long-term memory deficits in mice. CCI also induced the reduction of BDNF expression and synaptic plasticity impairments in the hippocampus, as represented by the dendritic spine density and postsynaptic density protein (PSD)-95 reduction, and long-term potential (LTP) dysfunction. Notably, EE can ameliorate the pain threshold and BDNF reduction, long-term memory deficits, and synaptic plasticity impairments in nerve-injured mice. However, the tropomyosin receptor kinase (Trk) B antagonist, ANA-12, blocked the EE-induced improvement in the long-term memory and synaptic plasticity impairment in nerve-injured mice. In conclusion, EE improved the pain threshold reduction, long-term memory and synaptic plasticity deficits in nerve-injured mice; BDNF / Trk B signaling may contribute to the relief of long-term memory and synaptic plasticity deficits induced by EE in nerve-injured mice.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Meio Ambiente , Potenciação de Longa Duração , Glicoproteínas de Membrana/metabolismo , Transtornos da Memória/fisiopatologia , Memória de Longo Prazo/fisiologia , Proteínas Tirosina Quinases/metabolismo , Nervo Isquiático/lesões , Animais , Constrição Patológica , Hipocampo/metabolismo , Masculino , Transtornos da Memória/etiologia , Camundongos Endogâmicos C57BL , Limiar da Dor , Transdução de Sinais
4.
J Cancer Res Ther ; 14(6): 1234-1238, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30488836

RESUMO

Background: Postoperative delirium is described as one of the most common complications for elderly patients with unknown pathophysiological pathways. In this present study, we analyzed the clinical and biochemical parameters in elderly patients with or without a delirium after open abdominal surgery to investigate the possible predicative factors for a delirium. Materials and Methods: Patients aged ≥60 years scheduled to undergo elective gastrointestinal tumor resection via laparotomy from July 2012 to June 2015 were enrolled in this study. Demographic and clinical data, characteristics of the surgical and anesthetic procedure, biochemical parameters were compared between patients with or without a delirium. Multivariate logistic regression testing was used for the evaluation of independent risk factors for postoperative delirium. Results: Overall, 112 participants were enrolled in this study, 49 of which were diagnosed with postoperative delirium. Patients with a delirium had an older age (P = 0.013) and a lower Mini-Mental State Examination (MMSE) score (P < 0.01) compared with those patients who had no delirium. The duration of surgery and anesthesia, the levels of neopterin, C-reactive protein, interleukin-6, insulin-like growth factor-1 in patients with a delirium were significantly higher than those without a delirium (P < 0.05). Independent risk factors in the logistic regression for postoperative delirium were the levels of neopterin and MMSE scores. Conclusions: Our present study suggested the potential roles of neopterin and MMSE scores in the pathophysiology and prediction of delirium in elderly patients after open abdominal surgery.


Assuntos
Biomarcadores/sangue , Delírio/sangue , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Neoplasias Gastrointestinais/cirurgia , Neopterina/sangue , Complicações Pós-Operatórias , Idoso , Proteína C-Reativa/análise , Estudos de Casos e Controles , Delírio/diagnóstico , Delírio/etiologia , Feminino , Seguimentos , Humanos , Fator de Crescimento Insulin-Like I/análise , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Testes Psicológicos , Fatores de Risco
5.
Inflammation ; 40(2): 387-400, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27913953

RESUMO

Sepsis-associated encephalopathy (SAE) is a common complication associated with poor prognosis in septic patients, but the underlying mechanism remains unclear. We hypothesized that disturbed neuregulin 1 (NRG1)-ErbB4 signaling in the parvalbumin interneurons was involved in sepsis-induced cognitive impairment in a mouse model of SAE. The SAE model was induced by cecal ligation/perforation (CLP). Animals were randomly divided into the following six groups: sham + vehicle group, sham + NRG1 group, CLP + vehicle group, CLP + NRG1 group, CLP + NRG1 + AG1478 (ErbB4 inhibitor) group, and CLP + minocycline group. Behavioral tests and in vivo electrophysiology were performed at the indicated time points. The brain tissues were harvested to determine the levels of hippocampcal cytokines, IBA1-positive cells, NRG1, ErbB4, and parvalbumin. In the present study, sepsis induced the anxiety-like behavior and hippocampal-dependent cognitive impairment, as reflected by significantly increased distance spent in the open field test and decreased freezing time to context in the fear conditioning test. The abnormal behavioral changes co-occurred with significant increases in hippocampal IBA1-positive cells, IL-1ß and IL-6 levels, and decreased NRG1, ErbB4, parvalbumin expressions, and evoked gamma activity. NRG1 treatment attenuated the sepsis-induced cognitive impairment and the associated biochemical markers, which were abolished by AG1478 administration. Notably, minocycline treatment attenuated neuroinflammation and mimicked the beneficial effects of NRG1 treatment. In summary, we provided additional evidence that the disruption of NRG1-ErbB4 signaling in the parvalbumin interneurons mediated by neuroinflammation might lead to abnormal gamma oscillations and thus contribute to cognitive impairment in a mouse model of SAE.


Assuntos
Encefalite/patologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Neuregulina-1/metabolismo , Receptor ErbB-4/metabolismo , Encefalopatia Associada a Sepse/fisiopatologia , Animais , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Modelos Animais de Doenças , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Ritmo Gama , Hipocampo/química , Interneurônios/metabolismo , Camundongos , Parvalbuminas , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Receptor ErbB-4/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Tirfostinas/farmacologia , Tirfostinas/uso terapêutico
6.
J Neuroinflammation ; 12: 182, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26416717

RESUMO

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction caused by many pathological events, including neuroinflammation and oxidative stress damage. Increasing evidence suggests that parvalbumin (PV) interneurons play a key role in the cognitive process, whereas the dysfunction of these interneurons has been implicated in a number of major psychiatric disorders. Here, we aimed to investigate whether enhanced inflammation and oxidative stress-mediated PV interneuron phenotype loss plays a role in sepsis-induced cognitive impairments. METHODS: Male C57BL/6 mice were subjected to cecal ligation and puncture or sham operation. For the interventional study, the animals were chronically treated with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin, at 5 mg/kg. The mice were euthanized at the indicated time points, and the brain tissues were harvested for determination of the PV, membrane subunit of NADPH oxidase gp91(phox), and markers of oxidative stress (4-hydroxynonenal and malondialdehyde) and inflammation (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10). A separate cohort of animals was used to evaluate the behavioral alterations by the open field and fear conditioning tests. Primary hippocampal neuronal cultures were used to investigate the mechanisms underlying the dysfunction of PV interneurons. RESULTS: Sepsis resulted in cognitive impairments, which was accompanied by selective phenotype loss of PV interneurons and increased gp91(phox), 4-hydroxynonenal, malondialdehyde, IL-1ß, and IL-6 expressions. Notably, these abnormalities could be rescued by apocynin treatment. CONCLUSION: Selective phenotype loss of PV interneurons, as a result of NADPH oxidase 2 (Nox2) activation, might partly contribute to cognitive impairments in a mouse model of SAE.


Assuntos
Transtornos Cognitivos/etiologia , Interneurônios/metabolismo , Glicoproteínas de Membrana/metabolismo , NADPH Oxidases/metabolismo , Parvalbuminas/metabolismo , Sepse/complicações , Sepse/patologia , Acetofenonas/farmacologia , Acetofenonas/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Células Cultivadas , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Medo/psicologia , Hipocampo/citologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidase 2 , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sepse/tratamento farmacológico , Superóxido Dismutase/metabolismo
7.
Arch Gerontol Geriatr ; 59(1): 181-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24745810

RESUMO

Few studies have examined the association between perioperative blood transfusion and postoperative delirium (POD) in aged patients undergoing total hip replacement surgery. In this prospective study, 186 patients older than 65 years undergoing elective unilateral total hip replacement surgery were enrolled. Of those, 94 patients were randomly assigned to the restrictive strategy transfusion strategy group, in which red blood cells were transfused in order to maintain 10.0 g/dL>hemoglobin≧8.0 g/dL. Ninety-two patients were randomly assigned to the liberal transfusion strategy group, in which red blood cells were transfused in order to maintain hemoglobin≧10.0 g/dL. POD was diagnosed by confusion assessment method. The baseline characteristics of patients, the length of hospital stay, the incidence of POD, myocardial infarction, stroke, wound infection, pulmonary embolism, and the transfusion volume were recorded. No difference was observed in the baseline characteristics, the length of hospital stay, and the incidence of POD, myocardial infarction, stroke, wound infection, and pulmonary embolism between the two groups (P>0.05). The proportion of patients transfused with red blood cell and frozen plasma was decreased in the restrictive transfusion group compared with the liberal transfusion group (P<0.05). In conclusion, restrictive transfusion does not influence the incidence of POD but reduces blood transfusion. Thus, restrictive transfusion may serve as an effective and safe strategy for aged patients following total hip replacement.


Assuntos
Artroplastia de Quadril , Delírio/epidemiologia , Transfusão de Eritrócitos/métodos , Complicações Pós-Operatórias/epidemiologia , Idoso , Biomarcadores/sangue , Delírio/sangue , Procedimentos Cirúrgicos Eletivos , Feminino , Hemoglobinas/análise , Humanos , Incidência , Tempo de Internação/estatística & dados numéricos , Masculino , Complicações Pós-Operatórias/sangue , Estudos Prospectivos
8.
Int J Clin Pharmacol Ther ; 52(8): 669-75, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24755130

RESUMO

OBJECTIVE: Acute pain can lead to immune dysfunction, which can be partly ameliorated by successful pain management. Opioids, which are widely used for analgesia, can result in the deterioration of immune function. This study aimed to investigate the influence of morphine with or without flurbiprofen as post-operative analgesics on the immune systems of patients undergoing gastric cancer surgery. METHODS: 60 patients undergoing gastric cancer surgery were equally randomized into two groups. They received post-operative patient-controlled intravenous (IV) analgesia using morphine either with or without flurbiprofen. Visual analogue scale (VAS) scores, Bruggemann comfort scale (BCS) scores, morphine consumption, time of first flatus, incidence of nausea/vomiting, and T-lymphocyte subsets (CD3⁺, CD4⁺, and CD8⁺) and natural killer cells (CD3⁻CD16⁺CD56⁺) were evaluated. RESULTS: No significant difference was observed in the VAS scores, BCS scores, and nausea/vomiting incidence between groups. Less morphine was consumed and the time of first flatus was earlier in patients receiving morphine with flurbiprofen than morphine alone. The expression of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and CD3⁻CD16⁺CD56⁺ decreased at 2 hours after incision and, except for CD3⁻CD16⁺CD56⁺, returned to baseline at 120 hours after surgery. Moreover, the expression of CD3⁻CD16⁺CD56⁺ at 2 hours after incision and the expression of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and CD3⁻CD16⁺CD56⁺ at 24 hours after surgery were higher in patients receiving morphine with flurbiprofen than morphine alone. CONCLUSION: The combination of morphine and flurbiprofen ameliorates the immune depression in Tlymphocyte subsets and natural killer cells and provides a similar analgesic efficacy to morphine alone in patients undergoing gastric cancer surgery.


Assuntos
Flurbiprofeno/farmacologia , Morfina/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Analgesia Controlada pelo Paciente/efeitos adversos , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Método Duplo-Cego , Feminino , Flurbiprofeno/administração & dosagem , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Medição da Dor , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/patologia
9.
Neurochem Res ; 38(9): 1973-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23836292

RESUMO

Chemotherapic drugs may elicit acute or chronic peripheral neuropathies. Mirtazapine, as an antidepressant, is also used for the treatment of neuropathic pain. The current study aimed to investigate the effect of mirtazapine on the oxaliplatin-induced neuropathy in rats as well as the underlying mechanism. A neuropathy model was established in Sprague-Dawley rats by intraperitoneal (i.p.) injection of oxaliplatin 4 mg/kg twice a week for 4 weeks. The therapeutic potential of mirtazapine 10, 20, and 30 mg/kg/day per-orally for 28 consecutive days was evaluated. Subsequently, a dose of 1 mg/kg of WAY100635 i.p., a selective antagonist of 5-HT1A receptor, was preadministrated before mirtazapine 20 mg/kg/day per-orally in oxaliplatin-induced neuropathy. The behavioral tests and the expression of NMDA receptor subunit NR2B were determined. The results displayed that repeated administration of mirtazapine 20 or 30 mg/kg/day for 28 consecutive days significantly attenuated the mechanical allodynia and the up-regulation of spinal cord NR2B but not the cold hyperalgesia in rats with oxaliplatin-induced neuropathy, which was reversed by WAY100635 preadministration. Our findings suggest that oxaliplatin-induced mechanical allodynia is associated with spinal NR2B up-regulation, which may be attenuated by mirtazapine administration.


Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Mianserina/análogos & derivados , Compostos Organoplatínicos/uso terapêutico , Receptores de N-Metil-D-Aspartato/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Antidepressivos Tricíclicos/administração & dosagem , Hiperalgesia/induzido quimicamente , Mianserina/administração & dosagem , Mianserina/uso terapêutico , Mirtazapina , Oxaliplatina , Ratos , Ratos Sprague-Dawley , Coluna Vertebral/efeitos dos fármacos
10.
J Anesth ; 27(6): 942-4, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23666452

RESUMO

This study aimed to evaluate the relationship between plasma cortisol levels and the occurrence of postoperative cognitive dysfunction (POCD) in aged patients following hip fracture surgery. A total of 175 patients, aged 65 years or older, who were scheduled for hip fracture surgery with spinal anesthesia were enrolled. Perioperative plasma levels of cortisol and neurocognitive tests were determined at 1 day preoperatively and 7 days postoperatively. Seventy-seven patients completed both blood sample collections and neurocognitive tests. POCD occurred in 29.9 % of patients at 7 days postoperatively. POCD patients presented significantly higher cortisol levels compared with non-POCD patients (P < 0.05). Furthermore, plasma cortisol levels were negatively correlated with mini-mental state examination (MMSE) scores at 7 days postoperatively (P < 0.0001). A specificity of 93 % and a sensitivity of 35 % were identified for the plasma cortisol measurement to discriminate POCD patients from non-POCD patients. The results suggest higher plasma cortisol levels are associated with POCD in aged patients following hip fracture surgery with spinal anesthesia.


Assuntos
Transtornos Cognitivos/sangue , Fraturas do Quadril/sangue , Fraturas do Quadril/cirurgia , Hidrocortisona/sangue , Idoso , Raquianestesia/métodos , Transtornos Cognitivos/psicologia , Fraturas do Quadril/psicologia , Humanos , Testes Neuropsicológicos , Complicações Pós-Operatórias/sangue , Período Pós-Operatório
11.
Neurosci Lett ; 543: 130-5, 2013 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-23583338

RESUMO

Neuroimmune activation contributes to the generation and maintenance of neuropathic pain after peripheral nerve injury. Peroxisome proliferator activated receptor gamma (PPAR-γ) agonists have potential neuroprotection. The current study aimed to determine the effects of a PPAR-γ agonist pioglitazone on mechanical hyperalgesia and neuroimmune activation in a rat model of neuropathic pain induced by L5 spinal nerve transection (SNT). Thirty-two rats were equally randomized into 4 groups: sham operation with vehicle; L5 SNT with vehicle or pioglitazone; or L5 SNT with pioglitazone and a PPAR-γ antagonist GW9662. Pioglitazone or vehicle was administered 1h before operation and continued daily to day 14 after operation. The paw pressure threshold (PPT) was measured before operation and on days 3, 7, 14 after operation. Glial fibrillary acidic protein (GFAP) expression, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 levels, and nuclear factor-kappa B (NF-κB) activity in the lumbar spinal cord were determined on day 14 after operation. The results displayed pioglitazone improved the mechanical hyperalgesia, and attenuated the astrocyte and NF-κB activation and the inflammatory cytokine upregulation in nerve-injured rats, which might be reversed by GW9662. In conclusion, pioglitazone ameliorates the mechanical hyperalgesia induced by L5 SNT via inhibiting the spinal neuroimmune activation in rats, suggesting spinal PPAR-γ signaling pathway may be involved in the pathogenesis of mechanical hyperalgesia.


Assuntos
Proteína Glial Fibrilar Ácida/metabolismo , Neuralgia/tratamento farmacológico , Neuroimunomodulação , Fármacos Neuroprotetores/farmacologia , PPAR gama/agonistas , Medula Espinal/efeitos dos fármacos , Nervos Espinhais/lesões , Tiazolidinedionas/farmacologia , Animais , Citocinas/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Masculino , NF-kappa B/metabolismo , Neuralgia/imunologia , Neuralgia/fisiopatologia , Fármacos Neuroprotetores/uso terapêutico , Limiar da Dor , Pioglitazona , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Medula Espinal/imunologia , Medula Espinal/metabolismo , Tiazolidinedionas/uso terapêutico , Tato
14.
Curr Ther Res Clin Exp ; 69(6): 480-7, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24692822

RESUMO

BACKGROUND: Fentanyl congeners have been found to induce cough during induction of general anesthesia. Studies of fentanyl and sufentanil have found incidence rates of 28% to 65% and 15%, respectively. However, no study has assessed the occurrence of cough induced by remifentanil. OBJECTIVE: The aim of this study was to assess the effect of equivalent doses of fentanyl, sufentanil, and remifentanil on cough. METHODS: Patients rated American Society of Anesthesiologists class I or II of either sex, aged 18 to 60 years, who were scheduled for elective abdominal surgery with general anesthesia were randomly and equally assigned to 3 groups using a computer-generated table of random numbers. The patients received equivalent doses of fentanyl 2 µg/kg, sufentanil 0.2 µg/kg, or remifentanil 2 µg/kg via IV push. Vital signs (systolic blood pressure [SBP], heart rate [HR], and oxygen saturation via pulse oximetry [SpO2]) and the occurrence and severity of cough were recorded for 2 minutes after drug administration by an anesthesiologist who was blinded to the drug treatment. The severity of cough was graded as none (0), mild (1-2), moderate (3-5), or severe (>5). RESULTS: A total of 315 Chinese patients (197 women, 118 men; mean [SD] age, 37.9 [10.4] years) were approached for enrollment and assigned to 3 groups of 105 patients each; all patients completed the study protocol. The 3 treatment groups were similar in terms of demographic characteristics and type of abdominal surgery. The incidence of cough was significantly greater in the remifentanil group (57 [54.3%] patients) than in the fentanyl group (35 [33.3%]; P < 0.01) or the sufentanil group (32 [30.5%]; P < 0.01). The severity of cough was significantly greater in the remifentanil group (severe, moderate, mild, none: 24, 7, 26, 48) than in the fentanyl (7, 9, 19, 70; P < 0.01) or sufentanil group (4, 2, 26, 73; P < 0.01). In all 3 groups, when the patients coughed, significant increases were observed in their SBP (128 [12]-139 [16] mm Hg; P < 0.01) and HR (74 [10]-87 [16] beats/min; P < 0.01). Within 2 minutes after drug administration, 62 patients (59%) in the remifentanil group experienced hypoxemia (SpO2 <90%) necessitating manually assisted mask ventilation, while no patients experienced hypoxemia in the fentanyl or sufentanil group. Three patients (2.9%) in the remifentanil group experienced muscle rigidity and deterioration of SBP, HR, and SpO2. No other adverse events were recorded. Cunclusion: Remifentanil was associated with a significantly greater incidence and severity of cough than equivalent doses of fentanyl or sufentanil. Fentanyl and sufentanil appeared comparable in these Chinese patients undergoing abdominal surgery.

15.
Cytokine ; 40(2): 151-6, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17942318

RESUMO

AIM: To explore whether propofol could in vivo, suppress intestinal permeability and proinflammatory cytokines in the intestine after traumatic brain injury (TBI). METHODS: The rats were randomly divided into four groups including control group with right parietal bone window alone and no brain injury, TBI group, TBI+propofol (5mg/kg/h), and propofol alone group. All animals were killed 72h later. Plasma endotoxin was assayed by the chromogenic limulus amebocyte lysate test. Intestinal permeability was quantified using the lactulose/mannitol (L/M) test. TNF-alpha and IL-6 in the intestine were measured using commercially available enzyme-linked immunoassay Kits. Nuclear factor kappa B (NF-kappaB) was analyzed by Electrophoretic mobility shift assay (EMSA). RESULTS: No rats died before sacrifice. Plasma endotoxin, L/M ratio, intestinal level of NF-kappaB, TNF-alpha, and IL-6 remained at baseline level in controlled animals. TBI promoted a significant increment in plasma endotoxin, L/M ratio, intestinal level of NF-kappaB, TNF-alpha, and IL-6. Propofol inhibited those parameters at the dose of 5mg/kg/h. CONCLUSION: Propofol has the protective effect on the intestine following traumatic brain injury in rats.


Assuntos
Lesões Encefálicas/metabolismo , Endotoxinas/sangue , Hipnóticos e Sedativos/farmacologia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Propofol/farmacologia , Animais , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/patologia , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-6/biossíntese , Mucosa Intestinal/patologia , Masculino , NF-kappa B/biossíntese , Permeabilidade/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/biossíntese
16.
J Neurosurg Anesthesiol ; 19(1): 31-7, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17198098

RESUMO

Epinephrine-containing lidocaine solution is commonly infiltrated on the scalp before craniotomy. But the hemodynamic changes caused by epinephrine-containing lidocaine solution have been less intensely studied. A prospective randomized double blind control study was designed to observe hemodynamic changes caused by epinephrine-containing lidocaine solution in neurosurgical operations under general anesthesia. One hundred twenty patients undergoing scheduled craniotomy were allocated randomly to 4 groups. All the patients received 1% lidocaine 16 mL with different dose (concentration) epinephrine: group 1 with 40 microg (2.5 microg/mL); group 2 with 80 microg (5 microg/mL); group 3 with 160 microg (10 microg/mL); and group 4 (control group) without epinephrine. mean arterial pressure (MAP) and heart rate were recorded at 30-second interval in 5 minutes after the beginning of local infiltration. In group 1, group 2, and group 3, the lowest MAP and the highest MAP during this period also were recorded. Bleeding was assessed after raising the craniotomy flap. Compared with the baseline, significant hemodynamic changes, particularly decrease in MAP with increase in heart rate at 1.5 minutes after the beginning of local infiltration, were observed in group 1, group 2, and group 3 (P<0.001), but not in group 4. The highest MAP increased significantly compared with the baseline in group 3 (P<0.05), but not in group 1 or group 2. Epinephrine-containing lidocaine solution reduced bleeding significantly (P<0.01). Infiltration with epinephrine-containing lidocaine solution elicits temporary but significant hemodynamic changes including hypotension before craniotomy. Commonly clinically used concentrations of epinephrine (2.5 to 10 microg/mL) can reduce the bleeding on the scalp.


Assuntos
Anestesia Local , Anestésicos Locais/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Craniotomia , Frequência Cardíaca/efeitos dos fármacos , Hipotensão/induzido quimicamente , Lidocaína/efeitos adversos , Adolescente , Adulto , Anestesia Geral , Anestesia Intravenosa , Anestésicos Locais/administração & dosagem , Dióxido de Carbono/sangue , Eletroencefalografia/efeitos dos fármacos , Epinefrina/efeitos adversos , Feminino , Hemorragia/epidemiologia , Humanos , Hipotensão/fisiopatologia , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vasoconstritores/efeitos adversos
17.
Indian J Med Res ; 124(3): 343-54, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17085838

RESUMO

BACKGROUND & OBJECTIVES: Erythropoietin (EPO), originally identified for its critical hormonal role in promoting erythrocyte survival and differentiation, has shown to a protective effect in myocardial ischaemia-reperfusion (I-R) injury in animal model. However, the precise mechanisms remain unclear. The objective of this study was to determine the roles of nuclear factor-kappa B (NF-kB) and associated cytokines induced by I-R in the cardioprotection by recombinant human erythropoietin (rhEPO). Morphopathological observations were also made on the ultrastructure of myocardial tissue. METHODS: Myocardial I-R rat model was established by 30 min ligation of left descending coronary and 3 h reperfusion. RhEPO or saline solution was intraperitoneally injected 24 h before I-R insult. The infarct sizes were measured by triphenyltetrazolium chloride (TTC)-Evans blue technique and ultrastructural organizations were observed by a transmission electron microscope. Tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-10 concentrations were analyzed by enzyme-linked immunosorbance assays and NF-kB by electrophoretic mobility shift assay. TNF-alpha and IL-6 mRNA expression were studied by the reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: A single bolus injection of 5,000 units/kg of rhEPO 24 h before insult remarkably reduced infarct size and improved ultrastructural organization of I-R myocardium. It greatly suppressed TNF-alpha and IL-6 expression, but enhanced IL-10 production. It modestly activated NF-kB before I-R insult and markedly attenuated subsequent NF-kB activation during sustained I-R. INTERPRETATION & CONCLUSION: The suppression of proinflammatory cytokines expression may act by inhibiting NF-kB activation during I-R, but not by induction of IL-10. This might be one of the molecular mechanisms of rhEPO in cardioprotection. In addition, NF-kB was suggested to play a dual role in cardioprotective effects of rhEPO.


Assuntos
Citocinas/metabolismo , Eritropoetina/farmacologia , Precondicionamento Isquêmico Miocárdico/métodos , Traumatismo por Reperfusão Miocárdica/metabolismo , NF-kappa B/metabolismo , Análise de Variância , Animais , Primers do DNA , Ensaio de Desvio de Mobilidade Eletroforética , Ensaio de Imunoadsorção Enzimática , Eritropoetina/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Miocárdio/ultraestrutura , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
J Pharm Pharm Sci ; 9(2): 190-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16959188

RESUMO

PURPOSE: Local infiltration of epinephrine-containing local anesthetics is widely used in clinics particularly in the procedure of surgeries on vascularity field to provide good analgesia and hemostasis. A prospective randomized double blind control study was designed to observe hemodynamic changes caused by local infiltration of epinephrine- containing lidocaine solution on nasal field under general anesthesia. METHODS: 90 adult patients undergoing elective functional endoscopic sinus surgery under general anesthesia were randomly allocated into three groups and received 1% lidocaine 4 mL with different dose of epinephrine (group I 20 microg; group II 40 microg; and group III 0 microg) respectively. Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and acceleration index (ACI) were recorded through impedance-cardiography at every 45 seconds in 6 minutes after the beginning of local infiltration. RESULTS: Compared with the intra-group baseline, statistically significant hemodynamic changes particularly decrease in MAP with increase in HR at 1.5 minutes time point (P < 0.01), and decrease in SVRI and increase in CI, ACI at and from 1.5 minutes time point (P > 0.05) were observed in group I and group II, but not in group III. CONCLUSION: Local infiltration of epinephrine-containing lidocaine solution on nasal field causes significant decrease in MAP and SVRI, and increase in HR, CI and ACI.


Assuntos
Cardiografia de Impedância/efeitos dos fármacos , Epinefrina/farmacologia , Hipotensão/induzido quimicamente , Vasoconstritores/farmacologia , Adolescente , Adulto , Anestesia Local , Anestésicos Locais , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Epinefrina/efeitos adversos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vasoconstritores/efeitos adversos
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