RESUMO
OBJECTIVES: To investigate the expression of microRNA-142 (miR-142) in children with autoimmune thyroid disease (AITD) and its relationship with the imbalance of helper T cell 17 (Th17) and regulatory T cell (Treg). METHODS: A total of 89 children hospitalized for AITD from January 2019 to December 2022 were prospectively selected as the study subjects, including 48 children with Graves' disease (GD group) and 41 children with Hashimoto's thyroiditis (HT group). Additionally, 55 healthy children undergoing physical examinations during the same period were selected as the control group. The differences in serum miR-142, antithyroglobulin antibody (TGAb), antithyroperoxidase antibody (TPOAb), Th17/Treg, and interleukin-17 (IL-17) expression were compared among the groups. RESULTS: The expression of miR-142, TPOAb, TGAb, Th17, Th17/Treg, and IL-17 in the GD group and HT group was higher than that in the control group, while Treg was lower than that in the control group (P<0.05). Pearson correlation analysis revealed that in the GD group, miR-142 was positively correlated with TPOAb, TGAb, Th17, Th17/Treg, and IL-17 (r=0.711, 0.728, 0.785, 0.716, 0.709, respectively; P<0.001) and negatively correlated with Treg (r=-0.725, P<0.001); in the HT group, miR-142 was positively correlated with TPOAb and TGAb (r=0.752, 0.717, respectively; P<0.001). CONCLUSIONS: miR-142 is highly expressed in children with AITD, and its expression may be related to the Th17/Treg imbalance in children with GD.
Assuntos
Interleucina-17 , MicroRNAs , Linfócitos T Reguladores , Células Th17 , Humanos , MicroRNAs/sangue , Células Th17/imunologia , Criança , Masculino , Feminino , Linfócitos T Reguladores/imunologia , Interleucina-17/sangue , Doença de Hashimoto/imunologia , Doença de Hashimoto/genética , Doença de Hashimoto/sangue , Pré-Escolar , Doença de Graves/imunologia , Doença de Graves/genética , Adolescente , Autoanticorpos/sangueRESUMO
BACKGROUND The guidelines recommend oral carbohydrates up to 2 hr before elective surgery. The objective of this study was to explore the safety and feasibility of preoperative carbohydrate drink in patients undergoing ambulatory surgery. MATERIAL AND METHODS Patients undergoing ambulatory surgery under general anesthesia were enrolled. They were fasted from midnight and randomly assigned to a study group (200 mL of a carbohydrate beverage) or the control group (pure water) and received the assigned drink 2 hr before surgery. Bedside ultrasonography was performed to monitor gastric emptying at T0 (before liquid intake), T1 (5 min after intake), T2 (1 hr after intake), and T3 (2 hr after intake). Subjective feelings of thirst, hunger, anxiety, and fatigue were assessed 1 hr after liquid intake using the visual analogue scale (VAS). RESULTS In both groups, gastric antrum cross-sectional area, gastric content volume, and weight-corrected gastric content volume increased at T1 and returned to baseline at T3. These parameters were significantly higher in the study group at T2 (6.28±1.38 vs. 4.98±0.78, 67.22±29.49 vs. 49.04±15.4, 1.10±0.51 vs. 0.85±0.37, P<0.05). Thirst and hunger VAS scores were reduced in both groups. The study group suffered significantly less hunger (28.44±10.41 vs. 36.03±14.42, P<0.05). Blood electrolytes (sodium, potassium, calcium) and glucose concentration levels were similar in both groups at T2. No gastric regurgitation or pulmonary aspiration was recorded. CONCLUSIONS Administration of 200 mL of oral carbohydrate beverage 2 hr before ambulatory surgery is safe, effective, and can be used for preoperative management of fasting patients.
Assuntos
Procedimentos Cirúrgicos Ambulatórios , Bebidas , Carboidratos da Dieta/administração & dosagem , Adulto , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Eletrólitos/sangue , Feminino , Esvaziamento Gástrico , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-OperatóriosRESUMO
BACKGROUND: Postoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol. METHODS: This multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint. RESULTS: The VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2 and T3. Adverse events and vital signs were similar for the two groups at each timepoint. CONCLUSIONS: Nalbuphine can provide effective and safe pain relief in patients after ambulatory surgery. TRIAL REGISTRATION: The registration number is ChiCTR-IOR-16010032 , the date of registration was 2016-11-28.
Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Analgésicos Opioides/administração & dosagem , Nalbufina/administração & dosagem , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Tramadol/administração & dosagem , Adulto , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Analgésicos Opioides/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nalbufina/efeitos adversos , Dor Pós-Operatória/diagnóstico , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Náusea e Vômito Pós-Operatórios/diagnóstico , Estudos Prospectivos , Tramadol/efeitos adversosRESUMO
Neuropathic pain is a type of chronic pain induced by either central or peripheral nerve injury. MicroRNAs have been recently linked to many diseases, including neuropathic pain. However, the role of miR-7a in neuropathic pain still remains elusive. Thus, we aim to investigate the effects of miR-7a on neuropathic pain based on the spinal nerve ligation rat model. After establishment of spinal nerve ligation rat models, rats were infected with adeno-associated virus-neurofilament light polypeptide, adeno-associated virus-miR-7a or treated with metformin. The paw withdrawal threshold and paw withdrawal latency were assessed afterward, and the expression of miR-7a and neurofilament light polypeptide as well as their interaction was determined. Subsequently, miR-7a was overexpressed or silenced in dorsal root ganglion cells to investigate the role of miR-7a in neuropathic pain. Furthermore, the regulatory effect of neurofilament light polypeptide on neuropathic pain was detected using plasmid overexpressing neurofilament light polypeptide. Spinal nerve ligation rat model exhibited upregulation of neurofilament light polypeptide but downregulation of miR-7a. In addition, neurofilament light polypeptide accumulation or miR-7a inhibition decreased paw withdrawal threshold and paw withdrawal latency. Then, neurofilament light polypeptide accumulation or miR-7a inhibition was observed to increase the phosphorylation level of signal transducer and activator of transcription. miR-7a was found to directly target neurofilament light polypeptide and downregulate neurofilament light polypeptide. In addition, inhibiting the signal transducer and activator of transcription signaling pathway was also revealed to increase paw withdrawal threshold and paw withdrawal latency. Collectively, our study demonstrated that miR-7a ameliorated neuropathic pain via blocking the signal transducer and activator of transcription signaling pathway by repressing neurofilament light polypeptide. These findings, if taken further, can be of important clinical significance in treating patients with neuropathic pain.
Assuntos
MicroRNAs/metabolismo , Neuralgia/genética , Proteínas de Neurofilamentos/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Nervos Espinhais/patologia , Animais , Sequência de Bases , Modelos Animais de Doenças , Regulação para Baixo/genética , Ligadura , Masculino , MicroRNAs/genética , Modelos Biológicos , Proteínas de Neurofilamentos/genética , Ratos Sprague-Dawley , Regulação para Cima/genéticaRESUMO
BACKGROUND: Perioperative anxiety is common in pediatric patients undergoing surgery. AIMS: The aim of this study was to determine whether an infusion of dexmedetomidine prior to hernia repair in children provides better postoperative anxiety outcomes that a preoperative infusion of midazolam. METHODS: Ninety 6-11-year-old children, who were scheduled to undergo elective hernia repair, were enrolled for this double-blind, randomized controlled trial. Group D (n = 45) received an intravenous infusion of dexmedetomidine (0.5 µg/kg) and Group M (n = 45) received an intravenous infusion of midazolam (0.08 mg/kg) in 20 mL of normal saline for 10 minutes before the induction of anesthesia. Pre- and postoperative scores on the modified Yale Preoperative Anxiety Scale were the main outcomes. Secondary outcomes included systolic blood pressure, diastolic blood pressure, heart rate, and postoperative pain measured on a visual analogue scale and patient satisfaction using a numerical rating scale. RESULTS: Postoperative anxiety in Group D was significantly lower than preoperative anxiety (2 hours postoperatively mean difference [95% CI]: 2.83 [0.87-4.79], P = 0.036, 4 hours postoperatively mean difference [95% CI]: 3.29 [1.39-5.20], P = 0.005). Preoperative and postoperative anxiety in Group M was similar. Anxiety scores in Group D were also significantly lower than anxiety in Group M 2 hours (mean difference [95% CI]: 1.89 [0.52-3.26], P = 0.01) and 4 hours (mean difference [95% CI]: 3.32 [1.98-4.66], P < 0.001) postoperatively. Systolic blood pressure, diastolic blood pressure and heart rate were lower in Group D than in Group M after administration of sedative drugs until children left PACU (SBP mean difference [95% CI]: 13.87 [10.30-17.43], P < 0.001, DBP mean difference [95% CI]: 5.96[3.80-8.11], P < 0.001, HR mean difference [95% CI]: 10.36 [7.58-13.13], P < 0.001). Pain was also significantly lower in Group D than in Group M at 2 hours (median difference [95% CI]: 1 [0.26-1.34], P = 0.004), 4 hours (median difference [95% CI]: 1 [0.31-1.02], P = 0.003), and 1 day (median difference [95% CI]: 0 [0.22-0.76], P = 0.003) postoperatively. Patient satisfaction scores were significantly higher in Group D than in Group M 1 day (median difference [95% CI]: 0 [-0.83 to -0.24], P = 0.006) and somewhat higher 1 week (median difference [95% CI]: 0 [-0.67 to -0.04], P = 0.06) postoperatively. CONCLUSION: Compared with midazolam, a single preoperative intravenous dose of dexmedetomidine appears to provide better postoperative anxiolytic effects for children undergoing same-day surgery.
Assuntos
Ansiedade/tratamento farmacológico , Dexmedetomidina/uso terapêutico , Herniorrafia , Hipnóticos e Sedativos/uso terapêutico , Midazolam/uso terapêutico , Pré-Medicação , Ansiolíticos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Criança , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Midazolam/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Medicação Pré-AnestésicaRESUMO
OBJECTIVES: To determine the role of neuroglobin in the pathology of sepsis-associated encephalopathy and ascertain if neuroglobin has any protective effects against sepsis-associated encephalopathy. DESIGN: Randomized laboratory animal study. SETTING: Research university animal laboratory. SUBJECTS: Two hundred and forty adult male Sprague-Dawley rats. INTERVENTIONS: Rats received cecal puncture and ligation (or sham) surgery to induce sepsis, then broken up into groups based on whether or not the rat developed sepsis-associated encephalopathy as determined by electroencephalograph and evoked potential recordings. The rats were then left untreated to examine the effect of sepsis-associated encephalopathy on neuroglobin, treated with a neuroglobin antisense nucleotide to block gene expression, or given hemin, a neuroglobin inducer. MEASUREMENTS AND MAIN RESULTS: Following sepsis induction, diagnosis, and treatment, the brains were analyzed for both gross and ultrastructural morphology. Also, neuronal neuroglobin immunoreactivity and apoptosis (via terminal uridine nucleotide end-labeling) were examined. Blood serum levels were then analyzed for neuroglobin, superoxide dismutase, and malondialdehyde levels. We determined that sepsis-associated encephalopathy induces damage evident when examining both gross and ultrastructural morphology, as well as induces neuronal neuroglobin expression. Also, blockade of neuroglobin expression via antisense treatment will exacerbate these pathological effects, while increasing neuroglobin levels via hemin will ameliorate them. Blood analysis found that levels of superoxide dismutase and malondialdehyde mirrored the level of pathology found in the brain, while plasma neuroglobin levels reflected the amount of neuronal neuroglobin immunoreactivity. CONCLUSIONS: We conclude that neuroglobin is involved in the pathogenesis of sepsis-associated encephalopathy and has neuroprotective effects. We also determined that hemin has protective effects against sepsis-associated encephalopathy as well, most probably due to its effect on neuroglobin.
Assuntos
Encefalopatias/etiologia , Globinas/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Sepse/complicações , Animais , Apoptose/fisiologia , Encéfalo/patologia , Encéfalo/ultraestrutura , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Modelos Animais de Doenças , Globinas/biossíntese , Masculino , Malondialdeído/sangue , Microscopia Eletrônica de Transmissão , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/sangue , Neuroglobina , Ratos , Ratos Sprague-Dawley , Sepse/patologia , Sepse/fisiopatologia , Superóxido Dismutase/sangueRESUMO
p300 and its homolog cyclic AMP response element binding protein (CBP) are coactivators that were identified to participate in many biological processes including neural development and cognition. Their roles within the rodent spinal cord have not been reported systematically; in this study, their spatiotemporal distribution in the spinal cord of adult rat following chronic constriction injury (CCI) was studied. p300 and CBP expressed predominantly in nuclei in the gray matter of rat spinal cord. Rats undergoing CCI surgery showed increased p300/CBP immunoreactivity (IR) compared with normal control and sham-operated rats. The number of IR cells reached the peak at day 14 following CCI compared with those on day 3, 7, and 21, accompanied with significant behavioral changes of neuropathic pain. Cell-type determination by immunofluorescence at day 14 following CCI revealed that p300 and CBP expressed in neurons, but not in astrocytes or microglial cells. These results suggest that p300 and CBP are probably involved in the maintenance of neuropathic pain on spinal cord level. Furthermore, p300 and CBP may serve as a sensor only in neurons but not in astrocytes or microglia cells in the adult rat spinal cord.
Assuntos
Envelhecimento/metabolismo , Proteína p300 Associada a E1A/metabolismo , Proteínas de Membrana/metabolismo , Fosfoproteínas/metabolismo , Células do Corno Posterior/metabolismo , Células do Corno Posterior/patologia , Animais , Comportamento Animal , Constrição , Imuno-Histoquímica , Masculino , Neuralgia/metabolismo , Neuralgia/patologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação , Fatores de TempoRESUMO
OBJECTIVE: In laryngeal microsurgery, the insertion of the suspension laryngoscope is a strong stimulus that may cause hemodynamic fluctuations and adverse cardiovascular events. The purpose of this study was to compare the effect of preemptive treatment with esketamine and sufentanil on maintaining hemodynamics and reducing the occurrence of adverse cardiovascular events during the insertion of suspension laryngoscope. METHODS: In this double-blind randomized controlled trial, patients undergoing general anesthesia for laryngeal microsurgery were randomly assigned (1:1) to esketamine 0.5 mg kg-1 (esketamine group) and sufentanyl 0.125 µg kg-1 (sufentanil group) before inserting the laryngoscope, respectively. RESULTS: During the insertion of suspension laryngoscope, the incidence of bradycardia (HR < 60 beats/min) was 39.3% (22/56) in esketamine group, lower than 60.0% (33/55) in sufentanil group (odds ratio [OR], 2.32 [95% CI, 1.11-5.08]; p = 0.029). The incidence of hypotension (MAP <65 mmHg) was 33.9% (19/56) in esketamine group, lower than 56.4% (31/55) in sufentanil group (odds ratio [OR], 2.52 [95% CI, 1.91-5.27]; p = 0.018). The frequency of hypotension in esketamine group was lower than that in sufentanil group (0.36 ± 0.52 vs. 0.56 ± 0.50, p = 0.035). The time-weighted average of HR dropping above 30% of baseline was smaller in esketamine group than in sufentanil group (0.52 ± 2.06 vs. 1.08 ± 2.77, p = 0.006). CONCLUSIONS: These findings showed that compared with preemptive treatment of sufentanil (0.125 µg kg-1 ), esketamine (0.5 mg kg-1 ) was effective in reducing the incidence of cardiovascular adverse events, including bradycardia and hypotension induced by the insertion of suspension laryngoscope during the laryngeal microsurgery. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3021-3027, 2023.
Assuntos
Hipotensão , Laringoscópios , Humanos , Sufentanil/efeitos adversos , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Método Duplo-CegoRESUMO
BACKGROUND: Neuropathic pain is detrimental to human health; however, its pathogenesis still remains largely unknown. Overexpression of pain-associated genes and increased nociceptive somato-sensitivity are well observed in neuropathic pain. The importance of epigenetic mechanisms in regulating the expression of pro- or anti-nociceptive genes has been revealed by studies recently, and we hypothesize that the transcriptional coactivator and the histone acetyltransferase E1A binding protein p300 (p300), as a part of the epigenetic mechanisms of gene regulation, may be involved in the pathogenesis of neuropathic pain induced by chronic constriction injury (CCI). To test this hypothesis, two different approaches were used in this study: (I) down-regulating p300 with specific small hairpin RNA (shRNA) and (II) chemical inhibition of p300 acetyltransferase activity by a small molecule inhibitor, C646. RESULTS: Using the CCI rat model, we found that the p300 expression was increased in the lumbar spinal cord on day 14 after CCI. The treatment with intrathecal p300 shRNA reversed CCI-induced mechanical allodynia and thermal hyperalgesia, and suppressed the expression of cyclooxygenase-2 (COX-2), a neuropathic pain-associated factor. Furthermore, C646, an inhibitor of p300 acetyltransferase, also attenuated mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord. CONCLUSIONS: The results suggest that, through its acetyltransferase activity in the spinal cord after CCI, p300 epigenetically plays an important role in neuropathic pain. Inhibiting p300, using interfering RNA or C646, may be a promising approach to the development of new neuropathic pain therapies.
Assuntos
Acetiltransferases/metabolismo , Dor Crônica/metabolismo , Epigenômica , Neuralgia/enzimologia , Neuralgia/genética , Acetiltransferases/genética , Animais , Dor Crônica/genética , Constrição Patológica , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição de p300-CBPRESUMO
There is an increasing body of evidence that a brief exposure to anesthesia induces ischemic tolerance in rat brain (anesthetic preconditioning). However, it is unknown whether preconditioning with sevoflurane, a commonly used volatile anesthetic in current clinical practice, produces a delayed window of neuroprotection against ischemia and what the mechanisms are for this protection. To address these issues, adult male Sprague-Dawley rats were subjected to middle cerebral arterial occlusion (MCAO) for 2 h. Sevoflurane preconditioning was induced 24 h before brain ischemia by exposing the animals to sevoflurane at 1.0 minimum alveolar concentration (2.4%) in oxygen for 60 min. Animals preconditioned with sevoflurane had lower neurological deficit scores and smaller brain infarct volumes than animals with brain ischemia at 6 and 24 h after MCAO, respectively. Application of a selective antagonist for mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel, 5-hydroxydecanoate (5-HD, 40 mg/kg i.p.) 30 min before sevoflurane exposure attenuated this beneficial effect. Moreover, protein kinase C ε (PKC ε) was translocated to the membrane fraction at 6 h, but not 24 h, after brain reperfusion in animals preconditioned with sevoflurane and this effect was also abolished by 5-HD. We concluded that sevoflurane preconditioning induces a delayed neuroprotection and that mitochondrial K(ATP) channels and PKC ε may be involved in this neuroprotection.
Assuntos
Ativação do Canal Iônico/efeitos dos fármacos , Éteres Metílicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Canais de Potássio/metabolismo , Proteína Quinase C-épsilon/metabolismo , Animais , Ativação Enzimática/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/enzimologia , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Precondicionamento Isquêmico , Masculino , Éteres Metílicos/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Oxigênio/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , SevofluranoRESUMO
BACKGROUND AND PURPOSE: The aim of this study was to investigate the association between daytime napping frequency and the incidence of essential hypertension or stroke as well as to validate causality in this relationship via Mendelian randomization (MR). METHODS: We conducted Cox regression analysis on 358 451 participants free of hypertension or stroke from UK Biobank. To validate the results of the observational analysis, we conducted a 2-sample MR for daytime napping frequency (123 single-nucleotide polymorphisms) with essential hypertension in FinnGen Biobank, stroke, and ischemic stroke in MEGASTROKE consortium and performed a corresponding 1-sample MR on the UK Biobank data. RESULTS: Compared with never napping, usually napping was associated with a higher risk of essential hypertension (hazard ratio, 1.12 [95% CI, 1.08-1.17]), stroke (hazard ratio, 1.24 [95% CI, 1.10-1.39], and ischemic stroke (hazard ratio, 1.20 [95% CI, 1.05-1.36]) in our prospective observational analysis. Both the 1-sample and 2-sample MR results indicated that increased daytime napping frequency was likely to be a potential causal risk factor for essential hypertension in FinnGEN (odds ratio, 1.43 [95% CI, 1.06-1.92]) and UK Biobank (odds ratio, 1.40 [95% CI, 1.28-1.58]). The 2-sample MR results supported the potential causal effect of nap frequency on ischemic stroke in MEGASTROKE (odds ratio, 1.29 [95% CI, 1.04-1.62]). CONCLUSIONS: Prospective observational and MR analyses provided evidence that increased daytime nap frequency may represent a potential causal risk factor for essential hypertension. The potential causal association of increased nap frequency with ischemic stroke was supported by 2-sample MR and prospective observational results.
Assuntos
Hipertensão , AVC Isquêmico , Acidente Vascular Cerebral , Hipertensão Essencial , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genéticaRESUMO
Background: With the development of fiberoptic bronchoscopy in the diagnosis and treatment of various pulmonary diseases, the anesthesia/sedation requirements are becoming more demanding, posing great challenges for patient safety while ensuring a smooth examination/surgery process. Remimazolam, a brand-new ultra-short-acting anesthetic, may compensate for the shortcomings of current anesthetic/sedation strategies in bronchoscopy. Methods: This study was a prospective, multicenter, randomized, double-blind, parallel positive controlled phase 3 clinical trial. Subjects were randomized to receive 0.2 mg/kg remimazolam besylate or 2 mg/kg propofol during bronchoscopy to evaluate the efficacy and safety of remimazolam. Results: A total of 154 subjects were successfully sedated in both the remimazolam group and the propofol group, with a success rate of 99.4% (95%CI of the adjusted difference -6.7 × 10%-6% to -5.1 × 10%-6%). The sedative effect of remimazolam was noninferior to that of propofol based on the prespecified noninferiority margin of -5%. Compared with the propofol group, the time of loss of consciousness in the remimazolam group (median 61 vs. 48s, p < 0.001), the time from the end of study drug administration to complete awakening (median 17.60 vs. 12.80 min, p < 0.001), the time from the end of bronchoscopy to complete awakening (median 11.00 vs. 7.00 min, p < 0.001), the time from the end of study drug administration to removal of monitoring (median 19.50 vs. 14.50 min, p < 0.001), and the time from the end of bronchoscopy to removal of monitoring (median 12.70 vs. 8.60 min, p < 0.001) were slightly longer. The incidence of Adverse Events in the remimazolam group and the propofol group (74.8% vs. 77.4%, p = 0.59) was not statistically significant, and none of them had Serious Adverse Events. The incidence of hypotension (13.5% vs. 29.7%, p < 0.001), hypotension requiring treatment (1.9% vs. 7.7%, p = 0.017), and injection pain (0.6% vs. 16.8%, p < 0.001) were significantly lower in the remimazolam group than in the propofol group. Conclusion: Moderate sedation with 0.2 mg/kg remimazolam besylate is effective and safe during bronchoscopy. The incidence of hypotension and injection pain was less than with propofol, but the time to loss of consciousness and recovery were slightly longer. Clinical Trial Registration: clinicaltrials.gov, ChiCTR2000039753.
RESUMO
BACKGROUND: Understanding the mechanism of trigeminal neuralgia may be elucidated by developing laboratory animal models that closely mimic the features of this specific type of neuropathic pain. We have developed an experimental animal model for trigeminal neuralgia using a technique of injecting cobra venom into the infraorbital nerve (ION) trunk. METHODS: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the ION trunk. Mechanical stimuli were applied to the ION territory in consecutive days after surgery. Mechanical thresholds were measured over a 90-day period on the bilateral facial region. Vascular permeability in the ION territory was measured using Evans blue dye. RESULTS: The cobra venom-treated rats developed mechanical allodynia 3 days after surgery that lasted for 60 days postoperatively at the ipsilateral side. The mechanical thresholds of the contralateral ION territory also showed a profound decrease but were sustained for only approximately 30 days. There was no change of mechanical thresholds in the control groups. The extravasation of Evans blue increased significantly in the skin after administration of cobra venom to the ION compared with control rats (P < 0.05). CONCLUSION: The cobra venom model may provide a reasonable model for investigating the mechanism of trigeminal neuropathic pain.
Assuntos
Modelos Animais de Doenças , Venenos Elapídicos , Hiperalgesia/induzido quimicamente , Órbita/inervação , Nervo Trigêmeo/fisiopatologia , Neuralgia do Trigêmeo/induzido quimicamente , Animais , Permeabilidade Capilar , Corantes/metabolismo , Azul Evans/metabolismo , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Órbita/irrigação sanguínea , Medição da Dor , Limiar da Dor , Ratos , Ratos Sprague-Dawley , Pele/irrigação sanguínea , Fatores de Tempo , Nervo Trigêmeo/metabolismo , Neuralgia do Trigêmeo/metabolismo , Neuralgia do Trigêmeo/fisiopatologiaRESUMO
OBJECTIVES: To describe patient characteristics associated with preoperative anxiety and subsequently assess the relationship between preoperative anxiety and postoperative anxiety, pain, sleep quality, nausea and vomiting. METHODS: The study collected data from patients undergoing elective operation from 12 hospitals in China. The State-Trait Anxiety Inventory (STAI) and the Athens Insomnia Scale (AIS) were used to assess anxiety and sleep quality before surgery. Evaluations of anxiety, pain, sleep quality, nausea and vomiting were quantified using the Visual Analogue Scale on postoperative days 1 and 2. RESULTS: Data from 997 patients were analyzed. Preoperatively, 258 (25.9%) patients had high anxiety (STAI-State>44). Multivariate analyses showed a significant relationship between high anxiety and female gender (OR: 1.66, 95% CI: 1.08-2.57, p = 0.02), highly invasive surgery (OR: 2.29, 95% CI: 1.29-4.06, p = 0.005), higher trait anxiety (OR: 1.24, 95% CI: 1.20-1.28, p < 0.001) and insomnia (AIS ≥ 6, OR: 1.79, 95% CI: 1.17-2.76, p = 0.008). Preoperative anxiety demonstrated a negative correlation with postoperative anxiety following highly invasive surgery; this became a positive relationship following less invasive surgery. Preoperative anxiety was also positively related to postoperative pain and poor sleep quality. The correlation between preoperative anxiety and postoperative nausea and vomiting was not statistically significant. CONCLUSION: Female gender, highly invasive surgery, higher trait anxiety and insomnia are independent risk factors for high preoperative anxiety. Surgical invasiveness influences association between pre- and postoperative anxiety. Higher preoperative anxiety is related to poorer sleep quality and more severe pain postoperatively.
Assuntos
Ansiedade , Distúrbios do Início e da Manutenção do Sono , Ansiedade/epidemiologia , Transtornos de Ansiedade , Feminino , Humanos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Período Pós-Operatório , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Inquéritos e QuestionáriosRESUMO
Certain microRNAs (miRNAs) can function as neuroprotective factors after reperfusion/ischemia brain injury. miRNA-142-3p can participate in the occurrence and development of tumors and myocardial ischemic injury by negatively regulating the activity of Rac1, but it remains unclear whether miRNA-142-3p also participates in cerebral ischemia/reperfusion injury. In this study, a model of oxygen-glucose deprivation/re-oxygenation in primary cortical neurons was established and the neurons were transfected with miR-142-3p agomirs or miR-142-3p antagomirs. miR-142-3p expression was down-regulated in neurons when exposed to oxygen-glucose deprivation/re-oxygenation. Over-expression of miR-142-3p using its agomir remarkably promoted cell death and apoptosis induced by oxygen-glucose deprivation/re-oxygenation and improved mitochondrial biogenesis and function, including the expression of peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor A, and nuclear respiratory factor 1. However, the opposite effects were produced if miR-142-3p was inhibited. Luciferase reporter assays verified that Rac Family Small GTPase 1 (Rac1) was a target gene of miR-142-3p. Over-expressed miR-142-3p inhibited NOX2 activity and expression of Rac1 and Rac1-GTPase (its activated form). miR-142-3p antagomirs had opposite effects after oxygen-glucose deprivation/re-oxygenation. Our results indicate that miR-142-3p down-regulates the expression and activation of Rac1, regulates mitochondrial biogenesis and function, and inhibits oxygen-glucose deprivation damage, thus exerting a neuroprotective effect. The experiments were approved by the Committee of Experimental Animal Use and Care of Central South University, China (approval No. 201703346) on March 7, 2017.
RESUMO
OBJECTIVE: To study the correlation between the Narcotrend index, cerebral state index and predicted effect site concentration during different state of consciousness in the absence of surgery in elderly patients with target controlled infusion of propofol. METHODS: Twenty patients aged from 65-75 years categorized as ASA class I - II who were scheduled to undergo general surgery under general anesthesia with target controlled infusion of propofol were recruited. During the target controlled infusion of propofol, the propofol infusion was set at an initial effect site concentration of 0.5 mg/L and increased by 0.5 mg /L every 5 min until the modified observer's assessment of alertness / sedation scale (OAA/S) values of zero. The predicted effect site concentration of propofol, the values of CSI and NCT were recorded and the sedation level was examined by the modified OAA/S every 20 s. The predicted effect site concentrations of propofol in target controlled infusion (TCI) system were recorded when they increased by more than 0.1 mg/L. The predicted effect site concentrations of propofol and the values of NCT and CSI at LVC and LOC of the patients were recorded. RESULTS: There was a good linear correlation between NCT and the predicted effect site concentration of propofol (R2 = 0. 867, P < 0.01), as well as that between CSI and the predicted effect site concentration of propofol (R2 = 0.893, P < 0.01). The predicted effect site concentrations of propofol at LVC was (1.56 +/- 0.13) mg/L while the values of NCT was 74.00 +/- 4.69 and CSI 69.82 +/- 5.47. The predicted effect site concentrations of propofol at LOC was (2.15 +/- 0.27) mg/L while the values of NCT and CSI were 63.30 +/- 7.50 and 58.78 +/- 6.90 respectively. All of the values of NCT, CSI and the predicted effect site concentrations had a good linear correlation with OAA/S. There was a negative correlation between OAA/S and the predicted effect site concentration. At the same time, there was a positive correlation between OAA/S and NCT as well as that between OAA/S and CSI. And the correlation coefficients were - 0.968, 0.938, 0.940 respectively (P < 0.01). The values of NCT were higher significantly than that of CSI in different degree of LOC (P < 0.01). CONCLUSION: During elder people's target controlled infusion of propofol, LVC and LOC occur within a definite range of predicted effect site concentrations. There is a good linear correlation between NCT, CSI and the predicted effect site concentrations of propofol. For the elders, both NCT and CSI reflect the sedation level of propofol. Although there is a significant correlation between NCT and CSI, a deviation does exist in a certain range. Therefore a simple 1:1 transfer from NCT to CSI is inadequate.
Assuntos
Anestesia/métodos , Sedação Consciente/métodos , Sedação Profunda , Propofol/administração & dosagem , Idoso , Anestésicos Intravenosos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Monitorização IntraoperatóriaRESUMO
INTRODUCTION: Fungal infection is increasingly common in critical illness with severe sepsis, but the influence of invasive fungal infection (IFI) on severe sepsis is not well understood. The aim of this study was to investigate the impact that IFI has on the outcomes of critically ill surgical patients with severe sepsis in China by means of matched cohort analysis; we also evaluated the epidemiologic characteristics of IFI in this population. METHODS: Records for all admissions to 10 university hospital surgical intensive care units (ICUs) from December 2004 to November 2005 were reviewed. Patients who met criteria for severe sepsis were included. IFI was identified using established criteria based on microbiologic or histological evidence. A matched cohort study was conducted to analyze the relationship between IFI and outcomes of severe sepsis. RESULTS: A total of 318 patients with severe sepsis were enrolled during the study period, of whom 90 (28.3%) were identified as having IFI. A total of 100 strains of fungi (58% Candida albicans) were isolated from these patients. Independent risk factors for IFI in patients with severe sepsis included mechanical ventilation (>3 days), Acute Physiology and Chronic Health Evaluation score, coexisting infection with both gram-positive and gram-negative bacteria, and urethral catheterization (>3 days). Compared with the control cohort, IFI was associated with increased hospital mortality (P < 0.001), high hospital costs (P = 0.038), and prolonged stay in the ICU (P < 0.001) and hospital (P = 0.020). CONCLUSION: IFI is frequent in patients with severe sepsis in surgical ICUs and is associated with excess risk for hospital mortality, longer ICU and hospital stays, and greater consumption of medical resources.
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Mortalidade Hospitalar , Micoses/complicações , Complicações Pós-Operatórias , Sepse/complicações , APACHE , Idoso , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Micoses/classificação , Fatores de Risco , Sepse/classificação , Sepse/terapia , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To investigate the antinociceptive effect of intrathecal (IT) injection of Herpes simplex virus type I (HSV-1) amplicon vector-mediated HPPE on chronic neuropathic pain. METHODS: 45 Sprague-Dawley rats underwent chronic constriction. Injury (CCI) of unilateral sciatic nerve and then were randomly divided into 3 equal groups: CCI + normal saline group, undergoing insertion of microspinal catheter into the subarachnoid space at the lumber region and intrathecal delivery of NS, CCI + pHSVIRES-LacZ (SHPZ) group undergoing intrathecal delivery of and recombinant HSV-I amplicon vector pHSVIRES-HPPE-LacZ containing human pre-proenkephalin (HPPE) gene, and CCI + blank vector (SHZ) group receiving pHSV-HPPE-LacZ. Another 15 rats underwent sham operation to be used as control group. One week after IT administration 9 rats from each group were killed with their lumber segments of spinal cord removed to detect the expression of LacZ by X-gal staining, HPPE mRNA expression by RT-PCR, and L-enkephalin (L-EK) content by radioimmunoassay. Paw mechanical withdrawal threshold (PMWT) and paw withdrawal thermal latency (PWTL) were measured before CCI (baseline) and 3 days after CCI and then once a week for 5 weeks after IT administration. RESULTS: After IT administration of SHPZ expression of HPPE mRNA was detected in the spinal cord. One week after the IT injection the L-EK level of the SHPZ group was (748 +/- 185 ng/L), significantly higher than those of the Sham operation, NS, and SHZ groups [(452 +/- 89), (453 +/- 92), and (451 +/- 99) ng/L respectively, all P < 0.05]. The PWMT and PWTL levels of the SHPZ group were significantly increased since 1 week after the IT administration in comparison with the baseline values and those of the other 3 groups (all P < 0.05), and these effects peaked in the third week and then lasted to the fifth week. However, the threshold to mechanical and thermal stimuli was not affected by intrathecal delivery of vehicle or SHZ compared with the threshold before intrathecal delivery. CONCLUSIONS: Intrathecal administration SHPZ can produce significant analgesic effects on chronic neuropathic pain in rats.
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Analgesia/métodos , Encefalinas/fisiologia , Vetores Genéticos/genética , Neuralgia/terapia , Precursores de Proteínas/fisiologia , Animais , DNA Viral/genética , Encefalinas/genética , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Herpesvirus Humano 1/genética , Humanos , Injeções Espinhais , Masculino , Neuralgia/etiologia , Medição da Dor/métodos , Precursores de Proteínas/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Nervo Isquiático/lesões , Medula Espinal/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: To observe the hemodynamic changes, recovery profiles, and side effects of propofol and remifentanil anesthesia by target controlled infusion (TCI). At different neurosurgical stages in patients undergoing neurosurgical operations. METHODS: 230 patients were scheduled for elective craniotomy in five hospitals in Beijing, Changsha, and Guangzhou. During the general anesthesia the plasma target-concentration of propofol remained unchangeable and the dose of remifentanil changed at different stages before skin incision, during skull opening, during intracranial procedure, and at skull closing. The hemodynamics changes and anesthetic recovery profiles were recorded. RESULTS: The plasma target-concentrations of remifentanil were set to 3.0, 3.5, 3.6 and 3.4 ng/ml respectively. The time of consciousness loss during induction was (2.0 +/- 0.9) min. The mean arterial pressure (MAP) and heart rate (HR) decreased after induction (both P < 0.05) and increased after intubation. The hemodynamic changes were stable at different surgical stages and the HR was significantly lower than the baseline value (P < 0.01). MAP and HR increased gradually when the spontaneous breathing was recovered. 80, 41, 9, and 12 patients received nicardipine, atropine, esmolol, and ephedrine respectively during the operation. The times of recovery of spontaneous breathing, eye opening, extubation, and orientation were (12 +/- 9) min, (13 +/- 7) min, (16 +/- 8) min, and (21 +/- 8) min respectively. CONCLUSION: When combined with 3 microg/ml propofol, the plasma target-concentrations of remifentanil, 3.0, 3.5, 3.6, and 3.4 ng/ml before skin incision, during skull opening, during intracranial procedure, and at skull closing respectively, can provide rapid induction, faster emergence , and better hemodynamic stability.
Assuntos
Anestésicos Intravenosos/administração & dosagem , Procedimentos Neurocirúrgicos/métodos , Piperidinas/administração & dosagem , Adolescente , Adulto , Idoso , Anestesia Intravenosa , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Propofol/administração & dosagem , Remifentanil , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To examine the characteristics of drug-induced fatal adverse effects in the United States from 1999 to 2004 and put forward suggestions for China's control of drug-induced adverse effects. METHODS: The data came from the compressed mortality file of Centers for Disease Control and Prevention (CDC) of the United States. Drug-induced mortality was used to analyze the effects of gender, race, age, and drug on drug-induced fatal adverse effects. RESULTS: During 1999-2004, 1 700 persons died of drug-induced adverse effects (mortality, 0.10/100,000). No difference was found in mortality between males and females. The drug-induced mortalities of whites, blacks and Native Americans, and other racial groups were respectively 0.10, 0.12, and 0.04 per 100,000 persons. The mortality increased quickly with the increase of age since the age group of 5-9. In this period, the 5 most common drugs that led to deaths were: (1) agents primarily affecting blood constituents; (2) analgesics, antipyretics, and anti-inflammatory drugs; (3) primarily systemic agents; (4) systemic antibiotics; and (5) hormones and their synthetic substitutes and antagonists, not elsewhere classified. At the age group of 20-84, 3 most common drugs leading to deaths for whites were: anticoagulants,opioids and related analgesics, and insulin and oral hypoglycaemic drugs. For blacks and Native Americans, they were: hydantoin derivatives, anticoagulants, and anaesthetic, unspecified. For people ages older than 84, anticoagulants, opioids and related analgesics, and drug or medicament, unspecified, were the 3 most common drugs resulting in deaths. For the rest of racial groups, the number of deaths caused by all kinds of drugs was less than 3. CONCLUSION: Obvious differences on race, gender, age, and drug were found for drug-induced fatal adverse effects in the United States during 1999-2004, and these differences should be considered by the government when interventions are developed. China can learn something from the United States in controlling drug adverse effects, and improve its surveillance system of drug adverse effects as soon as possible.