RESUMO
BACKGROUND AND AIMS: Hypoxemia is one of the most common adverse events during colonoscopy, particularly among patients who are diagnosed with obstructive sleep apnea (OSA) or are overweight. Consequently, the objective of this study was to evaluate the effectiveness of bilevel positive airway pressure (BPAP) ventilation for patients with high-risk hypoxemia during colonoscopy with sedation. METHODS: In this trial, 127 patients who met the eligibility criteria were randomly assigned to the BPAP oxygen group and nasal cannula (NC) group. The primary endpoint was the incidence of hypoxemia. RESULTS: Compared with the use of NC, BPAP ventilation exhibited a significant reduction in the incidence of hypoxemia, decreasing it from 23.8% to 6.3% (absolute risk difference, 17.5%; 95% conï¬dence interval, 5.4-29.6; P = .006). Importantly, BPAP ventilation prevented the occurrence of severe hypoxemia (9.5% vs 0%; absolute risk difference, 9.5%; 95% confidence interval, 2.3-16.7; P = .035). In addition, the BPAP group required fewer airway interventions (P < .05). CONCLUSIONS: In individuals with OSA or overweight status, the use of BPAP ventilation during colonoscopy significantly reduced the incidence of hypoxemia. (Clinical trial registration number: ChiCTR2300073193.).
Assuntos
Colonoscopia , Hipóxia , Apneia Obstrutiva do Sono , Humanos , Colonoscopia/métodos , Colonoscopia/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Hipóxia/etiologia , Estudos Prospectivos , Apneia Obstrutiva do Sono/terapia , Idoso , Sedação Consciente/efeitos adversos , Sedação Consciente/métodos , Sobrepeso/complicações , Respiração com Pressão Positiva/métodos , Cânula , AdultoRESUMO
BACKGROUND: Decreased bioavailability of nitric oxide (NO) under hypoxic conditions can lead to endothelial dysfunction. NO supplementation may protect endothelial function in ischemia-reperfusion (IR) injury. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to verify the protective effect of NO donors on endothelium in IR injury. METHODS: Medline, Embase, Cochrane Library, and Web of Science databases were searched from inception to April 1, 2023. The specific inclusion criteria were as follows: (1) RCTs; (2) trials comparing NO donors with placebo control groups; and (3) trials reporting the effects of these interventions on vascular endothelial functional outcomes in IR injury. Random-effects models were used to assess pooled effect sizes, which were expressed as standardized mean differences (SMD). RESULTS: Seven studies satisfied the inclusion criteria and consisted of a total of 149 participants. NO donors were protective of endothelial function in IR injury (SMD: - 1.60; 95% confidence interval [CI]: - 2.33, - 0.88, P < 0.0001; heterogeneity [I2 = 66%, P = 0.001]). Results of the subgroup analysis showed the following: absence of protective effect of NO donor use following ischemia on endothelial function in IR injury - 1.78 (95% CI: - 2.50, - 1.07) and loss of protective effect on endothelial function after prolonged NO donor use - 0.89 (95% CI: - 2.06, 0.28). CONCLUSION: The short-period use of NO donors before the onset of ischemia can protect endothelial function in IR injury.
Assuntos
Doadores de Óxido Nítrico , Traumatismo por Reperfusão , Humanos , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Endotélio Vascular , Traumatismo por Reperfusão/prevenção & controle , Óxido NítricoRESUMO
BACKGROUND: Hepatic ischemia reperfusion (HIR) leads to a lung inflammatory response and subsequent pulmonary barrier dysfunction. The gap junction communication protein connexin 32 (Cx32), which is widely expressed in the lungs, participates in intercellular signaling. This study determined whether the communication protein Cx32 could affect pulmonary inflammation caused by HIR. METHODS: Mice were randomly allocated into four groups (n = 8/group): (i) Cx32+/+ sham group; (ii) Cx32+/+ HIR model group; (iii) Cx32-/- sham group; and (iv) Cx32-/- HIR model group. Twenty-four hours after surgery, lung tissues were collected for bright field microscopy, western blot (Cx32, JAK2, p-JAK2, STAT3, p-STAT3), and immunofluorescence (ZO-1, 8-OHDG) analyses. The collected bronchoalveolar fluid was tested for levels of interleukin-6 (IL-6), matrix metalloproteinase 12 (MMP-12), and antitrypsin (α1-AT). Lung mmu-miR-26a/b expression was detected using a PCR assay. RESULTS: Increased expression of Cx32 mRNA and protein was noted in the lungs after HIR. Cx32 deletion significantly aggravated pulmonary function from acute lung injury induced by HIR. In addition, Cx32 deletion decreased the protein level of ZO-1 (pulmonary function) and increased the level of the oxidative stress marker 8-OHDG in the lungs. Moreover, in the Cx32-/- HIR model group, the levels of IL-6 and MMP-12 in bronchoalveolar lavage fluid were significantly increased leading to activation of the JAK2/STAT3 pathway, and decreased α1-AT levels. Furthermore, we found mmu-miR-26a/b was significantly downregulated in the Cx32-/- HIR model group. CONCLUSION: HIR leads to acute lung inflammatory injury. Cx32 deletion aggravates hepatic-derived lung inflammation, partly through blocking the transferring of mmu-miR-26a/b and leading to IL-6-related JAK2/STAT3 pathway activation.
Assuntos
Lesão Pulmonar Aguda/etiologia , Conexinas/metabolismo , Hepatopatias/complicações , Pulmão/metabolismo , Pneumonia/etiologia , Traumatismo por Reperfusão/complicações , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Conexinas/deficiência , Conexinas/genética , Modelos Animais de Doenças , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Hepatopatias/genética , Hepatopatias/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , MicroRNAs/metabolismo , Pneumonia/genética , Pneumonia/metabolismo , Pneumonia/patologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Proteína beta-1 de Junções ComunicantesRESUMO
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
BACKGROUND Effects of liver dysfunction on target-controlled infusion (TCI) with Marsh parameters of propofol remain poorly documented. The purpose of this study was to evaluate the performance of propofol TCI in a cohort of Chinese patients with severe hepatic insufficiency. MATERIAL AND METHODS We assigned 32 patients who underwent liver transplantation to 3 groups according to Child-Turcotte-Pugh (CTP) score. Anesthesia, preceding liver transplantation, was induced and maintained with TCI of 3 µg/mL propofol. Plasma propofol concentration was assessed. Propofol TCI system performance was analyzed in terms of error size, bias, and divergence. Data on plasma propofol concentrations were analyzed, and population pharmacokinetic parameters of propofol were fitted by NONMEM software. RESULTS In the CTP C group, measured concentrations of propofol were much higher than those of predictive concentrations, with significantly higher overshoots compared to CTP A patients. Overall, TCI system performance was significantly lower in CTP C patients. Linear regression equations of Cm vs. Cp and a regression model of pharmacokinetics were obtained. CONCLUSIONS Propofol TCI device performance with Marsh parameters was clinically acceptable in CTP A patients but may not be suitable for patients with severe hepatic impairment.
Assuntos
Insuficiência Hepática/metabolismo , Propofol/administração & dosagem , Propofol/farmacocinética , Adulto , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/farmacocinética , Povo Asiático , China , Estudos de Coortes , Feminino , Insuficiência Hepática/sangue , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Propofol/sangueRESUMO
BACKGROUND: Postoperative acute lung injury (ALI) is a severe complication after liver transplantation, which influences patient survival rate obviously. However, its mechanisms are unclear and effective therapies are still lacking. The current study focused on effects of propofol on liver transplantation-induced ALI and whether its underlying mechanism was relative with connexin43 (Cx43) alternation. The authors postulated that endotoxin induced enhancement of Cx43 gap junction (GJ) plays a critical role in mediating post liver transplantation ALI and that pretreatment with the anesthetic propofol, known to inhibit gap junction, can confer effective protection. METHODS: Male Sprague-Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx43 inhibitor, enanthol (0.1 mg/kg) and propofol (50 mg/kg), a commonly used anesthetic in clinical anesthesia. In vitro study, BEAS-2B cells, a kind of lung epithelial cell line expressing Cx43, exposed to lipopolysaccharide (LPS), which mainly contributed to ALI. Function of Cx43 GJ was regulated by Cx43 specific inhibitors, gap26 (300 µM) or enhancer, retinoic acid (10 µM) and two specific siRNAs. RESULTS: Compared with the sham group, AOLT results in ALI obviously with plasma endotoxin increase. Cx43 inhibition decreased ALI through inflammatory reaction reduction. In vitro studies, LPS-induced BEAS-2B cells damage was attenuated by Cx43 function inhibition, but amplified by enhancement. Another important finding was propofol reduced Cx43 function and protected against LPS-mediated BEAS-2B cells damage or AOLT-induced ALI, mechanisms of which were also associated with inflammatory reaction decrease. CONCLUSION: Cx43 plays a vital role in liver transplantation-induced ALI. Propofol decreased Cx43 function and protected against ALI in vivo and in vitro. This finding provide a new basis for targeted intervention of organ protection in liver transplantation, even in other kinds of operations.
Assuntos
Lesão Pulmonar Aguda/etiologia , Conexina 43/metabolismo , Junções Comunicantes/metabolismo , Transplante de Fígado/efeitos adversos , Propofol/farmacologia , Animais , Linhagem Celular , Conexinas/metabolismo , Junções Comunicantes/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Lipopolissacarídeos , Masculino , RNA Interferente Pequeno/metabolismo , Ratos Sprague-Dawley , Transplante Autólogo , Proteína beta-1 de Junções ComunicantesRESUMO
BACKGROUND: Intestinal ischemia-reperfusion (IIR) could lead to acute lung injury, associated with severe alveolar epithelial cells inflammatory and oxidative injury. Alpha7 nicotinic acetylcholine receptor (α7nAChR) is an essential component of the cholinergic anti-inflammatory pathway. The aim of this study was to investigate the important role of α7nAChR on the lung subjected to IIR. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups (n = 8 in each): sham group (group S), model group (group M), α7nAChR agonist PNU-282987-treated group (group PNU), and specific α7nAChR antagonist methyllycaconitine-treated group (group MLA). Intestinal IR damage was induced by clamping the superior mesenteric artery for 75 min, followed by a 120-min reperfusion. All rats were killed at 2 h after release of the clamps. The histologic examination of lungs was made, and lung water content was detected. Expression levels of malondialdehyde, tumor necrosis factor alpha, interleukin-6, and superoxide dismutase activity of the lungs were detected. Additionally, expression level of toll-like receptor (TLR)4 and nuclear factor-kappaB (NF-κB p65) in the nucleus of lung tissue and apoptosis-related protein (Bax, Bcl-2, and cleaved-caspase3) were detected using Western blot. RESULTS: Lungs were damaged after intestine IR, manifested by higher lung water content, histologic score, concentrations of interleukin-6, tumor necrosis factor alpha, and malondialdehyde of group M than those of group S, accompanied with decreased superoxide dismutase activity (P < 0.05). PNU treatment could significantly improve the pulmonary function of rats subjected to IIR. These effects of activation of α7nAChR were associated with suppression of TLR4/NF-κB pathway and subsequent reduction of apoptosis-related protein. However, MLA treatment aggravated lung injury. CONCLUSIONS: α7nAChR plays a role in acute lung injury induced by IIR via attenuating lung oxidative stress and inflammation through suppression of TLR4/NF-κB pathway, resulting in reduction of apoptosis in the lung.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Benzamidas/uso terapêutico , Compostos Bicíclicos com Pontes/uso terapêutico , Intestinos/irrigação sanguínea , Traumatismo por Reperfusão/complicações , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Avaliação Pré-Clínica de Medicamentos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , NF-kappa B/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND: Postliver transplantation acute kidney injury (AKI) severely affects patient survival, whereas the mechanism is unclear and effective therapy is lacking. The authors postulated that reperfusion induced enhancement of connexin32 (Cx32) gap junction plays a critical role in mediating postliver transplantation AKI and that pretreatment/precondition with the anesthetic propofol, known to inhibit gap junction, can confer effective protection. METHODS: Male Sprague-Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx32 inhibitor, 2-aminoethoxydiphenyl borate or propofol (50 mg/kg) (n = 8 per group). Also, kidney tubular epithelial (NRK-52E) cells were subjected to hypoxia-reoxygenation and the function of Cx32 was manipulated by three distinct mechanisms: cell culture in different density; pretreatment with Cx32 inhibitors or enhancer; Cx32 gene knock-down (n = 4 to 5). RESULTS: AOLT resulted in significant increases of renal Cx32 protein expression and gap junction, which were coincident with increases in oxidative stress and impairment in renal function and tissue injury as compared to sham group. Similarly, hypoxia-reoxygenation resulted in significant cellular injury manifested as reduced cell growth and increased lactate dehydrogenase release, which was significantly attenuated by Cx32 gene knock-down but exacerbated by Cx32 enhancement. Propofol inhibited Cx32 function and attenuated post-AOLT AKI. In NRK-52E cells, propofol reduced posthypoxic reactive oxygen species production and attenuated cellular injury, and the cellular protective effects of propofol were reinforced by Cx32 inhibition but cancelled by Cx32 enhancement. CONCLUSION: Cx32 plays a critical role in AOLT-induced AKI and that inhibition of Cx32 function may represent a new and major mechanism whereby propofol reduces oxidative stress and subsequently attenuates post-AOLT AKI.
Assuntos
Injúria Renal Aguda/prevenção & controle , Conexinas/efeitos dos fármacos , Junções Comunicantes/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Propofol/farmacologia , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Anestésicos Intravenosos/metabolismo , Anestésicos Intravenosos/farmacologia , Animais , Western Blotting/métodos , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Conexinas/genética , Conexinas/metabolismo , Modelos Animais de Doenças , Junções Comunicantes/genética , Junções Comunicantes/metabolismo , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transplante de Fígado/métodos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Complicações Pós-Operatórias/genética , Complicações Pós-Operatórias/metabolismo , Propofol/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína beta-1 de Junções ComunicantesRESUMO
BACKGROUND: Nuclear factor-E2-related factor 2 (Nrf2)-mediated antioxidant response is the main protective system of graft-liver against ischemia-reperfusion injury after liver transplantation. Propofol is considered to confer protective effects on different organs; thus, we explored the possibility that whether propofol could attenuate graft-liver injury in a rat autologous orthotopic liver transplantation (AOLT) model and mechanisms were associated with activation of Nrf2 pathway. METHODS: Sprague-Dawley rats were randomly divided into four groups: sham-operated group, saline-treated AOLT group, low-dose propofol intervention group, and high-dose propofol intervention group. Liver injury was determined, and concentration of hydroxyl free radical (â¢OH), superoxide anion (O2(â¢-)), and malondialdehyde in the liver tissue were detected. The expression of Keap1, Nrf2, HO-1, and NQO1 were explored by Western blotting, and also the change of Nrf2 and keap1 was assessed by immunofluorescence. RESULTS: Compared with sham group, pathologic damage of graft-livers was in a time-dependent manner, accompanied with the increased level of oxidative stress in the AOLT group, and nuclear Nrf2 expression and its downstream antioxidant enzyme, HO-1 and NQO1, were also increased in this group. However, in propofol pretreatment groups especially in the high-dose group, the pathologic score was significantly decreased, accompanied with a lower level of â¢OH, O2(â¢-), and malondialdehyde than that of the AOLT group. The change of oxidative stress might be related to the Nrf2 pathway, evidenced as the elevation of protein expression level of NQO1, HO-1, and nuclear Nrf2. CONCLUSIONS: Protective effects of propofol against liver transplantation-induced graft-liver injury may be related with Keap1-Nrf2 signal pathway activation.
Assuntos
Anestésicos Intravenosos/uso terapêutico , Hepatopatias/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Propofol/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Anestésicos Intravenosos/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/etiologia , Hepatopatias/metabolismo , Transplante de Fígado/efeitos adversos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Propofol/farmacologia , Distribuição Aleatória , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismoRESUMO
BACKGROUND: Little is known regarding the effect of ulinastatin (UTI) on acute lung injury (ALI) induced by orthotopic liver transplantation. This study aims to investigate the protective effect of UTI on ALI induced by orthotopic autologous liver transplantation (OALT) in a rat model and to explore the potential underlying mechanism. MATERIALS AND METHODS: Rats were randomly allocated into the following four groups (n = 8 each): (i) sham control group (group sham); (ii) model group (underwent OALT) (group model); (iii) low-dose UTI-treated group (group u1), with UTI (50 U/g) administered intravenously both before the portal vein was occluded and after liver reperfusion started; and (iv) high-dose UTI-treated group (group uh), with UTI (100 U/g) given in the same way as group ul. The lung pathologic parameters, lung water content, and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD) activity, RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1), and peroxiredoxin-2 (Prx-2) were assessed 8 h after OALT was performed. RESULTS: According to histology, there was severe damage in the lung of group model accompanied by increases in the TNF-α, IL-1ß, IL-6, and MDA levels and decreases in SOD activity and the expression of RBCK1 and Prx-2. UTI treatment significantly reduced the pathologic scores, lung water content, and TNF-α, IL-1ß, IL-6, and MDA levels while restoring the SOD activity and expression of RBCK1 and Prx-2. Furthermore, compared with group u1, treatment with a high dose of UTI resulted in a better protective effect on the lung when assessed by the TNF-α, IL-1ß, IL-6, and MDA levels and SOD activity. CONCLUSIONS: UTI dose-dependently attenuates ALI that is induced by OALT in this rat model, which is mainly due to the suppression of the inflammatory response and oxidant stress, which may, in turn, be mediated by the upregulation of RBCK1 and Prx-2 expression.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Glicoproteínas/administração & dosagem , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Inibidores da Tripsina/administração & dosagem , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Proteínas de Homeodomínio/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Complicações Pós-Operatórias/etiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Acute lung injury (ALI) is a severe complication of orthotopic liver transplantation (OLT) with unclear underline mechanism. Toll-like receptor 4 (TLR4) has been identified as a key receptor mediating inflammation. We hypothesized that TLR4-mediated pulmonary inflammation may contribute to development of ALI during OLT. Patients with or without ALI were observed for serum cytokines and expression of TLR4 on peripheral blood polymorphonuclear leukocytes (PMNs). Next, rats which underwent orthotopic autologous liver transplantation (OALT) were divided into sham and model groups. Pulmonary function and the level of TLR4 expression and cytokines were analyzed. Furthermore, the role of TLR4 in OALT-mediated ALI was assessed in rats treated with TLR4-siRNA before OALT. The PMNs TLR4 expression and the serum TNF-α and IL-ß level were higher in patients with ALI than those with non-ALI. Interestingly, lung TLR4 expression was significantly increased after 8 hours of OALT with increased levels of TNF-α and IL-ß, which lead to lung pathological damage and an increase of lung myeloperoxidase content. Moreover, knockdown of TLR4 reduced lung cytokines release and reversed the above pathologic changes after OALT and finally improved rats' survival rate. In conclusion, TLR4 overexpression, potentially by stimulating proinflammatory cytokine overproduction, contributes to the development of ALI after OLT.
Assuntos
Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Transplante de Fígado/efeitos adversos , Receptor 4 Toll-Like/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Adulto , Animais , Feminino , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/prevenção & controle , Interleucina-1beta/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Acute kidney injury associated with renal hypoperfusion is a frequent and severe complication during sepsis. Fluid resuscitation is the main therapy. However, heart failure is usually lethal for those patients receiving large volumes of fluids. We compared the effects of small-volume resuscitation using four different treatment regimens, involving saline, hypertonic saline (HTS), hydroxyethyl starch (HES), or hypertonic saline hydroxyethyl starch (HSH), on the kidneys of rats treated with lipopolysaccharide (LPS) to induce endotoxemia. LPS injection caused reduced and progressively deteriorated systemic (arterial blood pressure) and renal hemodynamics (renal blood flow and renal vascular resistance index) over time. This deterioration was accompanied by marked renal functional and pathological injury, as well as an oxidative and inflammatory response, manifesting as increased levels of tumor necrosis factor-α, nitric oxide, and malondialdehyde and decreased activity of superoxide dismutase. Small-volume perfusion with saline failed to improve renal and systemic circulation. However, small-volume perfusion with HES and HSH greatly improved the above parameters, while HTS only transiently improved systemic and renal hemodynamics with obvious renal injury. Therefore, single small-volume resuscitation with HES and HSH could be valid therapeutic approaches to ameliorate kidney injury induced by endotoxemia, while HTS transiently delays injury and saline shows no protective effects.
Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Endotoxemia/complicações , Hidratação/métodos , Derivados de Hidroxietil Amido/uso terapêutico , Animais , Endotoxemia/induzido quimicamente , Lipopolissacarídeos/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley , Solução Salina Hipertônica/uso terapêuticoRESUMO
Emerging evidence indicates that RUNX3 is a candidate tumor suppressor in several types of human tumors including hepatocellular carcinoma (HCC). However, the correlation between RUNX3 hypermethylation and incidence of HCC remains unclear. Here, we conducted a systematic review and meta-analysis aiming to comprehensively assess the potential role of RUNX3 hypermethylation in the pathogenesis of HCC. A detailed literature search was made from PubMed, EMBASE, and ISI web of knowledge to identify studies for related research publications. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed. Odds ratio (OR) was calculated and summarized, respectively. Final analysis of 821 HCC patients from 14 eligible studies was performed. We observed that RUNX3 hypermethylation was significantly higher in HCC than in normal liver tissue, the pooled OR from eight studies including 382 HCC and 161 normal liver tissue (OR = 39.32, 95 % confidence interval (CI) = 13.72-112.7, p < 0.00001). The pooled analysis showed significantly increased OR of RUNX3 hypermethylation (OR = 5.4, 95 % CI = 2.06-14.17, p < 0.00001) in HCC tissues and non-tumor liver tissues. In addition, statistically significant OR of RUNX3 hypermethylation was obtained from non-tumorous liver tissue of HCC patients and normal liver tissue (OR = 12.57, 95 % CI = 3.56-44.35, p < 0.0001). The results of this meta-analysis suggest that RUNX3 hypermethylation may be implicated in the pathogenesis of HCC. Thus, detection of RUNX3 hypermethylation may be a helpful and valuable biomarker for diagnosis of HCC.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Metilação de DNA/genética , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Razão de ChancesRESUMO
OBJECTIVE: We examined the value of inflammatory and oxidative biomarkers in predicting acute kidney injury (AKI) following orthotopic liver transplantation (OLT). METHODS: Urinary excretion of tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-10 (IL-10), superoxide dismutase (SOD), malondialdehyde (MDA), 6-keto prostaglandin F1α (6-keto-PGF1α), hydrogen peroxide (H2O2), and 8-keto prostaglandin F2α (8-iso-PGF2α), serum creatinine (SCr), blood urea nitrogen (BUN), urinary N-acetyl-beta-D-glucosaminidase (NAG), ß2-microglobulin (ß2-MG) and γ-glutamyl-transferase (γ-GT), were measured before surgery (baseline), at 2 h after graft reperfusion and 24 h after OLT in 28 liver transplantation patients. RESULTS: The levels of TNF-α, IL-8, IL-10, SOD, MDA, 6-keto-PGF1α, H2O2 and 8-iso-PGF2α in urine were all significantly higher in patients who had AKI than in those who did not at 2 h after graft reperfusion and 24 h after OLT (p < 0.01).
Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Biomarcadores/urina , Transplante de Fígado , 6-Cetoprostaglandina F1 alfa/urina , Adulto , Dinoprosta/análogos & derivados , Dinoprosta/urina , Feminino , Humanos , Peróxido de Hidrogênio/urina , Interleucina-10/urina , Interleucina-8/urina , Masculino , Malondialdeído/urina , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Curva ROC , Superóxido Dismutase/urina , Fatores de Tempo , Fator de Necrose Tumoral alfa/urinaRESUMO
Perioperative neurocognitive disorder (PND) is a common complication in surgical patients. While many interventions to prevent PND have been studied, the availability of treatment methods is limited. Thus, it is crucial to delve into the mechanisms of PND, pinpoint therapeutic targets, and develop effective treatment approaches. In this study, reduced dorsal tenia tecta (DTT) neuronal activity was found to be associated with tibial fracture surgery-induced PND, indicating that a neuronal excitation-inhibition (E-I) imbalance could contribute to PND. Optogenetics in the DTT brain region was conducted using upconversion nanoparticles (UCNPs) with the ability to convert 808 nm near-infrared light to visible wavelengths, which triggered the activation of excitatory neurons with minimal damage in the DTT brain region, thus improving cognitive impairment symptoms in the PND model. Moreover, this noninvasive intervention to modulate E-I imbalance showed a positive influence on mouse behavior in the Morris water maze test, which demonstrates that UCNP-mediated optogenetics is a promising tool for the treatment of neurological imbalance disorders.
Assuntos
Nanopartículas , Optogenética , Animais , Optogenética/métodos , Camundongos , Nanopartículas/química , Masculino , Aprendizagem em Labirinto , Complicações Cognitivas Pós-Operatórias/etiologia , Camundongos Endogâmicos C57BL , Neurônios , Fraturas da Tíbia/cirurgia , Raios InfravermelhosRESUMO
BACKGROUND: Acute lung injury (ALI) is a serious complication that commonly occurs during orthotopic liver transplantation (OLT). Toll-like receptor 2/4 (TLR2/4) are the main membrane receptors that respond to inflammatory stimuli and mediate NF-kappa B (NF-κB) signal pathway. We previously showed that TLR2/4 expression on monocytes and serum cytokine levels were increased in patients with ALI induced by OLT. Myeloid differentiation protein-2 (MD-2) expresses the functional domains that combines TLRs and play a key regulatory role in TLRs activation. Therefore, we hypothesized that blocking MD-2 would inhibit the TLR2/4-mediated inflammatory response and lessen ALI induced by liver transplantation. METHOD: Thirty-two Sprague Dawley (SD) rats were randomly divided into four groups. One group received a sham operation (Group S), and the other three groups underwent orthotopic autologous liver transplantation (OALT) 48 h after intratracheal administration of saline (Model group; Group M), non-targeting siRNA (negative siRNA control group; Group NC) or siRNA against MD-2 (intervention group; Group RNAi). Lung pathology, lung water content, PaO2, and expression levels of MD-2, TLR2/4, NF-κB, TNF-α, IL-1ß and IL-6 were assessed 8 h after OALT. RESULTS: In Groups M and NC, OALT produced marked lung pathology with decreased PaO2 levels and increased MD-2, TLR2/4 gene and protein expression levels. Furthermore, the nuclear translocation of the NF-κB P65 subunit, was increased, as were lung concentrations of TNF-α, IL-1ß and IL-6. The pathology of ALI and the severity of the above biochemical changes induced by OALT were significantly reduced in the group treated with MD-2 siRNA. CONCLUSION: MD-2 gene knock-down attenuated the increase in TLR2/4 activation and reduced ALI after OALT.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/fisiopatologia , Transplante de Fígado/efeitos adversos , Antígeno 96 de Linfócito/farmacologia , Animais , Modelos Animais de Doenças , Água Extravascular Pulmonar/metabolismo , Expressão Gênica , Inflamação/metabolismo , Inflamação/patologia , Interleucinas/biossíntese , Pulmão/patologia , Masculino , NF-kappa B/biossíntese , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor 2 Toll-Like/biossíntese , Receptor 4 Toll-Like/biossíntese , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The study aimed to investigate whether sevoflurane preconditioning can protect against small intestinal ischemia reperfusion (IIR) injury and to explore whether mast cell (MC) is involved in the protections provided by sevoflurane preconditioning. Sprague-Dawley rats exposed to sevoflurane or treated with MC stabilizer cromolyn sodium (CS) were subjected to 75-minute superior mesenteric artery occlusion followed by 2-hour reperfusion in the presence or absence of MC degranulator compound 48/80 (CP). Small intestinal ischemia reperfusion resulted in severe intestinal injury as demonstrated by significant elevations in intestinal injury scores and p47(phox) and gp91(phox), ICAM-1 protein expressions and malondialdehyde and IL-6 contents, and MPO activities as well as significant reductions in SOD activities, accompanied with concomitant increases in mast cell degranulation evidenced by significant increases in MC counts, tryptase expression, and ß-hexosaminidase concentrations, and those alterations were further upregulated in the presence of CP. Sevoflurane preconditioning dramatically attenuated the previous IIR-induced alterations except MC counts, tryptase, and ß-hexosaminidase which were significantly reduced by CS treatment. Furthermore, CP exacerbated IIR injury was abrogated by CS but not by sevoflurane preconditioning. The data collectively indicate that sevoflurane preconditioning confers protections against IIR injury, and MC is not involved in the protective process.
Assuntos
Intestino Delgado/patologia , Mastócitos/patologia , Éteres Metílicos/farmacologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Anestésicos Inalatórios/farmacologia , Animais , Cromolina Sódica/farmacologia , Feminino , Técnicas Imunoenzimáticas , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Malondialdeído/metabolismo , Mastócitos/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Artéria Mesentérica Superior/efeitos dos fármacos , Artéria Mesentérica Superior/patologia , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Sevoflurano , Triptases/metabolismo , beta-N-Acetil-Hexosaminidases/sangueRESUMO
STUDY OBJECTIVE: Hypoxemia is one of the most frequent adverse events during sedated gastroscopy, and there is still no effective means to prevent and cure it. Therefore, we conducted this randomized trial to confirm our hypothesis that, compared with the nasal cannula group, bilevel positive airway pressure (BPAP) would decrease the incidence of hypoxemia in patients with obstructive sleep apnea (OSA) or overweight status undergoing gastroscopy. DESIGN: In a single-center, prospective, randomized controlled clinical trial, 80 patients aged 18-65 years and with OSA or overweight status who underwent gastroscopy with sedation were randomly assigned to two groups: the nasal cannula and BPAP groups. The primary outcome was the incidence of hypoxemia (75% < peripheral oxygen saturation [SpO2] < 90% for >5 sand <60 s). MAIN RESULTS: Compared to the nasal cannula group, BPAP therapy significantly decreased the incidence of hypoxemia from 40.0% to 2.5% (absolute risk difference [ARD], 37.5% [95% confidence interval (CI), 21.6 to 53.4], p < 0.001), decreased subclinical respiratory depression from 52.5% to 22.5% (ARD, 30.0% [95% CI, 9.8 to 50.2], p = 0.006), and decreased severe hypoxemia from 17.5% to 0% (ARD, 17.5% [95% CI, 5.7 to 29.3], p = 0.006). The BPAP intervention also decreased the total propofol dosage and operation time and improved anesthesiologist's satisfaction. CONCLUSION: BPAP therapy significantly decreased the incidence of hypoxemia in patients with OSA or overweight status who underwent gastroscopy.