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1.
HPB (Oxford) ; 26(7): 949-959, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38705794

RESUMO

BACKGROUND: Risk assessment models for acute kidney injury (AKI) after major hepatectomy that differentiate between early and late AKI are lacking. This retrospective study aimed to create a model predicting AKI through machine learning and identify features that contribute to the development of early and late AKI. METHODS: Patients that underwent major hepatectomy were categorized into the No-AKI, Early-AKI (within 48 h) or Late-AKI group (between 48 h and 7 days). Modeling was done with 20 perioperative features and the performance of prediction models were measured by the area under the receiver operating characteristic curve (AUROCC). Shapley Additive Explanation (SHAP) values were utilized to explain the outcome of the prediction model. RESULTS: Of the 1383 patients included in this study, 1229, 110 and 44 patients were categorized into the No-AKI, Early-AKI and Late-AKI group, respectively. The CatBoost classifier exhibited the greatest AUROCC of 0.758 (95% CI: 0.671-0.847) and was found to differentiate well between Early and Late-AKI. We identified different perioperative features for predicting each outcome and found 1-year mortality to be greater for Early-AKI. CONCLUSIONS: Our results suggest that risk factors are different for Early and Late-AKI after major hepatectomy, and 1-year mortality is greater for Early-AKI.


Assuntos
Injúria Renal Aguda , Hepatectomia , Aprendizado de Máquina , Humanos , Hepatectomia/efeitos adversos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Medição de Risco , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Idoso , Valor Preditivo dos Testes , Complicações Pós-Operatórias/etiologia
2.
J Clin Periodontol ; 50(11): 1553-1567, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37621247

RESUMO

AIM: The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative effects of oral infection with Porphyromonas gingivalis (PG), the major pathogen for periodontitis, on intestinal microbiota and atherosclerosis. MATERIALS AND METHODS: ApoE-/- mice were fed a normal chow diet (NC), a Western diet (WD) or a WD with oral PG infection (PG). The PG infection was investigated by placing a total of 109 CFUs of live PG into the oral cavity of each mouse using a feeding needle five times a week for 3 weeks. Atherosclerotic lesions of the aortae were measured, and blood lipoproteins and the expression of molecules related to lipid metabolism in the liver were analysed. We also performed 16S RNA sequencing and a microbiome analysis using faeces. RESULTS: En face bloc preparation of the aortae showed that the PG group had a 1.7-fold increase in atherosclerotic lesions compared with the WD group (p < .01). Serum analyses showed that oral PG infection induced a significant decrease in high-density lipoprotein (HDL) and triglyceride. Western blots of hepatic tissue lysates revealed that PG infection reduced the expression of scavenger receptor class B type 1 (SR-B1) in the liver by 50%. Faecal microbiota analysis revealed that species richness estimates (Chao1, ACE) decreased immediately after PG infection. PG infection also induced a significant decrease in Shannon diversity and an increase in Simpson's indices in the WD-fed mice. PG infection significantly increased the phyla Actinobacteria and Deferribacteres, along with the species Mucispirillum schaedleri and Lactobacillus gasseri, in the mice. The functional study showed that PG infection increased the expression of proteins that function in carbohydrate and glucose metabolism, including phosphotransferase system (PTS) proteins and the GntR family transcriptional regulator. CONCLUSIONS: Oral PG infection promotes atherosclerosis and induces significant metabolic changes, including reduced serum HDL and reduced hepatic SR-B1 and ABCA1 expression, as well as changes in intestinal microbiota. Our study suggests that intestinal dysbiosis accompanies periodontitis and could play a role in atherosclerosis.


Assuntos
Aterosclerose , Microbioma Gastrointestinal , Periodontite , Camundongos , Animais , Porphyromonas gingivalis , Disbiose , Aterosclerose/microbiologia
3.
Clin Transplant ; 36(6): e14667, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35435293

RESUMO

Living donor liver transplantation was first developed to mitigate the limited access to deceased donor organs in Asia in the 1990s. This alternative liver transplantation option has become an established and widely practiced transplantation method for adult patients suffering from end-stage liver disease. It has successfully addressed the shortage of deceased donors. The Society for the Advancement of Transplant Anesthesia and the Korean Society of Transplant Anesthesia jointly reviewed published studies on the perioperative management of live donor liver transplant recipients. The review aims to offer transplant anesthesiologists and critical care physicians a comprehensive overview of the perioperative management of adult live liver transplantation recipients. We feature the status, outcomes, surgical procedure, portal venous decompression, anesthetic management, prevention of acute kidney injury, avoidance of blood transfusion, monitoring and therapeutic strategies of hemodynamic derangements, and Enhanced Recovery After Surgery protocols for liver transplant recipients.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Adulto , Transfusão de Sangue , Doença Hepática Terminal/cirurgia , Humanos , Transplante de Fígado/métodos , Doadores Vivos , Transplantados
4.
Can J Anaesth ; 69(4): 448-459, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34931289

RESUMO

PURPOSE: Ischemia-reperfusion injury is inevitable during donor organ harvest and recipient allograft reperfusion in kidney transplantation, and affects graft outcomes. Dexmedetomidine, an α2-adrenoreceptor agonist, has renoprotective effects against ischemia-reperfusion injury. We investigated the effects of intraoperative dexmedetomidine infusion on renal function and the development of delayed graft function after elective living donor kidney transplantation in a randomized controlled trial. METHODS: A total of 104 patients were randomly assigned to receive either an intraoperative infusion of dexmedetomidine 0.4 µg·kg-1·hr-1 or 0.9% saline. The primary outcome was the serum creatinine level on postoperative day (POD) 7. Secondary outcomes were renal function and the degree of inflammation and included the following variables: serum creatinine level and estimated glomerular filtration rate up to six months; incidence of delayed graft function; and levels of serum cystatin C, plasma interleukin (IL)-1ß, and IL-18 during the perioperative period. RESULTS: The mean (standard deviation) serum creatinine level on POD 7 was comparable between the groups (dexmedetomidine vs control: 1.11 [0.87] mg·dL-1 vs 1.06 [0.73] mg·dL-1; mean difference, 0.05; 95% confidence interval, -0.27 to 0.36; P = 0.77). Delayed graft function occurred in one patient in each group (odds ratio, 1.020; P > 0.99). There were no significant differences in the secondary outcomes between the groups (all P > 0.05). CONCLUSIONS: Intraoperative dexmedetomidine infusion did not produce any beneficial effects on renal function or delayed graft function in patients undergoing elective living donor kidney transplantation. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03327389); registered 31 October 2017.


RéSUMé: OBJECTIF: Les lésions d'ischémie-reperfusion sont inévitables lors du prélèvement d'organes du donneur et de la reperfusion de l'allogreffe chez le receveur pour une transplantation rénale, et affectent le devenir du greffon. La dexmédétomidine, un agoniste des adrénorécepteurs de type α2, a des effets néphroprotecteurs sur les lésions d'ischémie-reperfusion. Nous avons réalisé une étude randomisée contrôlée afin d'examiner les effets d'une perfusion peropératoire de dexmédétomidine sur la fonction rénale et l'apparition d'un retard de fonctionnement du greffon après une transplantation rénale élective issue de donneurs vivants. MéTHODE: Au total, 104 patients ont été aléatoirement répartis pour recevoir une perfusion peropératoire de 0,4 µg·kg-1·r-1 de dexmédétomidine ou une solution saline à 0,9 %. Le critère d'évaluation principal était la créatininémie au jour postopératoire (JPO) 7. Les critères d'évaluation secondaires étaient la fonction rénale et le degré d'inflammation et comprenaient les variables suivantes : créatininémie et infiltration glomérulaire estimée jusqu'à six mois; incidence de retard de fonctionnement du greffon; et taux sériques de cystatine C, d'interleukine plasmatique (IL)-1ß et d'IL-18 pendant la période périopératoire. RéSULTATS: Le taux moyen (écart type) de créatinine sérique au JPO 7 était comparable entre les groupes (dexmédétomidine vs témoin : 1,11 [0,87] mg·dL-1 vs 1,06 [0,73] mg·dL-1; différence moyenne, 0,05; intervalle de confiance à 95 %, -0,27 à 0,36; P = 0,77). Un patient de chaque groupe a subi un retard de fonctionnement du greffon (rapport de cotes, 1,020; P > 0.99). Aucune différence intergroupe significative n'a été observée en ce qui concerne les critères d'évaluation secondaires. CONCLUSION: La perfusion peropératoire de dexmédétomidine n'a produit aucun effet bénéfique sur la fonction rénale ou le retard de fonctionnement du greffon chez les patients bénéficiant d'une transplantation rénale élective issue de donneur vivant. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03327389); enregistrée le 31 octobre 2017.


Assuntos
Dexmedetomidina , Transplante de Rim , Dexmedetomidina/farmacologia , Taxa de Filtração Glomerular , Humanos , Rim/fisiologia , Doadores Vivos
5.
Int J Mol Sci ; 23(15)2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35955939

RESUMO

Dexmedetomidine (Dex), widely used as a sedative in surgical procedures and intensive care units, induces sympatholytic, anxiolytic, analgesic, and sedative effects. Postoperative cognitive dysfunction (POCD) is routinely observed in postoperative care following surgery and general anesthesia. The NLRP3 inflammasome complex plays a critical role in innate immune response by detecting pathogenic microorganisms and activating pro-inflammatory cytokines. Although there are numerous protective effects of Dex among the neurological diseases, specific mechanisms including NLRP3 inflammasome-mediated neuroinflammation via oxidative stress response in a POCD model are not fully understood. Here, we investigated whether Dex exhibits neurocognitive effects through the NLRP3 inflammasome signaling in a POCD mouse model using a neurobehavioral test and ELISA analysis. We also confirmed the level of oxidative stress-related response in the in vitro system in the POCD model. Furthermore, we evaluated the NLRP3 inflammasome complex by immunoprecipitation analysis. In summary, the results of the present study indicated that Dex showed a neuroprotective effect in the POCD model by reducing oxidative stress response through NLRP3 inflammasome-mediated neuroinflammation.


Assuntos
Disfunção Cognitiva , Dexmedetomidina , Fármacos Neuroprotetores , Complicações Cognitivas Pós-Operatórias , Animais , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Inflamassomos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais
6.
J Neuroinflammation ; 18(1): 93, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858422

RESUMO

BACKGROUND: Postoperative pain is a common phenomenon after surgery and is closely associated with the development of postoperative cognitive dysfunction (POCD). Persistent pain and systemic inflammation caused by surgery have been suggested as key factors for the development of POCD. Fractalkine (CX3CL1) and its receptor, the CX3C chemokine receptor 1 (CX3CR1), are known to play a key role in pain and inflammation signaling pathways. Recent studies have shown that the regulation of CX3CR1/L1 signaling influences the development of various diseases including neuronal diseases. We determined whether CX3CR1/L1 signaling is a putative therapeutic target for POCD in a mouse model. METHODS: Adult (9-11 weeks) male mice were treated with neutralizing antibody to block CX3CR1/L1 signaling both before and after surgery. Inflammatory and behavioral responses including pain were assessed postoperatively. Also, CX3CR1 mRNA level was assessed. Hippocampal astrocyte activation, Mao B expression, and GABA expression were assessed at 2 days after surgery following neutralizing antibody administration. RESULTS: The behavioral response indicated cognitive dysfunction and development of pain in the surgery group compared with the control group. Also, increased levels of pro-inflammatory cytokines and CX3CR1 mRNA were observed in the surgery group. In addition, increased levels of GABA and increased Mao B expression were observed in reactive astrocytes in the surgery group; these responses were attenuated by neutralizing antibody administration. CONCLUSIONS: Increased CX3CR1 after surgery is both necessary and sufficient to induce cognitive dysfunction. CX3CR1 could be an important target for therapeutic strategies to prevent the development of POCD.


Assuntos
Quimiocina CX3CL1/metabolismo , Procedimentos Ortopédicos/efeitos adversos , Complicações Cognitivas Pós-Operatórias/etiologia , Complicações Cognitivas Pós-Operatórias/metabolismo , Animais , Astrócitos/metabolismo , Receptor 1 de Quimiocina CX3C/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Masculino , Camundongos , Transdução de Sinais , Ácido gama-Aminobutírico/metabolismo
7.
Int J Mol Sci ; 22(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34360684

RESUMO

The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm-elevated levels of hyperactivated immune cells-and circulating pro-inflammatory cytokines, including interleukin (IL)-1ß and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1ß and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Inflamassomos/imunologia , Inflamassomos/metabolismo , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Imunidade Adaptativa/imunologia , Animais , COVID-19/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Humanos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/imunologia , Tratamento Farmacológico da COVID-19
8.
Int J Med Sci ; 17(2): 207-213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32038104

RESUMO

Background: The incidence of postoperative nausea and vomiting (PONV) remains high. The effects of sufentanil for PONV is not firmly confirmed. The aim of this study was to compare the effect of sufentanil- and fentanyl-based intravenous patient-controlled analgesia (IV-PCA) on the incidence of PONV after laparoscopic nephrectomy. Methods: Eighty-six patients were randomly allocated to receive either the sufentanil (n =43) or fentanyl (n =43). IV-PCA was prepared using either sufentanil 3 µg/kg or fentanyl 20 µg/kg, ramosetron 0.3 mg, and ketorolac 120 mg. The primary outcome of was the incidence of PONV during 24 h after post anesthesia care unit (PACU) discharge. The secondary outcomes were the modified Rhodes index and patient satisfaction scores at 24 h after PACU discharge, need for rescue antiemetics, pain score, need for additional analgesics, and cumulative consumption of IV-PCA Results: The incidence of PONV was comparable between the sufentanil and fentanyl groups (64.3% vs. 65%, p = 0.946; respectively). The number of patients who required antiemetics (p = 0.946) and the modified Rhodes index at 24 h after post-anesthesia care unit discharge (p = 0.668) were also comparable in both groups. No significant differences were found in the secondary outcomes, including the analgesic profiles and adverse events between the groups. Conclusions: In conclusion, sufentanil- and fentanyl-based IV-PCA showed similar incidence of PONV with comparable analgesic effects after laparoscopic nephrectomy. Based on these results, we suggest that sufentanil and fentanyl may provide comparable effects for IV-PCA after laparoscopic nephrectomy.


Assuntos
Analgesia Controlada pelo Paciente/métodos , Fentanila/uso terapêutico , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Sufentanil/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Humanos , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Estudos Prospectivos , Adulto Jovem
9.
Int J Mol Sci ; 21(3)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32046097

RESUMO

Cognitive symptoms are prevalent in the elderly and are associated with an elevated risk of developing dementia. Disease-driven changes can cause cognitive disabilities in memory, attention, and language. The inflammasome is an innate immune intracellular complex that has a critical role in the host defense system, in that it senses infectious pathogen-associated and endogenous danger-associated molecular patterns. An unbalanced or dysregulated inflammasome is associated with infectious, inflammatory, and neurodegenerative diseases. Due to its importance in such pathological conditions, the inflammasome is an emerging drug target for human diseases. A growing number of studies have revealed links between cognitive symptoms and the inflammasome. Several studies have shown that reducing the inflammasome component mitigates cognitive symptoms in diseased states. Therefore, understanding the inflammasome regulatory mechanisms may be required for the prevention and treatment of cognitive symptoms. The purpose of this review is to discuss the current understanding of the inflammasome and its relationships with cognitive symptoms in various human diseases.


Assuntos
Inflamassomos/metabolismo , Transtornos Neurocognitivos/metabolismo , Sepse/complicações , Animais , Apoptose , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Transtornos Neurocognitivos/etiologia
10.
Surg Endosc ; 32(1): 175-182, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28639043

RESUMO

BACKGROUND: Laparoscopic surgery involves the creation of a carbon dioxide (CO2) pneumoperitoneum to facilitate a clear surgical view, which may result in an elevated intracranial pressure (ICP). Depending on the surgical area, steep Trendelenburg positioning may be used as well, further increasing the ICP. The objective of this study was to assess the effects of laparoscopic surgery on changes in ICP assessed by ultrasonographic measurement of optic nerve sheath diameter (ONSD), which is a generally accepted simple, reliable, and non-invasive ICP measurement technique. METHODS: A computerized literature search was performed in August 2016 to identity prospective studies that measured ONSD to assess ICP changes during laparoscopic surgery. The primary outcome was the change in ONSD during the early (0-30 min) and late (30-120 min) periods after initiating pneumoperitoneum, compared with baseline values measured after anesthesia induction. Mean differences (MDs) with 95% confidence intervals [CIs] were calculated. RESULTS: Nine observational studies and one randomized controlled trial, with a total of 460 subjects, were analyzed. Compared to the baseline value after anesthesia induction, significant increases in ONSD were observed in both the early period (MD 0.46, 95% CI 0.31-0.61, P < 0.001, I 2 = 97.3%) and late period (MD 0.67, 95% CI 0.20-1.14, P = 0.005, I 2 = 99.2%). Comparing the ONSD during the early and late periods revealed no significant differences over time. CONCLUSIONS: The current meta-analysis revealed that ICP elevation during laparoscopy could be anticipated through a significant increase in the ONSD in the early (0-30 min) and late (30-120 min) periods during CO2 pneumoperitoneum.


Assuntos
Hipertensão Intracraniana/diagnóstico por imagem , Laparoscopia/efeitos adversos , Nervo Óptico/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Humanos , Hipertensão Intracraniana/etiologia , Pressão Intracraniana/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Int J Med Sci ; 15(8): 788-795, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008588

RESUMO

Background: Distraction osteogenesis for craniosynostosis is associated with significant hemorrhage. Additionally, patients usually require several transfusions. Tranexamic acid (TXA) is effective for reducing blood loss and the need for transfusions during surgeries. However, the significance of TXA infusion has not been thoroughly described yet. Methods: Forty-eight children undergoing distraction osteogenesis for craniosynostosis were administered intraoperative TXA infusion (loading dose of 10 mg/kg for 15 min, followed by continuous infusion at 5 mg/kg/h throughout surgery; n = 23) or normal saline (control, n = 25). Rotational thromboelastometry (ROTEMTM) was conducted to monitor changes in coagulation perioperatively. Results: Blood loss during surgery was significantly lower in the TXA-treated group than it was in the control group (81 vs. 116 mL/kg, P = 0.003). Furthermore, significantly fewer transfusions of red blood cells and fresh frozen plasma were required in the TXA group. In the control group, clotting time during the postoperative period was longer than it was during the preoperative period. Similarly, clot strength was weaker during the postoperative period. D-dimer levels dramatically increased in the control group compared with the TXA group after surgery. The duration of mechanical ventilation and the number of postoperative respiratory-related complications were significantly greater in the control group than they were in the TXA group. Conclusions: TXA infusion based on population pharmacokinetic analysis is effective in reducing blood loss and the need for transfusions during the surgical treatment of craniosynostosis. It can also prevent the increase in D-dimer levels without affecting systemic hemostasis.


Assuntos
Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Osteogênese por Distração , Tromboelastografia , Ácido Tranexâmico/uso terapêutico , Antifibrinolíticos/farmacocinética , Transfusão de Sangue , Criança , Craniossinostoses , Feminino , Humanos , Lactente , Masculino , República da Coreia , Ácido Tranexâmico/farmacocinética , Resultado do Tratamento
12.
Neurochem Res ; 42(5): 1533-1542, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28303501

RESUMO

Tissue plasminogen activator (tPA) is the only recommended pharmacological treatment for acute ischemic stroke. However, tPA can induce intracerebral hemorrhage by blood-brain barrier breakdown through an increase in matrix metalloproteinases (MMPs). Previously, we showed that isoflurane postconditioning reduced intracranial hemorrhage following tPA treatment after cerebral ischemia. Here, we investigated the mechanism by which isoflurane postconditioning reduces tPA-induced MMP-2 and MMP-9 activation following hypoxia/reoxygenation (H/R) in brain endothelial cells. Mouse brain endothelial cells (bEnd.3) were exposed to 6 h of oxygen-glucose deprivation and 3 h of reoxygenation with tPA. Cells were treated with isoflurane for 1 h of the reoxygenation condition and the effect of isoflurane postconditioning on MMP-2 and MMP-9 activation was assessed. Involvement of low-density lipoprotein receptor-related protein (LRP), which is a receptor for tPA, and the extracellular signal-regulated kinase (ERK) and NF-κB pathway in isoflurane postconditioning was assessed using LRP inhibitor (receptor-associated protein, RAP) and ERK-1/2 inhibitor (PD98059). Isoflurane postconditioning decreased tPA-induced MMP-2 and MMP-9 activation under H/R. tPA treatment under H/R increased expression of LRP and the active form of NF-κB. Isoflurane postconditioning suppressed LRP expression, increased ERK-1/2 activation, and suppressed MMP-2 and MMP-9 activation, comparable to the effect of RAP. Activation of ERK-1/2, inhibition of NF-κB activation, and suppression of MMP-2 and MMP-9 activation by isoflurane postconditioning were abolished with PD98059 treatment. These finding indicate that isoflurane postconditioning inhibits tPA-induced MMP-2 and MMP-9 activation following H/R via the LRP/ERK/NF-κB pathway in bEnd.3.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Pós-Condicionamento Isquêmico/métodos , Isoflurano/farmacologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Metaloproteinases da Matriz/metabolismo , Ativador de Plasminogênio Tecidual/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Camundongos , Ativador de Plasminogênio Tecidual/antagonistas & inibidores
13.
Int J Med Sci ; 14(10): 970-976, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28924368

RESUMO

Introduction: Perioperative anesthesia and analgesia exacerbate immunosuppression in immunocompromised cancer patients. The natural killer (NK) cell is a critical part of anti-tumor immunity. We compared the effects of two different anesthesia and analgesia methods on the NK cell cytotoxicity (NKCC) in patients undergoing breast cancer surgery. Methods: Fifty patients undergoing breast cancer resection were randomly assigned to receive propofol-remifentanil anesthesia with postoperative ketorolac analgesia (Propofol-ketorolac groups) or sevoflurane-remifentanil anesthesia with postoperative fentanyl analgesia (Sevoflurane-fentanyl group). The primary outcome was NKCC, which was measured before and 24 h after surgery. Post-surgical pain scores and inflammatory responses measured by white blood cell, neutrophil, and lymphocyte counts were assessed. Cancer recurrence or metastasis was evaluated with ultrasound and whole body bone scan every 6 months for 2 years after surgery. Results: The baseline NKCC (%) was comparable between the two groups (P = 0.082). Compared with the baseline value, NKCC (%) increased in the Propofol-ketorolac group [15.2 (3.2) to 20.1 (3.5), P = 0.048], whereas it decreased in the Sevoflurane-fentanyl group [19.5 (2.8) to 16.4 (1.9), P = 0.032]. The change of NKCC over time was significantly different between the groups (P = 0.048). Pain scores during 48 h after surgery and post-surgical inflammatory responses were comparable between the groups. One patient in the Sevoflurane-fentanyl group had recurrence in the contralateral breast and no metastasis was found in either group. Conclusions: Propofol anesthesia with postoperative ketorolac analgesia demonstrated a favorable impact on immune function by preserving NKCC compared with sevoflurane anesthesia and postoperative fentanyl analgesia in patients undergoing breast cancer surgery.


Assuntos
Analgesia/efeitos adversos , Anestesia/efeitos adversos , Neoplasias da Mama/imunologia , Imunidade Celular/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Manejo da Dor/efeitos adversos , Adulto , Idoso , Analgesia/métodos , Analgésicos Opioides/efeitos adversos , Anestesia/métodos , Anestésicos Inalatórios/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Fentanila/efeitos adversos , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Células Matadoras Naturais/imunologia , Éteres Metílicos/efeitos adversos , Pessoa de Meia-Idade , Manejo da Dor/métodos , Medição da Dor , Assistência Perioperatória/efeitos adversos , Piperidinas/efeitos adversos , Propofol/efeitos adversos , Estudos Prospectivos , Remifentanil , Sevoflurano
14.
Int J Med Sci ; 14(5): 425-433, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28539818

RESUMO

Tissue-type plasminogen activator (tPA) is the only treatment for ischemic stroke. However, tPA could induce the intracranial hemorrhage (ICH), which is the main cause of death in ischemic stroke patient after tPA treatment. At present, there is no treatment strategy to ameliorate tPA-induced brain injury after ischemia. Therefore, we investigated the effect of pre-treated isoflurane, which is a volatile anesthetic and has beneficial effects on neurological dysfunction, brain edema and infarct volume in ischemic stroke model. In this study, we used oxygen/glucose deprivation and reperfusion (OGD/R) condition to mimic an ischemic stroke in vitro. Matrix metalloproteinases (MMP) activity was measured in endothelial cell media. Also, neuronal cell culture was performed to investigate the effect of pretreated isoflurane on the neuronal cell survival after tPA-induced injury during OGD/R. Isoflurane pretreatment prevented tPA-induced MMP-2 and MMP-9 activity and suppressed tPA-triggered LRP/NF-κB/Cox-2 signaling after OGD/R. Neuronal cells, incubated with endothelial cell conditioned medium (EC-CM) after tPA + OGD/R, showed upregulation of pro-apoptotic molecules. However, neurons incubated with isoflurane-pretreated EC-CM showed increased anti-apoptotic molecules. Our findings suggest that isoflurane pretreatment could attenuate tPA-exaggerated brain ischemic injury, by reducing tPA-induced LRP/NF-κB/Cox-2 in endothelial cells, endothelial MMP-2 and MMP-9 activation, and subsequent pro-apoptotic molecule in neurons after OGD/R.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Isoflurano/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/complicações , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Meios de Cultivo Condicionados , Ciclo-Oxigenase 2/genética , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Glucose/metabolismo , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/genética , Hemorragias Intracranianas/patologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Metaloproteinase 2 da Matriz/genética , Camundongos , NF-kappa B/genética , Neurônios/efeitos dos fármacos , Neurônios/patologia , Oxigênio/metabolismo , Receptores de LDL/genética , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/genética , Proteínas Supressoras de Tumor/genética
15.
Paediatr Anaesth ; 27(7): 695-701, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28306195

RESUMO

BACKGROUND: Caudal block has been widely used in children undergoing genitourinary surgery. However, the influence of caudal block on postoperative oliguria is unclear. AIM: The aim of this study was to assess the effect of caudal block on urinary flow through the reimplanted ureter after ureteroneocystostomy and the incidence of postoperative oliguria in infants. METHODS: This retrospective study analyzed the medical records of 121 infants aged less than 12 months who underwent bilateral ureteroneocystostomy for vesicoureteral reflux at a tertiary medical center. In all study infants, a ureteral catheter was placed in one of the two ureters in order to relieve the clinical consequences of transient ureteral obstruction and a urethral catheter was placed at the end of the ureteroneocystostomy procedure. Urinary output was assessed separately for each catheter. Logistic regression analysis was performed to identify the risk factors for oliguria from the urethral catheter. RESULTS: Among the 121 patients, 63 (52%) received caudal block (caudal block group) and 58 (48%) did not (no caudal block group). Patient characteristics, preoperative vesicoureteral reflux grade and renal function, and intraoperative profiles were comparable between the groups. The incidence of oliguria from the urethral catheter for 8 h after the surgery was significantly higher in the caudal block group than in the no caudal block group. However, the incidence of oliguria from the ureteral catheter was comparable between the groups. In multivariate analysis, oliguria from the urethral catheter was associated with caudal block, anesthesia duration, and intraoperative dexamethasone administration. The odds for oliguria was 3.069-fold greater in patients who received caudal block than in those who did not (95%CI, 1.303-7.228, P = 0.010). On the other hand, intraoperative dexamethasone reduced the risk of oliguria. CONCLUSION: Caudal block may be associated with postoperative oliguria in infants undergoing ureteroneocystostomy.


Assuntos
Anestesia Caudal/efeitos adversos , Cistostomia/efeitos adversos , Oligúria/epidemiologia , Oligúria/etiologia , Complicações Pós-Operatórias/epidemiologia , Ureter/cirurgia , Antieméticos/efeitos adversos , Estudos de Coortes , Dexametasona/efeitos adversos , Feminino , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Cateterismo Urinário , Urodinâmica , Refluxo Vesicoureteral/cirurgia
16.
Int J Med Sci ; 13(9): 701-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27648000

RESUMO

BACKGROUND: Endothelial dysfunction associated with diabetes mellitus (DM) may influence arterial vasoreactivity after arterial stimulus, such as cannulation, and cause changes in diameter and blood flow. Despite the frequent use of arterial cannulation during anesthesia and critical care, little information is available regarding vasoreactivity of the radial and ulnar arteries and its influence on underlying DM. METHODS: Forty non-DM and 40 DM patients, who required arterial cannulation during general anesthesia, were enrolled. Using duplex Doppler ultrasonography, we measured the patients' arterial diameter, peak systolic velocity, end-diastolic velocity, resistance index, and mean volume flow of both arteries at five different time points. RESULTS: After radial artery cannulation, ulnar arterial diameter and blood flow did not significantly increase in DM group, as they did in non-DM group. Ulnar arterial resistance index significantly increased in both groups, but the degree of decrease in DM group was significantly less than non-DM. CONCLUSION: Ulnar artery's ability to increase blood flow for compensating the sudden reduction of radial arterial flow in DM patients was significantly less than that in non-DM patients under general anesthesia. Such attenuated vasoreactivity of ulnar artery to compensate the reduced radial arterial flow may have to be considered in radial arterial cannulation for DM patients.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Complicações do Diabetes/fisiopatologia , Artéria Radial/fisiopatologia , Artéria Ulnar/fisiopatologia , Adulto , Cateterismo/métodos , Complicações do Diabetes/diagnóstico por imagem , Células Endoteliais/patologia , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial/diagnóstico por imagem , Artéria Ulnar/diagnóstico por imagem , Ultrassonografia Doppler Dupla
17.
Biochem Biophys Res Commun ; 464(3): 711-7, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26159927

RESUMO

Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1ß, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration.


Assuntos
NF-kappa B/antagonistas & inibidores , Sepse/terapia , Animais , Células Cultivadas , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Feminino , Células HEK293 , Células HeLa , Humanos , Células Jurkat , Lipopolissacarídeos/toxicidade , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/imunologia , Estrutura Terciária de Proteína/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Sepse/etiologia , Sepse/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/imunologia , Transcrição Gênica , Transdução Genética
18.
Sleep Breath ; 19(2): 711-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25643766

RESUMO

PURPOSE: Drug-induced sleep endoscopy (DISE) allows for direct airway observation in patients with obstructive sleep apnea. This study compared the safety profiles and efficacies of three regimens for DISE. METHODS: Sixty-six patients were randomly assigned to receive propofol alone (n = 22), a propofol-remifentanil combination (n = 22), or a dexmedetomidine-remifentanil combination (n = 22). Remifentanil was infused at a concentration of 1.5 ng·ml(-1) in the propofol-remifentanil and dexmedetomidine-remifentanil groups, whereas saline was infused in the propofol group. The propofol and propofol-remifentanil groups received propofol at a starting concentration of 1.0 µg·ml(-1), then 0.1 µg·ml(-1) increments at 5 min intervals. The dexmedetomidine-remifentanil group received 1.0 µg·kg(-1) loading dose of dexmedetomidine for 10 min and then 0.2 µg·kg(-1)·h(-1) increments at 5 min intervals. RESULTS: The incidence of oxygen desaturation was significantly higher in the propofol-remifentanil group compared with that of the dexmedetomidine-remifentanil group (77 vs. 45%, respectively, P = 0.024). Even with a maximum dose of dexmedetomidine (1.4 µg·kg(-1)·h(-1)), 50% of the dexmedetomidine-remifentanil group did not reach sufficient sedation and required additional propofol. Cough reflex occurred in five patients of propofol group and in neither of the other groups (P = 0.004). CONCLUSIONS: The propofol-remifentanil combination was associated with a higher incidence of desaturation. The dexmedetomidine-remifentanil combination was associated with inadequate sedation in one half of the patients, even though it produced less respiratory depression. Addition of remifentanil reduced the cough reflex.


Assuntos
Resistência das Vias Respiratórias/fisiologia , Sedação Consciente/métodos , Dexmedetomidina/administração & dosagem , Endoscopia/métodos , Piperidinas/administração & dosagem , Polissonografia/métodos , Propofol/administração & dosagem , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Dexmedetomidina/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Piperidinas/efeitos adversos , Propofol/efeitos adversos , Remifentanil
19.
Korean J Anesthesiol ; 77(3): 345-352, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38467466

RESUMO

BACKGROUND: Liver transplantation (LT) may be associated with massive blood loss and the need for allogeneic blood transfusion. Intraoperative blood salvage autotransfusion (IBSA) can reduce the need for allogeneic blood transfusion. This study aimed to investigate the effectiveness of blood salvage in LT. METHODS: Among 355 adult patients who underwent elective living-donor LT between January 1, 2019, and December 31, 2022, 59 recipients without advanced hepatocellular carcinoma received IBSA using Cell Saver (CS group). Based on sex, age, model for end-stage liver disease (MELD) score, preoperative laboratory results, and other factors, 118 of the 296 recipients who did not undergo IBSA were matched using propensity score (non-CS group). The primary outcome was the amount of intraoperative allogenic red blood cell (RBC) transfusion. Comparisons were made between the two groups regarding the amount of other blood components transfused and postoperative laboratory findings. RESULTS: The transfused allogeneic RBC for the CS group was significantly lower than that of the non-CS group (1,506.0 vs. 1,957.5 ml, P = 0.026). No significant differences in the transfused total fresh frozen plasma, platelets, cryoprecipitate, and estimated blood loss were observed between the two groups. The postoperative allogeneic RBC transfusion was significantly lower in the CS group than in the non-CS group (1,500.0 vs. 2,100.0 ml, P = 0.039). No significant differences in postoperative laboratory findings were observed at postoperative day 1 and discharge. CONCLUSIONS: Using IBSA during LT can effectively reduce the need for perioperative allogeneic blood transfusions without causing subsequent coagulopathy.


Assuntos
Transfusão de Sangue Autóloga , Transplante de Fígado , Doadores Vivos , Recuperação de Sangue Operatório , Humanos , Masculino , Feminino , Transplante de Fígado/métodos , Recuperação de Sangue Operatório/métodos , Estudos Retrospectivos , Transfusão de Sangue Autóloga/métodos , Pessoa de Meia-Idade , Adulto , Estudos de Coortes , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Eritrócitos/métodos , Resultado do Tratamento
20.
Front Aging Neurosci ; 16: 1292942, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38282693

RESUMO

Introduction: Any persistent degree of cognitive impairment in older adults is a concern as it can progress to dementia. This study aimed to determine the incidence and risk factors for early postoperative cognitive dysfunction (POCD) in elderly patients undergoing spine surgery. Methods: Patients were enrolled from a previous prospective observational study after screening for normal cognitive function using the Mini Mental State Examination (MMSE). Cognitive function was evaluated before surgery and at 1 week, month, and year post-surgery using MMSE and Montreal Cognitive Assessment scores (MoCA). Mild cognitive impairment (MCI) was determined using the MoCA scores adjusted for age. POCD was defined as a drop of three or more points on the MMSE 1 week post-surgery. Multivariate logistic analysis was performed to identify POCD risk factors. Results: A total of 427 patients were included. Eighty-five (20%) had pre-existing MCI. The MCI group showed lower MoCA scores at each time point (baseline, 1 week after surgery, 1 month after surgery, 1 year after surgery) compared to the non-MCI group. Those in the MCI group had a higher rate of admission to intensive care unit after surgery, postoperative delirium, and POCD 1 week post-surgery, than those in the non-MCI group (16.5% vs. 6.7%, p = 0.008; 27.1% vs. 15.8%, p = 0.024; and 18.8% vs. 8.2%, p < 0.001, respectively). Among them, 10.3% were assessed for POCD on postoperative day 7 and self-reported poor social roles and physical functioning 1 week postoperatively. Conclusion: Preoperative MCI was seen in ~20% of surgical patients aged >70 years. POCD was seen in ~20% of patients with pre-existing MCI, and ~ 10% of those without. Benzodiazepine use, significant comorbidities, pre-existing MCI, and depressive tendencies were risk factors for POCD.

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