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1.
Food Chem Toxicol ; 158: 112662, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34743013

RESUMO

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical related to the carcinogenesis of estrogen-responsive organs. Although human exposure to BPA mainly occurs via the oral route, its association with colon cancer has not been fully elucidated. We investigated the effects of BPA on the proliferation, migration, and tumor growth of colon cancer cells. BPA significantly promoted the proliferation of HT-29 human colon adenocarcinoma cells in a time- and dose-dependent manner. BPA also increased HT-29 cells migration. BPA increased the phosphorylation of extracellular signal-regulated kinase (ERK), and inhibition of the ERK pathway attenuated BPA-induced proliferation and migration. In addition, BPA reduced E-cadherin expression, a key factor impeding epithelial-to-mesenchymal transition, and increased 5-HT3 receptors expression, a major mitogenic factor. In xenograft models, tumor volume of the BPA-treated nude mice was 4.6 times that of the saline-treated group. Our findings provide primary evidence regarding the link between BPA and human colon cancer by demonstrating that BPA promotes the proliferation, migration, and tumor growth of colon cancer cells in both in vitro and in vivo models. In addition, we provided the mechanism of action of BPA, involved in the activation of the ERK pathway, the decrease in E-cadherin, and the increase in 5-HT3 receptors.

2.
J Clin Med ; 10(9)2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33922880

RESUMO

Stroke volume variation (SVV) has been used to predict fluid responsiveness; however, it remains unclear whether goal-directed fluid therapy using SVV contributes to bowel function recovery in abdominal surgery. This prospective randomized controlled trial aimed to compare bowel movement recovery in patients undergoing colon resection surgery between groups using traditional or SVV-based methods for intravenous fluid management. We collected data between March 2015 and July 2017. Bowel function recovery was analyzed based on the gas-passing time, sips of water time, and soft diet (SD) time. Finally, we analyzed data from 60 patients. There was no significant between-group difference in the patients' characteristics. Compared with the control group (n = 30), the SVV group (n = 30) had a significantly higher colloid volume and lower crystalloid volume. Moreover, the gas-passing time (77.8 vs. 85.3 h, p = 0.034) and SD time (67.6 vs. 85.1 h, p < 0.001) were significantly faster in the SVV group than in the control group. Compared with the control group, the SVV group showed significantly lower scores of pain on a numeric rating scale and morphine equivalent doses during post-anesthetic care, at 24 postoperative hours, and at 48 postoperative hours. Our findings suggested that, compared with the control group, the SVV group showed a faster postoperative SD time, reduced acute postoperative pain intensity, and lower rescue analgesics. Therefore, SVV-based optimal fluid management is expected to potentially contribute to postoperative bowel function recovery in patients undergoing colon resection surgery.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33551075

RESUMO

OBJECTIVE: Malnutrition is a well-recognized risk factor for poor prognosis and mortality. We investigated whether preoperative malnutrition diagnosed with objective nutritional scores affects 1-year mortality in patients undergoing valvular heart surgery. METHODS: In this retrospective cohort observational study, we evaluated the association among the Controlling Nutritional Status score, Prognostic Nutritional Index, and Geriatric Nutritional Risk Index with 1-year mortality in 1927 patients undergoing valvular heart surgery. We identified factors for mortality using multivariable Cox proportional hazard analysis and investigated the utility of nutritional scores for risk stratification. RESULTS: Malnutrition, as identified by a high Controlling Nutritional Status score and low Prognostic Nutritional Index and Geriatric Nutritional Risk Index, was significantly associated with higher 1-year mortality. Kaplan-Meier survival curve showed that mortality significantly increased as the severity of malnutrition increased (log-rank test, P < .001). The predicted discrimination (C-index) was 0.79 with the Controlling Nutritional Status score, 0.77 with the Prognostic Nutritional Index, and 0.73 with the Geriatric Nutritional Risk Index. Each nutritional index (Controlling Nutritional Status; hazard ratio, 1.31, 95% confidence interval, 1.21-1.42, P < .001), the European System for Cardiac Operative Risk Evaluation II (hazard ratio, 1.07, 95% confidence interval, 1.04-1.09, P < .001), and chronic kidney disease (hazard ratio, 2.26, 95% confidence interval, 1.31-3.90, P = .003) were independent risk factors for mortality. The Controlling Nutritional Status score added to the European System for Cardiac Operative Risk Evaluation II significantly increased the predictive discrimination ability for mortality (C-index 0.82, 95% confidence interval, 0.78-0.87, P = .014) compared with the Controlling Nutritional Status or European System for Cardiac Operative Risk Evaluation II alone. CONCLUSIONS: Preoperative malnutrition as assessed by objective nutritional scores was associated with 1-year mortality after valvular heart surgery. The Controlling Nutritional Status score had the highest predictive ability and, when added to the European System for Cardiac Operative Risk Evaluation II, provided more accurate risk stratification.

4.
Can J Anaesth ; 68(5): 683-692, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33532995

RESUMO

PURPOSE: Ketamine's inhibitory action on the N-methyl-D-aspartate receptor and anti-inflammatory effects may provide beneficial immunomodulation in cancer surgery. We investigated the effect of subanesthetic-dose ketamine as an adjunct to desflurane anesthesia on natural killer (NK) cell activity and inflammation in patients undergoing colorectal cancer surgery. METHODS: A total of 100 patients were randomly assigned to a control or ketamine group. The ketamine group received a bolus of 0.25 mg·kg-1 ketamine five minutes before the start of surgery, followed by an infusion 0.05 mg·kg-1·hr-1 until the end of surgery; the control group received a similar amount of normal saline. We measured NK cell activity and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) before surgery and one, 24, and 48 hr after surgery. C-reactive protein (CRP) was measured before surgery and one, three, and five days after surgery. Carcinoembryonic antigen and cancer recurrence/metastasis were assessed two years after surgery. RESULTS: The NK cell activity was significantly decreased after surgery in both groups, but the change was not different between groups in the linear mixed model analysis (P = 0.47). Changes in IL-6, TNF-α, CRP, and carcinoembryonic antigen levels were not different between groups (P = 0.27, 0.69, 0.99, and 0.97, respectively). Cancer recurrence within 2 years after surgery was similar between groups (10% vs 8%, P = 0.62). CONCLUSIONS: Intraoperative low-dose ketamine administration did not convey any favourable impacts on overall postoperative NK cell activity, inflammatory responses, and prognosis in colorectal cancer surgery patients. TRIAL REGISTRATION: www.clinicaltrial.gov (NCT03273231); registered 6 September 2017.


Assuntos
Neoplasias Colorretais , Ketamina , Neoplasias Colorretais/cirurgia , Método Duplo-Cego , Humanos , Imunomodulação , Interleucina-6 , Fator de Necrose Tumoral alfa
5.
J Thorac Cardiovasc Surg ; 161(2): 681-688.e3, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959433

RESUMO

OBJECTIVE: The association between acute kidney injury (AKI) and chronic kidney disease (CKD) remains elusive in cardiac surgery. We investigated the association between postoperative AKI and CKD development, emphasizing the intermediary role of acute kidney disease (AKD), in patients undergoing valvular heart surgery. METHODS: We assessed the occurrence of postoperative AKI (7 days postsurgery), AKD (3 months postsurgery), and CKD (12 months postsurgery) in 1386 patients. The primary outcome was the development of AKD and CKD according to AKI occurrence. Relevant risk factors of AKI, AKD, and CKD were identified through multivariable regression analysis. RESULTS: AKI occurred in 23.9% of patients with normal preoperative renal function. Even with early recovery of renal function within 3 days, AKI increased the risk of AKD (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.98-5.20, P < .001) and CKD (OR, 2.86; 95% CI, 1.68-4.86, P < .001), whereas persistent AKI further increased the risk of AKD (OR, 12.07; 95% CI, 5.56-26.21, P < .001) and CKD (OR, 10.54; 95% CI, 4.01-27.76, P < .001). We also found these relationships in patients with pre-existing renal dysfunction. Multivariable analysis identified 3-month postoperative heart failure and high right ventricular systolic pressure as independent risk factors for CKD. CONCLUSIONS: Even after early recovery, postvalvular heart surgery AKI was associated with increased risk of CKD via AKD in a graded manner related to AKI severity and persistence. Postoperative cardiac dysfunction assessed 3 months postsurgery also significantly influenced CKD development, indicating a need for close follow-up of cardiac and renal function to improve patient outcomes.


Assuntos
Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Injúria Renal Aguda/patologia , Idoso , Progressão da Doença , Feminino , Valvas Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/patologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/patologia , Fatores de Risco
6.
J Clin Med ; 8(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835896

RESUMO

Patients undergoing laparoscopic gynecologic surgery and receiving postoperative analgesia with opioids have a high risk of postoperative nausea and vomiting (PONV). We compared the antiemetic efficacy of three doses of ramosetron in this high-risk population. In this prospective, double-blind trial, 174 patients randomly received ramosetron 0.3 mg (R0.3 group; n = 58), 0.45 mg (R0.45 group; n = 58), or 0.6 mg (R0.6 group; n = 58) at the end of surgery. The primary outcome was the incidence of PONV during the first postoperative 48 h. Nausea severity, pain scores, adverse events, and patient satisfaction (1-4; 4, excellent) were assessed. The incidence of PONV was not different between groups (35%, 38%, and 35% in R0.3, R0.45, and R0.6 groups; p = 0.905). Nausea severity, pain scores, and incidence of adverse events (dizziness, headache, or sedation) were similar between groups. Compared to the R0.3 group, the R0.45 and R0.6 groups had lower incidence of premature discontinuation of fentanyl-based patient-controlled analgesia primarily because of intractable PONV (9% and 5% vs. 24%; p = 0.038), and higher satisfaction scores (3.4 ± 0.8 and 3.3 ± 0.7 vs. 2.4 ± 0.9; p = 0.005). Compared to ramosetron 0.3 mg, ramosetron 0.45 and 0.6 mg did not reduce PONV, but reduced premature discontinuation of patient-controlled analgesia and increased patient satisfaction, without increasing adverse events.

7.
Cold Spring Harb Protoc ; 2019(4)2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30131367

RESUMO

Transcriptional regulatory elements are typically found in relatively nucleosome-free genomic regions, often referred to as "open chromatin." Deoxyribonuclease I (DNase I) can digest nucleosome-depleted DNA (presumably bound by transcription factors), but DNA in nucleosomes or higher-order chromatin fibers is less accessible to the nuclease. The DNase-seq method uses high-throughput sequencing to permit the interrogation of DNase hypersensitive sites (DHSs) across the entire genome and does not require prior knowledge of histone modifications, transcription factor binding sites, or high quality antibodies to identify potentially active regions of chromatin. Here, discontinuous iodixanol gradients are used as a gentle preparation of the nuclei from Xenopus embryos. Short DNase I digestion times are followed by size selection of digested genomic DNA, yielding DHS fragments. These DNA fragments are subjected to real-time quantitative polymerase chain reaction (qPCR) and sequencing library construction. A library generation method and pipeline for analyzing DNase-seq data are also described.


Assuntos
Cromatina/metabolismo , Desoxirribonuclease I/metabolismo , Xenopus/embriologia , Animais , Embrião não Mamífero/metabolismo , Sequências Reguladoras de Ácido Nucleico , Transcrição Genética
8.
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
9.
Surg Endosc ; 31(11): 4688-4696, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28389801

RESUMO

BACKGROUND: Although laparoscopic surgery significantly reduces surgical trauma compared to open surgery, postoperative ileus is a frequent and significant complication after abdominal surgery. Unlike laparoscopic colorectal surgery, the effects of epidural analgesia on postoperative recovery after laparoscopic gastrectomy are not well established. We compared the effects of epidural analgesia to those of conventional intravenous (IV) analgesia on the recovery of bowel function after laparoscopic gastrectomy. METHOD: Eighty-six patients undergoing laparoscopic gastrectomy randomly received either patient-controlled epidural analgesia with ropivacaine and fentanyl (Epi PCA group) or patient-controlled IV analgesia with fentanyl (IV PCA group), beginning immediately before incision and continuing for 48 h thereafter. The primary endpoint was recovery of bowel function, evaluated by the time to first flatus. The balance of the autonomic nervous system, pain scores, duration of postoperative hospital stay, and complications were assessed. RESULTS: The time to first flatus was shorter in the epidural PCA group compared with the IV PCA group (61.3 ± 11.1 vs. 70.0 ± 12.3 h, P = 0.001). Low-frequency/high-frequency power ratios during surgery were significantly higher in the IV PCA group, compared with baseline and those in the epidural PCA group. The epidural PCA group had lower pain scores during the first 1 h postoperatively and required less analgesics during the first 6 h postoperatively. CONCLUSIONS: Compared with IV PCA, epidural PCA facilitated postoperative recovery of bowel function after laparoscopic gastrectomy without increasing the length of hospital stay or PCA-related complications. This beneficial effect of epidural analgesia might be attributed to attenuation of sympathetic hyperactivation, improved analgesia, and reduced opioid use.


Assuntos
Analgesia Epidural/métodos , Analgesia Controlada pelo Paciente/métodos , Gastrectomia/efeitos adversos , Íleus/induzido quimicamente , Laparoscopia/efeitos adversos , Administração Intravenosa , Adulto , Idoso , Amidas/administração & dosagem , Amidas/efeitos adversos , Analgesia Epidural/efeitos adversos , Analgesia Controlada pelo Paciente/efeitos adversos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Defecação , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Gastrectomia/métodos , Humanos , Íleus/epidemiologia , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Dor Pós-Operatória/tratamento farmacológico , Estudos Prospectivos , Recuperação de Função Fisiológica/efeitos dos fármacos , Ropivacaina
10.
Dev Cell ; 40(6): 595-607.e4, 2017 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-28325473

RESUMO

The interplay between transcription factors and chromatin dictates gene regulatory network activity. Germ layer specification is tightly coupled with zygotic gene activation and, in most metazoans, is dependent upon maternal factors. We explore the dynamic genome-wide interactions of Foxh1, a maternal transcription factor that mediates Nodal/TGF-ß signaling, with cis-regulatory modules (CRMs) during mesendodermal specification. Foxh1 marks CRMs during cleavage stages and recruits the co-repressor Tle/Groucho in the early blastula. We highlight a population of CRMs that are continuously occupied by Foxh1 and show that they are marked by H3K4me1, Ep300, and Fox/Sox/Smad motifs, suggesting interplay between these factors in gene regulation. We also propose a molecular "hand-off" between maternal Foxh1 and zygotic Foxa at these CRMs to maintain enhancer activation. Our findings suggest that Foxh1 functions at the top of a hierarchy of interactions by marking developmental genes for activation, beginning with the onset of zygotic gene expression.


Assuntos
Endoderma/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Mesoderma/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus/embriologia , Xenopus/genética , Animais , Blástula/metabolismo , Fase de Clivagem do Zigoto/metabolismo , Proteínas Correpressoras/metabolismo , Embrião não Mamífero/metabolismo , Endoderma/embriologia , Elementos Facilitadores Genéticos/genética , Fatores de Transcrição Forkhead/genética , Genoma , Histonas/metabolismo , Lisina/metabolismo , Mesoderma/embriologia , Metilação , Proteína Nodal/metabolismo , Ligação Proteica/genética , RNA Polimerase II/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sequências Reguladoras de Ácido Nucleico/genética , Análise de Sequência de RNA , Transdução de Sinais/genética , Transcrição Genética , Xenopus/metabolismo , Proteínas de Xenopus/genética
11.
Crit Care ; 21(1): 3, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28057030

RESUMO

BACKGROUND: Patients with infective endocarditis (IE) have an elevated risk of renal dysfunction because of extensive systemic inflammation and use of nephrotoxic antibiotics. In this randomized, placebo-controlled trial, we investigated whether perioperative sodium bicarbonate administration could attenuate postoperative renal dysfunction in patients with IE undergoing cardiac surgery. METHODS: Seventy patients randomly received sodium chloride (n = 35) or sodium bicarbonate (n = 35). Sodium bicarbonate was administered as a 0.5 mmol/kg loading dose for 1 h commencing with anesthetic induction, followed by a 0.15 mmol/kg/h infusion for 23 h. The primary outcome was peak serum creatinine (SCr) level during the first 48 h postoperatively. The incidence of acute kidney injury, SCr level, estimated glomerular filtration rate, and major morbidity endpoints were assessed postoperatively. RESULTS: The peak SCr during the first 48 h postoperatively (bicarbonate vs. CONTROL: 1.01 (0.74, 1.37) mg/dl vs. 0.88 (0.76, 1.27) mg/dl, P = 0.474) and the incidence of acute kidney injury (bicarbonate vs. CONTROL: 29% vs. 23%, P = 0.584) were similar in both groups. The postoperative increase in SCr above baseline was greater in the bicarbonate group than in the control group on postoperative day 2 (0.21 (0.07, 0.33) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P = 0.028) and postoperative day 5 (0.23 (0.08, 0.36) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P = 0.017). CONCLUSIONS: Perioperative sodium bicarbonate administration had no favorable impact on postoperative renal function and outcomes in patients with IE undergoing cardiac surgery. Instead, it was associated with possibly harmful renal effects, illustrated by a greater increase in SCr postoperatively, compared to control. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01920126 . Registered on 31 July 2013.


Assuntos
Injúria Renal Aguda/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/métodos , Endocardite/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Bicarbonato de Sódio/administração & dosagem , Injúria Renal Aguda/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Endocardite/cirurgia , Feminino , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Estudos Prospectivos , República da Coreia , Bicarbonato de Sódio/uso terapêutico , Cloreto de Sódio/administração & dosagem
12.
Korean J Crit Care Med ; 32(4): 356-358, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31723657
14.
Kidney Int ; 89(5): 1164-1165, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27083294
15.
Am J Ther ; 23(2): e369-76, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-24832388

RESUMO

Sympathetic hyperactivation during tracheal intubation prolongs the QT interval and increases the risk of arrhythmias. We investigated if dexmedetomidine pretreatment affected autonomic nervous system balance and QT intervals during intubation. Sixty-six patients were randomized to receive 1.0 µg/kg fentanyl (group F, n = 22), 0.5 µg/kg dexmedetomidine (group D0.5, n = 22), or 1.0 µg/kg dexmedetomidine (group D1.0, n = 22) before induction. Autonomic nervous system balance was assessed by the ratio of low-frequency/high-frequency (LF/HF) power for heart rate variability at baseline (T0), before intubation (T1), and after intubation (T2). QT intervals were corrected by the Bazett's formula (QTc) and compared at baseline, before intubation, and 1, 2, and 3 minutes after intubation. The LF/HF ratio was higher after intubation compared with that at T0 in group F (P < 0.001). There were no significant changes in groups D0.5 and D1.0. The LF/HF ratio was significantly higher in group F compared with those in groups D0.5 and D1.0 after intubation (7.9 vs. 2.1 and 2.5; P < 0.001). The heart rate was increased for 3 minutes after intubation in group F, whereas only for 1 minute after intubation in groups D0.5 and D1.0, compared with that at baseline. More patients in group F had QTc greater than 440 ms compared with that in group D0.5 or D1.0 (8 vs. 1 and 2; P = 0.005) at 1 minute after intubation. In contrast to 1.0 µg/kg fentanyl, pretreatment with 0.5 or 1.0 µg/kg dexmedetomidine suppressed sympathetic hyperactivity and attenuated QTc prolongation during intubation.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Intubação Intratraqueal , Adulto , Eletrocardiografia/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Nervoso Simpático/fisiologia
16.
Kidney Int ; 89(3): 693-700, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26444030

RESUMO

Acute kidney injury (AKI) following cardiac surgery is closely interrelated with hemodynamic instability and sympathetic activity, and adversely influences prognosis. Here, we investigated in a randomized placebo-controlled trial whether dexmedetomidine, an α2 adrenoreceptor agonist, could prevent AKI after valvular heart surgery. Two hundred patients undergoing valvular heart surgery were randomly assigned to equal placebo or treatment groups. Dexmedetomidine was infused at a rate of 0.4 µg/kg/h starting immediately after anesthetic induction and continuing for 24 h after surgery. We then assessed the incidence of AKI during the first 48 postoperative hours, hemodynamic variables, and a composite of major morbidity end points. The incidence of AKI, based on Acute Kidney Injury Network criteria, was significantly lower in the treatment group compared with the control group (14 vs. 33%). The dexmedetomidine group exhibited a significantly lower incidence of a composite of major morbidity end points (21 vs. 38%) and a significantly shorter length of intensive care unit stay (3 [2, 3] days vs. 3 [2, 4] days) compared with the control group. Thus, perioperative infusion of dexmedetomidine effectively reduced both the incidence and severity of AKI, and improved outcome in patients undergoing valvular heart surgery without untoward hemodynamic side effects.


Assuntos
Injúria Renal Aguda/prevenção & controle , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Dexmedetomidina/administração & dosagem , Doenças das Valvas Cardíacas/cirurgia , Valvas Cardíacas/cirurgia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Idoso , Dexmedetomidina/efeitos adversos , Esquema de Medicação , Feminino , Doenças das Valvas Cardíacas/fisiopatologia , Valvas Cardíacas/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Incidência , Infusões Parenterais , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
17.
BMC Anesthesiol ; 15: 129, 2015 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-26415531

RESUMO

BACKGROUND: Pneumoperitoneum-induced oxidative stress and organ injury are known to be associated with nitric oxide (NO) inactivation. Because arginase competes with NO synthase (NOS) for a common substrate, L-arginine, arginase inhibition may increase NO bioavailability. Therefore, we evaluated the ability of the arginase inhibitor, 2 (S)-amino-6-boronohexanoic acid (ABH), to attenuate pneumoperitoneum-induced decrease of NO bioavailability and lung injury. METHODS: Thirty rats were randomly divided into the following groups: 1) the PP-ABH group received a subcutaneous injection of ABH (5 mg/kg) 1 h before induction of pneumoperitoneum (insufflation to intraperitoneal pressure of 15 mmHg for 60 min); 2) the PP group received saline by subcutaneous injection 1 h before induction of pneumoperitoneum; and 3) the control group received saline by subcutaneous injection before a sham procedure with no gas insufflation. After desufflation, blood was collected to determine levels of plasma nitrite, NOS, inflammatory cytokines, and malondialdehyde, a marker of oxidative stress. Lung tissue was obtained for histological evaluation. RESULTS: We found that plasma nitrite levels were lower in the PP group and higher in the PP-ABH group, compared with controls (P <0.01 and P <0.05, respectively). In the PP group, endothelial NOS activity was decreased and inducible NOS activity was increased compared with the PP-ABH and control groups. Malondialdehyde levels increased 3-fold in the PP group and 2-fold in the PP-ABH group compared with controls. Tumor necrosis factor-α, interleukin-6, and interleukin-1ß levels were elevated in the PP group compared to the control group, but the increase in cytokine production was attenuated or blocked in the PP-ABH group. Lung injury scores were 4.8-fold higher in the PP group and 2-fold higher in the PP-ABH group compared with controls (P <0.001 and P <0.01, respectively). DISCUSSION: Pneumoperitoneum decreases NO bioavailability and increases the inflammation cytokines, resulting in organ injuries. Inhibition of arginase activity could maintain NO bioavailability by attenuating pneumoperitoneum-induced changes in NOS activity. In addition, arginase inhibition attenuated the oxidative stress and inflammation and decreased the severity of lung injury caused by pneumoperitoneum. CONCLUSIONS: By increasing NO bioavailability and suppressing oxidative stress and inflammation, pretreatment with an arginase inhibitor may protect against lung injury caused by pneumoperitoneum.


Assuntos
Aminocaproatos/farmacologia , Arginase/antagonistas & inibidores , Compostos de Boro/farmacologia , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Pneumoperitônio/complicações , Aminocaproatos/administração & dosagem , Animais , Compostos de Boro/administração & dosagem , Citocinas/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Inflamação/etiologia , Injeções Subcutâneas , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Pneumoperitônio/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
18.
Medicine (Baltimore) ; 94(24): e959, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26091461

RESUMO

Sympathetic hyperactivation is one of the causes of postoperative ileus, which occurs frequently after abdominal surgery and adversely influences the patient's prognosis. We aimed to investigate whether dexmedetomidine (DEX) could attenuate postoperative ileus in patients undergoing laparoscopic gastrectomy. Ninety-two patients were randomized to the control (n = 46) or DEX group (n = 46). DEX was administered at a loading dose of 0.5 µg/kg for 10 minutes, followed by an infusion rate of 0.4 µg/kg/h from insufflation of the pneumoperitoneum to the end of surgery. The primary goal was to compare postoperative bowel movements by evaluating the time to first flatus. The balance of the autonomic nervous system, duration of postoperative hospital stay, and pain scores were assessed. The time to first flatus was shorter in the DEX group compared with the control group (67.2 ± 16.8 hours vs 79.9 ± 15.9 hours, P < 0.001). The low-frequency/high-frequency power ratio during pneumoperitoneum increased in the control group, compared with baseline values and the DEX group. The length of postoperative hospital stay was shorter in the DEX group compared with the control group (5.4 ± 0.7 days vs 5.8 ± 1.1 days, P = 0.04). Patients in the DEX group had lower pain scores and required fewer analgesics at 1 hour postoperatively. DEX facilitated bowel movements and reduced the length of hospital stay in patients undergoing laparoscopic gastrectomy. This may be attributed to the sympatholytic and opioid-sparing effects of DEX.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Dexmedetomidina/uso terapêutico , Gastrectomia/efeitos adversos , Íleus/tratamento farmacológico , Íleus/etiologia , Laparoscopia/efeitos adversos , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Adulto , Idoso , Dexmedetomidina/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos
19.
BMC Anesthesiol ; 15: 23, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25780349

RESUMO

BACKGROUND: Contrast medium used for radiologic tests can decrease renal function. However there have been few studies on contrast-associated acute kidney injury in intensive care unit (ICU) patients. The objective of this study was to evaluate the incidence, characteristics, and outcome of contrast-associated acute kidney injury (CA-AKI) patients using the Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) criteria in critically ill patients in the ICU. METHODS: We conducted a retrospective study of adult patients who underwent contrast-enhanced radiologic tests from January 2011 to December 2012 in a 30-bed medical ICU and a 24-bed surgical ICU. RESULTS: The study included 335 patients, and the incidence of CA-AKI was 15.5%. The serum creatinine and estimated glomerular filtration rate values in the CA-AKI patients did not recover even at discharge from the hospital compared with the values prior to the contrast use. Among 52 CA-AKI patients, 55.8% (n = 29) had pre-existing kidney injury and 44.2% (n = 23) did not. The CA-AKI patients were divided into risk (31%), injury (31%), and failure (38%) by the RIFLE classification. The percentage of patients in whom AKI progressed to a more severe form (failure, loss, end-stage kidney disease) increased from 38% to 45% during the hospital stay, and the recovery rate of AKI was 17% at the time of hospital discharge. Because the Acute Physiology and Chronic Health Evaluation (APACHE) II score was the only significant variable inducing CA-AKI, higher APACHE II scores were associated with a higher risk of CA-AKI. The ICU and hospital mortality of patients with CA-AKI was significantly higher than in patients without CA-AKI. CONCLUSIONS: CA-AKI is associated with increases in hospital mortality, and can be predicted by the APACHE score. TRIAL REGISTRATION: NCT01807195 on March. 06. 2013.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Meios de Contraste/efeitos adversos , Estado Terminal/epidemiologia , Unidades de Terapia Intensiva , Falência Renal Crônica/epidemiologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/fisiopatologia , Idoso , Creatinina/sangue , Estado Terminal/mortalidade , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Mortalidade Hospitalar , Humanos , Incidência , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
20.
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
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