RESUMO
Endosomal trafficking of TrkA is a critical process for nerve growth factor (NGF)-dependent neuronal cell survival and differentiation. The small GTPase ADP-ribosylation factor 6 (Arf6) is implicated in NGF-dependent processes in PC12 cells through endosomal trafficking and actin cytoskeleton reorganization. However, the regulatory mechanism for Arf6 in NGF signaling is largely unknown. In this study, we demonstrated that EFA6A, an Arf6-specific guanine nucleotide exchange factor, was abundantly expressed in PC12 cells and that knockdown of EFA6A significantly inhibited NGF-dependent Arf6 activation, TrkA recycling from early endosomes to the cell surface, prolonged ERK1/2 phosphorylation, and neurite outgrowth. We also demonstrated that EFA6A forms a protein complex with TrkA through its N-terminal region, thereby enhancing its catalytic activity for Arf6. Similarly, we demonstrated that EFA6A forms a protein complex with TrkA in cultured dorsal root ganglion (DRG) neurons. Furthermore, cultured DRG neurons from EFA6A knockout mice exhibited disturbed NGF-dependent TrkA trafficking compared with wild-type neurons. These findings provide the first evidence for EFA6A as a key regulator of NGF-dependent TrkA trafficking and signaling.
Assuntos
Fator 6 de Ribosilação do ADP , Fatores de Ribosilação do ADP , Endossomos , Fatores de Troca do Nucleotídeo Guanina , Fator de Crescimento Neural , Crescimento Neuronal , Receptor trkA , Animais , Camundongos , Ratos , Fatores de Ribosilação do ADP/metabolismo , Fatores de Ribosilação do ADP/genética , Endossomos/metabolismo , Gânglios Espinais/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Camundongos Knockout , Fator de Crescimento Neural/metabolismo , Células PC12 , Transporte Proteico , Receptor trkA/metabolismoRESUMO
The aim of this study was to analyze the population pharmacokinetics of total and unbound concentrations of prophylactic cefazolin (CFZ) in patients with prostatectomy or nephrectomy. We also aimed to calculate a pharmacodynamics target unbound concentration that exceeded the minimum inhibitory concentration (MIC), to design an effective dosing regimen. Briefly, 614 total concentration and 610 unbound concentration samples from 152 individuals were evaluated, using a nonlinear mixed-effects model. The obtained pharmacodynamics index target value reflected the probability of maintaining CFZ unbound trough concentrations exceeding MIC90, 0.5 mg/L, and MIC50, and 1.0 mg/L, to account for methicillin-susceptible Staphylococcus aureus (MSSA) or Escherichia coli. Population pharmacokinetics were estimated using a two-compartment model with nonlinear protein binding. Unbound systemic clearance (CL) was significantly associated with creatinine clearance, while the maximum protein-binding constant was significantly associated with albumin levels. The probability of achieving an unbound concentration exceeding the MIC50 for E. coli or MIC90 for MSSA in a patient with normal renal function following a 1 g CFZ infusion over 15 min was above 90% at 3 h after the initial dose. Our findings indicated that population pharmacokinetic parameters are useful for determining unbound CFZ pharmacokinetics and evaluating intraoperative CFZ redosing intervals.
Assuntos
Antibacterianos , Cefazolina , Escherichia coli , Testes de Sensibilidade Microbiana , Nefrectomia , Prostatectomia , Humanos , Cefazolina/farmacocinética , Cefazolina/sangue , Cefazolina/uso terapêutico , Masculino , Antibacterianos/farmacocinética , Antibacterianos/sangue , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Idoso , Feminino , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Adulto , Ligação Proteica , Idoso de 80 Anos ou maisRESUMO
The purpose of this study was to investigate the population pharmacokinetics of prophylactic flomoxef based on serum and liver tissue concentrations and to demonstrate a pharmacodynamic target concentration in the serum and liver tissue exceeding the MIC in order to design an effective dosing regimen. Serum samples (n = 210) and liver tissue samples (n = 29) from 43 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index target value was regarded as the probability of maintaining flomoxef serum trough and liver tissue concentrations exceeding the MIC90 values, 0.5 mg/L and 1.0 mg/L, for Escherichia coli and methicillin-susceptible Staphylococcus aureus, respectively. The final population pharmacokinetic model was a two-compartment model with linear elimination. Creatinine clearance (CLCR) was identified as a significant covariate influencing total clearance when CLCR was less than 60 mL/min. The probability of achieving concentrations in the serum and liver tissue exceeding the MIC90 for E. coli or methicillin-susceptible S. aureus for a 1 g bolus dose was above 90% at 2 h after the initial dose. Our findings suggest that population pharmacokinetic parameters are helpful for evaluating flomoxef pharmacokinetics and determining intraoperative flomoxef redosing intervals.
Assuntos
Escherichia coli , Staphylococcus aureus , Antibacterianos/uso terapêutico , Cefalosporinas , Humanos , Fígado/cirurgia , Meticilina , Testes de Sensibilidade MicrobianaRESUMO
[Figure: see text].
Assuntos
Diafragma/metabolismo , Inflamação/metabolismo , Linfangiogênese/efeitos dos fármacos , Vasos Linfáticos/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo , Linfócitos T/metabolismo , Tromboxano A2/metabolismo , Animais , Células Cultivadas , Diafragma/imunologia , Modelos Animais de Doenças , Humanos , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/fisiopatologia , Lipopolissacarídeos , Vasos Linfáticos/metabolismo , Macrófagos Peritoneais/imunologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Transdução de Sinais , Linfócitos T/imunologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fator D de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Preanesthetic medication is important to eliminate surgical anxiety in pediatric patients and facilitate their smooth transfer to the operating room. Midazolam is the most commonly used preanesthetic medication. However, it has been reported that the sedative effect varies from patient to patient. In this study, the pharmacokinetics of midazolam were examined, and the aim was to assess the factors affecting the quality of sedation. METHODS: The participants were children ranging in age from 6 months to 8 years scheduled for surgery. Midazolam 0.5 mg/kg was administered orally 30 min before entering the operating room, and the sedation level was evaluated at the time of mask application. Blood was collected after slow induction, and the serum concentration of midazolam was measured using high-performance liquid chromatography. RESULTS: A total of 98 patients were registered. There was no difference in serum concentrations between the effective sedation group and the ineffective sedation group (48.0 vs. 49.1 ng/mL), regardless of the effect of midazolam. Percentages of ineffective sedation by age (0 to 7 years) were 66.6%, 60%, 33.3%, 11.1%, 0%, 0%, 12.5%, and 0%, respectively. On multivariate logistic regression analysis, siblings (OR = 3.9, CI: 1.1-14.0, p = .03) and age (OR = 3.2, CI:1.2-8.5, p = .02) were related to an insufficient sedative effect. CONCLUSION: The serum concentration of oral midazolam reached effective levels even in patients in whom the sedative effect was inadequate. It is important to manage the perioperative period with appropriate concurrent premedication taking into account patient age and social background characteristics. CLINICAL TRIAL REGISTRATION: Clinical trial registry: UMIN R000052504.
Assuntos
Anestesia , Medicação Pré-Anestésica , Administração Oral , Ansiedade , Criança , Pré-Escolar , Método Duplo-Cego , Humanos , Hipnóticos e Sedativos , Lactente , Recém-Nascido , Midazolam , Medicação Pré-Anestésica/métodosRESUMO
INTRODUCTION: This study was conducted to evaluate the population pharmacokinetics of prophylactic cefmetazole sodium (CMZ) based on the serum concentrations and establish a pharmacodynamics target concentration exceeding the minimum inhibitory concentration (MIC) to design the re-dosing interval. METHODS: Serum (n = 362) samples from 107 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index obtained was regarded as the probability of maintaining CMZ serum trough exceeding the minimal inhibitory concentration (MIC) of 2 mg/L. This MIC was chosen to account for methicillin-susceptible Staphylococcus aureus (MSSA), E. coli, and Klebsiella pneumoniae RESULTS: The final population pharmacokinetic model was a two-compartment model with linear elimination. Creatinine clearance and body weight were identified as significant covariates influencing the central clearance and volume of distribution in the central compartment. The probability of achieving serum concentrations exceeding the MIC90 for MSSA, E. coli, and Klebsiella pneumoniae for a 1 g dose with a 10 min intravenous infusion was above 90% except for good renal function (CLcr ⧠95 mL/min) at 2 h after the initial dose. For patients with good renal function (CLcr ⧠95 mL/min), a CMZ of 2 g re-dosing interval seemed necessary to meet the achievement probability. In patients with impaired renal function (CLcr ≤20 mL/min), the probability of achievement exceeded 90% even when the dosing interval was extended to 8 h. CONCLUSIONS: We evaluated re-dosing intervals based on the population pharmacokinetics. Re-dosing intervals should be determined based on renal function.
Assuntos
Cefmetazol , Procedimentos Cirúrgicos do Sistema Digestório , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli , Humanos , Testes de Sensibilidade Microbiana , Staphylococcus aureusRESUMO
The cytohesin proteins, consisting of four closely related members (cytohesins-1, -2, -3, and -4), are a subfamily of the Sec7 domain-containing guanine nucleotide exchange factors for ADP ribosylation factors (Arfs), which are critical regulators of membrane trafficking and actin cytoskeleton remodeling. Recent advances in molecular biological techniques and the development of a specific pharmacological inhibitor for cytohesins, SecinH3, have revealed the functional involvement of the cytohesin-Arf pathway in diverse neuronal functions from the formation of axons and dendrites, axonal pathfinding, and synaptic vesicle recycling, to pathophysiological processes including chronic pain and neurotoxicity induced by proteins related to neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer's disease. Here, we review the physiological and pathological roles of the cytohesin-Arf pathway in neurons and discuss the future directions of this research field.
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Fatores de Ribosilação do ADP , Moléculas de Adesão Celular , Fatores de Ribosilação do ADP/metabolismo , Moléculas de Adesão Celular/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Neurônios/metabolismoRESUMO
Group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, in the spinal cord are implicated in nociceptive transmission and plasticity through G protein-mediated second messenger cascades leading to the activation of various protein kinases such as extracellular signal-regulated kinase (ERK). In this study, we demonstrated that cytohesin-2, a guanine nucleotide exchange factor for ADP ribosylation factors (Arfs), is abundantly expressed in subsets of excitatory interneurons and projection neurons in the superficial dorsal horn. Cytohesin-2 is enriched in the perisynapse on the postsynaptic membrane of dorsal horn neurons and forms a protein complex with mGluR5 in the spinal cord. Central nervous system-specific cytohesin-2 conditional knockout mice exhibited reduced mechanical allodynia in inflammatory and neuropathic pain models. Pharmacological blockade of cytohesin catalytic activity with SecinH3 similarly reduced mechanical allodynia and inhibited the spinal activation of Arf6, but not Arf1, in both pain models. Furthermore, cytohesin-2 conditional knockout mice exhibited reduced mechanical allodynia and ERK1/2 activation following the pharmacological activation of spinal mGluR1/5 with 3,5-dihydroxylphenylglycine (DHPG). The present study suggests that cytothesin-2 is functionally associated with mGluR5 during the development of mechanical allodynia through the activation of Arf6 in spinal dorsal horn neurons.
Assuntos
Fator 6 de Ribosilação do ADP/metabolismo , Proteínas Ativadoras de GTPase/genética , Hiperalgesia/genética , Neuralgia/genética , Células do Corno Posterior/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Medula Espinal/metabolismo , Fator 1 de Ribosilação do ADP/efeitos dos fármacos , Fator 1 de Ribosilação do ADP/metabolismo , Fator 6 de Ribosilação do ADP/efeitos dos fármacos , Animais , Proteínas Ativadoras de GTPase/antagonistas & inibidores , Proteínas Ativadoras de GTPase/metabolismo , Hiperalgesia/metabolismo , Inflamação/genética , Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/farmacologia , Camundongos , Camundongos Knockout , Neuralgia/metabolismo , Densidade Pós-Sináptica/metabolismo , Células do Corno Posterior/efeitos dos fármacos , Receptor de Glutamato Metabotrópico 5/agonistas , Receptores de Glutamato Metabotrópico/agonistas , Medula Espinal/efeitos dos fármacos , Corno Dorsal da Medula Espinal , Triazóis/farmacologiaRESUMO
OBJECTIVE: This study investigated the incidence and risk factors of postoperative delirium (POD) after transcatheter aortic valve replacement (TAVR) and to evaluate the association between preoperative conditions, particularly frailty, and POD. DESIGN: Observational, case-control study. SETTING: Single-center university hospital. PARTICIPANTS: The study comprised 124 patients who underwent TAVR and were divided into the following two groups: group D (patients diagnosed with POD) and group C (patients without POD). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients (21.7%) developed POD (95% confidence interval 14.9%-30.1%). POD was defined as a diagnosis of delirium using the Confusion Assessment Method for Intensive Care Unit scale during the patients' intensive care unit stay. Preoperative and postoperative data of patient characteristics were obtained from their medical records. A multivariate logistic regression analysis was performed using variables associated with POD incidence. Frailty scores were significantly higher in group D than in group C. The distance covered in the six-minute walk test (6MD) was significantly shorter in group D than in group C. The risk of developing POD was significantly higher in patients with a 6MD shorter than 220 m. Multivariate logistic regression analysis showed that a shorter 6MD was an independent risk factor for POD (odds ratio 5.66; pâ¯=â¯0.004). CONCLUSION: In the present study, POD was seen in 21.7% of the patients who underwent TAVR. A 6MD shorter than 220 m was an independent preoperative risk factor for POD. For patients at high risk of POD, more careful management in the perioperative period may reduce POD.
Assuntos
Delírio , Substituição da Valva Aórtica Transcateter , Valva Aórtica , Estudos de Casos e Controles , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Teste de CaminhadaRESUMO
Calcitonin gene-related peptide (CGRP) regulates inflammation via signaling through receptor activity-modifying protein (RAMP) 1. Here, we investigated the role of RAMP1 signaling in growth of lymphatic vessels during inflammation. Lymphangiogenesis in the diaphragm of RAMP1-deficient (-/-) mice or their wild-type (WT) counterparts was induced by repeated intraperitoneal injection of lipopolysaccharide (LPS). Compared with WT mice, LPS-induced lymphangiogenesis in RAMP1-/- mice was suppressed. This was accompanied by the reduced expression of vascular endothelial growth factor (VEGF)-C and VEGF-D. The number of CD4+ cells in diaphragm tissue from WT mice was greater than RAMP1-/- mice. Removing CD4+ cells attenuated lymphangiogenesis and expression of VEGF-C and VEGF-D. CD4+ cells isolated from RAMP1-/- mice exhibited reduced expression of VEGF-C and VEGF-D. The number of CD11b+ cells from RAMP1-/- mice was higher than WT mice and was associated with the upregulated expression of genes related to pro-inflammatory macrophage phenotype and downregulation of reparative macrophage phenotype-related expression. When fluorescein isothiocyanate (FITC)-dextran was injected into the peritoneal cavity, the amount of residual FITC-dextran in WT mice was lower than that in RAMP1-/- mice. The present results suggest that RAMP1 signaling in immune cells plays a critical role in inflammation-related lymphangiogenesis; therefore, it represents a novel target for controlling lymphangiogenesis.
Assuntos
Inflamação , Linfangiogênese , Proteína 1 Modificadora da Atividade de Receptores , Animais , Diafragma/metabolismo , Inflamação/genética , Inflamação/metabolismo , Linfangiogênese/genética , Linfangiogênese/fisiologia , Vasos Linfáticos/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteína 1 Modificadora da Atividade de Receptores/genética , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Transdução de Sinais/genética , Linfócitos T/metabolismo , Fatores de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: While many patients with lower limb ischemia also have severe infections, few studies have investigated whether the presence of preoperative sepsis affects patient prognosis following lower limb amputation (LLA). Therefore, we investigated the factors (including sepsis as defined in SEPSIS-3) that contribute to the acute mortality rate in patients who underwent LLA due to arteriosclerosis obliterans (ASO) or diabetes mellitus (DM). METHODS: In this retrospective, single-center, 10-year chart review study, 122 adult patients who underwent LLA due to ASO and/or DM were identified from 56,438 surgery cases. Patient characteristics, including co-morbidities, surgical conditions, the presence/absence of sepsis, and acute physiological condition after surgery, were investigated in patients who died within 30 days of LLA and those who survived. Univariate analysis between groups was performed using the chi-square test. Comparisons of age and American Society of Anesthesiologists-Physical Status classification between groups were performed using the Mann-Whitney U test. Risk factors for 30-day mortality after LLA were examined using stepwise logistic regression (backward elimination). Statistical results were considered significant at P < 0.05. RESULTS: Eight cases of mortality (6.6%) were found; we identified the causes as sepsis, myocardial infarction, fatal arrhythmia, and mesenteric artery occlusive disease in 5 (62.5%), 1 (12.5%), 1 (12.5%), and 1 (12.5%) cases, respectively. Using univariate analysis, we identified that age (≥74), delirium, sepsis, intensive care unit admission, non-DM (ASO only), hemodialysis, and acute kidney injury were significantly higher in the mortality group. In logistic regression analysis, non-DM (odds ratio [OR]: 35.2, 95% confidence interval [CI]: 2.8-432) and sepsis (OR: 80.7, 95% CI: 6.7-959) were potential risk factors for 30-day mortality. CONCLUSIONS: This study suggests that cases resulting in amputation due to ASO pathology alone might have poor prognosis and that preoperative sepsis can increase perioperative mortality; hence, the decision to amputate must be considered before the development of sepsis.
Assuntos
Amputação Cirúrgica/mortalidade , Arteriosclerose Obliterante/cirurgia , Diabetes Mellitus/cirurgia , Angiopatias Diabéticas/cirurgia , Extremidade Inferior/cirurgia , Sepse/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Retrospectivos , Fatores de RiscoRESUMO
In the original publication of the article, the acknowledgment section was not included and provided in this correction.
RESUMO
We report successful awake intubation in a morbidly obese patient (body mass index of 61.2) using an epidural catheter inserted through the external forceps channel of the fiberscope for delivery of local anesthetic. Direct application of local anesthetic to the pharyngolaryngeal area and proximal tracheal, through the use of a relatively firm epidural catheter. We conclude that awake intubation can be achieved by this method which spares the subsequent use of any sedative drugs.
Assuntos
Anestesia Epidural , Obesidade Mórbida , Tecnologia de Fibra Óptica , Humanos , Intubação Intratraqueal , Obesidade Mórbida/complicações , VigíliaRESUMO
Cerebral Oximetry by Near-infrared Spectroscopy (NIRS) has been used in cardiovascular anesthesia, but there was no guideline of regional cerebral oxygen saturation measured by cerebral oximetry by NIRS. This guideline provides recommendations applicable to patients at a risk of developing cerebral ischemia in cardiovascular surgery. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances, and should not replace clinical judgment. The Japanese Society of Cardiovascular Anesthesiologists (JSCVA) Task Force on Guidelines make an effort to ensure that the guideline writing committee contains broad views in using cerebral oximetry. Adherence to recommendations could be enhanced by shared decision making between healthcare providers and patients. This guideline was focused on cerebral oximetry of pediatric and adult cardiovascular disease. We hope this guideline would play an important role in using cerebral oximetry by measured NIRS.
Assuntos
Anestesia em Procedimentos Cardíacos/métodos , Oximetria/métodos , Oxigênio/análise , Adulto , Anestesiologistas , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular , Criança , Humanos , Japão , Espectroscopia de Luz Próxima ao Infravermelho/métodosRESUMO
Cytohesin-2 is a member of the guanine nucleotide exchange factors for ADP ribosylation factor 1 (Arf1) and Arf6, which are small GTPases that regulate membrane traffic and actin dynamics. In this study, we first demonstrated that cytohesin-2 localized to the plasma membrane and vesicles in various subcellular compartment in hippocampal neurons by immunoelectron microscopy. Next, to understand the molecular network of cytohesin-2 in neurons, we conducted yeast two-hybrid screening of brain cDNA libraries using cytohesin-2 as bait and isolated pallidin, a component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) involved in endosomal trafficking. Pallidin interacted specifically with cytohesin-2 among cytohesin family members. Glutathione S-transferase pull-down and immunoprecipitation assays further confirmed the formation of a protein complex between cytohesin-2 and pallidin. Immunofluorescence demonstrated that cytohesin-2 and pallidin partially colocalized in various subsets of endosomes immunopositive for EEA1, syntaxin 12, and LAMP2 in hippocampal neurons. Knockdown of pallidin or cytohesin-2 reduced cytoplasmic EEA1-positive early endosomes. Furthermore, knockdown of pallidin increased the total dendritic length of cultured hippocampal neurons, which was rescued by co-expression of wild-type pallidin but not a mutant lacking the ability to interact with cytohesin-2. In contrast, knockdown of cytohesin-2 had the opposite effect on total dendritic length. The present results suggested that the interaction between pallidin and cytohesin-2 may participate in various neuronal functions such as endosomal trafficking and dendritic formation in hippocampal neurons. Cover Image for this issue: doi: 10.1111/jnc.14197.
Assuntos
Proteínas de Transporte/fisiologia , Dendritos/fisiologia , Endossomos/fisiologia , Proteínas Ativadoras de GTPase/fisiologia , Lectinas/fisiologia , Neurônios/fisiologia , Animais , Proteínas de Transporte/genética , Membrana Celular/metabolismo , Células Cultivadas , Vesículas Citoplasmáticas/metabolismo , Dendritos/ultraestrutura , Endossomos/genética , Proteínas Ativadoras de GTPase/genética , Técnicas de Silenciamento de Genes , Glutationa Transferase/metabolismo , Células HeLa , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Lectinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Neurônios/ultraestruturaRESUMO
Early extubation in the operating room after congenital open-heart surgery is feasible, but extubation in the intensive care unit after the operation remains common practice at many institutions. The purpose of this study was to evaluate retrospectively the adequacy of our early-extubation strategy and exclusion criteria through analysis based on the Risk Adjustment in Congenital Heart Surgery method (RACHS-1).This retrospective analysis included 359 cases requiring cardiopulmonary bypass (male, 195; female, 164; weight > 3.0 kg; aged 1 month to 18 years). Neonates and preoperatively intubated patients were excluded. Other exclusion criteria included severe preoperative pulmonary hypertension, high-dose catecholamine requirement after cardiopulmonary bypass, delayed sternal closure, laryngomalacia, serious bleeding, and delayed awakening. The early-extubation rates were compared between age groups and RACHS-1 classes.Overall, 83% of cases (298/359) were extubated in the operating room, classified by RACHS-1 categories as follows: 1, 59/59 (100%); 2, 164/200 (84%); 3, 61/78 (78%); and 4-6, 10/22 (45%). The early extubation rate in categories 1-3 (86%, 288/337) was significantly higher than for categories 4-6 (45.5%, 10/22) (P < 0.001). Because they met one of the exclusion criteria, 61 patients (17%) were not extubated in the operating room. Eight patients (2.7%) required re-intubation after early extubation in the operating room, and longer operation time was significantly associated with re-intubation (P < 0.001).Extubation in the operating room after congenital open-heart surgery was feasible based on our criteria, especially for patients in the low RACHS-1 categories, and involves a very low rate of re-intubation.
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Extubação/métodos , Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas/cirurgia , Salas Cirúrgicas , Adolescente , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Duração da Cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
ADP-ribosylation factor 6 (Arf6) is a small GTPase that regulates endosomal trafficking and actin cytoskeleton remodeling. In the present study, we comprehensively examined the cellular and subcellular localization of Arf6 in adult mouse peripheral tissues by immunofluorescence and immunoelectron microscopy using the heat-induced antigen retrieval method with Tris-EDTA buffer (pH 9.0). Marked immunolabeling of Arf6 was observed particularly in epithelial cells of several tissues including the esophagus, stomach, small and large intestines, trachea, kidney, epididymis, oviduct, and uterus. In most epithelial cells of simple or pseudostratified epithelia, Arf6 exhibited predominant localization to the basolateral membrane and a subpopulation of endosomes. At an electron microscopic level, Arf6 was localized along the basolateral membrane, with dense accumulation at interdigitating processes and infoldings. Arf6 was present in a ring-like appearance at intercellular bridges in spermatogonia and spermatocytes in the testis and at the Flemming body of cytokinetic somatic cells in the ovarian follicle, thymus, and spleen. The present study provides anatomical clues to help understand the physiological roles of Arf6 at the whole animal level.
Assuntos
Fatores de Ribosilação do ADP/análise , Epididimo/química , Intestino Delgado/química , Rim/química , Oviductos/química , Testículo/química , Fator 6 de Ribosilação do ADP , Animais , Reações Antígeno-Anticorpo , Feminino , Imunofluorescência , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Microscopia ImunoeletrônicaRESUMO
We report the anesthetic management during the laparoscopic cholecystectomy in a 60-year-old woman (height 150 cm, 'Weight 46 kg) with mitochondrial encephalopathy (chronic progressive external ophthal- moplegia, or CPEO). CPEO causes a disorder of aero- bic energy metabolism in various organs due to mito- chondrial dysfunction. It is thus very important in anesthetic management to maintain energy balance of demand and supply in organs and to protect the patient's respiratory muscles. Our patient had devel- oped CPEO 46 years earlier, and at her presentation she was bedridden and receiving both respiratory assistance via tracheostomy and tube feeding. Her hearing and understanding were intact, but she was blind due to lagophthalmos. We performed intravenous anesthesia with propofol (TCI) and remifentanil com- bined with epidural anesthesia. Rocuronium was injected under a train-of-four (TOF) monitoring. The operative time for the laparoscopic cholecystectomy was 4 hours. A total of 50 mg of rocuronium and 2,050 ml of bicarbonic ringer was injected during the opera- tion. The patient's blood lactate and glucose remained at normal levels throughout the operation. Because of severe adhesion, the laparoscopic procedure was changed to a laparotomy. However, during the peri-and post-operative periods, epidural anesthesia was valuable for analgesia during the management of the patient's respiratory care with a decreasing amount of narcotic medication. Post-operatively, the patient was monitored in an intensive care unit with the spontaneous respira- tory rate of 15 · min⻹ under oxygen 1l without any analgesics. The day after the operation she was returned to the ward, as her general condition was satisfactory.
Assuntos
Colecistectomia Laparoscópica , Encefalomiopatias Mitocondriais , Anestesia Epidural , Anestesia Intravenosa , Combinação de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Propofol/administração & dosagem , Remifentanil/administração & dosagemRESUMO
PURPOSE: Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. METHODS: The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 µg/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. RESULTS: The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p < 0.001), and to 4 (1-8) after FENtd (p < 0.001). The effects of FENiv, as evaluated by ΔNRS, CGI-I, and SS, were significantly greater than those of FENtd (p < 0.001, each), but not by the frequency and the severity of adverse effects, with the exception of dizziness. ΔNRS, and severity of adverse effects (drowsiness, dizziness, nausea, dry mouth, and pruritus) of FENiv correlated significantly with those of FENtd (rs > 0.04, each). CONCLUSIONS: The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl.
Assuntos
Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Dor/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-IdadeRESUMO
Coronary vasospasm(CV)can cause severe arrhythmia and myocardial infarction(MI). Intraoperative CV is not limited to cardiac surgery alone. We report the case of a patient who experienced cardiac arrest after the induction of general anesthesia, but did not demonstrate any abnormalities on preoperative examination. The patient was a 60-year-old man with no history of ischemic heart disease, with NASCET 80% asymptomatic left internal carotid stenosis(ICS). We decided to perform carotid endarterectomy(CEA). Preoperative stress myocardial scintigraphy did not reveal decreased local uptake. General anesthesia was rapidly induced with propofol and remifentanil, and maintained with sevoflurane. Shortly before the start of CEA, systolic blood pressure dropped to 80 mmHg. Electrocardiography indicated decreased ST, followed by an increase, after which complete atrioventricular block occurred. Cardiopulmonary resuscitation was initiated immediately as the patient's pulse was not palpable;heart beat resumed quickly. CEA was canceled. CV was suspected by the test of nitrate administration to coronary artery performed afterwards. A temporary pacemaker was inserted and carotid artery stenting was performed under local anesthesia. Hence, no pacemaker was used intraoperatively and no abnormality was observed on electrocardiography. In the present case, CV in the coronary artery caused complete atrioventricular block, leading to cardiac arrest after inducing general anesthesia. For ICS treatment performed under general anesthesia, care must be taken regarding the possibility of the occurrence of CV.