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BACKGROUND: The withdrawal or continuation of angiotensin II receptor blockers (ARBs) before surgery continues to be debated. We hypothesized that this is because ARBs with different half-lives have not been studied individually. This retrospective study aimed to clarify whether the degree of hypotension during anesthesia induction differs among ARBs with different half-lives. METHODS: We included patients who received general anesthesia with regular oral administration of telmisartan (group T) or valsartan (group V), which have half-lives of approximately 24 and 6 hours, respectively. The frequency of hypotension and vasopressor frequency and dose during anesthesia induction were compared between the two groups. At our hospital, ARBs were withdrawn on the day of surgery in all patients. RESULTS: Groups T and V included 190 and 132 patients, respectively. Patient backgrounds in group V were significantly more strongly associated with the use of calcium channel blockers. No significant differences were observed in the use of other concomitant antihypertensive medications, cardiovascular complications, or renal function. The time during which the mean arterial blood pressure was < 60 mmHg during anesthesia induction was significantly greater in group T than in group V (11 min vs. 7 min, P=0.030). The proportion of patients who used vasopressors was significantly higher in group T than that in group V (74.2% vs. 56.0%, P < 0.001). CONCLUSION: Patients taking telmisartan showed more hypotensive during the induction of general anesthesia than those taking valsartan, even after withdrawal on the day of surgery.
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Background and Objectives: Minimally invasive trauma management, including interventional radiology and non-operative approaches, has proven effective. Consequently, our hospital established a trauma IVR protocol called "Ohta Nishinouchi Hospital trauma protocol (ONH trauma protocol) in 2013, mainly for trunk trauma. However, the efficacy of the ONH trauma protocol has remained unverified. We aimed to assess the protocol's impact using interrupted time-series analysis (ITSA). Materials and Methods: This retrospective cohort study was conducted at Ohta Nishinouchi hospital, a tertiary emergency hospital, from January 2004 to December 2019. We included patients aged ≥ 18 years who presented to our institution due to severe trauma characterized by an Abbreviated Injury Scale of ≥3 in any region. The primary outcome was the incidence of in-hospital deaths per 100 transported patients with trauma. Multivariable logistic regression analysis was conducted with in-hospital mortality as the outcome, with no exposure before protocol implementation and with exposure after protocol implementation. Results: Overall, 4558 patients were included in the analysis. The ITSA showed no significant change in in-hospital deaths after protocol induction (level change -1.49, 95% confidence interval (CI) -4.82 to 1.84, p = 0.39; trend change -0.044, 95% CI -0.22 to 0.14, p = 0.63). However, the logistic regression analysis revealed a reduced mortality effect following protocol induction (odds ratio: 0.50, 95% CI: 0.37 to 0.66, p < 0.01, average marginal effects: -3.2%, 95% CI: -4.5 to -2.0, p < 0.01). Conclusions: The ITSA showed no association between the protocol and mortality. However, before-and-after testing revealed a positive impact on mortality. A comprehensive analysis, including ITSA, is recommended over before-and-after comparisons to assess the impact of the protocol.
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Mortalidade Hospitalar , Análise de Séries Temporais Interrompida , Humanos , Feminino , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Protocolos Clínicos , Estudos de Coortes , Pelve/lesões , Modelos Logísticos , Japão/epidemiologia , Tronco/lesõesRESUMO
PURPOSE: This study was performed to evaluate the changes in oxygen supply-demand balance during induction of general anesthesia using an indirect calorimeter capable of measuring oxygen consumption (VO2) and carbon dioxide production (VCO2). METHODS: This study included patients scheduled for surgery in whom remimazolam was administered as a general anesthetic. VO2 and VCO2 were measured at different intervals: upon awakening (T1), 15 min after tracheal intubation (T2), and 1 h after T2 (T3). Oxygen delivery (DO2) was calculated simultaneously with these measurements. VO2 was ascertained using an indirect calorimeter and further calculated using vital signs, among other factors. DO2 was derived from cardiac output and arterial blood gas analysis performed with an arterial pressure-based cardiac output measurement system. RESULTS: VO2, VCO2, and DO2 decreased significantly from T1 to T2 and T3 [VO2/body surface area (BSA) (ml/min/m2): T1, 130 (122-146); T2, 107 (83-139); T3, 97 (93-121); p = 0.011], [VCO2/BSA (ml/min/m2): T1, 115 (105-129); T2, 90 (71-107); T3, 81 (69-101); p = 0.011], [DO2/BSA (ml/min/m2): T1, 467 (395-582); T2, 347 (286-392); T3, 382 (238-414); p = 0.0020]. Among the study subjects, a subset exhibited minimal reduction in VCO2. Although the respiratory frequency was titrated on the basis of end-tidal CO2 levels, there was no significant difference between the groups. CONCLUSION: General anesthetic induction with remimazolam decreased VO2, VCO2, and DO2.
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Anestesia Geral , Benzodiazepinas , Dióxido de Carbono , Consumo de Oxigênio , Oxigênio , Humanos , Anestesia Geral/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Oxigênio/sangue , Dióxido de Carbono/metabolismo , Benzodiazepinas/administração & dosagem , Gasometria/métodos , Adulto , Idoso , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologiaRESUMO
To investigate the relationship between antithrombin (AT) activity level and prognosis in patients requiring intensive care. Patients whose AT activity was measured within 24â h of intensive care unit (ICU) admission were enrolled for analysis. The primary endpoint was mortality at discharge. Prognostic accuracy was examined using receiver operating characteristic (ROC) curves and cox hazard regression analysis. Patients were divided into 6 groups based on predicted mortality, and a χ2 independence test was performed on the prognostic value of AT activity for each predicted mortality; P < .05 was considered significant. A total of 281 cases were analyzed. AT activity was associated with mortality at discharge (AT% [interquartile range, IQR]): survivor group, 69 (56-86) versus nonsurvivor group, 56 (44-73), P = .0003). We found an increasing risk for mortality in both the lowest level of AT activity (<50%; hazard ratio [HR] 2.43, 95% confidence interval [CI] 1.20-4.89, P = .01) and the middle-low level of AT activity (≥ 50% and < 70%; HR 2.06, 95% CI 1.06-4.02, P = .03), compared with the normal AT activity level (≥ 70%). ROC curve analysis showed that the prediction accuracy of AT was an area under the curve (AUC) of 0.66 (cutoff 58%, sensitivity 61.4%, specificity 68.2%, P = .0003). AT activity was significantly prognostic in the group with 20% to 50% predicted mortality (AUC 0.74, sensitivity: 24.0%-55.5%, specificity: 83.3%-93.0%). An early decrease in AT activity level in ICU patients may be a predictor of mortality at discharge.
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Antitrombinas , Sepse , Humanos , Prognóstico , Estudos Retrospectivos , Cuidados Críticos , Unidades de Terapia Intensiva , Antitrombina III , Curva ROC , AnticoagulantesRESUMO
Distinguishing pathological gait is challenging in neurology because of the difficulty of capturing total body movement and its analysis. We aimed to obtain a convenient recording with an iPhone and establish an algorithm based on deep learning. From May 2021 to November 2022 at Yamagata University Hospital, Shiga University, and Takahata Town, patients with idiopathic normal pressure hydrocephalus (n = 48), Parkinson's disease (n = 21), and other neuromuscular diseases (n = 45) comprised the pathological gait group (n = 114), and the control group consisted of 160 healthy volunteers. iPhone application TDPT-GT captured the subjects walking in a circular path of about 1 meter in diameter, a markerless motion capture system, with an iPhone camera, which generated the three-axis 30 frames per second (fps) relative coordinates of 27 body points. A light gradient boosting machine (Light GBM) with stratified k-fold cross-validation (k = 5) was applied for gait collection for about 1 min per person. The median ability model tested 200 frames of each person's data for its distinction capability, which resulted in the area under a curve of 0.719. The pathological gait captured by the iPhone could be distinguished by artificial intelligence.
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Inteligência Artificial , Captura de Movimento , Humanos , Marcha , Caminhada , Algoritmos , Fenômenos Biomecânicos , Movimento (Física)RESUMO
BACKGROUND: This study used an epidural anesthesia practice kit (model) to evaluate the accuracy of epidural anesthesia using standard techniques (blind) and augmented/mixed reality technology and whether visualization using augmented/mixed reality technology would facilitate epidural anesthesia. METHODS: This study was conducted at the Yamagata University Hospital (Yamagata, Japan) between February and June 2022. Thirty medical students with no experience in epidural anesthesia were randomly divided into augmented reality (-), augmented reality (+), and semi-augmented reality groups, with 10 students in each group. Epidural anesthesia was performed using the paramedian approach with an epidural anesthesia practice kit. The augmented reality (-) group performed epidural anesthesia without HoloLens2â and the augmented reality (+) group with HoloLens2â. The semi-augmented reality group performed epidural anesthesia without HoloLens2â after 30 s of image construction of the spine using HoloLens2â. The epidural space puncture point distance between the ideal insertion needle and participant's insertion needle was compared. RESULTS: Four medical students in the augmented reality (-), zero in the augmented reality (+), and one in the semi-augmented reality groups failed to insert the needle into the epidural space. The epidural space puncture point distance for the augmented reality (-), augmented reality (+), and semi-augmented reality groups were 8.7 (5.7-14.3) mm, 3.5 (1.8-8.0) mm (P = 0.017), and 4.9 (3.2-5.9) mm (P = 0.027), respectively; a significant difference was observed between the two groups. CONCLUSIONS: Augmented/mixed reality technology has the potential to contribute significantly to the improvement of epidural anesthesia techniques.
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Anestesia Epidural , Realidade Aumentada , Humanos , Anestesia Epidural/métodos , Espaço Epidural , Punção Espinal/métodos , PunçõesRESUMO
AIMS: Acetaminophen (APAP) is a relatively safe analgesic drug, but overdosing can cause acute liver failure. Ingested APAP is detoxified by metabolic conversion through conjugation reactions with glucuronate, sulfate, or glutathione (GSH). The consumption of GSH through conjugation as well as mitochondrial dysfunction is considered to be responsible for the increased susceptibility to APAP-induced hepatotoxicity. Compared to wild-type (WT) mice, Akr1a-knockout (KO) mice are vulnerable to developing hepatotoxicity due to the fact that ascorbate synthesis is attenuated. We used such KO mice to investigate how these conjugation reactions are involved in the hepatotoxicity caused by an overdose of APAP under ascorbate-deficient conditions. MAIN METHODS: APAP (400 mg/kg) was intraperitoneally administered to WT mice and KO mice. In addition to histological and blood biochemical analyses, metabolites in the liver, blood plasma, and urine were measured at several time points by liquid chromatography-mass spectrometry. KEY FINDINGS: Liver damage occurred earlier in the KO mice than in the WT mice. The levels of APAP-Cys, a final metabolite of GSH-conjugated APAP, as well as glucuronidated APAP and sulfated APAP were all higher in the KO mice compared to the WT mice. Treatment of the APAP-administered KO mice with N-acetylcysteine or supplementation of ascorbate suppressed the conjugation reactions at 6 h after APAP had been administrated, which mitigated the degree of liver damage. SIGNIFICANCE: An ascorbate deficiency coordinately stimulates conjugation reactions of APAP, which, combined with the mitochondrial damage caused by APAP metabolites, collectively results in the aggravation of the acute liver failure.
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Acetaminofen , Aldeído Redutase , Doença Hepática Induzida por Substâncias e Drogas , Acetaminofen/farmacocinética , Acetaminofen/toxicidade , Aldeído Redutase/deficiência , Aldeído Redutase/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
BACKGROUND: It is difficult to predict the return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). Cerebral tissue oxygen saturation during CPR, as measured by near-infrared spectroscopy (NIRS), is anticipated to predict ROSC. General markers of cerebral tissue oxygen saturation, such as the tissue oxygenation index (TOI), mainly reflect venous oxygenation, whereas pulse-wave cerebral tissue oxygen saturation (SnO2), which represents hemoglobin oxygenation in the pulse wave within the cerebral tissue, is an index of arterial and venous oxygenation. Thus, SnO2 may reflect arterial oxygenation to a greater degree than does TOI. Therefore, we conducted this study to verify our hypothesis that SnO2 measured during CPR can predict ROSC. METHODS: Cardiac arrest patients who presented at the Emergency Department of Yamagata University Hospital in Japan were included in this retrospective, observational study. SnO2 and TOI were simultaneously measured at the patient's forehead using an NIRS tissue oxygenation monitor (NIRO 200-NX; Hamamatsu Photonics, Japan). We recorded the initial, mean, and maximum values during CPR. We plotted receiver operating characteristic curves and calculated the area under the curve (AUC) to predict ROSC. RESULTS: Forty-two patients were included. SnO2 was significantly greater in the ROSC group than in the non-ROSC group in terms of the initial (37.5% vs 24.2%, p = 0.015), mean (44.6% vs 10.8%, p < 0.001), and maximum (79.7% vs 58.4%, p < 0.001) values. Although the initial TOI was not significantly different between the two groups, the mean (45.1% vs 36.8%, p = 0.018) and maximum (71.0% vs 46.3%, p = 0.001) TOIs were greater in the ROSC group than in the non-ROSC group. The AUC was 0.822 for the mean SnO2 (95% confidence interval [CI]: 0.672-0.973; cut-off: 41.8%), 0.821 for the maximum SnO2 (95% CI: 0.682-0.960; cut-off: 70.8%), and 0.809 for the maximum TOI (95% CI: 0.667-0.951; cut-off: 49.3%). CONCLUSION: SnO2 values measured during CPR, including immediately after arrival at the emergency department, were higher in the ROSC group than in the non-ROSC group.
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Reanimação Cardiopulmonar , Parada Cardíaca , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Humanos , Saturação de Oxigênio , Estudos Retrospectivos , Retorno da Circulação EspontâneaRESUMO
BACKGROUND: Pheochromocytomas produce hormones, cytokines, and catecholamines. We report perioperative anesthetic management of a rare interleukin-6 (IL-6)-producing pheochromocytoma. CASE PRESENTATION: A 32-year-old female was scheduled for laparoscopic adrenalectomy for pheochromocytoma. She had a sustained high fever with elevated serum noradrenaline and IL-6 levels. The persistent high inflammatory state, followed by anemia, malnutrition, and coagulopathy, led us to prepone her date of surgery. During general anesthesia, alpha-blockers allowed hemodynamic fluctuations to be controlled. During surgery, simultaneous increases in noradrenaline and IL-6 levels were observed, which rapidly declined after tumor removal. Her postoperative course was uneventful, without pulmonary edema caused by cytokine storms. CONCLUSIONS: The conventional pheochromocytoma strategy allowed surgical removal of an IL-6-producing pheochromocytoma under general anesthesia. However, management of high inflammatory states that induce anemia and coagulopathy is necessary.
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BACKGROUND: Tracheal intubation is the gold standard for securing the airway, and it is not uncommon to encounter intubation difficulties in intensive care units and emergency rooms. Currently, there is a need for an objective measure to assess intubation difficulties in emergency situations by physicians, residents, and paramedics who are unfamiliar with tracheal intubation. Artificial intelligence (AI) is currently used in medical imaging owing to advanced performance. We aimed to create an AI model to classify intubation difficulties from the patient's facial image using a convolutional neural network (CNN), which links the facial image with the actual difficulty of intubation. METHODS: Patients scheduled for surgery at Yamagata University Hospital between April and August 2020 were enrolled. Patients who underwent surgery with altered facial appearance, surgery with altered range of motion in the neck, or intubation performed by a physician with less than 3 years of anesthesia experience were excluded. Sixteen different facial images were obtained from the patients since the day after surgery. All images were judged as "Easy"/"Difficult" by an anesthesiologist, and an AI classification model was created using deep learning by linking the patient's facial image and the intubation difficulty. Receiver operating characteristic curves of actual intubation difficulty and AI model were developed, and sensitivity, specificity, and area under the curve (AUC) were calculated; median AUC was used as the result. Class activation heat maps were used to visualize how the AI model classifies intubation difficulties. RESULTS: The best AI model for classifying intubation difficulties from 16 different images was generated in the supine-side-closed mouth-base position. The accuracy was 80.5%; sensitivity, 81.8%; specificity, 83.3%; AUC, 0.864; and 95% confidence interval, [0.731-0.969], indicating that the class activation heat map was concentrated around the neck regardless of the background; the AI model recognized facial contours and identified intubation difficulties. CONCLUSION: This is the first study to apply deep learning (CNN) to classify intubation difficulties using an AI model. We could create an AI model with an AUC of 0.864. Our AI model may be useful for tracheal intubation performed by inexperienced medical staff in emergency situations or under general anesthesia.
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INTRODUCTION: Postoperative infection remains a serious complication of cardiac surgery; however, no existing biomarkers can detect infection in the early perioperative period. We investigated the usefulness of presepsin, a novel biomarker, in predicting postoperative infectious complications in cardiac surgery with cardiopulmonary bypass. MATERIAL AND METHODS: For patients aged > 18 years who underwent elective cardiac surgery with cardiopulmonary bypass between 2015 and 2017, data of clinical features, perioperative presepsin levels, and infectious complications were collected. We compared the perioperative presepsin levels between the infected and non-infected groups, performed a risk factor analysis for postoperative infection, and calculated the cut-off value of presepsin with postoperative infection. RESULTS: Among the 73 included patients, 20 developed postoperative infectious complications. The presepsin levels pre-operatively and on post-operative day (POD) zero were significantly higher in the infected than in the non-infected group (145.2 vs. 93.2, 514.0 vs. 328.1 [pg mL-1], p < 0.05, respectively). The odds ratio (OR) for postoperative infection included pre-operative presepsin (OR; 1.22 [confidence interval; 1.07-1.40]/10 pg mL-1) and presepsin on POD zero (OR; 1.31 [confidence interval; 1.05-1.64] /100 pg mL-1). The cut-off predictive values for postoperative infectious complications of pre-operative presepsin and on POD zero were 132 and 347 [pg mL-1], respectively. CONCLUSIONS: Perioperative presepsin levels could be an early predictor for postoperative infectious complications in cardiac surgery.
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Procedimentos Cirúrgicos Cardíacos , Receptores de Lipopolissacarídeos , Adolescente , Biomarcadores , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Fragmentos de Peptídeos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Estudos ProspectivosRESUMO
Cells cope with environmental changes through various mechanisms. Pathways involving HIF-1, SIRT1, and AMPK play major roles in energy homeostasis under stress conditions. Diacylglycerol kinase (DGK) constitutes an enzyme family that catalyzes conversion of diacylglycerol to phosphatidic acid. We reported earlier that energy depletion such as ischemia induces proteasomal degradation of DGKζ before cell death, suggesting involvement of DGKζ in energy homeostasis. This study examines how DGKζ depletion affects the regulation of HIF-1α, SIRT1, and AMPKα. Under hypoxia DGKζ depletion attenuates HIF-1α induction and SIRT1 expression, which might render cells vulnerable to energy stress. However, DGKζ depletion engenders enhanced AMPKα phosphorylation by upstream kinase TAK1 and an increase in intracellular ATP levels. Results suggest that DGKζ exerts a suppressive effect on TAK1 activity in the AMPK activation mechanism, and that DGKζ depletion might engender dysregulation of the AMPK-mediated energy sensor system.
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Proteínas Quinases Ativadas por AMP/metabolismo , Diacilglicerol Quinase/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Sirtuína 1/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Trifosfato de Adenosina/metabolismo , Animais , Hipóxia Celular , Ativação Enzimática , Células HeLa , Humanos , Camundongos Endogâmicos C57BL , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
AKR1A, an aldo-keto reductase, is involved in the synthesis of ascorbic acid as well as the reduction of a variety of aldehyde compounds. AKR1A-/- mice produce considerably less ascorbic acid (about 10%) compared to AKR1A+/+ mice and require ascorbic acid supplementation in order to breed. To elucidate the roles played by AKR1A in spatial memory, AKR1A-/- male mice were weaned at 4 weeks of age and groups that received ascorbic acid supplementation and no supplementation were subjected to a Morris water maze test. Juvenile AKR1A-/- mice that received no supplementation showed impaired spatial memory formation, even though about 70% of the ascorbic acid remained in the brains of the AKR1A-/- mice at day 7 after weaning. To the contrary, the young adult AKR1A-/- mice at 13-15 weeks of age maintained only 15% of ascorbic acid but showed no significant difference in the spatial memory compared with the AKR1A+/+ mice or ascorbic acid-supplemented AKR1A-/- mice. It is conceivable that juvenile mice require more ascorbic acid for the appropriate level of formation of spatial memory and that maturation of the neural system renders the memory forming process less sensitive to an ascorbic acid insufficiency.
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BACKGROUND: Although clinical studies of the high-flow nasal cannula (HFNC) and its effect on positive end-expiratory pressure (PEEP) have been done, the washout effect has not been well evaluated. Therefore, we made an experimental respiratory model to evaluate the respiratory physiological effect of HFNC. METHODS: An airway model was made by a 3D printer using the craniocervical 3D-CT data of a healthy 32-year-old male. CO2 was infused into four respiratory lung models (normal-lung, open- and closed-mouth models; restrictive- and obstructive-lung, open-mouth models) to maintain the partial pressure of end-tidal CO2 (PETCO2) at 40 mmHg. HFNC flow was changed from 10 to 60 L/min. Capnograms were recorded at the upper pharynx, oral cavity, subglottic, and inlet sites of each lung model. RESULTS: With the normal-lung, open-mouth model, 10 L/min of HFNC flow decreased the subglottic PETCO2 to 30 mmHg. Increasing the HFNC flow did not further decrease the subglottic PETCO2. With the normal-lung, closed-mouth model, HFNC flow of 40 L/min was required to decrease the PETCO2 at all sites. Subglottic PETCO2 reached 30 mmHg with an HFNC flow of 60 L/min. In the obstructive-lung, open-mouth model, PETCO2 at all sites had the same trend as in the normal-lung, open-mouth model. In the restrictive-lung, open-mouth model, 20 L/min of HFNC flow decreased the subglottic PETCO2 to 25 mmHg, and it did not decrease further. As HFNC flow was increased, PEEP up to 7 cmH2O was gradually generated in the open-mouth models and up to 17 cmH2O in the normal-lung, closed-mouth model. CONCLUSIONS: The washout effect of the HFNC was effective with relatively low flow in the open-mouth models. The closed-mouth model needed more flow to generate a washout effect. Therefore, HFNC flow should be considered based on the need for the washout effect or PEEP.
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[This corrects the article on p. 105 in vol. 70, PMID: 28184277.].
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Bone homeostasis is maintained by a balance between resorption of the bone matrix and its replacement by new bone. Osteoclasts play a crucially important role in bone metabolism. They are responsible for bone resorption under pathophysiological conditions. Differentiation of these cells, which are derived from bone marrow cells, depends on receptor activator of NF-κB ligand (RANKL). RANKL-induced osteoclastogenesis is regulated by the phosphoinositide (PI) signaling pathway, in which diacylglycerol (DG) serves as a second messenger in signal transduction. In this study, we examined the functional implications of DG kinase (DGK), an enzyme family responsible for DG metabolism, for osteoclast differentiation and activity. Of DGKs, DGKζ is most abundantly expressed in osteoclast precursors such as bone marrow-derived monocytes/macrophages. During osteoclast differentiation from precursor cells, DGKζ is downregulated at the protein level. In this regard, we found that DGKζ deletion enhances osteoclast differentiation and bone resorption activity under inflammatory conditions in an animal model of osteolysis. Furthermore, DGKζ deficiency upregulates RANKL expression in response to TNFα stimulation. Collectively, results suggest that DGKζ is silent under normal conditions, but it serves as a negative regulator in osteoclast function under inflammatory conditions. Downregulation of DGKζ might be one factor predisposing a person to osteolytic bone destruction in pathological conditions. J. Cell. Physiol. 232: 617-624, 2017. © 2016 Wiley Periodicals, Inc.
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Reabsorção Óssea/enzimologia , Reabsorção Óssea/patologia , Diferenciação Celular , Diacilglicerol Quinase/metabolismo , Regulação para Baixo , Inflamação/patologia , Osteoclastos/patologia , Animais , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/complicações , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Fibroblastos/metabolismo , Inflamação/complicações , Inflamação/enzimologia , Isoenzimas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Knockout , Osteoclastos/efeitos dos fármacos , Osteólise/complicações , Osteólise/enzimologia , Osteólise/patologia , Ligante RANK/genética , Ligante RANK/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo , Tomografia Computadorizada por Raios X , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/efeitos dos fármacosRESUMO
The endoplasmic reticulum (ER) comprises an interconnected membrane network, which is made up of lipid bilayer and associated proteins. This organelle plays a central role in the protein synthesis and sorting. In addition, it represents the synthetic machinery of phospholipids, the major constituents of the biological membrane. In this process, phosphatidic acid (PA) serves as a precursor of all phospholipids, suggesting that PA synthetic activity is closely associated with the ER function. One enzyme responsible for PA synthesis is diacylglycerol kinase (DGK) that phosphorylates diacylglycerol (DG) to PA. DGK is composed of a family of enzymes with distinct features assigned to each isozyme in terms of structure, enzymology, and subcellular localization. Of DGKs, DGKε uniquely exhibits substrate specificity toward arachidonate-containing DG and is shown to reside in the ER. Arachidonic acid, a precursor of bioactive eicosanoids, is usually acylated at the sn-2 position of phospholipids, being especially enriched in phosphoinositide. In this review, we focus on arachidonoyl-specific DGKε with respect to the historical context, molecular basis of the substrate specificity and ER-targeting, and functional implications in the ER.
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PURPOSE: Noninvasive positive pressure ventilation (NPPV) using a helmet is expected to cause inspiratory trigger delay due to the large collapsible and compliant chamber. We compared the work of breathing (WOB) of NPPV using a helmet or a full face-mask with that of invasive ventilation by tracheal intubation. METHODS: We used a lung model capable of simulating spontaneous breathing (LUNGOO; Air Water Inc., Japan). LUNGOO was set at compliance (C) = 50 mL/cmH2O and resistance (R) = 5 cmH2O/L/s for normal lung simulation, C = 20 mL/cmH2O and R = 5 cmH2O/L/s for restrictive lung, and C = 50 mL/cmH2O and R = 20 cmH2O/L/s for obstructive lung. Muscle pressure was fixed at 25 cmH2O and respiratory rate at 20 bpm. Pressure support ventilation and continuous positive airway pressure were performed with each interface placed on a dummy head made of reinforced plastic that was connected to LUNGOO. We tested the inspiratory WOB difference between the interfaces with various combinations of ventilator settings (positive end-expiratory pressure 5 cmH2O; pressure support 0, 5, and 10 cmH2O). RESULTS: In the normal lung and restrictive lung models, WOB decreased more with the face-mask than the helmet, especially when accompanied by the level of pressure support. In the obstructive lung model, WOB with the helmet decreased compared with the other two interfaces. In the mixed lung model, there were no significant differences in WOB between the three interfaces. CONCLUSION: NPPV using a helmet is more effective than the other interfaces for WOB in obstructive lung disease.