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1.
Braz J Anesthesiol ; 74(6): 844545, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39117065

RESUMO

BACKGROUND: The primary aim of this proof-of-concept study was to investigate whether the Cardiac Power Index (CPI) could be a novel alternative method to assess fluid responsiveness in the prone position. METHODS: Patients undergoing scheduled elective lumbar spine surgery in the prone position under general anesthesia were enrolled in the criteria of patients aged 19-75 years with American Society of Anesthesiologists (ASA) physical status I-II. The hemodynamic variables were evaluated before and after changes in posture after administering a colloid bolus (5 mL.kg-1) in the prone position. Fluid responsiveness was defined as an increase in the Stroke Volume Index (SVI) ≥ 10%. RESULTS: A total of 28 patients were enrolled. In responders, the CPI (median [1/4Q-3/4Q]) decreased to 0.34 [0.28-0.39] W.m-2 (p = 0.035) after the prone position. After following fluid loading, CPI increased to 0.48 [0.37-0.52] W.m-2 (p < 0.008), and decreased SVI (median [1/4Q-3/4Q]) after prone increased from 26.0 [24.5-28.0] mL.m-2 to 33.0 [31.0-37.5] mL.m-2 (p = 0.014). Among non-responders, CPI decreased to 0.43 [0.28-0.53] W.m-2 (p = 0.011), and SVI decreased to 29.0 [23.5-34.8] mL.m-2 (p < 0.009). CPI exhibited predictive capabilities for fluid responsiveness as a receiver operating characteristic curve of 0.78 [95% Confidence Interval, 0.60-0.95; p = 0.025]. CONCLUSION: This study suggests the potential of CPI as an alternative method to existing preload indices in assessing fluid responsiveness in clinical scenarios, offering potential benefits for responders and non-responders.

2.
Int J Med Inform ; 191: 105543, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39084087

RESUMO

INTRODUCTION: Preparing appropriate red blood cells (RBCs) before surgery is crucial for improving both the efficacy of perioperative workflow and patient safety. In particular, thoracic surgery (TS) is a procedure that requires massive transfusion with high variability for each patient. Hence, the precise prediction of RBC requirements for individual patients is becoming increasingly important. This study aimed to 1) develop and validate a machine learning algorithm for personalized RBC predictions for TS patients and 2) assess the usability of a clinical decision support system (CDSS) integrating this artificial intelligence model. METHODS: Adult patients who underwent TS between January 2016 and October 2021 were included in this study. Multiple models were developed by employing both traditional statistical- and machine-learning approaches. The primary outcome evaluated the model's performance in predicting RBC requirements through root mean square error and adjusted R2. Surgeons and informaticians determined the precision MSBOS-Thoracic Surgery (pMSBOS-TS) algorithm through a consensus process. The usability of the pMSBOS-TS was assessed using the System Usability Scale (SUS) survey with 60 clinicians. RESULTS: We identified 7,843 cases (6,200 for training and 1,643 for test sets) of TSs. Among the models with variable performance indices, the extreme gradient boosting model was selected as the pMSBOS-TS algorithm. The pMSBOS-TS model showed statistically significant lower root mean square error (mean: 3.203 and 95% confidence interval [CI]: 3.186-3.220) compared to the calculated Maximum Surgical Blood Ordering Schedule (MSBOS) and a higher adjusted R2 (mean: 0.399 and 95% CI: 0.395-0.403) compared to the calculated MSBOS, while requiring approximately 200 fewer packs for RBC preparation compared to the calculated MSBOS. The SUS score of the pMSBOS-TS CDSS was 72.5 points, indicating good acceptability. CONCLUSIONS: We successfully developed the pMSBOS-TS capable of predicting personalized RBC transfusion requirements for perioperative patients undergoing TS.


Assuntos
Algoritmos , Sistemas de Apoio a Decisões Clínicas , Aprendizado de Máquina , Procedimentos Cirúrgicos Torácicos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Transfusão de Eritrócitos , Idoso , Adulto , Medicina de Precisão
3.
J Clin Anesth ; 97: 111519, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38870700

RESUMO

STUDY OBJECTIVE: Elderly patients undergoing pathophysiological changes necessitate clinical tools for cerebral monitoring. This prospective randomized controlled study aimed to explore how cerebral monitoring using Δo2Hbi, ΔHHbi, and ΔcHbi manifests in elderly patients under either propofol or sevoflurane anesthesia. DESIGN: Single-center, prospective, randomization. SETTING: A single tertiary hospital (Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea). PATIENTS: Enrolled 100 patients scheduled for urologic surgery under general anesthesia. Inclusion criteria were (a) age 70-80 years, (b) American Society of Anesthesiologists (ASA) physical status I-II. INTERVENTION: Patients were double-blind randomized to receive propofol-based or sevoflurane anesthesia. Cerebral oximetry-related parameters were measured at 5, 10, 15, 20, and 30 min in a setting devoid of surgery-related factors. MEASUREMENTS: The primary outcome focused on the Δo2Hbi pattern in the left and right sides within the propofol and sevoflurane groups. MAIN RESULTS: We analyzed 100 patients, 50 patients in each group. In the propofol group, the left Δo2Hbi decreased from 1.4 (3.7) at 5 min to -0.1 (1.8) at 30 min (P < 0.0001), and the right Δo2Hbi decreased from 2.9 (4.2) at 5 min to -0.06 (2.3) at 30 min (P < 0.0001). In the sevoflurane group, the left Δo2Hbi decreased from 1.1 (3.4) at 5 min to -1.4 (4.4) at 30 min (P < 0.0001), and the right Δo2Hbi decreased from 2.0 (3.2) at 5 min to -1.2 (3.9) at 30 min (P < 0.0001). There were no significant differences between the two groups. ΔHHbi did not exhibit significant changes after an initial decrease at 5 min and showed no significant differences between the two groups. CONCLUSIONS: In cerebral oximetry, Δo2Hbi and ΔHHbi could emerge as a valuable approach for discerning changes in the underlying baseline status of the brain in elderly patients during anesthesia.


Assuntos
Anestésicos Inalatórios , Anestésicos Intravenosos , Encéfalo , Propofol , Sevoflurano , Humanos , Sevoflurano/administração & dosagem , Sevoflurano/farmacologia , Propofol/administração & dosagem , Propofol/efeitos adversos , Idoso , Masculino , Feminino , Estudos Prospectivos , Método Duplo-Cego , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Idoso de 80 Anos ou mais , Anestésicos Intravenosos/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Oximetria/métodos , Anestesia Geral/métodos , Procedimentos Cirúrgicos Urológicos , Oxigênio/sangue
4.
Medicine (Baltimore) ; 103(26): e38718, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941413

RESUMO

I-gel has been used in various clinical situations. The study investigated alterations in respiratory parameters following a stepwise lung recruitment maneuver (LRM) using the i-gel. The research involved 60 patients classified as American Society of Anesthesiologists class I-II, aged 30 to 75 years, undergoing elective urologic surgery. Various respiratory parameters, including lung compliance, airway resistance, leak volume, airway pressure, and oxygen reserve index, were recorded at different time points: before LRM, immediately after LRM, and at 5, 15, and 30 minutes after LRM, as well as at the end of the surgery. The primary outcome was to assess an improvement in lung compliance. Dynamic lung compliance (mean ±â€…SD) was significantly increased from 49.2 ±â€…1.8 to 70.15 ±â€…3.2 mL/cmH2O (P < .05) after LRM. Static lung compliance (mean ±â€…SD) was increased considerably from 52.4 ±â€…1.7 to 65.0 ±â€…2.5 mL/cmH2O (P < .05) after the LRM. Both parameters maintained a statistically significant increased status for a certain period compared to baseline despite a decreased degree of increment. Airway resistance (mean ±â€…SD) was significantly reduced after the LRM from 12.05 ±â€…0.56 to 10.41 ±â€…0.64 L/cmH2O/s (P < .05). Stepwise LRM using i-gel may improve lung compliance and airway resistance. Repeated procedures could lead to prolonged improvements in respiratory parameters.


Assuntos
Resistência das Vias Respiratórias , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Masculino , Feminino , Idoso , Complacência Pulmonar/fisiologia , Adulto , Resistência das Vias Respiratórias/fisiologia , Respiração com Pressão Positiva/métodos
5.
Eur J Med Res ; 28(1): 64, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36732838

RESUMO

BACKGROUND: Atelectasis can occur in many clinical practices. One way to prevent this complication is through the alveolar recruitment maneuver (ARM). However, hemodynamic compromise can accompany ARM. This study aims to predict ARM-induced hypotension using a non-invasive method. METHODS: 94 American Society of Anesthesiologists physical status I-II patients aged 19 to 75 with scheduled spinal surgery were enrolled. After anesthesia, we performed a stepwise ARM. Data on perfusion index, mean arterial pressure, heart rate, pleth variability index, cardiac index, and stroke volume variation was collected before induction of anesthesia (T0), just before ARM (T1), at the start of ARM (T2), 0.5 min (T3), 1 min (T4), 1.5 min (T5, end of ARM), and 2 min after the beginning of ARM (T6). Hypotension was defined as when the mean arterial pressure at T5 decreased by 20% or more compared to the baseline. The primary endpoint is that the perfusion index measuring before induction of anesthesia, which reflects the patients' own vascular tone, was correlated with hypotension during ARM. RESULTS: Seventy-five patients (79.8%) patients developed hypotension during ARM. The pre-induction persufion index (Pi) (95% confidence interval) was 1.7(1.4-3.1) in the non-hypotension group and 3.4(2.4-3.9) in the hypotension group. (p < 0.004) The hypotension group showed considerably higher Pi than the non-hypotension group before induction. The decrease of Pi (%) [IQR] in the non-hypotensive group (52.8% [33.3-74.7]) was more significant than in the hypotensive group. (36% [17.6-53.7]) (p < 0.05) The area under the receiver operating characteristic curve of Pi for predicting hypotension during ARM was 0.718 (95% CI 0.615-0.806; p = 0.004), and the threshold value of the Pi was 2.4. CONCLUSION: A higher perfusion index value measuring before induction of anesthesia can be used to predict the development of hypotension during ARM. Prophylactic management of the following hypotension during ARM could be considered in high baseline Pi patients.


Assuntos
Raquianestesia , Hipotensão , Humanos , Hipotensão/induzido quimicamente , Hemodinâmica , Frequência Cardíaca , Estudos Prospectivos
6.
Anaesth Crit Care Pain Med ; 41(2): 101034, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35167993

RESUMO

INTRODUCTION: Positive end-expiratory pressure (PEEP) following alveolar recruitment manoeuvre (RM) can effectively prevent anaesthesia-induced atelectasis in children. We aimed to evaluate the individual effect of PEEP following RM on atelectasis at the end of laparoscopic surgery in infants and small children. METHODS: Children undergoing laparoscopic inguinal hernia repair aged 5 weeks to 2 years were randomly allocated to either the PEEP or control group. A progressive RM was performed after intubation in all cases. The PEEP group received PEEP of 5 cmH2O until the end of mechanical ventilation, while the control group did not receive any PEEP. Lung ultrasonography was performed to compare the number of atelectatic regions between the two groups after anaesthesia induction, after RM, and at the end of surgery in 12 thoracic regions. RESULTS: Overall, 432 ultrasonographic images were acquired from 36 children. At the end of surgery, the number of atelectatic regions (median [interquartile range]) was significantly lower in the PEEP group compared to the control group (2.0 [1.0-3.0] versus 4.0 [3.0-4.0] out of 12 regions, respectively; p = 0.02). While no difference was observed between the number of atelectatic regions after induction and at the end of surgery in the control group (p = 0.30), a decrease was observed in the PEEP group (3.0 [2.0-4.0] to 2.0 [1.0-3.0], respectively; p = 0.02). CONCLUSION: RM followed by a PEEP of 5 cmH2O can effectively reduce the regions of pulmonary atelectasis at the end of laparoscopic surgery in infants and small children.


Assuntos
Laparoscopia , Atelectasia Pulmonar , Criança , Humanos , Lactente , Laparoscopia/efeitos adversos , Respiração com Pressão Positiva/métodos , Estudos Prospectivos , Atelectasia Pulmonar/diagnóstico por imagem , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/prevenção & controle , Ultrassonografia
7.
Paediatr Anaesth ; 31(12): 1276-1281, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34614266

RESUMO

BACKGROUND: In adults, the use of lower oxygen concentration during induction is associated with less atelectasis formation without an increase in incidence of hypoxia. However, it is unknown whether this remains true in the pediatric patients. METHODS: Fifty-four pediatric patients who were scheduled to undergo elective lower abdominal surgery were randomized to one of three oxygenation groups: 100%, 80%, or 60% oxygen (in air). During anesthesia induction, patients were ventilated with sevoflurane in 100%, 80%, or 60% oxygen. Endotracheal intubation and mechanical ventilation were performed. Atelectasis was diagnosed using LUS, which was performed after anesthetic induction and at the end of surgery. RESULTS: We assessed atelectasis after anesthetic induction and at the end of surgery. After anesthetic induction, the number of atelectatic lung regions was significantly different among the three groups (median [IQR], 2.0 [1.0-2.5], 2.0 [1.0-2.8], and 3.0 [2.0-3.0] in the 60%, 80%, and 100% oxygen groups, p = .033) and between the 60% and 100% groups (p = .015), but not between 80% and 100% groups (p = .074). However, no differences in the number of atelectatic lung regions were found among the three groups at the end of surgery (2.0 [1.3-3.8], 3.0 [1.8-3.0], and 4.0 [2.0-4.0] in the 60%, 80%, and 100% oxygen groups; p = .169). CONCLUSION: Lower oxygen concentration during anesthetic induction is associated with less atelectasis formation immediately after anesthetic induction in children. In addition, applying 80% oxygen instead of 100% oxygen is not enough to prevent atelectasis formation, and 60% oxygen should be applied to prevent atelectasis. However, this effect does not last until the end of surgery.


Assuntos
Respiração com Pressão Positiva , Atelectasia Pulmonar , Adulto , Anestesia Geral/efeitos adversos , Criança , Humanos , Pulmão , Oxigênio , Estudos Prospectivos , Atelectasia Pulmonar/prevenção & controle
8.
J Int Med Res ; 49(9): 3000605211044201, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34586942

RESUMO

Malignant hyperthermia (MH) is a potentially fatal hypermetabolic syndrome that occurs when susceptible individuals are exposed to triggering agents. Variability in the order and time of occurrence of symptoms often makes clinical diagnosis difficult. A late diagnosis or misdiagnosis of delayed-onset MH may lead to fatal complications. We herein report a case of delayed-onset MH in the postoperative recovery room. A 77-year-old man awoke from anesthesia and was transferred to the recovery room. Ten minutes after his arrival, his mental status became stuporous and he developed masseter muscle rigidity, hyperventilation, and a body temperature of 39.8°C. The patient was suspected to have MH, and 60 mg of dantrolene sodium (1 mg/kg) was administered via intravenous drip with symptomatic treatment. Within 10 minutes of dantrolene administration, the patient's clinical signs subsided. This case report demonstrates that rapid diagnosis and treatment are crucial to ensure a good prognosis for patients with MH. A high level of suspicion based on clinical symptoms and early administration of therapeutic drugs such as dantrolene will also improve the clinical course. Therefore, suspicion and prompt diagnosis are absolutely essential. This case report emphasizes the importance of continuous education in the diagnosis and treatment of MH.


Assuntos
Anestesia , Hipertermia Maligna , Idoso , Temperatura Corporal , Dantroleno/uso terapêutico , Humanos , Hipertermia , Masculino , Hipertermia Maligna/diagnóstico
9.
Sci Rep ; 11(1): 14589, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272425

RESUMO

Postural change from a steep Trendelenburg position to a supine position (T-off) during robot-assisted laparoscopic prostatectomy (RALP) induces a considerable abrupt decrease in the mean arterial pressure (MAP). We investigated the variables for predicting postural hypotension induced by T-off using esophageal Doppler monitoring (EDM). One hundred and twenty-five patients undergoing RALP were enrolled. Data on the MAP, heart rate, stroke volume index (SVI), cardiac index, peak velocity, corrected flow time, stroke volume variation, pulse pressure variation, arterial elastance (Ea), and dynamic arterial elastance were collected before T-off and at 1, 3, 5, 7, and 10 min after T-off using EDM. MAP < 60 mmHg within 10 min after T-off was considered to indicate hypotension, and 25 patients developed hypotension. The areas under the curves of the MAP, SVI, and Ea were 0.734 (95% confidence interval [CI] 0.623-0.846; P < 0.001), 0.712 (95% CI 0.598-0.825; P < 0.001), and 0.760 (95% CI 0.646-0.875; P < 0.001), respectively, with threshold values of ≤ 74 mmHg, ≥ 42.5 mL/m2, and ≤ 1.08 mmHg/mL, respectively. If patients have MAP < 75 mmHg with SVI ≥ 42.5 mL/m2 or Ea ≤ 1.08 mmHg/mL before postural change from T-off during RALP, prompt management for ensuing hypotension should be considered.Trial registration: NCT03882697 (ClinicalTrial.gov, March 20, 2019).


Assuntos
Pressão Arterial , Ecocardiografia Doppler/métodos , Ecocardiografia Transesofagiana/métodos , Hipotensão Ortostática/etiologia , Monitorização Intraoperatória/métodos , Posicionamento do Paciente/efeitos adversos , Prostatectomia/efeitos adversos , Idoso , Feminino , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Decúbito Dorsal
10.
Viruses ; 13(4)2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918958

RESUMO

Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.


Assuntos
Antivirais/farmacologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Animais , Infecções por Coronavirus/virologia , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Sinergismo Farmacológico , Humanos , Estágios do Ciclo de Vida/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/crescimento & desenvolvimento , Bibliotecas de Moléculas Pequenas/farmacologia , Tratamento Farmacológico da COVID-19
11.
Biochem Biophys Res Commun ; 545: 33-39, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33535104

RESUMO

Zika virus (ZIKV) infection in both infants and adults is associated with neurological complications including, but not limited to, microcephaly and Guillain-Barre syndrome. Antibody therapy can be effective against virus infection. We isolated ZIKV envelope domain III-specific neutralizing antibodies (nAbs) from two convalescent patients with ZIKV infection. One antibody, 2F-8, exhibited potent in vitro neutralizing activity against Asian and American strains of ZIKV. To prevent FcγR-mediated antibody-dependent enhancement, we prepared IgG1 with LALA variation. A single dose of 2F-8 in the context of IgG1 or IgG1-LALA prior to or post lethal ZIKV challenge conferred complete protection in mice.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Proteínas do Envelope Viral/imunologia , Zika virus/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Especificidade de Anticorpos , Modelos Animais de Doenças , Feminino , Humanos , Técnicas In Vitro , Camundongos , Camundongos da Linhagem 129 , Camundongos Knockout , Testes de Neutralização , Gravidez , Domínios Proteicos , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Proteínas do Envelope Viral/química , Zika virus/química , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle
12.
Medicine (Baltimore) ; 98(27): e15998, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277092

RESUMO

RATIONALE: Rigid bronchoscopy under general anesthesia enables performing diagnostic and/or therapeutic procedures in the tracheobronchial tree. As most patients undergoing rigid bronchoscopy have moderate to severe respiratory disease or central airway obstruction, the operators often face the risk of hypoxemia when inserting the rigid bronchoscope into the patients' airway. Applying high flow nasal cannula (HFNC) oxygen therapy before the insertion of the bronchoscope allows to maintain high fractional inspired oxygen (FiO2) and thus leading to maximizing apnea time before desaturation. PATIENT CONCERNS AND DIAGNOSIS: Case 1: A 70-year-old female patient was diagnosed with lung cancer in the left lower lobe and a tracheal mass of about 2.6 cm * 0.8 cm in size.Case 2: A male patient, 77 years old, 55.7 kg and 157.3 cm in height, had been diagnosed with chronic obstructive pulmonary disease, and was scheduled for the bronchoscopic volume reduction surgery upon exacerbation of his symptoms of dyspnea and cough with sputum. INTERVENTIONS: Preoxygenation was performed with HFNC (Fisher&Paykel Optiflow Thrive, New Zealand) for 3 minutes before the administration of anesthetic medications. The oxygen flow was set at 50 L/min and the FiO2 at 1.0. SpO2 increased to 100%. OUTCOMES: The HFNC oxygen has shown its effectiveness in safely maintaining the patients' SpO2 during the prolonged apneic period of inserting bronchoscope. LESSONS: HFNC oxygen is an effective tool in oxygenating the patients during the induction of rigid bronchoscopy, and that it may be a superior alternative to the conventional method of preoxygenation.


Assuntos
Anestesia Geral/métodos , Broncoscopia/métodos , Neoplasias Pulmonares/cirurgia , Oxigenoterapia/métodos , Doença Pulmonar Obstrutiva Crônica/cirurgia , Idoso , Cânula , Feminino , Humanos , Hipóxia/prevenção & controle , Masculino , Ventilação não Invasiva/instrumentação
13.
PLoS Pathog ; 15(2): e1007375, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30707748

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.


Assuntos
Anticorpos Neutralizantes/metabolismo , Phlebovirus/imunologia , Adulto , Animais , Anticorpos Neutralizantes/fisiologia , Anticorpos Antivirais/metabolismo , Infecções por Bunyaviridae/terapia , Epitopos/imunologia , Feminino , Febre , Glutamina/imunologia , Glutamina/metabolismo , Glicoproteínas/imunologia , Células HEK293 , Humanos , Leucopenia , Masculino , Camundongos , Camundongos Knockout , Testes de Neutralização , Phlebovirus/patogenicidade , República da Coreia , Trombocitopenia/imunologia , Proteínas do Envelope Viral/imunologia
14.
Viruses ; 9(10)2017 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-28946654

RESUMO

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.


Assuntos
Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Benzotiazóis/farmacologia , Isoquinolinas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos , Vírus/efeitos dos fármacos , Compostos de Anilina/farmacologia , Antivirais/química , Antivirais/uso terapêutico , Benzotiazóis/química , Benzotiazóis/uso terapêutico , Linhagem Celular , DNA Viral/genética , Humanos , Isoquinolinas/química , Isoquinolinas/uso terapêutico , Metabolômica , RNA Viral/genética , Sulfonamidas/farmacologia , Transfecção , Viroses/tratamento farmacológico , Viroses/prevenção & controle
15.
Am J Emerg Med ; 35(10): 1430-1434, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28529003

RESUMO

INTRODUCTION: Size 9 and 8 airways for men and women, respectively, have been proposed as most appropriate based on endoscopy. However, a limitation of this guideline is that ventilation was not assessed. METHODS: In this retrospective review of prospectively collected data, 149 patients requiring tracheal intubation for general anesthesia were included. The adequacy for manual and pressure-controlled mechanical ventilation and views at the distal end of each airway was assessed using a fiber-optic bronchoscope with various airway sizes (7, 8, 9, 10, and 11). RESULTS: For men, size 9, 10, and 11 airways permitted clear manual and adequate mechanical ventilation; size 7 and 8 airways caused partially obstructed manual and inadequate mechanical ventilation. On endoscopy, size 7 and 8 airways caused complete obstruction by the tongue; size 10 and 11 airways either touched or passed beyond the tip of the epiglottis. For women, the size 7 airway caused partially obstructed manual and inadequate mechanical ventilation; size 9 and 10 airways provided clear manual and adequate mechanical ventilation. The size 8 airway permitted clear manual ventilation, though mechanical ventilation was inadequate in one patient. On endoscopy, the size 7 airway caused complete obstruction in >50% of women; size 9, 10, and 11 airways either touched or passed beyond the tip of the epiglottis. CONCLUSIONS: With respect to adequate ventilation in conjunction with an acceptable endoscopic view, size 9 and size 8 oropharyngeal airways appear to be the most appropriate sizes for clinical use in men and women, respectively.


Assuntos
Anestesia Geral , Broncoscopia , Intubação Intratraqueal , Orofaringe/patologia , Respiração Artificial , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Estudos Retrospectivos , Fatores Sexuais , Adulto Jovem
16.
J Virol ; 91(12)2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28404846

RESUMO

The high mutation rates of the influenza virus genome facilitate the generation of viral escape mutants, rendering vaccines and drugs against influenza virus-encoded targets potentially ineffective. Therefore, we identified host cell determinants dispensable for the host but crucial for virus replication, with the goal of preventing viral escape and finding effective antivirals. To identify these host factors, we screened 2,732 human genes using RNA interference and focused on one of the identified host factors, the double plant homeodomain fingers 2 (DPF2/REQ) gene, for this study. We found that knockdown of DPF2 in cells infected with influenza virus resulted in decreased expression of viral proteins and RNA. Furthermore, production of progeny virus was reduced by two logs in the multiple-cycle growth kinetics assay. We also found that DPF2 was involved in the replication of seasonal influenza A and B viruses. Because DPF2 plays a crucial role in the noncanonical NF-κB pathway, which negatively regulates type I interferon (IFN) induction, we examined the relationship between DPF2 and IFN responses during viral infection. The results showed that knockdown of DPF2 resulted in increased expression of IFN-ß and induced phosphorylation of STAT1 in infected cells. In addition, high levels of several cytokines/chemokines (interleukin-8 [IL-8], IP-10, and IL-6) and antiviral proteins (MxA and ISG56) were produced by DPF2 knockdown cells. In conclusion, we identified a novel host factor, DPF2, that is required for influenza virus to evade the host immune response and that may serve as a potential antiviral target.IMPORTANCE Influenza virus is responsible for seasonal epidemics and occasional pandemics and is an ongoing threat to public health worldwide. Influenza virus relies heavily on cellular factors to complete its life cycle. Here we identified a novel host factor, DPF2, which is involved in influenza virus infection. Our results showed that DPF2 plays a crucial role in the replication and propagation of influenza virus. DPF2 functions in the noncanonical NF-κB pathway, which negatively regulates type I IFN induction. Thus, we investigated the relationship between the IFN response and DPF2 in influenza virus infection. Upon influenza virus infection, DPF2 dysregulated IFN-ß induction and expression of cytokines/chemokines and antiviral proteins. This study provides evidence that influenza virus utilizes DPF2 to escape host innate immunity.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Vírus da Influenza A/fisiologia , Interferon beta/biossíntese , Proteínas Adaptadoras de Transdução de Sinal , Motivos de Aminoácidos , Linhagem Celular , Quimiocina CXCL10/biossíntese , Quimiocina CXCL10/imunologia , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Humanos , Imunidade Inata , Vírus da Influenza A/crescimento & desenvolvimento , Vírus da Influenza A/imunologia , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Interferon beta/genética , Interleucina-6/biossíntese , Interleucina-6/imunologia , Interleucina-8/biossíntese , Interleucina-8/imunologia , Cinética , Proteínas de Resistência a Myxovirus/genética , Proteínas de Resistência a Myxovirus/imunologia , NF-kappa B/imunologia , NF-kappa B/metabolismo , Interferência de RNA , Proteínas de Ligação a RNA , Fator de Transcrição STAT1/química , Fator de Transcrição STAT1/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Replicação Viral
17.
Paediatr Anaesth ; 27(5): 540-544, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28332251

RESUMO

BACKGROUND: Caudal blocks are performed through the sacral hiatus in order to provide pain control in children undergoing lower abdominal surgery. During the block, it is important to avoid advancing the needle beyond the sacrococcygeal ligament too much to prevent unintended dural puncture. This study used demographic data to establish simple guidelines for predicting a safe needle depth in the caudal epidural space in children. METHODS: A total of 141 children under 12 years old who had undergone lumbar-sacral magnetic resonance imaging were included. The T2 sagittal image that provided the best view of the sacrococcygeal membrane and the dural sac was chosen. We used Picture Achieving and Communication System (Centricity® PACS, GE Healthcare Co.) to measure the distance between the sacrococcygeal ligament and the dural sac, the length of the sacrococcygeal ligament, and the maximum depth of the caudal space. RESULTS: There were strong correlations between age, weight, height, and BSA, and the distance between the sacrococcygeal ligament and dural sac, as well as the length of the sacrococcygeal ligament. Based on these findings, a simple formula to calculate the distance between the sacrococcygeal ligament and dural sac was developed: 25 × BSA (mm). CONCLUSION: This simple formula can accurately calculate the safe depth of the caudal epidural space to prevent unintended dural puncture during caudal block in children. However, further clinical studies based on this formula are needed to substantiate its utility.


Assuntos
Algoritmos , Anestesia Caudal/efeitos adversos , Anestesia Caudal/métodos , Dura-Máter/lesões , Espaço Epidural/anatomia & histologia , Espaço Epidural/diagnóstico por imagem , Fatores Etários , Estatura , Superfície Corporal , Peso Corporal , Criança , Pré-Escolar , Espaço Epidural/crescimento & desenvolvimento , Feminino , Humanos , Lactente , Ligamentos/anatomia & histologia , Ligamentos/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Agulhas , Estudos Retrospectivos , Região Sacrococcígea/anatomia & histologia , Região Sacrococcígea/diagnóstico por imagem
18.
Ultrasound Med Biol ; 41(5): 1241-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25726135

RESUMO

This study investigated the extent of the raised intracranial pressure resulting from carbon dioxide (CO2) pneumoperitoneum by ultrasonographically measuring optic nerve sheath diameter (ONSD) in children undergoing laparoscopic surgery. Twenty-five children aged less than 9 y (53.1 ± 23.3 mo, mean ± standard deviation) and scheduled for an elective laparoscopic surgery participated. ONSD was assessed using ocular ultrasonography 10 min after induction of anesthesia (T0), 10 min after induction of CO2 pneumoperitoneum at 10 mm Hg intra-abdominal pressure (T1) and in an anesthetized state without CO2 pneumoperitoneum at the conclusion of the surgery (T2). During CO2 pneumoperitoneum, ONSD increased significantly compared with ONSD after anesthesia induction (T0: 4.3 ± 0.3 mm, T1: 4.6 ± 0.3 mm, p < 0.05). In all enrolled patients, any neurologic complications were not observed during the intra-operative or post-operative period. In children undergoing laparoscopic surgery, an increase in ONSD was ascertained during CO2 pneumoperitoneum, and thus the corresponding increase in intracranial pressure could be predicted.


Assuntos
Hipertensão Intracraniana/diagnóstico por imagem , Laparoscopia/métodos , Monitorização Intraoperatória/métodos , Nervo Óptico/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana/métodos , Criança , Pré-Escolar , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Lactente , Recém-Nascido , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Cirurgia Assistida por Computador/métodos
19.
Biotechnol Lett ; 33(9): 1789-96, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21516311

RESUMO

Biodiesel [fatty acid methyl esters (FAMEs)] and glycerol carbonate were synthesized from corn oil and dimethyl carbonate (DMC) via transesterification using lipase (Novozyme 435) in solvent-free reaction in which excess DMC was used as the substrate and reaction medium. Glycerol carbonate was also simultaneously formed from DMC and glycerol. Conversions of FAMEs and glycerol carbonate were examined in batch reactions. The FAMEs and glycerol carbonate reached 94 and 62.5% from oil and DMC (molar ratio of 1:10) with 0.2% (v/v) water and 10% (w/w) Novozyme 435 (based on oil weight) at 60 °C. When Novozyme 435 was washed with acetone after each reaction, more than 80% activity still remained after seven recycling.


Assuntos
Biocombustíveis , Carbonatos/metabolismo , Óleo de Milho/metabolismo , Formiatos/metabolismo , Glicerol/metabolismo , Lipase/metabolismo , Temperatura , Água/metabolismo
20.
FEBS Lett ; 584(11): 2427-32, 2010 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-20416298

RESUMO

Catalase, which decomposes reactive oxygen species (ROS), is reduced in hepatocellular carcinoma (HCC); however, the reasons are poorly defined. In this study, it is demonstrated that prolonged exposure to ROS induced methylation of CpG island II on the catalase promoter and downregulated catalase expression at the transcriptional level in HCC cell lines. In addition, hypermethylation of CpG island II was also observed in tumor tissues, together with a decrease in catalase mRNA and protein expression levels when compared to non-tumor tissues. From these data, we suggest that ROS may downregulate catalase through the methylation of promoter during the development of HCC.


Assuntos
Catalase/genética , Ilhas de CpG , Metilação de DNA , Regulação para Baixo/efeitos dos fármacos , Espécies Reativas de Oxigênio/farmacologia , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Catalase/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metilação/efeitos dos fármacos , RNA Mensageiro/metabolismo , Sequências Reguladoras de Ácido Nucleico
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