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1.
Proc Natl Acad Sci U S A ; 121(2): e2315898120, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38165930

RESUMO

Protection against endothelial damage is recognized as a frontline approach to preventing the progression of cytokine release syndrome (CRS). Accumulating evidence has demonstrated that interleukin-6 (IL-6) promotes vascular endothelial damage during CRS, although the molecular mechanisms remain to be fully elucidated. Targeting IL-6 receptor signaling delays CRS progression; however, current options are limited by persistent inhibition of the immune system. Here, we show that endothelial IL-6 trans-signaling promoted vascular damage and inflammatory responses via hypoxia-inducible factor-1α (HIF1α)-induced glycolysis. Using pharmacological inhibitors targeting HIF1α activity or mice with the genetic ablation of gp130 in the endothelium, we found that inhibition of IL-6R (IL-6 receptor)-HIF1α signaling in endothelial cells protected against vascular injury caused by septic damage and provided survival benefit in a mouse model of sepsis. In addition, we developed a short half-life anti-IL-6R antibody (silent anti-IL-6R antibody) and found that it was highly effective at augmenting survival for sepsis and severe burn by strengthening the endothelial glycocalyx and reducing cytokine storm, and vascular leakage. Together, our data advance the role of endothelial IL-6 trans-signaling in the progression of CRS and indicate a potential therapeutic approach for burns and sepsis.


Assuntos
Receptor gp130 de Citocina , Subunidade alfa do Fator 1 Induzível por Hipóxia , Interleucina-6 , Receptores de Interleucina-6 , Sepse , Animais , Camundongos , Receptor gp130 de Citocina/genética , Síndrome da Liberação de Citocina , Células Endoteliais , Receptores de Interleucina-6/genética , Sepse/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
2.
Ann Gastroenterol Surg ; 8(1): 172-181, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38250679

RESUMO

Aim: Postoperative dysphagia after emergency abdominal surgery (EAS) in patients of advanced age has become problematic, and appropriate dysphagia management is needed. This study was performed to identify predictive factors of dysphagia after EAS and to explore the usefulness of swallowing screening tools (SSTs). Methods: This retrospective study included 267 patients of advanced age who underwent EAS from 2012 to 2022. They were assigned to a dysphagia group and non-dysphagia group using the Food Intake Level Scale (FILS) (dysphagia was defined as a FILS level of <7 on postoperative day 10). From 2018, original SSTs including a modified water swallowing test were performed by nurses. Results: The incidence of postoperative dysphagia was 22.8% (61/267). Patients were significantly older in the dysphagia than non-dysphagia group. The proportions of patients who had poor nutrition, cerebrovascular disorder, Parkinson's disease, dementia, nursing-care service, high intramuscular adipose tissue content (IMAC), and postoperative ventilator management were much higher in the dysphagia than non-dysphagia group. Using logistic regression analysis, high IMAC, postoperative ventilator management, cerebrovascular disorder, and dementia were correlated with postoperative dysphagia and were assigned 10, 4, 3, and 3 points, respectively, according to each odds ratio. The optimal cut-off value was 7 according to a receiver operating characteristics curve. Using 1:1 propensity score matching for high-risk patients, the incidence of postoperative dysphagia was reduced by SSTs. Conclusions: The new prediction score obtained from this study can identify older patients at high risk for dysphagia after EAS, and SSTs may improve these patients' short-term outcomes.

3.
Photochem Photobiol ; 100(1): 146-158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37477119

RESUMO

The effect of terahertz (THz) radiation has been studied in medicine. However, there is a lack of scientific information regarding its possible mutagenicity. Therefore, the present study aimed to assess the mutagenicity of 1.6 THz laser irradiation. The Ames test was conducted using five bacterial tester strains. The bacteria were subjected to (i) 1.6 THz laser irradiation at 3.8 mW/cm2 for 60 min using a tabletop THz pulse laser system, (ii) ultraviolet irradiation, (iii) treatment with positive control chemicals (positive control) or (iv) treatment with the solvent used in the positive control (negative control). After treatment, the bacterial suspensions were cultured on minimal glucose agar to determine the number of revertant colonies. In addition, the comet assay was performed using fibroblasts (V79) to assess possible DNA damage caused by the THz laser irradiation. The Ames test demonstrated that the THz laser irradiation did not increase the number of revertant colonies compared to that in the negative control group, whereas the ultraviolet irradiation and positive control treatment increased the number of revertant colonies. Thus, 1.6 THz laser irradiation is unlikely to be mutagenic. The comet assay additionally suggests that the THz laser irradiation unlikely induce cellular DNA damage.


Assuntos
Dano ao DNA , Mutagênicos , Mutagênicos/toxicidade , Ensaio Cometa , Mutagênese , Fibroblastos/efeitos da radiação , Testes de Mutagenicidade
4.
Gan To Kagaku Ryoho ; 50(9): 1001-1004, 2023 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-37800297

RESUMO

The patient was an elderly man in his early 80s who was admitted to our hospital due to anemia and tarry stools. An upper gastrointestinal endoscopy revealed a type 2 tumor in the second portion of the duodenum. An endoscopic biopsy revealed poorly differentiated adenocarcinoma. We performed a pancreaticoduodenectomy because neither lymphadenopathy nor distant metastases were found. Macroscopic findings revealed that the lesion was mainly in the second portion of the duodenum, and there was no evidence of invasion of the main pancreatic duct, the bile duct, or the ampulla of Vater. Histologically, the tumor was composed of atypical cells with polymorphic or spindle-shaped nuclei proliferating in a scattered fashion, and immunohistological examinations showed weakly positive results for cytokeratin(CK)AE1/AE3 and CK20 and positive results for vimentin but negative results for CK7. The tumor was diagnosed as undifferentiated carcinoma of the duodenum(pT4N0M0, pStage ⅡB). The patient recovered enough to be discharged and was followed up without postoperative adjuvant chemotherapy. He maintained recurrence-free survival for 27 months, after which lymph node and lung metastases reoccurred. This is a rare case of undifferentiated carcinoma of the duodenum treated by curative resection with a relatively favorable prognosis.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Carcinoma , Neoplasias do Ducto Colédoco , Humanos , Masculino , Adenocarcinoma/cirurgia , Ampola Hepatopancreática/cirurgia , Carcinoma/cirurgia , Neoplasias do Ducto Colédoco/patologia , Duodeno/patologia , Pancreatectomia , Pancreaticoduodenectomia , Idoso de 80 Anos ou mais
5.
Asian J Endosc Surg ; 16(4): 741-746, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37525942

RESUMO

PURPOSE: Textbook outcome (TO) is a novel composite measure of clinical outcomes that can be used to measure the quality of surgical outcomes. The aim of this cohort study was to propose TO criteria for laparoscopic cholecystectomy for acute cholecystitis and to identify reasons for TO failure and individual patient factors that predispose to failure. METHODS: We retrospectively analyzed data for 189 patients with acute cholecystitis who underwent laparoscopic cholecystectomy. TO was defined as laparoscopic cholecystectomy without conversion to open cholecystectomy, intraoperative complications, postoperative complications (Clavien-Dindo classification ≥2), prolonged length of stay (≥10 days), readmission within 30 days, or mortality. RESULTS: TO was achieved in 154 of 189 patients who underwent laparoscopic cholecystectomy for acute cholecystitis. Medical costs were lower in the TO-achieved group than in the TO-failure group. Factors associated with TO failure on multivariate analysis were age > 70 years, hemoglobin <11.9 g/dL, and white blood cells >18 000 / µL (all P < .05). CONCLUSIONS: Applying TO to patients with acute cholecystitis allowed us to evaluate the overall quality of care related to hospitalization. TO may provide better assessment of the quality of care and help determine the treatment choice and reduce costs.


Assuntos
Colecistectomia Laparoscópica , Colecistite Aguda , Humanos , Idoso , Estudos Retrospectivos , Estudos de Coortes , Colecistite Aguda/cirurgia , Colecistectomia , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento
6.
Clin Genitourin Cancer ; 21(6): e474-e484, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37301664

RESUMO

INTRODUCTION: The purpose of this study was to investigate the clinical value of combination of systematic inflammatory factors in predicting the outcomes of primary androgen deprivation therapy (ADT) plus first-generation antiandrogen treatment in metastatic hormone-naïve prostate cancer (mHNPC) patients. MATERIALS AND METHODS: A total of 361 consecutive mHNPC patients from the discovery (n = 165) and validation (n = 196) cohorts were analyzed. All patients received primary ADT with surgical castration or pharmacologic castration accompanied by first-generation antiandrogens. We evaluated the prognostic impact of pretreatment lymphocyte to C-reactive protein ratio (LCR) on overall survival (OS) in both cohorts. RESULTS: The median follow-up in the discovery and validation cohorts was 43.4 and 50.9 months, respectively. In the discovery cohort, low LCR (using an optimal cutoff threshold of 14,025) was significantly correlated with poor OS compared with high LCR (P < .001). Multivariate analysis revealed that the biopsy Gleason score and LCR were independent prognostic factors for OS. In the validation cohort, low LCR was also significantly correlated with poor OS compared with high LCR (P = .001). A multivariate analysis revealed that the extent of disease on bone scan grade, lactate dehydrogenase, and LCR were all independent predictors of OS. CONCLUSIONS: Pretreatment low LCR is an independent predictor of poor OS in mHNPC patients. This may be informative in predicting the susceptible patients' developing worse outcomes after being treated with primary ADT plus first-generation antiandrogen.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Proteína C-Reativa , Prognóstico , Hormônios , Linfócitos/patologia , Estudos Retrospectivos
7.
Hinyokika Kiyo ; 69(4): 113-116, 2023 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-37183042

RESUMO

A 63-year-old man presented with right scrotal swelling. A physical examination revealed a painless, palpable mass in the right scrotum. The mass was well defined and lobulated. Subsequently, a diagnosis of right epididymal tumor was made, and right high orchiectomy was performed. Hematoxylin-eosin and immunostaining revealed leiomyosarcoma of the epididymis. When a diagnosis of epididymal malignant tumor is made, the standard treatment is radical orchiectomy.


Assuntos
Neoplasias dos Genitais Masculinos , Leiomiossarcoma , Masculino , Humanos , Pessoa de Meia-Idade , Epididimo/diagnóstico por imagem , Epididimo/cirurgia , Epididimo/patologia , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/cirurgia , Neoplasias dos Genitais Masculinos/diagnóstico por imagem , Neoplasias dos Genitais Masculinos/cirurgia , Orquiectomia , Pelve
8.
Asian J Endosc Surg ; 16(3): 447-454, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37062535

RESUMO

INTRODUCTION: The management of patients with a cerebrospinal fluid (CSF) shunt located in the peritoneal cavity undergoing laparoscopic surgery is an issue that has not yet been settled. These patients are at risk of increased intracranial pressure caused by peritoneal insufflation, shunt dysfunction, and shunt infection/retrograde meningitis. This study aimed to determine the need for perioperative shunt intervention in CSF shunt patients undergoing laparoscopic cholecystectomy. METHODS: We reviewed and analyzed five shunt patients who underwent laparoscopic cholecystectomy in our institution between 2012 and 2022, as well as 17 patients described in previous reports. RESULTS: Among the 22 patients, shunt type was ventriculoperitoneal in 14 and lumboperitoneal in eight. The most common indication for CSF shunt was hydrocephalus caused by cerebral vascular accident (50.0%). Laparoscopic cholecystectomy was performed for cholecystolithiasis in 13 patients (59.1%), acute cholecystitis in eight (36.4%), and gallbladder polyp in one (4.5%). Shunt clamping or externalization was performed in six patients. Two patients in the group that did not undergo shunt clamping or externalization experienced complications (intra abdominal abscess and subcutaneous emphysema). However, the incidence of short-term complications (both overall and shunt-related) and median length of hospital stay did not significantly differ between the two groups. CONCLUSION: Routine shunt clamping, externalization, or removal might not be necessarily required in patients with a ventriculoperitoneal or lumboperitoneal shunt undergoing laparoscopic cholecystectomy.


Assuntos
Colecistectomia Laparoscópica , Hidrocefalia , Laparoscopia , Humanos , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Colecistectomia Laparoscópica/efeitos adversos , Hidrocefalia/cirurgia , Cavidade Peritoneal/cirurgia , Derivação Ventriculoperitoneal/efeitos adversos
9.
Food Funct ; 14(8): 3600-3612, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-36946764

RESUMO

The antioxidant properties of polyphenols, which are found in most plants, have been shown to be useful for maintaining health, including enhancing brain function and alleviating stress. We aimed to investigate the effect of a single intake of taxifolin-containing foods on cognitive task performance and whole blood gene expression in healthy young adults. This study was a randomized, placebo-controlled, double-blind, crossover trial in which healthy young adults were administered a single dose of either a placebo or food containing taxifolin. Cognitive tests (serial 3s, serial 7s, and rapid visual information processing) to examine brain activity and visual analog scale questionnaires to analyze mental fatigue were applied. The set of tests was repeated four times. The findings showed that taxifolin intake improved calculation abilities and reduced mental fatigue. An analysis of whole blood gene expression before and after the test revealed that the expression of foreign substance removal-related genes increased following the ingestion of taxifolin and that most differentially expressed genes were enriched in granulocytes. Taxifolin intake was shown to affect the brain activity of healthy young adults and demonstrated an antifatigue effect, thereby reducing subjective fatigue. A single intake of taxifolin may enhance the removal of foreign substances by strengthening the innate immune system and suppressing the occurrence of injury.


Assuntos
Cognição , Transcriptoma , Humanos , Adulto Jovem , Estudos Cross-Over , Fadiga Mental/tratamento farmacológico , Fadiga Mental/psicologia , Ingestão de Alimentos , Encéfalo , Método Duplo-Cego
10.
Am Surg ; 89(6): 2213-2219, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35392670

RESUMO

BACKGROUD: The systemic inflammation score (SIS), which is based on the preoperative lymphocyte-to-monocyte ratio (LMR) and serum albumin (Alb) level, is a prognostic indicator for several cancer types. However, the prognostic significance of the SIS in pancreatic ductal adenocarcinoma (PDAC) remains unknown. METHODS: Seventy-eight patients who underwent radical surgery for PDAC were categorized as follows: SIS 0 (LMR ≥3.51 and Alb ≥4.0 g/dl), n = 26; SIS 1 (LMR <3.51 or Alb <4.0 g/dl), n = 29 and SIS 2 (LMR <3.51 and Alb <4.0 g/dl), n=23. RESULTS: The tumour size sequentially increased in SIS 0, 1 and 2 groups. A higher SIS was associated with increased vascular invasion, perineural invasion and surgical margin positivity rate. Recurrence-free survival (RFS) rates between the SIS 1 and 2 groups showed no significant difference However, patients of the SIS 1 and 2 groups had poorer outcomes than those of the SIS 0 group for RFS. Overall survival (OS) rates between the SIS 1 and 2 groups also showed no significant difference. However, patients of the SIS 1 and 2 groups had poorer outcomes than those of the SIS 0 group for OS. The SIS was an independent prognostic factor for RFS and OS. DISCUSSION: The SIS is a simplified prognostic factor for patients with PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Prognóstico , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Inflamação , Estudos Retrospectivos , Neoplasias Pancreáticas
11.
Am Surg ; 89(11): 4452-4458, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35920820

RESUMO

BACKGROUND: Increasing evidence indicates that increased systemic inflammation is correlated with poorer cancer-specific survival in various cancer types. This study aimed to evaluate the prognostic value of various combinations of inflammatory factors in patients who underwent surgical resection for pancreatic cancer (PC). METHODS: We retrospectively analyzed 97 consecutive patients with PC who underwent pancreatectomy. We assessed the predictive impact for recurrence using a combination of 5 inflammatory markers and focused on the lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for recurrence-free survival (RFS) and overall survival (OS) in univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: Low preoperative LCR was correlated with low serum hemoglobin, low serum albumin concentration, high frequency of microscopic vascular invasion, and high frequency of microscopic perineural invasion. The low LCR group had significantly worse RFS and OS. Lower preoperative LCR was an independent predictor of shorter RFS and OS in this cohort. DISCUSSION: Preoperative LCR is a novel and convenient prognostic marker for patients with PC. Patients with low LCR may require more favorable intensive therapy.


Assuntos
Proteína C-Reativa , Neoplasias Pancreáticas , Humanos , Prognóstico , Proteína C-Reativa/metabolismo , Estudos Retrospectivos , Linfócitos/metabolismo , Neoplasias Pancreáticas
12.
Kyobu Geka ; 75(13): 1108-1111, 2022 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-36539228

RESUMO

An 86-year-old man was hospitalized urgently to our department because of his worsening hemoptysis. He had undergone open thoracic aortic grafting for the Stanford type B chronic aortic dissecting aneurysm 30 years earlier. Contrast enhanced computed tomography (CT) revealed the distal anastomotic aneurysm, leakage of the contrast medium around the distal anastomotic site. We urgently performed thoracic endovascular aneurysm repair( TEVAR) for the distal anastomotic aneurysm. TEVAR was done under local anesthesia because of his poor respiratory condition due to hemoptysis. He recovered well without hemoptysis. Patients after open aortic surgery are expected to survive longer. Thus, special attention should be paid to the occurrence of anastomotic aneurysms.


Assuntos
Aneurisma da Aorta Abdominal , Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Masculino , Humanos , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/etiologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Stents/efeitos adversos , Hemoptise/cirurgia , Resultado do Tratamento , Procedimentos Endovasculares/métodos
13.
Front Pharmacol ; 13: 965086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188606

RESUMO

Kv1.5 channels conduct the ultra-rapid delayed rectifier potassium current (I Kur). Pharmacological blockade of human Kv1.5 (hKv1.5) has been regarded as an effective treatment of re-entrant based atrial fibrillation, because Kv1.5 is highly expressed in human cardiac atria but scarcely in ventricles. The Kv1.5 blockade is also expected to be used in cancer therapeutics since Kv1.5 is overexpressed in some types of human tumors. Here, we investigated the blockade of hKv1.5 channels by HMQ1611, a symmetrical biphenyl derivative. hKv1.5 channels were heterologously expressed in Chinese hamster ovary cells. The effects of HMQ1611 on wild-type and 13 hKv1.5 mutant channels were examined using the whole-cell patch-clamp method, and molecular docking simulation was conducted to predict the docking position of HMQ1611 within Kv1.5 channels. We showed that HMQ1611 reversibly inhibited the hKv1.5 current in a concentration-dependent manner (IC50 = 2.07 µM). HMQ1611 blockade of hKv1.5 current developed with time during depolarizing voltage-clamp steps, and this blockade was also voltage-dependent with a steep increase over the voltage range for channel openings. HMQ1611 inhibition was significantly reduced in the T479A, T480A, V505A, I508A, L510A, V512A, and V516A hKv1.5 mutant channels. Molecular docking analysis predicted that V505, V512, and T480 were involved in the blocking action of HMQ1611 on hKv1.5 channels. These results suggest that HMQ1611 inhibits hKv1.5 currents as an open channel blocker. Amino acid residues located at the base of the selectivity filter (T479 and T480) and in the S6 segment (V505, I508, L510, V512, and V516) of hKv1.5 appear to constitute potential binding sites for HMQ1611.

14.
Front Immunol ; 13: 830061, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784283

RESUMO

Introduction: Resistin is reported to form a cytokine network and cause endothelial damage. The pathogenesis of coronavirus disease 2019 (COVID-19) remains unknown, but the association between cytokine storm and endothelial damage is crucial. This study aimed to evaluate resistin in COVID-19 pathogenesis compared with sepsis. Materials and Methods: First, we evaluated the association of plasma resistin levels and disease severity and clinical outcome in two large cohorts: a publicly available cohort including 306 COVID-19 patients in the United States (MGH cohort) and our original cohort including only intubated 113 patients in Japan (Osaka cohort 1). Second, to understand pathogenesis, we evaluate resistin, cytokines and endothelial cell adhesion molecules in COVID-19 compared with sepsis. Blood samples were collected from 62 ICU-treated COVID-19 patients and 38 sepsis patients on day 1 (day of ICU admission), days 2-3, days 6-8, and from 18 healthy controls (Osaka cohort 2). The plasma resistin, inflammatory cytokines (IL-6, IL-8, MCP-1 and IL-10) and endothelial cell adhesion molecules (ICAM-1 and VCAM-1) were compared between patients and control. Correlations among resistin, inflammatory cytokines and endothelial cell adhesion molecules were evaluated in COVID-19 and sepsis. Results: In the MGH cohort, the day 1 resistin levels were associated with disease severity score. The non-survivors showed significantly greater resistin levels than survivors on days 1, 4 and 8. In the Osaka cohort 1, 28-day non-survivors showed significantly higher resistin levels than 28-day survivors on days 6-8. Patients with late recovery (defined as the day of weaning off mechanical ventilation >12 or death) had significantly higher resistin levels than those with early recovery on day 1 and days 6-8. In the Osaka cohort 2, plasma resistin levels were elevated in COVID-19 and sepsis patients compared to controls at all measurement points and were associated with inflammatory cytokines and endothelial cell adhesion molecules. Conclusion: Resistin was elevated in COVID-19 patients and was associated with cytokines and endothelial cell adhesion molecules. Higher resistin levels were related to worse outcome.


Assuntos
COVID-19 , Sepse , Citocinas , Humanos , Resistina , Sepse/metabolismo , Molécula 1 de Adesão de Célula Vascular
15.
Sci Rep ; 12(1): 8108, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577892

RESUMO

A cytokine storm induces acute respiratory distress syndrome, the main cause of death in coronavirus disease 2019 (COVID-19) patients. However, the detailed mechanisms of cytokine induction due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. To examine the cytokine production in COVID-19, we mimicked the disease in SARS-CoV-2-infected alveoli by adding the lysate of SARS-CoV-2-infected cells to cultured macrophages or induced pluripotent stem cell-derived myeloid cells. The cells secreted interleukin (IL)-6 after the addition of SARS-CoV-2-infected cell lysate. Screening of 25 SARS-CoV-2 protein-expressing plasmids revealed that the N protein-coding plasmid alone induced IL-6 production. The addition of anti-N antibody further enhanced IL-6 production, but the F(ab')2 fragment did not. Sera from COVID-19 patients also enhanced IL-6 production, and sera from patients with severer disease induced higher levels of IL-6. These results suggest that anti-N antibody promotes IL-6 production in SARS-CoV-2-infected alveoli, leading to the cytokine storm of COVID-19.


Assuntos
Anticorpos Antivirais , COVID-19 , Proteínas do Nucleocapsídeo de Coronavírus , Interleucina-6 , SARS-CoV-2 , Anticorpos Antivirais/metabolismo , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/metabolismo , Citocinas , Humanos , Interleucina-6/metabolismo , Fosfoproteínas/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo
16.
Biomolecules ; 12(4)2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35454159

RESUMO

Propofol is a broadly used intravenous anesthetic agent that can cause cardiovascular effects, including bradycardia and asystole. A possible mechanism for these effects is slowing cardiac pacemaker activity due to inhibition of the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. However, it remains unclear how propofol affects the allosteric nature of the voltage- and cAMP-dependent gating mechanism in HCN channels. To address this aim, we investigated the effect of propofol on HCN channels (HCN4 and HCN2) in heterologous expression systems using a whole-cell patch clamp technique. The extracellular application of propofol substantially suppressed the maximum current at clinical concentrations. This was accompanied by a hyperpolarizing shift in the voltage dependence of channel opening. These effects were significantly attenuated by intracellular loading of cAMP, even after considering the current modification by cAMP in opposite directions. The differential degree of propofol effects in the presence and absence of cAMP was rationalized by an allosteric gating model for HCN channels, where we assumed that propofol affects allosteric couplings between the pore, voltage-sensor, and cyclic nucleotide-binding domain (CNBD). The model predicted that propofol enhanced autoinhibition of pore opening by unliganded CNBD, which was relieved by the activation of CNBD by cAMP. Taken together, these findings reveal that propofol acts as an allosteric modulator of cAMP-dependent gating in HCN channels, which may help us to better understand the clinical action of this anesthetic drug.


Assuntos
Anestésicos , Propofol , Anestésicos/farmacologia , AMP Cíclico/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/química , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Ativação do Canal Iônico/fisiologia , Canais de Potássio/metabolismo , Propofol/farmacologia
17.
Surg Case Rep ; 8(1): 19, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35067787

RESUMO

BACKGROUND: The number of reports of multiple primary cancer (MPC) is increasing because of the advancement in diagnostic imaging technology. However, the treatment strategy for MPCs involving pancreatic cancer is controversial because of the extremely poor prognosis. We herein report a patient with synchronous triple cancer involving the pancreas, esophagus, and lung who underwent conversion surgery after intensive chemotherapy for unresectable locally advanced pancreatic cancer. CASE PRESENTATION: A 59-year-old man was admitted to our hospital with epigastric pain, anorexia, and weight loss. Computed tomography and upper gastrointestinal endoscopy revealed that the patient had synchronous triple cancer of the pancreas, esophagus, and lung. While the esophageal and lung cancer were relatively non-progressive, the pancreatic tail cancer had invaded the aorta, celiac axis, and left kidney, and the patient was diagnosed with unresectable locally advanced disease. Because the described lesion could have been the prognostic determinant for this patient, we initiated intensive chemotherapy (gemcitabine plus nab-paclitaxel) for pancreatic cancer. After six courses of chemotherapy, the tumor size shrank remarkably and no invasion to the aorta or celiac axis was observed. No significant changes were observed in the esophageal and lung cancers; endoscopic submucosal dissection could be still a curative treatment for the esophageal cancer. Therefore, we performed curative resection for pancreatic cancer (distal pancreatomy, splenectomy, and left nephrectomy; ypT3N0cM0, ypStage IIA, UICC 8th). Pathologically, complete resection was achieved. The patient then underwent endoscopic submucosal dissection for early esophageal cancer (pT1a[M]-LPM) and video-assisted thoracoscopic right upper lobectomy in combination with right lower partial resection for early lung cancer (pT2aN0M0, pStage IB, UICC 8th). Eight months after pancreatic cancer surgery, the patient is alive and has no sign of recurrence; as a result of the successful treatment, the patient has a good quality of life. CONCLUSIONS: Treatment of MPC is challenging, especially for cases with unresectable tumors. Although synchronous triple cancer can involve unresectable pancreatic cancer, radical resection may be possible after careful assessment of the appropriate treatment strategy and downstaging of unresectable tumors.

18.
Burns ; 48(7): 1680-1689, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34961651

RESUMO

BACKGROUND: In current intensive care treatment, some patients with severe burns cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients. METHODS: This was a single-center, retrospective, observational study. Patients' blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured. RESULTS: Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801. CONCLUSIONS: In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns.


Assuntos
Queimaduras , Resistina , Humanos , Nicotinamida Fosforribosiltransferase , Leptina , Adiponectina , Sindecana-1 , Angiotensinogênio , Interleucina-6 , Interleucina-10 , Estudos Retrospectivos , Proteína Inibidora do Complemento C1 , Interleucina-8 , Citocinas , Adipocinas , Prognóstico
19.
Surg Today ; 52(7): 1023-1030, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34796402

RESUMO

PURPOSE: Excessive working hours have been reported to contribute to burnout among surgeons. In Japan, work-style reform is a problem that needs immediate attention. Acute appendectomy, which often occurs at nighttime, is one of the most common emergency surgeries. The feasibility of delayed and interval appendectomy remains to be investigated. METHODS: Two hundred forty-five consecutive patients who underwent laparoscopic appendectomy in our hospital were enrolled. They were divided into three groups: emergency appendectomy (immediate surgery, soon after the diagnosis [EA group], n = 153), delayed appendectomy (surgery during daytime the following day [DA group], n = 38) and interval appendectomy (antibiotics treatment followed by selective surgery three to four months later [IA group], n = 54). The clinical background and surgical outcomes were compared. Next, the residents' excess working time per month was calculated. RESULTS: The surgical outcomes (operation time, blood loss, length of hospital stay, postoperative complications) were similar between the EA and DA groups. However, no DA was performed during nighttime hours whereas 15.7% of EA was performed during nighttime hours (p = 0.0007). The surgical outcomes of the IA group were also comparable. The residents' excess working time declined following the introduction of DA and workstyle reform. CONCLUSION: Delayed and interval laparoscopic appendectomy are feasible, and can be performed to promote workstyle reform without impairing patient safety.


Assuntos
Apendicite , Laparoscopia , Apendicectomia , Apendicite/cirurgia , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
20.
Clin Case Rep ; 10(12): e6497, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36590663

RESUMO

A 73-year-old man taking lanthanum carbonate for hemodialysis showed progressing gastric mucosal changes with lanthanum deposition. Regular examination revealed concurrent gastric carcinoma. The extent and depth of its invasion were ambiguous because of the surrounding lanthanum deposition. Furthermore, there could be other potent carcinomas, and curative laparoscopic gastrectomy was performed.

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