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Osmotic therapy has been recognized as an important treatment option for patients with traumatic brain injury (TBI). Nevertheless, the effect of hypertonic saline (HTS) remains unknown, as findings are primarily based on a large database. This study aimed to elucidate the effect of HTS on the clinical outcomes of patients with TBI admitted to the intensive care unit (ICU). We retrospectively identified patients with moderate-to-severe TBI from two public databases: Medical Information Mart for Intensive Care (MIMIC)-IV and eICU Collaborative Research Database (eICU-CRD). A marginal structural Cox model (MSCM) was used, with time-dependent variates designed to reflect exposure over time during ICU stay. Trajectory modeling based on the intracranial pressure evolution pattern allowed for the identification of subgroups. Overall, 130 (6.65%) of 1955 eligible patients underwent HTS. MSCM indicated that the HTS significantly associated with higher infection complications (e.g., urinary tract infection (HR 1.88, 95% CI 1.26-2.81, p = 0.002)) and increased ICU LOS (HR 2.02, 95% CI 1.71-2.40, p < 0.001). A protective effect of HTS on GCS was found in subgroups with medium and low intracranial pressure. Our study revealed no significant difference in mortality between patients who underwent HTS and those who did not. Increased occurrence rates of infection and electrolyte imbalance are inevitable outcomes of continuous HTS infusion. Although the study suggests slight beneficial effects, including better neurological outcomes, these results warrant further validation.
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Lesiones Traumáticas del Encéfalo , Hipertensión Intracraneal , Humanos , Estudios Retrospectivos , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/complicaciones , Solución Salina Hipertónica/uso terapéutico , Hospitalización , Unidades de Cuidados Intensivos , Hipertensión Intracraneal/tratamiento farmacológicoRESUMEN
Sepsis is a complex, multifactorial syndrome characterized by a dysregulated host response to infection, leading to severe organ dysfunction and high mortality rates among critically ill patients. Hypovitaminosis C and vitamin C deficiency are frequently observed in septic patients, prompting interest in the potential therapeutic role of ascorbic acid. Although intravenous administration of ascorbic acid has been investigated in multiple clinical trials for sepsis treatment, the specific immunomodulatory mechanisms underlying its effects remain elusive. This study aimed to investigate the protective effects of high-dose ascorbic acid on experimental sepsis. Results show that intravenous administration of high-dose ascorbic acid (250 mg/kg) attenuated sepsis-induced organ dysfunctions in a cecal ligation and puncture (CLP)-induced septic mouse model. Ascorbic acid improved splenic cell apoptosis and increased the number of CD3+ T cells in septic mice induced by CLP. Furthermore, ascorbic acid downregulated PD-L1 expression in livers, reduced PD-1 expression in spleens, and inhibited the phosphorylation of STAT1 at Y701 in multiple organs of CLP-induced septic mice. The in vitro experiments also revealed that 800 µM ascorbic acid suppressed STAT1 phosphorylation and inhibited lipopolysaccharide (LPS) and IFN-γ-induced PD-L1 expression in macrophages. These findings suggest that ascorbic acid prevents sepsis-associated organ dysfunction through the p-STAT1/PD-L1 signaling pathway. Our study provides new insights into the potential therapeutic use of ascorbic acid in sepsis.
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Antineoplásicos , Sepsis , Humanos , Animales , Ratones , Antígeno B7-H1 , Insuficiencia Multiorgánica , Fosforilación , Sepsis/tratamiento farmacológico , Ácido Ascórbico/farmacología , Factor de Transcripción STAT1RESUMEN
INTRODUCTION: The T cell immunoglobulin and mucin domain 3 (Tim-3) mediated immunosuppressive pathway has been shown to play an essential role in the development of sepsis. However, the influence of Tim-3 blockade during sepsis and the possible effects on T cells' function remains largely unknown. Our study investigates the role of Tim-3 in cecal ligation and puncture (CLP)-induced sepsis in mice. METHODS: Sepsis was induced in C57BL/6 male mice via CLP. The expression of Tim-3 in CD8+ T cells after CLP challenge was measured. A dose of 50 µg anti-Tim-3 antibodies was injected intraperitoneally 30 min after surgery. Postoperative survival, bacterial clearance in the blood and peritoneal lavage ï¬uid, cytokine secretion in the blood, and lung and liver histology were evaluated. In addition, the apoptosis of immune cells in the spleen and thymus was examined, respectively. RESULTS: Tim-3 expression was elevated in the splenic CD8+ T cells of septic mice. At the early stage of CLP-induced sepsis, blocking Tim-3 with anti-Tim-3 antibodies reduced the severity of sepsis. The anti-Tim-3 antibodies alleviated the morphology of lung and liver injuries in septic mice. The anti-Tim-3 antibodies also reduced the severity of the inflammatory responses and lymphocyte apoptosis in septic mice. CONCLUSIONS: Anti-Tim-3 antibodies might be a potential therapeutic strategy for sepsis.
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Linfocitos T CD8-positivos , Sepsis , Animales , Apoptosis , Citocinas/metabolismo , Inmunoglobulinas , Masculino , Ratones , Ratones Endogámicos C57BL , MucinasRESUMEN
Mechanical ventilation is a life-sustaining therapy for patients with respiratory failure but can cause further lung damage known as ventilator-induced lung injury (VILI). However, the intrinsic molecular mechanisms underlying recovery of VILI remain unknown. Phagocytosis of apoptotic cells (also known as efferocytosis) is a key mechanism orchestrating successful resolution of inflammation. Here we show the positive regulation of macrophage Toll-like receptor (TLR) 4 in efferocytosis and resolution of VILI. Mice were depleted of alveolar macrophages and then subjected to injurious ventilation (tidal volume, 20 mL/kg) for 4 h. On day 1 after mechanical ventilation, Tlr4+/+ or Tlr4-/- bone marrow-derived macrophages (BMDMs) were intratracheally administered to alveolar macrophage-depleted mice. We observed that mice depleted of alveolar macrophages exhibited defective resolution of neutrophilic inflammation, exuded protein, lung edema, and lung tissue injury after ventilation, whereas these delayed responses were reversed by administration of Tlr4+/+ BMDMs. Importantly, these proresolving effects by Tlr4+/+ BMDMs were abolished in mice receiving Tlr4-/- BMDMs. The number of macrophages containing apoptotic cells or bodies in bronchoalveolar lavage fluid was much less in mice receiving Tlr4-/- BMDMs than that in those receiving Tlr4+/+ BMDMs. Macrophage TLR4 deletion facilitated a disintegrin and metalloprotease 17 maturation and enhanced Mer cleavage in response to mechanical ventilation. Heat shock protein 70 dramatically increased Mer tyrosine kinase surface expression, phagocytosis of apoptotic neutrophils, and rescued the inflammatory phenotype in alveolar macrophage-depleted mice receiving Tlr4+/+ BMDMs, but not Tlr4-/- BMDMs. Our results suggest that macrophage TLR4 promotes resolution of VILI via modulation of Mer-mediated efferocytosis.
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Macrófagos Alveolares/metabolismo , Neutrófilos/inmunología , Fagocitosis/fisiología , Receptor Toll-Like 4/metabolismo , Lesión Pulmonar Inducida por Ventilación Mecánica/patología , Proteína ADAM17/metabolismo , Animales , Apoptosis/fisiología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Células Cultivadas , Femenino , Proteínas HSP70 de Choque Térmico/metabolismo , Pulmón/patología , Macrófagos Alveolares/trasplante , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Respiración Artificial/efectos adversos , Transducción de Señal , Tirosina Quinasa c-Mer/metabolismoRESUMEN
BACKGROUND: To investigate the effect of extubation in the operating room (OR) on mechanical ventilation-related adverse outcomes in patients who undergo liver transplantation. METHODS: Patients who underwent liver transplantation between January 2016 and December 2019 were included. According to the timing of extubation, patients were divided into OR extubation group and intensive care unit (ICU) extubation group. The propensity score was used to match OR extubation group and ICU extubation group at a 1:2 ratio by demographical and clinical covariates. The primary outcome was a composite of mechanical ventilation-related adverse outcomes, including 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), and in-hospital moderate to severe pulmonary complications. Secondary outcomes included in-hospital moderate to severe infectious complications, unplanned reintubation rates, ICU and postoperative hospital lengths of stay, and total hospital cost. RESULTS: A total of 438 patients were enrolled. After propensity score matching, 94 patients were in OR extubation group and 148 patients were in ICU extubation group. Incidence of the composite mechanical ventilation-related adverse outcomes was significantly lower in OR extubation group than ICU extubation group, even after adjusting for confounding factors (19.1% vs. 31.8%; Odds Ratio, 0.509; 95% Confidence Index [CI], 0.274-0.946; P=0.031). The duration of ICU stay was much shorter in OR extubation group than ICU extubation group (median 4, Interquartile range [IQR] (3 ~ 6) vs. median 6, IQR (4 ~ 8); P<0.001). Meanwhile, extubation in the OR led to a significant reduction of total hospital cost compared with extubation in the ICU (median 3.9, IQR (3.5 ~ 4.6) 10000 US dollars vs. median 4.1, IQR (3.8 ~ 5.1) 10000 US dollars; P=0.021). However, there were no statistically significant differences in moderate to severe infectious complications, unplanned reintubation rates, and the length of postoperative hospital stay between groups. CONCLUSIONS: Among patients who underwent liver transplantation, extubation in the OR compared with extubation in the ICU, significantly reduced the primary composite outcome of 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), or in-hospital moderate to severe pulmonary complications. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov with registration number NCT04261816. Retrospectively registered on 1st February 2020.
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Extubación Traqueal/métodos , Trasplante de Hígado/métodos , Quirófanos , Respiración Artificial/efectos adversos , Lesión Renal Aguda/epidemiología , Adulto , Estudios de Cohortes , Femenino , Costos de Hospital , Mortalidad Hospitalaria , Humanos , Infecciones/epidemiología , Unidades de Cuidados Intensivos/estadística & datos numéricos , Intubación Intratraqueal/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Enfermedades Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: B7 family members and ligands have been identified as critical checkpoints in orchestrating the immune response during sepsis. V-domain Ig suppressor of T cell activation (VISTA) is a new inhibitory immune checkpoint involved in restraining T cell response. Previous studies demonstrated that VISTA engagement on T cells and myeloid cells could transmit inhibitory signals, resulting in reduced activation and function. The current study was designed to determine the potential therapeutic effects of a high-affinity anti-VISTA antibody (clone MH5A) in a murine model of sepsis. METHODS: Polymicrobial sepsis was induced in male C57BL/6 mice via cecal ligation and puncture. Expression profiles of VISTA on T lymphocytes and macrophage were examined at 24 and 72 h postsurgery. The effects of anti-VISTA mAb on the 7-day survival, lymphocyte apoptosis, cytokine expression, bacterial burden, and vital organ damage were determined. Furthermore, the effects of anti-VISTA mAb on CD3+ T cell apoptosis and macrophage activation were determined in vitro. RESULTS: VISTA was substantially expressed on T cells and macrophages in sham-operated mice; septic peritonitis did not induce significant changes in the expression profiles. Treatment with MH5A improved the survival of septic mice, accompanied by reduced lymphocyte apoptosis, decreased cytokine expression, and enhanced bacterial clearance. Engagement of VISTA receptor with MH5A mitigated CD3+ T cell apoptosis cultured from CLP mice and suppressed LPS-induced cytokine production by macrophage in vitro. CONCLUSION: The present study identified VISTA as a novel immune checkpoint in the regulation of T cell and macrophage response during sepsis. Modulation of the VISTA pathway might offer a promising opportunity in the immunotherapy for sepsis.
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Apoptosis , Antígenos B7/inmunología , Inflamación/metabolismo , Proteínas de la Membrana/metabolismo , Sepsis/prevención & control , Linfocitos T/patología , Animales , Complejo CD3/metabolismo , Ciego , Citocinas/metabolismo , Modelos Animales de Enfermedad , Sistema Inmunológico , Inmunoterapia , Activación de Linfocitos , Recuento de Linfocitos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Sustancias Protectoras/farmacología , Sepsis/microbiología , Bazo/metabolismo , Timo/metabolismoRESUMEN
The coronavirus disease 2019, named COVID-19 officially by the World Health Organization (Geneva, Switzerland) on February 12, 2020, has spread at unprecedented speed. After the first outbreak in Wuhan, China, Chinese anesthesiologists encountered increasing numbers of infected patients since December 2019. Because the main route of transmission is via respiratory droplets and close contact, anesthesia providers are at a high risk when responding to the devastating mass emergency. So far, actions have been taken including but not limited to nationwide actions and online education regarding special procedures of airway management, oxygen therapy, ventilation support, hemodynamic management, sedation, and analgesia. As the epidemic situation has lasted for months (thus far), special platforms have also been set up to provide free mental health care to all anesthesia providers participating in acute and critical caring for COVID-19 patients. The current article documents the actions taken, lesson learned, and future work needed.
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Anestesiología/normas , Infecciones por Coronavirus , Transmisión de Enfermedad Infecciosa/prevención & control , Control de Infecciones/normas , Pandemias , Neumonía Viral , Anestesiología/tendencias , COVID-19 , China/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Predicción , Humanos , Pandemias/prevención & control , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Neumonía Viral/transmisiónRESUMEN
The timely and efficient clearance of apoptotic neutrophils by macrophages (efferocytosis) is required for the resolution of inflammation and tissue repair, but the regulatory mechanisms remain unclear. In this study, we investigated the role of the small GTPase Ras-related protein in brain (Rab)11a in regulating efferocytosis, and on this basis the resolution of inflammatory lung injury. We observed that apoptotic neutrophil feeding induced a rapid loss of Rab11a activity in bone marrow-derived macrophages and found that depletion of Rab11a in macrophages by small interfering RNA dramatically increased the phagocytosis of apoptotic neutrophils compared with control cells. Additionally, overexpression of wild-type Rab11a inhibited macrophage efferocytosis, whereas overexpression of dominant-negative Rab11a (Rab11a S25N) increased the clearance of apoptotic neutrophils. Rab11a knockdown also increased the surface level of CD36 in macrophages, but it reduced cell surface expression of a disintegrin and metalloproteinase (ADAM) 17. Depletion of ADAM17 rescued the decreased surface CD36 expression found in macrophages overexpressing wild-type Rab11a. Also, blockade of CD36 abolished the augmented efferocytosis seen in Rab11a-depleted macrophages. In mice challenged with endotoxin, intratracheal instillation of Rab11a-depleted macrophages reduced neutrophil count in bronchoalveolar lavage fluid, increased the number of macrophages containing apoptotic neutrophils, and prevented inflammatory lung injury. Thus, Rab11a inactivation in macrophages as a result of apoptotic cell binding initiates phagocytosis of apoptotic neutrophils via the modulation of ADAM17-mediated CD36 cell surface expression. Our results raise the possibility that inhibition of Rab11a activity in macrophages is a promising strategy for activating the resolution of inflammatory lung injury.
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Apoptosis , Macrófagos/enzimología , Macrófagos/fisiología , Neutrófilos/inmunología , Fagocitosis , Proteínas de Unión al GTP rab/metabolismo , Proteína ADAM17/deficiencia , Proteína ADAM17/genética , Proteína ADAM17/inmunología , Animales , Líquido del Lavado Bronquioalveolar/citología , Antígenos CD36/deficiencia , Antígenos CD36/genética , Antígenos CD36/inmunología , Células Cultivadas , Inflamación/inmunología , Inflamación/prevención & control , Lesión Pulmonar/inmunología , Lesión Pulmonar/prevención & control , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Neutrófilos/fisiología , Proteínas de Unión al GTP rab/genéticaRESUMEN
BACKGROUND: Delayed gastric emptying and the resultant "full stomach" is the most important risk factor for perioperative pulmonary aspiration. Using point-of-care gastric sonography, we aimed to investigate the prevalence of full stomach and its risk factors in elective surgical patients with type 2 diabetes. METHODS: Type 2 diabetic and non-diabetic elective surgical patients were included from July 2017 to April 2018 in a 1:1 ratio. The study was retrospectively registered at July 2017, after enrollment of the first participant. Gastric ultrasound was performed 2 h after ingesting clear fluid or 6 h after a light meal. Full stomach was defined by the presence of gastric content in both semi-recumbent and right lateral decubitus positions. For patients with full or intermediate stomach, consecutive ultrasound scan was performed until empty stomach was detected. Logistic regression analyses were used to identify risk factors associated with full stomach. RESULTS: Fifty-two type 2 diabetic and fifty non-diabetic patients were analyzed. The prevalence of full stomach was 48.1% (25/52) in diabetic patients, with 44.0% for 2-h fast after clear fluid and 51.9% for 6-h fast after a light meal, significantly higher than 8% (4/50) in non-diabetic patients (P = 0.000). The average time to empty stomach in diabetic patients was 146.50 ± 40.91 mins for clear liquid and 426.50 ± 45.25 mins for light meal, respectively. Further analysis indicated that presence of diabetes-related eye disease was an independent risk factor of full stomach in diabetic patients (OR = 4.83, P = 0.010). CONCLUSIONS: Almost half of type 2 diabetic patients have a full stomach following the current preoperative fasting guideline. Preoperative ultrasound assessment of gastric content in type 2 diabetic patients is suggested, especially for those with diabetes -related eye disease. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov with registration number NCT03217630 . Retrospectively registered on 14th July 2017.
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Diabetes Mellitus Tipo 2/complicaciones , Vaciamiento Gástrico , Contenido Digestivo/diagnóstico por imagen , Ultrasonografía , Anciano , Estudios de Cohortes , Procedimientos Quirúrgicos Electivos , Oftalmopatías/epidemiología , Oftalmopatías/etiología , Femenino , Gastroparesia/diagnóstico por imagen , Gastroparesia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Estómago/diagnóstico por imagen , Factores de TiempoRESUMEN
BACKGROUND Ouabain, an inhibitor of Na+/K+-ATPase, is a type of endogenous hormone synthesized in the adrenal cortex and hypothalamus. Previous studies found that ouabain potently inhibited inflammatory reactions and regulated immunological processes. Our present study aimed to investigate the therapeutic role of ouabain on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. MATERIAL AND METHODS Ouabain (0.1 mg/kg) or vehicles were intraperitoneally injected into male C57BL/6J mice once a day for 3 consecutive days. One hour after the last injection of ouabain, LPS (5 mg/kg) was administrated through intranasal instillation to induce ALI. 6 hours and 24 hours later, bronchoalveolar lavage ï¬uid (BALF) and lung tissues were harvested to detect the protective effects of ouabain, including protein concentration, inflammation cell counts, lung wet-to-dry ratio, and lung damage. RESULTS The results showed that ouabain attenuated LPS-induced ALI in mice, which was indicated by alleviated pathological changes, downregulated TNF-α, IL-1ß, and IL-6 production, inhibited neutrophils infiltration and macrophages, and ameliorated pulmonary edema and permeability. Further results found the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were suppressed by ouabain in LPS-induced ALI. CONCLUSIONS These results suggest that ouabain negatively modulates the severity of LPS-induced ALI.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/patología , Ouabaína/farmacología , Lesión Pulmonar Aguda/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/citología , Inflamación/patología , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Sustancias Protectoras/farmacología , Transducción de Señal , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND Traumatic brain injury (TBI) leads to acute lung injury (ALI), in which the inflammatory response plays an important role in its pathophysiology. Recent studies suggest that dexmedetomidine (Dex) plays a protective role in acute inflammatory diseases. However, whether Dex has a protective effect on TBI-induced ALI is not clear. The aim of this study was to investigate the effect of Dex on TBI-induced ALI in mice. MATERIAL AND METHODS Mice were randomly divided into 5 groups: 1) sham group; 2) TBI group; 3) TBI+Dex group; 4) TBI+atipamezole (Atip) group; and 5) TBI+Dex+Atip group. Dex (50 µg/kg) was intraperitoneal injected immediately after TBI. The α2 adrenergic antagonist Atip (250 µg/kg) was intraperitoneal injected 15 minutes prior to Dex treatment. Then 24 hours later, the protein concentration in the bronchoalveolar lavage fluid (BALF), lung wet to dry weight ratio, hematoxylin and eosin (H&E) staining of lungs, the level of high-mobility group box protein 1(HMGB1) in serum, and the receptor for advanced glycation end products (RAGE) expression in lung were detected. RESULTS Dex ameliorated the score of lung histological examination, as well as the severity of pulmonary edema and permeability. Moreover, Dex was observed to significantly suppress the expression of HMGBI and RAGE. However, the protective effects of Dex were partially reversed by the administration of Atip. CONCLUSIONS Dex may protect against TBI-induced ALI via the HMGB1-RAGE signal pathway, and this protective effect is partly dependent on its α2 adrenoceptor agonist action.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Dexmedetomidina/farmacología , Lesión Pulmonar Aguda/prevención & control , Animales , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/metabolismo , Líquido del Lavado Bronquioalveolar , Dexmedetomidina/metabolismo , Proteína HMGB1/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Sustancias Protectoras/farmacología , Edema Pulmonar/tratamiento farmacológico , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Catheter-related bladder discomfort (CRBD), secondary to catheterization of urinary bladder is distressing. The aim of this study was to assess the efficacy of preoperative education on CRBD with image illustration for alleviating CRBD. METHODS: Sixty adult male patients, undergoing elective colonal and rectal surgery, were randomized to receive tetracaine mucilage instilled into the urethra and applied to the catheter (tetracain group), or receive tetracaine mucilage in combination with image illustration on CRBD (image group) before urethral catheterization. The incidence and severity of CRBD were assessed at 0.5, 1, 2, and 6 h after patients' extubation. The severity of postoperative pain, incidence of postoperative agitation and other adverse events were also recorded. RESULTS: Patients in image group reported remarkably less CRBD than those in tetracaine group at 0.5,1, 2 and 6 h after extubation (20, 20, 6.7 and 6.7% v.s. 60, 73.3, 53.3 and 53.3%, respectively, P<0.01). Severe CRBD was not reported in either group. However, the incidence of moderate CRBD was significantly lower in image group, with 6.7% at 1 h and thereafter none occurred, compared to 6.7% at 0.5 h, and increasing to 20% at 1 h, 2 h and 6 h in tetracaine group, respectively. Moreover, patients in image group suffered less moderate to severe postoperative pain than that of tetracaine group (13.3% v.s. 40.0% at 1 h, P = 0.039, 33.3% v.s. 60% at 2 h and 6 h, P = 0.038). CONCLUSIONS: Preoperative education on uretheral catheterization via image illustrations could enhance the effect of tetracaine mucilage in reducing both the incidence and severity of CRBD. TRIAL REGISTRATION: The trial was registered at www,clinicaltrials.gov with registration number NCT03199105 (retrospectively registered). Date of trial registration which is "June 26, 2017".
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Anestésicos Locales/administración & dosificación , Dolor Postoperatorio/prevención & control , Tetracaína/administración & dosificación , Cateterismo Urinario/métodos , Adulto , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Educación del Paciente como Asunto/métodos , Proyectos Piloto , Cuidados Preoperatorios , Estudios Prospectivos , Factores de Tiempo , Cateterismo Urinario/efectos adversos , Catéteres UrinariosRESUMEN
Septic liver injury/failure that is mainly characterized by oxidative stress, inflammation, and apoptosis led to a great part of terminal liver pathology with limited effective intervention. Here, we used a lipopolysaccharide (LPS) stimulation model to simulate the septic liver injury and investigated the effect of sophocarpine on LPS-stimulated mice with endotoxemia. We found that sophocarpine increases the survival rate of mice and attenuates the LPS-induced liver injury, which is indicated by pathology and serum liver enzymes. Further research found that sophocarpine ameliorated hepatic oxidative stress indicators (H2O2, O2â-, and NO) and enhanced the expression of antioxidant molecules such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). In addition, sophocarpine also attenuated regional and systematic inflammation and further reduced apoptosis of hepatocytes. Mechanistic evidence was also investigated in the present study as sophocarpine inhibited hepatic expression of the CYP2E/Nrf2 pathway during oxidative stress, inactivated p38/JNK cascade and NF-κB pathway, and, meanwhile, suppressed PI3K/AKT signaling that reduced apoptosis. Conclusively, the present study unveiled the protective role of sophocarpine in LPS-stimulated oxidative reaction, inflammation, and apoptosis by suppressing the CYP2E/Nrf2/ROS as well as PI3K/AKT pathways, suggesting its promising role in attenuating inflammation and liver injury of septic endotoxemia.
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Alcaloides/uso terapéutico , Inflamación/tratamiento farmacológico , Lipopolisacáridos/toxicidad , Animales , Antioxidantes/uso terapéutico , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Glutatión/metabolismo , Peróxido de Hidrógeno/metabolismo , Inflamación/metabolismo , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: As a common and life-threatening infectious syndrome, sepsis contributes significantly to morbidity and mortality in clinical settings. Vascular endothelial injury and hyperpermeability play an important role in the development of sepsis-induced organ dysfunction. Heat shock protein A12B (HSPA12B) is one of the HSP70 superfamily members and is mainly expressed in vascular endothelial cells. The present study was performed to investigate the role of HSPA12B in endothelial barrier dysfunction during sepsis. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with 1 µg/mL of lipopolysaccharide (LPS) and harvested at 0, 3, 6, 9, 12, and 24 h. The messenger RNA and protein levels of HSPA12B were detected by Real Time-polymerase chain reaction and Western blot. Upregulation of HSPA12B was induced by transfection of pIRES2-EGFP plasmid carrying the HSPA12B complementary DNA. The in vitro effect of HSPA12B overexpression on endothelial permeability was manifested by the transendothelial electrical resistance value, expression of the adhesion molecules VE-cadherin, and the level of permeability-related kinase myosin light chain, SRC, and CDC42. Mice received cecal ligation and puncture surgery followed by nasal inhalation of nano-polymer-mediated siRNA. Lung endothelial permeability was assessed via intrajugular vein injection of Evans Blue 30 h after cecal ligation and puncture. RESULTS: After LPS induction, the messenger RNA and protein level of HSPA12B in HUVECs increased and peaked at 12 h, whereas they returned to the baseline level at 24 h. Overexpression of HSPA12B can reduce the permeability of HUVEC stimulated by LPS in vitro, while increasing the expression of VE-Cadherin, myosin light chain, and CDC42. On the other hand, downregulating the expression of HSPA12B can significantly increase lung permeability in mice with sepsis-induced vascular injury. CONCLUSIONS: HSPA12B plays a protective role in vascular endothelial barrier dysfunction by preserving the endothelial permeability during sepsis.
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Endotelio Vascular/metabolismo , Proteínas HSP70 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP70 de Choque Térmico/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Sepsis/metabolismo , Animales , Biomarcadores/metabolismo , Western Blotting , Escherichia coli , Células Endoteliales de la Vena Umbilical Humana/microbiología , Humanos , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos C57BL , Permeabilidad , Reacción en Cadena en Tiempo Real de la Polimerasa , Sepsis/microbiología , Regulación hacia ArribaRESUMEN
BACKGROUND: Salidroside (SDS) is the main effective component of Rhodiola rosea L with a variety of pharmacologic properties. The objective of this study was to investigate the efficacy of SDS in the treatment of experimental sepsis in mice and explore the possible underlying action mechanisms. METHODS: Sepsis was induced in C57BL/6 male mice via cecal ligation and puncture (CLP). The animals were divided into three groups as follows: sham, CLP, and CLP plus SDS. SDS (50 mg/kg) was injected intraperitoneally 1 h after operation. Postoperative survival of the mice, bacterial clearance in blood and peritoneal lavage fluid, cytokine secretion in blood, and histology of lung were evaluated. In addition, apoptosis of immune cells in the spleen and thymus were examined, respectively. RESULTS: SDS administration prolonged the survival of the septic mice, inhibited the proinflammatory responses, and enhanced bacterial clearance. It also alleviated the pathologic changes in the lung and inhibited the apoptosis of immune cells in the spleen and thymus after CLP challenge. CONCLUSIONS: SDS exerts a protective effect in CLP-induced sepsis by attenuating the proinflammatory responses, enhancing bacterial clearance, and preserving adaptive immunity. SDS may be a promising therapeutic strategy for the treatment of sepsis.
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Glucósidos/uso terapéutico , Fenoles/uso terapéutico , Fitoterapia , Rhodiola , Sepsis/tratamiento farmacológico , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/prevención & control , Animales , Apoptosis/efectos de los fármacos , Citocinas/sangre , Evaluación Preclínica de Medicamentos , Glucósidos/farmacología , Inflamación/tratamiento farmacológico , Masculino , Ratones Endogámicos C57BL , Fenoles/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Distribución Aleatoria , Sepsis/sangre , Sepsis/complicaciones , Bazo/efectos de los fármacos , Timo/efectos de los fármacosRESUMEN
OBJECTIVE: The aim of this meta-analysis is to compare the potential effects of inhalation anesthetics with total intravenous anesthetics on alveolar cytokine expression and lung-related clinical outcomes in patients undergoing one-lung ventilation (OLV) for thoracic surgery. METHODS: We retrieved the PubMed, EMBASE, and the Cochrane Library respectively to identify randomized controlled trials comparing different anesthetics (volatile anesthetics vs. intravenous anesthetics) on the pulmonary inflammatory response to OLV. The primary outcomes were the levels of alveolar concentrations of inflammatory cytokines. RESULTS: Eight randomized controlled trials that included 365 patients were screened. Overall, there were significant differences in the concentration of alveolar inflammatory mediators between volatile group and intravenous group, in which volatile group had lower levels of TNF-α (SMD -1.51; 95 % CI -2.15 to -0.87; p < 0.001), IL-6 (SMD -0.70; 95 % CI -0.99 to -0.41; p < 0.001) and IL-8 (SMD -1.32; 95 % CI -2.20 to -0.45; p = 0.003). The overall number of pulmonary complications in the volatile group was smaller (RR 0.42; 95 % CI 0.23-0.77; p = 0.005) and patients in that group had significantly abridged hospitalization stay (WMD -3.59 days; 95 % CI -5.70 to -1.48 days; p = 0.001). CONCLUSIONS: Inhalation anesthetics might be preferable in patients undergoing OLV for thoracic surgery and their protective effects might work via attenuating inflammatory responses.
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Anestésicos por Inhalación/administración & dosificación , Anestésicos Intravenosos/administración & dosificación , Ventilación Unipulmonar/métodos , Propofol/administración & dosificación , Citocinas/metabolismo , Humanos , Tiempo de Internación , Pulmón/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Procedimientos Quirúrgicos Torácicos/métodosRESUMEN
BACKGROUND: Ginsenoside Rg1, the major effective component of ginseng, possesses a variety of pharmacologic activities. The objective of this study was to investigate the effects of Rg1 on liver ischemia-reperfusion (IR) injury and explore its potential mechanisms. MATERIALS AND METHODS: Liver warm IR injury was achieved by occluding the portal vein and hepatic artery for 1 h followed by 6-h reperfusion. Eighteen mice were equally randomized into three groups: sham group, IR group, and IR plus Rg1 group (n = 6 mice per group). Mice received an intravenous dose of 20 mg/kg Rg1 or an equivalent volume of saline before ischemic insult. Liver samples and serum were collected for analyses. Serum aminotransferase, histopathology, and apoptosis were determined. Cytokines were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The phosphorylation of nuclear factor kappa B (NF-κB) p65 was assessed by Western blotting. In addition, the effect of Rg1 in a simulated IR model in vitro was also investigated. Rg1 (100 ug/mL and 500 ug/mL) was administered 1 h before hypoxia insult, and then apoptosis was measured after 12-h reperfusion. RESULTS: Liver IR injury led to a dramatic increase in aminopherase activity, apoptosis and necrosis of hepatocytes, and production of proinflammatory cytokines. Pretreatment with Rg1 protected mice from IR-induced liver injury. Treatment with a high-dose Rg1 (500 ug/mL) significantly suppressed apoptosis compared with a lower dose or control (both P < 0.001). Phosphorylation of NF-κB p65 was increased significantly in IR group, and administration with Rg1 suppressed the level of phosphorylation. CONCLUSIONS: Pretreatment of mice with Rg1 reduced hepatocellular apoptosis and inhibited inflammatory response, which was in part through the NF-κB signaling pathway. Rg1 may provide a novel therapeutic strategy for the treatment of IR-induced liver injury.
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Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Ginsenósidos/farmacología , Hepatitis/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Animales , Moléculas de Adhesión Celular/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Medicamentos Herbarios Chinos/farmacología , Hepatitis/inmunología , Hepatitis/patología , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Necrosis/tratamiento farmacológico , Daño por Reperfusión/inmunología , Daño por Reperfusión/patología , Inmunología del Trasplante/efectos de los fármacos , Isquemia TibiaRESUMEN
BACKGROUND: Ventilator-associated pneumonia (VAP) is common in intensive care units (ICUs). Some evidence indicates that probiotics may reduce the incidence of VAP. Several additional published studies have demonstrated that probiotics are safe and efficacious in preventing VAP in ICUs. We aimed to systematically summarise the results of all available data to generate the best evidence for the prevention of VAP. OBJECTIVES: To evaluate the effectiveness and safety of probiotics for preventing VAP. SEARCH METHODS: We searched CENTRAL (2014, Issue 8), MEDLINE (1948 to September week 1, 2014) and EMBASE (2010 to September 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing probiotics with placebo or another control (excluding RCTs that use probiotics in both study groups) to prevent VAP. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and the quality of trials, and extracted data. MAIN RESULTS: We included eight RCTs, with 1083 participants. All studies compared a form of probiotic (Lactobacillus casei rhamnosus; Lactobacillus plantarum; Synbiotic 2000FORTE; Ergyphilus; combination Bifidobacterium longum + Lactobacillus bulgaricus + Streptococcus thermophilus) versus a control group (placebo; glutamine; fermentable fibre; peptide; chlorhexidine). The analysis of all RCTs showed that the use of probiotics decreased the incidence of VAP (odds ratio (OR) 0.70, 95% confidence interval (CI) 0.52 to 0.95, low quality evidence). However, the aggregated results were uncertain for ICU mortality (OR 0.84, 95% CI 0.58 to 1.22 very low quality evidence), in-hospital mortality (OR 0.78, 95% CI 0.54 to 1.14, very low quality evidence), incidence of diarrhoea (OR 0.72, 95% CI 0.47 to 1.09, very low quality evidence), length of ICU stay (mean difference (MD) -1.60, 95% CI -6.53 to 3.33, very low quality evidence), duration of mechanical ventilation (MD -6.15, 95% CI -18.77 to 6.47, very low quality evidence) and antibiotic use (OR 1.23, 95% CI 0.51 to 2.96, low quality evidence). Antibiotics for VAP were used for a shorter duration (in days) when participants received probiotics in one small study (MD -3.00, 95% CI -6.04 to 0.04). However, the CI of the estimated effect was too wide to exclude no difference with probiotics. There were no reported events of nosocomial probiotic infections in any included study.The overall methodological quality of the included studies, based on our 'Risk of bias' assessments, was moderate with half of the included studies rated as a 'low' risk of bias; however, we rated four included studies as a 'high' risk of bias across one or more of the domains. The study limitations, differences in probiotics administered and participants, and small sample sizes across the included studies mean that the power to detect a trend of overall effect may be limited and chance findings cannot be excluded.To explore the influence of some potential confounding factors in the studies, we conducted an intention-to-treat (ITT) analysis, which did not change the inference of per-protocol analysis. However, our sensitivity analysis did not indicate a significant difference between groups for instances of VAP. AUTHORS' CONCLUSIONS: Evidence suggests that use of probiotics is associated with a reduction in the incidence of VAP. However, the quality of the evidence is low and the exclusion of the one study that did not provide a robust definition of VAP increased the uncertainty in this finding. The available evidence is not clear regarding a decrease in ICU or hospital mortality with probiotic use. Three trials reported on the incidence of diarrhoea and the pooled results indicate no clear evidence of a difference. The results of this meta-analysis do not provide sufficient evidence to draw conclusions on the efficacy and safety of probiotics for the prevention of VAP in ICU patients.
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Neumonía Asociada al Ventilador/prevención & control , Probióticos/uso terapéutico , Humanos , Lactobacillus , Ensayos Clínicos Controlados Aleatorios como Asunto , SimbióticosRESUMEN
Salidroside, isolated from the medicinal plant Rhodiola, was reported to serve as an "adaptogen." This study was designed to explore the protective effect of salidroside on concanavalin A- (Con A-) induced hepatitis in mice and investigate potential mechanisms. C57BL/6 mice were randomly divided into control group, Con A group, and salidroside group. Salidroside (50 mg/kg) was injected intravenously followed by Con A administration. The levels of ALT, AST, inflammatory cytokines and CXCL-10 were examined. The pathological damage of livers was assessed, the amounts of phosphorylated IκBα and p65 were measured, and the numbers of CD4(+) and CD8(+) T lymphocytes in the blood, spleen and infiltrated in the liver were calculated. Our results showed that salidroside pretreatment reduced the levels of ALT, AST dramatically and suppressed the secretion of proinflammatory cytokines through downregulating the activity of NF-κB partly. Salidroside altered the distribution of CD4(+) and CD8(+) T lymphocyte in the liver and spleen through regulating CXCL-10 and decreased the severity of liver injuries. In conclusion, these results confirm the efficacy of salidroside in the prevention of immune mediated hepatitis in mice.
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Concanavalina A/farmacología , Citocinas/metabolismo , Glucósidos/uso terapéutico , Hepatitis/tratamiento farmacológico , Hepatitis/inmunología , Linfocitos/citología , Fenoles/uso terapéutico , Animales , Movimiento Celular/fisiología , Citometría de Flujo , Linfocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Due to its high infectivity, the pandemic has rapidly spread and become a global health crisis. Emerging evidence indicates that endothelial dysfunction may play a central role in the multiorgan injuries associated with COVID-19. Therefore, there is an urgent need to discover and validate novel therapeutic strategies targeting endothelial cells. PIEZO1, a mechanosensitive (MS) ion channel highly expressed in the blood vessels of various tissues, has garnered increasing attention for its potential involvement in the regulation of inflammation, thrombosis, and endothelial integrity. This review aims to provide a novel perspective on the potential role of PIEZO1 as a promising target for mitigating COVID-19-associated endothelial dysfunction.