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1.
Clin Immunol ; 259: 109880, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38142902

RESUMEN

Monocyte aberrations have been increasingly recognized as contributors to renal damage in systemic lupus erythematosus (SLE), however, recognition of the underlying mechanisms and modulating strategies is at an early stage. Our studies have demonstrated that brain-derived neurotrophic factor precursor (proBDNF) drives the progress of SLE by perturbing antibody-secreting B cells, and proBDNF facilitates pro-inflammatory responses in monocytes. By utilizing peripheral blood from patients with SLE, GEO database and spontaneous MRL/lpr lupus mice, we demonstrated in the present study that CX3CR1+ patrolling monocytes (PMo) numbers were decreased in SLE. ProBDNF was specifically expressed in CX3CR1+ PMo and was closely correlated with disease activity and the degree of renal injury in SLE patients. In MRL/lpr mice, elevated proBDNF was found in circulating PMo and the kidney, and blockade of proBDNF restored the balance of circulating and kidney-infiltrating PMo. This blockade also led to the reversal of pro-inflammatory responses in monocytes and a noticeable improvement in renal damage in lupus mice. Overall, the results indicate that the upregulation of proBDNF in PMo plays a crucial role in their infiltration into the kidney, thereby contributing to nephritis in SLE. Targeting of proBDNF offers a potential therapeutic role in modulating monocyte-driven renal damage in SLE.


Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Animales , Humanos , Ratones , Riñón , Ratones Endogámicos MRL lpr , Monocitos , Regulación hacia Arriba , Precursores de Proteínas
2.
Clin Immunol ; 263: 110206, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38599263

RESUMEN

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.


Asunto(s)
Lesión Pulmonar Aguda , Ratones Endogámicos C57BL , Neutrófilos , Fagocitosis , Receptores de IgG , Receptores de Factor de Crecimiento Nervioso , Sepsis , Animales , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/etiología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Sepsis/inmunología , Sepsis/complicaciones , Humanos , Receptores de IgG/metabolismo , Receptores de IgG/genética , Receptores de IgG/inmunología , Ratones , Masculino , Fagocitosis/inmunología , Receptores de Factor de Crecimiento Nervioso/metabolismo , Receptores de Factor de Crecimiento Nervioso/genética , Receptores de Factor de Crecimiento Nervioso/inmunología , Ratones Noqueados , Lipopolisacáridos , Citocinas/metabolismo , Citocinas/inmunología , Pulmón/inmunología , Pulmón/patología , Femenino , FN-kappa B/metabolismo , FN-kappa B/inmunología , Proteínas del Tejido Nervioso
3.
Inflammopharmacology ; 31(5): 2401-2410, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37646897

RESUMEN

BACKGROUND: QP001, a novel meloxicam formulation, has been developed to manage moderate to severe postoperative pain. This study aimed to evaluate the efficacy and safety of QP001 injections for moderate to severe pain following abdominal surgery. METHOD: This prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial enlisted patients experiencing moderate to severe pain following abdominal surgery. These patients were randomized to receive either QP001 injections (30 mg or 60 mg) or a placebo pre-surgery. The primary efficacy endpoint was the total morphine consumption within 24 h after the first administration. RESULTS: A total of 108 patients were enrolled, and 106 patients completed the study. The total morphine consumption in the QP001 30 mg group and 60 mg group, versus placebo group, were significantly lower over the following 24 h (5.11[5.46] vs 8.86[7.67], P = 0.011; 3.11[3.08] vs 8.86[7.67], P < 0.001), respectively. The total morphine consumption in the QP001 30 mg and 60 mg groups, versus placebo group, was also significantly decreased over the following 48 h, including the 24-48 h period (P ≤ 0.001). The QP001 30 mg and 60 mg groups, versus placebo, showed a significant decrease in the area under the curve for pain intensity-time as well as a significant decrease in the effective pressing times of the analgesic pump over the 24 h and 48 h periods (P < 0.05). The QP001 groups, versus placebo, show no significant different in Adverse Events or Adverse Drug Reactions (P > 0.05). CONCLUSION: Preoperative/preemptive QP001 provides analgesia and reduces opioid consumption in patients with moderate to severe pain following abdominal surgery, while maintaining a favorable safety profile.


Asunto(s)
Analgesia , Analgésicos Opioides , Humanos , Analgésicos Opioides/efectos adversos , Meloxicam/uso terapéutico , Estudios Prospectivos , Morfina/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico
4.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(11): 1629-1638, 2023 Nov 28.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38432853

RESUMEN

OBJECTIVES: Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection. Due to lack of effective treatments, it has always been the difficulty and focus of clinical treatment of sepsis. Studies have shown that pro-brain-derived neurotrophic factor (proBDNF) binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor (p75NTR), which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis. This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75NTR in patients with sepsis and its effect on lymphocyte differentiation. METHODS: From the healthy donors (control group, n=40) and sepsis patients (sepsis group, n=40) admitted to the hospital for the first time, peripheral blood samples and blood routine clinical detection indicators were obtained. By using flow cytometry, the proportion of lymphocyte subsets and their expression of proBDNF/p75NTR were examined. The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide (LPS). Flow cytometry analysis technology was used to detect the expression of proBDNF/p75NTR on LPS-treated lymphocyte subsets. On this basis, we investigated the effects on lymphocyte differentiation by inhibiting p75NTR. RESULTS: White blood cell count, neutrophil count, and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group; on the contrary, lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group (all P<0.001). The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group (both P<0.05). In the peripheral blood of sepsis patients, proBDNF expression was upregulated on CD19+ B cells, whereas p75NTR expression was elevated on B cells, CD4+ T cells, and CD8+ T cells (all P<0.05). ProBDNF/p75NTR expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group (P<0.05), and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group. Inhibition of p75NTR increased CD4+ T cell and CD19+ B cell percentages, cytokine expression of IL-4 and IL-10, and reduced IL-1ß and IL-6 production (all P<0.05). CONCLUSIONS: The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils. ProBDNF/p75NTR expression is upregulated in the peripheral blood lymphocytes of sepsis patients, and p75NTR inhibition may control lymphocyte differentiation involved in sepsis progression.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Sepsis , Humanos , Linfocitos T CD8-positivos , Lipopolisacáridos , Linfocitos
5.
Int J Med Sci ; 19(11): 1706-1714, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36237986

RESUMEN

Objective: The aim of this study is to compare the effect of bronchial blockers (BB) and double-lumen tubes (DLT) on patients' postoperative recovery after lung resection. Method: 4,636 patients undergoing lung resection and receiving either BB or DLT intubation were reviewed and matched using the propensity score matching method. The primary outcome was the surgical duration. The secondary outcomes included diagnostic results of postoperative chest X-ray, postoperative oxygenation index, incidence of hypercapnia, hypoxemia and sore throat, chest tube duration, incidence of ICU admission, length of hospital stay and incidence of the 30-day readmission. Results: After matching, 401 patients receiving BB were matched to 3,439 patients receiving DLT. There was no statistical difference on the surgical duration between the two groups (P>0.05). However, compared with the DLT group, patients in the BB group showed more infiltrate especially at the surgery side (14.96% versus 9.07%, P<0.001) based on the chest X-ray, together with higher incidence of ICU admission (5.23% versus 2.61%, P<0.05). Additionally, no statistical differences were found between the two groups about chest tube duration, oxygenation index, incidence of hypercapnia, hypoxemia and sore throat, duration of surgery, hospital stays and 30-day readmission (P>0.05). Conclusions: Compared with the DLT, patients receiving BB technique tend to have increased pulmonary infiltrate (especially the surgery side) and higher incidence of ICU admission at the early post-operative stage, which may have an influence on the patients' recovery.


Asunto(s)
Faringitis , Procedimientos Quirúrgicos Torácicos , Bronquios , Estudios de Cohortes , Humanos , Hipercapnia/complicaciones , Hipoxia/complicaciones , Intubación Intratraqueal/efectos adversos , Faringitis/etiología , Puntaje de Propensión , Procedimientos Quirúrgicos Torácicos/efectos adversos , Procedimientos Quirúrgicos Torácicos/métodos
6.
FASEB J ; 34(2): 2541-2553, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31908023

RESUMEN

Brain-derived neurotrophic factor precursor (proBDNF) has been reported to strengthen the dysfunction of monocytes/macrophages in animal studies. However, it is still unknown the roles of proBDNF in the dysfunction of monocytes in the inflammatory diseases in humans. In the present study, we showed that proBDNF and pan neurotrophic receptor p75 were significantly upregulated in monocytes from healthy donors (HD) after lipopolysaccharide treatment. Exogenous proBDNF treatment upregulated CD40 and proinflammatory cytokines expression in monocytes including interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. In Stanford type-A acute aortic dissection (AAD) patients, proBDNF was upregulated in CD14+ CD163+ CX3CR1+ M2- but not CD14+ CD68+ CCR2+ M1-like monocytes. In addition, sera from AAD patients activated gene expression of proinflammatory cytokines in cultured PBMCs from HD, which was attenuated by proBDNF monoclonal antibody (Ab-proB) treatment. These findings suggested that upregulation of proBDNF in M2-like monocytes may contribute to the proinflammatory response in the AAD.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Citocinas/metabolismo , Macrófagos/metabolismo , Monocitos/metabolismo , Precursores de Proteínas/metabolismo , Adulto , Disección Aórtica/metabolismo , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba
7.
EMBO Rep ; 20(6)2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30979708

RESUMEN

Type I interferon (IFN)-induced Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling drives the expression of IFN-stimulated genes (ISGs) to mediate antiviral response. The strength and duration of JAK-STAT signaling are tightly regulated to ensure effective antiviral defense while avoiding pathological inflammation and autoimmunity. Here, we report that cTAZ, an isoform of the Hippo pathway effector TAZ, is transcribed by an alternative promoter. Although majority of C-terminal sequences of TAZ is retained, cTAZ is not regulated by the Hippo signaling and does not mediate its growth-inhibitory functions. Instead, cTAZ negatively regulates JAK-STAT signaling by inhibiting STAT1/2 nuclear localization and ISG expression, and its expression is induced by type I IFN Thus, cTAZ functions as a modulator of JAK-STAT signaling and may play a role in fine-tuning cellular antiviral response.


Asunto(s)
Quinasas Janus/metabolismo , Regiones Promotoras Genéticas , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Transactivadores/genética , Transcripción Genética , Animales , Perfilación de la Expresión Génica , Vía de Señalización Hippo , Humanos , Ratones , Modelos Biológicos , Fosforilación , Unión Proteica , Multimerización de Proteína , Proteínas Serina-Treonina Quinasas/metabolismo , Transporte de Proteínas , Isoformas de ARN , Factores de Transcripción STAT/química , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ
8.
J Neuroinflammation ; 17(1): 169, 2020 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-32466783

RESUMEN

BACKGROUND: Sepsis-associated encephalopathy (SAE) increases the mortality of septic patients, but its mechanism remains unclear. The present study aimed to investigate the roles of T lymphocytes, proBDNF, and their interaction in the pathogenesis of SAE. METHODS: Fear conditioning tests were conducted for cognitive assessment in the lipopolysaccharide (LPS, 5 mg kg-1)-induced septic mice. Meninges and peripheral blood were harvested for flow cytometry or qPCR. FTY720 and monoclonal anti-proBDNF antibody (McAb-proB) were used to investigate the effect of lymphocyte depletion and blocking proBDNF on the impaired cognitive functions in the septic mice. RESULTS: In the septic mice, cognitive function was impaired, the percentage of CD4+ T cells were decreased in the meninges (P = 0.0021) and circulation (P = 0.0222), and pro-inflammatory cytokines were upregulated, but the anti-inflammatory cytokines interleukin (IL)-4 (P < 0.0001) and IL-13 (P = 0.0350) were downregulated in the meninges. Lymphocyte depletion by intragastrically treated FTY720 (1 mg kg-1) for 1 week ameliorated LPS-induced learning deficit. In addition, proBDNF was increased in the meningeal (P = 0.0042) and peripheral (P = 0.0090) CD4+ T cells. Intraperitoneal injection of McAb-proB (100 µg) before LPS treatment significantly alleviated cognitive dysfunction, inhibited the downregulation of meningeal (P = 0.0264) and peripheral (P = 0.0080) CD4+ T cells, and normalized the gene expression of cytokines in the meninges. However, intra-cerebroventricular McAb-proB injection (1 µg) did not have such effect. Finally, exogenous proBDNF downregulated the percentage of CD4+ T cells in cultured splenocytes from septic mice (P = 0.0021). CONCLUSION: Upregulated proBDNF in immune system promoted the pathogenesis of SAE through downregulating the circulating CD4+ T cells, limiting its infiltration into the meninges and perturbing the meningeal pro-/anti-inflammatory homeostasis.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/inmunología , Linfocitos T CD4-Positivos/inmunología , Meninges/inmunología , Precursores de Proteínas/inmunología , Encefalopatía Asociada a la Sepsis/inmunología , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Precursores de Proteínas/metabolismo , Encefalopatía Asociada a la Sepsis/inducido químicamente , Encefalopatía Asociada a la Sepsis/metabolismo
9.
Acta Anaesthesiol Scand ; 64(3): 354-360, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31715023

RESUMEN

BACKGROUND: Post-operative cognitive dysfunction (POCD) is a decline of cognitive status that commonly occurs after surgery in elderly patients. Whether DNA methylation is associated with the development of POCD remains unclear. METHODS: Subjects (N = 124) older than 65 years-of-age undergoing hip replacement surgery were enrolled. A battery of neuropsychiatric tests was used to examine the perioperative cognitive function of the patients. Early POCD was analyzed using the reliable change index (RCI), and subjects were diagnosed with POCD if RCI < -1.96. Peripheral leukocyte DNA was isolated, and DNA methylation was measured via 5-methylcytosine (mC) using Elisa. RESULTS: Twenty-four patients (19.4%) developed early POCD. There was no difference in baseline 5-mC levels by POCD status. The 5-mC levels significantly decreased on day 7 after surgery in patients who developed early POCD (P = .004), but did not change in non-POCD patients. Moreover, post-operative 5-mC levels were significantly lower in POCD patients than those in non-POCD patients (P = .003). Bivariate logistic models adjusted for age, gender, BMI, duration of anesthesia, and education level clearly demonstrated an independent association between post-operative 5-mC level and early POCD. CONCLUSIONS: Post-operative global hypomethylation of leukocyte DNA was associated with the development of early POCD. TRIAL REGISTRATION: ClinicalTrial, NCT02965235. Registered 16 November 2016, https://www.clinicaltrials.gov/ct2/results?term=NCT02965235&rank=1#rowId0.


Asunto(s)
Artroplastia de Reemplazo de Cadera/métodos , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Metilación de ADN/fisiología , Complicaciones Posoperatorias/metabolismo , Complicaciones Posoperatorias/fisiopatología , Anciano , Disfunción Cognitiva/diagnóstico , Femenino , Evaluación Geriátrica/métodos , Humanos , Masculino , Pruebas Neuropsicológicas , Complicaciones Posoperatorias/diagnóstico
10.
Paediatr Anaesth ; 30(5): 599-606, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32162448

RESUMEN

BACKGROUND: A recent consensus statement in Europe has suggested that the fasting time for clear liquid in children can be shortened to 1 hour before a surgery. However, the study to show that 1-hour fasting time for clear fluids is safe in young children is still lacking. This study aimed to investigate the gastric emptying time for carbohydrate-rich drink and regular 5% glucose solution in children aged 3-7 years. METHODS: After overnight fasting, individuals were randomly assigned to ingest 5 mL kg-1 of either carbohydrate-rich drink or 5% glucose solution. One week later, the same subjects were asked to ingest the other one. Ultrasonography was performed to examine the gastric contents. Gastric antral cross-sectional area was measured, and the gastric fluid volume was calculated before and after fluid ingestion within 120 minutes. The primary outcome was the gastric emptying time for both the clear fluids calculated using the antral cross-sectional area and logarithms of gastric fluid volume. The degrees of thirst and hunger of two drinks were evaluated using a visual analogue scale as the secondary outcomes. RESULTS: Data from 16 individuals were analyzed. In the glucose solution group, the antral cross-sectional area and logarithms of gastric fluid volume returned to baseline at 30 minutes after ingestion. However, in the carbohydrate-rich drink group, the median [interquartile range; range] antral cross-sectional area (3.69 [2.64-5.15; 1.83-8.93] cm2 vs 2.41 [2.10-2.96; 1.81-4.37] cm2 , P < .001) and mean (95% confidence interval) logarithms of gastric fluid volume (2.54 [2.30-2.79] mL vs 2.12 [1.94-2.30] mL, P = .048) were still higher than at 60 minutes and returned to the baseline values at 90 minutes after ingestion, respectively. The degree of thirst was lower in the glucose solution group than that in the carbohydrate-rich drink group. CONCLUSIONS: Gastric emptying of carbohydrate-rich drink is slower than that of 5% glucose solution but the residual gastric fluid volume is low one hour after ingestion of 5 mL kg-1 of either fluid.


Asunto(s)
Bebidas , Carbohidratos de la Dieta/administración & dosificación , Vaciamiento Gástrico/fisiología , Contenido Digestivo/diagnóstico por imagen , Ultrasonografía/métodos , Niño , Preescolar , Estudios Cruzados , Femenino , Humanos , Masculino
11.
BMC Musculoskelet Disord ; 21(1): 58, 2020 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32000742

RESUMEN

BACKGROUND: Hydrogen peroxide has been widely used in Orthopaedics including Orthopaedic oncology, trauma and joint surgeries. However, we encountered an oxygen embolism and myoglobinuria after hydrogen peroxide was used to irrigate a septic hip arthroscopically. CASE PRESENTATION: A 61-year-old male patient with right hip septic arthritis underwent an arthroscopic hip washout and debridement. During the operation, the surgeon used 100 ml of 3% hydrogen peroxide to irrigate the joint cavity. Two minutes after irrigation, there was a transient decrease in oxygen saturation, heart rate and blood pressure, with significant subcutaneous emphysema around the wound. Concentrated urine was drained out 8 h after operation which resolved the following day. Post-operatively, the patient was managed in the intensive care unit for a pulmonary embolism and discharged without further complications. CONCLUSION: Medical staff should be aware of the risk of oxygen embolism and be extremely careful when using hydrogen peroxide in patient care. Oxygen embolism following hydrogen peroxide use is rare, however, once encountered, it may bring serious consequences. Therefore, the use of hydrogen peroxide in closed spaces or arthroscopic procedures should be discontinued.


Asunto(s)
Artritis Infecciosa/cirugía , Artroscopía/efectos adversos , Embolia Aérea/etiología , Peróxido de Hidrógeno/efectos adversos , Huesos Pélvicos/cirugía , Irrigación Terapéutica/efectos adversos , Artritis Infecciosa/diagnóstico por imagen , Artroscopía/métodos , Desbridamiento/efectos adversos , Desbridamiento/métodos , Embolia Aérea/diagnóstico por imagen , Humanos , Peróxido de Hidrógeno/administración & dosificación , Masculino , Persona de Mediana Edad , Oxígeno , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/microbiología , Irrigación Terapéutica/métodos
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 603-608, 2020 May 28.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-32879114

RESUMEN

Since the outbreak of COVID-19, the prevention and control of nosocomial infections has been highly valued. Airway management, including endotracheal intubation, extubation, and suction, has been considered as the high-risk virus-spreading procedures, which can put the health providers at a high risk of nosocomial infections. As hospitals at all levels will gradually resume their routine medical work, effective managements for the airway of the silent asymptomatic carriers and patients with delayed symptoms, treatment for severe patients, and prevention of cross infection in hospital have become the focus for the current prevention and control of nosocomial infections. Under the guidance of partitioned and graded prevention and differential control strategies at this stage, we comprehensively analyzed four main intubation methods used in the current clinical work including rapid sequence intubation, laryngeal mask insertion, intubation guided by video flexible intubating scope and awake tracheal intubation. Furthermore, we discussed and summarized intubation and protection strategies for 3 categories of patients during the COVID-19 pandemic, providing evidence for protecting medical stuff in operating room and ICU against severe acute respiratory syndrome coronavirus 2 infection.


Asunto(s)
Manejo de la Vía Aérea , Infecciones por Coronavirus/terapia , Infección Hospitalaria/prevención & control , Neumonía Viral/terapia , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/prevención & control , Humanos , Intubación , Máscaras Laríngeas , Pandemias/prevención & control , Neumonía Viral/prevención & control , SARS-CoV-2
13.
BMC Neurosci ; 17: 3, 2016 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-26754043

RESUMEN

BACKGROUND: In highly complex social settings, an animal's motivational drive to pursue an object depends not only on the intrinsic properties of the object, but also on whether the decision-making animal perceives an object as being the most desirable among others. Mimetic desire refers to a subject's preference for objects already possessed by another subject. To date, there are no appropriate animal models for studying whether mimetic desire is at play in guiding the decision-making process. Furthermore, the neuropharmacological bases of decision-making processes are not well understood. In this study, we used an animal model (rat) to investigate a novel food-foraging paradigm for decision-making, with or without a mimetic desire paradigm. RESULTS: Faced with the choice of foraging in a competitive environment, rats preferred foraging for the desirable object, indicating the rats' ability for decision-making. Notably, treatment with the non-competitive N-methyl-D-aspartate receptor antagonist MK-801, but not with the dopamine D1 or D2 receptor antagonists, SCH23390 and haloperidol, respectively, suppressed the food foraging preference when there was a competing resident rat in the cage. None of these three antagonists affected the food-foraging preference for palatable food. Moreover, MK-801 and SCH23390, but not haloperidol, were able to abolish the desirable environment effect on standard food-foraging activities in complex social settings. CONCLUSIONS: These results highlight the concept that mimetic desire exerts a powerful influence on food-foraging decision-making in rats and, further, illustrate the various roles of the glutamatergic and dopaminergic systems in mediating these processes.


Asunto(s)
Conducta Competitiva/fisiología , Toma de Decisiones/fisiología , Receptores de Dopamina D1/fisiología , Receptores de Dopamina D2/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Animales , Benzazepinas/administración & dosificación , Conducta Competitiva/efectos de los fármacos , Toma de Decisiones/efectos de los fármacos , Maleato de Dizocilpina/administración & dosificación , Antagonistas de los Receptores de Dopamina D2/administración & dosificación , Preferencias Alimentarias/efectos de los fármacos , Preferencias Alimentarias/fisiología , Haloperidol/administración & dosificación , Masculino , Ratas , Ratas Sprague-Dawley , Receptores de Dopamina D1/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores
14.
BMC Neurosci ; 16: 14, 2015 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-25884414

RESUMEN

BACKGROUND: Neuropathic pain evoked by nerve injury is frequently accompanied by deterioration of emotional behaviors, but the underlying signaling mechanisms remain elusive. Glutamate (Glu) is the major mediator of excitatory synaptic transmission throughout the brain, and abnormal activity of the glutamatergic system has been implicated in the pathophysiology of pain and associated emotional comorbidities. In this study we used the partial sciatic nerve ligation (PSNL) model of neuropathic pain in rats to characterize the development of anxiety-like behavior, the expression of glutamatergic receptors, and the phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, the region that encodes memories related to emotions. RESULTS: We found that the mechanical withdrawal threshold was significantly reduced and an anxiety-like behavior was increased as determined via open field tests and elevated plus-maze tests at 28 days after injury. No significant differences were found in the ratio of sucrose preference and immobility time detected by sucrose preference tests and forced swimming tests respectively, possibly due to the timing factor. The expression of N-methyl-D-aspartate (NMDA) receptor subtypes NR1 and NR2B, but not NR2A, GluR1, or GluR2 (the main subtype of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] receptor) in the hippocampus of injured rats was significantly reduced. Moreover, PSNL resulted in decreased phosphorylation of ERK1/2 in the hippocampus. Intriguingly, treatment with D-serine (a co-agonist of NMDA receptor, 1 g/kg intraperitoneally) reduced the anxiety-like behavior but not the mechanical hypersensitivity induced by PSNL. CONCLUSIONS: PSNL can induce significant anxiety-like but not depression-like behavior, and trigger down-regulation of NMDA but not AMPA receptors in the hippocampus at 28 days after injury.


Asunto(s)
Ansiedad/fisiopatología , Hipocampo/metabolismo , Neuralgia/fisiopatología , Receptores de Glutamato/metabolismo , Neuropatía Ciática/fisiopatología , Anhedonia/efectos de los fármacos , Anhedonia/fisiología , Animales , Ansiolíticos/farmacología , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Sacarosa en la Dieta/administración & dosificación , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/etiología , Hiperalgesia/fisiopatología , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Neuralgia/complicaciones , Neuralgia/tratamiento farmacológico , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Distribución Aleatoria , Ratas Sprague-Dawley , Nervio Ciático/fisiopatología , Neuropatía Ciática/complicaciones , Neuropatía Ciática/tratamiento farmacológico , Serina/farmacología
15.
Neurochem Res ; 40(6): 1179-87, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25894685

RESUMEN

Chronic neuropathic pain has currently become a remarkable public health concern, considerably damaging not only the physiological but also the psychological aspects of humans. This study investigated whether neuropathic pain affects maternal care and assessed the effect of parental neuropathic pain on the development of neuropathic pain and emotion among offspring. Our results showed that mother rats suffered from chronic constriction injury (CCI) exhibited defective maternal care. The offspring fed by CCI mother rats (own or cross-fed) showed a significant increase in anxiety and anxiety-related behavior compared with that fed by sham-operated mother rats. The offspring fed by CCI mother rats also displayed decreased oxytocin expression in their supraoptic nucleus than that fed by sham-operated mother rats. Moreover, DNA methyltransferase (DNMT)1 expression in the amygdale was increased, whereas DNMT3a and DNMT3b expressions remained the same in offspring fed by CCI mother rats, as detected with immunohistochemistry and western blot analysis. In addition, the total DNA methylation in amygdale was upregulated in offspring fed by CCI mother rats. Considering the above findings, the data of this study suggest that parental neuropathic pain influences emotion-related behavior in offspring through maternal feeding behavior rather than through genetic factors and pregnancy experience that was associated with DNA methylation of amygdale in offspring.


Asunto(s)
Amígdala del Cerebelo/metabolismo , Metilación de ADN , Emociones , Conducta Materna , Neuralgia/psicología , Animales , Ansiedad/etiología , Ansiedad/psicología , Constricción Patológica/psicología , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Femenino , Oxitocina/metabolismo , Dimensión del Dolor , Umbral del Dolor , Ratas , Ratas Sprague-Dawley , Núcleo Supraóptico/metabolismo
16.
Zhonghua Yi Xue Za Zhi ; 95(33): 2664-7, 2015 Sep 01.
Artículo en Zh | MEDLINE | ID: mdl-26711818

RESUMEN

OBJECTIVE: To explore impact of coronary CT angiography findings on preventive medical treatment and control of coronary artery disease (CAD) risk factors. METHODS: Consecutive patients with atherosclerotic plaque detected by coronary CT angiography were enrolled in our study from September 2013 to December 2014, grouped as <50% stenosis and ≥ 50% stenosis.Baseline and follow-up data were recorded.Comparative analysis was performed both between stenosis groups and pre- and post-CT angiography data.Multivariable Logistic regression were preformed to investigate association between coronary CT angiography findings and subsequent medical therapies. RESULTS: Totally 160 patients were enrolled in our study, 99 were <50% stenosis and 61 were ≥ 50% stenosis.Significant reduction of total cholesterol (5.06 ± 1.04 vs 4.54 ± 1.09 mmol/L, P<0.01), low-density lipoprotein cholesterol (3.16 ± 0.95 vs 2.60 ± 0.88 mmol/L, P<0.01), and triglyceride (1.66 (1.14, 2.28) vs 1.55(1.07, 2.05) mmol/L, P=0.004) were observed Pre- versus post-CT angiography. Compared to patients with <50% stenosis, patients with ≥ 50% stenosis demonstrated more significant reduction with regard to total cholesterol (-0.70 ± 0.94 vs -0.42 ± 0.96 mmol/L, P=0.035) and low-density lipoprotein cholesterol (-0.78 ± 0.99 vs -0.43 ± 0.79 mmol/L, P=0.016). After CT angiography, aspirin (13.8% vs 65.6%, P<0.01) and statin (20.0% vs 71.9%, P<0.01) use were significantly increased, blood pressure medication (53.1% vs 63.1%, P=0.07) use showed no statistical differences. Adjusted for baseline risk factors and pretest medications, CT angiography findings were independently associated with increased post-CT angiography use of aspirin (adjusted OR (95% CI) : 3.58 (1.61-7.99), P=0.002) and statin (adjusted OR (95% CI) : 15.01 (4.40-51.22), P<0.01). CONCLUSION: Coronary CT angiography findings demonstrated direct impact on subsequent medical therapies and control of CAD risk factors, and offered important guidance for prevention strategies of CAD.


Asunto(s)
Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Aspirina , Colesterol , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Modelos Logísticos , Placa Aterosclerótica , Factores de Riesgo , Tomografía Computarizada por Rayos X , Triglicéridos
17.
Eur J Med Res ; 29(1): 201, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528564

RESUMEN

Big data technologies have proliferated since the dawn of the cloud-computing era. Traditional data storage, extraction, transformation, and analysis technologies have thus become unsuitable for the large volume, diversity, high processing speed, and low value density of big data in medical strategies, which require the development of novel big data application technologies. In this regard, we investigated the most recent big data platform breakthroughs in anesthesiology and designed an anesthesia decision model based on a cloud system for storing and analyzing massive amounts of data from anesthetic records. The presented Anesthesia Decision Analysis Platform performs distributed computing on medical records via several programming tools, and provides services such as keyword search, data filtering, and basic statistics to reduce inaccurate and subjective judgments by decision-makers. Importantly, it can potentially to improve anesthetic strategy and create individualized anesthesia decisions, lowering the likelihood of perioperative complications.


Asunto(s)
Anestesia , Anestesiología , Anestésicos , Humanos , Macrodatos , Nube Computacional , Técnicas de Apoyo para la Decisión
18.
Heliyon ; 10(15): e35053, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39157327

RESUMEN

Background: This study compared the efficacy of oropharyngeal airways (OA) and nasopharyngeal airways (NA) in maintaining oxygenation during painless fiberoptic bronchoscopy (PFB) in patients sedated with remimazolam besylate. Methods: Two hundred and fifty-two patients were randomized to the OA or NA group. Remimazolam besylate was used for anesthesia induction and maintenance in both groups. We measured and recorded several physiological parameters, including mean arterial pressure, heart rate and oxygen saturation (SpO2), at various time points: before anesthesia (T1), after anesthesia induction (T2), immediately after the bronchoscope reached the trachea (T3), during the procedure (T4), and 5 min after transfer to the post-anesthesia care unit (T5). The incidence and frequency of hypoxemia, minimum SpO2 during the procedure and patient awakening time after flumazenil administration were also recorded. Additionally, the relationship between minimum SpO2 and body mass index (BMI) was investigated. Results: Patients in the NA group experienced a higher incidence of hypoxemia compared to the OA group. Patients in the OA group maintained higher SpO2 levels at T3 and had a higher minimum SpO2 during the procedure than the NA group. Furthermore, a significant negative correlation was observed between minimum SpO2 and BMI. Following flumazenil anesthesia reversal, nearly 97 % of patients awakened within 1 min. Conclusions: This study suggests that OA may provide a better safety profile than NA by preserving respiratory function during PFB.

19.
Cell Death Dis ; 15(9): 669, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266539

RESUMEN

Acute type A aortic dissection (ATAAD) is a lethal pathological process within the aorta with high mortality and morbidity. T lymphocytes are perturbed and implicated in the clinical outcome of ATAAD, but the exact characteristics of T cell phenotype and its underlying mechanisms in ATAAD remain poorly understood. Here we report that CD4+ T cells from ATAAD patients presented with a hypofunctional phenotype that was correlated with poor outcomes. Whole transcriptome profiles showed that ferroptosis and lipid binding pathways were enriched in CD4+ T cells. Inhibiting ferroptosis or reducing intrinsic reactive oxygen species limited CD4+ T cell dysfunction. Mechanistically, CD36 was elevated in CD4+ T cells, whose blockade effectively alleviated palmitic acid-induced ferroptosis and CD4+ T cell hypofunction. Therefore, targeting the CD36-ferroptosis pathway to restore the functions of CD4+ T cells is a promising therapeutic strategy to improve clinical outcomes in ATAAD patients.


Asunto(s)
Disección Aórtica , Antígenos CD36 , Linfocitos T CD4-Positivos , Ferroptosis , Homeostasis , Ferroptosis/genética , Ferroptosis/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Humanos , Disección Aórtica/patología , Disección Aórtica/metabolismo , Disección Aórtica/genética , Antígenos CD36/metabolismo , Antígenos CD36/genética , Masculino , Especies Reactivas de Oxígeno/metabolismo , Persona de Mediana Edad , Animales , Femenino , Ratones
20.
Zhonghua Xin Xue Guan Bing Za Zhi ; 41(11): 935-9, 2013 Nov.
Artículo en Zh | MEDLINE | ID: mdl-24370221

RESUMEN

PURPOSE: To compare coronary plaque burden, composition, distribution and the degree of coronary artery stenosis in invasive coronary angiography (ICA) diagnosed coronary artery disease (CAD) patients with or without metabolic syndrome (MetS). METHODS: From January 2008 to June 2011, consecutive patients underwent both coronary computed tomography angiography (CCTA) and ICA within three months were enrolled. Patients with history of previous percutaneous coronary interventions (PCI) and coronary artery bypass grafting (CABG) were excluded. Plaque characteristics and maximal luminal diameter stenosis were analyzed on a 16-segment basis as suggested by the American Heart Association classification. RESULTS: The study population consisted of 872 patients [age (60.2 ± 10.0) years, 72.70% males] including 377 patients with MetS and 495 patients without MetS. The median coronary artery calcium score (CACS) was higher in MetS patients than in non-MetS patients [102 (10, 410) vs. 58 (0, 274) , P < 0.01]. Percentage of patients with no coronary artery calcium was significantly lower in MetS group than in non-MetS group [19.63% (74/377) vs. 30.71% (152/495) , P < 0.01], while percentage of patients with severe coronary calcium (CACS ≥ 1000) were significantly higher in MetS than non-MetS group [8.22% (31/377) vs. 4.65% (23/495) , P = 0.03]. The proportion of patients with 1-vessel disease was lower [23.61% (89/377) vs. 36.77% (182/495), P < 0.01], 2-vessel [29.71% (112/377) vs. 22.83% (113/495), P < 0.05] and 3-vessel disease [35.54% (134/377) vs. 24.44% (121/495) , P < 0.01] were higher in MetS group than in non-MetS group. Calcified plaque of LM and the middle and distal coronary artery were significantly higher in MetS group than in non-MetS group (all P < 0.05) . CONCLUSIONS: CAD patients with MetS are associated with severer coronary artery calcium deposition and higher percentage of calcified plaque in the middle and distal coronary arteries and severer obstructive coronary vessels.


Asunto(s)
Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Vasos Coronarios/patología , Síndrome Metabólico/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico por imagen , Anciano , Enfermedad de la Arteria Coronaria/complicaciones , Vasos Coronarios/diagnóstico por imagen , Femenino , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
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