Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
J Med Microbiol ; 73(7)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38958241

RESUMEN

Objectives. Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat Candida organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, N-acetylcysteine (NAC), on adhesion and biofilm formation in Candida parapsilosis clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes (CpALS6, CpALS7, CpEFG1 and CpBCR1) when administrated with NAC in C. parapsilosis strains, furthermore, to explore the mechanism of drug interference on biofilms.Hypothesis/Gap statement. N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.Methods. To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of C. parapsilosis isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related factors (CpEFG1 and CpBCR1) in the BCR1 knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of C. parapsilosis, RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.Results. A high concentration of NAC reduces the total amount of biofilm formation in C. parapsilosis. Following co-incubation with NAC, the expression of CpEFG1 in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of CpBCR1 compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.Conclusions. The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections.


Asunto(s)
Acetilcisteína , Biopelículas , Candida parapsilosis , Candidemia , Infecciones Relacionadas con Catéteres , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Acetilcisteína/farmacología , Humanos , Candida parapsilosis/efectos de los fármacos , Candida parapsilosis/genética , Candida parapsilosis/fisiología , Infecciones Relacionadas con Catéteres/microbiología , Candidemia/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Antifúngicos/farmacología
2.
Curr Med Sci ; 43(4): 723-732, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37326886

RESUMEN

OBJECTIVE: This study aimed to establish a nomogram model to predict the mortality risk of patients with dangerous upper gastrointestinal bleeding (DUGIB), and identify high-risk patients who require emergent therapy. METHODS: From January 2020 to April 2022, the clinical data of 256 DUGIB patients who received treatments in the intensive care unit (ICU) were retrospectively collected from Renmin Hospital of Wuhan University (n=179) and the Eastern Campus of Renmin Hospital of Wuhan University (n=77). The 179 patients were treated as the training cohort, and 77 patients as the validation cohort. Logistic regression analysis was used to calculate the independent risk factors, and R packages were used to construct the nomogram model. The prediction accuracy and identification ability were evaluated by the receiver operating characteristic (ROC) curve, C index and calibration curve. The nomogram model was also simultaneously externally validated. Decision curve analysis (DCA) was then used to demonstrate the clinical value of the model. RESULTS: Logistic regression analysis showed that hematemesis, urea nitrogen level, emergency endoscopy, AIMS65, Glasgow Blatchford score and Rockall score were all independent risk factors for DUGIB. The ROC curve analysis indicated the area under curve (AUC) of the training cohort was 0.980 (95%CI: 0.962-0.997), while the AUC of the validation cohort was 0.790 (95%CI:0.685-0.895). The calibration curves were tested for Hosmer-Lemeshow goodness of fit for both training and validation cohorts (P=0.778, P=0.516). CONCLUSION: The developed nomogram is an effective tool for risk stratification, early identification and intervention for DUGIB patients.


Asunto(s)
Hemorragia Gastrointestinal , Nomogramas , Humanos , Estudios Retrospectivos , Pronóstico , Curva ROC , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia
3.
Comb Chem High Throughput Screen ; 26(8): 1571-1577, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36683371

RESUMEN

BACKGROUND AND OBJECTIVE: Dizziness is a common complication of gastrointestinal endoscopy under general anesthesia. Dizziness is primarily caused by a lack of energy and blood volume following fasting and water deprivation. Hypertonic glucose solution (HGS) is an intravenous energy replenishment, that increases blood volume due to its hyperosmotic characteristics and can be directly absorbed from blood circulation. This study aimed to HGS can prevent dizziness after gastrointestinal endoscopy. METHODS: This was a double-blind, randomized, controlled study. Eligible patients were randomly allocated into two groups based on the intravenous agent administered before gastrointestinal endoscopy: Group A, saline (0.9%; 20 mL); and group B, HGS (50%; 20 mL). Overall, 840 patients were included in the statistical analysis. The scores and incidence of dizziness were assessed. RESULTS: The dizziness score were higher in group A than in group B (1.92 ± 0.08 vs. 0.92 ± 0.06; p < 0.01). The incidence of mild dizziness and moderate-to-severe dizziness was significantly lower in group B than in group A (40.10% vs. 51.78% and 3.10% vs. 19.72%, respectively; p < 0.01). The incidence and score of dizziness were significantly lower in males than in females (30.81% vs. 51.82% and 0.64 ± 0.08 vs. 1.12 ± 0.08, respectively; p < 0.01) after pretreatment with HGS. CONCLUSION: Pretreatment with HGS effectively prevents dizziness after gastrointestinal endoscopy under general anesthesia. The mechanism of action is unclear but might be related to body energy replacement and an increase in blood volume following HGS administration.


Asunto(s)
Mareo , Solución Hipertónica de Glucosa , Masculino , Femenino , Humanos , Administración Intravenosa , Endoscopía Gastrointestinal , Anestesia General/efectos adversos
4.
Curr Med Sci ; 42(2): 317-326, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35290603

RESUMEN

OBJECTIVE: To examine the independent risk factors of type-2 myocardial infarction (T2MI) elicited by acute upper gastrointestinal bleeding (AUGIB), and to establish a nomogram model for the prediction of AUGIB-induced T2MI. METHODS: A nomogram model was established on the basis of a retrospective study that involved 533 patients who suffered from AUGIB in the Department of Critical Care Medicine (CCM) or Emergency Intensive Care Unit (EICU) of Renmin Hospital of Wuhan University, Wuhan, China, from January 2017 to December 2020. The predictive accuracy and discriminative power of the nomogram were initially evaluated by internal validation, which involved drawing the receiver operating characteristic (ROC) curve, calculating the area under the curve (AUC), plotting the calibration curve derived from 1000 resampled bootstrap data sets, and computing the root mean square error (RMSE). The predictive ability of the nomogram was further validated through the prospective and multicenter study conducted by the investigators, which enrolled 240 AUGIB patients [including 88 cases from Renmin Hospital of Wuhan University, 73 cases from Qilu Hospital of Shandong University (Qingdao), and 79 cases from Northern Jiangsu People's Hospital)], who were admitted to the Department of CCM or EICU, from February 2021 to July 2021. RESULTS: Among the 533 patients in the training cohort, 78 (14.6%) patients were assigned to the T2MI group and 455 (85.4%) patients were assigned to the non-T2MI group. The multivariate analysis revealed that age >65, hemorrhagic shock, cerebral stroke, heart failure, chronic kidney disease, increased blood urea nitrogen, decreased hematocrit, and elevated D-Dimer were independent risk factors for AUGIB-induced T2MI. All these factors were incorporated into the nomogram model. The AUC for the nomogram for predicting T2MI was 0.829 (95% CI, 0.783-0.875) in the internal validation cohort and 0.848 (95% CI, 0.794-0.902) in the external validation cohort. The calibration curve for the risk of T2MI exhibited good consistency between the prediction by the nomogram and the actual clinical observation in both the internal validation (RMSE=0.016) and external validation (RMSE=0.020). CONCLUSION: The nomogram was proven to be a useful tool for the risk stratification of T2MI in AUGIB patients, and is helpful for the early identification of AUGIB patients who are prone to T2MI for early intervention, especially in emergency departments and intensive care units.


Asunto(s)
Infarto del Miocardio , Nomogramas , Enfermedad Aguda , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos
5.
J Pain Res ; 13: 865-871, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32431534

RESUMEN

PURPOSE: Pectoral nerve block I (PECS I) and serratus-intercostal plane block (SIPB) can anesthetize the majority mammary region, while parasternal intercostal block (PSI) targets the internal area during breast resection surgery. The aim of this study was to determine whether including PSI with PECS I and SIPB is more effective compared to PECS I and SIPB alone. PATIENTS AND METHODS: Sixty-two adult females undergoing unilateral modified radical mastectomy (MRM) were randomly assigned to receive either PECS I and SIPB (PS group, n=31) or a combination of PECS I, SIPB, and PSI (PSP group, n=31). The outcomes were measured with a numerical rating scale (NRS) score, and in terms of opioid consumption and anesthesia-related complications within 48 h after surgery. RESULTS: Although there were no differences in the NRS scores between the two groups during the inactive periods, the combination of three nerve blocks significantly reduced the NRS scores during movement. In addition, morphine equivalent consumption was lower in the PSP group compared to the PS group. Postoperative adverse events were similar in both groups in terms of regional anesthesia-related complications. CONCLUSION: The combination of PECS I block, SIPB, and PSI block provides superior pain relief and postoperative recovery for patients undergoing MRM.

6.
EClinicalMedicine ; 21: 100331, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32292899

RESUMEN

BACKGROUND: The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China, has spread rapidly worldwide. In the early stage, we encountered a small but meaningful number of patients who were unintentionally scheduled for elective surgeries during the incubation period of COVID-19. We intended to describe their clinical characteristics and outcomes. METHODS: We retrospectively analyzed the clinical data of 34 patients underwent elective surgeries during the incubation period of COVID-19 at Renmin Hospital, Zhongnan Hospital, Tongji Hospital and Central Hospital in Wuhan, from January 1 to February 5, 2020. FINDINGS: Of the 34 operative patients, the median age was 55 years (IQR, 43-63), and 20 (58·8%) patients were women. All patients developed COVID-19 pneumonia shortly after surgery with abnormal findings on chest computed tomographic scans. Common symptoms included fever (31 [91·2%]), fatigue (25 [73·5%]) and dry cough (18 [52·9%]). 15 (44·1%) patients required admission to intensive care unit (ICU) during disease progression, and 7 patients (20·5%) died after admission to ICU. Compared with non-ICU patients, ICU patients were older, were more likely to have underlying comorbidities, underwent more difficult surgeries, as well as more severe laboratory abnormalities (eg, hyperleukocytemia, lymphopenia). The most common complications in non-survivors included ARDS, shock, arrhythmia and acute cardiac injury. INTERPRETATION: In this retrospective cohort study of 34 operative patients with confirmed COVID-19, 15 (44·1%) patients needed ICU care, and the mortality rate was 20·5%. FUNDING: National Natural Science Foundation of China.

7.
Neural Regen Res ; 15(7): 1333-1339, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31960821

RESUMEN

Glucagon-like peptide-1 receptor has anti-apoptotic, anti-inflammatory, and neuroprotective effects. It is now recognized that the occurrence and development of chronic pain are strongly associated with anti-inflammatory responses; however, it is not clear whether glucagon-like peptide-1 receptor regulates chronic pain via anti-inflammatory mechanisms. We explored the effects of glucagon-like peptide-1 receptor on nociception, cognition, and neuroinflammation in chronic pain. A rat model of chronic pain was established using left L5 spinal nerve ligation. The glucagon-like peptide-1 receptor agonist exendin-4 was intrathecally injected into rats from 10 to 21 days after spinal nerve ligation. Electrophysiological examinations showed that, after treatment with exendin-4, paw withdrawal frequency of the left limb was significantly reduced, and pain was relieved. In addition, in the Morris water maze test, escape latency increased and the time to reach the platform decreased following exendin-4 treatment. Immunohistochemical staining and western blot assays revealed an increase in the numbers of activated microglia and astrocytes in the dentate gyrus of rat hippocampus, as well as an increase in the expression of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6. All of these effects could be reversed by exendin-4 treatment. These findings suggest that exendin-4 can alleviate pain-induced neuroinflammatory responses and promote the recovery of cognitive function via the glucagon-like peptide-1 receptor pathway. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Renmin Hospital of Wuhan University of China (approval No. WDRM 20171214) on September 22, 2017.

8.
J Diabetes Res ; 2019: 8520856, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30906786

RESUMEN

BACKGROUND: A substantial increase in histone deacetylase 3 (HDAC3) expression is implicated in the pathological process of diabetes and stroke. However, it is unclear whether HDAC3 plays an important role in diabetes complicated with stroke. We aimed to explore the role and the potential mechanisms of HDAC3 in cerebral ischemia/reperfusion (I/R) injury in diabetic state. METHODS: Diabetic mice were subjected to 1 h ischemia, followed by 24 h reperfusion. PC12 cells were exposed to high glucose for 24 h, followed by 3 h of hypoxia and 6 h of reoxygenation (H/R). Diabetic mice received RGFP966 (the specific HDAC3 inhibitor) or vehicle 30 minutes before the middle cerebral artery occlusion (MCAO), and high glucose-incubated PC12 cells were pretreated with RGFP966 or vehicle 6 h before H/R. RESULTS: HDAC3 inhibition reduced the cerebral infarct volume, ameliorated pathological changes, improved the cell viability and cytotoxicity, alleviated apoptosis, attenuated oxidative stress, and enhanced autophagy in cerebral I/R injury model in diabetic state in vivo and in vitro. Furthermore, we found that the expression of HDAC3 was remarkably amplified, and the Bmal1 expression was notably decreased in diabetic mice with cerebral I/R, whereas this phenomenon was obviously reversed by RGFP966 pretreatment. CONCLUSIONS: These results suggested that the HDAC3 was involved in the pathological process of the complex disease of diabetic stroke. Suppression of HDAC3 exerted protective effects against cerebral I/R injury in diabetic state in vivo and in vitro via the modulation of oxidative stress, apoptosis, and autophagy, which might be mediated by the upregulation of Bmal1.


Asunto(s)
Hipoxia de la Célula/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Inhibidores de Histona Desacetilasas/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Modelos Animales de Enfermedad , Inhibidores de Histona Desacetilasas/farmacología , Masculino , Malondialdehído/metabolismo , Ratones , Fármacos Neuroprotectores/farmacología , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/complicaciones , Daño por Reperfusión/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismo
9.
Biomed Pharmacother ; 107: 818-823, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30142543

RESUMEN

MicroRNA are significant regulators of neuropathic pain development. Neuroinflammation contributes a lot to the progression of neuropathic pain. miR-381 is involved in various pathological processes. However, the role of miR-381 in neuropathic pain development remains barely understood. Therefore, in our study, we aimed to investigate the effects of miR-381 on the process of neuropathic pain progression by establishing a rat model using chronic sciatic nerve injury (CCI). Here, we observed that miR-381 was dramatically decreased in CCI rats. Up-regulation of miR-381 strongly reduced neuropathic pain behaviors including mechanical and thermal hyperalgesia. In addition, inflammatory cytokine expression, including IL-6, IL-10 and TNF-α were significantly repressed by overexpression of miR-381. High mobility group box 1 protein (HMGB1) and Chemokine CXC receptor 4 (CXCR4) participate in neuropathic pain development. In our present study, HMGB1 and CXCR4 were predicted as direct targets of miR-381 by employing bioinformatics analysis. Overexpression of miR-381 was able to restrain the expression of HMGB1 and CXCR4 greatly. The direct correlation between HMGB1 and CXCR4 and miR-381 was confirmed in our research. Furthermore, we found that HMGB1 and CXCR4 were increased in CCI rats time-dependently. Moreover, it was demonstrated that silence of HMGB1 and CXCR4 in CCI rats depressed neuropathic pain progression greatly. In conclusion, it was indicated that miR-381could inhibit neuropathic pain development through targeting HMGB1 and CXCR4.


Asunto(s)
Proteína HMGB1/metabolismo , MicroARNs/metabolismo , Neuralgia/genética , Receptores CXCR4/metabolismo , Animales , Secuencia de Bases , Enfermedad Crónica , Modelos Animales de Enfermedad , Femenino , Silenciador del Gen , Células HEK293 , Humanos , Inflamación/genética , Inflamación/patología , MicroARNs/genética , Neuralgia/patología , Ratas Sprague-Dawley , Nervio Ciático/lesiones
10.
Mol Med Rep ; 17(5): 6327-6336, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29488614

RESUMEN

Blunt chest trauma with hemorrhagic shock (THS) frequently induces pulmonary inflammation that leads to acute lung injury (ALI). Penehyclidine hydrochloride (PHC) possesses anti­inflammatory properties that may attenuate the systemic inflammatory response. The present study aimed to evaluate the molecular mechanism of PHC in modifying THS­induced ALI in rats. Rats underwent either THS or a sham procedure. At 6 h subsequent to blunt chest trauma, arterial blood was drawn for blood gas and pro­inflammatory factors analyses, and lung tissue samples were collected to examine pulmonary histopathological alterations, the wet/dry weight ratio, myeloperoxidase activity, and the protein expression levels of Toll-like receptor 4 (TLR4), phosphorylated (p­)p38 mitogen­activated protein kinase (MAPK), nuclear factor (NF)­κB and activator protein­1 (AP­1). THS caused significant reductions in heart rate and mean arterial blood pressure, and was associated with significant increases in tumor necrosis factor­α, interleukin (IL)­6, IL­1ß, p­p38MAPK, NF­κB and AP­1 activation, in addition to TLR4 expression, in the lung. PHC effectively attenuated THS­induced ALI, and inhibited TLR4 expression, reduced the activation of p­p38MAPK, NF­κB and AP­1, and downregulated the expression of pro­inflammatory mediators. In conclusion, the results of the present study demonstrated that PHC may exert an anti­inflammatory effect and attenuate THS­induced ALI by inhibiting the TLR4 signaling pathway. These preclinical findings may offer a novel therapeutic strategy to restrict TLR4 overactivation in ALI.


Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Quinuclidinas/farmacología , Choque Hemorrágico/tratamiento farmacológico , Receptor Toll-Like 4/metabolismo , Heridas no Penetrantes/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Masculino , Ratas , Ratas Sprague-Dawley , Choque Hemorrágico/metabolismo , Choque Hemorrágico/patología , Tórax , Heridas no Penetrantes/metabolismo , Heridas no Penetrantes/patología
11.
Rev. bras. anestesiol ; 67(6): 600-606, Nov.-Dec. 2017. graf
Artículo en Inglés | LILACS | ID: biblio-897789

RESUMEN

Abstract Background and objectives Dexmedetomidine (DEX) has demonstrated the preconditioning effect and shown protective effects against organize injury. In this study, using A549 (human alveolar epithelial cell) cell lines, we investigated whether DEX preconditioning protected against acute lung injury (ALI) in vitro. Methods A549 were randomly divided into four groups (n = 5): control group, DEX group, lipopolysaccharides (LPS) group, and D-LPS (DEX + LPS) group. Phosphate buffer saline (PBS) or DEX were administered. After 2 h preconditioning, the medium was refreshed and the cells were challenged with LPS for 24 h on the LPS and D-LPS group. Then the malondialdehyde (MDA), superoxide dismutase (SOD), Bcl-2, Bax, caspase-3 and the cytochrome c in the A549 were tested. The apoptosis was also evaluated in the cells. Results Compare with LPS group, DEX preconditioning reduced the apoptosis (26.43% ± 1.05% vs. 33.58% ± 1.16%, p < 0.05) in the A549, which is correlated with decreased MDA (12.84 ± 1.05 vs. 19.16 ± 1.89 nmoL.mg-1 protein, p < 0.05) and increased SOD activity (30.28 ± 2.38 vs. 20.86 ± 2.19 U.mg-1 protein, p < 0.05). DEX preconditioning also increased the Bcl-2 level (0.53 ± 0.03 vs. 0.32 ± 0.04, p < 0.05) and decreased the level of Bax (0.49 ± 0.04 vs. 0.65 ± 0.04, p < 0.05), caspase-3 (0.54 ± 0.04 vs. 0.76 ± 0.04, p < 0.05) and cytochrome c. Conclusion DEX preconditioning has a protective effect against ALI in vitro. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation.


Resumo Justificativa e objetivos Dexmedetomidina (DEX) demonstrou ter efeito pré-condicionante e também efeitos protetores contra lesão organizada. Neste estudo, com células A549 (células epiteliais alveolares humanas), investigamos se o pré-condicionamento com DEX proporcionaria proteção contra lesão pulmonar aguda (LPA) in vitro. Métodos Células A549 foram aleatoriamente distribuídas em quatro grupos (n = 5): controle, DEX, lipopolissacarídeos (LPS) e D-LPS (DEX + LPS). Administramos solução de PBS (tampão fosfato-alcalino) ou DEX. Após 2 h de pré-condicionamento, o meio foi renovado e as células desafiadas com LPS por 24 h nos grupos LPS e D-LPS. Em seguida, malondialdeído (MDA), superóxido dismutase (SOD), Bcl-2, Bax, caspase-3 e em A549 foram testados. Apoptose também foi avaliada nas células. Resultados Em comparação com o grupo LPS, o pré-condicionamento com DEX reduziu a apoptose (26,43% ± 1,05% vs. 33,58% ± 1,16%, p < 0,05) em células A549, o que está correlacionado com a diminuição de MDA (12,84 ± 1,05 vs. 19,16 ± 1,89 nmol.mg-1 de proteína, p < 0,05) e aumento da atividade de SOD (30,28 ± 2,38 vs. 20,86 ± 2,19 U.mg-1 de proteína, p < 0,05). O pré-condicionamento com DEX também aumentou o nível de Bcl-2 (0,53 ± 0,03 vs. 0,32 ± 0,04, p < 0,05) e diminuiu o nível de Bax (0,49 ± 0,04 vs. 0,65 ± 0,04, p < 0,05), caspase-3 (0,54 ± 0,04 vs. 0,76 ± 0,04, p < 0,05) e citocromo c. Conclusão O pré-condicionamento com DEX tem efeito protetor contra LPA in vitro. Os potenciais mecanismos envolvidos são inibição da morte celular e melhoria da antioxidação.


Asunto(s)
Humanos , Lipopolisacáridos/efectos adversos , Dexmedetomidina/farmacología , Células Epiteliales Alveolares/efectos de los fármacos , Hipnóticos y Sedantes/farmacología , Distribución Aleatoria , Células Cultivadas , Lipopolisacáridos/antagonistas & inhibidores
12.
Rev Bras Anestesiol ; 67(6): 600-606, 2017.
Artículo en Portugués | MEDLINE | ID: mdl-28818492

RESUMEN

BACKGROUND AND OBJECTIVES: Dexmedetomidine (DEX) has demonstrated the preconditioning effect and shown protective effects against organize injury. In this study, using A549 (human alveolar epithelial cell) cell lines, we investigated whether DEX preconditioning protected against acute lung injury (ALI) in vitro. METHODS: A549 were randomly divided into four groups (n=5): control group, DEX group, lipopolysaccharides (LPS) group, and D-LPS (DEX+LPS) group. Phosphate buffer saline (PBS) or DEX were administered. After 2h preconditioning, the medium was refreshed and the cells were challenged with LPS for 24h on the LPS and D-LPS group. Then the malondialdehyde (MDA), superoxide dismutase (SOD), Bcl-2, Bax, caspase-3 and the cytochrome c in the A549 were tested. The apoptosis was also evaluated in the cells. RESULTS: Compare with LPS group, DEX preconditioning reduced the apoptosis (26.43%±1.05% vs. 33.58%±1.16%, p<0.05) in the A549, which is correlated with decreased MDA (12.84±1.05 vs. 19.16±1.89nmol.mg-1 protein, p<0.05) and increased SOD activity (30.28±2.38 vs. 20.86±2.19U.mg-1 protein, p<0.05). DEX preconditioning also increased the Bcl-2 level (0.53±0.03 vs. 0.32±0.04, p<0.05) and decreased the level of Bax (0.49±0.04 vs. 0.65±0.04, p<0.05), caspase-3 (0.54±0.04 vs. 0.76±0.04, p<0.05) and cytochrome c. CONCLUSION: DEX preconditioning has a protective effect against ALI in vitro. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation.


Asunto(s)
Células Epiteliales Alveolares/efectos de los fármacos , Dexmedetomidina/farmacología , Hipnóticos y Sedantes/farmacología , Lipopolisacáridos/efectos adversos , Células Cultivadas , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Distribución Aleatoria
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(3): 423-8, 2016 Mar.
Artículo en Chino | MEDLINE | ID: mdl-27063176

RESUMEN

OBJECTIVE: To investigate that the role of Axin in regulating the invasion and migration ability of lymphoma cells and explore the molecular mechanisms. METHODS: The expressions of Axin, ß-catenin, MMP7, and MMP9 were detected in different lymphoma cell lines by RT-PCR and Western blotting. A lymphoma cell line with low Axin expressions was transiently transfected with pCMV5-HA-Axin and pcDNA5-His-ß-catenin plasmid, and the expressions of ß-catenin, MMP7, and MMP9 mRNA and protein were observed. A lymphoma cell model stably overexpressing Axin was transfected with AXIN-shRNA and ß-catenin-shRNA, and the changes in ß-catenin, MMP7, and MMP9 cexpressions were observed. The changes in the invasion and migration abilities of this cell model were assessed following Axin knockdown. RESULTS: In the lymphoma cell lines tested, the Axin expression showed a negative correlation with ß-catenin, MMP7, and MMP9 expressions. In Raji cells with a low Axin expression, overexpression of Axin resulted in decreased expressions of ß-catenin, MMP7, and MMP9 at the protein levels but not the mRNA levels, and overexpression of ß-catenin obviously increased MMP7 and MMP9 mRNA and protein expressions. In the cells with stable Axin overexpression, Axin knockdown caused increased expressions of ß-catenin, MMP7, and MMP9 at the protein levels but not the mRNA levels, while ß-catenin knockdown caused lowered expressions of MMP7 and MMP9 and suppressed cell invasion and migration. CONCLUSION: In lymphoma cells, Axin overexpression can decrease the expression of ß-catenin, which in turn decreases the expressions of MMP7 and MMP9 to inhibit the cell invasion and migration.


Asunto(s)
Proteína Axina/metabolismo , Linfoma/patología , Metaloproteinasa 7 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , beta Catenina/metabolismo , Proteína Axina/genética , Línea Celular Tumoral , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Humanos , Linfoma/genética , Linfoma/metabolismo , Invasividad Neoplásica , Metástasis de la Neoplasia , ARN Mensajero , ARN Interferente Pequeño , Transfección
14.
Injury ; 43(2): 232-6, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22055139

RESUMEN

BACKGROUND AND OBJECTIVE: Toll-like receptor 4 (TLR4) is widely recognised as a pattern recognition receptor (PRR) in the triggering of innate immunity. Lung inflammation and systemic innate immune responses are dependent on TLR4 activation undergoing pulmonary contusion. Therefore, the author investigated the effects of penehyclidine hydrochloride (PHC) on the expression of TLR4 and inflammatory responses of blunt chest trauma-induced pulmonary contusion. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were randomly assigned into three groups: normal control (NC) group, pulmonary contusion (PC) group and penehyclidine hydrochloride treatment (PHC) group. Pulmonary contusion was induced in anesthetised rats at fixed chest impact energy of 2.45J. Lung injury was assessed by the histopathology changes, arterial blood gas and myeloperoxidase (MPO) activity of lung. The serum tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assays (ELISA). The expression of TLR4 was determined by immunohistochemistry. RESULTS: Blunt chest trauma produced leucocytosis in the interstitial capillaries, hypoxemia, and increased MPO activity. The expressions of TNF-α, IL-6 and TLR4 in the lung were significantly enhanced during pulmonary contusion. PHC treatments effectively attenuated pulmonary inflammation responses, as shown by improved pulmonary oxygenation, histopathology damage, decreased the MPO activity, the expressions of TNF-α, IL-6, and TLR4 after lung injury. CONCLUSION: It might be concluded that PHC exhibit anti-inflammatory and protective effects in traumatic lung injury via the inhibition of the TLR4 pathway.


Asunto(s)
Antiinflamatorios/farmacología , Contusiones/patología , Lesión Pulmonar/patología , Lesión Pulmonar/prevención & control , Sustancias Protectoras/farmacología , Quinuclidinas/farmacología , Traumatismos Torácicos/patología , Receptor Toll-Like 4/efectos de los fármacos , Heridas no Penetrantes/patología , Animales , Contusiones/inmunología , Contusiones/prevención & control , Ensayo de Inmunoadsorción Enzimática , Inmunidad Innata , Inmunohistoquímica , Interleucina-6/metabolismo , Lesión Pulmonar/enzimología , Lesión Pulmonar/inmunología , Masculino , Peroxidasa/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Heridas no Penetrantes/inmunología
15.
Chin J Traumatol ; 13(1): 15-9, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20109362

RESUMEN

OBJECTIVE: To investigate the effects of penehyclidine hydrochloride on apoptosis of lung tissue cells and its mechanism in acute lung injury following blunt chest trauma in rats. METHODS: Sprague Dawley (SD) rats (n equal to 54) weighing (250+/-5) g were divided equally and randomly into three groups: normal control group (C group, n equal to 18), trauma model group (T group, n equal to 18) and penehyclidine hydrochloride treatment group (P group, n equal to 18). Each group was further divided into three subgroups according to the time points of 3, 12 and 24 hours after experiment (at each time point, n equal to 6 for each subgroup). Rats of P group were intraperitoneally injected with penehyclidine hydrochloride for 2 mg/kg immediately after blunt chest trauma and rats in its 24 hours subgroup were once again injected with penehyclidine hydrochloride in the same dose 12 hours after injury. Lung tissue samples were collected at every time point and cell apoptosis in lung tissues were measured by TUNEL. Apoptotic index (AI) was calculated, expressions of bax and bcl-2 were detected by immunohistochemical staining of SABC, and lung tissue sections were taken for light and electron microscopic observation. RESULTS: As compared with C group, at every time point, AI and expressions of bax and bcl-2 in T group were higher (P less than 0.05), and the ratio of bcl-2/bax markedly decreased (P less than 0.05), especially in the 24 hours subgroup. The ratio in T group (0.468+/-0.007) was lower than that in C group (1.382+/-0.058, t equal to 12.5, P less than 0.01). Lung tissue injuries were significant under a light microscope, and the number of apoptotic cells increased obviously under a transmission electron microscope. As compared with T group at the same phase, AI and expression of bax decreased in P group (P less than 0.05 and P less than 0.01), while the expression of bcl-2 increased significantly (P less than 0.01), and the ratio of bcl-2/bax markedly increased (P less than 0.05), especially in the 24 hours subgroup. The ratio in P group (1.012+/-0.070) was much higher than that in T group (0.468+/-0.007, t equal to 8.3, P less than 0.01). The injury of lung tissues was relieved, and apoptosis of cells decreased obviously under a transmission electron microscopic observation. CONCLUSIONS: Apoptosis and expressions of bax and bcl-2 in lung tissues might be involved in the pathogenesis of lung injury induced by blunt chest trauma. Penehyclidine hydrochloride can alleviate lung injuries by inhibiting apoptosis of lung tissue cells, during which effects of penehyclidine hydrochloride on regulating expressions of bax and bcl-2 may play an important role.


Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Pulmón/patología , Quinuclidinas/uso terapéutico , Traumatismos Torácicos/complicaciones , Heridas no Penetrantes/complicaciones , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Ratas , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/análisis
16.
Chin J Traumatol ; 9(3): 181-6, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16723077

RESUMEN

OBJECTIVE: To investigate the effect of Radix Paeoniae Rubra (RPR) on the expression of heme oxygenase (HO-1) and induced nitric oxide synthase (iNOS) in endotoxin-induced acute lung injury in rats and its protective mechanism. METHODS: Forty Wistar rats were divided randomly into 5 groups with 8 rats in each group: saline control group (NS group), lipopolysaccharide group (LPS group), RPR-treatment group, RPR-prevention group and Hemin group. The effect of RPR on protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid, malondialdehyde (MDA) content in the lung and the activity of serum NO were observed. Arterial blood was drawn for blood-gas analysis. The expression of HO-1 and iNOS in lung tissues was detected by immunohistochemistry and morphometry computer image analysis. The histological changes of the lung were observed under light microscope. RESULTS: Compared with that in NS group, the expression of HO-1 and iNOS was markedly increased in LPS group (P<0.01). In RPR-treatment, RPR-prevention, and Hemin groups, the expression of iNOS was significantly lower, while the expression of HO-1 was higher than that in LPS group (P<0.05). The protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid, the content of MDA and the activity of serum NO in LPS group were significantly higher than those in NS group (P<0.01). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in the LPS group (P<0.01); these parameters of lung injury however, were significantly lower in RPR-treatment, RPR-prevention, and Hemin groups than LPS group (P<0.05 or P<0.01). The pathologic changes of lung tissues were substantially attenuated in RPR-treatment, RPR-prevention, and Hemin groups than LPS group. CONCLUSIONS: The high expression of HO-1 reflects an important protective function of the body during lipopolysaccharide-induced acute lung injury. The protective effect of RPR on lipopolysaccharide-induced acute lung injury is related to the inhibition of iNOS expression and the induction of HO-1 expression.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Hemo-Oxigenasa 1/biosíntesis , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/enzimología , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Paeonia , Fitoterapia , Análisis de Varianza , Animales , Endotoxinas , Enfermedades Pulmonares/inducido químicamente , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar
17.
J Thorac Cardiovasc Surg ; 130(2): 258-64, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16077384

RESUMEN

OBJECTIVE: This study was undertaken to demonstrate that gastrointestinal mucosal injury occurs during cardiopulmonary bypass in children, increasing systemic inflammatory responses, and to determine whether shen-fu injection (the major components of which are ginsenosides compound, extract of Panax ginseng shown to have antioxidant properties) could attenuate gastrointestinal mucosal injury and subsequent inflammatory responses. METHODS: Twenty-four children undergoing heart surgery for congenital heart defects were randomly assigned to groups C (placebo control, n = 12) and G (1.35 mg/kg ginsenosides compound intravenously before and throughout the course of cardiopulmonary bypass, n = 12). Central venous blood samples were taken before cardiopulmonary bypass and at 60 and 120 minutes after aortic declamping (reperfusion). Gastric intramucosal pH was measured by perioperative tonometry. Plasma lipid peroxidation product malondialdehyde, myocardium-specific creatine kinase isoenzyme MB activity, diamine oxidase, lipopolysaccharide, and interleukin 6 were all measured. RESULTS: Significant decrease in gastric intramucosal pH and increase in plasma diamine oxidase were seen during reperfusion in group C, accompanied by increases in plasma levels of malondialdehyde, lipopolysaccharide, interleukin 6, and creatine kinase isoenzyme MB (P < .01 vs before cardiopulmonary bypass). Shen-fu injection significantly attenuated these changes (P < .05). Consequently, fewer patients in group G (2/12) than in group C (7/12) needed postoperative inotropic support. Postoperative intensive care unit stay was shorter in group G than in group C. A tight positive correlation was seen between diamine oxidase and interleukin 6 at 60 minutes after aortic declamping and between diamine oxidase and lipopolysaccharide at 120 minutes after aortic declamping (r = 0.79, P < .0001). CONCLUSION: Ginsenosides compound may attenuate gastrointestinal injury and inhibit inflammatory response after cardiopulmonary bypass in patients with congenital heart disease.


Asunto(s)
Antioxidantes/uso terapéutico , Puente Cardiopulmonar/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Enfermedades Gastrointestinales/prevención & control , Cardiopatías Congénitas/cirugía , Adolescente , Amina Oxidasa (conteniendo Cobre)/sangre , Antioxidantes/farmacología , Niño , Creatina Quinasa/sangre , Forma MB de la Creatina-Quinasa , Método Doble Ciego , Medicamentos Herbarios Chinos/farmacología , Femenino , Mucosa Gástrica/efectos de los fármacos , Fármacos Gastrointestinales/farmacología , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Gastrointestinales/sangre , Enfermedades Gastrointestinales/etiología , Cardiopatías Congénitas/sangre , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacos , Interleucina-6/sangre , Isoenzimas/sangre , Lipopolisacáridos/sangre , Masculino , Malondialdehído/sangre
18.
Chin J Traumatol ; 6(6): 359-62, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14642057

RESUMEN

OBJECTIVE: To study the effect of methylprednisolone (MP) on reperfusion injury in severe uncontrolled hemorrhagic shock and explore the possible mechanism involved. METHODS: Twelve dogs were randomly divided into two groups, control group (Group I, n=6) and MP group (Group II, n=6). The animals were bled continuously from a femoral artery catheter to produce uncontrolled hemorrhagic shock models. Resuscitation with lactated Ringer's (LR) solution was initiated when mean arterial pressure (MAP) decreased to 20 mm Hg, and MAP was maintained at 30-40 mm Hg. MP (4 mg/kg) was injected intravenously in Group II when resuscitation began. While in Group I, normal saline (NS) was injected instead. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured before exsanguination (T(1)), when MAP decreased to 20 mm Hg (T(2)), 60 min (T(3)) and 120 min (T(4)) after resuscitation. Heart rate, MAP and cardiac output (CO) levels were recorded concomitantly. RESULTS: Infusion volume and hemorrhage volume shed from the superior mesenteric artery in Group I were higher than those in Group II (P<0.01 and P<0.05). After reperfusion, blood SOD levels decreased progressively and MDA levels increased rapidly in Group I. In Group II, blood SOD levels at T(3) and T(4) decreased as compared with that at T(1) but a stepwise increase was present. At T(4), blood SOD level was significantly higher in Group II than in Group I (Plt;0.01). At T(3) and T(4), MDA levels were markedly lower in Group II than in Group I. During reperfusion, MAP was more steady in Group II than in Group I and survival rate after 120 min (at T(4)) was higher in Group II than in Group I (P<0.05). CONCLUSIONS: MP has a protective effect on severe uncontrolled hemorrhagic shock and subsequent reperfusion injury. The mechanism mainly involves the anti-lipid peroxidation activity of MP.


Asunto(s)
Metilprednisolona/farmacología , Daño por Reperfusión/tratamiento farmacológico , Choque Hemorrágico/tratamiento farmacológico , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Peroxidación de Lípido , Masculino , Probabilidad , Distribución Aleatoria , Valores de Referencia , Daño por Reperfusión/fisiopatología , Sensibilidad y Especificidad , Choque Hemorrágico/fisiopatología , Tasa de Supervivencia
19.
Chin J Traumatol ; 6(4): 245-8, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12857521

RESUMEN

OBJECTIVE: To investigate the effect of Shen-Fu (SF) injection on gastrointestinal tract injury and its potential mechanism. METHODS: Thirty-eight patients undergoing elective open heart surgery were assigned to Group C (control group, n=18) and Group SF (n=20) randomly. In Group SF, the patients received intravenous injection of SF (0.5 ml/kg) at the beginning of the surgery followed by a continuous infusion of 100 ml SF (1.0 ml/kg) solution diluted by saline at a rate of 0.004 ml x Kg(-1) x min(-1) with a Grasby pump. The control group was injected with normal saline in the same volume. Gastric intramucosal pH (pHi), activity of blood diamine oxidase (DAO), and concentrations of blood LPS and IL-6 were measured before CPB (S0) and 1 h (S1) and 2 h (S2) after aortic declamping, respectively. RESULTS: In Group C, pHi value was significantly lower at S1 and S2 than at S0 (mean P<0.01) and blood DAO and concentrations of LPS and IL-6 were significantly higher at S1 and S2 than at S0 (mean P<0.01). In Group SF, pHi was obviously lower at S1 and S2 than at S0 (P<0.05) but LPS and IL-6 levels and DAO were higher at S0 (mean P<0.05). Blood DAO and LPS level demonstrated significant negative correlations with pHi (mean P<0.01) while LPS concentration showed a positive correlation with blood DAO (P<0.01) and IL-6 concentration (P<0.05). At S1 and S2 after aortic declamping, the levels of pHi were higher in Group SF than in Group C (mean P<0.01 ) but DAO and LPS and IL-6 levels were significantly lower in Group SF than in Group C (P<0.01). CONCLUSIONS: SF has a protective effect on gastrointestinal tract and can reduce inflammatory actions.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente Cardiopulmonar/efectos adversos , Sistema Digestivo/efectos de los fármacos , Medicina Tradicional China , Sustancias Protectoras , Adolescente , Adulto , Amina Oxidasa (conteniendo Cobre)/sangre , Niño , Femenino , Humanos , Concentración de Iones de Hidrógeno , Interleucina-6/sangre , Lipopolisacáridos/sangre , Masculino , Persona de Mediana Edad , Sustancias Protectoras/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...