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1.
BMJ Open ; 9(10): e028464, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31672709

RESUMO

INTRODUCTION: Postoperative pulmonary complications (PPCs), strongly associated with higher mortality risk, can develop in up to 58% of patients undergoing abdominal surgery. More and more evidence shows that the use of a lung-protective ventilation strategy has a lung protection effect in patients undergoing abdominal surgery, however, the role of positive end-expiratory pressure (PEEP) during the intraoperative period in preventing PPCs for laparoscopic surgery is not clearly defined. METHODS AND ANALYSIS: A total of 208 patients with a high risk of PPC, undergoing laparoscopic abdominal surgery, will be enrolled and randomised into a standard PEEP (6-8 cm H2O) group and a low PEEP (≤2 cm H2O) group. Both groups will receive a fraction of inspired oxygen of 0.50 and a tidal volume of 8 mL/kg ideal body weight (IBW). Standard perioperative fluid management and analgesic treatments are applied in both groups. The primary end point is PPC within 7 days after surgery. Secondary end points are the modified Clinical Pulmonary Infection Score, postoperative extrapulmonary complications, postoperative surgical complications, intensive care unit length of stay, hospital length of stay, 30-day mortality. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medicine College) (registration number KY2018026) on 22 October 2018. The first participant was recruited on 15 April 2019 and the estimated completion date of the study is October 2021. The results of this trial will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: http://www.chictr.org.cn, ID: ChiCTR1800019865. Registered on 2 December 2018; preresults.

2.
Zootaxa ; 4586(2): zootaxa.4586.2.5, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-31716131

RESUMO

The paper describes three new species of Meganola (M. subseima sp. n., M. rongjiangensis sp. n. and M. wulongensis sp. n.) from China. Meganola mediofascia (Inoue, 1958) is reported for the first time from China. Adults and genitalia are illustrated.

3.
Acta Pharmacol Sin ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700088

RESUMO

Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L., which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1-15 µM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg-1·d-1, ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma.

4.
Sleep Med ; 64: 101-105, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31677484

RESUMO

OBJECTIVES: Patients with obstructive sleep apnea (OSA) experience sympathetic hyperactivation during sleep, which is associated with increased cardiovascular risk factors. However, the difference in cardiac autonomic activity in OSA patients according to position dependency has not been evaluated. This study aimed to evaluate the differences between positional OSA (pOSA) and nonpositional OSA (npOSA) using heart rate variability (HRV) analysis. METHODS: This was a single-center cross-sectional study. Twenty-eight patients with npOSA and 28 age-, sex-, and AHI-matched patients with pOSA underwent standard polysomnography. A five-minute R-R interval from stable waking conditions before bedtime was collected from each subject and analyzed for HRV. RESULTS: Patients with pOSA had lower body-mass index (BMI, 25.8 ± 2.9 vs 28.9 ± 3.7 kg/m2, p = 0.001), shorter apnea duration (24.1 ± 7.1 vs 30.3 ± 12.7 s, p = 0.028) and higher minimum oxygen saturation (78.2 ± 7.1 vs 71.5 ± 11.4%, p = 0.011) than those with npOSA. HRV analysis showed higher parasympathetic activity in pOSA patients than in npOSA patients, including a higher square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD, 31.3 ± 29.0 vs 18.6 ± 9.2, p = 0.032), percentage of pairs of adjacent NN intervals that differ by more than 50 ms (pNN50%, 10.7 ± 17.1 vs 3.3 ± 6.5, p = 0.024), and high-frequency (HF) power (534.7 ± 986.8 vs 146.7 ± 150.5, p = 0.026). The group difference was insignificant after adjusting for age and BMI. The log-transformed supine/nonsupine AHI ratio was the sole independent predictor of HRV parameters. CONCLUSION: The waking HRV was higher in pOSA patients than in npOSA patients due to the lower BMI of pOSA patients. The difference was especially apparent in parasympathetic indices. Higher parasympathetic activity in pOSA may suggest a lower risk for cardiovascular morbidity and mortality.

5.
J Mater Chem B ; 7(43): 6737-6741, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31647490

RESUMO

Galectin-3 is a vital biomarker for cancer progression. An aggregation-induced emission (AIE)-active nanoparticle probe is designed and synthesized for label-free detection of galectin-3 based on carbohydrate-protein interactions. The probe employs tetraphenylethene (TPE) as the fluorescent core structure and N-acetyllactosamine (LacNAc) as galactoside residues and self-aggregates into uniform nanoparticles with multiple binding sites on the surface targeting galectin-3. Upon crosslinking of the nanoparticles and galectin-3, large complexes are formed and a significant fluorescence change is measured, allowing rapid, sensitive and specific detection of galectin-3 via a fluorometric assay. Its demonstrated superior anti-interference ability and applicability in serum samples offer promising applications in cancer diagnoses.

6.
Chemosphere ; 241: 125012, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606575

RESUMO

BACKGROUND: Research argued that daily excessive concentration hours (DECH) could be more informative through accounting for within-day variations, when assessing population-level exposure to ambient fine particle (PM2.5). However, few studies have comparatively investigated PM2.5-associated risks using DECH and two common metrics of daily mean and hourly peak concentration. METHODS: We collected daily records of all-cause emergency department visits (EDVs) and hourly data on air pollutants and meteorological factors from Shenzhen, China, 2015-2018. According to guidelines proposed by the World Health Organization, DECH was calculated by summing up daily concentrations exceeding 25 µg/m3. Based on time-stratified case-crossover design, we adopted conditional logistic regression models to assess short-term attributable risks of EDVs associated with PM2.5 using three exposure metrics. RESULTS: DECH and daily average of PM2.5 strongly elevated risks of EDVs, while less evident associations were observed using hourly peak metric. Estimated excess relative risks at lag 0 day were 0.56% (95% confidence interval [CI]: 0.21 to 0.91), 0.69% (95% CI: 0.25 to 1.13) and 0.37% (95% CI: 0.02 to 0.76), respectively, associated with an interquartile range increase in DECH (420.2 µg/m3), 24-h average (24.9 µg/m3) and hourly peak concentration (38 µg/m3). More emergency visits could be attributed to DECH than daily mean PM2.5, with attributable fractions of 2.02% (95% CI: 1.42 to 2.61) and 1.09% (95% CI: 0.69 to 1.49), respectively. CONCLUSIONS: This study added evidence for increased risk of EDVs associated with exposure to ambient PM2.5. DECH was a potential alternative exposure metric for PM2.5 assessment, which may have implications for future revision of air quality standards.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31655873

RESUMO

This study investigated the levels, spatial distribution, sources, and ecological risks of 16 perfluorinated compounds (PFCs) in 68 surface soil samples (0-20 cm) from 7 cities in the Pearl River Delta (PRD), China. Sixteen target PFCs, including perfluoroalkyl carboxylic acids (PFCAs, C5-C14, C16, and C18) and perfluoroalkyl sulfonic acids (PFSAs, C4, C6, C8, and C10), were analyzed by high-performance liquid chromatography-negative electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS). Concentrations of total PFCs (∑PFCs) ranged from 2.19 to 98.5 µg kg-1 (dry weight, dw), with an average of 5.97 µg kg-1 dw. Perfluorooctane sulfonate (PFOS) was the dominant PFC, accounting for 23.9% of ∑PFCs. The highest ∑PFCs was found in the soil sample collected from Dongguan with a large number of manufacturing industries. There were no significant differences of ∑PFCs among unban, industrial, and agricultural soils, indicating similar pollution sources in soil of the PRD. More than 70% of ∑PFCs in soil of the PRD could be attributed to the four principal components, represented by PFOS and perfluorooctanoic acid (PFOA), perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA). Ecological risk assessment indicated that PFOA had low risk to soil plants and animals. However, the risk of PFOS to soil plants was relatively high in some studied regions.

8.
Environ Sci Technol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31633339

RESUMO

Given the lack of understanding of the complex physiochemical and environmental processes of persistent organic pollutants (POPs) in the Arctic and around the globe, atmospheric models often yield large errors in the predicted atmospheric concentrations of POPs. Here, we developed a recurrent neural network (RNN) method based on nonparametric deep learning algorithms. The RNN model was implemented to predict monthly air concentrations of polycyclic aromatic hydrocarbons (PAHs) at the high Arctic monitoring station Alert. To train the RNN system, we used MODIS satellite remotely sensed forest fire data, air emissions, meteorological data, sea ice cover area, and sampled PAH concentration data from 1996 to 2012. The system was applied to forecast monthly PAH concentrations from 2012 to 2014 at the Alert station. The results were compared with monitored PAHs and an atmospheric transport model (CanMETOP) for POPs. We show that the RNN significantly improved PHE and BaP predictions from 2012 to 2014 by 62.5 and 91.1%, respectively, compared to CanMETOP predictions. The sensitivity analysis using the Shapley value reveals that air emissions determined the magnitude of PAH levels in the high Arctic, whereas forest fires played a significant role in the changes in PAH concentrations in the high Arctic, followed by air temperature and meridional wind fields.

9.
Metab Eng ; 56: 181-189, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31600571

RESUMO

Metabolic engineering of microorganisms for production of succinate from glycerol remains challenging. It was thought that energy supply is a severe problem for anaerobic fermentation of glycerol to produce succinate. In this study, an energy-conserving glycerol utilization pathway was recruited to improve anaerobic succinate production in Escherichia coli. ATP dependent dihydroxyacetone kinase (DhaK) from Klebsiella was used to replace the native phosphoenolpyruvate (PEP) dependent dihydroxyacetone kinase (DhaKLM) of E. coli so that 2 NADH, instead of 1 NADH and 1 menaquinol, can be produced from glycerol to PEP. Besides consumption of 1 NADH and 1 menaquinol for converting PEP to succinate, NADH dehydrogenase I transfers electrons from 1 NADH to 1 menaquinone and pumps 4 protons. Proton-motive force are generated as the additional energy to support cell growth and succinate export. After using this energy-conserving glycerol utilization pathway, succinate titer, productivity and intercellular ATP content increased 282%, 63% and 338% respectively. The best strain YY-GS004 produced 483 mM succinate in 96 h with a yield of 0.92 mol mol-1 glycerol under anaerobic conditions. The specific succinate productivity was 0.47 g g-1 (DCW) h-1, which was the highest one up to date for succinate production from glycerol. This study demonstrated that the energy-conserving glycerol utilization pathway GldA-DhaK can solve the energy problem during anaerobic fermentation of glycerol to produce succinate.

10.
Chem Commun (Camb) ; 55(83): 12467-12470, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31566628

RESUMO

Optical nanosensors capable of distinguishing D2O from H2O are rarely reported. Herein, we explore a scalable synthetic route for multicolor carbon polymer dots (CPDs) by utilizing Fe3+-catalyzed oxidative polymerization at as low as 80 °C. Notably, the CPDs exhibit differential optical responses to H2O and D2O.

11.
J Immunol ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645417

RESUMO

The pharyngeal organ is located at the crossroad of the respiratory and digestive tracts in vertebrate, and it is continuously challenged by varying Ags during breathing and feeding. In mammals, the pharyngeal mucosa (PM) is a critical first line of defense. However, the evolutionary origins and ancient roles of immune defense and microbiota homeostasis of PM are still unknown. In this study, to our knowledge, we are the first to find that diffuse MALT is present in PM of rainbow trout, an early vertebrate. Importantly, following parasitic infection, we detect that strong parasite-specific mucosal IgT and dominant proliferation of IgT+ B cell immune responses occurs in trout PM, providing, to our knowledge, the first demonstration of local mucosal Ig responses against pathogens in pharyngeal organ of a nonmammal species. Moreover, we show that the trout PM microbiota is prevalently coated with secretory IgT and, to a much lesser degree, by IgM and IgD, suggesting the key role of mucosal Igs in the immune exclusion of teleost pharyngeal bacteria. Overall, to our knowledge, our findings provide the first evidence that pharyngeal mucosal immunity appear earlier than tetrapods.

12.
Clin Epigenetics ; 11(1): 137, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590682

RESUMO

While the aberrant translocation of the mixed-lineage leukemia (MLL) gene drives pathogenesis of acute myeloid leukemia (AML), it represents an independent predictor for poor prognosis of adult AML patients. Thus, small molecule inhibitors targeting menin-MLL fusion protein interaction have been emerging for the treatment of MLL-rearranged AML. As both inhibitors of histone deacetylase (HDAC) and menin-MLL interaction target the transcription-regulatory machinery involving epigenetic regulation of chromatin remodeling that governs the expression of genes involved in tumorigenesis, we hypothesized that these two classes of agents might interact to kill MLL-rearranged (MLL-r) AML cells. Here, we report that the combination treatment with subtoxic doses of the HDAC inhibitor chidamide and the menin-MLL interaction inhibitor MI-3 displayed a highly synergistic anti-tumor activity against human MLL-r AML cells in vitro and in vivo, but not those without this genetic aberration. Mechanistically, co-exposure to chidamide and MI-3 led to robust apoptosis in MLL-r AML cells, in association with loss of mitochondrial membrane potential and a sharp increase in ROS generation. Combined treatment also disrupted DNA damage checkpoint at the level of CHK1 and CHK2 kinases, rather than their upstream kinases (ATR and ATM), as well as DNA repair likely via homologous recombination (HR), but not non-homologous end joining (NHEJ). Genome-wide RNAseq revealed gene expression alterations involving several potential signaling pathways (e.g., cell cycle, DNA repair, MAPK, NF-κB) that might account for or contribute to the mechanisms of action underlying anti-leukemia activity of chidamide and MI-3 as a single agent and particularly in combination in MLL-r AML. Collectively, these findings provide a preclinical basis for further clinical investigation of this novel targeted strategy combining HDAC and Menin-MLL interaction inhibitors to improve therapeutic outcomes in a subset of patients with poor-prognostic MLL-r leukemia.

13.
Ecotoxicol Environ Saf ; 186: 109697, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31629905

RESUMO

Although the acute and/or chronic exposure to AFB1 has been widely investigated, the study on the toxic effects resulted from the subchronic exposure of AFB1 which is more close to the real scenario in view of the regional and seasonal characters of aflatoxin-producing strains is still limited. To understand the subchronically toxic effects of AFB1, we studied the AFB1-induced oxidative damage, reproductive impairment as well as their potential correlations and mechanisms at the molecular level. Generally, our results showed that subchronic exposure of AFB1 gave rise to pathological and oxidative damages in mice, disrupted oxidation-reduction homeostasis, activated mitochondrial apoptotic and p53-regulated signaling pathways, induced DNA and chromosomal damages and increased the rate of sperm malformation. Importantly, reproductive toxic effects were detected in AFB1-treated mice under a subchronic exposure, which was evidenced by the ascended sperm malformation. Based on our pilot study, it's speculated that the partial mechanism of reproductive toxicity may be the oxidative damages, especially DNA damages directly induced by AFB1. In short, our study demonstrated that severe damages can be caused even by a subchronic exposure as well as hinted that reproductive toxicity also should be taken into consideration when conducting risk assessments of the subchronic exposure of AFB1.

14.
J Orthop Surg Res ; 14(1): 299, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488174

RESUMO

PURPOSE: Our purpose was to combine intravoxel incoherent motion diffusion-weighted MR imaging (IVIM-DWI) and magnetic resonance spectroscopy (MRS) to differentiate osteoporotic fractures from osteolytic metastatic vertebral compression fractures (VCFs). METHODS: A total of 70 patients with VCFs were included and divided into two groups, according to their causes of fractures based on pathological findings or clinical follow-up. All patients underwent conventional sagittal T1WI, T2WI, STIR, IVIM-DWI, and single-voxel MRS. The diffusion coefficient (D), pseudo diffusion (D*), and perfusion fraction (f) parameters from IVIM-DWI and the lipid water ratio (LWR) and fat fraction (FF) parameters from MRS were obtained and compared among groups. Furthermore, the diagnostic performance of MRS, IVIM-DWI, and IVIM-DWI combined with MRS for differentiation between osteoporotic and osteolytic metastatic VCFs was assessed by using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared with the osteoporotic group, the metastatic group had significantly lower values for f, D, and FF, but higher D* (all P < 0.05). The area under the receiver operating characteristic (ROC) curve of MRS, IVIM-DWI, and IVIM-DWI combined with MRS were 0.73, 0.88, and 0.94, respectively. Among these, the IVIM-DWI combined with MRS showed the highest sensitivity, specificity, and accuracy, which are 90.63% (29/32), 97.37 % (37/38), and 94.29% (66/70), respectively. CONCLUSIONS: IVIM-DWI combined with MRS can be more accurate and efficient for differentiation between osteoporotic and osteolytic metastatic VCFs than single MRS or IVIM-DWI.

15.
iScience ; 19: 821-835, 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31499339

RESUMO

The buccal mucosa (BM) is a critical first line of defense in terrestrial animals. To gain further insights into the evolutionary origins and primordial roles of BM in teleosts here we show that rainbow trout, a teleost fish, contains a diffuse mucosal associated lymphoid tissue (MALT) within its buccal cavity. Upon parasite infection, a fish immunoglobulin specialized in mucosal immunity (sIgT) was induced to a high degree, and parasite-specific sIgT responses were mainly detected in the buccal mucus. Moreover, we show that the trout buccal microbiota is prevalently coated with sIgT. Overall our findings revealed that the MALT is present in the BM of a non-tetrapod species. As fish IgT and mucus-producing cells are evolutionarily unrelated to mammalian IgA and salivary glands, respectively, our findings indicate that mucosal immune responses in the BM of teleost fish and tetrapods evolved through a process of convergent evolution.

16.
J Cell Physiol ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498430

RESUMO

Gastric cancer has the fifth highest incidence of disease and is the third leading cause of cancer-associated mortality in the world. The etiology of gastric cancer is complex and needs to be fully elucidated. Thus, it is necessary to explore potential pathogenic genes and pathways that contribute to gastric cancer. Gene expression profiles of the GSE33335 and GSE54129 datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were compared and identified using R software. The DEGs were then subjected to gene set enrichment analysis and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Survival analyses based on The Cancer Genome Atlas database were used to further screen the essential DEGs. A knockdown assay was performed to determine the function of the candidate gene in gastric cancer. Finally, the association between the candidate gene and immune-related genes was investigated. We found that GPNMB serves as an essential gene, with a high expression level, and predicts a worse outcome of gastric cancer. Knockdown of GPNMB inhibited gastric cancer cell proliferation and migration. In addition, GPNMB may augment the immunosuppressive ability of gastric cancer by recruiting immunosuppressive cells and promoting immune cell exhaustion through PI3K/AKT/CCL4 signaling axis. Collectively, these data suggest that GPNMB acts as an important positive mediator of tumor progression in gastric cancer, and GPNMB could exert multimodality modulation of gastric cancer-mediated immune suppression.

17.
Math Biosci Eng ; 16(5): 6103-6120, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31499754

RESUMO

Robustness is an important property of image hashing. Most of the existing hashing algorithms do not reach good robustness against large-angle rotation. Aiming at this problem, we jointly exploit visual attention model and ring partition to design a novel image hashing, which can make good rotation robustness. In the proposed image hashing, a visual attention model called PFT (Phase spectrum of Fourier Transform) model is used to detect saliency map of preprocessed image. The LL sub-band of saliency map is then divided into concentric circles invariant to rotation by ring partition, and the means and variances of DWT coefficients on concentric circles are taken as image features. Next, these features are encrypted by a chaotic map and the Euclidean distances between normalized encrypted features are finally exploited to generate hash. Similarity between hashes is measured by L 1 norm. Many experimental tests show that our image hashing is robust to digital operations including rotation and reaches good discrimination. Comparisons demonstrate that classification performance of our image hashing outperforms those of some well-known hashing algorithms in terms of receiver operating characteristics curves. Simulation of image copy detection is carried out on an open image database called UCID and the result validates effectiveness of our hashing.

18.
Biomed Environ Sci ; 32(8): 614-623, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31488237

RESUMO

OBJECTIVE: To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes. METHODS: The power functions of the Fieller-type confidence interval and the asymptotic confidence interval in crossover designs with serial-sampling data are here derived. Simulation studies were conducted to evaluate the derived power functions. RESULTS: Simulation studies show that two power functions can provide precise power estimates when normality assumptions are satisfied and yield conservative estimates of power in cases when data are log-normally distributed. The intra-correlation showed a positive correlation with the power of the bioequivalence test. When the expected ratio of the AUCs was less than or equal to 1, the power of the Fieller-type confidence interval was larger than the asymptotic confidence interval. If the expected ratio of the AUCs was larger than 1, the asymptotic confidence interval had greater power. Sample size can be calculated through numerical iteration with the derived power functions. CONCLUSION: The Fieller-type power function and the asymptotic power function can be used to determine sample sizes of crossover trials for bioequivalence assessment of topical ophthalmic drugs.

19.
J Burn Care Res ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31504640

RESUMO

INTRODUCTION: This study investigated changes in plasma fibrinogen metabolism and changes in coagulation in severely burned adults. METHODS: Ten patients (27±3 years; 91± 6kg) with 51±3% TBSA were consented and enrolled into an institutional review board approved prospective study. On the study day, stable isotope infusion of 1-13C-phenylalanine and d5-phenylalanine was performed to quantify fibrinogen production and consumption. During the infusion, vital signs were recorded and blood samples were drawn every hour. Coagulation was measured by thromboelastograph (TEG). Ten normal healthy volunteers (37±7years; 74±4 kg) were included as the control group. RESULTS: Burned adults had elevated heart rates (120±2 vs. 73±5 (control) beats/min), respiration rates (23±2 vs. 15±1 breaths/min), plasma glucose (127±10 vs 89±2 mg/dL) and fibrinogen levels (613±35 vs 239±17 mg/dL); and decreased albumin (1.3±0.2 vs. 3.7±0.1 g/dL) and total protein (4.4±0.2 vs. 6.8±0.1 g/dL, all p<0.05). Fibrinogen breakdown was elevated in the burn group (2.3±0.4 vs. 1.0±0.3 µmol/kg/min); and fibrinogen synthesis was further enhanced in the burn group (4.4±0.7 vs 0.7±0.2 µmol/kg/min, both p<0.05). Clotting speed (TEG-alpha) and clot strength (TEG-MA) were increased in the burn group (62±4 vs. 50±4°, and 76±2 vs. 56±2 mm, respectively, both p<0.05). Fibrinolysis of TEG-LY60 was accelerated in the burn group (16±6 vs. 3±1) and so was the increase in D-dimer level in the burn group (4.5±0.4 vs 1.9±0.3 mg/L, both p<0.05). CONCLUSIONS: The hypercoagulable state postburn is in part a result of increased fibrinogen synthesis, over and above increased fibrinogen breakdown.

20.
J Cell Mol Med ; 23(11): 7830-7843, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502361

RESUMO

Mitochondrial dynamic disorder is involved in myocardial ischemia/reperfusion (I/R) injury. To explore the effect of mitochondrial calcium uniporter (MCU) on mitochondrial dynamic imbalance under I/R and its related signal pathways, a mouse myocardial I/R model and hypoxia/reoxygenation model of mouse cardiomyocytes were established. The expression of MCU during I/R increased and related to myocardial injury, enhancement of mitochondrial fission, inhibition of mitochondrial fusion and mitophagy. Suppressing MCU functions by Ru360 during I/R could reduce myocardial infarction area and cardiomyocyte apoptosis, alleviate mitochondrial fission and restore mitochondrial fusion and mitophagy. However, spermine administration, which could enhance MCU function, deteriorated the above-mentioned myocardial cell injury and mitochondrial dynamic imbalanced. In addition, up-regulation of MCU promoted the expression and activation of calpain-1/2 and down-regulated the expression of Optic atrophy type 1 (OPA1). Meantime, in transgenic mice (overexpression calpastatin, the endogenous inhibitor of calpain) I/R model and OPA1 knock-down cultured cell. In I/R models of transgenic mice over-expressing calpastatin, which is the endogenous inhibitor of calpain, and in H/R models with siOPA1 transfection, inhibition of calpains could enhance mitochondrial fusion and mitophagy, and inhibit excessive mitochondrion fission and apoptosis through OPA1. Therefore, we conclude that during I/R, MCU up-regulation induces calpain activation, which down-regulates OPA1, consequently leading to mitochondrial dynamic imbalance.

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