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1.
Emerg Microbes Infect ; 9(1): 680-686, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32207377

RESUMO

Pseudoviruses are useful virological tools because of their safety and versatility, especially for emerging and re-emerging viruses. Due to its high pathogenicity and infectivity and the lack of effective vaccines and therapeutics, live SARS-CoV-2 has to be handled under biosafety level 3 conditions, which has hindered the development of vaccines and therapeutics. Based on a VSV pseudovirus production system, a pseudovirus-based neutralization assay has been developed for evaluating neutralizing antibodies against SARS-CoV-2 in biosafety level 2 facilities. The key parameters for this assay were optimized, including cell types, cell numbers, virus inoculum. When tested against the SARS-CoV-2 pseudovirus, SARS-CoV-2 convalescent patient sera showed high neutralizing potency, which underscore its potential as therapeutics. The limit of detection for this assay was determined as 22.1 and 43.2 for human and mouse serum samples respectively using a panel of 120 negative samples. The cutoff values were set as 30 and 50 for human and mouse serum samples, respectively. This assay showed relatively low coefficient of variations with 15.9% and 16.2% for the intra- and inter-assay analyses respectively. Taken together, we established a robust pseudovirus-based neutralization assay for SARS-CoV-2 and are glad to share pseudoviruses and related protocols with the developers of vaccines or therapeutics to fight against this lethal virus.

2.
Stem Cell Res ; 44: 101737, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32114296

RESUMO

Niemann-Pick disease, type C (NPC) is a rare autosomal recessive genetic disease caused by mutations in either NPC1 or NPC2, which encodes an intracellular cholesterol-binding protein in lysosome. Deficiency of either NPC1 or NPC2 protein results in malfunction of intracellular cholesterol trafficking and lysosomal accumulation of unesterified cholesterols. A human induced pluripotent stem cell (iPSC) line was generated from dermal fibroblasts of a male patient that has a homozygous p.I1061T missense mutation in NPC1 using a non-integrating Sendai virus technique. This NPC1 iPSC line offers a useful resource for disease modeling and drug development.

4.
Br J Anaesth ; 124(3): 324-335, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32007240

RESUMO

BACKGROUND: The debate on lung-protective ventilation strategies for surgical patients is ongoing. Evidence suggests that the use of low tidal volume VT improves clinical outcomes. However, the optimal levels of PEEP and recruitment manoeuvre (RM) strategies incorporated into low VT ventilation remain unclear. METHODS: Several electronic databases were searched to identify RCTs that focused on comparison between low VT strategy and conventional mechanical ventilation (CMV), or between two different low VT strategies in surgical patients. The primary outcome was postoperative pulmonary complications (PPCs). The secondary outcomes were atelectasis, pneumonia, acute respiratory distress syndrome, and short-term mortality. Bayesian network meta-analyses were performed using WinBUGS. The odds ratios (ORs) and corresponding 95% credible intervals (CrIs) were estimated. RESULTS: Compared with CMV, low VT ventilation with moderate-to-high PEEP reduced the risk of PPCs (moderate PEEP [5-8 cm H2O]: OR 0.50 [95% CrI: 0.28, 0.89]; moderate PEEP+RMs: 0.39 [0.19, 0.78]; and high PEEP [≥9 cm H2O]+RMs: 0.34 [0.14, 0.79]). Low VT ventilation with moderate-to-high PEEP and RMs also specifically reduced the risk of atelectasis compared with CMV (moderate PEEP+RMs: OR 0.36 [95% CrI: 0.16, 0.87]; and high PEEP+RMs: 0.41 [0.15, 0.97]), whilst low VT ventilation with moderate PEEP was superior to CMV in reducing the risk of pneumonia (OR 0.46 [95% CrI: 0.15, 0.94]). CONCLUSIONS: The combination of low VT ventilation and moderate-to-high PEEP (≥5 cm H2O) seems to confer lung protection in surgical patients undergoing general anaesthesia. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42019144561).


Assuntos
Pneumopatias/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Respiração Artificial/métodos , Teorema de Bayes , Humanos , Pneumopatias/etiologia , Pneumonia/etiologia , Pneumonia/prevenção & controle , Respiração com Pressão Positiva/métodos , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/prevenção & controle , Volume de Ventilação Pulmonar
5.
Mol Cancer ; 19(1): 41, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32103760

RESUMO

BACKGROUND: The poor prognosis of esophageal squamous cell carcinoma (ESCC) highlights the need for novel strategies against this disease. Our previous study suggested the involvement of CCL2 and tumor associated macrophages (TAMs) in esophageal carcinogenesis. Despite the recognition of TAMs as a promising target for cancer treatment, mechanisms underlying its infiltration, activation and tumor-promotive function in ESCC remain unknown. METHODS: Human esophageal tissue array and TCGA database were used to evaluate the clinical relevance of CCL2 and TAMs in ESCC. F344 rats and C57BL/6 mice were treated with N-nitrosomethylbenzylamine (NMBA) to establish orthotopic models of esophageal carcinogenesis. CCL2/CCR2 gene knockout mice and macrophage-specific PPARG gene knockout mice were respectively used to investigate the role of infiltration and polarization of TAMs in ESCC. CCL2-mediated monocyte chemotaxis was estimated in malignantly transformed Het-1A cells. THP-1 cells were used to simulate TAMs polarization in vitro. RNA-sequencing was performed to uncover the mechanism. RESULTS: Increasing expression of CCL2 correlated with TAMs accumulation in esophageal carcinogenesis, and they both predicts poor prognosis in ESCC cohort. Animal studies show blockade of CCL2-CCR2 axis strongly reduces tumor incidence by hindering TAMs recruitment and thereby potentiates the antitumor efficacy of CD8+ T cells in the tumor microenvironment. More importantly, M2 polarization increases PD-L2 expression in TAMs, resulting in immune evasion and tumor promotion through PD-1 signaling pathway. CONCLUSION: This study highlights the role of CCL2-CCR2 axis in esophageal carcinogenesis. Our findings provide new insight into the mechanism of immune evasion mediated by TAMs in ESCC, suggesting the potential of TAMs-targeted strategies for ESCC prevention and immunotherapy.

6.
Haematologica ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32079695

RESUMO

Human leukocyte antigen-G is a non-classical major histocompatibility complex class I antigen with potent immune-inhibitory function. Human leukocyte antigen-G benefit patients in allotransplantation and autoimmune diseases by interacting with its receptors, immunoglobulin-like transcripts. Here we observed significantly less human leukocyte antigen-G in plasma from immune thrombocytopenia patients positive for anti-platelet autoantibodies compared with autoantibodies-negative patients or healthy controls. Besides, human leukocyte antigen-G is positively correlated with platelet counts in both patients and healthy controls. We also found less membrane-bound human leukocyte antigen-G and immunoglobulin-like transcripts on CD4+ and CD14+ cells in patients. Recombinant human leukocyte antigen-G upregulated immunoglobulin-like transcript 2 expression on CD4+ and immunoglobulin-like transcript 4 on CD14+ cells. Human leukocyte antigen-G upregulated IL-4 and IL-10, and downregulated tumor necrosis factor-α, IL-12 and IL-17 secreted by patient peripheral blood mononuclear cells, suggesting a stimulation of Th2 differentiation and downregulation of Th1 and Th17 immune response. Human leukocyte antigen-G-modulated dendritic cells from immune thrombocytopenia patients showed decreased expression of CD80 and CD86, and suppressed CD4+ T-cell proliferation compared to unmodulated cells. Moreover, human leukocyte antigen-G modulated cells from patients induced less platelet apoptosis. Human leukocyte antigen-G administration also significantly alleviated thrombocytopenia in a murine model of ITP. In conclusion, our data demonstrated that impaired expression of human leukocyte antigen-G and immunoglobulin-like transcripts is involved in the pathogenesis of immune thrombocytopenia; Recombinant human leukocyte antigen-G can correct this abnormality via upregulation of immunoglobulin-like transcripts, indicating that human leukocyte antigen-G can be a diagnostic marker and a therapeutic option for immune thrombocytopenia.

7.
Biotechnol Lett ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002712

RESUMO

OBJECTIVE: To investigate the feasibility of producing human IgG1 Fc fragment fused factor IX (FIX-Fc) in the milk of transgenic animals, for an alternative possible solution to the unmet need of FIX-Fc products for hemophilia B treatment. RESULTS: Six founder lines of transgenic mice harboring FIX-Fc cassette designed to be expressed specifically in the mammary gland were generated. FIX-Fc protein was secreted into the milk of transgenic mice with preserved biological activity (with the highest value of 6.2 IU/mL), similar to that of the non-fused FIX transgenic milk. RT-PCR and immunofluorescence analysis confirmed that FIX-Fc was specifically expressed in the mammary gland. The blood FIX clotting activities were unchanged, and no apparent health defects were observed in the transgenic mice. Moreover, the stability of FIX protein in milk was increased by the Fc fusion. CONCLUSIONS: It is feasible to produce biologically functional FIX-Fc in the mammary gland of transgenic mice. Our preliminary results provide a foundation for the potential scale-up production of FIX-Fc in the milk of dairy animals.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31944645

RESUMO

We report a microlens array with a controllable focal length that is based on a selective wetting surface. A substrate modified with a hydrophobic layer that has an array of microholes exhibits different wettability for inside holes (hydrophilic) versus outside holes (hydrophobic). When liquid flows over the surface, a small amount of liquid is adhered to hydrophilic holes and forms a lens-shaped droplet array that self-assembles because of surface tension. A large-sized plano-convex lens array that has good uniformity is obtained via the blade coating method, and controlling the amount of liquid enables control of the focal length. Our self-assembled microlens array has the merits of high optical performance, a simple fabrication procedure, and good mechanical stability, and thus, it has potential applications in imaging processing, light extraction, protein detection, light-emitting diodes, sensors, and displays.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 229: 118001, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31935657

RESUMO

Hypochlorous acid, a type of reactive oxygen species, has been shown to play an important role in organisms. Nowadays, there are many kinds of fluorescence detecting mechanisms to detect hypochlorous acid in vivo. Due to the high selectivity, the mechanism of using the strong oxidation of hypochlorous acid to break carbon­carbon double bonds has been favored by many scientists. However, the reported probes of breaking carbon­carbon double bonds still had drawback such as slow response. Based on this, we introduced electron-withdrawing group malonitrile to accelerate the oxidation of hypochlorous acid, resulting in reaction time less than 150 s. Meanwhile, the probe exhibited excellent selectivity, optical stability, high sensitivity and the detection limit as low as 0.19 µM. More importantly, we also successfully proved the potential application of the probe for the detection of intracellular ClO- living cells and Arabidopsis root tip by fluorescence imaging.

10.
Nanotechnology ; 31(15): 155502, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31891929

RESUMO

Researchers have made a lot of effort for the lightweight and high flexibility of wearable electronic devices, which also requires the associated energy harvesting equipment to have ultra-thin thickness and high stretchability. Therefore, a piezoelectric-triboelectric hybrid self-powered sensor (PTHS) has been proposed which can be used as the second layer of the human body. This elastic PTHS can even work on a person's fingers without disturbing the body's movements. The open circuit voltage and short circuit current of devices with a projected area of 30 mm × 25 mm can reach 1.2 V and 30 nA, respectively. Two piezoelectrically-triboelectrically sensors with machine learning optimized identification strategies were experimentally proven as the potential applications of the PTHS. The PTHS's ultra-thin thickness, high stretchability and superior geometry control features are promising in electronic skin, artificial muscle and soft robotics. The novelty of this work is that a smart mask integrated with PTHS can generate a signal of the hybrid sensor for the biomechanical motion classifier. After suitable training, an overall accuracy of 87.9% using long short-term memory can be achieved.

11.
Int J Mol Med ; 45(3): 947-955, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31922248

RESUMO

Early repolarization syndrome (ERS) is associated with genetic mutations, but the role of the glycerol­3­phosphate dehydrogenase 1­like (GPD1­L) mutation remains unclear. The aim of the present study was to investigate the role and potential underlying mechanism of GPD1­L mutation P112L in the pathogenesis of ERS. Whole­genome sequencing was performed on samples from a family with ERS, and the gene sequencing results were analyzed using bioinformatics. 293 cells were transfected with wild­type (WT) or mutant­type (MT) GPD1­L and SCN5A plasmids. Successful transfection of GPD1­L in 293 cells was verified by western blotting. Whole­cell patch­clamp recording, confocal microscopic observation and western blotting were used to uncover the potential mechanism of GPD1­L P112L in ERS. The results of western blotting indicated that the expression of the GPD1­L protein was lower in the MT group compared with that in the WT group, but the mock group did not express the GPD1­L protein. The whole­cell patch­clamp recording results indicated that the activation current density of INa (at ­30 mV) was ~60% lower in the MT group compared with the WT group (P<0.01). The mutation caused the inactivation voltage to move in a negative direction by ~3 mV compared with that of the WT group. However, there were no significant between­group differences in the steady activation, steady inactivation, and steady recovery of INa. Confocal microscopy demonstrated that MT GPD1­L was less expressed near the cell membrane and more expressed in the cytoplasm compared with WT GPD1­L. Both WT and MT GPD1­L were highly expressed in the cytoplasm and in small amounts in the nucleus. In conclusion, the GPD1­L P112L mutation decreased INa activation and GPD1­L cell expression, including in the region near the cell membrane. These results suggest that GPD1­L P112L may be a pathogenic genetic mutation associated with ERS.

12.
Glob Chang Biol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31991046

RESUMO

Soil organic carbon (SOC) is essential for soil fertility and climate change mitigation, and carbon can be sequestered in soil through proper soil management, including straw return. However, results of studies of long-term straw return on SOC are contradictory and increasing SOC stocks in upland soils is challenging. This study of North China upland agricultural fields quantified the effects of several fertilizer and straw return treatments on SOC storage changes and crop yields, considering different cropping duration periods, soil types, and cropping systems to establish the relationships of SOC sequestration rates with initial SOC stocks and annual straw C inputs. Our meta-analysis using long-term field experiments showed that SOC stock responses to straw return were greater than that of mineral fertilizers alone. Black soils with higher initial SOC stocks also had lower SOC stock increases than did soils with lower initial SOC stocks (fluvo-aquic and loessial soils) following applications of nitrogen-phosphorous-potassium (NPK) fertilizer and NPK+S (straw). Soil C stocks under the NPK and NPK+S treatments increased in the more-than-20-year duration period, while significant SOC stock increases in the NP and NP+S treatment groups were limited to the 11- to 20-year period. Annual crop productivity was higher in double-cropped wheat and maize under all fertilization treatments, including control (no fertilization), than in the single-crop systems (wheat or maize). Also, the annual soil sequestration rates and annual straw C inputs of the treatments with straw return (NP+S and NPK+S) were significantly positively related. Moreover, initial SOC stocks and SOC sequestration rates of those treatments were highly negatively correlated. Thus, long-term straw return integrated with mineral fertilization in upland wheat and maize croplands leads to increased crop yields and SOC stocks. However, those effects of straw return are highly dependent on fertilizer management, cropping system, soil type, duration period, and the initial SOC content.

13.
Sleep Med ; 65: 36-44, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707287

RESUMO

OBJECTIVES: To characterize eye movements during rhythmic masticatory muscle activities (RMMAs) in patients with sleep bruxism (SB). METHODS: Polysomnographic (PSG) recordings were performed on SB patients and normal controls during sleep (n = 8 for each group) and wakefulness (n = 9 for each group). The eye movements associated with episodes of RMMAs/SB during sleep and jaw movements during wakefulness were analyzed. RESULTS: During sleep, all episodes of RMMAs/SB in the SB patients and controls were associated with eye movements and most of the RMMAs/SB related slow eye movements (SB patients: 96.29%, 1583/1644; Controls: 97.49%, 543/557) were horizontal in the SB patients and controls. During wakefulness, all of the series of jaw movements were associated with eye movements. Most of cycles of jaw movements (SB patients: 88.89%, 200/225; Controls: 95.11%, 214/225) were associated with slow eye movements and most of the eye movements (SB patients: 52.50%, 105/200; Controls: 61.21%, 131/214) were vertical. There were significant correlations between the durations of episodes of eye movements and RMMAs/SB during sleep and between the duration of episodes of eye movements and duration of series of jaw movements during wakefulness in the SB patients and controls. CONCLUSIONS: Most of RMMAs/SB episodes during sleep and jaw movements during wakefulness are associated with eye movements in SB patients and normal controls.

14.
J Oral Rehabil ; 47(2): 170-179, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31697853

RESUMO

Most sleep bruxism (SB) episodes are accompanied by an increase in sympathetic tone and heart rate (HR). To characterise heart rate (HR) changes in relation to rhythmic masticatory muscle activities (RMMAs) in SB patients, polysomnographic recordings were performed on 10 SB patients and 11 normal controls. The duration of movement events, amplitude and duration of HR increases, and time to reach HR peak associated with RMMAs and limb movements (LMs) were determined, and the relationships of the parameters of HR increases with types of movements and RMMAs were analysed. All of the parameters of HR increases associated with three types of movements (RMMAs, RMMAs + LMs and LMs) and masseter activities (phasic, tonic and mixed) were significantly different (two-way ANOVA, P < .001 for all) in both SB patients and controls. The duration of RMMAs/LMs was positively correlated with the parameters (SB patients: R2  = .24-.85, P < .0001; controls: R2  = .23-.68, P < .0001). The amplitude of HR increases was also positively correlated with respiration changes in the SB patients (R2  = .3258, P < .0001) and controls (R2  = .09469, P < .05). The proportions of phasic RMMAs associated with awakenings, microarousals and no cortical arousals were significantly different and so were the proportions of tonic and mixed RMMAs (Friedman's tests, P < .05-.001). The HR increases associated with RMMAs may be intrinsic to the cortical arousal response and autonomic activation, and differences in HR increases associated with different types of movements and RMMAs might be related to the changes in respiration and differences in cortical arousal levels.


Assuntos
Bruxismo do Sono , Frequência Cardíaca , Humanos , Músculos da Mastigação , Movimento , Polissonografia
15.
J Colloid Interface Sci ; 558: 47-54, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31580954

RESUMO

The unique antibacterial characteristics of Ag nanomaterials offer a wide potential range of applications, but achieving rapid and durable antibacterial efficacy is challenging. This is because the speed and durability of the antibacterial function make conflicting demands on the structural design: the former requires the direct exposure of Ag to the surrounding environment, whereas the durability requires Ag to be protected from the environment. To overcome this incompatibility, we synthesize sandwich-structured polydopamine shells decorated both internally and externally with Ag nanoparticles, which exhibit prompt and lasting bioactivity in applications. These shells are biocompatible and can be used in vivo to counter bacterial infection caused by methicillin-resistant Staphylococcus aureus superbugs and to inhibit biofilm formation. This work represents a new paradigm for the design of composite materials with enhanced antibacterial properties.


Assuntos
Antibacterianos/química , Materiais Biocompatíveis/química , Indóis/química , Nanopartículas Metálicas/química , Polímeros/química , Prata/química , Animais , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Escherichia coli/efeitos dos fármacos , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ratos , Ratos Sprague-Dawley
16.
Anal Chim Acta ; 1096: 174-183, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883584

RESUMO

In this study, by rational regulating the competitive redox reaction of Au-NCs/MnO2 nanocomposite between the dye indigo carmine (IC) and the enzymatic product L-ascorbic acid (AA), we have established a colorimetric and fluorometric double-channel responsive assay for acid phosphatase (ACP), which could serve as an indicator of soil cadmium (Cd) contamination. Initially, the gold nanoclusters (Au-NCs) were added to the suspension of MnO2 nanosheets to form Au-NCs/MnO2 nanocomposite with enhanced oxidative degradation ability. When IC was subsequently added, the blue color of IC faded due to oxidative degradation, and the mixture showed the yellow color of Au-NCs/MnO2 nanocomposite. Meanwhile, based on the inner filter effect (IFE), the fluorescence of Au-NCs was suppressed by MnO2 nanosheets during this process. However, with the presence of AA, hydrolyzed from L-ascorbic-2-phosphate (AAP) by ACP, the MnO2 nanosheets in Au-NCs/MnO2 nanocomposite were reduced to Mn2+ immediately. As a consequence, IC remained its blue color, in the meantime, the fluorescence of Au-NCs recovered, which essentially constituted a new mechanism for ACP detection with colorimetric and fluorometric double-channel response. With the method we developed, soil ACP activity can either be directly visualized by bare eyes or detected reliably through double channels. Furthermore, the dynamic changes of ACP activity during soil Cd contamination could also be monitored; the sharp increase of ACP activity at an appropriate time point could serve as a unique alarm for cadmium (Cd) contamination in soil, which is of great importance for soil quality evaluation and ecological risk assessment.

17.
Mol Med Rep ; 20(5): 4695-4705, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702022

RESUMO

Treatment of cancer­induced bone pain (CIBP) is challenging in clinical settings. Oxycodone (OXY) is used to treat CIBP; however, a lack of understanding of the mechanisms underlying CIBP limits the application of OXY. In the present study, all rats were randomly divided into three groups: The sham group, the CIBP group, and the OXY group. Then, a rat model of CIBP was established by inoculation of Walker 256 tumor cells from rat tibia. Phosphoproteomic profiling of the OXY­treated spinal dorsal cords of rats with CIBP was performed, and 1,679 phosphorylated proteins were identified, of which 160 proteins were significantly different between the CIBP and sham groups, and 113 proteins were significantly different between the CIBP and OXY groups. Gene Ontology analysis revealed that these proteins mainly clustered as synaptic­associated cellular components; among these, disks large homolog 3 expression was markedly increased in rats with CIBP and was reversed by OXY treatment. Subsequent domain analysis of the differential proteins revealed several significant synaptic­associated domains. In conclusion, synaptic­associated cellular components may be critical in OXY­induced analgesia in rats with CIBP.

18.
Ann Palliat Med ; 8(5): 559-564, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31735036

RESUMO

BACKGROUND: Endovascular embolization was successfully used in treatment of brain arteriovenous malformations (bAVM), respectively or in combination with surgical resection. Deliberate employment of post-operative hypotension was widely recommended by neurosurgeons. Researches on predictors of difficulties in deliberate postoperative hypotension remain scarce. This study aimed to analyze the potential risk factors of difficult cases of deliberate post-operative hypotension. METHODS: We retrospectively reviewed all patients who received bAVM embolization between January 2010 and December 2015. Demographic features, clinical presentation, AVM characteristics, peri-operative medication, hemodynamic features, treatment-related information and outcome-related data were recorded. Univariate analysis and logistic regression were performed to find out associated risk factors. RESULTS: Difficulty in deliberate postoperative hypotension was observed in 75 patients the first post-operative day. Logistic regression indicated that higher S-M grade was an independent risk factor of difficult deliberate postoperative hypotension following embolization (OR=2.058; 95% CI, 1.364-3.105; P=0.001). While intra-operative Dexmedetomidine administration was a potential independent protective factor (OR=0.356; 95% CI, 0.133-0.956; P=0.040). CONCLUSIONS: Higher S-M grade was an independent risk factor of difficult cases of deliberate postoperative hypotension after endovascular embolization, while Intra-operative Dexmedetomidine administration was potential protective predictor.

19.
Pharm Res ; 36(12): 171, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31654287

RESUMO

PURPOSE: Physiologically-based pharmacokinetic (PBPK) modeling offers a unique modality to predict age-specific pharmacokinetics. The objective of this study was to assess the ability of PBPK model to predict plasma exposure of oxycodone, a widely used opioid for pain management, in adults and children. METHODS: A full PBPK model of oxycodone following intravenous and oral administration was developed using a 'bottom-up' and 'top-down' combined strategy. The model was then extrapolated to pediatrics through a reasonable scaling method. The adult and pediatric model was evaluated using data from 17 clinical PK studies by testing predicted/observed goodness of fit. The mean fold error for PK parameters was calculated. Finally, we used the validated PBPK model to visualize adult-children dose conversion for oxycodone. RESULTS: The developed PBPK model successfully predicted the oxycodone disposition in adults, wherein the predicted versus observed AUC, Cmax, and tmax were within 0.90 to 1.20-fold difference. After scaling anatomy/physiology, protein binding, and clearance, the model showed satisfactory prediction performance for pediatric populations as predicted AUC were within the 1.50-fold range of the observed values. According to the application of PBPK model, we found that different intravenous doses should be given in children of different ages compared to a standard 0.1 mg/kg in adults, while a progressive increasing dose with age growth following oral administration is recommended for children. CONCLUSIONS: The current example provides the opportunity for using the PBPK model to guide dose adjustment of oxycodone in the design of future pediatric clinical studies.


Assuntos
Analgésicos Opioides/farmacocinética , Oxicodona/farmacocinética , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Criança , Pré-Escolar , Simulação por Computador , Relação Dose-Resposta a Droga , Humanos , Lactente , Recém-Nascido , Taxa de Depuração Metabólica , Modelos Biológicos , Oxicodona/administração & dosagem , Pediatria
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