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1.
J Clin Pharmacol ; 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35048362

RESUMO

Melphalan is an alkylating agent used as part of conditioning prior to pediatric hematopoietic cell transplantation (HCT). We performed a single center, prospective pharmacokinetic (PK) study of 37 pediatric patients undergoing HCT from March 2015 to 2019. The primary objective was to develop and validate a population PK model for melphalan in a diverse group of pediatric HCT recipients. Nonlinear mixed-effects modeling was implemented to describe plasma time-concentration data of melphalan. A two compartment, proportional error model with weight on clearance best fit the data. Final parameter estimates were: clearance 19.1 L/hr/25 kg; volume of the central compartment 8.5 L/25 kg; volume of the peripheral compartment 5.8 L/25 kg; and inter-compartmental clearance, 12.4 L/hr/25 kg. Residual unexplained variability was low at 12.5%. Results suggested the empiric weight-based dosing (mg/kg) used in children less than 12kg or 2 years of age may result in subtherapeutic exposure. Model-based dosing of melphalan in pediatric HCT may help inform individualized dosing strategies to improve clinical outcomes and limit drug-related adverse events in pediatric HCT recipients.  This article is protected by copyright. All rights reserved.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34723475

RESUMO

Flexible wearable pressure sensors have attracted great interest from researchers in recent years because of their important applications in human-machine interaction, human behavior detection, medical diagnosis, and other fields. At present, integrating multiple functions such as pressure and temperature sensing and self-cleaning into a single material remains a challenging task. Here, by in situ reduction of graphene oxide (GO) grown on a sponge surface and deposition of polypyrrole (PPy) nanoparticles, we have built a highly sensitive, stable, and multifunctional rGO/PPy/poly(dimethylsiloxane) (PDMS) polyurethane (PU) sponge (GPPS) sensor for the detection of pressure, water level, and temperature. This multifunctional sensor shows excellent pressure-sensing performance, ultrasensitive loading sensing of a leaf (98 mg), and outstanding reproducibility over 5000 cycles. Due to the stability of the superhydrophobic surface water contact angle (WCA) = 153.3°, our sensor can work in an underwater environment, which can sense water levels from 1 cm (∼98 Pa) to 40 cm and also a variety of underwater behaviors (knock, ultrasonication, blow, etc.) with high stability. In addition, the sensor can be integrated into a circuit for the water level and pressure detection. The sensor can also be used as a smart underwater-temperature sensor; it shows a linear temperature coefficient of resistance (TCR) of 0.48% °C-1 in a temperature range of 35-80 °C. This multifunctional sensor shows potential application prospects in wearable electronic devices for sensing.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34648457

RESUMO

This article investigates the local stability and local convergence of a class of neural network (NN) controllers with error integrals as inputs for reference tracking. It is formally proved that if the input of the NN controller consists exclusively of error terms, the control system shows a non-zero steady-state error for any constant reference except for one specific point, for both single-layer and multi-layer NN controllers. It is further proved that adding error integrals to the input of the (single- and multi-layers) NN controller is one sufficient way to remove the steady-state error for any constant reference. Due to the nonlinearity of the NN controllers, the NN control systems are linearized at the equilibrium points. We provide proof that if all the eigenvalues of the linearized NN control system have negative real parts, local asymptotic stability and local exponential convergence are guaranteed. Two case studies were explored to verify the theoretical results: a single-layer NN controller in a 1-D system and a four-layer NN controller in a 2-D system applied to renewable energy integration. Simulations demonstrate that when NN controllers and the corresponding generalized proportional-integral (PI) controllers have the same eigenvalues, all control systems exhibit almost the same responses in a small neighborhood of their respective equilibrium points.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34512778

RESUMO

The purpose of this study was to investigate the diagnostic value of color Doppler ultrasound combined with superb microvascular imaging (SMI) in the detection of small renal tumors less than 3 cm treated with Jinkui Shenqi pills. 50 cases were randomly selected from the patients with angioleiomyoma (a kind of small renal tumor) less than 3 cm confirmed by pathological examination and treated in our hospital from January 2018 to January 2020. All patients were treated with Jinkui Shenqi pills. All patients were first detected by color Doppler ultrasound and then by SMI. The results of color Doppler ultrasound were used as the control group, while those of color Doppler ultrasound combined with SMI were used as the experimental group. After that, the specificity, sensitivity, positive and negative detection results, and detection accuracy were compared between the two groups. The specificity and sensitivity in the experimental group were significantly higher than those in the control group, with statistical significance (P < 0.05). The cases of positive and negative detection results in the experimental group were significantly higher than those in the control group, with statistical significance (P < 0.05). The detection accuracy in the experimental group was significantly higher than that in the control group, with statistical significance (P < 0.05). The specificity, sensitivity, positive and negative detection results, and detection accuracy of color Doppler ultrasound combined with SMI in the detection of small renal tumors less than 3 cm treated with Jinkui Shenqi pills were all significantly higher than those of color Doppler ultrasound; therefore, the application of color Doppler ultrasound combined with SMI for the diagnosis of small renal tumors is of high value.

7.
J Exp Clin Cancer Res ; 40(1): 300, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556175

RESUMO

BACKGROUND: The global epidemiological studies reported lower cancer risk after long-term use of contraceptives. Our systematic studies demonstrated that abortifacients are effective in preventing cancer metastases induced by circulating tumor cells (CTCs). However, the molecular and cellular mechanisms by which abortifacients prevent CTC-based cancer metastases are almost unknown. The present studies were designed to interdisciplinarily explore similarities and differences between embryo implantation and cancer cell adhesion/invasion. METHODS: Biomarker expressions on the seeding embryo JEG-3 and cancer MCF-7 cells, as well as embedding uterine endometrial RL95-2 and vascular endothelial HUVECs cells were examined and compared before and after treatments with 17ß-estradiol plus progesterone and abortifacients. Effects of oral metapristone and mifepristone on embryo implantation in normal female mice and adhesion/invasion of circulating tumor cells (CTCs) in BALB/C female mice were examined. RESULTS: Both embryo JEG-3 and cancer MCF-7 cells expressed high sLex, CD47, CAMs, while both endometrial RL95-2 and endothelial HUVECs exhibited high integrins and ICAM-1. Near physiological concentrations of 17ß-estradiol plus progesterone promoted migration and invasion of JEG-3 and MCF-7 cells via upregulating integrins and MMPs. Whereas, mifepristone and metapristone significantly inhibited migration and invasion of JEG-3 and MCF-7 cells, and inhibited JEG-3 and MCF-7 adhesion to matrigel, RL95-2 cells and HUVECs, respectively. The inhibitions were realized by downregulating sLex, MMPs in JEG-3 and MCF-7 cells, and downregulating integrins in RL95-2 cells and HUVECs, respectively. Mifepristone and metapristone significantly inhibited both embryo implantation and cancer cell metastasis in mice. CONCLUSIONS: The similarities between the two systems provide fundamentals for abortifacients to intervene CTC adhesion/invasion to the distant metastatic organs. The present studies offer the rationale to repurpose abortifacients for safe and effective cancer metastasis chemoprevention.

8.
Exp Cell Res ; 406(1): 112755, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34332981

RESUMO

Liver cancer is one of the most common and high recurrence malignancies. Besides radiotherapy and surgery, chemotherapy also plays an essential role in the treatment of liver cancer. Sorafenib and sorafenib-based combination therapies have been proven efficacy against tumors. However, previous clinical studies have indicated that some patients with liver cancer are resistant to sorafenib treatment and the existing strategies are not satisfactory in the clinic. Therefore, it is urgent to investigate strategies to improve the effectiveness of sorafenib for liver cancer and to explore effective drug combinations. In the present study, we found that dichloroacetate (DCA) could significantly enhance the anti-tumor effect of sorafenib on liver cancer cells, including reduced viability and dramatically promoted apoptosis in liver cancer cells. Moreover, compared to sorafenib alone, the combination of DCA and sorafenib markedly increased the degradation of anti-apoptotic protein Mcl-1 by enhancing its phosphorylation. Overexpression of Mcl-1 could significantly attenuate the synergetic effect of DCA and sorafenib on apoptosis induction in liver cancer cells. Furthermore, we found that the ROS-JNK pathway was obviously activated in the DCA combined sorafenib group. The levels of ROS and p-JNK were dramatically up-regulated in the two drug combination groups. Antioxidant NAC could alleviate the synergetic effects of DCA and sorafenib on ROS generation, JNK activation, Mcl-1 degradation, and cell apoptosis. Moreover, DCA and sorafenib's effects on Mcl-1 degradation and apoptosis could also be inhibited by JNK inhibitor 'SP'600125. Finally, the synergetic effects of DCA and sorafenib on tumor growth suppression, Mcl-1 degradation and induction of apoptosis were also validated in liver cancer xenograft in vivo. These findings indicate that DCA enhances the anti-tumor effect of sorafenib via the ROS-JNK-Mcl-1 pathway in liver cancer cells. This study may provide new insights to improve the chemotherapeutic effect of sorafenib, which may be beneficial for further clinical application of sorafenib in liver cancer treatment.


Assuntos
Ácido Dicloroacético/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/tratamento farmacológico , MAP Quinase Quinase 4/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Sorafenibe/farmacologia , Acetilcisteína/farmacologia , Animais , Antracenos/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos Nus , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Small ; 17(37): e2101154, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34331375

RESUMO

2D van der Waals heterojunction provides an attractive opportunity for realizing novel electronic or optoelectronic devices. It remains challenging to realize high-quality heterostructures through scalable methods such as molecular epitaxy growth (MBE). Here, growth of few-layer SnS thin films is reported on mica and Nb-doped SrTiO3 (100) substrates by MBE. Then the top layer of SnS film is uniformly sulfurized to monolayer SnS2 in a sulfur atmosphere, resulting in a high-quality SnS2 /SnS 2D heterojunction. Furthermore, the SnS2 layer can be recovered to SnS by annealing SnS2 /SnS without sulfur supply, indicating the heterojunction formation is reversible. The scanning tunneling spectroscopy measurements on SnS2 /SnS heterostructure indicate the type-II band alignment in SnS2 /SnS. The work provides a promising approach to construct artificial 2D heterojunctions with desired properties, which could be extended to other sulfide and selenide systems.

10.
iScience ; 24(6): 102665, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34189434

RESUMO

Efficiently cleaning up high-viscosity crude oil spills is still a serious global problem. In this paper, a composite filler PPy-polydopamine/BN (PPB) with high photothermal effect and high thermal conductivity was first prepared. Then the polyurethane sponge is decorated with polydimethylsiloxane and PPB to obtain a solar-assisted isotropically thermoconductive adsorbent (PPB@PU), which exhibits remarkable stability and durable mechanical properties. Meanwhile, the PPB@PU sponge has good thermal conductivity, and its surface temperature rises to 91°C in just 1 min under irradiation (1 sun). Therefore, the PPB@PU sponge can quickly heat and adsorb the crude oil contacted by the surface, significantly speed up the crude oil recovery process, and the adsorption capacity is as high as about 45 g/g. Finally, the oil adsorption method of the three-dimensional adsorbent is demonstrated, which provides a new idea for the subsequent development of advanced oil spill adsorbent.

11.
Nat Commun ; 12(1): 3751, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145228

RESUMO

When light propagates through opaque material, the spatial information it holds becomes scrambled, but not necessarily lost. Two classes of techniques have emerged to recover this information: methods relying on optical memory effects, and transmission matrix (TM) approaches. Here we develop a general framework describing the nature of memory effects in structures of arbitrary geometry. We show how this framework, when combined with wavefront shaping driven by feedback from a guide-star, enables estimation of the TM of any such system. This highlights that guide-star assisted imaging is possible regardless of the type of memory effect a scatterer exhibits. We apply this concept to multimode fibres (MMFs) and identify a 'quasi-radial' memory effect. This allows the TM of an MMF to be approximated from only one end - an important step for micro-endoscopy. Our work broadens the applications of memory effects to a range of novel imaging and optical communication scenarios.

12.
Sci Total Environ ; 773: 145545, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33940731

RESUMO

During 2020, the COVID-19 pandemic resulted in a widespread lockdown in many cities in China. In this study, we assessed the impact of changes in human activities on air quality during the COVID-19 pandemic by determining the relationships between air quality, traffic volume, and meteorological conditions. The megacities of Wuhan, Beijing, Shanghai, and Guangzhou were selected as the study area, and the variation trends of air pollutants for the period January-May between 2016 and 2020 were analyzed. The passenger volume of public transportation (PVPT) and the passenger volume of taxis (PVT) along with data on precipitation, temperature, relative humidity, wind speed, and boundary layer height were used to identify and quantify the driving force of the air pollution variation. The results showed that the change rates of fine particulate matter (PM2.5), NO2, and SO2 before and during the lockdown in the four megacities ranged from -49.9% to 78.2% (average: -9.4% ± 59.3%), -55.4% to -32.3% (average: -43.0% ± 9.7%), and - 21.1% to 11.9% (average: -10.9% ± 15.4%), respectively. The response of NO2 to the lockdown was the most sensitive, while the response of PM2.5 was smaller and more delayed. During the lockdown period, haze from uninterrupted industrial emissions and fireworks under the effect of air mass transport from surrounding areas and adverse climate conditions was probably the cause of abnormally high PM2.5 concentrations in Beijing. In addition, the PVT was the most significant factor for NO2, and meteorology had a greater impact on PM2.5 than NO2 and SO2. There is a need for more national-level policies for limiting firework displays and traffic emissions, as well as further studies on the formation and transmission of secondary air pollutants.


Assuntos
Poluição do Ar , COVID-19 , Poluição do Ar/análise , Pequim/epidemiologia , China/epidemiologia , Cidades , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Humanos , Conceitos Meteorológicos , Pandemias , SARS-CoV-2
13.
J Neuroinflammation ; 18(1): 107, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957945

RESUMO

BACKGROUND: Tuberous sclerosis complex 1 (Tsc1) is known to regulate the development and function of various cell types, and RORγt is a critical transcription factor in the immune system. However, whether Tsc1 participates in regulating RORγt-expressing cells remains unknown. METHODS: We generated a mouse model in which Tsc1 was conditionally deleted from RORγt-expressing cells (Tsc1RORγt) to study the role of RORγt-expressing cells with Tsc1 deficiency in brain homeostasis. RESULTS: Type 3 innate lymphoid cells (ILC3s) in Tsc1RORγt mice displayed normal development and function, and the mice showed normal Th17 cell differentiation. However, Tsc1RORγt mice exhibited spontaneous tonic-clonic seizures and died between 4 and 6 weeks after birth. At the age of 4 weeks, mice in which Tsc1 was specifically knocked out in RORγt-expressing cells had cortical neuron defects and hippocampal structural abnormalities. Notably, over-activation of neurons and astrogliosis were observed in the cortex and hippocampus of Tsc1RORγt mice. Moreover, expression of the γ-amino butyric acid (GABA) receptor in the brains of Tsc1RORγt mice was decreased, and GABA supplementation prolonged the lifespan of the mice to some extent. Further experiments revealed the presence of a group of rare RORγt-expressing cells with high metabolic activity in the mouse brain. CONCLUSIONS: Our study verifies the critical role of previously unnoticed RORγt-expressing cells in the brain and demonstrates that the Tsc1 signaling pathway in RORγt-expressing cells is important for maintaining brain homeostasis.

14.
Light Sci Appl ; 10(1): 88, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883544

RESUMO

The measurement of the optical transmission matrix (TM) of an opaque material is an advanced form of space-variant aberration correction. Beyond imaging, TM-based methods are emerging in a range of fields, including optical communications, micro-manipulation, and computing. In many cases, the TM is very sensitive to perturbations in the configuration of the scattering medium it represents. Therefore, applications often require an up-to-the-minute characterisation of the fragile TM, typically entailing hundreds to thousands of probe measurements. Here, we explore how these measurement requirements can be relaxed using the framework of compressive sensing, in which the incorporation of prior information enables accurate estimation from fewer measurements than the dimensionality of the TM we aim to reconstruct. Examples of such priors include knowledge of a memory effect linking the input and output fields, an approximate model of the optical system, or a recent but degraded TM measurement. We demonstrate this concept by reconstructing the full-size TM of a multimode fibre supporting 754 modes at compression ratios down to ∼5% with good fidelity. We show that in this case, imaging is still possible using TMs reconstructed at compression ratios down to ∼1% (eight probe measurements). This compressive TM sampling strategy is quite general and may be applied to a variety of other scattering samples, including diffusers, thin layers of tissue, fibre optics of any refractive profile, and reflections from opaque walls. These approaches offer a route towards the measurement of high-dimensional TMs either quickly or with access to limited numbers of measurements.

15.
J Med Chem ; 64(6): 3381-3391, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33688738

RESUMO

Nitroimidazoles are one of the most common radiosensitizers investigated to combat hypoxia-induced resistance to cancer radiotherapy. However, due to poor selectivity distinguishing cancer cells from normal cells, effective doses of radiosensitization are much closer to the doses of toxicity induced by nitroimidazoles, limiting their clinical application. In this work, a tumor-targeting near-infrared (NIR) cyanine dye (IR-808) was utilized as a targeting ligand and an NIR fluorophore tracer to chemically conjugate with different structures of hypoxia-affinic nitroimidazoles. One of the NIR fluorophore-conjugated nitroimidazoles (808-NM2) was identified to preferentially accumulate in hypoxic tumor cells, sensitively outline the tumor contour, and effectively inhibit tumor growth synergistically by chemotherapy and radiotherapy. More importantly, nitroimidazoles were successfully taken into cancer cell mitochondria via 808-NM2 conjugate to exert the synergistic effect of chemoradiotherapy. Regarding the important roles of mitochondria on cancer cell survival and metastasis under hypoxia, 808-NM2 may be hopeful to fight against hypoxic tumors.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Carbocianinas/uso terapêutico , Corantes/uso terapêutico , Nitroimidazóis/uso terapêutico , Animais , Antineoplásicos/química , Neoplasias da Mama/patologia , Carbocianinas/química , Quimiorradioterapia , Corantes/química , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Nitroimidazóis/química , Hipóxia Tumoral
16.
ACS Omega ; 6(4): 3079-3089, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33553925

RESUMO

Protein carbamylation has been linked with diseases commonly associated with patients with reduced kidney function. Carbamylated human serum albumin (cHSA), which has been proven to be nephrotoxic and associated with heart failure for chronic kidney disease (CKD) patients, was chosen for our study. Through phage display against cHSA, one specific peptide sequence (cH2-p1) was identified with higher selectivity toward cHSA over native HSA. The cH2-p1 peptide was synthesized, and its target binding was analyzed through isothermal titration calorimetry (ITC). The result showed that cH2-p1 was able to bind cHSA of different levels of carbamylation with a similar dissociation constant of ∼1.0 × 10-4 M. This peptide also showed a binding specificity to carbamylated fibrinogen (cFgn), while not binding to native Fgn at all. For better understanding of the binding mechanism of cH2-p1, competitive binding of cH2-p1 and anti-homocitrulline to cHSA was performed, and the result revealed that cH2-p1 may bind to homocitrulline residues in a similar manner to the antibody. A molecular docking study was further performed to investigate the favored binding conformation of homocitrulline residue to cH2-p1. This work demonstrates the potential of peptides as a specific binding element to carbamylated proteins.

17.
Br J Clin Pharmacol ; 87(9): 3531-3541, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33576009

RESUMO

AIMS: The population pharmacokinetics (PK) and pharmacodynamics (PD) of tranexamic acid (TXA) have not been studied to prevent postpartum haemorrhage (PPH) in pregnant women. It is unclear which TXA dose assures sufficient PPH prevention. This study investigated population PK/PD of TXA in pregnant women who underwent caesarean delivery to determine the optimal prophylactic doses of TXA for future studies. METHODS: We analysed concentration (PK) and maximum lysis (PD) data from 30 pregnant women scheduled for caesarean delivery who received 5, 10 or 15 mg/kg of TXA intravenously using population approach. RESULTS: TXA PK was best described by a two-compartment model with first-order elimination and the following parameters: clearance (between-subject variability) of 9.4 L/h (27.7%), central volume of 10.1 L (47.4%), intercompartmental clearance of 22.4 L/h (66.7%), peripheral volume of 14.0 L (13.1%) and additive error of 1.4 mg/L. The relationship between TXA concentration and maximum lysis was characterized by a sigmoid Emax model with baseline lysis of 97%, maximum inhibition of 89%, IC50 of 6.0 mg/L (65.3%), hill factor of 8.5 (86.3%) and additive error of 7.3%. Simulations demonstrated that 500 and 650 mg of TXA maintained therapeutic targets for 30 minutes and 1 hour, respectively, in 90% of patients. CONCLUSION: This is the first population PK and PD study of TXA in pregnant women undergoing caesarean delivery. Our analysis suggests that a 650 mg dose provides adequate PPH prophylaxis up to 1 hour, which is less than the currently used 1000 mg of TXA in pregnant women.


Assuntos
Antifibrinolíticos , Hemorragia Pós-Parto , Ácido Tranexâmico , Cesárea , Feminino , Humanos , Hemorragia Pós-Parto/tratamento farmacológico , Hemorragia Pós-Parto/prevenção & controle , Gravidez
18.
J Thromb Haemost ; 19(1): 221-232, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001565

RESUMO

Essentials Tranexamic acid (TXA) is an antifibrinolytic drug used to reduce bleeding. Assaying plasmin generation (PG) in plasma detects clinically relevant TXA levels in vitro and ex vivo. 3.1-16.2 µg/mL TXA half-maximally inhibits PG in plasma from women undergoing cesarean delivery. PG velocity shows the strongest dose-relationship at low TXA concentrations (≤10 µg/mL). ABSTRACT: Background Tranexamic acid (TXA) is used to reduce bleeding. TXA inhibits plasmin(ogen) binding to fibrin and reduces fibrinolysis. TXA antifibrinolytic activity is typically measured by clot lysis assays; however, effects on plasmin generation (PG) are unclear due to a lack of tools to measure PG in plasma. Aims Develop an assay to measure PG kinetics in human plasma. Determine effects of TXA on PG and compare with fibrinolysis measured by rotational thromboelastometry (ROTEM). Methods We characterized effects of plasminogen, tissue plasminogen activator, fibrinogen, and α2 -antiplasmin on PG in vitro. We also studied effects of TXA on PG in plasma from 30 pregnant women administered intravenous TXA (5, 10, or 15 mg/kg) during cesarean delivery. PG was measured by calibrated fluorescence. PG parameters were compared with TXA measured by mass spectrometry and ROTEM of whole blood. Results The PG assay is specific for plasmin and sensitive to tissue plasminogen activator, fibrin(ogen), and α2 -antiplasmin. Addition of TXA to plasma in vitro dose dependently prolonged the clot lysis time and delayed and reduced PG. For all doses of TXA administered intravenously, the PG assay detected delayed time-to-peak (≤3 hours) and reduced the velocity, peak, and endogenous plasmin potential (≤24 hours) in plasma samples obtained after infusion. The PG time-to-peak, velocity, and peak correlated significantly with TXA concentration and showed less variability than the ROTEM lysis index at 30 minutes or maximum lysis. Conclusions The PG assay detects pharmacologically relevant concentrations of TXA administered in vitro and in vivo, and demonstrates TXA-mediated inhibition of PG in women undergoing cesarean delivery.


Assuntos
Antifibrinolíticos , Cesárea , Fibrinolisina , Ácido Tranexâmico , Antifibrinolíticos/farmacologia , Feminino , Fibrinolisina/farmacologia , Fibrinólise , Humanos , Gravidez , Ativador de Plasminogênio Tecidual/farmacologia , Ácido Tranexâmico/farmacologia
19.
ACS Appl Mater Interfaces ; 13(3): 4740-4749, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33370088

RESUMO

Superhydrophobic conductive materials have received a great amount of interest due to their wide applications in oil-water separation, electrically driven smart surface, electromagnetic shielding, and body motion detection. Herein, a highly conductive superhydrophobic cotton cloth is prepared by a facile method. A layer of polydopamine/reduced graphene oxide (PDA/rGO) was first coated on the cotton fabric, and then copper nanoparticles were in situ grown on the prepared surface. After further modification with stearic acid (STA), the wettability of the cotton surface changed from superhydrophilic to superhydrophobic (water contact angle (WCA) = 153°). The electrical conductivity of the PDA/rGO/Cu/STA cotton is as high as 6769 S·m-1, while the stearic acid effectively protects Cu NPs from oxidation. As a result, the superhydrophobic PDA/rGO/Cu/STA cotton has shown excellent electrical stability and can be used in detecting human motions in both ambient and underwater conditions. The sensor can recognize human motion from air into water and other underwater activities (e.g., underwater bending, stretching, and ultrasound). This multifunctional cotton device can be used as an ideal sensor for underwater intelligent devices and provides a basis for further research.


Assuntos
Técnicas Biossensoriais/instrumentação , Fibra de Algodão/análise , Grafite/química , Indóis/química , Polímeros/química , Dispositivos Eletrônicos Vestíveis , Técnicas Biossensoriais/métodos , Condutividade Elétrica , Desenho de Equipamento , Humanos , Interações Hidrofóbicas e Hidrofílicas , Movimento (Física) , Oxirredução , Ácidos Esteáricos/química , Água/química , Molhabilidade
20.
Am J Obstet Gynecol ; 225(1): 85.e1-85.e11, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33248975

RESUMO

BACKGROUND: Every 2 minutes, there is a pregnancy-related death worldwide, with one-third caused by severe postpartum hemorrhage. Although international trials demonstrated the efficacy of 1000 mg tranexamic acid in treating postpartum hemorrhage, to the best of our knowledge, there are no dose-finding studies of tranexamic acid on pregnant women for postpartum hemorrhage prevention. OBJECTIVE: This study aimed to determine the optimal tranexamic acid dose needed to prevent postpartum hemorrhage. STUDY DESIGN: We enrolled 30 pregnant women undergoing scheduled cesarean delivery in an open-label, dose ranging study. Subjects were divided into 3 cohorts receiving 5, 10, or 15 mg/kg (maximum, 1000 mg) of intravenous tranexamic acid at umbilical cord clamping. The inclusion criteria were ≥34 week's gestation and normal renal function. The primary endpoints were pharmacokinetic and pharmacodynamic profiles. Tranexamic acid plasma concentration of >10 µg/mL and maximum lysis of <17% were defined as therapeutic targets independent to the current study. Rotational thromboelastometry of tissue plasminogen activator-spiked samples was used to evaluate pharmacodynamic profiles at time points up to 24 hours after tranexamic acid administration. Safety was assessed by plasma thrombin generation, D-dimer, and tranexamic acid concentrations in breast milk. RESULTS: There were no serious adverse events including venous thromboembolism. Plasma concentrations of tranexamic acid increased in a dose-proportional manner. The lowest dose cohort received an average of 448±87 mg tranexamic acid. Plasma tranexamic acid exceeded 10 µg/mL and maximum lysis was <17% at >1 hour after administration for all tranexamic acid doses tested. Median estimated blood loss for cohorts receiving 5, 10, or 15 mg/kg tranexamic acid was 750, 750, and 700 mL, respectively. Plasma thrombin generation did not increase with higher tranexamic acid concentrations. D-dimer changes from baseline were not different among the cohorts. Breast milk tranexamic acid concentrations were 1% or less than maternal plasma concentrations. CONCLUSION: Although large randomized trials are necessary to support the clinical efficacy of tranexamic acid for prophylaxis, we propose an optimal dose of 600 mg in future tranexamic acid efficacy studies to prevent postpartum hemorrhage.


Assuntos
Hemorragia Pós-Parto/prevenção & controle , Ácido Tranexâmico/administração & dosagem , Adulto , Cesárea , Relação Dose-Resposta a Droga , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Idade Gestacional , Humanos , Leite Humano/química , Gravidez , Tromboelastografia , Ácido Tranexâmico/efeitos adversos , Ácido Tranexâmico/farmacocinética , Resultado do Tratamento , Adulto Jovem
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