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1.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38456755

RESUMO

A simple measurement scheme is proposed to reconstruct the geometry of an axisymmetric void propagating through a conducting liquid using a pair of parallel wire conductivity probes. An experimental study allows for obtaining the time variation of the resistance of the film surrounding the void. Analytical modeling and numerical simulation has been adopted to correlate the resistance between the wire electrodes and the film thickness. Finally, the shape of the void can be estimated by combining the predicted resistance-film thickness relationship and the measured time variation of resistance. For validation, this scheme has been used to reconstruct the shape of a rising Taylor bubble. There is a fair match between the reconstructed shape of the bubble and its photographic image. The probable errors in the measurement scheme have been discussed and assessed mathematically.

2.
ChemMedChem ; 19(9): e202300551, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38328976

RESUMO

Hypoxia, a key aspect of the tumor microenvironment, plays a vital role in cell proliferation, angiogenesis, metabolism, and the immune response within tumors. These factors collectively promote tumor advancement, aggressiveness, metastasis and result in a poor prognosis. Hypoxia inducible factor 1α (HIF-1α), activated under low oxygen conditions, mediates many of these effects by altering drug target expression, metabolic regulation, and oxygen consumption. These changes promote cancer cell growth and survival. Hypoxic tumor cells develop aggressive traits and resistance to chemotherapy and radiotherapy, leading to increased mortality. Targeting hypoxic tumor offers a potential solution to overcome the challenges posed by tumor heterogeneity and can be used in designing diagnostic and therapeutic nanocarriers for various solid cancers. This concept provides an overview of the intricate relationship between hypoxia and the tumor microenvironment, highlighting its potential as a promising tool for cancer therapies. The article explores the development of hypoxia in cancer cells and its role in cancer progression, along with the latest advancements in hypoxia-triggered cancer treatment.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/patologia , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Hipóxia Celular , Proliferação de Células/efeitos dos fármacos , Animais
3.
Mol Pharm ; 20(12): 6391-6406, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37933877

RESUMO

Metabolic reprogramming is a significant hallmark of cancer that promotes chemoresistance by allowing tumor tissues to adapt to changes in the tumor microenvironment caused by anticancer therapies. Hepatocellular carcinoma (HCC), one of the most common types of primary tumors, is associated with recurrent metabolic reprogramming that maximizes cancer cell growth and proliferation. Herein, we developed metformin (MET)-loaded hyaluronic acid (HA)-derived carbon dots (HA-CD-MET) by a simple and green method with no involvement of any additives. HA-CD-MET was utilized for specifically binding the CD44 receptor overexpressed in HCC and induced glutamine metabolic rewiring to inhibit HCC cell proliferation. Exposure to HA-CD-MET resulted in ∼6.5-fold better anticancer efficacy against CD44+ Hep3B cells in comparison to CD44-, HepG2, and noncancerous HEK293 cells at a very low dose of 80 µg/mL. Moreover, treatment of three-dimensional (3D) tumor spheroid model of HCC (Hep3B) with HA-CD-MET resulted in ∼4.9-fold reduction in tumor size. This improved anticancer efficacy of HA-CD-MET was attributed to the inhibition of glutaminase-1 (GLS-1), a mitochondrial enzyme that hydrolyzes glutamine into glutamate as confirmed from immunofluorescence and immunoblotting experiments. Furthermore, treatment with HA-CD-MET resulted in downregulation of glucose transporter-1 (GLUT-1) in Hep3B cells. Consequently, cancer cells were starved from essential nutrients, glutamine, and glucose, leading to the enhancement in intracellular ROS generation. This increase in intracellular ROS accumulation activated AMP-activated protein kinase (AMPK) and inhibited AKT phosphorylation, leading to cancer cell apoptosis. Thus, this study offers the targeting of metabolic reprogramming by HA-CD-MET that opens up a promising strategy for therapeutic intervention in hepatocarcinoma.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Metformina , Humanos , Carcinoma Hepatocelular/patologia , Metformina/farmacologia , Metformina/uso terapêutico , Ácido Hialurônico , Glutamina , Neoplasias Hepáticas/patologia , Carbono , Espécies Reativas de Oxigênio/metabolismo , Células HEK293 , Linhagem Celular Tumoral , Receptores de Hialuronatos/metabolismo , Microambiente Tumoral
4.
Langmuir ; 39(44): 15690-15704, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37874762

RESUMO

Fluorometric sensors have gained considerable attention in various fields, including environmental monitoring, biomedical research, and clinical diagnostics. This article delineates the fabrication of an orange emitting naphthalene diimide (NDI) derivative consisting of maleimide moiety (NDI-mal) for fluorometric sensing of thiols. Spherical shaped organic nanoparticles (∼100-150 nm) were constructed by NDI-mal in dimethyl sulfoxide (DMSO)/dimethylformamide (DMF)-water through J-type aggregation. NDI-mal displayed self-assembly driven aggregation-induced emission (AIE) through excimer formation at λem= 588 nm at fw = 99 vol % DMSO/DMF-water. Naphthyl residue at both terminals of NDI-mal facilitates intramolecular charge transfer (ICT) from the donor naphthyl residue to the acceptor NDI core. The fluorescence intensity of NDI-mal fluorescent organic nanoparticles (FONPs) got quenched in the presence of thiols due to thiol-maleimide adduct formation (Michael addition). NDI-mal FONPs selectively probed thiol functionalized small molecules (4-aminothiophenol), biomolecules (glutathione (GSH)), and proteins (reduced BSA) with high sensitivity having a limit of detection of 15.3 nM, 6.0 nM, and 9.2 ng/mL, respectively. Importantly, thiol sensing was selective against analogous small molecules, biomolecules, and proteins devoid of thiol moieties. Cellular imaging demonstrated selective diagnosis of cancer cells by NDI-mal FONPs through quenching of its emission upon interaction with thiols in B16F10 cells due to the high abundance of GSH in cancer cells compared to NIH3T3 cells. NDI-mal FONPs emitted their native fluorescence inside cells subjected to reactive oxygen species mediated thiol oxidation via Fenton's reaction. Notably, GSH-maleimide adduct formation by NDI-mal FONPs displayed notable therapeutic efficacy against cancer cells having ∼2.4-fold higher killing of B16F10 in comparison to NIH3T3 cells possibly through oxidative stress induced apoptosis owing to the depletion in the GSH level. Thus, NDI-mal AIE-gen successfully emerged as a selective and sensitive probe toward thiols through thiol-maleimide click chemistry with therapeutic ability against cancer cells in the absence of systematic intervention.


Assuntos
Dimetil Sulfóxido , Compostos de Sulfidrila , Animais , Camundongos , Células NIH 3T3 , Compostos de Sulfidrila/química , Maleimidas/química , Proteínas , Corantes Fluorescentes/química , Água
5.
Anal Chem ; 95(36): 13638-13648, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37651212

RESUMO

Aggregation-induced emission (AIE)-based fluorescent organic nanoparticles (FONPs) with distinctive characteristics are emerging as superior sensors due to their facile fabrication, high signal-to-noise ratio, and good biocompatibility. The present article delineates the detection and analysis of the redox behavior of the protein disulfide isomerase (PDI) enzyme by exploitation of the AIE of novel naphthalimide (NI) derivatives having thiol (-SH) and disulfide (-S-S-) moieties. Self-aggregated spherical-shaped organic nanoparticles were prepared by synthesized NI-based amphiphiles (NISH, NISS, NINSS, and TNINSH) through J-type aggregation in DMSO-water (fw = 99 vol %). Naphthyl residue containing NI-derived amphiphiles (NINSS and TNINSH) exhibited AIE (blue and yellow) at 470 and 550 nm, respectively, in DMSO-water (fw = 99 vol %). NINSS and TNINSH FONPs were suitably utilized in sensing PDI through their redox nature of thiol-disulfide exchange. Fluorescence quenching of NINSS FONPs was observed due to reduction of disulfide to thiol by PDI, whereas emission intensity was progressively red-shifted and enhanced ("Dual-AIE") for TNINSH (containing ER-targeting N-tosylethylenediamine), owing to oxidation of thiol to disulfide by PDI. NINSS and TNINSH FONPs were found to be highly efficient in sensing PDI through the AIE-based "fluorescence off/on" mechanism having limits of detection of ∼12.6-17.7 and ∼11.7-16.5 ng/mL, respectively. In vitro cell imaging for NIH3T3 (noncancer) and B16F10 (melanoma) cells with NINSS and TNINSH FONPs displayed excellent diagnosis of eukaryotic cells upon interaction with indigenous PDI. Notably, detection of cancer cells was more sensitive over the noncancerous cells by these FONPs due to overexpression of PDI within cancer cells.


Assuntos
Dimetil Sulfóxido , Isomerases de Dissulfetos de Proteínas , Camundongos , Animais , Células NIH 3T3 , Naftalimidas , Corantes , Dissulfetos , Oxirredução , Compostos de Sulfidrila , Água
6.
Eur J Cardiothorac Surg ; 64(2)2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37341638

RESUMO

OBJECTIVES: Core temperature monitoring is critical during cardiopulmonary bypass (CPB). In this prospective observational study, we investigated the performance of the transoesophageal echocardiography (TOE) probe for core (oesophageal) temperature monitoring during CPB. METHODS: Thirty adult patients, 18-70 years of either gender, undergoing cardiac surgery with CPB were enrolled. All patients received a reusable nasopharyngeal probe for monitoring core temperatures. In addition, the oesophageal temperatures were monitored with the TOE probe. The arterial outlet temperatures at the membrane oxygenator were also monitored and taken as the reference standard. Monitoring was performed every 5 min until 20 min, and then at 30 min during both the cooling and rewarming periods. RESULTS: During cooling, the oesophageal and nasopharyngeal temperatures lagged behind the arterial outlet temperatures. However, the intra-class correlation of the oesophageal temperatures with the arterial outlet temperatures was better (range 0.58-0.74) than the correlation of the nasopharyngeal temperatures with the arterial outlet temperatures (range 0.46-0.62). During rewarming, the performance of the TOE probe was significantly superior to the nasopharyngeal probe. After 15 and 20 min of rewarming, there was a difference of ∼1°C between the oesophageal and nasopharyngeal temperatures. At 30 min of rewarming, the oesophageal and the arterial outlet temperatures were similar, while the nasopharyngeal temperatures still lagged by 0.5°C. Bias was significantly less both during cooling and warming between the oesophageal temperatures and arterial outlet temperatures. CONCLUSIONS: Performance of the TOE probe as an oesophageal temperature probe is superior to the nasopharyngeal probe during CPB. CLINICAL TRIAL REGISTRATION NUMBER: CTRI no 2020/10/028228; ctri.nic.in.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Hipotermia Induzida , Adulto , Humanos , Ponte Cardiopulmonar/efeitos adversos , Temperatura , Ecocardiografia Transesofagiana , Temperatura Corporal , Procedimentos Cirúrgicos Cardíacos/efeitos adversos
7.
Chembiochem ; 24(18): e202300253, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37232377

RESUMO

The present work depicts the development of stable nanogels in an aqueous medium that were exploited for efficient surface-active lipase-catalyzed hydrolysis of water-insoluble substrates. Surfactant-coated gel nanoparticles (neutral NG1, anionic NG2, and cationic NG3) were prepared from peptide amphiphilic hydrogelator (G1, G2, and G3, respectively) at different hydrophilic and lipophilic balance (HLB). Chromobacterium viscosum (CV) lipase activity towards hydrolysis of water-insoluble substrates (p-nitrophyenyl-n-alkanoates (C4-C10)) in the presence of nanogels got remarkably improved by ~1.7-8.0 fold in comparison to that in aqueous buffer and other self-aggregates. An increase in hydrophobicity of the substrate led to a notable improvement in lipase activity in the hydrophilic domain (HLB>8.0) of nanogels. The micro-heterogeneous interface of small-sized (10-65 nm) nanogel was found to be an appropriate scaffold for immobilizing surface-active lipase to exhibit superior catalytic efficiency. Concurrently, the flexible conformation of lipase immobilized in nanogels was reflected in its secondary structure having the highest α-helix content from the circular dichroism spectra.


Assuntos
Lipase , Água , Hidrólise , Nanogéis , Água/química , Lipase/química , Catálise
8.
Cureus ; 15(3): e36095, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37065324

RESUMO

Background People's perceptions of the COVID-19 pandemic and its associated risk are very essential to prevent the spread of the infection. The awareness among individuals may contribute to preventing COVID-19 infections. Coronavirus disease is a serious public health issue. However, preventive practices toward COVID-19 are relatively unknown. The present study aims to survey the risk perception and preventive practice during the COVID-19 pandemic among the general population in Odisha. Method A cross-sectional online survey among 395 participants was conducted by adopting the convenience sampling technique. The tools used for the survey consist of three divisions: collection of sociodemographic data, assessment of risk perception toward COVID-19, and assessment of preventive practices during COVID-19 through an online survey method. Results The majority (83.29%) of the participants strongly agreed that social distancing is necessary to control the transmission of COVID-19, 65.82% strongly agreed that lockdown is relevant to control COVID-19 spread, 49.62% strongly agreed that wearing a mask protects from the infection, and 40.25% strongly agreed that they will be able to connect with healthcare professionals if they are infected with COVID-19 infection. The finding revealed that the highest number of participants are always practicing all the preventive measures such as maintaining hand hygiene (77.21%), wearing a mask (68.10%), avoiding shaking hands (87.59%), willingness to seek medical help (90.37%), avoiding going to the market or meeting friends (80.75%), discussing preventive measures related to COVID-19 with their family members (76.45%), and eating only homemade food (87.34%). Conclusion This study found that an average number of study participants who had the highest level of practice on preventive measures are those who had higher perceived risk among the general population. Expanding the knowledge regarding the infection and its ill effect on health through the proper channel can bring a drastic change in the attitude of the general public. As many people depend on television and social media for acquiring information about COVID-19, any information that reaches the public should be accurate and based on evidence. To avoid miscommunication and the further spread of COVID-19, health education and awareness have to be implemented to increase self-efficacy and risk identification among the general public, which eventually increases the practice of preventive measures.

9.
Eur Phys J Spec Top ; 232(6): 781-815, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36532608

RESUMO

A wide range of applications are possible with paper-based analytical devices, which are low priced, easy to fabricate and operate, and require no specialized equipment. Paper-based microfluidics offers the design of miniaturized POC devices to be applied in the health, environment, food, and energy sector employing the ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment free and Deliverable to end users) principle of WHO. Therefore, this field is growing very rapidly and ample research is being done. This review focuses on fabrication and detection techniques reported to date. Additionally, this review emphasises on the application of this technology in the area of medical diagnosis, energy generation, environmental monitoring, and food quality control. This review also presents the theoretical analysis of fluid flow in porous media for the efficient handling and control of fluids. The limitations of PAD have also been discussed with an emphasis to concern on the transformation of such devices from laboratory to the consumer.

10.
Comput Biol Med ; 151(Pt A): 106309, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36410098

RESUMO

Due to the unavailability of donors, the use of left ventricular assist devices has emerged to be a reliable line of alternative treatment for heart failure. However, ventricular assist devices (VAD) have been associated with several postoperative complications such as thrombosis, hemolysis, etc. Despite considerable improvements in technology, blood trauma due to high shear stress generation has been a major concern that is largely related to the geometrical feature of the VAD. This study aims to establish the design process of a centrifugal pump by considering several variations in the geometrical feature of a base design using the commercial solver ANSYS-CFX. To capture the uncertain behavior of blood as fluid, Newtonian, as well as non-Newtonian (Bird-Carreau model), models are used for flow field prediction. To assess the possibility of blood damage maximum wall shear stress and hemolysis index have been estimated for each operating point. The results of the simulations yield an optimized design of the pump based on parameters like pressure head generation, maximum shear stress, hydraulic efficiency, and hemolysis index. Further, the design methodology and the steps of development discussed in the paper can serve as a guideline for developing small centrifugal pumps handling blood.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Humanos , Hemólise , Hemodinâmica , Insuficiência Cardíaca/cirurgia , Estresse Mecânico
11.
Environ Monit Assess ; 194(6): 404, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35513507

RESUMO

The vulnerability of the power generation industries vulnerability to the availability of water is widespread and growing. In this regard, water footprint (WF) is one method to assess this challenge. The present study conducts the WF of a naphtha-fired combined cycle power plant (CCPP) and a coal-fired steam power plant (CSPP). For carrying out WF, it is prudent to look after water consumption during operations and the supply chain stages. Hence, in this regard, two methods have been adopted to investigate the WF of both power plants. The first method deals with the water balance mass diagram (direct WF), and the second method deals with the water supply chain (indirect WF). Evaporation loss appears to be a significant contributing factor to the direct WF. On the other hand, operational WF seems to be an essential contributing factor to indirect WF. Furthermore, the result also shows that specific water consumption in CSPP is 3.54 m3/h, whereas, in CCPP, it is 0.9 m3/h. Finally, some methods have also been suggested to reduce WF in both power plants.


Assuntos
Petróleo , Vapor , Alcanos , Carvão Mineral , Monitoramento Ambiental , Centrais Elétricas , Água
12.
Med Biol Eng Comput ; 60(6): 1705-1721, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35441317

RESUMO

This article describes the numerical efforts made to investigate the influence of a left ventricular assist device (LVAD) on the patient-specific left heart's hemodynamics. Two different computational geometries with left heart have been simulated over the entire cardiac cycle (case 1: healthy heart without LVAD and case 2: diseased heart with LVAD). The blood flow was simulated by implementing Bird-Carreau non-Newtonian model. Simulation results show that implantation of LVAD pump imparts major influence on the hemodynamics of the heart; it also provides a cardiac output of 4.87 L/min even at the diastolic phase. Furthermore, post LVAD implantation, approximately eight times more wall shear stress, is noticed at the aorta during the ventricular systole. In particular, major changes in the fluidics are observed inside the aortic region. A possibility of flow stagnation is noticed near the aortic root during the diastolic phase due to the bisection of incoming bloodstreams from the outflow graft. The flow characteristics of the LVAD pump are also observed to be significantly different from the idealized simulations (idealized tubular inlet situation). The observation of this study can help in understanding post-implant critical hemodynamic issues due to pump performance and its subsequent impact on the heart. A simulation approach-based study has been performed to investigate the influence of LVAD on the hemodynamics of a heart. A 3D computational model of a patient-specific heart has been created from CT scan datasets for diastole and systole phases (a). An axial flow blood pump has been implanted computationally into the left heart (b). The implanted blood pump enhances the cardiac output and elevates shear generation (c) and (d).


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Aorta , Simulação por Computador , Diástole , Insuficiência Cardíaca/terapia , Hemodinâmica/fisiologia , Humanos
13.
ACS Appl Bio Mater ; 5(5): 2389-2402, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35452214

RESUMO

Glucose oxidase (GOx)-induced cancer starvation has recently emerged for halting the abnormal proliferation of triple-negative breast cancer (TNBC). However, monotherapy with GOx or a conventional chemotherapeutic displays suboptimal efficacy in eliminating tumors and poses impending risks to healthy tissues. To augment therapeutic efficacy and tumor selectivity, folic acid (FA)-functionalized carbon dots (CDs) embedded with GOx and paclitaxel (PTX) [FA-CD-(PTX-GOx)] was developed that showed the efficient killing of TNBC, MDA-MB-468 cells over noncancerous HEK 293 cells through synergistic effects of cancer starvation-induced oxidative stress and chemotherapy. The cargo-laden FA-CD complex resulted in a 4-8 fold increase in cancer cell death at 60 µg/mL when compared to standalone therapy with the native compounds and individually loaded cargo on FA-CD. This improved cancer cell killing efficacy of the FA-CD-(PTX-GOx) complex could be endorsed by folate receptor (FR)-mediated target-specific cellular internalization of the FA-CD complex. The antitumorigenic efficacy of the FA-CD-(PTX-GOx) complex was further validated in a three-dimensional (3D) breast tumor spheroid model. A significant 4.5-fold reduction in spheroid dimension along with antiproliferation was observed with time up to 72 h following exposure to the FA-CD-(PTX-GOx) complex. This antitumorigenic potential of FA-CD-(PTX-GOx) could be attributed to the enhanced intratumoral reactive oxygen species generation following glucose depletion by GOx that has been facilitated by the chemotherapeutic efficacy of PTX resulting in the efficient killing of cancer cells. The present study provides a novel strategy of FR-mediated fluorescent CD-enabled combined formulation of GOx and PTX for the target-specific superior killing of TNBC cells in the synergism of glucose starvation with chemotherapy.


Assuntos
Paclitaxel , Neoplasias de Mama Triplo Negativas , Carbono/farmacologia , Linhagem Celular Tumoral , Ácido Fólico/farmacologia , Glucose , Glucose Oxidase , Células HEK293 , Humanos , Paclitaxel/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
14.
Langmuir ; 38(11): 3480-3492, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35261245

RESUMO

Supramolecular materials that respond to external triggers are being extensively utilized in developing spatiotemporal control in biomedical applications ranging from drug delivery to diagnostics. The present article describes the development of self-assembled vesicles in 1:9 (v/v), tetrahydrofuran (THF)-water by naphthalimide-based azo moiety containing amphiphile (NI-Azo) where azo moiety would act as the stimuli-responsive junction. The self-assembly of NI-Azo took place through H-type of aggregation. Microscopic and spectroscopic analyses confirmed the formation of supramolecular vesicles with a dimension of 200-250 nm. Azo (-N═N-) moiety is known to get reduced to amine derivatives in the presence of the azoreductase enzyme, which is overexpressed in the hypoxic microenvironment. The absorbance intensity of this characteristic azo (-N═N-) moiety of NI-Azo (1:9 (v/v), THF-water) at 458 nm got diminished in the presence of both extracellular and intracellular bacterial azoreductase extracted from Escherichia coli bacteria. The same observation was noted in the presence of sodium dithionite (mimic of azoreductase), indicating that azoreductase/sodium dithionite induced azo bond cleavage of NI-Azo, which was confirmed by matrix-assisted laser desorption ionization time-of-flight spectrometric data of the corresponding aromatic amine fragments. The anticancer drug, curcumin, was encapsulated inside NI-Azo vesicles that successfully killed B16F10 cells (cancer cells) in CoCl2-induced hypoxic environment owing to the azoreductase-responsive release of drug. The cancer cell killing efficiency by curcumin-loaded NI-Azo vesicles in the hypoxic condition was 2.15-fold higher than that of the normoxic environment and 2.4-fold higher compared to that of native curcumin in the hypoxic condition. Notably, cancer cell killing efficiency of curcumin-loaded NI-Azo vesicles was 4.5- and 1.9-fold higher than that of noncancerous NIH3T3 cells in normoxic and hypoxic environments, respectively. Cell killing was found to be primarily through the early apoptotic pathway.


Assuntos
Curcumina , Naftalimidas , Aminas , Animais , Compostos Azo/química , Curcumina/farmacologia , Ditionita , Hipóxia , Camundongos , Células NIH 3T3 , Água
15.
Anesth Analg ; 134(5): 1010-1020, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35027515

RESUMO

BACKGROUND: Different goals have guided goal-directed therapy (GDT). Protocols aiming for central venous-to-arterial carbon dioxide gap (DCO2) <6 mm Hg have improved organ function in septic shock. Evidence for use of DCO2 in the perioperative period is scarce. We aimed to determine if a GDT protocol using central venous saturation of oxygen (SCvo2) and DCO2 reduced organ dysfunction and intensive care unit (ICU) stay in American Society of Anesthesiologist (ASA) I and II patients undergoing major surgeries compared to pragmatic goal-directed care. METHODS: One hundred patients were randomized. Arterial and venous blood-gas values were recorded every 2 hours perioperatively for all patients. Intervention group (GrI) with access to both values was managed per protocol based on DCO2 and SCvo2. Dobutamine infusion 3 to 5 µg/kg/min started if DCO2 >6 mm Hg after correcting all macrocirculatory end points. Control group (GrC) had access only to arterial-gas values and managed per "conventional" goals without DCO2 or SCvo2. Patients were followed for 48 hours after surgery. Organ dysfunction, sequential organ failure assessment (SOFA) scores-primary outcome, length of stay in ICU, and duration of postoperative mechanical ventilation and hospital stay were recorded. The patient, surgeons, ICU team, and analyzer were blinded to group allocation. RESULTS: The groups (44 each) did not significantly differ with respect to baseline characteristics. Perioperative fluids, blood products, and vasopressors used did not significantly differ. The GrI had less organ dysfunction although not significant (79% vs 66%; P = .2). Length of ICU stay in the GrI was significantly less (1.52; standard deviation [SD], 0.82 vs 2.18; SD, 1.08 days; P = .002). Mechanical ventilation duration (0.9 days in intervention versus 0.6 days in control; P = .06) and length of hospital stay did not significantly differ between the groups. Perioperative DCO2 (5.8 vs 8.4 mm Hg; P < .001) and SCvo2 (73.5 vs 68.4 mm Hg; P < .001) were significantly better in the GrI. CONCLUSIONS: GDT guided by DCO2 did not improve organ function in our cohort. It resulted in greater use of dobutamine, improved tissue oxygen parameters, and decreased length of ICU stay. More evidence is needed for the routine use of DCO2 in sicker patients. In the absence of cardiac output monitors, it may be a readily available, less-expensive, and underutilized parameter for major surgical procedures.


Assuntos
Dióxido de Carbono , Objetivos , Dobutamina , Hemodinâmica , Humanos , Insuficiência de Múltiplos Órgãos , Oxigênio
17.
Soft Matter ; 17(8): 2170-2180, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33448273

RESUMO

The precise control of supramolecular self-assembly is gaining utmost interest for the demanding applications of manifested nano-architecture across the scientific domain. This study delineates the morphological transformation of naphthalene diimide (NDI) derived amphiphiles with varying water content in dimethyl sulfoxide (DMSO) and the selective sensing of lipase using its aggregation-induced emission (AIE) properties. To this end, NDI-based, benzyl alcohol protected alkyl chain (C1, C5, and C10) linked amphiphilic molecules (NDI-1,2,3) were synthesized. Among the synthesized amphiphiles, benzyl ester linked C5 tailored naphthalene diimide (NDI-2) exhibited AIE with an emission maximum at 490 nm in a DMSO-water binary solvent system from fw = 30% and above water content. The fibrous morphology of NDI-2 at fw = 30% got gradually transformed to spherical aggregated particles along with steady increment in the emission intensity upon increasing the amount of water in DMSO. At fw = 99% water in DMSO, complete transformation to fluorescent organic nanoparticles (FONPs) was observed. Microscopic and spectroscopic techniques demonstrated the solvent driven morphological transformation and the AIE property of NDI-2. Moreover, this AIE of NDI-2 FONPs was employed in the selective turn-off sensing of lipase against many other enzymes including esterase, through hydrolysis of a benzyl ester linkage with a limit of detection 10.0 ± 0.8 µg L-1. The NDI-2 FONP also exhibited its lipase sensing efficiency in vitro using a human serum sample.


Assuntos
Imidas , Lipase , Nanopartículas , Naftalenos , Humanos , Solventes
18.
Artif Organs ; 45(7): 665-681, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33434332

RESUMO

Continuous-flow left ventricular assist devices (LVADs) have gained tremendous acceptance for the treatment of end-stage heart failure patients. Among different versions, axial flow and centrifugal flow LVADs have shown remarkable potential for clinical implants. It is also very crucial to know which device serves its purpose better to treat heart failure patients. A thorough comparison of axial and centrifugal LVADs, which may guide doctors in deciding before the implant, still lacks in the literature. In this work, an assessment of axial and centrifugal LVADs has been made to suggest a better device by comparing their engineering, clinical, and technological development of design aspects. Hydrodynamic and hemodynamic aspects for both types of pumps are discussed along with their biocompatibility, bearing types, and sizes. It has been observed numerically that centrifugal LVADs perform better over axial LVADs in every engineering aspect like higher hydraulic efficiency, better characteristics curve, lesser power intake, and also lesser blood damage. However, the clinical outcomes suggest that centrifugal LVADs experience higher events of infections, renal, and respiratory dysfunction. In contrast, axial LVADs encountered higher bleeding and cardiac arrhythmia. Moreover, recent technological developments suggested that magnetic type bearings along with biocompatible coating improve the life of LVADs.


Assuntos
Coração Auxiliar , Centrifugação , Desenho de Equipamento , Hemodinâmica , Humanos , Hidrodinâmica
19.
IEEE Rev Biomed Eng ; 14: 327-341, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32746370

RESUMO

Blood flow in the human vascular system is a complex to understand example of fluid dynamics in a closed conduit. Any irregularities in the hemodynamics may lead to lethal cardiovascular disease like heart attack, heart failure and ischemia. Numerical simulation of hemodynamics in the blood vessel can facilitate a thorough understanding of blood flow and its interaction with the adjacent vessel wall. A good simulation approach for blood flow can be helpful in early prediction and diagnosis of the mentioned disease. The simulation outcomes may also provide decision support for surgical planning and medical implants. This study reports an extensive review of various approaches adopted to analyze the influence of blood rheological characteristics in a different class of blood vessels. In particular, emphasis was given on the identification of best possible rheological model to effectively solve the hemodynamics inside different blood vessels. The performance capability of different rheological models was discussed for different classes and conditions of vessels and the best/poor performing models are listed out. The Carreau, Casson and generalized power-law models were appeared to be superior for solving the blood flow at all shear rates. In contrast, power law, Walburn-Scheck and Herchel-Bulkley model lacks behind in the purpose.


Assuntos
Vasos Sanguíneos/fisiologia , Hemorreologia/fisiologia , Modelos Cardiovasculares , Circulação Sanguínea/fisiologia , Viscosidade Sanguínea/fisiologia , Simulação por Computador , Humanos , Masculino
20.
J Mater Chem B ; 9(2): 494-507, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33300911

RESUMO

Fluorescent organic nanoparticles (FONPs) have attracted considerable attention as a practical and effective platform for sensing and imaging applications. The present article delineates the fabrication of FONPs derived from the naphthalimide based histidine appended amphiphile, NID. The self-assembly of NID in 99 vol% water in DMSO led to the formation of FONPs through J-type aggregation. Aggregation-induced emission (AIE) was observed due to the pre-associated excimer of NID with bluish green emission at 470 nm along with intramolecular charge transfer (ICT). The emission of NID FONPs was utilized for selective sensing of Fe3+ and bioimaging of Fe3+ inside mammalian cells. The fluorescence intensity of the FONPs was quenched with the gradual addition of Fe3+ due to the formation of a 1 : 1 stoichiometric complex with the histidine residue of NID. The morphology of the FONPs transformed from spherical to spindle upon the complex formation of NID with Fe3+. The limit of detection (LOD) of this AIE based turn-off chemosensor for Fe3+ was found to be 12.5 ± 1.2 µM having high selectivity over other metal ions. On the basis of the very low cytotoxicity and selective sensing of Fe3+, NID FONPs were successfully employed for bioimaging of Fe3+ ions through fluorescence quenching within mammalian cells (NIH3T3, B16F10). Considering the varying oxidative stress inside different cells, NID FONPs were used for detecting Fe2+ to Fe3+ redox state transition selectively inside cancer cells (B16F10) in comparison to non-cancerous cells (NIH3T3). Selective sensing of cancer cells was substantiated by co-culture experiment and flow cytometry. Hence, NID FONPs can be a selective diagnostic probe for cancer cells owing to their higher H2O2 content.


Assuntos
Ferro/química , Nanopartículas/química , Naftalimidas/química , Animais , Modelos Animais de Doenças , Humanos , Camundongos
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