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1.
Environ Sci Pollut Res Int ; 31(11): 16735-16745, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38326682

RESUMEN

Sustainable mobility options such as electric vehicles (EVs) have the potential to improve the quality of life for Americans as well as those in other countries, as they can enhance the quality of the air we breathe, while reducing greenhouse gas emissions, fossil fuel consumption, and the adverse impacts of global warming. Despite their many benefits, however, the demand for EVs remains low. Therefore, this study aims to identify the barriers that affect the widespread EV adoption in the United States. Seventeen barriers were identified from the literature, and a questionnaire survey was designed and distributed to potential consumers of EVs. The survey yielded 733 responses, and various statistical tests like cluster analysis and chi-squared tests were performed. The results revealed that the high purchase price of the vehicle, high battery replacement cost, and the lack of public infrastructures for charging them were the primary concerns. The results also revealed that middle-aged men with high education and income are more enthusiastic about adopting EVs. The results presented in this study indicate a range of developments that different stakeholders could implement. To surmount the economic barriers to EV adoption, policymakers should strengthen incentives countrywide, and automakers should introduce more affordable EVs to the market. To overcome the challenges associated with charging, it is necessary to make investments in rapid charging infrastructure along the primary toll routes.


Asunto(s)
Gases de Efecto Invernadero , Emisiones de Vehículos , Persona de Mediana Edad , Estados Unidos , Humanos , Emisiones de Vehículos/análisis , Texas , Calidad de Vida , Motivación , Vehículos a Motor
2.
Nanotechnology ; 34(38)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37336192

RESUMEN

Molecular thin films, such as self-assembled monolayers (SAMs), offer the possibility of translating the optimised thermophysical and electrical properties of high-Seebeck-coefficient single molecules to scalable device architectures. However, for many scanning probe-based approaches attempting to characterise such SAMs, there remains a significant challenge in recovering single-molecule equivalent values from large-area films due to the intrinsic uncertainty of the probe-sample contact area coupled with film damage caused by contact forces. Here we report a new reproducible non-destructive method for probing the electrical and thermoelectric (TE) properties of small assemblies (10-103) of thiol-terminated molecules arranged within a SAM on a gold surface, and demonstrate the successful and reproducible measurements of the equivalent single-molecule electrical conductivity and Seebeck values. We have used a modified thermal-electric force microscopy approach, which integrates the conductive-probe atomic force microscope, a sample positioned on a temperature-controlled heater, and a probe-sample peak-force feedback that interactively limits the normal force across the molecular junctions. The experimental results are interpreted by density functional theory calculations allowing quantification the electrical quantum transport properties of both single molecules and small clusters of molecules. Significantly, this approach effectively eliminates lateral forces between probe and sample, minimising disruption to the SAM while enabling simultaneous mapping of the SAMs nanomechanical properties, as well as electrical and/or TE response, thereby allowing correlation of the film properties.


Asunto(s)
Oro , Nanotecnología , Propiedades de Superficie , Microscopía de Fuerza Atómica/métodos , Conductividad Eléctrica
3.
J Neurosci ; 43(22): 4062-4074, 2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-37127363

RESUMEN

Navigation requires steering and propulsion, but how spinal circuits contribute to direction control during ongoing locomotion is not well understood. Here, we use drifting vertical gratings to evoke directed "fictive" swimming in intact but immobilized larval zebrafish while performing electrophysiological recordings from spinal neurons. We find that directed swimming involves unilateral changes in the duration of motor output and increased recruitment of motor neurons, without impacting the timing of spiking across or along the body. Voltage-clamp recordings from motor neurons reveal increases in phasic excitation and inhibition on the side of the turn. Current-clamp recordings from premotor interneurons that provide phasic excitation or inhibition reveal two types of recruitment patterns. A direction-agnostic pattern with balanced recruitment on the turning and nonturning sides is primarily observed in excitatory V2a neurons with ipsilateral descending axons, while a direction-sensitive pattern with preferential recruitment on the turning side is dominated by V2a neurons with ipsilateral bifurcating axons. Inhibitory V1 neurons are also divided into direction-sensitive and direction-agnostic subsets, although there is no detectable morphologic distinction. Our findings support the modular control of steering and propulsion by spinal premotor circuits, where recruitment of distinct subsets of excitatory and inhibitory interneurons provide adjustments in direction while on the move.SIGNIFICANCE STATEMENT Spinal circuits play an essential role in coordinating movements during locomotion. However, it is unclear how they participate in adjustments in direction that do not interfere with coordination. Here we have developed a system using larval zebrafish that allows us to directly record electrical signals from spinal neurons during "fictive" swimming guided by visual cues. We find there are subsets of spinal interneurons for coordination and others that drive unilateral asymmetries in motor neuron recruitment for direction control. Our findings suggest a modular organization of spinal premotor circuits that enables uninterrupted adjustments in direction during ongoing locomotion.


Asunto(s)
Locomoción , Pez Cebra , Animales , Pez Cebra/fisiología , Larva/fisiología , Locomoción/fisiología , Neuronas Motoras/fisiología , Natación/fisiología , Interneuronas/fisiología , Médula Espinal/fisiología
4.
Nanoscale Adv ; 5(8): 2299-2306, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-37056609

RESUMEN

The synthesis of a family of alkanethiol molecules with planar aromatic head groups, designed to anchor molecules effectively to graphene electrodes, is reported. Characterisation of self-assembled monolayers of these molecules on a gold surface via conductive atomic force microscopy shows that when an aromatic head group is present, the conductance G graphene obtained using a graphene coated probe is higher than the conductance G Pt obtained using a platinum (Pt) probe. For Pt probe and graphene probe junctions, the tunnelling decay constant of benzyl ether derivatives with an alkanethiol molecular backbone is determined as ß = 5.6 nm-1 and 3.5 nm-1, respectively. The conductance ratio G graphene/G Pt increases as the number of rings present in the aromatic head unit, n, increases. However, as the number of rings increases, the conductance path length increases because the planar head groups lie at an angle to the plane of the electrodes. This means that overall conductance decreases as n increases. Density functional theory-based charge transport calculations support these experimental findings. This study confirms that planar aromatic head groups can function as effective anchoring units for graphene electrodes in large area molecular junctions. However, the results also indicate that the size and geometry of these head groups must be considered in order to produce effective molecular designs.

5.
J Am Pharm Assoc (2003) ; 62(6): 1761-1764, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36115758

RESUMEN

The coronavirus disease 2019 pandemic has escalated the ongoing problem of critical medication shortages, which has serious implications for the health of our patients. Currently, active pharmaceutical ingredients (APIs) are synthesized in large-scale batch operations and shipped to drug product manufacturers, where they are produced on a large scale at centralized facilities. In the centralized drug manufacturing process, the formulation components, operations, and packaging are structured to favor long-term storage and shipment of resultant medicines to the point of care, making this process vulnerable to supply chain disruptions. We propose a rethinking of the drug manufacturing paradigm with an upgraded pharmaceutical compounding-based manufacturing paradigm. This paradigm will be based on integration of continuous manufacturing of APIs and manufacturing of medicines at the point of care with application of machine learning, artificial intelligence, and 3-dimensional printing. This paradigm will support implementation of precision medicine and customization according to patients' needs. The new model of drug manufacturing will be less dependent on the supply chain while ensuring availability of medicines in a cost-effective manner.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Farmacia , Humanos , Tecnología Farmacéutica/métodos , Industria Farmacéutica , Inteligencia Artificial , Preparaciones Farmacéuticas
6.
Epidemics ; 40: 100599, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35763978

RESUMEN

Around the world, disease surveillance and mathematical modeling have been vital tools for government responses to the COVID-19 pandemic. In the face of a volatile crisis, modeling efforts have had to evolve over time in proposing policies for pandemic interventions. In this paper, we document how mathematical modeling contributed to guiding the trajectory of pandemic policies in the Philippines. We present the mathematical specifications of the FASSSTER COVID-19 compartmental model at the core of the FASSSTER platform, the scenario-based disease modeling and analytics toolkit used in the Philippines. We trace how evolving epidemiological analysis at the national, regional, and provincial levels guided government actions; and conversely, how emergent policy questions prompted subsequent model development and analysis. At various stages of the pandemic, simulated outputs of the FASSSTER model strongly correlated with empirically observed case trajectories (r=94%-99%, p<.001). Model simulations were subsequently utilized to predict the outcomes of proposed interventions, including the calibration of community quarantine levels alongside improvements to healthcare system capacity. This study shows how the FASSSTER model enabled the implementation of a phased approach toward gradually expanding economic activity while limiting the spread of COVID-19. This work points to the importance of locally contextualized, flexible, and responsive mathematical modeling, as applied to pandemic intelligence and for data-driven policy-making in general.


Asunto(s)
COVID-19 , COVID-19/epidemiología , Humanos , Pandemias , Filipinas/epidemiología , Políticas , Cuarentena
7.
Traffic Inj Prev ; 23(6): 333-338, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35639637

RESUMEN

OBJECTIVES: On-demand ridesharing services are suggested to provide several benefits, such as improving accessibility and mobility, reducing drive-alone trips and greenhouse gas emissions. However, the impacts of these services on traffic crashes are not completely clear. This paper investigates the availability of Via- an on-demand ridesharing service in Arlington, TX, to identify the effects of this service on traffic crashes. We hypothesize that the launch of Via would result in more shared rides, fewer drive-alone trips and fewer traffic crashes. METHODS: We implement an Interrupted Time Series Analysis (ITSA) approach to study the impact of Via service availability on traffic crashes using weekly counts of all traffic crashes, the number of injuries, and serious injuries that occurred in Arlington from 2014 to 2021. RESULTS: The results show a statistically significant reduction in the weekly number of total crashes and total injuries but do not show any significant impact on the number of serious injuries. Shared Autonomous Vehicles have the potential to reduce traffic crashes caused by driver's fault. CONCLUSIONS: This study reveals the potential impacts ridesharing services can have on traffic crashes and injuries in a mid-sized city. The results of this study can help decision and policymakers to understand the full potential of ridesharing services that can contribute to making relevant decisions toward creating sustainable and safer transportation systems in cities.


Asunto(s)
Accidentes de Tránsito , Proyectos de Investigación , Accidentes de Tránsito/prevención & control , Ciudades , Humanos , Análisis de Series de Tiempo Interrumpido , Factores de Tiempo
8.
Curr Biol ; 31(17): R1035-R1037, 2021 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-34520710

RESUMEN

Locomotion requires the segmental coordination of activity along the body. A new study in zebrafish reveals that spinal inhibitory interneurons are wired to execute different functions depending on whether their targets are nearby or further away.


Asunto(s)
Médula Espinal , Pez Cebra , Animales , Interneuronas , Locomoción , Sensación
9.
Infect Dis Poverty ; 10(1): 107, 2021 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-34372929

RESUMEN

BACKGROUND: Around the world, controlling the COVID-19 pandemic requires national coordination of multiple intervention strategies. As vaccinations are globally introduced into the repertoire of available interventions, it is important to consider how changes in the local supply of vaccines, including delays in administration, may be addressed through existing policy levers. This study aims to identify the optimal level of interventions for COVID-19 from 2021 to 2022 in the Philippines, which as a developing country is particularly vulnerable to shifting assumptions around vaccine availability. Furthermore, we explore optimal strategies in scenarios featuring delays in vaccine administration, expansions of vaccine supply, and limited combinations of interventions. METHODS: Embedding our work within the local policy landscape, we apply optimal control theory to the compartmental model of COVID-19 used by the Philippine government's pandemic surveillance platform and introduce four controls: (a) precautionary measures like community quarantines, (b) detection of asymptomatic cases, (c) detection of symptomatic cases, and (d) vaccinations. The model is fitted to local data using an L-BFGS minimization procedure. Optimality conditions are identified using Pontryagin's minimum principle and numerically solved using the forward-backward sweep method. RESULTS: Simulation results indicate that early and effective implementation of both precautionary measures and symptomatic case detection is vital for averting the most infections at an efficient cost, resulting in [Formula: see text] reduction of infections compared to the no-control scenario. Expanding vaccine administration capacity to 440,000 full immunizations daily will reduce the overall cost of optimal strategy by [Formula: see text], while allowing for a faster relaxation of more resource-intensive interventions. Furthermore, delays in vaccine administration require compensatory increases in the remaining policy levers to maintain a minimal number of infections. For example, delaying the vaccines by 180 days (6 months) will result in an [Formula: see text] increase in the cost of the optimal strategy. CONCLUSION: We conclude with practical insights regarding policy priorities particularly attuned to the Philippine context, but also applicable more broadly in similar resource-constrained settings. We emphasize three key takeaways of (a) sustaining efficient case detection, isolation, and treatment strategies; (b) expanding not only vaccine supply but also the capacity to administer them, and; (c) timeliness and consistency in adopting policy measures.


Asunto(s)
Vacunas contra la COVID-19/provisión & distribución , COVID-19/prevención & control , Algoritmos , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/transmisión , Vacunas contra la COVID-19/uso terapéutico , Países en Desarrollo , Humanos , Modelos Estadísticos , Filipinas/epidemiología , Vigilancia de la Población
10.
Am J Surg ; 221(6): 1164-1166, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33840447

RESUMEN

BACKGROUND: Wire localized breast biopsy (WLB) is the most commonly performed procedure for the removal of non-palpable breast cancer. It is associated with patient discomfort and high re-excision rates. Intraoperative ultrasound (IOUS) is an alternative technique that may improve patient experience and have lower re-excision rates. METHODS: A retrospective, single surgeon experience with IOUS is compared with WLB. Case matching for variables known to impact re-excision rates is performed. Fisher's exact test was performed for categorical variables, and a T-test for continuous variables. RESULTS: 28 patients underwent IOUS and WLB. Re-excision rates were the same in patients undergoing IOUS and WLB (10.7% vs 0%; p = 0.24). The calculated resection ratio was lower with IOUS than WLB (2.99 vs 3.46; p = 0.37), but did not reach statistical significance. CONCLUSION: In selected patients, intra-operative ultrasound can be performed with a favourable re-excision rate, and comparable amounts of tissue compared to wire localized breast biopsy.


Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía Segmentaria/métodos , Ultrasonografía Intervencional , Biopsia , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Ultrasonografía Intervencional/métodos
11.
J Control Release ; 328: 846-858, 2020 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-33166606

RESUMEN

The use of intraperitoneal administration of nanoparticles has been reported to facilitate higher concentrations of nanoparticles in metastatic peritoneal tumors. While this strategy is appealing for limiting systemic exposure of nanocarrier delivered toxic cargoes and increasing nanoparticle concentrations in avascular peritoneal tumors, little is known about the mechanism of nanoparticle accumulation on tumor tissues and currently, no nanoparticle-based product has been approved for intraperitoneal delivery. Here, we investigated the nanoparticle-specific characteristics that led to increased peritoneal tumor accumulation using MCM-41 type mesoporous silica nanoparticles as our model system. We also investigated the components of the peritoneal tumor stroma that facilitated nanoparticle-tumor interaction. The tumor extracellular matrix is the main factor driving these interactions, specifically the interaction of nanoparticles with collagen. Upon disruption of the collagen matrix, nanoparticle accumulation was reduced by 50%. It is also notable that the incorporation of targeting ligands did not increase overall tumor accumulation in vivo while it significantly increased nanoparticle accumulation in vitro. The use of other particle chemistries did not grossly affect the tumor targetability, but additional concerns arose when those tested particles exhibited significant systemic exposure. Mesoporous silica nanoparticles are advantageous for intraperitoneal administration for the treatment of peritoneal metastasis due to their physical stability, tumor targetability, strong interaction with the collagen matrix, and extended peritoneal residence time. Maximizing nanoparticle interaction with the tumor extracellular matrix is critical for developing strategies to deliver emerging therapeutics for peritoneal cancer treatment using nanocarriers.


Asunto(s)
Nanopartículas , Neoplasias Peritoneales , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Humanos , Inyecciones Intraperitoneales , Neoplasias Peritoneales/tratamiento farmacológico , Porosidad , Dióxido de Silicio
12.
Int J Pharm ; 590: 119938, 2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33011250

RESUMEN

The current investigation was carried out to identify appropriate parameters for measuring the in vitro release of tobramycin (TOB) ophthalmic ointments and to evaluate the feasibility of in vitro release testing methods to assess the product performance. Drug release was assessed using USP dissolution apparatus IV and a modified USP dissolution apparatus I with simulated tear solution (STS) as the dissolution medium. The study variables included temperature, membrane material, source and pore size. The results demonstrated a significant influence of the membrane source and pore size on the release of TOB from the ointments. A dissolution medium temperature of 40 °C was found to be appropriate for the release studies. Both of the apparatuses were able to discriminate between the release profiles of ointments with different physicochemical/rheological properties. Maximum release rate of TOB was observed in the first hour which followed a logarithmic time dependent release. The correlation between the release rates/amounts and yield stress of the ointments was observed in both the dissolution apparatuses. These results support a rational approach to guide the in vitro release testing of TOB ophthalmic ointments.


Asunto(s)
Tobramicina , Administración Oftálmica , Liberación de Fármacos , Pomadas , Reología , Solubilidad
13.
ISME J ; 14(8): 2090-2104, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32398661

RESUMEN

Habitual supplementation of fish oil is thought to provide benefits to the developing infant; however, the effects on infant microbial establishment and immune development are unknown. A 6-month observational cohort study was conducted where 47 out of 91 women self-administered dietary fish oil during breastfeeding. Infant stool and mothers' breast milk were collected each month over 6 months. Gas chromatography was used to quantify breast milk fatty acids and high-throughput sequencing was used to assess the infant fecal microbiota. Immune markers and parent-reported questionnaires were used to assess infant immunity and health up to 2 years. Our results reveal that fish oil supplementation decreased secretory immunoglobulin A and increased IL-10 production in lactating women along with increased breast milk eicosapentaenoic acid, and this corresponded to increased abundances of fecal Bifidobacterium and Lactobacillus spp. in their infants. Docosahexaenoic acid levels in breast milk aligned with decreases in infant gut bacterial richness and the predicted bacterial phenotypes suggested that fish oil lowers commensal traits involved in pathogen colonization resistance. Despite this, there were no differences in sickness incidence in toddlers. This study revealed that fish oil associates with decreases in breast milk defensive inflammatory responses and corresponds with infant fecal microbiota with anti-inflammatory potential.


Asunto(s)
Aceites de Pescado , Microbioma Gastrointestinal , Preescolar , Suplementos Dietéticos , Femenino , Humanos , Lactante , Inflamación , Lactancia , Leche Humana
14.
Am J Surg ; 219(5): 816-822, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31053234

RESUMEN

BACKGROUND: Patient reported outcomes (PROs) are an important addition to oncologic breast surgical care. The majority of BREAST-Q PRO literature has been focused on mastectomy with reconstruction (MR), with a paucity of information on more common surgical approaches in practice namely, breast conserving therapy (BCT) and mastectomy (M). This information will help inform patients around decision-making regarding surgical options. METHODS: 837 women underwent surgery between 2010 and 2012, and were later invited to complete the postoperative BREAST-Q module specific to their most recent surgery. Multivariate analysis was performed to compare BREAST-Q subscale scores between each of the three surgical cohorts. RESULTS: 257 women participated (161 BCT, 84 M, 12 MR). Patients undergoing BCT reported scores in the satisfaction with breasts domain 8 points higher than those undergoing mastectomy (p = 0.046). BCT also reported higher scores than mastectomy in the areas of psychosocial well being (12 points higher) as well as sexual well-being (17 points higher) (p = 0.0006). CONCLUSIONS: BCT appears superior to mastectomy in terms of satisfaction with breasts, sexual well-being and now psychosocial well-being. Overall, BCT is associated with excellent patient reported outcomes.


Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía Segmentaria/psicología , Mastectomía/psicología , Medición de Resultados Informados por el Paciente , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Satisfacción del Paciente , Encuestas y Cuestionarios
15.
J Am Assoc Nurse Pract ; 32(10): 652-659, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31855871

RESUMEN

BACKGROUND: Schools of nursing are challenged with recruiting and retaining nurse practitioner (NP) clinical faculty in a job market where the few qualified candidates have competing professional opportunities. The role transition from clinician to clinical faculty is stressful, and many faculty have unmet needs for support. OBJECTIVES: This article will identify strategies universities can implement to increase retention in the faculty role by facilitating the transition from clinician to NP clinical faculty. DATA SOURCES: Articles were identified from the following databases: PubMed, Embase, PsychInfo, CINAHL Plus, Web of Science, Google Scholar, and Cochrane Library. CONCLUSIONS: The transition from clinician to the NP role can be very difficult. New faculty experience culture shock and concerns about maintenance of clinical practice. Orientation, peer support, and mentoring can mitigate the challenges and support the transition. IMPLICATIONS FOR PRACTICE: Schools of nursing can facilitate the transition from clinician to NP clinical faculty by developing an onboarding program that integrates mentoring, orientation, and ongoing support.


Asunto(s)
Gestión del Cambio , Docentes de Enfermería/psicología , Enfermeras Practicantes/educación , Enfermeras Practicantes/psicología , Rol de la Enfermera , Enfermeras y Enfermeros/psicología , Humanos
16.
Angew Chem Int Ed Engl ; 59(2): 882-889, 2020 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-31714641

RESUMEN

As the field of molecular-scale electronics matures and the prospect of devices incorporating molecular wires becomes more feasible, it is necessary to progress from the simple anchor groups used in fundamental conductance studies to more elaborate anchors designed with device stability in mind. This study presents a series of oligo(phenylene-ethynylene) wires with one tetrapodal anchor and a phenyl or pyridyl head group. The new anchors are designed to bind strongly to gold surfaces without disrupting the conductance pathway of the wires. Conductive probe atomic force microscopy (cAFM) was used to determine the conductance of self-assembled monolayers (SAMs) of the wires in Au-SAM-Pt and Au-SAM-graphene junctions, from which the conductance per molecule was derived. For tolane-type wires, mean conductances per molecule of up to 10-4.37  G0 (Pt) and 10-3.78  G0 (graphene) were measured, despite limited electronic coupling to the Au electrode, demonstrating the potential of this approach. Computational studies of the surface binding geometry and transport properties rationalise and support the experimental results.

17.
Curr Opin Physiol ; 8: 188-192, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31667448

RESUMEN

In all bilaterally symmetric animals, movements across the body are coordinated by interneurons that traverse the midline. Recent work is beginning to tease apart the functional complexity of interneurons labeled by the homeodomain transcription factor even-skipped, which provide a phylogenetically-conserved source of commissural excitation during locomotion in both vertebrates and invertebrates. Here we review recent studies of the roles of even-skipped neurons during locomotion in flies (EL neurons), fishes, frogs, and mice (V0v neurons). Comparisons across species reveal commonalities, which include the functional organization of even-skipped circuits based on birth order, the link between increased muscular complexity and even-skipped neuron diversity, and the hierarchical organization of even-skipped circuits based on their control of escape versus exploratory movements. We discuss how stronger links between different species enable testable predictions to further the discovery of principles of locomotor network organization.

18.
Magn Reson Imaging ; 55: 140-144, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30321663

RESUMEN

OBJECTIVE: To determine if gadolinium (Gd) can be rechelated once released from Gd-based contrast agents (GBCAs) and deposited in vivo. Despite extensive research comparing GBCAs and GBCA formulations as well as the ongoing debate about their risks of deposition and the role of Gd release, it remains unknown if retained Gd can be eliminated by administering chelating agents. MATERIALS AND METHODS: Rats were injected intravenously with 10 doses of 1 mmol/kg gadodiamide and treated with intravenous Zn-DTPA (30 µmol/kg) concomitantly or 1, 4 or 8 h after GBCA administration (N = 3 rats per group). After euthanization, tissues were harvested three days after the last dose of gadodiamide and tissue Gd concentrations were assessed by ICP-MS. Additionally, a simulation of a single 0.1 mmol/kg gadopentetate dose with 30 µmol/kg DTPA given either concomitantly or within the first 24 h after GBCA was run; simulated tissue Gd concentrations were compared with those observed in rats to determine if simulated trends were accurate. RESULTS: Concomitant DTPA did not produce a significant reduction in Gd concentration in any organ for rats. There was a time-dependent trend in liver Gd reduction. The 1 h timepoint was associated with a non-significant increase in kidney, brain and femur Gd relative to untreated controls. There were no significant deviations from the model-predicted Gd changes. DISCUSSION: Both the simulation and rat study did not identify major benefits for chelation at the doses given, despite the simulation assuming all Gd deposited in tissues is unchelated. The potential redistribution in the rat study provide a compelling result that may impact the clinical relevance of further work investigating rechelation of Gd. Future work should further describe the three-dimensional dose-time-response relationship for preventing Gd deposition, and how that relates to long-term Gd toxicities.


Asunto(s)
Encéfalo/diagnóstico por imagen , Quelantes/administración & dosificación , Gadolinio DTPA/administración & dosificación , Gadolinio/administración & dosificación , Hígado/diagnóstico por imagen , Animales , Encéfalo/efectos de los fármacos , Medios de Contraste/administración & dosificación , Esquema de Medicación , Femenino , Procesamiento de Imagen Asistido por Computador , Hígado/efectos de los fármacos , Ácido Pentético/administración & dosificación , Ratas , Ratas Sprague-Dawley
19.
AAPS PharmSciTech ; 20(1): 8, 2018 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-30560428

RESUMEN

The present work investigated the physical and thermal characteristics of three polymorphic forms (namely, PF1, PF2, and PF3) of a diethyl ester analog of diethylenetriaminepentaacetic acid (C2E2) produced under varying conditions. The identity of each form of C2E2 was confirmed by 1H-NMR, 13C-NMR, and mass spectroscopy. The different polymorphic forms exhibited solubilities ranging from 40 to 150 mg/mL. Powder X-ray diffraction (PXRD) and electron microscopy confirmed that all three forms were crystalline, two of which being scaly, and the third being well-formed. Infrared and Raman spectroscopy revealed differences in the C = O bonding region while differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) showed widely different melting points with only one thermal event for each compound. The comparison of the melting points and heats of fusion show that the PF1 is monotropically related to both PF2 and PF3, while PF2 and PF3 are enantropically related. Our finding indicates that PF3 is the thermodynamically stable polymorph and will be used for in vitro and in vivo experiments.


Asunto(s)
Ácido Pentético/química , Administración Oral , Espectroscopía de Resonancia Magnética , Solubilidad , Termodinámica
20.
Pharm Res ; 35(9): 179, 2018 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-30046909

RESUMEN

PURPOSE: The main purpose of this study was to evaluate qualitative (Q1) and quantitative (Q2) equivalent oleaginous ophthalmic ointments of tobramycin (TOB) with different physicochemical properties and identify critical process/quality attributes using various in vitro methods of characterization. METHODS: Various sources of petrolatum and TOB, and two mixing methods were employed to generate Q1/Q2 equivalent ointments. Characterization studies included content uniformity, microscopy, modulated temperature differential scanning calorimetry (MTDSC), gas chromatography-mass spectrometry (GC/MS), thermogravimetric analysis (TGA) and rheology. RESULTS: The particle size distribution of TOB influenced the content uniformity of ointments. Differences in the MTDSC endothermic and exothermic peaks of TOB suggested the presence of different polymorphic forms. GC/MS revealed variations in the composition and distribution of linear and branched hydrocarbons of petrolatums. Differences were also observed in the TGA derivative weight loss peaks demonstrating differences in the composition of petrolatum that may be the source of the observed variations in the rheological parameters of the ointments. CONCLUSIONS: Source and composition of the petrolatum played a more critical role in determining the rheological properties compared to the method of preparation. Results demonstrated the impact of the source of TOB, excipients and manufacturing processes on the quality attributes of TOB ophthalmic ointments.


Asunto(s)
Antibacterianos/administración & dosificación , Tobramicina/administración & dosificación , Administración Oftálmica , Antibacterianos/química , Composición de Medicamentos , Pomadas , Tamaño de la Partícula , Vaselina/química , Reología , Tobramicina/química
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