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1.
Artigo em Inglês | MEDLINE | ID: mdl-39270670

RESUMO

Although plastic pollution and exposure to plastic-related compounds have received worldwide attention, health risks associated with micro- and nanoplastics (MNPs) are largely unknown. Emerging evidence suggests MNPs are present in human biofluids and tissue, including blood, breast milk, stool, lung tissue, and placenta; however, exposure assessment is limited and the extent of human exposure to MNPs is not well known. While there is a critical need to establish robust and scalable biomonitoring strategies to assess human exposure to MNPs and plastic-related chemicals, over 10,000 chemicals have been linked to plastic manufacturing with no existing standardized approaches to account for even a fraction of these exposures. This review provides an overview of the status of methods for measuring MNPs and associated plastic-related chemicals in humans, with a focus on approaches that could be adapted for population-wide biomonitoring and integration with biological response measures to develop hypotheses on potential health effects of plastic exposures. We also examine the exposure risks associated with the widespread use of chemical additives in plastics. Despite advancements in analytical techniques, there remains a pressing need for standardized measurement protocols and untargeted, high-throughput analysis methods to enable comprehensive MNP biomonitoring to identify key MNP exposures in human populations. This review aims to merge insights into the toxicological effects of MNPs and plastic additives with an evaluation of analytical challenges, advocating for enhanced research methods to fully assess, understand, and mitigate the public health implications of MNPs.

2.
Plant Cell ; 33(7): 2235-2257, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-33895820

RESUMO

Endosperm is an angiosperm innovation central to their reproduction whose development, and thus seed viability, is controlled by genomic imprinting, where expression from certain genes is parent-specific. Unsuccessful imprinting has been linked to failed inter-specific and inter-ploidy hybridization. Despite their importance in plant speciation, the underlying mechanisms behind these endosperm-based barriers remain poorly understood. Here, we describe one such barrier between diploid Mimulus guttatus and tetraploid Mimulus luteus. The two parents differ in endosperm DNA methylation, expression dynamics, and imprinted genes. Hybrid seeds suffer from underdeveloped endosperm, reducing viability, or arrested endosperm and seed abortion when M. guttatus or M. luteus is seed parent, respectively, and transgressive methylation and expression patterns emerge. The two inherited M. luteus subgenomes, genetically distinct but epigenetically similar, are expressionally dominant over the M. guttatus genome in hybrid embryos and especially their endosperm, where paternal imprints are perturbed. In aborted seeds, de novo methylation is inhibited, potentially owing to incompatible paternal instructions of imbalanced dosage from M. guttatus imprints. We suggest that diverged epigenetic/regulatory landscapes between parental genomes induce epigenetic repatterning and global shifts in expression, which, in endosperm, may uniquely facilitate incompatible interactions between divergent imprinting schemes, potentially driving rapid barriers.


Assuntos
Mimulus/metabolismo , Genoma de Planta/genética , Impressão Genômica/genética , Impressão Genômica/fisiologia , Hibridização Genética , Mimulus/genética , Sementes/genética , Sementes/metabolismo
3.
Inorg Chem ; 62(4): 1628-1635, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36650095

RESUMO

Significant oxide ion conductivity has previously been reported for the Ba3M'M″O8.5 family (M' = Nb5+, V5+; M″ = Mo6+, W6+) of cation-deficient hexagonal perovskite derivatives. These systems exhibit considerable structural disorder and competitive occupation of two distinct oxygen positions (O3 site and O2 site), enabling two-dimensional (2D) ionic conductivity within the ab plane of the structure; higher occupation of the tetrahedral O3 site vs the octahedral O2 site is known to be a major factor that promotes oxide ion conductivity. Previous chemical doping studies have shown that substitution of small amounts of the M' or M″ ions can result in significant changes to both the structure and ionic conductivity. Here, we report on the electrical and structural properties of the Ba3Nb1-xTaxMoO8.5 series (x = 0.00, 0.025, 0.050, 0.100). AC impedance measurements show that substitution of Nb5+ with Ta5+ leads to a significant increase in low-temperature (<500 °C) conductivity for x = 0.1. Analysis of neutron and X-ray diffraction (XRD) data confirms that there is a decrease in the M1O4/M1O6 ratio upon increasing x from 0 to 0.1 in Ba3Nb1-xTaxMoO8.5, which would usually coincide with a lowering in the conductivity. However, neutron diffraction results show that Ta doping causes an increase in the oxide ion conductivity as a result of longer M1-O3 bonds and increased polyhedral distortion.

4.
J Soc Work End Life Palliat Care ; 18(2): 160-176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35317703

RESUMO

The purpose of this study was to investigate responses to death at multiple levels within the assisted living (AL) system and to characterize the psychosocial impact of death on surviving residents. This study used secondary thematic analysis of multiple data sources collected as part of a larger quantitative-focused study with 21 ALs. Data sources included: (a) community documents, e.g., newsletters; (b) descriptive and reflective observational field notes; and (c) memos and key statements from interviews with residents (n = 18). Three themes emerged from the data: administrative memorialization practices, resident perceptions of staff communication related to death, and resident psychosocial responses to death. Surviving residents reported using both adaptive and avoidant strategies to cope with psychological responses to death; noting that grief responses extended to the loss of the deceased resident's family, friends, and pets. Residents also perceived staff-resident communication and community memorialization practices as incongruent with a "family-like" social climate. Findings highlight the potential utility of a multi-level approach to improving psychosocial aspects of end-of-life care and grief management by targeting AL administration, workforce, and individuals. Social workers are well-positioned to lead these types of psychosocial interventions but must contend with staffing barriers limiting clinical roles in AL.


Assuntos
Luto , Assistência Terminal , Comunicação , Amigos , Pesar , Humanos , Assistentes Sociais
5.
Inorg Chem ; 60(17): 13550-13556, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34405996

RESUMO

The hexagonal perovskite derivatives Ba3NbMoO8.5, Ba3NbWO8.5, and Ba3VWO8.5 have recently been reported to exhibit significant oxide ion conductivity. Here, we report the synthesis and crystal structure of the hexagonal perovskite derivative Ba3-xVMoO8.5-x. Rietveld refinement from neutron and X-ray diffraction data show that the cation vacancies are ordered on the M2 site, leading to a structure consisting of palmierite-like layers of M1Ox polyhedra separated by vacant octahedral layers. In contrast to other members of the Ba3M'M″O8.5 family, Ba3-xVMoO8.5-x is not stoichiometric and both barium and oxygen vacancies are present. Although synthesized in air at elevated temperatures, Ba3-xVMoO8.5-x is unstable at lower temperatures, as illustrated by the formation of BaCO3 and BaMoO4 by heat treatment in air at 400 °C. This precludes measurement of the electrical properties. However, bond-valence site energy (BVSE) calculations strongly suggest that oxide ion conductivity is present in Ba3-xVMoO8.5-x.

6.
Inorg Chem ; 60(1): 263-271, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33320647

RESUMO

We present a structural and magnetic study of two batches of polycrystalline LiNi0.8Mn0.1Co0.1O2 (commonly known as Li NMC 811), a Ni-rich Li ion battery cathode material, using elemental analysis, X-ray and neutron diffraction, magnetometry, and polarized neutron scattering measurements. We find that the samples, labeled S1 and S2, have the composition Li1-xNi0.9+x-yMnyCo0.1O2, with x = 0.025(2), y = 0.120(2) for S1 and x = 0.002(2), y = 0.094(2) for S2, corresponding to different concentrations of magnetic ions and excess Ni2+ in the Li+ layers. Both samples show a peak in the zero-field-cooled (ZFC) dc susceptibility at 8.0(2) K, but the temperature at which the ZFC and FC (field-cooled) curves deviate is substantially different: 64(2) K for S1 and 122(2) K for S2. The ac susceptibility measurements show that the transition for S1 shifts with frequency whereas no such shift is observed for S2 within the resolution of our measurements. Our results demonstrate the sample dependence of magnetic properties in Li NMC 811, consistent with previous reports on the parent material LiNiO2. We further establish that a combination of experimental techniques is necessary to accurately determine the chemical composition of next-generation battery materials with multiple cations.

7.
Clin Gerontol ; 44(4): 439-449, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33100187

RESUMO

OBJECTIVES: Research suggests a link between loneliness, depression, and anxiety. Multiple studies have examined treatment programs for loneliness; however, none have examined the efficacy of Cognitive Behavioral Therapy (CBT) for depression and anxiety in reducing loneliness. METHODS: Change in loneliness in sixty-two older adults (≥60 yrs; 65% female) who took part in a previously reported randomized controlled trial for the treatment of comorbid depression and anxiety was examined. Older adults were randomized to a 12-week group CBT or waitlist control condition. Participants who took part in CBT were followed-up three months later. RESULTS: Linear Mixed Model analyses indicated that after controlling for baseline cognition, depression, and anxiety, participants who completed CBT experienced a significant decrease in loneliness while the control group did not. This reduction was maintained at follow-up. CONCLUSIONS: CBT programs for depression and anxiety are likely to be effective at reducing loneliness. This may be due to shared underlying cognitive and behavioral mechanisms between loneliness, depression, and anxiety such as sensitivity to perceived threat and social withdrawal. Further research is needed to understand if specific loneliness interventions are more effective. CLINICAL IMPLICATIONS: CBT may be effective at reducing loneliness among older adults with depression and anxiety.


Assuntos
Terapia Cognitivo-Comportamental , Solidão , Idoso , Ansiedade/terapia , Transtornos de Ansiedade , Depressão/terapia , Feminino , Humanos , Masculino
9.
Plant Cell ; 29(9): 2150-2167, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28814644

RESUMO

Recent studies have shown that one of the parental subgenomes in ancient polyploids is generally more dominant, having retained more genes and being more highly expressed, a phenomenon termed subgenome dominance. The genomic features that determine how quickly and which subgenome dominates within a newly formed polyploid remain poorly understood. To investigate the rate of emergence of subgenome dominance, we examined gene expression, gene methylation, and transposable element (TE) methylation in a natural, <140-year-old allopolyploid (Mimulus peregrinus), a resynthesized interspecies triploid hybrid (M. robertsii), a resynthesized allopolyploid (M. peregrinus), and progenitor species (M. guttatus and M. luteus). We show that subgenome expression dominance occurs instantly following the hybridization of divergent genomes and significantly increases over generations. Additionally, CHH methylation levels are reduced in regions near genes and within TEs in the first-generation hybrid, intermediate in the resynthesized allopolyploid, and are repatterned differently between the dominant and recessive subgenomes in the natural allopolyploid. Subgenome differences in levels of TE methylation mirror the increase in expression bias observed over the generations following hybridization. These findings provide important insights into genomic and epigenomic shock that occurs following hybridization and polyploid events and may also contribute to uncovering the mechanistic basis of heterosis and subgenome dominance.


Assuntos
Genoma de Planta , Hibridização Genética , Mimulus/genética , Poliploidia , Metilação de DNA/genética , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , Filogenia , Especificidade da Espécie
10.
Nature ; 511(7508): 216-9, 2014 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-25008529

RESUMO

The urban heat island (UHI), a common phenomenon in which surface temperatures are higher in urban areas than in surrounding rural areas, represents one of the most significant human-induced changes to Earth's surface climate. Even though they are localized hotspots in the landscape, UHIs have a profound impact on the lives of urban residents, who comprise more than half of the world's population. A barrier to UHI mitigation is the lack of quantitative attribution of the various contributions to UHI intensity (expressed as the temperature difference between urban and rural areas, ΔT). A common perception is that reduction in evaporative cooling in urban land is the dominant driver of ΔT (ref. 5). Here we use a climate model to show that, for cities across North America, geographic variations in daytime ΔT are largely explained by variations in the efficiency with which urban and rural areas convect heat to the lower atmosphere. If urban areas are aerodynamically smoother than surrounding rural areas, urban heat dissipation is relatively less efficient and urban warming occurs (and vice versa). This convection effect depends on the local background climate, increasing daytime ΔT by 3.0 ± 0.3 kelvin (mean and standard error) in humid climates but decreasing ΔT by 1.5 ± 0.2 kelvin in dry climates. In the humid eastern United States, there is evidence of higher ΔT in drier years. These relationships imply that UHIs will exacerbate heatwave stress on human health in wet climates where high temperature effects are already compounded by high air humidity and in drier years when positive temperature anomalies may be reinforced by a precipitation-temperature feedback. Our results support albedo management as a viable means of reducing ΔT on large scales.


Assuntos
Cidades , Clima , Temperatura Alta , Modelos Teóricos , Monitoramento Ambiental , Humanos , Umidade , América do Norte , Densidade Demográfica
11.
BMC Bioinformatics ; 20(1): 149, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894122

RESUMO

BACKGROUND: Gene duplications are a major source of raw material for evolution and a likely contributor to the diversity of life on earth. Duplicate genes (i.e., homeologs, in the case of a whole genome duplication) may retain their ancestral function, sub- or neofunctionalize, or be lost entirely. A primary way that duplicate genes evolve new functions is by altering their expression patterns. Comparing the expression patterns of duplicate genes gives clues as to whether any of these evolutionary processes have occurred. RESULTS: We develop a likelihood ratio test for the analysis of the expression ratios of duplicate genes across two conditions (e.g., tissues). We demonstrate an application of this test by comparing homeolog expression patterns of 1448 homeologous gene pairs using RNA-seq data generated from leaves and petals of an allotetraploid monkeyflower (Mimulus luteus). We assess the sensitivity of this test to different levels of homeolog expression bias and compare the method to several alternatives. CONCLUSIONS: The likelihood ratio test derived here is a direct, transparent, and easily implemented method for detecting changes in homeolog expression bias that outperforms alternative approaches. While our method was derived with homeolog analysis in mind, this method can be used to analyze changes in the ratio of expression levels between any two genes in any two conditions.


Assuntos
Duplicação Gênica , Perfilação da Expressão Gênica , Genes de Plantas , Mimulus/genética , Poliploidia , Análise de Sequência de RNA/métodos , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genoma de Planta
12.
J Am Chem Soc ; 141(4): 1446-1451, 2019 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-30636410

RESUMO

A new approach to radical ring-opening polymerization is presented that employs a new thionolactone monomer to generate polymers with thioester-containing backbones. The use of a thiocarbonyl acceptor overcomes longstanding reactivity problems in the field to give complete ring-opening and quantitative incorporation into a variety of acrylate polymers. The resulting copolymers readily degrade under hydrolytic conditions, in addition to cysteine-mediated degradation through transthioesterification. The strategy is compatible with reversible addition-fragmentation chain transfer (RAFT) polymerization and permits the synthesis of block polymers for the preparation of well-defined macromolecular structures.

13.
Anal Chem ; 91(10): 6894-6901, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31009215

RESUMO

It has been estimated that approximately 50% of all marketed drug molecules are manufactured and administered in the form of salts, often with the goal of improving solubility, dissolution rate, and efficacy of the drug. However, salt disproportionation during processing or storage is a common adverse effect in these formulations. Due to the heterogeneous nature of solid drug formulations, it is essential to characterize the drug substances noninvasively at micrometer resolution to understand the molecular mechanism of salt disproportionation. However, there is a lack of such capability with current characterization methods. In this study, we demonstrate that stimulated Raman scattering (SRS) microscopy can be used to provide sensitive and quantitative chemical imaging of the salt disproportionation reaction of pioglitazone hydrochloride (PIO-HCl) at a very low drug loading (1% w/w). Our findings illuminate a water mediated pathway of drug disproportionation and highlight the importance of noninvasive chemical imaging in a mechanistic study of solid-state chemical reactions.


Assuntos
Pioglitazona/análise , Comprimidos/análise , Química Farmacêutica/métodos , Excipientes/química , Concentração de Íons de Hidrogênio , Análise dos Mínimos Quadrados , Microscopia Óptica não Linear/métodos , Pioglitazona/química , Ácidos Esteáricos/química , Comprimidos/química
14.
Biomed Microdevices ; 22(1): 7, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31845070

RESUMO

Minimally invasive delivery of peptide and protein molecules represents a significant opportunity for product differentiation and value creation versus standard injectable routes of administration. One such technology utilizes microneedle (MN) patches and it has made considerable clinical advances in systemic delivery of potent macromolecules and vaccines. A sub-class of this technology has focused on preparation of solid dense MN arrays followed by precision formulation coating on the tips of the MN. The objective of this study was to develop a drug product using the MN technology that has similar bioperformance when compared to subcutaneous route of delivery and can provide improved stability under storage. Therapeutic peptide (Peptide A, Merck & Co., Inc., Kenilworth, NJ, USA) is being developed as a subcutaneous injection for chronic dosing with a submilligram estimated therapeutic dose. Peptide A has chemical and physical stability challenges in solution and this led to exploration of a viable drug product which could provide therapeutic dosages while overcoming the stability issues seen with the compound. This work focused on developing a coated solid microstructure transdermal system (sMTS) for Peptide A followed by detailed in vitro and preclinical evaluation for two different coating formulations. Based on initial assessment, ~250 µg of Peptide A could be coated with precision on a 1.27cm2 patch which contained 316 MN's. The delivery from these systems was achieved with absolute bioavailability being similar to the subcutaneous delivery (88% and 74% for coated sMTS 1 & 2 and 75% for subcutaneous delivery). Stability of Peptide A was also found to be significantly improved when coated on the sMTS system with minimal degradation recorded at room temperature storage as compared to the subcutaneous liquid formulation. Additionally, skin irritation (on pig skin) was also measured in this study and it was found to be minimal and self-resolving. This evaluation provided a viable option for developing a drug product with improved stability and successful delivery of the investigated molecule. Graphical abstractSchematic showing uncoated sMTS, resulting product with coated peptide, successful skin penetration with high delivery efficiency and bioavailability.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Agulhas , Peptídeos/administração & dosagem , Pele , Animais , Feminino , Peptídeos/farmacocinética , Peptídeos/uso terapêutico , Suínos , Distribuição Tecidual
15.
Inorg Chem ; 58(14): 9016-9027, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31241907

RESUMO

Here we report a high-pressure investigation into the structural and magnetic properties of the double perovskite La2NiMnO6 using neutron scattering over a temperature range of 4.2-300 K at ambient pressure and over a temperature range of 120-1177 K up to a maximum pressure of 6.6 GPa. X-ray diffraction was also used up to a maximum pressure of 64 GPa, over a temperature range of 300-720 K. The sample was found to exist in a mixed rhombohedral/monoclinic symmetry at ambient conditions, the balance of which was found to be strongly temperature- and pressure-dependent. Alternating current magnetometry and X-ray absorption near-edge structure measurements were made at ambient pressure to characterize the sample, suggesting that the transition-metal sites exist in a mixed Ni3+/Mn3+ and Ni2+/Mn4+ state at ambient temperature and pressure. Analysis of the magnetic properties of the sample shows that the Curie temperature can be enhanced by ∼12 K with 2 GPa applied pressure, but it is highly stable at pressures beyond this. We report a pressure-volume-temperature equation of state for this material over this combined temperature and pressure range, with an ambient temperature bulk modulus of ∼179(8) GPa. The previously reported transition from monoclinic to rhombohedral symmetry upon heating to 700 K is seen to be encouraged with applied pressure, transforming fully by ∼1.5 GPa. Raman spectroscopy data were collected up to ∼8 GPa and show no clear changes or discontinuities over the reported phase transition to rhombohedral symmetry or any indication of further changes over the range considered. The ambient-pressure Grüneisen parameter γth was determined to be γth = 2.6 with a Debye temperature of 677 K. The individual modal parameters γj at ambient temperature were also determined from the high-pressure Raman data.

16.
Clin Gerontol ; 42(2): 198-203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29877759

RESUMO

OBJECTIVES: To assess mental health providers' experience with LGBT older adults in long-term care (LTC) settings and perceived barriers to quality care. METHODS: Providers (N = 57) completed an online survey on demographics and practice characteristics. They were also asked about: number of LGBT residents they've worked with, relevance of LGBT issues to their practice, preparedness, willingness to learn, hours of formal/informal training, and barriers to providing care to LGBT patients. RESULTS: Respondents were 63% psychologists, 16% social workers, 14% psychiatrists, and 5% nurses, most of whom practiced in LTC consulting roles. Most providers felt working with LGBT issues was relevant to their practice and felt well-prepared and willing to learn, though they were unaware of evidence based practices (EBTs), especially for LTC settings. They had little coursework on LGBT issues, and identified lack of training, stigma, and residents concealing their identity as the greatest barriers to quality care. CONCLUSIONS: Mental health providers in LTC facilities would benefit from more training in LGBT-specific mental health problems and evidence-based treatments, and efforts to destigmatize LGBT identities in these settings might improve access to mental health care. CLINICAL IMPLICATIONS: LGBT-specific training and EBTs are needed. Facilities need to address stigma with residents and providers.


Assuntos
Equidade em Saúde/normas , Pessoal de Saúde/educação , Assistência de Longa Duração/psicologia , Minorias Sexuais e de Gênero/psicologia , Idoso , Feminino , Geriatria/educação , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Inquéritos e Questionários
17.
Am J Med Genet A ; 176(6): 1455-1462, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29693785

RESUMO

KIAA2022 is an X-linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19-years-old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, café-au-lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10-years-old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified KIAA2022 variant c.652C > T(p.Arg218*) in Patient 1, and a novel nonsense de novo variant c.2707G > T(p.Glu903*) in Patient 2. We also summarized features of all reported males with KIAA2022 variants to date. This report not only adds knowledge of a novel pathogenic variant to the KIAA2022 variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, café-au-lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together.


Assuntos
Deficiências do Desenvolvimento/genética , Mutação , Proteínas do Tecido Nervoso/genética , Comportamento Agonístico/efeitos dos fármacos , Criança , Pré-Escolar , Deficiências do Desenvolvimento/etiologia , Face/anormalidades , Gastroenteropatias/etiologia , Gastroenteropatias/genética , Humanos , Masculino
18.
Mol Pharm ; 15(12): 5793-5801, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30362772

RESUMO

Localized drug delivery systems (DDSs) provide therapeutic levels of drug agent while mitigating side effects of systemic delivery. These systems offer controlled release over extended periods of time making them attractive therapies. Monitoring drug dissolution is vital for developing safe and effective means of drug delivery. Currently, dissolution characterization methods are limited to bulk analysis and cannot provide dissolution kinetics at high spatial resolution. However, dissolution rates of drug particles can be heterogeneous with influences from many factors. Insights into finer spatiotemporal dynamics of single particle dissolution could potentially improve pharmacokinetic modeling of dissolution for future drug development. In this work, we demonstrate high-resolution chemical mapping of entecavir, a hepatitis B antiviral drug, embedded in a slow release poly(d,l-lactic acid) formulation with stimulated Raman scattering (SRS) microscopy. By tracking the volume change of individual micron-sized drug particles within the polymer matrix, we establish an analytical protocol for quantitatively profiling dissolution of single crystalline particles in implant formulations in an in situ manner.


Assuntos
Portadores de Fármacos/química , Implantes de Medicamento/farmacocinética , Liberação Controlada de Fármacos , Guanina/análogos & derivados , Química Farmacêutica/métodos , Implantes de Medicamento/administração & dosagem , Guanina/administração & dosagem , Guanina/farmacocinética , Microscopia/métodos , Tamanho da Partícula , Poliésteres/química , Análise Espectral Raman/métodos
19.
Inorg Chem ; 57(19): 11942-11947, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30207462

RESUMO

The oxide ionic conductor Ba3W1.2Nb0.8O8.6 has been synthesized as part of an investigation into the new class of Ba3M'M''O8.5 (M' = W, Mo; M'' = Nb) oxide-ion conducting hexagonal perovskite derivatives. The substitution of W6+ for Nb5+ in Ba3W1+ xNb1- xO8.5+ x/2 leads to an increase in the oxygen content, which enhances the low-temperature ionic conductivity. However, at 400 °C, the ionic conductivity of Ba3W1.2Nb0.8O8.6 is still significantly lower than the molybdenum compound Ba3MoNbO8.5. Remarkably, at 600 °C the bulk oxide ionic conductivities of Ba3MoNbO8.5, Ba3WNbO8.5, and Ba3W1.2Nb0.8O8.6 are very similar (σb = 0.0022, 0.0017, and 0.0016 S cm-1, respectively). The variable-temperature neutron diffraction results reported here demonstrate that Ba3W1.2Nb0.8O8.6 undergoes a similar structural rearrangement to Ba3MoNbO8.5 above 300 °C, but the ratio of (W/Nb)O4 tetrahedra to (W/Nb)O6 octahedra rises at a faster rate upon heating between 300 and 600 °C. There is a clear relationship between the ionic conductivity of Ba3M'1+ xM''1- xO8.5+ x/2 (M' = W, Mo; M'' = Nb) phases and the number of tetrahedrally coordinated M' and M ″ cations present within the crystal structure.

20.
Phys Chem Chem Phys ; 20(6): 3979-3987, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29349442

RESUMO

The half-Heuslers NbCoSn and NbCoSb have promising thermoelectric properties. Here, an investigation of the NbCo1+ySn1-zSbz (y = 0, 0.05; 0 ≤ z ≤ 1) solid-solution is presented. In addition, the p-type doping of NbCoSn using Ti and Zr substitution is investigated. Rietveld analysis reveals the gradual creation of Nb vacancies to compensate for the n-type doping caused by the substitution of Sb in NbCoSn. This leads to a similar valence electron count (∼18.25) for the NbCo1+ySn1-zSbz samples (z > 0). Mass fluctuation disorder due to the Nb vacancies strongly decreases the lattice thermal conductivity from 10 W m-1 K-1 (z = 0) to 4.5 W m-1 K-1 (z = 0.5, 1). This is accompanied by a transition to degenerate semiconducting behaviour leading to large power factors, S2/ρ = 2.5-3 mW m-1 K-2 and figures of merit, ZT = 0.25-0.33 at 773 K. Ti and Zr can be used to achieve positive Seebeck values, e.g. S = +150 µV K-1 for 20% Zr at 773 K. However, the electrical resistivity, ρ323K = 27-35 mΩ cm, remains too large for these materials to be considered useful p-type materials.

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