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1.
Materials (Basel) ; 16(23)2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38068036

RESUMO

This article proposes a generalizable, data-driven framework for qualifying laser powder bed fusion additively manufactured parts using part-specific in situ data, including powder bed imaging, machine health sensors, and laser scan paths. To achieve part qualification without relying solely on statistical processes or feedstock control, a sequence of machine learning models was trained on 6299 tensile specimens to locally predict the tensile properties of stainless-steel parts based on fused multi-modal in situ sensor data and a priori information. A cyberphysical infrastructure enabled the robust spatial tracking of individual specimens, and computer vision techniques registered the ground truth tensile measurements to the in situ data. The co-registered 230 GB dataset used in this work has been publicly released and is available as a set of HDF5 files. The extensive training data requirements and wide range of size scales were addressed by combining deep learning, machine learning, and feature engineering algorithms in a relay. The trained models demonstrated a 61% error reduction in ultimate tensile strength predictions relative to estimates made without any in situ information. Lessons learned and potential improvements to the sensors and mechanical testing procedure are discussed.

2.
Life (Basel) ; 13(5)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37240795

RESUMO

The search for life on other planets relies on the detection of biosignatures of life. Many macromolecules have been suggested as potential targets, among which are proteins that are considered vital components of life due to their essential roles in forming cellular structures, facilitating cellular communication and signaling, and catalyzing metabolic reactions. In this context, accurate quantification of protein signatures in soil would be advantageous, and while several proposed methods exist, which are limited by their sensitivity and specificity, their applicability needs further testing and validation. To this aim, we optimized a Bradford-based assay with high sensitivity and reproducibility and a simple protocol to quantify protein extracted from a Martian soil simulant. Methods for protein spiking, extraction, and recovery were optimized, using protein standards and bacterial proteins as representative models. The proposed method achieved high sensitivity and reproducibility. Taking into account that life remains could exist on the surface of Mars, which is subjected to UV radiation, a simulation of UV exposure was performed on a spiked soil simulant. UV radiation degraded the protein spike, thus highlighting the importance of searching for the remaining signal from degraded proteins. Finally, the applicability of the method was explored in relation to the storage of the reagent which was stable even up to 12 months, thus making its application possible for future planetary exploration missions.

3.
Nat Commun ; 11(1): 2041, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341341

RESUMO

How complex, multi-component macromolecular machines evolved remains poorly understood. Here we reveal the evolutionary origins of the chemosensory machinery that controls flagellar motility in Escherichia coli. We first identify ancestral forms still present in Vibrio cholerae, Pseudomonas aeruginosa, Shewanella oneidensis and Methylomicrobium alcaliphilum, characterizing their structures by electron cryotomography and finding evidence that they function in a stress response pathway. Using bioinformatics, we trace the evolution of the system through γ-Proteobacteria, pinpointing key evolutionary events that led to the machine now seen in E. coli. Our results suggest that two ancient chemosensory systems with different inputs and outputs (F6 and F7) existed contemporaneously, with one (F7) ultimately taking over the inputs and outputs of the other (F6), which was subsequently lost.


Assuntos
Substâncias Macromoleculares/química , Methylococcaceae/fisiologia , Pseudomonas aeruginosa/fisiologia , Shewanella/fisiologia , Vibrio cholerae/fisiologia , Evolução Biológica , Quimiotaxia , Biologia Computacional , Tomografia com Microscopia Eletrônica , Escherichia coli/fisiologia , Proteínas de Escherichia coli , Flagelos/fisiologia , Gammaproteobacteria/fisiologia , Genoma Bacteriano , Proteínas Quimiotáticas Aceptoras de Metil/química , Filogenia
4.
Methods Enzymol ; 613: 349-383, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30509473

RESUMO

Microbial methane utilization-a key node in the global carbon cycle-controls and often eliminates emission of methane into the atmosphere. The diversity and distribution of microbes capable of methane oxidation is astounding. However, from a biochemical point of view, only a very narrow set of unique enzymes underlies their metabolic capabilities. Despite this restriction, the successful integration of the enzymes into nonmethanotrophs, if judged by the ability of the trait to grow on methane, remains to be achieved. Failures and small victories with heterologous expression have highlighted a set of challenges linked to structure, compartmentalization, and regulation of the methanotrophic metabolic network. A better understanding of how these challenges are handled by cells of native methane-consuming bacteria is required. In this chapter we focus on key experimental aspects of working with native methanotrophic bacteria, including routine cultivation strategies, lab-scale bioreactor setups, genetic alteration, imaging, and basic -omic-level approaches.


Assuntos
Metano/metabolismo , Reatores Biológicos/microbiologia , Methylococcaceae/metabolismo , Oxirredução
5.
Front Microbiol ; 9: 2735, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30542328

RESUMO

Background: Rare Earth Elements (REEs) control methanol utilization in both methane- and methanol-utilizing microbes. It has been established that the addition of REEs leads to the transcriptional repression of MxaFI-MeDH [a two-subunit methanol dehydrogenase (MeDH), calcium-dependent] and the activation of XoxF-MeDH (a one-subunit MeDH, lanthanum-dependent). Both enzymes are pyrroquinoline quinone-dependent alcohol dehydrogenases and show significant homology; however, they display different kinetic properties and substrate specificities. This study investigates the impact of the MxaFI to XoxF switch on the behavior of metabolic networks at a global scale. Results: In this study we investigated the steady-state growth of Methylomicrobium alcaliphilum 20ZR in media containing calcium (Ca) or lanthanum (La, a REE element). We found that cells supplemented with La show a higher growth rate compared to Ca-cultures; however, the efficiency of carbon conversion, estimated as biomass yield, is higher in cells grown with Ca. Three complementary global-omics approaches-RNA-seq transcriptomics, proteomics, and metabolomics-were applied to investigate the mechanisms of improved growth vs. carbon conversion. Cells grown with La showed the transcriptional activation of the xoxF gene, a homolog of the formaldehyde-activating enzyme (fae2), a putative transporter, genes for hemin-transport proteins, and nitrate reductase. In contrast, genes for mxaFI and associated cytochrome (mxaG) expression were downregulated. Proteomic profiling suggested additional adjustments of the metabolic network at the protein level, including carbon assimilation pathways, electron transport systems, and the tricarboxylic acid (TCA) cycle. Discord between gene expression and protein abundance changes points toward the possibility of post-transcriptional control of the related systems including key enzymes of the TCA cycle and a set of electron-transport carriers. Metabolomic data followed proteomics and showed the reduction of the ribulose-monophosphate (RuMP) pathway intermediates and the increase of the TCA cycle metabolites. Conclusion: Cells exposed to REEs display higher rates of growth but have lower carbon conversion efficiency compared to cells supplemented with Ca. The most plausible explanation for these physiological changes is an increased conversion of methanol into formate by XoxF-MeDH, which further stimulates methane oxidation but limits both the supply of reducing power and flux of formaldehyde into the RuMP pathway.

6.
J Evid Based Integr Med ; 23: 2515690X18801581, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30295047

RESUMO

The purpose of the present study was to identify the factors that are the strongest predictors of intentions and use of integrative medicine approaches in clinical practice. Ajzen's theory of planned behavior was used to guide our examination of these questions. Health care professionals exposed to a Veterans Health Administration program (N = 288) who completed survey instruments prior to and immediately after the program and 3 months later were the participants for this study. Findings suggest that the theory of planned behavior performs reasonably well in explaining our data showing the integration of integrative medicine approaches into clinical practice. We found that self-efficacy to use integrative health approaches and perceived preparedness to discuss nonpharmaceutical approaches with patients were the strongest predictors of intentions to use integrative health approaches and self-reported change in clinical practice. The implications of these findings are discussed.


Assuntos
Pessoal de Saúde/psicologia , Medicina Integrativa/educação , Percepção , Adulto , Feminino , Pessoal de Saúde/educação , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Autoeficácia , Autorrelato , Inquéritos e Questionários
7.
Glob Adv Health Med ; 7: 2164957X18757463, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29468093

RESUMO

BACKGROUND: Although studies of health coaching for behavior change in chronic disease prevention and management are increasing, to date no studies have reported on what concepts and skills providers integrate into their clinical practice following participation in health coaching courses. The purpose of this qualitative study was to assess Veterans Health Administration (VHA) providers' perceptions of the individual-level and system-level changes they observed after participating with colleagues in a 6-day Whole Health Coaching course held in 8 VHA medical centers nationwide. METHODS: Data for this study were from the follow-up survey conducted with participants 2 to 3 months after completing the training. A total of 142 responses about individual-level changes and 99 responses about system-level changes were analyzed using content analysis. RESULTS: Eight primary themes emerged regarding individual changes, including increased emphasis on Veterans' values, increased use of listening and other specific health coaching skills in their clinical role, and adding health coaching to their clinical practice.Four primary themes emerged regarding system-level changes, including leadership support, increased staff awareness/support/learning and sharing, increased use of health coaching skills or tools within the facility, and organizational changes demonstrating a more engaged workforce, such as new work groups being formed or existing groups becoming more active. CONCLUSIONS: Findings suggest that VHA providers who participate in health coaching trainings do perceive positive changes within themselves and their organizations. Health coaching courses that emphasize patient-centered care and promote patient-provider partnerships likely have positive effects beyond the individual participants that can be used to promote desired organizational change.

8.
Foodborne Pathog Dis ; 14(9): 531-536, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28696788

RESUMO

Studies indicate that persistent Salmonella colonization occurs in poultry that are infected early in life, leading to both food safety and public health concerns. Development of improved preharvest Salmonella management strategies is needed to reduce poultry product contamination. The objective of this study was to evaluate the efficacy of a product containing medium chain fatty acids (MCFA) for reducing early Salmonella colonization in turkey poults. Day-of-hatch turkeys were provided a standard starter diet supplemented with MCFA at 0 (negative and positive controls), 1.5, 3, 4.5, or 6 lbs/ton of feed. Positive control and MCFA treated birds were also crop-gavaged with 108 colony forming units (CFU) of bioluminescent Salmonella Typhimurium. Gastrointestinal tissue samples were collected at 3 days postinoculation for bioluminescence imaging (Meckel's diverticulum to the cloaca) and selective enumeration (cecal contents). Quantification of bioluminescence indicated that the 4.5 and 6 lbs/ton MCFA groups had significantly less colonization than the positive control group (p = 0.0412 and p < 0.0001, respectively). Similarly, significantly lower numbers (1-log10 CFU/g reduction) of Salmonella were observed in the ceca of the 6 lbs/ton MCFA group compared to the positive control group (p = 0.0153). These findings indicate that incorporation of MCFA in turkey diets can significantly reduce early Salmonella colonization. In addition, this study highlights the utility of bioluminescence imaging as a screening methodology for assessing the efficacy of treatments that may reduce Salmonella in poultry.


Assuntos
Suplementos Nutricionais , Ácidos Graxos/administração & dosagem , Contaminação de Alimentos/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Salmonelose Animal/prevenção & controle , Salmonella typhimurium/isolamento & purificação , Ração Animal/análise , Animais , Dieta/veterinária , Feminino , Inocuidade dos Alimentos , Trato Gastrointestinal/citologia , Trato Gastrointestinal/microbiologia , Humanos , Medições Luminescentes/veterinária , Doenças das Aves Domésticas/microbiologia , Distribuição Aleatória , Salmonelose Animal/microbiologia , Salmonella typhimurium/crescimento & desenvolvimento , Perus
9.
J Clin Pharmacol ; 57(10): 1322-1329, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28543352

RESUMO

The glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) exenatide and lixisenatide reduce cholecystokinin (CCK)-induced gallbladder emptying in healthy subjects. It is unknown if all GLP-1 RAs share this effect; therefore, the effect of the GLP-1 RA albiglutide on gallbladder function was assessed. In this randomized, double-blind, 2-way crossover study, a single dose of subcutaneous albiglutide 50 mg or placebo was administered to 17 healthy subjects, and CCK-induced gallbladder contractility was measured by ultrasonography. CCK (0.003 µg/kg) was infused intravenously over 50 minutes on study day 4 (3 days after dosing, to coincide with albiglutide's expected time to maximum concentration). Gallbladder volume, ejection fraction, and the main pancreatic and common bile-duct diameters were measured before, during, and following CCK infusion. Gallbladder volume was significantly greater in the albiglutide vs placebo groups before, during, and after CCK infusion, and the mean difference from placebo increased numerically during CCK infusion. The area under the volume-effect curve was significantly greater with albiglutide (P = .029). Starting at the 30-minute CCK infusion time point, the gallbladder ejection fraction was significantly lower with albiglutide than placebo. Changes in pancreatic duct diameter and common bile-duct diameter were not significantly different between albiglutide and placebo. Similar incidences of adverse events were observed between the albiglutide and placebo treatment periods. No new albiglutide safety signals were detected, and no serious adverse events were reported. In conclusion, similar to other GLP-1 RAs, albiglutide decreased CCK-induced gallbladder emptying compared with placebo in healthy individuals. Clinical implications of the gallbladder effects are unclear at this time.


Assuntos
Colecistocinina , Esvaziamento da Vesícula Biliar/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/farmacocinética , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia , Adulto Jovem
10.
AIDS Care ; 29(8): 966-973, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28276255

RESUMO

African-American females in the U.S. are disproportionately affected by HIV/AIDS, and a large majority of new infections in this population are attributed to heterosexual contact. Risk factors include substance abuse, lack of knowledge about male partners' possible HIV infection risk, incarceration, disruptions of social networks, and intimate partner violence. This study assessed the effects of a comprehensive, evidence-based prevention intervention, Creating Lasting Family Connections (CLFC) that was implemented with sensitivity to African-American females, using a quasi-experimental design. The CLFC program was implemented with 175 women and their results were compared to a convenience sample of 44 women who were similar on background characteristics. Results showed significant (p < .05, two-tailed) increases in the proportion of individuals getting HIV tested and getting the results from these tests, a larger decrease in intimate partner abuse within the past three months, and larger increases in three relationship skills (emotional expression, interpersonal skills, and relationship satisfaction) relative to the comparison group.


Assuntos
Negro ou Afro-Americano/psicologia , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Relações Interpessoais , Maus-Tratos Conjugais/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Adolescente , Adulto , Negro ou Afro-Americano/educação , Feminino , Infecções por HIV/etnologia , Infecções por HIV/etiologia , Infecções por HIV/psicologia , Heterossexualidade , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Assunção de Riscos , Parceiros Sexuais , Transtornos Relacionados ao Uso de Substâncias/etnologia , Estados Unidos , Adulto Jovem
11.
Fam Med ; 48(9): 711-719, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27740671

RESUMO

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess whether a 2.5 day clinical education course focused on integrative medicine (IM), complementary health (CH), and patient-centered care strategies delivered to staff at Veteran Health Administration (VHA) facilities resulted in changes in attitudes, self-efficacy, preparedness, intentions, and self-reported use of IM strategies. The study also assessed whether there were differential impacts by participant characteristics. METHODS: The study used a pre-post intervention group-only design with participants who completed self-report pre, post, and 2-month follow-up surveys. The course was delivered to 15 VHA facilities, reaching a total of 655 participants with 407 participants completing the 2-month follow-up survey (65% response rate). RESULTS: Findings suggest that the clinical course was associated with changes in all outcomes at the 2-month follow-up, including attitudes, self-efficacy to engage in IM strategies, institutional support, perceived preparedness to discuss non-pharmaceutical approaches to care, intentions to engage in IM strategies, and greater engagement in IM behaviors during clinical encounters. Differential impacts were found for younger participants, longer tenured staff, non-nursing compared to nursing staff, and among those who volunteered as opposed to those who were required to attend. DISCUSSION AND CONCLUSIONS: The study found significant positive changes in all outcomes measured at the 2-month follow-up. Positive impacts were found across a variety of participant characteristics. Findings suggest that this brief experiential course, designed to be a foundational strategy in driving transformation is effective in shifting attitudes, self-efficacy, preparedness, intentions, and self-reported use of IM strategies.


Assuntos
Educação Continuada/métodos , Pessoal de Saúde/educação , Medicina Integrativa , Assistência Centrada no Paciente , Atitude Frente a Saúde , Feminino , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Autocuidado , Autoeficácia , Teoria Social , Inquéritos e Questionários , Estados Unidos , United States Department of Veterans Affairs/organização & administração
12.
J Prim Care Community Health ; 6(4): 250-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26089032

RESUMO

BACKGROUND: The purpose of this study was to determine whether a health coaching (HC) course for providers and staff in Veterans Health Affairs medical facilities resulted in increased attitudes toward, intentions to use, and actual use of HC. METHODS: A Whole Health Coaching Course was developed and implemented in national sites in 2014. A pre-post intervention group only design was used to assess changes in HC outcomes, including use of HC skills. RESULTS: There were large pre- to posttest increases in preparedness and self-efficacy that were sustained at follow-up. Initial small increases in attitudes toward patient-centered care and intentions to use HC skills were not sustained at follow-up. There was a medium-sized increase in actual use of HC skills between pre-test and follow-up. CONCLUSIONS: Findings suggest that participation in the HC course is an effective means for providers and staff to increase preparedness, self-efficacy, and actual use of health coaching skills.


Assuntos
Promoção da Saúde/métodos , Hospitais de Veteranos , Currículo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente/métodos , Avaliação de Programas e Projetos de Saúde , Autoeficácia , Ensino , Saúde dos Veteranos
13.
J Drug Assess ; 4(1): 24-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27536459

RESUMO

OBJECTIVE: To evaluate the bioequivalence of five 0.1 mg dutasteride capsules to one 0.5 mg dutasteride capsule in healthy adult male subjects under fasting conditions. METHODS: This was a single-center, open-label, randomized, single dose, two-way cross-over study (ClinicalTrials.gov identifier NCT01929330). Thirty-six healthy male subjects aged 18-65 years received 5 × 0.1 mg dutasteride softgel capsules and 1 × 0.5 mg dutasteride softgel capsule in a randomized order, with a minimum washout of 28 days between each drug administration. Serial blood samples were collected for the measurement of serum dutasteride concentrations by a validated HPLC-MS/MS method. Dutasteride pharmacokinetic parameters were calculated using non-compartmental analysis. Maximum concentration (Cmax) and area under the concentration-time curve to the last quantifiable concentration (AUC[0-t]) were compared between treatments. Safety and tolerability were monitored throughout the study. RESULTS: Five 0.1 mg dutasteride capsules were demonstrated to be bioequivalent to 1 × 0.5 mg dutasteride capsule, as the 90% confidence intervals for Cmax and AUC were within the accepted bioequivalence range of 0.80-1.25. The geometric least squares means ratios and associated 90% confidence intervals for 5 × 0.1 mg capsules vs 1 × 0.5 mg capsule were 1.01 (0.97-1.05) for Cmax and 0.91 (0.84-1.00) for AUC(0-t). Adverse events (AEs) were reported for 42% (15/36) and 36% (12/33) of subjects in the 5 × 0.1 mg and 1 × 0.5 mg dosing sessions, respectively. The most frequent AE for both treatments was headache. No subject had a serious AE. CONCLUSIONS: Five 0.1 mg dutasteride capsules were shown to be bioequivalent to one 0.5 mg dutasteride capsule in healthy adult male subjects under fasted conditions, suggesting that the two dose strengths can be interchanged. Both treatments were generally well tolerated in healthy male subjects.

14.
PLoS One ; 9(4): e92494, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24699248

RESUMO

UNLABELLED: GPR119 receptor agonists improve glucose metabolism and alter gut hormone profiles in animal models and healthy subjects. We therefore investigated the pharmacology of GSK1292263 (GSK263), a selective GPR119 agonist, in two randomized, placebo-controlled studies that enrolled subjects with type 2 diabetes. Study 1 had drug-naive subjects or subjects who had stopped their diabetic medications, and Study 2 had subjects taking metformin. GSK263 was administered as single (25-800 mg; n = 45) or multiple doses (100-600 mg/day for 14 days; n = 96). Placebo and sitagliptin 100 mg/day were administered as comparators. In Study 1, sitagliptin was co-administered with GSK263 or placebo on Day 14 of dosing. Oral glucose and meal challenges were used to assess the effects on plasma glucose, insulin, C-peptide, glucagon, peptide tyrosine-tyrosine (PYY), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). After 13 days of dosing, GSK263 significantly increased plasma total PYY levels by ∼ five-fold compared with placebo, reaching peak concentrations of ∼ 50 pM after each of the three standardized meals with the 300 mg BID dose. Co-dosing of GSK263 and metformin augmented peak concentrations to ∼ 100 pM at lunchtime. GSK263 had no effect on active or total GLP-1 or GIP, but co-dosing with metformin increased post-prandial total GLP-1, with little effect on active GLP-1. Sitagliptin increased active GLP-1, but caused a profound suppression of total PYY, GLP-1, and GIP when dosed alone or with GSK263. This suppression of peptides was reduced when sitagliptin was co-dosed with metformin. GSK263 had no significant effect on circulating glucose, insulin, C-peptide or glucagon levels. We conclude that GSK263 did not improve glucose control in type 2 diabetics, but it had profound effects on circulating PYY. The gut hormone effects of this GPR119 agonist were modulated when co-dosed with metformin and sitagliptin. Metformin may modulate negative feedback loops controlling the secretion of enteroendocrine peptides. TRIAL REGISTRATION: Clinicaltrials.gov NCT01119846 Clinicaltrials.gov NCT01128621.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Hormônios Gastrointestinais/metabolismo , Hipoglicemiantes/farmacologia , Mesilatos/farmacologia , Metformina/farmacologia , Oxidiazóis/farmacologia , Pirazinas/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Triazóis/farmacologia , Glicemia/análise , Peptídeo C/sangue , Estudos Cross-Over , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Peptídeo YY/metabolismo , Prognóstico , Fosfato de Sitagliptina
15.
Clin Drug Investig ; 34(5): 335-49, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24615171

RESUMO

BACKGROUND AND OBJECTIVES: The combination of dutasteride and tamsulosin may be more effective for the treatment of symptomatic benign prostatic hyperplasia than either treatment alone. We report the results of three pharmacokinetics and tolerability studies, which used a dutasteride/tamsulosin HCl (0.5 mg/0.2 mg) fixed-dose combination (FDC) capsules containing a small dutasteride soft gelatin capsule (smaller than commercial Avodart™) and modified-release tamsulosin pellets that have different amounts of enteric coating. These studies compared the test products to commercial Avodart™ (dutasteride 0.5 mg) and two different commercial tamsulosin HCl 0.2 mg products, Harnal™ Capsules or Harnal-D™ Tablets, which are reportedly bioequivalent to each other. METHODS: All three studies were randomized single-dose studies in healthy male adults. Study 1 [N = 86 (NCT01254071)] was a two-period crossover study of a dutasteride/tamsulosin HCl FDC versus coadministered Avodart™ and Harnal-D™ Tablets. The pharmacokinetics of both dutasteride and tamsulosin were studied. Study 2 [N = 27 (NCT01471678)] was a four-period crossover study of dutasteride/tamsulosin HCl FDC formulations versus Avodart™ and Harnal™ Capsules or Harnal-D™ Tablets. Only the pharmacokinetics of tamsulosin were studied. Study 3 [N = 40 (NCT01495026)] was a two-period study of dutasteride/tamsulosin HCl FDC formulations versus coadministered Avodart™ and Harnal-D™ Tablets. In this study, only the pharmacokinetics of tamsulosin were studied. Study 2 assessed fed-state pharmacokinetics. Studies 1 and 3 assessed fed- and fasted-state pharmacokinetics. RESULTS: All dutasteride/tamsulosin HCl FDC formulations and coadministered treatments were well-tolerated. In Study 1, the FDC dutasteride was bioequivalent to Avodart™ coadministered with tamsulosin under fed and fasted conditions. In Study 1, the FDC tamsulosin had a slower release than commercial Harnal-D™ Tablets coadministered with dutasteride (fed and fasted state). In Study 2, the FDC tamsulosin containing 15 % by weight enteric-coated tamsulosin pellets was bioequivalent to Harnal™ Capsules coadministered with dutasteride in the fed state. In Study 3, the FDC containing 15 % by weight enteric-coated tamsulosin pellets combined with uncoated tamsulosin pellets (coated:uncoated = 10:90) were bioequivalent to Harnal-D™ Tablets coadministered with dutasteride in the fasted state but not the fed state. CONCLUSIONS: The FDC formulations were well-tolerated and some FDC formulations were comparable with concomitant administration of commercially available dutasteride and tamsulosin.


Assuntos
Azasteroides/farmacocinética , Sulfonamidas/farmacocinética , Adulto , Azasteroides/administração & dosagem , Azasteroides/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Tolerância a Medicamentos , Dutasterida , Voluntários Saudáveis , Humanos , Masculino , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Tansulosina , Equivalência Terapêutica , Resultado do Tratamento
16.
Analyst ; 139(6): 1292-302, 2014 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-24358459

RESUMO

This review covers the latest developments and applications of porous layer open tubular columns in capillary liquid chromatography. Here, the authors provide a concise background on the fundamentals of porous layer open tubular columns, their fabrication and application. Over the past two decades, growing interest in the areas of proteomics and hyphenated LC-MS techniques have played a large part in the development of porous layer structures within capillary formats due to their high permeability, excellent efficiency and exceptional peak capacity. This review gives a brief overview of open tubular columns in general, however, it focuses predominantly on the applications of covalently bonded porous layer open tubular columns in liquid chromatography. Open tubular columns containing non-bonded or electrostatically attached layers will not be discussed in detail.

17.
Fam Process ; 52(3): 477-98, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24033244

RESUMO

Divorce proportions are currently high in the US and they are even higher among those who are incarcerated with substance abuse problems. Although much research has examined marital interventions, only two studies have examined marital interventions with prison populations. There is some empirical evidence that incarcerated couples benefit from traditional marital therapy (O'Farrell and Fals-Stewart, 1999, Addictions: A comprehensive guidebook, New York, Oxford University Press). An adaptation of the evidence-based Creating Lasting Family Connections program was implemented with 144 married couples, where one spouse was incarcerated, in a southern state with particularly high divorce and incarceration proportions. Results suggested that married men exposed to the program had larger improvements in some relationship skills relative to a convenience sample of men not so exposed. Both husbands and wives exposed to the program exhibited similar and significant increases in relationship skills. The results were comparable to a Prevention and Relationship Enhancement Program adaptation for inmates. The implications of the findings for prevention practitioners are discussed.


Assuntos
Relações Familiares , Terapia Conjugal/métodos , Casamento/psicologia , Prisioneiros/psicologia , Socialização , Adulto , Comunicação , Divórcio/prevenção & controle , Divórcio/psicologia , Tráfico de Drogas/prevenção & controle , Tráfico de Drogas/psicologia , Feminino , Seguimentos , Humanos , Kentucky , Masculino , Negociação , Avaliação de Processos e Resultados em Cuidados de Saúde , Satisfação Pessoal , Fatores Socioeconômicos , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Inquéritos e Questionários
18.
Analyst ; 138(9): 2540-5, 2013 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-23397575

RESUMO

A technique for the in-process measurement of polymer stationary phase growth inside fused silica capillaries during the fabrication of monolithic porous layer open tubular (monoPLOT) columns is presented. In this work, capacitively coupled contactless conductivity detection (C4D) was applied as an online measurement tool for porous polymer layer growth within fused silica capillaries. The relationship between effective capillary diameter and C4D response was investigated for two polymers, butyl methacrylate-ethylene dimethacrylate (BuMA-EDMA) and polystyrene-divinylbenzene (PS-DVB) over a range of capillary diameters and layer thicknesses. The described technique can be used with both thermal and photo-initiated approaches for monoPLOT fabrication and provides an accurate, real-time measurement of the porous layer growth within the capillary, which should vastly improve column-to-column reproducibility. The technique was shown to be very precise, with a measured %RSD < 10%.

19.
Subst Use Misuse ; 47(12): 1339-48, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22943304

RESUMO

This article presents results from a study of a home environmental strategy (HES) designed to reduce availability of harmful legal products (HLPs) in the home that can be used by youth to get high. HLPs include inhalants, prescription and nonprescription drugs, and household products that can be ingested to get high. Availability is one of the most consistent predictors of substance use among youth. Parents of 5th- to 7th-grade students in four Alaskan communities participated in telephone interviews as part of a larger study of a multicomponent community prevention model (CPM) that included a HES. The strategy was designed to encourage parents to reduce availability of HLPs by removing them from the home, and by locking up and monitoring the supplies of HLPs in the home. Data from 402 parents at Wave 1 and 371 parents at Wave 2 were analyzed using hierarchical non-Linear modeling (HNLM). Results show there was a significant decrease in HLPs in the home from Wave 1 to Wave 2, mostly inhalants and prescription and nonprescription drugs. Parents also reported a significant increase in locking up prescription and nonprescription drugs in the home. Parents' direct exposure to the HES was marginally associated with the change over time in HLP availability in the home. Indirect exposure through others and media was not associated with this change. Study lessons learned and conclusions are highlighted.


Assuntos
Redução do Dano , Produtos Domésticos/provisão & distribuição , Medicamentos sem Prescrição/provisão & distribuição , Medicamentos sob Prescrição/provisão & distribuição , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Alaska , Criança , Coleta de Dados , Produtos Domésticos/efeitos adversos , Habitação , Humanos , Medicamentos sem Prescrição/efeitos adversos , Uso Indevido de Medicamentos sob Prescrição , Medicamentos sob Prescrição/efeitos adversos , Segurança
20.
Anal Chem ; 84(7): 3465-72, 2012 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-22364508

RESUMO

An automated column fabrication technique that is based on a ultraviolet (UV) light-emitting diode (LED) array oven, and provides precisely controlled "in-capillary" ultraviolet (UV) initiated polymerization at 365 nm, is presented for the production of open tubular monolithic porous polymer layer capillary (monoPLOT) columns of varying length, inner diameter (ID), and porous layer thickness. The developed approach allows the preparation of columns of varying length, because of an automated capillary delivery approach, with precisely controlled and uniform layer thickness and monolith morphology, from controlled UV power and exposure time. The relationships between direct exposure times, intensity, and layer thickness were determined, as were the effects of capillary delivery rate (indirect exposure rate), and multiple exposures on the layer thickness and axial distribution. Layer thickness measurements were taken by scanning electron microscopy (SEM), with the longitudinal homogeneity of the stationary phase confirmed using scanning capacitively coupled contactless conductivity detection (sC(4)D). The new automated UV polymerization technique presented in this work allows the fabrication of monoPLOT columns with a very high column-to-column production reproducibility, displaying a longitudinal phase thickness variation within ±0.8% RSD (relative standard deviation).

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