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1.
Endocrine ; 82(2): 319-325, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37286745

RESUMEN

BACKGROUND: The inverse log-linear relationship between Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is well established and reliably used for evaluation of hypothalamus-pituitary-thyroid (HPT) axis function. However, there are limited data regarding oncologic states in the TSH-FT4 relationship. The purpose of this study was to evaluate thyroid pituitary hypothalamic feedback regulation by the inverse log TSH and FT4 relationship in the cancer patient population at the Ohio State University Comprehensive Cancer Center (OSUCCC-James). METHODS: This retrospective study analyzed the correlation between TSH and FT4 results from 18846 outpatient subjects collected in August 2019-November 2021 at the Department of Family Medicine (OSU Wexner Medical Center), Department of Oncology (OSUCCC-James). Patients with diagnoses related to cancers were included in the oncology group. Patients with diagnoses not related to cancers were included in the non-oncology group. Patients of the Department of Endocrinology, Department of Cardiology, Department of Obstetrics & Gynecology and Department of Hematology were excluded from this study. Time of collection for TSH and FT4 was from 7am to 7 pm. Data were analyzed by morning (7am-12pm) and afternoon (12pm-7pm). Spearman correlation and non-linear fit were used for data analysis. Sex differences were analyzed as well in each group. RESULTS: Overall, an inverse correlation was observed between TSH and FT4 in both groups (non-oncology and oncology) regardless of sample collection time and sex differences. Further analysis by linear model in log TSH and FT4 showed a significant inverse fit in males compared with females in the group of oncology, both in the afternoon (p < 0.05). Data were further analyzed by ranges of FT4, as lower or higher (pathophysiology) or within (physiology) the reference interval of FT4. There was no statistical significance between the non-oncology and oncology groups, but relatively good correlation in non-oncology group in either physiologic or pathophysiologic FT4 levels and sample collection time. Interestingly, the best correlation between TSH and FT4 was found in the non-oncology group at pathophysiologic FT4 concentrations (abnormally high). In addition, at pathophysiologic FT4 concentrations (abnormally low), the oncology group demonstrated a significant TSH response in the morning than in the afternoon (p < 0.05). CONCLUSIONS: Though overall the TSH-FT4 curves showed an inverse relationship, there are variations of TSH-FT4 relationship for collection times when considering FT4 in physiologic or pathophysiologic states. The results advance understanding of TSH response, which is beneficial for the interpretation of thyroid disease. We recommend re-evaluation for interpretation of pituitary hypothalamic axis by TSH results when FT4 is abnormally high in oncology patients or low in non-oncology patients, due to poor predictability and the potential for misdiagnosis. A better understanding of the complex nature of the TSH-FT4 relationship may need further study with better defining subclinical states of cancer patients.


Asunto(s)
Neoplasias , Tirotropina , Embarazo , Humanos , Femenino , Masculino , Tiroxina , Pacientes Ambulatorios , Estudios Retrospectivos , Hormonas Tiroideas
2.
J Vasc Surg ; 77(6): 1669-1673.e1, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36781115

RESUMEN

OBJECTIVE: Since 2005, the United States Preventative Services Task Force has recommended abdominal aortic aneurysm (AAA) ultrasound screening for 65- to 75-year-old male ever-smokers. Integrated health systems such as Kaiser Permanente and the Veterans Affairs (VA) health care system report 74% to 79% adherence, but compliance rates in the private sector are unknown. METHODS: The IBM Marketscan Commercial and Medicare Supplemental databases (2006-2017) were queried for male ever-smokers continuously enrolled from age 65 to 75 years. Exclusion criteria were previous history of AAA, connective tissue disorder, and aortic surgery. Patients with abdominal computed tomographic or magnetic resonance imaging from ages 65 to 75 years were also excluded. Screening was defined as a complete abdominal, retroperitoneal, or aortic ultrasound. A logistic mixed-effects model utilizing state as a random intercept was used to identify patient characteristics associated with screening. RESULTS: Of 35,154 eligible patients, 13,612 (38.7%) underwent screening. Compliance varied by state, ranging from 24.4% in Minnesota to 51.6% in Montana (P < .05). Screening activity increased yearly, with 0.7% of screening activity occurring in 2008 vs 22.2% in 2016 (P <.05). In a logistic mixed-effects model adjusting for state as a random intercept, history of hypertension (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03-1.13), coronary artery disease (OR, 1.17; 95% CI, 1.10-1.22), congestive heart failure (OR, 1.14; 95% CI, 1.01-1.22), diabetes (OR, 1.1; 95% CI, 1.06-1.16), and chronic kidney disease (OR, 1.4; 95% CI, 1.24-1.53) were associated with screening. Living outside of a census-designated metropolitan area was negatively associated with screening (OR, 0.92; 95% CI, 0.87-0.97). CONCLUSIONS: In a private claims database representing 250 million claimants, 38.7% of eligible patients received United States Preventative Services Task Force-recommended AAA screening. Compliance was nearly one-half that of integrated health systems and was significantly lower for patients living outside of metropolitan areas. Efforts to improve early detection of AAA should include targeting non-metropolitan areas and modifying Medicare reimbursement and incentivization strategies to improve guideline adherence.


Asunto(s)
Aneurisma de la Aorta Abdominal , Enfermedad de la Arteria Coronaria , Humanos , Masculino , Estados Unidos , Anciano , Medicare , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , United States Department of Veterans Affairs , Tamizaje Masivo/métodos
3.
World J Urol ; 40(12): 2911-2918, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36357601

RESUMEN

PURPOSE: The risk of treatment-related toxicity is important for patients with localised prostate cancer to consider when deciding between treatment options. We developed a model to predict hospitalisation for radiation-induced genitourinary toxicity based on patient characteristics. METHODS: The prospective South Australian Prostate Cancer Clinical Outcomes registry was used to identify men with localised prostate cancer who underwent curative intent external beam radiotherapy (EBRT) between 1998 and 2019. Multivariable Cox proportional regression was performed. Model discrimination, calibration, internal validation and utility were assessed using C-statistics and area under ROC, calibration plots, bootstrapping, and decision curve analysis, respectively. RESULTS: There were 3,243 patients treated with EBRT included, of which 644 (20%) patients had a treated-related admission. In multivariable analysis, diabetes (HR 1.35, 95% CI 1.13-1.60, p < 0.001), smoking (HR 1.78, 95% CI 1.40-2.12, p < 0.001), and bladder outlet obstruction (BOO) without transurethral resection of prostate (TURP) (HR 7.49, 95% CI 6.18-9.08 p < 0.001) followed by BOO with TURP (HR 4.96, 95% CI 4.10-5.99 p < 0.001) were strong independent predictors of hospitalisation (censor-adjusted c-statistic = 0.80). The model was well-calibrated (AUC = 0.76). The global proportional hazards were met. In internal validation through bootstrapping, the model was reasonably discriminate at five (AUC 0.75) years after radiotherapy. CONCLUSIONS: This is the first study to develop a predictive model for genitourinary toxicity requiring hospitalisation amongst men with prostate cancer treated with EBRT. Patients with localised prostate cancer and concurrent BOO may benefit from TURP before EBRT.


Asunto(s)
Braquiterapia , Neoplasias de la Próstata , Traumatismos por Radiación , Resección Transuretral de la Próstata , Obstrucción del Cuello de la Vejiga Urinaria , Masculino , Humanos , Estudios Prospectivos , Australia , Neoplasias de la Próstata/cirugía , Traumatismos por Radiación/cirugía , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Hospitales , Braquiterapia/efectos adversos
4.
Poult Sci ; 101(9): 102038, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35921733

RESUMEN

Two experiments investigated broiler growth performance and processing characteristics when fed increasing Gly concentrations in reduced CP diets fed from 0 to 48 d. In experiment 1, birds were allocated to 1 of 4 dietary treatments: a control (CTL) diet containing feed-grade L-Met, L-Lys, and L-Thr, a reduced CP (RCP) diet with additions of feed-grade L-Val and L-Ile, or the RCP diet with moderate (M Gly) or high Gly (H Gly) inclusion levels to achieve a total Gly + Ser of 100 or 112%, respectively, of the CTL diet. Birds in experiment 2 were assigned to 1 of 6 dietary treatments: a CTL diet, a RCP diet, or a low CP (LCP) diet without or with added Gly to achieve 88, 100, 112, or 124% total Gly + Ser concentrations of the RCP diet. For experiment 1, 0 to 14 d broiler performance was similar (P > 0.05) among dietary treatments. From 0 to 48 d, broilers fed the H Gly diet had the lowest (P = 0.006) body weight gain (BWG) and highest (P = 0.003) feed conversion ratio (FCR). Feeding either the RCP or M Gly diet resulted in similar (P > 0.05) growth and processing characteristics to the CTL. For experiment 2, increasing Gly levels in the LCP diet linearly reduced (P ≤ 0.027) 0 to 14 d FI and FCR. From 0 to 48 d, broilers had similar (P > 0.05) performance when fed the CTL or RCP diet, but had a higher (P < 0.001) FCR when fed the LCP88 diet. Increasing Gly levels linearly reduced (P = 0.033) FCR. Total breast meat yield was negatively affected (P ≤ 0.020) when feeding the LCP88 diet and did not respond to Gly levels. In conclusion, effects of increasing total Gly + Ser levels on 0 to 48 d broiler performance are likely dependent on the content of dietary CP and other potentially interacting nutrients.


Asunto(s)
Pollos , Fabaceae , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta con Restricción de Proteínas/veterinaria , Suplementos Dietéticos , Glicina/metabolismo
5.
J Int Soc Sports Nutr ; 19(1): 150-163, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35599916

RESUMEN

It is well-established that appropriate hydration practices are essential in promoting health and optimizing performance and recovery. However, evidence-based hydration guidelines may not be adopted due to cultural differences across countries, such as religious beliefs, traditions, preferences, and beverage availability. Examples of hydration practices influenced by culture include beer consumption after sports in Western countries, consumption of sugarcane juice in India and Ramadan fasting among Muslims. For most cultural hydration practices, there is limited scientific evidence on their effects on rehydration, exercise performance, and recovery. Despite possible benefits of various hydration practices on exercise performance and recovery, they are inconsistent with current evidence-based hydration recommendations. More research on the impacts of cultural hydration differences on physiology, performance, and recovery is warranted to allow evidence-based guidelines and advisories. Abbreviations: ABV: alcohol by volume, ACSM: American College of Sports Medicine, NATA: National Athletic Trainers' Association, ROS: reactive oxygen species, TCM: Traditional Chinese Medicine.


Asunto(s)
Deportes , Ejercicio Físico/fisiología , Fluidoterapia , Humanos , Deportes/fisiología , Estados Unidos , Universidades
6.
Exp Physiol ; 107(10): 1122-1135, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35521757

RESUMEN

NEW FINDINGS: What is the topic of this review? The potential role of nutrition in exertional heat stroke. What advances does it highlight? Certain nutritional and dietary strategies used by athletes and workers may exert a protective effect the pathophysiological processes of exertional heat stroke, whereas others may be detrimental. While current evidence suggests that some of these practices may be leveraged as a potential countermeasure to exertional heat stroke, further research on injury-related outcomes in humans is required. ABSTRACT: Exertional heat stroke (EHS) is a life-threatening illness and an enduring problem among athletes, military servicemen and -women, and occupational labourers who regularly perform strenuous activity, often under hot and humid conditions or when wearing personal protective equipment. Risk factors for EHS and mitigation strategies have generally focused on the environment, health status, clothing, heat acclimatization and aerobic conditioning, but the potential role of nutrition is largely underexplored. Various nutritional and dietary strategies have shown beneficial effects on exercise performance and health and are widely used by athletes and other physically active populations. There is also evidence that some of these practices may dampen the pathophysiological features of EHS, suggesting possible protection or abatement of injury severity. Promising candidates include carbohydrate ingestion, appropriate fluid intake and glutamine supplementation. Conversely, some nutritional factors and low energy availability may facilitate the development of EHS, and individuals should be cognizant of these. Therefore, the aims of this review are to present an overview of EHS along with its mechanisms and pathophysiology, discuss how selected nutritional considerations may influence EHS risk focusing on their impact on the key pathophysiological processes of EHS, and provide recommendations for future research. With climate change expected to increase EHS risk and incidence in the coming years, further investigation on how diet and nutrition may be optimized to protect against EHS would be highly beneficial.


Asunto(s)
Glutamina , Golpe de Calor , Aclimatación , Carbohidratos , Ejercicio Físico , Femenino , Humanos
7.
Nutrients ; 13(1)2021 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-33467087

RESUMEN

Fructus lycii (F. lycii) is an exotic "berry-type" fruit of the plant Lycium barbarum that is characterized by a complex mixture of bioactive compounds distinguished by their high antioxidant potential. F. lycii is used in traditional Chinese home cooking and in the Chinese Pharmacopeia as an aid to vision and longevity as well as a remedy for diabetes to balance "yin" and "yang" in the body for about two centuries. Although a myriad of bioactive compounds have been isolated from F. lycii, polysaccharides, carotenoids, flavonoids, and phenolics represent the key functional components of F. lycii. F. lycii has been shown to exhibit a wide range of biological activities in experimental settings including antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects. Despite its medicinal role dating back to the eighteenth century in the Far East and robust evidence of beneficial effects on ocular health and retinal diseases originating mainly from studies in animal models, the role of F. lycii in the clinical management of retinal diseases is yet to be established. This article comprehensively reviews the literature germane to F. lycii and retinal diseases with particular emphasis on age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa, which are commonly seen in clinical practice.


Asunto(s)
Suplementos Dietéticos , Frutas , Lycium , Fitoterapia , Enfermedades de la Retina/dietoterapia , Animales , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Carotenoides/administración & dosificación , Carotenoides/aislamiento & purificación , Retinopatía Diabética/dietoterapia , Frutas/química , Humanos , Lycium/química , Degeneración Macular/dietoterapia , Retinitis Pigmentosa/dietoterapia
8.
Sci Rep ; 10(1): 15469, 2020 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-32963285

RESUMEN

Mechanical forces are important in the regulation of physiological homeostasis and the development of disease. The application of mechanical forces to cultured cells is often performed using specialized systems that lack the flexibility and throughput of other biological techniques. In this study, we developed a high throughput platform for applying complex dynamic mechanical forces to cultured cells. We validated the system for its ability to accurately apply parallel mechanical stretch in a 96 well plate format in 576 well simultaneously. Using this system, we screened for optimized conditions to stimulate increases in Oct-4 and other transcription factor expression in mouse fibroblasts. Using high throughput mechanobiological screening assays, we identified small molecules that can synergistically enhance the increase in reprograming-related gene expression in mouse fibroblasts when combined with mechanical loading. Taken together, our findings demonstrate a new powerful tool for investigating the mechanobiological mechanisms of disease and performing drug screening in the presence of applied mechanical load.


Asunto(s)
Reprogramación Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Embrión de Mamíferos/metabolismo , Células Madre Embrionarias/metabolismo , Fibroblastos/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Estrés Mecánico , Animales , Embrión de Mamíferos/citología , Embrión de Mamíferos/efectos de los fármacos , Células Madre Embrionarias/citología , Células Madre Embrionarias/efectos de los fármacos , Femenino , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Ensayos Analíticos de Alto Rendimiento , Masculino , Ratones
9.
Biofouling ; 35(8): 870-882, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31603038

RESUMEN

Steel marine structures provide foci of biodiversity when they develop into artificial reefs. Development begins with deposition of a biofilm. The effects of contaminants from oil spills on biofilm microbiomes, microbially-induced corrosion (MIC) and metal loss may impact preservation of marine metal structures. A microcosm experiment exposed biofilms on carbon steel disks (CSDs) to crude oil, dispersant, and dispersed oil to address their impacts on bacterial composition and metal loss and pitting. Biofilm diversity increased over time in all exposures. Community composition in dispersant and dispersed oil treatments deviated from the controls for the duration of a 12-week experiment. As biofilms matured, Pseudomonadaceae increased while Rhodobacteraceae decreased in abundance in dispersed oil treatments compared to the controls and dispersant treatments. Greatest mass loss and deepest pitting on CSDs were observed in dispersed oil treatments, suggesting impacts manifest as a consequence of increased MIC potential on carbon steel.


Asunto(s)
Biopelículas/efectos de los fármacos , Materiales Manufacturados/microbiología , Microbiota/efectos de los fármacos , Contaminación por Petróleo/efectos adversos , Proteobacteria/efectos de los fármacos , Acero , Biodiversidad , Biopelículas/crecimiento & desarrollo , Carbono/química , Corrosión , Petróleo/análisis , Petróleo/toxicidad , Contaminación por Petróleo/análisis , Proteobacteria/clasificación , Proteobacteria/aislamiento & purificación , ARN Ribosómico 16S/genética , Acero/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
10.
J Altern Complement Med ; 25(5): 475-502, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30892910

RESUMEN

Objectives: Massage therapy has been proposed for painful conditions, but it can be difficult to understand the breadth and depth of evidence, as various painful conditions may respond differently to massage. The authors conducted an evidence mapping process and generated an "evidence map" to visually depict the distribution of evidence available for massage and various pain indications to identify gaps in evidence and to inform future research priorities. Design: The authors searched PubMed, Embase, and Cochrane for systematic reviews reporting pain outcomes for massage therapy. The authors assessed the quality of each review using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) criteria. The authors used a bubble plot to depict the number of included articles, pain indication, effect of massage for pain, and strength of findings for each included systematic review. Results: The authors identified 49 systematic reviews, of which 32 were considered high quality. Types of pain frequently included in systematic reviews were cancer pain, low back pain, and neck pain. High quality reviews concluded that there was low strength of evidence of potential benefits of massage for labor, shoulder, neck, low back, cancer, arthritis, postoperative, delayed onset muscle soreness, and musculoskeletal pain. Reported attributes of massage interventions include style of massage, provider, co-interventions, duration, and comparators, with 14 high-quality reviews reporting all these attributes in their review. Conclusion: Prior reviews have conclusions of low strength of evidence because few primary studies of large samples with rigorous methods had been conducted, leaving evidence gaps about specific massage type for specific pain. Primary studies often do not provide adequate details of massage therapy provided, limiting the extent to which reviews are able to draw conclusions about characteristics such as provider type.


Asunto(s)
Masaje , Manejo del Dolor/métodos , Humanos , Revisiones Sistemáticas como Asunto
11.
J Chem Phys ; 149(20): 204313, 2018 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-30501230

RESUMEN

The photodissociation dynamics of CH3I and CH2ClI at 272 nm were investigated by time-resolved Coulomb explosion imaging, with an intense non-resonant 815 nm probe pulse. Fragment ion momenta over a wide m/z range were recorded simultaneously by coupling a velocity map imaging spectrometer with a pixel imaging mass spectrometry camera. For both molecules, delay-dependent pump-probe features were assigned to ultraviolet-induced carbon-iodine bond cleavage followed by Coulomb explosion. Multi-mass imaging also allowed the sequential cleavage of both carbon-halogen bonds in CH2ClI to be investigated. Furthermore, delay-dependent relative fragment momenta of a pair of ions were directly determined using recoil-frame covariance analysis. These results are complementary to conventional velocity map imaging experiments and demonstrate the application of time-resolved Coulomb explosion imaging to photoinduced real-time molecular motion.

12.
ChemSusChem ; 10(10): 2192-2201, 2017 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-28388018

RESUMEN

Oxide-supported amine materials are widely known to be effective CO2 sorbents under simulated flue-gas and direct-air-capture conditions. Most work has focused on amine species loaded onto porous silica supports, though potential stability advantages may be offered through the use of porous alumina supports. Unlike silica materials, which are comparably inert, porous alumina materials can be tuned to have substantial acidity and/or basicity. Owing to their amphoteric nature, alumina supports play a more active role in CO2 sorption than silica supports, potentially directly participating in the adsorption process. In this work, primary amines associated with 3-aminopropyltriethoxysilane are grafted onto two different mesoporous alumina materials having different levels of basicity. Adsorbent materials with different amine loadings are prepared, and the CO2 -adsorption behavior of similar amines on the two alumina supports is demonstrated to be different. At low amine loadings, the inherent properties of the support surface play a significant role, whereas at high amine loadings, when the alumina surface is effectively blocked, the sorbents prepared on the two supports behave similarly. At high amine loadings, amine-CO2 -amine interactions are shown to dominate, leading to adsorbed species that appear similar to the species formed over silica-supported amine materials. The sorbent properties are comprehensively characterized using N2 physisorption analysis, in situ FTIR spectroscopy, and adsorption microcalorimetry.


Asunto(s)
Óxido de Aluminio/química , Dióxido de Carbono/química , Dióxido de Silicio/química , Adsorción , Calorimetría , Difracción de Polvo , Espectroscopía Infrarroja por Transformada de Fourier
13.
Eur J Pharm Biopharm ; 117: 286-291, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28411056

RESUMEN

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied as potential carriers for both dermal and transdermal drug delivery. SLN contain lipid droplets that are fully crystallized and have a highly-ordered crystalline structure. NLC are modified SLN in which the lipid phase contains both solid and liquid lipids at room temperature. SLN and NLC are thought to combine the advantages of polymeric particles, liposomes and emulsions. Therefore they provide high encapsulation percentages, better protection for incorporated actives and allow for control of desired release profile. In this work, Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent antioxidants known to provide protection to the skin, were formulated into lipid nanoparticles. Several different formulations were successfully developed and demonstrated high uniformity and stability. Both resveratrol and VE lipid nanoparticles provided effective protection of actives against UV induced degradation. However, lipid nanoparticles did not show protection from UV degradation for EGCG in this work. An active release study exhibited a sustained release of resveratrol over 70% after 24h. Skin penetration studies showed that lipid nanoparticles directionally improved the penetration of resveratrol through the stratum corneum. Our findings suggest that lipid nanoparticles are promising viable carriers for the delivery of resveratrol and VE to provide longlasting antioxidant benefits to the skin.


Asunto(s)
Catequina/análogos & derivados , Nanopartículas/metabolismo , Cuidados de la Piel/métodos , Piel/metabolismo , Estilbenos/metabolismo , Vitamina E/metabolismo , Catequina/administración & dosificación , Catequina/síntesis química , Catequina/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Femenino , Humanos , Metabolismo de los Lípidos , Lípidos/administración & dosificación , Lípidos/química , Persona de Mediana Edad , Nanopartículas/administración & dosificación , Nanopartículas/química , Técnicas de Cultivo de Órganos , Resveratrol , Piel/efectos de los fármacos , Estilbenos/administración & dosificación , Estilbenos/síntesis química , Vitamina E/administración & dosificación , Vitamina E/síntesis química
14.
Eur J Nucl Med Mol Imaging ; 43(12): 2122-2130, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27329046

RESUMEN

PURPOSE: The aim of this study was to synthesize and preclinically evaluate an 18F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined. METHODS: Several conditions for the labeling of 18F-PSMA-11 via 18F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed. RESULTS: Quantitative labeling yields could be achieved with >97 % radiochemical purity. The 18F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4 ± 3.3 %ID/g and 0.795 ± 0.260 %ID/g, respectively; p < 4.2e-5). Results were confirmed by ex vivo gamma counter analysis of tissues after the last imaging time point. The highest absorbed dose was reported for the kidneys. The maximum effective dose for an administered activity of 200 MBq was 1.72 mSv. CONCLUSION: 18F-PSMA-11 using direct labeling of chelate-attached peptide with aluminum-fluoride detected PSMA-expressing tumors with high tumor-to-liver ratios. The kidneys were the dose-limiting organs. Even by applying the most stringent dosimetric calculations, injected activities of up to 0.56 GBq are feasible.


Asunto(s)
Antígenos de Superficie/metabolismo , Biomarcadores de Tumor/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Compuestos Organometálicos/farmacocinética , Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/metabolismo , Exposición a la Radiación/análisis , Animales , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Ácido Edético/análogos & derivados , Radioisótopos de Flúor/farmacocinética , Isótopos de Galio , Radioisótopos de Galio , Marcaje Isotópico/métodos , Masculino , Tasa de Depuración Metabólica , Ratones , Ratones Endogámicos C57BL , Oligopéptidos , Especificidad de Órganos , Compuestos Organometálicos/síntesis química , Neoplasias de la Próstata/diagnóstico por imagen , Dosis de Radiación , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución Tisular , Recuento Corporal Total
15.
Blood ; 127(21): 2575-86, 2016 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-26941401

RESUMEN

Herein we demonstrate that oncolytic herpes simplex virus-1 (HSV-1) potently activates human peripheral blood mononuclear cells (PBMCs) to lyse leukemic cell lines and primary acute myeloid leukemia samples, but not healthy allogeneic lymphocytes. Intriguingly, we found that UV light-inactivated HSV-1 (UV-HSV-1) is equally effective in promoting PBMC cytolysis of leukemic cells and is 1000- to 10 000-fold more potent at stimulating innate antileukemic responses than UV-inactivated cytomegalovirus, vesicular stomatitis virus, reovirus, or adenovirus. Mechanistically, UV-HSV-1 stimulates PBMC cytolysis of leukemic cells, partly via Toll-like receptor-2/protein kinase C/nuclear factor-κB signaling, and potently stimulates expression of CD69, degranulation, migration, and cytokine production in natural killer (NK) cells, suggesting that surface components of UV-HSV-1 directly activate NK cells. Importantly, UV-HSV-1 synergizes with interleukin-15 (IL-15) and IL-2 in inducing activation and cytolytic activity of NK cells. Additionally, UV-HSV-1 stimulates glycolysis and fatty acid oxidation-dependent oxygen consumption in NK cells, but only glycolysis is required for their enhanced antileukemic activity. Last, we demonstrate that T cell-depleted human PBMCs exposed to UV-HSV-1 provide a survival benefit in a murine xenograft model of human acute myeloid leukemia (AML). Taken together, our results support the preclinical development of UV-HSV-1 as an adjuvant, alone or in combination with IL-15, for allogeneic donor mononuclear cell infusions to treat AML.


Asunto(s)
Herpesvirus Humano 1/inmunología , Inmunidad Celular , Células Asesinas Naturales/inmunología , Leucemia/inmunología , Rayos Ultravioleta , Inactivación de Virus/efectos de la radiación , Degranulación de la Célula/inmunología , Movimiento Celular/inmunología , Femenino , Humanos , Interleucina-15/inmunología , Interleucina-2/inmunología , Células Jurkat , Masculino , FN-kappa B/inmunología , Proteína Quinasa C/inmunología , Transducción de Señal/inmunología , Receptor Toll-Like 2/inmunología
16.
Perspect Psychol Sci ; 9(2): 161-79, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25544856

RESUMEN

Mental disorders are prevalent and can lead to significant impairment. Some progress has been made toward establishing treatments; however, effect sizes are small to moderate, gains may not persist, and many patients derive no benefit. Our goal is to highlight the potential for empirically supported psychosocial treatments to be improved by incorporating insights from cognitive psychology and research on education. Our central question is: If it were possible to improve memory for the content of sessions of psychosocial treatments, would outcome substantially improve? We leverage insights from scientific knowledge on learning and memory to derive strategies for transdiagnostic and transtreatment cognitive support interventions. These strategies can be applied within and between sessions and to interventions delivered via computer, the Internet, and text message. Additional novel pathways to improving memory include improving sleep, engaging in exercise, and using imagery. Given that memory processes change across the lifespan, services to children and older adults may benefit from different types and amounts of cognitive support.

17.
Appl Environ Microbiol ; 80(3): 943-50, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24271165

RESUMEN

Probiotics have been demonstrated to promote growth, stimulate immune responses, and improve food safety of poultry. While widely used, their effectiveness is mixed, and the mechanisms through which they contribute to poultry production are not well understood. Microbial phytases are increasingly supplemented in feed to improve digestibility and reduce antinutritive effects of phytate. The microbial origin of these exogenous enzymes suggests a potentially important mechanism of probiotic functionality. We investigated phytate degradation as a novel probiotic mechanism using recombinant Lactobacillus cultures expressing Bacillus subtilis phytase. B. subtilis phyA was codon optimized for expression in Lactobacillus and cloned into the expression vector pTRK882. The resulting plasmid, pTD003, was transformed into Lactobacillus acidophilus, Lactobacillus gallinarum, and Lactobacillus gasseri. SDS-PAGE revealed a protein in the culture supernatants of Lactobacillus pTD003 transformants with a molecular weight similar to that of the B. subtilis phytase. Expression of B. subtilis phytase increased phytate degradation of L. acidophilus, L. gasseri, and L. gallinarum approximately 4-, 10-, and 18-fold over the background activity of empty-vector transformants, respectively. Phytase-expressing L. gallinarum and L. gasseri were administered to broiler chicks fed a phosphorus-deficient diet. Phytase-expressing L. gasseri improved weight gain of broiler chickens to a level comparable to that for chickens fed a control diet adequate in phosphorus, demonstrating proof of principle that administration of phytate-degrading probiotic cultures can improve performance of livestock animals. This will inform future studies investigating whether probiotic cultures are able to provide both the performance benefits of feed enzymes and the animal health and food safety benefits traditionally associated with probiotics.


Asunto(s)
6-Fitasa/genética , 6-Fitasa/metabolismo , Lactobacillus/enzimología , Lactobacillus/metabolismo , Ácido Fítico/metabolismo , Probióticos/administración & dosificación , Animales , Bacillus subtilis/enzimología , Bacillus subtilis/genética , Peso Corporal , Pollos/crecimiento & desarrollo , Clonación Molecular , Expresión Génica , Lactobacillus/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
18.
Eur J Appl Physiol ; 114(2): 375-84, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24318656

RESUMEN

PURPOSE: To assess the efficacy of neck cooling on cognitive performance following exertional hyperthermia. METHODS: Twelve healthy men completed two experimental trials [control (CON) and neck cooling collar (NCC)] in a counter-balanced design. They ran on a treadmill at 70% VO2peak under warm and humid conditions (dry bulb temperature: 30.2 ± 0.3 °C, relative humidity: 71 ± 2 %) for 75 min or until volitional exhaustion. Gastrointestinal, neck and skin temperatures, heart rate and subjective ratings were assessed. Serum brain-derived neurotrophic factor (BDNF) levels were measured before and after each run. Cognitive performance comprising symbol digit matching, search and memory, digit span, choice reaction time and psychomotor vigilance test (PVT) were assessed before and after exercise. RESULTS: Mean gastrointestinal temperature was similar after exercise between trials (CON: 39.5 ± 0.4 °C vs. NCC: 39.6 ± 0.3 °C; p = 0.15). Mean neck temperature was lowered in NCC compared to CON after the run (36.4 ± 1.6 °C vs. NCC: 26.0 ± 0.3 °C; p < 0.001). Exercise-induced hyperthermia improved mean reaction time in the symbol digit matching test (-134 ± 154 ms; p < 0.05) and the PVT (-18 ± 30 ms; p < 0.05). Maximum span was increased in the digit span test (1 ± 2; p < 0.05). Application of NCC reduced the number of search errors made in level 3 of the search and memory test (p < 0.05). Mean serum BDNF levels were increased following exercise-induced hyperthermia in both trials (p < 0.05). CONCLUSION: Exercise-induced hyperthermia improves working memory and alertness. Neck cooling may only enhance performance in tasks of higher complexity.


Asunto(s)
Temperatura Corporal , Cognición , Ejercicio Físico , Hipotermia Inducida , Cuello/fisiología , Adulto , Factor Neurotrófico Derivado del Encéfalo/sangre , Estudios de Casos y Controles , Frecuencia Cardíaca , Humanos , Hipertermia Inducida , Masculino , Memoria , Consumo de Oxígeno , Desempeño Psicomotor
19.
J Nanosci Nanotechnol ; 11(5): 4153-7, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21780419

RESUMEN

The cytotoxic enhancement of cisplatin by magnetic fluid hyperthermia (MFH) was investigated in human colon adenocarcinoma cells (Caco-2). A nanoparticle platform based on iron oxide functionalized with carboxymethyl dextran was employed to produce heat at the nanoscale. To assess the synergistic effect of hyperthermia and the anticancer drug cis-Diamminedichloroplatinum, commonly known as cisplatin (CIS), cell viability was measured 24, 48, and 72 hours after three different combined hyperthermia and CIS exposure sequences. These included CIS incubation prior to hyperthermia or magnetic fluid hyperthermia, CIS exposure only during hyperthermia or MFH, and additional CIS incubation following hyperthermia or MFH. Additional incubation of CIS after hyperthermia treatment appears to be more effective than prior CIS incubation for both hyperthermia treatments. Viability data also indicated that MFH combined with CIS is significantly more effective than hot water hyperthermia at the same temperature. A CIS concentration an order of magnitude lower than the calculated IC50 was found to be very effective in reducing cell viability. Such dramatic differences suggest that MFH may enhance the passive transport of CIS.


Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , Hipertermia Inducida , Magnetismo , Nanopartículas , Células CACO-2 , Humanos
20.
Cancer Biol Ther ; 10(8): 814-23, 2010 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-20703095

RESUMEN

Phaleria macrocarpa, also known as Mahkota dewa, is an Indonesian native plant that has been used as a remedy for many diseases. However, the molecular mechanism of Phaleria macrocarpa is still limited. In this study, we evaluate its molecular mechanism using a bioactivity-guided DLBS1425, an extract of Phaleria macrocarpa on MDA-MB-231 breast cancer cell line. DLBS1425 exhibited inhibition of proliferative, migratory and invasive potential of MDA-MB-231 in a dose-dependent manner, and significantly reduced phosphoinositide-3 (PI3)-kinase/protein kinase B (AKT) signalling by reducing PI3K transcript level and subsequent reduction in AKT phosphorylation. Further, it induced pro-apoptotic genes including BAX, BAD and PUMA and consequently induces cellular death signal by caspase-9 activation, promoting PARP cleavage and DNA fragmentation. Our results suggest that DLBS1425 is a potential anticancer agent which targets genes involved in both cell survival and apoptosis in MDA-MB-231 breast cancer cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Thymelaeaceae/química , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Ciclo Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Femenino , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HCT116 , Células Hep G2 , Humanos , Immunoblotting , Estructura Molecular , Fosfatidilinositol 3-Quinasas/genética , Fosforilación/efectos de los fármacos , Extractos Vegetales/química , Proteínas Proto-Oncogénicas c-akt/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
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