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1.
J Biol Regul Homeost Agents ; 30(4): 1115-1123, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28078862

RESUMEN

There is an ever growing emergence in the popularity of patient-driven care. As this health and wellness model grows, inquiries into diet, lifestyle, and supplemental approaches will continue to become a focal point for the healthcare consumer. Because of this, the aim of this study is to determine the tolerability, and overall effectiveness of a proprietary multi-ingredient lipid-lowering supplement in subjects with dyslipidemia. Forty participants were recruited for a single-center, double-blind randomized, placebocontrolled trial. Study participants were recruited between December 2014 and March 2015. Initial screening included a physical examination, renal and hepatic function, serum lipid, serum electrolytes, complete blood counts, and urine analysis. The 40 participants were randomly assigned to receive either the proprietary multi-ingredient lipid-lowering supplement (PMILLS) n= 20 or placebo n= 20. The trial consisted of a screening visit, a two-week run-in, and a four-month treatment period. Samples were taken at baseline, one month and four months of treatment. Results from the trial showed that the PMILLS significantly reduced total cholesterol (TC), low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C), oxidized LDL (oxLDL), Apo-lipoprotein B, triglycerides (TG), LDL particle number (LDL-P), heart rate, and diastolic blood pressure compared to placebo at one month and four months. The PMILLS significantly increased high density lipoprotein (HDL) particle number (HDL-P), and low density lipoprotein (LDL) particle size from dense type III and IV to larger type I and II LDL particle, compared to placebo at one month and four months. In addition, the PMILLS significantly reduced high sensitivity C-reactive protein (hs-CRP), tumor necrosis alpha (TNF-α), and interleukin 6 (IL-6) within the treatment group from baseline. There were no adverse effects noted in the treatment group after four months of supplementation. The present study demonstrates this PMILLS improves all relevant lipid parameters, such as particle numbers and particles sizes, as well as showing a significant reduction in inflammatory markers linked to cardiovascular health. With such combined changes in lipids, lipid sub-fractions, and inflammation, which are considered among the most effective means of reducing coronary heart disease (CHD), this PMILLS represents a new addition to safe and effective lipid-modifying strategies.


Asunto(s)
Suplementos Dietéticos , Dislipidemias/tratamiento farmacológico , Adulto , Anciano , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos/sangre
2.
N Z Vet J ; 61(3): 174-6, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23227890

RESUMEN

AIMS: To undertake disease surveillance for Chlamydia psittaci in native birds as part of a pilot study to examine pathogen diversity on Hauturu-o-Toi/Little Barrier Island. To retrospectively review the Massey University post-mortem database to determine previous cases of avian chlamydiosis in New Zealand. METHODS: Mistnetting of forest birds was conducted across an elevational gradient on Hauturu-o-Toi/Little Barrier Island. Minitip culture swabs were used to collect cloacal samples from native birds. These swabs were screened for Chlamydia family DNA using two PCR methods. Positive results were sequenced. A retrospective review of the Massey University post-mortem database of all avian cases from 1990 to 2011 was conducted. RESULTS: Ten native birds including four bellbirds (Anthornis melanura), three rifleman (Acanthisitta chloris), two hihi (Notiomyces cincta), and one whitehead (Mohoua albicilla) were sampled and one otherwise healthy female hihi was positive by both PCR screening methods for Chlamydophila. Sequencing confirmed 99-100% genetic similarity to C. psittaci. A retrospective review of the Massey University post-mortem database revealed no previous diagnoses of avian chlamydiosis in wild native New Zealand birds although it has been detected in captive parrots, and wild and captive exotic pigeons. CONCLUSIONS: This is the first report of the detection of C. psittaci from a wild native bird in New Zealand. The bird was a Passeriforme from an endangered species that was captured free-living on Little Barrier Island. The incidence of avian chlamydiosis in native birds in New Zealand appears to be very low, based on the retrospective review of the post-mortem database. CLINICAL RELEVANCE: It is unlikely that avian chlamydiosis is a significant problem for hihi population health. The detection of this organism has greater significance for other more susceptible species on Little Barrier Island and for human health, particularly for conservation workers involved in wildlife translocations. It further suggests that passerine birds may be a reservoir for C. psittaci in New Zealand ecosystems.


Asunto(s)
Infecciones por Chlamydophila/veterinaria , Chlamydophila psittaci/aislamiento & purificación , Passeriformes , Animales , Animales Salvajes , Infecciones por Chlamydophila/epidemiología , Chlamydophila psittaci/genética , Cloaca/microbiología , ADN Bacteriano/aislamiento & purificación , Nueva Zelanda/epidemiología , Reacción en Cadena de la Polimerasa/veterinaria
3.
West Indian Med J ; 61(3): 271-9, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23155986

RESUMEN

Standard drug monographs (SDMs) have been described as deficient in providing information in a manner simplified enough for patient reading. The aim of this study was to design patient information leaflets for hydrochlorothiazide, nifedipine and enalapril with content indicated by patients as relevant and to evaluate them against the SDM. Patient information leaflet (PIL) for each drug was designed to contain information on name, use of drug, how it works, how it is to be taken, common side effects, storage, missed dose action, things to avoid and when to contact the physician. Appropriateness was assessed by 10 practising pharmacists. For each drug, 40 patients were recruited, of which 20 were given SDM and 20 PIL. The knowledge of each participant was examined before and after exposure to SDM or PIL, as well as opinion on ease of reading and attractiveness using Pearson s Chi-square analysis. The results showed that both SDM and PIL improved knowledge of common side effects when compared with responses before exposure (chi2 = 24.26 for SDM and 27.64 for PIL, p < 0.001) with no difference between the groups. Respondents receiving PILs were better able to recall "things to avoid" after exposure to PIL (chi2 =10.85, p < 0.001). After exposure to SDM or PIL, the respondents who received PIL were more aware of when to contact the physician, compared to the SDM group (chi2 = 8.41, p < 0.01). When compared with SDM, respondents receiving PIL were more likely to indicate that PIL was easy to read (chi2 = 20.00, p < 0.001), attractive (chi2 = 12.45, p < 0.001) and they were more likely to recommend distribution of their reading material to other patients (chi2 = 22.11, p < 0.001). We conclude that there is benefit in designing information leaflets that simplify language and medication information contained in SDMs, including better understanding of precautions to take while on medication and when to consult physicians.


Asunto(s)
Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Diuréticos/uso terapéutico , Etiquetado de Medicamentos , Enalapril/uso terapéutico , Hidroclorotiazida/uso terapéutico , Nifedipino/uso terapéutico , Folletos , Educación del Paciente como Asunto , Prioridad del Paciente , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Diuréticos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad
4.
West Indian med. j ; 61(3): 271-279, June 2012. ilus, tab
Artículo en Inglés | LILACS | ID: lil-672899

RESUMEN

Standard drug monographs (SDMs) have been described as deficient in providing information in a manner simplified enough for patient reading. The aim of this study was to design patient information leaflets for hydrochlorothiazide, nifedipine and enalapril with content indicated by patients as relevant and to evaluate them against the SDM. Patient information leaflet (PIL) for each drug was designed to contain information on name, use of drug, how it works, how it is to be taken, common side effects, storage, missed dose action, things to avoid and when to contact the physician. Appropriateness was assessed by 10 practising pharmacists. For each drug, 40 patients were recruited, of which 20 were given SDM and 20 PIL. The knowledge of each participant was examined before and after exposure to SDM or PIL, as well as opinion on ease of reading and attractiveness using Pearson's Chi-square analysis. The results showed that both SDM and PIL improved knowledge of common side effects when compared with responses before exposure (χ² = 24.26for SDM and 27.64 for PIL, p < 0.001) with no difference between the groups. Respondents receiving PILs were better able to recall "things to avoid" after exposure to PIL (χ² =10.85, p < 0.001). After exposure to SDM or PIL, the respondents who received PIL were more aware of when to contact the physician, compared to the SDM group (χ² = 8.41, p < 0.01). When compared with SDM, respondents receiving PIL were more likely to indicate that PIL was easy to read (χ² = 20.00, p < 0.001), attractive (χ² = 12.45, p < 0.001) and they were more likely to recommend distribution of their reading material to other patients (χ² = 22.11, p < 0.001). We conclude that there is benefit in designing information leaflets that simplify language and medication information contained in SDMs, including better understanding of precautions to take while on medication and when to consult physicians.


Las monografías de medicamentos estandarizadas se han considerado deficientes a la hora de proporcionar información de manera suficientemente simple para que el paciente pueda entenderlas. El objetivo de este estudio fue disenar prospectos con información sobre la hidroclorotiazida, la nifedipina y el analapril con contenidos indicados como relevantes por los pacientes, y evaluarlos en comparación con las monografías estandarizadas de medicamentos (MEM). El prospecto de información para el paciente (PIP) fue disenado de modo que apareciera información sobre el nombre del medicamento, su uso, modo de operar, manera de tomarse, efectos secundarios comunes, almacenamiento, qué hacer en caso de perder una dosis, cosas que deben evitarse, y cuando debe contactarse el médico. Se evaluó la adecuación por parte de 10 farmacéuticos practicantes. Para cada medicamento, se reclutaron 40 pacientes, a 20 de los cuales se les dio monografías (MEM), en tanto que a 20 se les ofreció prospectos (PIP). El conocimiento de cada participante se examinó antes y después de la exposición a MEM o PIP, así como la opinión en cuanto a facilidad de lectura y grado de atracción, usando el análisis del Chi-cuadrado de Pearson. Los resultados mostraron que tanto MEM como PIP mejoraron el conocimiento sobre los efectos secundarios comunes, cuando se hacía una comparación con las respuestas antes de la exposición (χ² = 24.26para MEMy 27.64para PIP, p < 0.001) sin diferencia entre los grupos. Los encuestados que recibieron prospectos pudieron recordar mejor las "cosas a evitar" luego de la exposición a PIP (χ² =10.85, p < 0.001). Después de la exposición a MEM o PIP, los encuestados con PIP tenían mayor conciencia en cuanto a cuando contactar a un médico, en comparación con el grupo MEM (χ² = 8.41, p < 0.01). Cuando se les comparó con el grupo MEM, los encuestados que recibieron PIP mostraron por una parte mayor probabilidad de indicar que PIP era más fácil de leer (χ² = 20.00, p < 0.001) y atractivo (χ² = 12.45, p < 0.001), y por otra, una mayor tendencia a recomendar la distribución de su material de lectura a otros pacientes (χ² = 22.11, p < 0.001). Se llegó a la conclusión de que es beneficioso disenar prospectos que simplifiquen el lenguajey la información médica contenida en las monografias estándar del medicamento, incluyendo una mejor comprensión de las precauciones a tomar mientras se está bajo medicación, y sobre cuándo consultar al médico.


Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Diuréticos/uso terapéutico , Etiquetado de Medicamentos , Enalapril/uso terapéutico , Hidroclorotiazida/uso terapéutico , Nifedipino/uso terapéutico , Folletos , Educación del Paciente como Asunto , Prioridad del Paciente , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Diuréticos/efectos adversos
5.
Br J Radiol ; 84 Spec No 1: S70-8, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22374550

RESUMEN

The aim of this study was to display malignant induction probability (MIP) maps alongside dose distribution maps for radiotherapy using X-ray and charged particles such as protons. Dose distributions for X-rays and protons are used in an interactive MATLAB® program (MathWorks, Natick, MA). The MIP is calculated using a published linear quadratic model, which incorporates fractionation effects, cell killing and cancer induction as a function of dose, as well as relative biological effect. Two virtual situations are modelled: (a) a tumour placed centrally in a cubic volume of normal tissue and (b) the same tumour placed closer to the skin surface. The MIP is calculated for a variety of treatment field options. The results show that, for protons, the MIP increases with field numbers. In such cases, proton MIP can be higher than that for X-rays. Protons produce the lowest MIPs for superficial targets because of the lack of exit dose. The addition of a dose bath to all normal tissues increases the MIP by up to an order of magnitude. This exploratory study shows that it is possible to achieve three-dimensional displays of carcinogenesis risk. The importance of treatment geometry, including the length and volume of tissue traversed by each beam, can all influence MIP. Reducing the volume of tissue irradiated is advantageous, as reducing the number of cells at risk reduces the total MIP. This finding lends further support to the use of treatment gantries as well as the use of simpler field arrangements for particle therapy provided normal tissue tolerances are respected.


Asunto(s)
Modelos Biológicos , Neoplasias Inducidas por Radiación/etiología , Terapia de Protones , Protones/efectos adversos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada , Animales , Iones Pesados , Humanos , Transferencia Lineal de Energía , Probabilidad , Dosificación Radioterapéutica , Efectividad Biológica Relativa , Rayos X
6.
J Sports Med Phys Fitness ; 51(4): 583-94, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22212260

RESUMEN

AIM: There are numerous variables that can impact a triathletes' performance. Research with this population has primarily focused on physical training habits to determine performance predictors, thus the purpose of this study was to explore the impact of nutritional and mental preparation strategies in addition to physical training on race times of Olympic-distance triathletes. METHODS: Triathletes were asked to complete an online survey that focused on physical conditioning, nutritional habits, mental training, and educational experience related to triathlon training. Participants included 272 age-group triathletes (146 males, 126 females). ANOVAs and MANOVAs were conducted to identify variables that significantly related to race time, while a logistic regression was used to determine variables that predicted performance. RESULTS: Race time was predicted by competitive motivation to participate, participation in strength training, and use of intervals during run and swim training. Mental strategies that predicted faster race times included pre-competition routines, use of energizing strategies before a race, and setting outcome goals for races. Nutritional habits did not have an impact on race time. CONCLUSION: The results support the need to go beyond investigating physical training preparation.


Asunto(s)
Rendimiento Atlético/fisiología , Rendimiento Atlético/psicología , Dieta , Procesos Mentales , Entrenamiento de Fuerza , Adulto , Ciclismo/fisiología , Ciclismo/psicología , Conducta Competitiva , Suplementos Dietéticos , Femenino , Objetivos , Humanos , Masculino , Persona de Mediana Edad , Educación y Entrenamiento Físico , Carrera/fisiología , Carrera/psicología , Encuestas y Cuestionarios , Natación/fisiología , Natación/psicología
8.
Am J Physiol Endocrinol Metab ; 297(6): E1395-413, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19843876

RESUMEN

The adipocyte-specific protein FSP27, also known as CIDEC, is one of three cell death-inducing DFF45-like effector (CIDE) proteins. The first known function for CIDEs was promotion of apoptosis upon ectopic expression in mammalian cells. Recent studies in endogenous settings demonstrated key roles for CIDEs in energy metabolism. FSP27 is a lipid droplet-associated protein whose heterologous expression enhances formation of enlarged lipid droplets and is required for unilocular lipid droplets typical of white adipocytes in vivo. Here, we delineate relationships between apoptotic function and lipid droplet localization of FSP27. We demonstrate that ectopic expression of FSP27 induces enlarged lipid droplets in multiple human cell lines, which is indicative that its mechanism involves ubiquitously present, rather than adipocyte-specific, cellular machinery. Furthermore, promotion of lipid droplet formation in HeLa cells via culture in exogenous oleic acid offsets FSP27-mediated apoptosis. Using transient cotransfections and analysis of lipid droplets in HeLa cells stably expressing FSP27, we show that FSP27 does not protect lipid droplets from action of ATGL lipase. Domain mapping with eGFP-FSP27 deletion constructs indicates that lipid droplet localization of FSP27 requires amino acids 174-192 of its CIDE C domain. The apoptotic mechanism of FSP27, which we show involves caspase-9 and mitochondrial cytochrome c, also requires this 19-amino acid region. Interaction assays determine the FSP27 CIDE C domain complexes with CIDEA, and Western blot reveals that FSP27 protein levels are reduced by coexpression of CIDEA. Overall, our findings demonstrate the function of the FSP27 CIDE C domain and/or regions thereof for apoptosis, lipid droplet localization, and CIDEA interaction.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis/fisiología , Caspasas/metabolismo , Metabolismo de los Lípidos/fisiología , Animales , Western Blotting , Células COS , Línea Celular , Chlorocebus aethiops , Citocromos c/metabolismo , Fragmentación del ADN , Dimerización , Metabolismo Energético , Células HeLa , Humanos , Inmunohistoquímica , Lipasa/biosíntesis , Lipasa/metabolismo , Relación Estructura-Actividad , Técnicas del Sistema de Dos Híbridos
9.
Evid Based Complement Alternat Med ; 4(4): 455-62, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18227913

RESUMEN

Because micronutrients from plants may have beneficial cardiovascular effects, the hypothesis that an encapsulated juice powder concentrate might affect several measures of vascular health was tested in free living adults at low cardiovascular risk. Blood pressure, vascular compliance, lipid and antioxidant markers, and serial electron beam tomography (to calculate a coronary artery calcium score as a measure of atherosclerosis burden), were monitored in 51 pre-hypertensive and hypertensive subjects over 2 years. By the end of follow-up, systolic and diastolic blood pressure decreased significantly (-2.4 +/- 1.0 mmHg, P < 0.05 and -2.2 +/- 0.6 mmHg, P < 0.001), and large artery compliance improved significantly (1.9 +/- 0.6 ml mmHg(-1) x 100, P < 0.01). The progression of coronary artery calcium score was smaller than expected compared with a historical database (P < 0.001). Laboratory testing showed a significant decrease in homocysteine (P = 0.05), HDL cholesterol (P = 0.025) and Apo A (P = 0.004), as well as a significant increase in beta-carotene, folate, Co-Q10 and alpha-tocopherol (all P < 0.001). The phytonutrient concentrate we utilized induced several favorable modifications of markers of vascular health in the subjects. This study supports the notion that plant nutrients are important components of a heart healthy diet.

11.
J Pept Res ; 59(1): 34-43, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11906605

RESUMEN

The yeast Saccharomyces cerevisiae has three cell types distinguished by the proteins encoded in their mating-type (MAT) loci: the a and alpha haploids, which express the DNA-binding proteins a1, and alpha1 and alpha2, respectively, and the a/alpha diploid which expresses both a1 and alpha2 proteins. In a/alpha cells, a1-alpha2 heterodimers repress haploid-specific genes and MATalpha1, whereas alpha2 homodimers repress a-specific genes, indicating dual regulatory functions for alpha2 in mating-type control. We previously demonstrated that the two leucine zipper-like coiled-coil motifs, called alpha2A and alpha2B, in the alpha2 N-terminal domain are important to a1-alpha2 heterodimerization. A unique feature of alpha2B is the occurrence of three atypical amino acid residues at a positions within the hydrophobic core. We have conducted mutational analyses of alpha2B peptides and the full-length protein. Our data suggest that these residues may play a critical role in partitioning of the alpha2 protein between heterodimerization with a1 and homodimerization with itself.


Asunto(s)
Proteínas de Homeodominio/química , Proteínas Represoras/química , Proteínas de Saccharomyces cerevisiae/química , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Secuencia de Bases , Dicroismo Circular , Dimerización , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Isoleucina , Datos de Secuencia Molecular , Mutación , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
12.
Horm Metab Res ; 33(12): 721-6, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11753757

RESUMEN

Excessive glucose production by the liver contributes significantly to diabetic hyperglycemia. The enzyme system glucose-6-phosphatase plays a key role in regulating hepatic glucose production and therefore its inhibition is a potential therapeutic target for the correction of hyperglycemia. It has previously been shown that sulfated steroids, such as estrone sulfate and dehydroepiandrosterone sulfate, inhibit the glucose-6-phosphatase system in vitro, principally through inhibition of endoplasmic reticulum glucose-6-phosphate transport. We report here that in the obese/diabetic ob/ob mouse model, orally administered estrone sulfate reduces the abnormally elevated hepatic glucose-6-phosphatase enzyme activity and enzyme protein levels that are characteristic in the ob/ob mouse, and that this reduction is associated with normalization of blood glucose levels. Other sulfated and non-sulfated steroids also reduced, to a lesser extent, glucose-6-phosphatase enzyme activity - with the exception of dehydroepiandrosterone sulfate, which had no apparent effect on this system in ob/ob mice. Estrone sulfate is therefore an effective antihyperglycemic agent in ob/ob mice, and the glucose-6-phosphatase system can be successfully targeted for the therapeutic management of hyperglycemia in this animal model of non-insulin-dependent diabetes mellitus.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Estradiol/análogos & derivados , Estrona/análogos & derivados , Estrona/uso terapéutico , Glucosa-6-Fosfatasa/metabolismo , Hipoglucemiantes/uso terapéutico , Hígado/enzimología , Obesidad , Envejecimiento , Animales , Glucemia/análisis , Sulfato de Deshidroepiandrosterona/farmacología , Diabetes Mellitus/enzimología , Diabetes Mellitus/genética , Estradiol/farmacología , Estrona/farmacología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Microsomas Hepáticos/enzimología
13.
J Cell Physiol ; 189(2): 133-43, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11598898

RESUMEN

PR-39 is proline-rich peptide produced at sites of tissue injury. While the functional properties of this peptide have not been fully defined, PR-39 may be an important regulator of processes related to cell-matrix adhesion since it reportedly upregulates syndecan-4, which is a critical determinant of focal adhesion formation. The ability of PR-39 to modulate the adhesion and chemokinetic migration behavior of arterial smooth muscle cells (SMCs) in a fashion coordinated with syndecan-4 expression was investigated. Treatment of SMCs with PR-39 did not alter syndecan-1 mRNA, but did induce a two-fold increase in syndecan-4 mRNA (P < 0.0001) and significantly enhanced cell surface expression of both syndecan-4 (P < 0.01) and heparan sulfate (HS) (P < 0.05). These observations were consistent with an observed increase in cell-matrix adhesive strength (P < 0.05) and a reduction in cell speed (P < 0.01) on fibronectin-coated substrates. Incubation of PR-39 treated cells with a soluble fibronectin derived heparin-binding peptide, as a competitive inhibitor of heparan sulfate/matrix interactions, abolished these effects. These data suggest that PR-39 mediated alterations of cell adhesion and motility may be related, in part, to the increased expression of heparan sulfate glycosaminoglycans (GAGs) that accompany the upregulation of cell surface syndecan-4. Furthermore, this investigation supports the notion that factors which control syndecan-4 expression may play an important role in regulating adhesion related cell processes.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/farmacología , Adhesión Celular , Movimiento Celular , Matriz Extracelular/metabolismo , Heparitina Sulfato/metabolismo , Músculo Liso Vascular/fisiología , Animales , Adhesión Celular/efectos de los fármacos , Membrana Celular/metabolismo , Movimiento Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Matriz Extracelular/fisiología , Fibronectinas/metabolismo , Heparitina Sulfato/fisiología , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Músculo Liso Vascular/efectos de los fármacos , Proteoglicanos/biosíntesis , Proteoglicanos/genética , ARN Mensajero/biosíntesis , Ratas , Sindecano-4 , Células Tumorales Cultivadas , Regulación hacia Arriba
14.
Cancer Res ; 61(16): 6297-302, 2001 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-11507085

RESUMEN

Sulindac, a nonsteroidal anti-inflammatory drug, inhibits intestinal tumorigenesis in humans and rodents. Sulindac induced complex alterations in gene expression, but only 0.1% of 8063 sequences assayed were altered similarly by the drug in rectal biopsies of patients treated for 1 month and during response of colonic cells in culture. Among these changes was induction of the cyclin-dependent kinase inhibitor, p21(WAF1/cip1). In Apc1638(+/-) mice, targeted inactivation of p21 increased intestinal tumor formation in a gene-dose-dependent manner, but inactivation of p21 completely eliminated the ability of sulindac to both inhibit mitotic activity in the duodenal mucosa and to inhibit Apc-initiated tumor formation. Thus, p21 is essential for tumor inhibition by this drug. The array data can be accessed on the Internet at http://sequence.aecom.yu.edu/genome/.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Ciclinas/fisiología , Mucosa Intestinal/efectos de los fármacos , Sulindac/farmacología , Animales , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/biosíntesis , Ciclinas/genética , Duodeno/citología , Duodeno/efectos de los fármacos , Duodeno/fisiología , Femenino , Dosificación de Gen , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Silenciador del Gen/fisiología , Genes APC , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/fisiología , Masculino , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Recto/citología , Recto/efectos de los fármacos , Recto/fisiología
15.
Exerc Sport Sci Rev ; 29(3): 129-33, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11474961

RESUMEN

Increased aerobic production of ATP at the onset of exercise could be limited by availability of metabolic substrates independent of O2, or interaction between O2 and metabolic substrates. We point out the importance of feedback control to match O2 supply to demand and discuss metabolic control at the onset of exercise.


Asunto(s)
Ejercicio Físico/fisiología , Músculo Esquelético/metabolismo , Consumo de Oxígeno/fisiología , Adenosina Trifosfato/metabolismo , Umbral Anaerobio/fisiología , Animales , Fenómenos Fisiológicos Cardiovasculares , Perros , Retroalimentación Fisiológica/fisiología , Glucólisis/fisiología , Humanos , Modelos Biológicos , Músculo Esquelético/irrigación sanguínea , Fosforilación Oxidativa , Factores de Tiempo
17.
Cancer Res ; 61(9): 3535-40, 2001 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-11325813

RESUMEN

Inducible activation of nuclear factor-kappaB (NF-kappaB) inhibits the apoptotic response to chemotherapy and irradiation. Activation of NF-kappaB via phosphorylation of an inhibitor protein IkappaB leads to degradation of IkappaB through the ubiquitin-proteasome pathway. We hypothesized that inactivation of proteasome function will inhibit inducible NF-kappaB activation, thereby increasing levels of apoptosis in response to chemotherapy and enhancing antitumor effects. To assess the effects of proteasome inhibition on chemotherapy response, human colorectal cancer cells were pretreated with the dipeptide boronic acid analogue PS-341 (1 microM) prior to exposure to SN-38, the active metabolite of the topoisomerase I inhibitor, CPT-11. Inducible activation of NF-kappaB and growth response were evaluated in vitro and in vivo. Effects on p53, p21, p27 and apoptosis were determined. Pretreatment with PS-341 inhibited activation of NF-kappaB induced by SN-38 and resulted in a significantly higher level of growth inhibition (64-75%) compared with treatment with PS-341 alone (20-30%) or SN-38 alone (24-47%; P < 0.002). Combination therapy resulted in a 94% decrease in tumor size compared with the control group and significantly improved tumoricidal response to treatment compared with all treatment groups (P = 0.02). The level of apoptosis was 80-90% in the treatment group that received combination treatment compared with treatment with single agent alone (10%). Proteasome inhibition blocks chemotherapy-induced NF-kappaB activation, leading to a dramatic augmentation of chemosensitivity and enhanced apoptosis. Combining proteasome inhibition with chemotherapy has significant potential to overcome the high incidence of chemotherapy resistance. Clinical studies are currently in development to evaluate the role of proteasome inhibition as an important adjuvant to systemic chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Ácidos Borónicos/farmacología , Camptotecina/análogos & derivados , Camptotecina/farmacología , Inhibidores Enzimáticos/farmacología , FN-kappa B/antagonistas & inhibidores , Pirazinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Ácidos Borónicos/administración & dosificación , Bortezomib , Camptotecina/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Cisteína Endopeptidasas , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Inhibidores Enzimáticos/administración & dosificación , Femenino , Humanos , Irinotecán , Ratones , Ratones Desnudos , Complejos Multienzimáticos/antagonistas & inhibidores , Complejo de la Endopetidasa Proteasomal , Pirazinas/administración & dosificación , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Cancer Res ; 60(23): 6704-13, 2000 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11118056

RESUMEN

We have identified an alternative apoptotic cascade induced in SW620 human colonic carcinoma cells by the protein kinase antagonist staurosporine (stsp). Consistent with its effect in other colonic epithelial cells, stsp induced G2-M arrest and apoptosis of SW620 cells. However, despite the paradigm that growth arrest triggers apoptotic cascades, apoptosis was detected before G2-M arrest. Reports have linked dissipation of the mitochondrial membrane potential (deltapsim) to the initiation of apoptosis and have linked elevation of the deltapsim to the escape from apoptosis However, neither apoptosis nor cell cycle arrest were altered by the collapse of the deltapsim, and increased deltapsim enhanced the initiation of apoptosis but blocked G2-M arrest. Although reactive oxygen species (ROS) have been implicated in some colonic epithelial cell and stsp-induced cascades, neither antioxidants nor the inhibition of RNA or protein synthesis altered apoptosis of SW620 cells. Finally, cytosolic cytochrome c has been linked to activation of caspase-3 and dissipation of the deltapsim. However, caspase-3 activation preceded the accumulation of cytochrome c in the cytosol and was accompanied by transient elevations in both the deltapsim and mitochondria-associated cytochrome c. Therefore, we have identified a distinct apoptotic cascade in SW620 cells that was induced independently of growth arrest, dissipation of the deltapsim, ROS production, or synthesis of de novo RNA or protein, and we have linked its efficient initiation to early elevation of the deltapsim.


Asunto(s)
Apoptosis/fisiología , Neoplasias del Colon/patología , Inhibidores Enzimáticos/farmacología , Fase G2/fisiología , Mitocondrias/fisiología , Mitosis/fisiología , Estaurosporina/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3 , Caspasas/metabolismo , División Celular/fisiología , Neoplasias del Colon/enzimología , Neoplasias del Colon/metabolismo , Neoplasias del Colon/fisiopatología , Grupo Citocromo c/metabolismo , Citosol/efectos de los fármacos , Citosol/metabolismo , Fragmentación del ADN/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Fase G2/efectos de los fármacos , Humanos , Membranas Intracelulares/efectos de los fármacos , Membranas Intracelulares/fisiología , Ionóforos/farmacología , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitosis/efectos de los fármacos , Proteínas de Neoplasias/biosíntesis , Nigericina/farmacología , ARN/antagonistas & inhibidores , Células Tumorales Cultivadas
19.
BMJ ; 321(7256): 305A, 2000 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-10915144
20.
Am J Obstet Gynecol ; 182(5): 1033-5, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10819819

RESUMEN

OBJECTIVE: Our purpose was to determine the differences in postoperative morbidity in obese women who had a supraumbilical or a Pfannenstiel incision at cesarean delivery. STUDY DESIGN: A case-control retrospective review was conducted of all patients who were at >150% ideal body weight when undergoing cesarean delivery between 1989 and 1995 by means of either a supraumbilical or a Pfannenstiel incision. Patients were excluded if medical records were unavailable. A total of 15 women who had a supraumbilical incision and 54 who had a low transverse incision were included in the analysis. Antenatal complications were examined, as were age, weight, and training level of the surgeon. Postoperative complications were then compared. RESULTS: The groups were similar in age and antepartum complications. However, mean weight and percentage of ideal body weight in the supraumbilical group were both higher (P <.00001 and P <.0001, respectively), with the supraumbilical group 83 lb heavier on average. No significant differences were seen in any postoperative complication. CONCLUSION: Postoperative morbidity in morbidly obese women undergoing cesarean delivery does not differ between a supraumbilical approach and the low transverse abdominal incision.


Asunto(s)
Cesárea/métodos , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones del Embarazo , Peso Corporal , Femenino , Humanos , Morbilidad , Embarazo , Ombligo
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