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1.
Ecology ; 93(5): 981-91, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22764485

RESUMEN

Ecological specialization is a fundamental and well-studied concept, yet its great reach and complexity limit current understanding in important ways. More than 20 years after the publication of D. J. Futuyma and G. Moreno's oft-cited, major review of the topic, we synthesize new developments in the evolution of ecological specialization. Using insect-plant interactions as a model, we focus on important developments in four critical areas: genetic architecture, behavior, interaction complexity, and macroevolution. We find that theory based on simple genetic trade-offs in host use is being replaced by more subtle and complex pictures of genetic architecture, and multitrophic interactions have risen as a necessary framework for understanding specialization. A wealth of phylogenetic data has made possible a more detailed consideration of the macroevolutionary dimension of specialization, revealing (among other things) bidirectionality in transitions between generalist and specialist lineages. Technological advances, including genomic sequencing and analytical techniques at the community level, raise the possibility that the next decade will see research on specialization spanning multiple levels of biological organization in non-model organisms, from genes to populations to networks of interactions in natural communities. Finally, we offer a set of research questions that we find to be particularly pressing and fruitful for future research on ecological specialization.


Asunto(s)
Evolución Biológica , Ecosistema , Insectos/genética , Insectos/fisiología , Plantas/genética , Adaptación Fisiológica/genética , Animales , Conducta Animal , Variación Genética , Herbivoria , Oviposición
2.
Sci Total Environ ; 414: 646-52, 2012 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-22153606

RESUMEN

Particle-induced X-ray emission and particle-induced gamma-ray emission spectrometry were successfully applied in a study of the elemental composition of decomposing filamentous algae. Fresh brown (Pilayella littoralis) and green (Cladophora glomerata) algal materials were placed in cages at 4m depth in a water column of 8m in the Archipelago Sea, northern Baltic Sea. Every second week decaying algae were sampled from the cages to allow measurements of changes in the elemental compositions. In the study of the elemental losses the concentrations were compensated for the mass reduction. The results show that sulphur, chlorine and partly potassium were lost during decomposition of P. littoralis and C. glomerata. Most of the other elements studied were recovered in the remaining algal mass. Special attention was paid to sorption and desorption of elements, including metal binding capacity, in the decaying algal materials. The affinity order of different cations to the two algal species was established by calculation of conditional distribution coefficients, D'(M). For instance for P. littoralis the following series of binding strength (affinity) of cations were obtained: Al>Ti>Fe >> Mn>Ni, Cu>Ba, Cr, Zn>>Rb>K, Sr>Pb>>Ca>>Na>Mg. Notably is that the binding strength of strontium was more than 10 times higher for P. littoralis than for C. glomerata. Due to their high binding capacity and good affinity and selectivity for heavy metal ions these algae have great potential as biological sorbents. Large variations in elemental content during decomposition complicate the use of algae for environmental monitoring.


Asunto(s)
Chlorophyta/metabolismo , Monitoreo del Ambiente/métodos , Rayos gamma , Phaeophyceae/metabolismo , Espectrometría por Rayos X/métodos , Adsorción , Cationes/química , Cloro/química , Finlandia , Metales/química , Océanos y Mares , Potasio/química , Especificidad de la Especie , Azufre/química , Factores de Tiempo
3.
Appl Radiat Isot ; 67(11): 2037-9, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19110436

RESUMEN

Elemental production cross sections were measured for (p,x) reactions on natural Cu targets, leading to the formation of (62,63,65)Zn. These reactions are generally used for monitoring the proton beam intensity and energy e.g. in isotope production facilities. Cross sections were obtained by activation of stacked foils and subsequent gamma spectroscopy. The production data for (62,63,65)Zn between 7 and 16.5 MeV proton energy are presented as well as comparisons with literature values. Good agreement with the evaluated values was found for most of the cross-section values.


Asunto(s)
Cobre/química , Cobre/efectos de la radiación , Modelos Químicos , Isótopos de Zinc/química , Isótopos de Zinc/efectos de la radiación , Simulación por Computador , Relación Dosis-Respuesta en la Radiación , Transferencia de Energía , Dosis de Radiación
4.
Nature ; 448(7154): 696-9, 2007 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-17687325

RESUMEN

For numerous taxa, species richness is much higher in tropical than in temperate zone habitats. A major challenge in community ecology and evolutionary biogeography is to reveal the mechanisms underlying these differences. For herbivorous insects, one such mechanism leading to an increased number of species in a given locale could be increased ecological specialization, resulting in a greater proportion of insect species occupying narrow niches within a community. We tested this hypothesis by comparing host specialization in larval Lepidoptera (moths and butterflies) at eight different New World forest sites ranging in latitude from 15 degrees S to 55 degrees N. Here we show that larval diets of tropical Lepidoptera are more specialized than those of their temperate forest counterparts: tropical species on average feed on fewer plant species, genera and families than do temperate caterpillars. This result holds true whether calculated per lepidopteran family or for a caterpillar assemblage as a whole. As a result, there is greater turnover in caterpillar species composition (greater beta diversity) between tree species in tropical faunas than in temperate faunas. We suggest that greater specialization in tropical faunas is the result of differences in trophic interactions; for example, there are more distinct plant secondary chemical profiles from one tree species to the next in tropical forests than in temperate forests as well as more diverse and chronic pressures from natural enemy communities.


Asunto(s)
Dieta , Ecosistema , Lepidópteros/fisiología , Árboles , Clima Tropical , Animales , Biodiversidad , Larva/fisiología , Especificidad de la Especie
5.
Proc Natl Acad Sci U S A ; 102(48): 17384-7, 2005 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-16293686

RESUMEN

Insect outbreaks are expected to increase in frequency and intensity with projected changes in global climate through direct effects of climate change on insect populations and through disruption of community interactions. Although there is much concern about mean changes in global climate, the impact of climatic variability itself on species interactions has been little explored. Here, we compare caterpillar-parasitoid interactions across a broad gradient of climatic variability and find that the combined data in 15 geographically dispersed databases show a decrease in levels of parasitism as climatic variability increases. The dominant contribution to this pattern by relatively specialized parasitoid wasps suggests that climatic variability impairs the ability of parasitoids to track host populations. Given the important role of parasitoids in regulating insect herbivore populations in natural and managed systems, we predict an increase in the frequency and intensity of herbivore outbreaks through a disruption of enemy-herbivore dynamics as climates become more variable.


Asunto(s)
Efecto Invernadero , Lepidópteros/parasitología , Avispas/fisiología , Animales , Geografía , Interacciones Huésped-Parásitos , Larva/parasitología , Larva/fisiología , Lepidópteros/fisiología , Dinámica Poblacional , Análisis de Regresión
6.
Sci Total Environ ; 343(1-3): 231-41, 2005 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-15862848

RESUMEN

Bark and wood samples were taken from the same individuals of Scots pine (Pinus sylvestris L.) from a polluted area close to a Cu-Ni smelter in Harjavalta and from some relatively unpolluted areas in western Finland. The samples were analysed by thick-target particle induced X-ray emission (PIXE) after preconcentration by dry ashing at 550 degrees C. The elemental contents of pine bark and wood were compared to study the impact of heavy metal pollution on pine trees. By comparison of the elemental contents in ashes of bark and wood, a normalisation was obtained. For the relatively clean areas, the ratios of the concentration in bark ash to the concentration in wood ash for different elements were close to 1. This means that the ashes of Scots Pine wood and bark have quite similar elemental composition. For the samples from the polluted area the mean concentration ratios for some heavy metals were elevated (13-28), reflecting the effect of direct atmospheric contamination. The metal contents in the ashes of pine bark and wood were also compared to recommendations for ashes to be recycled back to the forest environment. Bark from areas close to emission sources of heavy metal pollution should be considered with caution if aiming at recycling the ash. Burning of bark fuel of pine grown within 6 km of the Cu-Ni smelter is shown to generate ashes with high levels of Cu, Ni as well as Cd, As and Pb.


Asunto(s)
Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Metales Pesados/análisis , Pinus sylvestris/química , Corteza de la Planta/química , Finlandia , Madera
7.
J Immunol Methods ; 262(1-2): 5-19, 2002 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-11983215

RESUMEN

Electrospray ionisation (ESI) mass spectrometry (MS) has been used extensively for the detection of peptides presented by major histocompatibility complex (MHC) molecules. This review focuses on the optimisation of electrospray mass spectrometry and the use of tandem mass spectrometry to sequence MHC class I peptides. We review the isolation of MHC class I peptides from the surface of cells with particular reference to tumour cells. In addition, we also discuss the advantages and disadvantages of the methods available to concentrate and fractionate the peptides prior to analysis by electrospray mass spectrometry.


Asunto(s)
Antígenos de Histocompatibilidad Clase I/análisis , Neoplasias/química , Neoplasias/inmunología , Péptidos/análisis , Animales , Antígenos de Histocompatibilidad Clase I/química , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Péptidos/química , Péptidos/inmunología , Espectrometría de Masa por Ionización de Electrospray
8.
Nature ; 417(6885): 170-3, 2002 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-12000959

RESUMEN

Patterns of association between herbivores and host plants have been thought to reflect the quality of plants as food resources as influenced by plant nutrient composition, defences, and phenology. Host-plant-specific enemies, that is, the third trophic level, might also influence the distribution of herbivores across plant species. However, studies of the evolution of herbivore host range have generally not examined the third trophic level, leaving unclear the importance of this factor in the evolution of plant-insect herbivore interactions. Analysis of parasitoid rearings by the Canadian Forest Insect Survey shows that parasitism of particular Lepidoptera species is strongly host-plant-dependent, that the pattern of host-plant dependence varies among species of caterpillars, and that some parasitoid species are themselves specialized with respect to tree species. Host-plant-dependent parasitism suggests the possibility of top-down influence on host plant use. Differences in parasitism among particular caterpillar-host plant combinations could select for specialization of host plant ranges within caterpillar communities. Such specialization would ultimately promote the species diversification of Lepidoptera in temperate forests with respect to escape from enemies.


Asunto(s)
Mariposas Diurnas/fisiología , Larva/fisiología , Mariposas Nocturnas/fisiología , Plantas/parasitología , Árboles/parasitología , Animales , Mariposas Diurnas/clasificación , Mariposas Diurnas/crecimiento & desarrollo , Distribución de Chi-Cuadrado , Bases de Datos como Asunto , Interacciones Huésped-Parásitos , Larva/clasificación , Mariposas Nocturnas/clasificación , Mariposas Nocturnas/crecimiento & desarrollo , Plantas/clasificación , Árboles/clasificación
9.
Blood ; 98(10): 2887-93, 2001 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-11698267

RESUMEN

The BCR-ABL oncogene is central in the pathogenesis of chronic myeloid leukemia (CML). Here, tandem nanospray mass spectrometry was used to demonstrate cell surface HLA-associated expression of the BCR-ABL peptide KQSSKALQR on class I-negative CML cells transfected with HLA-A*0301, and on primary CML cells from HLA-A3-positive patients. These patients mounted a cytotoxic T-lymphocyte response to KQSSKALQR that also killed autologous CML cells, and tetramer staining demonstrated the presence of circulating KQSSKALQR-specific T cells. The findings are the first demonstration that CML cells express HLA-associated leukemia-specific immunogenic peptides and provide a sound basis for immunization studies against BCR-ABL.


Asunto(s)
Presentación de Antígeno , Antígenos de Neoplasias/inmunología , Antígenos de Superficie/inmunología , Proteínas de Fusión bcr-abl/inmunología , Antígeno HLA-A3/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Proteínas de Neoplasias/inmunología , Células Madre Neoplásicas/inmunología , Fragmentos de Péptidos/inmunología , Adulto , Secuencia de Aminoácidos , Antígenos de Neoplasias/química , Antígenos de Superficie/química , Femenino , Proteínas de Fusión bcr-abl/química , Antígeno HLA-A3/genética , Humanos , Células K562/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/química , Fragmentos de Péptidos/química , Proteínas Recombinantes de Fusión/inmunología , Espectrometría de Masa por Ionización de Electrospray , Linfocitos T Citotóxicos/inmunología , Transfección
10.
Rofo ; 173(9): 822-9, 2001 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-11582562

RESUMEN

PURPOSE: Aim of the study was to evaluate the postoperative changes in patients with single (SLTX) or double lung transplantation (DLTX) with HRCT and to correlate those findings with the clinical diagnosis. MATERIAL AND METHODS: 29 patients with SLTX (n = 14) or DLTX (n = 15) were observed for more than 6 years after transplantation by HRCT (n = 82). CT examinations were performed in inspiration and expiration (n = 70) with a slice thickness of 1 mm and a feed of 10 mm. The image material was evaluated by 2 experienced radiologists in consensus. Criteria for acute rejection at HRCT were: ground glass opacities and focal air trapping in expiration. Criteria for chronic transplant rejection were: bronchial dilatation, bronchial wall thickening and thickening of interlobar septae. The clinical evaluation consisted of laboratory tests, lung function tests, and bronchoscopy including bronchial lavage in special cases. RESULTS: 20/29 patients are still alive (mean 21 months). 5/9 patients died because of chronic transplantant rejection, 1 patient suffered from a non-Hodgkin's lymphoma localised at the right hilus. Severe threatening pneumonia occurred in 13 cases. 10/29 patients showed symptoms of acute rejection. Expiratory HRCT found a focal air trapping in all cases and extended ground glass opacities in 11/14 cases. Also a bronchial dilatation was observed in more than 50 % (9/14). 12/29 patients suffered from chronic transplant rejection. HRCT showed bronchial dilatation in 26/27 investigations and severe ground glass opacities in 21/27 investigations. Thickening of the interlobal septa as well as centrilobular opacities were found in more than 50 % of the examinations. CONCLUSION: High resolution CT of the chest in patients after lung transplantation is able to show numerous pathological alterations. Without clinical information a confident differentiation in acute or chronic transplant rejection or pneumonia can be difficult or impossible.


Asunto(s)
Rechazo de Injerto/diagnóstico por imagen , Trasplante de Pulmón , Intensificación de Imagen Radiográfica , Tomografía Computarizada por Rayos X , Enfermedad Aguda , Adulto , Bronquiolitis Obliterante/diagnóstico por imagen , Bronquiolitis Obliterante/mortalidad , Enfermedad Crónica , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Rechazo de Injerto/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia
12.
Thorax ; 56(7): 557-60, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11413355

RESUMEN

BACKGROUND: Sputum induction is a non-invasive procedure for measuring inflammatory processes of the lower respiratory tract. The aim of this study was to establish sputum cell counts and differentials in patients after lung transplantation (LTx), with or without chronic transplant rejection. METHODS: Sputum induction was performed in 41 LTx patients (25 single LTx (sLTx), 16 double LTx (dLTx) and 15 healthy non-smoking volunteers. Sputum was processed according to standard protocols. Total cell count was calculated as mean (SE) cells x 10(6)/ml sputum and cell differential (%) was evaluated after staining. Cellular profiles were correlated with lung function. RESULTS: Total sputum cell counts were increased in sLTx (9 (1.9) cells x 10(6)/ml, p=0.01) and dLTx patients (7.2 (1.5) x 10(6)/ml, p=0.01) compared with healthy controls (2.6 (0.6) x 10(6)/ml). There was also a marked sputum neutrophilia in both patient groups (59 (6)% and 62 (6)%, respectively, p<0.001 v controls). Moreover, in both sLTx and dLTx patients with chronic transplant rejection there was an increased number of sputum neutrophils compared with patients with normal graft function (p<0.05 both comparisons), and neutrophils were inversely correlated with lung function (forced expiratory volume in one second (FEV(1)) % predicted): sLTx, r=-0.61, p=0.001; dLTx, r=-0.75, p=0.001, respectively). Sputum lymphocytes and eosinophils were similar in both groups. No relevant side effects occurred during sputum induction. CONCLUSIONS: Sputum induction is a safe and non-invasive tool for monitoring lower respiratory tract inflammation in LTx patients. Both sLTx and dLTx patients with chronic rejection had increased sputum neutrophils compared with patients with normal transplant function. These data support findings of other authors highlighting a possible role for neutrophils in the pathogenesis of chronic transplant rejection.


Asunto(s)
Bronquiolitis Obliterante/patología , Rechazo de Injerto/patología , Trasplante de Pulmón/patología , Neutrófilos , Esputo/citología , Adolescente , Adulto , Bronquiolitis Obliterante/etiología , Recuento de Células , Enfermedad Crónica , Estudios Transversales , Femenino , Volumen Espiratorio Forzado , Rechazo de Injerto/fisiopatología , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad
14.
Eur Radiol ; 11(6): 982-9, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11419175

RESUMEN

In tracheo- and bronchomalacia, localisation and determination of collapse is necessary for planning of surgical procedure. We compared inspiratory and expiratory spiral CT, cine CT, bronchoscopy, exemplary cine MR, and evaluated the clinical relevance. Twenty-nine patients (2 follow-ups; mean age 61 years, age range 27-85 years) with suspected or verified tracheal stenosis or collapse (post-tracheotomy: n = 17; neoplasm: n = 5; other: n = 7) underwent paired breath-hold inspiratory and expiratory spiral CT. Forty-five additional cine CT were performed at 1-4 levels (mean 1.5) during continuous respiration (increment 100 ms) to clarify respiratory collapse. The tracheal cross-sectional diameters of both techniques were calculated. Comparison with bronchoscopy, follow-up, and influence upon therapy were evaluated retrospectively. Exemplary comparison with cine MR (8 frames/s) was done in 3 cases. In addition to bronchoscopy, further information concerning localisation, extent, collapse, stability of the tracheal wall, distal portions of the stenosis and extraluminal compressions were obtained. A significantly higher degree and more pathological collapses (> 50%) were seen using cine CT (38%) compared with paired spiral CT (13%; degree: p < 0.0001; number: p < 0.001). The findings changed the further therapeutic procedure in 16 of 29 patients. Further stenoses were excluded and bronchoscopy was verified in another 13 of 29. Temporal resolution of cine CT and cine MR is sufficient; however, spatial resolution of cine MR is inferior. Paired inspiratory and expiratory spiral CT localises tracheal stenoses and demonstrates relevant extraluminal compression. Significantly improved evaluation of respiratory collapse and further information of localised tracheal instability is obtained by cine CT. Cine MR promises more functional information especially due to free choice of imaging plane.


Asunto(s)
Aumento de la Imagen , Ventilación Pulmonar/fisiología , Tomografía Computarizada por Rayos X , Enfermedades de la Tráquea/diagnóstico por imagen , Estenosis Traqueal/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Broncografía , Femenino , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Tráquea/diagnóstico por imagen
15.
Invest Radiol ; 36(2): 110-4, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11224759

RESUMEN

RATIONALE AND OBJECTIVES: To develop a validated post-processing routine for volumetry of the ventilated airspaces by 3He MRI. METHODS: 3Helium MRI and pulmonary function tests were performed in seven healthy volunteers. After segmentation of ventilated airspaces, their volumes were calculated. Functional residual capacity (FRC) was used as a reference. For comparison of absolute volumes, correction factors were evaluated. RESULTS: Mean lung volume (+/- standard deviation) calculated from 3He MRI was 4,082 +/- 908 mL and mean FRC was 3,696 +/- 1166 mL, with a mean difference of 386 mL (r = 0.88). After correction for the relative pulmonary air content (factor 0.82), posture (0.72), and the individual tidal volume, 3He MRI volume was 3,348 +/- 744 mL and mean FRC was 3,422 +/- 817 mL, with the mean difference down to -74 mL (r = 0.9). Comparison on an individual basis confirmed an improvement in the estimation of absolute lung volume. CONCLUSIONS: Volumetry of ventilated lung from 3He MRI shows high correlation and good agreement with the results of pulmonary function tests.


Asunto(s)
Helio , Mediciones del Volumen Pulmonar/métodos , Imagen por Resonancia Magnética , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Isótopos , Masculino
16.
Evolution ; 55(11): 2236-47, 2001 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-11794783

RESUMEN

The timing of life-history events in insects can have important consequences for both survival and reproduction. For insect herbivores with complex life histories, selection is predicted to favor those combinations of traits that increase the size at metamorphosis while minimizing the risk of mortality from natural enemies. Studies quantifying selection on life-history traits in natural insect herbivore populations, however, have been rare. The purpose of this study was to measure phenotypic selection imposed by elements of the first and third trophic levels on variation in two life-history traits, the timing of egg hatch and pupal mass, in a population of oak-feeding caterpillars, Psilocorsis quercicella (Lepidoptera: Oecophoridae). Larvae were collected from the field throughout each of two generations per year for three years and reared to determine the effects of the date of egg hatch on both the risk of attack from parasitoids and the pupal mass of the survivors. The direction and strength of phenotypic selection attributed to aspects of the first and third trophic levels, as well as their combined effects, on the date of egg hatch was measured for each of the six generations. Heritabilities of and genetic correlations between pupal mass and the date of adult emergence from diapause (the life-history trait expected to have the largest influence on the timing of egg hatch, and thus larval development) were estimated from laboratory matings. In four of the six generations examined, significant directional selection attributed to the first trophic level was detected, always favoring early-hatching cohorts predicted to experience higher leaf quality than late-hatching cohorts. Directional phenotypic selection by the third trophic level was detected in only one of three years, and in that year the direction of selection was in opposite directions during the two successive generations. The combined effect of selection by both trophic levels indicated that the third trophic level acted to either reduce or enhance the more predictable pattern of selection attributed to the first trophic level. In addition, I found evidence of truncation selection acting to increase the mean and decrease the variance of pupal mass during the pupa-adult transition in the laboratory. Pupal mass and diapause duration were found to vary significantly among full-sibling families; upper bounds for heritability estimates were 0.57 and 0.30, respectively. Furthermore, these two traits were found to be positively genetically correlated (families with larger pupae had longer diapause durations), resulting in a fitness trade-off, because larger pupae enjoy higher survival through metamorphosis and female fecundity but emerge later, when average leaf quality for offspring is generally poorer.


Asunto(s)
Estadios del Ciclo de Vida , Mariposas Nocturnas/fisiología , Selección Genética , Animales , Femenino , Larva/crecimiento & desarrollo , Larva/fisiología , Metamorfosis Biológica , Mariposas Nocturnas/genética , Mariposas Nocturnas/crecimiento & desarrollo , Fenotipo , Pupa/crecimiento & desarrollo , Pupa/fisiología , Factores de Tiempo
17.
Phys Rev Lett ; 84(25): 5784-7, 2000 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-10991054

RESUMEN

The method of Parrinello and Rahman is generalized to include slip in addition to deformation of the simulation cell. Equations of motion are derived, and a microscopic expression for traction is introduced. Lagrangian constraints are imposed so that the combination of deformation and slip conform to the invariant plane shear characteristic of martensites. Simulation of a model transformation demonstrates the nucleation and propagation of a glissile dislocation interface.

18.
Am J Health Syst Pharm ; 57(17): 1579-84, 2000 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-10984808

RESUMEN

Cyclosporine-drug interactions in adult transplant patients and the impact of age were studied. The medical records of transplant patients receiving cyclosporine therapy were identified. Data on patient demographics, cyclosporine dosages, dosage form, blood trough concentrations, clinical laboratory test values, and concurrent medications were collected. One-compartment models for oral and i.v. administration were used to fit cyclosporine concentration data to population pharmacokinetic and statistical models. Nonlinear mixed-effect modeling (NONMEM) software was used. The influence of covariates, including but not limited to concomitant medications and age, on cyclosporine pharmacokinetics was evaluated. The records of 100 patients (36 women and 64 men) were reviewed. A mean +/- S.D. of 9 +/- 2 and 9 +/- 1 medications per day were consumed by patients < 60 and > or = 60 years old, respectively. Mean population pharmacokinetic values of 0.407 L/hr/kg for clearance, 4.0 L/kg for volume of distribution, 31% for bioavailability, and 10.6 hours for half-life were determined on the basis of 569 blood cyclosporine levels. Twelve medications (sertraline, losartan, valsartan, quinine, atorvastatin, simvastatin, pravastatin, fluvastatin, alendronate, digoxin, acyclovir, and oxycodone) with previously unconfirmed pharmacokinetic interactions with cyclosporine were identified as interacting. There was no correlation between age and interactions. Patients taking cyclosporine were at risk for pharmacokinetic drug interactions when cyclosporine was used in combination with sertraline, losartan, valsartan, quinine, atorvastatin, simvastatin, pravastatin, fluvastatin, alendronate, digoxin, acyclovir, and oxycodone. Transplant patients 60-75 years of age had cyclosporine-drug interactions similar to those in younger patients.


Asunto(s)
Ciclosporina/farmacocinética , Sistema Enzimático del Citocromo P-450/metabolismo , Rechazo de Injerto/metabolismo , Inmunosupresores/farmacocinética , Oxigenasas de Función Mixta/metabolismo , Adulto , Factores de Edad , Anciano , Intervalos de Confianza , Ciclosporina/sangre , Citocromo P-450 CYP3A , Interacciones Farmacológicas/fisiología , Femenino , Humanos , Inmunosupresores/sangre , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos
19.
Analyst ; 125(4): 599-603, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10892016

RESUMEN

The formation of copper/peptide complex ions by nano-electrospray and microbore HPLC-electrospray mass spectrometry has been investigated for major histocompatibility complex (MHC) class I and class II restricted peptides. Post-column addition of copper(II) acetate following microbore HPLC-MS separation was carried out using a mixing T-piece or via the sheath flow inlet of the electrospray source. Optimal analytical conditions for copper complex ion formation were determined by variation of copper concentration, pH, nebulization gas supply and spray voltage. Tandem mass spectrometry of copper/peptide complex ions provides peptide sequence information and insight into the peptide chelation sites. Copper associated y fragment ions dominate the product ion spectrum for non-histidine containing peptides, but both b and y copper complex ions were observed for the histidine containing MHC class I associated peptide gp70.


Asunto(s)
Quelantes , Cobre , Antígenos de Histocompatibilidad/análisis , Animales , Humanos , Espectrometría de Masas/métodos , Ratones
20.
NMR Biomed ; 13(4): 182-9, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10867694

RESUMEN

MRI with hyperpolarized helium-3 ((3)He) provides high-resolution imaging of ventilated airspaces. The first aim of this (3)He-study was to compare observations of localized signal defects in healthy smokers and non-smokers. A second aim was to describe relationships between parameters of lung function, volume of inspired (3)He and signal-to-noise ratio. With Ethics Committee approval and informed consent, 12 healthy volunteers (seven smokers and five non-smokers) were studied. Imaging was performed in a 1.5 T scanner using a two-dimensional FLASH sequence at 30V transmitter amplitude (TR/TE/alpha = 11 ms/4.2 ms/<10 degrees ). Known amounts of (3)He were inhaled from a microprocessor-controlled delivery device and imaged during single breath-holds. Images were evaluated visually, and scored using a prospectively defined 'defect-index'. Signal-to-noise ratio of the images were correlated with localization, (3)He volumes and static lung volumes. Due to poor image quality studies of two smokers were not eligible for the evaluation. Smokers differed from non-smokers in total number and size of defects: the 'defect-index' of smokers ranged between 0.8 and 6.0 (median = 1.1), that of non-smokers between 0.1 and 0.8 (median = 0.4). Intraindividually, an anteroposterior gradient of signal-to-noise ratio was apparent. Signal-to-noise ratio correlated with the estimated amount of hyperpolarization administered (r = 0. 77), but not with static lung volumes. We conclude that (3)He MRI is a sensitive measure to detect regional abnormalities in the distribution of ventilation in clinically healthy persons with normal pulmonary function tests.


Asunto(s)
Mediciones del Volumen Pulmonar/métodos , Pulmón/fisiología , Imagen por Resonancia Magnética/métodos , Fumar/fisiopatología , Adulto , Helio/farmacocinética , Humanos , Isótopos , Pulmón/fisiopatología
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