Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 53
Filter
Add more filters










Publication year range
1.
Clin Transl Sci ; 10(3): 194-200, 2017 05.
Article in English | MEDLINE | ID: mdl-28160427

ABSTRACT

Emerging data from global markets outside the United States, where many generic iron sucrose formulations are available, have revealed that non-US generic intravenous (i.v.) iron formulations may have iron release profiles that differ from the reference listed drug (RLD). The first generic i.v. iron approved in the United States was sodium ferric gluconate complex in 2011. We evaluated chelatable and redox labile iron assay methods to measure the amount of labile iron released from i.v. iron formulations in biorelevant matrices in vitro. The majority of published labile iron assays evaluated were not suitable for use in vitro due to overwhelming interference by the presence of the i.v. iron products. However, an optimized high-performance liquid chromatography (HPLC)-based method performed well for use in vitro labile iron detection in a biorelevant matrix. Application of this method may enhance bioequivalence evaluation of generic i.v. iron formulations in the future.


Subject(s)
Biological Assay/methods , Iron Chelating Agents/pharmacology , Iron/metabolism , Administration, Intravenous , Animals , Bleomycin , Calibration , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Oxidation-Reduction , Rats
2.
Domest Anim Endocrinol ; 59: 37-43, 2017 04.
Article in English | MEDLINE | ID: mdl-27930936

ABSTRACT

Traditional confinement practices limit exposure to sunlight and vitamin D synthesis, and vitamin insufficiency occurs even with dietary supplementation. The aim of this study was to determine the effect of limited sun exposure on serum concentration of vitamin D and the expression of vitamin D synthesizing enzymes in the liver and kidney of pigs on a vitamin D sufficient diet. White-pigmented grower pigs (29.7 ± 2.3 kg) fed 15% CP diet ad libitum providing >1,200 IU vitamin D3/kg of feed were exposed to sunlight for 1 h each day at solar noon for 14 d at the spring equinox (March pigs, n = 10) or summer solstice (June pigs, n = 5) and again before slaughter in June (March pigs) and September (June pigs). Blood for the analysis of 25(OH)D was collected before and after sunlight exposure. Traditionally housed pigs served as controls. After initial sun exposure, blood samples were collected from June pigs daily for 5 d and weekly for 8 wk to determine vitamin D3 and 25(OH)D decay, respectively. Kidney and liver samples were collected from the June pigs at slaughter after sun exposure for analysis of messenger RNA expression of vitamin D binding protein and synthesizing/degrading enzymes. Average daily gain (ADG) was not influenced (P > 0.5) by sunlight exposure. June pigs had fewer days on feed, lower (P = 0.003) ADG and were slaughtered at a lighter (P < 0.001) weight. Exposure to sunlight increased (P < 0.001) 25(OH) vitamin D for all pigs. March pigs, obtained from a Midwest producer, had lower (P < 0.001) concentration of 25(OH)D than June pigs born on-farm. Initial sunlight exposure increased serum concentration of 25(OH)D in March pigs by 200% and June pigs by 67%. Serum concentration of vitamin D3 was decreased (P < 0.05) by 72 h with 25(OH)D decreased (P < 0.05) by wk 4 after exposure. Expression of vitamin D binding protein, vitamin D synthesizing CYP2R1, CYP27A1, CYP2D25, or degrading enzyme CYP24A1 were not influenced (P ≥ 0.19) by sunlight exposure. Expression of CYP27B1 was decreased (P = 0.04) in the kidney but tended to be increased (P = 0.06) in the liver after sun exposure. These results suggest limited sun exposure can efficiently increase serum concentration of vitamin D in growing pigs with varying levels of vitamin sufficiency. The lack of major changes in vitamin synthesizing enzymes suggests the 14-d exposure period did not saturate the capacity of slaughter-weight pigs to synthesize vitamin D.


Subject(s)
Animal Feed/analysis , Diet/veterinary , Sunlight , Swine/growth & development , Vitamin D/administration & dosage , Vitamin D/biosynthesis , Animal Nutritional Physiological Phenomena , Animals , Female , Housing, Animal , Male , Seasons
3.
Diabetologia ; 54(4): 869-75, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21181394

ABSTRACT

AIMS/HYPOTHESIS: We hypothesised that ectopic fat deposition is present in liver and skeletal muscle before puberty and that both are potentially important factors in the early pathogenesis of insulin resistance. METHODS: Proton magnetic resonance spectroscopy was used to evaluate intramyocellular and intrahepatic lipids in 50 male and 42 female multi-ethnic, prepubertal (Tanner < 2) children (8.1 ± 0.8 years; 35.4 ± 10.7 kg; 27.9 ± 8.3% body fat; means ± SD). Intramyocellular lipid was measured in soleus muscle and intrahepatic lipid in the middle right lobe. Abdominal fat was measured by magnetic resonance imaging, body fat by dual energy X-ray absorptiometry, and insulin resistance using homeostatic model assessment. RESULTS: Intrahepatic lipid ranged from 0.11% to 4.6% relative to the liver water signal (mean 0.79 ± 0.79%) whereas intramyocellular lipid ranged from 0.13% to 1.86% relative to the muscle water signal (mean 0.51 ± 0.28%). Intramyocellular and intrahepatic lipids were significantly correlated with total adiposity (r = 0.49 and 0.59), abdominal adiposity (r = 0.44 and 0.54), and each other (r = 0.39, p < 0.05, Spearman). Both intramyocellular and intrahepatic lipid were positively correlated with fasting insulin (r = 0.37 and 0.38 respectively) and insulin resistance (r = 0.37 and 0.37; p < 0.01). After adjustment for race and sex, the relations between ectopic fat and insulin resistance remained, whereas both disappeared when further adjusted for body fat or BMI z scores. CONCLUSIONS/INTERPRETATIONS: These results suggest that typical relations between body composition, ectopic fat and insulin resistance are present in children before puberty. Thus, interventions aimed at reducing adiposity have the potential to decrease ectopic fat accumulation, delay the onset of insulin resistance and decrease the risk for development of type 2 diabetes in children.


Subject(s)
Insulin Resistance/physiology , Lipids/analysis , Liver/metabolism , Muscle, Skeletal/metabolism , Absorptiometry, Photon , Body Composition/physiology , Child , Female , Humans , Magnetic Resonance Spectroscopy , Male
4.
Environ Prog Sustain Energy ; 28(4): 507-518, 2009 Jan 30.
Article in English | MEDLINE | ID: mdl-20526423

ABSTRACT

Iron nanoaggregates have been prepared using the sodium borohydride reduction method and post-coated with Pd using aqueous phase electro-deposition. The Fe/Pd nanoaggregates were used to examine dechlorination of trichloroethylene (TCE) with regard to matrix effects using materials representative of a potential zero-valent metal remediation site surrounding the Paducah gaseous diffusion plant in Paducah, KY. A surface-area-normalized first-order rate constant of 1.4 x 10(-1) L m(-2) h(-1) was obtained for the case of ideal dechlorination of 19.6 mg L(-1) TCE at room temperature and pH 6.2 using 0.5 g L(-1) Fe/Pd (0.42 wt % Pd) loading. This value decreases by an order of magnitude to 1.9 x 10(-2) L m(-2) h(-1) when the reaction is carried out in a realistic background matrix when the pH is high (8.8). For all variables tested, Pd content has the most impact on reaction rates. Circulating batch-column experiments are used to study dechlorination under flow conditions and demonstrate the ability of nonstabilized Fe/Pd nanoaggregates to remove significant amounts of TCE (80-90%) over a broad range of groundwater velocities (12.9-83 ft per day) using moderate metal loadings (0.23-0.5 g L(-1)).

5.
J Phys Chem B ; 111(25): 7142-54, 2007 Jun 28.
Article in English | MEDLINE | ID: mdl-17530798

ABSTRACT

The use of membrane immobilization to carry out the batch dechlorination of trichloroethylene (TCE) using bimetallic Fe/Ni (4:1, Fe to Ni) nanoparticles in cellulose acetate membranes is examined using modeling of transport phenomenon based on experimental results. Membranes are synthesized using both gelation and solvent evaporation techniques for phase inversion. The reduction of metal ions within cellulose acetate phase-inversion membranes was accomplished using sodium borohydride reduction to obtain up to 2 wt % total metals. Characterization of the mixed-matrix structure reveals a bimodal particle distribution ranging between 18 and 80 nm within the membrane cross section. The distribution is the result of changes in the morphology of the cellulose acetate support. The diffusivity and linear partitioning coefficient for the chlorinated organic were measured and are 2.0 x 10(-8) cm2.s-1 and 3.5 x 10(-2) L.g-1, respectively. An unsteady-state model for diffusion through a membrane with reaction was developed to predict experimental results with an error of only 7.2%. The error can be attributed to the lack of the model to account for loss of reactivity through pH effects, alloy effects (bimetallic ratio), and oxidation of nanoparticles. Simulations were run to vary the major transport variables, partitioning and diffusivity, and determine their impact on reaction kinetics. Of the two, diffusivity was less significant because it really only influences the time required for maximum TCE partitioning to the membrane to be achieved and has no effect on the limiting capacity of the membrane for TCE. Therefore, selection of an appropriate support material is crucial for development of highly reactive mixed-matrix membrane systems.


Subject(s)
Cellulose/analogs & derivatives , Chlorine/chemistry , Iron/chemistry , Metal Nanoparticles/chemistry , Nickel/chemistry , Trichloroethylene/chemistry , Cellulose/chemistry , Kinetics , Metal Nanoparticles/ultrastructure , Microscopy, Electron, Scanning , Models, Chemical , Particle Size
6.
Protein Eng Des Sel ; 17(1): 57-66, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14985538

ABSTRACT

The limited throughput, scalability and high cost of protein purification by chromatography provide motivation for the development of non-chromatographic protein purification technologies that are cheaper and easier to implement in a high-throughput format for proteomics applications and to scale up for industrial bioprocessing. We have shown that genetic fusion of a recombinant protein to an elastin-like polypeptide (ELP) imparts the environmentally sensitive solubility property of the ELP to the fusion protein, and thereby allows selective separation of the fusion protein from Escherichia coli lysate by aggregation above a critical temperature (T(t)). Further development of ELP fusion proteins as widely applicable purification tools necessitates a quantitative understanding of how fused proteins perturb the ELP T(t) such that purification conditions (T(t)) may be predicted a priori for new recombinant proteins. We report here the effect that fusing six different proteins has on the T(t) of an ELP. A negative correlation between T(t) and the fraction hydrophobic surface area on the fused proteins was observed, which was determined from computer modeling of the available three-dimensional structure. The thermally triggered aggregation behavior of ELP-coated, functionalized gold colloids as well as ligand binding to the tendamistat-ELP fusion protein support the hypothesis that hydrophobic surfaces in molecular proximity to ELPs depress the ELP T(t) by a mechanism analogous to hydrophobic residue substitution in the ELP repeat, Val-Pro-Gly-Xaa-Gly.


Subject(s)
Peptides/chemistry , Protein Engineering/methods , Recombinant Fusion Proteins/chemistry , Amino Acid Sequence , Databases as Topic , Escherichia coli/metabolism , Gold Colloid/chemistry , Ligands , Models, Molecular , Molecular Sequence Data , Plasmids/metabolism , Protein Conformation , Protein Folding , Sequence Homology, Amino Acid , Solubility , Surface Plasmon Resonance , Temperature , Thermodynamics
7.
Muscle Nerve ; 24(12): 1665-76, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11745976

ABSTRACT

The relationships between in vivo (31)P magnetic resonance spectroscopy (MRS) and in vitro markers of oxidative capacity (mitochondrial function) were determined in 27 women with varying levels of physical fitness. Following 90-s isometric plantar flexion exercises, calf muscle mitochondrial function was determined from the phosphocreatine (PCr) recovery time constant, the adenosine diphosphate (ADP) recovery time constant, the rate of change of PCr during the initial 14 s of recovery, and the apparent maximum rate of oxidative adenosine triphosphate (ATP) synthesis (Q(max)). Muscle fiber type distribution (I, IIa, IIx), citrate synthase (CS) activity, and cytochrome c oxidase (COX) activity were determined from a biopsy sample of lateral gastrocnemius. MRS markers of mitochondrial function correlated moderately (P < 0.05) with the percentage of type IIa oxidative fibers (r = 0.41 to 0.66) and CS activity (r = 0.48 to 0.64), but only weakly with COX activity (r = 0.03 to 0.26, P > 0.05). These results support the use of MRS to determine mitochondrial function in vivo.


Subject(s)
Mitochondria/metabolism , Muscle, Skeletal/metabolism , Oxygen Consumption/physiology , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Adult , Biopsy , Citrate (si)-Synthase/metabolism , Electron Transport Complex IV/metabolism , Female , Humans , In Vitro Techniques , Isometric Contraction/physiology , Magnetic Resonance Imaging , Middle Aged , Muscle, Skeletal/cytology , Phosphocreatine/metabolism
8.
Int J Obes Relat Metab Disord ; 25(9): 1309-15, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11571592

ABSTRACT

OBJECTIVE: To investigate whether skeletal muscle anaerobic metabolism, oxidative metabolism or metabolic economy during controlled sub-maximal and near-maximal exercises is altered in overweight women after diet-induced weight reduction, and whether these parameters are different between normal-weight, obesity-prone and normal-weight obesity-resistant women with similar physical fitness levels. DESIGN: A prospective weight loss study of overweight women and their comparison with never overweight controls. SUBJECTS: Thirty overweight, nondiabetic, premenopausal women and 28 never overweight controls were included in this analysis. All were participating in a longitudinal investigation of the role of energy metabolism in the etiology of obesity. The overweight women were recruited specifically to have a positive family history of obesity and have a body mass index (BMI) between 27 and 30 kg/m(2) and were studied in the overweight state and after reduction to a normal weight. The never-overweight controls were recruited specifically to have no personal and family history of obesity and were group matched with the weight-reduced post-overweight subjects in terms of premenopausal status, age, BMI, race and sedentary lifestyle. MEASUREMENTS: All testing was performed following one month of weight maintenance and during the follicular phase of the menstrual cycle. Hydrostatic weighing was performed to measure body composition and a whole-body maximal oxygen uptake (VO(2max)) test was done to measure aerobic fitness. (31)P MRS was used to determine ATP production from oxidative phosphorylation (OxPhos), 'anaerobic' glycolysis (AnGly), and creatine kinase (CK), as well as muscle metabolic economy. The time constant of ADP (TC(ADP)), V(PCr) (ie the initial rate of PCr resynthesis following exercise), and Q(max) (ie the apparent maximal oxidative ATP production rate) were also calculated as additional markers of mitochondrial function. RESULTS: Diet-induced weight loss did not have any effects on the anaerobic metabolism markers (AnGly and CK). The aerobic metabolism markers calculated from the initial recovery data (OxPhos and V(PCr)) were unaffected by diet-induced weight loss. However, diet-induced weight loss resulted in improvements in the TC(ADP) and Q(max) in the post-overweight state as compared to their overweight state. There were no differences in any of the anaerobic (AnGly and CK) or oxidative metabolism markers (OxPhos, V(PCr), Q(max) and TC(ADP)) between the post-overweight and control groups. CONCLUSIONS: Once the overweight women were reduced to a normal-weight state, their skeletal muscle energy metabolism and economy was similar to the never overweight control women. In overweight women, oxidative metabolism or mitochondrial function may be limited by blood flow to the muscle following the cessation of exercise.


Subject(s)
Exercise/physiology , Muscle, Skeletal/metabolism , Obesity/metabolism , Weight Loss/physiology , Adult , Body Mass Index , Case-Control Studies , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Muscle, Skeletal/blood supply , Obesity/etiology , Oxygen Consumption , Phosphorus Isotopes , Physical Fitness , Prospective Studies , Reproducibility of Results
9.
J Control Release ; 74(1-3): 213-24, 2001 Jul 06.
Article in English | MEDLINE | ID: mdl-11489497

ABSTRACT

We report a new thermal targeting method in which a thermally responsive drug carrier selectively accumulates in a solid tumor that is maintained above physiological temperature by externally applied, focused hyperthermia. We synthesized two thermally responsive polymers that were designed to exhibit a lower critical solution temperature (LCST) transition slightly above physiological temperature: (1) a genetically engineered elastin-like polypeptide (ELP) and (2) a copolymer of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm). The delivery of systemically injected polymer-rhodamine conjugates to solid tumors was investigated by in vivo fluorescence video microscopy of ovarian tumors implanted in dorsal skin fold window chambers in nude mice, with and without local hyperthermia. When tumors were heated to 42 degrees C, the accumulation of a thermally responsive ELP with a LCST of 40 degrees C was approximately twofold greater than the concentration of the same polymer in tumors that were not heated. Similar results were also obtained for a thermally responsive poly(NIPAAM-co-AAm), though the enhanced accumulation of this carrier in heated tumors was lower than that observed for the thermally responsive ELP. These results suggest that enhanced delivery of drugs to solid tumors can be achieved by conjugation to thermally responsive polymers combined with local heating of tumors.


Subject(s)
Drug Delivery Systems , Hyperthermia, Induced , Polymers/chemistry , Acrylamides/chemistry , Animals , Chemical Phenomena , Chemistry, Physical , Elastin/chemistry , Mice , Mice, Nude , Microscopy, Fluorescence , Microscopy, Video , Nephelometry and Turbidimetry , Spectrophotometry, Ultraviolet
10.
Biotechnol Prog ; 17(4): 720-8, 2001.
Article in English | MEDLINE | ID: mdl-11485434

ABSTRACT

Elastin-like polypeptides (ELPs) undergo a reversible, soluble-to-insoluble phase transition in aqueous solution upon heating through a characteristic transition temperature (T(t)). Incorporating a terminal ELP expression tag into the gene of a protein of interest allows ELP fusion proteins to be purified from cell lysate by cycles of environmentally triggered aggregation, separation from solution by centrifugation, and resolubilization in buffer. In this study, we examine the effect of ELP length on the expression and purification of a thioredoxin-ELP fusion protein and show that reducing the size of the ELP tag from 36 to 9 kDa increases the expression yield of thioredoxin by 4-fold, to a level comparable to that of free thioredoxin expressed without an ELP tag, while still allowing efficient purification. However, truncation of the ELP tag also results in a more complex transition behavior than is observed with larger tags. For both the 36 kDa and the 9 kDa ELP tag fused to thioredoxin, dynamic light scattering showed that large aggregates with hydrodynamic radii of approximately 2 microm form as the temperature is raised to above the T(t). These aggregates persist at all temperatures above the T(t) for the thioredoxin fusion with the 36 kDa ELP tag. With the 9 kDa tag, however, smaller particles with hydrodynamic radii of approximately 12 nm begin to form at the expense of the larger, micron-size aggregates as the temperature is further raised above the T(t). Because only large aggregates can be effectively retrieved by centrifugation, efficient purification of fusion proteins with short ELP tags requires selection of solution conditions that favor the formation of the micron-size aggregates. Despite this additional complexity, our results show that the ELP tag can be successfully truncated to enhance the yield of a target protein without compromising its purification.


Subject(s)
Elastin/isolation & purification , Recombinant Fusion Proteins/isolation & purification , Thioredoxins/isolation & purification , Base Sequence , Centrifugation/methods , Chromatography, Affinity , Elastin/genetics , Escherichia coli/genetics , Light , Molecular Sequence Data , Nephelometry and Turbidimetry , Particle Size , Peptides/genetics , Peptides/isolation & purification , Recombinant Fusion Proteins/genetics , Scattering, Radiation , Temperature , Thioredoxins/genetics
11.
J Exp Psychol Hum Percept Perform ; 27(4): 763-97, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11518143

ABSTRACT

In 4 experiments, participants alternated between different tasks or performed the same task repeatedly. The tasks for 2 of the experiments required responding to geometric objects in terms of alternative classification rules, and the tasks for the other 2 experiments required solving arithmetic problems in terms of alternative numerical operations. Performance was measured as a function of whether the tasks were familiar or unfamiliar, the rules were simple or complex, and visual cues were present or absent about which tasks should be performed. Task alternation yielded switching-time costs that increased with rule complexity but decreased with task cuing. These factor effects were additive, supporting a model of executive control that has goal-shifting and rule-activation stages for task switching. It appears that rule activation takes more time for switching from familiar to unfamiliar tasks than for switching in the opposite direction.


Subject(s)
Cognition , Humans , Models, Psychological , Neuropsychological Tests , Psychological Theory , Reaction Time
12.
Psychol Sci ; 12(2): 101-8, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11340917

ABSTRACT

A fundamental issue for psychological science concerns the extent to which people can simultaneously perform two perceptual-motor tasks. Some theorists have hypothesized that such dual-task performance is severely and persistently constrained by a central cognitive "bottle-neck," whereas others have hypothesized that skilled procedural decision making and response selection for two or more tasks can proceed at the same time under adaptive executive control. The three experiments reported here support this latter hypothesis. Their results show that after relatively modest amounts of practice, at least some participants achieve virtually perfect time sharing in the dual-task performance of basic choice reaction tasks. The results also show that observed interference between tasks can be modulated by instructions about differential task priorities and personal preferences for daring (concurrent) or cautious (successive) scheduling of tasks. Given this outcome, future research should investigate exactly when and how such sophisticated skills in dual-task performance are acquired.


Subject(s)
Choice Behavior , Cognition , Practice, Psychological , Refractory Period, Psychological , Task Performance and Analysis , Adult , Female , Humans , Individuality , Male , Models, Psychological , Time Factors
13.
Muscle Nerve ; 24(5): 654-61, 2001 May.
Article in English | MEDLINE | ID: mdl-11317275

ABSTRACT

It is not known what causes the well-established inverse relationship between whole-body exercise economy and exercise intensity. The purpose of this study was to: (1) evaluate muscle exercise economy at 45%, 70%, and maximum isometric strength using 31P magnetic resonance spectroscopy (31P-MRS); and (2) determine the relationship between percent type II muscle fiber cross-section, whole-body exercise economy, and muscle exercise economy. Subjects included 32 premenopausal women. Muscle exercise economy was significantly different across the three exercise intensities (28.1 +/- 10.4, 24.8 +/- 8.2, and 20.2 +/- 7.5 N/cm2. mmol/L adenosine triphosphate [ATP] for the 45%, 70%, and maximum intensities, respectively). Percent type II muscle area was significantly related to whole-body metabolic economy during activities of daily living (r = -0.68) and 31P-MRS muscle metabolic economy during isometric plantar flexion (r = -0.53). These data suggest that skeletal muscle becomes less economical as force production increases, and that these decreases in metabolic economy may be related to increased dependence on inefficient type II muscle.


Subject(s)
Exercise/physiology , Muscle Fibers, Fast-Twitch/physiology , Muscle, Skeletal/metabolism , Adipose Tissue/physiology , Body Composition/physiology , Carbon Dioxide/metabolism , Female , Histocytochemistry , Humans , Isometric Contraction/physiology , Magnetic Resonance Imaging , Middle Aged , Oxygen Consumption/physiology
14.
Cancer Res ; 61(4): 1548-54, 2001 Feb 15.
Article in English | MEDLINE | ID: mdl-11245464

ABSTRACT

Elastin-like polypeptides (ELPs) are biopolymers of the pentapeptide repeat Val-Pro-Gly-Xaa-Gly that undergo an inverse temperature phase transition. They are soluble in aqueous solutions below their transition temperature (T1) but hydrophobically collapse and aggregate at temperatures greater than T1. We hypothesized that ELPs conjugated to drugs would enable thermally targeted drug delivery to solid tumors if their T1 were between body temperature and the temperature in a locally heated region. To test this hypothesis, we synthesized a thermally responsive ELP with a T1 of 41 degrees C and a thermally unresponsive control ELP in Escherichia coli using recombinant DNA techniques. In vivo fluorescence videomicroscopy and radiolabel distribution studies of ELP delivery to human tumors (SKOV-3 ovarian carcinoma and D-54MG glioma) implanted in nude mice demonstrated that hyperthermic targeting of the thermally responsive ELP for 1 h provides a approximately 2-fold increase in tumor localization compared to the same polypeptide without hyperthermia. We observed aggregates of the thermally responsive ELP by fluorescence videomicroscopy within the heated tumor microvasculature but not in control experiments, which demonstrates that the phase transition of the thermally responsive ELP carrier can be engineered to occur in vivo at a specified temperature. By exploiting the phase transition-induced aggregation of these polypeptides, this method provides a new way to thermally target polymer-drug conjugates to solid tumors.


Subject(s)
Elastin/pharmacokinetics , Glioma/metabolism , Hyperthermia, Induced , Ovarian Neoplasms/metabolism , Peptides/pharmacokinetics , Amino Acid Sequence , Animals , Base Sequence , Drug Stability , Elastin/chemistry , Elastin/genetics , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Microscopy, Fluorescence , Microscopy, Video , Molecular Sequence Data , Peptides/chemistry , Peptides/genetics , Protein Engineering , Temperature , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
15.
Rev Gaucha Enferm ; 22(2): 21-38, 2001 Jul.
Article in Portuguese | MEDLINE | ID: mdl-12229020

ABSTRACT

With this paper I intend to join to theorists who have discussed issues of difference and identity, with the aim of problematising some of the knowing/doing dimensions of nursing in contemporaneity. I am using as an analytical-theoretical background the Cultural Studies and Gender theories that develop a critical approach to post-structuralism. In the light of such a background I analyse some elements or constitutive aspects of the current theories on Care. I argue that to think care from the perspective of difference is to accept the challenge of not thinking about it as an action underpinned by scientific, philosophical and universal humanitarian assumptions, and start its theorisation and exercise as an action that is fundamentally political.


Subject(s)
Nursing Care/trends , Philosophy, Nursing , Cultural Characteristics , Cultural Diversity , Ethics, Nursing , Female , Humanism , Humans , Male , Nursing Care/methods , Nursing Care/standards , Sex Factors
16.
Med Sci Sports Exerc ; 32(7): 1307-13, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10912898

ABSTRACT

PURPOSE: It is well accepted that maximum strength is related to muscle size. The primary purpose of this study was to determine whether anthropometric or dual-energy x-ray absorptiometry (DEXA) estimates of muscle size were valid predictors of plantar flexor maximum voluntary contraction (MVC) strength and could be used in lieu of more sophisticated techniques (e.g., magnetic resonance imaging (MRI)). Additionally, we compared the relationship among MVC and three MRI-determined muscle size measures; anatomical (ACSA) and physiological (PCSA) cross-sectional areas; and muscle volume (VOLm). METHODS: We measured plantar flexor MVC at 1.83 rad and various indices of muscle size: 1) body weight, 2) total body lean mass (LM) (DEXA), 3) lower leg LM (DEXA), 4) lower leg circumference, 5) estimated muscle+bone cross-sectional area (CSA) from circumference and calf skin-fold, 6) triceps surae ACSA, 7) triceps surae PCSA, and (8) triceps surae volume (VOLm), in 39 premenopausal women (mean +/- SD: 36 +/- 8 yr, 165 +/- 6 cm, and 65 +/- 9 kg). RESULTS: Zero-order correlations showed significant (P < 0.05) associations between MVC and total body LM (r = 0.365), lower leg LM (r = 0.381), circumference (r = 0.584), estimated muscle+bone CSA (r = 0.447), ACSA (r = 0.733), PCSA (r = 0.715), and VOLm (r = 0.649). By using the Fisher Z-transformation, ACSA and PCSA correlated significantly higher with MVC (P < 0.05) than anthropometric and DEXA indices. Further, only ACSA and PCSA regressed to the origin, indicating the ability to predict MVC was greatest with these two measures. CONCLUSIONS: The MRI-determined muscle size indices, which were specific to the triceps surae, correlated with strength better than whole limb anthropometric and DEXA indices. In this group of women, both ACSA and PCSA appeared superior to VOLm for predicting strength. PCSA was not found to be more precise than ACSA. ACSA appears to provide adequate precision for estimating plantar flexor specific tension in vivo.


Subject(s)
Isometric Contraction/physiology , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/physiology , Absorptiometry, Photon , Adult , Anthropometry , Female , Humans , Magnetic Resonance Imaging , Sensitivity and Specificity , Tensile Strength
17.
NMR Biomed ; 13(1): 14-27, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10668050

ABSTRACT

The reliability, relation to whole-body maximal oxygen uptake (VO(2max)), and force-level sensitivity of (31)P MRS markers of mitochondrial function were studied in 39 normal-weight women. Following 90 s isometric plantar-flexion exercises at 45, 70 and 100% of maximum voluntary contraction, skeletal muscle mitochondrial function was determined from the phosphocreatine recovery time constant (TC(PCr)), the ADP recovery time constant (TC(ADP)), and the rate of change in PCr during the first 14 s of recovery (OxPhos). VO(2max) was measured on a treadmill. Test-retest measurements were obtained in a subset of seven women. Overall, TC(PCr), TC(ADP) and OxPhos were reproducible for all exercises (coefficients of variation = 2.3-19.3%). With increasing force-level, TC(PCr) was prolonged (29.0 +/- 8.2, 31.9 +/- 9.0 and 35.4 +/- 9.5 s), OxPhos was increased (0.159 +/- 0.081, 0.247 +/- 0.090 and 0.310 +/- 0.114), and TC(ADP) was shortened (22.4 +/- 7.9, 21.3 +/- 6.2, and 19.5 +/- 6.7; p < 0.01). All MRS markers of mitochondrial function were correlated with VO(2max) (r = 0.41-0.72; p < 0.05). These results suggest that measurements of TC(PCr), TC(ADP) and OxPhos yield reproducible results that correlate with whole-body VO(2max) and that vary in force-level sensitivity.


Subject(s)
Magnetic Resonance Spectroscopy , Mitochondria/physiology , Muscle, Skeletal/physiology , Oxygen Consumption , Adenosine Diphosphate/analysis , Adult , Biomarkers , Female , Humans , Hydrogen-Ion Concentration , Middle Aged , Phosphocreatine/analysis , Phosphorus Isotopes , Reproducibility of Results
18.
Am J Physiol Endocrinol Metab ; 278(1): E153-61, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10644550

ABSTRACT

We used (31)P magnetic resonance spectroscopy to measure maximal mitochondrial function in 12 obesity-prone women before and after diet-induced weight reduction and in 12 matched, never-obese, and 7 endurance-trained controls. Mitochondrial function was modeled after maximum-effort plantar flexion from the phosphocreatine recovery time constant (TC(PCr)), the ADP recovery time constant (TC(ADP)), and the rate of change in PCr during the first 14 s of recovery (OxPhos). Weight reduction was not associated with a significant change in mitochondrial function by TC(PCr), TC(ADP), or OxPhos. Mitochondrial function was not different between postobese and never-obese controls by TC(PCr) [35.1 +/- 2.5 (SE) vs. 34.6 +/- 2.5 s], TC(ADP) (22.9 +/- 1.8 vs. 21.2 +/- 1.8 s), or OxPhos (0.26 +/- 0. 03 vs. 0.25 +/- 0.03 mM ATP/s), postobese vs. never-obese, respectively. However, TC(ADP) was significantly faster (14.5 +/- 2. 3 s), and OxPhos was significantly higher (0.38 +/- 0.04 mM ATP/s) in the endurance-trained group. These results suggest that maximal mitochondrial function is not impaired in normal-weight obesity-prone women relative to their never-obese counterparts but is increased in endurance-trained women.


Subject(s)
Exercise/physiology , Mitochondria, Muscle/physiology , Muscle, Skeletal/physiology , Obesity/physiopathology , Physical Fitness/physiology , Weight Loss/physiology , Adult , Disease Susceptibility , Female , Humans , Isometric Contraction , Magnetic Resonance Spectroscopy , Oxygen Consumption , Physical Endurance/physiology
19.
Psychol Aging ; 15(4): 571-95, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11144318

ABSTRACT

The apparently deleterious effect of aging on dual-task performance is well established, but there is little agreement about the source of this effect. Studies of the psychological refractory period (PRP) indicate that young adults can flexibly control dual-task performance through task-coordination strategies. Thus, the performance of older adults might differ from young adults because older adults use different task-coordination strategies. To test this hypothesis, the executive-process interactive control (EPIC) architecture was applied to quantify the reaction time data from two PRP experiments conducted with young (age 18-26) and older (age 60-70) adults. The results show that participants' ability to coordinate the processing of two tasks did not decline with age. However, dual-task time costs were greater in the older adults. Three sources for this increase were found: generalized slowing, process-specific slowing, and the use of more cautious task-coordination strategies by the older adults.


Subject(s)
Aging/psychology , Cognition , Refractory Period, Psychological , Adult , Aged , Female , Humans , Male , Middle Aged , Task Performance and Analysis
20.
Nat Biotechnol ; 17(11): 1112-5, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10545920

ABSTRACT

Elastin-like polypeptides (ELPs) undergo a reversible, inverse phase transition. Below their transition temperature (Tt), ELPs are soluble in water, but when the temperature is raised above Tt, phase transition occurs, leading to aggregation of the polypeptide. We demonstrate a method for purification of soluble fusion proteins incorporating an ELP tag. Advantages of this method, termed "inverse transition cycling," include technical simplicity, low cost, ease of scale-up, and capacity for multiplexing. More broadly, the ability to environmentally modulate the physicochemical properties of recombinant proteins by fusion with ELPs will allow diverse applications in bioseparation, immunoassays, biocatalysis, and drug delivery.


Subject(s)
Peptides/metabolism , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Amino Acid Sequence , Base Sequence , Elastin/genetics , Elastin/metabolism , Molecular Sequence Data , Peptides/genetics , Thioredoxins/genetics , Thioredoxins/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...