Modification of Shape Memory Polymer Foams Using Tungsten, Aluminum Oxide, and Silicon Dioxide Nanoparticles.

Shape memory polymer (SMP) foams were synthesized with three different nanoparticles (tungsten, silicon dioxide, and aluminum oxide) for embolization of cerebral aneurysms. Ultra-low density SMP foams have previously been utilized for aneurysm occlusion, resulting in a rapid, stable thrombus. However, the small cross section of foam struts can potentially lead to fracture and particulate generation, which would be a serious adverse event for an embolic device. The goal of this study was to improve the mechanical properties of the system by physically incorporating fillers into the SMP matrix. Thermal and mechanical characterization suggested minimal changes in thermal transition of the SMP nanocomposites and improved mechanical strength and toughness for systems with low filler content. Actuation profiles of the three polymer systems were tuned with filler type and content, resulting in faster SMP foam actuation for nanocomposites containing higher filler content. Additionally, thermal stability of the SMP nanocomposites improved with increasing filler concentration, and particulate count remained well below accepted standard limits for all systems. Extraction studies demonstrated little release of silicon dioxide and aluminum oxide from the bulk over 16 days. Tungstun release increased over the 16 day examination period, with a maximum measured concentration of approxiately 2.87 µg/mL. The SMP nanocomposites developed through this research have the potential for use in medical devices due to their tailorable mechanical properties, thermal resisitivity, and actuation profiles.

Solvent stimulated actuation of polyurethane-based shape memory polymer foams using dimethyl sulfoxide and ethanol.

Solvent exposure has been investigated to trigger actuation of shape memory polymers (SMPs) as an alternative to direct heating. This study aimed to investigate the feasibility of using dimethyl sulfoxide (DMSO) and ethanol (EtOH) to stimulate polyurethane-based SMP foam actuation and the required solvent concentrations in water for rapid actuation of hydrophobic SMP foams. SMP foams exhibited decreased Tg when submerged in DMSO and EtOH when compared to water submersion. Kinetic DMA experiments showed minimal or no relaxation for all SMP foams in water within 30 min, while SMP foams submerged in EtOH exhibited rapid relaxation within 1 min of submersion. SMP foams expanded rapidly in high concentrations of DMSO and EtOH solutions, where complete recovery over 30 min was observed in DMSO concentrations greater than 90% and in EtOH concentrations greater than 20%. This study demonstrates that both DMSO and EtOH are effective at triggering volume recovery of polyurethane-based SMP foams, including in aqueous environments, and provides promise for use of this actuation technique in various applications.

Tonic sympathetic support of metabolic rate is attenuated with age, sedentary lifestyle, and female sex in healthy adults.

We recently demonstrated in young adult humans that the sympathetic nervous system contributes to the control of resting metabolic rate via tonic beta-adrenergic receptor stimulation. In the present follow-up study we determined the respective effects of age, habitual exercise status, and sex on this regulatory mechanism. Resting metabolic rate (ventilated hood, indirect calorimetry) was determined in 55 healthy sedentary or endurance exercise-trained adults, aged 18-35 or 60-75 yr (29 men and 26 women), before (baseline) and during the infusion of either a nonselective beta-adrenergic receptor antagonist (propranolol) or saline (control). Relative to baseline values, during beta-adrenergic receptor antagonism resting metabolic rate adjusted for fat-free mass was reduced to a lesser extent in older (mean +/- SE, -130 +/- 46 kJ/d) compared with young (-297 +/- 46) adults, sedentary (-151 +/- 50) compared with endurance exercise-trained (-268 +/- 46) adults, and women (-105 +/- 33) compared with men (-318 +/- 50; all P < 0.01). Reductions in resting metabolic rate during beta-adrenergic receptor antagonism were positively related to higher baseline resting metabolic rate and plasma catecholamine concentrations and negatively related to adiposity (all P < 0.05). Resting metabolic rate was unchanged in response to saline control in all groups. These results provide experimental support for the hypothesis that aging, sedentary living, and female sex are associated with attenuated sympathetic nervous system support of resting metabolic rate in healthy adult humans.

Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans.

The sympathetic nervous system (SNS) plays an important role in the regulation of energy expenditure. However, whether tonic SNS activity contributes to resting metabolic rate (RMR) in healthy adult humans is controversial, with the majority of studies showing no effect. We hypothesized that an intravenous propranolol infusion designed to achieve complete beta-adrenergic blockade would result in a significant acute decrease in RMR in healthy adults. RMR (ventilated hood, indirect calorimetry) was measured in 29 healthy adults (15 males, 14 females) before and during complete beta-adrenergic blockade documented by plasma propranolol concentrations > or =100 ng/ml, lack of heart rate response to isoproterenol, and a plateau in RMR with increased doses of propranolol. Propranolol infusion evoked an acute decrease in RMR (-71 +/- 11 kcal/day; -5 +/- 0.7%, P < 0.0001), whereas RMR was unchanged from baseline levels during a saline control infusion (P > 0.05). The response to propranolol differed from the response to saline control (P < 0.01). The absolute and percent decreases in RMR with propranolol were modestly related to baseline plasma concentration of norepinephrine (r = 0.38, P = 0.05; r = 0.44, P = 0.02, respectively). These findings provide direct evidence for the concept of tonic sympathetic beta-adrenergic support of RMR in healthy nonobese adults.

Relation of leptin and insulin to adiposity-associated elevations in sympathetic activity with age in humans.

OBJECTIVE: To determine whether plasma leptin and insulin concentrations are related to adiposity-associated elevations in muscle sympathetic nerve activity (MSNA) with age in healthy adult humans. DESIGN: Cross-sectional investigation of young and older adult men. SUBJECTS: Thirty healthy adult men, 16 young (25+/-1 y, mean+/-s.e.) and 14 older (61+/-1 y). MEASUREMENTS/RESULTS: The older men had higher (P<0.05) levels of body mass, BMI, total fat mass and truncal fat mass (dual energy X-ray absorptiometry) than the young men. MSNA burst frequency (microneurography) was approximately 75% higher in the older men (P<0.001). Plasma leptin concentrations were approximately 150% higher (P<0.01), whereas plasma insulin concentrations were approximately 70% higher (P<0.05) in the older subjects. MSNA was related to both total (r=0.51, P<0.01) and truncal (r=0.56, P<0.01) fat mass. Plasma leptin concentrations were related to total and truncal fat mass (both r=0.83, P<0.001), and to MSNA (r=0.49, P<0.01). Plasma insulin concentrations were related to MSNA (r=0.38, P<0.05). We used partial correlation analyses to assess whether leptin and/or insulin are potential contributors to the relation between body fat and MSNA. Adjusting for the effects of plasma leptin, but not insulin, concentrations eliminated the significant relations between MSNA and total and truncal fat mass. CONCLUSION: Our results: (1) demonstrate a positive relation between MSNA and plasma leptin concentrations in young and older healthy men; and (2) support the concept that circulating leptin concentrations may act as a humoral signal contributing to adiposity-associated elevations in MSNA with age in adult humans.

Lower daily energy expenditure as measured by a respiratory chamber in subjects with spinal cord injury compared with control subjects.

BACKGROUND: This study was designed to determine the effect of chronic spinal cord injury on daily energy expenditure. OBJECTIVE: We hypothesized that both resting and total energy expenditure would be lower in spinal cord-injured (SCI) subjects than in control subjects because of lower sympathetic nervous system activity and reduced levels of physical activity in SCI subjects. DESIGN: Twenty-four-hour energy expenditure (24-h EE), resting metabolic rate (RMR), sleeping metabolic rate, spontaneous physical activity, the thermic effect of food (TEF), and 24-h respiratory quotient were measured by using a respiratory chamber in 10 male SCI subjects (injury ranged from level C6 to L3) and 59 age-matched, noninjured, male control subjects. RESULTS: The 24-h EE was lower in SCI than in control subjects (7824 +/- 305 compared with 9941 +/- 188 kJ, P < 0.01). After adjustment for fat-free mass, fat mass, and age, 24-h EE was still lower (-753 kJ/d, P < 0.01) in SCI than in control subjects. Spontaneous physical activity measured by a radar system was also significantly lower (4.6 +/- 0.6% compared with 6.5 +/- 0.3% of time, P < 0.01) in SCI than in control subjects. In absolute value (7347 +/- 268 compared with 9251 +/- 1326 kJ/d, P < 0.01) or after adjustment for fat-free mass, fat mass, and age (-678 kJ/d, P < 0.01), RMR was also lower in SCI than in control subjects. TEF was significantly lower in SCI than in control subjects (987 +/- 142 compared with 1544 +/- 213 kJ/d, representing 12.9% and 15.9% of total energy intake, respectively, P < 0.05). The sleeping metabolic rate and 24-h respiratory quotient did not differ significantly between groups. CONCLUSIONS: The 24-h EE was significantly lower in SCI than in control subjects. This difference can be explained by the lower levels of physical activity, and lower RMR and TEF values, in SCI subjects.

In situ lipolytic responses to isoproterenol and physiological stressors are similar in obese Pima Indians and Caucasians.

Evidence suggests that impaired lipolysis may contribute to fat accumulation. To test whether the lipolytic response to adrenergic stimulation is lower in Pima Indians, a population prone to obesity and type 2 diabetes mellitus, than in Caucasians, 48 healthy, non-diabetic subjects were studied: 27 Pima Indians (12 males and 15 females, 30 +/- 7 yr, 85 +/- 18 kg, 36 +/- 10% body fat; mean +/- SD) and 21 Caucasians (11 males and 10 females, 34 +/- 7 yr, 105 +/- 26 kg, 39 +/- 11% body fat). Lipolysis in the abdominal s.c. adipose tissue was assessed in situ by glycerol concentration in microdialysis samples at baseline and during local infusion of the nonselective beta-adrenergic agonist isoproterenol (10(-6) mol/L), mental stress, and submaximal exercise. The baseline dialysate glycerol concentrations were similar in Pima Indians and Caucasians. Lipolytic response (relative increment in dialysate glycerol concentration, percentage above the baseline) was similar in Pima Indians and Caucasians in response to local isoproterenol infusion (77 +/- 36% and 76 +/- 40%) and exercise (38 +/- 38% and 41 +/- 41%). During mental stress, the dialysate concentration did not change significantly from baseline in either group. Changes in local blood flow, determined by ethanol dilution, did not differ between the two groups. In conclusion, the high propensity for obesity in Pima Indians does not seem to be due to an impaired lipolytic response to stimuli.

Whole body fat oxidation is related to in situ adipose tissue lipolytic response to isoproterenol in males.

A high 24-h respiratory quotient (RQ), i.e., low fat oxidation, predicts weight gain. To determine whether impaired fat mobilization (lipolysis) may contribute to weight gain, we studied the relation between lipolytic response to nonselective beta-adrenergic stimulation and RQ measured in a respiratory chamber in 21 males (11 Caucasians, 10 Pima Indians; age 32 +/- 5 yr, weight 93 +/- 24 kg, body fat 30 +/- 8%; means +/- SD) and 23 females (10 Caucasians, 13 Pima Indians; age 32 +/- 9 yr, weight 95 +/- 26 kg, body fat 44 +/- 8%). Lipolytic response was assessed as the relative increase in dialysate glycerol concentration (% above baseline) when isoproterenol (1 micromol/l) was added to the perfusate of a microdialysis probe inserted in the abdominal subcutaneous adipose tissue. In males, but not in females, basal RQ measured during sleep from 0500 to 0630 and adjusted for waist circumference was negatively correlated to lipolytic response (r = -0.66, P = 0.001). The results suggest that in males, impaired beta-adrenergic-mediated lipolysis may contribute to low rates of fat oxidation, a condition known to predispose to weight gain.

Adiposity, plasma leptin concentration and reproductive function in active and sedentary females.

OBJECTIVE: Circulating leptin has recently been proposed as the peripheral signal indicating the adequacy of nutritional status for reproductive function. To test whether low plasma leptin concentration for a given degree of adiposity is associated with menstrual dysfunction, we measured plasma leptin concentration and body composition in young premenopausal women with normal or abnormal reproductive function. DESIGN: Fasting plasma leptin concentration (ELISA), body composition (dual energy X-ray absorptiometry) and menstrual status (menstrual history and hormonal profile) were assessed in 34 premenopausal women characterized by different levels of physical activity. RESULTS: Body fat content and plasma leptin concentration were both reduced in women with impaired reproductive function (amenorrheic < anovulatory < eumenorrheic women). However, after adjusting plasma leptin concentration for percentage body fat, there was no independent association between leptin and menstrual function. CONCLUSION: Menstrual abnormalities in young premenopausal women seem to occur as a consequence of the linear decline in adiposity and plasma leptin concentration observed in response to inadequate nutritional status. Levels of adiposity below 15% and plasma leptin concentration below 3 ng/ml are more likely to be associated with impaired reproductive function.

No effect of the Trp64Arg beta 3-adrenoceptor variant on in vivo lipolysis in subcutaneous adipose tissue.

A Trp64Arg variant in the human beta 3-adrenoceptor is associated with earlier onset of non-insulin-dependent diabetes mellitus and obesity in several populations. The present study investigated in vivo lipolysis in individuals homozygous for the 'variant' allele coding for arginine (Arg) in position 64 of the beta 3-adrenoceptor or homozygous for the 'wild type' tryptophan (Trp) allele. Subjects were 25 healthy, non-diabetic Pima Indians, 8 Arg (2 males, 6 females; aged 34 +/- 9 years, BMI 36.2 +/- 7.7 kg/m2, 43 +/- 11% body fat [mean +/- SD]), and 17 Trp (9 males, 8 females; aged 30 +/- 5 years, BMI 30.4 +/- 6.1 kg/m2, 39 +/- 9% body fat). After an overnight fast, a microdialysis probe was inserted in the subcutaneous adipose tissue and perfused with Ringer's solution. Dialysate was collected in 10-min fractions during a 30-min baseline and during 40 min with isoproterenol, a non-selective beta-adrenergic agonist, added to the perfusate (1 mumol/l). Changes in rate of lipolysis were assessed as changes in dialysate glycerol concentration. The relative changes in dialysate glycerol concentrations in response to isoproterenol, expressed as percent over baseline, were similar in the two groups (i.e. 63 +/- 30 and 74 +/- 28% in the Arg and Trp subjects, respectively). The results were also similar in the two groups after adjustment for sex and percentage of body fat. No differential effect of isoproterenol on blood flow was demonstrated between the two groups (assessed by the ethanol dilution technique). These results are consistent with in vitro studies showing no functional effect of the beta 3-adrenoceptor variant, and/or indicate that the beta 3-adrenoceptor is not very important for subcutaneous adipose tissue lipolysis.