Effects of an oral biodegradable device used for 12 weeks on weight reduction, cardiovascular risk factors, satiety, snacking, and meal size.

Background: The Epitomee Capsule (EC) is an, oral, self-use, bio-degradable device for weight management, composed of absorbent polymers that self-expands in the stomach (pH-sensitive) and creates a triangular shape, space-occupying super-absorbent gel structure. A recent study reported that 42 % of study completers obtained >5 % weight reduction at 12 weeks. We performed exploratory analyses of this study to evaluate its effect on cardiovascular risk factors and on self-reported satiety, between-meal snacking and meal-size. Methods: This single-center observational study (Israel) enrolled 78 volunteers, with mean age 41 years, BMI 32.5 kg/m2, systolic/diastolic blood pressure (SBP/DBP) 124/77 mmHg. The EC was given in addition to diet and physical activity counseling. Assessments included anthropometrics, BP, lipids, and three questions (translated from Hebrew) scored 1 (not at all) to 5 (very much) for "Do you feel the EC - Q1:helps you to consume less snacks in between meals? Q2:helps you to eat less in the meal?; Q3:is causing an early sense of satiety?". Changes from baseline were assessed using a mixed model and included all patients with at least one measure. Correlation-analysis between weight-change and PROs used Kendall's tau. Result: Compared to baseline, at 12 weeks, SBP/DBP were reduced (ΔSBP: -5.5 mmHg, p = 0.0003/ΔDBP: -1.9 mmHg, p = 0.1341), with a larger effect in people with hypertension at baseline (ΔSBP: -13.2 mmHg, p < 0.00001/ΔDBP: -6.1, p = 0.008). Triglyceride-level was also significantly reduced, but not other lipids. Mean scores to Q1-3 were high throughout, with slight decreases (Q1 at W2 3.9 ± 1.1/W12 3.0 ± 1.6; Q2 at W2 3.7 ± 1.1/W12 3.1 ± 1.6; Q3 at W2 3.8 ± 1.2/W12 2.9 ± 1.6). There was a moderate correlation between PROs and weight reduction, although significance was not observed for all weeks. Conclusions: Exploratory analyses of 12 weeks treatment with EC demonstrated significant reductions in SBP, DBP, and triglycerides. The weight reduction correlated with satiety, less snacking, and reduced meal size.

New and Advanced Picosecond Lasers for Tattoo Removal.

Early methods of tattoo removal ultimately resulted in unacceptable cosmetic outcomes. While the introduction of laser technology was an improvement over the existing chemical, mechanical, and surgical procedures, the use of nonselective tattoo removal with carbon dioxide and argon lasers led to scarring. Q-switched lasers with nanosecond (10-9) pulse domains were considered to have revolutionized tattoo treatment, by selectively heating the tattoo particles, while reducing the adverse sequelae to adjacent normal skin. Theoretical considerations of restricting pulse duration, to heat tattoo particles to higher temperatures, proposed the use of sub-nanosecond pulses to target particles with thermal relaxation times lower than the nanosecond pulses in Q-switched lasers. Initial studies demonstrated that picosecond (10-12) pulses were more effective than nanosecond pulses in clearing black tattoos. Advances in picosecond technology led to the development of commercially available lasers, incorporating several different wavelengths, to further refine pigment targeting.

A Multicenter Controlled Study to Evaluate Multiple Treatments With Nonthermal Focused Ultrasound for Noninvasive Fat Reduction.

BACKGROUND: Demand for nonsurgical esthetic body procedures has led to the development of noninvasive techniques for reducing localized subcutaneous adipose tissue. OBJECTIVE: This study assessed multiple treatments with nonthermal focused ultrasound for noninvasive abdominal treatment of excess fat deposits. MATERIALS AND METHODS: Subjects were randomly assigned to Group 1 for a 4-week control phase before undergoing 3 abdominal fat reduction treatments, at 2-week intervals, or to Group 2 for immediate treatment. Weight, abdominal circumference, tolerability to treatment, subject satisfaction, and adverse events were recorded. RESULTS: Weight remained stable in the 126 participants. Mean reduction in midline circumference was 2.5 ± 2.1 cm in the Group 1 and 3.5 ± 2.7 cm in the Group 2 at Week 22. The effect of multiple treatments was cumulative with a steady decrease in abdominal circumferences during the study. Erythema was observed in 28% of treatments but was mild and transient in nature. Subjects tolerated the treatments well and were satisfied with treatment outcome. CONCLUSION: The study demonstrated the efficacy and safety of multiple nonthermal focused ultrasound treatments of excess abdominal fat deposits. Although the remodeling effect is minor compared with traditional surgical procedures, successive focused ultrasound treatments significantly reduced treatment area circumference, while avoiding invasive techniques and their associated disadvantages.

The response of circulating brain natriuretic peptide to academic stress in college students.

Brain natriuretic peptide (BNP), a cardiac peptide, has been implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. The influence of academic stress on circulating concentration of the N-terminal fragment of BNP precursor (NT-proBNP), and in relation to the stress hormone (cortisol) response was studied in 170 college students undergoing major examinations. Just prior to the examination, we measured self-estimated stress level, systolic, and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma levels of cortisol, and NT-proBNP. These parameters were compared to the participants' baseline measurements, taken at the same hour of a different 'control day', without a major examination to induce stress. Hemodynamic variables (SBP, DBP, and HR) increased on the examination day compared with baseline values ( p < 0.001). Circulating cortisol concentration increased before examinations (+42%, p < 0.001). The response to stress was marked by a significant decrease in plasma NT-proBNP concentration (-40%, p < 0.001). We found in males a significant interaction between the cortisol elevation with examination stress and the NT-proBNP reduction ( p = 0.02). In response to academic stress, the plasma cortisol elevation was accompanied by a marked reduction in plasma NT-proBNP level. These data may indicate that mental stress entails an interface between the HPA axis and the peripheral natriuretic peptide system, leading to reciprocating changes in circulating levels of the corresponding hormones.

Serum oxidative stress level correlates with clinical parameters in chronic systolic heart failure patients.

BACKGROUND: Serum oxidative stress (OS) level has an important role in the inflammatory process of heart failure. HYPOTHESIS: The study was designed to analyze serum OS levels in chronic heart failure (HF) patients and to examine the relation between OS levels and other clinical and prognostic parameters of HF. METHODS: We studied 82 consecutive chronic symptomatic HF patients with systolic LV dysfunction (ejection fraction <45%). The serum OS level was determined using thermochemiluminescence assay. We compared the serum OS levels with patients' clinical and prognostic parameters. RESULTS: Higher serum OS levels were associated with higher New York Heart Association class (P = .01), worse renal function (serum urea, creatinine, and creatinine clearance) (P<.001) and higher serum levels of hs-C-reactive protein and N-terminal pro brain natriuretic peptide (P = .001, P<.001, respectively). CONCLUSIONS: In chronic systolic HF patients, high serum OS levels correlate with advanced disease and known markers of poor prognosis.

The guanine nucleotide binding protein beta polypeptide 3 gene C825T polymorphism is associated with elite endurance athletes.

A functional C825T polymorphism in the human guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene has been associated with enhanced G protein activation. Since reports regarding the interaction between physical activity and the GNB3 C825T polymorphism are limited and inconsistent, the aim of this study was to determine the frequency of C825T alleles among 155 elite Israeli athletes (endurance athletes and sprinters) and 234 healthy control subjects. Genotyping for GNB3 C825T was performed using polymerase chain reaction on DNA from leucocytes. Results showed that there was a significant difference in GNB3 C825T polymorphism genotype frequencies between endurance athletes and sprinters (P = 0.045) as well as between endurance athletes and control subjects (P = 0.046). We also observed a significantly higher proportion of the GNB3 TT genotype in the group of endurance athletes (19%) compared with the sprinters (5%, P = 0.014) and the control subjects (8.5%, P = 0.026). In the group of athletes, the odds ratio of GNB3 TT genotype being an endurance athlete was 4.49 (95% confidence interval 1.4-14.3) and of GNB3 CC genotype was 0.91 (95% confidence interval 0.47-1.77). These results were even more pronounced when we compared between the subgroups of 20 top-level endurance athletes and 24 top-level sprinters. We conclude that in Israeli athletes the GNB3 TT genotype is higher in elite endurance athletes than it is in sprinters, and within the endurance group it is higher in top-level athletes, suggesting a positive association between the TT genotype and the likelihood of being an elite endurance athlete.

Relation between AT1R gene polymorphism and long-term outcome in patients with heart failure.

OBJECTIVES: Angiotensin II plays a key role in the pathophysiology of heart failure (HF). This study examined the angiotensin II type 1 receptor (AT1R) polymorphism in patients with systolic HF and its relation to clinical manifestations and patient outcome. METHODS: We genotyped 134 patients with HF and reduced systolic function for the AT1R A1166C genotype using polymerase chain reaction and restriction fragment length polymorphism. We analyzed the relationship between the AT1R A1166C polymorphism and clinical, electrocardiographic, echocardiographic and laboratory parameters in patients with ischemic and non-ischemic etiology and examined the relation between the AT1R genotype and long-term (30 months) patient survival. RESULTS: In HF patients, frequency of the AT1R 1166C allele and specifically the CC genotype was similar to the general population, but associated with an ischemic and not a non-ischemic etiology (p = 0.02). The CC genotype was associated with more advanced disease and more severe abnormalities of renal function (p = 0.008). Survival analysis showed that AT1R CC homozygous patients had significantly higher mortality (p = 0.008; adjusted odds ratio for mortality 6.35, 95% confidence interval 1.49-11.21, p = 0.01). CONCLUSION: The CC AT1R genotype was associated with poor prognostic markers and increased mortality. The findings support the principle of genome-based therapies in the future treatment of HF patients.

IL6 (-174) and TNFA (-308) promoter polymorphisms are associated with systemic creatine kinase response to eccentric exercise.

Exertional rhabdomyolysis is a complex and poorly understood entity. The inflammatory system has an important role in muscle injury and repair. Serum creatine kinase (CK) is often used as systemic biomarker representing muscle damage. Considerable variation exists in CK response between different subjects. Genetic elements may act as predisposition factors for exertional rhabdomyolysis. Based on their biological activity, we hypothesized that in healthy subjects IL6 G-174C and TNFA G-308A promoter polymorphisms would be associated with CK response to exercise. We determined serum CK activity pre- and post-maximal eccentric contractions of the elbow flexor muscles. IL6 G-174C and TNFA G-308A genotypes were analyzed for possible relationship with changes in serum CK activity. IL6 G-174C genotype was associated with CK activity in a dose-dependent fashion. Subjects with one or more of the -174C allele had a greater increase and higher peak CK values than subjects homozygous for the G allele (mean +/- SE U/L: GG, 2,604 +/- 821; GC, 7,592 +/- 1,111; CC, 8,403 +/- 3,849, ANOVA P = 0.0003 for GG + GC genotypes versus CC genotype, P = 0.0005 for linear trend). IL6-174CC genotype was associated with a greater than threefold increased risk of massive CK response (adjusted odds ratio 3.29, 95% confidence interval 1.27-7.85, P = 0.009). A milder association (P = 0.06) was noted between TNFA G-308A genotype and CK activity. In conclusion, we found a strong association of the IL6 G-174C genotype with systemic CK response to strenuous exercise. Data suggest that homozygosity for the IL6-174C allele is a clinically important risk factor for exercise-induced muscle injury, further supporting the central role of cytokines in the reactive inflammatory process of muscle damage and repair.

Aldosterone synthase gene polymorphism as a determinant of atrial fibrillation in patients with heart failure.

We analyzed the possible association between aldosterone synthase (CYP11B2) T-344C polymorphism, which is associated with increased aldosterone activity, and the prevalence of atrial fibrillation (AF) in 196 consecutive patients who had symptomatic systolic heart failure (HF; left ventricular ejection fraction <40%) for > or =3 months before recruitment. Genomic DNA was extracted from peripheral blood leukocytes using a standard protocol. Subjects were genotyped for the CYP11B2 polymorphism using the polymerase chain reaction/restriction fragment length polymorphism approach. AF was present in 63 patients (33%) with HF. We found the -344 CC genotype to be a strong independent marker for AF. Almost 1/2 (45%) of patients with this genotype had AF compared with 1/4 (27%) with -344 TT and TC genotypes (p = 0.01). A multivariate stepwise logistic regression model that included age, gender, New York Heart Association class, CYP11B2 -344CC genotype, and echocardiographic measurements of left ventricular ejection fraction, left atrial dimension, left ventricular end-diastolic diameter, and mitral regurgitation severity showed that the CYP11B2 CC genotype (adjusted for age and left atrial size) was an independent predictor of AF (adjusted odds ratio 2.35, 95% confidence interval 1.57 to 3.51, p = 0.03). In conclusion, CYP11B2 T-344C promoter polymorphism predisposes to clinical AF in patients with HF.

Genotype-phenotype associations between chymase and angiotensin-converting enzyme gene polymorphisms in chronic systolic heart failure patients.

PURPOSE: Angiotensin II, which plays a crucial role in the myocardial remodeling process of heart failure, is generated via the angiotensin-converting enzyme and chymase pathways. We studied angiotensin-converting enzyme and chymase-1 polymorphisms in patients with systolic heart failure and the correlation with clinical status and left ventricular function. METHODS: We genotyped 195 patients with heart failure and systolic left ventricular dysfunction (ejection fraction <40%) for angiotensin-converting enzyme insertion (I)/deletion (D) and chymase-1 (-1903G/A) polymorphisms. Heart failure etiology and patients' clinical manifestations were analyzed in relation to genotype subtypes. RESULTS: The chymase-1 -1903 GG genotype was associated with a nonischemic heart failure etiology (chi = 6.67, P = 0.009). In the group of heart failure patients, the odds ratio of chymase-1 GG genotype having a nonischemic etiology was 2.48 (95% CI 1.23-5.00). The chymase-1 GG genotype was associated with lower ejection fraction (P = 0.005). Conversely, the angiotensin-converting enzyme D allele had no detectable impact on systolic heart failure phenotype. CONCLUSIONS: In patients with chronic systolic heart failure, the chymase-1 polymorphism was related to nonischemic etiology of heart failure. Patients homozygous for the G allele had a significantly greater reduction in systolic left ventricular function.

The effect of long-term beta-adrenergic receptor blockade on the oxygen delivery and extraction relationship in patients with coronary artery disease.

PURPOSE: We evaluated the effects of long-term beta-blocker treatment on the balance between oxygen delivery and extraction at peak oxygen uptake (VO2) and at target heart rate training (anaerobic threshold). METHODS: Fifteen patients with coronary artery disease performed paired peak cardiopulmonary and submaximal exercise tests on a cycle ergometer with and without atenolol treatment. Thirty minutes following the submaximal tests, participants pedaled 10 minutes at a workload corresponding to that of the anaerobic threshold attained. Arterial oxygen was defined from echocardiography and venous oxygen content. RESULTS: At rest, stroke volume, heart rate, and cardiac output were lower (P < .05), whereas arteriovenous oxygen difference [(a - v)O2] was higher with the use of atenolol (P < .05). At peak exercise, heart rate, lactate, and systolic blood pressure were lower (P < .05), whereas (a - v)O2 was higher (P < .05) with the use of atenolol. At anaerobic threshold, stroke volume, heart rate, cardiac output, and systolic blood pressure were lower (P < .05), whereas (a - v)O2 was higher (P < .05) with the use of atenolol. Absolute VO2 and workload during maximal (P = .67 and P = .49, respectively) and submaximal (P = .13 and P = .44, respectively) exercises were similar between conditions. CONCLUSIONS: Results demonstrate that atenolol treatment in patients with coronary artery disease does not alter VO2 and workload at the anaerobic threshold and peak exercise because of an increase in oxygen extraction and stroke volume in the face of reduced heart rate. These findings indicate that with long-term beta-adrenergic receptor blockade, there is interplay between oxygen delivery and extraction, suggesting a link between cardiac hemodynamic responses and skeletal muscle metabolic adaptations.

Left ventricular contractility in response to upright isometric exercise in heart transplant recipients and healthy men.

PURPOSE: We evaluated left ventricular contractility during upright isometric exercise, in heart transplant recipients (HTRs) and in healthy controls, using ejection fraction and end-systolic pressure/volume ratio indexes. METHODS: Fifteen healthy men (40 +/- 13 years) and 10 HTRs (42 +/- 12 years) underwent dead lift (DL) test at 30% of maximal effort for 3 minutes. Echocardiographic variables were measured during the final 45 seconds. RESULTS: During DL test, HTRs were significantly different (P < .01) from controls in all parameters except end-diastolic volume. DL test had lower mean values of ejection fraction (49.9% +/- 8.3% vs 67.0% +/- 4.3%, respectively) and left ventricular end-systolic pressure/volume ratio (3.5 +/- 0.7 vs 5.5 +/- 1.2, respectively) whereas higher values of end-systolic volume (51.0 +/- 9.4 mL vs 34.1 +/- 5.3 mL, respectively). Importantly, an intergroup effect was found in end-systolic pressure/volume ratio, further signifying differential response of HTRs. End-systolic pressure/volume ratio increased consistently (P < .001) in both groups, whereas the overall main effect of ejection fraction response was not significant. CONCLUSIONS: Left ventricular function during upright isometric exercise displays differential pattern of response in HTRs in comparison with healthy controls. However, cardiac contractility in HTRs remained stable at peak systolic blood pressure produced by the isometric DL exercise. Results suggest that both ejection fraction and end-systolic pressure/volume ratio indexes can be used for assessment of ventricular function in patients after heart transplantation.

ACE ID genotype affects blood creatine kinase response to eccentric exercise.

Unaccustomed exercise may cause muscle breakdown with marked increase in serum creatine kinase (CK) activity. The skeletal muscle renin-angiotensin system (RAS) plays an important role in exercise metabolism and tissue injury. A functional insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene (rs4646994) has been associated with ACE activity. We hypothesized that ACE ID genotype may contribute to the wide variability in individuals' CK response to a given exercise. Young individuals performed maximal eccentric contractions of the elbow flexor muscles. Pre- and postexercise CK activity was determined. ACE genotype was significantly associated with postexercise CK increase and peak CK activity. Individuals harboring one or more of the I allele had a greater increase and higher peak CK values than individuals with the DD genotype. This response was dose-dependent (mean +/- SE U/L: II, 8,882 +/- 2,362; ID, 4,454 +/- 1,105; DD, 2,937 +/- 753, ANOVA, P = 0.02; P = 0.009 for linear trend). Multivariate stepwise regression analysis, which included age, sex, body mass index, and genotype subtypes, revealed that ACE genotype was the most powerful independent determinant of peak CK activity (adjusted odds ratio 1.3, 95% confidence interval 1.03-1.64, P = 0.02). In conclusion, we indicate a positive association of the ACE ID genotype with CK response to strenuous exercise. We suggest that the II genotype imposes increased risk for developing muscle damage, whereas the DD genotype may have protective effects. These findings support the role of local RAS in the regulation of exertional muscle injury.

What maintains energy supply at peak aerobic exercise in trained and untrained older men?

BACKGROUND: Aging-related changes occur mainly in the cardiopulmonary system and skeletal muscles, bringing about a reduction in physical performance. Consequently, maximal oxygen uptake (VO(2)max) decreases. OBJECTIVES: The current study investigated exercise oxygen utilization during maximal aerobic exercise in trained and untrained elderly. METHODS: Fifteen trained (59.3 +/- 1.1 years) and 15 untrained (60.1 +/- 1.1 years) elderly underwent a peak cardiopulmonary exercise test on a bicycle ergometer. Arterial O(2 )was defined from echocardiograph and venous oxygen content. RESULTS: At rest, trained compared to untrained elderly had significantly (p < 0.05) higher values of end diastolic volume (108.1 +/- 5.8 and 100.7 +/- 6.2 ml, respectively) and stroke volume (68.1 +/- 4.3 and 57.3 +/- 6.5 ml, respectively), while heart rate (68.7 +/- 9.3 and 81.3 +/- 8.2 beats . min(-1), respectively), and mean arterial blood pressure (90.6 +/- 6.9 and 95.4 +/- 7.2 mm Hg, respectively) were significantly lower. At peak aerobic test, the trained elderly, compared to the untrained subjects, achieved significantly (p < 0.05) higher values of end diastolic volume (156.1 +/- 8.2 and 134.1 +/- 7.6 ml, respectively), stroke volume (123.0 +/- 7.9 and 96.0 +/- 4.8 ml, respectively), cardiac output (20.2 +/- 1.5 and 15.0 +/- 1.3 liters.min(-1), respectively) and oxygen uptake (42.1 +/- 2.1 and 31.1 +/- 2.4 ml.kg(-1).min(-1), respectively), while diastolic blood pressure (70.3 +/- 5.6 and 77.5 +/- 4.2 mm Hg, respectively) and total peripheral resistance [4.3 +/- 0.8 and 5.9 +/- 1.41 (dyn.s(-1).cm(-5)).10(-1), respectively], were significantly (p < 0.05) lower. CONCLUSIONS: The present study suggests that the differences between trained and untrained elderly in absolute oxygen uptake of the working muscles and peak power output at maximal exercise test are due to physical activity status. The higher aerobic capacity in the trained elderly is related to increased cardiovascular function and to a lesser extent to increased muscle mitochondria concentration and capillarity. Although untrained elderly have reduced maximal oxygen uptake at peak aerobic exercise, intrinsic regulation of mitochondrial function does not seem to be significantly altered because of aging associated physical inactivity. Therefore, untrained elderly can partially compensate for their lower cardiac output by increasing oxygen extraction to levels comparable with those of trained elderly.

The ACE deletion allele is associated with Israeli elite endurance athletes.

An Alu insertion (I)/deletion (D) polymorphism in the angiotensin I converting enzyme (ACE) gene has been associated with ACE activity. Opposing effects on elite athletic performance have been proposed for the I and D alleles; while the D allele favours improved endurance ability, the I allele promotes more power-orientated events. We tested this hypothesis by determining the frequency of ACE ID alleles amongst 121 Israeli top-level athletes classified by their sporting discipline (marathon runners or sprinters). Genotyping for ACE ID was performed using polymerase chain reaction on DNA from leucocytes. The ACE genotype and allele frequencies were compared with those of 247 healthy individuals. Allele and genotype frequencies differed significantly between the groups. The frequency of the D allele was 0.77 in the marathon runners, 0.66 in the control subjects (P = 0.01) and 0.57 in the sprinters (P = 0.002). The ACE DD genotype was more prevalent among the endurance athletes (0.62) than among the control subjects (0.43, P = 0.004) and the power athletes (0.34, P = 0.004). In the group of elite athletes, the odds ratio of ACE DD genotype being an endurance athlete was 3.26 (95% confidence interval 1.49-7.11), and of ACE II genotype was 0.41 (95% confidence interval 0.14-1.19). We conclude that in Israeli elite marathon runners the frequency of the ACE D allele and ACE DD genotype seems to be higher than in sprinters, suggesting a positive association between the D allele and the likelihood of being an elite endurance athlete in some ethnic groups.

What maintains the metabolic cost at maximal exercise in heart transplant recipients and coronary artery disease patients?

BACKGROUND: In this study we assess the influence of disease status on hemodynamic and cardiac output values, as measured by oxygen utilization at peak aerobic exercise, in heart transplant recipients (HTRs) and coronary artery disease patients (CAD). METHODS: Fifteen CAD patients and 13 HTRs (40.2 +/- 12.6 and 41.7 +/- 11.7 years, respectively) underwent a peak cardiopulmonary exercise test on bicycle ergometry. Arterial oxygen was defined on the basis of echocardiography and venous oxygen content. RESULTS: At rest, except for cardiac output, oxygen uptake and lactate levels, all variables were significantly (p < 0.01) different between groups. At peak exercise, compared with HTRs, CAD patients had significantly (p < 0.0001) higher values for cardiac output (12.4 +/- 0.8 and 20.2 +/- 1.7 liters/min, respectively), stroke volume (87.3 +/- 5.4 and 129.3 +/- 9.7 ml, respectively) and oxygen uptake (22.7 +/- 3.6 and 29.7 +/- 2.7 ml/kg/min, respectively) (p < 0.01), whereas (a - v)O2 was significantly lower (127.0 +/- 4.3 and 141.9 +/- 6.4 O2 ml/liter, respectively; p < 0.0001). CONCLUSIONS: The differences in oxygen utilization at peak exercise may be attributed to differences in energy metabolism, namely higher oxygen extraction in HTRs, compensating for the dramatically reduced oxygen delivery. It is further suggested that CAD patients and HTRs respond to a greater extent to maximal aerobic testing by reducing their left ventricular systolic function despite increased after-load.

Igf-I and fgf-2 responses to wingate anaerobic test in older men.

REDUCED ACTIVITY OF THE POTENT ANABOLIC EFFECTORS: insulin-like growth factor-I (IGF-I) and fibroblast growth factor-2 (FGF-2), play a role in aging associated muscle loss. The effect of fitness level on IGF-I and FGF-2 responses to all-out anaerobic exercise in older men was studied. Twenty four healthy older males: 12 higher fit (58 ± 1y) and 12 lower fit (59 ± 1y) underwent the Wingate anaerobic test. Serum levels of IGF-I and FGF-2 were measured before, immediately after exercise, and 50 min into recovery. Immediately post exercise, the average peak power output and serum lactate were higher (p < 0.05) in the higher fit (446.0 ± 14. 9 kgm·min(-1) for mean (± SD) peak power and 12.6 ± 1.1 mml·l(-1) for lactate) compared with the lower fit individuals (284.0 ± 6.5 kgm·min(-1) and 8.5 ± 0.7 mml·l(-1), respectively). Pre-exercise IGF-I was lower and FGF-2 was higher in the higher fit (335.0 ± 54.0 ng·ml(-1) and 1.6 ± 0.1 ng·ml(-1), respectively) compared with lower fit individuals (402.0 ± 50.0 ng·ml(-1) and 1.4 ± 0.2 ng·ml(-1), respectively). Following the anaerobic exercise, in both groups, FGF-2 decreased dramatically (p < 0.05); in the higher fit individuals FGF-2 level was 0.4 ± 0.1 pg·ml(-1) compared to 0.1 ± 0.02 pg·ml(-1) in the lower fit individuals. In contrast to FGF-2, IGF-I increased transiently to levels of 405.0 ± 62.0 ng·ml(-1) in the higher fit individuals and to levels of 436 ± 57.0 ng·ml(-1) in the lower fit individuals. However, the IGF-I elevation was significant (p < 0. 05) only in the higher fit individuals. In conclusion, the present study demonstrates that during aging, fitness level can alter circulating levels of IGF-I and FGF-2. Furthermore, fitness level can affect the response of both mediators to all-out anaerobic exercise. Key pointsThe present study suggests that during aging, fitness level can alter circulating levels of IGF-I and FGF-2.Furthermore, fitness level can affect the response of both mediators to all-out anaerobic exercise.Anaerobic muscle activity is represented in many daily life activities of elderly individuals.This may have clinical implications during aging, where the declined activity of growth factors is a major determinant of the loss of muscle strength and function.

Left ventricular systolic function during treadmill walking with load carriage in adolescents.

Backpack carriage occurs in day-to-day tasks and has applications in school, physical training, recreational activities and sports. Using metabolic cart and echocardiograph, this study determined and examined the effects of two different load carriages on left ventricular function during 30 min. of treadmill walking in healthy adolescent male subjects. Seventeen males (13.1 ± 0.5 yrs.) walked on a treadmill at a speed of 4 km·h(-1), each carrying a load relative to his body mass at 333 gr·kg(-1) body weight during one session and without weight during the other session. Significant (p < 0.05) differences were noted between the 333 gr·kg(-1) body weight and the no weights with regard to: VO2 13.6 ± 1.3 and 10.5 ± 1.1 ml·kg(-1)·min(-1); heart rate: 133.2 ± 7.1 and 121.4 ± 5.6 beats·min(-1); mean arterial blood pressure; 95. 4 ± 4.3 and 87.5 ± 3.8 mmHg and systolic blood pressure 147.7 ± 7.0 and 129.8 ± 7.1 mmHg respectively. No significant differences were noted between the two exercises with regard to left ventricular function variables. This study suggests that in adolescents as in adults, the vasodilatation mechanism dominates during combined dynamic and isometric exercises. Thus, the opposing force to the left ventricular ejection is reduced which in turn does not change the left ventricular global function. In addition, the vasodilatation mechanism enables oxygen supply to the contracting muscles via aerobic energy pathways. Key PointsThis study suggests that in adolescents as in adults, the vasodilatation mechanism dominates during combined dynamic and isometric exercises.Thus, the opposing force to the left ventricular ejection is reduced which in turn does not change the left ventricular global function.In addition, the vasodilatation mechanism enables oxygen supply to the contracting muscles via aerobic energy pathways.

Newborn screening and prenatal diagnosis for Rett syndrome: implications for therapy.

Most girls with Rett syndrome develop normally prior to the appearance of the typical symptoms. A presymptomatic phase is also observed in many inborn errors of metabolism that are included in newborn screening programs. Diagnostic testing for mutations or large genomic rearrangements involving methyl-CpG binding protein 2 gene (MECP2) is highly sensitive and identifies mutations in up to 95% of female individuals with classic Rett syndrome. This has prompted some to ask whether MECP2 testing should be included in newborn and prenatal screening programs. We review current and evolving practices in these programs, emphasizing their relevance to Rett syndrome. The availability of a reliable test and the characteristic early latent phase, which creates a window of opportunity for early treatment, favor universal newborn screening for Rett syndrome. However, the high cost and the lack of an effective presymptomatic treatment make universal newborn screening for Rett syndrome impractical at present. In contrast, prenatal diagnosis should be offered to the parents of an affected child if the responsible mutation has been identified in the index case.

Mechanism of processing of the NF-kappa B2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of NEDD8-modification on the SCF(beta-TrCP) ubiquitin ligase.

Processing of the NF-kappa B2 precursor p100 to the mature p52 subunit is regulated via a unique pathway. NF-kappa B-inducing kinase (NIK) induces I kappa B kinase alpha (IKK alpha)-mediated phosphorylation of specific serine residues in the C-terminal domain of p100, leading to recruitment of the SCF(beta-TrCP) ubiquitin ligase. We identified a single lysine residue, K855, that serves as the ubiquitin-anchoring residue required for signal-induced processing of p100. In a reconstituted system containing purified components, p100-K855R could not be ubiquitinated. In a crude extract and cells, only residual, signal-independent ubiquitination and processing were retained. Importantly, K855 is located in a site homologous to K22 that serves as an ubiquitination site in I kappa B alpha. This suggests a common recognition mechanism for the two molecules. In contrast, p105, the p100 homologue, lacks a similar Lys residue. We also demonstrate that the NEDD8 pathway is essential for the SCF(beta-TrCP) activity. In a reconstituted system, efficient ubiquitination of p100 required all three components of the pathway - E1, the UBC12 E2 and NEDD8. Experiments in reconstituted systems and in cells demonstrated that SCF(beta-TrCP), which contains a mutant Cul-1 that cannot be NEDDylated, cannot stimulate ubiquitination and processing. Similarly, dominant negative UBC12 inhibits, in a reversible manner, both ubiquitination and processing of p100.