hGH Concentrations Research Articles

The Impact of Liver Steatosis on Interleukin and Growth Factors Kinetics during Chronic Hepatitis C Treatment.

Background/Objectives: Various biological response modifiers play important roles in the immunopathogenesis of chronic hepatitis C (CHC). While serum levels of cytokines and growth factors change with the disease severity and treatment responses, the impact of concomitant liver steatosis on systemic inflammatory response is largely unknown. The aim of this study was to analyze the characteristics and kinetics of serum profiles of interleukins and growth factors in CHC patients with steatotic liver disease (SLD). Methods: Serum concentrations of 12 cytokines (IL-5, IL-13, IL-2, IL-6, IL-9, IL-10, IFN-γ, TNF-α, IL-17A, IL-17F, IL-4 and IL-22) and 6 growth factors (Angiopoietin-2, EGF, EPO, HGF, SCF, VEGF) were analyzed in 56 CHC patients at four time points (baseline, week 4, week 8 and SVR12) with bead-based flow cytometry assay. Results: At baseline, patients with SLD had significantly lower IL-9, IL-10, IL-13 and IL-22 and higher serum concentrations of EGF, VEGF and ANG. In a subgroup of patients with advanced liver fibrosis, SLD was linked with lower serum concentrations of IL-4, IL-5, IL-9, IL-10, IL-13 and IL-22 and higher concentrations of HGH and VEGF. Distinct cytokine kinetics during DAA treatment was observed, and SLD was identified as the main source of variation for IL-5, IL-9, IL-10, IL-13, IL-17A, IL-22, EGF, VEGF and ANG. Patients with SLD at SVR12 had significantly higher VEGF and HGF serum concentrations. Conclusions: SLD is associated with distinct cytokine and growth factor profiles and kinetics during CHC treatment, which might be associated with disease severity and the capacity for liver regeneration and contribute to fibrosis persistence.

Application of the Athlete Biological Passport Approach to the Detection of Growth Hormone Doping.

Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population-derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay. We tested the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse. Insulin-like growth factor 1 (IGF-1) and procollagen III peptide (P-III-NP) distributions were obtained from 7 years of anti-doping data in elite athletes (n = 11 455) and applied as priors to analyze individual profiles from an hGH administration study in recreational athletes (n = 35). An open-label, randomized, single-site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated. An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5% to 71.4% across the hGH concentrations tested following 7 days of treatment, peaking at 57.1% to 100% after 21 days of treatment, and was maintained between 37.5% and 71.4% for the low and high dose groups 1 week after cessation of treatment. These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.

Detection of Human Growth Hormone (hGH) via Cyclodextrin-Promoted Fluorescence Modulation

The ability to detect human growth hormone (hGH) via sensitive, selective, and easy-to-use methods is a high priority research area from a variety of public health, law enforcement, and scientific objectives. Reported herein is the use of cyclodextrin-promoted fluorescence modulation of a high-quantum yield BODIPY fluorophore in the presence of low concentrations of hGH, leading to a system that can detect hGH in concentrations as low as 0.279 µM and with a 96% accuracy in distinguishing different hGH concentrations.

The effects of training on hormonal concentrations in young soccer players.

To test the hypothesis that football training would be accompanied by physiological adaptations and hormonal changes, we analyzed the effects of a whole football season on physical fitness and hormonal concentrations in youth football players. Male football players (n = 29, age 16.51 ± 0.7 years) in a regional professional league and male healthy control subjects (n = 30, age 17.1 ± 1 years) participated to the study. Blood cortisol, testosterone, and growth hormone (hGH) concentrations were assayed before the beginning of the training period (T0), just after the training period (T1), at the middle of the season (T2), and at the end of the season (T3). In each period physical tests and anthropometric measurements were also performed. Results showed significant differences in basal values of cortisol, testosterone, and growth hormone (hGH) in the four time points evaluated (P < 0.01). In addition, the concentrations of hGH were higher in the soccer players group than in control subjects (P < 0.001). Between the start of the training period and the end of the football season significant differences were observed in the anthropometric characteristics and in the physical form of the football players. Furthermore, the hormonal status was significantly correlated with the indicators of the lower limb power (squat-jump [SqJ], and counter-movement-jump [CMJ]) and those of aerobic performance (Yo-Yo intermittent recovery test level 1 (YYIRT1) and maximal oxygen consumption (VO2max )).These data underscore the importance of establishing training protocols that present the potential to promote positive adaptations without, at the same time, provoking overtraining of young players.

Bioactive growth hormone in older men and women: It's relationship to immune markers and healthspan

ObjectiveThe consequences of age-related decline in the somatotropic axis of humans are complex and remain largely unresolved. We tested the hypothesis that hGH measurements of plasma by bioassay vs immunoassay from samples obtained from free-living, elderly individuals would reveal a dichotomy in GH activities that are correlated with the functional status of the donors, i.e. their healthspan. DesignForty-one men and women of advanced age (men: N=16, age, 80.5±6.5years; height, 173.1±6.9cm; body mass, 81.8±13.0kg) and (women: N=25, age, 80.7±7.2years; height, 157.7±6.0cm; body mass, 68.8±17kg), were recruited for a cross-sectional study. Participants filled out PROMIS (Patient-Reported Outcomes Measurement Information System, U. S. Department of Health and Human Services) scales, undertook physical performance tests and had fasted blood samples obtained at rest for measurement of hormonal and immunology biomarkers. ResultsWhen measured by the well-established rat tibial line GH bioassay, one half of the plasma samples (n=20) contained bioassayable GH (bGH), but the other half (n=21) failed to mount increases in tibial plate width above saline injected controls. This difference did not correlate with the age, sex or physical functionality of the plasma donor. It also did not correlate with hGH concentrations measured by immunoassay. In those cases in which bGH was detected, various hierarchical regression models predicted that GHRH, c-peptide, VEGF, NPY, IL-4 and T-regulatory lymphocytes were associated with the difference and predicted bGH. ConclusionResults from this study suggest that the actions of bGH at the cellular level may be modified by other factors and that this may explain the lack of correlations observed in this study.

Age-independent effects of hyaluronan amide derivative and growth hormone on human osteoarthritic chondrocytes

Aim: Increased age is the most prominent risk factor for the initiation and progression of osteoarthritis (OA). The effects of human growth hormone (hGH) combined or not with hyaluronan amide derivative (HAD) were evaluated on human OA chondrocytes, to define their biological action and potentiality in OA treatment.Material and methods: Cell viability, metabolic activity, gene expression and factors released were tested at different time points on chondrocytes treated with different concentrations of hGH (0.01–10 μg/ml) alone or in combination with HAD (1 mg/ml).Results: We found that OA chondrocytes express GH receptor and that the different doses of hGH tested did not affect cell viability, metabolic activity or the expression of collagen type 2, 1, or 10 nor did it induce the release of IGF-1 or FGF-2. Conversely, hGH treatment increased the expression of hyaluronan receptor CD44. HAD combined with hGH reduced metabolic activity, IL6 release and gene expression, but not the suppressor of cytokine signaling 2 (SOCS2), which was significantly induced and translocated into the nucleus. The parameters analyzed, independently of the treatments used proportionally decreased with increasing age of the patients.Conclusions: hGH only induced CD44 receptor on OA chondrocytes but did not affect other parameters, such as chondrocytic gene markers or IGF-1 or FGF-2 release. HAD reduced all the effects induced by hGH partially through a significant induction of SOCS2. These data show that GH or HAD treatment does not influence the response of the OA chondrocytes, thus the modulation of cellular response is age-independent.

Specific and nonspecific interactions in ultraweak protein-protein associations revealed by solvent paramagnetic relaxation enhancements.

Weak and transient protein–protein interactions underlie numerous biological processes. However, the location of the interaction sites of the specific complexes and the effect of transient, nonspecific protein–protein interactions often remain elusive. We have investigated the weak self-association of human growth hormone (hGH, KD = 0.90 ± 0.03 mM) at neutral pH by the paramagnetic relaxation enhancement (PRE) of the amide protons induced by the soluble paramagnetic relaxation agent, gadodiamide (Gd(DTPA-BMA)). Primarily, it was found that the PREs are in agreement with the general Hwang-Freed model for relaxation by translational diffusion (J. Chem. Phys.1975, 63, 4017–4025), only if crowding effects on the diffusion in the protein solution are taken into account. Second, by measuring the PREs of the amide protons at increasing hGH concentrations and a constant concentration of the relaxation agent, it is shown that a distinction can be made between residues that are affected only by transient, nonspecific protein–protein interactions and residues that are involved in specific protein–protein associations. Thus, the PREs of the former residues increase linearly with the hGH concentration in the entire concentration range because of a reduction of the diffusion caused by the transient, nonspecific protein–protein interactions, while the PREs of the latter residues increase only at the lower hGH concentrations but decrease at the higher concentrations because of specific protein–protein associations that impede the access of gadodiamide to the residues of the interaction surface. Finally, it is found that the ultraweak aggregation of hGH involves several interaction sites that are located in patches covering a large part of the protein surface.

HGH isoform differential immunoassays applied to blood samples from athletes: Decision limits for anti-doping testing

ObjectiveTo detect hGH doping in sport, the World Anti-Doping Agency (WADA)-accredited laboratories use the ratio of the concentrations of recombinant hGH (‘rec’) versus other ‘natural’ pituitary-derived isoforms of hGH (‘pit’), measured with two different kits developed specifically to detect the administration of exogenous hGH. The current joint compliance decision limits (DLs) for ratios derived from these kits, designed so that they would both be exceeded in fewer than 1 in 10,000 samples from non-doping athletes, are based on data accrued in anti-doping labs up to March 2010, and later confirmed with data up to February–March 2011. In April 2013, WADA asked the authors to analyze the now much larger set of ratios collected in routine hGH testing of athletes, and to document in the peer-reviewed literature a statistical procedure for establishing DLs, so that it be re-applied as more data become available. DesignWe examined the variation in the rec/pit ratios obtained for 21,943 screened blood (serum) samples submitted to the WADA accredited laboratories over the period 2009–2013. To fit the relevant sex- and kit-specific centiles of the logs of the ratios, we classified ‘rec/pit’ ratios based on low ‘rec’ and ‘pit’ values as ‘negative’ and fitted statistical distributions to the remaining log-ratios. The flexible data-driven quantile regression approach allowed us to deal with the fact that the location, scale and shape of the distribution of the modeled ‘rec/pit’ ratios varied with the concentrations of the ‘rec’ and ‘pit’ values. The between-kit correlation of the ratios was included in the fitting of the DLs, and bootstrap samples were used to quantify the estimation error in these limits. We examined the performance of these limits by applying them to the data obtained from investigator-initiated hGH administration studies, and in athletes in a simulated cycling stage race. ResultsThe mean and spread of the distribution of the modeled log-ratios depended in different ways on the magnitude of the rec and pit concentrations. Ultimately, however, the estimated limits were almost invariant to the concentrations, and similar to those obtained by fitting simpler (marginal) log-normal and Box–Cox transformed distributions. The estimated limits were similar to the (currently-used) limits fitted to the smaller datasets analyzed previously. In investigator-initiated instances, the limits distinguished recent use of rec-hGH from non-use. ConclusionsThe distributions of the rec/pit ratios varied as a function of the rec and pit concentrations, but the patterns in their medians and spreads largely canceled each other. Thus, ultimately, the kit- and sex-specific ratio DL obtained from the simpler model was very close to the ‘curve of DLs’ obtained from the more complex one. Both were close to previously established limits.

Acute Hormonal Responses Before and After 2 Weeks of HIT in Well Trained Junior Triathletes

The aim was to compare the acute hormonal response to a single HIT session at the beginning and end of a HIT shock microcycle. 13 male junior triathletes (15.8±1.8 yrs.) performed 16 HIT sessions within a 2 week period. Venous blood samples were collected before and after the first and last HIT session. Significant increases in cortisol (first session +89.7%; last session +70.3%) and hGH (first session +435.1%; last session +314.6%) concentrations were observed after both training sessions (P<0.05). The acute responses of cortisol, hGH, T3, and fT3 were not different between the first and last HIT sessions (P=1.00). Although no acute changes in testosterone were detected after the training sessions, testosterone concentrations were significantly higher at all time points (62.6-80.1%) during the last compared to first training session (P≤0.001). Findings from the present study reveal that 16 sessions of HIT led to significant increases in baseline concentrations of serum testosterone. This might indicate a heightened anabolic state even in junior triathletes. Based on the hormonal data, we conclude that at the end of this 2 week microcycle no familiarization effect was evident and that the training stimulus produced by HIT was still great enough to "stress" the athletes and induce positive training adaptations.

Effects of a Pre-Exercise Meal on Plasma Growth Hormone Response and Fat Oxidation during Walking

The purpose of this study was to determine the effects of a pre-exercise meal on the plasma human growth hormone (hGH) response and fat oxidation during walking. Subjects (n=8) were randomly provided with either 1 g/kg body weight of glucose in 200 mL water (CHO) or 200 mL water alone (CON) 30 min prior to exercise and subsequently walked on a treadmill at 50% of VO2max for 60 min. Plasma hGH concentrations were significantly higher in subjects who received CHO compared to those who received CON at 15 and 30 min. The fat oxidation rate in the CHO was significantly lower than the CON while walking for 5~15, 25~35 and 45~55 min. Plasma FFA levels were also significantly lower in the CHO compared to the CON at 30, 45 and 60 min. Plasma glucose levels in the CHO were significantly lower while plasma insulin levels were significantly higher than in the CON at 15 and 30 min. Therefore, the results of this study suggest that the elevation of plasma hGH levels due to the intake of a pre-exercise meal may not be strongly related to fat oxidation and plasma free fatty acid (FFA) levels during low-intensity exercise.

A chemiluminescent metalloimmunoassay based on copper-enhanced gold nanoparticles for quantification of human growth hormone

A chemiluminescence (CL) immunoassay was developed to determine human growth hormone (hGH) based on copper-enhanced gold nanoparticles. In this method, gold nanoparticles were deposited on polystyrene wells for adsorption of human growth antibodies as well as catalyst for reducing of copper ions from the copper enhancer solution. The reduction of copper ions was prevented where the gold nanoparticles were covered by the antibody-antigen immunocomplex. The deposited copper on Au nanoparticles was then dissolved in HNO3 solution and quantified using the CL method. The CL intensity response was logarithmically dependent on the hGH concentrations over the range 0.2-50 ng/mL, with a detection limit (3σ) of 0.036 ng/mL.

Harmonization of growth hormone measurements with different immunoassays by data adjustment

The aim of our study was to evaluate the between-assay variability of commercially available immunoassays for the measurement of human growth hormone (hGH). In addition, we asked whether the comparability of the diagnosis of childhood onset growth hormone deficiency could be improved by adjusting hGH results by statistical methods, such as linear regression, conversion factors, and quantile transformation. In archived sera from 312 children and adolescents (age: 17 days-17 years) hGH values between 0.01 and 16.5 ng/mL were determined by using the following immunoassays: AutoDELFIA (PerkinElmer), BC-IRMA (Beckman-Coulter), ELISA (Mediagnost), IMMULITE 2000 (Siemens), iSYS (IDS), Liaison (DiaSorin), UniCel DxI 800 Access (BeckmanCoulter) and "In house"-RIA (Tübingen). The assays differed in median hGH concentrations by as much as 5.44 ng/mL (Immulite), and as little as 2.67 ng/mL (BC-IRMA). The mean difference between assays ranged from 0.35 to 2.71 ng/mL, whereas several samples displayed differences up to 11.4 ng/mL. The best correlation (r=0.992) was found between AutoDELFIA and Liasion, the lowest (r=0.864) was between an in-house RIA and iSYS. The between-assay CV (mean ± SD) of values within the cut-off range was 24.3% ± 7.4%, resulting in an assay-dependent diagnosis of growth hormone deficiency (GHD) in more than 27% of patients. Yet, adjustment of this data by linear regression or a conversion factor reduced the CV below 14%, and the ratio of assay-dependent diagnoses below 8%. Using quantile transformation, the CV and ratio were reduced to 11.4% and <1%, respectively. hGH measurements using different assays vary significantly. Linear regression, conversion factors, or particularly quantile transformation are useful tools to improve comparability in the diagnostic procedure for the confirmation of GHD in childhood and adolescence.

Effect of high- and low-intensity exercise and metabolic acidosis on levels of GH, IGF-I, IGFBP-3 and cortisol

Objective The purpose of the present study was to examine the acute hormonal response of a short term high-intensity training (HIT) versus a high volume endurance training (HVT) and to determine the contribution of the metabolic acidosis as a stimulus for possibly different reactions of circulating hGH, IGF-1, IGFBP-3 and cortisol. Design Eleven subjects participated in three experimental trials separated by one week. Two times subjects performed four 30 s maximal effort exercise bouts on a cycle ergometer separated by 5 min rest each. Before the exercise subjects either received (single-blinded) bicarbonate (HIT (B)) or a placebo (HIT (P)). The third exercise trail consisted of a constant load exercise for 1 h at 50% VO 2max (HVT). Venous blood samples were taken under resting conditions, 10 min, 60 min and 240 min after each exercise condition to determine hGH, IGF-1, IGFBP-3 and cortisol serum concentrations. Capillary blood samples were taken to determine lactate concentrations and blood gas parameters. Results Power output, mean lactate concentrations and mean pH values were significantly higher during HIT (B) compared to HIT (P). Serum cortisol and hGH concentrations were significantly increased 10 min post exercise in both HIT interventions. IGFBP-3 was only significantly increased after HIT (P), whereas IGF-1 was not affected by any of the interventions. HVT showed no significant effects on cortisol, hGH, IGF-1 and IGFBP-3 levels. Additionally it was shown that the diminished acidosis during HIT (B) attenuates the cortisol and hGH response. Conclusions The present study suggests that HIT/acidosis is a stimulus for exercise-induced cortisol/hGH secretion, but not for IGF-1 and IGFBP-3 under these experimental conditions. These findings might be relevant for arrangements of interval training, due to the fact that active or passive recovery during rest periods influence the acid base status and may therefore influence the hormonal response.

Specific monoclonal antibodies and ultrasensitive immunoassays for 20K and 22K human growth hormone

Generation of specific monoclonal antibodies (mAbs) against 20K and 22K human growth hormone (hGH) and development of ultrasensitive immunoassays to quantify 20K and 22K hGH. Mice were immunized with recombinant 20K or 22K hGH. Hybridoma cells were screened with biotinylated 20K and 22K hGH simultaneously. The specific mAbs were further characterized and used for construction of isoform specific assays. The ultrasensitive chemiluminescent assays were developed with AMDEX streptavidin-HRP and a sensitive substrate. The 20K hGH specific mAb 1G12 and the 22K hGH specific mAb 5E1 showed less than 0.1% cross-reactivity to 22K or 20K hGH by competitive binding assay, respectively. Western blot analysis also confirmed the specificity of mAb 1G12 and mAb 5E1. Using mAb 1G12 and mAb 5E1, 20K and 22K specific assays with working range of 2-2000 pg/mL were constructed. The 22K hGH concentrations in 103 serum samples from different healthy subjects in the basal GH state were 343.7+/-421.5 pg/mL (18.6-1820 pg/mL). The 20K hGH concentrations were 30.7+/-37.5 pg/mL (2.4-205pg/mL). The ratios of 20K to 20K plus 22K hGH were 9.8+/-4.4% (3.3-28.3%). Both 22K hGH and 20K hGH concentrations in women (465.9+/-476.3 pg/mL and 43.7+/-46.1 pg/mL, n=47) were significantly higher than those (241.1+/-337.0 pg/mL and 20K hGH 19.8+/-23.0 pg/mL, n=56, P<0.01) in men. However, there was no difference in the proportion of 20K to 20K plus 22K between men and women (P>0.05). The strong correlation between 20K and 22K hGH (R=0.914, P<0.01) indicated the constant proportion between 20K and 22K hGH in the basal GH state of healthy subjects. Specific monoclonal antibodies and ultrasensitive chemiluminescent immunoassays for 20K and 22K hGH were generated. The ultrasensitive immunoassays are essential for the determination of 20K and 22K hGH in the basal GH state. This universal ultrasensitive immunoassay form can be adapted to other immunoassays for broad application.

Nanoparticle technology: amplifying the effective sensitivity of biomarker detection to create a urine test for hGH

Several clinical-grade immunoassays exist for the specific measurement of hGH or its isoforms in blood but there is an urgent need to apply these same reliable assays to the measurement of hGH in urine as a preferred 'non-invasive' biofluid. Unfortunately, conventional hGH immunoassays cannot attain the sensitivity required to detect the low concentrations of hGH in urine. The lowest limit of sensitivity for existing hGH immunoassays is >50 pg/mL, while the estimated concentration of urinary hGH is about 1 pg/m-50 times lower than the sensitivity threshold. We have created novel N-isopropylacrylamide (NIPAm)-based hydrogel nanoparticles functionalized with an affinity bait. When introduced into an analyte-containing solution, the nanoparticles can perform, in one step, (1) complete harvesting of all solution phase target analytes, (2) full protection of the captured analyte from degradation and (3) sequestration of the analyte, effectively increasing the analyte concentration up to a hundredfold. N-isopropylacrylamide nanoparticles functionalized with Cibacron Blue F3GA bait have been applied to raise the concentration of urinary hGH into the linear range of clinical grade immunoassays. This technology now provides an opportunity to evaluate the concentration of hGH in urine with high precision and accuracy.

Evidence that SOM230 can prevent experimental mammary hyperplasia by blocking IGF-I and thus estrogen action in the mammary gland: preliminary evidence for an effect in humans.

Abstract Abstract #5084 Background: Antiestrogens or aromatase inhibitors are used for breast cancer chemoprevention, however, they are poorly tolerated. We have shown that IGF-I is required to permit estrogen and progesterone action in the mammary gland. A novel somatostatin analog, SOM230, which binds to several somatostatin subtype receptors (SSTR), prevents estrogen action by reducing pituitary growth hormone, and also by a direct IGF-I action inhibitory effect on the mammary gland. Menopausal symptoms have not been observed in acromegalic patients receiving SOM230. Material and Methods: Several approaches have been undertaken. 1) We developed a model of hyperplasia in hypophysectomized and oophorectomized female rats. Hyperplasia was induced by treatment with 600 mcg hGH and follicular phase concentrations of estradiol. 2) To assess translatability to humans we cell proliferation (Ki67) and apoptosis (TUNEL) were measured in normal human breast from reduction mammoplasty and in samples of proliferative fibrocystic change (FCC). 3) We also measured expression of SSTR in atypical ductal hyperplasia and DCIS, and 4) A proof of principal trial with SOM230 has begun accrual to determine whether SOM230 acts in human breast as in rats. Results: 1) hGH and E2 caused florid hyperplasia in rat mammary glands within a week. Twenty-six percent of gland structures exhibited hyperplasia with 50% of those showing florid hyperplasia. SOM230 reduced the number of areas of florid hyperplasia to 7.5 ±0.5 from 18.9±1.3 (p&amp;lt;0.001). This was accomplished by a reduction in cell proliferation and an increase in apoptosis. Interestingly, co-administration with tamoxifen provided no additional benefit over that of SOM230. 2) Proliferative lesions from human breast had 8.09 % of cells stain for Ki67. 3) All 5 somatostatin subtype receptor (SSTR) were present in pathology samples of atypical hyperplasias and DCIS, but SSTR3 and 5 were present in highest concentrations. SSTR 3 is the receptor most likely to mediate the effect of SOM230 with SSTR5 being the next most likely. 4) In the first patient tested we found that SOM230 increased apoptosis and reduced cell proliferation (1000 cells counted).&amp;#x2028; &amp;#x2028; Discussion: Our data show that SSTR are present in ADH and DCIS and normal breast tissue. Our data also show that SOM230 can prevent cell proliferation and increase apoptosis both in rats and humans. Thus, further clinical trials will be important as SOM230 may have a role in breast cancer chemoprevention. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5084.

Patients with solid tumors treated with high-temperature whole body hyperthermia show a redistribution of naive/memory T-cell subtypes

An activation of the immune system might contribute to the therapeutic effect of whole body hyperthermia (WBH) in cancer patients. We explored immune and endocrine responses in patients undergoing high-temperature WBH. Identical parameters were investigated in a separate group of healthy volunteers undergoing physical exercise to rule out effects of sympathetic activation. Lymphocyte subpopulations, lymphocytic expression of a range of adhesion molecules, and serum concentrations of a variety of hormones and cytokines were assessed in cancer patients undergoing high-temperature (60 min at 41.0-41.8 degrees C) WBH (n = 25) and in a separate group of healthy volunteers (n = 10) performing strenuous physical exercise. WBH induced an increase in human growth hormone (hGH), ACTH, and cortisol as well as in TNF-alpha, IL-6, IL-8, and IL-12R. We observed an increase in natural killer (NK) cells and CD56+ NK T cells shortly after initiation of WBH. In contrast, we found a decrease in T cells expressing L-selectin (CD62L) or alpha4beta7 integrin adhesion molecules mediating homing to lymphatic tissues. Accordingly, we observed a decrease in CD45RA+CCR7+ naive and CD45RA-CCR7+ central memory T cells. Numbers of CD45RA-CCR7- memory effector and CD45RA+CCR7 terminally differentiated T cells, on the other hand, remained unchanged. No comparable changes were observed in the group of healthy volunteers. In conclusion, patients with solid tumors treated with WBH show an increase in NK and NK T cells. In a later phase, plasma concentrations of IL-8, hGH, and cortisol increase, correlated with an influx of neutrophils into the peripheral blood. The alterations in T-cell populations suggest that WBH may induce naive and central-memory T cells to enter lymphatic tissue to await antigen exposure and effector T cells to migrate into peripheral tissues to exert their effector function. Although the exercise group may not be an appropriate control to proof the effect of WBH, these changes were not seen in the healthy volunteers performing physical exercise.

Influence of Chronic Supplementation of Arginine Aspartate in Endurance Athletes on Performance and Substrate Metabolism

The intake of arginine aspartate has been shown to increase anabolic hormones like human growth hormone (hGH) and glucagon. The aim of our study was to investigate whether daily intake of two different dosages of arginine asparate during four weeks affects selected parameters of overtraining syndrome like performance, metabolic and endocrine parameters. Thirty male endurance-trained athletes were included in a randomized, double-blind, placebo-controlled study and divided into three groups. During four weeks, they ingested either arginine aspartate with a high concentration (H) of 5.7 g arginine and 8.7 g aspartate, with a low concentration (L) of 2.8 g arginine and 2.2 g aspartate or placebo (P).VO(2)peak and time to exhaustion were determined on a cycling ergometer in an incremental exercise test before and after supplementation. Before and after each incremental exercise test, concentrations of hGH, glucagon, testosterone, cortisol, ferritine, lactate, and urea were measured. Compared to placebo, no significant differences on endurance performance (VO(2)peak, time to exhaustion), endocrine (concentration of hGH, glucagon, cortisol, and testosterone) and metabolic parameters (concentration of lactate, ferritine, and urea) were found after chronic arginine aspartate supplementation. The chronic intake of arginine asparate during four weeks by male endurance athletes showed independent of dosage no influence on performance, selected metabolic or endocrine parameters. Consequently, there seems to be no apparent reason why the supplementation of arginine aspartate should be an effective ergogenic aid. The practice of using arginine aspartate as potential ergogenics should be critically reevaluated. Further investigations with higher dosage and extended supplementation periods should be performed.

Sleep enhances nocturnal plasma ghrelin levels in healthy subjects.

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been shown to promote slow-wave sleep (SWS, non-REM sleep stages 3 and 4). Plasma levels of ghrelin are dependent on food intake and increase in sleeping subjects during the early part of the night. It is unknown whether sleep itself affects ghrelin levels or whether circadian networks are involved. Therefore, we studied the effect of sleep deprivation on nocturnal ghrelin secretion. In healthy male volunteers, plasma levels of ghrelin, cortisol, and human growth hormone (hGH) were measured during two experimental sessions of 24 h each: once when the subjects were allowed to sleep between 2300 and 0700 and once when they were kept awake throughout the night. During sleep, ghrelin levels increased during the early part of the night and decreased in the morning. This nocturnal increase was blunted during sleep deprivation, and ghrelin levels increased only slightly until the early morning. Ghrelin secretion during the first hours of sleep correlated positively with peak hGH concentrations. We conclude that the nocturnal increase in ghrelin levels is more likely to be caused by sleep-associated processes than by circadian influences. During the first hours of sleep, ghrelin might promote sleep-associated hGH secretion and contribute to the promotion of SWS.

Endocrine responses to the oral ingestion of a physiological dose of essential amino acids in humans

The response of insulin, human growth hormone (hGH), cortisol, leptin and ghrelin, in addition to various metabolic parameters, was measured at 10 minute intervals following the oral ingestion of a standardised physiological dose of essential amino acids (AA). Twenty-eight healthy male, fasted volunteers (aged 18-40 yrs, BMI 18.0-24.5 kg/m(2)) took part in the study; 13 volunteers in the AA group, nine subjects in an iso-caloric control group, and a further six subjects served as fasting controls. Twenty minutes after ingestion, insulin reached peak concentrations that were up to 500% higher than basal values (P<0.0001). The AA group and iso-caloric control group showed a similar insulin response. AA ingestion led to an increase in hGH secretion with maximum concentrations being 2100+/-1013% higher than the basal values (P<0.0001). In contrast, no changes in hGH concentrations were observed in the iso-caloric controls; in the fasting controls only a slight increase in hGH was found towards the end of the fasting period. While cortisol decreased significantly (P<0.01) during the study in the AA group, neither control group showed a significant change in this parameter. Changes in leptin levels remained insignificant in all three groups, whereas ghrelin showed a different profile in each of the three groups, i.e. a continuous rise towards the end of the study period (P<0.001) in the AA group, a less significant effect for the fasting group, and no effect at all in the iso-caloric control group. There was no significant correlation between the concentrations or the area under curve of the hormones measured in any of the groups. The endocrine data provided in this study indicate that a single bolus of essential AA in fasted individuals is associated with both anabolic and catabolic hormonal responses.