Panagiotis Mylonas

Growth hormone and insulin-like growth factor I protect intestinal cells from radiation induced apoptosis.

We studied whether programmed cell death (or apoptosis) is the predominant mechanism in radiation-induced cell damage to rat intestinal mucosa and investigated the mechanism of the protective effect of GH and IGF-I in the same model. Male albino Wistar rats were divided into four groups: controls, radiation, radiation plus GH and radiation plus IGF-I. Radiation was administered on the first day and on day 4. All animals were sacrificed and segments of the terminal ileum were stained with hematoxylin-eosin. Apoptosis of the epithelial cells was identified at the cellular level by the TUNEL stain and was distinguished from necrosis by the characteristic morphology of the cells (cytoplasmic shrinkage, marginal chromatin condensation and generation of nuclear apoptotic bodies). Apoptotic cells in the control animals were few and detected only at the tips of the villi while in the irradiated animals almost all the epithelial cells were apoptotic, distributed from the crypts to the tips of the villi and the mucosa showed severe epithelial atrophy and ulceration. The histologic picture of the mucosa in the GH and IGF-I treated animals was similar to normal controls and apoptotic cells were restricted only at the tips of the villi. DNA and RNA from the mucosa cells were isolated and analyzed by electrophoresis. DNA fragmentation and RNA 28s band ribonuclease cleavage was observed only in the irradiated animals. We have shown that abdominal radiation causes intestinal epithelial cell damage mainly through the induction of apoptosis and the treatment with GH and IGF-I inhibits apoptosis of the cells and preserves the mucosal integrity.

Bombesin and neurotensin reduce endotoxemia, intestinal oxidative stress, and apoptosis in experimental obstructive jaundice.

Objective:To evaluate the effect of bombesin (BBS) and neurotensin (NT) on intestinal histopathology, intestinal oxidative stress, and endotoxemia in experimental obstructive jaundice. Summary Background Data:Obstructive jaundice compromises gut barrier function, resulting in endotoxemia. BBS and NT, exerting various biologic actions on gastrointestinal tissues, preserve gut mucosal integrity in cases of injury or atrophy. Methods:Seventy male Wistar rats were randomly divided into 5 groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL + BBS (30 μg/kg/d), V = BDL + NT (300 μg/kg/d). By the end of the experiment, on day 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically, and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content. To estimate intestinal oxidant/antioxidant equilibrium, lipid peroxidation, protein oxidation, and thiol redox state (reduced glutathione [GSH], oxidized glutathione [GSSG], total nonprotein mixed disulfides [NPSSR], protein thiols [PSH], and protein disulfides [PSSP]) were determined on tissue homogenates from the terminal ileum. Results:BBS or NT administration significantly reduced portal and systemic endotoxemia observed in obstructive jaundice. Both factors reversed obstructive jaundice-induced morphologic features of intestinal atrophy, increasing villus density and mucosal thickness. This effect was accompanied by induction of mitoses and reduction of apoptosis in intestinal crypts. Mucosal DNA and protein content were reduced, although not to significant levels, in BDL animals and restored to control levels after BBS or NT treatment. Moreover, BBS or NT administration protected the intestine in jaundiced rats against oxidative stress, as demonstrated by reduction of intestinal lipid peroxidation, increase of the antioxidant GSH, and decrease of the oxidized forms GSSG and NPSSR, while BBS additionally reduced protein oxidation as well. Conclusions:Administration of BBS or NT in bile duct–ligated rats exerts beneficial effects on intestinal oxidative stress, cell proliferation, apoptosis, and endotoxemia. This observation might be of potential value in patients with extrahepatic cholestasis.

Abolished circadian rhythm of salivary cortisol in elite artistic gymnasts

OBJECTIVE The aim of this study was to evaluate the effects of intensive physical exercise and acute psychological stress during high level athletic competition as reflected on the levels of salivary cortisol in elite artistic gymnasts (AGs). DESIGN The study included 239 AGs (142 females-97 males) who participated in the European Championship of Gymnastics in 2006 and 81 adolescents (40 females-41 males), matched for age, as controls. All athletes participated voluntarily in all or parts of the study, providing samples or data for each of the variables measured. Height, weight, body fat, lean body mass (LBM), bone age and Tanner stage of puberty were assessed and data concerning the time of thelarche, adrenarche and menarche as well as, the onset and the intensity (hours per week) of training were obtained. METHODS Saliva samples were collected, the morning before training and in the afternoon shortly after the competition. From controls, the saliva samples were collected in the morning. Cortisol concentrations were measured using a chemiluminescence method. Acute stress was assessed using a questionnaire designed for the study. RESULTS No difference was found between morning and afternoon salivary cortisol levels in both male and female AGs (females: AM: 15.45±7.45nmol/l vs PM: 15.73±9.38nmol/l; males: AM: 10.21±5.52nmol/l vs PM: 9.93±13.8nmol/l, p>0.05). Female AGs presented higher levels of morning salivary cortisol than female controls (p<0.05). Both male and female AGs had higher degree of psychological stress in comparison with controls (p<0.001, p<0.013, respectively). Female AGs had higher morning and afternoon salivary cortisol levels (p<0.01, p<0.01, respectively) and higher degree of stress (p<0.003) than males. CONCLUSIONS In elite AGs the diurnal rhythm of salivary cortisol has been abolished, probably due to the strenuous training and competition conditions. Female AGs presented higher levels of morning salivary cortisol and psychological stress compared to both male AGs and female controls. The long term consequences of these modifications of the HPA axis remain to be elucidated.

Adequacy of saliva 17-hydroxyprogesterone determination using various collection methods

Steroids determination in saliva offers several advantages. The collection of saliva is a noninvasive, less stressful technique than blood withdrawal and reflects the circulating unbound fractions. The suitability of saliva for 17-hydroxyprogesterone and cortisol determinations has been documented in healthy subjects as well as in diseases like Congenital Adrenal Hyperplasia and Cushing syndrome. The aim of the study was to compare the influence of different collection methods on the results of 17-hydroxyprogesterone measurement in saliva collected by different ways, using commercially available RIAs developed for plasma. 17-hydroxyprogesterone was determined in 64 healthy adult volunteers (30 males, 34 females) in serum (Group SE) and in saliva collected before meals at 8-10 p.m. by directly spitting into a plastic tube (Group SP), using a cotton swab (Group SA) and using a polyester swab Salivette (Group SB). We used a commercially available direct radioimmunoassay without separation technique. The 17-hydroxyprogesterone mean values (ng/ml) were 1.16+/-1.3 (Group SE), 0.056+/-0.046 (Group SP), 0.089+/-0.048 (Group SA) and 0.058+/-0.049 (Group SB). The detection limit was 0.010 ng/ml. The correlations between the values in serum (Group SE) and in saliva were: r=0.77, p<0.05 (Group SP); r=0.62, p<0.05 (Group SA); r=0.70, p<0.05 (Group SB). The saliva values corresponding to the serum cut-off point of 3 ng/ml upper limit of normal values were in ng/ml 0.13 (Group SP), 0.16 (Group SA) and 0.11 (Group SB). In conclusion, 17-hydroxyprogesterone determinations in saliva using commercially available RIAs primarily developed for serum, is a reliable and easy to perform procedure. The three different methods of saliva collection showed 17-hydroxyprogesterone concentrations to have good agreement.

Growth velocity and final height in elite female rhythmic and artistic gymnasts

PURPOSEThe aim of this study was to determine the impact of intensive training on adult final height in elite female rhythmic and artistic gymnasts.METHODSThe study included 215 rhythmic gymnasts (RG) and 113 artistic gymnasts (AG).RESULTSAG were below the 50th percentile, while RG were taller than average. Final adult height was lower than target height in AG, while in RG, it exceeded target height. AG started training earlier than RG (p<0.001) and reported lower intensity of training (p<0.001). RG were taller than AG, with higher target height, greater final height-target height and lower body fat and BMI (p<0.001). Using multiple regression analysis, the main factors influencing final height were weight SDS (p<0.001), target height SDS (p<0.001) and age of menarche (p<0.001) for RG, and weight SDS (p<0.001) and target height SDS (p<0.001) for AG.CONCLUSIONIn both elite female RG and AG, genetic predisposition to final height was not disrupted and remained the main force of growth. Although in elite RG genetic predisposition for growth was fully preserved, in elite female AG final adult height falls shorter than genetically determined target height, though within the standard error of prediction.

Treating Iodine Deficiency: Long-Term Effects of Iodine Repletion on Growth and Pubertal Development in School-Age Children

BACKGROUND Iodine deficiency (ID) is still a major universal health problem. Iodine deficiency disorders (IDDs) affect people of all ages, among whom the most vulnerable are children and adolescents. The aim of the present study was to assess the long-term effects on growth and pubertal development of correcting severe ID in areas of Azerbaijan between 1999 and 2000. METHODS Iodized oil was administered orally to 293,000 children, aged 6-16 years. Among those, 364 children were randomly selected and were examined 1 year before the administration of iodized oil (Group I-neg, iodine negative) and 295 children (Group I-Rx, iodine treated) were examined 4 years (Group I-R x 4, iodine treated 4 years later; n = 173) or 5 years (Group I-R x 5, iodine treated 5 years later; n = 122) after the last dose of iodide. RESULTS In Group I-neg the median urine iodine concentration (UIC) (mcg/L) was 36 (mean: 36.272 +/- 11.036) and increased significantly (p < 0.001) in Group I-R x 4: 188 (mean: 230.969 +/- 155.818) and in Group I-R x 5: 175 (mean: 201.176 +/- 130.369). The prevalence of goiter was 99% in Group I-neg and 2% in Group I-R x 4. Children in Group I-Rx had a greater standard deviation score (SDS) for height (-0.1364 +/- 1.279, n = 294) than children in Group I-neg (-0.5019 +/- 1.17, n = 363) (p < 0.001, t = -3.817), which was more significant for boys. SDS for weight was similar in both groups (Group I-neg: -0.17 +/- 0.78, n = 363; Group I-Rx: -0.115 +/- 0.917, n = 294). The rate of puberty development as judged by the development of breast and pubic hair was normalized in both sexes after the correction of ID. CONCLUSIONS Our results demonstrate that long-term correction of severe ID leads to sustained improvement of linear growth accompanied by a normalization of the time of onset of pubertal development for both sexes.