Poverty and immigration as a barrier to iodine intake and maternal adherence to iodine supplementation.

PURPOSE: Iodine deficiency still remains a significant health issue worldwide. Pregnant and lactating women are at risk for iodine deficiency when living in mild iodine-deficient areas such as Italy. This study aims at evaluating the consumption of iodized salt, iodine-rich-foods and maternal micronutrient supplements in a group of women with limited access to the Italian National Health System. METHODS: A cross-sectional survey was conducted among immigrant and Italian women living in poverty and referring to 40 Non-Governmental Organization throughout Italy for their health needs. 3483 women answered the ad hoc questionnaire between January 2017 and February 2018. RESULTS: The consumption of iodized salt was very low, and even lower among immigrant women. Determinants of iodized salt consumption were the period spent in Italy for immigrant women and living in a family-type setting, parity and, particularly, the degree of education for Italian ones. 17.5% of immigrant women and 8.6% of the Italian ones reported a diagnosis of thyroid disease. 521 women, 75.4% of whom were immigrants, were pregnant or breast-feeding. The majority (57.3%) had no specific maternal supplementation. CONCLUSIONS: Both Italian and immigrating women with a low income or without access to the public health system have a poor adherence both to the salt iodization policy and to folic acid and iodine supplements in preconception and pregnancy. They also referred a low-frequency intake of iodine-rich-foods. The identification of barriers to health care access could be useful to promote specific health interventions in this target population.

Obese adolescents exhibit a constant ratio of GH isoforms after whole body vibration and maximal voluntary contractions.

BACKGROUND: Growth hormone (GH) is a heterogeneous protein composed of several molecular isoforms, the most abundant ones being the 22 kDa- and 20 kDa-GH. Exercise-induced secretion of GH isoforms has been extensively investigated in normal-weight individuals due to antidoping purposes, particularly recombinant human GH (rhGH) abuse. On the other hand, the evaluation of exercise-induced responses in GH isoforms has never been performed in obese subjects. METHODS: The acute effects of whole body vibration (WBV) or maximal voluntary contraction (MVC) alone and the combination of MVC with WBV (MVC + WBV) on circulating levels of 22 kDa- and 20 kDa-GH were evaluated in 8 obese male adolescents [mean age ± SD: 17.1 ± 3.3 yrs.; weight: 107.4 ± 17.8 kg; body mass index (BMI): 36.5 ± 6.6 kg/m2; BMI standard deviation score (SDS): 3.1 ± 0.6]. RESULTS: MVC (alone or combined with WBV) significantly stimulated 22 kDa- and 20 kDa-GH secretion, while WBV alone was ineffective. In particular, 22 kDa- and 20 kDa-GH peaks were significantly higher after MVC + WBV and MVC than WBV. In addition, 22 kDa-GH (but not 20 kDa-GH) peak was significantly higher after MVC + WBV than MVC. Importantly, the ratio of circulating levels of 22 kDa- to 20 kDa-GH was constant throughout the time window of evaluation after exercise and similar among the three different protocols of exercise. CONCLUSIONS: The results of the present study confirm the ability of MVC, alone and in combination with WBV, to stimulate both 22 kDa- and 20 kDa-GH secretion in obese patients, these responses being related to the exercise workload. Since the ratio of 22 kDa- to 20 kDa-GH is constant after exercise and independent from the protocols of exercise as in normal-weight subjects, hyposomatotropism in obesity does not seem to depend on an unbalance of circulating GH isoforms. Since the present study was carried out in a small cohort of obese sedentary adolescents, these preliminary results should be confirmed in further future studies enrolling overweight/obese subjects with a wider age range.

GH responses to whole body vibration alone or in combination with maximal voluntary contractions in obese male adolescents.

BACKGROUND: The anabolic, lipolytic and anti-inflammatory effects of exercise-stimulated GH secretion could be usefully exploited in the multidisciplinary rehabilitative programs of obese patients, who are reported to suffer from hyposomatotropism. To date, evaluation of GH responses to whole body vibration (WBV) in combination with maximal voluntary contractions (MVC) has been performed in normal-weight subjects, but not obese patients. Thus, aim of the present study was to investigate the effects of WBV and MVC, alone and combined, on GH responsiveness in obese subjects. METHODS: The acute effects of WBV or MVC alone and the combination of MVC with WBV (MVC + WBV) on serum GH, cortisol and IGF-I and blood lactate (LA) levels were evaluated in 8 obese male adolescents [mean age ±â€¯SD: 17.1 ±â€¯3.3 yrs.; weight: 107.4 ±â€¯17.8 kg; body mass index (BMI): 36.5 ±â€¯6.6 kg/m2; BMI standard deviation score (SDS): 3.1 ±â€¯0.6]. RESULTS: WBV and MVC (alone or combined) significantly stimulated GH secretion. In particular, GH peaks and net areas under the curve (nAUCs) were significantly higher after MVC + WBV and MVC than WBV, without any difference between MVC + WBV and MVC groups; anyway, an additive effect on GH levels immediately after the execution of MVC + WBV test was found in comparison with MVC test. LA peaks significantly increased after each exercise (vs. basal condition), being significantly higher after MVC + WBV and MVC than WBV, without any difference between MVC + WBV and MVC groups. Peak LA values were significantly correlated with GH peaks and nAUCs. In contrast to the unchanged IGF-I levels, MVC + WBV and MVC (but not WBV) significantly stimulated cortisol secretion. CONCLUSIONS: The results of the present study confirm the ability of MVC and WBV to stimulate GH secretion in obese patients. Rehabilitative programs combining different types of exercise eliciting a potent GH response seem to be important to counteract the hyposomatotropism of obese patients. Due to its limited stress upon joints without provoking an excessive fatigue, WBV could be usefully employed in the initial stages of a weight loss program alone or in combination with more potent GH releasing stimuli, such as MVC.

Drugs Delivery by Charities: A Possible Epidemiologic Indicator in Children of Undocumented Migrants.

Describing the health status of a population is difficult, especially in the case of irregular migrants who are now a growing population in western Countries. Data for children of these families are almost inexistent. In the absence of databases on this peculiar pediatric population, we analyzed drugs dispensation by a major Charity to have an insight into their health needs. This observational retrospective study was carried out during the entire 2015 and enrolled 628 undocumented children. A cohort of 8438 adult patients belonging to the same ethnic groups was used for comparison. Respiratory drugs were those most commonly prescribed, followed by those for skin and ocular diseases and by those for gastrointestinal disorders. Also in adults respiratory medications were the most dispensed, but almost in equal measure than cardiovascular drugs.To our knowledge this is the first study on the health needs of undocumented children residing in a western Country. The method we used seems to be a useful method for epidemiological analysis. As could be expected, respiratory and skin diseases ranked first, possibly owing to environmental factors.

The burden of chronic noncommunicable diseases in undocumented migrants: a 1-year survey of drugs dispensation by a non-governmental organization in Italy.

OBJECTIVES: This study was carried out with two objectives. The first one was to have an insight into the prevalence of chronic noncommunicable diseases (CNCD) in undocumented migrants, and the second one was to evaluate if differences existed among different ethnic groups. STUDY DESIGN: The study is based on the collection of data on drug dispensation by a non-governmental organization (NGO) providing free medical assistance to undocumented migrants in Milan, Italy. All the prescriptions to adult subjects from January 1 to December 31 2014 (total 8438) were recorded and analyzed. All the data available for the patients receiving prescriptions (age, gender and country of birth) were also collected in anonymous form. Ethical approval for the study was given by the Ethics Committee of the NGO. METHODS: Drugs were grouped according to the anatomical therapeutic chemical (ATC) classification and their quantities expressed as daily defined doses (DDDs)/1000 patients/day. The 56 ATC levels were divided into three groups according to their use for acute, chronic, or both acute and chronic diseases. The statistical analysis of drug dispensation was performed for the whole population and for the five ethnic groups into which it had been divided. RESULTS: Prescription of medicines for chronic conditions was significantly greater than for acute (154.2 ± 45.9 vs 51.3 ± 18.4 DDD/1000 patients/day, P < 0.02) and for both acute and chronic conditions (57.9 ± 12.8 DDD/1000 patients/day, P < 0.02). Five ATC classes accounted for 60% of all chronic prescriptions. They were differently distributed among the five ethnic groups (e.g., Asians required more antihypertensives and antidiabetics, East Europeans required more lipid modifying drugs, antihypertensives and antithrombotics). CONCLUSIONS: Our data show an important use of medicines for chronic diseases in a population of undocumented migrants. Though with some limitations, this could be an indicator of a high prevalence of CNCD in this population, with significant differences among different ethnic groups. This situation should be considered when planning health interventions, also in consideration of the fact that it could have an impact on European Health Services in a short time.

GH responsiveness before and after a 3-week multidisciplinary body weight reduction program associated with an incremental respiratory muscle endurance training in obese adolescents.

Several studies have demonstrated that the obesity-related hyposomatropism is usually reversible after a consistent weight loss induced by diet and/or bariatric surgery. Recently, a single bout of respiratory muscle endurance training (RMET) by means of a specific commercially available device (Spiro Tiger®) has been reported to induce a marked GH response in obese adults, its GH-releasing effect being significantly lower in obese adolescents. The GH response disappeared in both obese adults and adolescents when RMET was repeated at 2-h intervals in-between. The aim of the present study was to evaluate GH responses to repeated bouts of RMET administered before and after a 3-week in-hospital multidisciplinary body weight reduction program (entailing energy-restricted diet, 90 min/daily aerobic physical activity, psychological counseling, and nutritional education) combined with a progressively increasing RMET (15 daily sessions, 5 sessions per week) in 7 obese male adolescents [age: 12-17 years; body mass index (BMI): 38.5±3.1 kg/m2; percent fat mass (FM): 37.0±2.0%]. Blood samplings for GH determinations were collected during the 1st and 15th sessions, which were composed of 2 consecutive bouts of RMET (of identical intensity and duration) at 2-h interval in-between. At the beginning of the study, baseline GH levels significantly increased after the first bout of RMET in all subjects (p<0.05). The administration of the second bout of RMET resulted in a significantly lower (p<0.05) GH increase in comparison with the first one. Three weeks of the integrated intervention significantly reduced both body weight (from 115.3±9.2 kg to 111.5±8.7 kg, p<0.05) and FM (from 43.1±5.7 kg to 41.9±5.3 kg, p<0.05), these combined effects being, however, not sufficient to influence GH responsiveness to the 2 repeated bouts of RMET (GH peaks to the first bout: 4.8±1.6 ng/ml vs. 4.8±1.6 ng/ml; GH peaks to the second bout: 0.9±0.2 ng/ml vs. 1.1±0.1 ng/ml, before and after 3 weeks of the treatment, respectively, p=NS). In conclusion, a 3-week incremental RMET combined with a body weight reduction intervention does not seem useful to positively influence the reduced GH responsiveness to 2 repeated RMET bouts in obese adolescents. More intensive and/or long-term RMET protocols, associated with energy-restricted diets, determining more consistent changes in body composition, are likely needed to restore the impaired GH-IGF-1 function of obese adolescents.

Unexpectedly increased anorexigenic postprandial responses of PYY and GLP-1 to fast ice cream consumption in adult patients with Prader-Willi syndrome.

OBJECTIVE: The effect of eating rate on the release of anorexigenic gut peptides in Prader-Willi syndrome (PWS), a neurogenetic disorder clinically characterized by hyperphagia and excessive obesity, has not been investigated so far. DESIGN AND PATIENTS: Postprandial PYY and GLP-1 levels to fast (5 min) and slow (30 min) ice cream consumption were measured in PWS adult patients and age-matched patients with simple obesity and normal-weighted subjects. Visual analog scales (VASs) were used to evaluate the subjective feelings of hunger and satiety. RESULTS: Fast ice cream consumption stimulated GLP-1 release in normal subjects, a greater increase being observed with slow feeding. Fast or slow feeding did not change circulating levels of GLP-1 in obese patients, while, unexpectedly, fast feeding (but not slow feeding) stimulated GLP-1 release in PWS patients. Plasma PYY concentrations increased in all groups, irrespective of the eating rate. Slow feeding was more effective in stimulating PYY release in normal subjects, while fast feeding was more effective in PWS patients. Slow feeding evoked a lower hunger and higher satiety compared with fast feeding in normal subjects, this finding being not evident in obese patients. Unexpectedly, fast feeding evoked a lower hunger and higher satiety in PWS patients in comparison with slow feeding. CONCLUSIONS: Fast feeding leads to higher concentrations of anorexigenic gut peptides and favours satiety in PWS adult patients, this pattern being not evident in age-matched patients with simple obesity, thus suggesting the existence of a different pathophysiological substrate in these two clinical conditions.

GH responses to 2 consecutive bouts of respiratory muscle endurance training in obese adolescents and adults.

Repeated bouts of GH-releasing stimuli (both pharmacological and physiological, such as aerobic exercise) at 2-h intervals are associated with a blunting of somatotropic responsiveness in normal adults, while a persistent GH responsiveness to consecutive stimuli is reported to occur in children and adolescents. Recently, a single bout of respiratory muscle endurance training (RMET) by means of a specific commercially available device (Spiro Tiger®) has been shown to induce relevant GH responses in both normal-weighted and obese adult subjects. The aim of the present study was to evaluate GH responses to repeated bouts of RMET in obese adolescents and adults. Seven obese male adolescents (age: 15.7±0.4 years; body mass index, BMI: 38.0±3.3 kg/m2) and 10 obese adults (age: 22.2±1.4 years; BMI: 39.9±1.0 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions. Blood samplings for GH determinations were collected during the 12th session, which was composed of 2 consecutive bouts of RMET (of identical intensity and duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) at a 2-h interval in-between. Baseline GH levels significantly increased after the first bout of RMET in all subjects, higher GH peaks being found in obese adults than in obese adolescents (peaks: 14.3±2.1 ng/ml vs. 4.8±1.6 ng/ml, respectively, p<0.05). The administration of the second bout of RMET resulted in significantly lower (p<0.05) GH increases in both obese adolescents and obese adults (peaks: 0.9±0.2 ng/ml and 1.6±0.2 ng/ml, respectively) in comparison with the first one. In conclusion, exercise protocols based on repeated bouts of RMET do not seem a valid strategy to persistently stimulate GH-IGF-1 release in obese adolescents, since GH responses to a single bout are actually modest in comparison with those of obese adults and completely abolished after repeated bouts at 2 h interval in-between.

Estrogens need insulin-like growth factor I cooperation to exert their neuroprotective effects in post-menopausal women.

BACKGROUND: The abrupt fall in estrogens levels during the menopausal transition may connote an hormonal state predisposing to neurodegenerative disorders, e.g. Alzheimer's disease (AD). Reportedly, the neurotrophic activity of estrogen involves an interaction with IGF-I. AIM: To evaluate the leukocyte gene expression of progesterone receptor (PR-A/B) and interleukin 6 (IL-6), two parameters under the control of estrogens and involved in the pathogenesis of AD. SUBJECTS: The study was conducted in non-demented women divided into two groups according to their pre- or post-menopausal state; each group being further divided into two subgroups based on their circulating levels of IGF-I (normal or low). An additional sample of AD-affected women served as a comparison group. RESULTS: Estrogens maintained their full activity only when IGF-I levels were in the range of normalcy. On the contrary, if the concentrations of one or both hormones were reduced, estrogens were not anymore capable to control the gene expression of PR-A/B or IL-6. CONCLUSIONS: Before administering hormone-based replacement therapy, characterization of the somatotropic function should be performed in the early phase of the menopause.

Anorexigenic postprandial responses of PYY and GLP1 to slow ice cream consumption: preservation in obese adolescents, but not in obese adults.

OBJECTIVE: Eating slowly increases the postprandial responses of some anorexigenic gut hormones in healthy lean subjects. As the rate of food intake is positively associated with obesity, the aim of the study was to determine whether eating the same meal at different rates evokes different postprandial anorexigenic responses in obese adolescent and adult subjects. DESIGN AND METHODS: Eighteen obese adolescents and adults were enrolled. A test meal was consumed on two different sessions by each subject, meal duration taking either 5  min (fast feeding) or 30  min (slow feeding). Circulating levels of glucagon-like peptide 1 (GLP1), peptide YY (PYY), glucose, insulin, and triglycerides were measured over 210  min. Visual analog scales were used to evaluate the subjective feelings of hunger and satiety. RESULTS: fast feeding did not stimulate GLP1 release in obese adolescent and adults, whereas slow feeding increased circulating levels of GLP1 only in obese adolescents. Plasma PYY concentrations increased both in obese adolescents and in adults, irrespective of the eating rate, but slow feeding was more effective in stimulating PYY release in obese adolescents than in adults. simultaneously, slow feeding evoked a higher satiety only in obese adolescents compared with fast feeding but not in obese adults. in obese adolescents, slow feeding decreased hunger (only at 210 min). irrespective of the eating rate, postprandial responses of insulin and triglycerides were higher in obese adults than in obese adolescents. CONCLUSION: Slow feeding leads to higher concentrations of anorexigenic gut peptides and favors satiety in obese adolescents, but this physiological control of food intake is lost in obese adults.

Growth hormone variants: a potential avenue for a better diagnostic characterization of growth hormone deficiency in children.

Human GH (hGH) is a heterogeneous protein hormone consisting of several isoforms. This heterogeneity is the consequence of multiple hGH genes, mRNA splicing, post-translational modifications, and peripheral metabolism, and it represents one important reason for the disparity among GH assay results from different laboratories. However, other factors are involved: a) interference from endogenous GH binding proteins; b) different specificities of anti- GH (monoclonal and polyclonal) antibodies; c) different matrix effects among the calibrators; d) the use of different calibrators. The measurement of GH levels in response to provocative testing is an essential part of the diagnosis of GH deficiency. For this purpose, an accurate, reproducible and universally valid GH measurement would be highly desirable, but, despite a huge number of efforts in clinical biochemistry, this goal remains elusive.

Growth hormone response induced by a respiratory muscle endurance training in healthy subjects.

To date, the large majority of studies evaluating growth hormone (GH) response to acute physical exercise has been performed involving gross muscle groups. To the best of our knowledge, none has evaluated the effects of a respiratory muscle endurance training (RMET) on hormonal secretions, particularly on GH release, though some respiratory devices have been widely used in athletes to train respiratory muscles and to improve cardiopulmonary function and physical performance. 8 healthy men underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger®). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, ghrelin, glucose, and lactate (LA) levels. GH and cortisol responses significantly increased after a 15-minute RMET session, which, in contrast, inhibited ghrelin secretion. There was a minimal, though significant, increase in LA levels with a significant elevation in glycemia. A 15-minute RMET session, administered after a 11-days incremental progressive RMET protocol, was capable of stimulating GH and cortisol release and suppressing ghrelin secretion. Optimization of incremental progressive RMET protocols would be important to maximize the positive chronic effects of this intervention on somatotropic function and muscle performance.

Growth hormone and lactate responses induced by maximal isometric voluntary contractions and whole-body vibrations in healthy subjects.

BACKGROUND: In contrast with maximal voluntary resistance exercise, which is allegedly considered a potent GH stimulus in young subjects, evaluation of GH response to whole-body vibrations (WBV) has yielded conflicting results. METHODS: The acute effects of WBV alone (test A), maximal voluntary isometric contractions (MVC) (test B), and combination of WBV and MVC (test C) on serum GH and blood lactate (LA) levels were studied in 9 healthy adult males. Muscle soreness was assessed 24 and 48 h after exercise by a visual analogue scale. RESULTS: GH responses were significantly higher after tests B and C than after test A (GH peaks: 18.8 ± 9.5 ng/ml or 20.8 ± 13.7 ng/ml, respectively, vs 4.3 ± 3.5 ng/ml; p<0.05), with no difference between tests B and C. LA concentrations significantly increased after tests A, B, and C, being significantly higher after tests B and C than after test A (LA peaks: 2.0 ± 0.5 mmol/l or 6.7 ± 2.3 mmol/l, respectively, vs 7.6 ± 0.9 mmol/l; p<0.05). Peak LA values were significantly correlated to GH peaks in the 3 tests (r=0.48; p<0.05). Muscle soreness was significantly higher 24-48 h after tests B and C than after test A, no significant differences being present between tests B and C. CONCLUSIONS: WBV stimulates GH secretion and LA production, with no additive effect when combined with repeated isometric voluntary contractions. Optimization of protocols based on WBV seems important to maximize the positive effects of this intervention on the somatotropic function.

Changes in plasma levels of ghrelin, leptin, and other hormonal and metabolic parameters following standardized breakfast, lunch, and physical exercise before and after a multidisciplinary weight-reduction intervention in obese adolescents.

OBJECTIVE: To investigate in severely obese adolescents the effects of a 3-week multidisciplinary weight-reduction intervention involving moderate energy restriction, individualised physical activity and behavior therapy on the response of some hormonal and metabolic parameters to meals and exercise. DESIGN: Clinical longitudinal study on inpatients in a specialised institution. SUBJECTS: A total of 20 obese adolescents (10 boys and 10 girls) aged 12-17 yr [body mass index (BMI): 37.7±6.1 kg/m2; fat mass (FM): 44.8±13.2 kg]. MEASUREMENTS: The changes in plasma concentration of leptin, ghrelin, GH, IGF-I, insulin, glucose, and non-esterified fatty acids (NEFA) in response to standardised meals and exercise bouts were measured before and after the weight-reduction intervention. At the same times, body composition was assessed by bioelectrical impedance as well as appetite sensations using a visual analog scale. RESULTS: At the end of the intervention, the adolescents had lost body weight and FM (expressed both in kg and %) (p<0.05), without any significant fat-free mass loss (in % terms). In response to both meals and exercise, after the 3-week intervention, plasma leptin concentration decreased significantly (p<0.05), whereas the other hormones (insulin, ghrelin, GH, and IGF-I) and metabolic parameters (glucose and NEFA) did not change. Interestingly, appetite was not affected by the intervention. CONCLUSION: This 3-week multidisciplinary intervention in obese adolescents induced a significant body weight loss with beneficial changes in body composition. However, despite there being no change in metabolic parameters and ghrelin in response to meals and exercise after the intervention, plasma concentrations of leptin were decreased. The failure of ghrelin levels to increase by this approach might explain the good control of appetite observed at the end of the study.

Muscle expressions of MGF, IGF-IEa, and myostatin in intact and hypophysectomized rats: effects of rhGH and testosterone alone or combined.

Myostatin and mechano-growth factor (MGF), an isoform of insulin-like growth factor-I (IGF-I), are two important regulators of muscle hypertrophy. The aim of the present study was to investigate the effects of recombinant human growth hormone (rhGH) and/or testosterone on muscle MGF/IGF-IEa/myostatin expression in intact and hypophysectomized rats treated for 15 d with 1) saline or rhGH, 2) sesame oil or testosterone, 3) saline+sesame oil, or rhGH+testosterone (first experiment) or for 7 d with saline or rhGH (second experiment). Animals were killed by decapitation 24 h or 4 d after the last injection (first or second experiment, respectively). Muscle expressions of MGF, IGF-IEa, and myostatin were determined by RT-PCR. A significant increase in the weight of gastrocnemius muscle was observed only in hypophysectomized rats treated with rhGH alone or in combination with testosterone. Administration of rhGH to hypophysectomized rats caused a marked increase in both MGF and IGF-IEa muscle mRNA levels (without any change in the muscle expression of myostatin), an effect that was abolished when testosterone was combined with rhGH. Conversely, in intact rats rhGH increased myostatin muscle mRNA levels without affecting those of MGF and IGF-IEa. Testosterone, alone or combined with rhGH, induced an inhibition of myostatin expression in the muscle of intact rats, but did not change muscle paradigms of hypophysectomized rats. In conclusion, rhGH and/or testosterone anabolic effects in the muscle are mediated by a different expression of MGF/IGF-IEa/myostatin, which is related to the pituitary function.

Menopausal transition: a possible risk factor for brain pathologic events.

BACKGROUND AND OBJECTIVE: Incidence and prevalence of Alzheimer's disease (AD) are higher in postmenopausal women than in age-matched men. Since at menopause the endocrine system and other biological paradigms undergo substantial changes, we thought to be of interest studying whether (and how) the balance between some biological parameters allegedly neuroprotective (e.g. related to estrogen, dehydroepiandrosterone and CD36 functions) and others considered pro-neurotoxic (e.g. related to glucocorticoid and interleukin-6 activities) vary during lifespan in either sex in either normalcy or neurodegenerative disorders. SUBJECTS AND METHODS: Along with this aim, we evaluated the gene expression levels of estrogen receptors (ERs), glucocorticoid receptors (HGRs), interleukin-6 (IL-6) and CD36, a scavenger receptor of class B allegedly playing a key role in the proinflammatory events associated with AD, in a population of 209 healthy subjects (73M, 106F, 20-91-year old) and 85 AD patients (36M, 49F, 65-89-year old). Results obtained were related to plasma titers of estrogens, cortisol and dehydroepiandrosterone sulfate (DHEAS). Studies were performed in peripheral leukocytes, since these cells (1) are easily obtainable by a simple blood sampling, (2) express many molecules and multiple receptors which are under the same regulatory mechanisms as those operative in the brain and (3) some of them, e.g. monocytes, share many functions with microglial cells. RESULTS: In healthy men all the study parameters were quite stable during lifespan. In women, instead, at menopausal transition, some changes that may predispose to neurodegeneration occurred. In particular, there was (1) an up-regulation of ERs, and a concomitant increase of IL-6 gene expression, events likely due to the loss of the inhibitory control exerted by estradiol (E(2)); (2) an increase of HGR alpha:HGR beta ratio, indicative of an augmented cortisol activity on HGR alpha not sufficiently counteracted by the inhibitory HGR beta function; (3) a reduced CD36 expression, directly related to the increased cortisol activity; and (4) an augmented plasma cortisol:DHEAS ratio, widely recognized as an unfavorable prognostic index for the risk of neurodegeneration. In AD patients of both sexes, the expression of the study parameters was similar to that found in sex- and age-matched healthy subjects, thus indicating their unrelatedness to the disease, and rather a better correlation with biological events. CONCLUSIONS: Menopausal transition is a critical phase of women's life where the occurrence of an unfavorable biological milieu would predispose to an increased risk of neurodegeneration. Collectively, the higher prevalence of AD in the female population would depend, at least in part, on the presence of favoring biological risk factors, whose contribution to the development of the disease occurs only in the presence of possible age-dependent triggers, such as beta-amyloid deposition.

The leukocyte expression of CD36 is low in patients with Alzheimer's disease and mild cognitive impairment.

CD36, a scavenger receptor of class B (SR-B), helps mediate microglial and macrophage response to beta-amyloid fibrils (betaA), and seems to play a key role in the proinflammatory events associated with Alzheimer disease (AD) in many tissues. Peripheral leukocytes express many molecules and multiple receptors which undergo the same regulatory mechanisms as those operative in the brain. Thus, these cells, easily obtainable through peripheral blood sampling, may be used as a tool to investigate changes occurring in inaccessible brain areas. Based on these premises, we investigated the leukocyte expression of CD36 in 70 AD patients and in 30 subjects with mild cognitive impairment (MCI). Results were compared to those of 20 young and 40 age-matched control subjects. Leukocyte expression of CD36 was significantly reduced versus controls in both AD and MCI patients, while in young and old controls there were no age-related changes. Although preliminary, these data indicate that the reduction of CD36 expression in leukocytes is a disease-related phenomenon, occurring since the early stages of AD (MCI). Irrespective of the mechanism(s) underlying such changes, assessment of leukocyte CD36 expression might represent an useful tool to support the diagnosis of AD and to screen MCI patients candidates to develop the disease.

Abuse of recombinant human growth hormone: studies in two different dog models.

The search for inappropriately high growth hormone (GH) titers in plasma has been widely used to detect GH abuse, despite many shortcomings especially related to the pulsatile nature of GH secretion. Hence, the need for new anti-doping strategies. In the present study dogs were used to evaluate the ability of recombinant human GH (rhGH) to affect canine GH (cGH) release ensuing after somatostatin (SS) infusion withdrawal (SSIW) - a purported stimulus for the release of endogenous GH-releasing hormone (GHRH) - or the cGH response to administration of a GH-releasing peptide (GHRP). In the SSIW experiments, 8 beagle dogs of either gender (4-6 years old) were given a subcutaneous bolus injection of physiological saline (0.1 ml/kg) or, alternatively, rhGH (0.2 IU/kg s.c.) 60 min before the starting a continuous infusion of SS (4 microg/kg g h i.v.) of 1.5 h duration. In the dogs given a saline bolus, SSIW was followed by a 'rebound' rise in plasma cGH levels. In contrast, in dogs which had received the bolus injection of rhGH, the cGH rise elicited by SSIW was completely abrogated. In the set of experiments with a GHRP challenge, 13 dogs of either gender (3-12 years old) received the following treatment schedule at least 15 days apart: (1) a single bolus injection of rhGH (0.2 IU/kg s.c.); (2) rhGH (0.05 IU/kg s.c.) daily for 12 days; (3) rhGH (0.2 IU/kg s.c.) on alternate days for 12 days, and (4) rhGH (0.2 IU/kg s.c.) daily for 12 days. For each treatment schedule, before treatment, during treatment (24 h from the previous rhGH injection) and 1, 5 and 10 days after treatment, all dogs received an intravenous injection of a GHRP, EP51216 (125 microg/kg). In all treatments under baseline conditions, a single injection of EP51216 elicited an abrupt rise in plasma cGH. Twenty-four hours after the injection of an acute bolus of rhGH, the C(max) and AUC(0-90) of the GHRP-stimulated cGH response were significantly lower than the baseline cGH response. Five days later, there was a trend in the C(max) and AUC(0-90) towards complete restoration of the original values. One, 5 and 10 days after the end of the daily treatment with rhGH (0.05 IU/kg s.c.), no significant changes in the GHRP-stimulated cGH responses vs. the baseline GH response were recorded. In contrast, treatment with rhGH at a dose of 0.2 IU/kg s.c., on either alternate or daily administration, markedly reduced the GHRP-stimulated cGH responses evaluated after 3 and 5 rhGH injections. One day after the last rhGH injection, the EP51216-stimulated cGH response was still significantly reduced when compared with that present under baseline conditions. Five and 10 days following termination of rhGH treatment on alternate days, no significant differences in the C(max) and AUC(0-90) of the cGH responses to EP51216 were present. Differently, following the end of daily rhGH treatment, a marked inhibition in the C(max) of the cGH response to EP51216 was still present at 1 and 5 days, though not at 10 days. In conclusion, these studies show that a single administration of rhGH can abrogate the cGH response ensuing SSIW or acute stimulation by a GHRP. The inhibitory effect of rhGH on the cGH response to GHRP is present even 5 days after termination of a short-lived treatment with rhGH at a dose (0.2 IU/kg) which, in the dog, is undoubtedly lower than that used in humans for doping purposes. Extrapolation of these preclinical results to humans may pave the way for the development of a new rhGH anti-doping test.

Maintenance of a normal meal-induced decrease in plasma ghrelin levels in children with Prader-Willi syndrome.

Ghrelin is a 28-amino acid peptide recently identified in the stomach as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). Ghrelin is a potent stimulator of GH secretion. It was recently shown that circulating ghrelin levels in humans rise shortly before and fall shortly after every meal, and that ghrelin administration increases voluntary food intake. The hypothesis that ghrelin hypersecretion might contribute to genetic obesity has never been investigated. In this context, Prader-Willi syndrome is the most common form of human syndromic obesity. As ghrelin affects appetite as well as GH secretion and both are abnormal in PWS, it has been surmised that these alterations might be due to ghrelin dysregulation. The aim of the study was to investigate whether ghrelin is suppressed by the meals differently in PWS children than in PWS adults. Overnight circulating fasting ghrelin levels and ghrelin levels 120 min after breakfast were assayed in 7 PWS children (10.2 +/- 1.7 yr), 7 subjects with morbid obesity (10.3 +/- 1.3 yr), and 5 normal controls (8.4 +/- 1.4 yr). Because of the data spread, no statistical difference was observed in fasting ghrelin levels between PWS and control children (p = NS); anyway, fasting ghrelin levels were significantly lower in obese children than in the other groups (p < 0.05 vs. control and PWS children). Ghrelin levels were slightly suppressed by the meal in control subjects (mean fasting ghrelin: 160.2 +/- 82 pg/ml; after the meal, 141.2 +/- 57 pg/ml, p = NS); the meal failed to suppress ghrelin levels in obese children (mean fasting ghrelin: 126.4 +/- 8.5 pg/ml; after the meal, 119.1 +/- 8.3 pg/ml, p = NS). Interestingly, the meal markedly suppressed ghrelin levels in PWS children (mean fasting ghrelin: 229.5 +/- 70.4 pg/ml; after the meal, 155.8 +/- 34.2 pg/ml, p < 0.01). In conclusion, since a lack of decrease in circulating ghrelin induced by the meal was previously reported in PWS adults, the finding of a meal-induced decrease in ghrelin levels in our population of young PWS would imply that the regulation of the ghrelin system involved in the orexigenic effects of the peptide is operative during childhood, although it progressively deteriorates and is absent in adulthood when hyperphagia and obesity progressively worsen.

The GABAB receptor and recognition memory: possible modulation of its behavioral effects by the nitrergic system.

Functional activation of the GABA(B) receptor inhibits learning and memory processes, though discrepant findings, in this context, have also been reported. The present study was designed to investigate the role of the GABA(B) receptor on recognition memory in the rat. For this purpose, the effects induced by the GABA(B) agonist baclofen and the GABA(B) antagonist P-(3-aminopropyl)-P-diethoxymethylphosphinic acid (CGP 35348) on memory were assessed by using the object-recognition task. In addition, the possible involvement of the nitrergic system on GABA(B) receptor's effects was also evaluated by using the same behavioral procedure. This is a working-memory paradigm based on the differential exploration of a new and familiar object. In a first dose-response study, baclofen (0.5, 2, and 4 mg/kg, i.p.), dose-dependently impaired animals' performance in this task, suggesting a modulation of acquisition and storage of information. CGP 35348 (100 and 300 mg/kg, i.p.), counteracted these baclofen-induced performance deficits. The nitric oxide donor molsidomine, at the dose of 4 but not 2 mg/kg, i.p, successfully antagonized the deficits on cognition induced by the highest dose of baclofen (4 mg/kg). These results indicate a) that the GABA(B) receptor is involved in recognition memory and b) that an NO component modulates the effects of the GABA(B) receptor on learning and memory.