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In this study, a population sample (n= 142) born in Friuli Venezia Giulia (FVG), a region of North-East Italy, was studied for C>T 667 mutation in the fourth exon of the 5,10-methylenetetrahydrofolate reductase gene by a PCR-RFLP based method. The genotype and allele frequencies are reported.

The patch-clamp, as a sophisticated tool to investigate the electrophysiological activity at the single cell and even at single channel levels, can be used for a systematic study of the effects of electromagnetic fields (EMF) on ion transport across the cell membrane. In the last years some hypotheses were put forward aimed at understanding EMF interaction mechanisms, focusing on the effects on specific ion kinetics such as Ca++, K+ and other ions involved in cell physiology. In order to verify these hypotheses a stable controlled combination of a static and oscillating magnetic fields (MF) is needed. For this purpose we have designed and fabricated a MF exposure system trying to reach a good compromise between MF homogeneity and accessibility to the patch-clamp set-up. The MF exposure system consists of 3 large orthogonal pairs of square coils surrounding the patch-clamp set-up, able to generate different combinations of static and alternating MF, reaching a 1% uniformity level in a 4 cm×4 cm × 4 cm region around the centre for the 3 components of MF.

GH deficient (GHD) adult patients, either from child- or adulthood onset, have impaired health (impairment in body composition and structure functions as well as derangement in lipoprotein and in carbohydrate metabolism leading to increased cardiovascular morbidity), which improves with GH replacement. For patients with childhood-onset GHD, the so called "transition phase", defined as the period between reaching the final height and the completion of the development of such organs, can be considered as the most important phase of life for the development of important target organs: heart, bones and muscles. Particularly, children with GHD may not attain the peak bone mass (PBM) at the time of discontinuation of GH therapy, as the complete achievement of PBM is likely reached later on, during the transition phase to adulthood. In addition, patients with GHD generally have a delayed timing of PBM compared to normal individuals. GH treatment should be continued until the attainment of PBM, independently of the final height achieved. Individual titration of the recombinant human GH (rhGH) dose is recommended, and measurement of IGF-I levels is needed for monitoring the adequacy of replacement. The GH dose for replacement in the transition adolescent is still higher than in adulthood; after puberty, the rhGH dose should be progressively decreased in the following years (probably up to 25 yr of age) in order to obtain the achievement of optimal PBM.

The aim of the present study was to measure dehydroepiandrosterone-sulphate (DHEA-S) levels in obesity and assess the relationships between DHEA-S and anthropometric, metabolic and hormonal variables.We evaluated the serum DHEA-S levels in 217 obese but otherwise normal female subjects (age (mean +/- SEM): 39.4 +/- 0.9, range 18-67 years, body mass index (BMI) = 36.1 +/- 0.4, range 27.1-57.1 kg/m2).DHEA-S levels showed an age-dependent fall similar to that observed in normal women (n = 156, age 46.2 +/- 1.2, range 22-69 years, BMI25 kg/m2). Adjusting for age, obese women had mean DHEA-S levels higher than the control group (P0.02). In obese patients, DHEA-S levels were directly associated with serum testosterone, androstendione, IGF-I, fT3 levels and 24 h-urinary cortisol. On the other hand, DHEA-S levels were negatively associated with age, total cholesterol, triglycerides levels and systolic blood pressure. No correlation was found with BMI, waist:hip ratio, basal and post-OGTT insulin and glucose, free fatty acids, GH, PRL, fT4, TSH, SHBG levels or diastolic blood pressure. Multiple regression analysis indicated that in obese women, DHEA-S levels were associated negatively to age and positively to testosterone, androstendione and IGF-I levels and daily urinary cortisol. In a subgroup of 20 obese women, DHEA-S levels significantly (P0.001) fell after OGTT without any correlation with the insulin response.The present results show that dehydroepiandrosterone-sulphate levels are not reduced in obesity, being slightly increased, particularly in young adulthood. Dehydroepiandrosterone-sulphate levels are positively and independently associated with androgen, 24-h urinary cortisol and IGF-I levels but do not seem associated with insulin levels or cardiovascular risk indices.

Diagnosing GH deficiency in adults is difficult due to the age-related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH replacement is allowed for patients with GH peak to provocative stimuli3 micrograms/L. Somatotrope insufficiency is present in hypopituitarism but also in obesity and hypercortisolism. However, to evaluate GH insufficiency in adults is difficult due to variations of GH and IGF-I levels as function of age and nutrition status.We aimed to verify the GH response to GHRH (1 microgram/kg i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine (ARG, 0.5 g/kg i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS).IGF-l levels in GHD were lower than those in OB (p0.01) and in CS (p0.01) which, in turn, were lower to those in NS (p0.02). In NS, the GH peak responses to GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak was 16.5 micrograms/L. GHD had GH responses similar, lower than those in NS (p0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks3 micrograms/L; conventionally, below this limit severe GH deficiency is shown and rhGH replacement is allowed. In OB, the GH responses to GHRH + PD and GHRH + ARG were similar, lower (p0.01) and higher (p0.01) than those in NS and GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but nobody3 micrograms/L. In CS the GH response to GHRH + PD was lower than that to GHRH + ARG (p0.01); both these responses were lower than those in NS (p0.01) and even in OB (p0.01) but higher than those in GHD (p0.01). All and 7/8 CS had GH peaks lower than normal limits after PD + GHRH and ARG + GHRH, respectively while 6/8 showed GH peak3 micrograms/L after PD + GHRH but only 1 after ARG + GHRH.Present data demonstrate that the maximal somatotrope secretory capacity is reduced in OB and even more in CS. From a diagnostic point of view, PD + GHRH and ARG + GHRH tests distinguish OB from severe GHD. As hypercortisolism impairs the activity of cholinesterase inhibitors, only ARG + GHRH, but not PD + GHRH is a reliable test to explore the maximal somatotrope secretory capacity in CS. Notably, even with the ARG + GHRH test, in CS the maximal somatotrope secretory capacity is sometimes so reduced as to overlap with that of severe GHD.

Spontaneous GH secretion as well as GH response to several stimuli including GHRH have been shown to be reduced in obesity. To clarify the pathogenesis underlying these alterations, in six obese patients (3 males and 3 females, age 20-44 yrs, BMI = 42.1 +/- 2.2) on unrestricted diet we studied the effect of 8 day GHRH pretreatment (1 micrograms/kg iv each day) on the acute somatotropic response to the neurohormone administered both alone and combined with arginine (ARG, 0.5 g/kg iv infused from 0 to 30 min) which likely inhibits the release of hypothalamic somatostatin. Before treatment the GH response to GHRH (AUC: 231.9 +/- 106.4 micrograms/l/h) was potentiated (p0.001) by ARG (932.6 +/- 166.2 micrograms/l/h). However, the GH responses to the neurohormone both alone and combined with ARG were lower (p0.02 and 0.002, respectively) than in normals (712.4 +/- 111.6 and 2608.3 +/- 453.2 micrograms/l/h, respectively). After repetitive GHRH administration, in obese subjects baseline GH and IGF-I levels were unchanged. Also the GH responses to GHRH both alone (217.3 +/- 68.1 micrograms/l/h) and combined with ARG (756.3 +/- 202.9 micrograms/l/h) were not modified. In conclusion, our data demonstrate the failure of GHRH pretreatment to improve the somatotrope hyporesponsiveness to GHRH both alone and combined with ARG suggesting the existence of a somatotropic defect in obesity.