Osteoporosis and beta-thalassemia major: role of the IGF-I/IGFBP-III axis.

Patients with beta-thalassaemia major are susceptible to osteopenia due to several factors which interfere with bone remodeling. It is known that bone metabolism and skeletal consolidation result from a complex sequence of hormonal changes, where the concerted actions of GH, IGF-I and sex hormones and their receptors, are responsible for the timing and attainment of skeletal consolidation. IGF-I and the corresponding binding protein (IGFBP-III), markers of bone metabolism and lumbar and femoral neck BMD were measured in 28 adult patients, undergoing hormonal replacement and chelation therapy and a hypertransfusion program, with beta-thalassaemia major (12 males with mean age 22.5+/-3.1 and 16 females with mean age 27.5+/-8.2), and in 28 healthy volunteers matched for age, anthropometric features and sex to the patients. BMD values, both at lumbar and femoral neck level were significantly lower (p<0.001 and p<0.05) by 18.7 and 4.2% respectively, in patients than in the controls. Markers of bone resorption [pyridinoline (Pyr) 78.1+/-15.7 vs 47.5+/-11.2 pmol/pmol urinary creatinine, p<0.001 and deoxypyridinoline (D-Pyr) 21.9+/-3.5 vs 14.5+/-5.4 pmol/ micromol urinary creatinine, p<0.001] were higher in patients than in controls, whereas the marker of bone formation was slightly lower [osteocalcin (BGP) 3.8+/-0.6 vs 4.6+/-1.7 pmol/ml, p<0.05]. Plasma levels of IGF-I (21.07+/-5.12 vs 35.25+/-8.33 nmol/ml, p<0.001) and IGF binding protein III (IGFBP-III) (1.9+/-0.4 vs 2.5+/-0.1 mg/ml, p<0.001) were lower in patients than in controls and positively correlated with BMD L2-L4 (r=0.57, p<0.05 and r=0.47, p<0.05 respectively), BMD neck (r=0.40, p<0.05 and r=0.34, p<0.05 respectively) and BGP (r=0.52, p<0.05 and r=0.34, p<0.05 respectively). Our beta-thalassaemic patients, in spite of normalizing hemoglobin levels, adequate hormone replacement and chelation therapies, showed osteopenia and an unbalanced bone turnover with an increased resorptive phase and a decreased formation phase probably correlated to low levels of IGF-I and IGFBP-III observed in our study.

Measurement of allergen-induced skin reactions by computerized dynamic telethermography (CDTT).

Cutaneous thermic changes induced by a skin prick test reaction were measured by an infrared thermography camera (computerized dynamic telethermography, CDTT). Changes in skin temperature (T degree) detected by CDTT were compared with the mean diameter of allergen-induced skin reactions. Cutaneous thermic increase detected by CDTT correlated well with the mean wheal diameter measured in millimeters (r = 0.938, p < 0.001). Average coefficient of variation for repeated CDTT measurements was 4.6%. CDTT provides a reproducible and precise method for measuring allergen-induced skin reactions. Moreover, the continuous recording of the skin temperature represents an additional parameter for the quantification of wheal reactions.

No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide.

The aim of this study was to investigate the relationship between plasma insulin levels, peripheral insulin sensitivity and androgen secretion in ten patients with polycystic ovary syndrome and in six obese women as compared with six normal-weight control subjects. During a euglycemic-hyper-insulinemic clamp no significant change of testosterone, androstenedione or dehydroepiandrosterone sulfate plasma levels was observed in the two groups of patients or in the control subjects; insulin sensitivity was clearly reduced and was similar in polycystic ovary patients and in obese women, in spite of the different plasma androgen levels. A long-term (5 months) androgen suppression with the gonadotropin-releasing hormone agonist leuprolide was not able to improve significantly the insulin sensitivity. These results demonstrate that the short-term hyperinsulinemia achieved with the clamp technique does not affect androgen secretion and that insulin resistance, measured with the same technique, is not influenced by long-term suppression of plasma androgen levels in polycystic ovary syndrome.

Recombinant human erythropoietin inhibits the cutaneous vasodilatation induced by acetylcholine.

We investigated by means of telethermography the contractile response of cutaneous vessels to recombinant erythropoietin (rHuEPO) and the effects of this hormone on the vasodilatation induced by either acetylcholine, which is endothelium-dependent, and nitroprusside, which is endothelium-independent. Experiments were carried out in 12 healthy volunteers. Graded doses of rHuEPO (25, 50, 500 U/min), acetylcholine (7.5 and 15 micrograms/min), sodium nitroprusside (3 and 10 micrograms/min), and saline solution (sodium chloride 0.9%) were infused in the dorsal pedal artery of the lower limb. rHuEPO reduced the cutaneous temperature in a dose-dependent manner compared to the saline solution, thus suggesting that the hormone causes vasoconstriction. In contrast graded doses of acetylcholine and nitroprusside provoked vasodilatation: in fact both increased the cutaneous temperature compared to controls in a dose-dependent manner. The infusion of vasoconstrictive doses of rHuEPO in association with acetylcholine (15 micrograms/min) reverted the increase in the cutaneous temperature induced by the endothelium-dependent vasodilator. In contrast rHuEPO administered in combination with nitroprusside failed to block the vasodilatation induced by the endothelium-independent vasodilator. Therefore our data suggest that rHuEPO exerts an indirect vasoconstrictive effect and that acetylcholine-induced vasodilatation, which is endothelium-dependent, is blunted by the vasoconstrictive activity of rHuEPO, thus demonstrating that the hormone may impair the synthesis of endothelial nitric oxide.