A. Di Lieto

Lowered serum dipeptidyl peptidase IV activity in patients with anorexia and bulimia nervosa.

Abstract The aim of this study was to examine whether anorexia nervosa and bulimia nervosa are accompanied by lower serum activity of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5), a membrane-bound serine protease that catalyses the cleavage of dipeptides from the amino-terminus of oligo- and polypeptides. Substrates of DPP IV are, amongst others, neuroactive eptides, such as substance P, growth hormone releasing hormone, neuropeptide Y, and peptide YY. DPP IV activity was measured in the serum of 21 women with anorexia nervosa, 21 women with bulimia nervosa and 18 normal women. Serum ¶DPP IV activity was significantly lower in patients with anorexia nervosa and bulimia nervosa than in the normal controls. In the total study group, there were significant and inverse relationships between serum DPP IV activity and the total scores on the Bulimic Investigatory Test, Edinburgh, the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale. In the total study group no significant correlations between DPP IV and age, body weight or body mass index could be found. It is concluded that lowered serum DPP IV activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesised that a combined dysregulation of DPP IV and neuroactive peptides, which are substrates of DPP IV, e.g. neuropeptide Y and peptide YY, could be an integral component of eating disorders.

Effects of gonadotropin-releasing hormone agonists on uterine volume and vasculature and on the immunohistochemical expression of basic fibroblast growth factor (bFGF) in uterine leiomyomas.

We investigated the effect of the GnRH agonist (GnRH-a) on the uterine volume and on the immunohistochemical expression of basic fibroblast growth factor (bFGF) and the vasculature of leiomyomas. Twenty-five women were treated with leuprorelin acetate for 3 months; 46 untreated patients were enrolled as a control group. The uterine volume was measured by ultrasonography. After myomectomy or hysterectomy, the immunoexpression of bFGF and the endothelial marker, CD34, was studied and compared in treated and untreated leiomyomas. Uterine volume decreased after therapy. The number of cells expressing bFGF and the vascularity were diminished in treated leiomyomas. Reduction in the blood supply might be responsible, in part, for uterine-volume shrinkage after GnRH-a therapy.

Atrial natriuretic factor in amniotic fluid and in maternal venous blood of pregnancies with fetal cardiac malformations and chromosomal abnormalities.

Objective: We evaluated the levels of atrial natriuretic factor (ANF) in amniotic fluid and in maternal venous blood in pregnancies with fetal cardiac malformations and chromosomal abnormalities. Method: Between the 16th and 18th week of pregnancy, 151 women were divided into three groups. Group A included patients at lowest risk, carrying a fetus with a normally developing heart and normal karyotype (control group). Group B included women with a fetus suffering from cardiac malformations, with or without associated chromosomal abnormalities. Group C included women carrying a fetus affected with chromosomal abnormalities without congenital cardiopathies. ANF was evaluated by radioimmunoassay. Results: In maternal venous blood, the mean levels of ANF were 42.1, 53.1 and 38.7 pg/ml in groups A, B and C, respectively. In amniotic fluid, the mean levels of ANF were 34.2, 101.8 and 35.8 pg/ml in groups A, B and C, respectively. In group A (control group) there was no statistical difference in ANF levels across the gestational age range of 16-18 weeks, either in amniotic fluid or in maternal venous blood. A significant difference of ANF content in maternal venous blood was revealed in comparing group A with group B (p < 0.01), and group C with group B (p < 0.01). A statistically significant difference in ANF levels was also found in amniotic fluid between group A and group B (p < 0.01), and between group C and group B (p < 0.01). No statistically significant differences were found between group C and group A in comparing ANF levels in maternal venous blood and amniotic fluid. Conclusion: ANF levels in amniotic fluid and in maternal venous blood are increased early in the case of fetuses with cardiac malformations, with or without associated karyotype alteration. Chromosomally abnormal fetuses without heart malformations have normal ANF levels. These results could be useful for elucidating fetal pathophysiology mechanisms.

Influence of goserelin depot therapy on epidermal growth factor receptor expression in pelvic endometriosis

We have studied epidermal growth factor (EGF) receptor expression in endometrium and in endometriotic implants, testing a group of 36 women before and after a 4-month gonadotropin-releasing hormone (GnRH) analog (GnRH-a) goserelin depot treatment. Each woman underwent laparoscopy twice. At the initial laparoscopy, before starting treatment, the disease was staged according to the American Fertility Society (AFS) classification and biopsies of endometriotic implants were undertaken. The follow-up laparoscopy was performed within 5 weeks of the last GnRH-a administration. Biopsies were taken from areas of previously noted disease, both visually persistent and visually free of disease. At the time of each laparoscopy, photographs of all areas of disease were taken. Specimens of eutopic endometrium were collected from each patient at the time of laparoscopy by a Novak curette. Endometrial and endometriotic samples were processed for immunohistochemical detection of EGF receptor, using anti-EGF receptor monoclonal antibody Ab-3. After treatment, the marked improvement of AFS score was associated with a dramatic reduction of EGF receptor immunostaining, but the exact meaning of this finding is still not completely understood. The dramatic reduction of EGF receptor expression in eutopic and ectopic endometrium samples after treatment is not obviously related to the hypoestrogenism induced by the drug. It has been suggested that steroid hormones and EGF play a role in regulation of EGF receptor expression, so that drugs such as goserelin depot could act directly at local peripheral level influencing the EGF receptor expression via the production of its ligand.

Desogestrel versus gestodene in oral contraceptives: influence on the clinical and histomorphological features of benign breast disease

Forty-four female volunteers asking for oral contraception, affected by symptomatic benign breast disease (BBD) were evaluated to compare the effects on mastalgia and breast nodularity of two different low dose oral contraceptives (OCs), containing 20 micrograms [corrected] ethinylestradiol + 150 micrograms desogestrel (EE+D) and 30 micrograms ethinylestradiol + 75 micrograms gestodene (EE+G), respectively. Physical examination, bilateral thermography, X-ray and/or ultrasonography of breast, and needle and screw-needle biopsies of mammary tissue were performed in all patients before OCs administration and after six cycles of treatment. OCs administration caused an overall improvement of mastalgia in 53%. Breast nodularity improved only in 8% of patients in both groups. Epithelial tissue modifications in mammary biopsies were observed, with involutive and/or secretory histomorphological and ultrastructural changes, frequently coexisting in different areas of the same breast.

Altered immunoreactive levels of G proteins in peripheral mononuclear cells of patients with anorexia nervosa and bulimia nervosa

Alterations of cellular G proteins have been implicated in the pathophysiology of some psychiatric disorders. So far, no study assessed G protein function in anorexia nervosa (AN) and bulimia nervosa (BN). Therefore, we measured immunoreactive levels of Gαs, Gαi, Gαq/11 and Gβ protein subunits in mononuclear leukocytes of 71 drug-free women, including 25 subjects with AN, 26 individuals with BN and 20 healthy controls. As compared to healthy women, anorexic patients exhibited significantly increased levels of Gαi and Gβ proteins, while bulimic patients had significantly increased levels of Gαs, Gαi and Gβ proteins. Immunoreactive levels of peripheral G protein subunits were not significantly correlated with demographic or nutritional parameters. These findings, although obtained in peripheral blood cells, may suggest a derangement of G protein-mediated signal transduction in the pathophysiology of eating disorders.