Two different single doses (400 and 600 micrograms) of the new long-acting dopamine agonist cabergoline (CBG) were given to 12 normal cycling women, 17 puerperal women, and 24 hyperprolactinemic ...women (12 with idiopathic hyperprolactinemia and 12 with pituitary adenoma). Plasma PRL was determined in blood samples collected before and at frequent intervals for 5 days after CBG administration. Both CBG doses induced marked inhibition of PRL secretion in all women. A decrease in plasma PRL levels was evident 1-2 h after CBG administration and persisted for up to 5 days. The 600-micrograms CBG dose had a more potent (P less than 0.05) PRL inhibitory effect than the 400-micrograms dose in normal, puerperal, and hyperprolactinemic women. Moreover, while 400 micrograms CBG prevented lactation in 3 of 7 puerperal women, 600 micrograms CBG prevented lactation in 5 of 5 puerperal women. A moderate blood pressure decrease occurred 3-6 h after CBG treatment, but no other side-effects occurred. These results demonstrate that CBG induces a dose-related inhibition of PRL secretion in normal women as well as in puerperal and hyperprolactinemic women. The potent long-lasting PRL inhibitory effect of CBG in conjunction with the absence of side-effects typical of dopaminergic compounds suggest that this drug is an advance in the medical treatment of hyperprolactinemia.
High-energy phenomena in the cosmos, and in particular processes leading to the emission of gamma- rays in the energy range 10 MeV - 100 GeV, play a very special role in the understanding of our ...Universe. This energy range is indeed associated with non-thermal phenomena and challenging particle acceleration processes. The technology involved in detecting gamma-rays is challenging and drives our ability to develop improved instruments for a large variety of applications. GAMMA-LIGHT is a Small Mission which aims at an unprecedented advance of our knowledge in many sectors of astrophysical and Earth studies research. The Mission will open a new observational window in the low-energy gamma-ray range 10-50 MeV, and is configured to make substantial advances compared with the previous and current gamma-ray experiments (AGILE and Fermi). The improvement is based on an exquisite angular resolution achieved by GAMMA-LIGHT using state-of-the-art Silicon technology with innovative data acquisition. GAMMA-LIGHT will address all astrophysics issues left open by the current generation of instruments. In particular, the breakthrough angular resolution in the energy range 100 MeV - 1 GeV is crucial to resolve patchy and complex features of diffuse sources in the Galaxy as well as increasing the point source sensitivity. This proposal addresses scientific topics of great interest to the community, with particular emphasis on multifrequency correlation studies involving radio, optical, IR, X-ray, soft gamma-ray and TeV emission. At the end of this decade several new observatories will be operational including LOFAR, SKA, ALMA, HAWK, CTA. GAMMA-LIGHT will "fill the vacuum" in the 10 MeV-10 GeV band, and will provide invaluable data for the understanding of cosmic and terrestrial high-energy sources.
To evaluate the efficacy of a single oral administration of the new ergot derivative Cabergoline in the prevention of post-partum lactation, we compared the effects of three different doses of the ...drug with those of placebo in 32 puerperal women. In a controlled, double-blind trial, the subjects were randomly allocated to four treatment groups receiving either placebo or 400, 600, or 800 micrograms Cabergoline (N = 8 in each group) within 24 hours after delivery. Treatment efficacy was assessed clinically by physical examination before (day 0) and at one, two, three, four, and 14 days after treatment. Plasma prolactin (PRL) concentrations were measured in blood samples collected before and at one, two, three, and four days after treatment. Lactation was prevented in four of the eight subjects (50%) who received 400 micrograms Cabergoline and in all subjects who received 600 or 800 micrograms Cabergoline. By contrast, only one of the eight subjects (12.5%) receiving placebo showed no signs of spontaneous lactation within the 14 days after delivery. No effects of placebo administration on plasma PRL levels were observed. Plasma PRL concentrations were significantly reduced starting from one day after Cabergoline administration, however, and the amount of inhibition of PRL secretion induced by different doses of the drug was not statistically different. These preliminary data demonstrate that Cabergoline has a dose-related effect in the prevention of postpartum lactation, and milk secretion can be prevented completely by a single oral administration of 600 or 800 micrograms of the drug.
BACKGROUNDPrimary ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea), a decrease in the initial primordial follicle number, high ...follicle-stimulating hormone (FSH) levels and hypoestrogenism. Although the etiology of a majority of POI cases is not yet identified, several data suggest that POI has a strong genetic component. Conventional cytogenetic and molecular analyses have identified regions of the X chromosome that are associated with ovarian function, as well as POI candidate genes, such as FMR1 and DIAPH2. Here we describe a 10.5-year-old girl presenting with high FSH and luteinizing hormone (LH) levels, pathologic GH stimulation arginine and clonidine tests, short stature, pterygium, ovarian dysgenesis, hirsutism and POI.RESULTSCytogenetic analysis demonstrated a balanced reciprocal translocation between the q arms of chromosomes X and 1, with breakpoints falling in Xq21 and 1q41 bands. Molecular studies did not unravel any chromosome microdeletion/microduplication, and no XIST-mediated inactivation was found on the derivative chromosome 1. Interestingly, through immunofluorescence assays, we found that part of the Xq21q22 trait, translocated to chromosome 1q41, was late replicating and therefore possibly inactivated in 30 % metaphases both in lymphocytes and skin fibroblasts, in addition to a skewed 100 % inactivation of the normal X chromosome. These findings suggest that a dysregulation of gene expression might occur in this region. Two genes mapping to the Xq translocated region, namely DIAPH2 and FMR1, were found overexpressed if compared with controls.CONCLUSIONSWe report a case in which gonadal dysgenesis and POI are associated with over-expression of DIAPH2 gene and of FMR1 gene in wild type form. We hypothesize that this over-expression is possibly due to a phenomenon known as "chromosomal position effect", which accounts for gene expression variations depending on their localization within the nucleus. For the same effect a double mosaic inactivation of genes mapping to the Xq21-q22 region, demonstrated by immunofluorescence assays, may be the cause of a functional Xq partial monosomy leading to most Turner traits of the proband's phenotype.
To determine whether antidopaminergic drug administration may modify endogenous opioid activity at the hypothalamic-pituitary level, the effects of naloxone infusion (1.6 mg/h for 4 h) on LH ...secretion were studied in six postmenopausal women before and after administration of the potent antidopaminergic drug veralipride for 20 days. Before veralipride administration, the naloxone infusion did not alter LH secretion. Chronic administration of veralipride resulted in a significant (P less than 0.01) decline in plasma LH levels. In addition, the naloxone infusion induced a significant (P less than 0.05) increase in plasma LH levels, which reached values similar to those before veralipride administration. These results demonstrate that in postmenopausal women the antidopaminergic drug veralipride can restore, at least in part, the activity of the endogenous opioid system. These findings suggest that endogenous opioid peptides may mediate the inhibitory effect exerted by chronic antidopaminergic drug administration on LH secretion in humans.
We evaluated the effects on glucose and lipid metabolism in 57 healthy volunteers randomly assigned to one of three low-dose oral contraceptives: two monophasic (desogestrel + ethinylestradiol, EE, ...and cyproterone acetate + EE) and one triphasic (gestodene + EE) contraceptives. Glucose and insulin responses during OGTT were slightly affected by the cyproterone pill. The insulin area/glucose area ratio and HbA1c level were unchanged in all women. No preparation affected total and LDL-cholesterol levels. Triglycerides rose in all groups, while HDL-CH did only in women taking the two monophasic pills. The three low-dose pills assessed in this study have negligible effects on glucose and lipid metabolism.
To find out whether the gamma-aminobutyric acid (GABA)ergic system affects PRL secretion in humans, sodium valproate (DPA or Na-dipropyl-acetate), a drug inducing increase of endogenous GABA, was ...administered to 20 normal and 15 hyperprolactinemic subjects. PRL circulating levels were measured by RIA in the samples obtained after acute oral treatment with 400 mg DPA. A significant decrease (P less than 0.01) in comparison with basal levels was observed in normal women from 30-180 min after drug administration. DPA treatment also lowered blood PRL levels in hyperprolactinemic subjects (seven females) without evidence of pituitary tumor. A decrease very similar to the one found in normal subjects (P less than 0.05 vs. basal levels) was observed within 180 min from drug ingestion. Conversely, no significant changes were found after the same treatment in hyperprolactinemic patients with evidence of prolactinoma (seven females and one male). Taken together, these data seem to demonstrate that pharmacological enhancement of endogenous GABAergic tone is followed by inhibition of PRL secretion. They also suggest that GABA may exert an inhibitory control on PRL release in humans. In hyperprolactinemic subjects, this GABAergic control appears to be present only when a pituitary tumor cannot be demonstrated.
Pharmacological doses of gonadotropin-releasing hormone (GnRH) are known to induce prolactin (PRL) release in different pathological states. The same effect can be observed in postmenopausal women ...and during the phases of menstrual cycle characterized by high estrogen levels. With the aim to evaluate whether nonpharmacological doses of GnRH are also able to induce PRL release, gonadotropin and PRL response to a low dose of GnRH (10 micrograms, i.v. bolus) was evaluated in 70 normal women during different phases of their menstrual cycle. A significant PRL increase was observed in 33% of subjects during the first days of the cycle (menstrual phase; days 1-3 from the beginning of menstrual bleeding: n = 6), in 24% of subjects during early follicular phase (days -10 to -8 from LH peak: n = 17); in 38% of subjects during midfollicular phase (days -6 to -4 from LH peak: n = 8); in 78% of subjects during preovulatory phase (days -2 to -1 from LH peak; n = 9); in 67% of subjects during postovulatory phase (days +1 to +2 from LH peak; n = 6) and in 42% of subjects during midluteal phase (days +5 to +8 from LH peak; n = 24). In brief, the increase of mean PRL levels after GnRH administration was only significant (p less than 0.05) during pre- and postovulatory phases. The percentage of patients who showed a PRL response during the different phases of menstrual cycle was significantly correlated to the mean maximal net increase of LH (r = 0.927; p less than 0.01) and to the mean maximal net increase of FSH (r = 0.926; p less than 0.01).
A novel β-chain, β26(H4)Val → Gly, electrophoretically silent, was detected by reverse-phase high performance liquid chromatography in three unrelated families from Naples (Southern Italy) and ...accounted for about 30% of the total β-chains. The amino acid substitution was detected by HPLC fingerprint. The eight heterozygous patients showed hematologic and biosynthetic alterations of mild β-thalassemia type. The hemoglobin variant showed abnormal stability features. It was unstable in the heat stability and isopropanol precipitation tests, but did not cause a hemolytic syndrome in vivo and was stable in a time-course experiment of biosynthesis in vitro. DNA polymerase chain reaction direct sequencing of the mutated gene from 135 nt upstream of the cap site to 106 nt downstream of the polyadenylation site showed only the β126 GTG → GGG mutation, which was confirmed in the other patients by allele-specific oligonucleotide hybridization. The mutation was found to be associated with a type II β-globin framework and restriction fragment length polymorphism haplotype V. The novel variant was named hemoglobin Neapolis.
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