bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketoconazole therapy: hormonal and clinical effects in non-tumoral hyperandrogenism
Authors: Vidal-Puig Antonio J , Muñoz-Torres Manuel , Jódar-Gimeno Esteban , García-Calvente Carlos J , Lardelli P , Ruiz-Requena María E , Escobar-Jiménez Fernando 
Published: December 2008

Vidal-Puig AJ, Muñoz-Torres M, Jódar-Gimeno E, García-Calvente CJ, Lardelli P, Ruiz-Requena ME, Escobar-Jiménez F. Ketoconazole therapy: hormonal and clinical effects in non-tumoral hyperandrogenism. Eur J Endocrinol 1994;130:333–8. ISSN 0804–4643.
The aim of this study was to assess the usefulness of ketoconazole as a therapeutic alternative to polycystic ovary syndrome. The study group comprised 37 women with signs of hyperandrogenism (hirsutism, acne) and oligomenorrhea. A low dose (400 mg/day) of ketoconazole was tested in a 9-month prospective clinical study. Clinical response (Ferriman & Gallway score, acne) and modifications in hormone pattern (luteinizing hormone, follicle-stimulating hormone, estradiol, testosterone, prolactin, 17-hydroxy-progesterone, androstenedione, steroid hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, adrenocorticotropin (ACTH) and free testosterone index) were measured, and ACTH stimulation tests were performed. Tolerance and side-effects also were assessed. After 9 months of ketoconazole treatment, the patients' Ferriman & Gallway scores (18.26 ± 4.6 vs 12.4 ± 4.1; p < 0.001) and acne had improved markedly. Hormone patterns also became more favorable, with decreases in androgenic steroids (testosterone, androstenedione, free testosterone index and dehydroepiandrosterone sulfate; p < 0.01) and increases in estradiol (p < 0.01). Basal cortisol levels and cortisol after ACTH stimulation were not changed significantly, remaining within the reference range. Increases in ACTH were observed only in the 3rd month (p < 0.01). Initial levels of androgenic steroids were correlated inversely with their percentage decrease in successive samplings. Decreases in adrenal androgenic steroids were associated with an increase in steroid hormone-binding globulin. The side-effects of treatment, although not severe, caused some discomfort and led to a high drop-out rate (30%). Our results suggest that low doses of ketoconazole (400 mg/day) are an alternative therapy for non-tumoral hyperandrogenism, although the bothersome side-effects, which require close monitoring and maximal patient compliance, make this treatment advisable only in selected patients.
Manuel Muñoz-Torres, Plaza Isabel la Católica no. 2, E-18009, Granada, Spain
Lack of vasoactive intestinal peptide-releasing property in prolactin cells from ovariectomized rats: contribution of post-transductional impairments
Authors: Pizzi Marina , Arrighi Virginia , Galli Paola , Memo Maurizio , Spano Pier Franco 
Published: December 2008

Pizzi M, Arrighi V, Galli P, Memo M, Spano PF. Lack of vasoactive intestinal peptide-releasing property in prolactin cells from ovariectomized rats: contribution of post-transductional impairments. Eur J Endocrinol 1994;130:361–5. ISSN 0804–4643
We have demonstrated recently that in menopausal women and in ovariectomized rats the deficiency of circulating oestrogens impairs vasoactive intestinal peptide (VIP) efficacy in stimulating prolactin (PRL) release. The present study was designed to investigate whether the lack of VIP-induced PRL release after ovariectomy is a consequence of a defect at the receptor-transductional or post-transductional level. For this purpose we evaluated the VIP receptor function, by measuring VIP-stimulated cyclic adenosine monophosphate (AMP) formation, and the efficacy of the cyclic AMP-dependent PRL release in pituitary cells from control and ovariectomized animals. We observed that VIP induced a significantly higher stimulation of adenylate cyclase in pituitary homogenates from ovariectomized rats than in those from control animals. This effect appeared to be linked to an increased efficiency of the Gs coupling protein, because superimposable results were obtained by using the non-hydrolysable guanosine triphosphate (GTP) analogue, 5-guanylylimidodiphosphate. On the contrary, the cyclic AMP analogue, 8-Br-cAMP, that potently stimulated PRL release from control pituitary cells was completely ineffective in cells from ovariectomized rats. The present data indicate that in PRL-secreting cells from ovariectomized rats a defect in the post-transductional mechanism that couples the VIP receptor to PRL secretion, rather than a reduction of receptor function, possibly accounts for the lack of VIP efficacy.
Marina Pizzi, Dept. Biomed. Sci. & Biotech., School of Medicine, Via Valsabbina 19, 25123 Brescia, Italy
Brain Lys-aminopeptidase activity. Changes during cycle and pregnancy
Authors: de Gandarias Juan M , Irazusta Jon , Fernández David , Echevarría Enrique , Casis Luis 
Published: December 2008

De Gandarias JM, Irazusta J, Fernández D, Echevarría E, Casis L. Brain Lys-aminopeptidase activity. Changes during cycle and pregnancy. Eur J Endocrinol 1994;130:373–7. ISSN 0804–4643
Lys-aminopeptidase activity levels during the estrous cycle (estrous and proestrous, in the morning and afternoon) and the pregnancy (2nd, 7th, 14th and 20th day postinsemination and the parturition day), in several areas of the rat brain, were studied in this research. The selected brain regions were the frontal, parietal and occipital cortices, olphactory bulbus, thalamus, hypothalamus, hippocampus, amygdala, striatum and pituitary gland. The most significant changes were shown in the hypothalamus and the pituitary gland. Thus, in these areas, the higher cyclic enzyme levels were found in the proestrous stage. During pregnancy, there was a rise on the 7th and 14th days, with a decrease on the 20th day. Also, similar changes in the occipital cortex, striatum, hippocampus and amygdala were appreciated, but fewer than those observed in the hypothalamus and the pituitary. In conclusion, the activity of the aminopeptidase under study fluctuates during the estrous cycle and during pregnancy, as well as in the hypothalamic–pituitary axis and also in several extrahypothalamic areas of the rat brain.
Luis Casis Saenz, Department of Physiology, Medical School, University of the Basque Country, PO Box 699, Bilbao, Spain
Effects of fluoride on human bone cells in vitro: differences in responsiveness between stromal osteoblast precursors and mature osteoblasts
Authors: Kassem Moustapha , Mosekilde Leif , Eriksen Erik F 
Published: December 2008

Kassem M, Mosekilde L, Eriksen EF. Effects of fluoride on human bone cells in vitro: differences in responsiveness between stromal osteoblast precursors and mature osteoblasts. Eur J Endocrinol 1994;130:381–6. ISSN 0804–4643
The cellular effects of sodium fluoride (NaF) on human bone cells in vitro have been variable and dependent on the culture system used. Variability could be attributed to differences in responsiveness to NaF among different populations of cells at various stages of differentiation in the osteoblastic lineage. In this study we compared the effects of NaF in serum-free medium on cultures of more differentiated human osteoblast-like (hOB) cells derived from trabecular bone explants and on osteoblast committed precursors derived from human bone marrow, i.e. human marrow stromal osteoblast-like (hMS(OB)) cells. Sodium fluoride (10−5 mol/l) increased proliferation of hMS(OB) cells (p<0.05, N = 10) but was not mitogenic to hOB cells (p>0.05, N= 10). Alkaline phosphatase (AP) production increased in both hMS(OB) (p<0.05, N=9) and hOB cells (p<0.05, N=9). No significant effects on procollagen type I propeptide production were obtained in either culture. In the presence of 1,25-dihydroxycholecalciferol (10−9 mol/l), NaF enhanced alkaline phosphatase (p<0.05, N=8), procollagen type I propeptide (p<0.05, N=7) and osteocalcin (p<0.05, N=7) production by hMS(OB) cells but not by hOB cells. Our results suggest that osteoblast precursors are more sensitive to NaF action than mature osteoblasts and that the in vivo effects of NaF on bone formation may be mediated by stimulating proliferation and differentiation of committed osteoblast precursors in bone marrow.
M Kassem, Mayo Clinic, Endocrine Research Unit, W-Joseph 5-164, Rochester, MN 55904, USA
Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats
Authors: Binz Katharina , Schmid Christoph , Bouillon Roger , Froesch E Rudolf , Jürgensen Kay , Hunziker Ernst B 
Published: December 2008

Binz K, Schmid C, Bouillon R, Froesch ER, Jürgensen K, Hunziker EB. Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats. Eur J Endocrinol 1994;130:387–93. ISSN 0804–4643
Glucocorticoid treatment causes osteoporosis and growth retardation in humans. Insulin-like growth factor I (IGF-I) stimulates differentiation and replication of cultured osteoblast-like cells and induces longitudinal bone growth in IGF-I-deficient rats. We investigated the influence of subcutaneously infused IGF-I on bone and mineral metabolism of male rats treated with a high dose of dexamethasone. Dexamethasone was added to the drinking water in a concentration of 1 mg/l. After 30 days of dexamethasone treatment, recombinant human IGF-I (300 μg/day) or solvent was infused sc by osmotic minipumps for 21 days while dexamethasone was continued. Age-matched untreated male rats served as healthy controls. Dexamethasone-treated rats lost weight. Their IGF-I levels were decreased to 36% of healthy controls. Infusion of IGF-I resulted in an increase in IGF-I serum levels (582% compared to healthy controls) and allowed some weight gain. Osteocalcin and calcitriol levels were markedly decreased in dexamethasone-treated rats and were not influenced significantly by IGF-I infusion. In contrast, IGF-I treatment restored the free calcitriol concentration (molar ratio of calcitriol to vitamin D-binding protein) towards normal. Furthermore, infusion of IGF-I partially corrected the dexamethasone-induced hyperinsulinemia. Histomorphometric analysis revealed no difference in vertebral trabecular bone density (i.e. growth-independent bone remodeling) between the three groups. In contrast, mean trabecular bone density in tibial metaphyses was increased markedly by dexamethasone, presumably due to osteoclast inhibition. Insulin-like growth factor I infusion did not significantly influence these structural metaphyseal bone parameters. We conclude that IGF I-infusion in male rats treated with high doses of dexamethasone reduces insulin resistance and restores calcitriol production but not osteoblast function or responsiveness to calcitriol.
K Binz, Division de Diabétologie, Hôpital Cantonal Universitaire, 1211 Geneva, Switzerland
Responsiveness to corticotropin-releasing hormone and vasopressin in canine Cushing's syndrome
Authors: van Wijk Petra A , Rijnberk Ad , Croughs Ronald JM , Wolfswinkel Jeannette , Selman Paulus J , Mol Jan A 
Published: December 2008

Van Wijk PA, Rijnberk A, Croughs RJM, Wolfswinkel J, Selman PJ, Mol JA. Responsiveness to corticotropin-releasing hormone and vasopressin in canine Cushing's syndrome. Eur J Endocrinol 1994;130:410–16. ISSN 0804–4643
Corticotropin-releasing hormone (CRH) and vasopressin are the most important hypothalamic factors regulating adrenocorticotropic hormone (ACTH) secretion. In this study we have investigated the responsiveness of the pituitary–adrenocortical axis to intravenous administration of CRH or lysine vasopressin (LVP) in 16 control dogs, 22 dogs with pituitary-dependent hyperadrenocorticism and five dogs with hyperadrenocorticism due to an adrenocortical tumor, using doses of CRH and LVP that caused equivalent ACTH responses in the control dogs. After CRH administration, the increment in plasma ACTH was significantly (p < 0.05) lower in dogs with pituitary-dependent hyperadrenocorticism (221 ± 53 ng/l) than that in control dogs (279 ± ng/l). In the dogs with pituitary-dependent hyperadrenocorticism, the relative increases in ACTH after CRH were significantly (p < 0.05) lower than those after LVP. Despite the absence of an increase in ACTH following LVP administration in dogs with hyperadrenocorticism due to an adrenocortical tumor, there was a significant increase in plasma cortisol, the increment (790 ±238 nmol/l) being not statistically different from that in the control dogs (412 ± 37 nmol/l). We conclude that in spite of the changes inherent to pituitary-dependent hyperadrenocorticism, i.e. neoplastic transformation of corticotropic cells and hypercortisolism, there is persistence of responsiveness to hypophysiotropic hormones. The ACTH secretion by corticotropic cells in pituitary-dependent hyperadrenocorticism was relatively less sensitive to stimulation with CRH than with LVP. Adrenocortical tumors develop an aberrant sensitivity to LVP.
A Rijnberk, Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.154, 3508 TD, Utrecht, The Netherlands
Effects of anti-prolactin autoantibodies on serum prolactin measurements
Authors: Hattori Naoki , Ikekubo Katsuji , Ishihara Takashi , Moridera Kunisaburo , Hino Megumu , Kurahachi Hiroyuki 
Published: December 2008

Hattori N, Ikekubo K, Ishihara T, Moridera K, Hino M, Kurahachi H. Effects of anti-prolactin autoantibodies on serum prolactin measurements. Eur J Endocrinol 1994:130:434–7. ISSN 0804–4643
The influence of anti-PRL autoantibodies on PRL measurements determined by immunoassays was investigated in 10 patients with anti-PRL autoantibodies. Four different immunoassay systems (two double-antibody radioimmunoassays (RIAs), a single-antibody RIA and an immunoradiometric assay (IRMA)) were examined. Total and free PRL were extracted from sera by precipitating γ-globulin with polyethylene glycol with and without acidification, respectively. PRL values determined by direct measurement were compared with total PRL values. The proportion of free to total PRL levels determined by each immunoassay in sera with anti-PRL autoantibodies was significantly lower than in control sera. Values obtained by direct measurement of PRL (a routine assay procedure) in control sera were similar to total PRL values, whereas in sera with anti-PRL autoantibodies the values varied from one immunoassay to the other. In sera with anti-PRL autoantibodies, double-antibody RIA I, RIA 2 and single-antibody RIA 3 yielded values lower for PRL than for total PRL (52 ±15% in RIA 1, 40±8.8% in RIA 2.40±14% in RIA 3), while PRL levels determined by IRMA were not significantly different (112 ±14%). Immunoglobulin G purified from serum with anti-PRL autoantibodies dosedependently decreased the recovery of PRL assayed by the double-antibody technique, while it did not affect that by IRMA. These data suggest that the presence of anti-PRL autoantibodies gives variable results depending on the immunoassays used. It is noteworthy that anti-PRL autoantibodies do not cause falsely high PRL values, as in the case of antithyroid hormone autoantibodies, rather they cause an underestimate, when a double-antibody RIA, a routine method for PRL measurement, is used.
Naoki Hattori, Department of Endocrinology. Kobe City General Hospital, 4-6 Minatojima Nakamachi, Chuoku, Kobe 650, Japan
Correlation of the antibody titers with serum prolactin levels and their clinical course in patients with anti-prolactin autoantibody
Authors: Hattori Naoki , Ikekubo Katsuji , Ishihara Takashi , Moridera Kunisaburo , Hino Megumu , Kurahachi Hiroyuki 
Published: December 2008

Hattori N, Ikekubo K, Ishihara T, Moridera K, Hino M, Kurahachi H. Correlation of the antibody titers with serum prolactin levels and their clinical course in patients with anti-prolactin autoantibody. Eur J Endocrinol 1994;130:438–45. ISSN 0804–4643
Patients with anti-prolactin (PRL) autoantibody were surveyed among 208 patients with hyperprolactinemia (PRL ≥ 30 μg/l) and 228 subjects with normal PRL levels, and the relationship of the antibody titers with serum PRL levels and their clinical course were studied. Diagnosis of possessing the anti-PRL autoantibody was based on the polyethylene glycol method, displacement of the binding of [125I]PRL with the serum by unlabeled PRL and the binding of PRL to protein G, the affinity gel for immunoglobulin G. Prolactin was measured by an immunoradiometric assay that we found was not affected by the anti-PRL autoantibody. A significantly high frequency of anti-PRL autoantibody in patients with idiopathic hyperprolactinemia (16%) and a positive correlation between titers of the autoantibody and serum PRL levels (r = 0.74, p < 0.01) may indicate that the anti-PRL autoantibody itself is another cause of hyperprolactinemia, probably owing to the delayed clearance of PRL. Most patients with anti-PRL autoantibody lacked the clinical symptoms of hyperprolactinemia, such as amenorrhea and galactorrhea, and spontaneous pregnancy occurred despite the marked hyperprolactinemic state, indicating that the biological activity of PRL was attenuated by the autoantibody. In addition, PRL levels and the titers of anti-PRL autoantibody were not changed significantly during the observation period of up to 5 years without any medical intervention. These results suggest that the anti-PRL autoantibody itself is one of the causes of hyperprolactinemia and that medical intervention is unnecessary for this type of hyperprolactinemia.
Naoki Hattori, Department of Endocrinology, Kobe City General Hospital, 4–6 Minatojima Nakamachi, Chuo-ku, Kobe 650, Japan
Decreased chemotaxis of neutrophils in acromegaly and hyperprolactinemia
Authors: Fornari M Cecilia , Palacios M Fernanda , Diez Roberto A , Intebi Alberto D 
Published: December 2008

Cecilia Fornari M, Fernanda Palacios M, Diez RA, Intebi AD. Decreased chemotaxis of neutrophils in acromegaly and hyperprolactinemia, Eur J Endocrinol 1994;130:463–8. ISSN 0804–4643
Both growth hormone (GH) and prolactin (PRL) modulate immune responses in vitro. We studied chemotaxis under agarose of polymorphonuclear cells from patients with acromegaly or hyperprolactinemia. Polymorphonuclear cells were purified by dextran sedimentation and subjected to stimulation with N-formylmethionyl-phenylalanine, The results showed a decrease in both directed migration (acromegaly: 971 ± 155 μm, hyperpolactinemia: 1123 ± 137 μm, expressed as mean± sem) and spontaneous migration (acromegaly: 270 ± 77 μm: hyperpolactinemia: 298 ± 77 μm) when compared to similar features from normal controls (directed migration: 2019 ± 99 μm: spontaneous migration: 590 ± 49 μm) and from patients with non-GH/PRL-secreting pituitary tumours (directed migration: 1633 ± 282 μm: spontaneous migration: 562 ± 116 μm), suggesting that this defect is selective for acromegaly and hyperprolactinemia. Our results point to a putative direct or indirect effect of GH and PRL on polymorphonuclear cell chemotaxis.
AD Intebi, Endocrinologia, Dpto de Medicina Interna, Hospital "Juan A Fernandez", Cerviño 3356 (125), Buenos Aires, Argentina
False negative results observed in anti-thyroid peroxidase autoantibody determination by competitive radioimmunoassays using monoclonal antibodies
Authors: Mariotti Stefano , Barbesino Giuseppe , Caturegli Patrizio , Atzeni Francesca , Manetti Luca , Marino Michele , Grasso Lucia , Velluzzi Fernanda , Loviselli Andrea , Pinchera Aldo , Martino Enio 
Published: December 2008

Mariotti S, Barbesino G, Caturegli P, Atzeni F, Manetti L, Marinò M, Grasso L, Velluzzi F, Loviselli A, Pinchera A, Martino E. False negative results observed in anti-thyroid peroxidase autoantibody determination by competitive radioimmunoassays using monoclonal antibodies. Eur J Endocrinol 1994;130:552–8. ISSN 0804–4643
Objective: Anti-thyroid peroxidase autoantibody (anti-TPO) and anti-thyroid microsomal antibody (anti-M) are strictly related, but discrepancies are sometimes observed. The aim of this study was to assess the incidence and to identify the causes of these discrepancies. Design and antibody measurements: Anti-M by passive hemagglutination and anti-TPO by two competitive monoclonal antibody-assisted radioimmunoassays (RIA-1 and RIA-2) were measured in 10 103 sera from 4232 subjects (663 male, 3569 female) screened for thyroid disease. Results: Anti-TPO and anti-M correlated quite well (r = 0.7 and p < 0.0001 by RIA-1; r = 0.74 and p < 0.0001 by RIA-2), with discrepancies mostly limited to sera with low antibody titers. After exclusion of the latter samples, anti-TPO were detected in only 79 (1.4%) out of 5317 anti-M negative sera, but were undetectable in a more consistent proportion (130/2880 = 4.5%) of sera from patients with autoimmune thyroid disease and positive anti-M. In 61 sera of the latter group, anti-TPO was measured by a non-competitive RIA (RIA-3). Forty-one (67.7%) were positive by RIA-3, suggesting the presence of anti-TPO not competing with the monoclonal antibodies of RIA-1 and RIA-2. The remaining 20 sera had undetectable anti-TPO also by RIA-3. Nineteen (95%) of these sera had positive anti-thyroglobulin (anti-Tg) autoantibody and preincubation with thyroglobulin inhibited the agglutination reaction of anti-M tests. Conclusion: Anti-TPO by competitive monoclonal antibody-assisted RIA is negative in a minority of sera of patients with autoimmune thyroid disease and positive anti-M. This could be accounted for by anti-Tg producing false positives in the anti-M assay and by a subset of anti-TPO not competing with the monoclonal antibodies in the RIA. When autoimmune thyroid disease is suspected on clinical grounds, a negative anti-TPO test with a competitive RIA should be confirmed always by a non-competitive assay.
Stefano Mariotti. Institute of Endocrinology. University of Pisa, Viale del Tirreno 64,1-56018 Tirrenia-Pisa, Italy
Serum carboxy-terminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery
Authors: Minisola Salvatore , Romagnoli Elisabetta , Scarnecchia Liliana , Rosso Rossana , Pacitti Maria T , Scarda Antonella , Mazzuoli Gianfranco 
Published: December 2008

Minisola S, Romagnoli E, Scarnecchia L, Rosso R, Pacitti MT, Scarda A, Mazzuoli G. Serum carboxyterminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery. Eur I Endocrinol 1994;130:587–91. ISSN 0804-4643
This study was carried out in order to evaluate serum carboxy-terminal propeptide of human type I procollagen (PICP) in patients with primary hyperparathyroidism and to examine its changes following parathyroidectomy. Seventeen patients (four males and 13 famels, aged 53.8 ± 3.1 sem years) were studied in basal conditions; six patients also were investigated after successful parathyroid surgery. Mean serum PICP values of patients with primary hyperparathyroidism (194.5 ± 27 sem μg/l) were significantly higher (p < 0.001) with respect to those found in normal subjects. However, deviations from the norm (Z score values) were significantly less with respect to deviations of serum osteocalcin, alkaline phosphatase and urinary hydroxyproline/creatinine ratio. Following parathyroidectomy, it was possible to observe a discrepancy between markers of bone resorption and those of bone formation. The former tend to decrease, while the latter either do not show any significant change (serum alkaline phosphatase and serum osteocalcin) or increase (serum procollagen). The results of our investigation indicate that in basal conditions the assay of serum procollagen may be of clinical value but it would be better to use it in combination with other biomarkers of skeletal remodelling. The results obtained after parathyroidectomy are the opposite of those obtained following parathyroid hormone infusion and should be ascribed to the effect of acute hormone deficiency on collagen synthesis. The positive biochemical uncoupling following surgery might lend support to the rise of bone mineral density consistently reported in the first few months following parathyroidectomy.
S Minisola, Istituto di II Clinical Medica, Policlinico Umberto I, Via del Policlinico 155, 00161 Rome, Italy