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Biomedical subjects

M Giusti

Publications and source records attributed to M Giusti.

At least 19 recordsLinked to original sources
PubMed2000

Gonadotropin-releasing hormone-induced partial empty sella clinically mimicking pituitary apoplexy in a woman with a suspected non-secreting macroadenoma.

Pituitary apoplexy has been reported as a rare complication of dynamic testing used for the study of pituitary functional reserve. In 1993, a diagnosis of non-secreting macroadenoma with moderate functional hyperprolactinaemia was made in a 43-year-old woman. Soon after the start of therapy with bromocriptine up to 5 mg/die, the patient complained of nausea and postural hypotension. As the symptoms persisted even when the dose was reduced to 2.5 mg/die, the patient was transferred to therapy with quinagolide at the dosage of 37.5 microg/die. PRL levels quickly normalized (range 1.4-5.7 ng/ml) as well as menstrual cycles, and no side-effect was reported. In 1995 a sellar magnetic resonance imaging (MRI) showed no shrinkage of the known macroadenoma. In 1996, few hours after a gonadotropin-releasing-hormone (GnRH) test, which showed normal LH and FSH response and with baseline PRL levels in the normal range, the patient started complaining of severe frontal headache, nausea and vomiting. No gross visual defects were present. An emergency computed tomography (CT) showed no evident hemorrhagic infarction in the macroadenoma. The symptoms completely resolved in few days with steroidal and antiemetic therapy. A new MRI performed in 1998 showed a partial empty sella and PRL levels were in the normal range under dopaminergic treatment. The pituitary functional reserve proved normal on dynamic testing. The temporal association between the onset of symptoms and the GnRH test strongly suggests an association between the two events. No evident signs of pituitary apoplexy (either on emergency CT or hormonal evaluation) were detected. The authors suggest that GnRH can cause severe side-effects that mimic pituitary apoplexy without related morphological evidence and that, in our particular case, it can have caused the gradual disappearance of the non-secreting macroadenoma. Moreover, a causal role of the chronic dopaminergic treatment cannot be completely ruled out.

Adenoma↗
PubMed1999

Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rheumatoid synovial macrophages and THP-1 cells.

Because some of the clinical symptoms related to rheumatoid arthritis (RA) synovitis, such as joint morning stiffness and gelling, might be related to the effects exerted by the diurnal rhythmicity of the neurohormone melatonin (MLT) on synovial immune cell activation, we decided to evaluate the influence of MLT on the production of IL-12 and nitric oxide (NO) on primary cultures of RA synovial macrophages. Synovial macrophages were also prestimulated with lipopolysaccaride (LPS). Results were compared with those obtained on cultured human myeloid monocytic cells (THP-1). A significant increase in IL-12 (p = 0.01) was found in media of MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a significant decrease of IL-12 (p < 0.0001) was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. A significant increase in NO levels (p = 0.01) was found in MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a nonsignificant increase of NO levels was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to cynovial macrophages treated with LPS alone. Finally, a significant increase in IL-12 (p = 0.03) and NO (p = 0.002) concentrations was observed in media of MLT-stimulated THP-1 cells versus RMPI-treated controls. Our results therefore show that MLT induces IL-12 secretion and NO production by unstimulated cultured RA synovial macrophages and human monocytic myeloid THP-1 cells. The unexpected and opposite effects on IL-12 and NO production in RA synovial macrophages treated with LPS may be related to dose-dependent mechanisms exerted by MLT or to altered cell priming in RA macrophages; these are matters of our further research. This study strongly supports the role of MLT in immune response modulation and in particular suggests a close relationship between diurnal rhythmicity of neuroendocrine pathways, cytokine and reactive oxygen intermediate production by monocyte/macrophages, and synovial arthritis symptomatology, at least in RA.

Adult↗
PubMed1999

Serum leptin levels in males with delayed puberty during short-term pulsatile GnRH administration.

Leptin may be a possible trigger for puberty. In normal males, it has been shown that leptin increases from the pre-pubertal to the early pubertal stage, and then declines in the late pubertal stage. We examined leptin levels in six male adolescents (mean age 16.3+/-0.6 yr; range 14.2-17.6 yr) with delayed puberty (constitutional delay of puberty no.=2; idiopathic hypogonadotropic hypogonadism no.=4) during 120 days of subcutaneous pulsatile GnRH administration. A group of subjects in pre-puberty (no.=11), early-puberty (n=10) and mid-puberty (no.=7) were evaluated as controls. Morning blood samples were taken for determination of leptin, testosterone, LH and FSH levels. In delayed puberty subjects blood samples were taken every 30 days after the start of GnRH administration. At each examination BMI and testicular volume were evaluated. A follow-up examination was performed in the 6 patients 1.3-7.5 yr after the end of the 120 days of GnRH therapy. At baseline evaluation in delayed puberty mean leptin levels were 11.3+/-2.0 microg/l (median 11.3 microg/l; range 4.7-17.3 microg/l) and were higher than those found in pre-puberty (p=0.04) and mid-puberty (p=0.001). During GnRH administration there was no change in BMI and leptin levels but there was an increase in gonadotrophin levels, testosterone and testicular volume. One hundred and twenty days after, mean serum leptin were 10.1+/-2.1 microg/l (median 9.1 microg/l; range 3.4-16.8 microg/l). At the end of the study, leptin levels were higher in delayed puberty than in mid-puberty (p=0.002). At the follow-up examination leptin levels were 4.3+/-1.3 microg/l (median 3.4 microg/l; range 1.4-9.1 microg/l) (p=0.03 vs end of 120 days GnRH therapy) while testosterone and BMI were not changed. In conclusion 120-day pulsatile GnRH administration induced in males with delayed puberty physiological-like pubertal changes but not the decline in leptin levels reported during the progression of puberty. Therefore, in males with delayed puberty an impairment in the phenomenon of leptin decline associated with progression of puberty could be suggested. However after retrospective diagnosis of pubertal delay and long-term therapy in subjects with idiopathic hypogonadotropic hypogonadism leptin levels declined. These data seem to indicate that time more than increase in testosterone levels and testicular volume is the determinant of leptin decline at puberty.

Adolescent↗
PubMed1999

Biphasic effect of nitric oxide on testosterone and cyclic GMP production by purified rat Leydig cells cultured in vitro.

Nitric oxide (NO) biphasically modulates osteoclast function and sperm motility by exerting a positive effect at low concentrations and a negative effect at high concentrations. We therefore tested whether NO exerts a comparable effect on testosterone secretion by cultured rat Leydig cells. Three NO-donors, S-nitroso-N-acetylpenicillamine (SNAP), diethylamine/nitric oxide complex sodium salt (DEA/NO) and diethylenetriamine nitric oxide adduct (DETA/NO) were administered in a wide range of concentrations (10(-8)-10(-3) M for 3 h) to Percoll-purified Leydig cells from adult rats. These drugs raised testosterone and cGMP secretion when used at low concentrations (10(-8)-10(-5) M); however, they inhibited testosterone, but did not affect cGMP, secretion at concentrations higher than 10(-5) M. Administration of the NO scavenger haemoglobin (160 micrograms/mL) prevented both the stimulatory and the inhibitory effect of these drugs. Nitrite accumulation was measured as a marker of NO released by the drugs in our in vitro system; it fell within the range of control media in the presence of NO-donor concentrations lower than 10(-5) M, but was several-fold higher in the media of cells treated with concentrations of the NO-donors greater than 10(-5) M. These data show that (1) NO exerts a biphasic effect on testosterone secretion, which is stimulatory at low and inhibitory at high concentrations; (2) the stimulatory effect of NO is mediated by cGMP, the classic second messenger for NO action.

Adult↗
PubMed1999

The role of rDNA genes in X chromosome association in the aphid Acyrthosiphon pisum.

Silver staining of mitotic metaphases of the aphid A. pisum reveals the presence of argentophilic bridges connecting the two X chromosomes. The presence of nucleolar material connecting sex chromosomes seems to be quite a common phenomenon in organisms belonging to very different phyla, and suggests a role of nucleolar proteins in chromosome association and disjunction. In somatic cells of A. pisum, bridges connecting X chromosomes are detectable not only after silver staining but also after CMA3 staining. This finding suggests that GC rich DNA is involved in this type of association. Molecular analysis of rDNA intergenic spacers shows several 247 bp repeats containing short sequences having a high level of homology with the chi sequence of Escherichia coli and with the consensus core region of human hypervariable minisatellites. Moreover, each 247 bp repeat presents a perfect copy of a promoter sequence for polymerase I. These aphid repeats show structural homologies with a 240 bp repeat, which is considered to be responsible for sex chromosome pairing in Drosophila, not only in view of their common presence within rDNA spacers but also for their length and structure. The presence of chi sequences in the IGS of A. pisum, by promoting unequal crossing-over between rDNA genes, could thus give rise to the nucleolar organizing region (NOR) heteromorphism described in different aphid species. Although X pairing at NORs is fundamental in aphid male determination, the presence of heteromorphism of rDNA genes does not inhibit male determination in the A. pisum clone utilized for our experiments.

Animals↗
PubMed1999

Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro.

OBJECTIVE: Somatostatin is a powerful inhibitor of hormone secretion and cell proliferation. Treatment with somatostatin analogs in humans causes a reduction in size and secretory activity of some endocrine tumors, including somatotropic pituitary adenomas. Less studied are the effects of somatostatin agonists on non-functioning pituitary adenomas (NFPAs). In this study we characterized the effects of somatostatin and its analog lanreotide on the proliferation of NFPAs in vitro and the intracellular mechanisms involved. DESIGN: Twenty-three NFPA post-surgical specimens were analyzed for somatostatin receptor (SSTR) expression and 12 of them were cultured in vitro to study somatostatin's effects on cell proliferation, assessed by means of [(3)H]thymidine uptake, and the intracellular signaling. RESULTS: One or more SSTR subtypes were expressed in 90% of the adenomas tested. Somatostatin and lanreotide treatment inhibited phorbol myristate acetate (PMA)-induced cell proliferation. Vanadate pretreatment reversed somatostatin and lanreotide inhibition of PMA-induced DNA synthesis suggesting an involvement of tyrosine phosphatase in this effect. In the only adenoma tested, somatostatin directly induced a tyrosine phosphatase activity. Somatostatin and lanreotide caused also a significant inhibition of voltage-sensitive calcium channel activity induced by 40mmol/l K(+) depolarization in microfluorimetric analysis. CONCLUSIONS: These data show that somatostatin and lanreotide inhibit human NFPA cell proliferation in vitro, and suggest that activation of tyrosine phosphatases and inhibition of the activity of voltage-dependent calcium channels may represent intracellular signals mediating this effect.

Adenoma↗
PubMed1999

A novel mechanism for the melatonin inhibition of testosterone secretion by rat Leydig cells: reduction of GnRH-induced increase in cytosolic Ca2+.

The site of inhibition, by melatonin, of GnRH-dependent testosterone secretion was investigated in adult rat Leydig cells cultured in vitro. The various effects downstream of the binding of GnRH to its own receptor were isolated and mimicked by specific drugs. Testosterone secretion was then evaluated after 3 h stimulation with GnRH, thapsigargin (1 microM), phorbol-12-myristate-13-acetate (100 nM), arachidonic acid (20 microM), and ionomycin (1 microM) in the presence or absence of melatonin (215 nM). The effect of melatonin on the GnRH-induced changes in cytoplasmic calcium concentration ([Ca(2+)](i)) was also studied, using Fura-2 as fluorescent Ca(2+) indicator. Melatonin attenuated the increase in [Ca(2+)](i) and inhibited the testosterone secretion induced by GnRH, but not that induced by ionomycin. Both ionomycin and thapsigargin potentiated GnRH-induced testosterone secretion; however, ionomycin, but not thapsigargin, partially prevented the inhibitory effect of melatonin on cells stimulated with GnRH. The effect of melatonin was probably dependent on the binding of melatonin to its Gi-protein-coupled receptor, as the inhibitory effect on GnRH-induced secretion was supressed in cells pretreated with pertussis toxin in a concentration of 180 ng/ml for 20 h. Assay of 17-hydroxy-progesterone showed that, irrespective of the treatment, cells cultured with melatonin secreted greater amounts than controls. We conclude that melatonin reduces GnRH-induced testosterone secretion by 1) decreasing [Ca(2+)](i), through impairment of the GnRH-dependent release of Ca(2+) from intracellular stores and 2) blocking 17-20 desmolase enzymatic activity, an effect that occurs irrespective of changes in [Ca(2+)](i).

17-alpha-Hydroxyprogesterone↗
PubMed1999

[Gonadotropin response to GnRH and seminal parameters in low grade varicocele].

The pathogenetic role of varicocele in male infertility is still controversial. Although epidemiological data have clearly shown a higher incidence of varicocele in the population of subfertile and infertile patients, the real effectiveness of the surgical repair of varicocele, expressed as increase in the pregnancy rate, is still debated. The presurgical gonadotropin releasing hormone (GnRH) test is the most reliable predictive index of successful surgical outcome in terms of fertility. Only patients with an increased gonadotropin response (in particular FSH) to GnRH will benefit from the surgery. The aim of the present study was to evaluate the gonadotropin response to GnRH 50 micrograms i.v. in a group of patients with low-medium grade varicocele. At the beginning of the test, a fine needle was inserted into the forearm and kept patent by a saline solution. Blood samples were collected at the following experimental times: 0, +15, +30, +60, +90, +120 min. The stimulus was administered i.v. as bolus at time 0. The gonadotropin response to the stimulus and baseline levels of testosterone, PRL, 17 beta oestradiol and SHBG were compared with those of a control group. Moreover, all the patients underwent semen analysis after 3-7 days' abstinence and to ultrasound-doppler of the testis. Finally, we preliminarily looked for the presence of microdeletions on the Yq chromosome by polymerase chain reaction. No difference in baseline hormonal levels was found between the patients with varicocele and the controls; the LH response to GnRH was also similar in the two groups. The patients with varicocele showed a significantly (p = 0.03) higher FSH response (13.6 +/- 5.9 mUI/ml) to GnRH than controls (3.8 +/- 0.5 mUI/ml). A significant positive correlation (r = 0.6, p = 0.05) was found between LH peaks after GnRH testing and varicocele grade. Nine of 11 patients with varicocele showed significant seminal abnormalities (i.e., oligoasthenospermia): all patients showed a normal karyotype and no microdeletions were detected on the Yq chromosome. The authors underline the importance of presurgical GnRH testing in patients with low grade varicocele, given the close correlation between gonadotropin-stimulated peaks and varicocele grade found in the study. The presence of significant seminal abnormalities, even in patients with low grade varicocele, suggests the use of molecular genetic techniques to detect possible microdeletions on the Yq chromosome, which may be responsible for the infertility.

Adolescent↗
PubMed1999

[An increased prevalence of thyroid echographic and autoimmune changes in hyperprolactinemic women on therapy with dopaminergic drugs].

Prolactin (PRL) possesses mitogenic and immunomodulatory properties. We evaluated the prevalence of ultrasonographic thyroid alterations and thyroid autoimmunity in hyperprolactinaemic (HPRL) women and correlated these with PRL levels. Furthermore, we studied the PRL binding in human benign nodular thyroid tissues. 133 HPRL patients (16-63 years) and 103 healthy female controls (16-63 years) with no known history of thyroid disease were studied. Blood samples were collected for PRL, FT3, FT4, TSH, thyroid peroxidase auto-antibodies (TPO Ab) and thyroglobulin auto-antibodies (Tg Ab) assays. All subjects underwent thyroid ultrasonography. PRL binding to thyroid membranes was determined by in-vitro radioreceptor assay in 5 human benign nodular thyroid fragments obtained from female patients. No difference in TSH levels was found, while FT3 (4.5 +/- 0.1 pmol/L) and FT4 (16.2 +/- 0.4 pmol/L) levels were significantly higher in controls than in HPRL (FT3: 3.8 +/- 0.1 pmol/L, p = 0.01, FT4: 15.4 +/- 0.2 pmol/L, p = 0.04). The prevalence of thyroid ultrasonographic alterations (simple goitre, uni-multinodular goitre, chronic thyroiditis) was significantly higher in HPRL (30.8%) than in controls (15.5%, p = 0.01) but did not correlate with mean initial and actual PRL levels or duration of the disease. The prevalence of autoantibodies was significantly higher in HPRL (29.6%) than in controls (14.3%, p = 0.04) but did not correlate with PRL levels. Very low specific PRL binding to thyroid membranes was detected. The high prevalence of thyroid ultrasonographic alterations and autoimmunity in HPRL suggests a possible role of PRL in the development of thyroid diseases. Clinical and instrumental thyroid screening may therefore be advisable in these patients.

Adolescent↗
PubMed1999

Assessment of quality of life in recently post-menopausal women on dopaminergic therapy for pathological hyperprolactinaemia.

BACKGROUND: Psychological distress has been reported in pre-menopausal hyperprolactinaemic women. The aim of this study was to assess quality of life in a group of recently post-menopausal women with a long-term history of hyperprolactinaemia. METHODS: Thirty-one recently post-menopausal hyperprolactinaemic women (age range 46-59 years) and 37 control women matched for age and menopausal status. Hyperprolactinaemia had been diagnosed 2-22 years before the study. All hyperprolactinaemic women were on dopaminergic therapy. The self-rating Kellner Symptom Questionnaire (KSQ) and the Hamilton Depression Scale (HDS) were used to evaluate psychiatric profile. Evaluation of climacteric symptoms was performed with the ad-hoc self-rating 21-item Menopausal Rating Scale (MRS). Serum PRL, E2, LH, FSH, and free-thyroid hormones were evaluated. RESULTS: Hyperprolactinaemic women showed normal PRL on dopaminergic therapy. No difference was noted in PRL, LH, FSH, free-T4, and E2 levels between groups. Free-T3 was significantly (p = 0.001) lower in hyperprolactinaemic than in control women. There was no difference in overall scores on the MRS between the groups. Only the item "rapid and strengthened heart-beat" was significantly (p = 0.04) lower in hyperprolactinaemic than in control women. Control women showed a significant correlation between the score for this item and free-thyroid hormone levels. Overall KSQ scores and subsection analysis of items did not show significant differences between groups. On HDS evaluation, depressive symptoms were similar in hyperprolactinaemic and control women. CONCLUSIONS: Quality of life seems unchanged in recently post-menopausal women with a long-term history of hyperprolactinaemia currently on dopaminergic therapy. The present study does not therefore support the differences in psychological profile reported in literature between untreated hyperprolactinaemic and control women unselected for age.

Dopamine Agents↗
PubMed1999

Hypothalamic-pituitary-adrenocortical axis function in premenopausal women with rheumatoid arthritis not treated with glucocorticoids.

OBJECTIVE: To assess hypothalamic-pituitary-adrenocortical axis function in patients with rheumatoid arthritis (RA) not previously treated with glucocorticoids in relation to their inflammatory condition and in comparison to healthy controls. METHODS: We evaluated, in 10 premenopausal patients with RA and 7 age matched controls, plasma dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and cortisol concentrations, together with inflammatory cytokine levels [interleukin 6 (IL-6) and IL-12], both in basal conditions and after stimulation with ovine corticotropin releasing hormone (oCRH) and with low dose intravenous (5 microg) adrenocorticotropic hormone (ACTH). RESULTS: DHEA and DHEAS basal concentrations were found to be significantly lower (p<0.05) in premenopausal patients with RA than in controls. As expected, significantly higher basal levels of IL-6 and IL-12 (p<0.05) were found in patients with RA. After the low dose ACTH testing, the DHEA area under the curve value was found to be significantly lower (p<0.01) in patients than controls. Similar results, but without statistical significance, were observed after oCRH stimulation. DHEA levels at basal time showed a significant negative correlation with the erythrocyte sedimentation rate and platelet count, as well as with the Steinbrocker class of the disease (p<0.05). Normal plasma cortisol levels during oCRH and ACTH testing were found in patients with RA in spite of their inflammatory condition. After ACTH testing, IL-6 levels decreased significantly (p<0.05), whereas IL-12 levels were unchanged. No significant changes in IL-6 and IL-12 levels were found after oCRH testing. CONCLUSION: The abnormal androgen concentrations observed during testing in patients with RA might support the implication of adrenal androgens in the immune/inflammatory cytokine mediated mechanisms involved in the pathophysiology and clinical aspects of RA.

Adrenocorticotropic Hormone↗
PubMed1998

Frequency of recovery from anorexia nervosa of a cohort patients re-evaluated on a long-term basis following intensive care.

The need to treat the acute onset of anorexia nervosa in a specialty unit is well known, but nevertheless, even "clinically recovered" patients show a high rate of relapse. The aim of our study was to re-evaluate various clinical (hemoglobin, transferrin, insulin-like growth factor I, TSH, PRL, gonadotropins and 17 beta-estradiol) and psychiatric [semistructured interview, Eating Disorder Inventory (EDI) Test] parameters in 19 female anorexic patients hospitalized in our department from 1983 to 1993 (with a 9-year median prior to the present study) for the treatment of anorexia nervosa, and to compare these results with those of a previous follow-up performed on the same subjects in 1993. In the present evaluation, no significant variation was found among the clinical, nutritional and hormonal parameters when compared to those of the first follow-up in which all parameters had improved with the exception of the PRL levels, which were significantly low. Meanwhile, the percentage of patients with spontaneous menses increased significantly from 50% to 70%, while the number of patients on psychopharmacological therapy decreased significantly throughout the study. Furthermore the percentage of patients with altered (severe or mild) EDI profiles decreased to 50%. This study emphasizes the positive prognostic role of hospitalization and intensive care in a cohort of anorexic patients. The present study, in addition to demonstrating both a general maintenance of body weight acquired over the years, albeit in the lower normal range, and an increase in the percentage of patients with a regular menstrual cycle, also highlights the persistence of psychiatric abnormalities in a large number of patients, even in those diagnosed as "clinically recovered", thus suggesting the need for long-term psychiatric care.

Adolescent↗
PubMed1998

Impact of recombinant human growth hormone treatment on psychological profiles in hypopituitary patients with adult-onset growth hormone deficiency.

BACKGROUND: We examined the effect of growth hormone (GH) administration on the psychological capacity and sense of well-being in 25 patients with adult-onset GH-deficiency (GHD). METHODS: Very low dosages [0.5-1.0 UIday(-1) s.c. at bed-time] of recombinant human (rh)-GH (n = 13; aged 50+/-15 years, mean+/-SD) or placebo (n = 12, 53+/-14 years) were given at random for a 6-month period. Quality of life was assessed by using the Italian version of the self-rating Kellner Symptom Questionnaire (KSQ) and the Hamilton Depression Scale (HDS). RESULTS: No difference in insulin-like growth factor I (IGF-I) levels was noted between groups on entry to the study. A significant increase in IGF-I [month 0 56.2+/-10.4 microg L(-1) vs. month 6 125.7+/-16.7 microg L(-1); P < 0.001] levels was noted only in the rh-GH-treated group. There was no difference in overall scores on the KSQ between the rh-GH-treated and control groups on entry. A slight, non-significant, decrease in overall scores was noted in both groups of subjects. Subsection analysis of items from the KSQ did not show significant differences in either group during the 6-month period. A significant decrease (month 0 28+/-1 vs. month 6 25+/-1; P = 0.02) in the HDS score was noted in rh-GH-treated but not in placebo-treated patients. There was a significant correlation (rs, -0.56, P = 0.05) between increase in IGF-I levels and decrease in HDS scores in rh-GH treated patients. CONCLUSION: The data demonstrate that low rh-GH dosages significantly improve psychological profiles as rated by HDS evaluation in adult-onset patients with GHD. On the other hand, a 6-month period of treatment does not produce any significant differences in quality of life as measured by KSQ between treated patients and placebo controls.

Adult↗