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Biomedical subjects

P Travaglini

Publications and source records attributed to P Travaglini.

At least 19 recordsLinked to original sources

Clinical phenotype and beta-cell autoimmunity in Italian patients with adult-onset diabetes.

OBJECTIVE: To characterize the phenotype of a large population of Italian patients with adult onset (> or =40 years) diabetes who were attending outpatient clinics and who were screened for glutamic acid decarboxylase 65 autoantibodies (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and IA-2beta/phogrin (IA-2betaA). DESIGN AND METHODS: This was a cross-sectional study comprising a total of 881 patients, aged < or = 70 years, diagnosed with type 2 diabetes after the age of 40 years, and consecutively recruited in five clinics located in different geographic areas of Italy (Milan, Florence, Rome, Naples and Catania). Their mean disease duration was 8.1 (6.9; s.d.) years. GADA, IA-2A and IA-2betaA were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2beta. Anthropometric and clinical data were collected and compared amongst patients with or without autoantibodies. RESULTS: Sixty-three (7.1%) patients had one or more autoantibodies, 58 (6.6%) had GADA, 22 (2.5%) had IA-2A, six (0.7%) had IA-2betaA and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2betaA, in the absence of GADA, were found in only five patients. Autoantibody-positive patients were more often female (63.5 vs 36.5%; P < 0.009), had higher glycated haemoglobin (Hb A1c) (P < 0.001), lower body mass index (BMI; P < 0.0005) and waist/hip ratio (WHR; P < 0.01); female gender being the main contributor to BMI and WHR. We did not observe any differences in age at diagnosis or duration of disease with respect to the presence or absence of islet autoantibodies. The proportion of patients on insulin therapy was higher in patients with two or more antibodies, compared with those with one antibody only, and no antibodies (P for trend < 0.001), and among patients with GADA, in those with higher antibody titre (73.9% in those with > 10 units vs 42.0% in those with < or = 10 units; P < 0.007). CONCLUSIONS: Patients with adult onset diabetes characterized by autoimmunity to beta-cells showed a clinical phenotype with anthropometric features that differed from those classically observed in patients with type 2 diabetes. The number and titre of autoantibodies, which reflect the severity of autoimmunity and beta-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings.

Aged↗

Assessing the presence of abnormal regulation of cortisol secretion by membrane hormone receptors: in vivo and in vitro studies in patients with functioning and non-functioning adrenal adenoma.

Regulation of cortisol secretion by aberrant hormone receptors may play a role in the pathogenesis of ACTH-independent Cushing's syndrome. In this study, the topic was evaluated by combining in vivo and in vitro approaches. Cortisol responses to various stimuli (standard meal, GnRH + TRH, cisapride, vasopressin, glucagon) were assessed in 6 patients with clinical or subclinical adrenal Cushing's syndrome, and non-functioning adrenal adenoma in two cases. Abnormal responses were observed in three patients with Cushing's syndrome; one patient showed a gastric inhibitory polypeptide (GIP)-dependent cortisol rise after meal, together with responses after GnRH and cisapride; the second patient showed an LH-dependent cortisol response to GnRH, and in the third cortisol rose after cisapride. The pattern of receptor expression performed by RT-PCR showed that while GIP-R was only expressed in tumor from the responsive patient, 5-hydroxytryptamine type 4 receptor and LH-R were also present in normal adrenal tissues and tissues from non-responsive patients. Interestingly, an activating mutation of Gsalpha gene was identified in one of these tumors. Therefore, cortisol responses to agents operating via Gs protein coupled receptors (in one case associated with Gsalpha mutation) were found in Cushing's patients, while these responses were absent in the others. The finding of receptor expression in normal and non-responsive tumors suggests that different mechanisms are probably involved in inducing in vivo cortisol responses.

Adenoma↗

Impaired estrogen-induced negative feedback on gonadotropin secretion in patients with gonadotropin-secreting and nonfunctioning pituitary adenomas.

BACKGROUND: Several in vitro studies suggest that gonadotropin-secreting pituitary adenomas (Gn-omas) and non functioning pituitary adenomas (NFPA) originate from gonadotroph cells. Patients with Gn-oma and NFPA frequently show abnormal gonadotropin response to TRH. The aim of the study was to investigate whether the estrogen-induced negative feedback is operating in either patients with Gn-oma or NFPA. MATERIALS AND METHODS: Serum gonadotropin levels were evaluated at 24 h after ethinylestradiol administration (1 mg per os; EE2 test) in seven patients with a diagnosis of Gn-oma, based on the presence of high follicle-stimulating hormone (FSH) and/or lutenising hormone (LH) levels with normal or high levels of sex steroids, in 22 patients with NFPA with normal or low levels of gonadotropin and sex steroids, and 30 sex- and age-matched healthy subjects. A normal response to EE2 test was arbitrarily defined as a serum LH and FSH decrease of at least 40 and 30% below basal levels. RESULTS: Among patients with Gn-oma, only one had a normal FSH inhibition and another, a normal LH inhibition. Among the 22 patients with NFPA, the EE2 test caused a normal FSH or LH reduction in 10 and 15, respectively, while a normal reduction of both FSH and LH was observed in nine. CONCLUSIONS: The study demonstrates that estrogen-induced negative feedback of gonadotropin secretion is disrupted in almost all patients with Gn-oma and in half of those with NFPA. This defective feedback is reminiscent of the resistance to thyroid hormones and glucocorticoids observed in patients with thyroid-stimulating hormone- (TSH-) and adrenocorticotropic hormone- (ACTH-)secreting adenomas, respectively.

Adenoma↗

Androgen secretion in ectopic ACTH syndrome and in Cushing's disease: modifications before and after surgery.

The role of ACTH in the control of adrenal androgen secretion is known, although the possible existence of other regulatory factors has been also suggested. While some data concerning Cushing's disease have been reported, only few studies concerned androgen levels in ectopic ACTH secretion. The aim of this study was to evaluate serum DHEA-S, androstenedione (A) and testosterone (T) levels in 36 women with ACTH-dependent Cushing's syndrome (30 with Cushing's disease and 6 with ectopic ACTH secretion) before and after surgery. Two men with ectopic ACTH production were also studied. In 30 women with Cushing's disease serum DHEA-S (9.6 +/- 0.9 micromol/l), A (15.2 +/- 1.2 nmol/l) and T (4.1 +/- 0.5 nmol/l) were higher than in controls (p < 0.01): elevated DHEA-S, A and T values were found in 8, 18 and 17 cases, respectively. After adenomectomy in 15 apparently cured patients DHEA-S, A and T levels were low at 1 - 3 months and at 6 - 12 months after surgery. At 18 - 24 months, DHEA-S remained low in spite of cortisol normalisation. In ectopic Cushing's syndrome, A levels were significantly higher (23.1 +/- 4.9 nmol/l) than in Cushing's disease (p < 0.05), while no differences were found in DHEA-S and T levels. Two patients had elevated DHEA-S values, 3 women had high T levels and 7 of the 8 patients had very high A concentration that was lowered in 3 operated cases. In conclusion, the pattern of adrenal androgen secretion is rather different in patients with pituitary or with ectopic Cushing's syndrome. While the frequency of DHEA-S and T alterations is similar, androstenedione secretion is greatly increased in the latter condition. It is suggested that in ACTH-secreting non-pituitary tumours, the production of a POMC-derived peptide, although unidentified, may lead to preferentially stimulated androstenedione secretion, without affecting other enzymatic pathways.

ACTH Syndrome, Ectopic↗

Effect of Thymomodulin on luteinizing hormone, prolactin and testosterone in male rats.

The effect of Thymomodulin (TMD), a calf thymus derivative, on luteinizing hormone, prolactin and testosterone was studied in male rats after acute and chronic treatment. The results showed that the stimulatory action on prolactin and testosterone secretion after acute (prolactin) or one month chronic (testosterone) treatments completely vanished during six month chronic administration. No effect was observed on luteinizing hormone after acute or chronic treatment.

Animals↗

Zinc and bromocriptine long-term administration in patients with prolactinomas: effects on prolactin and thymulin circulating levels.

Several studies have demonstrated zinc (Zn), prolactin (PRL) and thymulin (Zn-FTS) interplay: Zn inhibits, in a dose related manner, PRL release from lactotropes in vitro and stimulates thymulin synthesis in vivo both in humans and in animals. PRL receptors are present on thymic epithelial cells (TEC); PRL stimulates TEC trophism and activity. Little is known about the influence of PRL on Zn metabolism, though in prolactinomas we found reduced Zn and thymulin circulating levels. For this reason, we evaluated PRL, Zn, bioactive thymulin (Zn-FTS) and total thymulin (T-FTS: Zn-bound plus Zn-unbound form) serum levels in 58 patients with prolactinomas (PRL: 253 +/- 263 micrograms/L), Zn (82 +/- 23 micrograms/dl), Zn-FTS (2.2 +/- 0.20 log2(-1] and T-FTS (3.7 +/- 0.25 log2(-1] were significantly lower (p less than .01) than those found in age matched controls. Zn-unbound bioinactive thymulin form (FTS) levels were in the normal range. Bromocriptine administration (Brc) (2.5-5 mg p.o., b.i.d. for 9 months) to 20 patients with microprolactinomas lowered serum PRL levels (10.5 +/- 6.2 micrograms/L) and significantly increased (p less than .01) Zn (118.6 +/- 14.7 micrograms/dl), Zn-FTS (3.96 +/- 0.7 log2(-1)) and T-FTS (4.66 +/- 0.7 log2(1)) circulating levels. ZnSO4 administration (400 mg p.o. daily for 3 months) to 6 patients with microprolactinomas, significantly increased (p less than .01) Zn (136 +/- 18 micrograms/dl), Zn-FTS (4.5 +/- 0.5 log2(-1)) and T-FTS (5.6 +/- 0.9 log2(-1)) levels, while caused only a slight decrease in serum PRL concentrations (from 95 +/- 8 to 75 +/- 9 micrograms/L; p: NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Thymic endocrine activity in children with idiopathic growth-hormone deficiency.

Experimental and clinical evidences suggest that thymic endocrine function is modulated by the neuroendocrine network and in particular by growth hormone. The plasma of thymulin has been found reduced in congenital hypopituitarism and increased in acromegalic conditions when compared with the values observed in age-matched controls. In the present paper we have investigated in congenital GH-deficient children the effect of one year therapy with GH on the plasma level of thymulin, IGF-1 and plasma zinc; this last parameter has been checked because zinc is required for thymulin activity and modulates IGF-1 production. The basal thymulin and IGF-1 values are lower in GH deficient children than age-matched controls whereas zinc levels show a slight reduction. GH therapy induces a significant increment both of thymulin and IGF-1 levels and a slight increase of plasma zinc. A positive correlation has been found between zinc values and thymulin activity but not between GH and thymulin. Whether the recovery of thymulin production in GH deficient children by GH therapy is mediated by IGF-1 or by bioavailability of zinc ions remains to be established.

Adolescent↗

Prolactin, thymulin and zinc in chronic hemodialysis: effect of renal transplant.

The interrelationships between PRL, thymulin and Zn, were studied in 25 patients with chronic renal failure (CRF) undergoing kidney transplantation and immunosuppressed with cyclosporine A (CsA). The possible role of serum PRL levels in predicting allograft rejection was also investigated. Before the kidney transplant serum PRL levels were significantly higher than in normals (mean +/- SE, 28.3 +/- 7.1 vs 7.5 +/- 0.6 micrograms/l, p less than 0.001) and their response to TRH (200 micrograms iv) was impaired (mean delta % at peak, 45.4 +/- 9.5 vs + 641 +/- 47.5, p less than 0.001). After kidney transplantation a dramatic decrease in serum PRL concentrations was observed in all patients, followed by a slight upward trend in the following two weeks, while TRH test administered on 3rd, 7th and 14th day, induced a progressive increase in serum PRL responses (delta % at peak, 201 +/- 43.3, 220 +/- 37.1 and 305 +/- 15.5, respectively). No difference in serum PRL patterns was observed between patients with (8 cases) and without (17 cases) clinical features and kidney fine needle biopsies suggestive of rejection. Basal serum Zn levels of patients with CRF (18.1 +/- 0.6 mumol/l) were similar to those observed in normals (17.7 +/- 0.2 mumol/l) and without any correlation with serum PRL levels. A decrement in serum Zn was recorded during CsA infusion and on the first day after the surgery, followed by a slight and slow upward trend. Basal serum thymulin titers were low [2.92 +/- 0.18 (1/log2)], were further reduced after CsA infusion [1.68 +/- 0.15 (1/log2)] and returned to the pretransplant levels in the two weeks after grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of oral zinc administration on prolactin and thymulin circulating levels in patients with chronic renal failure.

High serum PRL and low zinc (Zn) levels are common findings in patients with chronic renal failure (CRF); in such patients serum Zn concentrations have been reported to be inversely correlated to serum PRL levels. Moreover, Zn regulates both thymus growth and the biological activity of the thymic hormone thymulin, and PRL-thymic interrelationships have been described. To determine whether hypozincemia alters serum PRL and plasma thymulin concentrations in CRF, 9 men with CRF treated by chronic hemodialysis were given 400 mg/day Zn sulfate, orally (4.96 meq/day Zn), for 6 months. Before treatment, serum PRL levels were significantly higher (P less than 0.001) in these patients than in normal men [mean, 28.7 +/- 20.7 (+/-SD) vs. 7.5 +/- 3.7 micrograms/L], and their serum PRL response to TRH (200 micrograms, iv) was impaired (mean maximal percent increase, 38.2 +/- 10.9 vs. 641 +/- 335; P less than 0.001). The plasma Zn-bound bioactive thymulin titer (1.3 +/- 0.7 1/log2), total thymulin titer (Zn-bound plus Zn-unbound forms, 2.1 +/- 0.8 1/log2), and serum Zn (13.1 +/- 2.4 mumol/L) were lower (P less than 0.001) in men with CRF than in normal men. Zn therapy did not induce any significant change in basal and TRH-stimulated serum PRL levels, while serum Zn levels significantly increased, reaching the normal range after the first week of treatment (17.8 +/- 6.3 mumol/L). Plasma total thymulin increased rapidly, reaching normal levels after 1 week, but Zn-bound thymulin increased modestly during the first month of treatment and more after 3 and 6 months of treatment. There was no age-related difference in plasma thymulin levels during therapy. We conclude that oral Zn administration in patients with CRF significantly increases both total and Zn-bound thymulin, but does not modify basal and TRH-stimulated serum PRL levels. The observation that Zn supplementation markedly increased plasma thymulin levels in uremic patients suggests that Zn is a potent stimulus for thymic hormone synthesis, and it can reverse the age-related diminution of thymic activity in CRF patients.

Adult↗

Vasoactive intestinal polypeptide and dopamine: effect on prolactin secretion in normal women and patients with microprolactinomas.

In order to investigate the influence of dopamine (DA) in modulating prolactin (PRL) response to vasoactive intestinal polypeptide (VIP), VIP (75 micrograms i.v. over 12 min) was administered to normal women and patients with microprolactinomas during saline or DA (0.06 micrograms/kg BW/min) infusion. In 8 normal women VIP caused PRL to rise from 7.9 +/- 0.8 (mean +/- SE) to 33.4 +/- 17.1 ng/ml (p less than 0.01), the peak occurring at 15 min, while it did not elicit any significant modification in serum PRL levels in 18 patients with microprolactinomas. DA infusion lowered serum PRL by 67 and 58.2% at 120 min in normal women and in patients with microprolactinomas, respectively, and abolished VIP-induced PRL response in normal women without influencing PRL response in patients with microprolactinomas. PRL responsiveness to VIP was not restored by dopaminergic disinhibition (domperidone 10 mg i.v.) in 4 patients tested. Two previously unresponsive patients showed a VIP-induced PRL increase, superimposable on that recorded in normal women, after successful selective adenomectomy. These data suggest that DA, although able to suppress VIP-induced PRL response in normals, does not play any major role in causing unresponsiveness to VIP in prolactinomas. The lack of PRL responsiveness to VIP might be intrinsic to the adenoma or due to alterations of PRL secretion regulatory mechanisms other than DA secondary to the presence of the tumor, or to a depletion of the readily releasable pool of PRL.

Adolescent↗

Dihydroergocriptine in management of microprolactinomas.

The effects of dihydroergocriptine (DHECP), a dihydrogenated ergot alkaloid with dopaminergic agonistic and alpha-adrenergic antagonistic properties, were studied in 22 women with PRL-secreting microprolactinomas and compared with those recorded in 36 previously studied patients treated with bromocriptine (BRC). After acute administration of 5 mg DHECP, orally, serum PRL decreased by 61 +/- 18% (+/- SD); only 1 patient was unresponsive. The nadir was reached at 300 min. Long term treatment with increasing DHECP doses caused a progressive PRL fall from 125 +/- 142 (+/- SD) to 81 +/- 159 micrograms/L after 1 week of a 3 mg twice daily regimen, to 64 +/- 88 micrograms/L after 1 week of 5 mg twice daily, 46 +/- 57 micrograms/L after 1 week of 10 mg twice daily, and 28 +/- 34 to 33 +/- 45 micrograms/L throughout 9 months of treatment with 10 mg DHECP 3 times daily. Seventy-seven percent of patients had normal serum PRL levels during chronic treatment. All women, including those with supranormal serum PRL levels, resumed regular menses, and 16 had ovulatory cycles; 1 woman became pregnant. Galactorrhea disappeared in all. During treatment the PRL response to TRH, initially absent in all patients, became positive in 10. In 7 patients, after DHECP treatment for 9 months, high definition computed tomographic scan no longer showed the focal lesions initially seen. After drug withdrawal, serum PRL increased again in all except 1 patient. Two patients had regular menses for 6 months, and 3 still had no adenoma imaged by high definition computed tomography. In BRC-treated patients the serum PRL changes and clinical results were very similar to those in the DHECP-treated patients, except for the persistence of normal serum PRL levels in 4 patients after drug withdrawal. On the other hand, side-effects were negligible during DHECP treatment, but remarkable during BRC. Systolic and diastolic blood pressures decreased by only 5.4 and 3.0 mm Hg, respectively, after acute 5 mg DHECP administration, but decreased by 12.8 and 14 mm Hg after acute 2.5 mg BRC administration. Orthostatic hypotension and peripheral vasomotor phenomena occurred in the long term DHECP treated patients except one, but they occurred in 9 and 3 of those treated with BRC, respectively. Gastric discomfort or mild nausea occurred in 12 DHECP-treated patients, while mild or severe nausea or vomiting were observed in 18, 11, and 2 of those taking BRC, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

A double-blind clinical trial for the evaluation of the therapeutical effectiveness of a calf thymus derivative (Thymomodulin) in children with recurrent respiratory infections.

The effectiveness of an orally administrable thymic derivative (Thymomodulin) for the treatment of the recurrent respiratory infections (RRI) in children has been studied in a double-blind clinical trial with historical comparison. In the Thymomodulin treated group a significant decrease of the monthly frequency of RRI has been observed in comparison with the previous year (P less than 0.05) and with the placebo treated group (P less than 0.002). The evaluation of the laboratory data at the beginning of the study didn't show in the two groups typical alterations of the common hematological and immunological parameters, but at the end of the trial a statistically significant increase of the levels of salivary IgA has been noticed only in the Thymomodulin treated group (P less than 0.02).

Administration, Oral↗

Abnormalities of sex hormones in men with systemic lupus erythematosus.

Sex hormone concentrations were studied in 10 men with systemic lupus erythematosus (SLE) before and after HCG stimulation and compared with those of 10 healthy volunteers. The SLE men had significantly lower testosterone/estradiol ratios (before HCG test) and significantly lower mean increases in testosterone after HCG stimulation than the normals. Our findings confirm that there are sexual hormone abnormalities in SLE and suggest that these abnormal patterns may be important in the modulation of immune responses in SLE.

Adult↗

Bromocriptine treatment of microprolactinomas: evidence of stable prolactin decrease after drug withdrawal.

Thirty-six women with PRL-secreting pituitary microadenomas [mean PRL, 114 +/- 12.5 (+/- SE) ng/ml] were treated with bromocriptine (BRC; 2.5-10 mg/day) for 12 months. During BRC treatment, serum PRL decreased in all patients. After termination of treatment, mean serum PRL levels, evaluated at 15, 30, and 45 days, were significantly decreased (-41.6%, -43.0%, and -40.2%, respectively) compared to pretreatment values. The patients were arbitrarily divided into 3 groups: 12 responders, in whom the PRL persistent posttreatment decrease was greater than 50%, 8 hyporesponders, in whom the PRL decrease was between 30% and 50%, and 16 nonresponders with absent or negligible PRL decrease. Four patients had normal PRL levels and clinical remission for 14-30 months after BRC withdrawal. In 18 women, BRC treatment was repeated for another 12 months. After termination of treatment, 11 patients were responders, 1 was a hyporesponder, and 6 were nonresponders. Four of these 18 patients still had normal PRL levels 8-28 months after drug discontinuation. The responses of PRL to TRH and domperidone were compared before and after termination of treatment at 30 and 45 days, respectively. Both mean peak values of PRL and absolute increases after TRH treatment were similar before and after BRC administration; however, a PRL response to TRH was present in 15% of 26 patients before treatment and in 42% after treatment. The mean peak values after domperidone were similar before and after BRC treatment, but the absolute increase over the basal value was much higher after BRC; PRL response to domperidone was present in 16% of 19 patients before BRC treatment and in 74% after BRC. These data suggest that BRC is effective in the treatment of some microprolactinomas; BRC effectiveness improves after prolonged periods of administration. The variations in PRL responses to TRH and domperidone suggest profound modification of PRL secretion after BRC treatment.

Adenoma↗