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Biomedical subjects

E Ciccarelli

Publications and source records attributed to E Ciccarelli.

At least 55 records · Page 3Linked to original sources
PubMed1992

Purification, primary structure and molecular cloning of a rat ribosomal protein showing homology with yeast ribosomal protein YL34.

1. A new 17-kDa mammalian ribosomal protein (PR17) was purified to homogeneity from the rat exocrine pancreas. The purification procedure was based on acidic extraction of a heat-denatured homogenate, ammonium-sulfate precipitation, hydrophobic chromatography on phenyl-Sepharose and analytical reverse-phase HPLC on mu Bondapak C18. Fractions of interest were collected using an antiserum directed against the first (1-14) moiety of somatostatin (1-28). 30 micrograms pure RP17 were obtained from 1 g fresh pancreas. 2. A short 111-b cDNA encoding RP17 was amplified from rat pancreatic first-strand cDNA template by using two 64-fold degenerate heptadecamer primers in the DNA-polymerase-chain reaction. From the sequence of amplified cDNA, an unambiguous oligonucleotide probe was designed to screen a rat pancreatic cDNA library. A cDNA clone coding for RP17 was isolated, whose nucleotide sequence, with an open reading frame coding for 155 amino acids (molecular mass of 17,199 Da), confirmed the partial amino acid sequences directly obtained from the purified protein. 3. Northern-blot analysis showed that a similar 0.75-kb transcript was present in rat pancreas, in the rat pancreatic acinar cell line AR 4-2J and in the human neuroblastoma cell-line NB-OK-1, the highest level being in the latter two preparations, despite similar levels of RP17 in all three preparations, as tested with a rabbit antiserum directed against purified RP17. 4. The N-terminal sequence of both RP17 and the ribosomal protein YL43 from Saccharomyces cerevisiae (39 amino acid residues) showed a high degree of identity (77%), indicating that RP17 is a mammalian homolog of yeast ribosomal protein YL43.

Amino Acid Sequence↗
PubMed1992

Normal development of lymphokine activated killing (LAK) in peripheral blood lymphocytes from hyperprolactinemic patients.

The effect of prolactin on the interleukin 2 (IL2)-driven development of Lymphokine Activated Killing (LAK) by normal PBL and by PBL from hyperprolactinemic patients was investigated. Concentrations of PRL corresponding to the physiological serum levels of the hormone and to the Kd of the PRL receptors on NK cells (6-20 ng/ml, 0.3-1 nM) had no effect on the generation of LAK activity by normal PBL, whereas 100-200 ng/ml were slightly, although significantly, inhibitory. By contrast, PBL from 16 hyperprolactinemic patients developed levels of LAK activity comparable with those generated by PBL from age- and sex-matched normoprolactinemic donors.

Adolescent↗
PubMed1992

Dose-dependent suppression of serum prolactin by cabergoline in hyperprolactinaemia: a placebo controlled, double blind, multicentre study. European Multicentre Cabergoline Dose-finding Study Group.

OBJECTIVE: Dopamine agonists have a well established place in the treatment of hyperprolactinaemic disorders but their use is associated with a high incidence of adverse effects. We have investigated the biochemical efficacy and side-effect profile of a range of doses of the novel, long-acting dopamine agonist, cabergoline, in suppressing prolactin (PRL) in hyperprolactinaemic women. DESIGN: Multicentre, prospective, randomized, placebo controlled and double blind. PATIENTS: One hundred and eighty-eight women with hyperprolactinaemia secondary to microprolactinoma (n = 113), idiopathic disease (n = 67), empty sella syndrome (n = 7) or following failed surgery for a macroprolactinoma (n = 1). MEASUREMENTS: Weekly assessment of adverse symptoms, blood pressure and pulse, serum PRL, blood count, liver and renal function. RESULTS: Patients received either placebo (n = 20) or cabergoline 0.125 (n = 43), 0.5 (n = 42), 0.75 (n = 42) or 1.0 mg (n = 41) twice weekly for 4 weeks. The five treatment groups were comparable in age (mean 31.8, range 16-46 years), diagnosis, previous therapy, and pretreatment serum PRL. PRL was suppressed to below half the pretreatment level in 5, 60, 90, 95 and 98% and normalized in 0, 30, 74, 74 and 95% of patients taking placebo or cabergoline 0.125, 0.5, 0.75 or 1.0 mg twice weekly respectively (Armitage's test, chi 2 = 39.3, P < 0.01). Cabergoline therapy (all doses) restored menses in 82% of the amenorrhoeic women not previously treated with dopamine agonists. Adverse events were recorded in 45% of patients in the placebo group and in 44, 50, 50 and 58% of those taking 0.125, 0.5, 0.75 and 1.0 mg cabergoline twice weekly (Armitage's test, P > 0.05). Over 95% of reported symptoms were relatively trivial, most frequently transient nausea, headache, dizziness, fatigue and constipation. More severe adverse events, interfering significantly with the patients' lifestyle, occurred in 13 (7.7%) patients taking cabergoline; treatment withdrawal was necessary in only one case. No adverse effects were detected on blood pressure or haematological or biochemical parameters. CONCLUSIONS: We have shown a linear dose-response relationship for cabergoline in the treatment of hyperprolactinaemia in the range 0.125-1.0 mg twice weekly, with normalization of PRL in up to 95% of cases and acceptable tolerability throughout the dose range.

Adolescent↗
PubMed1990

BiP expression is not increased by the accumulation of PiZ alpha 1-antitrypsin in the endoplasmic reticulum.

PiZ, a mutant human alpha 1-antitrypsin, is associated with liver and pulmonary disease and is characterized by defective secretion and accumulation of the protein in the endoplasmic reticulum. We tested the hypothesis that BiP (a protein that binds newly synthesized protein in the endoplasmic reticulum, prevents secretion of incorrectly folded protein, and solubilizes protein aggregates), could play a part in the retention of PiZ alpha 1-antitrypsin in the endoplasmic reticulum. Subcellular fractions from PiM (normal) and PiZ livers were prepared and analyzed by immunoblotting. No increase of BiP was detected in the PiZ liver. In addition, when total RNA from the same livers were analyzed by slot and Northern blot hybridization, no difference was found in the level of BiP mRNA between PiM and PiZ livers. Similar results were found in clones of CHO and MDCK cells transfected with PiM of PiZ alpha 1-antitrypsin cDNAs. These results indicate that BiP does not play a part in the retention of PiZ alpha 1-antitrypsin and suggest that PiZ protein is not misfolded.

Animals↗
PubMed1990

Subcutaneous growth hormone-releasing hormone augments pulsatile nocturnal GH release in GH-insufficient children, but may also raise basal GH secretion.

Growth hormone-releasing hormone (GHRH) when given s.c. to GH-insufficient children either as pulses, or once or twice daily, promotes linear growth. These treatment regimens, however, are not ideal as they require frequent drug administration and a significant proportion of patients do not show improved growth. We have now investigated the GH response to a nocturnal s.c. infusion of GHRH (1-29)NH2, at two dosages, 5 and 10 micrograms/kg/h, in a group of five GH-insufficient children. The s.c. infusion of GHRH between 2100 h and 0600 h augmented nocturnal pulsatile GH release in all five children. There was a dose-dependent response for the GH area under the curve (AUC), and mean total GH concentration. The AUC for GH was significantly greater after the 10 than 5 micrograms/kg/h GHRH which in turn was greater than that after placebo; mean (SD) AUC: 14816 (3978), 8125 (1931), 3032 (1582) mU min/l respectively (P less than 0.01 and P less than 0.05). There was no significant change in the number of GH pulses during the 9-h infusions when the subjects were infused with GHRH 10 or 5 micrograms/kg/h compared to placebo, and they occurred at similar times although the number of pulses tended to be greater after GHRH; the mean (SD) numbers of GH pulses were 5.0 (0.7), 3.8 (0.8), 3.2 (0.8), respectively. There was however a significant rise in the mean baseline GH concentration in all patients during the infusion of GHRH 10 micrograms/kg/h compared to placebo, but not with 5 micrograms/kg/h. Thus, GHRH(1-29)NH2 given s.c. augmented nocturnal pulsatile GH release in GH-insufficient children but it also increased baseline GH secretion. These results suggest that a sustained release preparation of GHRH could be a potential treatment for GH-insufficient children, and that a dose of 5 micrograms/kg/h would promote pulsatile GH release, but that at higher dosage it may also raise basal GH secretion.

Child↗
PubMed1990

Long-term follow-up of 'cured' prolactinoma patients after successful adenomectomy.

The long-term follow-up (greater than or equal to 4 years) of clinical, hormonal and radiological aspects in 22 'cured' prolactinoma patients after adenomectomy was studied. Dynamic secretion of PRL and TSH was also evaluated, in order to identify the persistence of any underlying abnormality of hypothalamic pituitary control and to predict relapses. A relapse into hyperprolactinaemia was shown in 36% of patients 5-90 months (mean 46) after surgery. This was accompanied by reappearance of clinical symptoms but not by the radiological demonstration of the adenoma in any patients. A significant PRL rise after domperidone, a dopaminergic antagonist drug, was shown in cured patients after surgery (mean +/- SEM peak, 2977 +/- 645 mU/l) but this was markedly lower than that observed in control subjects (5732 +/- 440 mU/l). In fact, normal PRL increments were shown in only 6/16 (37%) patients. TSH hyper-responsiveness to domperidone normalized in only 46% of patients. Similar PRL responses to those obtained with domperidone were shown when a TRH test was given. A relapse into hyperprolactinaemia was observed in six of ten (60%) non-responders to domperidone and in four of seven (57%) non-responders to TRH, whereas six normal responders to domperidone and TRH had not relapsed at that time. Plasma PRL levels during pregnancy showed increments lower than those observed in normal pregnant women only in domperidone and TRH non-responder patients. These results indicate that a relapse into hyperprolactinaemia and a blunted PRL rise during pregnancy were present only in patients with persistently reduced PRL response to dynamic tests.

Adenoma↗
PubMed1989

Porcine D-amino acid oxidase: production of the biologically active enzyme in Escherichia coli.

DNA molecules coding either for mature porcine D-amino acid oxidase or for truncated forms of the enzyme have been obtained by stepwise addition of synthetic oligonucleotides to a partial cDNA. Under the control of the lambda PL thermoregulatable promoter, these DNAs were respectively expressed in Escherichia coli as 36, 28 and 25 kilodalton polypeptides, specifically recognised by antibodies raised against the natural enzyme. None of the truncated proteins were biologically active whereas the mature recombinant species was able to hydrolyze D-alanine in vitro as efficiently as the natural product.

Animals↗
PubMed1989

Long-term treatment with a new repeatable injectable form of bromocriptine, Parlodel LAR, in patients with tumorous hyperprolactinemia.

A new long-acting repeatable injectable form of bromocriptine, (Parlodel LAR, Sandoz, Basle, Switzerland) has recently been developed. We studied the clinical, hormonal and radiological changes in six female patients with microprolactinomas and eight (3 female and 5 male) with macroprolactinomas receiving monthly injections of Parlodel LAR 50 to 100 mg for 6 months. Five patients with microadenomas and 4 with macroadenomas had normal prolactin (PRL) levels with Parlodel LAR 50 mg after one (5 patients), two (2 patients), or five (2 patients) injections; two patients with macroadenomas had normal or near normal PRL levels only after 4 monthly injections of 100 mg. Clinical improvement paralleled the changes in serum PRL. A complete normalization of a visual field defect occurred in one patient after 5 months of therapy. Marked shrinkage of the adenoma was shown by magnetic resonance and/or computed tomographical imaging in three patients with macroadenomas after 1 week. Side-effects were mild and usually transient. Parlodel LAR represents a novel treatment of hyperprolactinemic states which is both effective and well tolerated, and appears to be a useful alternative to oral therapy for long-term treatment.

Adenoma↗
PubMed1989

Effectiveness and tolerability of long term treatment with cabergoline, a new long-lasting ergoline derivative, in hyperprolactinemic patients.

Cabergoline (CAB) is a new oral dopaminergic compound showing a very long-lasting PRL-lowering activity and reported to be well tolerated. The efficacy and tolerability of chronic treatment with CAB in 30 female hyperprolactinemic patients, aged 18-52 yr (6 microadenomas, 3 macroadenomas, and 21 functional hyperprolactinemias), were studied. In a group of 10 patients who received CAB (0.8 mg once weekly or 0.4 mg twice weekly) for 8 weeks PRL levels normalized while on treatment and remained normal (8 patients) or greatly reduced (1 patient) for 1-2 months after discontinuation of the drug. Twenty-six patients underwent chronic treatment (6-12 months) with an initial dose of 0.5 mg once weekly, subsequently increased to 1-2 mg in 10 patients and decreased in the other 2. Due to severe side-effects CAB was discontinued in 3 patients, in 1, 8, and 12 weeks. A significant reduction of PRL levels was already observed after the first week of treatment (mean +/- SEM basal values, 90.1 +/- 13.3 vs. 29.5 +/- 6.3 micrograms/L; P less than 0.001). Twenty-two patients had normal PRL levels in 1-36 weeks (mean, 6 weeks) with 0.5-2 mg CAB. Twenty-two patients resumed regular menses; 2 patients became pregnant after 3-11 months of treatment. Thirteen patients complained of side-effects (nausea, hypotension, headache, gastric pain, dizziness, and weakness) that disappeared with time in 10 of them. The comparison with a previous bromocriptine treatment regimen in 20 patients had shown that the number of patients requiring discontinuation of the latter drug was significantly higher (7 vs. 3 patients; P less than 0.001). However, 2 patients who needed to discontinue CAB were able to tolerate bromocriptine therapy. A computed tomographic scan performed after 12 months of therapy in 7 patients showed a significant reduction (50%) of the adenoma in 5. In conclusion, our results show that CAB is a well tolerated new dopamine agonist with long-lasting activity that represents an advance in chronic medical treatment of hyperprolactinemic conditions.

Adenoma↗
PubMed1989

Insulin-like growth factor I and daily growth hormone profile in the assessment of active acromegaly.

A poor correlation exists between growth hormone levels and the severity of disease in patients with acromegaly. It has been suggested that insulin-like growth factor I correlates better with the clinical condition thaN GH itself, but the presence of a correlation between GH and IGF-I is still a matter of debate. We therefore studied the fasting concentration of acid-extracted IGF-I and the daily GH profile (at 08.00, 12.00, 16.00, 20.00 h) in 28 acromegalic patients, both in basal condition and at different times after treatment. All patients studied before treatment exhibited a GH mean daily concentration always above 5 micrograms/l (range 5.15-1.47 micrograms/l), and IGF-I values (1.99-6.85 U/l) always above the normal range (0.38-1.90 U/l). During the follow-up after medical, surgical or radiation therapy we did not observe normalization of the IGF-I concentration for a GH day curve value above 5 micrograms/l. Compared with the GH day curve, a single morning GH value was slightly less sensitive and definitely less specific. The analysis of covariance evidenced a good correlation (P less than 0.001) between the GH day curve and IGF-I concentration during the first 6 months of medical as well as during the first year of radiation therapy, and after surgical treatment. Our data indicate that a single determination of acid-extractable IGF-I is as reliable as GH multiple sampling to assess the acromegalic disease activity.

Acromegaly↗
PubMed1989

Long-term effects of radiotherapy for acromegaly on circulating prolactin.

In 61 acromegalic patients, serum PRL was assessed (off medical treatment) before and 2 to 12 (mean 6.4) years after external beam radiotherapy. Before radiotherapy elevated PRL levels were present in 22 of 35 males (63%) and 12 of 26 females (46%) and were above 1000 mU/l in 11 males and 5 females. When studied for up to 5 years after radiotherapy, 22 of 23 (96%) patients who had not had surgery and who had normal PRL pre-radiotherapy showed an increased PRL level and this was also seen in 17 of 27 (63%) who had been hyperprolactinaemic initially. In contrast, 10 of 27 patients (37%) who had elevated pre-radiotherapy levels (all greater than 1000 mU/l) had a reduction in PRL values after radiotherapy. In all 11 patients who underwent surgery before radiotherapy, an increase in PRL was seen after radiotherapy. In the 21 patients followed for 10-12 years, the peak PRL value occurred 1-6 years after radiotherapy. After this, a progressive reduction of PRL to normal was seen. Normal levels were reached 4 to 10 years after radiotherapy. No correlation was found between pretreatment PRL values and final GH values in the whole group, nor between changes in PRL and the development of impaired ACTH or TSH secretion. Thus, different patterns of PRL behaviour suggest that radiotherapy treatment may either produce hyperprolactinemia from mild hypothalamic damage or ablate PRL secreting cells if they were present in the tumour before treatment. These changes do not predict final GH results or the development of hypopituitarism after radiotherapy.

Acromegaly↗
PubMed1989

A case of methimazole-induced hypothyroidism in a patient with endemic goiter: effects of endogenous TSH hyperstimulation after discontinuation of the drug.

Serum thyroid hormone and TSH concentrations were monitored in a patient with multinodular endemic goiter and severe methimazole (MMI) induced hypothyrodism up to 190 days after drug withdrawal. Serum concentrations of TT3, TT4 and TSH returned to normal values at the 6th., the 140th, and the 120th. day respectively. Within the first 20 days after MMI withdrawal the increase of serum T3 levels was correlated with the observed decrease of serum TSH concentrations. Successively T3 values decreased and T4 levels progressively increased. Six months after MMI withdrawal basal serum TSH concentration was normal while an exaggerated response to TRH was observed. We think that this peculiar hormone pattern is due to iodine depletion. In this case TSH hyperstimulation increases predominantly T3 secretion demonstrating the reduced thyroidal ability to produce T4 when hyperstimulated.

Female↗
PubMed1988

Terguride--a new dopamine agonist drug: a comparison of its neuroendocrine and side effect profile with bromocriptine.

Terguride, the C9-10 dihydrogenated derivative of lisuride, is a new drug which inhibits pituitary prolactin (PRL) secretion. It has mixed dopaminergic-antidopaminergic and alpha 2-antiadrenergic activity, and has proved useful in the clinical management of hyperprolactinemia. However, no trial comparing its use with the standard dopamine agonist bromocriptine has been reported. We have therefore compared three doses of terguride with bromocriptine 2.5 mg and placebo in a randomized double-blind crossover trial in eight normal volunteers. Terguride showed a potent dose-dependent PRL-inhibiting and growth hormone (GH)-releasing effect, while no significant changes were observed in thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), or luteinizing hormone (LH) in comparison to placebo. The neuroendocrine profile of terguride 1 mg was identical to that of bromocriptine, with a significant reduction in PRL still evident at 24 hours. However, in this small group of normal subjects, the side effects experienced at any dose of terguride were significantly less than with bromocriptine. Terguride 1 mg was always preferred to bromocriptine, while the lower doses were indistinguishable from placebo. Terguride is therefore likely to play an important role in the treatment of hyperprolactinemia.

Adult↗
PubMed1988

Vertebral bone density in non-amenorrhoeic hyperprolactinaemic women.

Recently, a decrease in bone mineral content (BMC) in hyperprolactinaemic women with long-lasting amenorrhoea has been reported, and attributed either to a direct effect of PRL on bone or secondary to the oestrogen deficiency. To verify if PRL by itself has a direct effect on bone, we have studied BMC at the lumbar level by double-photon absorptiometry in 22 patients with hyperprolactinaemia, selected on the basis of normal or near-normal oestradiol levels. The results were compared with those obtained in 28 healthy closely-matched women, and seven hyperprolactinaemic patients with long-lasting amenorrhoea and oestrogen deficiency. No significant difference in BMC was observed between hyperprolactinaemic patients with normal oestrogen levels (mean +/- SEM = 3.87 +/- 0.10 gHA/cm) and normal subjects (mean +/- SEM = 3.76 +/- 0.10 gHA/cm). Moreover, no significant change was observed during a 6 month follow-up in 13 patients. On the other hand, a significant difference (P less than 0.05) was detected in BMC between the hyperprolactinaemic patients with normal oestradiol levels and those with long-lasting amenorrhoea and oestrogen deficiency (mean +/- SEM = 3.39 +/- 0.18). These results suggest that hyperprolactinaemia by itself is not a risk factor for the development of osteoporosis.

Adult↗
PubMed1987

Long term treatment with oral single administration of bromocriptine in patients with hyperprolactinemia.

In the treatment of hyperprolactinemia bromocriptine is generally administered in 3 daily doses during the day. Due to the limited compliance of patients under this long term regimen, in 16 hyperprolactinemic patients we investigated the efficacy and tolerability of the treatment with this dopaminergic drug administered as a single evening dose. This dose was the same which the patients had been assuming previously on a tid basis. Chronic treatment (4-12 months) with an oral single evening dose of bromocriptine is able to control plasma PRL at least as well as the traditional tid regimen (2.8-21.6 ng/ml vs 1.2-31.8 ng/ml). Furthermore, during this single dose regimen the side effects were of lesser intensity and extent. Since the compliance of the patients with the single dose regimen was very good and the efficacy the same in reducing plasma PRL and controlling the clinical manifestations with a lower rate of side effects, we suggest to extend this regimen to all patients with hyperprolactinemia treated with bromocriptine after successful reduction of plasma PRL levels is obtained.

Administration, Oral↗
PubMed1987

Effects of a new long-acting form of bromocriptine on tumorous hyperprolactinemia.

Recently, a new long-acting form of bromocriptine (Parlodel LA, Sandoz) has been developed and it has already been found to be effective in lowering plasma PRL levels in normal volunteers and postpartum women. This work reports the clinical, hormonal and radiological effects of a single 50 mg dose of long-acting bromocriptine in 10 patients with tumorous hyperprolactinemia (2 microprolactinomas, 6 macroprolactinomas, 1 acromegaly and 1 nonsecreting macroadenoma). A rapid and long-lasting (28 days) normalization of PRL levels was observed in patients with microprolactinoma, acromegaly and nonsecreting adenoma. None of the 6 patients with macroprolactinoma underwent normalization of plasma PRL, but the latter was markedly reduced (61-80% of basal levels). A second injection of the drug in 5 macroprolactinoma patients induced a further reduction of plasma PRL levels in 2 of them. No changes in the tumor size were observed either after the first or the second injection of long-acting bromocriptine in any of the patients. This injectable form of bromocriptine induced nausea and/or mild hypotension lasting a few h in 4 of the 10 patients and was better tolerated than the oral form as regards both the duration and intensity of the side effects. Thus, as this drug has proved to be efficacious and well tolerated by the patients, this long-acting form of bromocriptine may be a valid therapeutical approach for initiating medical treatment of patients with prolactinoma.

Acromegaly↗
PubMed1987

Porcine D-amino acid oxidase: determination of the mRNA nucleotide sequence by the characterization of genomic and cDNA clones.

Oligodeoxynucleotide probes derived from the published amino acid (aa) sequence for D-amino acid oxidase (DAO) [Ronchi et al. J. Biol. Chem. 259 (1982) 8824-8834] were used to screen cDNA libraries made from porcine kidney cortex and liver. Whereas no clones were obtained from kidney mRNAs, 20 independent ones were isolated from the liver library. Surprisingly, all of them carried only partial cDNAs for DAO starting around aa 100 in the coding sequence and extending for up to 250 bp in the 3'-noncoding sequence. One of these clones, pULB9103, was used to screen a porcine genomic library and allowed the isolation of DAO gene clone phULB001. Four exons encoding aa 1-151 were identified and sequenced, as well as the relevant exon-intron junctions. The mRNA sequence coding for DAO has been reconstituted from the genomic and cDNA sequences; its analysis by computer did not reveal any significant secondary structure, or particular feature, which could explain the failure to obtain full-length cDNAs.

Amino Acid Sequence↗