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Biomedical subjects

C Davoli

Publications and source records attributed to C Davoli.

At least 19 recordsLinked to original sources

Expression of nerve growth factor-like polypeptides and immunoreactivity related to the two types of neurotrophin receptors in earthworm tissues.

Nerve growth factor (NGF) belongs by sequence homology to the neurotrophins, a family of proteins binding the same p75 receptor and closely related members of the Trk family of receptor tyrosine kinases. Fundamental in the vertebrate nervous system, neurotrophin signals have also been suggested as essential for relatively complex nervous systems occurring in invertebrate species that live longer than Caenorhabditis elegans and Drosophila melanogaster. Mammalian neurotrophins have been found to influence invertebrate neuronal growth. However, there are only a few data on the presence of molecules related to neurotrophin signalling components in invertebrates. Our studies provide evidence that analogues of neurotrophins and neurotrophin receptors are expressed in Eisenia foetida earthworms. In particular, NGF-like and Trk-like immunoreactive proteins are both expressed in the nervous system, whereas p75-like positivity identifies tubular structures associated with dorsal pores that are involved in the earthworm response to mechanical irritation or stress.

Animals↗

p27: a potential main inhibitor of cell proliferation in digestive endocrine tumors but not a marker of benign behavior.

The immunohistochemical expression of the inhibitors of cyclin-dependent kinases p21 and p27 was investigated in 109 endocrine tumors of the pancreas and gastrointestinal tract and compared with that of Ki67 and p53. p21 was found to be scarcely expressed without significant differences between benign and malignant or between differentiated and undifferentiated tumors. This suggests no relationship between changes in p21 levels and clinical behavior in these endocrine tumors. p27 was found to be highly expressed in differentiated neoplasms and proved to be inversely related to Ki67 labeling (P =.02), which was usually low. These data indicate that p27 may have an important inhibiting role on the low proliferation rate of the tumors. Moreover, the protein may have a role in the resistance of differentiated endocrine tumors to chemotherapeutic agents. p27 high-expressor neoplasms were frequent in either benign (70.6%) or malignant (81.4%) differentiated tumors, thus not allowing the use of this protein for the differential diagnosis of malignant neoplasms as suggested for endocrine tumors of parathyroid and pituitary. Poorly differentiated endocrine carcinomas, which differred from the differentiated tumors for their very high Ki67 levels and frequent p53 expression, showed low or absent p21 and p27 in most cases. Classical midgut carcinoids were characterized by a sharp discrepancy between malignant behavior and very bland proliferative pattern, with Ki67 and p27 expressions similar to that of benign tumors.

Adenoma, Islet Cell↗

A comparison of cyclosporine, sulfasalazine, and symptomatic therapy in the treatment of psoriatic arthritis.

OBJECTIVE: To compare the efficacy and tolerability of cyclosporine (CSA) with that of symptomatic therapy (ST) alone and sulfasalazine (SSZ) in the treatment of psoriatic arthritis (PsA). METHODS: Twelve rheumatology centers recruited 99 patients with active PsA in a 24 week, prospective, randomized, open, controlled study. The patients were treated with CSA (3 mg/kg/day) or SSZ (2,000 mg/day) plus ST, or ST alone (nonsteroidal antiinflammatory drugs, analgesics, and/or prednisone < or = 5 mg/day). The primary endpoint was the 6 month change in pain. Analyses were on the basis of the intention-to-treat principle. RESULTS: In comparison with both SSZ and ST, there was a statistically significant difference in favor of CSA in terms of the mean changes in the pain score (p < 0.05), which was considered the primary response variable. A significant decrease in favor of CSA versus ST alone was also observed for swollen joint count (p = 0.05), tender joint count (p = 0.01), joint/pain tenderness score (p = 0.002), patient and physician global assessment by at least one point (p = 0.04 and 0.01, respectively), total Arthritis Impact Measurement Scale score (p = 0.002), and spondylitis functional index (p = 0.002). There was a statistically significant difference in the ACR 50% and ACR 70% response rates between the CSA and ST groups (p = 0.02, 0.05). Comparing the SSZ and ST alone groups, only the spondylitis functional index decreased significantly in the SSZ treated patients (p = 0.03). The Psoriasis Area and Severity Index was significantly lower in the CSA than in the ST and SSZ groups (p = 0.0001 and 0.01, respectively). Decrease in erythrocyte sedimentation rate was significant only in the SSZ versus the ST group (p = 0.02), whereas reduction in C-reactive protein was significant in the CSA treated patients compared with the ST group (p = 0.006). The most common adverse event in the CSA group was mild, reversible kidney dysfunction. CONCLUSION: The results of this open trial confirm that CSA is well tolerated by patients with PsA and suggest that it is more efficacious than ST or SSZ.

Adult↗

Extra-articular manifestations in 587 Italian patients with rheumatoid arthritis.

The aim of the study was to evaluate the frequency of extra-articular manifestations (EAMs) of rheumatoid arthritis (RA) in a series of patients from nine Italian rheumatology clinics. A total of 587 patients underwent direct questioning, complete physical evaluation, and review of medical records and laboratory data. The relationships between EAMs and the eosinophilic count, IgM rheumatoid factor (RF), and antinuclear antibodies (ANA) were studied. EAMs were present in 240/587 (40.9%) patients. The most common features were sicca syndrome (17.5%) and rheumatoid nodules (16.7%). EAMs were significantly more frequent in male patients (OR = 1.68), patients with ANA positivity (OR = 2.82), high anatomical class (OR = 2.3), and rheumatoid factor seropositivity (OR = 2.22). EAMs were more common in patients from southern Italy than in those from northern Italy (P < 0.001). EAMs seem to be rarer in Italy than in the Anglo-Saxon populations of northern Europe and the USA. Differences in prevalence of EAMs can exist even within the same country.

Adolescent↗

Recall of a lead-contaminated vitamin and mineral supplement in a clinical trial.

PURPOSE: The Treatment of Lead-exposed Children (TLC) trial tested whether developmental outcome differed between children treated for lead poisoning with succimer or placebo. On 7 July 1997, TLC was informed that the vitamin and mineral supplements it gave to all children were contaminated with about 35 microg of lead per tablet. METHODS: TLC recalled the contaminated supplements and measured the children's exposure. RESULTS: The families of 96% of the children were contacted with 30 days. Among the 571 children to whom the contaminated supplements were dispensed, the mean increase in blood lead was 0.06+/-0.01 micromol/L (1.2+/-0.2 microg/dL); among 78 children to whom they were not, it was 0.09+/-0.03 micromol/L (1.8+/-0.7 microg/dL). There was no evidence of a dose-response relation between estimated supplement consumption and increase in blood lead concentration. CONCLUSIONS: The children's blood lead concentrations were not detectably affected by the contamination. Since the association of cognitive delay with lead exposure is best described for blood lead, we believe that the trial's inference about the effect of drug therapy on lead induced cognitive delay should be unaffected.

Journal Article↗

Effect of nitric oxide on basal and TRH-or metoclopramide-stimulated prolactin release in normal men. volpi@ipruniv.cce.unipr.it.

In order to establish whether nitric oxide (NO) is involved in the regulation of basal and/or TRH- or metoclopramide (MCP)-stimulated PRL secretion, normal male subjects were treated i.v. with the NO-synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) (40 mg/kg injected plus 50 mg/kg infused over 60 min) in basal conditions (N.7 subjects) or just before the PRL releasing hormone TRH (20 or 200 microg iv) (N.7 subjects) or the antidopaminergic agent MCP (1 or 10 mg iv) (N.7 subjects). In control experiments, subjects received normal saline instead of L-NAME. The administration of L-NAME modified neither the basal secretion of PRL, nor the PRL release induced by TRH (20 or 200 microg) or MCP (1 or 10 mg). These data suggest that in humans, NO is not involved in the control of PRL release at the anterior pituitary level.

Adult↗

Age-dependent decrease in the growth hormone response to growth hormone-releasing hormone in normally cycling women.

OBJECTIVE: To establish possible changes in GH secretion in normally cycling women with increasing age. DESIGN: Controlled clinical study. PATIENTS: Nine younger (18 to 33 years) and nine older (41 to 46 years) healthy women. SETTING: Tests were performed on the 22d day of regular cycles. INTERVENTION: All subjects were tested with GH-releasing hormone (GH-RH) (1 mg/kg body weight), the acetylcholinesterase inhibitor pyridostigmine (120 mg by mouth), the somatostatin inhibitor arginine (30 g infused IV over a 30-minute period) alone, and the combination of GH-RH plus arginine or GH-RH plus pyridostigmine. MAIN OUTCOME MEASURES: Glucose, cortisol, androgens, estrogens, thyroid hormones, and insulin growth-like factor (IGF-I) were measured in basal samples. Serum GH levels were measured in samples taken before and over a 2-hour period after drug administration. RESULTS: All basal hormonal values were similar in younger and older women. Insulin growth like factor-I levels were lower in older women. The GH responses to GH-RH alone, pyridostigmine alone, or the combination were lower in the older than in the younger group and were correlated negatively with age. In contrast, either arginine alone or GH-RH plus arginine produced similar GH responses in the two groups. CONCLUSION: These data indicate that the cholinergic stimulatory regulation of GH release is reduced in the older cycling women. Because acetylcholine inhibits hypothalamic somatostatin release, the reduced cholinergic tone in other subjects may result in an increased somatostatinergic tone. Normalization in older women of the reduced GH response to GH-RH by arginine supports this hypothesis.

Adolescent↗

Influence of age on the GH response to sumatriptan administration in man.

The present study was undertaken in order to assess the influence of aging on the serotonergic control of GH secretion in humans. For this purpose, 6 mg 5-HT1D-serotonergic receptor agonist sumatriptan (or placebo during control tests) was injected subcutaneously in a group of 9 young (26-40 yr old) and a group of 9 elderly male subjects (64-80 yr old). Sumatriptan-induced plasma GH rise was recorded during the next 2 hours. Plasma ACTH levels were also measured. The administration of the placebo was without effects in all subjects. Sumatriptan induced a striking increase in plasma GH levels in the younger group, whereas it slightly increased GH secretion in the older group (f = 9.59, p < 0.02). Plasma ACTH levels showed a similar physiological decline in all subjects during tests, regardless of sumatriptan treatment. These data show impaired serotonergic stimulatory regulation of GH secretion in elderly subjects.

Adrenocorticotropic Hormone↗

Influence of thyroid status on the paradoxical growth hormone response to thyrotropin-releasing hormone in human obesity.

Thyrotropin-releasing hormone (TRH) tests were performed in 38 age- and weight-matched obese but otherwise healthy men. In all subjects, total thyroxine (T4) and triiodothyronine (T3) concentrations were in the normal range. According to basal and TRH-stimulated serum thyrotropin (TSH) levels, subjects were divided into the following three groups: group I (n = 14), euthyroid subjects; group II (n = 11), euthyroid subjects with normal basal but abnormally elevated TSH responses to TRH; group III (n = 13), subjects with elevated basal and TRH-induced TSH levels (subclinical hypothyroidism). Basal TSH levels were 1.8 +/- 0.4 mU/L in group I, 1.7 +/- 0.3 in group II, and 6.0 +/- 0.7 in group III. In both groups II and III, TRH-induced TSH increments were above the normal range (maximal increment > 14 mU/L) and were significantly higher than in group I. The definition of euthyroidism for groups I and II and of subclinical hypothyroidism for group III according to the basal levels of TSH was confirmed by clinical (Billewicz index), hormonal (serum free-T4 levels), and metabolic (serum apoprotein [apo] AI levels) parameters. Basal concentrations of growth hormone (GH) were similar in all groups. When GH levels after TRH stimulation were measured, significant increments (peak minus baseline > 5 micrograms/L) were observed in nine of 13 hypothyroid obese men. The overall mean peak GH increase in group III was 4.5 times higher than baseline and was observed at 45 minutes. None of the euthyroid obese subjects of groups I and II showed any significant change in GH levels in response to TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth Hormone↗

Different effects of delta-sleep-inducing peptide on arginine-vasopressin and ACTH secretion in normal men.

UNLABELLED: Delta-sleep-inducing peptide (DSIP) is a well-known inhibitor of pituitary ACTH secretion. In order to evaluate the possible influence of DSIP on basal arginine-vasopressin (AVP) secretion and/or on the AVP-response to osmotic and pressure/volumetric stimuli, DSIP (25 nmol/kg) was infused in 10 min to 8 normal men (23-34 years old) just before a 2-hour infusion of normal saline (NaCl 0.9%; DSIP test) or hypertonic saline (0.51 M NaCl; osmotic test) or before an orthostatic test (standing upright and maintaining an orthostatic position for 20 min). In different occasions, a 10-min infusion of normal saline (placebo) was given instead of DSIP. In an additional 7 subjects, DSIP or placebo was given 60 min before hypertonic saline or the orthostatic test. The results obtained after the administration of DSIP at time 0 and at -60 min were similar. RESULTS: The administration of DSIP or normal saline alone did not change the concentrations of circulating AVP. A slight physiological decline in ACTH levels was observed during saline infusion, whereas a significant decrease in ACTH levels was induced by DSIP administration. Osmotic stimulation of AVP secretion by hypertonic NaCl induced a significant increase in plasma AVP concentrations which was not modified by DSIP administration. The ACTH secretory patterns during hypertonic NaCl and hypertonic NaCl plus DSIP were similar to those observed during normal saline and normal saline plus DSIP, respectively. The orthostatic test provided similar plasma AVP increments, regardless of the previous treatment with DSIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Abnormal serotonergic control of prolactin and cortisol secretion in patients with seasonal affective disorder.

The effects of the serotonergic agent d,l-fenfluramine (60 mg PO) or a placebo on serum prolactin (PRL) and cortisol levels were evaluated in seven patients (five men and two women) with seasonal affective disorders (SAD) and in eight normal controls (eight men and two women). Both groups were tested in fall/winter when patients with SAD suffered depressive symptoms and in spring/summer, when patients were euthymic. Spring/summer and fall/winter tests gave similar results. PRL and cortisol patterns were similar in all subjects after placebo, whereas both hormonal responses to d,l-fenfluramine were significantly lower in patients with SAD than in normal controls. Correlation studies between the two hormonal responses revealed that on both periods the amplitudes of PRL and cortisol increments were significantly and positively correlated in patients with SAD. These data show diminished serotonergic responsiveness in SAD regardless of the actual depressive status of the patients. They are consistent with a decrease of central serotonergic activity in SAD.

Adult↗

Inhibitory effect of dexamethasone on the oxytocin response to insulin-induced hypoglycemia in normal men.

Glucocorticoids are known to reduce both ACTH and arginine vasopressin responses to insulin-induced hypoglycemia in normal men. The present study was undertaken in order to establish whether glucocorticoids are capable of modifying the oxytocin (OT) response to hypoglycemia. For this purpose, 8 normal men (28-33 yr) were tested with insulin (0.15 IU/kg in an iv bolus) [insulin tolerance test (ITT)] with and without pretreatment with dexamethasone (2 or 4 mg in an iv bolus 10 min before insulin). Eight different subjects (29-35 yr) were tested with dexamethasone alone. The administration of dexamethasone (2 or 4 mg) alone changed neither ACTH nor OT concentrations in the plasma during the next hour. Insulin produced similar hypoglycemic responses, regardless of dexamethasone treatment. ACTH levels rose significantly in response to insulin-induced hypoglycemia, with a mean peak response at 45 min (p less than 0.01 vs baseline). Two and four mg dexamethasone produced similar significant reductions of the ACTH response to hypoglycemia (p less than 0.02 at 45 min, p less than 0.05 at 30 and 60 min vs ITT). In the ITT, OT levels rose significantly in response to hypoglycemia, with a mean peak response at 45 min (p less than 0.01 vs basal value). The pretreatment with 2 or 4 mg dexamethasone reduced in a similar manner the hypoglycemia-induced OT rise (p less than 0.05 at 30 and 45 min vs ITT). These findings show a partial inhibition by dexamethasone of the OT response to hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Stimulation of ACTH/cortisol by intravenously infused substance P in normal men: inhibition by sodium valproate.

The effect of synthetic substance P (SP), infused intravenously in doses of 0.5, 1 or 1.5 pmol/kg-1/min-1 over 60 min on ACTH/cortisol secretion was evaluated in 7 healthy men. SP tests and a control test with normal saline were randomly performed at weekly intervals. During tests, SP infusion did not produce untoward side effects or changes in blood pressure. Plasma ACTH and cortisol levels were not modified when normal saline or the lowest dose of SP were infused, whereas they were significantly increased in a dose-dependent fashion when higher amounts of SP were administered. Further studies were performed in another 7 healthy men to test the possible influence of GABAergic neurotransmission on the ACTH/cortisol response to SP. For this purpose, subjects were tested with SP (1.5 pmol/kg-1/min-1) alone and on a different occasion with SP after pretreatment with the GABAergic agent sodium valproate (200 mg 16, 8 and 1 h before the SP test). Again, the administration of SP induced a significant increase in plasma ACTH and cortisol levels. The pretreatment with sodium valproate completely abolished both ACTH and cortisol responses to SP. These data demonstrate for the first time in humans that the systemic infusion of SP stimulates ACTH/cortisol secretion, suggesting the involvement of a GABAergic mechanism in the regulation of the action of SP.

Adrenocorticotropic Hormone↗

Gastric carcinoids and their precursor lesions. A histologic and immunohistochemical study of 23 cases.

A histologic and immunohistochemical study was carried out in 23 unselected nonantral gastric carcinoids and their precursor lesions classified according to Solcia et al. None of the patients showed Zollinger-Ellison syndrome. Two variants of carcinoids showing distinctive pathologic and pathogenetic characteristics were identified on the basis of presence or absence of associated chronic atrophic gastritis type A (A-CAG). Chronic atrophic gastritis type A was found in 19 cases showing either single or multiple neoplasms, tumor extension limited to the mucosa or submucosa, consistent endocrine cell precursor changes in extratumoral mucosa, and consistent hypergastrinemia and/or G cell hyperplasia. Associated precursor lesions were only hyperplastic in all but two cases with single carcinoids whereas they were also dysplastic in all but one case with multiple carcinoids. The four tumors arising in nonatrophic mucosa were all single, more aggressive, and not associated with extratumoral endocrine cell proliferations or with signs of gastrin hypersecretion. Tumor cells were diffusely immunoreactive for chromogranin A and synaptophysin but usually negative for chromogranin B or HISL-19. Scattered serotonin cells were found in ten carcinoids. They were more frequent in infiltrating than in intramucosal tumors as were the less represented pancreatic polypeptide cells whereas the reverse was found for alpha-subunit-containing cells. These results are of relevance for tumor pathogenesis and may provide the rationale for a less aggressive therapeutic approach in the patients.

Adolescent↗

Restoration of normal growth hormone responsiveness to GHRH in normal aged men by infusion of low amounts of theophylline.

In order to establish whether the age-related reduced growth hormone (GH) responsiveness to GH-releasing hormone (GHRH) could be improved by treatment with low amounts of theophylline, a drug mainly acting through cyclic adenosine 3', 5'-monophosphate (cAMP), and calcium-mediated mechanisms, eight adult subjects (aged 20-37) and eight elderly men (aged 64-79) were tested with GHRH (50 micrograms in an iv bolus), theophylline (1.67 mg/min for 3 h), or the combination of both drugs. The GH response to GHRH was significantly lower in the older than in the younger group (mean peaks were 4.5 and 7.5 times higher than baseline, respectively). Theophylline did not change basal GH levels in any subjects and GHRH-induced GH rise in the younger group, whereas it restored normal GH responses to GHRH in the older subjects (mean peak responses were eight times higher than baseline in both groups). These data show that in elderly subjects the mechanism underlying the GHRH-induced GH secretion may be fully activated by GHRH during treatment with low amounts of theophylline.

Adult↗

Reduced sensitivity to pirenzepine-induced blockade of growth hormone responses to arginine, exercise, and growth hormone-releasing hormone in type I diabetic subjects.

The present study was performed to establish whether the mechanism by which the cholinergic system influences growth hormone (GH) release was altered in type I diabetic patients. Therefore, we investigated in a dose-response fashion the inhibitory effect of the muscarinic cholinergic receptor antagonist pirenzepine on the GH responses to arginine infusion (30 g infused intravenously (IV) in 30 minutes), exercise (bicycle ergometer test at an intensity of 75 W for 30 minutes), or 1-44 GH-releasing hormone (GHRH) (1 microgram/kg in an IV bolus). In a preliminary study, IV injection of 17.5 mg pirenzepine failed to produce modification in the GH response to arginine infusion in both diabetic (N = 4) and normal subjects (N = 4), and to exercise (diabetics, N = 4; normals, N = 4). Therefore, other subjects were tested without and with 20, 25, and 30 mg pirenzepine during arginine (diabetics, N = 7; normals, N = 7) or exercise (diabetics, N = 7; normals, N = 7) tests. Each subject was tested four times. Diabetic patients presented higher GH responses to stimulation with arginine or exercise than normal controls. In both groups, pirenzepine administered at doses ranging from 20 to 30 mg produced a dose-related inhibition of the GH response to arginine and exercise, which was almost complete when 30 mg pirenzepine was administered. However, the percent inhibition produced by 20 or 25 mg pirenzepine in the arginine test and by 20 mg in the exercise test was significantly lower in the diabetic patients than in the normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of obesity and weight loss on arginine vasopressin response to metoclopramide and nicotine from cigarette smoking.

We have previously reported an impaired arginine vasopressin (AVP) response to insulin-induced hypoglycemia in obese men, suggesting a hypothalamic-posterior pituitary disorder in obesity. In the present study, we examined the AVP response to other releasing stimuli with a central site of action. The AVP response of 10 obese men to metoclopramide (MCP) or nicotine inhaled with cigarette smoking was compared with that obtained in eight sex- and age-matched controls. The AVP increase during nicotine and MCP tests were significantly lower in the obese patients than in the normal controls. Obese men were restudied after substantial weight loss. The AVP response to nicotine and MCP administration was significantly higher than before slimming and did not differ from that observed in the normal weight subjects. These results demonstrate obesity-related alterations in the AVP responsiveness to nicotine inhaled with cigarette smoking and MCP, supporting the hypothesis for a hypothalamic-posterior pituitary disorder in obesity.

Adult↗

Serotonergic control of TSH and PRL secretion in obese men.

To evaluate whether the inhibitory control of TSH and the stimulatory control of prolactin (PRL) secretion exerted by endogenous serotonin was altered in obesity, 22 obese men and 10 normal controls were tested with TRH (200 micrograms IV bolus) in the presence (experimental test) and absence (control test) of the serotonergic agonist fenfluramine (60 mg PO 90 min before TRH). Control and experimental tests were also performed in seven male patients with subclinical hypothyroidism and were repeated in the same obese subjects after substantial weight loss. Basal TSH levels were similar in control and obese men. Normal TSH responses to TRH (peak less than or equal to 14 mU/L) were observed in all normal controls (mean peak +/- SE 9.8 +/- 0.6 mU/L). In contrast, obese men were divided into two groups: nine in whom the TRH-induced TSH rise was higher than normal (group I: mean peak = 16.5 +/- 0.5 mU/L) and 13 in whom it was normal (group II: mean peak = 10.6 +/- 0.7 mU/L). The hypothyroid men all had elevated basal and TRH-stimulated TSH levels. Basal PRL concentrations were similar in the normal controls and both groups of obese subjects. The PRL response to TRH was lower in both group I and group II obese men than in normal controls and was similar between group I and group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗