Effects of consecutive doses of GHRH on GH secretion.
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Adult↗
Biomedical subjects
A Conti
Publications and source records attributed to A Conti.
Serum osteocalcin levels in patients with GH deficiency before and during GH treatment.
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Adolescent↗
Thyrotropin alpha- and beta-subunit responses to thyrotropin-releasing hormone and domperidone in normal subjects and in patients with microprolactinomas.
Microprolactinoma is a particular pathological situation characterized by the presence of increased hypothalamic dopaminergic tone reactive to tumoral hyperprolactinemia. Since dopamine (DA) is a physiological regulating factor of the secretion of thyroid-stimulating hormone (TSH), we investigated the responses of serum TSH (holo-TSH) and its subunits (alpha-subunit: alpha-sub, and TSH-beta) to thyrotropin-releasing hormone (TRH) and domperidone (DOM; an antidopaminergic drug acting outside the blood-brain barrier) in 36 euthyroid subjects (20 controls and 16 patients with microprolactinoma) in order to evaluate the possible in vivo effects of DA excess on TSH subunit secretion. No significant difference in serum TSH increase after TRH (200 micrograms i.v.) was observed between patients with microprolactinoma and controls (TSH net incremental area under the curve, nAUC: 146 +/- 9, mean +/- SE, and 143 +/- 7.7 micrograms/l/60 min, respectively), while serum alpha-sub and TSH-beta responses were markedly reduced in patients with microprolactinoma as compared to those found in normals (alpha-sub nAUC: 3.0 +/- 0.5 vs. 19.8 +/- 2.2 micrograms/l/60 min, p less than 0.001; TSH-beta nAUC: 5.0 +/- 0.8 vs. 9.5 +/- 0.9 micrograms/l/60 min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Anti-stress role of the melatonin-immuno-opioid network: evidence for a physiological mechanism involving T cell-derived, immunoreactive beta-endorphin and MET-enkephalin binding to thymic opioid receptors.
Our previous work showed that the pineal neurohormone melatonin induces activated T lymphocytes to release opioid peptides with immunoenhancing and anti-stress properties. Here we present evidence that these peptides crossreact with anti-beta-endorphin and anti-met-enkephalin antisera, and bind specifically to thymic opioid receptors. Furthermore, the same antisera injected in prednisolone treated mice prevented the normal recovery of thymus cellularity and of the capacity to mount a primary antibody response against T-dependent antigens. Surgical pinealectomy, i.e. inhibition of endogenous melatonin and absence of antigen activation negated the effect of such antisera demonstrating the physiological relevance of this melatonin-immuno-opioids network. It is proposed that function of this network may be that of driving a correct immune recovery after the depression caused by the elevated corticosteroids level associated with immune responses and/or stressful situations.
Animals↗
Immuno-derived opioids as mediators of the immuno-enhancing and anti-stress action of melatonin.
The pineal neurohormone melatonin was shown to stimulate the release of opioid peptides from activated CD4+, T lymphocytes. These immuno-derived opioids or "lymphomorphins" crossreact with anti-beta-endorphin and anti-metenkephalin antisera, bind to opioid receptors in the thymus and are the mediators of the immunoenhancing and anti-stress action of endogenous and/or exogenous melatonin. These findings proved the existence of a novel immunoneuroendocrine physiological mechanism which may be related for the long range maintenance of the immune homeostasis in spite of the unavoidable stress and/or infectious events occurring during the span of life in a normal unprotected environment.
Animals↗
[Comparison of iopamidol 150 and 370 with the same iodine dosage (37 g) in urography].
Two different volumes of iopamidol (250 and 100 ml, respectively) containing 37.5 and 37 g of iodine in different concentrations (150 mgI/ml and 370 mgI/ml) were injected in the same time (10 minutes) with varying injection rates, to compare diagnostic effectiveness, image quality, distension of the collecting system, and influence of the better iodine concentration. Sixty patients of both sexes were randomly subdivided into two groups. Their renal function, blood pressure and pulse rate were normal. Their weight ranged 55-85 kg, not to change the distribution volume of the contrast medium. None of them had been given iodine compounds recently. Radiographs were taken 2, 5, 15, 25, and 30 minutes after the end of the injection. The image quality of nephrograms, pyelograms, bladder views and the degree of collecting system filling were evaluated by a blind study, using grading scores (0 to 3). In both groups image quality and degree of filling were satisfying; the volume of injected iopamidol had poor significance. The clinical findings confirm that, with a nonionic contrast medium, iodine concentration in the collecting system is the most important factor for image quality.
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Screening of HBV-DNA in chronic HBsAg carriers.
A series of 52 serum samples from chronic HBsAg carriers was tested for the presence of HBV-DNA by means of the Polymerase Chain Reaction (PCR) and Liquid Phase Hybridization (LPH). The samples were obtained from two groups of patients: group A included 34 chronic HBsAg carriers ("healthy" individuals) without hepatocytolysis or viral replication; group B included 18 chronic HBsAg carriers with signs of hepatocytolysis (ALT levels at least twice the normal value) and activated markers of viral replication. PCR was superior to LPH in group A, with 7/34 versus 5/34 positive samples being detected, respectively. No difference in sensitivity was found between the two techniques in group B, since 9/18 samples were positive both cases. The data stress the need to adopt PCR for the HBV-DNA screening of HBeAg-/HBsAg+-carriers.
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[Relationship between blood insulin and arterial hypertension in obese adults].
The well know fact that high blood pressure and impaired glucose tolerance are frequently associated with obesity has suggested that hyperinsulinemia could represent one of the possible pathogenetic connections between obesity and systodiastolic hypertension. With the aim of verifying this hypothesis 67 obese subjects (36 hypertensive and 31 normotensive), males, were admitted to our study. All of the subjects underwent standard OGTT in order to measure their glycemic and insulinemic levels. No differences were found between two groups, as regard age and the degree of obesity; blood pressure values were significantly different (p less than 0.01). No significative differences were detected for glycemic and insulinemic levels between normotensive and hypertensive subjects; basal hyperinsulinemia was detected in a similar percentage (16.6 vs 19.3%) in the two groups. Under these circumstances it is not possible to confirm that hyperinsulinemia is the prominent link between obesity and high blood pressure, as previously observed by others.
Adult↗
[Visceral toxocariasis. Description of 3 cases].
Three cases of visceral toxocariasis in adult patients are here described. Toxocariasis is a not uncommon, probably underestimated infection and the diagnosis should be considered also in adults who present clinical signs and it must be confirmed by serological tests.
Adult↗
Role of 5-HT2 receptors in serotonin-induced contraction in the human mammary artery.
We studied the effects of serotonin (5-HT) on isolated human mammary arteries obtained from patients undergoing coronary by-pass grafting. 5-HT induced a concentration-dependent contractile response in the mammary artery, with an EC50 value of 0.34 microM. The 5-HT2 antagonist, ketanserin, reversed the contractions evoked by 5-HT in a competitive manner at a low concentration (10(-8) M), whereas non-competitive antagonism was apparent at higher concentrations (5 X 10(-8)-5 X 10(-7) M). To investigate whether the alpha 1-blocking component of ketanserin plays a role in the response observed in this vessel, we evaluated the effect of ketanserin on contractions induced by (-)-norepinephrine. Ketanserin, in concentrations up to 10(-7) M, did not influence the norepinephrine-induced contractions. Moreover, a threshold concentration of 5-HT (10(-7) M) amplified the contractile effect induced by norepinephrine (5 X 10(-8) M), and this response was inhibited by ketanserin (10(-7) M). The selective 5-HT3 antagonist, GR 38032F, did not affect the 5-HT-induced contractions. These findings indicate that the human mammary artery is a vascular tissue sensitive to 5-HT. The 5-HT2 receptor subtype appears to mediate the response.
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5-Hydroxytryptamine induces contraction in isolated human mammary artery: effect of ketanserin.
5-hydroxytryptamine (5HT) treatment produced dose-related contractions in the human internal mammary artery with an EC50 value of 3.4 X 10(-7) M. The 5HT2 receptor antagonist ketanserin reversed the contractions evoked by 5HT in a competitive manner at a low concentration (10(-8) M), whereas a noncompetitive antagonism was apparent at higher concentrations (5 X 10(-8) M to 5 X 10(-7) M). The alpha 1-blocking component of ketanserin was evaluated by studying the effect of ketanserin upon the contractile response evoked by norepinephrine. Up to 10(-7) M, ketanserin did not influence norepinephrine-induced contractions. These findings indicate that the mammary artery is a vascular tissue sensitive to contractions induced by 5HT and that the drug ketanserin antagonizes this contractile response through the 5HT2 receptor subtype.
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Effect of two consecutive administrations of GHRH in children with constitutional growth delay.
It has been suggested that children with constitutional growth delay might have a transient immaturity of the neurotransmitter pathways necessary for the control of growth hormone releasing hormone (GHRH) secretion. In this study we evaluated the effects of two consecutive GHRH boluses (1 microgram/kg, i.v.) in nine prepubertal boys with constitutional growth delay. Growth hormone (GH) responses to GHRH administration were similar to that observed in normal children (first GHRH bolus, GH net incremental area under the curve (nAUC) +/- SE: 788 +/- 244 vs 984 +/- 242 ng/ml per hour; second bolus, GHnAUC: 657 +/- 122 vs 541 +/- 129 ng/ml per hour, respectively). These data suggest that no relevant abnormalities in the mechanisms determining the somatotroph sensitivity to GHRH are present in children with constitutional growth delay.
Adolescent↗
Osteocalcin levels in patients with microprolactinoma before and during medical treatment.
Osteocalcin (OC) concentration, a specific index of bone formation, was measured in 29 female patients with microprolactinoma (serum prolactin, PRL: 105 +/- 10.9 ng/ml; mean +/- SE). Mean OC levels were significantly lower than in controls (1.7 +/- 0.2 vs 5.1 +/- 0.3 ng/ml; p less than 0.001), being below the normal range in 28 out of 29 patients. All patients were treated with dopaminergic agents (dihydroergocriptine, bromocriptine or cabergoline). After treatment mean serum PRL levels were significantly reduced (12 +/- 3.1 ng/ml; p less than 0.001), a full normalization being obtained in 26 patients. There were no significant differences in both basal and after treatment PRL levels among patients treated with different drugs, although a greater PRL decrease was induced by cabergoline. Serum OC levels significantly increased after 12 month therapy (4.7 +/- 0.6 ng/ml, p less than 0.001), a normal concentration being reached in 14 of 29 cases. During treatment there were no significant differences in serum estradiol and PRL concentrations between patients who normalized or not their OC levels, while the reduction in PRL levels with respect to baseline was more pronounced in the former group. The absolute increase in OC levels positively correlated with serum PRL decrements (p less than 0.01). It is noteworthy that serum OC normalized in 1/10 patients during dihydroergocriptine, 3/8 during bromocriptine and 10/11 during cabergoline. Four patients, previously treated with dihydroergocriptine and bromocriptine without normalizing OC and PRL levels, underwent a second course of therapy with cabergoline and then normalized OC concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Effects of the enkephalinase inhibitor SCH 34826 on the sleep-waking cycle and EEG activity in the rat.
The sedative effect of SCH 34826, an enkephalinase inhibitor, was evaluated by studying electroencephalographic (EEG) activity, behaviour and the sleep-waking cycle in the rat. The reference opioid, morphine, was used for comparison. After administration of morphine (10 mg/kg s.c.) the rats were motionless and stuporous at first and then hyperactive. An increase of slow wave sleep, at the expense of both wakefulness and REM sleep was recorded, with high-amplitude slow wave bursts appearing in the EEG tracings during the waking, albeit stuporous, phase. Relative spectral power in the 1-4 and 12-16 Hz bands was increased and there was a shift of the dominant frequency to a lower frequency. The specific opioid antagonist, naltrexone, readily reversed most of these effects. The drug SCH 34826 (10-100 mg/kg p.o.) had no effect on the parameters examined; large doses (300 and 1000 mg/kg p.o.) induced restlessness in some animals, resulting in increased waking. This effect was antagonized by naltrexone. The data indicate that SCH 34826, at doses far greater than those proposed for clinical use, is devoid of sedative liability and does not induce any of the behavioural or EEG effects typical of morphine.
Animals↗
The pineal neurohormone melatonin stimulates activated CD4+, Thy-1+ cells to release opioid agonist(s) with immunoenhancing and anti-stress properties.
In previous studies we showed that in mice the pineal gland modulates the immune response via the circadian synthesis and release of melatonin. Exogenous melatonin proved also to exert immunoenhancing effects and to counteract completely the immunologic effect of acute stress. Melatonin was active only in vivo, in mice primed with T-dependent antigens and its effects on the primary antibody response and thymus weight were abolished by the specific opioid antagonist naltrexone. Here we demonstrate that physiologic concentrations of melatonin stimulate, in vitro, activated L3T4+ (CD4+) cells to release opioid agonist(s) that can reproduce in vivo the immunoenhancing and anti-stress effects on thymus cellularity and antibody production of melatonin and compete with specific binding of [3H]naloxone to mouse brain membranes. Similar results were obtained when mitogen-activated human immunocompetent cells were incubated with melatonin. In the human model the results were, however, less consistent than those obtained with murine cells, in that only four out of ten blood donors provided cells that were responsive to melatonin. This finding elucidates the mechanism of a novel immuno-neuroendocrine connection with relevant implications for our understanding of the neuroendocrine factors that may influence the immune response in vivo in normal and stressful situations. In addition, it opens new perspectives in a wide range of research fields.
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The biological significance of soluble interleukin-2 receptors in solid tumors.
In an attempt to further understand the biological significance of soluble IL-2 receptors (sIL-2R) in solid tumors, we have evaluated 160 cancer patients (breast: 40; lung: 66; colon: 18; stomach: 22; uterine cervix: 14) and 58 healthy subjects, as controls. Serum mean levels of sIL-2R, measured with an enzyme immunoassay, were significantly higher in cancer patients than in controls. Metastatic cancer patients showed significantly higher values than the non-metastatic ones; this difference was significant in all tumor histotypes, except small cell lung carcinoma. Moreover, in 15 patients in whom sIL-2R were evaluated either before or after radical surgery, a significant surgery-induced increase in sIL-R mean values was seen. Finally, the chemotherapy-induced rise in sIL-2R appeared to be associated with a lack of clinical response. These results seem to suggest that sIL-2R may be a marker of host biological response in patients with solid tumors, the significance of which needs further investigation.
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Repetitive injections of GHRH in normal children and adults.
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Adult↗
Antibodies raised against bovine beta-lactoglobulin react with beta 2-microglobulin. A possible antigenic region at beta-LG positions 124-140.
beta-Lactoglobulin is a major whey protein in bovine milk. Its presence has been demonstrated in all mammals examined except rodents and humans. However a positive cross reaction was observed for human milk proteins with antibodies raised against bovine beta-lactoglobulin. We isolated and characterized a protein fraction of ca. 12 kDa responsible for the positive cross reaction. N-terminal sequencing and amino-acid analysis indicated that this protein is identical with human beta 2-microglobulin. We observed structural homology between beta-lactoglobulin region 124-140 and beta 2-microglobulin 71-86, which suggested that positions 124-140 could be the antigenic region for beta-lactoglobulin. Six highly conserved amino-acid residues are suggested as candidates for the antigenic site.
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