Biomedical subjects

A Valentini

Publications and source records attributed to A Valentini.

At least 37 records · Page 2Linked to original sources

PubMed1999

Structure, expression, and function of human pituitary tumor-transforming gene (PTTG).

Despite advances in characterizing the pathophysiology and genetics of pituitary tumors, molecular mechanisms of their pathogenesis are poorly understood. Recently, we isolated a transforming gene [pituitary tumor-transforming gene (PTTG)] from rat pituitary tumor cells. Here we describe the cloning of human PTTG, which is located on chromosome 5q33 and shares striking sequence homology with its rat counterpart. Northern analysis revealed PTTG expression in normal adult testis, thymus, colon, small intestine, brain, lung, and fetal liver, but most abundant levels of PTTG mRNA were observed in several carcinoma cell lines. Stable transfection of NIH 3T3 cells with human PTTG cDNA caused anchorage-independent transformation in vitro and induced in vivo tumor formation when transfectants were injected into athymic mice. Overexpression of PTTG in transfected NIH 3T3 cells also stimulated expression and secretion of basic fibroblast growth factor, a human pituitary tumor growth-regulating factor. A proline-rich region, which contains two PXXP motifs for the SH3 domain-binding site, was detected in the PTTG protein sequence. When these proline residues were changed by site-directed mutagenesis, PTTG in vitro transforming and in vivo tumor-inducing activity, as well as stimulation of basic fibroblast growth factor, was abrogated. These results indicate that human PTTG, a novel oncogene, may function through SH3-mediated signal transduction pathways and activation of growth factor(s).

3T3 Cells↗

PubMed1998

An erythroid-specific transcript generates the soluble form of NADH-cytochrome b5 reductase in humans.

Two forms of NADH-cytochrome b5 reductase (b5R), an erythrocyte-restricted soluble form, active in methemoglobin reduction, and a ubiquitous membrane-associated form involved in lipid metabolism, are produced from one gene. In the rat, the two forms are generated from alternative transcripts differing in the first exon, however, biogenesis of human b5R was less understood. Recently, two different transcripts (M and S), differing in the first exon were also described in humans. Here, we have investigated the tissue-specificity and the role of the S-transcript in the generation of soluble b5R. By RNase protection assays designed to simultaneously detect alternative b5R transcripts in the same sample, the S transcript was undetectable in nonerythroid and in erythroleukemic K562 cells induced to differentiate, but was present in terminal erythroblast cultures, and represented a major b5R transcript in reticulocytes. Analysis of the translation products of the M- and S-transcripts in HeLa cells transfected with the corresponding cDNAs demonstrated that the S-transcript generates soluble b5R, presumably from an internal initiation codon. Our results indicate that the S-transcript is expressed at late stages of erythroid maturation to generate soluble b5R.

Amino Acid Sequence↗

PubMed1998

Hypothalamic amenorrhea and cardiovascular hormones: changes of plasma calcitonin gene-related peptide and atrial natriuretic peptide levels.

Typical modifications of cardiovascular activity and water and salt homeostasis throughout female reproductive life are well known. Differences in plasma levels of calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) have been observed in conditions characterized by different estrogenic levels, suggesting a correlation between female reproductive function and these cardiovascular hormones. The aim of our study was to investigate in hypothalamic amenorrhea the relationship between estrogen deficiency and plasma ANP and CGRP response to adaptive tests (saline infusion test and upright posture test, respectively). Women with hypothalamic amenorrhea (aged 18-28 years) (n = 6) and age-matched healthy controls (n = 6) underwent both functional tests. Plasma CGRP and ANP levels were measured by specific radioimmunoassays before and in course of the tests. Basal plasma CGRP levels of amenorrheic patients did not significantly differ from those of normal women, while basal plasma ANP levels were significantly higher compared to controls (p < 0.01). In amenorrheic women, plasma CGRP levels showed a significant increase in response to upright posture test, though lower than the increase observed in normal women. In contrast, saline infusion test determined a significant increase in plasma ANP levels only in control subjects. In women with hypothalamic amenorrhea, the altered response of CGRP and ANP to adaptive stimuli indicates a partial derangement in the control of the secretion of these cardiovascular hormones. Nevertheless, the differences between such modifications and those observed in other conditions of altered estrogenic levels, suggest that in amenorrheic women hypogonadism is not the major factor influencing CGRP and ANP response to adaptive stimuli.

Adolescent↗

PubMed1998

Effect of delta-opioid receptor agonist deltorphin on circulating concentrations of luteinizing hormone and follicle stimulating hormone in healthy fertile women.

There is evidence that endogenous opioid peptides exert an inhibitory effect on pituitary luteinizing hormone (LH) secretion both in animals and in humans, by interacting with mu-opioid receptors. However, a role for delta-opioid receptors in the regulation of gonadotrophin releasing hormone (GnRH) secretion has recently been suggested. In the present study, we evaluated the effect of the highly selective delta-opioid receptor agonist deltorphin on the LH and follicle stimulating hormone (FSH) responses to naloxone in six healthy fertile women during the luteal phase of the menstrual cycle. Deltorphin infusion alone (7 microg/kg/min for 60 min) did not significantly change the basal serum concentrations of LH in this group of women. The intravenous (i.v.) bolus administration of naloxone (15 mg) induced a significant (P < 0.001) increase in serum LH concentrations (from a mean basal value of 4.24+/-1.10 IU/l to a peak of 13.27+/-1.8 IU/l). The LH response to naloxone was significantly (P < 0.001) blunted by preinfusion of deltorphin (13.27+/- 1.80 IU/l versus 4.80+/-1.18 IU/l). No significant changes in FSH concentrations were observed during deltorphin, naloxone or deltorphin plus naloxone administration. These data indicate that activation of delta-opioid receptors can reduce naloxone-induced LH release, suggesting a possible role of delta receptors in opioidergic modulation of LH secretion in women.

Adult↗

PubMed1998

Evidence for androgen receptor gene expression and growth inhibitory effect of dihydrotestosterone on human adrenocortical cells.

Evidence for the expression of the canonic androgen receptor (AR) in human adrenal cortex has not been provided so far. The aim of the present study was to demonstrate the expression of the AR gene in normal and neoplastic adrenocortical human tissues and in the human adrenocortical cancer cell line, NCI-H295, and then to evaluate the effect of dihydrotestosterone (DHT) on human adrenocortical cell growth. An AR cDNA fragment with the expected size of 262 bp was detected by using reverse transcription (RT)-PCR in normal and neoplastic adrenocortical human tissues and in the neoplastic cell line, demonstrating that the gene for AR is indeed expressed in human adrenal cells. In the human adrenocortical cancer cell line NCI-H295, DHT at physiological concentrations produced a significant reduction in cell proliferation and inhibition of colony formation in soft agar. The inhibitory effect on adrenocortical cell growth was evident after both 24 and 48 h of treatment. The antiandrogens, cyproterone acetate and hydroxyflutamide, were capable of reversing the effects exerted by DHT. The androgen-induced growth inhibitory effect was also detected in primary culture of three non-functioning adrenocortical adenomas. These findings show that the canonic AR is present in human adrenocortical cells and that androgens may have a role in the adrenal cortex by reducing cell proliferation.

Adrenal Cortex↗

PubMed1997

Evaluation of hormonal function in a series of incidentally discovered adrenal masses.

The discovery of an asymptomatic adrenal mass (incidentaloma) during the investigation of an unrelated condition is relatively common. In this study, we report the clinical, radiologic, and endocrine evaluation of 38 patients (22 women and 16 men aged 24 to 84 years) with adrenal incidentaloma (size, 1 to 12 cm). The patients underwent basal and dynamic evaluation of the hypothalamic-pituitary-adrenal (HPA) axis, renin-angiotensin-aldosterone system, and adrenomedullary function. Moreover, computed tomograpy (CT) scan and 131I-6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol(NP-59) and/or 131I-metaiodobenzylguanidine (MIBG) scintigraphy were performed. The endocrine evaluation indicated two cases of pheochromocytoma and four cases of preclinical Cushing's syndrome, three of which underwent surgery with histologic diagnosis of two adrenocortical adenomas and one carcinoma. Low levels of serum dehydroepiandrosterone sulfate (DHEA-S), associated with a markedly increased 17-hydroxyprogesterone (17-OHP) response to a corticotropin (ACTH) test, were found in patients with incidentaloma. On the basis of endocrine and morphologic data, 13 patients underwent surgical treatment: five adrenocortical adenomas (two functioning), two pheochromocytomas, two ganglioneuromas, one cortisol-secreting adrenal carcinoma, one lymphangiomatous cyst, one myelolipoma, and one hemorrhage were found. Careful diagnostic assessment of incidentally discovered adrenal masses must be performed to exclude the presence of malignant and/or functioning lesions and to verify the possibility that patients with incidentaloma have a genetic or acquired deficit of adrenal steroidogenic activity.

17-alpha-Hydroxyprogesterone↗

PubMed1997

Octreotide long-term treatment in patients with portal hypertension: persistent inhibition of postprandial glucagon response without major changes in renal function.

BACKGROUND/AIMS: Octreotide acutely decreases splanchnic blood flow and postprandial portal pressure in patients with portal hypertension. Inhibition of glucagon release parallels the hemodynamic changes. We studied the hormonal and renal effects of long-term treatment with octreotide (100 microg s.c., t.i.d., immediately before meals, for 2 weeks) in 12 patients with cirrhosis and portal hypertension. METHODS: Postprandial blood levels of glucagon, insulin and glucose, and renal function tests were monitored in a study where patients acted as their own controls. Eleven patients completed the study, octreotide being discontinued in one patient who developed jaundice after 6 days of therapy. RESULTS: Long-term treatment did not cause any change in fasting hormonal levels measured 12 h after the last injection of octreotide. However, pre-prandial injection of octreotide induced a marked fall in blood glucagon (163+/-49 pg/ml, after 20 min, vs. 254+/-71 pg/ml, basal; p<0.01), thus preventing the postprandial response occurring without treatment (322+/-102 pg/ml, 30 min-peak, vs. 249+/-77 pg/ml, basal; p<0.03). Inhibition of postprandial glucagon was maintained after 2 weeks of therapy (159+/-33 pg/ml, after 20 min, vs. 237+/-54 pg/ml, basal; p<0.01). Octreotide abolished the insulin postprandial response with no major change in glycemic control. Treatment had no long-term effect on renal plasma flow (effective renal plasma flow: 596+/-79 ml/min, baseline, vs. 609+/-71 ml/min, at 2 weeks; p>0.5), glomerular filtration rate (glomerular filtration rate: 99+/-11 vs. 99+/-12 ml/min; p>0.5), blood urea and creatinine, whereas it induced a mild decrease in plasma electrolyte levels (p<0.02). CONCLUSIONS: Long-term octreotide treatment persistently suppresses the postprandial glucagon response of patients with portal hypertension without causing deterioration in their renal function.

Adult↗

PubMed1997

AFLP markers for DNA fingerprinting in cattle.

This work reports on use of the recently described amplified fragment length polymorphism (AFLP) technology for DNA fingerprinting in cattle. The AFLP technology produces molecular markers through the high-stringency polymerase chain reaction (PCR)-amplification of restriction fragments that are ligated to synthetic adapters and amplified using primers, complementary to the adapters, which carry selective nucleotides at their 3' ends. While, for plants, the double digestion of genomic DNA with EcoRI and MseI is suggested, in mammals the enzyme combination EcoRI/TaqI produces clearer and more polymorphic AFLP patterns. In a sample of 47 Italian Holstein genotypes, 16 EcoRI/TaqI primer combinations identified 248 polymorphic bands in a species known for its low level of restriction polymorphism. In spite of the low information content carried by each AFLP polymorphism (average polymorphism information content = 0.31), the number of fragments revealed by each primer combination increased significantly the level of genetic information gained in each experiment. AFLP patterns are reproducible in independent experiments and polymorphic fragments segregate in cattle families according to Mendelian rules.

Animals↗

PubMed1996

Interrelationships between calcitonin gene-related peptide and sympathoadrenomedullary system: effects of administration of epinephrine and norepinephrine in healthy man.

To investigate the influence of the sympathoadrenomedullary system on the modulation of the circulating levels of calcitonin gene-related peptide (CGRP), the effects of epinephrine (E) and norepinephrine (NE) were studied in 8 normal subjects (4 females and 4 males). The mean basal levels of CGRP in normal subjects were 10.2 +/- 1 pmol/l. After the infusion of E (20 ng/kg per min for 30 min), a significant rise (P < 0.005) in plasma CGRP levels was observed with the expected increases in systolic blood pressure (BP), heart rate (HR) and plasma renin activity (PRA), and decrease in diastolic BP, whereas plasma aldosterone (PA) levels did not significantly change. The infusion of NE (40 ng/kg per min for 30 min) induced an increase in systolic and diastolic BPs, whereas it failed to modify CGRP, HR, PA and PRA. Our data demonstrate that the sympathoadrenomedullary system may modulate CGRP release in man perhaps via the beta-adrenergic pathway. It is likely that the modifications of plasma CGRP levels may be part of the acute vasal response to E.

Adrenal Medulla↗

PubMed1996

Antitumor effect of c-myc antisense phosphorothioate oligodeoxynucleotides on human melanoma cells in vitro and and in mice.

BACKGROUND: Phosphorothioate oligodeoxynucleotides ([S]ODNs) contain a modified internucleoside phosphate backbone. Antisense [S]ODNs targeted to specific oncogenes have been used with some therapeutic success in animal models human leukemia; however, the potential for antisense [S]ODN treatment of solid tumors has only recently been explored. PURPOSE: We evaluated the effects of antisense [S]ODNs targeted to the c-myc oncogene on the proliferation of human melanoma cells in vitro and on the growth of human melanoma xenografts in CD-1 nude (nu/nu) mice, METHODS: The effects of 15-mer [S]ODNs containing c-myc sense, c-myc antisense, and two different scrambled sequences on the proliferation and viability of cultures of three established human melanoma cell lines (M14, JR8, and PLF2) were determined by measuring cell numbers and use of the trypan blue exclusion test. The induction of apoptosis in these cells following treatment with [S]ODNs was evaluated by fluorescence-activated cell sorter (FACS) analysis. FACS analysis was also used to determine the effects of [S]ODN treatment on the proliferation of primary cultures of a human melanoma explant (NG cells). The expression of c-Myc protein in cultured NG cells after treatment with [S]ODNs was examined by western blot analysis. The antitumor activity and the toxic effects of several [S]ODN treatment regimens were monitored by measuring differences in tumor weight (percent tumor weight inhibition), tumor growth rate (tumor growth inhibition), animal lifespan (percent increase in lifespan), the number of toxic deaths and the median number of long metastases in treated and control mice bearing NG xenografts. c-Myc protein expression in NG tumor cells following [S]ODN treatment was evaluated by FACS analysis, and the extent of apoptosis in these cells was determined by FACS analysis and morphologic examination. RESULTS: Treatment with antisense [S]ODNs, but not the others, inhibited the growth of all tested melanoma cultures in vitro; FACS analysis revealed that growth inhibition was associated with the induction of apoptosis. Antisense [S]ODN treatment also led to reduced celluLar levels of c-Myc protein. In vivo, [S]ODN antitumor activity and toxicity were dose and schedule dependent; however, only antisense [S]ODNs exhibited antitumor activity. Mice bearing NG xenografts treated with antisense [S]ODNs showed a marked inhibition of tumor growth, a reduction in the number of long metastases, and an increase in life span. Reduced levels of c-Myc protein and increased levels of apoptosis were also observed in NG tumor cells following antisense [S]ODN treatment. CONCLUSIONS: treatment of human melanoma cells and solid tumors with antisense [S]ODNs targeted to c-Myc inhibits their growth and is associated with the induction of apoptosis.

Animals↗

PubMed1996

Random amplified polymorphic DNA (RAPD) interpretation requires a sensitive method for the detection of amplified DNA.

The random amplified polymorphic DNA technique (RAPD) has found wide use in molecular genetics because of its speed and ease of use. For various reasons, with this method the amplified DNA fragments are produced at different concentrations between genotypes and even between polymerase chain reaction (PCR) runs. Since the detection of the multiple amplified fragments is performed routinely by agarose gel, and seldom by acrylamide gel electrophoresis, we have found that by capillary zone electrophoresis (CZE), which is more sensitive and accurate than gel electrophoresis, it is possible to unequivocally detect amplified fragments even at low concentration, avoiding polymorphism misinterpretation. CZE is also useful to make more potentially polymorphic fragments evident per random primer used, with obvious economical benefits.

Animals↗

PubMed1996

Changes of plasma calcitonin gene-related peptide levels in postmenopausal women.

OBJECTIVE: Our purpose was to investigate whether the secretion of a cardiovascular hormone, calcitonin gene-related peptide, is modified in climateric women according to cardiovascular adaptive responses. STUDY DESIGN: Plasma calcitonin gene-related peptide levels were measured in climateric women in a basal condition (n = 15), in response to an upright position (n = 8), and during hot flushes (n = 12). The effect of hormonal replacement therapy on plasma calcitonin gene-related peptide was also studied (n = 9). Plasma calcitonin gene-related peptide levels were measured by a specific radioimmunoassay after an acidic extraction. RESULTS: Plasma calcitonin gene-related peptide levels in postmenopausal women were significantly lower than in the control group (p < 0.01). After the women assumed an upright posture, a lack of plasma calcitonin gene-related peptide increase was observed in control fertile women, who showed the typical significant hormonal increase (p < 0.01). In all patients the occurrence of hot flushes was associated with a significant and rapid increase of plasma calcitonin gene-related peptide levels. After 3 months of hormonal replacement therapy basal plasma calcitonin gene-related peptide levels returned to the range of healthy fertile women. CONCLUSIONS: The current data show that the secretion of plasma calcitonin gene-related peptide is lower in postmenopausal women and its response to postural stimulus is impaired. Vasomotor changes are associated with an increase of plasma levels of this cardiovascular hormone. An effect of hormonal replacement therapy on calcitonin gene-related peptide secretion has been shown.

Calcitonin Gene-Related Peptide↗

PubMed1996

Function of the GH/IGF-1 axis in healthy middle-aged male runners.

In an attempt to examine the effect of prolonged physical activity on the function of the GH/IGF-1 axis during the aging process in man, we have evaluated basal and GHRH (GHRH-29: 1 microgram/kg i.v. as a bolus) stimulated GH secretion as well as basal plasma IGF-1 levels in a group of 25 healthy runners (50-60 years, mean age 55.5 +/- 0.6) and 24 age-matched relatively sedentary normal controls (mean age 55.8 +/- 0.7). The runners had a minimum distance in kilometers of 26 km/week for at least 15 years, and competed in distances ranging from 16 km to the marathon. In runners, GHRH induced an increase of GH which was significantly higher (p < 0.001) than that observed in the age-matched controls. Baseline IGF-1 levels were significantly higher (p < 0.001) in trained runners (171 +/- 8.4 micrograms/1) compared to the controls (91.1 +/- 5.5 micrograms/1). These data show that in middle-age prolonged physical activity increases the function of the GH/IGF-1 axis. To clarify the possible mechanisms underlying the GH/IGF-1 secretory pattern in the runners, the GH responses to both single and combined administration of GHRH and arginine (ARG: 30 g infused over 30 min), a GH secretagogue likely acting via inhibition of hypothalamic somatostatin release, were investigated in 6 runners (mean age 55 +/- 1.9 years) and 6 controls (mean age 55 +/- 0.9 years). ARG clearly increased the GH response to GHRH in the controls, whereas it was unable to further potentiate the GH-releasing effect of GHRH in runners, thus suggesting that the increased GH responsiveness to GHRH might be due to an exercise-related decrease in endogenous hypothalamic somatostatinergic activity.

Aging↗

PubMed1996

Acute administration of human galanin in normal subjects reduces the potentiating effect of pyridostigmine-induced cholinergic enhancement on release of norepinephrine and pancreatic polypeptide.

The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems where it often coexists with catecholamines and acetylcholine. Recently we have reported that human GAL (hGAL) in man depresses the release of norepinephrine (NE) and the responses to both assumption of upright posture and insulin-induced hypoglycemia. To gain an insight into the action of hGAL on sympathetic nervous system activity in man, we investigated the effects of a 60-min infusion (80 pmol/kg/min) of hGAL or saline on the release of NE, epinephrine (E) and pancreatic polypeptide (PP) induced by an acetylcholinesterase inhibitor, pyridostigmine bromide (PD), in nine healthy volunteers. PD (120 mg orally) induced a significant rise in plasma concentrations of NE (1.6 +/- 0.04 vs. 1.08 +/- 0.06 nmol/l), E (0.34 +/ 0.05 vs. 0.12 +/- 0.04 nmol/l) and PP (178.06 +/- 33 vs. 37.57 +/- 7.35 pmol/l), whilst it significantly reduced heart rate (HR; 61 +/- 2 vs. 71 +/- 4 beats/min). Changes in plasma levels of PP were determined as an indirect measure of amplification of endogenous cholinergic activity produced by PD. Administration of hGAL blunted the release of NE and PP evoked by PD. The mean (+/- SEM) area under the curve produced by PD of NE (50.05 +/- 3.97 nmol/l.90 min) and PP (8,692.87 +/- 1,724 pmol/l.90 min) was significantly (p < 0.001) reduced by hGAL infusion (2.65 +/- 1.57 nmol/l.90 min and 248.1 +/- 148 pmol/l.90 min, for NE and PP, respectively). hGAL failed to affect significantly the E release evoked by PD. hGAL was able to enhance HR significantly (104 +/- 5 vs. 69 +/- 3 beats/min), and completely prevented the PD-induced slowing of HR. Both PD and hGAL did not alter supine systolic and diastolic blood pressure. We conclude that hGAL significantly reduces the release of NE and PP stimulated by PD-induced enhancement of cholinergic activity. These findings are consistent with a functional interrelationship between GAL and the cholinergic system in man, and may suggest the participation of a cholinergic pathway in the galaninergic modulation of the autonomic nervous system.

Adult↗

PubMed1996

Effect of the antitumor drug lonidamine on glucose metabolism of adriamycin-sensitive and -resistant human breast cancer cells.

The effect of lonidamine on glucose metabolism, hexokinase activity and adenylate pool of MCF-7 human breast cancer cells sensitive and resistant to adriamycin has been investigated. The following summarizes the results: 1. In both cell types the greatest part of glucose was metabolized to lactate, whereas only a small proportion of glucose carbon atoms was incorporated into CO2, lipids, nucleic acids, and supporting structures. 2. Glucose utilization, lactate production, and ATP content were higher in resistant cells due to a greater activity of mitochondrial hexokinase. 3. Lonidamine decreased glucose utilization, aerobic glycolysis and ATP content in both cell types and the effect was significantly higher on resistant cells. 4. The extent of inhibition in sensitive and resistant cells overlapped that found for mitochondrially bound hexokinase, thus indicating that the greater sensitivity of resistant cells to lonidamine was due to their higher amount of bound hexokinase. These findings confirmed a modified glucose metabolism in cells with resistant phenotype and suggested that lonidamine might be usefully used to reduce or overcome multidrug resistance of those cells with a reduced ability to accumulate and retain antitumor drugs.

Adenine Nucleotides↗

PubMed1995

Differential effects of deltorphin on arginine and galanin-induced growth hormone secretion in healthy man.

Recently we demonstrated the inhibitory action on Growth Hormone (GH) secretion of an opioid heptapeptide, deltorphin (DT), that is highly selective in binding delta-opioid receptors. To investigate the possible mechanism leading to the decrease in GH secretion by specific activation of delta-opioidergic pathway in man, we compared, in normal subjects, the effect of DT on GH secretion responses to two different GH secretagogues, namely arginine (ARG) and galanin (GAL). DT completely blunted the GH response to ARG, whereas it attenuated the GH response to GAL, but not at a statistically significant level. We suggest that the specific activation of delta-opioid receptors in man may exert an inhibitory influence on GH secretion principally by modulating endogenous hypothalamic somatostatin (SRIH) release.

Adult↗

PubMed1995

Involvement of mu-opioid receptors in the modulation of pituitary-adrenal axis in normal and stressed rats.

The availability of the most selective, high-affinity, natural opioid agonists for mu-receptors (dermorphin-DM) and delta-receptors (deltorphin-DT) has provided the possibility for in vivo studying of the role of acute and chronic activation of mu- and delta-opioid receptors on the functional activity of the hypothalamus-pituitary-adrenocortical (HPA) axis, both in basal conditions and in response to an acute stress in adult male rats. Plasma corticosterone (CS) and beta-endorphin-like-immunoreactivity (beta-EP-LI) levels were measured by specific radioimmunoassays before and after 5 and 30 minutes from the exposure to cold (3 +/- 0.5 C) water and forcing them to swim for 10 minutes (acute cold swimming stress). Acute administration of DM, the specific mu-receptor agonist, enhanced basal and stress induced plasma levels of CS and beta-EP-LI. These effects were antagonized by pretreatment with naloxone, specific mu-opioid receptor antagonist, but not by naltrindole, a delta-opioid receptor antagonist. Long-term administration of DM did not alter resting plasma levels of CS and beta-EP-LI, but significantly reduced stress-induced increase of these hormones. Both the acute and chronic administration of the DT, highly selective delta-opioid receptors agonist, failed to modify resting and stress induced hormone levels. Our present data show that DM throughout mu-opioid receptors, but not DT, modulates the response of HPA axis to acute stress in rats, increasing or decreasing the release of CS and beta-EP-LI when acutely or chronically administered, respectively.

Adrenal Glands↗

PubMed1995

SPET imaging of intracranial tumours with 99Tcm-sestamibi.

Single photon emission tomography (SPET) employing 99Tcm-sestamibi (MIBI) injected intravenously was performed in 27 patients for pre-surgical evaluation of intraparenchymal brain tumours. A computerized tomography (CT) scan was performed in 26 patients, magnetic resonance imaging (MRI) in 8 patients and digital subtraction angiography (DSA) in 14 patients. Visual analysis of the SPET scans was performed using a 4-point scale relating to background activity, to evaluate MIBI uptake in the tumour. The vascular supply and the cellular component were also evaluated using DSA and CT scans. In normal controls, MIBI uptake was observed in the scalp, in the choroid plexus and in the pituitary gland, but never in normal parenchyma. Among the astrocytoma group of patients, a trend between MIBI uptake and grade of tumour was noted. MIBI uptake in meningiomas depends primarily on the vascular supply. Our results support the hypothesis that vascular supply, integrity of the blood-brain barrier, the degree of malignancy of the neoplasm and the viability of the tumour cells may be related to MIBI uptake.

Adult↗