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Biomedical subjects

M Serio

Publications and source records attributed to M Serio.

At least 109 records · Page 6Linked to original sources

Decrease of phagocytic functions in hypertensive rats.

The present investigation was aimed to examine non-specific immunologic capabilities of spontaneously hypertensive rats (SHR) during the development of hypertension. In vitro phagocytosis and oxidative killing exerted by monocytes, polymorphonuclear cells (PMN) and splenic macrophages (SpM0) were evaluated in SHR at 5-, 8-, and 24-weeks of age. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls. Results showed that in pre-hypertensive stage (5-wk) there was no difference between SHR and WKY rats with regard to non-specific immunologic functions. Statistically significant differences in both phagocytosis and oxidative killing arose in early hypertensive stage (8-wk) and became more marked in adult SHR with established hypertension (24-wk). In conclusion, our data provide evidence of novel immunologic abnormalities in SHR in terms of ingestion and bactericidal phagocytic capabilities. The mechanisms responsible for these impaired immunologic functions may depend on various suppressive factors which will be object of discussion.

Aging↗

Oxandrolone in constitutional delay of growth: analysis of the growth patterns up to final stature.

In order to evaluate the effects of low-dosage, 6-12 months course of oxandrolone treatment in constitutional delay of growth, we compared the growth responses on treatment, the pattern of sexual development and pubertal growth events, up to final stature of 11 prepubertal boys, aged 10.6-14.1 yr, with those of 11 prepubertal, age-matched untreated controls. Treatment caused a significant increase of height velocity, from 4 to 9 cm/yr, and a significant acceleration of bone maturation, without affecting the timing of onset of puberty, the progression of sexual development or the onset of pubertal growth spurt. On the other hand, oxandrolone induced an earlier skeletal growth arrest but did not affect the expected final height. Treated boys showed an adult stature not significantly different from that of control subjects. Our data suggest that 6 months-1 year, low dosage oxandrolone treatment in constitutionally delayed growth has no significant effect on the pattern of pubertal growth, nor on the rate of sexual maturation or on final height.

Adolescent↗

Estrogenic suppression by different administration schedules of goserelin depot for treatment of endometriosis.

Eighteen patients affected by laparoscopically confirmed endometriosis were randomly assigned to three different schedules of treatment with gonadotropin-releasing hormone agonist (GnRH-a) (goserelin depot formulation 3.6 mg) every 28 days for 6 months. Six women received the first implant in early follicular phase, 4 in late luteal phase and 8 in 3rd and 17th day from onset of menses. Pretreatment and posttreatment laparoscopic score, performed according to the American Fertility Society scoring system, were compared; a significant reduction in the extent of disease was observed in each group investigated (A and C: p < 0.01; B: p < 0.05). In each treatment group after the second GnRH-a implant the mean levels of estrone-3-glucuronide (E1-3G), daily measured in early morning urine specimens during the control cycle and the first three months of therapy, were suppressed to menopausal women range. In group B during the 2nd and 3rd month of therapy, the urinary mean levels of E1-3G were significantly lower than in group A and C. In conclusion the different goserelin depot administration schedules gave similar laparoscopic improvement, in spite of the first GnRH-a administration in luteal phase allowed a more marked estrogenic suppression.

Adult↗

Pharmacokinetics of 4-hydroxyandrostenedione in man after intramuscular injection of different formulations and the effect of this drug on plasma aromatizable androgens and 17beta-estradiol concentrations.

Pharmacokinetics of 4-hydroxyandrostenedione (4-OHA), a potent aromatase inhibitor under investigation for treatment of postmenopausal breast cancer, were studied using two formulations with different particle sizes of 4.2 and 8.0 microm, respectively. A single 250 mg dose of 4-OHA of each of the two formulations was administered in two different periods to six healthy male volunteers and blood samples were collected for up to 14 days. 4-OHA plasma levels were determined using the isotope dilution mass spectrometry method. Comparison of the pharmacokinetic profiles of the two formulations did not show any statistically significant difference, even though the 4.2 microm particle size gave apparently higher levels at 24 h. Using this formulation, the effects of 4-OHA on the plasma levels of aromatizable androgens (testosterone and androstenedione) and 17beta-estradiol were studied. An isotope dilution mass spectrometry method was developed for the simultaneous quantitative determination of these steroids in human plasma. The analysis of plasma samples showed a significant reduction of plasma estradiol concentrations (50%) which coincided with the maximum concentration peak of the inhibitor, whereas no significant changes in androgen levels were observed.

Androgens↗

Natriuretic hormone receptors and actions on bone endothelial cells.

[125I]Atrial natriuretic peptide (ANP) was used to identify ANP receptors on a clonal line of bovine bone endothelial (BBE) cells. Specific binding of [125I]ANP was saturable and of high affinity. Computer analysis of the equilibrium binding data indicated that the Scatchard plots are best fit by a straight line (Kd = 69.3 +/- 20.9 pM; binding capacity = 37.9 fmol/10(6) cells). The order of potency for competing with [125I]ANP binding was human ANP (hANP) > rat atriopeptin-1 (rAP-1) > porcine brain natriuretic peptide (pBNP) > porcine C-type natriuretic peptide. Affinity cross-linking studies indicated the presence of two major 130- and 70-kilodalton bands that specifically bound to hANP, rAP-1, pBNP, and porcine C-type natriuretic peptide. The binding of natriuretic peptides to BBE cells resulted in an increase in cGMP production and a significant decrease in Na+/K+/Cl- cotransport, without effects on cAMP intracellular accumulation. hANP, rAP-1, and pBNP at 100-nM concentrations, significantly inhibited PTH-induced cAMP production. Treatment with natriuretic hormones was also associated with an increase in 6-keto-prostaglandin F1 alpha levels in the culture medium of BBE cells and a higher cell growth rate. These studies demonstrate that bone endothelial cells bear receptors for natriuretic hormones associated with changes in PTH-induced cAMP production, prostaglandin production, and cell proliferation.

Animals↗

Immunolocalization of inhibin alpha-subunit in the human testis. A light- and electron-microscopy study.

The localization of inhibin alpha-subunit in the human testis was studied at the light- and electron-microscope level with immunostaining techniques. Antibodies against specific fragments of porcine and human inhibin alpha-subunits were utilized. At light microscopy, inhibin alpha-subunit immunoreactivity was detected in Sertoli cells, spermatocytes and in some Leydig cells. At electron microscopy, gold labeling was found in the cisternae of the Golgi apparatus and in the endoplasmic reticulum of Sertoli and Leydig cells. Gold labeling for inhibin was also found in coated vesicles in the cytoplasm of Sertoli cells as well as in coated pits and coated vesicles in the cytoplasm of some spermatocytes. The results of the present study suggest that, in the human testis, inhibin is produced by Sertoli and Leydig cells and is taken up by spermatocytes, on which it might act in a paracrine manner.

Coated Pits, Cell-Membrane↗

Sertoli-germ cells interactions in the human testis.

In previous histoimmunochemical studies we reported that transferrin (TF) and insulin-like growth factor I (IGF-I) are present in the cytoplasm of the Sertoli cells of the adult human testis. Receptors for TF were found mainly in adluminal germ cells and type I receptors for IGF-I both in Sertoli and germ cells. Using electron microscopy, evidence of transfer of both TF and IGF-I from the Sertoli to the germ cells through a receptor-mediated endocytosis mechanism was also found. In this paper we report the results of the histoimmunochemical localization of alpha inhibin in the human fetal, prepubertal and adult testis. In 8- to 14-week-old fetal testes a positive immunostaining was found mainly in the interstitial cells, whereas no staining was found in the germ cords. In the prepubertal testis the immunostaining was present in the Sertoli cells but not in the interstitial cells. In the adult human testis the immunostaining was present not only in the Sertoli cells but also in the spermatocytes and in several Leydig cells. Using electron microscopy and immunogold labeling the presence of alpha inhibin immunoreactivity was found in the rough endoplasmic reticulum and in the Golgi cisternae of both Sertoli and Leydig cells. Moreover we found evidence of transfer of alpha inhibin from the Sertoli to the germ cells through receptor-mediated endocytosis.

Adult↗

Beta-endorphin concentration in the femoral and spermatic venous blood of males affected by varicocele.

Several studies in the rat indicate that opioid peptides produced in the testicular interstitial compartment can affect events in the tubular compartment. For example, it is thought that some specific functions of Sertoli cells, such as androgen-binding protein production are decreased by a paracrine mechanism. In this study ACTH beta-endorphin and cortisol were measured in the femoral and spermatic venous blood drawn from 18 patients affected by varicocele during catheterization for venous occlusion. The results showed the absence of a significant secretory gradient of beta-endorphin in the human testis and also demonstrated that this opioid is circulating at picomolar concentrations within human testis under stress conditions.

Adrenocorticotropic Hormone↗

Frequency of prolactin pulsatile release in normal men and in agonadal patients is neither coupled to LH release nor influenced by androgen modulation.

OBJECTIVE: We wished to examine and characterize the prolactin pulsatile secretory pattern in both normal and agonadal males in order to assess whether there was any concordance with LH secretion. DESIGN: Patients were sampled every 5 minutes for 12 hours. PATIENTS: We studied five normal and four agonadal men, the latter group before and on testosterone enanthate (TE) (200 mg i.m. every 15 days) treatment. MEASUREMENTS: Prolactin and luteinizing hormone plasma levels were determined using commercial RIA systems. Pulse detection was performed using the DETECT program and the degree of concordance between luteinizing hormone and prolactin was established computing the specific concordance index. RESULTS: We demonstrated the presence of a frequent PRL secretory pattern in normal men (22.8 +/- 1.8 peaks/12h; mean +/- SEM) and in agonadal patients, both in basal conditions and during testosterone treatment (20.5 +/- 2.8 and 18 +/- 1.6 peaks/12h, respectively). The testosterone treatment in agonadal men significantly reduced luteinizing hormone pulse frequency (baseline: 27.5 +/- 2, testosterone administration: 18 +/- 1.3 peaks/12h, P < 0.01) but did not affect pulsatile prolactin release. Using a 10 and 15 minute sampling protocol, we observed that prolactin pulse frequency significantly decreased (P < 0.01) and was similar to the frequencies estimated in previous reports. When luteinizing hormone and prolactin time series were studied to evaluate the possible presence of a specific concordance (SC) between the secretory events of the two hormones, no significant degree of concomitancy was observed neither using the specific concordance index or the cross-correlation analysis. CONCLUSIONS: This report demonstrates (a) the presence of frequent pulsatile release of prolactin in both controls and agonadal patients (baseline and on testosterone enanthate), (b) the use of an appropriate sampling interval (5 minutes) to unmask the prolactin pulsatile release, (c) that in men, luteinizing hormone secretory events are not temporally linked to prolactin secretion, and (d) that androgens, even if reducing luteinizing hormone pulse frequency in agonadal patients, do not significantly affect prolactin pulsatile secretion, suggesting that testosterone and its metabolites do not affect lactotroph activity.

Adult↗

The effects of (+/-)-idazoxan and its stereoisomers on mouse vas deferens motility in vitro. A comparison with yohimbine.

The effects of idazoxan (IDZ) and its stereoisomers were compared to that of a classical alpha 2-antagonist, yohimbine (YOH), on para-aminoclonidine (PAC)- and norepinephrine (NE)-mediated inhibition of the twitch response evoked in the mouse vas deferens by low-frequency (0.1 Hz) field stimulation. (+/-)-IDZ and (+)-IDZ antagonized the inhibitory effects of PAC, (+)-IDZ being twice as potent as (+/-)-IDZ; in contrast, antagonism by (-)-IDZ failed to meet Schild criteria for a competitive mechanism. YOH completely reversed the inhibition of twitch response induced by NE, but not that induced by PAC; in the latter case, residual inhibition was almost fully reversed by (+)-IDZ and to a lesser extent by (+/-)-IDZ, while (-)-IDZ proved ineffective. These results provide pharmacological evidence of alpha 2-receptor heterogeneity at the vas deferens level. A possible additional mechanism involving imidazoline binding sites is discussed.

Adrenergic alpha-Antagonists↗

Endothelin in rabbit uterus during pregnancy.

Specific immunostaining for endothelin-1 (ET-1) was observed in the uterine mucosa of pregnant and nonpregnant rabbits. During gestation, giant cells immunopositive for ET-1 were identified in either endometrium or myometrium. In the latter, they were located in close proximity to the muscular fibers. High-affinity (dissociation constant = 0.25 nM) high-capacity [maximal binding (Bmax) = 7 pmol/mg protein] receptors for ET-1 were present in myometrial membranes of estrous rabbits. During pregnancy the concentration of ET-1 receptors progressively decreased (Bmax on day 29 = 4 pmol/mg protein), rising again at the time of spontaneous delivery. Conversely, ET-1 receptors in the aorta did not change during pregnancy and parturition. The presence of giant cells immunopositive for ET-1 in close proximity to the myometrial cells, together with the evidence of an increase in ET-1 receptors in myometrium of parturient rabbits, suggests a paracrine role for endometrial ET-1 during delivery. Because we previously demonstrated that oxytocin releases ET-1 from endometrial cells in primary culture and that endometrial and myometrial oxytocin receptors abruptly rise at the time of parturition, we propose that ET-1 might participate in the complex cell-to-cell interactions that occur during labor.

Animals↗

Sex steroid modulation of neurohypophysial hormone receptors in human nonpregnant myometrium.

Neurohypophysial hormone receptors were studied in myometrial specimens obtained from nonpregnant women using binding and in vitro contractility studies. The mathematical modeling of self- and cross-competition curves among [3H]oxytocin (OT), [3H]arginine vasopressin, the V1 vasopressin (VP) antagonist [3H]d(CH2)5TyrMeAVP, the corresponding unlabeled peptides, and the OT agonist [Thr4, Gly7] OT strongly indicates the presence of multiple classes of OT and arginine vasopressin receptors. The latter show the same pharmacological characteristics as the neurohypophysial hormone receptors described by our group for the human pregnant myometrium; in addition, they regulate the contractility of uterine strips. Blocking experiments were performed to evaluate the relative OT and V1 VP receptor distribution in 30 uterine specimens obtained from normal cycling and postmenopausal women. The glucuronoconjugate metabolites of 17 beta-estradiol and progesterone were also measured in 16 patients in early morning urine samples taken the same day as surgery. Our results show that V1 VP receptors are not only present but also biologically active in all the uterine specimens studied with virtually equal density in normal cycling and postmenopausal women. However, their concentrations do not correlate with either estrogen or progesterone urinary levels. The lowest OT receptor density was found at mid-cycle and in menopause, independently of any correlation with the urinary estrogens. Conversely, OT receptors rise sharply in the late luteal phase and during menstruation. In addition they show a positive relationship with glucuronoconjugate metabolites of progesterone levels. These results indicate that progesterone does not inhibit the expression of uterine OT receptors in the human uterus. Furthermore, they imply that neurohypophysial hormones are involved in the control of uterine activity during the menstrual cycle.

Adult↗

Natriuretic peptide receptors regulate endothelin synthesis and release from parathyroid cells.

Cloned rat parathyroid cells (PTr cell line) that produce parathyroid hormone-related peptide plus endothelin 1 and primary cultures of human parathyroid cells were tested for growth and differentiation responses to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). High- and low-affinity binding sites for ANP were found on PTr cells; BNP appeared to bind to the same receptors with similar affinities. Either ANP or BNP stimulated production of cGMP and caused a 30% decrease in Na(+)-K(+)-Cl- cotransport. Each peptide increased synthesis and secretion of endothelin 1 by PTr cells in a dose-dependent fashion, but cell growth was not affected. Human parathyroid cells (normal and pathological) also responded to ANP or BNP with an increase in cGMP production. The finding of receptors for natriuretic hormones on parathyroid cells with consequent effects on release of endothelin 1 might be of relevance in understanding the clinical association between hyperparathyroidism and hypertension.

Animals↗

Effects of ipriflavone and its metabolites on a clonal osteoblastic cell line.

Protective effects of ipriflavone, an isoflavone derivative, in osteoporosis are believed to be caused by the inhibitory action on bone resorption. A direct effect of ipriflavone on bone formation is as yet unknown. Ipriflavone and four of its metabolites (I, II, III, and V) were examined for their effects on parathyroid hormone response, collagen synthesis, alkaline phosphatase activity, and cell proliferation in a clonal cell population of rat osteoblastic cells. Pretreatment of osteoblasts with high concentrations of ipriflavone for 48 h significantly inhibited the cAMP response to parathyroid hormone, producing a shift in the dose-response curve; at lower concentrations metabolites II and III potentiated the cAMP accumulation induced by low doses of parathyroid hormone. The 48 h treatment with metabolite V at the 1 nM dose significantly stimulated collagen synthesis in osteoblastic cells. Ipriflavone and metabolite I showed a biphasic stimulatory action on the alkaline phosphatase activity of osteoblasts, with a maximal effect at the 0.1 and 1 nM doses, respectively. A similar biphasic response was observed with ipriflavone and metabolite I on osteoblastic cell growth, with a maximal effect at the 0.1 nM concentration. These results suggest a direct role of ipriflavone in modulating the synthetic and growth properties of osteoblast-like cells.

Alkaline Phosphatase↗