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Biomedical subjects

S Nicosia

Publications and source records attributed to S Nicosia.

At least 73 records · Page 4Linked to original sources
PubMed1990

Successful therapy of metastatic embryonal carcinoma coexisting with gonadoblastoma in a patient with 46,XY pure gonadal dysgenesis (Swyer's syndrome).

A case of gonadoblastoma associated with metastatic embryonal carcinoma occurring in a phenotypic female with 46,XY pure gonadal dysgenesis is presented. Two years after treatment with surgery and combination chemotherapy the patient is disease free. This is the third reported case and first reported cure in the English-language literature over the past 25 years. Current management is reviewed.

Adolescent↗
PubMed1990

Contractile and binding activities of structural analogues of LTC4 in the longitudinal muscle of guinea-pig ileum.

High affinity binding sites for LTC4 have been identified in various tissues, including guinea-pig ileal longitudinal muscle. More recently, it has been shown that LTC4 binds to non-receptor sites as well, particularly to glutathione transferases. In the present study, LTC4 and 9 chemically synthesized analogues, as well as the SRS-A antagonist FPL 55712 and S-decyl-glutathione, were tested for their ability to inhibit 3H-LTC4 binding in membranes from guinea-pig ileal longitudinal muscle and to affect the tone of the ileum in vitro. A significant correlation between binding and contractile activities was found for the LTC4 analogues and FPL 55712. However, S-decyl-glutathione, although possessing some affinity for LTC4 binding sites, was devoid of any effect on guinea-pig ileum tone at least up to 10(-5) M, thus indicating that these sites cannot be functional receptors, although they may represent other units involved in leukotriene action, e.g. uptake sites.

Animals↗
PubMed1989

Iloprost binding and inhibition of aggregation in platelet rich plasma. Differences between normal and type IIa hypercholesterolemic subjects.

Platelets from type IIa hypercholesterolemic subjects have been previously shown to be less sensitive than normal platelets to the antiaggregatory effect of PGI2. We demonstrate here that these platelets display a reduced response to iloprost, a chemically stable analogue of PGI2, as well. In fact, the concentration of iloprost yielding 50% inhibition of PRP aggregation was higher in type IIa patients (0.77 +/- 0.08 nM) than in controls (0.51 +/- 0.06 nM, P less than 0.01). In addition, an inverse relationship existed between the threshold aggregatory concentration for collagen and the concentration of iloprost yielding 50% inhibition of PRP aggregation, both in type IIa and normal individuals. In order to elucidate the mechanism of the different sensitivity of platelets to prostacyclin and its analogue, we characterized the binding of 3H-iloprost to platelet rich plasma from single individuals. The binding was rapid, reversible, inhibited by iloprost, PGI2 and PGE1 (Kd = 50.7; 346.2 and 7500 nM, respectively); no heterogeneity of sites could be demonstrated in the PRP from a single individual. When binding studies were carried out in PRP of type IIa patients and controls, it appeared that the amount of 3H-iloprost bound at a fixed (300 nM) concentration was significantly lower in platelets from type IIa individuals (0.94 +/- 0.17 vs. 1.77 +/- 0.27 fmol/10(6) platelets, for patients and controls, respectively). It is concluded that such difference in binding might represent the mechanism underlying the reduced response to PGI2 and iloprost observed in platelets from type IIa patients.

Adult↗
PubMed1989

Eicosanoid biosynthesis and action: novel opportunities for pharmacological intervention.

Novel eicosanoid biosynthetic pathways and receptors are reviewed as potential targets for pharmacological intervention. In addition to the cyclooxygenase and lipoxygenase pathways of arachidonate metabolism, a cytochrome P450-dependent monooxygenase has been identified in corneal and renal epithelial cells. Elucidation of the enzymatic pathways of thromboxane (TX) disposition and development of analytical techniques for measuring urinary metabolites have allowed a reliable assessment of TXA2 biosynthesis in health and disease, and provide a rationale for the combined use of TX-synthase inhibitors and TXA2-receptor antagonists in the setting of platelet activation. Recent evidence for a transcellular metabolism of neutrophil-derived leukotriene (LT) A4 by other human blood cells might link platelet and neutrophil activation to the occurrence of vasospastic phenomena. Prostacyclin (PG1(2)), PGE2, PGD2, TXA2/PGH2, and sulfidopeptide-LT receptors are being characterized in terms of distribution, signal-transduction mechanisms, and agonist-mediated regulation. Development of relatively selective agonists and antagonists of these receptors is providing novel therapeutic strategies for several human diseases.

Animals↗
PubMed1989

[Correlation between the sites of mitral annular calcification and conduction disturbances: echocardiographic evaluation].

A clinical, electrocardiographic and echocardiographic (M-Mode, 2D) study was performed to explain the causal relationship between mitral annular calcification and cardiac conduction disturbances. Forty-seven patients, 28 women and 19 men (mean age 69) with mitral annular calcification were studied. In 18 patients A-V and/or intraventricular conduction disturbances were present. In this study we have found: a greater incidence of posterior than anterior mitral annular calcification; the anterior mitral annular calcification is often associated with aortic valve calcification and ultimately the common association between anterior mitral annular calcification and conduction disturbances.

Aged↗
PubMed1989

The pharmacology of leukotrienes in human airways: in vitro and in vivo studies.

Immunological challenge of human lung parenchyma causes formation of arachidonate metabolites: prostaglandin D2 (PGD2) (70% of the formed mediators), leukotrienes E4 (LTE4) (15%) and D4 (LTD4) (10%). Leukotriene B4 (LTB4) was barely detectable (2%). Inhibition of PGD2 formation by indomethacin (15 microM) was approximately 90%, but was not accompanied by redistribution of arachidonate metabolism towards sulphidopeptide leukotrienes, as postulated for aspirin-sensitive asthma. Specific binding sites for leukotrienes C4 (LTC4) have been identified in membrane preparations of human bronchi. Binding of 3H-LTC4 is rapid (1 min) and quickly reversible following addition of excess. The sites are specific for LTC4 and competition curves fitted a two-site model. Moreover, clinical studies on specific endobronchial challenge of patients allergic to Dermatophagoides pteronyssinus, revealed narrowing of bronchial diameter and oedema of the bronchial mucosa; these symptoms were accompanied by an increase of immunoreactive-LTC4 and PGD2 present in the bronchial lavage fluids.

Asthma↗
PubMed1988

(5Z)-carbacyclin displays agonist-antagonist properties on prostacyclin-receptors in platelets and vascular myocytes.

(5E)- and (5Z)-carbacyclin are chemically stable analogues of prostacyclin (PGI2), which mimic PGI2 actions. In particular, they inhibit platelet aggregation and relax vascular smooth muscle, through the activation of adenylate cyclase (AC) being, however, less potent than PGI2. The characteristics of AC activity modulation by the two isomeric carbacyclins in membranes of human platelets and of myocytes cultured from rabbit mesenteric artery have been investigated. In human platelet membranes, both carbacyclins stimulated AC activity with the same efficacy as PGE1 and PGI2; in addition, these two prostaglandins inhibited the aggregation of human and rabbit platelets to the same extent as PGE1. On the contrary, in myocytes (5Z)-carbacyclin fails to produce the same degree of stimulation of AC elicited by PGI2, (5E)-carbacyclin and PGE1, nor does it induce the maximal relaxation of rabbit mesenteric artery attained with the other prostaglandins. (5Z)-carbacyclin is also able to antagonize the activation of AC by PGE1, PGI2 or (5E)-carbacyclin, acting therefore as a partial agonist. In conclusion, (5Z)-carbacyclin is a full agonist at the platelet level both in human and rabbit, thus excluding possible interspecies differences, but it is a partial agonist on myocytes. Therefore, (5Z)-carbacyclin appears to discriminate between PGI2 -receptors in the two target cells.

Adenylyl Cyclases↗
PubMed1987

(5Z)-carbacyclin discriminates between prostacyclin-receptors coupled to adenylate cyclase in vascular smooth muscle and platelets.

(5E)- and (5Z)-carbacyclin are prostacyclin (PGI2) analogues endowed with antiaggregating and vasodilator properties, which stimulate adenylate cyclase activity in membranes from human platelets and cultured myocytes from rabbit mesenteric artery. In platelets they display the same efficacy as prostaglandin E1 (PGE1), and hence PGI2 both as activators of adenylate cyclase and as inhibitors of aggregation. In contrast, in vascular smooth muscle cells (5Z)-carbacyclin fails to produce the same degree of stimulation of the enzyme as PGI2, (5E)-carbacyclin and PGE1, nor does it induce the maximal relaxation of the mesenteric artery as do the other prostaglandins. (5Z)-carbacyclin is also able to antagonize the activation of adenylate cyclase and the relaxation elicited by PGE1 or PGI2 in the mesenteric artery, and therefore it displays partial agonist properties in these cells. We conclude that the receptors for PGI2 coupled to adenylate cyclase in platelets and vascular smooth muscle cells are different from each other, because (5Z)-carbacyclin can discriminate between them, being a partial agonist at myocyte but not at platelet level.

Adenylyl Cyclases↗
PubMed1987

Characteristics and distribution of specific binding sites for leukotriene C4 in human bronchi.

The binding of [3H]leukotriene (LT) C4 to membranes from human bronchi has been characterized. The specific binding, measured at 4 degrees C, was very rapid, equilibrium being attained within 1 to 5 min. The binding was also rapidly reversible and saturable (maximum binding = 187 pmol/mg of protein). LTC4, LTD4, LTE4 and the LT antagonist FPL 55712 competed with [3H]LTC4 for its binding sites, with the following IC50 values: 0.12; 2.3; 30; and 20 microM. Therefore, the binding sites displayed a higher affinity for LTC4 than for the other sulfidopeptide LTs. Computer-assisted analysis of either the saturation or the competition curves for LTC4 indicated the existence of two classes of binding sites with different affinities (Kd1 and Kd2 = 70 nM and 0.58 microM, respectively), in agreement with the curved semilog plot of the dissociation time course. CaCl2 or MgCl2 increased and GTP or 5'-guanylylimidodiphosphate did not decrease the specific binding. In addition, the distribution of the binding sites for [3H]LTC4 along the human respiratory tree was investigated. At a fixed (10 nM) [3H]LTC4 concentration, membranes obtained from bronchi removed at different levels of the airway tree did not bind LTC4 in a significantly different amount. This is compatible with the finding that LTC4 receptors should be present on bronchi of various caliber, as both small and large airways respond to LTs.

Binding, Competitive↗
PubMed1986

Inhibitory effects of calcitonin on adenylate cyclase activity in different rat brain areas.

We have investigated the effect of calcitonin (CT) on adenylate cyclase in membranes from different rat brain areas. Salmon calcitonin (sCT) dose-dependently inhibited the enzyme activity in midbrain, hypothalamus, medulla, pons and caudate nucleus, but was ineffective in adenohypophysis. The inhibitory effect was enhanced by GTP. Comparison of calcitonins of different origin indicated that sCT was the most potent in inhibiting the enzyme in hypothalamic membranes, eel CT (eCT) was slightly less potent, and human CT (hCT) was ineffective. Chronic I.C.V. pretreatment with sCT did not modify the subsequent in vitro sensitivity of adenylate cyclase to sCT. It is concluded that some of CNS actions of CT might involve modulation of intracellular cAMP levels.

Adenylyl Cyclase Inhibitors↗
PubMed1985

Identification of specific binding sites for leukotriene C4 in membranes from human lung.

Leukotriene C4 (LTC4), one of the major components of the slow-reacting substance of anaphylaxis (SRS-A), is a potent constrictor of bronchial smooth muscle in many species including humans. Here we report the identification and characterization of specific binding sites for LTC4 in membranes from human lung parenchyma. At 4 degrees, 3H-LTC4 binding is specific, saturable (Bmax = 32-41 pmoles/mg prot.), rapid (equilibrium being attained within 15 min), reversible and of high affinity (Kd = 3.6-7 X 10(-8) M). The binding sites are sensitive to heat and probably possess a protein moiety, being inactivated upon trypsinization. CaCl2 affects both the association and the dissociation rate and dose-dependently enhances the binding of 3H-LTC4 at equilibrium; maximal enhancement (4-fold) occurred at 10(-2)M CaCl2. Unlabelled LTC4 is able to complete with 3H-LTC4 for its binding sites with an IC50 of 7.8 X 10(-8) M. The addition of 10(-2) M CaCl2 increases the potency of LTC4 in inhibiting the binding (2.2-fold); both the competition curves are monophasic, indicating the existence of a homogeneous class of binding sites. In the presence of CaCl2, LTD4, LTE4 and the SRS-A antagonist FPL 55712 can inhibit 3H-LTC4 specific binding, being, however, less potent than LTC4 (IC50 S = 2.2 X 10(-6), 2.4 X 10(-5) M, for LTD4, LTE4 and FPL 55712, respectively). FPL 55712 displayed a competitive mechanism; its affinity, however, was lower if absorption to glass was not prevented. The present studies indicate that specific binding sites for 3H-LTC4 exist in human lung parenchyma, and that a receptor-mediated process might be involved in the bronchoconstriction induced by LTC4.

Calcium Chloride↗