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Biomedical subjects

A Ricci

Publications and source records attributed to A Ricci.

At least 199 records · Page 11Linked to original sources
PubMed1992

Dopexamine hydrochloride in the human heart: receptor binding and effects on cAMP generation.

Dopexamine hydrochloride is a synthetic catecholamine proposed for the short-term treatment of heart failure and postoperative low cardiac output. The pharmacological profile and anatomical localization of dopexamine binding were investigated in sections of right and left ventricle using [3H]-dopexamine and ligand techniques associated with light microscope autoradiography. Its effects on the 3-5-cyclic adenosine monophosphate (cAMP) generating system in membrane particles of the human right or left ventricle were also studied. [3H]-Dopexamine was specifically bound to sections of human right or left ventricle. The binding was time-, temperature- and concentration-dependent and was dissociable. The apparent equilibrium constant of dissociation was 3.5 nM. A decreased [3H]-dopexamine binding capacity from the base to the apex and ventricles was noticeable. The pharmacological profile of [3H]-dopexamine binding to sections of right or left ventricle was consistent with the labelling of both beta 2-adrenoceptors and dopamine DA-2 receptors. The most potent displacer of [3H]-dopexamine was the beta 2-adrenoceptor antagonist ICI 118,551 followed by dopamine, noradrenaline and domperidone. The beta 1-adrenoceptor antagonist metoprolol or the dopamine DA-1 receptor antagonist SCH 23390 were ineffective as displacers of [3H]-dopexamine binding. Light microscope autoradiography revealed the localization of [3H]-dopexamine binding sites within the wall of the human right and left ventricle. The density of silver grains was slightly higher in the right than in the left ventricle and showed a uniform transmural distribution across the ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Fibrinolytic enhancement in diabetic microangiopathy with defibrotide.

Skin microcirculation was evaluated in 117 patients with diabetic microangiopathy over a period of six months. They were divided into two groups. Group 1 (64 patients) was treated with oral defibrotide, a new profibrinolytic drug, in association with diet and oral antidiabetic drugs. Group 2 (53 patients) was treated only with diet and antidiabetic agents. The microcirculation was studied by means of laser-Doppler flowmetry transcutaneous partial pressure of oxygen and carbon dioxide pressure measurements, and evaluation of capillary filtration. After six months, patients in group 1 improved their microcirculatory parameters in association with an improvement in signs and symptoms. Moreover, 30 patients in group 1 and 36 in group 2 were followed up for eighteen months, and the authors observed that the deterioration of the microcirculatory parameters was significantly slowed in diabetics treated with defibrotide. A decrease in plasma fibrinogen during defibrotide treatment was observed in all treated patients in association with an increased fibrinolytic activity. In conclusion, it appears that defibrotide, enhancing fibrinolysis, improved the microcirculation in diabetics, preventing further, progressive deterioration.

Adult↗
PubMed1992

Pharmacological characterization and autoradiographic localization of dopamine receptors in human epicardial arteries.

The pharmacological properties and the anatomical localization of dopamine (DA) D1 and D2 receptor sites were studied in normal samples of the human right coronary and anterior interventricular arteries by assessing the effect of DA on the cyclic AMP generating system and by using combined radioreceptor binding and autoradiographic techniques. DA caused a concentration-dependent accumulation of cyclic AMP in membranes of right and anterior interventricular coronary arteries. This effect was antagonized by the selective D1 receptor antagonist SCH 23390 and by other DA receptor antagonists. D2 receptor responses negatively coupled to cyclic AMP generation were obtained by incubating membranes of coronary arteries with DA together with SCH 23390 or with D2 receptor agonists. This D2 effect was abolished by the selective D2 receptor antagonist (-)-sulpiride. [3H]SCH 23390 was bound to sections of the coronary arteries in a manner consistent with the labeling of D1 sites. Light microscope autoradiography revealed the localization of D1 sites in the medial layer of the coronary arteries. [3H]Spiroperidol, in the presence of ketanserin, was bound to sections of the coronary arteries in a manner consistent with the labeling of D2 sites. D2 receptor sites were located within the adventitia and the adventitial-medial border of the two arteries, and are probably prejunctional in nature. These findings indicate the existence of both D1 and D2 receptor sites in human right and anterior interventricular arteries. Moreover, they suggest that coronary vasodilation induced by DA or DA receptor agonists may be the result of a direct coronary vasodilatory activity.

Adolescent↗
PubMed1992

Detection of occult metastatic lobular carcinoma in axillary lymph nodes using anticytokeratin monoclonal antibodies.

To examine the importance of immunocytochemically detectable occult axillary lymph node metastases in patients with lobular carcinoma of breast, tumor registry data from 54 cases indexed as lobular carcinoma during the period 1973-82 were reviewed. Recurrences and/or deaths due to cancer were essentially confined to the group of patients with a component of invasive lobular carcinoma (ILC), therefore this subset was selected for further study. Seven of 20 cases had lymph node metastases diagnosed histologically at the time of mastectomy. Follow-up of these patients showed four dead of disease (DOD) at one, three, three, and seven years; one alive with disease (AWD) at one year; and two with no evidence of disease (NED) at four and five years. Eleven of 20 were node negative. Follow-up of this group showed nine NED and two DOD at two and four years. Two of 20 had unknown node status. Formalin-fixed, paraffin embedded lymph node blocks were available in 12 of 20 cases with a component of ILC. Of these, 4/12 cases had histologically positive nodes while 8/12 were originally diagnosed as negative. A cytokeratin monoclonal antibody cocktail (MAK-6, CAM 5.2 and AE1/AE3) was applied to all 12 cases. Cytokeratin immunoreactivity (CK-IR) was found in all four cases that were histologically positive. Five of eight histologically negative nodes lacked CK-IR, however the other three cases showed CK-IR in micrometastases. Review of newly prepared hematoxylin-eosin sections from the paraffin blocks failed to demonstrate metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Deficits in cholinergic neurotransmission markers induced by ethylcholine mustard aziridinium (AF64A) in the rat hippocampus: sensitivity to treatment with the monoamine oxidase-B inhibitor L-deprenyl.

Assessment was made of the effects of intracerebroventricular (i.c.v.) administration of ethylcholine mustard aziridinium (AF64A) and of the monoamine oxidase (MAO)-B inhibitor L-deprenyl on the acetylcholine (ACh) biosynthetic enzyme choline acetyltransferase (ChAT), on the ACh catabolic enzyme acetylcholinesterase (AChE) and on the density of ACh muscarinic M-1 and M-2 receptor sites. In addition, the effect of AF64A and of L-deprenyl treatment on the localization of AChE activity in the CA-1 and CA-3 fields of the hippocampus was evaluated by combined enzyme histochemistry and microdensitometry techniques. I.c.v. injection of AF64A induced, 4 weeks after administration of the neurotoxin, a remarkable increase of MAO-B activity, and a significant reduction of ChAT and AChE activities in the hippocampus but not in the neostriatum which was used as a reference tissue. Hippocampal muscarinic M-1 receptors were unaffected by AF64A administration, whereas M-2 sites were reduced after neurotoxin injection. Enzyme histochemistry analysis showed that the loss of AChE induced by AF64A was more pronounced in the CA-3 than in the CA-1 field of the hippocampus. Treatment with L-deprenyl induced, from a dose of 11.17 microM/kg/day, a significant reduction of MAO-B activity in the hippocampus. The expression of ChAT and AChE, as well as the density of M-2 receptors, was increased after L-deprenyl administration in the hippocampus but not in the neostriatum. An increase in AChE reactivity was noticeable in the CA-1 and CA-3 fields of the hippocampus of AF64A-injected rats treated with L-deprenyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1992

Endothelial dopamine DA-1 receptor sites in the rabbit pulmonary artery: autoradiographic demonstration.

Combined in vivo radioreceptor binding and autoradiographic techniques were used to characterized the pharmacological profile and to study the anatomical localization of dopamine (DA) DA-1 receptor sites in sections of rabbit pulmonary artery. [3H]R-(+)-8-chloro-2,3,4,5-tetrahydro-5-phenyl-1H-3-benzazepin-7- alhemimaleate (SCH 23390), which was used as a ligand, was bound by sections of rabbit pulmonary artery in a manner consistent with the binding of DA DA-1 sites. The Kd value was 4.75 nM, whereas the Bmax value was 78.3 +/- 5.7 fmol/mg tissue. Light microscope autoradiography demonstrated specific [3H]SCH 23390 binding sites primarily in the endothelium of the rabbit pulmonary artery. Moreover, sparse receptor sites were visualized in the medial layer. Mechanical removal of endothelium caused the disappearance of [3H]SCH 23390 binding sites showing the endothelial localization, but was without effect on the receptor sites of the medial layer. The present findings suggest that differently from systemic arteries, where DA-1 receptor sites are localized in the medial layer, probably within smooth muscle, the majority of DA-1 sites in the rabbit pulmonary artery are endothelial. The possible significance of these sites visualized in the present study for the first time is discussed.

Animals↗
PubMed1992

Acute effects of hydroxyethylrutosides on capillary filtration in normal volunteers, patients with venous hypertension and in patients with diabetic microangiopathy (a dose comparison study).

The acute effects of hydroxyethylrutosides on capillary filtration were studied in 12 normal subjects, 25 patients with venous hypertension and 22 diabetics with microangiopathy. The two groups of patients randomly received a single oral dose (500 or 1000 mg) of hydroxyethylrutosides. A single dose of 500 mg was used for normal volunteers. In the following 6 hours capillary filtration was studied with straingauge plethysmography. The decrease in capillary filtration was evident within the first hour and was at its peak between the second and fourth hour. After 6 hours it was still significantly below baseline values in patients. The 1000 mg dose was significantly more effective in both groups of patients. This study confirms the efficacy of hydroxyethylrutosides in decreasing capillary filtration. It suggests that the effect of one dose lasts at least 6 hours and also that the higher dose is more effective.

Adult↗
PubMed1991

Cyclic AMP modulates sensory-neural communication at the vestibular end organ.

Adenosine 3':5'-cyclic phosphate (cAMP) is a second messenger that plays an important role in mediating neuronal interactions in many systems. A possible role for cAMP in sensorineural communication at the vestibular end organ was studied. The putative roles for cAMP action investigated here were: the ability of cAMP to act as the second messenger for the efferent transmitter, acetylcholine, and the possible involvement of cAMP in modulating spontaneous or mechanically-evoked afferent nerve firing. Levels of cAMP were increased pharmacologically with forskolin, 3-isobutyl-1-methyl xanthine (IBMX) and dibutyryl cAMP. Changes in multiunit afferent nerve firing measured from the ampullar nerve of the semicircular canal, and the transepithelial potential measured across the neuroepithelium of the semicircular canal were recorded. At selected doses, all drugs produced a similar increase in spontaneous multiunit afferent nerve firing with a concomitant decrease in the transepithelial potential. Mechanically-evoked hair cell activity and the response to exogenously applied acetylcholine were unaffected by these drugs. We are suggesting that the excitatory aspects of the acetylcholine response are not mediated via a cAMP-dependent mechanism. However, cAMP does play an important role in modulating spontaneous afferent nerve firing in the semicircular canal. The finding that spontaneous afferent nerve firing can be biochemically modulated without altering mechanically-induced afferent firing is novel and deserves further investigation.

1-Methyl-3-isobutylxanthine↗
PubMed1991

[Plication of the sapheno-femoral junction].

Plication of the long saphena at the sapheno-femoral junction (SFJ) is an alternative to flush ligation and stripping. This technique abolishes reflux at the SFJ without altering the vein which may be used for arterial surgery or coronary grafting. The selection of the candidate for plication is done with ambulatory venous pressure measurements and duplex scanning which indicate and quantify the superficial incompetence. The plication of the SFJ reduces the calibre of the vein to 60-70% for a length of 1.5 cm allowing the valvular cusps to close when flow in the femoral vein is reversed. In this study we evaluated 20 limbs (in 20 patients) 6, 12 and 24 months after plication. Venous reflux was significantly reduced with improvement of signs and symptoms. In conclusion, SFJ plication seems to be an effective physiological alternative to flush ligation. However long term results (greater than 5 years) must be still evaluated.

Adult↗
PubMed1991

Autoradiographic localization of dopamine receptors in rat cerebral blood vessels.

Combined in vitro radioreceptor binding and autoradiographic techniques were used to analyze the pharmacological profile and the anatomical localization of dopamine (DA) DA1 and DA2 receptor sites in the arteries and arterioles of the pial-arachnoid membrane in the rat. [3H]SCH 23390, used as a ligand of DA1 receptors, was bound by sections of rat cerebral vessels in a manner consistent with the labeling of DA1 receptors, with a value of 2.2 nM for the dissociation constant (Kd) and of 68.4 fmol/mg protein for the density of binding sites (Bmax). The ligand was bound primarily by the medial layer of cerebral arteries. The density of silver grains developed after exposure of cerebral vessel sections to [3H]SCH 23390 was unchanged after chemical sympathectomy with 6-hydroxydopamine (6-OHDA) and was not significantly different in either the circle of Willis arteries or in the pial-arachnoid arteries and arterioles. [3H]Spiroperidol was used as ligand of DA2 receptors in the presence of ketanserin to block the possible binding to 5-HT2 receptors. [3H]Spiroperidol was bound by sections of rat cerebral vessels in a manner consistent with labeling of DA2 receptors, with Kd and Bmax values of 1.9 nM and 39.8 fmol/mg protein, respectively. The ligand was bound primarily by the adventitia and the adventitial-medial border as well as by the intimal layer of cerebral arteries. The accumulation of adventitial and adventitial-medial silver grains developed after exposure of cerebral vessels sections to [3H]spiroperidol did not occur in 6-OHDA-treated animals. In contrast, chemical sympathectomy was without effect on the density of intimal silver grains. The density of adventitial silver grains was higher in the anterior than in the posterior circle of Willis and pial-arachnoid arteries and arterioles, as well as in the pial-arachnoid arteries and arterioles than in circle of Willis arteries. These findings indicate the existence of both DA1 and DA2 receptor sites in the rat cerebrovascular tree.

Animals↗
PubMed1991

Dopamine DA-2 receptor sites in the rat renal cortex: a light microscope autoradiographic study.

The binding of the DA-2 receptor antagonist [3H]-spiroperidol, in the presence of appropriate concentrations of ketanserin to avoid the possible labelling of 5-HT-2 sites, was studied in sections of rat kidney using combined radioreceptor assay and light microscope autoradiography. [3H]-Spiroperidol was bound by sections of rat kidney in a manner consistent with the labelling of a single class of high affinity of DA-2 sites. Scatchard analysis of the binding isotherms showed a Kd value of 2.5 +/- 0.2 nmol/l and a Bmax value of 129.5 +/- 6.8 fmol/mg protein. Light microscope autoradiography, centered on the renal cortex, revealed the development of silver grains within cortical convoluted tubules. Silver grains were rather homogeneously distributed to both proximal and distal convoluted tubules, with no specific glomerular localization. These findings do not support the assumption of the existence of glomerular DA-2 receptors in the rat kidney.

Animals↗
PubMed1991

Biochemical, autoradiographic and pharmacological evidence for the involvement of tubular DA-1 receptors in the natriuretic response to dopexamine hydrochloride.

Dopexamine hydrochloride (DPX) is a dopamine analog and it possesses agonistic action at DA-1 receptors and beta 2-adrenoceptors. It also is a weak agonist at DA-2 receptors. In the present study, we have examined the anatomical localization of DPX binding sites in rat kidney and their functional significance in terms of the renal effects of this compound. In receptor-ligand binding studies, [3H]-DPX was found to bind specifically to sections of rat kidney in a time (maximum binding at 60 min), temperature (optimal temperature 25 degrees C) and concentration (highest specific/non-specific ratio at 2 nmol/l) dependent manner. Autoradiographic studies revealed the presence of [3H]-DPX binding sites in renal tubules, glomerulus and various layers of small and large blood vessels. Inhibition studies with SCH 23390, ICI 118.551 and 1-sulpiride showed that DPX binds primarily to DA-1 receptors in tubules, only to beta 2-adrenoceptors in glomerulus and to beta 2-adrenoceptors, DA-1 and DA-2 receptors in blood vessels. Also, DPX caused concentration related increases in cyclic AMP levels in rat kidney membrane particles, which could be completely abolished by a combined presence of SCH 23390 and propranolol suggesting that both binding sites of DPX are linked to adenylate cyclase. In functional studies DPX (1 microgram/kg.min for 30 min) produced a modest fall in blood pressure, pronounced tachycardia and slight but significant increase in renal blood flow (11%). These responses were accompanied by increases in urine output (97%), urinary sodium excretion (89%), and fractional excretion of sodium (132%). There was no change in glomerular filtration rate. Propranolol pretreatment abolished DPX-induced hypotension and tachycardia but seemed to potentiate the natriuretic responses to DPX. On the other hand, SCH 23390, a DA-1 receptor antagonist completely abolished DPX-induced hypotension, natriuresis and diuresis without affecting tachycardia. These results indicate that (1) DPX binds predominantly to DA-1 receptors in renal tubules, to beta 2-adrenoceptors in glomerulus and to beta 2-adrenoceptors, as well as DA-1 and DA-2 receptors in renal blood vessels (2) DPX stimulates cAMP formation in the kidney by activating both DA-1 and beta 2-adrenoceptors and (3) DPX produces natriuresis and diuresis by selectively activating DA-1 receptors located on renal tubules.

Adenylyl Cyclases↗
PubMed1991

Immunocytochemical analysis of estrogen and progesterone receptors in benign stromal lesions of the breast. Evidence for hormonal etiology in pseudoangiomatous hyperplasia of mammary stroma.

Five cases of pseudoangiomatous hyperplasia of mammary stroma, together with seven examples of mammary hamartoma, were probed with monoclonal antibodies H222 and KD68 to investigate the possible role of estrogen and progesterone receptor expression in the pathogenesis of these benign stromal proliferations. All five cases of pseudoangiomatous hyperplasia showed patchy, intense labelling of the stromal cells with progesterone receptor antibodies, a pattern contrasting markedly with the absence of immunoreactivity in normal (nongestational) mammary stroma or the stromal component of common juvenile mammary hyperplasia. The stroma of the hamartoma group labeled inconsistently, with the notable exception of three myoid hamartomas. Stromal immunoreactivity was diffuse and intense in two of these, and patchy and distinct in the remaining case. These findings (a) support the contention that pseudoangiomatous hyperplasia represents a localized form of stromal overgrowth with a hormonal (primarily progestagenic) etiology and (b) further highlight the heterogeneity of so-called mammary hamartomas by demonstrating dramatically different progesterone receptor immunoreactivity patterns in myoid lesions as compared with other hamartoma variants.

Adult↗
PubMed1991

Thalassaemia trait and myocardial infarction: low infarction incidence in male subjects confirmed.

A total of 4401 subjects admitted to the Medical Division of St Camillo Hospital in Comacchio (Ferrara, Italy) over a period of 7 years were prospectively evaluated in order to determine whether the heterozygous beta-thalassaemic (HBT) could be considered as a protective factor against the occurrence of acute myocardial infarction (AMI). Of the total patient sample, 3954 subjects were non beta-thalasaemics (NBTs), and 447 subjects were heterozygous beta-thalassaemics (HBTs). AMI was diagnosed in 384 patients, of whom 17 individuals were HBTs and 367 subjects were NBTs. The prevalence of HBTs in this group was significantly lower than expected (4.43%, P less than 0.0001). Furthermore, an analysis by sex showed that this lower prevalence could be attributed to male patients. Moreover, only in male subjects was a significant negative correlation observed between AMI and HBT. The mean age at which AMI occurred in male HBTs was significantly higher than in male NBTs (72 +/- 2.69 vs. 63 +/- 0.7 years, P less than 0.05), while no differences were found in the mean age at which AMI occurred between HBT and NBT female subjects. This study demonstrates that the thalassaemic trait may afford some protection against the occurrence of AMI in men.

Aged↗
PubMed1991

Dopamine receptors mediating inhibition of the cyclic adenosine monophosphate generating system in the rat renal cortex.

1. In vitro addition of dopamine (DA) or of DA-1 receptor agonists increases 3'- 5'-cyclic adenosine monophosphate (cAMP) levels through the stimulation of DA-1 receptors. 2. Although receptor binding studies suggest the existence of DA-2 receptors in the renal cortex, the presence of DA receptors negatively coupled to cAMP generation (DA-2 effect) has not been so far characterized. 3. In this study we have shown that the addition of DA plus the selective DA-1 receptor antagonist SCH 23390 to membrane fractions of rat renal cortex decreased cAMP concentration below basal levels. 4. DA-2 receptor responses were also elicited with the DA-2 receptor agonists bromocriptine and quinpirole in the absence of SCH 23390. These inhibitory effects on cAMP generation were abolished by the DA-2 receptor antagonist 1-sulpiride. 5. The above findings are indicative of the existence in the rat renal cortex of DA-2 receptors showing an effect upon cAMP generation similar to that found in the brain and in several peripheral tissues.

Animals↗
PubMed1991

Anatomical localization of the binding and functional characterization of responses to dopexamine hydrochloride in the rat mesenteric vasculature.

Dopamine receptors of the DA1 subtype have been identified in mesenteric blood vessels, stimulation of which leads to vasodilation. In this study, we have determined the anatomical localization of dopexamine-hydrochloride-binding sites and carried out functional characterization of responses to this DA1-receptor and beta 2-adrenoceptor agonist in rat mesenteric vasculature. Autoradiographic studies showed the presence of [3H]-dopexamine-binding sites in all the different layers of the mesenteric artery. The DA1 receptor antagonist, SCH 23390 (IC50 = 4.9 mumol/l), and the beta-adrenoceptor antagonist, propranolol (IC50 = 6.0 mumol/l), inhibited the binding of dopexamine. The inhibitory effect of these compounds on dopexamine binding was selective for different regions of the mesenteric artery. Also, dopexamine produced concentration-related increases in cAMP formation in membrane particles from superior mesenteric artery and its main branches. The presence of both SCH 23390 and propranolol was required to completely abolish dopexamine-induced increases in cAMP formation. In functional studies, dopexamine (1 and 3 micrograms/kg/min) produced dose-related increases in mesenteric blood flow (23 and 38%, respectively) which were accompanied by concomitant decreases in the calculated mesenteric vascular resistance. As seen with increases in cAMP, the vascular responses to dopexamine could be completely abolished only by prior treatment with both SCH 23390 and propranolol. These results suggest that in mesenteric vasculature of rat dopexamine binds primarily to DA1 receptors and beta 2-adrenoceptors. The activation of these receptors by dopexamine leads to vasodilation which is mediated by an increase in the intracellular levels of cAMP.

Adenylyl Cyclases↗