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Biomedical subjects

F Ferrante

Publications and source records attributed to F Ferrante.

At least 55 records · Page 3Linked to original sources

Muscarinic cholinergic receptors in the human right coronary artery: a receptor binding and autoradiographic study.

We used a combination of radioreceptor binding and autoradiographic techniques to study the pharmacological characteristics and anatomical localization of [3H]-quinuclidinyl benzilate (QNB) binding sites in the human right coronary artery. The ligand was bound to sections of the human right coronary artery in a manner consistent with the labelling of muscarinic receptors. The addition of pirenzepine or of carbachol to the incubation medium to generate displacement curves was indicative of the presence of M1 and M2 receptors in the right coronary artery. Autoradiography showed the localization of M1 sites primarily in the medial layer of the right coronary artery. M2 sites were located primarily in the adventitia. No [3H]-QNB binding sites were observed in the endothelium. A possible role of muscarinic receptors in the pathogenesis of coronary vasospasm is discussed.

Adolescent↗

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↗

Effect of nicardipine treatment upon cardiac hypertrophy in spontaneously hypertensive rats: a morphometric and ultrastructural study.

OBJECTIVE: The present study was designed to investigate the effect of nicardipine administration upon systolic blood pressure (SBP) and cardiac hypertrophy in spontaneously hypertensive rats (SHR). DESIGN: SBP, heart: and left ventricle: body weight ratios, the cross-sectional area of cardiocytes, and the ultrastructure of the left ventricle were evaluated. METHODS: Ten-week old male SHR and age-matched normotensive Wistar-Kyoto rats were studied for 12 weeks. One group of SHR was treated for 12 weeks with a daily oral dose of 1 mg/kg nicardipine and another group with 1 mg/kg hydralazine; Wistar-Kyoto rats were used as a normotensive control group. Light and electron microscope techniques associated with image analysis and morphometry were used. RESULTS: Nicardipine administration normalized SBP values and significantly reduced the heart: and left ventricle: body weight ratios. Moreover, administration reduced the cross-sectional area of cardiocytes by approximately 38% in subendocardium and by 24% in subepicardium. Hydralazine administration significantly reduced SBP values but had no effect upon heart: or left ventricle: body weight ratios or the cross-sectional area of cardiocytes. Electron microscopy showed that nicardipine treatment was able to reduce the hypertension-dependent changes in cardiac ultrastructure consisting of alternations to intercalated discs and line Z morphology as well as in the decrease of the mitochondria: myofibrils ratio. CONCLUSIONS: The above data indicate that nicardipine administration is able to reduce SBP and to counter the development of structural and ultrastructural changes in cardiac morphology which represent a common complication of arterial hypertension.

Animals↗

Autoradiographic localization of the gamma-aminobutyric acid type A receptor agonist 3H-muscimol in the rat superior cervical ganglion.

The anatomical localization of gamma-aminobutyric acid type A (GABA-A) receptor sites in the rat superior cervical ganglion was studied using combined radioreceptor binding and autoradiographic techniques. 3H-Muscimol was used as a ligand of GABA-A receptor sites. The binding was consistent with the labelling of GABA-A sites. The dissociation constant value was 6.4 nmol/l, and the maximum density of binding sites was 146 +/- 7.8 fmol/mg tissue. Light microscope autoradiography revealed the accumulation of 3H-muscimol mainly in superior portions of the ganglion. Binding sites are located primarily in the neuropil rather than within ganglionic neurons. It is probable that the sites revealed by autoradiography are involved in the inhibition of acetylcholine release from ganglionic neurons.

Animals↗

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↗

Effect of ethylcholine mustard aziridinium (AF64A) and of the monoamine oxidase-B-inhibitor L-deprenyl on the morphology of the rat hippocampus.

The effect of intracerebroventricular (ICV) administration of ethylcholine mustard aziridinium (AF64A) and of the monoamine oxidase (MAO)-B inhibitor L-deprenyl on MAO-A and MAO-B activities and on the morphology of the rat neostriatum and hippocampus were studied. The ICV administration of AF64A was without effect on MAO-A and MAO-B in the neostriatum and caused an increase of MAO-B but not of MAO-A in the hippocampus. No changes in neostriatal micro-anatomy were noticeable in AF64A-injected rats, whereas the neurotoxin caused an impairment in hippocampal micro-anatomy consisting in the loss of nerve cells and of silver-gold impregnated fibres in the CA-1--CA-3 fields. The treatment of AF64A-injected animals with doses of L-deprenyl from 11.17 microM/kg/day significantly reduced MAO-B activity in the hippocampus and improved the morphology of the hippocampus formation. L-deprenyl was without effect on MAO-A activity both in the neostriatum and in the hippocampus, as well as on neostriatal MAO-B activity and morphology. The possibility that MAO-B inhibition may represent a principle for the treatment of age-related physiological and pathological changes characterized by increased MAO-B activity is discussed.

Animals↗

[Acute cholecystitis associated with calculosis of the biliary tract in a high-risk patient. Combined emergency surgical and peroperative endoscopic treatment].

Patient age (over 65), and lithiasis of the common bile duct are two factors which increase the morbidity and mortality rate in emergency surgery for biliary lithiasis. Normally, calculi in the CBD can be cleared by means of supraduodenal or transduodenal access. In both cases, however, complications are frequent in high risk patients. Treatment of gallstones can be modified to achieve a reduction in the morbidity and mortality rate. This study presents an initial survey of 4 elderly patients, presenting with acute gallbladder disease and CBD stones, treated with surgical cholecystectomy and contemporary perioperative endoscopic papillotomy and CBD clearance. The underlying rationale and the good initial results support this combined surgical and endoscopic approach.

Aged↗

Nicardipine and vascular hypertrophy.

The effects of nicardipine administration on the morphology of coronary, renal, and pulmonary vascular trees were studied in spontaneously hypertensive rats (SHRs). Male 10-week-old SHRs received 1 mg/kg/day of nicardipine or vehicle orally for 12 weeks. Age-matched Wistar-Kyoto rats were used as normotensive reference animals. Blood pressure, heart weight, heart/body weight ratio, the area occupied by the medial layer, and area occupied by the vascular wall/area of lumen ratio increased significantly (p less than 0.001) in SHRs compared with normotensive Wistar-Kyoto rats. Nicardipine reduced blood pressure, as well as relative heart weight, the area occupied by vascular smooth muscle, and the area occupied by the vascular wall/area of lumen ratio. In addition, the size of laminae of smooth muscle of the pulmonary artery was reduced in nicardipine-treated SHRs; coronary artery branches were the most sensitive. The results of the study provide direct evidence that nicardipine reduces not only blood pressure but is also able to counteract the development of hypertension-dependent changes in the morphology of the cardiovascular system.

Animals↗

Intrinsic innervation of the rat knee joint articular capsule and ligaments.

In spite of the practical importance of having a detailed knowledge of knee joint innervation to understand the pathophysiologic aspects, little information is now available concerning the density and pattern of the nerve fibres which are distributed to it. The present study has been designed to investigate the density and distribution of nerve fibres and receptor corpuscles in the knee joint articular capsule, cruciate and collateral ligaments in the rat, using the acetylcholinesterase (AChE) histochemical in toto staining technique. The investigation was performed on male Wistar rats of 3 months of age, some of which had been treated with capsaicin to deplete their afferent 'C' fibres of their content of neuropeptides. AChE-positive nerve fibres and different types of receptor corpuscle endings were found within articular capsule and ligaments. The highest density of AChE-positive nerve fibres was noticeable in the fibular collateral ligament followed by the tibial collateral ligament, the posterior cruciate ligament, the anterior cruciate ligament and the articular capsule. In the articular capsule the number of type I endings was higher than in the ligaments. The opposite is true for the other type of receptor corpuscles found as well as for nerve endings. Capsaicin treatment significantly reduced the density of AChE-positive nerve fibres in knee joint ligaments but did not affect nerve fibres in the articular capsule. Moreover, it caused the disappearance of some kind of receptor corpuscles within the collateral and cruciate ligaments. The above data collectively suggest that the AChE in toto staining technique may represent a good method for investigating joint innervation and that a significant percentage of nerve fibres supplying knee joint ligaments is represented by C fibre afferents.

Acetylcholinesterase↗

Autoradiographic localization of beta-adrenergic receptors in human large coronary arteries.

The distribution of beta-adrenergic receptors in sections of the human right and left coronary arteries and of the anterior intraventricular branch was studied by the use of combined in vitro radioreceptor binding and autoradiographic techniques. [125I]Cyanopindolol was used as a ligand for beta-adrenergic receptors. Binding of the radioligand to sections of the three coronary arteries under study was saturable, stereoselective, reversible, and displaceable by antagonists and agonists with the rank order of potency expected for beta-adrenergic receptors. Analysis of binding isotherms indicated maximum binding capacities of 41.5 fmol/mg protein for the right coronary artery, 35.4 fmol/mg protein for the left coronary artery, and 25.7 fmol/mg protein for the anterior interventricular branch. Dissociation constants were approximately 35 pM in the arteries examined. The relative amounts of beta 1- and beta 2-receptor subtypes were as follows: 72% beta 1-receptors and 28% beta 2-receptors in the right coronary artery; 65% beta 1-receptors and 35% beta 2-receptors in the left coronary artery; 40% beta 1-receptors and 60% beta 2-receptors in the anterior interventricular branch. The results of autoradiographic analysis revealed a predominance of beta 1-receptors in the medial layer. beta 2-Receptors were localized primarily in the adventitia, in the adventitia-media border, and in the intimal layer. These results should lead to a better understanding of the mechanisms involved in the control of coronary circulation in humans.

Adolescent↗

Effect of long-term isradipine treatment on the hypertension-dependent changes in coronary arteries in spontaneously hypertensive rats.

The present study was designed to assess the effect of long-term isradipine treatment on the morphology of different-sized coronary artery branches in spontaneously hypertensive rats (SHR). Male SHR (12-week-old) received 1 mg/kg/day isradipine or vehicle (control group) orally for 12 weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as a reference group and did not receive any treatment. The animals were perfused with a fixative solution through the left ventricle and left ventricle blocks were embedded in resin. Sections including different-sized coronary artery branches were examined under a light microscope connected with an image analyser. The area occupied by the medial layer and the wall-to-lumen ratio were assessed in coronary artery branches of small (diameter less than 100 microns), medium (diameter 100-250 microns) and large (diameter greater than 250 microns) size. In control SHR, the blood pressure values and morphometric parameters examined significantly increased (p less than 0.001) in comparison with normotensive WKY rats. Isradipine treatment normalized blood pressure values in SHR and significantly reduced the area occupied by the medial layer and the wall-to-lumen ratio in small and medium-sized, but not in large-sized, coronary artery branches. These results indicate that isradipine treatment is able not only to reduce blood pressure elevation in SHR, but also to counteract the hypertension-dependent changes in the morphology of arterial branches controlling coronary resistances.

Animals↗

The noradrenergic innervation of the ovary in old rats.

The influence of ageing on the noradrenergic innervation of the ovary was studied in female Wistar rats using high pressure liquid chromatography (HPLC) with electrochemical detection and catecholamine histofluorescence techniques. Old age was accompanied by a significant decrease in ovarian noradrenaline levels. In young animals (3-month-old) noradrenergic nerve fibres were distributed primarily to blood vessels and in lesser amounts to the interstitial glands. In aged animals (24-month-old) perivascular noradrenergic fibres were reduced by more than 40%; interstitial gland nerve fibres were reduced by approximately 20%. The possibility that impaired noradrenergic ovarian innervation occurring in old age may be in some way related with age-dependent failure in reproductive activity is discussed.

Aging↗

Age-related changes in adrenaline content of rat splanchnic blood vessels.

The influence of ageing on the adrenaline content of the superior mesenteric artery and vein, renal artery and vein and portal vein was studied in 3-month- (young), 12-month- (adult) and 24-month-old (old) male Wistar rats using radioenzymatic assay for the measurement of catecholamine levels. Adrenaline concentrations were unchanged in the vascular wall of the blood vessels examined in adult rats, but were significantly decreased in the vascular wall of the superior mesenteric, renal and portal veins of old rats. In contrast, no age-dependent changes of adrenaline levels were found in the vascular wall of the superior mesenteric or renal arteries. The possibility that the loss of adrenaline concentrations in the venous vascular wall may be in some way related to the cardiovascular impairment occurring with age is discussed.

Aging↗

Intracerebroventricular injection of hemicholinium-3 prevents the ACTH-induced, but not the physostigmine-induced, reversal of hemorrhagic shock in rats.

In rats bled to hypovolemic shock, the intracerebroventricular injection of hemicholinium-3 (20 micrograms/rat) completely prevented the shock reversal induced by the intravenous injection of ACTH (1-24) (160 micrograms/kg), but had no influence on the shock reversal induced by the intravenous injection of physostigmine (70 micrograms/kg). These data indicate that brain cholinergic neurons are involved in the anti-shock effect of ACTH-peptides, but not in that of centrally acting cholinergic drugs.

Adrenocorticotropic Hormone↗

Prostaglandin-stimulated recovery of the human duodenal epithelium: effects of misoprostol on ethanol damage.

This study was designed to determine whether prostaglandins can stimulate the repair of human duodenal epithelium. Ten healthy volunteers were given 50 ml 40% ethanol through an endoscope onto the duodenal mucosa 1-7 cm from the pyloric sphincter; 3 min later, misoprostol (200 micrograms) or inert vehicle (5 ml) was given locally in the same way. One and 5 h later, endoscopy was repeated to evaluate the damage. The conditions of the mucosa were evaluated by endoscopy and by scanning and transmission electron microscopy in biopsies taken at time 0 and 3 min, 1 and 5 h after ethanol. The study was double-blind with a cross-over balanced design. Three minutes after ethanol administration, the duodenal mucosa showed hyperemia with hemorrhagic lesions. Under the electron microscope, the lesions were caused by vascular engorgement or red blood cell extravasation into the submucosa; the epithelium underlining lesions showed loss of superficial cells and damage to the upper layer of the mucosa. One hour after ethanol, there was a striking difference between the two treatment groups, with a substantial recovery of the duodenal epithelium in the misoprostol-treated volunteers. Although spontaneous recovery was evident in the control group, there was also a significant difference at 5 h. Our results suggest that prostaglandins are able to stimulate the recovery of the duodenal epithelium after acute damage.

Alprostadil↗

Autoradiographic localization of vasoactive intestinal polypeptide receptors in the rat mesenteric vascular tree.

By the use of combined in vitro radioreceptor binding and autoradiographic techniques, we analyzed the pharmacological properties and the anatomical localization of the vasoactive intestinal polypeptide (VIP) receptor in rat superior mesenteric artery and in medium and small mesenteric artery branches. 125I-VIP was bound by sections of rat superior mesenteric artery in a manner consistent with the labeling of specific VIP receptors, with Kd and Bmax values of 0.23 nM and 0.71 pmol/mg protein respectively. Inhibition of 125I-VIP binding with VIP and related peptides gives the following rank order of potency: VIP greater than peptide histidine methionine greater than secretin. Light microscope autoradiography reveals specific VIP binding sites within the medial layer of superior mesenteric artery and its branches. Medium and small sized vessels are richer in 125I-VIP binding sites than the larger ones.

Animals↗

Effect of acetyl-L-carnitine treatment on the density of muscarinic receptors in the brain of methylazoxymethanol-microencephalic rats.

The effect of methylazoxymethanol (MAM), administered on the 15th gestational day, on the density and pattern of muscarinic cholinergic receptors in some brain areas was assessed using combined radioreceptor binding and autoradiographic techniques. The effect of 15 days' treatment with acetyl-L-carnitine on the same parameter was also assessed. The density of muscarinic cholinergic receptors was found to be increased in the brain of MAM-microencephalic rats. Acetyl-L-carnitine administration caused a significant reduction in the density of receptors under study. A possible role of acetyl-L-carnitine in restoring central cholinergic neurotransmission is discussed.

Acetylcarnitine↗