Biomedical subjects
Publications and source records attributed to L Felici.
A case of mycobacterial lymphadenitis due to Mycobacterium malmoense was recently diagnosed in a 5-year-old girl. The organism was isolated from pus and tissue fragments obtained by surgical excision of the affected nodes. This is the first documented case of human infection due to this organism in Italy.
The study was designed to assess whether Ca2+ channel blockers of the dihydropyridine family (felodipine, nicardipine, nifedipine, nimodipine, nitrendipine and nisoldipine), and of the phenylalkylamine family (verapamil) have any effect on alpha-adrenoceptor binding to sections of the human right coronary and mammary arteries, measured using [3H]-dihydroergocryptine (DHT) as a ligand. Increasing concentrations of nicardipine, verapamil and nitrendipine competed with [3H]-DHT binding to sections of the human coronary and mammary arteries. The other compounds tested were without effect. Among the competitors of [3H]-DHT binding, nicardipine was the most powerful, with a 50% inhibition (IC50) value of approximately 10 nM. The pharmacological profile of competition with [3H]-DHT binding by nicardipine, in the presence or in the absence of guanosine triphosphate and NaCl, is consistent with antagonist activity of the dihydropyridine derivative at the alpha-adrenoceptor. This property may account for the lower sympathetic stimulatory activity elicited by nicardipine, in comparison with other Ca2+ channel blockers used in cardiovascular therapy.
1. The subtype and anatomical localization of beta-adrenoceptors mediating facilitation of stimulus-induced overflow of noradrenaline ('prejunctional beta-adrenoceptors') are not conclusively known to date. The present study was undertaken to characterize these receptors by use of pharmacological methods as well as to define their localization (prejunctional or postjunctional) with radio-ligand binding and autoradiography techniques combined with surgical denervation of the sympathetic innervation to the rat kidney. 2. Exposure of the kidney to (-)-isoprenaline, the nonselective beta-adrenoceptor agonist, resulted in a dose-dependent facilitation of stimulus-induced neurotransmitter overflow. This response was inhibited by propranolol, the beta 1- and beta 2-adrenoceptor antagonist, with a pA2 of 9.20 suggesting that the prejunctional beta-adrenoceptors are not of the beta 3-subtype. 3. The rank order of potency and potency ratios of beta-adrenoceptor agonists at renal prejunctional beta-adrenoceptors (EC50 for agonist/EC50 for (-)-isoprenaline) were: (-)-isoprenaline (1) > procaterol (2) > salbutamol (3) > adrenaline (10) > (+)-isoprenaline (25). However, dobutamine, the beta 1-adrenoceptor agonist, failed to enhance stimulus-induced overflow of noradrenaline. These results are indicative of the presence of beta 2-adrenoceptors as prejunctional beta-adrenoceptors. 4. Facilitation elicited by (-)-isoprenaline and procaterol, the selective beta 2-adrenoceptor agonist, was inhibited by ICI 118,551, the selective beta 2-adrenoceptor antagonist, with pKb values of 9.20 and 9.35, respectively at renal prejunctional beta-adrenoceptors. Similarly, the pKb values of metoprolol, the selective beta 1-adrenoceptor antagonist, at renal prejunctional beta-adrenoceptors were determined to be 6.25 and 6.18 against (-)-isoprenaline and procaterol, respectively. These results suggest the presence of a homogeneous population of beta 2-adrenoceptors as prejunctional beta-adrenoceptors. 5. Radio-ligand binding analysis of renal beta-adrenoceptors revealed the prevalence of the beta 1-subtype as compared to the beta 2-subtype (63% vs 37%). However, surgical denervation of the rat kidney, resulting in more than 90% reduction in renal noradrenaline content, selectively reduced the beta 2-adrenoceptor population by 80%, implying the presence of beta 2-adrenoceptors on renal sympathetic nerve terminals. 6. Autoradiographic analysis demonstrated the presence of beta 1-adrenoceptors on cortical structures such as glomeruli and tubules. beta-Adrenoceptors were found to be present on tubules (minor population), collecting tubules in outer medulla and the adventitia and adventitial-medial border of intraparenchymal branches of the renal artery. Surgical denervation of the rat kidney resulted in the disappearance of Beta2-adrenoceptors associated with the intraparenchymal branches, without affecting the Beta-adrenoceptor populations at other sites. These results support the notion that the Beta2-subtype is present on renal sympathetic nerve terminals and demonstrate that these prejunctional Beta2-adrenoceptors are associated with the renal vasculature and not with renal tubules.7. The results of the present investigation demonstrate that renal prejunctional Beta-adrenoceptors are of the Beta2-subtype in nature. These receptors are present on sympathetic nerve terminals which are associated with the renal vasculature.
The present study assesses the effect of unilateral lesions of the nucleus basalis magnocellularis (NBM) and of treatment with L-alpha-glyceryl phosphorylcholine (GFC, choline alfoscerate) on the acetylcholine-synthesizing (choline acetyltransferase (ChAT)), and acetylcholine-degradating (acetylcholinesterase (AChE)) enzymes in the rat fronto-parietal cortex ipsilateral to the lesion. Ibotenic acid injections in the right NBM area caused a significant decrease of both ChAT and AChE activities as well as of histochemically reactive stores of AChE in the right fronto-parietal cortex. Treatment with GFC restored in part the loss of ChAT and AChE activities. Moreover, AChE reactivity is restored in the fronto-parietal cortex of NBM-lesioned rats treated with GFC. GFC is a precursor in the biosynthesis of brain phospholipids which increases the bioavailability of acetylcholine in the nervous tissue. The possible relevance of the restoration of the marker enzymes of cholinergic neurotransmission by GFC in an animal model of cholinergic hypofunction is considered.
Muscarinic cholinoceptor subtypes (M1 and M2) were studied in membrane particles of the rat frontoparietal cortex 72 h and 1, 2, 3, and 4 weeks after ipsilateral lesioning of the nucleus basalis magnocellularis (NBM). The affinity of the ligand used to characterize muscarinic cholinoceptors, 3H-quinuclidinyl benzilate did not significantly change in lesioned compared with sham-operated rats as well as the density of high affinity (M1) sites. Low affinity muscarinic cholinoceptors (M2 sites) were significantly decreased in NBM-lesioned rats 72 h and 1 week after lesioning. The density of M2 sites did not significantly differ in lesioned rats 2 or 3 weeks after NBM lesioning, but increased, in comparison with sham-operation 4 weeks after NBM lesioning. These findings suggest that frontoparietal M2 muscarinic cholinoceptors, which probably have a presynaptic localization, are sensitive to NBM lesions. Their changes at different times after NBM lesioning suggest the occurrence of loss, compensation and upregulation of cholinergic projections arising to the neocortex from the NBM.
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.
A detailed analysis of immunophenotype of 112 infants aged less than 18 months with acute lymphoblastic leukaemia (ALL) was performed. Patients were divided into three groups on the basis of age at presentation (under 6 months: group 1: 6-12 months: group 2; 13-18 months: group 3). There were three cases of T-ALL (2.6%). The proportion of other subtypes was: common ALL in 59 patients (52.68%), pre-B ALL in 15 patients (13.3%), pre-pre-B ALL in 27 (24.1%) and acute undifferentiated leukaemia (AUL) in eight patients (7.14%). In non-T ALL, positivity to CD10 (corresponding to C-ALL and pre-B ALL) was distributed in the three age groups as follows: 38.88% (group I) 65.38% (group II) and 86.36% (group III). Conversely, immature phenotypes (pre-pre-B and AUL) were found more often in the younger patients of groups I and II, as well as anomalous phenotypes, such as the presence of myeloid antigens (MyAg) and of CD7. Prognostic significance was evaluated as event-free survival (EFS) by statistical analysis. A better outcome in CD10-positive ALL than in CD10-negative ones (48% v. 25% of long-term survivors) was demonstrated in all infants. Similarly, EFS was significantly better in MyAg-negative than in MyAg-positive cases. These results were confirmed also when adjusting for white blood cell count. This allowed the identification of CD10-negative, MyAg-positive ALL, which were relatively more frequent in infants and had a poorer clinical outcome with the current therapies. This study stresses the prognostic relevance of the immunological study in infant leukaemias and its utility in choosing different therapeutic modalities for poor risk phenotypes.
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.
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.
Hemoglobin Volga is a rare unstable hemoglobin in which there is a replacement of an internal alanine residue, beta 27 (B9), by an aspartate. From a clinical point of view it is characterized by a moderately severe Heinz body hemolytic anemia. A possible clue to the cause of the hemolysis is the increased vulnerability to oxidation of Hb Volga, with increased free radical turnover and consequent damage to the red cell membrane. Splenectomy performed on carriers of Hb Volga may have a positive outcome leading to improvements in both the clinical condition of the patient and hematological variables such as hemoglobin concentration and bilirubin concentration. With the aim of defining a more complete biochemical picture of the beneficial effect of splenectomy in this disease, we have evaluated some enzymic activities of the red cells of a young patient with Hb Volga disease, before and after splenectomy. In particular, we have investigated the activity of superoxide dismutase (superoxide: superoxide oxidoreductase), glutathione peroxidase (GSH peroxidase, glutathione: hydrogen-peroxidase oxidoreductase) and catalase (hydrogen-peroxide: hydrogen-peroxide oxidoreductase) that catalyze reactions relevant to the steady-state concentration of potentially toxic oxygen derivatives such as O2- and H2O2. Besides, we have carried out experiments on the erythrocytic membrane to evaluate eventual changes on the chemical (i.e. peroxidation) and physico-chemical (i.e. fluidity) properties following surgery.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The influence of ageing on glutamate dehydrogenase activity was studied in the cerebellar cortex of 3-month-old (young), 12-month-old (adult) and 26-month-old (aged) male Sprague-Dawley rats by using an enzyme histochemical technique. In young rats the enzyme reactivity was observed in the neuropil of the molecular layer as well as in the perikarya of basket cells and of stellate cells; within the cytoplasm of Purkinje neurons and in synaptic glomeruli of the granular layer. Glutamate dehydrogenase activity was significantly increased in the cerebellar cortex of adult rats and decreased in old animals. The synaptic glomeruli of the granular layer were the structures of the cerebellar cortex more remarkably affected by age-related changes. The possibility that decreased glutamate catabolism occurring in the ageing cerebellar cortex may result in an excess of the amino acid and may contribute to the nerve cell loss occurring in the cerebellum of old rats is discussed.
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.
Explore the source record for details and available documents.