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Biomedical subjects

F Magni

Publications and source records attributed to F Magni.

At least 37 records · Page 2Linked to original sources

Interference of the new antiinflammatory compound flunoxaprofen with eicosanoid formation in various biological systems.

S-(+)-2-(4-Fluorophenyl)-alpha-methyl-5-benzoxazolacetic acid (flunoxaprofen, Priaxim is a new antiinflammatory compound, which in various biological systems interferes with the generation and release of arachidonic acid metabolites of the cyclo-oxygenase pathways without affecting the formation of 5- and 12-lipoxygenase products. Flunoxaprofen reduces the concentration of thromboxane (TX)B2 (ED50 = 35.4 mg/kg p.o.) and prostaglandin (PG)E2-like activity (ED50 = 39.9 mg/kg p.o.) in the inflammatory exudate of rats 8 h after implantation of sponges soaked with carrageenan, whereas the concentration of leukotriene (LT)B4 remains in the range of that of the untreated animals (3.1 ng/ml). Flunoxaprofen inhibits cell infiltration in the exudate and this suggests that LTB4 does not initiate cell recruitment but may represent a mechanism for amplifying the inflammatory response. Using human platelets challenged with collagen, flunoxaprofen only at higher concentration (10(-4) mol/l) reduces TXB2 formation without altering generation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid. This suggests a low capacity of flunoxaprofen of affecting platelet aggregation regulated by arachidonic acid metabolites. Flunoxaprofen prevents pulmonary changes due to secondary release of TXA2 in the guinea-pig. In fact this drug prevents changes due to immunological reaction and antagonizes bronchoconstriction due to exogenous administration of histamine and LTC4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The effect of syringeal deafferentation on the stimulated vocalization in the domestic chick (Gallus gallus).

The rôle of syringeal feedback on the electrically elicited vocalization in chickens (Gallus gallus) was studied. The vocalization patterns elicited by stimulating the low-threshold "calling areas" in the midbrain, was examined before and after syringeal deafferentation obtained by cutting the X-XII anastomosis on either the left and right side. The results show that section of the X-XII anastomosis on the left side produces consistently a clear-cut lowering of the threshold for vocalization and an increase of the amplitude of the individual calls with no change in the repetition rate of the call sequences. All these effects are enhanced when the contralateral anastomosis is also severed. These results show that the bilateral syringeal deafferentation does not change the overall song pattern performance, that remains stereotyped both in duration and complexity, consistent with the hypothesis that, in adult birds, stable song patterns are not dependent on peripheral sources of feedback, but are ruled by a learned central control program. However the modification of vocalization threshold and amplitude suggests the hypothesis that the syringeal feedback plays an inhibitory rôle on vocalization by modulating the excitability of the central structures involved in the vocalization activity.

Afferent Pathways

Platelet formation of 12-hydroxyeicosatetraenoic acid and thromboxane B2 is increased in type IIA hypercholesterolemic subjects.

The formation of the major metabolic products of endogenous arachidonic acid (AA) via cyclooxygenase and lipoxygenase pathways in platelets from normal and type IIA hypercholesterolemic subjects was evaluated. 12-Hydroxyeicosatetraenoic acid (12-HETE) and thromboxane B2(TXB2) were determined by selected ion monitoring (SIM) after extraction and purification of collagen stimulated platelet-rich plasma (PRP). The levels of both arachidonic acid metabolites in the non-stimulated PRP of control and type IIA subjects were below the detection limit of the method, rising significantly after collagen stimulation. Both 12-HETE and TXB2 levels in collagen-stimulated PRP samples from the patients were significantly higher than levels in controls (P less than 0.001). In view of the key role of 12-HETE in mediating smooth muscle cell migration and proliferation and in stimulating macrophage activity, these data may provide information for the understanding of the elevated incidence of thrombosis and atheromatous lesion in patients with type IIA hypercholesterolemia.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

Stimulus-related difference in the formation of leukotrienes and PGD2 after immunological and non-immunological challenge of human lung parenchyma "in vitro".

The stimulation of human lung parenchymal fragments with A-23187 induces formation of leukotrienes as well as of PGD2: LTE4 is the compound found in larger amount and independently of the intensity of the stimulus the % of metabolized precursor which is converted to leukotrienes or PGD2 is remarkably similar. However, under conditions of IgE-Anti IgE challenge the predominant conversion of arachidonic acid occurs to PGD2, LTB4 is almost negligible and LTD4 and E4 together represent less than 30% of the oxidative products of arachidonic acid. Whether PGD2 and leukotrienes derive from the same or different subset of cells is unresolved.

Antibodies

Aspirin inhibits platelet 12-hydroxy-eicosatetraenoic acid formation.

The effects of aspirin on platelet 12-hydroxyeicosatetraenoic acid (12-HETE) formation were studied after administration to humans in platelet-rich plasma (PRP) and in vitro in human PRP and in washed platelets (WPs). Healthy volunteers were given orally either single or repeated (1 week) daily doses (20 and 500 mg) of aspirin. Two hours after a single 20 mg aspirin dose, 12-HETE formation by PRP was significantly inhibited. With the highest aspirin dose used (500 mg), the inhibition of 12-HETE formation was more pronounced and long lasting. Thromboxane B2 (TXB2) synthesis was significantly inhibited at 2 hours with the lowest dose. At the 500 mg dose, platelet aggregation was significantly reduced, and TXB2 formation was almost completely suppressed for at least 24 hours. The degree of inhibition of 12-HETE formation at 2 hours after 1 week of daily treatment (20 and 500 mg) was similar to that achieved at 2 hours after the single dose. As far as TXB2 and platelet aggregation are concerned, the effect of 20 mg aspirin was cumulative. In vitro studies show that aspirin (0.25 to 3 mmol/L concentration) significantly inhibits 12-HETE formation in PRP, but not in WPs, suggesting that plasma is required for the aspirin effect on lipoxygenase products. These results indicate that aspirin, even at low doses, not only affects the platelet cyclooxygenase activity but also exerts reversible inhibition of 12-HETE formation, both in vitro and ex vivo. These data may help to further elucidate the role of hydroxyacids in the anti-inflammatory and antipyretic action of aspirin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

Differential distribution of vagal afferent neurons from the rat liver.

Selective injection of horseradish peroxidase (HRP) into the left and median lobes (LM) and into the right and caudate (RC) lobes of the liver is followed by labeling of neuronal somata in the right and left nodose ganglia. The size distribution of the labeled neuronal population shows that the afferent neurons from the two parts of the liver can be grouped in two corresponding classes; a third class is apparent following injection into the LM lobes. Small neurons are more numerous after injection into the LM lobes, whereas large ones are labeled in the left nodose ganglion after injection into the RC lobes. It is suggested that the two parts of the liver may have a different functional role in conveying afferent signals.

Animals

Capsaicin-sensitive afferent vagal neurons innervating the rat liver.

The effects of neonatal capsaicin treatment on the vagal afferent neurons innervating the liver have been studied in the rat. The smallest neurons (up to 180 microns 2) innervating the left and median lobes and the right and caudate lobes of the liver are completely destroyed by neonatal capsaicin administration and the number of neurons up to 300 microns 2 is reduced. It is suggested that the capsaicin-sensitive neurons in the nodose ganglion innervating the liver may be involved in nociception.

Animals

Role of the interval between axotomy and nerve suture on the success of muscle reinnervation: an experimental study in the rabbit.

The influence of the time interval between nerve transection and neurorrhaphy on motor and sensory reinnervation was studied experimentally in the rabbit. We evaluated the maximal tetanic tension, the amplitude of the compound action potential, and the retrograde transport of horseradish peroxidase 30 and 60 days after neurorrhaphy carried out at 0, 10, or 20 days after transection of the nerves to the medial and lateral gastrocnemius and soleus muscles. The results showed that the suture 20 days after transection was followed by a more precocious motor reinnervation, whereas the outgrowth of motor axons past the suture was not affected by the time interval between transection and neurorrhaphy. On the contrary, the best regrowth of afferent axons was obtained after an interval of 10 days between transection and suture. We conclude that the time interval did not influence motor axon growth, but was involved in the operation of mechanism(s) involved in the reestablishment of impulse conduction and/or synaptic efficacy. In contrast, the time interval appeared to be related to factors involved directly in the axonal elongation of afferent fibers.

Action Potentials

Neural nature of the time-dependent factor(s) involved in motor reinnervation.

The influence of a time interval between nerve transection and reimplantation into a foreign muscle on the effectiveness of reinnervation was studied in the rat. We evaluated the weight loss and the maximal twitch and tetanic tensions developed by the reinnervated muscle upon nerve stimulation 60 days after reimplantation (i) of an acutely severed nerve onto an acutely denervated muscle; (ii) of a chronically (20 days) severed nerve onto an acutely denervated muscle, and (iii) of an acutely severed nerve onto a chronically denervated muscle. The best recovery was obtained when a chronically severed nerve was implanted into an acutely denervated muscle. We conclude that a neural time-dependent factor(s) is involved in motor reinnervation.

Animals

Effect of selective parasympathetic denervation on the daily rhythm of tyrosine transaminase in the rat liver.

The effect of section of the rostral hepatic nerve (RNH), branch of the left abdominal vagus, on the circadian rhythm of tyrosine transaminase (TAT) activity in rat liver has been investigated. It has been shown that the midnight peak of TAT activity is suppressed after section of the rostral hepatic nerve and by subdiaphragmatic vagotomy, but is unaffected by sham-operation and section of the ventral abdominal vagus caudal to the emergence of the rostral hepatic nerve. It is concluded that the rhythm of TAT activity is under neural control, either directly or reflexely.

Animals

Synaptic effects elicited in the Retzius cells of the leech Hirudo medicinalis by stimulation of the segmental roots.

Electrical stimulation of the segmental roots of each ganglion of Hirudo medicinalis, elicits in both Retzius' cells inhibitory and excitatory effects. The IPSP and EPSP are chemical in nature, being dependent on the membrane potential, and suppressed by high Mg++. Selective inactivation of one RC shows that the responses of the contralateral RC are not due to electrotonic coupling between the two cells, but to synaptic actions impinging upon the membrane of both RCs. The two synaptic potentials appear to be mediated by two set of fibres with a different threshold to electrical stimulation. Their actions on the RCs appear to be polysynaptic on the basis of central latency. Simultaneous stimulation of two roots shows evidence for occlusion for IPSP and summation for EPSP, confirming the polysynaptic nature of the effects. The possible functional significance of the inhibitory and excitatory pathways, is discussed.

Animals

Cephalometers.

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Cephalometry

The afferent and preganglionic parasympathetic innervation of the rat liver, demonstrated by the retrograde transport of horseradish peroxidase.

The afferent and parasympathetic preganglionic innervations of the rat liver were investigated by the use of retrograde transport of horseradish peroxidase (HRP). Vagal nerve fibers reach the rat liver by way of the left and right hepatic nerves, which originate from the homonimous abdominal vagal trunks. Three different experimental protocols were used: (i) intraparenchymal HRP injections; (ii) retrograde HRP injection through the common bile duct; (iii) HRP application to the central end of the severed hepatic nerves. The technical problems inherent in these 3 methods were experimentally investigated, with regard to the possible leakage of HRP from the liver after retrograde injection. It is concluded that leakage of HRP occurs, but it is not sufficient to cause non-specific labeling. Neurons of the lower thoracic dorsal root ganglia (DRG) are bilaterally labeled following intraparenchymal and retrograde HRP injections. Bilateral labeling of the nodose ganglia (NGs) following retrograde injection is still observed after subdiaphragmatic section of the left abdominal vagus, whereas cervical transection prevents labeling of the ipsilateral NG. Labeling produced by exposure of the left hepatic nerve to HRP is prevented by subdiaphragmatic transection of the left abdominal vagus. Efferent neurons located bilaterally in the dorsal motor nucleus (DMN) and in the left nucleus ambiguus (NA) are labeled following retrograde HRP injection. Only ipsilateral labeling is observed after HRP application to the cut left hepatic nerve. HRP exposure of the left abdominal vagus yields bilateral labeling in both DMN and NA. It is concluded that: (i) the afferent innervation of the rat liver is provided by the lower thoracic DRG and by the NGs of both vagi, mostly by the left; partial crossing of vagal afferent fibers takes place at thoracic level; and (ii) the liver receives efferent fibers bilaterally from the DMN and from the left NA; the DMN neurons project to the liver via the homolateral hepatic nerves, and those of the NA via the left hepatic nerve.

Animals

Identification of the motoneurons innervating the stapedius muscle in Gallus gallus: a horseradish peroxidase study.

The location of the stapedial motoneurons in Gallus gallus was investigated by means of the retrograde transport of HRP, injected into the stapedius muscle. The labeled neurons are located in both the ventral and dorsal divisions of the VII nerve nucleus, in a lateral and ventral position respectively, facing the superior olivary nucleus. The neurons are distributed in two size classes. The functional implications of these findings are discussed, in relation both to the absence of the acoustic stapedial reflex in birds and to the functional properties of the stapedius muscle.

Animals

The afferent innervation of the liver: a horseradish peroxidase study in the rat.

Scattered injections of horseradish peroxidase (HRP) into the rat liver produced labeling of a small number of large neurons located only in the rostral pole of the left nodose ganglion. The same amount injected in a single lobe also produced labeling of a few cells in Th7-Th10 dorsal root ganglia. No retrograde marking followed subcapsular injections. HRP injections around the porta hepatis yielded labeling of large and small neurons in the left nodose ganglion only. This indicates that most of the afferent fibers are of vagal origin, and that different receptors are located in different parts of the liver.

Afferent Pathways

Two bidirectional nerve cord systems converging with electrical and chemical synapses on the Retzius cells of the leech Hirudo Medicinalis.

Electrical stimulation of the ventral cord of H. medicinalis elicits in both Retzius' cells of each segmental ganglion an EPSP which is composed by an early and a late component. The early EPSP is electrical in nature, since it is unaffected by displacements of the membrane potential and by high Mg2+, whereas the late one is chemical, being reversed in sign by membrane depolarization and suppressed by high Mg2+. Latency measurements show that the electrical and chemical EPSP components are mediated by two different pathways characterized by conduction velocities of 0.5 and 0.3 m/sec respectively. Both pathways run in each of the lateral connectives and propagate impulses in anterior and posterior direction. Collision experiments show that ascending and descending impulses along the pathway mediating the electrical EPSP travel along the same fibres. Separate stimulation of the lateral connectives and selective inactivation of one Retzius' cell show that both pathways converge onto each Retzius' cell show that both pathways converge onto each Retzius cell. The possible functional significance of the two excitatory pathways is discussed.

Animals

A direct connection between visual Wulst and Tectum opticum in the pigeon (Columba livia) demonstrated by horseradish peroxidase.

Labelled neurons were observed bilaterally in part of the visual Wulst (Hyperstriatum accessorium and Hyperstriatum intercalatum superior) following unilateral injection of the enzyme horseradish peroxidase into the Tectum opticum of pigeons. No labelling was observed in Hyperstriatum dorsale. Horseradish peroxidase positive fibres running through the Tractus septomensencephalicus and ending bilaterally in the Tectum opticum were found following injection of the enzyme into Hyperstriatum accessorium. Labelled fibres were also found to end in the Hyperstriatum ventrale ventro-ventrale. These findings provide evidence for a bilateral projection of the telencephalic station of the thalamofugal pathway onto the tectofugal system, as suggested by electrophysiological data. The functional organization of these projections is discussed.

Animals