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Biomedical subjects

F Magni

Publications and source records attributed to F Magni.

At least 73 records · Page 4Linked to original sources

Nonsteroidal antiinflammatory drugs aggravate acute myocardial ischemia in the perfused rabbit heart: a role for prostacyclin.

Myocardial ischemia was induced in perfused paced isovolumic left heart preparation of the rabbit by reducing, for a period of 40 min, the flow rate from 20 ml/min to 0.2 ml/min (severe model) and to 1 ml/min (moderate model). The relationship between prostaglandin biosynthesis and cardiac ischemic damage was evaluated in the two experimental models. The results obtained indicate that the total amount of 6-keto-PGF1 alpha generated increases with the severity of the ischemia, particularly during the 20 min of reperfusion (moderate model 81.8 +/- 13.7 ng: severe model 375 +/- 102 ng). The inhibition of the prostaglandin synthesis, prostaglandin-E2, and 6-keto-prostaglandin-F1 alpha (PGE2 and 6-keto-PGF1 alpha levels below the detection limits) by Aspirin (20 micrograms/ml) and Indomethacin (1 microgram/ml) in moderate myocardial ischemia was correlated with greater increments in resting diastolic tension (nearly 100% and 40%, respectively). This phenomenon was also associated to a further decrease on cardiac contractility and increase on coronary perfusion pressure upon reperfusion. On the contrary drugs which stimulated prostaglandin generation in myocardial tissue, such as Defibrotide (400 micrograms/ml), completely protected the organ from ischemia. U-60257 (3 micrograms/ml) and FPL-55712 (2 micrograms/ml), compounds, which respectively inhibits biosynthesis and the effects of leukotrienes, displayed a beneficial activity on this moderate model of ischemia. The present data suggests that the deleterious effect of nonsteroidal antiinflammatory drugs in low flow myocardial ischemia and reperfusion damage may be associated with removal of PGI2 and PGE2 from ischemic myocardium.

Animals↗

New pharmacological data on the bronchospasmolytic activity of bamifylline.

Resistance to lung inflation and blood pressure were monitored together with biological and radioimmunological determination of circulating thromboxane A2 (TxA2) in anaesthetized guinea-pig. Bamifylline, a 2-benzyl-[4,5-d]-imidazopyrimidine derivative, and theophylline were compared for their antagonistic activity against the pulmonary effect of histamine (0.05 mumol/kg i.v.), leukotriene C4 (LTC4, 0.016 mumol/kg i.v.), platelet-activating factor (PAF, 0.0002 mumol/kg i.v.) and acetylcholine (0.1 mumol/kg i.v.). Bamifylline, as well as theophylline, showed a dose-dependent antagonistic activity against both bronchoconstriction and TxA2 generation induced by the above agonists. However, except for histamine where the two compounds were equiactive, bamifylline was 2 times more potent than theophylline. The maximal inhibitory activity was found against bronchoconstriction induced by PAF (ED50 = 6.5 mumol/kg i.v.) followed by histamine (ED50 = 9.5 mumol/kg i.v.), acetylcholine (ED50 = 24.3 mumol/kg i.v.) and LTC4 (ED50 = 31.6 mumol/kg i.v.). Bamifylline (3, 10, 30, 100 mumol/kg i.v.) and theophylline (3, 10, 30, 100 mumol/kg i.v.) protected guinea-pig from antigen-induced bronchoconstriction and TxA2 generation in ovalbumin actively sensitized animals. Also in this series of experiments bamifylline was more potent than theophylline, the ED50 being 9.3 mumol/kg i.v. and 22.9 mumol/kg i.v., respectively. These pharmacological data represent new support for the protecting effect of bamifylline against respiratory damage induced by well known anaphylaxis mediators.

Acetylcholine↗

The afferent innervation of the thymus gland in the rat.

The afferent nervous supply to the thymus gland has been investigated by means of the retrograde transport of horseradish peroxidase. It has been shown that the thymus receives an afferent supply from the nodose ganglia of the vagus and from the dorsal root ganglia C1-C7. The afferent innervation of the right and left thymic lobes is bilaterally organized; the fibers of a small celled population of nodose ganglion neurons cross outside the thymus and those of a larger celled population cross within the thymus gland. The functional implications of these findings are discussed in the context of central nervous system-immune system interactions.

Afferent Pathways↗

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↗