Search PubMed⌕ Search

Biomedical subjects

F Nava

Publications and source records attributed to F Nava.

At least 37 records · Page 2Linked to original sources
PubMed1997

Interleukin-1 inhibits drinking behaviour through prostaglandins, but not by nitric oxide formation.

Interleukin-1 beta (IL-1 beta) causes inhibition of drinking behaviour. Moreover it induces formation of prostaglandins (PGs) and nitric oxide (NO). Both PGs and NO are able to inhibit drinking stimulated by water deprivation or by intracerebroventricular (i.c.v.) administration of angiotensin II. In this study, we studied in the preoptic area (POA) the possible role of PGs and NO in the antidipsogenic action induced by IL-1 beta. IL-1 beta was injected in the lateral cerebral ventricle (i.c.v.) (2.5, 10, 20, and 40 ng/rat) or into POA (0.625, 1.25, 2.5, and 10 ng/rat). L-arginine (12.5, 25, 50, and 100 ng/rat), the precursor of NO, or NG-nitro-L-arginine methyl ester (L-NAME) (25, 50, and 100 ng/rat), an inhibitor of nitric oxide synthase (NOS), were injected only into POA. Drinking behaviour was induced by water deprivation (24 h). IL-1 beta injected either i.c.v. or into POA caused dose dependent inhibition of drinking. In the POA a treatment with acetylsalicylic acid (ASA) (33, 66, and 135 micrograms/rat), but not with L-NAME, antagonized the inhibition of drinking behaviour induced by the highest doses of IL-1 beta in the POA. In the POA, a treatment with ASA or L-NAME antagonized the inhibition of drinking behaviour caused by injection of the highest doses of L-arginine. Our data suggest that the central inhibition of drinking behaviour of IL-1 beta is mediated through the formation of PGs, but not NO, in the POA.

Animals↗
PubMed1997

Effects of interleukin-10 on water intake, locomotory activity, and rectal temperature in rat treated with endotoxin.

Intracerebroventricular (i.c.v.) interleukin-10 (25, 50, and 100 ng/rat) effects on water intake, exploratory behaviour, and rectal temperature were evaluated in rats treated intraperitoneally (i.p.) with lipopolysaccharide (0.32, 0.64, and 0.96 mg/kg). Endotoxin administration induced fever and inhibition of thirst in water-deprived rats, and a decrease in lococomotory activity in normohydrated and water-deprived animals. Our data show that interleukin-10 during lipopolysaccharide administration controlled fever, increases exploratory behaviour, but did not reverse lipopolysaccharide inhibition of thirst. These effects suggest that fever, depression in locomotory activity but not inhibition of thirst, induced by endotoxin are influenced by interleukin-10 levels.

Animals↗
PubMed1997

Multiple organ failure following zymosan-induced peritonitis is mediated by nitric oxide.

In the present study we tested the hypothesis that nitric oxide may play a role in the pathogenesis of multiple organ failure induced by peritoneal injection of zymosan in the rat. A severe inflammatory response characterized by peritoneal exudation, high plasma and peritoneal levels of nitrate/ nitrite (breakdown products of nitric oxide), prostaglandin E2 and leukocyte infiltration into peritoneal exudate was induced by zymosan administration. This inflammatory process started within 3 h of administration and onset occurred at 18 h, coinciding with damage of lung, small intestine and liver, as assessed by histological examination and by increase of myeloperoxidase activity, indicative of neutrophil infiltration. Furthermore, at 18 h after zymosan-induced peritonitis, expression of inducible nitric oxide synthase enzyme was found mainly in the macrophages of inflamed lungs. Subcutaneously administration of a nonisoform selective nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, reduced formation of peritoneal exudate fluid, blocked plasma and peritoneal nitrate/nitrite accumulation, and attenuated the elevated release of peritoneal prostaglandin E2. In addition, nitric oxide synthase inhibition was effective in preventing the development of organ failure since tissue injury and neutrophil infiltration, by myeloperoxidase evaluation, was reduced in lung, small intestine, and liver. In conclusion, major findings of our study are that nitric oxide exerts a proinflammatory role in the development of multiple organ failure and nitric oxide synthase inhibition is an effective antiinflammatory therapeutic tool, since inhibits not only nitric oxide but also prostaglandin production and cellular infiltration in inflamed organs.

Acute Disease↗
PubMed1997

Effects of some excitatory amino acid antagonists and drugs enhancing gamma-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice.

The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone derivative, were studied after intraperitoneal (i.p.) administration to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA) antagonists acting at N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and of some compounds enhancing gamma-aminobutyric acid (GABA)-ergic transmission against seizures induced by PEFLO were also evaluated. The present study demonstrated that both groups of compounds administered i.p. or intracerebroventricularly were able to protect against seizures induced by PEFLO. However, ifenprodil and (+/-)-alpha-(chlorophenyl)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethan ol (SL 82.0715), two compounds acting on the polyamine site of the NMDA receptor complex, were unable to provide any protection. The relationship between the different sites of action and the anticonvulsant activities of these derivatives were discussed. Although the main mechanisms of PEFLO-induced seizures cannot be easily determined, potential interactions with the receptors of EAA exist. In fact, antagonists of EAA, and in particular, those acting at NMDA receptors, were able to increase the threshold for the seizures or to prevent the seizures induced by PEFLO, while compounds acting at the polyamine site did not provide any protection. The AMPA-KA receptor antagonists were also able to exert anticonvulsant activity, but with minor potency in comparison to those of NMDA antagonists. In addition, the fact that compounds enhancing GABA-ergic neurotransmission were also able to protect the mice against seizures induced by PEFLO suggests an involvement of GABA system.

4-Quinolones↗
PubMed1996

Interleukin-1 receptor antagonist does not reverse lipopolysaccharide-induced inhibition of water intake in rat.

The involvement of interleukin-1 in antidipsogenic effects induced by intraperitoneal (i.p.) administration of lipopolysaccharide (0.32, 0.64 and 0.96 mg/kg) in 24-h water-deprived rats, was evaluated by injection of human interleukin-1 receptor antagonist (10, 25 and 50 micrograms/rat) into the lateral cerebral ventricle (i.c.v.). The effects of either lipopolysacharide or human interleukin-1 receptor antagonist treatment on rectal temperature of 24-h water-deprived rats, were examined. Our date show that human interleukin-1 receptor antagonist administration is able to reverse, dose dependently, fever, but not lipopolysaccharide inhibition of thirst. The reduction of pyrogenic, but not of antidipsogenic, effects of lipopolysaccharide following human interleukin-1 receptor antagonist administration suggests that lipopolysaccharide inhibition of thirst is not dependent on interleukin-1 induced fever and that interleukin-1 is not a direct mediator implicated in inhibition of water intake provoked by peripheral injection of lipopolysaccharide.

Animals↗
PubMed1996

Lamotrigine potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice.

Lamotrigine [0.5-10 mg/kg, intraperitoneally (i.p.)] was able to antagonize the audiogenic seizures in DBA/2 mice in a dose-dependent manner. Lamotrigine at doses of 0.5 and 1.25 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, markedly potentiated the anticonvulsant activity of carbamazepine, diazepam, phenytoin, phenobarbital and valproate against sound induced seizures in DBA/2 mice. The degree of potentiation by lamotrigine was greatest for diazepam and valproate, lower for phenobarbital, and least for phenytoin and carbamazepine. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of combined treatment of diazepam + lamotrigine or valproate + lamotrigine was more favourable than the diazepam + saline or valproate + saline treatment. Since lamotrigine did not significantly influence the plasma levels of the anticonvulsant drugs studied we might suggest that pharmacokinetic interactions, in terms of total plasma levels, are not probable. However, the possibility that lamotrigine alters protein binding and increases the relative free vs protein bound ratio may not be excluded. Lamotrigine did not significantly affect the hypothermic effects of the anticonvulsant compounds studied. Lamotrigine showed an additive effect when administered in combination with some classical anticonvulsants, most notably valproate and diazepam.

Acoustic Stimulation↗
PubMed1995

Effects of some excitatory amino acid antagonists on imipenem-induced seizures in DBA/2 mice.

The behavioural and convulsant effects of imipenem (Imi), a carbapenem derivative, were studied after intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid antagonists and muscimol (Msc), a GABAA agonist, against seizures induced by i.p. or i.c.v. administration of Imi were also evaluated. The present study demonstrated that the order of anticonvulsant activity in our epileptic model, after i.p. administration, was (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine maleate (MK-801) > (+/-)(E)-2-amino-4-methyl-5-phosphono-3-pentenoate ethyl ester (CGP 39551) > 3-((+/-)-2-carboxypiperazin-4-yl)propenyl-1-phosphonic acid (CPPene) > 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CCP) > 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline (NBQX). Ifenprodil, a compound acting on the polyamine site of NMDA receptor complex was unable to protect against seizures induced by Imi, suggesting that the poliamine site did not exert a principal role in the genesis of seizures induced by Imi. In addition, the order of anticonvulsant potency in our epileptic model, after i.c.v. administration, was CPPene > MK-801 > Msc > (-)-2-amino-7-phosphonic acid (AP7) > gamma-D-glutamylaminomethylsulphonate (gamma-D-GAMS) > NBQX > kynurenic acid (KYNA) > 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX). The relationship between the different site of action and the anticonvulsant activity of these derivatives was discussed. Although the main mechanism of Imi induced seizures cannot be easily determined, potential interactions with the receptors of the excitatory amino acid neurotransmitters exists. In fact, antagonists of excitatory amino acids are able to increase the threshold for the seizures or to prevent the seizures induced by Imi. In addition, Imi acts on the central nervous system by inhibition of GABA neurotransmission and Msc, a selective GABAA agonist, was able to protect against seizures induced by Imi.

2-Amino-5-phosphonovalerate↗
PubMed1995

Role of calcium in brain aging.

1. Calcium is a universal messenger of extracellular signals in a great variety of cells; it regulates several neuronal functions, such as neurotransmitter synthesis and release, neuronal excitability, phosphorylation and so on. Calcium is also involved in long-term processes, like memory. 2. Recent studies demonstrated that brain aging is characterized by alterations in neuronal function due to the changes in calcium homeostasis. This occurs for various reasons, such as changes in calcium channels, decrease of ion binding to specific proteins and changes in the mechanisms involved in its sequestration and extrusion from neuronal cell. 3. Moreover, it has been shown that high levels of glucocorticoids are neurotoxic, because they alter calcium homeostasis on hypothalamic neurons by increasing calcium voltage-dependent flow, especially in aged neurons. 4. New information about the role of calcium in brain aging could derive from the expansion of new imaging techniques, such as positron emission tomography, single photon emission tomography and nuclear magnetic resonance, which allow in vivo quantitative measurements of functional parameters and their comparison with behavioural data.

Aging↗
PubMed1994

Fenbufen pretreatment potentiates the anticonvulsant activity of CPPene and NBQX in DBA/2 mice.

The anticonvulsant activity of 3-((+/-)-2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid (CPPene) and 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxoline (NBQX), two excitatory amino acid antagonists, was studied against audiogenic seizures in DBA/2 mice, following intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration. Maximal anticonvulsant protection was observed 15-30 min following NBQX and 45-180 min after CPPene. Coadministration with fenbufen (20 mg kg-1, i.p.), a non-steroidal anti-inflammatory agent, enhanced and prolonged the anticonvulsant actions of CPPene and NBQX and also potentiated and prolonged the impairment of rotarod performance. The enhancement of the anticonvulsant activity and the prolonged impairment of rotarod performance suggests that fenbufen may have some pharmacokinetic interactions with CPPene and NBQX and that fenbufen is able to increase the brain levels of these excitatory amino acid antagonists. In particular, fenbufen was able to exert a major degree of potentiation of effects of NBQX rather than those of CPPene, suggesting that the chemical structures of these excitatory amino acid antagonists are responsible for the different degree of interactions between CPPene or NBQX and fenbufen. NBQX appears to have a notable similarity with quinolones whilst CPPene does not. Additionally fenbufen may displace CPPene and NBQX from plasma binding sites or inhibit the renal excretion. The present data are also consistent with previous studies showing pharmacokinetic interactions between fenbufen and quinolones.

Acoustic Stimulation↗
PubMed1986

Dissociation of morphine withdrawal diarrhea and jumping in mice by the peripherally selective opioid antagonist SR 58002 C.

Mice were rendered physically dependent by repeated administration of morphine, 25 mg/kg s.c., 5 times daily for 4 days, and on the 5th day, 2 h after the last morphine dose, they were challenged with a s.c. injection of either naloxone, 25 mg/kg, or the peripherally selective opioid antagonist SR 58002 C (N-methyl levallorphan mesilate), 75 mg/kg. Naloxone provoked jumping and diarrhea in all the animals; mice challenged with SR 58002 C presented no significant jumping but a high frequency of withdrawal diarrhea. When naloxone, 12 mg/kg, or SR 58002 C, 50 mg/kg, were given s.c. in combination with repeated morphine as above, mice which had received naloxone with morphine presented virtually no diarrhea or jumping upon naloxone challenge; those repeatedly treated with morphine plus SR 58002 C were substantially protected from naloxone-precipitated diarrhea, but not jumping. These results further support the remarkable selectivity for peripheral opioid receptors of SR 58002 C, even after repeated high-dose treatment, and are strongly consistent with the primary role of a local intestinal mechanism in the development and expression of opioid withdrawal diarrhea in mice. The in vivo dissociation of central and peripheral components of dependence on morphine is illustrated, apparently for the first time.

Animals↗