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G Nistico

Publications and source records attributed to G Nistico.

At least 19 recordsLinked to original sources
PubMed1998

Cocaine induced T cell proliferation in the rat: role of amygdala dopamine D1 receptors.

The immunomodulatory effects of local administration of cocaine into the amygdala were studied in the rat. Intra-amygdala infusion of cocaine significantly and dose-dependently increased the proliferative response of splenocytes to concanavalin A (Con A). A similar effect on the immune response was also observed in rats, microinfused into the central amygdala with the selective D1 receptor agonist SKF 38393. The increase of the proliferative response of splenocytes to Con A was inhibited by coinfusion within the central amygdala of the dopamine D1 receptor antagonist SCH 23390, together with cocaine, but not by coinfusion of the dopamine D2 receptor antagonist eticlopride. These results suggest that cocaine may produce at least some of its effects on the immune system through the activation of brain dopamine neurotransmission and that the central amygdala may represent a critical structure mediating cocaine-induced T cell proliferation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

The effect of nitric oxide on cytokine-induced release of PGE2 by human cultured astroglial cells.

1. The role of the L-arginine-nitric oxide (NO) pathway on the formation of prostaglandin E2 (PGE2) by human cultured astroglial cells incubated with interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) was investigated. 2. Incubation of T 67 astroglial cell line with IL-beta (10 ng ml(-1)) and TNF-alpha (500 u ml(-1)) produced a significant (P<0.05) increase of both nitrite (the breakdown product of NO), cyclic GMP and PGE2 levels in cell supernatants. N omega-nitro-L-arginine methyl ester (L-NAME; 20-300 microM), an inhibitor of NO synthase (NOS), inhibited the increase of cyclic GMP and nitrite levels found in supernatants of cytokine-treated astroglial cells and reduced the release of PGE2. The latter effect showed that the enhanced arachidonic acid (AA) metabolism subsequent to stimulation of astroglial cells with IL-1beta and TNF-alpha was, at least in part, induced by NO. This occurred also when sodium nitroprusside (SNP; 120 microM), an NO donor, was incubated with astroglial cells, an effect antagonized by oxyhaemoglobin (OxyHb; 10 microM). 3. The inhibition elicited by L-NAME on PGE2-release by cytokine-treated astroglial cells was reversed by adding AA (40 microM), showing that the effect of NO on cytokine-dependent PGE2 release occurred at the cyclo-oxygenase (COX) level. Furthermore, the release of PGE2 in cytokine-treated astroglial cells was inhibited by indomethacin (10 microM), a COX inhibitor as well as by preincubating cells with dexamethasone (20 microM), an inhibitor of inducible enzymes, showing that the inducible isoform of COX (COX-2) was involved. 4. On the other hand, pretreating astroglial cells with methylene blue (MB; 10 microM), an inhibitor of NO biological activity acting at the guanylate cyclase level, failed to affect PGE2 release in cytokine-treated astroglial cells, leading to the conclusion that cyclic GMP changes related to NO formation are not involved in the generation of AA metabolites. 5. The present experiments demonstrated that the release of PGE2 by astroglial cells pretreated with IL-1beta and TNF-alpha is due to enhanced COX-2 activity via activation of the L-arginine-NO pathway, and this may be relevant to the understanding of the pathophysiological mechanisms underlying neuroimmune disorders.

Astrocytes↗
PubMed1996

N omega-nitro-L-arginine methyl ester prevents apoptosis induced in the lateral geniculate nucleus by light deprivation in adult rabbit.

Exposure of adult rabbits to darkness for 48 h produces bilateral DNA fragmentation in the lateral geniculate nucleus as revealed in brain sections by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL) technique, suggesting an apoptotic type of cell death. In agreement with the latter deduction, light microscopy assessment of the morphological characteristics showed marginalization and condensation of nuclear chromatin, typical features of apoptosis. These effects were abolished by systemic administration of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthesis, whereas the D isomer was ineffective. In conclusion, the present data demonstrate that light deprivation for 48 h produces apoptosis in the lateral geniculate nucleus of rabbit and suggest that NO might be involved.

Animals↗
PubMed1995

NMDA-dependent prostaglandin E2 release by human cultured astroglial cells is driven by nitric oxide.

The role of the L-arginine-NO pathway on the formation of PGE2 by human cultured astroglial cells incubated with NMDA has been investigated. Preincubation of T 67 astroglial cell line with NMDA (10-600 microM) produced a significant dose-dependent increase of both nitrite (the breakdown product of NO), PGE2 and cGMP levels in cell supernatant. This effect was inhibited by coincubation of cells with L-NAME (20-300 microM), an inhibitor of NO synthase showing that the release of PGE2 subsequent to NMDA receptor stimulation was driven by NO. The release of PGE2 but not elevation of nitrite and cGMP levels was affected by indomethacin (10 microM), an inhibitor of cyclooxygenase. The inhibitory effect of L-NAME on PGE2 release by NMDA-pretreated astroglial cells was reverted by arachidonic acid, showing that the effect of NO on PGE2 release occurred at the cyclo-oxygenase level. Thus, the present experiments demonstrate that the release of PGE2 by astroglial cells pretreated with NMDA is driven by activation of the L-arginine-NO pathway, and this may be relevant in the pathophysiological mechanisms where glutamatergic neurotransmission is involved.

Arachidonic Acid↗
PubMed1995

Age-dependent changes of NO synthase activity in the rat brain.

We report that NO synthase activity, as expressed by citrulline and nitrite formation in brain homogenates, is decreased in 24-month old in comparison to 3-month old rats. In particular, a Ca(++)-dependent NO synthase activity was detected in homogenates obtained from cortical, hippocampal, cerebellar and lower brain stem slices from both 3- and 24 month-old rats. The amount of citrulline generated from L-arginine was significantly decreased in the hippocampus and lower brain stem by 40 and 48%, respectively. No changes were observed in NO synthase activity in cortical and cerebellar homogenates. Thus, the L-arginine-NO pathway seems to be impaired in selected areas of rat brain and this may contribute to the understanding of pathophysiological mechanisms underlying age-related cerebral disorders.

Aging↗
PubMed1995

Potent protective effect of melatonin on in vivo paraquat-induced oxidative damage in rats.

The in vivo effect of melatonin on paraquat-induced oxidative damage in rat lung and liver was studied using two parameters: the concentration of malonaldehyde and 4-hydroxyalkenals as indices of lipid peroxidation; changes in total and oxidized glutathione. Melatonin (10 mg/kg) or an equal volume of saline were administered intraperitoneally (ip) to rats 30 min prior to an ip injection of paraquat (20 mg/kg or 70 mg/kg). After paraquat treatment, the animals received melatonin or saline ip injections every six hours for 24 hours. Rats were killed 24 hours after paraquat injection. In lung, both the low and high dose of paraquat, when administered with saline, augmented lipid peroxidation (100% and 18%, respectively) above levels found in control animals. Treatment with melatonin completely reversed this effect. In liver, paraquat (70 mg/kg) increased lipid peroxidation by 40% over the levels of control animals. The increase was completely abolished by treatment with melatonin. Paraquat at 20 mg/kg did not induce any significant change in liver lipid peroxidation. Paraquat treatment resulted in a significant decrease of total glutathione concentration and increased oxidized glutathione in both lung and liver. These effects were abolished by treatment with melatonin. The results suggest that melatonin confers marked protection against paraquat-induced oxidative toxicity in both the lung and liver.

Aldehydes↗
PubMed1995

Nitric oxide release during hypothermic versus normothermic cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) produces hemodynamic and inflammatory disorders involving changes in vascular permeability and regional blood flow and alterations of coagulation and complement systems. It has been reported that an abnormal release of vasoactive substances during CPB, like bradykinin or nitric oxide, could play a role. The aim of this study was to investigate the changes in nitric oxide (NO) release occurring in patients undergoing CPB, under both hypothermic and normothermic conditions. Forty patients (mean age 61.4 +/- 8.4 years) undergoing coronary bypass surgery were studied. In 20 patients (group A) systemic hypothermic CPB and antegrade cold intermittent crystalloid cardioplegia were used. The remaining 20 cases (group B) underwent surgery under systemic normothermic CPB and with antegrade warm blood intermittent cardioplegia. Nitric oxide was measured as the nitrite plasma level (NPL) by the Gries reaction. The time course of changes in NPL were obtained by collecting five whole blood samples: before CPB, 10 and 30 min after the start of CPB, and 10 and 60 min after the end of CPB. Although there were no significant variations of NPL shortly after the start of CPB (10 min after), values measured 30 min after CPB commencement and 10 min after the end of CPB showed a significant increase (P < 0.0001) in both groups. Considering the two groups separately, NPL changes seemed to be similar, so independent of temperature; however, in group B higher values of NPL were measured during (30 min) and after (60 min) CPB (P < 0.0001). In conclusion, during CPB there is a progressive increase, independent of temperature in NO release.

Blood Pressure↗
PubMed1994

Dopamine D1 receptors in the amygdala enhance the immune response in the rat.

Indirect evidence suggests that dopamine within the brain may participate in the regulation of immune responses in both man and rodents. The aim of the present study was to investigate the possible role played by the specific dopamine D1 receptor subtype within the central amygdala in the modulation of immunity. Mitogen responsiveness of splenocytes and NK cell activity were measured in rats following local microinfusion of SKF 38393, a specific dopamine D1 receptor agonist. Microinfusion of SKF 38393 (100 nmol) within the central amygdala increased the proliferative response of splenocytes to Con A, whereas it did not modify the proliferative response of splenocytes to LPS or NK cell activity. The effects of SKF 38393 were prevented by prior systemic administration of SCH 23390 (0.3 mg/kg ip), a specific D1 receptor antagonist. These results indicate that activation of dopamine D1 receptors within the central amygdala induced selective stimulation of mitogen responsiveness of splenocytes and suggest that specific activation of dopamine neurotransmission within selected areas of the limbic system may produce immunoenhancing effects. These findings further confirm the immunomodulatory role played by dopaminergic mechanisms in the brain.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

HIV coating gp 120 glycoprotein-dependent prostaglandin E2 release by human cultured astrocytoma cells is regulated by nitric oxide formation.

The role of the L-arginine-NO pathway on the formation of PGE2 by cultured astroglial cells incubated with the HIV coating glycoprotein gp120 was investigated. Preincubation of human cultured T 67 astrocytoma cells with gp 120 (100-500 nM) produced a significant increase of nitrite (the breakdown product of NO) and PGE2 in cell supernatants. The effect of gp 120 on both nitrite and PGE2 production was antagonized by inhibition of NO synthase by L-NAME (20-300 microM). The inhibition of gp120-induced PGE2 production by L-NAME was reverted by addition of arachidonic acid (30 microM), an effect antagonized by the cyclo-oxygenase inhibitor indomethacin (10 microM). Methylen bleu, an inhibitor of the biological activity of NO acting at the guanylate cyclase level failed to affect gp 120-mediated PGE2 release showing that the increase of cGMP subsequent to NO production was not involved in the modulatory activity of NO on arachidonic acid cascade. On the basis of present experiments we conclude that gp-120-induced release of PGE2 by astroglial cells is driven by NO, thereby contributing in the involvement of glial cells in HIV-related cerebral disorders.

Amino Acid Oxidoreductases↗
PubMed1994

Nitroblue tetrazolium inhibits oxidation of glyceryl trinitrate to nitric oxide in bovine aortic smooth muscle cells.

The effects of nitroblue tetrazolium (NBT), a well-known scavenger of superoxide anions and an inhibitor of nicotinamide adenine dinucleotide (NADPH)-dependent oxidations, were assessed on the metabolism of glyceryl trinitrate (GTN) to nitric oxide (NO) by bovine aortic smooth muscle cells (SMC). The extent of this metabolism was determined by measuring NO formed, using the inhibition of thrombin-induced platelet aggregation and relaxation of rabbit aortic strips as bioassay systems. In addition, NO produced from GTN by SMC was measured as nitrite (NO2-), one of its breakdown products. The antiplatelet effect of GTN (44 microM) was potentiated by SMC (0.12-0.46 x 10(5) cells) treated with indomethacin (10 microM) and this was inhibited in a concentration-dependent manner when the cells were pretreated with NBT (100 microM). NBT (3-100 microM) also reduced the formation of NO2- from GTN (600 microM) by SMC (3 x 10(5) cells). Furthermore, relaxations of endothelium-denuded strips of the rabbit aorta by GTN (10(-9)-10(-6) M) were attenuated when the strips were pretreated with NBT (100 or 500 microM). The formation of NO from L-arginine (L-Arg) by SMC was not affected by NBT. The hypotensive responses to GTN (0.25-1 mg/kg, i.v.) in anaesthetized rats were inhibited by pretreatment with NBT (1.25 mg/kg, i.v.) but NBT did not alter the hypotensive responses induced by SIN-1. Thus, NBT inhibited the bioconversion of GTN to NO both in vitro and in vivo. NBT may be a useful pharmacological tool to investigate the enzymic pathway(s) involved in the conversion of GTN to NO by smooth muscle cells or other cells.

Animals↗
PubMed1994

Hippocampal damage produced in rats by alpha-dendrotoxin--a selective K+ channel blocker--involves non-NMDA receptor activation.

The epileptogenic and neurodegenerative effects induced by intra-hippocampal injection of a selective K+ channel inhibitor, alpha-dendrotoxin (DTx), were investigated in normal rats and those bearing a monolateral surgical lesion of the Schaffer collaterals that causes degeneration of their nerve terminals and also, isolates the CA3 area. In addition, these effects have also been studied in rats pretreated with NBQX, an AMPA receptor antagonist. Injection of DTx (35 pmol) into one dorsal hippocampus induced motor and electrocortical (ECoG) seizures in all the treated animals that were rapid in onset (within 2-3 min). The seizures were accompanied at 24 h by significant neuronal cell loss which occurred in the CA1, CA3 and CA4 pyramidal cell layers of the hippocampus, ipsilateral to the side of injection. This neuronal loss was paralleled by a significant decrease in the density of radioiodinated DTx labelled acceptors. Lesioning of the excitatory afferents to the CA1 pyramidal cells, gave a substantial reduction in the density of radioiodinated DTx labelled acceptors in the strata oriens and radiatum, revealing that a proportion of these K+ channels are present on the Schaffer collateral terminals. Under these conditions, motor and ECoG seizures persisted. As expected, the lesion prevented loss of the isolated CA3 pyramids, normally produced by the administration of DTx, leaving unaffected CA1 and CA4 pyramidal cell damage, consistent with an observed diminution of DTx binding sites in the latter areas. In unlesioned rats pre-treated with NBQX (30 mg/kg i.p.), subsequent injection of DTx evoked epileptogenic effects after a latency of 15 min and caused significant cell loss in the CA1 but not in the CA3 and CA4 pyramidal cell layers, ipsilateral to the side of toxin injection. A lower dose of NBQX (15 mg/kg i.p.) proved ineffective. In conclusion, these data together with our published results on NMDA antagonists indicate that motor and ECoG seizures and CA1 pyramidal cell loss elicited by intra-hippocampal injection of the K+ channel blocker, DTx, are independent from mechanisms involving glutamate-mediated excitotoxicity whereas CA3 and CA4 pyramidal cell loss may be the consequence of excessive activation of AMPA receptors.

Animals↗
PubMed1993

HIV gp120 glycoprotein stimulates the inducible isoform of no synthase in human cultured astrocytoma cells.

The effect of the HIV coating glycoprotein gp 120 on the generation of NO by human cultured T67 astrocytoma cells was investigated. Preincubation of astrocytoma cells with gp 120 (10 pM, 100 and 500 nM) produced a significant, dose-dependent increase of nitrite levels in supernatant of pretreated cells which was higher when compared to untreated cells. This effect was prevented by coincubation of cells with monoclonal antibodies directed against gp 120, or by pretreatment of cells with the selective NO synthase inhibitor L-NAME (100 microM). The rise of nitrite following pretreatment of astrocytoma cells with gp 120 was accompanied by an increase in NO synthase activity which was mainly Ca(++)-independent. Also this effect was inhibited by antibodies against gp 120, showing the specificity of the activation of the L-Arg-NO pathway subsequent to incubation of astrocytoma cells with the HIV coating protein. In conclusion, the present results are consistent with an activation of the inducible, Ca(++)-independent isoform of NO synthase in cultured astrocytoma cells following coincubation with gp 120. This may contribute to explain some of the neuropathological changes accompanying HIV-related cognitive disorders.

Amino Acid Oxidoreductases↗
PubMed1993

Cytokine-induced nitric oxide generation by cultured astrocytoma cells involves Ca(++)-calmodulin-independent NO-synthase.

The effect of several cytokines (IL1 beta and TNF alpha) on the inducible biosynthesis and release of NO by cultured astrocytoma cells was investigated and compared to that observed following pretreatment of cells with LPS. Preincubation for 4, 12, 24 and 48 h of astrocytoma cells with IL1 beta (10 ng ml-1), TNF alpha (500 U ml-1) and LPS (0.5 micrograms ml-1) enhanced their ability to inhibit thrombin-induced platelet aggregation through the release of an NO-like factor and increased nitrite levels in supernatants of stirred cells. The enhancement of NO production induced by cytokines as well as LPS was mediated by a time-dependent increase of NO-synthase activity in cell homogenates being mainly Ca(++)-calmodulin-independent. However, LPS activated earlier than cytokines the inducible NO-synthase and its effect was, at least in part, related to the release of IL1 beta by astrocytoma cells. In conclusion, the present data show, for the first time, that astrocytoma cells possess a cytokine-inducible Ca(++)-calmodulin-independent NO-synthase, whose activation seems to occur with a mechanism different from that described for LPS.

Amino Acid Oxidoreductases↗
PubMed1991

Age-related changes in Cu,Zn superoxide dismutase, Se-dependent and -independent glutathione peroxidase and catalase activities in specific areas of rat brain.

Oxidative injury of tissues involves both accumulation of damage due to persistent oxidative stress and loss of the proper balance of antioxidative enzymes. These events may produce a faster rate of tissue senescence. In this regard, we have assayed the antioxidative enzyme activities (Cu,Zn superoxide dismutase, glutathione peroxidase and catalase), in various areas of rat brain (prefrontal cortex, parietal cortex, hippocampus, hypothalamus, caudate nucleus, mesencephalon and lower brain stem) for the age groups of 3, 6, 12, 24 months. The results obtained show that the levels of antioxidant enzyme activities differed considerably in the various brain parts studied. Furthermore, changes in the specific activities of superoxide dismutase, catalase, and glutathione peroxidase did not follow the same pattern as a function of aging. In particular, in prefrontal cortex and caudate nucleus, superoxide dismutase and glutathione peroxidase activities did not change, while catalase activity decreased. In parietal cortex and mesencephalon, superoxide dismutase and glutathione peroxidase activities increased, but the catalase activity decreased in parietal cortex and did not change in mesencephalon. In lower brain stem, the activities of glutathione peroxidase and catalase decreased in 3-12-month-old rats. The activity of glutathione peroxidase was increased in the hippocampus and was decreased in hypothalamus during aging. In this area the catalase activity was also significantly diminished.

Aging↗
PubMed1991

Age-dependent changes in cardiovascular responses induced by muscimol infused into the nucleus tractus solitarii and nucleus parabrachialis medialis in rats.

1. The effects of muscimol and bicuculline on mean arterial blood pressure (MAP) and heart rate (HR) were studied after their microinfusion into the nucleus tractus solitarii (NTS) and into the nucleus parabrachialis medialis (NPBmed) in 3 and 24 month old rats. 2. In 3 month old rats a dose of 0.01 microgram of muscimol given into the NTS increased MAP, whereas higher doses (0.05, 0.1 and 0.25 microgram) produced dose-dependent bradycardia with either no change (0.05 and 0.1 microgram) or a decrease (0.25 microgram) in MAP. 3. On the other hand, in 24 month old rats, the same doses of muscimol given into the NTS failed to change MAP, whereas in comparison to 3 month old rats they produced a significantly lesser bradycardia. 4. The cardiovascular changes elicited by infusion of muscimol into the NTS in 3 and 24 month old rats were prevented by prior microinfusion of bicuculline into the same site. 5. Muscimol given into the NPBmed in doses from 0.05 to 0.25 microgram produced, in 3 month old rats dose-dependent decreases in MAP and HR which were prevented by prior administration of bicuculline. These effects were significantly reduced in 24 month old rats. 6. The present experiments show that with aging there is impairment of GABA-ergic mechanisms involved in the regulation of cardiovascular activity in the NTS and NPBmed.

Aging↗
PubMed1990

Behavioural and ECoG spectrum changes induced by intracerebral infusion of interferons and interleukin 2 in rats are antagonized by naloxone.

Rat interferon, alpha-interferon, interleukin 2 and recombinant interleukin-2 injected into the third cerebral ventricle produced typical behavioural sedation and/or sleep and ECoG synchronization in rats while beta-interferon produced no behavioural sleep or ECoG synchronization. A slight sedation was observed after the largest dose of beta-interferon only. During sleep induced by lymphokines, a dose-dependent increase in total voltage power as well as in the 0.5-3, 4-7 and 12-16 Hz frequent bands was observed. Much smaller doses were required to produce similar behavioural and ECoG spectrum effects after infusion of interferons and interleukin-2 into the locus coeruleus. No significant behavioural and ECoG changes were obtained after infusion of the same doses of interferons and interleukin-2 into other areas of the brain (caudate nucleus, dorsal hippocampus, substantia nigra pars compacta, ventromedial hypothalamus). The behavioural and ECoG effects of alpha-interferon, rat interferon and interleukin-2 were blocked in animals pretreated with naloxone. These results are consistent with the hypothesis that the behavioural and ECoG effects of these lymphokines are mediated at locus coeruleus level by stimulation of opiate receptors.

Animals↗