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Biomedical subjects

G Nisticò

Publications and source records attributed to G Nisticò.

At least 55 records · Page 3Linked to original sources
PubMed1994

Melatonin restores immunodepression in aged and cyclophosphamide-treated mice.

Melatonin, the main hormone of the pineal gland, when chronically injected into young mice or mice immunodepressed by aging or by cyclophosphamide treatment, was able to enhance the antibody response to a T-dependent antigen. The enhancement of antibody response was associated with increased induction of T helper cell activity and IL-2 production as evidenced in mice immunodepressed by aging or by cyclophosphamide treatment. These observations suggest that melatonin may be successfully used in the therapy of immunodepressive conditions.

Adjuvants, Immunologic↗
PubMed1994

N-methyl-D-aspartate-induced excessive formation of nitric oxide in CHP100 neuroblastoma cells produces death of BMEL melanoma cells in co-culture.

In the present experiments we planned to ascertain whether an abnormal production of nitric oxide (NO) by human CHP100 neuroblastoma cells in culture following stimulation of N-methyl-D-aspartate (NMDA) receptors, produced lethal effects in co-cultured human BMEL melanoma cells. Human BMEL melanoma cells in culture were found to be positive to the nicotinamide adenine dinucleotide phosphate diaphorase (NADPH diaphorase) histochemical reaction and produced NO as revealed by measurements of nitrite under basal culture conditions. Exposure for 50 min to aspartate (1-2 mM) or to NMDA (0.5-1.5 mM) did not evoke significant melanoma cell death. The dose of 1.0 mM NMDA applied for 1 min to BMEL cell cultures did not increase significantly nitrite concentrations in comparison to controls. Incubation for 50 min of human CHP100 neuroblastoma cells with NMDA (0.5-1.5 mM) elicited dose-dependent death of BMEL melanoma cells co-cultured in trans-wells. Under these experimental conditions, nitrite levels in cell culture-inserts containing melanoma cells increased by 120% 1 min after application of the excitotoxin (1 mM) to CHP100 neuroblastoma cultures. The lethal effects produced in BMEL cell culture-inserts by application of NMDA (1.0 mM) to CHP100 cultures were prevented by pretreatment of neuroblastoma cultures with MK801 (200 nM). Similar protection was also afforded by N omega-nitro-L-arginine methyl ester (L-NAME; 0.2 mM) and N omega-monomethyl-L-arginine (L-NMMA; 0.2 mM), two inhibitors of nitric oxide synthase, and by haemoglobin (10 microM), a nitric oxide trapping agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1994

Nitric oxide inhibition aggravates ischemic damage of hippocampal but not of NADPH neurons in gerbils.

BACKGROUND AND PURPOSE: Nitric oxide may influence pathophysiology of brain ischemia in a complex way depending on the sources of its production either from neurons or endothelial cells. We investigated whether inhibition of nitric oxide synthesis affects postischemic neuronal death in hippocampus. Moreover, we evaluated whether the presence of nitric oxide synthase activity in specific neurons protects these against ischemia in the hippocampus, striatum, and sensorimotor cortex. METHODS: To inhibit nitric oxide synthase, several dosing regimens of NG-nitro-L-arginine methyl ester (L-NAME) were used (5 or 50 mg/kg IP, twice a day for 4 days, or 30 mg/kg IV) in gerbils. Control animals received either the isomer NG-nitro-D-arginine methyl ester or the vehicle. The gerbils underwent 10-minute occlusion of carotid arteries under ether anesthesia and controlled body temperature while physiological parameters were monitored. Neuronal damage was assessed 5 days after ischemia using Nissl-stained sections of hippocampus. Nitric oxide synthase neurons were histochemically stained for reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity. RESULTS: L-NAME treatments, but not the chronic one at 5 mg/kg, induced elevation of blood pressure (30% to 80% greater than the control level, P < .01), as observed shortly before and after bilateral carotid occlusion. Postischemic neuronal loss in the CA1 through CA4 sectors was worsened by chronic pretreatment with L-NAME at 50 mg/kg (eg, CA1 neuronal counts per 100-microns length: 3.2 +/- 2.74, mean +/- SD; n = 19; P < .01). After the acute (30 mg/kg) or chronic pretreatment at lower dosage (5 mg/kg) with L-NAME, neuronal loss was comparable to that of animals treated with the D-isomer or the vehicle (CA1 counts in vehicle-treated animals: 7.65 +/- 6.51, mean +/- SD; n = 14). None of the L-NAME treatments affected postischemic survival of NADPH diaphorase-positive neurons in hippocampus, striatum, and sensorimotor cortex. CONCLUSIONS: These observations demonstrate that inhibition of endothelial and neuronal nitric oxide synthase activity does not modify resistance of nitric oxide-producing neurons to transient ischemia. The severe inhibition of nitric oxide production aggravates postischemic neuronal death in the hippocampus, whereas the mild inhibition is ineffective.

Amino Acid Oxidoreductases↗
PubMed1993

Lithium and tacrine increase the expression of nitric oxide synthase mRNA in the hippocampus of rat.

The expression of nitric oxide synthase mRNA and the enzyme activity were studied in the hippocampus of rats treated with lithium chloride (LiCl; 12 mEqkg-1 i.p.) and tacrine (5 mgkg-1 i.p.). In comparison to vehicle treated animals, mRNA signal was augmented by 2-fold 24 h after administration of LiCl and by 4-fold 15 min after tacrine. In LiCl pretreated rats, tacrine yielded a 6-fold mRNA increase and this was prevented by corticosterone (35 mgkg-1, given i.p. 30 min before tacrine). Combined administration of LiCl and tacrine also produced an approx. 80% increase in Ca(2+)-calmodulin-dependent nitric oxide synthase activity. The present results represent the first demonstration that in the hippocampus mRNA expression of constitutive brain nitric oxide synthase can be augmented with consequent increase in nitric oxide synthesis.

Amino Acid Oxidoreductases↗
PubMed1993

Determination of paraquat in rat brain by high-performance liquid chromatography.

The applications of a method based on ion-pair solid-phase extraction and reversed-phase HPLC are reported. The method was used to measure paraquat concentrations in discrete brain areas at different times after its systemic administration in rats. In addition, the method was employed in the determination of paraquat levels in whole-brain samples from rats of various ages systemically treated with several doses of the herbicide.

Aging↗
PubMed1993

Systemic administration of lithium chloride and tacrine increases nitric oxide synthase activity in the hippocampus of rats.

We planned to ascertain whether the administration of the anticholinesterase, tacrine (5 mg/kg i.p.), to rats pretreated 24 h before with lithium chloride (LiCl; 12 mEq/kg i.p.) produced any change in nitric oxide (NO) synthase activity in the hippocampus. A significant increase in hippocampal Ca(2+)-calmodulin-dependent NO synthase activity occurred 15 min after tacrine injection and was blocked by atropine (5 mg/kg i.p. given 15 min before tacrine) and by N omega-nitro-L-arginine methyl ester (300 micrograms given into one lateral cerebral ventricle 10 min before tacrine), a NO synthase inhibitor. A consistent cyclic guanosine 3',5'-monophosphate (cGMP) accumulation was also seen. In conclusion, the present results show that tacrine given to LiCl-pretreated rats produces a significant increase in NO synthase activity in the hippocampus and this may be responsible, at least in part, for seizures and related brain damage elicited by these drugs.

Amino Acid Oxidoreductases↗
PubMed1993

Antagonists of N-methyl-D-aspartate receptors block seizures induced by putrescine in the deep prepiriform cortex.

The role of excitatory amino acid receptors in the genesis of motor and electrocortical seizures, elicited by administration of the polyamine putrescine into the deep prepiriform cortex, has been evaluated in rats. Motor and electrocortical seizures occurred in rats receiving unilateral local injections into the deep prepiriform cortex, of putrescine (10 or 20 nmol). The selective N-methyl-D-aspartate receptor antagonist, 2-amino-7-phosphonoheptanoate (AP7), injected previously (15 min) into the deep prepiriform cortex, prevented the development of seizures induced by putrescine, injected at the same site. In addition, dizocilpine (MK-801), a non-selective NMDA antagonist or ifenprodil, a specific inhibitor of the polyamine site at the NMDA receptor, when injected into the deep prepiriform cortex, 15 min prior to putrescine, significantly protected against seizures elicited by this polyamine. A subconvulsant dose of putrescine (5 nmol) potentiated the convulsant effects of NMDA, when injected into the deep prepiriform cortex. These data indicate a potential role of polyamines in the genesis of seizures, elicited from the deep prepiriform cortex. They further suggest that activation of the polyamine site, located at excitatory amino acid NMDA receptors, within the deep prepiriform cortex, may contribute to the genesis of seizure activity in this area.

2-Amino-5-phosphonovalerate↗
PubMed1993

The generation of nitric oxide participates in gamma IFN-induced MHC class II antigen expression by cultured astrocytoma cells.

The effects of interferon gamma (gamma IFN) on the MHCII antigen expression by human cultured astrocytoma cells were investigated. The co-incubation of gamma IFN with T67 astrocytoma cells produced a dose-dependent increase of MHCII antigen expression as evaluated by flow cytometric (FACS) analysis and confocal laser microscopy analysis. The number of MHCII molecules expressed by gamma IFN-pretreated astrocytoma cells was reduced by co-incubation with N omega-nitro-L-arginine methyl ester (L-NAME), a selective inhibitor of the nitric oxide (NO)-synthesizing enzyme. In addition, methylene blue, which inhibits the biological activity of NO acting at the guanylate cyclase level, strongly antagonized the MHCII antigen expression on astrocytoma cells induced by gamma IFN. Furthermore, gamma IFN increased the activity of the inducible isoform of NO-synthase as well as the concentration of nitrite, one of the breakdown products of NO and the antiplatelet activity of astrocytoma cells. In conclusion, the present data show that gamma IFN increases the synthesis and release of NO by cultured astrocytoma cells and this could co-participate in the MHCII antigen expression by this cell type. Therefore, the generation of NO by cultured astrocytoma cells may represent an important step in the development of the immunocompetent activity of astrocytes.

Amino Acid Oxidoreductases↗
PubMed1993

Inhibition by N omega-nitro-L-arginine methyl ester of the electrocortical arousal response in rats.

In rats chronically implanted with cannulae into one lateral cerebral ventricle and recording electrodes onto the fronto-parietal cortex, the effects of systemic or intraventricular administration of the nitric oxide (NO) synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), on electrocortical (ECoG) arousal response evoked by sound stimulation were studied. In control animals, a single acoustic stimulation (80 dB for 15 s) produced a significant decrease in ECoG total voltage power lasting approximately 25 s. No tolerance developed after repeating the same sound stimulation at 15, 30, 60 min and 24 h intervals. Under these experimental conditions, pretreatment with L-NAME, given systemically (10 mg kg-1, i.p.) or intracerebroventricularly (300 micrograms), significantly reduced the sound-evoked arousal response 1 h and 15 min later, respectively. In conclusion, the present data are in favour of a physiological role of NO in the control of arousal mechanisms.

Acoustic Stimulation↗
PubMed1992

Altered sensitivity of alpha 2-adrenoceptors in the brain during aging in rats.

The soporific and cardiovascular responses to the injection of clonidine into the locus coeruleus and nucleus tractus solitarius, respectively, were studied in rats of different ages. Clonidine (0.09, 0.19, 0.28, and 0.56 nmol) microinfused into the LC of young rats induced dose-dependent behavioral and ECoG SWS with a significant increase in total voltage in the lower frequency bands. In contrast to young rats, clonidine (0.19 and 0.28 nmol) given into the LC did not affect the behavior and ECoG spectrum power in old rats. However, after higher doses of clonidine (0.56 and 1.2 nmol) a small, short-lasting period of behavioral and ECoG SWS was still evident. In 3-month-old rats clonidine (0.25, 0.5 and 1 micrograms) injected into the nucleus tractus solitarius in anesthetized rats produced a significant fall in blood pressure and a significant decrease in heart rate. In contrast, in 12-month-old rats the maximum fall in blood pressure and heart rate was significantly less than in young animals. In addition, in older rats (24-month old) clonidine at the same or larger doses given into the nucleus tractus solitarius did not produce any significant changes in the cardiovascular parameters studied. In conclusion, the present experiments provide evidence that during aging there is a progressive decrease in the soporific and cardiovascular responses to alpha 2-adrenoceptor stimulation in the locus coeruleus and nucleus tractus solitarius, respectively.

Aging↗
PubMed1992

Evidence that CHP100 neuroblastoma cell death induced by N-methyl-D-aspartate involves L-arginine-nitric oxide pathway activation.

Evidence suggests that nitric oxide (NO) may mediate, at least in part, excitotoxic effects of excessive N-methyl-D-aspartate (NMDA) receptor activation both in vivo and in vitro. In the present experiments, NMDA-induced excitotoxicity has been studied in CHP100 neuroblastoma cell cultures. Application of NMDA (0.25-1.5 mM) produced concentration-dependent cell death. These effects were antagonized by co-application of dizocilpine (MK801), a selective and non-competitive NMDA receptor complex antagonist. Protection from NMDA-induced lethal effects was also afforded by N omega-nitro-L-arginine methyl ester, a potent NO-synthase inhibitor, and by hemoglobin, a NO-trapping agent. In addition, substitution of L-arginine, normally present in the exposure solution with its D-isomer, abolished the cell death induced by the excitotoxin. In conclusion, the present experiments support the suggestion that excitotoxic effects induced by NMDA receptor stimulation involve L-arginine-NO pathway activation.

Amino Acid Oxidoreductases↗
PubMed1992

Tacrine-induced seizures and brain damage in LiCl-treated rats can be prevented by N omega-nitro-L-arginine methyl ester.

The effects of tacrine (5 mg/kg i.p.), a potent acetylcholinesterase inhibitor, were studied in rats pretreated (24 h beforehand) with a single dose (12 mEq/kg i.p.) of LiCl. Tacrine and LiCl were ineffective when given individually. Tacrine elicited seizures and brain damage in 90% of the rats treated. The intracerebroventricular microinfusion of N omega-nitro-L-arginine methyl ester (300 micrograms given 24 h after LiCl administration) significantly reduced the seizures and brain damage produced by tacrine (given 15 min later). These experiments suggest that the seizures and brain damage elicited by tacrine may be due, in part, to increased nitric oxide production in the brain.

Animals↗
PubMed1992

Epileptogenic effects of skin extracts from the Australian frog Pseudophryne coriacea after intracerebral microinfusion in rats.

The behavioural and electrocortical (ECoG) effects induced by a methanol extract of the skin of the Australian frog Pseudophryne coriacea, directly microinjected into several areas of the brain, were studied in freely moving rats. Administration of the P. coriacea extract (5, 10, 15 and 20 micrograms) into the dorsal hippocampus produced a dose-dependent and reversible behavioural stimulation and ECoG spikes lasting 20-140 min. Similar but less intense effects were elicited in rats receiving injections into the III cerebral ventricle, amygdala and caudate nucleus. In conclusion, the present experiments show that the skin extract of P. coriacea produces behavioural stimulation and ECoG spikes when injected into the rat brain, the most sensitive area being the hippocampus.

Amphibian Venoms↗
PubMed1992

Glutamate transmission is involved in the mechanisms of neuronal degeneration produced by intrahippocampal tetanus toxin in rats.

Tetanus toxin (TT) blocks GABA-mediated inhibitory neurotransmission in the mammalian CNS via selective inhibition of transmitter release. The loss of central inhibition produces an excitatory focus resembling human limbic epilepsy. We now report that the net excitation caused by an unopposed action of glutamic acid may also produce neuronal degeneration in the rat brain. Anaesthetized rats were placed in a stereotaxic frame and TT (1 microliter dissolved in phosphate buffer, pH 7.0) was injected unilaterally into the dorsal hippocampus. Injection of TT (1000 mouse minimum lethal doses, MLDs; n = 3-6 rats per group) produced time-dependent neuronal loss in the CA1 pyramidal cell layer which was significant (p < 0.05) 7 and 10 days, but not 1 day, after the injection. Systemic treatment with competitive (CGP 37849, 3 mg/kg i.p) or non-competitive (MK801, 0.3 mg/kg i.p.) antagonists at the N-methyl D-aspartate (NMDA) receptor complex 1 h before and 1 h after TT and then once daily for 10 days protected rats from the hippocampal damage produced by TT (1000 MLDs). In addition, in rats bearing a monolateral surgical lesion of the Schaffer collaterals, through which CA1 neurones receive a robust excitatory input from CA3 pyramids, the bilateral injection of TT (1000 MLDs/side) produced significant neuronal loss in the unlesioned hippocampus whereas the contralateral appeared to be preserved. In conclusion, these results demonstrate that excitatory neurotransmission may be involved in the neuropathology elicited by intrahippocampal TT in rats.

2-Amino-5-phosphonovalerate↗