Biomedical subjects

E Esposito

Publications and source records attributed to E Esposito.

At least 19 recordsLinked to original sources

PubMed1995

Differential effects of acute and chronic fluoxetine administration on the spontaneous activity of dopaminergic neurones in the ventral tegmental area.

1. Electrophysiological techniques were used to study the effects of fluoxetine and citalopram on the basal activity of dopaminergic neurones in the ventral tegmental area (VTA) and substantia nigra, pars compacta (SNc) of rats. 2. Acute i.v. injection of fluoxetine (20-1280 micrograms kg-1) caused a dose-dependent inhibition of the firing rate of VTA dopaminergic neurones, but did not affect the activity of dopaminergic cells in the SNc. Citalopram (20-1280 micrograms kg-1, i.v.) inhibited the firing rate of dopaminergic neurones in the VTA, but its effect (maximal inhibition: 14 +/- 7%) was less pronounced than that of fluoxetine (maximal inhibition: 34 +/- 7%). 3. Pretreatment with mesulergine (80 micrograms kg-1, i.v.), a 5-hydroxytryptamine2C/2B (5-HT2C/2B) receptor antagonist, blocked the inhibitory effect of fluoxetine on VTA dopaminergic cells. Selective lesions of 5-hydroxytryptaminergic neurones by the neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), abolished the fluoxetine-induced reduction of VTA dopaminergic activity. 4. In a series of experiments, fluoxetine (10 mg kg-1, i.p.) was administered once daily for 21 consecutive days. Acute i.v. administration of fluoxetine (20-1280 micrograms kg-1, 72 h after the last i.p. injection) did not cause any change in the basal firing rate of VTA dopaminergic neurones in treated rats, whereas it induced the typical inhibitory effect in control animals. A group of rats chronically treated with fluoxetine, received i.v. m-chlorophenylpiperazine (mCPP; 10-320 micrograms kg-1), a 5-HT2C/2B receptor agonist. This drug significantly inhibited VTA dopaminergic function in control rats, but did not modify the basal activity of dopaminergic cells in animals given chronic fluoxetine. 5 It is concluded that fluoxetine inhibits dopaminergic function in the VTA by enhancing the synaptic levels of 5-HT, which possibly acts through the 5-HT2C/2B receptor subtype. Repeated treatment with fluoxetine induces tolerance to its inhibitory effect on dopaminergic activity, possibly as a consequence of down-regulation of 5-HT2C/2B receptors. The effects of fluoxetine on VTA dopaminergic cell activity might be relevant for its therapeutic actions and may explain the origin of the reported cases of akathisia.

Animals↗

PubMed1994

Activation of glutamate receptors stimulates the formation of nitrite in synaptosomes from rat cerebellum.

Synaptosomes from rat cerebellum were used to investigate the involvement of different glutamate receptor subtypes in the control of the synthesis of nitric oxide (NO), measured as its breakdown product nitrite (NO2-). Synaptosomes incubated in the presence of NADPH and L-arginine produced measurable levels of NO2-, which were reduced by addition of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. The selective ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) induced a pronounced increase in NO2- formation, which was prevented by N omega-nitro-L-arginine methyl ester and by the specific NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5). The NMDA-induced increase in NO2- formation was blocked by chelation of extracellular Ca2+ with EGTA. Both L-glutamate and the selective agonist for the metabotropic glutamate receptors (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid raised NO2- production, which returned to control levels after addition of N omega-nitro-L-arginine methyl ester. The selective glutamate ionotropic receptor agonist (R,S)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid did not cause any change in NO2- formation. The stimulatory effect of L-glutamate was blocked by the metabotropic glutamate receptor antagonist DL-2-amino-4-phosphonobutyric acid but was unaffected by the selective NMDA receptor blocker AP-5. Removal of extracellular Ca2+ by EGTA did not affect the action of L-glutamate; whereas W-7, an inhibitor of calmodulin, and dantrolene, a compound that blocks the mobilization of Ca2+ from intracellular stores, abolished the effect of L-glutamate on NO2- formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Serotonin-dopamine interaction in the rat ventral tegmental area: an electrophysiological study in vivo.

Electrophysiological techniques were used to study the effects of various serotonin (5-HT) agonists and antagonists on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) of rats. Systemic administration of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.25-80 micrograms/kg i.v.) increased the firing rate of the majority (75%) of DA cells studied and stimulated their bursting activity. A subpopulation (25%) of DA neurons was inhibited by 8-OH-DPAT. Selective lesions of 5-HT neurons by the neurotoxin 5-7-dihydroxytryptamine abolished completely the excitatory effect of 8-OH-DPAT on both firing rate and bursting activity of DA neurons. Microiontophoretic application of 8-OH-DPAT into the VTA did not cause any change in the firing rate of DA neurons. Treatment with the selective 5-HT1B agonist CGS 12066B (7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrolo[1,2-a] quinoxaline 1:2 maleate salt) (1.25-160 micrograms/kg i.v.) did not cause any change in basal firing rate of VTA DA cells. Systemic administration of trifluoromethylphenylpiperazine (TFMPP) (1.25-160 micrograms/kg i.v.) and m-chlorophenylpiperazine (mCPP) (1.25-320 micrograms/kg i.v.), two mixed 5-HT1B/5-HT1C receptor agonists, significantly reduced the firing rate of all VTA DA neurons studied. The effect of mCPP (maximal inhibition, 40%) was more pronounced compared to that of TFMPP (maximal inhibition, 25%). Microiontophoretic application of mCPP into the VTA caused a marked inhibition of the basal activity of DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1993

Rapid and simple method for the determination of nitrite in synaptosomal superfusates by liquid chromatography with electrochemical detection.

A rapid and simple technique using reversed-phase high-performance liquid chromatography with electrochemical detection (HPLC-ED) was developed for the determination of nitrite. Standard solutions of sodium nitrite produced a linear current response over the concentration range 1.5-30 microM. The chromatographic peaks of sodium nitrite were superimposable with peaks obtained after injection into the chromatograph of supernatants from rat cerebellar synaptosomes. The concentrations of nitrite in synaptosomes measured with HPLC-ED were similar to those found with a widely used colorimetric procedure. Therefore, this new method may represent a useful means of measuring nitrite in biological samples.

Animals↗

PubMed1993

Growth of Helicobacter pylori in media containing cyclodextrins.

We show that solid and liquid media, supplemented only with cyclodextrins and free of blood and its derivatives, support the growth of Helicobacter pylori. These media can be used for primary isolation of the bacteria from biopsy samples, routine laboratory growth, and large-scale industrial fermentation.

Bacterial Proteins↗

PubMed1993

[Use of enoximone in the postoperative course of heart surgery].

The aim of this study was to evaluate the efficacy and safety of enoximone, an imidazolonic compound inhibiting cardiac phosphodiesterase III, during the postoperative period. The drug was administered prior to the usual stages of weaning the patient off extracorporeal circulation, to a group of 20 subjects who presented an ejection fraction of less than 35% following hemodynamic studies. Patients were randomly subdivided into 4 groups each of which received a different dose of enoximone according to the following protocol: Group A, 1 mg/kg bolus and slow infusion at 10 gamma/kg/min; Group B, 0.5 mg/kg bolus and slow infusion at 15 gamma/kg/min; Group C, 0.5 mg/kg bolus and slow infusion at 10 gamma/kg/min; Group D, slow infusion at 10 gamma/kg/min. The best results in hemodynamic terms and with regard to the positive inotropic and vasodilatory action of the drug in question were obtained in Group C. Increased cardiac output was observed in all patients within 120 minutes of enoximone administration and reduced systemic vascular resistance after approximately 6 hours of infusion. Special attention should be drawn to the use of the drug in patients who do not respond to conventional therapy due to its mechanism of action which is not dependent on beta receptors, thus enabling good results to be achieved even when these are down regulated. Special care must be taken however in administrating enoximone to platelet-deficient patients since the reduction of platelet levels is one of its collateral effect. Other collateral effects observed were: supraventricular arrhythmias and ventricular tachyarrhythmias.

Cardiac Output↗

PubMed1993

Tertatolol, a new beta-blocker, is a serotonin (5-hydroxytryptamine1A) receptor antagonist in rat brain.

The interaction of tertatolol (d,l-hydroxy-2'-t-butylamino-3'propyloxy-8-thiochromane HCl) with 5-hydroxytryptamine (serotonin; 5-HT) receptors in several brain areas were investigated. Both ligand binding techniques and an electrophysiological approach were used. First, the affinity of tertatolol for different 5-HT receptor subtypes was measured, as assayed by a competition binding experiment using specific ligands in several brain areas. It was found that (-)-tertatolol binds to 5-HT1 receptor subtypes in rat brain, particularly the 5-HT1A subtype in the hippocampus (Ki = 5.9 nM). (-)-Tertatolol showed much lower affinity for 5-HT1B (Ki = 118.4 nM), 5-HT1C (Ki = 699.6 nM) and 5-HT2 (Ki = 678.6 nM) receptors. The binding of tertatolol to hippocampal 5-HT1A receptors was stereospecific in that the affinity of (+)-tertatolol to these receptors (Ki = 311.6 nM) was about 20 times lower as compared to that of (-)-tertatolol. There was no significant binding of tertatolol to 5-HT1D, 5-HT3, alpha-1 adrenergic receptors or to the serotonin uptake site. Electrophysiological techniques were used to study the effects of (-)-tertatolol on the activity of 5-HT-containing neurons in the rat dorsal raphe nucleus. Acute i.v. injection of (-)-tertatolol caused a slight increase in the basal firing rate of the majority of 5-HT neurons studied. Pretreatment with (-)-tertatolol (1 mg/kg i.v.) significantly reduced the inhibitory effect of 8-hydroxy-2-(di-n-proylamino) tetralin (0.25-64 micrograms/kg i.v.) on the firing rate of dorsal raphe nucleus 5-HT neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

DNA binding activity and inhibition of DNA-protein interactions. Differential effects of tetra-p-amidino-phenoxyneopentane and its 2'-bromo derivative.

In the present study are reported the differential DNA binding activity of the anti-tumor polyamidine tetra-p-amidinophenoxyneopentane (TAPP-H) and its 2'-halo derivative (TAPP-Br), and their effects on the binding of the recombinant Epstein-Barr virus (EBV) nuclear antigen to a synthetic oligonucleotide mimicking the target DNA sequence present in the EBV genome. In addition, the proliferation kinetics and cell cycle analysis of human leukemia K562 cells treated with TAPP-H and TAPP-Br are reported. The possible in vivo relationship between DNA binding affinity and cytotoxicity is also discussed.

Antigens, Viral↗

PubMed1992

Chronic treatment with DAU 6215, a new 5-HT3 receptor antagonist, causes a selective decrease in the number of spontaneously active dopaminergic neurons in the rat ventral tegmental area.

Electrophysiological techniques were used to study the effects of the new compound, DAU 6215 ((3-alpha-tropanyl) 1H-benzimidazolone-3-carboxamide chloride), a selective 5-HT3 receptor antagonist, on the activity of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Acute i.v. injections of DAU 6215 did not cause any change in the basal firing rate of DA neurons in the SNc or in the VTA. Pretreatment with DAU 6215 did not modify the inhibitory effect of apomorphine on the firing rate of midbrain DA neurons. Acute s.c. administration of DAU 6215 caused a significant increase in the number of spontaneously active DA neurons in the VTA but not in the SNc. This effect was similar to that of acute clozapine, whereas acute haloperidol caused a significant increase of spontaneously active DA neurons in both the SNc and the VTA. Repeated consecutive s.c. administration of DAU 6215 and clozapine for 21 days produced a significant decrease in the number of spontaneously active DA neurons in the VTA but not in the SNc. Chronic haloperidol (21 days) decreased the number of DA cells both in the SNc and VTA. The effect of chronic DAU 6215 on the activity of VTA DA neurons was reversed by apomorphine, suggesting that these neurons were probably under a state of depolarization block. These findings indicate that DAU 6215 may have potential antipsychotic activity, probably associated with a low incidence of extrapyramidal side-effects.

Animals↗

PubMed1991

[Exclusive radiotherapy of carcinoma of the hypopharynx. Retrospective study of a series of 100 patients].

From January 1980 to December 1987, 100 patients with carcinoma of the hypopharynx, staged according to TNM (UICC-1978) criteria, received exclusive radiation therapy at the Radiotherapy Department of the General Hospital of Varese. The median follow-up is 9 months (range: 1-97). Irradiation was delivered with 60Co or with 10 MV photons and tissue-equivalent bolus. Two opposed parallel lateral fields or rotational technique were used, with progressive shrinking of treated volume in order to spare the spinal cord after 45 Gy. Direct fields of electron beams (6-15 MeV) were employed as boosts on the residual nodes. Median total doses: 64.5 Gy to T and N1-3, 45 Gy to N0. A conventional fractionation (2 Gy once a day, 5 times a week) was used in 37 outpatients, while an accelerated hyperfractionated regimen (1.5 Gy twice a day, 5 times a week, with a six hours' interval between each fraction) was employed in 63 inpatients, in order to shorten hospitalization. The five-year overall survival (Kaplan-Meier) of the 100 treated patients is 10%, while the five-year disease-free survival of the 40 patients in complete clinical remission at the end of radiation therapy is 19.8%. The five-year loco-regional control rate after exclusive radiotherapy is 19.1%. Complete remission at the end of treatment seems to represent the only significant prognostic variable affecting survival: five-year overall survival is 32% for the 40 patients achieving complete remission and only 4.4% for the others (p less than 0.05). On the contrary, tumor extension (T class) seems to affect only the two-year local control rate: 35.2% and 10.9% for T1 + T2 and T3 + T4 respectively (p less than 0.1). The main cause of failure after radiation therapy is represented by the lack of control at the primary site (T) alone or associated with regional adenopathies (N). The analysis of isoeffect parameters, according to CRE model, has not shown any evident dose-response relationship for local control. Late effects were observed in 7% of the patients and were similar to those reported in the literature. The occurrence of both distant metastases, 3% in our experience, and secondary tumors (9%) is lower than those previously reported. The present retrospective study strongly reconfirms the inadequacy of exclusive radiation therapy as the sole treatment modality for carcinoma of the hypopharynx and suggests the need of combination therapy (surgery and radiation) as primary treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1990

Calditol tetraether lipids of the archaebacterium Sulfolobus solfataricus. Biosynthetic studies.

Lipids from the archaebacterium Sulfolobus solfataricus are based on 72-membered macrocyclic tetraethers made up from two C40 diol units differently cyclized and either two glycerol moieties or one glycerol moiety and a unique branched-chain nonitol named calditol (glycerodialkylnonitol tetraethers, GDNTs). To elucidate the biosynthesis of calditol and related tetraethers, labelled precursors, [U-14C,1(3)-3H]glycerol, [U-14C,2-3H]glycerol, D-[1-14C,6-3H]glucose, D-[6-14C,1-3H]glucose, D-[1-14C,2-3H]glucose, D-[1-14C,6-3H]fructose and D-[1-14C]galactose, were fed to S. solfataricus. Without regard to stereochemistry or phosphorylation, incorporation experiments provided evidence that the biosynthesis of calditol occurs via an aldolic condensation between dihydroxyacetone and fructose, through a 2-oxo derivative of calditol as an intermediate. The latter is in turn reduced and then alkylated to yield the GDNTs. The biogenetic origins of both glycerol and C40 isoprenoid moieties of GDNTs are also discussed.

Acetylation↗

PubMed1989

The effect of acute and chronic treatment with SCH 23390 on the spontaneous activity of midbrain dopamine neurons.

The effect of acute and chronic administration of SCH 23390 on the spontaneous activity of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) was studied. Two groups of rats were given an acute subcutaneous (s.c.) injection of the specific D-1 DA receptor block SCH 23390 (0.5 or 1.0 mg/kg). In four separate chronic experiments, SCH 23390 was administered repeatedly for 21 days either s.c. (0.5 or 1 mg/kg) or orally (5 or 10 mg/kg). No change in the number of spontaneously active DA neurons was found either after acute or chronic treatment with SCH 23390. On the other hand, chronic (21 days) haloperidol (0.5 mg/kg per os) produced a marked reduction in the number of spontaneously active DA neurons both in the SNc and VTA, a finding previously shown to be due to the development of depolarization block. It is concluded that chronic D-1 DA receptor blockade, may not be involved in the development of depolarization block produced by chronic treatment with antipsychotic drugs.

Animals↗

PubMed1987

Dopamine denervation of the nucleus accumbens induces a selective increase in the number of delta-opioid binding sites.

Selective lesions of dopamine (DA) neurons of the nucleus accumbens were made in rats by local injections of 6-hydroxydopamine (6-OHDA). Seven days after 6-OHDA, the binding affinities and capacities at mu-, delta- and kappa-opioid binding sites were determined in the nucleus accumbens by selective labelling techniques. 6-OHDA pretreatment caused a significant increase in the number of delta-opioid binding sites (+30%) while the number of mu-, kappa- and total sites was not modified. The affinity at mu-, delta- and kappa-sites was unchanged after 6-OHDA pretreatment.

Animals↗

PubMed1987

Effects of peripheral and central administration of calcium channel blockers in the naloxone-precipitated abstinence syndrome in morphine-dependent rats.

The effects of two calcium channel blockers (verapamil and flunarizine) were evaluated on the naloxone-precipitated syndrome in morphine-dependent rats. The withdrawal signs in saline-treated rats were mainly diarrhea, body weight loss, jumping and ptosis. On i.p. administration, verapamil and flunarizine prevented diarrhea and body weight loss but not jumping. Verapamil also reduced the incidence of ptosis at the highest dose tested (40 mg/kg). Administered i.c.v., 160 micrograms verapamil reduced the body weight loss and the number of jumps without modifying diarrhea or ptosis. The results show that calcium channel blockers inhibit morphine abstinence syndrome manifestations through both peripheral and central mechanisms.

Animals↗

PubMed1987

Further evidence that noradrenaline is not involved in the anti-immobility activity of chronic desipramine in the rat.

The effect of 10 mg/kg per day desipramine for 7 days on performance in the forced swimming test was studied in rats given various treatments aimed at reducing central noradrenergic transmission. 6-Hydroxydopamine-induced destruction of noradrenaline-containing neurons originating in the locus coeruleus or ascending in the ventral bundle had no effect on the anti-immobility activity of desipramine. Likewise, no changes in the effect of desipramine were seen with an intraperitoneal injection of DSP-4 (50 mg/kg) which destroyed brain noradrenergic neurons, particularly those of the dorsal bundle ascending to the forebrain. The results argue against a role of noradrenaline in the mechanism by which repeated treatment with desipramine reduces the immobility of rats in the forced swimming test.

Animals↗

PubMed1987

Noradrenergic and behavioural effects of naloxone injected in the locus coeruleus of morphine-dependent rats and their control by clonidine.

Naloxone HCl (10 micrograms/0.5 ml) was injected in the locus coeruleus (LC) of morphine-dependent rats and the behavioural manifestations of morphine withdrawal and the cortical levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) were measured 30 min later. Naloxone precipitated a withdrawal syndrome and raised cortical MHPG-SO4 in animals made dependent by ascending doses of morphine for 11 days. An injection of clonidine intraperitoneally (200 micrograms/kg) or in the LC (5 micrograms/0.5 microliter) blocked most aspects of the withdrawal syndrome except jumping and had no effect on the naloxone-induced rise in cortical MHPG-SO4. The findings confirm the hypothesis that the LC is one of the sites where naloxone and clonidine, respectively, precipitate and reduce the narcotic withdrawal syndrome but argue against a role of noradrenergic neurons originating in the LC and innervating the cortex in the ability of clonidine to suppress some aspects of withdrawal syndrome precipitated by naloxone in morphine-dependent animals.

Animals↗

PubMed1986

Evidence of the involvement of dopamine in the analgesic effect of nefopam.

The involvement of brain monoamines in the mechanism of action of nefopam, a new analgesic, was investigated in rats. The study was designed to evaluate the effect of various means of impairing monoaminergic transmission on nefopam analgesia as measured with the hot plate method. Pretreatment with reserpine (2 mg/kg) significantly reduced the antinociceptive action of nefopam (40 mg/kg), indicating that the interaction of this drug with the monoaminergic systems is important for its effects. A role for serotonin (5-HT) or norepinephrine (NE) was ruled out by the fact that selective depletion of 5-HT (using 5,7-dihydroxytryptamine) or NE (using DSP-4 or FLA-63) did not affect nefopam analgesia. A significant reduction of the effect of nefopam was found in rats pretreated with 6-hydroxydopamine (6-OHDA). Also 6-OHDA plus desipramine, which selectively depleted brain DA, markedly reduced the antinociceptive effect of nefopam. The data strongly suggest that a critical dopaminergic synapse is involved in the mechanism by which nefopam inhibits nociceptive responses in rats.

5,7-Dihydroxytryptamine↗

PubMed1986

The effect of different lesions of the median raphe on morphine analgesia.

The effect of different manipulations of the nucleus medianus raphe (MR) on morphine analgesia was investigated in rats using the tail-immersion test. Electrolytic lesions of this structure antagonized morphine analgesia, while injections of 5,7-dihydroxytryptamine (to destroy serotonergic neurons) or ibotenic acid (to destroy cell bodies) in the medianus raphe did not alter the effect of morphine. Injection of naloxone (0.5 and 0.1 micrograms) in the MR antagonized morphine analgesia. These results suggest the importance of this structure for morphine analgesia in this test, although the substrates within the nucleus that mediate this action are still unknown.

5,7-Dihydroxytryptamine↗