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Biomedical subjects

G Colombo

Publications and source records attributed to G Colombo.

At least 127 records · Page 7Linked to original sources

Substitution of the 5-HT1 agonist trifluoromethylphenylpiperazine (TFMPP) for the discriminative stimulus effects of ethanol: effect of training dose.

The role of the ethanol training dose on the ability of the selective 5-HT1 agonist TFMPP (m-trifluoromethylphenylpiperazine) to produce ethanol-like discriminative stimulus effects was evaluated in three groups of rats trained to discriminate 1.0 g/kg (n = 5), 1.5 g/kg (n = 6) or 2.0 g/kg (n = 7) ethanol (IG) from water using a two-lever procedure with food reinforcement available under a fixed ratio 20 (FR 20) schedule. Ethanol generalization gradients were comparable in the three groups, indicating few potency differences in the ethanol stimulus across training dose. However, the ability of TFMPP (0.1-1.7 mg/kg; IP) to substitute for ethanol was dependent on the training dose. TFMPP resulted in partial substitution in the 1.0 g/kg group, complete substitution for 1.5 g/kg group and no substitution in the 2.0 g/kg ethanol training group. The results indicate a serotonergic component to the discriminative stimulus effects of an intermediate dose of ethanol that is not prominent as the dose of ethanol is raised. These data add further support for the hypothesis that ethanol produces a mixed discriminative cue, the components of which are not uniformly amplified when the dose of ethanol is increased.

Animals↗

Chronic ethanol intoxication induces differential effects on GABAA and NMDA receptor function in the rat brain.

The effect of long-term treatment with ethanol was investigated on the function of gamma-aminobutyric acid A (GABAA) and N-methyl-d-aspartic acid (NMDA) receptors. Rats were rendered ethanol-dependent by repeated forced administration of a 20% ethanol solution (12 to 18 g/kg/day po) for 6 days and tested while still intoxicated or at different time intervals after withdrawal. t-[35S]Butylbicyclophosphorothionate (35S-TBPS) binding was increased by 30% in cortical homogenates of rats killed 1 to 3 hr after last ethanol administration, when compared with saline-treated animals. However, GABA-stimulated 36Cl- uptake and its enhancement by flunitrazepam was decreased in the ethanol-treated animals. 35S-TBPS binding and 36Cl- influx measured 9 to 24 hr following the last ethanol injection, when withdrawal signs were present, were unmodified with respect to saline-treated rats. Moreover, the effects of both isoniazid and FG 7142 on 35S-TBPS binding were unchanged in ethanol-dependent rats tested at 1 to 3 and 9 to 24 hr, compared with controls. In contrast, ethanol-withdrawn rats tested at 9 to 24 hr showed a dramatic enhancement in their sensitivity to the convulsant action of isoniazid (50 to 250 mg/kg, sc). The same animals were also more susceptible to the convulsant action of NMDA (0.5 to 5 micrograms/5 microliters/rat intracerebroventricularly) and kainic acid (12 mg/kg, ip), and this effect was paralleled by an enhancement (+25%) in the density of 3H-MK 801 recognition sites in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Withdrawal Delirium↗

Pharmacological analysis of the mixed discriminative stimulus effects of ethanol.

Ligands acting at separate receptor systems are independently recognizable as ethanol in drug discrimination procedures. These findings suggest that the internal stimulus effects of ethanol are composed of actions at more than one receptor system and that these mixed effects remain distinct and do not blend to form a single subjective state. Furthermore, the relative contributions of these receptor systems to the ethanol cue depend upon the ethanol training dose and are not uniformly amplified when the dose of ethanol is increased. The data gathered from these studies can be used to identify transmitter systems that may contribute to dose-specific behavioral effects of ethanol.

Animals↗

[Psychiatric emergency: between outer and inner world].

After a brief premise on social change factors of our contemporary society and on their impact on the affections and relationships of individuals, psychiatric emergency is considered as it relates to institutional response. "Maternal" and "paternal" roles of the hospital as it assists those who request help and some defensive modalities for decompensated patients are proposed. The article ends by hoping for a greater readiness to listen: this approach would favour the capacity of the mind to avoid defensive acting-out.

Acting Out↗

Discriminative stimulus effects of ethanol: effect of training dose on the substitution of N-methyl-D-aspartate antagonists.

The ethanol-like discriminative stimulus effects of N-methyl-D-aspartate (NMDA) antagonists that act at the NMDA recognition site [(D)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CPPene) and cis-4-phosphonomethyl-2-piperidine carboxylic acid] or within the NMDA associated cation channel [phencyclidine (PCP) and dizocilpine] were evaluated in rats trained to discriminate ethanol or PCP from vehicle in a two-lever discrimination procedure. Three groups of rats were trained to discriminate 1.0, 1.5 or 2.0 g/kg of ethanol from water and one group was trained to discriminate 1.5 mg/kg of PCP from saline. In the ethanol-trained groups, both PCP (1.0-5.6 mg/kg; i.p.) and dizocilpine (0.03-0.3 mg/kg; i.p.) completely substituted for ethanol in every rat tested, although the dizocilpine resulted in only partial substitution in rats trained to discriminate 1.0 g/kg of ethanol. As the training dose of ethanol increased, the potency of PCP and dizocilpine to substitute for ethanol increased. In contrast, CPPene (1-17 mg/kg; i.p.) and cis-4-phosphonomethyl-2-piperidine carboxylic acid (5.6-17 mg/kg; i.p.) resulted in partial substitution for ethanol, with lower amounts of ethanol-appropriate responding as the training dose of ethanol increased. These data indicate that uncompetitive antagonism of NMDA neurotransmission at sites within the cation channel produce discriminative stimulus effects that are similar to those of ethanol, particularly to higher ethanol doses. Neither ethanol (0.5-1.5 g/kg; i.p.) nor CPPene (5.6 and 10 mg/kg) completely substituted for the discriminative effects of PCP. The asymmetrical generalizations between ethanol and PCP are discussed in terms of the mixed discriminative effects of ethanol.

Animals↗

Cognitive and psychiatric evaluation of 40 patients with myotonic dystrophy.

We evaluated 40 patients suffering from a severe form a myotonic dystrophy (MD) with neuropsychological (WAIS-R, MMSE) and psychiatric tests (SADS, SRT) for the assessment of cognitive and psychiatric symptoms. We tested 20 normal volunteers as control group. Patients with MD scored significantly, lower on WAIS Full Scale (p less than 0.001), Verbal Scale (p less than 0.001), and Performance Scale (p less than 0.001) and on the MMSE (p less than 0.05) than the controls. 35% of patients met the Research Diagnostic Criteria for a psychiatric diagnosis; 17.5% of them had a depressive disorder. The scores on SADS subscales and on the SRT scale of depression were also significantly higher in patients than in controls. Our data confirm that mental impairment and psychiatric disorders are important clinical manifestations of CNS dysfunction in the severe form on MD.

Adult↗

Decreased performance in a delayed alternation task by rats genetically deficient in vasopressin.

Acquisition and retention of a delayed alternation task by rats genetically deficient in vasopressin (AVP) due to the homozygous occurrence of the Brattleboro diabetes insipidus (DI) gene (M520/DI) were compared to the response of rats that were heterozygous (M520/HZ) or normal (M520/N) with respect to the DI gene. No significant difference in the adaptation to the apparatus was observed between the groups. However, the rate at which the M520/DI rats acquired the alternation task was significantly slower than the acquisition rates of M520/HZ and M520/N rats. In addition, the maximum intertrial interval reached by the M520/DI rats was significantly shorter than the intertrial intervals reached by the M520/HZ and M520/N rats, indicating the ability to retain information was impaired in the M520/DI rats. These results are consistent with the hypothesis that AVP modulates the acquisition and retention of information for normal memory processes.

Animals↗

Increased expression of IgG Fc receptor type I on neutrophils and monocytes from HIV-infected subjects.

Interferon-gamma (IFN-gamma) induces de novo expression of IgG Fc receptor type I (FcRI) on neutrophils and significantly raises the level of these receptors on monocytes. Since increased concentrations of IFN-gamma have been observed in sera from patients with HIV infection, FcRI expression might also be increased on these subjects' phagocytes. FcRI expression was assessed by indirect immunofluorescence staining of phagocytes in whole blood from 40 healthy controls and 55 HIV+ subjects, 24 belonging to CDC class III and 31 to CDC class IV; 42 were intravenous drug abusers (IVDA) and 13 were homosexual men. Plasma levels of IFN-gamma were measured using a modified immunoradiometric assay. The mean linear fluorescence intensity, used as a relative measure of receptor expression, was significantly higher on unseparated neutrophils from HIV+ subjects in CDC classes III (P < 0.001) and IV (P < 0.0001) than from controls. Similar changes in FcRI expression were observed on monocytes from HIV+ subjects. While no differences were observed between IVDA and homosexual HIV+ patients, there was a significant association between FcRI expression and the patients' CDC stage, those in class IV having the highest FcRI levels. Plasma IFN-gamma concentrations were significantly higher in HIV+ patients than in controls and a positive correlation with the stages of HIV infection was again observed. FcRI expression was also increased on freshly purified neutrophils from five HIV+ patients in CDC class IV but did not increase further after 18 h incubation with IFN-gamma, a treatment that up-regulated FcRI expression on control neutrophils. These data suggest that: (i) FcRI evaluation may be a sensitive marker for the biological activity of IFN-gamma in vivo; (ii) phagocytes from HIV+ subjects are activated in vivo by IFN-gamma, expressing increased levels of FcRI; (iii) these IFN-gamma-activated cells may play a role in the pathogenesis of AIDS.

Adult↗

Membrane expression and function of complement receptors CR1 and CR3 on neutrophils from HIV-infected subjects: modulation by rTNF-alpha and rGM-CSF.

We evaluated membrane expression and function of complement receptors CR1 and CR3 on neutrophils from 27 HIV-positive (HIV+) subjects (14 in the CDC class III and 13 class IV) as well as their modulation in vitro by recombinant tumour necrosis factor-alpha (rTNF-alpha) and granulocyte-macrophage colony stimulating factor (rGM-CSF). While CR1 was expressed at similar levels on neutrophils from controls and HIV+ subjects, CR3 expression was significantly higher in CDC class IV subjects than in healthy controls. CR1 and CR3 expression was significantly increased after treatment of neutrophils with both cytokines, without differences between controls and HIV+ subjects. Similarly, the superoxide anion (O2-) production in response to C3-coated zymosan (C3zy) was significantly enhanced on neutrophils from CDC class IV subjects when compared with controls. rGM-CSF and rTNF-alpha treatment significantly enhanced the spontaneous as well as C3zy-stimulated O2- production by neutrophils from controls and CDC class III subjects, and induced an upward trend in the CDC class IV group. These results indicate that the neutrophils of HIV+ patients are preactivated in vivo but they also indicate that these cells may correctly respond to a subsequent particulate stimulus as well as to activating cytokines. Our findings suggest that desensitization or functional exhaustion of complement receptors are not implicated in the abnormalities observed on neutrophils from HIV+ patients.

Adult↗

Isradipine and other calcium channel antagonists attenuate ethanol consumption in ethanol-preferring rats.

The present work is concerned with studying of the ability of different calcium channel antagonists to modify voluntary ethanol ingestion by rats selectively bred for high ethanol preference. The compounds were given s.c. thrice daily for 5 days at doses that did not produce locomotor impairment. While nifedipine, darodipine, and verapamil (each at the dose of 20 mg/kg thrice daily) produced a modest reduction in ethanol intake, isradipine (at the dose of 1 mg/kg three times a day) reduced ethanol intake by over 70%. For all compounds, the reduction in ethanol intake was compensated by a proportional increase in water consumption and the inhibitory effect persisted throughout the 5 days of treatment. The data indicate that calcium channel antagonists exhibit quite different potency in reducing ethanol preference, however this action is a general property of this class of compounds.

Alcohol Drinking↗

Dose-dependent effects of aluminum on osteocalcin synthesis in osteoblast-like ROS 17/2 cells in culture.

This in vitro study evaluates the effect of aluminum (Al3+) on osteocalcin, a small protein that is produced by the osteoblast. After stimulation with various doses of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; 10(-11) to 10(-9) M], osteocalcin was consistently lower in the culture medium of ROS 17/2 osteoblastic cells conditioned with 5 microM Al(3+)-saturated transferrin (AlTR) than in apotransferrin (ApoTR)-treated controls. In a second experiment, cultures were conditioned with various doses of AlTR or ApoTR (1.6-8.0 microM) and stimulated with 10(-9) M 1,25(OH)2D3. High doses of AlTR (4.8-8.0 microM) resulted in lower medium and unchanged intracellular content of osteocalcin than treatment with equal amounts of ApoTR. However, in the same experiment, lower doses of AlTR or ApoTR (1.6 and 3.2 microM) yielded different results, i.e., increased medium and intracellular contents of osteocalcin in the Al(3+)-treated cells. Expression of osteocalcin mRNA was not altered in cultures conditioned with low (1.6 microM) or high (8.0 microM) concentrations of AlTR or ApoTR. Similarly, no effect of Al3+ was observed on total protein content, the rate of total protein synthesis, and the degradation of secreted osteocalcin in cultures conditioned with various doses of AlTR or ApoTR. These findings suggest that AlTR affects osteocalcin synthesis in a specific manner, without concomitant effects on the rate of total protein synthesis or on the rate of degradation of osteocalcin. This effect is dose dependent, i.e., low doses of AlTR stimulate and high doses suppress osteocalcin synthesis and/or secretion, and it appears to be posttranscriptional, since the expression of osteocalcin mRNA is not affected.

Aluminum↗

MDL 72222, a selective 5-HT3 receptor antagonist, suppresses voluntary ethanol consumption in alcohol-preferring rats.

The effect of the selective 5-HT3 receptor antagonist MDL 72222 on voluntary ethanol consumption was examined in Sardinian ethanol-preferring (SP) rats in a free choice (10% ethanol and water) experiment. SP rats consumed 8.1 +/- 1.1 g/kg ethanol daily. MDL 72222 treatment (3.0, 5.0 and 7.0 mg/kg i.p. 3 times daily for 6 days) inhibited ethanol consumption during the 6 days of treatment by 25%, 50% and 75%, respectively, without modifying total fluid intake. We suggest that 5-HT3 receptor activation plays a permissive role in alcohol preference.

Alcohol Drinking↗

The effect of cytokines on human neutrophil Fc receptor-mediated phagocytosis.

The recombinant (r) cytokines interferon-gamma (rIFN-gamma), granulocyte/macrophage-colony stimulating factor (rGM-CSF) and tumor necrosis factor-alpha (rTNF-alpha) all activate neutrophils. The aim of this work was to determine the effect of these cytokines on neutrophil Fc-receptor (FcR)-mediated phagocytosis and membrane expression of FcR, particularly FcRII and FcRIII. A short treatment (greater than or equal to 15 min) of neutrophils with rGM-CSF and rTNF-alpha at concentrations greater than or equal to 62.5 U/ml significantly increased their ability to bind and phagocytize IgG-coated erythrocytes (EA). Both cytokines also showed more enhancing activity when suboptimally sensitized EA were used for binding and ingestion assays. A similar treatment of neutrophils with rIFN-gamma at doses up to 500 U/ml was ineffective. The effect of rGM-CSF and rTNF-alpha was blocked by a monoclonal anti-GM-CSF antibody and by a polyclonal anti-TNF-alpha antibody respectively, thus establishing that the cytokines were responsible for the activity of the recombinant preparations. The cytokine-induced enhancement of FcR-mediated phagocytosis did not correlate with an enhancement of FcRII membrane expression on treated neutrophils; rGM-CSF significantly increased FcRIII expression, but rTNF-alpha and rIFN-gamma were both ineffective in this respect. Since different roles of FcRII and FcRIII have been reported on ligand binding and ingestion, we also studied the effect of rGM-CSF and rTNF-alpha on the functional properties of these FcR, using specific monoclonal antibodies (mAbs). In the blocking experiments the pretreatment of neutrophils with rGM-CSF and rTNF-alpha did not modify the blocking properties of either anti-FcRII or anti-FcRIII mAbs, suggesting that cytokine-pretreatment does not affect the individual contribution of each type of FcR to ligand binding and internalization. Our data point to a new activity for both rGM-CSF and rTNF-alpha in augmenting FcR-mediated phagocytosis on neutrophils, but the mechanism of this enhancement remains to be elucidated.

Cell Adhesion↗

Genetic sensitivity to effect of ethanol on dopaminergic system in alcohol preferring rats.

The effect of ethanol (etOH) on dopamine (DA) metabolism in the caudate nucleus (CN), olfactory tubercle (OT) and medial prefrontal cortex (MPFC) was compared in 2 selectively bred lines of rats, one etOH-preferring (sP) and the other -non preferring (sNP). EtOH (2 g/kg per os), administered 60 min before killing, caused a significant increase in concentrations of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and reduced DA levels in CN and OT in sNP rats. On the other hand in sP rats, etOH increased the content of DA metabolites in all the 3 areas analyzed. These changes induced by etOH in DA metabolism were significantly greater in sP than in sNP rats. The above data indicate that sP rats have a genetic high sensitivity to etOH effect on DA metabolism probably linked to etOH preference.

3,4-Dihydroxyphenylacetic Acid↗

MOv18 monoclonal antibody in diagnostic applications: capability to recognize the histotype of the original tumor.

Cells from 52 ascitic fluids and 28 abdominopelvic cavity washings, obtained from 46 ovarian cancer patients, 17 patients bearing malignancies of non ovarian sites and 17 patients with non-malignant ovarian diseases, were tested using 2 methods: traditional cytology and monoclonal antibody immunofluorescence. The immunologic test using the MOv18 MAb, raised against ovarian carcinoma, revealed immunoreactive cells in 83% of the 36 cytologically positive fluids and in one of the 8 negative fluids from ovarian carcinoma patients and in 18% of the 17 fluids from patients with non-malignant ovarian disease. Forty six cytologically positive ascitic fluids from malignant patients were analyzed in order to evaluate the ability of this MAb to identify the histotype of metastatic cells. Ninety-three percent (26/28) of the effusions from nonmucinous ovarian carcinomas contained MOv18-positive cells, whereas no reactive cells were found in cytologically malignant fluids from patients with ovarian tumors of other oncotypes or with carcinomas of non-ovarian origin. The MOv18 reagent, used as an adjuvant in cytological analysis, can help in the identification of the histotype of metastatic cells of unknown origin.

Adenocarcinoma↗