Showing papers by "University of Cagliari published in 1993"
TL;DR: In this article, the synthesis and biological activity of heterocyclic compounds synthesized by carbon suboxide was investigated and some 2-oxo (2H) 1-benzopyran-3-carboxamide derivatives were screened.
621 citations
TL;DR: This reversal suggests that the abrupt cessation of chronic ethanol administration plays a causal role in the reduction of mesolimbic dopaminergic activity seen in the ethanol-withdrawal syndrome, which may be relevant to the dysphoric state associated with ethanol withdrawal in humans.
Abstract: Activity of the mesolimbic dopaminergic system was investigated in rats withdrawn from chronic ethanol administration by single-cell extracellular recordings from dopaminergic neurons of the ventrotegmental area, coupled with antidromic identification from the nucleus accumbens, and by microdialysis-technique experiments in the nucleus accumbens. Spontaneous firing rates, spikes per burst, and absolute burst firing but not the number of spontaneously active neurons were found drastically reduced; whereas absolute and relative refractory periods increased in rats withdrawn from chronic ethanol treatment as compared with chronic saline-treated controls. Consistently, dopamine outflow in the nucleus accumbens and its acid metabolites were reduced after abruptly stopping chronic ethanol administration. All these changes, as well as ethanol-withdrawal behavioral signs, were reversed by ethanol administration. This reversal suggests that the abrupt cessation of chronic ethanol administration plays a causal role in the reduction of mesolimbic dopaminergic activity seen in the ethanol-withdrawal syndrome. Results indicate that during the ethanol-withdrawal syndrome the mesolimbic dopaminergic system is tonically reduced in activity, as indexed by electrophysiological and biochemical criteria. Considering the role of the mesolimbic dopaminergic system in the reinforcing properties of ethanol, the depressed activity of this system during the ethanol-withdrawal syndrome may be relevant to the dysphoric state associated with ethanol withdrawal in humans.
313 citations
TL;DR: Plasma and platelet levels of excitatory amino acids were measured in psychiatric out-patients and in comparison subjects, and the glutamate plasma levels were significantly higher in the patients with mood disorders than in the comparison group.
Abstract: Plasma and platelet levels of excitatory amino acids were measured in 38 psychiatric outpatients and in 1 9 comparison subjects; the patients had DSM-III-R diagnoses of organic mental disorders (N=3), mood disorders (N=1 5), schizophrenia (N=13), and anxiety disorders (N=7). The glutamate plasma levels were significantly higher in the patients with mood disorders than in the comparison group. (Am J Psychiatry 1993; 150:1731-1733)
249 citations
TL;DR: It is suggested that both the oral absorption and the elimination of GHB are capacity-limited processes in treatment of the alcohol and opiate withdrawal syndromes.
Abstract: Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg-1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.
219 citations
TL;DR: The study demonstrates that transvaginal ultrasonography has an efficiency of 88% in differentiating endometriomas from other ovarian masses with a specificity of 90%.
200 citations
01 May 1993
TL;DR: In this article, the distribution and biochemical composition of organic matter were analyzed in surface sediments (0-15 cm) of 22 continental and bathyal stations (110-2401 m; Ionian and Aegean Seas).
Abstract: The distribution and the biochemical composition of organic matter were analysed in surface sediments (0–15 cm) of 22 continental and bathyal stations (110–2401 m; Ionian and Aegean Seas). Variations of labile organic matter (LOM), total organic matter (TOM), bacterial density and biomass were related to the benthic bacterial populations and to the environmental conditions. TOM was significantly correlated with water depth, but not with LOM, which was mostly composed of carbohydrates (89.6) followed by proteins and lipids (5.4 and 5.0.%). LOM ranged between 1.5 adn 2.7 mg g −1 sediment dry weight, declining in concentration from the sediment surface of 15 cm depth. Bacterial counts ranged betweem 0.16 and 9.42 × 10 8 cells g t-1 sediment dry weight. Bacterial density and biomasses in surface sediments (0–1 cm) were significantly correlated with carbohydrates and DNA concentrations. Although the overlying waters are oligotrophic and low concentrations of TOM are present, the relatively high percentage of LOM and bacterial density suggest that organic matter in deep-sea sediments of the Eastern Mediterranean Sea is not totally depleted of nutritional value.
196 citations
TL;DR: In contrast, ethanol-withdrawn rats tested at 9 to 24 hr showed a dramatic enhancement in their sensitivity to the convulsant action of isoniazid, and this effect was paralleled by an enhancement in the density of 3H-MK 801 recognition sites in the hippocampus.
Abstract: 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)
182 citations
TL;DR: It is proposed that the T → C(8356) transition is responsible for the mitochondrial encephalomyopathy found in the family, and must be added to the expanding list of the pathogenetically relevant mutations of human mtDNA.
Abstract: Several members of a three-generation kindred from Sardinia were affected by a maternally inherited syndrome characterized by features of both myoclonus epilepsy with ragged-red fibers (MERRF) and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Clinically, symptoms such as myoclonus epilepsy, neural deafness and ataxia were variably associated with stroke-like episodes and/or migrainous attacks. Morphologically, numerous ME-LAS-associated SDH-stained vessels were observed in muscle biopsies, either alone or in combination with ragged-red fibers, the morphological hallmark of MERRF. Sequence analysis of the mtDNA tRNA genes revealed the presence of a single, heteroplasmic T → C transition at nt 8356, in the region of the tRNALys gene corrsponding to the T-Ψ-C stem. The T → C(8356) transition was exclusively found in the maternal lineage of our family, and the relative amount of the mutant mtDNA species in muscle was correlated with the severity of the clinical presentation. Therefore, we propose that the T → C(8356) transition is responsible for the mitochondrial encephalomyopathy found in our family, and must be added to the expanding list of the pathogenetically relevant mutations of human mtDNA.
148 citations
TL;DR: It is concluded that the preferential effect of amphetamine in the Acc is related to precise topographical boundaries and might be related to the existence of a sharp anatomical and functional heterogeneity within the Acc.
Abstract: Concentric dialysis probes were vertically implanted in rats in the nucleus accumbens (Acc) of one side and in the dorsal caudate-putamen (CPu) of the other side. On the day after the implant the output of dopamine was monitored and the changes elicited byd-amphetamine sulphate were compared in the two areas. Amphetamine preferentially stimulated dopamine release in the Acc in a wide range of doses (0.25, 0.5, 1.0, 2.0 mg/kg SC) when Acc probes were located in the medial aspect of the Acc. In contrast, no significant differences between the Acc and the dorsal CPu were obtained in response to amphetamine (0.5 mg/kg SC) when Acc probes were located about 0.7 mm lateral to the previous site. It is concluded that the preferential effect of amphetamine in the Acc is related to precise topographical boundaries. This in turn might be related to the existence of a sharp anatomical and functional heterogeneity within the Acc.
127 citations
TL;DR: Naltrindole, a specific delta-opioid antagonist, infused by reverse dialysis in the nucleus accumbens of freely moving rats completely prevented the increase in extracellular dopamine concentrations elicited by ethanol.
123 citations
TL;DR: The molecular characterization of HLA class II genes in 120 IDDM sporadic patients and 89 healthy subjects of Sardinian origin suggests that IDDM susceptibility cannot be completely explained by the model in which only DQ alpha 52 and DQ beta 57 residues are taken into account.
TL;DR: The present results suggest that nitric oxide in the PVN may be involved in the stress response and the differences observed in NOS mRNA between young and old rats could be related to an age-dependent different responsiveness to stressful stimuli.
Abstract: Nitric oxide synthesizing (NOS) enzyme has been localized in distinct neural populations, including the hypothalamic paraventricular nucleus (PVN) Using in situ hybridization, we have investigated possible changes in NOS mRNA in the PVN of young and old rats after 2 h of immobilization stress In old rats a 3-fold increase in NOS mRNA was observed in the PVN immediately after the stressor, whereas in young rats the increase reached significance when animals were killed 3 h after the end of the stress procedure The present results suggest that nitric oxide in the PVN may be involved in the stress response The differences observed in NOS mRNA between young and old rats could be related to an age-dependent different responsiveness to stressful stimuli
TL;DR: Gamma-hydroxybutyric acid (GHB) (25 mg/kg orally) was shown to suppress most of the withdrawal symptomatology in 14 heroin addicts and 13 methadone-maintained subjects as mentioned in this paper.
TL;DR: It is suggested that in right brain-damaged patients with neglect the position sense deficit has a nonsensory component, related to neglect, which may be affected by optokinetic stimulation.
TL;DR: The GC-MS method is simple, specific and accurate, and may be applied for analytical purposes related to pharmacokinetic studies and therapeutic drug monitoring.
01 Jan 1993
TL;DR: It is argued that drugs of abuse act on specific neurotransmitter pathways and by this mechanism elicit neurochemical changes that mimic some aspects of the overall pattern of the neurochemical effects of natural rewarding stimuli, which predicts that biochemical mechanisms important for the rewarding properties of drugs of Abuse are expected to play a role also in natural reward.
Abstract: In this paper it is argued that drugs of abuse act on specific neurotransmitter pathways and by this mechanism elicit neurochemical changes that mimic some aspects of the overall pattern of the neurochemical effects of natural rewarding stimuli. Thus, drugs of abuse are biochemically homologous to specific aspects of natural rewarding stimuli. The behavioral similarity between drugs of abuse and natural stimuli, including that of being rewarding, results from their common property of activating neurochemically specific pathways. Natural stimuli accomplish this result indirectly through their sensory properties and incentive learning while drugs stimulate by a direct central action the critical reward pathways. Many drugs of abuse mimic the incentive properties of natural stimuli and their ability to stimulate mesolimbic dopamine pathways (Fig. 1). Both natural rewards and drugs of abuse, including amphetamine, cocaine and other psychostimulants, preferentially stimulate dopamine transmission in the mesolimbic nucleus accumbens compared with the dorsal caudate, an area related to the extrapyramidal motor system. Although many drugs of abuse mimic the incentive aspect of natural reward, this is probably not an absolute prerequisite for conferring to a drug some abuse liability. It might be predicted that certain drugs might be abused as a result of their action at sites located beyond dopamine or by mimicking other aspects of naturally rewarding stimuli such as the 'functional' (or trophotropic). This might be the case with opiates (which also mimic the 'incentive' aspect) and of benzodiazepines, as a result of activation of the central opioid reward system and of the central gamma-aminobutyric acid (GABA)-benzodiazepine system respectively. The hypothesis appears to have heuristic value as it predicts that biochemical mechanisms important for the rewarding properties of drugs of abuse are expected to play a role also in natural reward. One test of this hypothesis is offered by the observation that the 5-hydroxytryptamine (5-HT) system, through 5-HT3 receptors, and the central opioid system, through delta-opioid receptors, can contribute to the mechanism of the dopamine-activating properties of certain drugs of abuse. On this basis it would be predicted that drugs acting on 5-HT3 and on delta-opioid receptors would interfere with or mimic certain aspects of natural rewarding stimuli.
TL;DR: The results indicated that, despite large geographical differences, POM was quite homogeneous, of phytoplankton origin and mostly detrital, and that a large amount of food was available to higher trophic levels.
Abstract: The biochemical composition and spatial distribution of particulate organic matter (POM) were studied in the Ross Sea (Antarctica) in summer 1989 to assess the quantitative role of organic carbon fractions in the cycling of organic matter in the water column. Large differences in chemical composition were observed between surface and deep layers. The results indicated that, despite large geographical differences, POM was quite homogeneous, of phytoplankton origin and mostly detrital. Different ratios were used to investigate the changes in biochemical composition of particulate organic matter in relation to the ice-melting: C∶N (organic carbon∶organic nitrogen ratio) and C-POM∶POC (sum of carbohydrate, protein and lipid carbon∶total organic carbon ratio) were used to analyse the percentage of refractory organic material. PPRT∶PCHO (protein∶carbohydrate ratio) were used to establish POM “age” and RNA∶DNA ratios as a relative measure of particulate activity; POC∶Chl a and N-PPRT∶Chl a ratios were used to estimate the autotrophic contribution to the suspended particulate organic matter. Despite its low caloric value (5.3 Kcal g POM−1), an high caloric content in the photic layer (1.6 Kcal m−3 of POM and 2.5 Kcal m−3 of POC) was found thus indicating that a large amount of food was available to higher trophic levels.
TL;DR: The present results suggest that ethanol suppresses glutamate release through an inhibition of NMDA glutamate receptors in the rat striatum.
TL;DR: The results suggest that a fall in mesolimbic dopamine output may be associated with depressive states and indicate that changes in the functional status of the dopamine system contribute to the mechanism of action of imipramine.
TL;DR: The results show that cocaine and d-amphetamine, by increasing dopaminergic transmission, enhance the extracellular concentrations of acetylcholine in both brain areas, and suggest that endogenous dopamine, by facilitating the release ofacetyl choline in the hippocampus, may participate in the regulation of hippocampal cognitive processes.
TL;DR: Results show that activation of dopaminergic transmission either at D1 and/or at D2 receptors enhances ACh output in the hippocampus.
TL;DR: It is reported that two cases of this type of benign tumor with chromosome rearrangements in 12q14-15 are reported, allowing identification of a second cytogenetic subgroup in endometrial polyps.
TL;DR: In acutely infected MT-4 cells, compounds 3e, 3o, 3q and 3r showed an anti-HIV-1 activity as potent and/or selective as HEPT and ddl.
Abstract: A series of novel 3,4-dihydro-6-benzyl-4-oxopyrimidines substituted at both the C-5 and the C-2 positions were synthesized as potential anti-HIV agents. Preparation of the title compounds was achieved by condensation of O-methylisourea with methyl 2-alkyl-4-phenylacetylacetate and subsequent displacement of the methoxy group by reaction with a series of linear, ramified and cyclic alkoxy groups containing from three to six carbon units. Methyl 2-alkyl-4-phenylacetylacetates were prepared by alkylation of methyl 4-phenylacetylacetate, which was obtained starting from Meldrum's acid and phenacetyl chloride. Acid hydrolysis of 3,4-dihydro-6-benzyl-2-methoxy-4-oxopyrimidines furnished the corresponding 1,2,3,4-tetrahydro-6-benzyl-2,4-dioxopyrimidines. In acutely infected MT-4 cells, compounds 3e, 3o, 3q and 3r showed an anti-HIV-1 activity as potent and/or selective as HEPT and ddl. Unlike HEPT, the replacement of a methyl for an hydrogen atom at position C-5 of 3,4-dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines ...
TL;DR: The results suggest that central nitric oxide is involved in the expression of penile erection and yawning induced by apomorphine and oxytocin.
Journal Article•
TL;DR: H. pylori positivity (antibody titer above or equal to 10 micrograms/ml), 45% overall, increased with age and was inversely associated with social class but showed little geographical variation or association with dietary variables and blood nutrients.
Abstract: In a survey of 930 adults aged 35-74 years randomly sampled from the general population of four areas of Italy, two at low and two at high risk for gastric cancer, plasma levels of Helicobacter pylori IgG antibodies were assayed in order to investigate associations with the geographical distribution of gastric cancer and other dietary and life-style factors, as assessed by personal interview. H. pylori positivity (antibody titer above or equal to 10 micrograms/ml), 45% overall, increased with age and was inversely associated with social class but showed little geographical variation or association with dietary variables and blood nutrients. H. pylori positivity was also associated with increased blood levels of pepsinogens, particularly pepsinogen II. The authors discuss these findings in relation to those from a previous case-control study of gastric cancer in the same areas.
TL;DR: Evidence for a saturable, Mg2+/ATP‐ and temperature‐dependent, tetrabenazine‐, dopamine‐, and amphetamine‐sensitive uptake of 1‐methyl‐4‐phenylpyridinium ion (MPP+) in synaptic vesicles from mouse striatum is provided and a role in MPP+ neurotoxicity is suggested for this region‐specific, vesicular storage of the toxin.
Abstract: 1. In the present study we provide evidence for a saturable, Mg2+/ATP- and temperature-dependent, tetrabenazine-, dopamine-, and amphetamine-sensitive uptake of 1-methyl-4-phenylpyridinium ion (MPP+) in synaptic vesicles from mouse striatum. 2. Similarity in the properties of the vesicular uptake suggests that in the striatum dopamine and MPP+ share the vesicular carrier. 3. The presence of MPP+ vesicular uptake in dopamine-rich regions such as striatum, olfactory, tubercles and hypothalamus, as well as its absence in cerebellum, cortex and pons-medulla, suggest that monoamine vesicular carriers differ between highly and poorly dopamine-innervated regions. 4. The restriction of active MPP+ uptake to the dopaminergic regions, which reflects the previously shown distribution of [3H]-MPP+ binding sites in mouse brain membranes, indicates MPP+ as a marker of the vesicular carrier for dopamine in dopaminergic neurones. 5. A role in MPP+ neurotoxicity is suggested for this region-specific, vesicular storage of the toxin.
TL;DR: The pattern of antibody response with first-generation assay was characterized by clearance of anti-HCV with time, in most of the patients who recovered, and by persistence ofAnti- HCV in the majority of those who progressed to chronicity, whereas second-generation ELISA usually showed persistence of anti -HCV over time, regardless to the outcome of the disease.
Abstract: During an 8-year prospective study of post-transfusion hepatitis conducted at the Thalassemic Center of Cagliari (Italy), including 135 newly diagnosed thalassemic children on long-term transfusion maintenance, 83 children (61%) developed non-A, non-B hepatitis (NANBH). Resolution of NANBH was observed in 17 (20%) cases, and chronicity in 57 (69%), whereas the remaining 9 (11%) experienced one or two additional bouts of acute NANBH. Of the 83 children with NANBH, 75 (90%) showed anti-hepatitis C virus (HCV) seroconversion when tested by second-generation enzyme-linked immunosorbent assay (ELISA), whereas first-generation ELISA showed anti-HCV in only 59 (71%) cases (p = 0.003). Moreover, the newly developed assay allowed an earlier detection of anti-HCV response in most of the patients who seroconverted by both assays, reducing significantly the mean onset-seroconversion interval (5 +/- 9.4 weeks vs. 14.5 +/- 20.8 weeks, p < 0.05). It was significantly more sensitive for the identification of HCV infection, not only in resolving NANBH, but also in NANBH progressing to chronicity (79 vs. 35%, respectively, p = 0.008; and 93 vs. 79%, p = 0.028). The pattern of antibody response with first-generation assay was characterized by clearance of anti-HCV with time, in most of the patients who recovered, and by persistence of anti-HCV in the majority of those who progressed to chronicity, whereas second-generation ELISA usually showed persistence of anti-HCV over time, regardless to the outcome of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: It is suggested that depending on the nature of the proliferative stimulus, an increased expression of c‐fos, c‐jun and c‐myc may not be necessary for in vivo induction of liver cell proliferation.
Journal Article•
TL;DR: Different prophylactic strategies for long-term treatment of major depressive disorder are suggested in relation to factors like severity of symptoms, frequency of episodes, compliance, and susceptibility to side effects.
Abstract: Present strategies for long-term treatment of major depressive disorder stem from the following three observations: the high frequency of recurrent depression, the length of a depressive episode, and the ability of antidepressants to prevent recurrences. Two different phases of long-term antidepressant treatment are now considered: continuation and a «true» maintenance or prophylactic phase. Moreover, it seems important to discriminate between relapse (from a previous episode) and recurrence (a new episode). However, there are some unresolved questions, such as (1) the duration of antidepressant treatment, (2) the type and posology of antidepressants to be used, and (3) some methodological aspects, such as the choice of comparators, definition of response, and combination with other therapies
TL;DR: The distribution pattern of rat liver parenchymal cells of different ploidy classes was investigated in Wistar rats following cell proliferation induced by surgical partial hepatectomy or primary mitogens, and it appears that polyploid cells are not preferentially eliminated.
Abstract: The distribution pattern of rat liver parenchymal cells of different ploidy classes was investigated in Wistar rats following cell proliferation induced by surgical partial hepatectomy (compensatory regeneration) or primary mitogens (direct hyperplasia). Animals were killed at 1, 2, 3, 4 and 15 days after the proliferative stimulus, and ploidy and nuclearity were measured using a computer-assisted imaging system in hepatocytes isolated by collagenase perfusion. Analysis of hepatocytes from animals undergoing regeneration after partial hepatectomy revealed a large increase in tetraploid and octoploid mononucleate cells. The most striking feature was the almost complete disappearance of binucleate cells (from 20% to < 1%) at 3 days after partial hepatectomy. On the contrary, when hepatocytes were analyzed after treatment with the mitogen lead nitrate, a high number of binucleate cells (40%) was observed. The increase that was maximal at 3 days after treatment occurred mainly in 4 x 2c and in 8 x 2c compartments. This resulted in an overall increase in the ratio of binucleate/mononucleate cells as well as in the ratio (8c + 16c):(2c + 4c). The cytological changes induced by lead nitrate were not reversible 2 weeks after treatment. Because a massive elimination of excess liver cells occurred by apoptosis during this time period, it appears that polyploid cells are not preferentially eliminated. The hepatic content of DNA at the end of the regression phase was similar to control values. However, because of the higher ploidy state, the number of cells present in the liver 2 weeks after treatment appears to be lower than that of controls (approximately -16%). When liver growth was induced by a single treatment with another mitogen, the peroxisome proliferator nafenopin, a slight increase in the ploidy state of the liver was observed; because of the shift towards higher ploidy classes (8c), the increase in DNA content observed 3 days after a single treatment with nafenopin (+21%) appears to be almost entirely justified by polyploidy rather than by a hyperplastic event.