Showing papers by "University of Cagliari published in 1988"

Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.

Abstract: The effect of various drugs on the extracellular concentration of dopamine in two terminal dopaminergic areas, the nucleus accumbens septi (a limbic area) and the dorsal caudate nucleus (a subcortical motor area), was studied in freely moving rats by using brain dialysis. Drugs abused by humans (e.g., opiates, ethanol, nicotine, amphetamine, and cocaine) increased extracellular dopamine concentrations in both areas, but especially in the accumbens, and elicited hypermotility at low doses. On the other hand, drugs with aversive properties (e.g., agonists of kappa opioid receptors, U-50,488, tifluadom, and bremazocine) reduced dopamine release in the accumbens and in the caudate and elicited hypomotility. Haloperidol, a neuroleptic drug, increased extracellular dopamine concentrations, but this effect was not preferential for the accumbens and was associated with hypomotility and sedation. Drugs not abused by humans [e.g., imipramine (an antidepressant), atropine (an antimuscarinic drug), and diphenhydramine (an antihistamine)] failed to modify synaptic dopamine concentrations. These results provide biochemical evidence for the hypothesis that stimulation of dopamine transmission in the limbic system might be a fundamental property of drugs that are abused.

Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats.

Abstract: We studied the effect of opiates acting preferentially on mu receptors, like morphine, methadone and fentanyl (mu agonists) and on kappa receptors, like U50,488, bremazocine and tifluadom (kappa agonists) on the release of dopamine (DA) and of its metabolites, dihydroxyphenylacetic acid and homovanillic acid, from the nucleus accumbens and from the dorsal caudate of freely moving rats using brain dialysis coupled to high-performance liquid chromatography with electrochemical detection. Spontaneous behavior was videotaped and analyzed by estimating the percentage of time spent by the animals in performing certain specific behavioral items. Mu agonists stimulated DA-release and metabolism in the accumbens at lower doses than in the caudate. Maximal stimulation of DA release did not exceed 100% except after high doses of methadone (10 mg/kg) which stimulated DA release in the accumbens by more than 300%, possibly as a result of hypoxia. Stimulation of DA release was associated to stimulation of behavior at low doses and to a biphasic inhibitory-stimulatory syndrome after higher doses of the opiates. Pretreatment with low doses of naloxone (0.1 mg/kg s.c.) or with the irreversible mu antagonist beta-funaltrexamine (10 nmol i.c.v.) increased the ED50 for the stimulation of DA release by the three opiates. In contrast with mu agonists, agonists of kappa receptors like U50,488, bremazocine and tifluadom decreased DA release in the accumbens and in the caudate and reduced motor activity. These effects were antagonized only by rather high doses of naloxone (2.5 mg/kg s.c.) and were not affected by pretreatment with beta-funaltrexamine (10 nmol i.c.v.).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological profile of dopamine receptor agonists as studied by brain dialysis in behaving rats.

Abstract: Using the technique of brain dialysis in freely moving rats we have investigated the effect of various dopamine (DA) receptor agonists on the release and metabolism of DA in two terminal dopaminergic areas, the nucleus accumbens and the dorsal caudate. Low doses of various DA receptor agonists such as apomorphine (12-100 micrograms/kg s.c.), LY 171555 (5-50 micrograms/kg s.c.), pergolide (5-25 micrograms/kg s.c.), (+)-3PPP (0.5-2.5 mg/kg s.c.) and BHT 920 (10-250 micrograms/kg s.c.) reduce DA release and elicit hypomotility. The potency of the drugs and their effectiveness is similar in the two areas. Inhibition of DA release appears related to the ability of the various agonists to stimulate D-2 rather than D-1 receptors. Thus, the reportedly selective D-1 agonist, SKF 38393, was inactive on DA release and metabolism even at doses fully active in eliciting D-1-mediated effects (grooming); on the other hand apomorphine, a D-1/D-2 agonist, and pergolide, a D-2 agonist with rather weak D-1 activity, reduced DA release in a manner which was related to their agonist activity at D-2 receptors; finally LY 171555, (+)-3PPP and BHT 920, which selectively stimulate D-2 receptors, were fully active at reducing DA release in vivo. Apomorphine, pergolide, LY 171555 and (+)-3PPP given at higher doses elicited behavioral stimulation. In contrast, BHT 920 failed to do so. In further contrast (-)-3PPP (0.1-10 mg/kg s.c.), which failed to reduce DA release at low doses, actually stimulated it at high doses (10 mg/kg s.c.) and elicited hypomotility, thus resembling DA receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Sardinian multiple sclerosis is associated with HLA‐DR4 A serologic and molecular analysis

Abstract: HLA haplotypes in 45 unrelated Sardinian multiple sclerosis patients and in six multiplex families were defined, using both serologic and restriction fragment length polymorphism (RFLP) analysis. In unrelated MS patients, we found an association with HLA-DR4 (p less than 0.01, relative risk = 2.5) and DQw3 (p less than 0.04, relative risk = 2.2). Using a beta-DR cDNA probe, we observed no variation of the DR4 RFLP profile in sporadic or related MS patients compared with DR4-specific pattern in controls. Using a beta-DQ cDNA probe, we identified two DQw3 patterns (DQw3.1 and DQw3.2) with similar frequency in patients and in controls. No specific RFLPs were observed in association with different disease courses. The frequency of haplotype sharing in affected members of multiplex families was not different from that expected by chance. This study shows that Sardinian MS patients carry predominantly the HLA-DR4 allele, in contrast to the DR2 prevalence reported in Caucasian populations. The lack of association with HLA haplotypes in affected members of multiplex families may indicate that genetic factors outside the HLA system play a substantial role in families with MS.

Order of the deconfining phase transition in pure-gauge QCD.

Abstract: We study the behavior of the string tension in the SU(3) lattice pure-gauge theory close to the deconfining critical point. We find very large correlation lengths, increasing with the lattice size. This result is strongly suggestive of a second-order phase transition, and excludes the presence of a strong first-order transition.

Foot‐Shock Stress and Anxiogenic β‐Carbolines Increase t‐[35S]Butylbicyclophosphorothionate Binding in the Rat Cerebral Cortex, an Effect Opposite to Anxiolytics and γ‐Aminobutyric Acid Mimetics

Abstract: The effect of foot-shock stress on t-[35S]-butylbicyclophosphorothionate ([35S]TBPS) binding to fresh unwashed membrane preparations from rat cerebral cortex was studied and was compared to those of GABAA receptor agonists and antagonists and to positive and negative modulators of the GABAergic transmission. [35S]TBPS binding was increased in the cerebral cortex of rats exposed to foot shock compared to that of nonstressed rats. Scatchard analysis revealed that the effect of foot shock was due to an increase in the total number of [35S]TBPS binding sites. In contrast, the in vitro addition of muscimol or GABA induced a dose-dependent inhibition of [35S]TBPS binding, an effect abolished by the concomitant addition of the GABA receptor antagonist, bicuculline, which, per se, enhanced [35S]TBPS binding by 73%. Thus, bicuculline, similar to stress, increased [35S]TBPS binding in the same membrane preparation. In contrast to stress, the anxiolytic and positive modulators of the GABAergic transmission (ZK 93423, ZK 91296, and di-azepam) inhibited the specific binding of [35S]TBPS in a concentration-dependent manner. The greatest inhibitory effect was produced by ZK 93423 at 30 μM (31% of control), followed by diazepam (54% of control) and by the partial agonist ZK 91296 (61 % of control). Scatchard plot analysis indicated that the inhibition induced by ZK 93423 and diazepam was due to a decrease in the density of [35S]TBPS recognition sites. On the other hand, the anxiogenic β-carbolines DMCM and FG 7142 mimicked the effect of stress. Thus, at a 10 μf concentration, DMCM and FG 7142 increased [35S]TBPS binding by 22% and 26%, respectively. The inhibitory effect of ZK 93423, ZK 91296, and diazepam and the stimulatory effect of FG 7142 and DMCM were blocked by the benzo-diazepine receptor antagonists Ro 15–1788 and ZK 93426. The demonstration that stress, similar to the GABA receptor antagonist bicuculline and to anxiogenic β-carbolines and opposite to GABA agonists, anxiolytic β-carbolines, and benzodiazepines, increases [35S]TBPS binding in the rat cerebral cortex, suggests that some emotional state related to stress and anxiety may result from a diminished GABAergic transmission at the level of the GABAA/benzodiazepine receptor/chloride ionophore complex.

Isometry groups of Lorentz manifolds

Abstract: Soit V une variete de Lorentz a n dimensions. Si (V,g) est compacte, analytique reelle, simplement convexe, alors le groupe d'isometrie Is (V,g) est compact

Yawning and penile erection: central dopamine-oxytocin-adrenocorticotropin connection.

Abstract: Repeated episodes of yawning and penile erection can be induced in rats and other experimental animals by the systemic administration of low doses of dopamine (DA) agonists, such as apomorphine (see ref. 1 for review), by the central administration of adrenocorticotropin (ACTH), a-melanocyte-stimulating hormone (a-MSH) and related peptides (see ref. 2 for review), and by the intracerebroventricular (i.c.v.) injection of o~ytoc in .~ While the importance of penile erection in reproduction does not need to be further stressed, it is pertinent to recall that yawning, alone or associated with stretching, is considered to be an ancestral vestige surviving throughout evolution, that subserves the purpose of arousal. In particular, the role of yawning could be that of increasing attention when sleep is imminent due to fatigue or boredom but cannot be engaged in, as in face of a danger or social circumstances (for a review on the physiological significance of yawning, see ref. 4). The capability of the above unrelated substances to induce such similar symptomatology raises the possibility that a neuronal link exists among DA, oxytocin, and ACTH in the central nervous system. The results of the experiments presented below, which were performed with the aim of demonstrating the existence of such a link and to clarify the neural mechanisms underlying the expression of yawning and penile erection as well, provide evidence for the first time that DA, oxytocin, and ACTH act in the hypothalamus in a sequence to induce these behavioral responses.

Radioactive iodine thyroid uptake in patients with amiodarone-iodine-induced thyroid dysfunction

Abstract: Amiodarone, an iodine-rich drug, represents at the present, at least in Europe, one of the most common sources of iodine-induced thyroid dysfunction. The drug may induce both hypothyroidism and thyrotoxicosis. In spite of the large iodine intake occurring during amiodarone therapy, 131I thyroid uptake is detectable in patients with amiodarone-iodine-induced hypothyroidism, irrespective of the presence or absence of underlying thyroid disease. In contrast, in patients with amiodarone-iodine-induced thyrotoxicosis, 131I thyroid uptake is normal or even elevated in those with co-existent underlying thyroid disorders, whereas it is very low in those with an apparently normal thyroid gland. Perchlorate discharge test was performed in 8 patients with hypothyroidism and in 5 patients with hyperthyroidism induced by amiodarone: a positive test was found in all hypothyroid patients and a negative test in all hyperthyroid patients.

Acetylcholine and Dopamine Promote the Production of Platelet Activating Factor in Immature Cells of Chick Embryonic Retina

Abstract: We have previously shown that platelet-activating factor (PAF), a naturally occurring lipid mediator of cell-to-cell communication, was produced by 3-day-old chick retina stimulated with acetylcholine (ACh) and dopamine (DA), but not with other neurotransmitters. ACh and DA stimulated PAF synthesis via a dithiothreitol (DTT)-insensitive cholinephosphotransferase, without affecting the acetyltransferase pathway, which was stimulated only by the calcium ionophore A23187. Therefore, we attempted to study the effects of neurotransmitters on PAF production and on the activities of the DTT-insensitive cholinephosphotransferase and acetyltransferase in the developing chick embryo retina up to hatching. Our results show that PAF was produced already at 8 days of development, when retinal cells are still rather immature and ganglion and Mueller cells are the only differentiated cells. The stimulation of PAF production occurred with ACh and not with other neurotransmitters. In older stages, DA also stimulated PAF production, as already described in the chick after hatching. DTT-insensitive cholinephosphotransferase and acetyltransferase activities were present in 8-day-old embryos, the earliest stage analyzed. Both enzymatic activities increased with age; DTT-insensitive cholinephosphotransferase increased rapidly from day 12 up to day 18, whereas acetyltransferase activity increased linearly up to the time of hatching. To promote PAF production, ACh and DA activate DTT-insensitive cholinephosphotransferase, but not acetyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

Localized epileptiform activity induced by murine CRF in rats.

Abstract: Summary: Murine corticotropin releasing factor (rCRF), injected intracerebroventricularly into rats at a dose of 10 |Ag produced increased motor activity, grooming, and recurrent episodes of epileptic activity localized in the hippocampal leads. Such activity persisted for ˜5 h and was characterized by recurrent trains of biphasic spikes never associated with behavioral signs of epilepsy. The intraperitoneal administration of carbamazepine (15 and 30 mg/kg) reduced the epileptic activity for ˜90 and 120 min, respectively, whereas that of naloxone (8 mg/kg) was ineffective. The results suggest that rCRF-induced spiking activity might be a model of temporal lobe epilepsy.

β-thalassemia mutations in the Portuguese population

Abstract: In this study we have carried out haplotype analysis on the β-globin gene cluster and characterized the β-thalassemia mutation by oligonucleotide hybridization in 14 patients with thalassemia major and 5 with sickle cell/β-thalassemia originating from southern Portugal. We found that three mutations, namely the β°-39, β° IVS-1 nt 1 and β+ IVS-1 nt 110 are prevalent accounting for 53%, 32% and 10% of the β-thalassemia chromosomes respectively. In general each mutation was associated with a specific chromosomal haplotype; the β° mutation, however, was linked to three different haplotypes. These results indicate that three oligo-probes complementary to the most common mutations allow prenatal diagnosis by oligonucleotide analysis in 96% of the couples at risk of having offspring with thalassemia major in southern Portugal.

NADH oxidase from the extreme thermophile Thermus aquaticus YT-1. Purification and characterisation.

Abstract: A protein with NADH oxidase activity from the extreme thermophile Thermus aquaticus YT-1 was purified and characterised. The enzyme was found to have a relative molecular mass of 110000 and be composed of two subunits of identical size. FAD was found to be present at a concentration of 0.7 mol/mol dimer and was required for activity. During the oxidation of NADH, oxygen uptake takes place with the production of hydrogen peroxide. The enzyme had, with the exception of a higher glutamic acid and tryptophan content, a similar amino acid composition as the NADH oxidase isolated from the mesophile Bacillus megaterium. Purified NADH oxidase was found to have a Km, of 39 μM for β-NADH and a VmaX of 4.68 μmol NADH mg-−1 min−1 and was still active at 95°C. Enzymatic activity was found to be independent of pH between 5.0 and 10.5.

Intraocular pressure changes in secondary positions of gaze in normal subjects and in restrictive ocular motility disorders.

Abstract: One hundred normal Caucasian eyes and 29 eyes with restrictive disorders of ocular motility were studied in order to delineate intraocular pressure changes in secondary positions of gaze. Applanation tonometry was performed in the primary position and at an angle of 22°. In patients with restrictive syndromes the changes of intraocular pressure in the secondary positions of gaze were significantly higher (p < 0.0001) than in normal subjects. The range of variation in normal subjects was 0, +3 mmHg for supraduction and −3, +1 mmHg for abduction. Patients with restrictive syndromes showed changes between +1 and +15 mmHg for supraduction and between +3 and +10 mmHg for abduction. Results obtained in the two groups showed the existence of false negatives. This test is thus a practical and useful diagnostic tool, but its results must be evaluated cautiously.

Fe-Co-B amorphous alloy powder by chemical reduction

Abstract: Fine boride powders, prepared by reactions between sodium or potassium borohydride and aqueous (or alcoholic) solutions of transition metal salts have long been known to be good catalysts for hydrogenation reactions. New interest around them has recently grown, because they were found to exhibit amorphous structure. Classical chemical reactions may thus offer a simple route to prepare amorphous metal powders, paralleling more sophisticated methods so far used to reach the same goal. To explore the potential of these reactions, we considered the system Fe-Co-B with the aim of examining the characteristics of the product obtained in the easiest way and without any particular precautions. The structure of the amorphous alloy appears to be different from that of materials with a similar Me/B ratio prepared via melt spinning.

Effect of pH on growth of mixed cultures in batch reactor.

Abstract: This work has studied the effect of pH on specific growth rate mu, yield factor Y, and specific substrate consumption rate U for two mixed microbial populations (sludge A and B) in a batch reactor with a limiting substrate (phenol). The mathematical analysis of mu and U as a function of pH has been applied not only to the results of the present work but also to other published data. On the basis of the results obtained, the following remarks can be made: (a) The effect of pH on bacterial activity differed for the two sludges; (b) variations in pH of one unit more or less than optimum pH can give rise to appreciable variations in mu and U; and (c) with regard to the mixed populations used in this study, the mu or U and pH data for the range investigated can be suitably described by a parabolic relation.

Ultrastructural observations on human sublingual gland

Abstract: That part of the human sublingual gland that corresponds in morphology to the conventional description of this organ presented in most histology texts (probably the major sublingual gland, in contradistinction to the aggregated small glands that compose the minor sublingual glands) was studied by electron microscopy. The gland is mixed, with slightly more mucous elements than seromucous ones. The mucous cells are arranged in tubules that usually are capped by seromucous demilunes. Seromucous cells also form occasional acini or may be scattered in the walls of the mucous tubules. The appearance of the mucous cells varies with the stage of the secretory cycle that they may be in. Their secretory droplets increase in number and progressively compress cytoplasmic organelles. Filamentous bodies also may be present. Based on secretory-granule substructure, four different kinds of seromucous cells can be recognized; these may be a morphological expression of asynchronous synthesis of different secretory proteins. The duct system is an abbreviated one compared to the other major salivary glands. The first duct segments, into which the mucous tubules drain, are similar to intercalated ducts. Larger ducts contain mitochondria-rich cells but lack the basal striations that characterize striated ducts. The paucity of typical striated ducts may be correlated with the elaboration of sodium-rich saliva by the human sublingual gland.

Symbionts in the oocytes of Blattella germanica (L.) (Dictyoptera : Blattellidae): Their mode of transmission

Abstract: In Blattodea, the transmission of symbionts from one generation to the next is of transovarial type. The symbionts in Blattella germanica (L.) (Dictyoptera : Blattellidae) reach the ovary inside bacteriocytes in the 5-day-old nymphal instar, and are located among the ovarioles. Between the 11th and 17th day, the symbionts leave the bacteriocytes, cross the ovariole sheath, the tunica propria, and the follicular epithelium, and reach the space between the latter and the oocyte. In 17-day-old nymphs, the symbionts are in contact with the microvilli of the oocyte, remaining in this position until the end of the vitellogenic phase, when the microvillar border is progressively reduced. At this stage, the symbionts are actively phagocytosed by the oocyte before chorion formation.

Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment.

Abstract: Plasma concentration of fibrinogen and Bβ 15–42, a specific product of fibrinogen metabolism induced by plasmin, were measured in a group of patients with untreated hyperthyroidism and in controls. Significantly increased plasma levels of both parameters were observed in hyperthyroid patients. The restoration of euthyroidism either by antithyroid drug or by radioiodine caused a significant decrease of fibrinogen and Bβ15–42. These data indicate that hyperthyroidism is another clinical condition associated with increased concentration of fibrinogen and Bβ 15–42.