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Biomedical subjects

W Balduini

Publications and source records attributed to W Balduini.

46 records · Page 3Linked to original sources

Inhibition of nucleic acids and protein synthesis by deazaadenosine derivatives: a study on structure-activity relationships.

The effect of four deaza-analogues of adenosine on the synthesis of nucleic acids and proteins was investigated in monkey kidney cell line Vero. Cells in exponential growth phase were exposed for two hours to 1, 3 or 10 microM concentrations of 1-deazaadenosine (c1Ado), 3-deazaadenosine (c3Ado), 7-deazaadenosine (c7Ado) or 1,3-dideazaadenosine (c1,3Ado) in a serum free medium; the rate of macromolecules synthesis was estimated after one hour pulse treatment with radiolabelled precursors. At the concentrations used, c1Ado and c3Ado produced no or very little change in the rate of macromolecules synthesis: c1Ado slightly increased RNA synthesis whereas c3Ado was a weak inhibitor of DNA synthesis. Conversely, c7Ado was a potent inhibitor of macromolecules synthesis. Two hours of drug exposure at a concentration of 10 microM, resulted in a 40-50% inhibition in DNA, RNA and protein synthesis rates. c1,3Ado did not significantly affect RNA or protein metabolism but produced a dramatic increase in DNA synthesis. No DNA breaks could be detected in cells exposed to the agents tested in this study.

Animals↗

Brain and blood levels of bismuth after oral or parenteral administration of tripotassium-dicitrato bismuthate to rats.

Bismuth levels in blood and brain of rats have been measured following acute or subchronic administration of tri-potassium-dicitrato bismuthate (TDB) by intraperitoneal injection or by gavage. After parenteral administration, the presence of bismuth in blood was associated with appreciable bismuth concentrations in brain of treated animals (approximately equal to 10-30% of blood levels). In contrast, following oral treatment, no bismuth was detected in brain of animals, even at doses of TDB able to produce blood bismuth concentrations comparable with those obtained after intraperitoneal administration. The formation of different bismuth species in blood of treated animals depending upon the route of administration of TDB is suggested.

Administration, Oral↗

Long-lasting tolerance to stimulatory effects of perinatal caffeine treatment.

Pregnant rats were treated with caffeine in their drinking water at doses of 136.3 mg/kg/day during gestation and 222.2 mg/kg/day during lactation. The resulting offspring at 60 days of age (40 days after drug withdrawal) were tested in an activity monitor cage. Spontaneous locomotor activity and that induced by caffeine (10, 30, 60 mg/kg/day) were observed. Treated rats showed apparent tolerance to caffeine-induced motility. Therefore perinatal caffeine treatment seems to induce long-lasting tolerance. This finding contrasts with those previously reported for chronic caffeine treatment in adult rats, where tolerance disappears after only 2-3 weeks following drug withdrawal.

Animals↗

Loss of intrinsic striatal neurons after methylazoxymethanol acetate treatment in pregnant rats.

Treatment of pregnant rats with methylazoxymethanol (MAM) induces a marked microencephaly in the offspring. The striatum is one of the brain areas affected by treatment. We show that in striatum there is a 30% loss of dopamine (DA)-dependent adenylate-cyclase activity: this indicates that cells bearing type 1 DA receptors are affected by MAM treatment. Moreover, since kainic acid retains its neurotoxic activity, corticostriatal fibers do not seem to be affected, despite the dramatic reduction of cortex size.

Adenylyl Cyclases↗

Methylazoxymethanol microencephaly in rats: neurochemical characterization and behavioral studies with the nootropic oxiracetam.

The administration of methylazoxymethanol (MAM) to pregnant rats induced a marked reduction in the weight of the offspring's brain. This reduction was due to aplasia of the cortex and hippocampus, whose thicknesses were 50% of those of control animals. A significant reduction was also observed in the striatum. This aplasia could be ascribed to the antimitotic effect of MAM, which, when given at gestational day 15, prevented the development of neurons in the three brain areas mentioned. Indeed, we infer here that the total number of GABA-receptor complexes, as measured by [3H]muscimol and [3H]flunitrazepam binding, was reduced to the same degree as was the weight of the cortex. Similarly, total [3H]haloperidol binding sites were reduced in the striatum. From the behavioral point of view, offspring of MAM-treated rats (MAM rats) showed impaired acquisition in the water-maze and pole-climbing tests, indicating that this brain aplasia had disrupted cognitive processes. In contrast, these animals showed normal growth, and grossly their behavior appeared normal. Oxiracetam, a new compound that belongs to the recently described class of nootropic drugs, was able to restore acquisition processes in MAM rats. We propose therefore that MAM rats might become an interesting and quite simple animal model for evaluation of new acquisition-enhancing drugs. Moreover, this model could also be useful to study the neurochemical correlates of cognitive processes.

Abnormalities, Drug-Induced↗

Early postnatal chlordiazepoxide administration: permanent behavioural effects in the mature rat and possible involvement of the GABA-benzodiazepine system.

The long term behavioural and biochemical effects of chronic chlordiazepoxide treatment during the period of neuronal maturation in the rat have been investigated. The administration to lactating mothers of chlordiazepoxide at very low doses (0.22 and 2.6 mg/kg) in their drinking water affects both behavioural and biochemical parameters in offspring at 60 days of age and undrugged since weaning. A deficit in the acquisition of the conditioned avoidance response in treated rats was observed, although no significant difference in spontaneous locomotor activity between control and treated rats was found. 3H-Flunitrazepam binding sites in cerebral cortex and hippocampus were decreased by the treatment, whereas no change was detected in cerebellum. Moreover, 3H-muscimol binding sites increased in hippocampus with no changes in cerebral cortex and cerebellum. According to the different regional distribution of benzodiazepine type 1 and type 2 receptors, we suggest that type 2 receptors are selectively affected by the treatment, and that the GABAergic receptor system is also permanently altered by administration of chlordiazepoxide during early postnatal life.

Animals↗

Behavioral and biochemical effects of postnatal parathion exposure in the rat.

Preweanling rat pups were exposed daily to parathion (1.3 mg/kg or 1.9 mg/kg) or vehicle (corn oil) on postnatal days 5-20, a time period critical to development of behavioral and biochemical parameters of the cholinergic nervous system. This exposure resulted in dose-dependent reductions in acetylcholinesterase activity and muscarinic receptor binding in the cortex. During the preweanling period, there were no differences among the groups in most reflex measures, eye opening or incisor eruption. Postweanling behavioral assessment revealed small deficits in tests of spatial memory in both the T-maze and the radial arm maze. There were no differences in neuromuscular abilities or spontaneous activity measures. Thus, biochemical and behavioral deficits in cholinergic nervous system functioning occurred in the absence of severe signs of toxicity and in the absence of generalized nonspecific behavioral disturbances.

Acetylcholinesterase↗

Nocturnal hyperactivity induced by prenatal methylazoxymethanol administration as measured in a computerized residential maze.

Treatment of female Sprague-Dawley rats with 15 or 25 mg/kg (IP) of methylazoxymethanol acetate (MAM) at gestational day 15 (15 DG) resulted in a dose-dependent reduction of total brain weight of the adult offspring. When tested for spontaneous activity in a residential maze over a 23 hour period, those animals treated with the highest dose of MAM showed an increase in both locomotion and local activity during night hours without changes in the structure of behavior. Animals treated with 15 mg/kg of MAM showed no difference in activity compared to controls despite a significant reduction in brain weight.

Animals↗

Prenatal exposure to ethanol causes differential effects in nerve growth factor and its receptor in the basal forebrain of preweaning and adult rats.

In this study we investigated nerve growth factor (NGF) levels in the cortex and hippocampus of the offspring of pregnant female Sprague-Dawley rats receiving a single intragastric administration of acute ethanol on the 15th day of gestation and compared them with a control group of rats that received an injection of sucrose. We also examined the distribution of the low-affinity NGF receptor, p75NGFR, on NGF-responsive neurons that are localized in the septum and the nucleus of Meynert, which receive the respective trophic support from the hippocampus and the cortex. In the ethanol-treated group, the results show that at post-natal age 15 days, the NGF septohippocampal pathways were markedly affected. At day 15, the NGF level was significantly higher in the offspring of ethanol-treated rats. By day 40, NGF values in both groups decreased to similar levels. At day 60, however, the NGF level in the ethanol-treated animals decreased to a significantly lower value than that of the control group, which remained essentially unchanged. In parallel, at day 60 the numbers of septal cholinergic neurons expressing p75NGFR were also significantly lower in ethanol-treated rats than in control animals. Because ethanol is known to induce neurological disorders, as well as deficits in cell proliferation and differentiation, the results suggest that one cause of the deleterious effects induced by ethanol is the low availability of NGF during certain stages of postnatal brain development.

Animals↗