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M Baraldi

Publications and source records attributed to M Baraldi.

At least 55 records · Page 3Linked to original sources
PubMed1994

Methyl mercury during late gestation affects temporarily the development of cortical muscarinic receptors in rat offspring.

Pregnant Sprague-Dawley rats were treated by gavage with a single dose of 8 mg/kg of methyl mercury on gestational day 15. Offspring of control and treated rats were killed at 14, 21 and 60 days of age. The binding characteristics of muscarinic receptors labelled in cortical membrane preparation by 3H-L-quinuclidinyl benzilate were studied together with the assessment of mercury level in the same brain area. Furthermore, the performance in passive avoidance tasks was evaluated in 8 weeks old rats. Perinatal exposure to methyl mercury significantly reduced the maximum number of muscarinic receptors (Bmax) in the brain of 14 (53%) and 21 day old rats (21%), while this change was no more present in 60 day old rats. This phenomenon seems to be strictly related to the presence of mercury in the cortex since it disappeared with the normalization of mercury levels in the brain. Despite the recovery of muscarinic receptor densities in methyl mercury exposed rats at 8 weeks of age, the avoidance latency was reduced in passive avoidance test as an indication of learning and memory deficits in these animals. Results from this study indicate that prenatal methyl mercury exposure induces latent cognitive dysfunction which does not seem to be related to transient muscarinic receptor alteration found in the early period of postnatal life.

Animals↗
PubMed1993

Modulation of AMPA/kainate receptors by analogues of diazoxide and cyclothiazide in thin slices of rat hippocampus.

Among the non-NMDA (non-N-methyl-D-aspartic acid) glutamate receptors, the AMPA (alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid) selective receptors are characterized by a fast occurring desensitization. We and others have searched for specific modifiers of the rapid desensitization of AMPA responses in hippocampal slices using the patch-clamp technique. Aniracetam (1-(4-methoxybenzoyl)-2-pyrrolidinone) and diazoxide (7-chloro-3-methyl-2H-1,2,4-benzo-thiadiazine 1,1-dioxide) (1 mM) increased glutamate-activated currents recorded from voltage-clamped CA1 pyramidal neurons in presence of 5 microM MK-801 (dizocilpine; 10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine) by 2.5 fold. Cyclothiazide (3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-3,4-dihydro-2H-1,2,4-benzoth ia diazine-7-sulfonamide 1,1-dioxide) (100 microM), a chemical congener of diazoxide, completely removed the desensitization of the AMPA response measured with fast application in excised outside-out patches. At this concentration cyclothiazide produced an 18 fold enhancement of the glutamate current. Eighteen diazoxide analogues (2H-1,2,4-benzothiadizines: IDRA 2-19) were then tested but none of them was as effective as diazoxide. Three analogues of cyclothiazide (3,4-dihydro-2H-1,2,4-benzothiadiazines: IDRA 20-22) were also tested and none of them were as potent as the parent compound. However, IDRA 21 produced a response 3 times larger than diazoxide. Moreover, while cyclothiazide and diazoxide potentiated kainate responses for all the doses that decreased AMPA receptor desensitization, IDRA 21, similarly to aniracetam, inhibited AMPA receptor desensitization preferentially. These results suggest that similarly to NMDA receptors the structure of AMPA receptors may include a center that regulates desensitization.

Action Potentials↗
PubMed1993

Synthesis and antiinflammatory activity of 2,6-bis(1,1-dimethylethyl)phenol derivatives.

The influence of 11 newly synthesized 2,6-bis(1,1-dimethylethyl)phenol derivatives substituted in the 4 position as measured on the carrageenan paw edema assay in Sprague-Dawley rats, was studied using indomethacin as a reference drug. Furthermore we studied the possible interference of few of these compounds on the calcium binding sites by using the specific ligand [3H]-PN 200-110 in "in vitro" experiments. As far as regard the antiinflammatory activity only the compounds 2b, 2j and 2k, dosed at 20 mg/Kg/os, exerted an inhibitory effect on paw edema which was practically equal, after 6 h, to that of indomethacin (approximately 30%) dosed at 2.5 mg/Kg. The compound 2k, however, showed, in comparison with indomethacin and the other new tested compounds, a longer lasting effect, reaching, after 8 h, a 56.7% inhibition of the edema. Finally the above mentioned compounds, when tested alone or in combination with nitrendipine, did not exert any displacing activity on [3H]-PN 200-110 binding to synaptosomal membranes. It is noteworthy however that compound 2e, which incidentally was inactive as antiinflammatory agent, showed a negative allosteric modulatory activity on the ability of nitrendipine to displace [3H]-PN 200-110 binding.

Animals↗
PubMed1991

Alterations of GABA-A and dopamine D-2 brain receptors in dogs with portal-systemic encephalopathy.

The binding characteristics of gamma-aminobutyric acid-A (GABA-A) receptors and the kinetic characteristics of the target enzyme of GABA synthesis in nerve terminals, glutamic acid decarboxylase (GAD), were studied in a dog model of portal-systemic encephalopathy obtained by porta-caval shunt performed in dimethylnitrosamine pretreated animals. Furthermore the properties of dopamine receptors and the levels of catecholamines of encephalopathic dogs were investigated. The mild stage of encephalopathy was characterized by an up-regulation of the inhibitory GABA-A receptors probably related to a decrese of GABA in nerve terminals since GAD was decreased and by a slight decrease of catecholamines and by an increased synthesis of octopamine associated with a decreased affinity of dopamine receptors. In the severe stage there was a selection of high affinity GABA-A receptors with an increased number of benzodiazepine recognition sites which were supersensitive to GABA stimulation, a decreased number of Dopamine D-2 receptors and a marked reduction of catecholamines. These data seem to suggest that the neurological disturbances of experimental portal-systemic encephalopathy might be the result of an imbalance between inhibitory and excitatory systems leading to a prevalence of the first one.

Animals↗
PubMed1990

Neurotransmission in hepatic encephalopathy.

After a careful characterization, a rat model of fulminant hepatic failure galactosamine-induced was utilized in order to evaluate the neurochemical changes and the histological alterations which occur during the developing of the encephalopathy. Following these studies, normal rats were treated with toxins claimed to be the primary agents of hepatic encephalopathy to recognize those which are able to mimic the behavioral, electrophysiological and neurochemical changes found in the rat model of fulminant hepatic failure. With the limit due to informations coming from an experimental model, the symptoms of HE seem to be attributable to neurotoxic agents such as ammonia. The toxicity of ammonia does not seem to be due to a mere decrease of general brain metabolism, but seems rather to be mediated by an increase, at least in some compartment, of neurotoxic amino acids such as glutamate. Both accumulation of ammonia and the neurotoxic effect of glutamate seem to be potentiated by the described zinc depletion (both in liver and in brain). Hence the final effect of these phenomena is the development of the symptoms of encephalopathy triggered by an imbalance between inhibitory and excitatory receptor systems in the brain associated with neuronal alterations which take place early and before the appearance of brain edema.

Animals↗
PubMed1990

Supersensitivity of GABA-A receptors in hepatic encephalopathy.

During the past decade a new approach to pathogenetic studies of hepatic encephalopathy has been undertaken to identify the neurochemical alterations which characterize the syndrome. Using animal models of hepatic encephalopathy electrophysiological, behavioral, pharmacological and biochemical evidence were provided of an increased functional activity of the GABA-A receptors, including the Benzodiazepine site. These demonstrations seem to explain the increased sensitivity of patients with acute or chronic liver disease to sedative administration. The described increased tone of the GABAergic receptor complex seems to play a key role in the generalized depression of the central nervous system which characterizes hepatic encephalopathy, but other factors seem to contribute to the neuronal derangement present in this syndrome leading to an imbalance between inhibitory and excitatory receptor systems in the brain. Based on these findings a new symptomatic treatment with anti-benzodiazepine compounds which seem temporarily to counteract the symptoms of hepatic encephalopathy, was introduced.

Animals↗
PubMed1990

Evidence that bremazocine prevents urine retention induced by intraspinal cord injection of colchicine in rats.

Intra-spinal cord injection of colchicine (2.5-5 micrograms/rat) produced an inhibition of reflex micturition leading to voiding suppression, bladder hypertrophy and overflow incontinence. Intraperitoneal administration of bremazocine, a kappa-receptor agonist with antagonistic properties for mu- and delta-receptors minimized the colchicine induced effects. The selective kappa-receptors agonist, U-69593, had little effect, while eledoisin or naloxone administration worsened rather than counteracted urine retention.

Analgesics↗
PubMed1990

Endogenous benzodiazepine receptor ligands in human and animal hepatic encephalopathy.

The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in humans and in rat models of hepatic encephalopathy. Endogenous benzodiazepine ligands were extracted from rat brain and human CSF by acid treatment and purification by HPLC. Detection and partial characterization of these endogenous benzodiazepine ligands were carried out using both radioreceptor binding assays and radioimmunoassays with anti-benzodiazepine antibodies. Four different benzodiazepine receptor ligands were identified in human and rat tissue, two of which may be diazepam and desmethyldiazepam, based on elution profiles and anti-benzo-diazepine antibody reactivity. Human CSF and serum from patients with hepatic encephalopathy contained approximately 10 times more endogenous benzodiazepine receptor ligand than CSF from controls or nonencephalopathic patients with liver disease. The levels of brain benzodiazepine receptor ligand compounds were also increased approximately 10-fold in rats suffering from fulminant hepatic failure, but not in rats with portacaval shunts, a model of chronic hepatic disease. The increased concentrations of these substances could be behaviorally significant and may contribute to the pathogenesis of hepatic encephalopathy.

Adult↗
PubMed1990

Rigid analogs of taurine as potential taurine antagonists.

In this study we tested the potential taurine-antagonistic properties of three rigid analogs of taurine, 3-amino- (1), 3-hydrazino- (2) and 3-aminomethyl-1,2,4-benzothiadiazine-1,1-dioxide (3), which were prepared in our laboratory, using TAG (6-aminomethyl-3-methyl-1,2,4-benzothiadiazine-1,1- dioxide) (4), the only antagonist of taurine so far available, as reference compound in "in vivo" and "in vitro" experiments. Some physicochemical properties of (1), (2) and (3) were studied and the synthesis of TAG (4) was improved with a new preparative method. A dose-effect study performed by injecting intracerebroventricularly (1), (2) and (3) showed that these compounds have none of exciting effects exerted by the high doses of TAG (4). (1) and (3) as well as TAG (4), were found to antagonize the controlateral turning induced by the intracerebro injection of taurine and to potentiate the sedative effect of diazepam. We failed to find specific binding for taurine in different brain synaptic membrane preparations using 3H-taurine as radioligand and taurine, (1) and (3) as binding displacer. (1), (3) and TAG (4) however were found to antagonize the inhibitory effect of taurine on 3H-diazepam binding. These results seem to indicative that at least (1) and (3), which were more extensively studied than (2) because of their better solubility, are taurine antagonists with an apparent better selectivity than TAG (4).

Animals↗
PubMed1987

An increase in cerebral benzodiazepine receptors induced by a subacute administration of ammonia, mercaptans and short-chain fatty acids in rats.

1. In the search to identify peripheral toxins which could be responsible for the supersensitivity of brain benzodiazepine receptors in experimental models of hepatic encephalopathy, [3H]diazepam-binding studies have been performed on brain tissues of normal rats treated with ammonium chloride, dimethyldisulphide and octanoic acid administered alone or in combination. 2. The subacute administration of the three toxins in combination induced a 30% increase in the number of benzodiazepine recognition sites. The administration of these toxins alone or in combination showed that this increase was mainly linked to the synergistic action of dimethyldisulphide or octanoic acid with ammonia, since dimethyldisulphide plus octanoic acid was ineffective. 3. These observations seem to reinforce the suggestion that these three toxins are able to induce neurochemical derangements similar to those described in experimental hepatic encephalopathy.

Ammonium Chloride↗
PubMed1986

Evidence that dopamine receptors identified by [3H]dopamine in the ventricles of guinea-pig heart are of DA2 type.

Apomorphine and LY 171555, but not SKF 38393 displaced [3H]Dopamine binding to membranes of guinea-pig heart. Domperidone and 1-sulpiride but not SCH 23390 competitively antagonize the [3H]Dopamine binding performed with 100 microM cold dopamine as displacer. In conclusion the DA2 receptor agonists and antagonists used are able to interfere with the receptors labelled by [3H]Dopamine in cardiac muscle.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1985

Evidence that 2-phenylpyrazolo[4,3-c]-quinolin-3(5H)-one antagonises pharmacological, electrophysiological and biochemical effects of diazepam in rats.

The effects of the acute administration of 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one on diazepam-induced behaviour and electrophysiological activity were studied in rat. The compound, in doses of 5-10 mg/kg (i.p.), which per se did not induce alterations in spontaneous locomotor activity, antagonised the sedative effect induced by 5-10 mg/kg (i.p.) of diazepam. The injection of diazepam in rats, induced a profound reduction in the first negative wave of the recording of the visual evoked potential used as a sensitive electrophysiological test, in vivo. 2-Phenylpyrazolo[4,3-c]quinolin-3(5H)-one (10 mg/kg, i.p.) caused a recovery of the amplitude of the first negative wave within a few minutes. This result was confirmed by the finding that 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one, injected acutely in rats, pretreated with diazepam exhibited the capacity to antagonise the binding of [3H]diazepam determined in vitro on synaptic membrane preparations from cortex. The comparison of the pattern of the visual-evoked potential, recorded after the injection of 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one (50 mg/kg) with the patterns recorded after the injection of ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazolo(1,5a) (1,4)benzodiazepine-3-carboxylate (50 mg/kg) and ethyl-beta-carboline-3-carboxylate and 1-methyl-beta-carboline demonstrated that 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one is devoid of intrinsic activity.

Animals↗
PubMed1985

Regulatory effect of calcium on 3H-dopamine binding to guinea-pig heart membrane preparations.

The effects of various cations on the specific binding of dopamine to its recognition sites are described using guinea-pig heart membranes as a substrate. Only CaCl2 provoked a dose-dependent facilitatory effect, while KCl, NaCl and MgCl2 acted in the opposite sense. Moreover, Na2EDTA also had an inhibitory effect on dopamine binding and completely prevented the facilitatory action of CaCl2 on 3H-dopamine binding. This effect is partially counteracted by trifluoperazine but unaffected by verapamil. We can conclude from this that calcium seems to be essential to optimizing 3H-dopamine binding to cardiac membrane preparations.

Animals↗