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Biomedical subjects

G Peruzzi

Publications and source records attributed to G Peruzzi.

At least 55 records · Page 3Linked to original sources
PubMed1990

Synthesis and dopamine receptor affinities of 2-(4-fluoro-3- hydroxyphenyl)ethylamine and N-substituted derivatives.

The synthesis of 2-(4-fluoro-3-hydroxyphenyl)ethylamine (26) and of some N,N-dialkyl derivatives (27-30) starting from 4-fluoro-3-hydroxytoluene and their in vitro binding affinities for dopamine (DA) receptor are reported. The amine 26 can be regarded as a molecular modification of DA in which the para hydroxyl group is replaced by fluorine. The new compounds 26-30 were evaluated for their affinity at D-1 and D-2 DA receptor subtypes by displacement of [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective). The amine 26 had about 2-fold less affinity for D-1 and D-2 binding sites than DA. The substitution of the amino group with ethyl, n-propyl, and 2-phenylethyl groups decreased the affinity for D-1 binding sites but greatly enhanced the effectiveness on D-2 binding sites. The N-ethyl- (28) and N-n-propyl-N-(2-phenylethyl)-2-(4-fluoro-3- hydroxyphenyl)ethylamine (30) were the most potent members of the series with high selectivity for D-2 binding sites. A similar effect was observed with isomeric N-n-propyl-N-(2-phenylethyl)-2-(3-fluoro-4-hydroxyphenyl)ethylamine (31) which was approximately 65 times more selective for D-2 sites vs D-1 sites. The introduction of a 2-phenylethyl group on the nitrogen atom induce the highest effect, perhaps as a consequence of an increased liposolubility or of binding to a complementary lipophilic site on the receptor.

Animals↗
PubMed1989

[Study of the interactions of atrial natriuretic peptides with the autonomic nervous system. Effects on cardiocirculatory and respiratory reflexes caused by activation of chemosensitive muscle receptors].

In order to verify the hypothesis that possible interactions with the autonomic nervous system may contribute to the cardiovascular effects of atrial natriuretic factor (ANF), 9 rabbits were anesthetized to study the effect of the infusion of synthetic human ANP (2 mcg/kg in bolus followed by 0.2 mcg/kg/min for 20 min iv) on the reflex responses induced by intra-arterially injected BK (250 ng) and hypertonic NaCl (10%) or glucose (40%). The infusion of ANP provoked a decrease in systolic (SBP, 14%) and diastolic (DBP, 8%) pressure without any significant changes in heart rate (HR). The injection of BK and hypertonic NaCl into femoral arteries carried out during ANP infusion produced cardiorespiratory response patterns similar to those observed in control conditions. After injecting BK, a fall in SBP (25%), DBP (50%) and HR (16%), and an increase in breathing frequency were observed. After injecting NaCl, an increase occurred in SBP (20%), DBP (25%), HR (10%) and in depth of breathing. In the present experimental conditions, ANP has not been found to be capable of significantly interfering with the reflex pattern of cardiorespiratory responses either from the inhibition or activation of the sympathetic nervous system induced by chemical stimulation of muscle receptors.

Animals↗
PubMed1989

[Cardiocirculatory and respiratory reflexes of muscular origin during prolonged experimental dynamic exercise. Effects of sectioning of the sino-carotid and aortic nerves and bilateral vagotomy].

In anesthetized rabbits we have evaluated the effects of denervation of sino-aortic areas and vagotomy on the reflex cardiorespiratory responses during 2 min of contractions of gastrocnemius muscle induced by electrical stimulation of tibial nerve. The following parameters were examined: blood pressure (BP), heart rate (HR), respiratory frequency (f), tidal volume (Vt) and pulmonary ventilation (Ve) while arterial pH, pCO2 and pO2 and end-tidal CO2 (petCO2) were monitored. During steady state of rhythmic contractions we observed a decrease of BP, a slight decrease in HR and marked rise of Ve due to an increase of f with a slight increase of Vt. The sectioning of carotid-sinus, aortic and vagus nerves does not substantially modify the cardiorespiratory responses to muscular exercise; all the responses are abolished from the sectioning of somatic nerves in exercising limbs. The importance of the role of the peripheral nervous control by muscles (peripheral drive) is confirmed in the regulation of cardiorespiratory participation in motory activity, also in the steady state phase of muscular exercise in which components of a chemometabolic or hemodynamic nature could be more effective.

Animals↗
PubMed1987

Clinical and hormonal conditions associated with sodium retention in cirrhotic patients with ascites. Evaluation by univariate and multivariate analyses.

Using multiple regression analysis, we have evaluated the clinical and hormonal conditions associated with impaired urinary sodium excretion in normoazotemic patients with cirrhosis and ascites. We retrospectively identified 13 patients with a urinary sodium excretion lower than 15 mmol/day and 13 patients with a sodium excretion higher than 15 mmol/day. Using univariate analysis, all the patients with poor sodium excretion had abnormally high levels of plasma renin activity, plasma aldosterone, and arginine vasopressin. In addition, they had a diastolic blood pressure lower than patients with high urinary sodium excretion, although otherwise were comparable as regards clinical and biochemical data. The consistency of the above associations was then tested by multiple-regression analysis in an attempt to control for potentially confounding factors and to identify only true, independent associations. After a discriminant stepwise procedure, we found that low diastolic blood pressure (P less than 0.01) and high plasma aldosterone levels (P less than 0.05) were the only two conditions independently associated with abnormally low urinary sodium excretion. These findings are consistent with the view that sodium retention in decompensated cirrhosis results from a concomitant severe contraction in the effective blood volume and an increased production and/or retention of aldosterone. The concordance between our results and several pathophysiological findings supports the validity of this statistical approach to confirm physiological and/or clinical predictions.

Adult↗
PubMed1986

Microencephalic rats as a model for cognitive disorders.

The administration of the antimitotic compound methylazoxymethanol (MAM) to gestating rats induces a dose-dependent atrophy of specific brain areas in the offspring. This specificity is strictly dependent upon the time of MAM administration. When given at day 15 of gestation only the cortex, hippocampus, and striatum are affected, whereas when given to rat pups at postnatal day 1, the atrophy is apparent only in the cerebellum. The microencephalic offspring of dams treated at day 15 of gestation develop normally to adulthood, without manifest signs of this profound telencephalic contraction. Behavioral abnormalities are observable when subjecting these animals to tests that involve learning. The deficit in associative behavior might have its anatomical and neurochemical counterpart in the disruption of the neuronal circuitry in the neocortex, where about 50% of interneurons are absent in layers II-IV after a dose of MAM of 25 mg/kg. Loss of intrinsic neurons occurs also in the striatum, as revealed by neurochemical and pharmacological analysis. Indeed, MAM rats show a reduced dopamine-dependent adenylate cyclase activity and a reduced motor stimulation in response to dopaminergic stimulants. MAM rats are therefore an interesting animal model of chronic brain damage induced transplacentally, which could serve for studying adaptive mechanisms of the CNS to this damage and its pharmacological manipulation.

Animals↗
PubMed1985

Cardiorespiratory reflexes from muscles during dynamic and static exercise in the dog.

Cardiorespiratory reflex responses during the initial phase of dynamic and static contraction of hindlimb muscles were studied in anesthetized dogs. Muscle contractions were elicited by stimulating the femoral and gastrocnemius nerves at 3 and 100 Hz with the intensity of 2.0-2.5 times the motor threshold for a 20-s period. Rhythmic contractions caused a decrease in arterial pressure (Pa) and heart rate (HR) and increased pulmonary ventilation (VE) by increasing frequency (f) without significantly changing VT. Tetanic contractions provoked an increase in Pa and HR and a hyperpnea resulting from a rise in both f and VT. Similar responses were also obtained in anesthetized dogs with carotid sinuses denervated and cervical vagi cut. The abrupt increase in VE at the start of both types of exercise was not associated with immediate significant decreases in end-tidal CO2 values. These two patterns of cardiocirculatory and respiratory responses were closely similar to those reported in anesthetized rabbits in previous studies. Both patterns of responses were reflexes initiated by activation of muscle receptors verified by interrupting the afferents from the contracting muscles. It is concluded that, during dynamic and static work, two distinct muscular reflex mechanisms might exert their drives, related to the muscular metabolic rate, on the circulatory and respiratory function.

Animals↗
PubMed1984

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↗
PubMed1984

Behavioral and neurochemical differentiation of specific projections in the septal-hippocampal cholinergic pathway of the rat.

In the rat, an intraseptal injection of the gamma-aminobutyric acid (GABA) agonist muscimol decreases the turnover rate of acetylcholine in the hippocampus and, during extinction of a food-reinforced lever-press response, increases extinction responding in a dose-dependent manner. Intraseptal beta-endorphin decreases the turnover rate of hippocampal acetylcholine through activation of septal GABAergic interneurons and increases extinction responding. On the other hand, intraseptal substance P, which decreases the turnover rate of hippocampal acetylcholine in a manner unrelated to septal GABAergic mechanisms, fails to increase extinction responding. The turnover rate of acetylcholine in various hippocampal regions after intraseptal injection of muscimol and substance P was also studied. Muscimol decreases the acetylcholine turnover rate only in the ventral hippocampus, whereas substance P decreases it only in the dorsal hippocampus. We hypothesize that a lowering in the cholinergic input to the ventral hippocampus is capable of increasing extinction responding, whereas a decrease in the input to the dorsal hippocampus is without such an effect. Hence, the cholinergic projections to the two hippocampal areas are modulated by different transmitter systems and have different physiological functions.

Acetylcholine↗