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Biomedical subjects

L Rusconi

Publications and source records attributed to L Rusconi.

At least 19 recordsLinked to original sources
PubMed1991

Bombesin receptor antagonists. 2. Analogues based on substance P antagonists.

Although bombesin (BN) and substance P share only the C-terminal dipeptide amide, some substance P receptor antagonists are also weak bombesin receptor antagonists. In order to increase the selectivity of the antagonism for the BN receptor, a series of hybrid peptides were synthesized by the solid-phase methodology, and screened on 3T3 fibroblasts for binding and mitogenic activity. The analogues inhibiting BN-induced thymidine incorporation were further tested for peripheral (amylase release and urinary bladder contraction) and central activity (grooming behaviour).

3T3 Cells↗
PubMed1988

Role of dopamine in manganese neurotoxicity.

Manganese chloride increased cell mortality when added to human fibroblast cultures. The toxicity of the metal was greatly enhanced by dopamine; this effect was antagonized by the presence in the culture medium of catalase and superoxide dismutase enzymes. Manganese chloride also caused a marked decrease of striatal dopamine concentrations when infused into rat substantia nigra. Manganese neurotoxicity was lowered by pretreating the animals with drugs that reduced striatal dopamine turnover rate. Administration of an antioxidant, such as vitamin E, also partially prevented striatal dopamine decline induced by intranigral manganese infusion. Therefore, the decreased availability or autoxidation of dopamine attenuated manganese neurotoxicity. These findings are in agreement with previous observations suggesting that manganese increases toxic products originating from dopamine catabolism.

Animals↗
PubMed1988

Effect of aspirin on serotonin and met-enkephalin in brain: correlation with the antinociceptive activity of the drug.

Intravenous administration of acetyl salicylate of lysine, a soluble salt of aspirin, reduced in rats the firing discharge of thalamic neurones, evoked by noxious stimuli. Concomitantly, concentrations of 5-hydroxyindole acetic acid increased, while those of met-enkephalin-like immuno-reactive derivatives were decreased in several areas of the brain. Similar electrophysiological and biochemical responses were obtained by administering tryptophan or 5-hydroxytryptophan plus carbidopa. The effect of aspirin on the evoked firing of the thalamic neurones was counteracted by pretreating the animals with metergoline. On the other hand, naloxone did not antagonize the inhibitory effect of aspirin and 5-hydroxytryptophan on pain-induced neuronal excitation. These data indicate that a serotonin-, but not a naloxone-sensitive opiate mechanism, may be relevant for aspirin-mediated antinociception.

Analgesics↗
PubMed1988

Serotonergic control of phenylephrine-induced cyclic 3,5'-adenosine monophosphate and inositol phosphates formation in rat hippocampus.

Chemical lesion of serotonergic afferents to the hippocampus resulted in a potentiation of phenylephrine (PHE) stimulation of cyclic AMP (cAMP) formation in rat hippocampal slices. The concentration-response curve of the alpha-1-agonist in lesioned rats was shifted markedly to the left with the peak increase occurring at a concentration 200 times lower (500 nM) than that required to raise cAMP to the same extent in slices of the sham-operated controls. Adenylate cyclase activity measured on crude homogenate preparations was increased by the lesion, too. The alpha-1 antagonist WB-4101 (dimethyloxyphenoxy-ethylamino-methyl benzo-1,4-dioxan) was the most potent inhibitor of PHE in lesioned rats with an IC50 of 125 nM, 110 times lower than that of prazosin (14 microM); yohimbine and propranolol, respectively, alpha-2 and beta-antagonists caused inhibition only at very high concentrations. Serotonin (10 microM) induced a marked rightward shift in the concentration response of PHE in lesioned rats, without any effect of its own on the cAMP level. PHE stimulated inositol phosphates accumulation in hippocampal slices in a concentration-dependent manner with an EC50 of 20 microM. Chemical lesion of the serotonergic median raphe nuclei caused a significant reduction of PHEs maximal effect on inositol phosphate accumulation by 50% with no change detectable in the EC50. The results imply that both second messenger responses to PHE stimulation are modulated by serotonin. Whether cAMP and phosphatidylinositol-4,5-bisphosphate generated second messengers act in a cooperative manner, or independently, is discussed.

5,7-Dihydroxytryptamine↗
PubMed1987

Absence of D1 dopamine receptors that stimulate prolactin release in the rat pituitary.

It has been shown recently that SKF 38393-A (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine-7-ol), a D-1 receptor agonist, possesses a prolactin-releasing effect in the rat, though the pituitary or central nervous system location of the receptors involved has not been clarified. The aim of our study was to elucidate this point. SKF 38393-A administered to freely moving adult female and male rats induced a striking, short-lived increase of basal prolactin levels. The prolactin stimulatory effect of SKF 38393-A was counteracted by pretreatment with SCH 23390, A D-1 receptor blocker. SKF 38393-A (10(-11)-10(-6)M) added to monolayer primary cultures of anterior pituitary cells from rats of both sexes failed to modify prolactin release. At higher concentrations (10(-5)-10(-4) M) the drug induced a slight inhibition of prolactin release. Similarly, SKF 38393-A failed to stimulate adenylate cyclase activity in anterior pituitary membranes from rats of both sexes at low concentrations, while it inhibited enzyme activity at higher concentrations (10(-5)-10(-3) M). The latter effect was counteracted by concomitant addition of the antagonist of D-2 receptors, 1-sulpiride. These data demonstrate that: (1) the anterior pituitary does not contain D-1-dopamine receptors (positively coupled to adenylate cyclase) stimulatory to prolactin release; (2) the striking prolactin-releasing effect of SKF 38393-A in the rat is due to activation of extra-pituitary D-1 dopamine receptors; (3) SKF 38393-A, at high concentrations, is capable of activating pituitary D-2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Behavioural and biochemical studies on 6-methylamino-4,5,6,7-tetrahydrobenzothiazole (14.839JL), a new potent dopaminergic agonist.

6-Methylamino-4,5,6,7-tetrahydrobenzothiazole monochlorhydrate (14.839JL) is a new, potent dopaminergic agonist. The stereotypy induced by this drug was greater than that induced by an equivalent dose of apomorphine, was antagonized by pretreatment with sulpiride and counteracted the hypomotility induced by reserpine. Striatal levels of the dopamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) were significantly lowered for up to 4-6 h by doses from 0.05 to 1 mg/kg. The drug was also very effective in lowering prolactine secretion. 14.839JL displaced [3H]N-n-propylnorapomorphine [3H]NPA from striatal binding sites with an IC50 similar to dopamine (DA). Conversely, the ability of 14.839JL to displace 3H spiperone from its binding sites was 100 and 10 times lower than that of haloperidol and sulpiride, and similar to that of SCH 23390. Differently from the latter, however, 14.839JL did not modify adenylate cyclase activity. All these data suggest that 14.839JL is a new, potent, long-lasting direct DA agonist, probably acting on D2 receptors.

Adenylyl Cyclases↗
PubMed1987

Different regulation of growth hormone-releasing factor-sensitive adenylate cyclase in the anterior pituitary of young and aged rats.

Low basal GH secretion and reduced GH responsiveness to different GH secretagogues, including GHRF, have been reported in aged animals and humans. Parallel to the in vivo findings, an impaired GH responsiveness to GHRF is evident in somatotropes from old rats of either sex. We report here that in anterior pituitaries (APs) from aged male and female rats GHRF-induced stimulation of adenylate cyclase (AC) activity was strikingly reduced (male rats, change from baseline 700% in young and 100% in old rats) or lacking (female rats, change from baseline 430% in young and 13% in old rats) when compared to that evoked by GHRF in the APs from young counterparts. Pretreatment with GHRH (5 micrograms/rat iv for 3 days) decreased the high basal AC activity of old male rats [from 33.38 +/- 3.60 to 15.99 +/- 5.75 (SEM) pmol cAMP/min.mg protein], did not alter the GHRF-stimulated rise in AC activity in old male rats, and induced a small but unequivocal rise in AC activity in old female rats (change from baseline 35% vs. 13%, respectively). Pretreatment with GHRF markedly reduced the acute effect of GHRF in the APs from young rats of both sexes (male rats, change from baseline 360% and 700%; female rats, change from baseline 230% and 430% in GHRF-pretreated and control rats, respectively). In parallel studies performed in female rats, it was shown that in vivo pretreatment with GHRF at the same schedule markedly reduced the effect of acute GHRF stimulation on GH secretion from cultured pituitary cells of young rats but left unchanged GHRF-induced stimulation of GH secretion from pituitary cells of old rats. In all, these data suggest that deficiency of endogenous GHRF synthesis and/or release may underlie defective GH secretion in old rats and that a GHRF replacement regimen that reduces the sensitivity of the young somatotrope cells does not alter the sensitivity of (male rats) or exerts a priming effect (female rats) on the old somatotrope cell.

Adenylyl Cyclases↗
PubMed1986

Dopamine receptor changes in response to prolonged treatment with L-dopa.

Unilateral lesions of the nigro-striatal dopamine (DA) pathway induced contralateral rotations to apomorphine, increased (3H)-spiroperidol binding and enhanced the sensitivity of striatal adenylate cyclase to DA stimulation. Prolonged L-dopa administration counteracted the increased density of (3H)-spiroperidol binding sites but further enhanced the hypersensitivity of adenylate cyclase to DA and decreased the inhibitory effect of opiates on this enzyme. The apomorphine-induced contralateral rotations were also strongly potentiated. On the contrary the binding of (3H)-SCH-23390 was affected neither by DA nerve degeneration nor by chronic L-dopa treatment. These results suggest that DA-D1 and DA-D2 receptors are differently affected by prolonged L-dopa treatment. The biochemical changes of DA-D1 receptors associated with adenylate cyclase seem to be correlated with the enhanced behavioural responses to apomorphine and could be a consequence of a decreased opiate inhibitory tone on the enzyme. The increased supersensitivity of the DA-D1 receptors may play a role in the clinical changes seen in parkinsonian patients following chronic use of L-dopa.

Adenylyl Cyclases↗
PubMed1985

Bicyclic compounds with potential antiulcer and/or antisecretory activity. I. 4,5,6,7-Tetrahydrobenzimidazoles.

The remarkable antiulcer and antisecretory activity of some previously described 4,5,6,7-tetrahydroimidazo[4,5-c]pyridine derivatives prompted us to further investigate related bicyclic systems. Accordingly, a series of 5-amino- and 5-aminomethyl-4,5,6,7-tetrahydrobenzimidazoles, regiospecifically alkylated in position 1, were synthesized and tested. Only a few 1-ethyl-5-amino derivatives displayed a reasonable antiulcer activity in comparison with our former class of compounds.

Animals↗
PubMed1983

Synthesis of native 60S and 40S ribosomal subunits in Yoshida rat ascites hepatoma AH-130 cells: correlation with the rate of cell growth.

The 60Sn and 40Sn subunit ribosome synthesis declined significantly in Yoshida rat ascites hepatoma AH-130 cells from the log phase to the plateau phase of the in vivo growth. Two main classes of 40Sn particles with protein/RNA ratios of 1.82 (p2) and 1.20 (p3) and a minor "heavy" one with protein/RNA ratio of 0.96 (p1) could be distinguished reproducibly by their ultraviolet absorption after sucrose zone sedimentation. The p2 particles appeared the dominating class in log phase cells. In plateau phase cells a decrease of p2 and an increase of p3 particles was observed. Under these conditions the p1 particles and the peaks corresponding to 60Sn subunits and to 80S ribosomes were also increased. Newly synthetized 40Sn particles banded in the p3 region of the gradient and p2 particles originated from them. These particles entered into the ribosomal cycle and contained poly(A) RNA. Formation of radioactive 80S couples by subunits entering into the ribosomal cycle was markedly stimulated in log phase cells and almost completely blocked in cells at the plateau phase of growth.

Animals↗
PubMed1982

[Use of hyperbaric oxygen therapy in a case of inguino-genital gangrene].

A case of inguinogenital gangrene in a 63 years old man is reported. The patient was admitted to the hyperbaric medicine centre in a serious general condition. The use of HOT, antibiotics and selective surgery as treatment of metabolic disturbances effectively improved the patient's general condition, and HOT also proved effective in the treatment of hepatic insufficiency.

Gangrene↗
PubMed1981

Solution characterization of starch nicotinates with different degrees of esterification.

A series of starch-nicotinic acid copolymers with a degree of esterification ranging from about 15% to about 90% was prepared, and the stability in solution of two representative samples of the series was tested. The variation of some physico-chemical characteristics in the series was examined by solubility tests, viscometry and refractometry, and found to be not simply correlatable to the nicotinylation degree.

Esters↗
PubMed1981

Synthesis and pharmacological evaluation of poly(oxyethylene) derivatives of 4-isobutylphenyl-2-propionic acid (ibuprofen).

The synthesis of three oligomeric derivatives of 4-isobutylphenyl-2-propionic acid (ibuprofen), namely, the monoester of tetraethylene glycol (I) and the diesters of poly(oxyethylene) samples having molecular weights of 1000 (+/- 50) and 2000 (+/- 150) (II and III), has been performed via the imidazolide method. The antiinflammatory activity of I-III, and of equivalent amounts of free drug, was determined in the carrageenan-induced rat paw edema assay at different times after oral administration and found to be considerably prolonged in the case of the three derivatives. The lowest molecular weight derivative (I) also had an enhanced initial activity with regard to 4-isobutylphenyl-2-propionic acid. These results were confirmed by measuring the plasma levels of 4-isobutylphenyl-2-propionic acid in rats at different times after oral administration.

Animals↗
PubMed1980

[The left posterior fascicular block: is the diagnosis possible only by ECG? (author's transl)].

The diagnosis of Left Posterior Fascicular Block based on clinical ECG and VCG tracings alone is possible when ECG and VCG allow to recognize asynchronous left ventricular activation. The delayed inscription time of the intrinsecoid deflection in aVF (or V6) in absolute and relative to aVL permits the diagnosis if intrinsecond deflection in aVL exceeds 0,035". Il more premature, a further control is required to distinguish Left Ventricular Hypertrophy from Left Posterior Fascicular Block, both in anatomically vertical heart.

Electrocardiography↗
PubMed1979

[Lidocaine administration in a patient with Wolff-Parkinson-White syndrome and atrial fibrillation (author's transl)].

This report describes a case of Wolff-Parkinson-White syndrome with atrial fibrillation in which the ventricular complexes conducted over the accessory pathway have promptly disappeared with the use of intravenously administered lidocaine. Lidocaine is suggested as the most suitable drug in such situations. Finally possible connections are presented between high dosage administered lidocaine and conversion to normal sinus rhythm.

Atrial Fibrillation↗
PubMed1976

[The right bundle branch blocks with posterior loop (author's transl)].

The AA. have analysed 39 VCG which show terminal slowed down forces definitely directed towards the right and the back. It is presumed that such electrical patterns have to be classified amongst defects which deal with right intraventricular conduction. Both the ECG and UCG test have been classified in groups: some of them simulating BFA, others BFP. An analysis of the different developing ways of the vectorial loops has been made. The AA. think that in some cases the particular direction of the terminal forces could be compatible with an isolated and zonal right conduction defect in the posterior region of the right ventricle. In other cases the coexisting electrical pathology of the left ventricle is likely to be responsible for it. At the end the distinguishing diagnostic criteria of the ECG are discussed.

Adolescent↗