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Biomedical subjects

M Ciuffi

Publications and source records attributed to M Ciuffi.

At least 37 records · Page 2Linked to original sources

Capsaicin and anaphylactic reactions in the guinea-pig.

The influence of capsaicin on anaphylactic reactions in the guinea-pig was studied both in vivo and in vitro. In guinea-pigs actively sensitized with ovalbumin, Herxheimer microshock was elicited by antigen aerosol and the preconvulsion time recorded. The preconvulsion time was reduced by about 30% in animals pretreated with capsaicin (1 mg/kg) injected i.p. 30 min before antigen aerosol, whereas it remained unchanged when the drug was administered two days before aerosol treatment. Capsaicin shows a partial protective effect when the provocative aerosol was administered 3 h after the last of three doses of capsaicin (100 micrograms/kg, i.p.), which had been injected for three consecutive days. Ileum longitudinal muscle strips were used for in vitro anaphylaxis studies. These were isolated from guinea-pigs actively sensitized with ovalbumin and histamine release evoked by antigen was measured. Preparations perfused with capsaicin (10(-6)-10(-4) M) and desensitized to the drug, showed a lower anaphylactic release of histamine. This effect was dose-dependent, with the histamine release reduced by 35% at higher concentrations (10(-5)-10(-4) M) of capsaicin. The mechanism of the influence of capsaicin on anaphylactic reactions is discussed briefly.

Anaphylaxis↗

[Low-malignancy duodenal leiomyosarcoma].

The authors report a case of duodenal leiomyosarcoma presenting a low degree of histological malignancy. The main anatomoclinical features of the neoplasm are summarized. The authors conclude indicating not aggressive surgical therapy as adequate in such cases. However, a prolonged post-operative follow-up is always necessary, in order to detect recurrences as early as possible.

Adult↗

Decreased response to GABA-B agonists in longitudinal smooth muscle-myenteric plexus preparations from morphine-tolerant guinea-pigs.

1) Responsiveness of guinea-pig ileal longitudinal smooth muscle-myenteric plexus preparations to drugs activating GABA-B receptors was studied in morphine-tolerant animals. For this purpose morphine pellets (75 mg each) were implanted subcutaneously in guinea-pigs and experiments were performed three days later in electrically-stimulated ileal strips. 2) Activation of GABA-B receptors with GABA (10(-6) -10(-3) M) or (-)-baclofen (10(-6)-10(-3) M) caused a dose-related inhibition of twitch response that was about 80% lower in preparations from morphine-tolerant animals than in controls. This was found both in preparations maintained in the presence of morphine (10(-6) M) and in morphine-free Krebs. The effect was evident also in ileal preparations from morphine-tolerant animals in which a withdrawal syndrome was induced by the administration of naloxone before sacrifice. 3) The phenomenon was specific since the dose-response curve of the adenosine-inhibitory effect was comparable in preparations from tolerant animals and controls. 4) The hyporesponsiveness to GABA-B receptor activation began 12 h after pellet implantation and was maximal on the third day. 5) It is concluded that during tolerance to and withdrawal from morphine there is a hyporesponsiveness of GABA-B receptors in "in vitro" guinea-pig ileal longitudinal muscle-myenteric plexus preparations.

Animals↗

Effect of various GABA-receptor agonists and antagonists on anaphylactic histamine release in the guinea-pig ileum.

In this paper we confirm the previously reported inhibition by GABA of anaphylactic histamine release from isolated guinea-pig ileum longitudinal muscle. Moreover we report that: GABA-inhibition of anaphylactic histamine release is mimicked both by GABA-A and GABA-B agonists; both GABA-A and GABA-B antagonists are effective in reversing GABA's inhibitory effect; the effect is exerted specifically by GABA-ergic drugs: taurine and beta-alanine are ineffective; the GABA-ergic effect seems not to involve cholinergic and adrenergic transmission. It is concluded that it might be interesting to assess the clinical value of GABA-ergic drugs in allergic gut disorders.

Anaphylaxis↗

Effect of baclofen on different models of bronchial hyperreactivity in the guinea-pig.

In this paper we report an inhibitory effect of (-)-baclofen on many models of bronchial hyperreactivity both in vivo and in vitro. (-)-Baclofen protects guinea-pigs from the anaphylactic bronchospasm induced in sensitized animals by an ovalbumin aerosol and from that induced by aerosols of histamine and PGF2 alpha. Moreover (-)-baclofen reduces the TXA2 and TXB2 output induced by ovalbumin from isolated sensitized guinea-pig lungs. On the other hand (-)-baclofen does not show antihistaminic, anticholinergic or antiprostaglandinic action on isolated tracheal preparations. It is concluded that baclofen can provide protection from bronchial hyperreactivity possibly through a modulation of autonomic nervous system activity.

Acetylcholine↗

Effects of nesosteine on Herxheimer microshock in guinea-pigs.

In this paper we firstly report the inhibitory effect of nesosteine, a mucolytic drug, on Herxheimer microshock in guinea-pigs. Nesosteine (5-50 mg/kg) is able to protect sensitized animals from ovalbumin-induced bronchospasm. On the other hand, the drug is ineffective against the bronchospasm induced by histamine and acetylcholine. These results have also been confirmed in in vitro experiments where it has been demonstrated that nesosteine (10(-5) M) inhibits ovalbumin-induced histamine release in the trachea of sensitized animals. In the same preparation, the drug is ineffective against the contractions induced by histamine or acetylcholine. In conclusion, the drug presented here may be helpful in pathological conditions where reductions both of mucolysis and bronchospasm are sought.

Anaphylaxis↗

The effect of lipoxygenase inhibitors and leukotriene antagonists on anaphylaxis.

The experiments whose results are reported here were carried out with the aim of showing a possible role for lipoxygenase products in the modulation of the Schultz-Dale reaction. For this purpose, the actions of nordihydroguaieretic acid (NDGA) and of FPL 55712 were tested during anaphylaxis in guinea-pig ileum and trachea in vitro. Isolated preparations from guinea-pigs, which had been subcutaneously sensitized with ovalbumin and incomplete Freund adjuvant, were challenged with increasing concentrations of antigen; in preparations isolated from the same animal an antigen-concentration anaphylactic-reaction curve was performed in the presence of the drugs. NDGA 3.3 X 10(-6) M was capable of inhibiting anaphylaxis in the trachea to a maximum extent of 40% but it did not affect anaphylactic reaction in the intestinal smooth muscle. FPL 55712 2 X 10(-6) M did not exert any activity on anaphylaxis in either preparations. The difference between SRS-A and histamine as mediators of anaphylaxis in the tissue preparations used could explain the fact that NDGA acted on the trachea alone.

Anaphylaxis↗

Effects of GABA agonists on Herxheimer microshock in guinea pigs.

In this paper we describe the first observation of GABA inhibition in an experimental model of asthma in vivo. Guinea-pigs were actively sensitized with ovalbumin i.p. and 20 days later the Herxheimer microshock was performed. GABA and (-)-baclofen injected 20 min previously significantly prevented the development of microshock. Therefore GABAergic drugs appear to modulate in vivo anaphylactic reaction. The value of this observation with regard to the physiopathology and therapy of asthma remains to be elucidated.

Anaphylaxis↗

GABA-related activities of amino phosphonic acids on guinea-pig ileum longitudinal muscle.

The effects of phosphonic analogues of GABA, beta-alanine and glycine on guinea-pig ileum longitudinal muscle were measured. Aminomethylphosphonic acid (AMPh) and 2-aminoethylphosphonic acid (2-AEPh) were devoid of any effect both in non-stimulated preparations and in electrically-stimulated preparations. The phosphonic analogue of GABA, 3-aminopropylphosphonic acid (3-APPh) possessed a GABAB agonistic effect (relaxation and inhibition of twitch response) at doses of 10(-3)M. No agonistic effect on GABAA receptors was observed. 3-APPh at doses tested (2 X 10(-4)M and 10(-3)M) also displayed antagonistic action on the effects of GABAB agonists producing a parallel shift of the log dose-effect curves of GABA- and (-)-baclofen-inhibition of twitch responses. In contrast 3-APPh did not antagonize the inhibitory effect of morphine and noradrenaline. The contractile effect of GABA, mediated via GABAA receptors, was unaffected by 3-APPh(10(-3)M). It is concluded that 3-APPh is a partial agonist at the GABAB site in guinea-pig ileum.

Animals↗

Diazepam potentiates GABA-contraction in guinea-pig ileum.

Both GABA-receptors and benzodiazepine receptors have recently been described in the ileum. In this work we tested whether an interaction between diazepam and GABA-A- or GABA-B-mediated effects took place in guinea-pig ileum longitudinal muscle. We found that diazepam dose-dependently (10(-9) M-10(-6) M) potentiates the contractions caused by the activation of GABA-A receptor while it is ineffective at the same doses on GABA-B- mediated effects (relaxation and inhibition of twitch response). The drug "per se" does not affect the ileum. Diazepam potentiation is specific since this drug does not potentiate contractions caused by acetylcholine (10(-8) M), 5-HT (10(-7) M), histamine (10(-7) M), and electrical stimulation. Diazepam potentiating effect was not evident in the presence of bicuculline (10(-5) M) or hyoscine (2 X 10(-7) M). Ro 15-1788 (10(-5)M) and beta CCE (10(-5)M) antagonized diazepam potentiation of GABA contraction, while PK 11195 (10(-5) M) was ineffective. We conclude that diazepam modulates the effects evoked by stimulation of peripheral GABA-A receptors, while it is ineffective on GABA-B mediated effects.

Animals↗

Inhibition of anaphylactic histamine release in vitro by GABA.

Inhibitory effect of GABA on anaphylactic histamine release in vitro is not mimicked by 2-aminoethansulphonic acid (taurine), an aminoacid unrelated to GABA neuro-transmission. Tetrodotoxin (TTX) 6 X 10(-7) M, a concentration known to block neuronal mechanism but not to modify muscle membrane and anaphylactic histamine release, strongly prevented the inhibition caused by GABA in the Schultz-Dale reaction and in anaphylactic histamine release. The inhibitory effect of GABA on anaphylactic reaction in vitro thus appears to be specific for this aminoacid and is neurogenic in nature, in that it requires integrity of neuronal mechanisms.

Anaphylaxis↗

Estradiol and progestin receptors, 17-beta-hydroxysteroid-dehydrogenase and histopathologic grade in endometrial carcinoma.

The possible correlation between steroid receptor systems, 17-beta-HSD and histopathologic examinations were investigated. The well-differentiated tumors showed higher steroid receptor and 17-beta-HSD values than undifferentiated carcinomas. The steroid receptors did not present a statistically significant correlation with 17-beta-HSD. Nevertheless, some neoplastic endometria (29%) show higher values of progestin receptors and 17-beta-HSD, with a progestin:estrogen receptor ratio greater than one.

17-Hydroxysteroid Dehydrogenases↗

[Anticytogram (author's transl)].

In the last few years in an attempt to solve problems of antiblastic chemotherapy, the anticytogram has been developed to test in vitro sensitivity of human neoplastic cell cultures to antiproliferative agents. This method, although not without limitations and criticism, can be considered valid in particular tumor forms where these exists a histological type standardization and possibility of comparison with other known specifically active drugs. It may also be justified in the preclinical pharmacological phase, as the first stage in validity testing of new anticytoproliferative substances.

Antineoplastic Agents↗