Biomedical subjects

P Baroldi

Publications and source records attributed to P Baroldi.

7 recordsLinked to original sources

PubMed1990

Venous blood platelets decrease during allergen-induced asthmatic reactions.

To determine whether circulating platelets alter during asthmatic reactions induced by allergens, we studied nine subjects previously shown to develop an early or dual asthmatic reaction after inhalation challenge with extracts of house dust mite or grass pollen. In each subject, FEV1, circulating platelets and leucocytes were measured before, 15, 30 and 60 min, and 2, 4, 6 and 8 hr after inhalation of allergen and diluent control administered in a single-blind, randomized fashion. The same procedure was repeated in six of the nine subjects after bronchoconstriction induced by methacholine. Each subject developed an early asthmatic reaction after allergen inhalation challenge, which was followed by a late asthmatic reaction in six subjects and by an equivocal late asthmatic reaction in two of them (fall in FEV1 of 15 and 17% respectively). Compared with the control day, circulating platelets significantly decreased during the allergen-induced early asthmatic reaction (P less than 0.025, at 30 min). Platelet counts returned to baseline values within 4 hr and remained steady thereafter both in subjects who did and did not develop a late asthmatic reaction. No changes in platelet counts occurred after bronchoconstriction induced by methacholine. Diurnal increase of leucocyte numbers occurred after challenge with both allergen and diluent control. These results suggest that platelets may be involved in the pathogenesis of allergen-induced asthmatic reactions.

Adolescent↗

PubMed1990

Immunoblockade by a specific tachykinin antiserum of the non-cholinergic contractile responses in the guinea-pig isolated bronchus.

1. In the guinea-pig isolated bronchus, capsaicin produced a concentration-dependent contraction which was tetrodotoxin- (1 microM) resistant but abolished by previous exposure to capsaicin. 2. Previous incubation with E7 antiserum (which crossreacts with neurokinin A but not with substance P), but not with control rabbit serum, strongly inhibited the contractile response to capsaicin. 3. The E7 antiserum shifted to the right the concentration-response curve to exogenous neurokinin A but not that to substance P. 4. The E7 antiserum also inhibited the non-cholinergic, slowly developing contraction produced by electrical field stimulation (1-5 Hz). 5. These findings provide additional evidence that tachykinin-like peptides play a major role in the bronchoconstrictor response produced by transmitter secretion from peripheral endings of capsaicin-sensitive afferents in guinea-pig bronchi evoked either by capsaicin or by electrical field stimulation.

Airway Resistance↗

PubMed1989

Octylonium bromide interacts competitively with the PAF receptor.

To clarify the nature of the interaction of octylonium bromide with the PAF receptor, saturation studies of 3H-PAF binding were made in the presence of increasing concentrations of the radioligand (from 0.06 to 7.4 nM) and of octylonium bromide (1 X 10(-8), 5 X 10(-8) and 1 X 10(-7) M) or of a potent PAF antagonist L 652,731 (2.5 X 10(-7) M), or in the absence of competing drugs. Saturation binding data were plotted according to the non-linear fitting analysis and to Scatchard transformation. Both mathematical models indicated that the presence of added drugs decreased the affinity of the complex 3H-PAF/PAF receptors, leaving unaffected the maximum number of PAF binding sites. Receptor parameters in the absence of competitors were: KD = 1.2 nM, Bmax = 950 fmoles 3H-PAF bound/10(8) platelets. Octylonium bromide increased, in a concentration-dependent manner, KD values from 1.5 to 2.1 nM, while Bmax ranged from 910 to 980 fmoles 3H-PAF specifically bound/10(8) platelets. Likewise, L 652,731 did not influence Bmax (980 fmoles) but increased KD (1.9 nM). The binding behaviour of octylonium bromide and L 652,731 indicates that the two compounds inhibit competitively the binding of 3H-PAF to its receptors.

Animals↗

PubMed1988

Prolactin-lowering effect of acute and once weekly repetitive oral administration of cabergoline at two dose levels in hyperprolactinemic patients.

To further evaluate the potency and time course of the PRL-lowering effect of single oral doses of cabergoline, two doses of the drug were given to 51 hyperprolactinemic patients who also received 2.5 mg bromocriptine according to a randomized cross-over design. One group (n = 26) received 0.3 mg, and the other (n = 25) received 0.6 mg. Both cabergoline doses induced a significant fall in serum PRL levels, which lasted, on the average, from 3 h to 5 days after 0.3 mg and from 3 h to 14 days after 0.6 mg; the mean maximum decrease after 0.3 mg was -65 +/-4% (+/- SEM), significantly (P less than 0.05) less than that after bromocriptine (group mean, -73 +/- 4%), and it was -76 +/- 3% after 0.6 mg, not significantly different from that induced by bromocriptine (group mean, -71 +/- 4%). The effect of 0.6 mg cabergoline was significantly greater than that of 0.3 mg (P less than 0.01). In a second study designed to evaluate the possible therapeutic use of the new drug, 0.3 or 0.6 mg cabergoline was administered orally once weekly for 9 weeks to 2 groups of 15 and 16 hyperprolactinemic patients, respectively. Serum PRL levels fell significantly by the first week and reached a plateau after 2 doses in the 0.6 mg cabergoline-treated group and after 5 doses in the 0.3 mg-treated group; the absolute PRL decrease was greater in the former. Ten patients in each group achieved normal serum PRL levels, and a marked decrease (greater than 50% of pretreatment values) occurred in all patients treated with 0.6 mg and in 13 treated with 0.3 mg weekly. Resumption of menses occurred during the treatment period in 15 of the 17 premenopausal women with amenorrhea. Six patients who had poor responses had better responses when given higher drug doses for 4 weeks, and serum PRL levels became normal in the 3 receiving 0.6 mg twice weekly. These data confirm that cabergoline is a long-acting oral dopaminergic drug and suggest that it may be a useful agent for the treatment of patients with hyperprolactinemia.

Adolescent↗

PubMed1987

Dose-related prolactin inhibitory effect of the new long-acting dopamine receptor agonist cabergoline in normal cycling, puerperal, and hyperprolactinemic women.

Two different single doses (400 and 600 micrograms) of the new long-acting dopamine agonist cabergoline (CBG) were given to 12 normal cycling women, 17 puerperal women, and 24 hyperprolactinemic women (12 with idiopathic hyperprolactinemia and 12 with pituitary adenoma). Plasma PRL was determined in blood samples collected before and at frequent intervals for 5 days after CBG administration. Both CBG doses induced marked inhibition of PRL secretion in all women. A decrease in plasma PRL levels was evident 1-2 h after CBG administration and persisted for up to 5 days. The 600-micrograms CBG dose had a more potent (P less than 0.05) PRL inhibitory effect than the 400-micrograms dose in normal, puerperal, and hyperprolactinemic women. Moreover, while 400 micrograms CBG prevented lactation in 3 of 7 puerperal women, 600 micrograms CBG prevented lactation in 5 of 5 puerperal women. A moderate blood pressure decrease occurred 3-6 h after CBG treatment, but no other side-effects occurred. These results demonstrate that CBG induces a dose-related inhibition of PRL secretion in normal women as well as in puerperal and hyperprolactinemic women. The potent long-lasting PRL inhibitory effect of CBG in conjunction with the absence of side-effects typical of dopaminergic compounds suggest that this drug is an advance in the medical treatment of hyperprolactinemia.

Administration, Oral↗

PubMed1987

Inhibition of basal and metoclopramide-induced prolactin release by cabergoline, an extremely long-acting dopaminergic drug.

The aim of this study was to evaluate the effectiveness of the ergoline derivative cabergoline in inhibiting the serum PRL response to metoclopramide (MCP; 5 mg, iv) and the duration of this effect. Seven normal men received cabergoline (600 micrograms, orally) on day 0 and underwent a MCP test on days -1, 1, 4, 8, 15, and 28. Fasting serum PRL levels were significantly depressed from days 1-14; the nadir value occurred on day 4. MCP-induced PRL release was significantly inhibited up to day 28, with a nadir on day 4. Two months later, four of the men received placebo on day 0, and tests with MCP were performed on days -1, 8, and 28; basal serum PRL levels and PRL responses to MCP were superimposable on days -1, 8, and 28. These data indicate that cabergoline is an effective long-acting inhibitor of PRL release in normal men, suitable for use in the management of hyperprolactinemic patients.

Adult↗

PubMedDate not supplied

Autoradiographic localization of octylonium bromide binding sites in the rat gastrointestinal tract.

The anatomical localization of the binding sites of the spasmolytic drug octylonium bromide (OB) in the rat gastrointestinal tract was analyzed by use of light microscope autoradiography. The drug was visualized after in vitro incubation of frozen sections of the gastrointestinal tract with a 10 nM concentration of 14C-OB and after in vivo injection into the ascending, transverse, descending and sigmoidal portions of the colon. In vitro experiments demonstrated the specific accumulation of 14C-OB within the colonic and rectal smooth muscle. In contrast, no specific binding of the radiolabeled drug was noticeable in the stomach or in the small intestine. In vivo intracolonic injection of 14C-OB showed a significant accumulation of the drug in the colonic musculature 2 min after administration. The predominant localization of 14C-OB in the colonic and rectal musculature could explain its effectiveness in suppressing the amplitude and frequency of colonic contractions and in controlling the irritable bowel syndrome.

Animals↗