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Biomedical subjects

P Preziosi

Publications and source records attributed to P Preziosi.

At least 19 recordsLinked to original sources

The effects of 5-HT3 receptor antagonists on cisplatin-induced emesis in the pigeon.

In the present study, the emetic effect of the anticancer drug cisplatin, and the protective effects of 5-HT3 receptor antagonists against cisplatin emesis were investigated in the pigeon. The experimental set-up involved the i.v. administration of drugs and subsequent observation of the percentage of vomiting animals and the number of emetic episodes per vomiting animal. It was observed that cisplatin induced dose-dependent emesis in the pigeon. 5-HT3 receptor antagonists afforded partial protection against cisplatin emesis, although some of them, i.e. indole, indole-like derivatives and zacopride, displayed intrinsic emetic activity. A serotonergic mechanism appears to be involved in both cisplatin- and 5-HT3 receptor antagonist-induced emesis, since pretreatment with an inhibitor of 5-HT synthesis, para-chlorophenylalanine (pCPA), prevented vomiting induced by either cisplatin or 5-HT3 receptor antagonists. It is concluded that the intrinsic emetic effects of 5-HT3 receptor antagonists provide pharmacological evidence of species differences in the properties of 5-HT3 receptors.

Animals

The influence of aging on plasma sex hormones in men: the Telecom Study.

From April 1985 to July 1987, 1,408 healthy white men aged 20-60 years in Paris, France, recruited on an occupational basis, underwent a physical examination and measurements of plasma sex hormones in a cross-sectional study. Both total testosterone and estradiol showed a significant stepwise decrease with age (p less than 0.001) starting in the early adult years, while estrone did not vary. These relations of testosterone and estradiol with age remained significant after adjustment for body mass index, subscapular skinfold, and tobacco and alcohol consumptions, and they were not modified by exclusion of the men who reported chronic disease. Both the mechanism for the early decrease in testosterone and its clinical significance merit further investigation.

Adult

Interrelation between plasma testosterone and plasma insulin in healthy adult men: the Telecom Study.

Plasma insulin is a risk factor for diabetes mellitus and cardiovascular disease in men. We investigated the association between plasma testosterone and plasma insulin in an occupational sample of 1292 healthy adult men. Total plasma testosterone decreased with each decade of age and insulin increased with each decade of age. In these cross-sectional data, this significant graded inverse association between testosterone and insulin was independent of age. The association was reduced but not explained by the addition of obesity and subscapular skinfold to the model. Adjustment for alcohol consumption, cigarette smoking and plasma glucose did not materially alter the association. These results are the reverse of the positive association of androgens with insulin in women and suggest alternative possible explanations for the effect of hyperinsulinaemia on cardiovascular disease risk. Prospective studies will be necessary to determine the direction and causal nature of this association.

Adult

A dual effect of some 5-HT3 receptor antagonists on cisplatin-induced emesis in the pigeon.

In the present study, the emetic effect of the anticancer drug cisplatin, and protective effects of 5-HT3 receptor antagonists against cisplatin emesis were investigated in the pigeon. The experimental setting involved the i.v. administration of drugs and subsequent observation of the percentage of vomiting animals and number of emetic episodes per vomiting animal over a period of 5 h. In some experiments, the 5-HT and 5-HIAA content in tissues was estimated by the HPLC technique. It was observed that cisplatin (2.5-10 mg/kg) is able to induce dose-dependent emesis in the pigeon. 5-HT3 receptor antagonists (500 micrograms/kg) afford partial protection against cisplatin emesis, although some of them, i.e. indolic derivatives and zacopride, display intrinsic emetic activity at doses of 50-500 micrograms/kg. A serotonergic mechanism appears to be involved in both cisplatin- and 5-HT3 receptor antagonist-induced emesis, since pretreatment with an inhibitor of 5-HT synthesis, para-chlorophenylalanine (300 mg/kg x 3 days), is able to hamper vomiting induced by either cisplatin or 5-HT3 receptor antagonists. It is concluded that the intrinsic emetic effects of 5-HT3 receptor antagonists in the pigeon provide pharmacological evidence of species differences in the properties of 5 HT3 receptors.

Animals

The effects of (+/-)-idazoxan and its stereoisomers on mouse vas deferens motility in vitro. A comparison with yohimbine.

The effects of idazoxan (IDZ) and its stereoisomers were compared to that of a classical alpha 2-antagonist, yohimbine (YOH), on para-aminoclonidine (PAC)- and norepinephrine (NE)-mediated inhibition of the twitch response evoked in the mouse vas deferens by low-frequency (0.1 Hz) field stimulation. (+/-)-IDZ and (+)-IDZ antagonized the inhibitory effects of PAC, (+)-IDZ being twice as potent as (+/-)-IDZ; in contrast, antagonism by (-)-IDZ failed to meet Schild criteria for a competitive mechanism. YOH completely reversed the inhibition of twitch response induced by NE, but not that induced by PAC; in the latter case, residual inhibition was almost fully reversed by (+)-IDZ and to a lesser extent by (+/-)-IDZ, while (-)-IDZ proved ineffective. These results provide pharmacological evidence of alpha 2-receptor heterogeneity at the vas deferens level. A possible additional mechanism involving imidazoline binding sites is discussed.

Adrenergic alpha-Antagonists

Kallikrein-kinin,enkephalin, renin-aldosterone and catecholamine systems in the vanadate (as vanadyl)-induced arterial hypertension.

Exposure to vanadate was found to induce arterial hypertension through effects on renin-angiotensin-aldosterone, renal peptidergic, and central and peripheral catecholaminergic systems. Vanadate increased, mainly in vascular myocells, both receptor-operated Ca2+ channel- and cyclic-AMP-dependent availability of Ca2+ for contractile processes. Vanadate was selectively accumulated by tissues in the +4 oxidation state (vanadyl).

Aldosterone

Galanin increases potassium evoked release of [3H]5-hydroxytryptamine from rat hypothalamic synaptosomal preparations.

The effects of galanin (GAL) have been evaluated on the depolarization evoked release of [3H]5-HT (serotonin or 5-hydroxytryptamine) from rat hypothalamic synaptosomal preparations, using low concentrations of potassium (15 mM). In the same preparation effects of GAL were also evaluated on [3H]5-HT uptake, using kinetic analysis to determine effects on Vmax values and Km values. GAL concentrations of 0.1-10 nM caused a concentration-related increase of the depolarization-evoked release of [3H]5-HT without influencing [3H]5-HT uptake. The results indicate the existence of high affinity GAL receptors on the hypothalamic 5-HT nerve terminals, exerting a facilitatory influence on depolarization-evoked [3H]5-HT release.

Animals

Effect of folic acid deficiency upon lymphocyte subsets from lymphoid organs in mice.

1. Three groups of weanling C57BL/6 female mice were fed one of two folate-deficient diets (0 and 0.1 mg folic acid/kg diet) or a normal folate-containing diet (2 mg folic acid/kg diet) for 8 weeks. A control pair-fed group was introduced with the most severe folate-deficient diet. Seven mice were fed the 0 mg folic acid/kg diet for 8 weeks, then rehabilitated (R) on the 2 mg folic acid/kg diet for 10 days. 2. Mice fed 0 mg folic acid/kg diet were severely folate-deficient (SFD), whereas mice fed 0.1 mg folic acid/kg diet were moderately folate-deficient (MFD), as shown by their folate status parameters. 3. Thymus weight, thymocyte content and positive immature CD4+8+ cells were decreased in SFD mice compared to controls. These values were normalized after 10 days of rehabilitation. 4. Mesenteric lymph node cells were apparently not affected by folate deficiency. 5. The proportion of Thy-1+ splenocytes was mildly lower in SFD mice than in controls. In R mice, mean spleen weight and spleen cellularity were increased compared to the other groups, but the proportions of Thy-1+, CD4+8- and CD4-8+ cells were markedly lower than control values.

Animals

Idazoxan inhibits hyperprolactinaemia in ovariectomized estrogen-treated rats.

The alpha 2-antagonist idazoxan (IDZ) has previously been shown to inhibit hyperprolactinaemia triggered by various stimuli such as lactation, stress, serotonergic agents and morphine (Preziosi, Martire, Navarra, Pistritto and Vacca 1989; Krulich, Jurcovicova and Le 1989). In this study, we investigated the PRL-lowering activity of IDZ in ovariectomized estrogen-treated (OET) rats; since a PRL surge usually occurs in normal cycling rats on the day of proestrus, the effect of IDZ on pulsatile PRL release in intact female rats was also studied. IDZ significantly lowered plasma PRL levels in OET rats; no elevated PRL values were observed in normal cycling rats, indicating that IDZ might inhibit PRL surges in these animals. It is concluded that IDZ is an effective PRL-lowering agent in a number of physiological and pharmacological hyperprolactinaemic models.

Animals

Alpha 2-adrenoceptor-mediated inhibition of prolactin release in suckling- or fenfluramine-induced hyperprolactinemia.

It has recently been shown that the specific and selective alpha 2-antagonist idazoxan (IDZ) displays prolactin-lowering activity on hyperprolactinemia induced in the rat either by suckling or serotonergic drugs. In an attempt better to understand the role of alpha 2-adrenoceptors under the above conditions, experiments were carried out to compare the effects of IDZ with that of the classic alpha 2-antagonist yohimbine (YOH), and also of the alpha 2-agonists clonidine (CLO) and B-HT 920, on prolactin (PRL) release during lactation and in hyperprolactinemia induced in male rats by the serotonergic drug fenfluramine (FEN). In lactating rats, both alpha 2-agonists decreased PRL release; this effect was enhanced by prior separation of the animals from their pups for several hours. A decrease of plasma PRL levels was also induced by IDZ but not by YOH, which tended further to increase hyperprolactinemia. In male rats treated with FEN, IDZ and CLO, a significant decrease of plasma PRL was produced, but YOH further enhanced PRL secretion. It is concluded that the alpha 2-agonists tested and also the alpha 2-antagonist IDZ display a unique inhibitory activity on PRL release during suckling or serotonergic-induced hyperprolactinemia.

Adrenergic alpha-Agonists

Lymphocyte subpopulations in the thymus, lymph nodes and spleen of iron-deficient and rehabilitated mice.

Three groups of weanling female mice were fed one of two iron-deficient diets (5 and 12 mg Fe/kg diet) or a normal diet (30 mg Fe/kg diet) for 6 wk. A control pair-fed group was included. Seven mice received the 5 mg Fe/kg diet for 6 wk, then were rehabilitated using the 30 mg Fe/kg diet for 10 d. Mice fed the 5 mg Fe/kg diet were moderately iron-deficient, as shown by indices of iron status. No significant differences were observed in thymus weight or in the proportion and number of thymocyte subsets in thymuses of anemic, moderately iron-deficient and control mice. Thymus weight was decreased in pair-fed mice. No significant difference was found in lymph node subsets. In the spleen of anemic mice, the proportions and total number of Thy-1+ splenocytes, CD4-8+ and CD4+8- cells were very low compared with control (P less than 0.01) and iron-deficient (P less than 0.02) mice. The decrease was not only observed for the percentage of subsets but also for the absolute number of cell subtypes per spleen. Thy-1+ splenocyte subpopulations were normalized after rehabilitation. These quantitative modifications could explain alterations in the blastogenic response of splenic lymphocytes described by other authors.

Administration, Oral

Iron and folate status in Zairian mothers and their newborns.

An evaluation of iron and folate status was carried out on 166 Zairian pregnant women from Kinshasa at delivery and in cord blood from their newborns. Anemia, defined as a low hematocrit value (less than 33%), was observed in 38% of pregnant women. Iron deficiency, recognized by a combination of abnormal values for serum ferritin level (less than or equal to 12 micrograms/l) and transferrin saturation (less than 16%) was present in 54% of pregnant women. Folate deficiency, defined by a red blood cell folate of less than 100 micrograms/l, was observed in 6% of cases. In anemic mothers, anemia was associated with iron deficiency in 57% of cases and with folate deficiency in 5%. Correlations between maternal and newborn iron and folate indicators were found. This study points out the necessity for developing strategies in African countries to combat nutritional anemias during pregnancy by specific measures combined with general strategies.

Adolescent

Effects of the increasing consumption of dairy products upon iron absorption.

The effect of the increasing consumption of dairy products upon the iron absorption was tested in vivo on volunteers using the extrinsic tag method (with 55 Fe and 59 Fe). The total iron absorption coefficient of a typical French meal and of the same meal after addition of a glass of low-fat skimmed milk or plain yoghurt was measured. Non-heme iron absorption was 2.2% for the standard meal alone, 2.0% with the yogurt and 2.1% with the glass of milk. Total iron absorption (i.e. measured non-heme iron absorption plus estimated heme iron absorption) for the three meals was, respectively, 9.7%, 9.5% and 9.4%. These results suggest that, under real-life conditions, increasing the amount of dairy products probably has no effect upon iron absorption in meals containing appreciable amounts of dairy products.

Adult

[The value of erythrocytic protoporphyrin measurement for screening blood donors for iron deficiency: a decision analysis].

Blood donors are considered as a group with increased risk of iron deficiency. Therefore it seems particularly useful to have a simple screening test at one's disposal in blood centers to detect easily early iron deficiency. Erythrocyte protoporphyrin assay on an hematofluorometer is very easy and of a low cost. So we studied its diagnostic value on a sample of 285 blood donors (131 men and 154 women). Prevalence of iron deficiency, defined by the coexistence of, at least, two abnormal indicators (serum ferritin, transferrin saturation, erythrocyte protoporphyrin, mean corpuscular volume), was 5.6% in this sample; sensitivity of erythrocyte protoporphyrin used alone was 75% and its specificity was 91.5%. We used a decision analysis to evaluate the opportunity of screening with this test, accompanied where indicated by iron supplements. The results, though preliminary, suggest that erythrocyte protoporphyrin measurement could be of interest in screening blood donors for iron deficiency.

Adolescent

[Dietary intake of a representative sample of the population of Val-de-Marne: I. Contribution of diet to energy supply].

Dietary intakes and its nutritional value were assessed during a nutritional survey performed in a population living in a district in the Paris area (Val-de-Marne). Data were obtained from 1108 subjects, aged 6 months to 97 years, randomly selected from the telephone directories of 12 of 47 towns and cities in the district. Dietary intake was evaluated in individual home interviews conducted by specialized dietitians, using the dietary history method. Age appears to be an important determining factor in variations in nutritional intake. Large differences exist between men and women for most types of food consumption. But the relative contribution of the main groups of food groups to the structure of energy intake is very similar in both sexes and virtually constant in the different age groups after the age of 6.

Adolescent