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Biomedical subjects

R Bernardini

Publications and source records attributed to R Bernardini.

At least 109 records · Page 6Linked to original sources

Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami.

Experimental evidence suggests that serotonin (5HT) is excitatory to the hypothalamic-pituitary-adrenal axis and that this effect involves activation of both hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH secretion. The present study was undertaken to examine the mechanism by which 5HT stimulates the central component of the HPA axis. To accomplish this we employed an in vitro rat hypothalamic organ culture system in which CRH secretion from single explanted hypothalami was measured by specific radioimmunoassay (IR-rCRH). All experiments were performed after an overnight (15-18 hr) preincubation. Serotonin stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped and the peak effect was observed at the concentration of 10(-9) M. The stimulatory effect of 10(-9) M 5HT was antagonized by the 5HT1 and 5HT2 receptor metergoline and by the selective 5HT2 receptor antagonists ketanserin and ritanserin. The muscarinic antagonist atropine, the nicotinic antagonist hexamethonium and the alpha-adrenergic receptor antagonist phentolamine, on the other hand, did not inhibit 5HT-induced IR-rCRH secretion. The specific 5HT2 receptor agonist 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped with peak of effect reached at the concentration of 10(-9) M. We also tested the ability of the 5HT agonist meta-chlorophenylpiperazine (m-CPP) and of the selective 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) to cause CRH secretion. Although both m-CPP and 8-OH-DPAT stimulated IR-rCRH secretion in a dose-dependent fashion, several differences were observed when their effect was compared to that of 5HT. These included a different shape of the dose-response curve, a lower maximal stimulatory effect and a different maximal stimulatory concentration. These findings suggest that serotonin stimulates CRH secretion by explanted rat hypothalami and that this effect appears to be mediated mainly through a 5HT2 receptor mechanism.

Animals↗

Radioprotective effects of the association thymopentin-interleukin-1 alpha in the C57BL/6 mouse.

We investigated whether thymopentin, a synthetic pentapeptide derivative of thymopoietin, could enhance the protective effect of interleukin-1 alpha when both administered prior to sublethal irradiation in the C57BL/6 mouse. Thymopentin (10 mg/kg/day/7 days) was injected intraperitoneally in groups of C57BL/6 mice. Then, interleukin-1 alpha was administered on day 7. Twenty hr later, all groups were given whole body sublethal irradiation of 750 rad by 60Co elements. In some groups of mice, treatment with thymopentin was continued for 1 week after irradiation. Efficacy of the combination treatment was assessed by evaluation of mortality, as well as by histologic examination of the brain, testis, bone marrow, heart and spleen. The combination of relatively low doses of interleukin-1 alpha (700 U) with thymopentin yielded a survival which was nearly that observed with interleukin-1 alpha (1000 U) given alone (about 100%). The optimal effect was observed in animals treated for 15 days with thymopentin, either in combination or alone. In addition, incidence and severity of histological lesions were also lower in animals with the some treatment schedule. Our results suggest that the combined treatment thymopentin-interleukin-1 alpha prevents radiation damage in the mouse.

Animals↗

Modulating effects of the synthetic thymic dipeptide pidotimod on the immune system in the aging rat.

We have investigated the in vivo and in vitro effect of pidotimod, a synthetic thymic-derived drug, on the immune response in young (2 month-old), and aging (24 month-old) Sprague-Dawley rats. We studied the effect of different doses of pidotimod on the responsiveness of both cultured peripheral blood lymphocytes and splenocytes to mitogenic stimuli, as well as on interleukin-2 production by peripheral blood lymphocytes after stimulation with interleukin-1 and phytohemagglutinin. Treatment with pidotimod in vivo as well as in vitro resulted in an increase of tritiated thymidine incorporation in both mitogen-stimulated lymphocytes and splenocytes from 24 month-old rats. Production of IL-2 from lymphocytes of 24 month-old rats was significantly increased in groups of animals treated with pidotimod. On the other hand, treatment with pidotimod did not influence the responsiveness of 2 month-old rat lymphocytes to mitogens, nor affected IL-2 production. Our results suggest a possible specific modulatory activity of pidotimod on the aging immune system.

Adjuvants, Immunologic↗

Cross-reactivity between IgE-binding proteins from Anisakis simplex and Dermatophagoides pteronyssinus.

An association was found between Anisakis simplex (As) and Dermatophagoides pteronyssinus (Dp) sensitization. One recent study shows a cross-reactivity between As and Dp and tropomyosin (tr)is suspected as being one of the proteins responsible of this cross-reaction. The aim of our study was: 1) to confirm the cross-reactivity between Dp and As; 2) to determine the importance of tr in this cross reaction. SDS-PAGE analysis of Dp and As (metabolic and somatic) extracts was carried out. Then an IgE immunoblotting test using serum from a patient who had specific IgE only to Dp and As and immunoblotting inhibition experiments using Dp extract and tr as inhibitors were performed. We found that patients serum reacted: 1) against larval As antigens with a molecular weight (mw) of 25 kilodalton (kD) and a mw > than 100 kD, 2) against various metabolic As antigens with a mw > than 100 kD, a mw ranging approximately from 35 to 50 kD, and a mw around 20 kD, and 3) against Dp proteins with mw between 35 and 55 kD. Preincubation of patient's serum with Dp extract caused the disappearance of reactivity against antigens with a mw > than 100 kD in both larval and metabolic As extracts and against proteins with mw ranging approximately from 35 to 50 kD in the metabolic As extract. Preincubation of patients serum with As extract caused the disappearance of reactivity against antigens with mw between 35 and 55 kD in the Dp extract. Pre-incubation of patients serum with tr did not induce any change in the immunoblotting profile. The results show that 1) cross-reactive components between Dp and As are some proteins with a mw ranging approximately from 35 to 50 kD and with a mw > than 100 kD, and 2) tr is not involved in cross-reactivity between As and Dp.

Adult↗

Biphasic anaphylactic reaction to Ketorolac tromethamine.

Ketorolac tromethamine is a recent injectable non-steroidal anti-inflammatory drug (NSAID) with analgesic properties approved for short-term pain management. In spite of its increasing use both in adults and children, relatively few allergic-like reactions have been reported. Reactions are often severe, and a death occurred following an intramuscular injection of ketorolac.

Adolescent↗

High intracytoplasmatic levels of Il-4 and Il-5 in a patient with Gleichs syndrome: case report.

Gleichs syndrome is characterized by recurrent localized angioedema, hypereosinophilia, elevated levels of IgM, rapid weight gain, itchy urticaria and fever. Little is known about the pathogenesis of this disease. Increased serum levels for IL5, IL6 and C5a have been reported before and during clinical exacerbations. In order to better understand the role of the T cells in Gleichs syndrome we analyzed the intracellular cytokine expression in CD3+ cells of a patient affected by the disease. As hypereosinophilia was documented, we asked whether IL-4 and IL-5 levels were increased, and the intracytoplasmatic expression of these Th2-cytokines was determined. The percentage of T lymphocytes (CD3-gated cells) of both CD8- and CD8+ phenotype expressing different cytokines showed an unusually high percentage of Th2-related cytokine (IL-4, IL-5 and IL-13) expressing T lymphocytes. The two new variants (myeloproliferative and lymphoproliferative) seem to account for hypereosinophilia in patients with hypereosinophilic syndrome (HES). In the lymphroliferative variant, the presence of a clonal CD3-CD4+ Th2 like lymphocyte secreting IL-4 and IL-5 in peripheral blood, may explain the hypereosinophilia and the hyper-IgE. In our study we show that the patient had a lymphoproliferative variant and her T cell had a Th2 type phenotype. Moreover, we suggest that Th2 lymphocytes may play a role in the pathogenesis of Gleichs syndrome. Further studies are needed to evaluate the possibility that a polyclonal aspecific activation of Th2 type cells can lead to hypereosinophilia, IgE production and the other manifestations typical of Gleichs syndrome.

Adolescent↗

Eosinophil cationic protein (ECP) and tryptase in the nasal lavage fluid (NLF) of children with grass pollen rhinitis: levocabastine effect.

This study was carried out to determine the concentrations of eosinophil cationic protein (ECP) and tryptase in the nasal lavage fluid (NLF) of 24 children (C) with grass pollen rhinitis as well as rhinitis symptoms before and after nasal provocation tests with or without a levocabastine (anti-H1 topical antihistamine) pretreatment. All C were monosensitized to grasses only. Twelve patients (Active Group = AG) were tested with a nasal provocation test with grass pollen (NPT) carried out by the insufflation of increasingly higher doses of an allergenic extract powder, while the other 12 patients (Placebo Group = PG) underwent just a nasal provocation test with lactose (placebo) (NPTp). The prechallenge NLF, obtained both before (C) and after (AG) levocabastine pretreatment, was compared to that obtained after periods of 2 and 24 hours postchallenge. In the AG, before and after levocabastine pretreatment, the tryptase concentrations had not significantly increased, whereas the ECP concentrations were found to be significantly higher (p < 0.05) in just the 24-hour postchallenge samples. In the PG the rhinitis symptoms were not induced by the NPTp and there was no significant change in either ECP or tryptase concentrations. In the AG a levocabastine pretreatment induced a significant increase (p < 0.05) in the cumulative allergen doses administered by the NPT. There was a reduction of the nasal symptoms in 7 patients, while in 3 subjects there was only a slight improvement, but in 2 subjects no effect was encountered. In conclusion this study shows that a levocabastine pretreatment before an NPT in patients with grass pollen rhinitis, outside the grass pollen season, induces a significant increase in the cumulative allergen doses (administered by the NPT) which provoked rhinitis symptoms but is not able to demonstrate any significant reduction in the ECP concentrations of the NLF.

Blood Proteins↗

[Pseudoallergies].

Pseudo-allergic-reactions (PAR) are clinical manifestations including urticaria, angioedema, conjunctivitis, rhinitis, asthma, and anaphylaxis. The prevalence of PAR ranges from 0.1% to 75% according to various studies. The pathogenetic mechanism of these diseases is not immunologically mediated. Food, additives, and drugs are the main responsibilities for PAR. The diagnosis of PAR is characterized by the absence of specific IgE for the suspected products. The absence of immunological mechanisms is confirmed by in vitro and in vivo tests. The treatment of PAR is similar to that of allergic diseases (antihistamine drugs, steroids, B2 agonists, epinephrine).

Humans↗

[Unusual reactions to food additives].

The most important symptoms caused by food additives are urticaria and angioedema, but rhinitis, asthma and gastrointestinal disturbances are also reported. Only seldom food additives have been shown to induce symptoms in other organs such central nervous system or joints and with a sparse objective evidence. In this study, we report two cases of unusual reactions to food additives (tartrazine and benzoates) involving mainly the central nervous system (headache, migraine, overactivity, concentration and learning difficulties, depression) and joints (arthralgias), confirmed with diet and double blind challenge. The possible pathogenetic mechanisms are also discussed.

Adolescent↗

[Preventive effect of thymomodulin in recurrent respiratory infections in children].

Recurrent respiratory infections (RRI) are a common occurrence in early childhood. Several investigations report the primary role of environmental factors (as early social mixing and passive smoking) in inducing RRI. In RRI children immunological defects, transient and not typical, have been often observed, but it is reasonable to suppose that they are essentially secondary to infections. Since immune modifications involve essentially cell-mediated immunity, several therapeutical attempts with thymic hormones have been carried out. In the present study the efficacy of thymomodulin was evaluated in a clinical trial in a group of children with RRI. Forty-six children suffering from RRI were enrolled on the basis of RI number in the previous year. Twenty-three children were treated with thymomodulin, twenty-three were not treated and were studied as control group. A significant reduction in the frequency of RI was noted only in treated children. Interleukin-2 production was assayed in all children before and after the trial, but not significant modification was observed in this immunological parameter. This study confirms the effectiveness of treatment with thymomodulin in RRI children, even though immunological background of clinical improvement remains to be elucidated.

Child↗

[Radiologic examination of the paranasal sinuses in asthmatic children].

We examined the prevalence of abnormalities found by sinus X-Rays in 80 asthmatic children classified into three groups in relation to severity of their symptoms. All the children underwent skin tests and some of them methacholine challenge. 63.7% of asthmatics showed abnormalities in sinus X-Rays. No correlation was found between the severity of asthma, radiographic findings, and atopic status. Bronchial hyperreactivity studied using metacholine challenge according to the method of Chai was the same both in patients with asthma and sinusitis and in those with asthma only. In conclusion, abnormal sinus X-Rays do not seem to be an aggravating factor in asthmatic status.

Asthma↗

[Bronchial response to a provocation test in children allergic to Dermatophagoides pteronyssinus].

Bronchial provocation tests with allergens are becoming recognized as one of the most important diagnostic parameters for the detection and confirmation of the role of the allergic component directly on the reaction site. Twenty-seven children with positive skin tests and RAST for Dermatophagoides Pteronyssinus were challenged with solutions of the same antigen. Twenty-one (77%) had positive responses expressed by different patterns: Six (28.5%) showed isolated early reaction, seven (33.3%) had biphasic responses. Six (28.5%) showed dual response with prolonged (1-2 hours) late reaction. One child had dual late reaction after 35 hours (ultra-late reaction). Six (28.5%) patients had negative reactions. The results suggest that bronchial provocation tests with antigens performed as outlined in this study can also be applied in the diagnosis of pediatric allergy.

Adolescent↗

[Incidence of asthma caused by food allergy in childhood].

Both upper and lower respiratory tracts can be affected by food allergy. In infants these symptoms may be due exclusively to food allergy or may result from the effect of food allergy and another co-factor (gastro-esophageal reflux, immunodeficiency, concomitant allergy to inhalants, etc.). The incidence of food-induced asthma is not well know. In this study, using open and double blind food challenge, we found that the incidence of IgE-mediated, food-induced asthma in children is 5.7%. The most offending foods were milk, eggs, and peanuts. Food allergy respiratory symptoms were almost always associated with other clinical manifestations (cutaneous, gastrointestinal). In fact we have been able to demonstrate only one isolated case of cough due to food allergy. It follows that the recognition of food dependent-IgE-mediated asthma is essentially limited to these cases characterized by food allergy with asthmatic expression.

Adolescent↗

Effect of glutamine and nucleosides on prolactin secretion in the rat.

The effect of glutamine and some nucleosides (cytidine and uridine) on basal and stimulated prolactin release was investigated in vivo and in vitro. Acute injection of glutamine did not modify serum prolactin concentration, both in basal and stimulated conditions; conversely repeated administrations of the aminoacid significantly reduced (p less than 0.05) the prolactin surge which occurs at 04:00 p.m. in male rats as well as that induced by the injection of the dopamine antagonist sulpiride. The hypoprolactinemic effect of glutamine was significantly potentiated by uridine and cytidine, which per se were not effective. No significant change in prolactin release was observed when anterior pituitary glands were incubated in presence of the above mentioned drugs. However, repeated in vivo injections of glutamine, uridine and cytidine were able to potentiate the inhibitory effect of dopamine on prolactin release in vitro. These results suggest that both glutamine and the nucleosides cytidine and uridine may influence the activity of the hypothalamic-hypophyseal-prolactin axis, probably via an interference with endogenous neurotransmitters.

Animals↗