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Several studies suggest that the N/OFQ (nociceptin/orphanin FQ)-NOP (N/OFQ peptide) receptor pathway is involved in airway physiology. We previously demonstrated a modulation of the endogenous N/OFQ levels in allergen-sensitized mice. Here, we investigated the effects of NOP receptor activation in allergen sensitization using a murine model of allergen-induced airway hyperresponsiveness (AHR). BALB/c mice were intraperitoneally treated with the NOP receptor agonist UFP-112, either during the sensitization phase (30 min before ovalbumin administration) or at the end of sensitization process (15 min before bronchopulmonary reactivity evaluation). At day 21 from the first allergen exposure, bronchopulmonary reactivity and total and differential cell count in bronchoalveolar lavage fluid were evaluated. In a separate set of experiments cell proliferation in lymphocytes, cytokine levels, IgE serum levels, and the effect of UFP-112 on IL-13-induced AHR were evaluated. Pretreatment with UFP-112, during the sensitization phase, caused a significant reduction in allergen-induced AHR and total cell lung infiltration. No effect on allergen-induced AHR was observed when the treatment was performed at the end of sensitization process, on tissues harvested from OVA-sensitized mice and on IL-13-induced AHR. The in vitro proliferative response of lymphocytes was significantly reduced by pretreatment during the sensitization phase with UFP-112. This effect was paralleled by a significant modulation of cytokine secretion in pulmonary tissues and lymphocytes. In conclusion, we demonstrated a role for the NOP receptor and N/OFQ pathway in the AHR induced by allergen, probably through a modulation of the immune response that triggers the development of AHR that involves pro- and anti-inflammatory cytokines.

International audience; Self-Collimation (SC) [1] in Photonic Crystals (PhC) represents a new mean for achieving structure-less light confinement in optical devices - no typical confining mechanisms, like bandgaps or index guiding, being actually involved. However, it reveals to be quite constrictive in terms of degrees of freedom left for design. Recently, mesoscopic SC (MSC) in mesoscopic PhC (MPCs) [2] has loosen this design constrictiveness, extending the application range especially thanks to the possibility to combine SC with other desired optical features as slow light, controlled reflectivity [3] and microcavities with planar reflectors [4]. This contribution aims to achieve MSC even in arbitrary directions. Moreover this allows to obtain MSC even below the light line, neatly addressing the main drawback of the MPCs: out of plane losses due to the long mesoscopic period.

The use of probiotics in the form of whole bacteria to achieve health benefits in humans is evolving by the development of recombinant probiotic bacteria as carriers of specific genes achieving a probiotic effect. Studies have demonstrated that bacteria carrying either the gene for IL-10 or for trefoil factors when given in an animal model or as part of a human trial can ameliorate inflammatory conditions of the colon. Such an approach has the advantages of a long-term delivery, the potential for fewer side effects and utility in many other conditions including other autoimmune diseases, dental caries, candidiasis and allergies. Other health benefits are also under investigation in relation to altering the fatty acid composition of adipose tissue by colonizing the intestine with a bacterium carrying the gene involved in fatty acid metabolism. Not only is the lean body mass advantageously affected but the enzyme is active in inducing apoptosis in cancer cells. Benefits may also be obtained not only by adding a gene but deletion of a gene from a bacterium which modulates the production of pro-inflammatory cytokines or may make the probiotic bacterium act as a more effective delivery system by enhancing colonization

This study was performed on 36 obese subjects aged 8.5-17.4 yr, 14 boys and 22 girls (prepubertal: 5 boys and 5 girls [stage I, according to Tanner]; BMI: 35.5 +/- 1.4 [mean +/- SEM] and 35 +/- 1.3 respectively; pubertal: 9 boys and 17 girls [stage IV-V]; BMI: 36.2 +/- 1.8 and 36 +/- 1.5 respectively) before and after 8 weeks of a 1000 kCal/day diet. The responses of serum TSH and PRL to TRH (200 micrograms iv as a bolus) were evaluated as Area Under the Curve (AUC) and net increase in respect to basal values (delta TSH and delta PRL). Serum T4, fT4 and rT3 were assayed at the baseline and T3 and fT3 at the baseline and 120' after TRH injection. A similar analysis was performed on 14 age- and sex-matched lean subjects as controls. In females at baseline fT4 serum levels were greater than controls and were significantly reduced after weight loss; rT3 increased after weight loss in the whole study group. In patients of both sexes the PRL peak after TRH injection was earlier but not greater (15') than in controls (30'). After weight loss PRL peak after TRH was found at 30' (as controls) in females only. Taking into consideration the stage of pubertal development, the results were the following: a) in puberal girls, after weight loss, TSH and PRL peaks after TRH were delayed with respect to baseline and to the other considered subgroups; b) in prepubertal girls TSH and PRL peaks, delta TSH, delta PRL, AUC-TSH and AUC-PRL were blunted with respect to pubertal ones; c) the other considered variables were unchanged after the period of caloric deprivation. No correlation between BMI and the AUC of TSH and PRL was found. These data suggest that thyroid function is substantially normal in adolescent obese subjects and not influenced by a prolonged period of caloric restriction, even though a reduced hypothalamic dopaminergic tone on pituitary thyreotrophs and lactotrophs could cause subtle alterations on TSH and PRL release, partially influenced by gender and sexual development.

In questo articolo viene illustrata la possibilità di generazione di ceppi probiotici ricombinanti in grado di esprimere molecole con vantaggiose proprietà farmacologiche. Attraverso studi effettuati su modelli murini prima e su esseri umani poi è stato sperimentato l’uso di batteri geneticamente modificati per il rilascio di proteine terapeutiche nel trattamento continuativo delle malattie croniche intestinali a partire dal trattamento, con ceppi ricombinanti di Lactobacillus lactis, del morbo di Crohn, di malattie croniche intestinali, coliti acute e croniche. Sono altresì stati indagati gli effetti di molecole bioattive quali allergeni, enzimi digestivi e anticorpi a singola catena ottenuti usando batteri produttori di acido lattico in candidosi vaginali, carie dentali, allergie, malattie autoimmuni, tumori indotti da HPV e insufficienza pancreatica. La superficie cellulare del Lactobacillus acidophilus è infine stata utilizzata come potenziale strategia per il trattamento di patologie infiammatorie intestinali.

The current study was carried out to evaluate the influence of thyrotrophin releasing hormone (TRH) on melatonin secretion in healthy subjects. The study included 31 subjects of both sexes (prepubertal subjects: 15; pubertal subjects: 16). They were treated with TRH (0.2 mg i.v. as a bolus) with blood samples being collected at 0, 20, 60, 120, 180 min. after hormone administration; the results were compared with those of subjects infused with saline only. Serum levels of melatonin were measured with a double antibody RIA method. A significant increase in melatonin levels after TRH was seen only in the prepubertal females, with a peak at 120 min. On the contrary, no significant melatonin changes were seen in the prepubertal males or in either pubertal males and females. These results suggest the existence of sex- and age-related differences in melatonin responses to TRH in humans.