Are the school prevention programmes - aimed at de-normalizing smoking among youths - beneficial in the long term? An example from the Smoke Free Class Competition in Italy.

Tobacco smoking by young people is of great concern because it usually leads to regular smoking, nicotine addiction and quitting difficulties. Young people "hooked" by tobacco maintain the profits of the tobacco industry by replacing smokers who quit or die. If new generations could be tobacco-free, as supported by tobacco endgame strategies, the tobacco epidemic could end within decades. Smoking prevention programmes for teens are offered by schools with the aim to prevent or delay smoking onset. Among these, the Smoke Free Class Competition (SFC) was widely implemented in Europe. Its effectiveness yielded conflicting results, but it was only evaluated at short/medium term (6 - 18 months). The aim of this study is to evaluate its effectiveness after a longer follow-up (3 to 5 years) in order to allow enough time for the maturing of the students and the internalization of the experience and its contents. Fifteen classes were randomly sampled from two Italian high schools of Bologna province that regularly offered the SFC to first year students; 382 students (174 participating in the SFC and 208 controls) were retrospectively followed-up and provided their "smoking histories". At the end of their last year of school (after 5 years from the SFC), the percentage of students who stated that they were regular smokers was lower among the SFC students than in controls: 13.5% vs 32.9% (p=0.03). From the students' "smoking histories", statistically significant protective ORs were observed for SFC students at the end of 1st and 5th year: 0.42 (95% CI 0.19-0.93) and 0.32 (95% CI 0.11-0.91) respectively. Absence of smokers in the family was also a strongly statistically significant factor associated with being a non-smoker student. These results suggest that SFC may have a positive impact on lowering the prevalence of smoking in the long term (5 years).

Lessons learned on the road to a smoke-free Italy.

In the face of strong and protracted opposition by the Tobacco Industry (TI) and its allies, Italy's national smoke-free legislation came into force in 2005 prohibiting smoking in all indoor public places and workplaces including offices, bars, and restaurants. Using internal TI documents made public through US litigation, we reveal the industry's nearly 40-year effort to influence health policy related to secondhand smoke, including attempts to block Italy's national smoke-free legislation. Strategies included manipulating hospitality groups and establishing front organizations, manipulating journalists and media, and manipulating the science and direct lobbying against smoking restrictions. The TI's extensive plan to thwart smoke-free efforts in Italy can be used to inform other countries about the industry's tactics and Italy's experience in overcoming them by ultimately implementing a comprehensive workplace smoke-free law.

Oestrogens regulate pituitary alpha2,3-sialyltransferase messenger ribonucleic acid levels in the female rat.

Follicle-stimulating hormone (FSH) is synthesized by the anterior pituitary gland in multiple molecular forms. Increased acidic/sialylated FSH charge isoforms are associated with conditions characterized by a low oestrogen output. In the present study, we analysed the dynamics of the changes in mRNA levels of the enzyme Galbeta1,3[4]GlcNAc alpha2,3-sialyltransferase (2,3-STase) (one of the enzymes that incorporate sialic acid residues into the FSH molecule) in intact and ovariectomized rats. The anterior pituitaries of 4-day regularly cyclic adult female Wistar rats were obtained at 1000 h on the days of pro-oestrus (P), oestrus (O), dioestrus 1 (D1) and dioestrus 2 (D2), at 0200 h, 1400 h, 1800 h and 2200 h on D1, at 1800 h on day of O and at 1000 h after 7, 14, 21, 28 and 45 days of oophorectomy performed on the morning of P. Total RNA was isolated from each gland and the 2,3-STase levels were measured by Northern blot hybridization analysis employing a 346-base pair cDNA probe encoding for a non-conserved amino acid sequence of the catalytic domain of the enzyme. Maximal levels of the enzyme mRNA were detected at 1000 h on D1; thereafter, they progressively decreased by 60% during the ensuing 24 h, reaching the lowest concentration values (26% of the maximally observed level on D1) at 1000 h on day of P and remaining unchanged during the morning of O. Administration of the potent oestradiol receptor antagonist ICI 182,780 at 1000 h on D1 completely reverted the time-dependent decrease in 2,3-STase mRNA levels observed during the afternoon of D1, whereas oestradiol benzoate administered at 1000 h on day of O significantly reduced the enzyme mRNA levels (to 21% of the levels detected in vehicle-treated controls). In ovariectomized rats, the alpha2,3-STase mRNA progressively increased from day 21 to day 45 post castration. Administration of oestradiol benzoate on day 28 after oophorectomy significantly reduced the 2,3-STase mRNA levels (to 36% of the levels detected in vehicle-injected controls); ICI 182,780 partially counteracted this oestradiol-mediated effect. The dynamics of these changes in 2,3-STase mRNA levels partially correlated with changes in the relative abundance of the FSH charge isoforms separated by preparative chromatofocusing of anterior pituitary extracts, particularly in glands obtained during the morning of P and O. These data demonstrate for the first time that pituitary 2,3-STase is a hormonally-regulated enzyme and that the changes in transcription and/or stability of its mRNA may be involved, in part, in the post-translational processing of the FSH molecule during certain physiological conditions.

The oestrogenic effects of gestodene, a potent contraceptive progestin, are mediated by its A-ring reduced metabolites.

Gestodene (17 alpha-ethynyl-13 beta-ethyl-17 beta-hydroxy-4, 15-gonadien-3-one) is the most potent synthetic progestin currently available and it is widely used as a fertility regulating agent in a number of contraceptive formulations because of its high effectiveness, safety and acceptability. The observation that contraceptive synthetic progestins exert hormone-like effects other than their progestational activities, prompted us to investigate whether gestodene (GSD) administration may induce oestrogenic effects, even though the GSD molecule does not interact with intracellular oestrogen receptors (ER). To assess whether GSD may exert oestrogenic effects through some of its neutral metabolites, a series of experimental studies were undertaken using GSD and three of its A-ring reduced metabolites. Receptor binding studies by displacement analysis confirmed that indeed GSD does not bind to the ER, whereas its 3 beta,5 alpha-tetrahydro reduced derivative (3 beta GSD) interacts with a relative high affinity with the ER. The 3 alpha,5 alpha GSD isomer (3 alpha GSD) also binds to the ER, though to a lesser extent. The ability of the A-ring reduced GSD derivatives to induce oestrogenic actions was evaluated by the use of two different molecular bioassays: (a) transactivation of a yeast system co-transfected with the human ER alpha (hER alpha) gene and oestrogen responsive elements fused to the beta-galactosidase reporter vector and (b) transactivation of the hER alpha-mediated transcription of the chloramphenicol acetyl transferase (CAT) reporter gene in a HeLa cells expression system. The oestrogenic potency of 3 beta GSD was also assessed by its capability to induce oestrogen-dependent progestin receptors (PR) in the anterior pituitary of castrated female rats. The results demonstrated that 3 beta GSD and 3 alpha GSD were able to activate, in a dose-dependent manner, the hER alpha-mediated transcription of both the beta-galactosidase and the CAT reporter genes in the yeast and HeLa cells expression systems respectively. In both assays the 3 beta derivative of GSD exhibited a significantly greater oestrogenic effect than its 3 alpha isomer, while unchanged GSD and 5 alpha GSD were completely ineffective. Neither 3 beta GSD nor 3 alpha GSD exhibited oestrogen synergistic actions. Interestingly, the pure steroidal anti-oestrogen ICI-182,780 diminished the transactivation induced by 3 beta GSD and 3 alpha GSD in the yeast expression system. Furthermore, administration of 3 beta GSD resulted in a significant increase of oestrogen-dependent PR in the anterior pituitaries of castrated rats in comparison with vehicle-treated animals. The characteristics of the 3 beta GSD-induced PR were identical to those induced by oestradio benzoate. The overall results demonstrate that 3 beta GSD and its 3 alpha isomeric alcohol specifically bind to the ER and possess a weak intrinsic oestrogenic activity, whereas unmodified GSD does not. The data contribute to a better understanding of the GSD mechanism of action and allow the hypothesis to be advanced that the slight oestrogenlike effects attributable to GSD are mediated by its non-phenolic, tetrahydro reduced metabolites.

[Bronchogenic cysts of the mediastinum]. / Le cisti broncogene del mediastino.

The case of a bronchial cyst found on the mediastinal carina whose early symptoms resulted from compression of the airways is reported. The clinical, pathogenic and diagnostic aspects of these often congenital cystic malformations of the mediastinum are discussed.