[Adolescence yesterday and today: care issues]. / L'adolescenza ieri e oggi: aspetti assistenziali.

In ancient Greece, the chronological boundaries of the stages of life hinged upon Solon's theory of human life as divided into ten seven year stages. At the peak of Latin civilization, the chronological limits of the infant, pueritia and adulescentia were respectively 0-8 years, 8-16 years and 16-17 years, when in a ceremony the adolescent (a term derived from adolescente (m) present participle of the Latin verb adolescere = to grow) wearing the "toga of manhood" is declared an adult (teenager adult) and up to 30 years later iuventus. Throughout the following centuries, the chronological boundaries of the various ages came to acquire only a theoretical worth, since the child, once introduced to the world of work, used to suddenly become an adult. Only in the wave of Humanism in the XVI-XVII century, people started to rediscover the Greek 'paideia' (education), the Latin Humanitas' (recognition and respect towards manhood in every man), and, through the Christian 'caritas' (to recognize and to love the son of God in every man) begins a moral vision of childhood, of his weakness and innocence, a reflection of the 'divine purity'. In this evolution, the twentieth century identifies itself with adolescence, so that history moves from an era devoiced of adolescence to an age in which adolescence appears to be the privileged age: the adolescent is the hero of the twentieth century. Several and many important institutions have proceeded to recognize the essential rights of adolescent care in pediatric departments, but many are still admitted to adult wards with suboptimal therapeutic results, particularly for blood-cancer. The pediatrician, both the family one and the one in the hospital, must be the referees for the health of the adolescent, especially in cases of chronic diseases or in those of psychosocial relevance, following her in the path of the disease especially if other specialists are involved with a view to further investigation, and establishing, since early childhood, communication, dialogue and compliance with her and the whole family. One of the greatest philosophers and sophists of Magna Graecia, Gorgia of Lentini, used to state that the word has tremendous power: it can instill the joy, eliminate pain, enhance compassion, put an end to fear: then be medicine for the suffering. The doctor is in fact, in certain situations of life, a drug for his patient. He is the most widely used drug because drugs are not the only thing that matters: the soul of medicine lies in the relationship, in the communication between the healer and the healed.

[The role of eggs in the diet: nutraceutical and epigenetic aspects]. / Il ruolo delle uova nella dieta: aspetti nutraceutici ed epigenetici.

The use of eggs in human diet has been object of many prejudices which are not yet completely disappeared The evolution of knowledge in the field of nutrition has, partially, countered these prejudices by highlighting the biological importance of several compounds present in the eggs. The nutritional and commercial revaluation of the eggs are passed through the enrichment of the lipid fraction in omega3 polyunsaturated fatty acids (PUFA omega3) which, have shown positive effects against cardiovascular diseases and development of the central nervous system and retina. The enrichment of eggs lipid with omega3 fatty acids is carried out by the integration of feeding hens with oils rich in omega3 fatty acids such as plant or marine oils. The results showed that the accumulation of omega3 in the egg yolk lipids is strongly affected by the type of oil used as supplement and by the amounts of oils administrated to the hens.

[Proper antibiotic therapy. From penicillin to pharmacogenomic]. / Terapia antibiotica appropriata: dalla penicillina alla farmacogenomica.

Antibiotics have always been considered one of the wonder discoveries of the 20th century. The use of penicillin by Flaming, opened up the golden era of antibiotics and now is hard to imagine the practice of medicine without antibiotics. Life-threatening infections, such as meningitis, endocarditis, bacteremic pneumonia sepsis, would again prove fatal. Also aggressive chemotherapy and transplant procedures would prove impossible. Another real wonder has been the rise of antibiotic resistance soon after the clinical use of penicillin in hospitals and communities. Several study demonstrated an excessive amount of antibiotic prescribing for communities patients and inpatients and in some hospital up to 50% of antibiotic usage is inappropriate: the benefits of antibiotic treatment come with the risk of antibiotic resistance development. In hospitals, infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. A variety of strategies has been proposed to reduce the cost and improve the quality of medication use. Education, guidelines and evidence based recommendations are considered to be essential elements of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies. Evidence-based recommendations, an approach to clinical practice helping to make decisions based on clinical expertise and on intimate knowledge of the individual patient's situations, beliefs, and priorities, enhance antimicrobial stewardship, that include appropriate selection, dosing, route, and duration of antimicrobial therapy can maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost. These evidence-based guidelines are not a substitute for clinical judgment, and clinical discretion is always required in their application. Genome studies have identified hundreds of genetic polymorphism important determinants of the efficacy of therapy and several trial demonstrated the successful use of pharmacogenomic testing to reduce the incidence of hypersensitivity reactions in patients. Knowing the phenotype of a patient prior to therapy, optimal dose and type drugs can be prescribed to achieve better management of patients.

[The essential fatty acids omega-6 and omega-3: from their discovery to their use in therapy]. / Gli acidi grassi essenziali omega-3 ed omega-6: dalla loro scoperta alle prospettive terapeutiche.

In 1929 Burr and Burr discovered the essential fatty acids omega-6 and omega-3. Since then, researchers have shown a growing interest in unsaturated essential fatty acids as they form the framework for the organism's cell membranes, particularly the neurones in the brain, are involved in the energy-transformation process, regulate the information flows between cells. Polyunsaturated fatty acids are also precursors of ''hormonal'' molecules, often with opposing effects, prostaglandins, prostacyclins, thromboxanes, leukotrienes, lipossines, resolvines, protectines that regulate immunity, platelet aggregation, inflammation, etc. They showed that raised levels of polyunsaturated fatty acids omega-3 in tissue correlate with a reduced incidence of degenerative cardiovascular disease, some mental illnesses such as depression, and neuro-degenerative diseases such as Alzheimer's. The balance between omega-3 and omega-6 acids allows the cell membranes to develop with exactly the right flexibility and fluidity, to carry messages between neurones, that is a determining factor in physical and mental well-being and has a profound influence on all the body's inflammatory responses. The results of a number of scientific studies suggest that omega-3 acids contribute to measuring and restricting inflammatory symptoms, whereas omega-6 acids (and saturated fats) give free range to inflammatory responses and amplify allergic reactions. Today in the Western countries, the ratio of omega-3 acids to omega-6 in the diet is weighted 1:10 in favour of omega-6 to up to 1:25 in some areas, while for proper functioning a 4:1 ratio of omega-6 acids to omega-3 acids is generally considered the optimum. In addition, the type of diet followed in the Western countries is very rich in saturated fats like butter and animal fats, but because of an excessive supply of these less noble fats, the cell membranes lose flexibility and this can affect the way they work. An appropriate supplement can be an efficient, effective and often necessary way to meet the body's needs, enhance its daily functions and promote health and longevity.

[Omega-3: from cod-liver oil to nutrigenomics]. / Omega-3: dall'olio di fegato di merluzzo alla nutrigenomica.

The leading role of cod-liver oil on rickets was a relevant factor in the knowledge of this disease. In 1922 the preventive and therapeutic value of cod-liver oil and sunlight against rickets in young infants was confirmed. The seasonal variation in the incidence of rickets, the role of skin pigmentation, of diet and the fact that breast milk was not an adequate source of vitamin D were understood. The discovery of essential fatty acids omega-6 and omega-3 have shown that deficiencies, mainly of omega-3 long chain polyunsaturated fatty acids, result in visual and cognitive impairment and disturbances in mental functions in infants and also in cognitive function in adults, as fatty acids are beneficial to vascular health and may forestall cerebrovascular disease and thus dementia. An adequate ratio of n-6 and n-3 fatty acids may promote a healthier balance of eicosanoids, which would protect membrane function with a nutraceutical function. Dietary lipids not only influence the biophysical state of the cell membranes but, via direct and indirect routes, they also act on multiple pathways including signalling, gene and protein activities, protein modifications and they probably play important role in modulating protein aggregation. Significant advances have been made in understanding the relation between dietary factors and inflammation, which is a central component of many chronic diseases, including coronary artery disease, rheumatoid arthritis, cancer prevention. However, the identification of those who will or will not benefit from dietary intervention strategies remains a major obstacle. Adequate knowledge about how the responses depend on an individual's genetic background (nutrigenetic effects), the cumulative effects of food components on genetic expression profiles through nutrigenomics mechanism, may assist in identifying responders and non-responders. Thus, fish and fish oil consumption might encourage brain development and gene expression to brain maintenance during aging through nutrigenomic mechanism.

[Virgin olive oil. From legend to scientific knowledge of the nutraceutical aspects]. / L'olio extra vergine d'oliva. Dalla leggenda al razionale scientifico degli aspetti nutraceutici.

Proper nutrition has been considered the basis of good health since ancient times. Hippocrates (460-377 BC), father of modern medicine in the western world, claimed that "good health implies an awareness of the powers of natural or processed foods", the Salernitan School (eleventh-twelfth centuries) maintained that "the doctor must observe what food consists of, how much, and when it must be eaten", while Leonardo da Vinci (1452-1519) believed that "a man's life depends on what he eats". We know that lipids are important in nutrition and extra-virgin olive oil plays a predominant role in this field, recognised for its high levels of monounsaturated fatty acids. An example of a "nutraceutic" or "functional" food right from infancy, it is one of the best medicaments for delaying aging, and is also a good source of phytochemicals including polyphenolic compounds, squalene, alpha-tocopherol, carotenoid that may contribute to its overall therapeutic characteristics. An integral ingredient of the Mediterranean diet, extra-virgin olive oil has always been considered a middle road between food and medicine and there is growing evidence that its health benefits include reduction of coronary heart disease risk factor, prevention of several types of cancer, and the modification of immune and inflammatory responses. The origins of the olive tree date back to the Eneolithical era, or Copper Age, in the sixth millennium BC. Having first appeared in Italy during the Bronze Age, the fruit and oil of the olive tree were widely used in nutrition, medicine, art, literature, and daily life during the Etruscan and Roman civilisations, and throughout the Middle Ages and Renaissance. Mysteriously entwined with our own history, the olive tree has a human shape, strong, resilient, tenacious, filled with fruit, but also wounded, suffering and moving. Well-grounded reasons exist for considering olive oil the best nutritional gift we can offer ourselves as it preserves good health, improves the quality of our life and also makes it more enjoyable.

Fatty acids composition of plasma phospholipids and triglycerides in children with cystic fibrosis. The effect of dietary supplementation with an olive and soybean oils mixture.

Cystic fibrosis (CF) is characterized by abnormal levels of essential fatty acids (EFA) in plasma phospholipids. The reduced availability of EFA has been reported to alter patterns of circulating and tissue esterified acids and may determine profound changes in membrane fluidity and cell signaling mechanisms. In the current study, the results of a new strategy aimed at the realization of a practical, low cost integrator, for daily use in the dietary management of FC subjects, are reported. We investigated the plasma phospholipids and triglycerides fatty acids composition of CF patients subjected to a dietary supplement constituted of a mixture of 50% extra virgin olive oil and 50% soybean oil and studied the clinical effects of this supplementation. The study included fourteen young subjects, aged between 6 and 15 years, affected by cystic fibrosis, with pancreatic insufficiency and heterozygotes or homozygotes for the delta F508 mutation. The subjects were matched by age and randomly assigned to either an oil mixture supplemented (OM) group (n = 7), or to a control (C) group (n = 7). In contrast to the control group, the patients with supplemented diet achieved significant increases of the relative amount of C18:1 in the triglycerides as well as a significant decrease in saturated fatty acids (C 16:0, C 17:0, C 18:0, C 22:0). Moreover, the ratio between LA acid and AA significantly increased in the triglycerides of the OM group. In the phospholipids of the OM group, the relative amount of C 18:1 and of palmitic acid increased significantly whereas the relative amount of the most important polyunsaturated fatty acids (PUFA) decreased. These results show that oleic acid can be absorbed and incorporated into the plasma triglycerides of CF patients receiving pancreatic enzymes, whereas poor incorporation of LA occurs. Despite the reduction in the relative amounts of phospholipid PUFA, the supplemented subjects did not reported adverse effects There were no significant differences between groups in the clinical indexes recorded (height, weight, BMI, Schwachman-Kulczycki score and FEV 1s). The results of this study showed that the supplementation with a mixture of extravirgin olive and soybean oil was safe in seven CF patients treated during a 2-months period and no negative clinical effects were evident. However, further clinical trials will be necessary in order to better evaluate the consequence of the observed changes in plasma fatty acids composition in a longer testing period.

The efficacy of E.P.D., a new immunotherapy, in the treatment of allergic diseases in children.

A double blind study was made on a group of 35 children, 8 of whom were allergic to Grass and 27 allergic to Pteronyssinus and Farinae Dermatophagoides. We verified the efficacy and tolerability of a new immunotherapy called E.P.D. (Enzyme Potentiated Desensitization). This particular immunotherapy consists in an intradermal injection of a mix made up of an allergic solution at extremely low doses and an enzyme, beta-glucuronidase. The vaccine is administered once a year, two weeks before pollen peaks for children with seasonal allergies and two times a year, in February and November, for children with non-seasonal allergies (Dermatophagoides). The results, statistically analyzed on the basis of a symptoms score, showed good clinical efficacy in patients affected by both seasonal and non-seasonal allergies. Due to the clinical effectiveness, easy administration and excellent tolerability of the immunotherapy, E.P.D. is particularly suited for treating or reducing allergic symptoms in allergic children.

Role of the low zinc bioavailability on cellular immune effectiveness in cystic fibrosis.

An altered cellular immune response as a secondary phenomenon has been suggested to be probably involved in the bronchopulmonary infections by Pseudomonas aeruginosa in cystic fibrosis (CF). The difficulty to eradicate with modern anti-pseudomonal antibiotics the bronchopulmonary infections has led us to further investigate the possible existence of other cellular immune defects and their cause. Alterations in zinc turnover are present in CF. Zinc is relevant for good immune functioning. In particular, zinc is required to confer biological activity to thymulin (ZnFTS), a biochemically defined thymic hormone with a modulating action on cell-mediated immunity. The zinc-unbound form (FTS) is inactive and it can be unmasked by in vitro zinc addition to the plasma samples revealing the total amount of circulating thymulin (active + inactive). Marginal zinc deficiencies may prevent peripheral biological activation of active thymulin. Total zinc-saturable thymulin fractions in CF are similar to those observed in normal subjects, whereas the active quota is strongly reduced associated with concomitant high plasma levels of inactive thymulin compared to the values of healthy children (P < 0.01). A strict correlation exists between zinc and thymic hormone-saturable fraction (r = 0.87, P < 0.01) in CF. These findings suggest that the defect is not due to a thymic failure but to a reduced peripheral saturation of thymulin by zinc ions. This defect might depend on augmented plasma concentration of alpha 2-macroglobulin, which has a higher binding affinity for zinc than thymulin. T cell subsets are normal in CF. Reduced NK cell number and activity are present. Also, plasma IL-2 levels are reduced. The existence of positive correlations between zinc and IL-2 (r = 0.79, P < 0.01) and between zinc or active thymulin and NK activity (r = 0.70, P < 0.01 and r = 0.88, P < 0.01, respectively) suggest a close link among zinc failure, impaired IL-2 activity, low thymulin level, and reduced NK activity in CF patients with both normal and growth retardation. Although the role of NK cells is unknown in CF, a zinc supplementation, in order to induce a complete saturation of thymulin molecules, to correct some cellular immune defects and to improve the growth, may be suggested.

Efficacy and safety of pidotimod in the treatment of recurrent respiratory infections in children.

The activity of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was evaluated in a double-blind, placebo-controlled, randomized, multicentre trial, on 120 pediatric patients affected by recurrent respiratory infections. The clinical course of acute infections was favourable both in placebo and in treatment group, but recovery was quicker with pidotimod than with placebo. Antibiotic therapy and time of hospitalization were shorter in the patients taking pidotimod, and main symptomatic parameters (pharyngalgia, dysphagia, mucous membrane inflammation, adenopathy, anorexia) receded quickly. In patients receiving the drug as well as in placebo group changes in laboratory parameters, indicating recovery from the acute infectious events, were observed. A significant trend to normalization of the immune response, evidenced by chemotaxis and leukocyte phagocytosis index, was found only in patients treated with pidotimod. A significant decrease in the risk of relapses was observed in patients treated with pidotimod (35%), as well as a reduction of hospitalization (86%) and a decreased antibiotic therapy (47%). If a relapse occurred, the response of treated patients was quicker (fever, antibiotic therapy, hospitalization). These findings allow to correlate the individual immune response activation to the resistance to recurrent infections and also to a better response to therapy in case of clinically relevant disease. No side effects were observed. Only in 12 patients (5 pidotimod, 7 placebo) mild reactions were observed, but they were attributed to concomitant antibiotic treatment or other factors. No alterations in main laboratory parameters were seen.(ABSTRACT TRUNCATED AT 250 WORDS)