Rare PECAM1 variants in three families with lymphedema.

PECAM1 is a member of the immunoglobulin superfamily and is expressed in monocytes, neutrophils, macrophages and other types of immune cells as well as in endothelial cells. PECAM1 function is crucial for the development and maturation of B lymphocytes. The aim of this study was to link rare PECAM1 variants found in lymphedema patients with the development of lymphatic system malformations. Using NGS, we previously tested 246 Italian lymphedema patients for variants in 29 lymphedema-associated genes and obtained 235 negative results. We then tested these patients for variants in the PECAM1 gene. We found three probands with rare variants in PECAM1. All variants were heterozygous missense variants. In Family 1, the unaffected mother and brother of the proband were found to carry the same variant as the proband. Lymphoscintigraphy was performed to determine possible lymphatic malformations and showed that in both cases a bilateral slight reduction in the speed and lymphatic clearance of the lower limbs. PECAM1 function is important for lymphatic vasculature formation. We found variants in PECAM1 that may be associated with susceptibility to lymphedema.

Mediterranean diet and the prevention of non-alcoholic fatty liver disease: results from a case-control study.

OBJECTIVE: Few studies report that Mediterranean dietary (MD) pattern has a beneficial role in the progression of non-alcoholic fatty liver disease (NAFLD). Evidence on its potential effect on the onset of disease are, however, scanty. With our study, we evaluated whether MD affects the risk of NAFLD with a large case-control study performed in Italy. PATIENTS AND METHODS: Three hundred and seventy-one cases of NAFLD and 444 controls were questioned on the demographic data and their dietary habits before diagnosis. Additionally, information about lifestyles and other related diseases, such as hypertension and diabetes mellitus were collected. The MD adherence was assessed using a pre-defined Mediterranean Diet Score (MDS). Odds ratios (OR) and 95% confidence intervals (CI) were obtained using a multiple logistic regression model. RESULTS: A high adherence to the MD is significantly associated with decreased risk of NAFLD (OR: 0.83 95% CI: 0.71-0.98). When the different MD components were examined separately, higher legumes consumption (OR: 0.62 95% CI: 0.38-0.99) and high fish consumption (OR 0.38 95% CI: 0.17-0.85) were reported to be protective against NAFLD. CONCLUSIONS: Our study shows that a high adherence to the MD decreases the risk of NAFLD.

CYP26B1 and its implications in lymphangiogenesis: Literature review and study of rare variants in two families.

CYP26B1 is a member of the cytochrome P450 family and is responsible for the break-down of retinoic acid for which appropriate levels are important for normal development of the cardiovascular and lymphatic systems. In a cohort of 235 patients with lymphatic malformations, we performed genetic testing for the CYP26B1 gene. These probands had previously tested negative for known lymphedema genes. We identified two heterozygous missense CY-P26B1 variants in two patients. Our bioinformatic study suggested that alterations caused by these variants have no major effect on the overall stability of CYP26B1 protein structure. Balanced levels of retinoic acid maintained by CYP26B1 are crucial for the lymphatic system. We identified that CYP26B1 could be involved in predisposition for lymphedema. We propose that CYP26B1 be further explored as a new candidate gene for genetic testing of lymphedema patients.

Taste, olfactory and texture related genes and food choices: implications on health status.

OBJECTIVE: The food choices are due to a mixture of sensory signals including gustatory, olfactory, and texture sensations. The aim of this quality review was to update data about studies concerning genetics of taste, olfactory and texture receptors and their influence on the health status in humans. MATERIALS AND METHODS: An electronic search was conducted in MEDLINE, Pubmed database and Scopus, for articles published in English until December 2018. Two independent researches selected the studies and extracted the data. RESULTS: The review confirms the importance of inter-individual variations in taste, olfactory and texture related genes on food choices and their implications in the susceptibility to nutrition-related conditions such as obesity, dental caries, diabetes, cardiovascular disease, hypertension, hyperlipidemia and cancer. CONCLUSIONS: The knowledge of variants in taste, olfactory and texture related genes can contribute to the prevention of diseases related to unhealthy nutrition. Further studies would be useful to identify other variants in the genes involved in these systems.

Plasma amino acids of the transsulfuration pathway and plasma lactate in septic patients.

OBJECTIVES: In sepsis increasing plasma lactate, even if unrelated to hypoperfusion and hypoxia, is a cause of concern. Among the patterns associated with increasing lactate, several plasma amino acid (AA) abnormalities, more in particular those of sulfur AAs, have remained unexplored, and their assessment has been the purpose of our study. MATERIALS AND METHODS: A systematic and detailed analysis of 183 simultaneous determinations of plasma AA-grams and lactate, from 12 trauma surgery patients who had developed sepsis, was performed. Sepsis severity ranged from moderate to extreme illness. Correlations between changes in lactate and in AA levels were assessed by regression analysis. RESULTS: Increasing lactate was related to increasing alanine, proline, asparagine, tyrosine, cystathionine, histidine, glutamine, citrulline, methionine, phenylalanine and hydroxyproline (r from 0.62 to 0.36, p < 0.001 for all) and to decreasing taurine (r = -0.62, p < 0.001). Furthermore, increasing lactate was strongly related to increasing cystathionine/taurine ratio (r = 0.77, p < 0.001). These correlations were independent of the simultaneous relationship found between increasing lactate and decreasing mixed venous O2 tension. CONCLUSIONS: The overall findings and the correlation with the cystathionine/taurine ratio support the hypothesis that increasing lactate in sepsis may be paralleled by impaired hepatic AA transsulfuration. Because this may disable antioxidant protection by limiting glutathione and taurine availability, the metabolic perturbations associated with septic hyperlactatemia may include enhanced exposure to oxidative stress.

Nutritional support in acute pancreatitis: from physiopathology to practice. An evidence-based approach.

Acute Pancreatitis (AP) is a potentially fatal syndrome, associated with a hyper-catabolic state as well as early and late complications that may lead to multi-organ failure and death. Clinical researches produced in recent years suggest that acute pancreatitis may benefit from early oral or enteral nutrition. Nevertheless, many clinicians still believe erroneously that fasting - particularly in the early phase - may reduce AP complications and mortality. The goal of our review is to demonstrate that such false belief may harm the patients and that the whole management paradigm must change, adopting a more rational, evidence-based approach. First, we will describe AP physiopathology and the clinical assessment of its severity. Then we will discuss evidence-based data supporting early oral or enteral nutrition in AP. Finally, we will offer some practice recommendations as regards nutritional support.

Nutrition and IBD: Malnutrition and/or Sarcopenia? A Practical Guide.

Malnutrition is a major complication of inflammatory bowel disease (IBD). This mini review is focusing on main determinants of malnutrition in IBD, the most important components of malnutrition, including lean mass loss and sarcopenia, as an emerging problem. Each one of these components needs to be well considered in a correct nutritional evaluation of an IBD patient in order to build a correct multidisciplinary approach. The review is then focusing on possible instrumental and clinical armamentarium for the nutritional evaluation.

Frailty of Obese Children: Evaluation of Plasma Antioxidant Capacity in Pediatric Obesity.

Background: Obese children are subject to the same chronic oxidative and inflammatory stress, responsible for the onset of all the complications typical of adult age, such as insulin resistance, type 2 diabetes, dyslipidemia and cardiovascular disease. Objectives: Since few studies are reported in prepubertal obese children, we investigated the relationship between oxidative stress, body composition and metabolic pattern in childhood obesity in comparison with adult obese patients. Methods: We enrolled 25 prepubertal children (12 males and 13 females) aged 5-12 years with a mean value of standard deviation of BMI (SDS-BMI)±SEM of 1.96±0.09. We performed oral glucose tolerance test, hormonal and metabolic evaluation, bioimpedentiometry, evaluation of total antioxidant capacity using spectroscopical method using a radical cation, 2,2I- azinobis(3-ethylbenzothiazoline-6 sulphonate) (ABTS), as indicator of radical formation, with a latency time (LAG) proportional to antioxidant in the sample. Results: LAG values significantly correlate with % fat mass, waist circumference and waist/hip ratio. However mean LAG values were significantly lower than in obese adults. Conclusions: We suggest that children are more susceptible to oxidative stress than adults, possibly to incomplete development of antioxidant system. Prognostic and therapeutical implications need to be further investigated.

[Alcohol and work. Consensus Document of the La.R.A. (Workers representing a risk for others) group]. / Alcol e Lavoro. Documento di consenso del gruppo La.R.A.

AIM: Current Italian legislation obliges employers to prevent workers who are occupationally at risk or who perform jobs that may be hazardous for the safety or health of third parties from consuming alcohol. The LaRA Group undertook to assess whether the law fully safeguards the health and safety of both workers and third parties, without impinging upon the civil rights of workers. METHOD: A written document expressing agreement was produced following discussions between doctors, lawyers, bioethicists and social partners. RESULTS: There are gaps and inconsistencies in current laws; the differences in local and regional provisions prevent authorities from applying a single strategy at national level. There should be a change in existing rules under which the employer's obligation to enforce the ban on consumption alcohol in the workplace is enacted solely by the "competent" physician whose institutional role is to safeguard and promote health. Some occupational categories that are subject to a ban on alcohol consumption do not currently under-go health surveillance. For example, if road transport drivers are not exposed to a specific occupational risk foreseen under another law, they can be placed under health surveillance only in those regions where the local laws contemplate this type of control. In other cases, the practice of assessing the risk to third parties and providing for compulsory health surveillance in the Risk Assessment Document, is considered by some jurists to be a "consuetudo praeter legem" and therefore acceptable in a field not yet covered by a specific law, but to be "contra legem" or unlawful by other jurists. Moreover, the competent physician who uses a breathanalyser or tests for alcohol addiction faces an ethical dilemma, since by communicating the results to an employer or authorities responsible for the issuing of licenses, he may be violating his professional oath of secrecy. Furthermore, the emphasis placed on testing has induced companies and inspectors to overlook educational and rehabilitation aspects. It is essential to involve general practitioners, educators and specialist services in addressing the problems of alcohol abuse so as to inform/train, recover and rehabilitate. The few studies available indicate that the rules are poorly enforced and that non-compliance may go unobserved. CONCLUSIONS: The Group urges all employers to assess the risk for third parties caused by alcohol abuse and to devise a policy on alcohol. Controlling alcohol-related risks in the workplace calls for a better definition of the roles of Vigilance Bod-ies and Company Physicians together with a shift from a reactive to a proactive attitude of all the parties involved.

[Diet and nutrition in nephrolitiasis]. / Dieta e nutrizione nella calcolosi renale.

Nephrolitiasis is a frequent metabolic disease, with a high rate of recurrences. Epidemiological studies reveal that about 80% of all kidney stones are composed of calcium salts (75% calcium oxalate), while about 5% are pure uric acid. Urolithiasis is a multifactorial disease with several underlying disorders of metabolism: that is why diet is an important treatment, especially in the prevention of recurrences. Nutritional intervention is based on a high water intake, physiological calcium intake, modest sodium and animal protein restriction and vitamin C intake <2 gr daily. In case of diagnosed disorders of specific metabolic pathways, a low oxalate, low purine-diet should be advisable.

[Diabetes and diet revisited]. / Dieta e diabete: una rivisitazione.

In the treatment of diabetes the diet has an important role complementary to the pharmaceutical treatment. The diet must provide the right amount of nutrients and calories in order for the individual to reach and maintain the ideal weight, stabilize the blood glucose levels close to the norm, and attain an optimal lipid profile. The daily caloric intake is represented by 55-60% of carbohydrates with a preference for nutrients rich in fiber and with a low blood glucose index. Of the daily caloric intake 10% may include sucrose as long as it is consumed in the context of a balanced meal. A moderate use of fructose is allowed, and an increased intake of fiber is encouraged. The consumption of proteins represents about 10-15% of the daily caloric intake. A consumption close to the lower limits of the range (about 0,8 gr/kg of body weight) is required for diabetes patients with nephropathy, while a daily intake of 0,6 gr/kg of body weight is considered to be the malnutrition risk factor for lower levels. The total intake of fats required is < or = 30%, of which saturated fatty acids are less than 8-10% (with a further restriction to 7-8% for individuals with LDL cholesterol of > or = 100mg/dl and other cardiovascular risk factors), the polyunsaturated fatty acids less than 10%, and the monounsaturated fatty acids at 10-15% of the total caloric intake. The intake of cholesterol through the diet should be <300 mg/die and still lower (< 200 mg/die) for individuals with high levels of LDL cholesterol. Multivitamin supplements are recommended only for certain categories of diabetic patients that may be at risk of micronutrient deficiency. A moderate quantity of alcohol (5-15 gr/die) is allowed in the case of stabilized diabetes and lack of hypertrigliceridemia. Although the diet may determine a ponderal decrease of up to 10% of the initial weight, it is good to insert a correct nutritional program into a well defined behavioral program that, other than a reduced caloric intake, takes into consideration an increased energetic expenditure through physical activity.

[Nutritional genomics: toward a personalized diet]. / Nutrigenomica: verso una dieta personalizzata.

Nutrigenomics is the application of high-throughput genomics tools to the study of diet-gene interactions in order to identify dietetic components having beneficial or detrimental health effects. Nutrition becomes indeed one of the environmental factors influencing gene expression. We can consider nutrigenomics as a multidisciplinary science that comes after the human genome characterization and that put the genomic techniques besides the biochemical and epidemiological aspects, with the aim to understand the etiologic aspects of chronic diseases such as cancer, type 2 diabetes mellitus (T2DM), obesity, cardiovascular diseases (CVD), metabolic syndrome, etc. Nutrigenomics is linked to nutrigenetics, which studies the genetic basis of the different individual response to the same nutritional stimulus. This phenomenon arises from gene polymorphism. As a consequence genes are important in determining a function, but nutrition is able to modify the degree of gene expression. These are however theories only at an early stage, but a perspective in the change of dietetic intervention is emerging. A really personalized diet will be a diet considering the nutritional status, the nutritional needs based on age, body composition, work and physical activities, but also considering the genotype. The integration of all these information and in particular the ones arising from genomic, proteomic and metabolomic analyses will be useful to define the "nutritional phenotype".

[Metabolic response to food and diet in paediatric obesity]. / Risposta metabolica al pasto e dieta nell'obesità dell'infanzia.

Obesity has reached today epidemic proportions in industrialized countries with negative effects on children and adult's health, and excessive costs for society. Although genetics and ambient are surely implicated in determining the positive energy balance in the organism, to our known few has been written on the role of macronutrient (proteins, fats and carbohydrates) in diet, particularly in children, in the onset and develop of obesity. Children's eating patterns and habitudes have been hanged in the last years, so that there is an higher intake of PUFA (poliinsatured fat acids) and lower of MFA (monoinsatured fat acids), and an elevated density of carbohydrate in the diet. Considering the effects of macronutrients on body energetic metabolism , it is clear that in obese children there is an higher oxidation of exogenous carbohydrates and a lower oxidation of endogenous ones; this effect conducts in short term to an increment of tissue fat and to a consequent increment of body weight. High fat intake and fat oxidation influence the accumulation of fat mass rather over a long term in children. Fat oxidation is favourite also by the assumption of high glycemic index foods, that conducts to insulin-resistance. A low fat diet, rich in low glycemic index carbohydrates that can reduce hungry and avoid insulin resistance, acts together to a regular and aerobic constant physical activity, which helps fat mobilization from adipose tissue and from muscles, and can reduce insulin-resistance, so favouring weight loss.

[Vitamin K-controlled diet: problems and prospects]. / La dieta controllata in vitamina K: problemi e prospettive.

Different natural (phylloquinone and menaquinone) and synthetic (menadione) compounds carry out the same action of Vitamin K in the human body. Vitamin K is a substrate for the enzyme catalysing the posttranslational conversion of specific glutamyl residues to gamma-carboxyglutamyl residues in certain proteins connected with the coagulation (Factors II, VII, IX, X), the anticoagulation (Proteins C and S) and other organic functions (osteocalcin). Foods rich in Vitamin K (1/4) and the action of gut bacteria (3/4) can give rise to changes in Vitamin K status. Dietary factors, alterations of gut bacteria or/and troubles in the absorption of this vitamin can cause a lack, which at first interferes in the normal hemostatic function and later on it leads to modifications in the bone structure. Therefore, it is necessary to pay a lot of attention to dietary intake, adequacy, bioavailability, absorption and metabolism of Vitamin K and compounds with an action similar to it for understanding the signs of lack, choosing the most suitable therapy and managing accurately the coumarin-based oral anticoagulants.

[Diet, nutrition and bone health]. / Dieta, nutrizione e salute dell'osso.

Nutrition is an important "modifiable" factor in the development and maintenance of bone mass and in the prevention of osteoporosis. The improvement of calcium intake in prepuberal age translates to gain in bone mass and, with genetic factor, to achievement of Peak Bone Mass (PBM), the higher level of bone mass reached at the completion of physiological growth. Individuals with higher PBM achieved in early adulthood will be at lower risk for developing osteoporosis later in life. Achieved the PBM, it is important maintain the bone mass gained and reduce the loss. This is possible adopting a correct behaviour eating associated to regular physical activity and correct life style. The diet is nutritionally balanced with caloric intake adequate to requirement of individual. This is moderate in protein (1 g/kg/die), normal in fat and the carbohydrates provide 55-60% of the caloric intake. A moderate intake of proteins is associated with normal calcium metabolism and presumably does'nt alter bone turnover. An adequate intake of alkali-rich foods may help promote a favorable effect of dietary protein on the skeleton. Lactose intolerance may determinate calcium malabsorption or may decrease calcium intake by elimination of milk and dairy products. Omega3 fatty acids may "down-regulate" pro-inflammatory cytokines and protect against bone loss by decreasing osteoclast activation and bone reabsorption. The diet is characterized by food containing high amount of calcium, potassium, magnesium and low amount of sodium. If it is impossible to reach the requirement with only diet, it is need the supplement of calcium and vitamin D. Other vitamins (Vit. A, C, E, K) and mineral (phosphorus, fluoride, iron, zinc, copper and boron) are required for normal bone metabolism, thus it is need adequate intake of these dietary components. It is advisable reduce ethanol, caffeine, fibers, phytic and ossalic acid intake. The efficacy of phytoestrogens is actually under investigation. Some drugs may interfere with calcium and other nutrients and produce an unfavourable effect on bone health.

[Diet, nutrition and rheumatoid arthritis]. / Dieta, nutrizione e artrite reumatoide.

Rheumatoid Arthritis (RA) is a chronic inflammatory disease resulting in diarthrodial joints inflammation (particularly joints of hands, wrists, feet, knees, cubitus, ankles, shoulder, etc.) that is manifested by swelling and functional impairment. The associated complications, osteoporosis and cardiovascular disease, make RA important in public health terms. During the active phase of disease, elevated plasma concentrations of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and acute-phase proteins, lead to reduction of fat free body mass (FFM) with a loss mean of 15% of cell body mass (CM) and consequent reduction of muscle strength. The pharmacological therapy (non steroidal anti inflammatory drugs (NSAIDs), slow acting antirheumatic drugs and corticosteroids), have the potential to cause side-effects, such as gastrointestinal bleeding, bone loss beyond to increase the requirement of some nutrients and reduce their absorption. The diet may play role in the management of RA, particularly in alleviating the symptoms of the disease, combating the side-effects of therapy and reducing the risk of complications. The increase of the caloric and proteic intake is not sufficient to offset a increased metabolic rhythm and important proteic catabolism but a diet balanced may warrant an adequate intake of nutrients. The carbohydrates of the diet provide 55-60% of the caloric intake, the diet is normo-proteinic or hyper-proteinic in the active phase of disease, and lipids represent 25-30% of the caloric intake (saturated, monounsaturated, polyunsaturated fatty acids in the ratio 1:1:1). omega-3 fatty acids supplementation, in combination with reduction of fatty acids omega-6 and adequate intake of monounsaturated fatty acids induce improvement in symptoms and sometimes a reduction in NSAIDs usage. Proper antioxidant nutrients (Vitamin A, Vitamin C, selenium) may provide an important defence against the increased oxidant stress and a supplementation of folate and vitamin B12, in patients treated with methotrexate (MTX), reduce the incidence of side effects and offset the elevation in plasma homocysteine frequent in these patients. Calcium and vitamin D, in patients treated with corticosteroids, reduce the bone loss, while a supplementation with iron may prevent anaemia. Finally, elimination diets may be feasible therapy only in patients with positive skin prick test.

[Diet and management of degenerative diseases of the retina (retinitis pigmentosa)]. / Dieta e Vitamina A nel trattamento di forme "sensibili" di retinite pigmentosa.

Considerable progress has been made in the understanding and management of degenerative diseases of the retina. The dietetic intervention has been favourably proposed in the most common forms of retinitis pigmentosa, a condition potentially leading to blindness. Vitamin A has been shown to be effective in delaying progression of the disease. In these patients such treatment is the only possible therapy, to date, and a lifetime generous supplementation of retinol is advisable, together with a vitamin A-rich diet and/or a dietary supplement (e.g. carrot flour) or pharmacologic supplement of vitamin A. Supply of vitamin A in doses up to 25000 IU (7500 igr/day), even for several years, has so far proved safe from risk of occurrence of liver disease. A possible effect on hypercholesterolemia related to a very prolonged treatment in predisposed individuals can be avoided by using a special diet, particularly enriched with beta-carotene. Guidelines for preparing a diet, specially formulated to provide an elevated weekly supply of vitamin and/or its precursor (equal to 15000 IU or 5000 microg of RE, retinol equivalent) and to control possible risk factors related to dietetic manipulation (supply of fat lower than 30% of total calories, variable levels of cholesterol and polyunsaturated fatty acids n-3, n-6) are presented. As long as resolutive therapy is lacking, dietetic intervention plays a primary role, although underestimated, in the management of the patients suffering from retinitis pigmentosa. The diet is specifically characterized by presence of food with a high content of carotenoids, substances with a favourable and additive effect.

[Malnutrition detected by "bioelectrical status" of total and segmental body mass to nutritional management of patients]. / Rilevazione del tipo e grado di Malnutrizione con l'esame dello "Stato bioelettrico" della Massa Corporea Segmentaria e "a tutto corpo".

We examined 182 controls with Body Mass Index (BMI) between 20 and 25 kg/m2 and 246 hospitalised patients divided into 3 groups: the first one consisted of 70 severe malnourished with (BMI) < 20 kg/m2, the second one of 43 light malnourished with BMI between 20 and 25 kg/m2 and the last one of 133 obese with BMI > 25 kg/m2. The Resistance (Rs) and Reactance (Xc), with the Phase angle ((phi), are detected from total and segmental (Arm and "Trunk + Leg") body. We analysed electric parameters plotting them on 4 different graphs which reported the values of: 1) total Rs vs total Xc; 2) segmental Rs vs segmental Xc; 3) total Rs/height vs weight/ height; 4) total Xc/height vs weight/height. Rs and Xc were different in all groups: the severe malnourished patients (1st group) gave evidence of a paradoxical increase of Rs and a decrease of phi. The mean values decreased for the patient of the 2nd and 3rd group (the (phi reduced especially for the 2nd group). Referring to the segmental measures, "Trunk + Leg" biases total Rs and Xc much more than Arm. In addition the phi of "Trunk + Leg" is more similar to the total o than the Arm one. If compared with the total, this last one highly decreases in the patients of the 1st and 2nd group. We conclude that segmental bioelectrical values (Rs, Xc, phi) integrate the total one, because they allow to find out the correlation between total parameters and a specific body segment. Total and segmental Rs, Xc (and phi) values and segmental phi ratio are related to the malnutrition. The approach together with the analysis of the Graphics result to a prompt inspection of the individual bioelectrical status in subjects.

[Strategy for safe nutrition in swallowing disorders]. / Strategia per alimentazione sicura nei disturbi della deglutizione.

Swallowing deficits may affect the ability of patients to feed properly and sufficiently, therefore inducing malnutrition. In order to provide effective and durable treatment, a team of experts should evaluate the swallowing function of each individual patient. Treatment protocols must be carefully analyzed, and adapted to progression of the disease. We refer paradigmatically to patients with Huntington disease, although indications may be conveniently extended to other patients with impaired transit of food.

[Diet and chronic corticosteroid therapy]. / La dieta in corso di terapia corticosteroidea cronica.

Corticosteroid therapy is widely used in the acute and chronic treatment of different diseases, with consequent possible onset of typical side effects on multiple systems of the organism, including also energy metabolism and metabolism of water and minerals (sodium, potassium, calcium and phosphorus). Clinical signs, related to the type and dosage of the steroidal drug, may lead to secondary illnesses with variable degrees of severity, depending on proneness of the individual patient and on the underlying disease that motivated the treatment. The role of dietetic intervention in the management of a patient chronically receiving corticosteroid therapy is not ancillary, although often underestimated, its aim being the reduction of some long-term therapy related side effects, and the correction of major metabolic derangements. In particular, the diet shall be moderately rich in protein (1.5 g/Kg/day of proteins) and low in fat (< 30% of calories, obtained mostly from unsaturated fatty acids), based mainly on complex carbohydrates (80%), providing 50% of the caloric intake. Diet has to be specifically characterized by food containing little sodium and yielding high amounts of water, calcium, magnesium and potassium. Minor directions concern the reduced intake of ethanol and purines. The efficacy of supplementation with antioxidant vitamins (vitamin C and E) and selenium is currently under investigation.