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The central role of T regulatory cells in the responses against harmless environmental antigens has been confirmed by many studies. Impaired T regulatory cell function is implicated in many pathological conditions, particularly allergic diseases. The "hygiene hypothesis" suggests that infections and infestations may play a protective role for allergy, whereas environmental pollutants favor the development of allergic diseases. Developing countries suffer from a variety of infections and are also facing an increasing diffusion of environmental pollutants. In these countries allergies increase in relation to the spreading use of xenobiotics (pesticides, herbicides, pollution, etc.) with a rate similar to those of developed countries, overcoming the protective effects of infections. We review here the main mechanisms of non-self tolerance, with particular regard to relations between T regulatory cell activity, infections and infestations such as helminthiasis, and exposure to environmental xenobiotics with relevant diffusion in developing countries.

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BACKGROUND AND AIM: Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. MATERIALS: Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin > or =10 mg/dL and at least one of the following: hepatic encephalopathy (HE) > or =II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin > or =5 mg/dL and HE > or =I grade for acute patients. RESULTS: MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. CONCLUSIONS: Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.

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BACKGROUND AND AIM: Oxidative injury occurs as a direct result of hepatitis C virus (HCV) core protein expression both in vitro and in vivo, and may be due to a direct effect on mitochondria. The ketoisocaproic acid (KICA) breath test is a simple, reliable, and noninvasive test to evaluate hepatic mitochondrial function. Albumin dialysis (MARS) is an effective bridge treatment for patients with acute failure superimposed on chronic liver disease. The aim of our study was to evaluate the improvement of mitochondrial function measured by KICA in patients undergoing MARS for acute-on-chronic HCV liver failure. MATERIALS AND METHODS: Five patients with HCV chronic infection undergoing MARS treatment for acute decompensation were enrolled. Before and after each MARS treatment, patients underwent blood testing for the main hematochemical parameters as well as for mitochondrial function by the KICA breath test and the arterial ketone bodies ratio (AKBR). RESULTS: MARS treatment effectively decreased the serum level of total bilirubin, bile acids, urea, and ammonium. Moreover, MARS treatment produced an increase in AKBR and in the cumulative percentage of (13)CO(2) recovered in exhaled air 2 hours after KICA ingestion. CONCLUSION: Liver mitochondrial function appears to be beneficially affected by MARS treatment.

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Among the different approaches for diabetes mellitus-pancreas and pancreatic islet transplantation-the use of stem cells represent a renewable alternative source of insulin-producing cells. Stem cells capable of differentiating into beta-like cells can be isolated namely from embryonic cells, bone marrow, and umbilical cord blood, but also from adult organs such as pancreas, liver, and spleen. Several studies have demonstrated that by manipulating culture conditions and using growth and transcription factors of beta-cell lineage (in particular pdx-1 and pax4), embryonic stem cells can differentiate in vitro after formation of embryoid bodies. Bone marrow stem cells can give rise to mesenchymal; endodermal-, and ectodermal-derived cells. In vivo it has been shown that after bone marrow transplantation, using a murine sex-mismatched model, insulin-producing cells expressing the Y chromosome can be detected in the donor pancreas, although not in a significantly number. Cells characterized by a group of markers (Nestin, CK-8, CK-18) and transcription factors (Isl-1, Pdx-1, Pax-4, Ngn-3) important for beta-cell differentiation have been detected in umbilical cord blood. The recent evidence of the possibility to transdifferentiate stem cells to beta cells encourages further studies in animal models to exhaustively determine the differentiation pathways of stem cells to insulin producing cells. These findings might open the way to a successful human investigation.

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BACKGROUND AND AIM: Tissue homeostasis and turnover require reserve stem proliferating cells. Several studies performed on immunodeficient animals have suggested a degree of plasticity by the hematopoietic stem cell compartment that may represent source for liver regeneration. We sought to explore the hepatic differentiation potential of hematopoietic stem cells from human cord blood, after toxic liver damage induced by allyl-alcohol in immunocompetent rats. MATERIALS AND METHODS: Wistar rats were divided into groups (A) allyl-alcohol intraperitoneal injection with hematopoietic stem cell intraperitoneal infusion at 1 day and sacrifice 3 days later; (B) stem cell injection and sacrifice 3 days later; (C) allyl-alcohol infusion and sacrifice 4 days later; and (D) sacrifice without any treatment. Livers, spleens, and bone marrows were analysed for human stem cells using flow-cytometry; livers were also tested by histology and immunohistochemistry to study the pattern of hepatic regeneration after damage and human stem cell conversion into hepatocyte-like cells, respectively. RESULTS: Flow-cytometry revealed selective recruitment of human hematopoietic stem cells by damaged livers (group A) compared with control group B. In addition, liver damage was reduced in animals treated with stem cells. Immunohistochemistry demonstrated that human stem cells could convert hepatic cells. CONCLUSIONS: Our study demonstrated that hematopoietic stem cells selectively recruited by injured livers can contribute to hepatic regeneration after acute toxic damage in immunocompetent recipients.

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Adult stem cells (ASC) have becoming a great domain of research by their promising interest for the regenerative medicine. For some years, the number of publications has been increasing, displaying the potential of ASC to differentiate in all tissue-lineages, challenging the previous dogma that ASC were restricted to give rise only to specific cells from their tissue of origin. Among the diversity of ASC, hematopoietic stem cells (HSC) have been the most studied and their use in the clinical setting is largely documented. Commonly, HSC have been harvested from the bone marrow, but for some years, two others sources, the peripheral blood and the umbilical cord blood have been introduced. All these HSC posses their own molecular characteristics and degree of maturity and represent a more or less good candidate to participate in the cellular-based tissue regeneration. We have reviewed the different parameters allowing to define which subset could be the more favorable such as the accessibility to the pool of HSC; the quantity of available cells; the tolerability of host-engraftment and the capacity of the cells to home correctly to the required site of damaged. Besides, recently, the molecular profiling of HSC has allowed identifying which subset posses the more promising characteristics.

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In Lazio region, in which Rome is located and 5,300,000 inhabitants live, an Information System has been started since 1999 to collect personal and clinical data of the admissions to Emergency Departments. The present work describes the fundamental aspects of the Region refund system for the emergency services made by the Emergency Departments. The article shows both the features of the information flow, on which the financial evaluation is based, and the fundamental steps of the regional deliberations for the years 2000 and 2001. We introduce the refund evaluations by 13 local health authorities (ASL) constituting the regional health service, for the years 2000-2001, and we point out the major problems related to calculation procedures. The total amount of emergency admissions in the region is 1,973,930 (year 2000) and 2,188,885 (year 2001). The evaluated charge for the region is 145,569,340 Euro (year 2000), and 170,004,718 Euro (year 2001).

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Occupational asthma is defined as variable airflow obstruction and airways hyperresponsiveness caused by exposure to agents present in the workplace. Low molecular weight agents such as isocyanates, aldehydes, anhydrides, colophony, dyes, persulphate, amines, acrylates and metals are steadily increasing as causative agents of occupational asthma. Isocyanates, aldehydes and anhydrides my cause sensitisation through an IgE mediated response in some workers. These agents act as haptens which combine with a carrier protein to form a complete antigen. Assays for the detection of specific IgE are standardized for very few agents and have a good specificity, but poor sensitivity. The diagnosis of occupational asthma relies not only on a suggestive hystory showing that asthma is caused or exacerbated specifically by work exposure, but in most cases needs to be confirmed by objective means. Combined monitoring of lung function parameters, such as peak expiratory flow rate at the work site and non specific bronchial hyperresponsiveness during and away from exposure, is necessary. The "gold standard" for confirming a diagnosis in an individual worker still remains the specific bronchoprovocation test, which has now reached a high degree of sensitivity, specificity and reproducibility for agents such a s isocyanates. In occupation asthma due to low molecular weight agents there are no individual risk factors which could predict the susceptibility to develop the disease. The primary prevention is based on appropriate interventions tn the workplace. The strict medical surveillance of workers may allow the early diagnosis and removal from further exposure in order to prevent morbidity and disability.

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Data on nickel immunomodulation are contradictory. The most consistent immune effects are suppression of immune responses. It has been shown that T-lymphocytes and NK cells are more susceptible to nickel toxicity than are B lymphocytes or macrophages. Data reported about cytokine production in human and nickel reactive T-cell clones are also conflicting. Some authors studied showed a higher synthesis of IL4, IL5 and IL13 but not of IFN gamma and TNFalpha in Ni allergic subjects. We found that the addiction on NiSo4 to the PBMC cultures of non sensitised subjects induces a reduction of release of IL5, IFN gamma and TNFalpha. Our studies demonstrate a clear difference in the NK cell activity between nickel-tolerant and intolerant individuals. In particular NK cell activity in reduced in sensitised patients respect to the normal subjects and the addition of Ni has immunotoxic potential. Researches are in progress in an Attempt to correlate the present data with other immune parameters and to measure the effects of a Ni Free diet on the immune system of subjects with Ni intolerance. The comprehension of the mechanisms inducing these changes requires further studies in the uptake and intracellular distribution and binding of the metal.

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Here, we report our experience on benzoate hypersensitivity. Drug and food additives are known to induce pseudo-allergic reactions such as urticaria, eczema, asthma and rhinitis. These reactions are often under-diagnosed, above all in allergic patients treated with additive containing drugs. On the contrary, attention to the additives present in some drug formulations and foods may often permit more correct diagnosis.

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