Lysosomal Acid Lipase Deficiency Leading to Liver Cirrhosis: a Case Report of a Rare Variant Mutation.

Lysosomal acid lipase deficiency is a poorly diagnosed genetic disorder, leading to accumulation of cholesterol esters and triglycerides in the liver, with progression to chronic liver disease, dyslipidemia, and cardiovascular complications. Lack of awareness on diagnosis of this condition may hamper specific treatment, which consists on enzymatic replacement. It may prevent the progression of liver disease and its complications. We describe the case of a 53-year-old Brazilian man who was referred to our center due to the diagnosis of liver cirrhosis of unknown etiology. He was asymptomatic and had normal body mass index. He had dyslipidemia, and family history of myocardial infarction and stroke. Abdominal imaging tests showed liver cirrhosis features and the presence of intrahepatic calcifications. Initial investigation of the etiology of the liver disease was not elucidated, but liver biopsy showed microgoticular steatosis and cholesterol esters deposits in Kuppfer cells. The dosage of serum lysosomal acid lipase was undetectable and we found the presence of a rare homozygous mutation in the gene associated with the lysosomal acid lipase deficiency, (allele c.386A > G homozygous p.H129R).

[Italian Program for Surveillance of Acute Pesticide-Related Illnesses: cases identified in 2005]. / Sistema di Sorveglianza delle Intossicazioni Acute da Fitosanitari: la casistica rilevata nel 2005.

In 2005, the Italian System for Surveillance of Acute Pesticide-Related Illnesses (SIAF) identified 625 cases, among which 520 unintentionally exposed. The majority of these subjects were men (75%) and aged 26-65 years (65%). About 63% of all exposures occurred at work. Severity for these illnesses was low for 94% and moderate for 5%. Four cases were classified as illnesses of high severity. Some 70% of all the reported exposures occurred between May and September. The active ingredients responsible for the largest number of cases were: glyphosate (n. 56), copper sulphate (n. 55), methomyl (n. = 52), metam-sodium (n. 24). Three episodes of collective environmental exposure to soil fumigants involving 23 subjects were also detected.

Recent experimental data on Extremely Low Frequency (ELF) magnetic field carcinogenic risk: open questions.

The NTP experimental studies on Extremely Low Frequency (ELF) magnetic fields (two-year studies in rats and mice and magnetic field promotion/DMBA initiation in female rats studies, NTP 1999) are of main interest because of the value and completeness of the information produced on neoplastic and non-neoplastic effects. Ajoint evaluation of the two-year study data indicates a thyroid C-cell focal hyperplasia increase in female rats at the same exposures at which the neoplasm increment of the same cells has been observed only in male rats (on which the "equivocal evidence" NTP classification is based). The significant exposure-related trichoepithelioma and trichoepithelioma plus other skin neoplasms reported for male rats in the two year studies finds some support in the female rat data relative to trichoepithelioma reported in incidence summary of the NTP 26-week initiation/promotion study, even if the experimental designs of the two studies are different. An indication of exposure-related increase of single mammary carcinomas emerges from the summary of neoplasm incidence, together with a dose-related decrease of mammary gland multiple carcinomas. A significant decrease of lung alveolar/bronchiolar adenoma incidence was observed in exposed groups in both mouse genders. It seems improbable to attribute the above effects only to chance. The present debate, dividing science in two opposite fields: one of them denying any appreciable carcinogenic effect of magnetic fields, and the other one hypothesising their dramatic effects, are presently devoid of reliable and exhaustive scientific support, which could only be provided by further research.

Classifications for carcinogenesis of antitumoral drugs.

The aim of this review is to support the medical staff engaged in tumor therapy with the carcinogenicity, mutagenicity, developmental toxicity classification of a large number of chemiotherapic drugs by national and international Agencies; it also gives their rationale and the few cases for which the classification varies among, for example, the European Union and the United States of America. A large list of such drugs, producers, commercial names, CAS numbers and chemical names is reported. This list is subject to changes for the quick development in this field: many drugs are retired and many more are introduced in clinical practice. The list is updated to the summer 2003 and retains many drugs which have more than one use or have limited use. The protection of the medical personnel using antitumor chemiotherapics can need retrospective epidemiological investigations and obsolete drugs are of importance for some of the past exposures.

[Vinyl chloride and 1,2-dichloroethane: classification and assessment of carcinogenicity, guidelines, threshold values, and standards developed by national and international entities, organizations, and agencies]. / Vinile cloruro e 1,2-dicloroetano: classificazioni e valutazioni di cancerogenità, linee guida, valori limite e standard emessi da enti, organismi e agenzie nazionali e internazionali.

International, national and regulatory classification, evaluation, guidelines and occupational exposure values regarding vinyl chloride and 1,2-dichloroethane, carried out by European Union (EU). Environmental Protection Agency (US EPA), International Agency for Research on Cancer (IARC), Italian National Advisory Toxicological Committee (CCTN), Occupational Safety and Health Administration (OSHA), World Health Organization (WHO), National Institute for Occupational Safety and Health (NIOSH), American Conference of Governmental Industrial Hygienists (ACGIH) and other institutions, have been considered with particular reference to the carcinogenic effects. Moreover information is reported in support of classification and evaluation and a short historical review since early 1970s, when first evidence that occupational exposure to VC could lead to angiosarcoma was published.

Risk assessment of complex mixtures: some considerations on polycyclic aromatic hydrocarbons in urban areas.

The comparative examination of experimental and epidemiological data, together with risk evaluations concerning coke-oven, diesel, and gasoline motor emissions, as well as specific PAH fractions and single PAHs, indicates that, at least under risk additivity hypothesis, benzo(a)pyrene (B(a) may account for only a relatively small amount of the whole carcinogenic potential of PAH mixtures. This finding emerges from the comparison of risk evaluations of coke-oven and diesel emissions (based on epidemiological and/or experimental data) with risk evaluations of B(a)P as a single substance (based on carcinogenic bioassay data), as well as from the results of experimental studies evaluating the carcinogenic potency of motor exhaust condensates, of specific condensate fractions (particularly, the 4-7 ring PAH fraction), and of B(a)P. These data indicate that B(a)P might account for a percentage of the whole mixture carcinogenic response, at least in the hypothesis of an additive effect of PAHs. However, the overall carcinogenic response and risk still appear at least approximately related to the B(a)P concentration in the examined PAH mixtures. Finally, recent findings on PAH relative potencies (compared with B(a)P potency) indicate that several PAH present in mixtures commonly detected in occupational and in the general environment are characterized by a carcinogenic potency comparable with or even higher than that of B(a)P. This confirms the above hypothesis with respect to the significant, but minor role, of B(a)P. This relatively coherent picture appears to confirm that the reference to B(a)P as a complex mixture index may still represent a reasonable solution. However, the selection of a few other indicators from among the PAH whose relative concentrations and relative carcinogenic potencies are higher might improve the analysis.

Crude oil spill in sea water: an assessment of the risk for bathers correlated to benzo(a)pyrene exposure.

In the spring of 1991, there was a shipwreck of the oil tanker "Haven" off the Ligurian coast of Italy. This resulted in the spillage of a very large amount of crude oil, some of which was burned off by fire. The accident caused several serious problems (sea and air pollution, damage to the marine fauna, risk of human exposure, etc.). In this context, an assessment was carried out at the Istituto Superior di Sanità with the aim of determining any possible risks to humans which might derive from bathing activities during the following summer season. The whole evaluation carried out after the accident demonstrated that the impacts induced were not serious enough to require bathing restrictions in the coastal areas involved. Assuming a benzo(a)pyrene (BaP) concentration in sea water of 1 microgram/m3 cancer risk is in the order of 10(-8) and in the case of 10-kg child, a 10(-6) risk level correspond to about 0.18 microgram/l of BaP in sea water.

Features of the Italian National Inventory of Chemical Substances.

The Italian National Inventory of Chemical Substances (Inventario nazionale delle sostanze chimiche, INSC), a factual data bank on chemical toxicology produced by the Istituto Superiore di Sanità (ISS), consists of a computerized system on existing chemicals developed for routinary and emergency needs. Historical background, current status and future direction of INSC are discussed. The structure and the feature of INSC are briefly examined. Aspects of retrieval of information and the criteria for the inclusion of data and priority selection are also considered.

Global migration from plastic materials into olive oil and isooctane: an experimental comparison.

Global migration from several plastics (phthalate-plasticized PVC, polyurethane, polyether-polyamide copolymer and silicone rubber) into olive oil, used as a liquid simulant for fatty foods, was compared with global migration into isooctane, which has been proposed as a new fatty-food simulant. The results showed that the isooctane test (involving contact for 2 hr at 40 degrees C) is not suitable as a substitute for the olive oil test (contact for 10 days at 40 degrees C) for some types of commercial plastic materials.