Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases.

Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild-type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty-five of 393 (7%) patch-tested wild-type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41-86.6, P < 0.001). Our results in general indicate a low frequency of FLG null mutations in the studied Croatian population supporting a theory of a latitude-dependent distribution of FGL null mutations in Europe, with a decreasing north-south gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirmed.

Upper respiratory impairment in restorers of cultural heritage.

BACKGROUND: There is a paucity of data regarding respiratory health in restorers of cultural heritage or similar occupations, such as visual artists or museum workers, although they are exposed to a complex mixture of various respiratory hazards. AIMS: To evaluate atopy and respiratory health parameters, including bronchial and nasal non-specific reactivity, in restorers and conservators of cultural heritage (restorers). METHODS: Fifty-six restorers and 62 controls provided general data and data on ever experienced rhinitic or asthma-like symptoms, spirometry, non-specific bronchial and nasal responsiveness to histamine, skin prick testing to common inhalational allergens and serum total IgE levels. RESULTS: Spirometry values were in the range of normal values in 55 of 56 restorers and did not differ significantly from those in control subjects. However, restorers had more than two times higher prevalence of nasal hyper-responsiveness (NHR), with 2.3 times higher risk of NHR compared to controls [95% confidence interval (CI): 1.4-3.6, P < 0.001]. The risk of NHR was slightly reduced by increasing age (odds ratio 0.95, 95% CI: 0.91-0.99, P < 0.05). NHR was not associated with gender, smoking status, bronchial hyperresponsiveness (BHR), upper or lower respiratory symptoms or atopy status. CONCLUSIONS: Compared with controls, the studied group of workers occupationally exposed to respiratory hazards during restoration/conservation activities had no deterioration of lung function but had an increased non-specific nasal responsiveness that was not correlated with upper and lower respiratory symptoms, BHR or atopy. The relationship of this finding to future clinical outcome should be investigated in a longitudinal study.

Increasing trend in atopy markers prevalence in a Croatian adult population between 1985 and 1999.

BACKGROUND: Reports about the increasing prevalence of atopy and atopic diseases are common, but recently they have been critically reviewed and the need for relevant research methods has been established. OBJECTIVES: This study evaluated a 15-year trend in the prevalence of atopy markers [elevated total IgE, positive skin prick test (SPT) to common aeroallergens and positive atopic symptoms] in Croatian adults, separately for women and men. METHODS: The study included 721 subjects (445 men and 276 women), 18-45 years old, examined for allergies within a pre-employment preventive examination. All subjects underwent medical history, SPT with common inhalatory allergens and total serum IgE measurement. The trend analysis of atopy prevalence was performed after stratification of subjects into three consecutive 5-year periods from 1985 to 1999. RESULTS: The prevalence of concurrently elevated total IgE and positive atopic symptoms significantly increased during the studied period in men [odds ratio (OR) 2.44, 95% confidence interval (CI) 1.39-4.29, P=0.002]. Women showed an increased prevalence of positive SPT only, with borderline significance (OR 1.65, 95% CI 1.00-2.71, P=0.050). In women, rural residence was found to be a predictor of elevated total IgE (OR 5.36, 95% CI 2.41-11.93, P=0.000) and smoking to be a predictor of concurrently elevated total IgE and positive SPT (OR 6.20, 95% CI 1.67-23.07, P=0.006). CONCLUSIONS: An increasing trend in the prevalence of concurrently elevated total IgE and positive atopic symptoms was found in the Croatian adult male population between 1985 and 1999, but not in the female population. Sex differences responsible for the production and regulation of IgE were suggested.

Succimer treatment during ongoing lead exposure reduces tissue lead in suckling rats.

There is a concern that oral treatment with succimer (meso-2, 3-dimercaptosuccinic acid, DMSA) can promote gastrointestinal lead absorption if not performed in a lead-safe environment. The scope of our investigation was to evaluate the efficacy of oral DMSA treatment during oral lead exposure on tissue lead in suckling rats. Six-day-old Wistar rats of both genders were divided into two groups-untreated (Pb) and treated (Pb + DMSA)-with 10 animals per group. Lead (as acetate) was given orally at a dose of 2 mg kg(-1) body weight day(-1) for eight consecutive days (total dose 16 mg kg(-1), i.e. 0.08 mmol kg(-1)). During this period the treated group received a daily dose of 0.5 mmol DMSA kg(-1) body weight p.o. six times on days 1-3 and 6-8 of the experiment (total dose 3 mmol kg(-1)). Tissue lead was determined by means of atomic absorption spectrometry. The DMSA efficiently reduced the lead concentration in the analysed tissues (carcass, liver, kidneys and brain) by approximately 50% compared with untreated controls. The pups' growth and organ weights were not affected. In conclusion, our results indicate that DMSA is an efficient oral lead chelator in sucklings even if challenged with ongoing lead exposure.

Calcium supplementation efficiently reduces lead absorption in suckling rats.

The effect of calcium supplementation on tissue lead was evaluated in suckling Wistar rats. Such data are not yet available in the literature. The following artificial feeding regimen was used for calcium supplementation: cow's milk by addition of 1%, 3% or 6% Ca as CaHPO(4)x2H(2)O suspension to increase the daily calcium intake about 1.4, 2 or 3 times above control values. Artificial feeding was applied during 7 hr each day for nine consecutive days (from day 6 through 15 after birth). The effect of such treatment on lead absorption and elimination was evaluated in two separate experiments: calcium supplementation during oral lead exposure (as acetate; daily dose 2 mg Pb/kg body wt.; total Pb dose 18 mg/kg body wt.) or after a single intraperitoneal lead administration (5 mg/kg body wt.). At the end of experiments, lead in tissues (liver, kidneys, brain and carcass), and essential elements (Ca, Fe, Zn, Cu) were analysed by atomic absorption spectrometry. Calcium supplementation caused a statistically significant decrease of lead in all tissues of sucklings orally exposed to lead. This decrease was dose-related being about 1.3, 1.5 and 2 times lower in groups supplemented with 1%, 3%, or 6% calcium compared to controls, respectively. Increased calcium intake had no effect on incorporated lead after parenteral lead exposure. Calcium supplementation increased carcass calcium and had no effect on trace elements in tissues, pups' general appearance and body weight gain. It is concluded that higher calcium intake might be a way of efficient reduction of lead absorption during the suckling period.

Chelation of aluminium by combining DFO and L1 in rats.

The hypothesis that two known chelators 1, 2-dimethyl-3-hydroxypyrid-4-one (L1) and desferrioxamine (DFO) might be more efficient as combined treatment than as monotherapies in removing aluminium from the body was tested in a new acute rat model. Five-week old female rats received chelators: L1 (p.o.), DFO (i.p.) or L1+DFO as 100 or 200 mg/kg dose half an hour after a single i.p. administration of 6 mg Al/kg body weight in the form of chloride. Serum aluminium concentration and urinary aluminium and iron excretions were determined by electrothermal or flame atomic absorption spectrometry. Both chelators were effective only at the higher dose level. While DFO was more effective than L1 in enhancing urinary aluminium excretion, L1 was more effective than DFO in enhancing urinary iron excretion. In the combined treatment group L1 did not increase the DFO effect on aluminium and DFO did not increase the effect of L1 on iron elimination. However, in this group a simultaneous increase in both aluminium and iron elimination was observed. Our results support the usefulness of this animal model for preliminary in vivo testing of aluminium chelators. Urinary values were more useful because of the high variability of serum results. Result of combined chelators treatment should be confirmed in a different experimental model before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for evaluating the efficiency of chelating agents in aluminium toxicity.