Exposure, Intake and Effects of Toxic and Essential Elements

The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006)

Principal investigator: Maja Blanuša

SUMMARY
In the forthcoming period factors influencing an increase in toxic metal concentrations in the body at an early age will be studied on suckling rats. Special attention will be given to some dietary components like calcium, selenium, and vitamin C. New data on the interaction of essential dietary components with toxic metals (lead, cadmium, mercury) will be obtained. The efficiency of chelation therapy at an early age, especially during ongoing exposure to toxic metals, is investigated as a contribution to treatment of metal poisoning in children. The following chelating agents are used: meso-2,3-dimercaptosuccinic acid (DMSA), sodium-(RS)-2,3-dimercapto-1-propanesulfonate (DMPS) and calcium-trisodium-diethylenetriaminepentaacetate (DTPA). Dietary supplementation and/or chelation therapy are administered during or after exposure to lead or cadmium to obtain highest reduction in tissue concentrations of these toxic metals. The health effect of such treatments and tissue essential element concentrations will be also evaluated. The efficiency of combined chelation therapy with DMSA and DTPA will be evaluated in older rats for treatment of acute cadmium poisoning. The influence of selenium on the efficiency of chelating agents, DMSA and DMPS for reducing tissue mercury concentrations will be also studied. The effect of cigarette smoking on concentrations of metals and steroid hormones is evaluating in human placental tissues. For monitoring purposes the ratio of heavy metals in soil, plants (mushrooms), and isopods is measured. The importance of calcium intake during the suckling period for bone mineral contents in adult age is assessed in an animal model. In epidemiological studies the effects of environmental and nutritional factors as compared to genetic factors on bone mineral content will be estimated in children and adults.

022-0222411-2406 Biological Markers of the Activity of Electromagnetic Nonionizing Radiation

MINISTRY OF SCIENCE, EDUCATION AND SPORTS OF THE REPUBLIC OF CROATIA (2007-2014)

Principal Investigator: Ivančica Trošić

SUMMARY
Electromagnetic radiation (EM) of microwave frequencies in the range of 300 MHz-3000 MHz (MW) has become one of the major physical environmental pollutants. This raises concern about health hazards related to the interaction between microwave EM fields and life processes. Depending on the field strength, frequency, wave form, modulation, and duration of exposure, microwave radiation is absorbed in the molecules and manifests as a change in vibration energy or heat. So far, studies of microwave radiation risk in a variety of life forms have produced controversial results. The effects that have been positively established include changes in the cell membrane functionality, calcium metabolism, cellular signal communication, cell proliferation and differentiation, proto-oncogens, heat-shock protein activation, and the cell death. Beside genotoxic action, microwaves seem to have a neurodegenerative potential. Studies in the field of bioelectromagnetism should aim at defining the biological markers of target systems susceptibility to the MW radiation at nonthermal level. The biomarkers of susceptibility and the biomarkers of the effect of low-intensity microwave radiation will be investigated using complex approach, including the basic experimental model; cell cultures, and experimental animals. The study is expected to reveal the indicators of harmful effects of low-intensity microwave radiation in vivo. The mechanisms of MW radiation activity at the cellular and subcellular level will be examined in vitro using continuous cell cultures. Cell survival, proliferation and colony-forming ability will be examined after microwave exposure in addition to macromolecular structures, and cytoskeleton proteins, microtubules, intermediate or actin filaments. The results will give some direction to the in vivo investigation, which in turn will reveal matching target cells suitable to create a primary MW-sensitive cell culture. With an adequate methodological approach, such primary cell culture could help to determine biomarkers of the effects of non-thermal MW radiation in vivo. Biological effects which reveal physical and chemical changes at the molecular, cell or tissue level might disturb homeostasis and stimulate whole body response.

General Exposure to Radiofrequent Microwave Radiation

The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006)

Principal investigator:
Ivančica Trošić
Institute for Medical Research and Occupational Health, Zagreb

SUMMARY
General exposure to radiofrequent microwave radiation threats fromelectroenergetic, radar and RTV systems, telecommunication, medical and household devices. Nonionizing radiation mechanism of influence on biological system is not known.

Integral insight into the biological effects of radiation might be reached by means of animal models, otherwise, action mechanism requires cell culture research. Recently obtained results revealed  that microwaves (RF/MW) in rats cause decrease in peripheral lymphocyte, increase in erythrocytes count, inhibition of bone marrow lymhocytopoiesis, stimulation of mucociliary clearance, and time-dose related appearance of multinucleated phagocytes in the lungs.

Investigation will be continued by research of cellular and intracellular responds related to applied dose-time exposure of particular physical agents including animal model and cell culture treatment. Search for biomarkers of nonthermal effects of nonionizing radiation will proceed followed by genesis and function related parameters at the cell level including several biological systems: bone marrow, peripheral blood and free cells from lungs and peritoneum.

The proliferation, differentiation and cell maturation in the bone marrow, and their possible reflection on body cell circulation will be followed. Supposing that RF/MW affects the synthesis of melatonin, a regulator of hematopoiesis and immunological response, the melatonin metabolite will be determined in the rat nocturnal urine. The erythrocyte hemolysis time, and possible chromosomeand/or spindle apparatus damage will be explored. Possible intracellular events will be evaluated by means of cytoskeleton staining. Biological effects of nonionizing radiation in vivo, elucidation of their mechanisms in vitro will be achieved by relevant statistical approach.

Allergic Disorders of Respiratory System and Skin

Principal Investigator: Božica Kanceljak Macan
(The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006))

Principal Investigator: Božica Kanceljak Macan
Since January 1 2005, Principal Investigator Davor Plavec; since November 1 2005, Principal Investigator Jelena Macan

SUMMARY
The pathophysiological mechanism involved in  allergic diseases (ADs) is still not clear. It is not clear if ADs are local or systemic disorders (Bousquet J. ACI International 2000;12:141.2). Sensitization isn’t always followed by clinical symptoms (Wahn U. Allergy 2000;55:591-9).

Increased prevalence of respiratory ADs , especially asthma, is related to antigens of biologic origin, i.e. from bacteria, moulds, mites, animals, insects (Lacey J. Clinical Application of Aerobyology. Braine-l Alleud, Belgium: The UCB Institute of Allergy 1996;45-55). The relationship between biological activity, way of exposure and the development of sensitization is not clear.

Aim is to examine:

1. The composition and concentration of biological allergens  (mites, cat, dog, cockroach) and endotoxin in indoors dust  from urban and rural areas of the Croatian continental and Mediterranean regions,

2. Prevalence of the sensitization markers by skin testing, measuring IgE and IgG, nasal and bronchial reactivity, and analysis of induced sputum in general population and patients with asthma and rhinitis. The main hypothesis is that the level of exposure  and different environmental conditions are related to the  prevalence of  the sensitization markers and specific symptoms.

The importance of this investigation is in studying the relationship between level of allergens and endotoxin  in the dust from homes, public and occupational indoor environments with modern characteristics, and life habits. It is also important to establish risk concentrations of the  allergens and endotoxin for the occurrence of sensitization markers and relevant clinical symptoms  in  adult population of Croatia and to suggest effective preventive measures.