Principal Investigator: BoĹľica Kanceljak Macan
(The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006))
Principal Investigator: BoĹľica 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.
The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006)
Principal Investigator: Vilena Kašuba
Field: Biology
Branch: Biology
SUMMARY
In last few decades, the number and quantity of toxic agents, which are threat to the environment, was rashly increased with the development of industry. Consequently humans are exposed to them directly or by nourishment.
It is long appreciated that environmental mutagens can have clastogenicand/or aneugenic activities. The event, which irreversibly affects the cell-integrity, is double-strand break (DSB) of the DNA molecule. DNA DSBs may arise either spontaneously during cellular processes or as a result of exposure to DNA-damaging agents such as ionizing radiation, or chemical agents.
It is widely accepted that nonrepaired or misrepaired DSB are the main lesions leading to the production of chromosomal aberrations, mutagenesis,oncogenic transformation, and cell death. Studies focusing on this relationship, as well as the possible modulation of DNA repair mechanisms, are currently of major interest. Great characters in these studies have methods that insure quick results with small quantity of the test material. Mutagen effects of ionizing radiation, heavy metals, and some organic combinations present in human environment and work-places, will be studied in human peripheral blood lymphocytes, rat reticulocytes, and in animal cell-cultures.
In our investigations we will use the following methods: comet assay, chromosomal aberration analysis, sister chromatid exchange analysis, micronucleus assay in cytochalasin B blocked human lymphocytes, rat bone-marrow and peripheral blood reticulocytes, and LDH (lactat-dehydrogenase) colorimetric determination in cell culture medium (as a result of the cell membrane damage because of activity of different environmental and professional agents). The results should contribute to better understanding of effects of agents from environment to a genome and cell membrane, and, consequently, to organization and protection exposed subjects.
MINISTRY OF SCIENCE, EDUCATION AND SPORTS OF THE REPUBLIC OF CROATIA (2007-2014)
Principal Investigator: Spomenka Telišman (until 31 December 2007), Alica Pizent (since 1 January 2008)
SUMMARY
Recent evidence has indicated a deterioration in the reproductive health of men in many countries over the past few decades, particularly a decrease in semen quality and an increase in prevalence of prostate cancer, but also great differences between and within some countries. The cause of these phenomena is unknown, although a complex role of environmental and lifestyle factors has been implicated. Lead (Pb) and cadmium (Cd) are toxic metals, pervasive in the human environment and accumulate in the human body over a lifetime. In addition to direct toxicity, they can interfere with the metabolism of several essential metals by reducing their bioavailability in the body, can contribute to oxidative stress (implicated in the pathogenesis of male infertility), and can inhibit DNA repair. Copper (Cu), zinc (Zn) and selenium (Se) are essential elements required for optimum activity of many enzymes, including the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) that are protective against oxidative stress. Particularly Zn and Se are important for male reproductive function and can reduce the toxicity of Pb and Cd. Varicocele belongs to the most important causes of male infertility, although the mechanism behind its adverse action is poorly known. Recent data indicate the association of varicocele with an increase in Cd and a decrease in Zn, and with altered activity of antioxidant enzymes in men. Prostate cancer is the 4th most common cancer in men worldwide, and the most common cancer in men in the USA as well as in Croatia. Recent data show a protective role of relatively high serum Se levels against the risk of prostate cancer in men, whereas chronic exposure to Pb and Cd has been shown to decrease Zn and Se, and cause impaired secretory function or damage of the prostate. The objective of this study is to determine the inter-relationship of the blood levels of Pb and Cd, serum levels of Cu, Zn and Se, activities of SOD and GPx in blood, and age, smoking, and alcohol consumption with respect to clinically defined presence and intensity of varicocele, and of prostate damage, in men with no occupational exposure to metals. The purpose is to provide relevant data concerning the etiology, possible substitutional therapy, and prevention of a further deterioration in the reproductive health in men, as well as to evaluate the contribution of each specific environmental and lifestyle factors. The study is important in view of a considerably lower serum Se level, and somewhat higher blood Pb and Cd levels, in the general population of Croatia than in many other countries.
The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006)
Principal Investigator: Božica Radić
SUMMARY
A toxic effects of anticholinesterases (organophosphorous compounds (OPs) with highly toxic nervous warfare agents and carbamates) is irreversible inhibition of hydrolytic enzymes: acethylcholinesterase (AChE), the enzyme of vital importance, and buthyrilcholinesterase (BuChE).
The physiological role of AChE is to hydrolyse the neurotransmitter acethylcholine released in the process of cholynergic transmission of nerve impulses. AChE inhibited by OPs and carbamates does not hydrolyse acethylcholine. The consequence is the blocking of nerve impulses in the central and peripheral nervous system. The therapy of anticholinesterase poisoning includes specific drugs, called antidotes (atropine, oximes etc.). As there is no universal therapy for anticholinesterase poisoning, research of new antidotes aims at finding better therapeutic solutions. We are investigating in vitro and in vivo abilities of new potential antidotes: pyridinium compounds and derivatives of tenocyclidine-adamantane. Terrorist activities in the world have shown that chemical warfare agents are the still a threat, and have given new impulse and importance to this type of research.
A part of this project is focused on investigation of the efficiency of new antidotes on inhibited AChE. The physiologic role of BuChE is unknown. Scarce literature data show that BuChE is involved in the metabolism of lipids.
Additionally this project proposes to investigate the effects of BuChE inhibition on changes in the concentrations of lipids (cholesterol and triglycerides) and lipoproteins (HDL, LDL, IDL) in rat’s plasma, as well as the activity of some enzymes involved in the metabolism of lipoproteins (lipoprotein lipase, lecitin-cholesterol-acyl transferase). The results may have clinical application in the diagnosis of patients with hiperlipidemia. Research will be performed in vitro and in vivo on experimental animals (mice, rats).
