Fibrinogen Modification and Fibrin Formation in Patients with an End-Stage Renal Disease Subjected to Peritoneal Dialysis.

End-stage renal disease (ESRD) is a condition accompanied by increased inflammation, oxidative stress, risk of cardiovascular complications, and coagulopathies. The structure of fibrinogen and characteristics of fibrin from plasma samples of ESRD patients on peritoneal dialysis (PD) was investigated. Fibrinogen from ESRD patients had a higher degree of carbonylation than fibrinogen from healthy individuals. The Aα chain was the most susceptible to oxidation, followed by the Bß chain, whereas the γ-chain was the most resistant to oxidation. Spectrofluorimetric analysis suggested a higher extent of modification of amino acid side chains in fibrinogen from ESRD patients. The tertiary structure of fibrinogen was more affected than its secondary structure. The kinetics (time and rate) of fibrinogen coagulation did not differ between the tested groups. Fibrin prepared from the isolated fibrinogen had a similar structure in both groups. Our results confirm that oxidation and structural alterations of fibrinogen occur in ESRD patients on PD, although these modifications produce no direct effect on the fibrin formation. Taking into account that some patients suffer from bleeding, whereas others develop thrombotic complications, further research on this subject is required to identify other components and processes that contribute to the outcome.

Enhanced Platelet Sensitivity to IGF-1 in Patients with Type 2 Diabetes Mellitus.

Diabetes mellitus is characterized by increased platelet activation which is determined by many factors including changes in the expression of membrane proteins. The aim of this study was to investigate the sensitivity of human platelets to the insulin-like growth factor (IGF) system in patients with poorly controlled type 2 diabetes mellitus (DM2). Ligand binding was analyzed using 125I-labelled IGF-1 and insulin, and relative expression of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) was evaluated by Western blotting. Platelet aggregation in the presence of IGF-1 was studied by the plate aggregometry assay. We found that platelets from DM2 patients exhibited significantly higher IGF-1 binding and upregulation of IGF-1R expression in comparison with healthy individuals. Both insulin binding and IR expression were lower in the DM2 group, but the differences with the healthy control were statistically insignificant. The potentiating effect of IGF-1 on the thrombin-induced activation of platelets was detected in both groups but was significantly more pronounced in the DM2 patients. The initial rate of platelet activation in the presence of IGF-1 positively correlated with the concentration of glycated hemoglobin. Platelets isolated from DM2 patients displayed elevated expression of the IGF-1R subunits, which might have contributed to the higher sensitivity of these cells to IGF-1 in thrombin-initiated aggregation by increasing the rate of platelet activation. However, further experiments are needed to investigate the role of IGF-1 in thrombotic complications that usually accompany diabetes.

Analysis of Four Circulating Complexes of Insulin-Like Growth Factor Binding Proteins in Human Blood during Aging.

The primary role of insulin-like growth factor binding proteins (IGFBPs) is to regulate availability of IGFs for interacting with receptors, but IGFBPs perform IGF-independent actions as well. The availability and activity of IGFBPs in the circulation is influenced primarily by their concentration and structural modifications, but possibly also by interaction with major plasma proteins such as transferrin, alpha-2-macroglobulin (α2M), and fibrinogen. Four types of circulating IGFBP complexes were examined in this study by immuno- and ligand-binding assays in adults of different age. The amounts of IGFBP-3/transferrin and IGFBP-1/fibrinogen complexes were similar in middle- and old-aged persons, whereas the amounts of IGFBP-1 (or -2)/α2M monomer complexes were lower in the old-aged group and negatively correlated with total IGFBP-1 (or -2) amounts in blood. In contrast to IGFBP-1, IGFBP-2 was present in significantly greater quantities in complexes with α2M dimer than α2M monomer in older individuals. IGFBP complexes did not bind 125I-labeled IGF-I in amounts detectable by ligand blotting. According to the results of this study, the quantities of IGFBP-1 and IGFBP-2, which interact with α2M, are age-dependent and, in the case of complexes with α2M monomer, they are negatively correlated with the total circulating levels of these two IGFBPs.

Interaction between Fibrinogen and Insulin-Like Growth Factor-Binding Protein-1 in Human Plasma under Physiological Conditions.

Fibrinogen is a plasma glycoprotein and one of the principle participants in blood coagulation. It interacts with many proteins during formation of a blood clot, including insulin-like growth factors (IGFs) and their binding proteins (IGFBP). Fibrinogen complexes were found as minor fractions in fibrinogen preparations independently of the coagulation process, and their presence influences the kinetics of polymerization. The idea of this work was to investigate whether fibrinogen in human plasma interacts with IGFBPs independently of the tissue injury or coagulation process. The results have shown that fibrinogen forms complexes with IGFBP-1 under physiological conditions. Several experimental approaches have confirmed that complexes are co-isolated with fibrinogen from plasma, they are relatively stable, and they appear as a general feature of human plasma. Several other experiments excluded the possibility that alpha-2 macroglobulin/IGFBP-1 complexes or IGFBP-1 oligomers contributed to IGFBP-1 immunoreactivity. The role of fibrinogen/IGFBP-1 complexes is still unknown. Further investigation in individuals expressing both impaired glucose control and coagulopathy could contribute to identification and understanding of their possible physiological role.

Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction.

Placental insulin receptor (IR) and insulin-like growth factor receptors (IGFRs) are essential for fetal growth. We investigated structural changes of these receptors exposed to increased oxidative stress in mothers diagnosed with diabetes mellitus (DM) or preeclampsia (PE) complicated with intrauterine growth restriction. Increased amount of IR and decreased amounts of IGF1R and IGF2R were found in both pathologies, accompanied by significant elevation in protein carbonyls. When isolated receptors were examined, increased carbonylation of IR and IGF1R in PE placentas was detected, whereas the amounts of carbonylated IR and IGF1R were similar in DM and healthy placentas. Carbonylation status of IGF2R did not change due to pathology, confirming the detrimental role of primary structure and conformation in oxidative susceptibility. Ligand binding was similar in all three groups of samples and did not seem to be affected by receptor oxidation. Since babies delivered by mothers with PE were smaller than the referent population, increased carbonylation of receptors might have affected downstream receptor signaling post-ligand binding.

Analysis of protein carbonylation--pitfalls and promise in commonly used methods.

Oxidation of proteins has received a lot of attention in the last decades due to the fact that they have been shown to accumulate and to be implicated in the progression and the pathophysiology of several diseases such as Alzheimer, coronary heart diseases, etc. This has also resulted in the fact that research scientists are becoming more eager to be able to measure accurately the level of oxidized protein in biological materials, and to determine the precise site of the oxidative attack on the protein, in order to get insights into the molecular mechanisms involved in the progression of diseases. Several methods for measuring protein carbonylation have been implemented in different laboratories around the world. However, to date no methods prevail as the most accurate, reliable, and robust. The present paper aims at giving an overview of the common methods used to determine protein carbonylation in biological material as well as to highlight the limitations and the potential. The ultimate goal is to give quick tips for a rapid decision making when a method has to be selected and taking into consideration the advantage and drawback of the methods.

Molecular effects of advanced glycation end products on cell signalling pathways, ageing and pathophysiology.

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the Maillard chemical process of non- enzymatic glycation of free amino groups of proteins, lipids and nucleic acids. This chemical modification of biomolecules is triggered by endogeneous hyperglycaemic or oxidative stress-related processes. Additionally, AGEs can derive from exogenous, mostly diet-related, sources. Considering that AGE accumulation in tissues correlates with ageing and is a hallmark in several age-related diseases it is not surprising that the role of AGEs in ageing and pathology has become increasingly evident. The receptor for AGEs (RAGE) is a single transmembrane protein being expressed in a wide variety of human cells. RAGE binds a broad repertoire of extracellular ligands and mediates responses to stress conditions by activating multiple signal transduction pathways being mostly responsible for acute and/or chronic inflammation. RAGE activation has been implicated in ageing as well as in a number of age-related diseases, including atherosclerosis, neurodegeneration, arthritis, stoke, diabetes and cancer. Here we present a synopsis of findings that relate to AGEs-reported implication in cell signalling pathways and ageing, as well as in pathology. Potential implications and opportunities for translational research and the development of new therapies are also discussed.

Influence of placental mannose/n-acetyl glucosamine-binding proteins on the interaction of insulin and insulin-like growth factors with their receptors.

Placenta is a source of carbohydrate-binding proteins that function as molecular scavengers, but they could also be involved in interactions that assist in metabolic control. Mannose/N-acetyl-glucosamine (Man/GlcNAc)-binding proteins from placenta were isolated and their reactivity towards placental insulin and insulin-like growth factor receptors (IR and IGF-Rs) was analyzed. The lectins reduced the binding of insulin and IGF-I in a dose-dependent manner, while almost no effect was observed on the binding of IGF-II. The shape of the inhibition curves changed, suggesting altered binding specificity. The presence of sugar could not reverse completely the effect of the lectins, implicating both lectin-sugar and protein-protein conformational recognition. Since biological molecules in our experimental system were those that are in close relation in vivo, placental Man/GlcNAc-specific lectins may be regarded as potential allosteric modulators of ligand-receptor interactions in a system of homologous ligands, selectively affecting only binding to tyrosine kinase type receptors (IR and IGF-1R).

Association between the pattern of IGFBP-1 alteration and the glucose/insulin metabolic control.

Little is known on the possible association between impaired glucose/insulin metabolism, the pattern of IGFBP-1 phosphorylation and the complex formation with other serum proteins. In this study, the concentration, isoform, multimer and complex pattern of IGFBP-1 was compared in healthy persons and patients with type 2 diabetes mellitus or with hypoglycemia. Concentrations of insulin and IGFBP-1 were determined by radioimmunoassay. Metal affinity and immunoaffinity chromatography were used for the separation of molecular forms of IGFBP-1, which were detected by immunoblotting and SELDI. The counter directional change in insulin and IGFBP-1 concentrations, expressed as a factor that takes into consideration the rate of insulin increase and IGFBP-1 decrease after glucose intake was approximately twice more pronounced in patients with diabetes than in healthy and hypoglycemic persons. The alteration in the phosphorylation pattern of IGFBP-1 due to diabetes or hypoglycemia was not observed. IGFBP-1 multimers found in the circulation of patients with diabetes type 2 differed from those detected in the circulation of others: there were 3 molecular forms between 90 and 100 kDa (compared to one in patients with hypoglycemia or 2 in healthy persons), 2 of which were α (2)M-reactive and one not. These results suggest a possible greater involvement of IGF system in glucose regulation in patients with diabetes type 2.

Differential diagnosis of liver diseases using serum biomarkers.

PURPOSE: Many human blood proteins are synthesised in the liver. Their serum levels may decrease or increase due to liver disorders and some of them serve as useful biomarkers. Determination of serum concentration of different biomarkers has important role in diagnosis of liver diseases and in monitoring the course of disease. In this work 3 serum markers associated with liver disorders were compared. The aim was to assess whether these biomarkers exhibit specific distribution pattern in different types of liver disease: liver neoplasia (primary hepatocellular carcinoma [HC] or metastatic liver disease [MLD] from colon cancer), viral hepatitis C (HCV) and the parasitic infection echinococcosis. METHODS: Serum concentrations of alpha-fetoprotein (AFP), ferritin and insulin-like growth factor I (IGF-I) were determined in patients with liver disease and compared between patient groups and with healthy persons. RESULTS: Serum AFP and ferritin levels exhibited similar pattern of change in patients with liver neoplasia or HCV, and concentrations of these 2 markers were significantly increased compared to the control group (p < 0.01 in each case). On the other hand, the concentration of IGF-I was significantly decreased in patients with liver neoplasia or echinococcosis compared to the control group (p < 0.05 for both). The concentration of IGF-I was significantly lower and the concentration of ferritin significantly higher in patients with HC than in patients with MLD from colorectal cancer (p < 0.01 for both). CONCLUSION: The results have shown that each hepatic pathology studied exhibited specific profile of the analysed set of biomarkers. Therefore, the simultaneous determination of the 3 mentioned biomarkers may help in differential diagnosis of liver diseases.

Isolated compared to membrane-bound receptors exhibit altered insulin/IGF interaction.

Insulin and insulin-like growth factors (IGFs) bind to their cognate receptors with high affinities, but due to their homology they may cross-react with each other's receptors. We performed a series of binding studies to reanalyze the cross-reactivity of insulin, IGF-I, and IGF-II to affinity-purified insulin (IR) and type 2 IGF receptors (IGF-2R) from human placental membranes. IR and IGF-2R were purified using insulin- and mannose-6-phosphate affinity chromatography (I-AC and M6P-AC). Binding studies were performed with (125)I-labeled and unlabeled ligands. According to immunoblotting, the only receptor species isolated by I-AC was IR, whereas the only receptor isolated by M6P-AC was IGF-2R. Isolated IR reacted to similar extent with (125)I-labeled insulin and (125)I-labeled IGF-II and significantly less with (125)I-labeled IGF-I, implicating predominance of IR-A. The affinity of IR towards heterologous ligands increased after its separation from other membrane proteins. Affinity-purified IGF-2R was almost unable to bind ligands under experimental conditions used in this work, but when incubated with (125)I-labeled ligands prior to affinity chromatography, IGF-2R interacted not only with IGF-II, but to a certain extent with the other two ligands. In the competitive M6P-AC, the binding of labeled ligands was inhibited with either homologous or heterologous ligands, in a dose dependent manner. In competitive ligand-blotting, specific interactions between (125)I-labeled insulin and IR, and (125)I-labeled IGF-II and IGF-2R were also inhibited with all unlabeled ligands, although to a different extent. The results presented in this work imply that isolation of IR an IGF-2R from their membrane milieu increases their reactivity towards all members of the insulin/IGF ligand family.

Association of elevated IGFBP-1 with increased IGF-II concentration in patients with carcinoma of the liver.

Insulin-like growth factors (IGFs) are mitogens for numerous types of cells including cancer cells. The aim of this work was to analyze some of the components of the IGF system to assess which could be potential clinical biomarkers for monitoring patients diagnosed with liver cancer. Compared to healthy persons, patients with liver cancer had a lower concentration of IGF-I and a higher concentration of IGFBP-1, whereas the concentrations of IGF-II and IGFBP-3 remained unchanged. The IGF-I:IGFBP-3 ratio decreased in patients with cancer, while the IGF-II:IGFBP-1 ratio was not altered. Patients with primary carcinoma and those scheduled for surgery had lower IGF-I and higher IGF-II and IGFBP-1 concentrations than patients with secondary carcinoma and those not eligible for surgery. It may be postulated that a liver with primary cancer is induced to increase IGF-II and IGFBP-1 synthesis more than a liver involved in metastatic response. Similarly, in patients eligible for liver surgery an increase in IGF-II may reflect a gradual change in the concentration associated with a different stage of disease. As increased synthesis of certain IGFBPs is necessary to compensate decreased production of the others or increased IGF production, determination of serum IGF-II, IGFBP-1 and their ratio may aid in estimating the compensatory capacity of the liver affected by cancer.

The influence of laparoscopic and open surgery on the concentration and structural modifications of insulin-like growth factor binding protein 3 in the human circulation.

Insulin-like growth factor binding protein 3 (IGFBP-3) is the most abundant insulin-like growth factor binding protein in the circulation. The aim of the present work was to investigate the influence of surgery (laparoscopy and open) on the concentration and carbohydrate content of IGFBP-3. The concentration of IGFBP-3 was measured using an immunoradiometric assay (IRMA), its protein profile was characterised using immunoblotting and its sialic acid content was examined by means of Sambucus nigra agglutinin (SNA) affinity chromatography. The concentration of IGFBP-3 was significantly (p < 0.001) lower in preoperative patients compared with healthy subjects. Only patients that underwent open surgery showed a further significant decrease in the concentration of IGFBP-3. Immunoblotting detected two intact IGFBP-3 isoforms, as well as proteolytic fragments. SNA-affinity chromatography showed that in patients that underwent surgery the ratio between the two IGFBP-3 glycoforms was lower than the ratio in healthy subjects. Patients with gallbladder inflammation that underwent laparoscopy had an increased percentage of specifically bound IGFBP-3 to SNA compared with healthy subjects. Our conclusion is that open surgery decreased the level of IGFBP-3 compared with laparoscopy, whereas patients with gallbladder inflammation that underwent laparoscopy had an increased content of sialic acid in IGFBP-3.

Gastrointestinal inflammation and the circulating IGF system in humans.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have important anabolic functions in normal tissue growth, which in excess may lead to tumorigenesis. In the present study, circulating IGF-I, IGF-II and their binding proteins (IGFBP-3, IGFBP-2 and IGFBP-1) were determined in 92 adult patients with gastrointestinal inflammation (Crohn's disease, colitis ulcerosa, gastritis, duodenitis errosiva, gastrointestinal candidiasis, and rotaviral and adenoviral enteritis). Serum IGF concentrations were measured by radioimmunoassay, while IGFBP profiles and IGFBP proteolytic patterns were characterized by immunoblotting. Concentrations of both IGF-I and IGF-II were significantly (p < 0.001) lower in patients than in healthy subjects. Immunoblotting demonstrated a decreased amount of intact IGFBP-3 (by approximately 60%), whereas IGFBP-2 and IGFBP-1 were increased (approximately 1.7 and 3.5-fold, respectively). No alteration in either fragmentation pattern or relative degree of proteolysis was detected in patients compared to the control group. It may be concluded that the IGF system is seriously imbalanced in patients with gastrointestinal inflammation, regardless of primary cause. These findings may help towards a better understanding of the metabolic outcome of the inflammatory process, and possibly in predicting the efficiency of patient recovery.

Radiocesium accumulation in mosses from highlands of Serbia and Montenegro: chemical and physiological aspects.

The aim of this work was (i) to determine the activity levels of 137Cs in mosses from highland ecosystems of Serbia and Montenegro, (ii) to find out if radiocesium is associated with essential biomacromolecules, and (iii) to investigate 137Cs distribution among intracellular compartments. It was found that biomolecules of mosses do not bind significant amounts of radiocesium (2.3-3.3% of the absorbed 137Cs), a behavior that was independent of the moss species. Cellular fractionation of mosses showed that membranes are the primary 137Cs-binding sites at the cellular level. They contained 26.1-43.1% of the initial radiocesium activity. It seems that 137Cs-binding molecules in different mosses are of similar chemical nature, and their distribution between various cellular compartments is not species specific.

Thyroid hormone synthesis and storage in the thyroid gland of human neonates.

The aim of this study was to evaluate the morphological and biochemical maturation of the thyroid gland in human neonates. The mean iodine concentration in the thyroid gland of very premature infants (less than 32 weeks gestational age, 0-3 days survival, n = 12) was significantly lower than in the older group (34-41 weeks gestational age, 0-30 days survival; n = 15; p < 0.05). For the whole group of neonates there was a statistically significant linear correlation between duration of life, i.e. gestational age and survival, and iodine concentration (r = 0.64, p < 0.01). Although there was wide dispersion of the results the same tendency was seen for thyroglobulin (Tg) concentration in the thyroid gland (r = 0.52, n = 21; p < 0.05). Comparative histological examination of the fetal thyroids gave results in accordance with the biochemical data as intrafollicular colloid appeared to be more abundant in more mature thyroids. The iodine content in Tg was found to be 0.63 +/- 0.22% in very preterm neonates and was slightly but not significantly lower than that found in the thyroids of the older group (0.82 +/- 0.14%; p = 0.055). The content of T4 and T3 per Tg molecule in the neonates was related to the iodine content. The differences in mean values of T4/Tg and T3/Tg molar ratios between the two groups were not significant: T4: 2.8 +/- 1.8 mol/ mol, T3: 0.29 +/- 0.12 mol/mol in very preterm neonates; and T4: 3.5 +/- 0.7 mol/mol, T3: 0.34 +/- 0.09 mol/mol in the older group. These results offer useful information for further analysis of the development of thyroid function in the human neonate.

Periparturient endocrine and metabolic changes in healthy cows and in cows affected by mastitis.

Transition from pregnancy to lactation in dairy cows involves considerable metabolic adaptation. Additional stress is incurred during infections such as periparturient mastitis. Multiparous Holstein-Friesian cows kept under normal production conditions (n = 15) were used to evaluate changes in circulating metabolite and hormone concentrations from 5 days before to 5 days after calving. Insulin-like growth factor binding protein (IGFBP) profiles were also monitored. Marked time-related changes were observed for plasma thyroid hormone, IGF, cortisol, insulin, beta-hydroxybutyrate (BHB) and non-esterified fatty acid (NEFA) concentrations but not for plasma leptin. A decrease in IGF-II concentration and maximal intensity of the putative IGFBP-1 band occurred at parturition. When compared with the five healthy cows,low IGF-II levels were prolonged to day 2 post-partum in five cows with Escherichia coli-associated mastitis. However, marked decreases in IGFBP-2 band intensity were evident only in two of the four cases examined. Individual total ligand (IGF-I + IGF-II) concentration and IGFBP pattern prepartum were largely regained 5 days post-partum in all cows. Hormone and metabolite concentrations in the two cows with Staphylococcus aureus-associated mastitis were very similar to those in the five healthy cows. Plasma thyroxine (T4) was lower 2 days prepartum in the cows, which later developed Gram-negative mastitis. Multiregression analysis showed that variance in T4 concentration was significantly and independently associated with triiodothyronine (T3) and IGF-I positively and with cortisol negatively (R2 = 0.648). This study confirms the close inter-relationship between the thyroid hormone and IGF axes in cattle and indicates possible effects of Gram-negative mastitis infection on IGF-II metabolism.

Peripheral circulating insulin-like growth factor-I and -II in cattle.

Interrelationships between circulating concentrations of the insulin-like growth factors (IGF-I and IGF-II) were investigated in 235 blood samples taken from 145 healthy beef or dairy calves, bulls and cows of different breeds and ages. Autoradiography of Western ligand blots indicated different IGF binding protein (IGFBP) profiles between sera from different categories of cattle. Each IGF radioimmunoassay was validated by determining the effects of IGFBPs, ligand and contraligand, as well as serial dilution and comparison with results obtained after molecular sieve chromatography in acid. In female cattle mean values for IGF-I varied from 5.1 nmol/l in postparturient Holstein cows to 18.5-20.5 nmol/l in growing beef heifers, while mean IGF-II concentrations ranged from 30.0 nmol/l in the cows to 14.7-15.7 nmol/l in the beef heifer calves. In male cattle mean serum IGF-I ranged widely from 8.2 nmol/l in 1-day-old Holstein calves to 67.4 nmol/l in 16-month-old Simmental-type bulls. Mean IGF-II concentrations decreased from 22.9 nmol/l in 1-day-old Holstein bull calves to 11.9 nmol/l in 12-month-old beef bulls. Thus, total molar IGF concentrations were fairly stable in female cattle (24.7-35.1 nmol/l) but extended from 27.3 nmol/l to 81.8 nmol/l in the male cattle. The tendency for a reciprocal relationship between serum concentrations of these growth factors was most obvious in the periparturient cows.

[Noise as a stress factor for the onset of hearing disorders in workers using drilling equipment]. / Buka kao stresni faktor za nastanak ostecenja sluha kod radnika na busacim postrojenjima.

INTRODUCTION: Noise is one of the commonest environmental pollutants and it is defined as a sound which bothers, irritates, which is unpleasant and can damage hearing. The degree of negative effects of noise depends on its intensity, spectrum of frequency, nature, duration of exposition and individual sensibility. PURPOSE: This work is supposed to establish the degree of correlation between hearing damage and professional exposition to one of physical stressors of work environment--noise. MATERIAL AND METHODS: Investigation regarding work conditions included intensity and frequency analysis of noise at workplaces. The examination sample included 101 workers of "NIS--Naftagas" section "Hidrosonda" employed as drilling workers. The control group consisted of 50 workers not exposed to noise or any other professional influences, like workers from the examination sample. RESULTS: The results on the observed workplaces show that noise is of high intensity and bad frequency spectrum. Exposition of workers to noise is a highly important factor for hearing damages (p = 0.002). The relative risk for hearing damage is four times greater in relation to the control group (odds ratio 4.1). Attributable fraction (preventive potential) of noise factor is 61%. Smoking associated with exposition to noise multiplies the risk of hearing damage (odds ratio 5.8) while with non-smokers the risk decreases (odds ratio 3.0). DISCUSSION: Professional hearing disorders occur slowly and increase with time spent at noisy workplaces. At the beginning it presents with buzzing in ears and dizziness followed by latent phase after which hearing disorders occur. Tone audiometry is used to register first signs of hearing loss, whereas manifestations in social contacts come later. CONCLUSION: Once diagnosed hearing disorders cannot be cured so a lot more care should be paid to this problem. It is necessary to provide adequate work conditions by applying appropriate technologies, tools, work organisation, personal protection equipment, as well as previous and periodical examinations of hearing by tone audiometry before employing workers and during their work in noisy conditions.

Job stress and cardiovascular diseases with health workers.

Due to increasing number of patients, reduced possibilities of diagnostics and therapy as well as poor living conditions as a result of total socio-political and economic situation in our country in the last ten years, health workers have been exposed to additional stress factors. Therefore, we wonted to establish to what extent professional stress affects appearance of complications in arterial hypertension with health workers. The examination included employees treated in the health centers "Hospital" and "Novi Sad". According to register for chronic mass non-contagious diseases of MONICA Project, younger patients suffering from arterial hypertension were excluded. From the aspect of possible causative factors of occupation on appearance of cardiovascular complications in patients already suffering from arterial hypertension, the examined group involved doctors and nurses. The control group included laboratory technicians, clerks, cleaners and service workers. It was established that doctors and nurses with hypertension registered in earlier life periods, were more vulnerable to angina pectoris, myocardial infarction and cerebrovascular insult as complications, compared to the rest of employees (if age as a risk factor is excluded) (RR = 3.7; 95% confidence interval 1.6 < RR < 8.6).