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The aim of our study was to measure the flow in coronary artery bypass grafts and to compare the flow between two groups of patients. In group A the arterial revascularization was performed with both internal thoracic arteries using as a Y graft and in group B conventional revascularization using left internal thoracic artery (ITA) attached to the left anterior descending artery (LAD) and venous grafts to the other branches of the left coronary artery was performed. The flow in all grafts was measured at six time points during the operation. The cumulative flow at the end of the operation in the group A (arterial Y graft) was 51.8 ± 24.5 ml/min and in group B (conventional technique) it was 96.8 ± 41.1ml/min (p < 0.05). The flow in left ITA to LAD was similar in both groups (27.3 ± 15.9 ml/min and 26.3 ± 16.1 ml/min in group A and B). The flow in right ITA (25.2 ± 18.4ml/min) was significantly lower than in venous grafts (72.5 ± 45.5 ml/min). The calculated flow reserve was 2.2 in group A and 2.1 in group B. We found that the cumulative flow in arterial Y graft was lower in comparison with conventional revascularization. This is due to the lower flow in the right ITA branch of the Y graft compared to venous grafts. However based on clinical results, we can postulate that the flow in the Y graft is sufficient to meet the demand of the myocardium originally supplied by the left coronary artery.

Background: The aim of this review was to summarise the experience on implementation of information technology to support the teaching and learning process in medicine. Particular attention was paid to web-based tutorials, their impact on increasing the effectiveness of medical instruction and motivation of students towards self-directed learning. Most of the studies selected for the purpose of the review comprised evaluation of the web-tutorials in view of practical implementation, strengths, weaknesses, and main preferences in comparison with traditional lecture-based education. Method and results: We searched MEDLINE via PubMed using MeSH term "computer-assisted learning" between 1996 and 2005 and selected for inclusion in this review were studies on the implementation and evaluation of web based tutorials in medical education. Additional related papers were obtained through cross-referencing. We found that overall, students prefer Web tutorials to traditional lecture-based classes for accessibility, ease of use, freedom of navigation, high medical image quality and advantage of repeated practice, that web-based learning has been continually developing and that it is a very important tool in Evidence Based Medicine. Conclusions: Web based education is an important tool in medical training. It will require transformation in the way medicine is taught from instructor based to self directed learning. It is above all seen as a device for information retrieval and storage.

In 2000-2005, a survey on the consumption of legal and illegal drugs of abuse was conducted in 1571 students of Faculty of Pharmacy in Hradec Králové, Charles University in Prague. The availability of cannabis and the prevalence rates of its use in university students were investigated. A standardized anonymous questionnaire was employed for the survey. The average age of respondents was 20 years. The number of females was higher (82.8 %) than that of males. Marijuana was the most available and the most commonly used illegal drug of abuse in the group of pharmacy students. Its offer and the life-time prevalence increased over the 5 year period of the survey from 55.8 % to 72.9 % and from 30.3 % to 48.4 %, respectively. There was a predominance of the male users over the female ones, mainly in a category of high frequency of marijuana consumption ("used more than five times"). Almost three quarters of marijuana consumers admitted more than one experience with marijuana. Our data provide worrying statistics and support the need of continuous education also in university students to advise them on the risks of drug misuse.

Background: hMLH1 and hMSH2 genes are both known to play a role in DNA mismatch repair. Nonetheless, the clinical significance of hMLH1 and hMSH2 protein expression in lung cancers remains unclear. Aim: The aim of this study was to investigate the immunohistochemical expression of hMLH1 and hMSH2 proteins in tumor specimens from 179 non-small cell lung cancer (NSCLC) patients using a tissue microarray technique and to correlate these results with other clinicopathological variables, including the disease specific and overall survivals. Method: hMLH1 and hMSH2 protein expression was evaluated by immunohistochemistry using monoclonal antibodies G168-728 for hMLH1 and FE11 for hMSH2 protein expression analysis. The Pearson χ² test was used to compare the hMLH1 and hMSH2 alterations among the cases and between various clinical and laboratory variables. P < or = 0.05 was considered statistically significant. Results: Alteration of hMLH1 and hMSH2 protein expression was observed in 10 % of patients. No significant correlation was found between the protein expression and patient age, smoking status, tumor histology or disease stage and disease free and overall survival. Conclusions: Alterations in the expression of hMLH1 and hMSH2 proteins did not have any prognostic value in stage III. NSCLC patients.

Background: Crohn's disease (CD) is a chronic relapsing disease. Especially acute period may be associated with metabolic disturbances. Alteration of lipid metabolism has been described in critically ill patients and hypocholesterolemia is associated with poor prognosis. The human organism acquires cholesterol by two principal processes - synthesis de novo, and absorption from the diet. It is possible to assess, using cholesterol synthesis markers (lathosterol) and cholesterol absorption markers (sitosterol, campesterol) the leading form of cholesterol acquisition. Aim: The aim of this study is assess the association between the lipid profile in plasma and the plasma concentration of sterols in active CD patients and in control subjects. Method: Routine laboratory tests, CDAI, lipid and non-cholesterol sterols plasma levels were performed on days 3, 14 and 28. The metabolic parameters have been compared with a control cohort of 100 healthy blood donors. Results: Presently, complete data for 8 patients are available The serum total cholesterol, LDL and HDL cholesterol, and triglyceride concentrations were lower in patients with acute Crohn's disease than in the control group. Moreover lathosterol, campesterol and sitosterol concentrations were lower, whereas squalene concentration was higher than in controls. As mentioned above, complete data are not currently available. Therefore statistical analysis has not been finished. Conclusion: Our pre-results show substantial abnormalities in the concentrations of plasma lipids and non-cholesterol sterols, which are presented as markers of cholesterol requirement, in patients with acute CD.

Background: About 20 percent of the population in developing countries is composed of women of reproductive age. These women face one of the catastrophic risks of pregnancy "uterine rupture". Studies conducted in the developing world give strong evidence that uterine rupture is a major health problem in these countries with the rate being high in rural areas. Aim: The purpose of the study was to estimate the incidence and determine the risk factors and outcome of uterine rupture among women using the referral hospital Al-thawra in Sana'a City, Yemen republic and to extrapolate the data to the whole of Yemen. Methods: The data was collected retrospectively; by interviewing, examining and following up all the cases of uterine rupture coming to the hospital during a period of 9 months between September 1996 and May 1997. A descriptive analysis and distribution frequency of the commonest causes of uterine rupture in 37 cases are presented taking into account medical, reproductive, health services provided and sociodemographic factors. Results: Incidence of uterine rupture in Yemen was found to be (0.63), obstructed labor 83 %, contracted pelvis 19 %, previous surgery in 48 %, Oxytocine infusion in 42 %. Grand-multiparty was in 65 % and maternal age over 35 years in 50 %. Antenatal care was only in 34 %. Conclusion: The high percentage of malpresentation, cephalopelvic disproportion, previous uterine surgery accompanied by the high percentage of use of Oxytocin in this study highlights very clearly the role of this medication in increasing the risk of uterine rupture in Yemen.

Background: Chemokines and chemokine receptors are major mediators of leukocyte trafficking into the sites of the immune response. They participate in defence against microbial infection, in Th1/Th2 polarization of the immune response, allograft rejection and angiogenesis/angiostasis as well as in tumorigenesis and metastasis. To date, several functional polymorphisms of chemokine and chemokine receptor genes have been discovered that are able to deregulate chemokine system and, therefore, they may interfere with the pathogenesis of a large number of inflammatory and other diseases. In this review we focus on the known polymorphisms of two chemokines: CCL2, CCL5 and their corresponding receptors (CCR2, CCR5) and we also discuss their associations with susceptibility and progression to selected immune-mediated diseases. Methods And Results: Based on relevant literature this article gives a short overview of case-control and family studies regarding effect of the genetic factors on diseases such as coronary artery disease, systemic lupus erythematosus, diabetes mellitus, lung diseases and others. Conclusion: Recent advance in the identification of chemokine genetic background of the diseases could provide opportunity for pharmacological treatment. However, we need more information about posttranscriptional events to understand functional relevance of polymorphisms and to discovery new avenues to blocking disease de velopment.

Objectives: The purpose of this study was to investigate the effect of milk and fluoridated milk on bacterially induced caries-like lesions. Sample and methods: Extracted impacted human molars were cut in half and covered with a varnish leaving a 4*4 mm window. The samples were coated with biofilm of S. sobrinus and were further divided into three experimental groups of S. sobrinus, S. sobrinus and milk and S. sobrinus and fluoridated milk. As negative controls served teeth incubated in saline. Of twenty tooth halves serial ground sections were cut through the lesions and investigated with polarization light microscopy (PLM) and scanning electron microscopy (SEM) and EDX element analysis. The PLM photographs were used for 3D reconstruction, volumetric assessment and determination of the extension of the lesion zones. Of eight tooth halves the biofilm on the enamel surface was studied with SEM and EDX element analysis. Results: Volumetric assessment showed a statistically significant difference in the volume of the body of the lesion and the translucent zone between the milk group and fluoridated milk group. Quantitative element analysis demonstrated significant differences between sound enamel and the superficial layer in the fluoridated milk group. The biofilm on the enamel surface showed an increased Ca content in the milk group and fluoridated milk group. Conclusions: Milk as a common nutrient seems to play a complex role in in-vitro biofilm - enamel interactions stimulating bacterial demineralization on one hand, and, as effective fluoride carrier, inhibits caries-like demineralization.

OLOMOUC, 2 – 4 OCTOBER 2003

A significant number of myocardial diseases are accompanied by increased synthesis and degradation of the extracellular matrix (ECM) as well as by changed maturation and incorporation of ECM components. Important groups of enzymes responsible for both normal and pathological processes in ECM remodeling are matrix metaloproteinases (MMPs). These enzymes share a relatively conserved structure with a number of identifiable modules linked to their specific functions. The most important function of MMPs is the ability to cleave various ECM components; including such rigid molecules as fibrillar collagen molecules. The amount and activity of MMPs in cardiac tissue are regulated by a range of activating and inhibiting processes. Although MMPs play multifarious roles in many myocardial diseases, here we have focused on their function in ischemic cardiac tissue, dilated cardiomyopathy and hypertrophied cardiac tissue. The inhibition of MMPs by means of synthetic inhibitors seems to be a promising strategy in cardiac disease treatment. Their effects on diseased cardiac tissue have been successfully tested in several experimental studies.

Metallothioneins belong to the group of intracellular, high molecular and cysteine-rich proteins whose content increase with increasing concentration of a heavy metal. Here we applied the adsorptive transfer stripping differential pulse voltammetry Brdicka reaction for the determination of metallothionein in human blood serum of patient poisoned by lead and/or treated by platinum. The increased metallothionein concentrations in both cases were observed.

Ellipticine is a potent antineoplastic agent, whose mode of action is considered to be based mainly on DNA intercalation and/or inhibition of topoisomerase II. Recently, we found that ellipticine also forms the cytochrome P450 (CYP)-mediated covalent DNA adducts. Here, we study the effect of ellipticine on CYP enzymes in rat hepatic microsomes, studying its binding to the enzymes and its potential to inhibit the CYP activities measured with their selective substrates. Although ellipticine was reported to be a selective and strong inhibitor of CYP1A1/2, we found that its inhibitory potential is non-specific. Ellipticine is the most potent inhibitor for CYP3A-dependent 6β-hydroxylation of progesterone, followed by CYP1A1/2-dependent ethoxyresorufin O-deethylation and CYP2B-mediated pentoxyresorufin O-depentylation. Lower inhibition was detected for 1'-hydroxylation of bufurarol, 21-hydroxylation of progesterone and 6-hydroxylation of chlorzoxazone catalyzed by CYP2D, CYP2C and CYP2E1, respectively. Ellipticine binds to several CYPs of rat hepatic microsomes. The binding titration of ellipticine typically give reverse type I spectrum with CYPs in rat hepatic microsomes. The results indicate that inhibition of CYPs by ellipticine cannot be explained only by its differential potency to bind to individual CYPs.

Breast cancer is considered to be a multifactorial disorder caused by both genetic and non-genetic factors. Different histological types of breast cancer differ in response to treatment and may have a divergent clinical course. Breast tissue is heterogeneous, with components of epithelial, mesenchymal, endothelial and lymphopoietic derivation. The genetic heterogenity of invasive breast cancer is reflected by the wide spectrum of histological types and differentiation grades. Nevertheless, the influences of these cell types on the tumour's total pattern of gene expression can be estimated analytically. Microarrays permit total tissue analysis and provide a stable molecular portrait of tumours. Some investigations suggest differences in the gene expression profiling for ductal and lobular carcinomas. It has been reported that inactivating mutations of the E-cadherin gene are very frequent in infiltrating lobular breast carcinomas. Other than altered expression of E-cadherin, little is known about the underlying biology that distinguishes ductal and lobular tumour subtypes. However, about 8 genes have been identified differentially which are expressed in lobular and ductal cancers: E-CD, survivin, cathepsin B, TPI1, SPRY1, SCYA14, TFAP2B, and thrombospondin 4, osteopontin, HLA-G, and CHC1. Expression profiling of breast cancers can be used diagnostically to distinguish individual histologic subclassifications and may guide the selection of target therapeutics. However, future approaches will need to include methods for high throughput clinical validation and the ability to analyze microscopic samples.

The goal of the study was to monitor the antioxidative effect of stobadine derivative under conditions of ischemiareperfusion of laboratory rat kidney tissue. 40 animals were subjected to kidney tissue ischemia (60 min) followed by reperfusion (10 min). After that, the animals were divided by random selection into 4 groups (n = 10). The treated groups were given stobadine derivative in peroral doses of 5, 10 and 20 mg/kg in 0.5% solution of Avicel once a day, the placebo group was given only the solution of Avicel. One group (n = 10) was an intact group (without ischemiareperfusion and without treatment), for comparison. Once a week, selected laboratory parameters were determined in all animals. On the 15^th day the animals were exsanquined and organs were recovered for histopathological examination. We discovered a statistically significant changes of the superoxiddismutase and glutathione peroxidase catalytic activity; changes of total antioxidative capacity and malondialdehyde in the treated groups compared to the groups of placebo and intact. Other examined laboratory parameters (creatinine, urea and uric acid in blood; creatinine, urea, total protein in urine; diuresis) exhibited significant changes too. The results of biochemical examination show a protective antioxidative effect of the compound studied. The results of histopathological examination support this assumption.

The effects of non-esterified fatty acids (NEFA) and hormone dehydroepiandrosterone (DHEA) on the levels of mRNAs of protein kinase C (PKC) -δ and -ε isoforms and those of liver fatty acid binding protein (L-FABP) were investigated in the human hepatoma HepG2 cell line. The cells were kept in low-serum, low-albumin medium during experiments. Low FA levels (100 μM) and time intervals of 4 h and 20 h were used. In these conditions, the saturated (palmitic, stearic) and monounsaturated (oleic) acids rather selectively stimulated PKC-ε mRNA levels. Unexpectedly, we found that these acids also suppressed liver fatty-acid binding protein (L-FABP) mRNA levels. DHEA in pharmacological doses (100 μM) produced a significant increase in PKC-δ and -ε mRNA levels. Although molecular mechanisms underlying the identified changes have not been investigated in this paper, our findings emphasize that NEFA-induced modulation of mRNA levels of key signalling components represent an additional mechanism for how the ambient NEFA can influence metabolic homeostasis in cells.

The thalidomide tragedy stimulated an intense research in the etiology, prevention and treatment of congenital malformations. The Government requires that drugs and food additives be evaluated pre-clinically for toxicity, including developmental toxicity, before being marketed. The number of compounds which must be tested has increased dramatically with the continuous development of therapeutic, cosmetic and food additive chemicals. Such tests include: in vitro studies which can serve as efficient pre-screens to rank chemicals for further batteries of in vivo tests on pregnant animals. However, the safety of any drug would be determined only by a post-marketing epidemiological survey. Taking into account the altered susceptibility to different drugs in a pregnant individual, it could be said that administration of any drug during the first trimester is an experiment in human teratology.

Oxidative stress impairs endothelial function and may play an important role in the pathogenesis of acute cardiovascular diseases. Advanced oxidation protein products (AOPP) were proposed as one of the possible markers of oxidative injury, which originates under oxidative and carbonyl stress and increase global inflammatory activity. The present study was undertaken to compare AOPP concentrations in a control group of healthy individuals without ICHS (I), patients with stable angina pectoris (II), patients with acute coronary syndrome over 48 hours without ST elevations (III), and patients with ST elevation myocardial infarction (IV). Coronaronary angiography, risk factors and anamnestic data were analyzed. We examined 73 probands with signs of myocardial ischemia, mean age of 61.5 years (64 % males) subjected to coronarography and 21 healthy individuals. No significant difference was found between venous blood and coronary samples, or between infarction and non-infarction arteries in the group IV. AOPP concentrations in healthy individuals in the group I (82.9 ± 29.3 mmol/l) did not differ significantly from patients in group II (89.6 ± 26.7 mmol/l) and group III (112.3 ± 54.6 mmol/l). A significant difference in AOPP values was found between the groups I and IV, and between the groups II and IV (82.9 ± 29.3 mmol/l vs. 125.8 ± 101 mmol/l, p = 0.02, and 89.6 ± 26.7 mmol/l vs. 125.8 ± 101 mmol/l, p = 0.02). No correlations were found between AOPP and body mass index (BMI), nicotinism, left ventricular ejection fraction, parameters of glucose and lipid metabolism. ROC analysis revealed that AOPP concentrations of 89 mmol/l had 64 % sensitivity and 71 % specificity for revealing an acute coronary syndrome (AUC 0.65, 95 % CI 0.55-0.80). AOPP are significantly increased in patients with acute coronary syndromes with ST segment elevation, but also tend to increase in patients with non-ST elevation myocardial infarction. Our observations suggest that AOPP may be used as a marker of oxidative stress and as a prognostic factor for severe forms of cardiovascular disease. A cut-off value of 89 mmol/l can be used with 64 % sensitivity and 71 % specificity for revealing acute coronary syndrome.

The goal of the study was to monitor the antioxidative effect of stobadine derivative in the conditions of ischemiareperfusion of laboratory rat kidney tissue. The animals were divided by random selection into 5 groups (n = 10). The treated groups were given stobadine derivate in peroral doses of 5, 10 and 20 mg/kg in 0.5 % solution of Avicel once a day; the placebo group was given only the solution of Avicel. The last group was an intact group (without ischemiareperfusion and without treatment). After conclusion of medication on the 15^th day all animals were subjected to kidney tissue ischemia (60 min.) followed by reperfusion (10 min.). All animals were subsequently exsanquined and single identification of superoxiddismutase, glutathion peroxidase, total antioxidative capacity, and malondialdehyde level in the blood were determined. Kidneys were recovered for histopathological examination. A statistically significant decrease of the superoxiddismutase and statistically significant increase of the glutathione peroxidase catalytic activity in the treated groups compared to the groups of placebo and intact was discovered. There was also a statistically highly significant increase of total antioxidative capacity in the treated groups compared to the groups of placebo and intact. A statistically significant decrease of malondialdehyde level was identified in the treated groups compared to the groups of placebo and intact. The results of biochemical examination show a protective antioxidative effect of stobadine derivative. The results of histopathological examination support this assumption.

In a group of 117 patients with multiple myeloma (MM) examined at the time of diagnosis, i.e. excluding previous chemotherapy, we analysed the levels of propidium-iodide (proliferative) - PC-PI/CD₁₃₈ and annexin-V (apoptotic) - PC-AI/CD₁₃₈ indices of myeloma plasmocytes using the method of flow-cytometry to determine their relationship to prognosis. It was revealed that patients with high values of PC-PI/CD₁₃₈ had substantially worse overall survival than those with low values. Patients with a level of propidium-iodide index ≥ 2,8 % exprimed a median survival of 13 months only in comparison with 42 months in patients with levels < 2,8 % (p = 0,0005). In the PC-AI/CD₁₃₈ index a reverse trend was registered. Patients with PC-AI/CD₁₃₈ ≥ 4,0 % had long overall survival (median was not assessable at the time of evaluation), whereas patients with low apoptosis values < 4,0 % had median overall survival 16 months only (p = 0,01). Based on the sequentional graphic analysis of the curves of overall survival was found that the optimal discrimination level sequestering patients with good and poor prognosis was, in the case of PC-PI/CD138 value 2,8 %, whereas in the case of PC-AI/CD₁₃₈ value 4,0 %. Among patients with good prognosis, there were no statistically significant differences in overall survival according to different levels of proliferative and apoptotic index. We conclude that evaluation of the propidium-iodide and annexin-V index using flow-cytometry is a quick, useful, and easily accessible method for the evaluation of plasma cell kinetics and thus prognosis of the disease, multiple myeloma.

The human glucocorticoid receptor (hGR) plays a pivotal role in cellular processes such as development, differentiation, homeostasis, immune response and in regulation of xenobiotic metabolism. It has been demonstrated recently that colchicine inhibits hGR transcriptional activity in primary cultures of human hepatocytes by a mechanism involving impairment of hGR nucleo-cytoplasmic shuttling. In the present work, we investigated the role of the nuclear factor kappa B (NFκB) and c-jun-N-terminal kinase (JNK), the functional hGR antagonists, in this process. We found that microtubule disarray caused by colchicine, vincristine or nocodazole does not activate NFκB in human hepatocytes as revealed by p50 and p65 subunits nuclear translocation. On the other hand, we demonstrate that JNK mediates hGR transcriptional inhibition by microtubules disarray, because a specific inhibitor of JNK, 1,9-pyrazoloanthrone (SP600125), partially blocked tyrosine aminotransferase mRNA suppression due to colchicine treatment. In conclusion, JNK is at least partly involved in hGR transcriptional inhibition by colchicine in human hepatocytes, while NFκB involvement is doubtful.

Microtubule disruptors, widely known as antimitotics, have broad applications in human medicine, especially as anti-neoplastic agents. They are subject to biotransformation within human body frequently involving cytochromes P450. Therefore antimitotics are potential culprits of drug-drug interactions on the level of activity as well as expression of cytochromes P450. This review discusses the effects of four well-known natural antimitotics: colchicine, taxol (paclitaxel), vincristine, and vinblastine, and a synthetic microtubule disruptor nocodazole on transcriptional activity of glucocorticoid and aryl hydrocarbon receptors. It appears that microtubules disarray restricts the signaling by these two nuclear receptors regardless of cell cycle phase. Consequently, intact microtubules play an important role in the regulation of expression of cytochromes P450, which are under direct or indirect control of the two nuclear receptors.

Authors discuss problems with identification and determination of flunitrazepam and zolpidem in biological material (BM). Over the recent years, these two structurally different substances have become the most frequently used as well as abused hypnotic drugs. This study presents applicability of immunochemical methods in the screening of flunitrazepam, one of the most commonly prescribed drugs among the benzodiazepines. Herein described techniques, a liquid-liquid (L-L) extraction, solid phase extraction (SPE) and the so-called "freeze out" method are used for isolation of the above mentioned compounds from BM. Besides the thin layer chromatography (TLC) and gas chromatography - mass spectrometry (GC-MS) applied in qualitative analysis, the study also describes a gas chromatography with electron capture detector (GC-ECD) and gas chromatography with nitrogen phosphorus detector (GC-NPD) optimized for the determination of flunitrazepam and zolpidem in blood (serum). Successful analyses of these two substances are of major importance, especially in interpreting the results of forensic toxicological examinations.

Familial combined hyperlipidemia (FCH) is the most common familial hyperlipidemia with a high risk for early atherosclerosis. The aim of this study was to compare levels of soluble intercellular cell adhesion molecule 1 (s-ICAM-1) and soluble vascular cell adhesion molecule 1 (s-VCAM-1) in asymptomatic members of FCH families with healthy controls and to determine the relation between s-ICAM-1, s-VCAM-1 and risk factors accompanying FCH. We also investigated the association between adhesion molecules and the intima-media thickness (IMT) of the common carotid artery, a recognized morphological marker of early atherosclerosis. 82 members of 29 FCH families were divided into the 2 groups: HL (probands and hyperlipidemic first-degree relatives, n = 47) and NL (normolipidemic first-degree relatives, n = 35). The control groups - HL-C (n = 20) and NL-C (n = 20) - consisted of sex- and age-matched healthy individuals. Hyperlipidemic members had significantly higher concentration of s-ICAM-1 (633.7 ± 169.6 ng/ml versus 546.2 ± 155.9 ng/ml, p < 0.05). The elevation of s-VCAM-1 was not significant (880.8 ± 202.9 ng/ml versus 826.5 ± 174.6 ng/ml, N.S.). Levels of s-ICAM-1 and of s-VCAM-1 in normolipidemic relatives were not significantly different from the control group (530.8 ± 113.9 ng/ml versus 530.0 ± 101.0 ng/ml and 860.2 ± 265.7 ng/ml versus 822.1 ± 197.0 ng/ml respectively). There was a significant correlation between s-ICAM-1 and apoB (r = 0.42; p < 0.01) in hyperlipidemic subjects and between s-ICAM-1 and proinsulin (r = 0.54; p < 0.01) in normolipidemic subjects. S-ICAM-1 correlated with IMT (r = 0.32; p < 0.05) in all members of FCH families. The increase of s-ICAM-1 in asymptomatic hyperlipidemic members of FCH families reflects their high cardiovascular risk. The positive association between s-ICAM-1 and IMT could indicate s- ICAM-1 as a potential predictor of atherosclerosis manifestation.

Isothiocyanates (ITCs) are phytochemicals with promising cancer-preventive potential. To elucidate the mechanism of cytotoxicity of ITCs, their accumulation by cells and the role of intracellular glutathione, fluorescent 9-isothiocyanatoacridine (AcITC) was synthesized. The kinetic parameters for the reactions of AcITC with thiols were estimated and the influence of AcITC on human chronic myeloid leukemia cell line (K562) in regard to intracellular glutathione was studied. Cytotoxicity was evaluated by MTT assay, IC₅₀=29.2 ± 2.5 μM (48 h incubation). This acridine derivative was able to induce apoptosis of cells (morphological changes of cells and DNA fragmentation were observed) at least within certain dose that only decreased the level of intracellular glutathione, excessive doses (completely depleted intracellular pool of glutathione) induced necrosis rather than apoptosis. Our results indicated that apoptosis of leukemia cells induced by ITC is possible only if intracellular glutathione is not entirely depleted.

The anti-arrhythmic effect was tested on the model of aconitine-induced arrhythmia. The experiment was performed in vivo with 31 male Wistar laboratory rats. Group A was first administered aconitine and, after the onset of the first sinus rhythm disorders, the 44Bu compound was administered. Group B was first administered the 44Bu compound and only after that the aconitine. The control group was administered aconitine and saline as a replacement of the tested compound. In group A, there was a decrease in the ventricular fibrillation occurrence from 100 % to 8 % (p < 0.001) after the administration of the 44Bu compound. In the B group, the onsets of all monitored arrhythmia types were delayed by an average of 15.6 min. Ventricular rhythm occurrence was decreased from 100 to 20 %, as well as ventricular fibrillations, from 100 to 0 % (p < 0.001).

A review on applicability of in silico methods for toxicity testing by calculation for regulatory purposes, their survey and background of QSAR (Quantitative Structure-Activity Relationships) analysis are presented.

The most significant precancerosis in the esophageal cancer is Barrett's esophagus. The risk of malignant transformation is determined primarily in accordance with the degree of dysplastic alterations of the mucosa. Indication of "preventive" extirpation of the esophagus should be supported by other factors, for example by detection of p53 mutation or expression. The study reports on the evaluation of a group of 20 patients with Barrett's esophagus treated at the 1^st Department of Surgery, the p53 level and its correlation with histological findings evaluated in these patients. A good correlation was found between the grade of Barrett's esophagus dysplasia and high p53 positivity. This correlation was also confirmed by detection of early carcinoma in patients with "preventive" extirpation of the esophagus due to a high-grade dysplasia. Preliminary results show that examination of p53 level in specimens taken from the esophageal mucosa may be helpful for the estimation of malignant potential of the dysplastic mucosa.

The mechanism of intoxication with organophosphorus compounds, including highly toxic nerve agents, is based on the formation of irreversibly inhibited acetylcholinesterase (AChE; EC 3.1.1.7) that could be followed by a generalized cholinergic crisis. Nerve agent poisoning is conventionally treated using a combination of a cholinolytic drug (atropine mostly) to counteract the accumulation of acetylcholine at muscarinic receptors and AChE reactivators (pralidoxime or obidoxime) to reactivate inhibited AChE. At the Department of Toxicology, the strategy of the development of new more potent AChE reactivators consists of several steps: description of the nerve agent intoxication mechanism on the molecular basis (molecular design), prediction of the biological active structure of AChE reactivators (artificial neural networks), their synthesis, in vitro evaluation of their potencies (potentiometric titration and Ellman's method), in vivo studies (therapeutic index, LD₅₀ of newly synthesized reactivators, reactivation in different tissues, neuroprotective efficacy).

This article aims to review critically literature published mainly within this millennium on the new and emerging applications of silymarin, the polyphenolic fraction from the seeds of Silybum marianum and its main component silybin. Silymarin and silybin used so far mostly as hepatoprotectants were shown to have other interesting activities as e.g., anticancer and canceroprotective. These activities were demonstrated in a large variety of illnesses of different organs as e.g., prostate, lungs, CNS, kidneys, pancreas and others. Besides the cytoprotective activity of silybin mediated by its antioxidative and radical-scavenging properties also new activities based on the specific receptor interaction were discovered - e.g., inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors and some others. New derivatives of silybin open new ways to its therapeutic applications. Pharmacology dealing with optically pure silybin diastereomers may suggest new mechanisms of its action.

Industrial fibrous dusts are applied in many industrial branches and represent adverse factors in occupational and enviromental area. Refractory ceramic fibers (RCFs) - amorphous alumina silicates - are used as one kind of asbestos substitutes. Because RCFs are relatively durable and some RCFs are respirable, they may present a potential health hazard by inhalation. The aim of present work was to find out the subchronic effect of RCFs on selected parameters of bronchoalveolar lavage (BAL) in W-rats, confirm the biopersistence of RCFs after 6 month instillation and contribute to the understanding of the pathomechanism of lung injury after fibrous dust exposure. Wistar rats were intratracheally instilled with 4 mg/animal of RCFs - exposed group and with 0.4 ml saline solution/animal - control group. Animals were sacrificed after 6 month exposure. Bronchoalveolar lavage (BAL) was performed and selected BAL parameters (mainly inflammatory and cytotoxic) were examined. After treatment with RCFs the following changes were observed: statistically significant increase in proportion of lymphocytes and polymorphonuclears as well as in % of immature alveolar macrophages (AM) and phagocytic activity of AM; statistically significant decrease in viability of AM and proportion of AM (from the differential cell count) in comparison with the control group. The results of this study indicated that RCFs even 6 months after intratracheal instillation very significantly changed the majority of examined BAL parameters. The presence of inflammatory and cytotoxic response in lung may signalize beginning or developing disease process.