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Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM.Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, GGT, uric acid, total leukocyte/neutrophil count, and urinary 8-oxo-deoxyguanosine (u-8-oxodG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications.BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-oxodG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Age-dependent increase in u-8-oxodG suggests that aging process, rather than metabolic disturbances or diabetes per se plays a pivotal role in development of oxidative DNA-damage in T2DM. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

Cilj ovog istraživanja je ispitati koncentracije vitamina D u serumu u djece sa zloćudnom bolešću.

There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen per- oxide (H2O2) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialde- hyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H2O2 and possible reduction of enzyme activities including in H2O2 metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxi- dation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis.

Background: It was suggested that statins exerted their protective effect against Alzheimer disease (AD) due to inhibition of cholinesterase (ChE) activity. Results of some nonclinical and clinical studies have shown that statins either do not influence or decrease enzyme catalytic activity. Our previous studies showed that simvastatin increased plasma and liver ChE activity in normolipidemic rats. In respect to these findings we studied influence of simvastatin (SIMV) and fenofibrate (FENO) on ChE activity in hyperlipidemic rats. Methods: Twenty-one male hyperlipidemic Zucker rats were divided into one control and two experimental groups. One experimental group was on SIMV treatment (50 mg/kg/day) and another on FENO treatment (30 mg/kg/day). Both agents were given orally for 3 weeks, as well as saline for control group. Animals were sacrificed 24 hours after the last dose. Blood samples were obtained directly from heart. Liver and brain tissue were rinsed with saline. ChE activity was determined by Ellman’s spectrophotometric method using butyrylthiocholine and acetylthiocholine as substrates. In liver tissue the ChE activity was measured with and without ethopropazine hydrochloride. Enzyme activities were expressed as μmol of substrate hydrolysed per min per ml of serum or g of tissue. Data were analyzed using ANOVA and Dunnett's test. Results were considered as significant with p

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Growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin are involved in brain development, and also act as neuroprotective factors. The values of these hormones in healthy population have not been published so far. We measured concentrations of GH, IGF-1 and insulin in cerebrospinal fluid (CSF) of 57 healthy people (35 male and 22 female), undergoing lumbar puncture for spinal anesthesia before surgery of the knee joint. In men, the mean (SD ; min-max) concentrations of GH, IGF-1 and insulin in CSF were 0.67 (0.11 ; 0.50-0.90) µU/mL ; 7.49 (0.92 ; 6.00-9.00) µg/L and 0.71 (0.13 ; 0.40-0.90) µU/mL, respectively. In women, the mean CSF concentrations of GH, IGF-1 and insulin were 0.69 (0.10 ; 0.50-0.90) µU/mL ; 7.32 (0.95 ; 6.00-9.00) µg/L and 0.68 (0.13 ; 0.40-0.90) µU/mL, respectively. None of the study hormones showed statistically significant sex difference. There were no significant bivariate correlation between GH, IGF-1 and insulin. The hormones did not correlate with age either. Determination of the normal range of GH, IGF-1 and insulin in CSF could help identify deviations in CSF hormone status in particular neurologic diseases. These values could prove important in the screening, diagnosis and management of various diseases involving the central nervous system.

The pathogenesis of recurrent urinary tract infections (UTIs) in preschool children with anatomically correct urinary tract (UT) is rather obscure. In girls, the bladder wall changes of cystitis cystica (CC) may be per se responsible for UTIs recurrence. During the 20-year period, 127 preschool children (125 girls ; median age: 6.1 years) with CC, in whom UT anomalies were excluded, were diagnosed. The mean duration of UTIs symptoms prior to diagnosis was 3.31 +/- 2.51 years. Cystoscopical findings were labelled as mild, moderate and severe in 22.8%, 39.4% and 37.8% of patients, respectively. Following the confirmation of CC, long-term chemoprophylaxis with sulfamethoxazole- trimethoprim/nitrofurantoin was administered. A one year UTI-free period after chemoprophylaxis discontinuation was defined as therapeutic success. With 2.5 years median duration of regular chemoprophylaxis this goal was achieved in 58 children mainly with mild/ moderate CC. Thirty children from "improved/unchanged" group taking regular prophylaxis had significant reduction of UTIs ("improved"). Only 12 children belonging to the same group taking regular prophylaxis and all children with irregular prophylaxis had approximately the same number of UTIs as before treatment ("unchanged"). The "improved/unchanged" outcomes were predominantly found in children with severe form of CC. Although urodynamic disturbances detected in more than 50% of patients in whom urodynamics was performed were not found influential on the disease outcome, they could be responsible for its development. The results of our study suggest that regular and long-lasting chemoprophylaxis remains a basis for successful treatment for majority of patients with CC, even those with severe forms. If not treated properly with chemoprophylactic agents and without fair compliance in taking drugs, the disease is prone to recurrent UTIs.

The pathogenesis of recurrent urinary tract infections (UTIs) in preschool children with anatomically correct urinary tract (UT) is rather obscure. In girls, the bladder wall changes of cystitis cystica (CC) may be per se responsible for UTIs recurrence. During the 20-year period, 127 preschool children (125 girls; median age: 6.1 years) with CC, in whom UT anomalies were excluded, were diagnosed. The mean duration of UTIs symptoms prior to diagnosis was 3.31 +/- 2.51 years. Cystoscopical findings were labelled as mild, moderate and severe in 22.8%, 39.4% and 37.8% of patients, respectively. Following the confirmation of CC, long-term chemoprophylaxis with sulfamethoxazole-trimethoprim/nitrofurantoin was administered. A one year UTI-free period after chemoprophylaxis discontinuation was defined as therapeutic success. With 2.5 years median duration of regular chemoprophylaxis this goal was achieved in 58 children mainly with mild/ moderate CC. Thirty children from "improved/unchanged" group taking regular prophylaxis had significant reduction of UTIs ("improved"). Only 12 children belonging to the same group taking regular prophylaxis and all children with irregular prophylaxis had approximately the same number of UTIs as before treatment ("unchanged"). The "improved/unchanged" outcomes were predominantly found in children with severe form of CC. Although urodynamic disturbances detected in more than 50% of patients in whom urodynamics was performed were not found influential on the disease outcome, they could be responsible for its development. The results of our study suggest that regular and long-lasting chemoprophylaxis remains a basis for successful treatment for majority of patients with CC, even those with severe forms. If not treated properly with chemoprophylactic agents and without fair compliance in taking drugs, the disease is prone to recurrent UTIs.

The model of ICAM-1 and LFA-1 molecular interaction was used to test the application of the Molecular Recognition Theory for the identification of several discontinuous binding regions, i.e. ligand-receptor sites, within large antigenic molecules. Molecular Recognition Theory is an applicable heuristic algorithm for identification of possibly interacting amino acid pairs in short linear epitope/paratope sites within larger molecules. However, in order to achieve better efficiency this heuristic algorithm of molecular recognition has to be combined to several other procedures: molecular hydropathy analyses, secondary structure prediction methods and protein database search. The limitation of the combined MRT-hydropathy analyses is in the fact that it cannot explain 3D protein interactions, but it can be a valuable starting point for a more complex computational and experimental analysis.

Prostaglandins synthesis (PGE2 and PGI2) was determined in the liquors and serum of 19 hypoxic neonates by using ELISA method. Control group consisted of 8 children of the same age whose samples were taken because initial suspicion of neonatal meningitis. The prostaglandin concentrations in liquor were correlated with initial hypoxic-ischemic encephalopathy (HIE) stage and neurological findings of patients at age of 12 months. The values of PGE2 and PGI2 in the liquor of children with PNH were significantly higher than in the children from the control group. The values of PGI2 in serum were significantly higher than in liquor of patients with PNH. Although average values of PGE2 and PGI2 in the liquor were higher in children with advanced stage of HIE, the differences between different stages were not statistically significant. We did not find any significant correlation between average concentrations of prostaglandins and neurological findings of the 12-month-old children.

The hydropathic profile, secondary structure, epitope and binding site of the alpha-melanotropin molecule were investigated. It was shown that the standard algorithm according to Kyte and Doolittle may be combined with complex methods of the secondary structure prediction to extract the information relevant for the epitope location and modeling. The binding ligand-receptor motifs of the hormone were investigated by means of the SSpro8 method. The Molecular Recognition Theory combined with an NCBInr protein database search was applied to find the possible paratope (receptor) structures for the predicted a-melanotropin epitope (ligand). The described concept constitutes a useful and simple set of procedures for deriving new biologically active peptides and antibodies and also for performing modulation of peptide-receptor interaction.

Aim: Met-enkephalin is an endogenous opioid pentapeptide with cytokine properties that has been investigated in many in vitro and in vivo models of inflammation. This study was conducted in order to examine the possible effect of met- enkephalin on changes in pulmonary function provoked by histamine. Methods: Experimental animals were Hartley guinea-pigs (6 animals per group, male-female 1:1, weight 500-700g). Classic Konzett and Rössler’ s method of whole body plethysmography modified by Gjuris was applied to monitor changes in the respiratory rate, type of respirations or amplitude of respirations. Bronchoconstriction was induced in anesthetized animals by i.v. histamine (10 μ g/kg) and the protective effect of met-enkephalin was defined as the percentage of histamine blockade (the reduction of histamine-induced bronchoconstriction ; each animal its own control). Three doses of met-enkephalin were applied: 0.1 mg/kg, 1 mg/kg, and 10 mg/kg. Data were compared by t-test. Results: Met-enkephalin doses of 1 mg/kg and 10 mg/kg caused significant reduction of the histamine induced bronchoconstriction (p

The aim of the study was to investigate the dose-dependent in vivo effect of alpha-melanocyte stimulating hormone (alpha-MSH) in a rat model of inflammatory bowel disease induced by 2, 4, 6-tri nitrobenzene sulphonic acid (TNBS). Laboratory animals (male Wistar rats weighing 200-250 g) were given 3 doses of alpha-MSH (0.5 mg/kg, 1 mg/kg, 2 mg/kg) intraperitoneally 1 hour prior to inducing colitis with a TNBS enema. Control animals received saline solution i.p. Rats were sacrificed after 72 hours and the area of mucosallesions, involving the distal 10 cm of colon, was detennined in mm2 by means of image analysis software. Alpha-MSH structure was analyzed by means of NMR spectroscopy. The area of colonic darnage was significantly reduced following pretreatment with a single dose of 1 mg/kg alpha-MSH, as compared to control animals (p = 0.0147). Higher and lower doses had no significant effects. A single dose of 1 mg/kg a-MSH provided strong, statistically significant and pharmacologically relevant cytoprotection. The results point to alpha-MSH effectiveness in controlling inflarnmation and imply that further in vitro and in vivo experiments should be carried out to judge the importance and relevance of alpha MSH in the control of inflammatory bowel disease. NMR data support a hairpin loop conformation of alpha MSH in water solution, which includes conserved message sequence.

The effectiveness of latanoprost (Xalatan TM) monotherapy in primary open angle glaucoma (POAG) was evaluated. Latanoprost is a prostaglandin analogue, the pure 15(R) epimer of 13, 14 dihydro 17 phenyl 18, 19, 20 trinor PGF2alpha isopropyl ester. As a prodrug it is being activated by enzymatic hydrolysis in the cornea after which it becomes active acid of latanoprost. Latanoprost is lowering the intraocular pressure (IOP) by increasing the uveoscleral outflow. In this study, latanoprost was used once daily as monotherapy what offers much better compliance for the patients than other combinations of drugs, preserving good IOP control. Based on the significant reduction of the IOp, measured on the day 60 ofthe trial (mean change in IOP was -5.1 mmHg, with 95% confidence interval in range from -5.6 to -4.5), it is concluded that use of latanoprost is advisable when calculating better IOP control, few side-effects and reductions in costs of potential surgical procedures.

Što je strojno reprezentiranje znanja, jesu li nam odredivi njegovi dosezi, koja je njegova uloga u informatiziranom obrazovnom sustavu, koji su njegovi svjetski trendovi i projekti, kakvi se postupci, alati, standardi i jezici koriste za njegovu pripremu, u kakvom je odnosu prema obrazovnom planiranju i izradi kataloga znanja i hoćemo li u sklopu promicanja informacijskog obrazovanja dio snaga i resursa našeg znanstvenoobrazovnog sustava organiziranije usmjeriti i u tom pravcu? Kontakt e-mail zlatko et kbsm.hr

Secrets of knowledge management tools are: the knowledge may be textually explicated, those categories must be marked-up, and those representations can be edited. Such editing may be supported by different tools today's in rapid development. Precisely defined knowledge can be more or less quickly and amazingly presented to human and represented to machine and exchanged through recommended categorical frame based languages (OWL) due to Semantic Web project of the World Wide Web Consortium to extending ability of the World Wide Web. Categorical represented data can be integrated from different application and locations, searched and inferenced with machine programs based on description logic. Choosing and working with some of semantic oriented tools, not ignoring Web semantic integration is vision of leaving information confusion and facilitating methodologies of modern knowledge society not on declarative way. Such approach is tending to redefine not only e-learning but whole concept of education and working. What some communities can push on that way?

Proteklo je pet godina od kako smo na ovom skupu, još u Rovinju, prikazali "Nove nastavničke tehnike zasnovane na Web-usmjerenoj edukaciji - http://skola.sys.hr/topclass.htm. Od tada pa do danas Web je postao nezaobilazna sastavnica stvarnosti razvijenih, a i naši su fakulteti i škole u međuvremenu razvili različite web portale. No takvi su, danas prošireni načini, pokazali i ograničenja u pronalaženju sadržaja samo na osnovu pretraživanja objavljenih dokumenata. Novim Internet tehnologijama zasnovanim na koncepciji tzv. Semantičkog Weba ali i srodnim, ta se ograničenja nastoje nadvladati. Razvijanjem i objavljivanjem (u tzv. Ontologijama) tekstualno opisanih iskaza o "resursima" na osnovu ljudskoga iskustva združenih u klase i druge relacije, strojnim bi se tehnikama zaključivanja nastojalo povezati diversificirano objavljivana znanja, makar se njima tvrdilo i različito o istom, smatra njihovo predlagatelj i tvorac prvih Web tehnologija, i osnivač World Wide Web Consortiuma (W3C), Tim Berner Lee. Pretpostavka je da bi se združenim nastojanjima takvim objavljivanjem na standardiziran način uspjelo strukturirati znanje u male opise "resursa" ili stvari. Iskazi formalno imaju strukturu tripleta: subjet – predikat – objekt, oblikovani tzv. "Resorce Description Framework" (RDF) formalizacijom i predstavljaju jedinice znanja manje od udžbenika ili nastavne jedinice, a čitljive današnjim strojevima. Time bi se, smatra se, poboljšala upotreba Web-a a i uspješnije poduprle osobitosti edukacijskih potreba svakoga (učenika, od nas) u situaciji učenja. Postupci razvitka sigurnosti u izvornost kao i meritornost tako objavljivanih iskaza bili bi preduvjet radu nezavisnih Edukacijskih servisa koji bi trebali klasirati primjerenost sadržaja i podržavati načine korištenja Internetom dostupnih objavljenih izvora znanja. Kao primjer spomenimo npr. Faster Finder (http://www.onelook.com) server koji pretražuje 272 riječnika ili Cyc Knowledge Server (http://www.cyc.com/products2.html#cycl)

Dialysis related amyloidosis is the accumulation and deposition of beta(2)-microglobulin derived fibrils in bones and joints, due to insufficient elimination during therapy or slowly progressing renal failure. The aim of this study was to analyse biochemical, morphologic and anamnestic parameters that may be relevant for the onset and developement of dialysis related amyloidosis. In addition to standard statistical procedures, we also applied the machine-learning based methods of data mining to quantify the risk factors for asymptomatic patients. Extraction of: risk factors for the onset of the dialysis related amyloidosis syndrome could enable the clinician to predict the symptoms and consider medical procedures to prevent the onset of the disease. The C4.5 machine learning algorithm extracted a simple and highly accurate tree for discrimination of asymptomatic and symptomatic patients suffering from dialysis related amyloidosis. It remains an open question if our findings may contribute to the problem of accurately predicting the onset of dialysis related arthropathy in the asymptomatic patient group.

Maximal plasma creatine kinase (CPK) values are often used as an enzymatic test in acute myocardial infarction. The cardiovascular functional ability (FA) is a reliable parameter, which may define the lesion of the cardiovascular system following myocardial infarction. We have applied the Cubist machine learning tool to set up a model that defines the residual cardiovascular functional ability after a myocardial infarction by means of the maximal CPK in the acute phase of the disease. Cubist models numeric data and generates values by means of a collection of rules associated with the linear expression for computing target values. Based on the literature data set of Miric et al.,(1) we have derived and tested a reliable and accurate Cubist model for acute inferior and anteroseptal myocardial infarction consisting of three simple rules. The rules enable simple prediction of the expected cardiovascular functional ability in myocardial infarction following recovery. The model is based on two clinical parameters related to the disease, maximal CPK in the acute phase of the myocardial lesion, and anteroseptal or inferior cardial localisation of the infarction. Strong correlation (r anteroseptal = 1.00, r inferior = 0.94, n = 56), insignificant differences of real and predicted values, and low average error of the leave-one-out test (anteroseptal 1.72, inferior 3.54) confirm the accuracy of the method and its applicability in clinical medicine. In addition to the prognostic and diagnostic application, the extracted rules enable more efficient evaluation of new drugs and therapeutic procedures in Cardiology.

The model of ethanol induced gastric lesions is useful in the evaluation of gastric cytoprotection. We used it to measure cytoprotective effects of two neuropeptides, Met-enkephalin (Peptid-M, LUPEX(R)) and alpha -melanocyte stimulating hormone (alpha -MSH). Both peptides exhibited significant and synergistic cytoprotective effects. The best therapeutic efficacy was obtained with Met-enkephalin and alpha -MSH mixture 3-5:1. Significant cytoprotective action on ethanol induced lesions was also observed by means of two thymus peptide immunomodulators, Thymus Peptide C(R) and JAN 50(R). Thymus Peptide C(R) exhibited a more significant synergistic effect with Met-enkephalin than JAN 50(R). In addition to the cytoprotection of rat gastric mucosa, Met-enkephalin also induced statistically significant and dose dependent Straub tail response versus control in mice. Haloperidol, naloxone and Peptide-D antagonised its effects. NMR spectrospic data supported molecular interaction of Metenkephalin and haloperidol, while neutralization of Met-enkephalin induced Straub tail response by means of Peptide-D indicated the presence of new non-opioid (naloxone independent) receptor system containing Peptide-D sequence (calpastatin 201-205 aa).

We applied the machine learning procedure to the analysis of serum and aqueous humor albumin, IgG and interferon-gamma patterns. The data were analyzed with respect to the cataract, type of diabetes, retinopathy and blood-aqueous humor barrier damage. Intraocular production of IgG was detected in diabetic patients, since the IgG index values were increased in some diabetic groups (especially those with type I diabetes and retinopathy). Comparison of numerical methods and clonal IgG detection suggested that intraocular IgG patterns in diabetes are predominately polyclonal. Interferon-gamma (IFN-gamma) was pathological in serum and aqueous humor of patients with type I diabetes and to a lesser extent in the type II diabetes group. Machine learning system based on C5.0 classifier extracted 98.5% accurate rules for discrimination of the senile cataract group, diabetes group and diabetic retinopathy group. Our results confirm that the combination of immunochemical and numerical methods with a proper statistical analysis may contribute to the diagnosis of the pathologic ocular immune response and the related retinal or vascular disorders in diabetes. Significant savings in laboratory material and efforts may be obtained by means of the machine learning based optimization of the tests.

BPC 157, a gastrointestinal tract pentadecaptide described firstly few years ago, showed so far a vast variety of organoproteefive effects in different type of injury. One of the morn prominent actions was antiia~mmatory and entiedematous activity. Also a prominent effect on healing of different wound type was described.

The structure, complementary structure and cytogenetic/proliferative effects of the Met-enkephalin on human peripheral blood lymphocytes were analyzed. Met-enkephalin, i.e. Peptid-M (LUPEX(R)), is a low molecular weight synthetic pentapeptide that corresponds to thymus Met-enkephalin, Its structure was examined by means of NMR spectroscopy. The influence of Met-enkephalin on in vitro normalization of chromosomally aberrant lymphocytes of patients suffering from different immune-mediated diseases, was analyzed by the sensitive cytogenetic tests for screening and detection of genome damages in human lymphocytes. The tests showed that in vitro stimulation of human lymphocytes with the Met-enkephalin led to disappearance of different types of chromosome aberrations, reduction in the number of micronuclei, decrease in the frequency of sister chromatid exchange (SCE) and apoptosis as well as a cytostatic effect on mitosis cycles. They have also confirmed normalization of chromosomally aberrant cell findings in patients suffering from different immune-mediated diseases. These results suggest a possible role of Met-enkephalin (Peptid-M) in immunotherapy of different diseases which involve chromosomal aberrations as well as abnormal cell proliferation and offer new approaches to immunotherapy by the use of Peptid-M. Based on the molecular recognition theory and the SCA method, peptide complementary to Peptid-M was designed, synthesized and denoted Peptide-D. Peptide-D isa calpastatin fragment. Predicted ligand-receptor interaction between both peptides is confirmed by the results showing that Peptide-D blocked the Peptid-M induced lymphocyte proliferation in a dose-dependent manner.