Positive regulation of ERK activation and MKP-1 expression by peroxovanadium complex bpV (phen)

Lower micromolar concentrations of peroxovanadium compound potassium bisperoxo(1,10-phenanthroline)oxovanadate (V) [bpV (phen)] stimulate RINm5F cell metabolic activity. 1 and 3 mol/L bpV (phen) induces strong and sustained activation of extracellular signal-regulated kinase (ERK). However, it seems that bpV (phen) does not effect c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. In addition, bpV (phen) induces mitogen-activated protein kinase phosphatase-1 (MKP-1) expression. We found that ERK activation could be completely abolished if RINm5F cells were incubated with both bpV (phen) and PD 98059, a specific inhibitor of upstream ERK kinase MEK1. On the other hand, this combined treatment up-regulated activation of stress kinases, JNK and p38 MAPK, significantly suppressed MKP-1 expression and induced cell death. Thus, our results suggest that the mechanism underlying bpV (phen) survival-enhancing effect could be associated with induced ERK activation and MKP-1 expression.     

Complementation of SOD-deficient Escherichia coli by manganese porphyrin mimics of superoxide dismutase activity

Cationic Mn(III) porphyrins substituted on the methine bridge carbons (meso positions) with N-alkylpyridinium or N,N'-diethylimidazolium groups have been prepared and characterized, both chemically and as SOD mimics. The ortho tetrakis N-methylpyridinium compound was substantially more active than the corresponding para isomer. This ortho compound also exhibited a more positive redox potential and greater ability to facilitate the aerobic growth of a SOD-deficient Escherichia coli. Analogs with longer alkyl side chains and with methoxyethyl side chains, as well as with N,N'-diethylimidazolium and N,N'-dimethoxyethylimidazolium groups on the meso positions, have been prepared in anticipation of greater penetration of the cells due to greater lipophilicity. We now report that the more lipophilic compounds were effective at complementing the SOD-deficient E. coli at lower concentrations than were needed with the less lipophilic compounds. The greater efficacy of the more lipophilic compounds was achieved at the cost of greater toxicity that became apparent when these compounds were applied at higher concentrations.     

The results after transrectal prostate biopsy with 12 biopsy cores taken

This report describes the clinical value of transrectal prostate biopsy during which 12 biopsy cores are taken in comparison to the classical sextant method. There were 106 patients included in the study, who had transrectal prostate biopsy (TRB) due to abnormal finding after digitorectal examination (DRE) and/or values of PSA > 4 ng/ml in the period from 4 October 2001 till 14 August 2002. There were 117 biopsies with 12 biopsy cores taken, 6 cores from each lobe. Prostate cancer was confirmed in 49 patients (46%). Out of total number of confirmed cancer cases, initial biopsy detected 94%. There were three patients who had suspicious DRE finding, with PSA value of < 4 ng/ml, but cancer was not detected in any of them. In the patient group with PSA value between 4-10 ng/ml, cancer was detected in 26% of them and in the group with PSA value > 10 ng/ml cancer was detected in 58%. The most common Gleason score in the case of cancer was 7 (43%). During the biopsy procedure, 3 patients experienced strong vasovagal reactions, meaning that out of 117 biopsies incidence of complications was 2.6%. Few days after the biopsy, two patients developed urogenital tract infections (1.7%) and right after the procedure, there was one case of strong hematuria (0.8%) and strong rectal bleeding (0,8%) that needed hospitalization. Our results regarding the incidence of complications do not differ much from the results in the literature. According to data in the literature regarding sextant biopsy, 15-34% of cancer cases remain undiagnosed at initial biopsy. The method of 12 biopsy cores fails to diagnose only 6% of all cancers, but it is important to note that in the mentioned period, re-biopsy was indicated only in 11 from 60 patients with negative biopsies.     

Performance of WHO Angina Questionnaire in measuring burden of coronary heart disease in human isolate populations

Isolated human populations represent good candidates for studying genetic and environmental causes of common complex diseases because of their decreased genetic and environmental diversity. The possibility of inexpensive and reliable detection of disease prevalence in such populations is therefore of considerable importance, as comprehensive routine health data and disease registries are rarely available in these populations. In this study, we validated the performance of the WHO Rose Angina Questionnaire (RQ) in measuring the burden of coronary heart disease (CHD) in 9 settlements in these Croatian Adriatic islands. CHD was defined as myocardial infarction (MI) diagnosed by a specialist in the local general hospital, or angina pectoris (AP) by a local general practitioner (GP). The true prevalence of CHD in 1,001 adult persons was 10.5%. The results of the RQ screening based on the first 3, 5 and 6 questions were compared with medical record of CHD. Increasing the number of RQ questions from 3 to 6 resulted in decreasing test sensitivity (from 59.0% to 30.5%) and increasing test specificity (from 86.3% to 93.0%) in the prediction of true CHD status. CHD prevalence was overestimated by 76% when subset of the first 3 questions of RQ was used and by 25% when the first 5 questions were used. However, it was underestimated by 10% when the first 6 questions were used. We conclude that RQ is a useful screening method for measuring burden of CHD in isolate human populations, and that the result based on the first 6 questions is a good approximation of the true CHD prevalence in the population, although it should be considered a slight underestimate.     

The incidence of optic neuritis in Split-Dalmatia county, Croatia

The aim of the study was to determine the incidence of monosymptomatic optic neuritis (MON) in residents of Split-Dalmatia County, Croatia. The 127 cases (83 female, aged 26.2+/-9.9 and 44 male aged 26.9+/-11.2) with MON presented between January 1985 and December 2001 were analyzed from hospital data. The annual incidence was 1.6 per 100,000 (95% CI, 0-3). The incidence among females was 2.2 (95% CI, 0-4.6) cases / 100,000 per year and 1.1 (95% CI, 0-3) among males. The difference in incidence rates for women vs. men was not significant (chi2=0.41; p=0.52), although it is more likely that a true difference exists. The peak incidence in both sexes observed in the group 20-29 years of age was 4.2 (95% CI, 0-10). The highest incidence of MON was found in spring (46 cases). In summary, the incidence of MON in Split-Dalmatia County during the 17 years period is relatively low.     

ApoE genotyping and response to galanthamine in Alzheimer's disease--a real life retrospective study

This study was undertaken to evaluate the effect of galanthamine, a new cholinesterase inhibitor on cognitive performances in 84 patients with various apoE genotype and Alzheimer's disease (AD) during the six-month treatment. The diagnosis of AD was made on the basis of NINCDS/ADRDN criteria. ApoE4 genotype was determined by PCR procedure. The cognitive performance was assessed MMSE at baseline and six months later. The difference among the groups was statistically analyzed by ANOVA model and Pearson's chi2-test. The MMSE at baseline in all completes was 18.0 +/- 3.73, whereas the mean value of MMSE after 6 months was 16.4 +/- 5.61 indicating significant deterioration (p < 0.01). Of the 84 patients, 14 (169%) were apoE4 homozygous, 41 (49%) were heterozygous, whereas 29 (35%) were apoE4 negative. The significant number of responders was observed among apoE4 homozygous patients (71%; chi2 = 6.89; p = 0.032). The subgroup of apoE4 homozygous patients with AD in its mild to moderate stage may be considered as responders to galanthamine.     

The role of the von Willebrand factor in renal diseases and haemodialysis patients

During a period of twenty years, the von Willebrand factor (VWf) biological activity was evaluated in 805 patients with vein thrombosis, diabetes mellitus, chronic renal failure and ischemic heart disease. The examined patients were 168 with vein thrombosis, 129 with diabetes mellitus, 412 with chronic renal failure (CRF), and 96 with ischemic heart disease. The biological activity was also determined in 104 haemodialysis patients using four different haemodialytic membranes: 30 on cuprophan membrane, 30 on polymethylmetacrylate membrane (PMMA), 24 on hemophane and 20 patients on polysulphone (PS) membrane. In 42 patients with arterio-venous fistula prone to thrombosis, the biological activity of the von Willebrand Factor was 178% in comparison to 106% in the control group. The biological activity of VWF was increased in patients with vein thrombosis (p < 0.02), in patients with diabetes mellitus (p < 0.01), CRF (p < 0.05), and in patients with ischemic heart disease (p < 0.01). The highest biological activity was found in patients on PMMA (p < 0.001), then cuprophan (p < 0.05) and hemophane membrane (p < 0.01), while the lowest increase of its concentration was noticed in patients on PS without statistical significance. In arteriovenous fistula prone to thrombosis patients biological activity of the von Willebrand Factor was significantly increased (p < 0.01). Our investigations show the importance of VWF as a marker of endothelial disfunction, a possible predictor of A-V fistula thrombosis, and a possible marker of haemodialysis membranes biocompatibility.     

Respiratory findings in art students

Art students are exposed to many noxious agents during their training. We studied respiratory findings in a cohort of the 117 art students in order to investigate the potential effects of these toxic agents in the art student's environment. A group of 88 medical students matched for age, sex and smoking, not exposed to known environmental pollutants were studied as controls for respiratory symptoms. Respiratory symptoms acute and chronic were evaluated by modifying the British Medical Research Council questionnaire. Lung function studies were performed with a spirometer (Jaeger, Germany) measuring maximum expiratory flow-volume (MEFV) curves. Significantly higher prevalences of most of the chronic respiratory symptoms were recorded in art compared to medical students (p < 0.05). Art students who were smokers had significantly higher prevalences of many of the chronic respiratory symptoms than nonsmoking art students. High prevalences of acute symptoms related to the study environment were recorded for art students. Odds ratios in male art students were significant for chronic cough, chronic phlegm and chronic bronchitis for the risk factors of exposure and smoking. Significantly decreased lung function was recorded for FVC, FEF50 and FEF25 in male and FVC, and FEF25 in female art students. Smokers and nonsmokers had similar reductions of lung function. Our data indicate that art students may be at risk of developing chronic respiratory symptoms and lung function changes as a result of their exposure and their smoking habits.     

What the Croatian doctors want to be learning about?

The aim of the study was to examine doctor's attitude about topics in continuing medical education (CME) using anonymous questionnaire that was given to the members of the Croatian Medical Association in Rijeka. The questions concerned doctor's interest of certain medical fields, influence of CME to their everyday practice, and importance of getting credits for re-licensure as a motive to participate in CME. The highest interest was shown for CME in emergency/intensive medicine and the lowest for transplantation medicine. The doctors in primary care showed statistically significantly higher interest for CME in family medicine, pulmology, rheumatology and rehabilitation medicine than hospital doctors. The influence of CME in everyday practice and the importance of getting credits for re-licensure as a reason to participate in CME, in the most cases, have been graded with medium grade 3. The results indicated the existence of specific needs in CME and stressed the importance of having CME with topics from clinical practice.     

Smoking habits, signs of chronic diseases and survival in inland and coastal regions of Croatia: a follow-up study

Aim of the study was to estimate, the relationship between survival, smoking habits, and the results of medical examinations in inland and coastal regions of Croatia. Age and sex stratified sample of general population (1,571 men and 1,793 women, 37-56 years old in 1972; followed in 1982: N = 1,090 men; 1,325 women and/or 1972-1999 controlling vital status). Relative risks and 95% confidence limits were estimated using Cox regression in the model with time dependent covariates, separately by sex. In all regions, the proportion of male smokers decreased between 1972 and 1982. The proportion of female smokers increased, differently in urban and rural regions. During the follow-up between 1972 and 1999, 568 deaths were recorded among men and 382 among women. In men, in addition to age, significant hazards of death were the number of smoked cigarettes per day, body mass index, sedative intake, vital lung capacity (FVC), 100FEV1/VC, systolic blood pressure, electrocardiogram, history of heart attack, and region. In women, in addition to age, significant predictors were the number of smoked cigarettes per day, systolic blood pressure, electrocardiogram, history of heart disease (excluding coronary diseases), and region. Survival relative risk increased with each additional smoked pack of cigarettes by 2.4% in women and 1.3% in men. Regional differences vs. smoking habit were observed. These data emphasize the need for prevention of smoking.