Alzheimer disease (AD) is common worldwide and almost every case has comorbidities. One of the most common comorbidities of AD is Diabetes mellitus (DM), with or without metabolic syndrome. Both diseases effect nerve tissue and successful treatment would improve the status of the patient. In patients with Alzheimer disease treatment of DM, the treatment could be harmful to the AD, because of that high insulin intake. This may lead to progression of AD. Insulin is considered the best treatment for DM, but insulin therapy could increase comorbidity with AD. No specific therapy for AD is known up to date, so because of that DM is one of the most important risk for AD, concomitant therapy for DM should be planned very carefully. All options of DM therapy should be considered, and different mechanisms of anti-diabetic drugs are preferable. Treatment of AD is more complex metabolic syndrome is present. Any inflammation causes local tissue damage, including brain tissue during AD. Release of interleukins, primarily TNF-α, IL-6, IL-1β in the presence of adipokine leptin, maintains chronic inflammatory status in local brain tissue. Thus, low doses of immunosuppressant therapy should be considered for treatment of AD in future. To delay apoptosis of nerve tissue cells, brain and nerve tissue defend against free oxygen radicals and improve metabolic status.

Aim To analyse frequency of chronic obstructive pulmonary disease (COPD) exacerbation in patients on therapy with inhaled corticosteroids (ICS) and relevant factors that influence the rate of COPD exacerbations in a subgroup of moderate illness, like FEV1, comorbidities and other concomitant therapy. Methods The study included patients with moderate COPD with at least 10 pack-years history of smoking and accompanying cardiovascular comorbidity. Demographic data, frequency of exacerbations and information about proscribed treatments - ICS alone or in combination with long acting beta agonist (LABA), were collected from medical records for the previous 12 months from the index date. Results Data were collected for 210 patients (170 males) with the mean age 65.63±8.66 years, 72 of which were treated with a fixed combination of long acting beta blocker (LABA) and ICS. Significantly more frequent exacerbations were detected in patients using ICS p<0.0001) and having higher Modified British Medical Research Council (mMRC) score p=0.004). No statistically significant difference was registered related to ratio of FEV1 /FVC (p=0.121) or a number of cardiovascular comorbidities per patient (p=0.969). CONCLUSIONS Our results present a small contribution to the current scientific discussion about the use of ICS in COPD treatment. Further prospective studies are needed to confirm the impact of ICS on the frequency of COPD exacerbations.

Despite intensive treatment, considerable proportion of patients with asthma remains symptomatic. Anti-inflammatory activity of curcumin has been shown. Aim: analyse the impact of add-on therapy with curcumin in asthma patients on inflammatory parameters, lung function and asthma control. During 2 months, 100 non-smokers (46.8±12.4 years, F/M ratio 1.04) with moderate, partially controlled asthma were treated with moderate dose of inhaled glucocorticoids (IGK) with no changes in dose. Patients were divided into two groups (n=50): curcumin group receiving curcumin 500 mg per os twice daily and control group. Before study, sputum and blood eosinophils (Eo), blood neutrophils, high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) were similar between groups. After study, in curcumin group blood Eo count and hsCRP decreased, and FEV1, ACT and AQLQ increased significantly (before vs. after study: Eo: 5.9±0.6 vs. 4.1±0.4; hsCRP: 4.2±0.3 vs. 3.4±0.2; FEV1%: 77.7±0.8 vs. 83.9±0.5; ACT: 14.5 (6,19) vs. 18 (14,21); AQLQ: 3.4±0.2 vs. 4.1±0.2). There was no change in the control group. Compared to control curcumin group showed significantly lower blood Eo and hsCRP and higher FEV1% (curcumin vs. control: Eo: 4.1±0.4 vs. 5.4±0.5; hsCRP: 3.4±0.2 vs. 4.0±0.3; FEV1%: 83.9±0.5 vs. 78.3± 0.8), and improved ACT and AQLQ (ACT change>3: 72% vs. 28%; AQLQ change>0.5: 54% vs. 32%) after study. Add-on therapy with curcumin in patients with moderate partially controlled asthma seems to improve response to IGK regarding lung function, asthma control and quality of life. Further placebo controlled trials are needed.

Aim To analyse the long-term impact of altered metabolism on the level of mediators of inflammatory response in female patients with type 2 diabetes. Methods This study included 97 female patients with type 2 diabetes and 107 female, nondiabetic control subjects, who were recruited at the Clinical Centre University of Sarajevo and the General Hospital Tešanj. The effects of glycaemic control on markers of inflammatory response represented by C-reactive protein (CRP), fibrinogen, leukocytes, sedimentation rate, and cytokine IL-6 were tested. All subjects were free of evidence of infections, surgery, thyroid disease, polycystic ovarian syndrome, active liver and kidney damage. All biochemical analyses were performed according to standard International Federation of Clinical Chemistry (IFCC) protocols. Results A significant increase of fibrinogen (p<0.001), CRP (p=0.001), interleukin-6 (p=0.013), leukocytes (p<0.001) and sedimentation rate (p=0.008) in diabetic female population compared to control subjects was found. A significant correlation between CRP and haemoglobin A1c (p=0.035), interleukin-6 and glucose (p=0.032), IL-6 and body mass index (p=0.007) was found. Conclusion Our data suggest that inflammation plays an important role in the pathogenesis of diabetes in female diabetic population. A more detailed study on a far larger number of subjects is needed if they were to be used effectively as biomarkers in the primary prevention of type 2 diabetes in this population.

Objective: Tobacco cigarette smoking is one of the major leading causes of death throughout the world. Smoking has both acute and chronic effect on haematological parameters. The aim of the present study was to assess the extent of adverse effects of cigarette smoking on biochemical characteristics in healthy smokers. Subjects and Method: One hundred and fifty six subjects participated in this study, 56 smokers and 100 non-smokers. The smokers were regularly consuming 10-20 cigarettes per day for at least 3 years. Complete blood cell count was analyzed by CELL-DYN 3700 fully automatic haematological analyzer. Results: The smokers had significantly higher levels of white blood cell (p<0,001), hemoglobin (p=0,042), mean corpuscular volume (p=0,001) and mean corpuscular hemoglobin concentration (p<0,001). All other measured parameters did not differ significantly. Cigarette smoking caused a significant increase (p<0,001) in red blood cells, white blood cells (p=0,040), hemoglobin (p<0,001), hematocrit (p=0,047) and mean corpuscular hemoglobin (p<0,001) in males in comparison to female smokers. Conclusion: In conclusion, our study showed that continuous cigarette smoking has severe adverse effects on haematological parameters (e.g., hemoglobin, white blood cells count, mean corpuscular volume, mean corpuscular hemoglobin concentration, red blood cells count, hematocrit) and these alterations might be associated with a greater risk for developing atherosclerosis, polycythemia vera, chronic obstructive pulmonary disease and/or cardiovascular diseases.

Introduction: Cysteine protease are biological catalysts which play a pivotal role in numerous biological reactions in organism. Much of the literature is inscribed to their biochemical significance, distribution and mechanism of action. Many diseases, e.g. Alzheimer’s disease, develop due to enzyme balance disruption. Understanding of cysteine protease’s disbalance is therefor a key to unravel the new possibilities of treatment. Cysteine protease are one of the most important enzymes for protein disruption during programmed cell death. Whether protein disruption is part of cell deaths is not enough clear in any cases. Thereafter, any tissue disruption, including proteolysis, generate more or less inflammation appearance. Review: This review briefly summarizes the current knowledge about pathological mechanism’s that results in AD, with significant reference to the role of cysteine protease in it. Based on the summary, new pharmacological approach and development of novel potent drugs with selective toxicity targeting cysteine protease will be a major challenge in years to come.

Introduction: Because of increasing prevalence of T2MD worldwide, it’s very important to recognize risk factors for diabetic complications, as soon as possible. Symptoms of complications appear a few or many years after tissue damage. So, it’s imperative to establish surveillance of diabetics with laboratory and other diagnostic procedures for early recognition of diabetic complications. Follow up of clinical curs of diabetes, by using databases of patients, provide possibility for permanent analysis of important laboratory parameters and any changes could be registered. Although an emerging evidence suggests a strong association of ALT (alanine aminotransferase) and γGT (gamma glutamyl transferase) activity with type 2 diabetes mellitus (T2DM), only a limited number of studies have analyzed the association of AST (aspartate aminotransferase), ALT, γGT, and ALP (alkaline phosphatase) activities in controlled T2DM. Material and Methods: Gender differences are of special interest in trying to follow diabetes progression and development of its complications. Here the activities of ALT, AST, γGT, ALP were analyzed as well as levels of glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) in 40 T2DM patients and 40 age-matched healthy subjects. Blood samples were collected from all participants in regular 3-months intervals up to 6 months period. Standard IFCC enzyme protocols were used to determine enzyme activities. Results and discussion: In first measured interval, significantly higher activities of ALT (p= 0,050) and glucose levels (p=0,045) were shown in male. A significant correlation was shown between ALT and AST activity with FPG and HbA1c levels in first and third measured interval. ALT activity was much higher in the group of patients with poor glycemia control. Average levels of activities of enzymes stay nearly in normal limits, but changes of enzymes activities should be recognized as soon as possible, earlier than tissue changes and diabetic complications become irreversible.

P Herzegovina Introduction: The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and carries a poor survival rate. Increased understanding of cancer biology and technological advances have enabled identification of a multitude of pathological, genetic, and molecular events that drive hepatocarcinogenesis leading to discovery of numerous potential biomarkers in this disease. The transforming growth factor-beta (TGF- β ) cytokine and its isoforms initiate a signaling cascade which is closely linked to liver fibrosis, cirrhosis and subsequent progression to HCC. Methods: Totalof 150 subjects were divided into four groups, depending on the stage of HCC (BCLC scoring system). Group1: earlystage; group 2: intermediate stage; group 3: advanced stage; group 4: terminal stage and the control group. The analysis included serum levels of cytokine TGF- β 1. Used statistical methods: discriminant multivariate analysis, ANOVA test, multiple correlation test and Student ’ st-testfor independent samples. Charlson comorbidity index was determined forany possible influence of othercomorbid conditions. The analysis of serum levels of TGF- β 1 in HCC patients, according to BCLC scoring system has been performed, to evaluate its role as biomarker. Results: The highest mean concentration of this cytokine was in group 3 (advanced stage of HCC): 1023,55 pg/ml. ANOVA analysis provesthat serum levels of TGF- β 1 in the control group differed with respect to the otheras follows: in relation to group 1 at the level of statistical significance p=0.0028 (F=143.67); in relation to a group of 2 to p=0.0001 level (F=230.23); in relation to group 3 at p<0.0001 (F=2584). By Student ’ s T

New prognostic factor of lung cancer are being intensively studied currently. A small number of studies compare the importance of molecular makers with so far known functional and clinical prognostic factors. Purpose of this study was to find out whetherp16(ink4) expression is more superior prognostic factor in survival rates in non-small lung cancer (NSCLC) patients than spirometry tests. 100 NSCLC patients (50 squamous and 50 adenocarcinoma) with IIIB and IVA stage and 80 healthy individuals were included. p16(ink4) was immunohistochemicaly detected on formalin-fixed tissues. We measured s pirometry tests : vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in first second (FEV1), Tiffeneau index (FEV1/FVC ratio) and forced expiratory flow 25% to 75%. 2-year progression-free survival (PFS) and overall survival (OS) were observed. Low p16(ink4) expression and impared spirometry parameters correlated with worse 2-year survival outcomes, in both adenocarcinoma and squamous carcinoma. In squamous carcinoma p16(ink4) expression was an independent negative prognostic marker. Severe impairments of spirometry tests had similar prognostic value as low p16(ink4) expression in both NSCLC subtypes. In contrast to p16 (ink4) as a negative molecular prognostic factor, spirometry testings are widely achievable and affordable and could be serviceable prognostic marker in NSCLC patients in advanced NSCLC. Further studies including all clinical stages of NSCLC are needed.

AIM To determine an influence of alpha-lipoic acid to reduction of body weight and regulation of total cholesterol concentration, triglycerides and glucose serum levels in obese patients with diabetes mellitus type 2. METHODS A prospective study includes two groups of obese patients with diabetes mellitus and signs of peripheral polyneuropathia: examined group (30 patients; 15 females and 15 males), and control group (30 patients; 12 females and 18 males). All were treated with metformin (850-1700 mg/day). Examined patients were additionally treated with alpha-lipoic acid 600 mg/day during 20 weeks. Body mass index and concentrations of total cholesterol, triglycerides and glucose in serum were compared before and after the treatment. RESULTS The group treated with 600 mg alpha-lipoic acid lost significantly more weight, and had lower triglyceride level than the control group. There were no significant differences in total cholesterol and glucose serum levels between the groups. CONCLUSION Alpha-lipoic acid of 600 mg/day treatment have influenced weight and triglycerides loss in obese patients with diabetes mellitus type 2. It should be considered as an important additive therapy in obese patients with diabetes mellitus type 2.