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Alzheimer;s disease (AD) is a multifactorial disease but its aetiology and pathophisiology are still not fully understood. Epidemiologic studies examining the association between lipids and dementia have reported conflicting results. High total cholesterol has been associated with both an increased, and decreased, risk of AD and/or vascular dementia (VAD), whereas other studies found no association. The aim of this study was to investigate the serum lipids concentration in patients with probable AD, as well as possible correlation between serum lipids concentrations and cognitive impairment. Our cross-sectional study included 30 patients with probable AD and 30 age and sex matched control subjects. The probable AD was clinically diagnosed by NINCDS-ADRDA criteria. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels were determined at the initial assessment using standard enzymatic colorimetric techniques. Low-density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) levels were calculated. Subjects with probable AD had significantly lower serum TG (p<0,01), TC (p<0,05), LDL-C (p<0,05) and VLDL-C (p<0,01) compared to the control group. We did not observe significant difference in HDL-C level between patients with probable AD and control subjects. Negative, although not significant correlation between TG, TC and VLDL-C and MMSE in patients with AD was observed. In the control group of subjects there was a negative correlation between TC and MMSE but it was not statistically significant (r = -0,28). Further studies are required to explore the possibility for serum lipids to serve as diagnostic and therapeutic markers of AD.

The evolution of homocysteine (Hcy) changes after acute myocardial infarction is still not elucidated. Serum Hcy concentration has been shown to increase between acute and convalescent period after myocardial infarction and stroke. Also a decrease in serum Hcy during acute phase was observed. It is still not clear whether the Hcy is a culprit or an innocent bystander in cardiovascular diseases. Addressing the discrepancies in Hcy changes in patients with acute myocardial infarction might give insight in Hcy role in cardiovascular diseases and offer implications both for the clinical interpretation and patients risk stratification. The aim of the study was to evaluate serum Hcy concentration changes during early post myocardial infarction. The study included 55 patients with AMI from the Clinics for Heart Diseases and Rheumatism at University of Sarajevo Clinics Centre. For Hcy analysis blood was collected on day 2 and 5 after the AMI onset. Serum Hcy concentration was determined quantitatively with fluorescent polarisation immunoassay on AxSYM system. Cluster analysis revealed two groups of AMI patients with different trends of serum Hcy changes. Increase in serum Hcy concentration was observed in 33 (60,0%) patients (AMI 1 group), while in 22 (40,0%) patients a decrease was observed (AMI 2 group). On day 2, patients in AMI 2 group had significantly higher mean Hcy concentration compared to AMI 1 group of patients (15,27+/-0,96 and 11,59+/-0,61 micromol/L p<0,05). On day 5, no significant difference in mean Hcy level between AMI 1 and AMI 2 group of patients was observed (14,86+/-1,1 vs. 12,75+/-0,74 micromol/L respectively). Significant differences between AMI 1 and AMI 2 patients were observed in VLDLC levels and CK-MB activity on day 2. Patients in AMI 1 group had significant increase in platelets count from day 2 to day 5 (230,1+/-11,6 vs. 244,2+/-11,0; p<0,05). Our study of serial Hcy changes in patients with AMI revealed two different patterns of Hcy changes in early post infarction period which might reflect two distinct populations of AMI patients. Although further research is necessary, possible explanation for the observed findings could be a different genetic background, vitamin and oxidative status of patients with AMI.

The present study was carried out to evaluate the renoprotective antioxidant effect of Spirulina platensis on gentamicin-induced acute tubular necrosis in rats. Albino-Wistar rats, (9male and 9 female), weighing approximately 250 g, were used for this study. Rats were randomly assigned to three equal groups. Control group received 0,9 % sodium chloride intraperitoneally for 7 days at the same volume as gentamicin group. Gentamicin group was treated intraperitoneally with gentamicin, 80 mg/kg daily for 7 days. Gentamicin+spirulina group received Spirulina platensis 1000 mg/kg orally 2 days before and 7 days concurrently with gentamicin (80 mg/kg i.p.). Nephrotoxicity was assessed by measuring plasma nitrite concentration, stabile metabolic product of nitric oxide with oxygen. Plasma nitrite concentration was determined by colorimetric method using Griess reaction. For histological analysis kidney specimens were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stain. Plasma nitrite concentration and the level of kidney damage were significantly higher in gentamicin group in comparison both to the control and gentamicin+spirulina group. Spirulina platensis significantly lowered the plasma nitrite level and attenuated histomorphological changes related to renal injury caused by gentamicin. Thus, the results from present study suggest that Spirulina platensis has renoprotective potential in gentamicin-induced acute tubular necrosis possibly due to its antioxidant properties.

We investigated serum concentration of C-reactive protein (CRP) and measures of adiposity in 30 patients with type 2 diabetes mellitus (15 male, 15 female) and 30 age and sex-matched apparently healthy subjects. CRP concentration was determined by laser nephelometry (BN II Analyzer) and CardioPhase high-sensitivity CRP (DADE BEHRING) was used as reagent which consists of polystyrene particles coated with mouse monoclonal antibodies to CRP. Results have shown that serum CRP concentration in patients with type 2 diabetes mellitus was statistically significantly higher compared to control group of healthy subjects (p<0,05). Body mass index (BMI) correlated significantly with serum concentration of CRP in patients with type 2 diabetes mellitus (r=0.614; p<0.001). Statistically significant positive correlation was also found between waist to hip ratio and serum CRP concentration in patients with type 2 diabetes mellitus (r=0.426; p<0.05). Elevated serum CRP concentration in patients with type 2 diabetes mellitus is probably caused by the presence of chronic low-grade inflammation in these patients. It is possible that determined increase of CRP concentration reflects activation of innate immune system components in patients with type 2 diabetes mellitus. Implications of established association between measures of adiposity and serum CRP level in type 2 diabetes mellitus remain unclear.

The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in gentamicin-induced acute tubular necrosis in rats using the iNOS inhibitor L-N6-(1-iminoethyl) lysine (L-NIL). Wistar rats, both sexes (n=18), were equally divided into three groups. Gentamicin group received intraperitoneally (i.p.) gentamicin in 0.9 % NaCl at a dose of 80 mg/kg/day for five consecutive days. L-NIL+gentamicin group received L-NIL at a dose of 3 mg/kg i.p. 36, 24 and 12 h before first dose of gentamicin. Control group received 0.9 % NaCl i.p. for five consecutive days at the equal volume as gentamicin group. Griess reaction was used for determination plasma level of NO. Semiquantitative histological analysis was used for the evaluation of kidney damage level. The plasma NO level and the level of kidney damage were statistically higher in gentamicin group in comparison to the control group (p=0.046). Application of L-NIL prior to gentamicin led to certain decrease in the plasma level of NO as well as in the level of kidney damage. Application of L-NIL, prior to gentamicin administration, did not provide complete protective effects of L-NIL on the kidney, which was demonstrated on kidney sections. The lack of anticipated protective effect of L-NIL on kidney tissue might be explained with the fact that we have used L-NIL prior but not during/after gentamicin administration. It would be necessary to examine the effects of L-NIL administration not only before, but as well during and possibly after the administration of gentamicin.

Almira Hadžović-Džuvo, E. Kučukalić-Selimović, E. Nakas-ićindić, Asija Začiragić, Zdenka Drazeta

Brain natriuretic peptide (BNP) is a cardiac hormone secreted predominantly from the ventricles. This hormone is produced as pre-prohormone BNP (pro BNP), than cleaved by corine to biologically active 32-aminoacid BNP and non-biologically active N-terminal-pro brain natriuretic peptide (NTproBNP). NTproBNP has been found to be a useful marker for the diagnosis of heart failure and left ventricular systolic dysfunction. Recent studies showed that concentration of BNP and NTproBNP predict cardiovascular disease in apparently healthy individuals but their full screening characteristics are not firmly established. As NTproBNP serum concentration is altered by numerous factors there are also interindividual variations in NTproBNP values. There are no previous results for Bosnian population so the aim of this study was to asses normal range of NTproBNP serum concentrations in apparently healthy women using electrochemiluminescence immunoassay (Elecsys, Roche Diagnostic). A group of 45, healthy females, aged 39.19 (+/-6.62), were enrolled in this study. Mean serum concentration of NTproBNP was 60.32 (+/-36.25) pg/ml, with the range of 112,60 pg/ml (minimum-maximum: 13.6-126.00 pg/ml). We conclude that NTproBNP serum concentration in apparently healthy Bosnian women was not different from the average values of NTproBNP obtained on Europen's population. Thus, we suggest that the NTproBNP serum upper cut off values measured by using electrochemiluminescence immunoassay "ECLIA" (Elecsys 2010, Roche Diagnostic) for Bosnian females, aged < or =50 years, should be 155 pg/ml as reported by Roche Diagnostic.

Eldan Kapur, I. Vucković, F. Dilberović, Asija Začiragić, E. Ćosović, Kucuk-Alija Divanović, Z. Mornjaković, M. Babić et al.

Background:  Inadvertent intraneural injection of local anesthetics may result in neurologic injury. We hypothesized that an intraneural injection may be associated with higher injection pressures and an increase in the risk of neurologic injury.

Studies indicate that inflammatory mechanisms may play an important role in the pathogenesis of Alzheimer's disease (AD). C-reactive protein (CRP), marker and mediator of inflammation, has been detected in lesions typical for the affected areas of AD brain. There have been conflicting reports on serum CRP concentration in AD. Scarce data exist on association of CRP and measures of adiposity in AD patients. Thus, we investigated serum CRP concentration in fifteen overweight institutionalized patients with probable AD and fifteen age-matched control subjects. Body mass index (BMI) and waist/hip ratio (WHR) were calculated for each subject included in the study. Age, systolic and diastolic blood pressure, BMI and WHR did not differ significantly between the two groups. Serum CRP concentration was significantly higher in patients with AD compared to controls (p<0.0001). Although not significant, positive correlations between serum levels of CRP and BMI and WHR were found. Obtained results support the notion that low-grade inflammation is present in patients with AD. Absence of significant association between CRP and measures of total and central adiposity in overweight AD patients needs further investigation and explanation.

E. Nakas-ićindić, Almira Hadzović, E. Kučukalić-Selimović, N. Avdagić, Asija Začiragić

Physical effort is a strong physiological stimulus that provokes an increase in blood growth hormone (GH) concentration. Interactions between GH and body composition are very complex. Seven athletes and seven age-matched controls completed a single 30-min bout of upright cycling exercise (5 % of VO(2max).) in order to estimate the influence of body composition on serum GH concentration during exercise. The serum GH concentration was measured in blood samples by standard immunoradiometric (IRMA) method. Anthropometric measurements were used for the calculation of body composition. There were no significant differences in total body mass or body mass index between the groups. The athletes had significantly less fat and higher bone and muscle mass. Serum GH concentration was 2.39 times higher in the athlets versus the control in the period of rest. During acute exercise, the serum GH concentration increased in both groups. No statistically significant differences between the groups in serum GH concentration were found either during the exercise or in the recovery. No correlation between body composition and serum GH concentration was found. Body composition depends on the level of physical activities but if the total body mass is in physiologycal range it does not influence the serum GH response to acute exercise.

Xenobiotic solutions of different concentrations were analyzed by TLC method before and after passing trough the column with adsorbent M and compared with adsorption on the active charcoal. The efficiency of adsorption on adsorbent M was higher, compared to active charcoal. The best adsorption, in the value 90 - 100%, have shown certain organochlorine and organophosphorus pesticides, that were dissolved in non-aqueous solvents. Efficiency of adsorbent M was also proven in vivo, when solutions of tested xenobiotics before adsorption have caused death of experimental animals, and after the adsorption on adsorbent M, all treated animals have survived and had just mild symptoms of poisoning.

Nitric oxide (NO) level in serum and renal tissue has been examined in 15 male Wistar rats, body weight 200-250 g, 7 days after unilateral nephrectomy. All rats were ether-anaesthetized and the kidneys were removed by dorsolateral approach. NO concentration in serum and renal tissue was determined by classic colorimetric Griess reaction. Conversion of NO(3)(2-) into NO(2)(2-) was done with elementary zinc. Results have shown that NO concentration in renal tissue is statistically higher in rats 7 days after unilateral nephrectomy then in control renal tissue before compensatory kidney growth (p<0,02). There is no difference between NO concentration in serum before unilateral nephrectomy and 7 days after nephrectomy. These findings suggest that NO may play an important role in mediating the hemodynamic changes associated with reduced renal mass.

E. Nakas-ićindić, N. Avdagić, M. Mijanović, S. Prašović, Asija Začiragić, Almira Hadzović, Gordan Tahirović

Gentamicin is still widely used in clinical practice in spite of its renal toxicity. The role of nitric oxide (NO) in that process is not completely elucidated. The aim of this study was to investigate the relationship between plasma level of NO and the histopathological changes of kidney in acute tubular necrosis (ATN) induced by gentamicin in rats. Study was carried out in Albino-Wistar rats, both sexes (n=16), average body weight 200-250 g. divided in two equal groups: control and gentamicin group. The control group was injected with 0.9% NaCl i.p. and gentamicin group was injected with gentamicin in the dose of 80 mg/kg/day i.p. in a period of 5 consecutive days. NO plasma level was determined by the production of nitrates and nitrites using classical colorimetrical Griess reaction. Kidney specimens were stained with hematoxylin-eosin (H-E) and Periodic acid-Schiff (PAS) stain. Semiquantitative histological analysis was used for the evaluation of the level of kidney damage. Both, the plasma NO level and the level of kidney damage were statistically higher in rats with gentamicin-induced ATN in comparison to the control group. In spite of that the correlation between plasma NO level and the level of kidney damage was not found. The rise of plasma level NO in gentamicin induced ATN in rats could possibly indicate on the role of NO in renal damage caused by gentamicin.

Angiotensin converting enzyme (ACE) plays an important role in blood pressure regulation not only in the state of rest, but also during physical exercise. The aim of this study was to estimate the serum ACE activity in response to acute dynamic exercise. The study involved a group of young, healthy, male volunteers (average 22 years of age). Exercise testing was carried out on ergometer bicycle according to the protocol of individually adjusted continuous, constant workload (3 W/kg). The activity of ACE in serum was measured in venous blood, in the period of rest, in 4th, 8th and 12th minute of exercise and 1st, 3rd and 6th minute of recovery by spectrophotometric method. Marked inter-individual differences in basal serum ACE activity were determined (range 8, 31-63, 72 U/L). Serum ACE activity did not significantly vary during exercise and in the period of recovery. Systolic blood pressure changed during exercise compared to values during rest period in accordance with the applied type of dynamical exercise. Diastolic blood pressure did not vary considerably during exercise. Statistically significant correlation between mean arterial blood pressure and ACE activity in the serum was not found. The lack of increase of ACE activity in the serum, in spite of changes in blood pressure values, most likely shows the presence of alternative ACE independent pathway involved in the production of vasoactive substances that have important role in the regulation of cardiovascular system response to acute dynamic exercise.

Almira Hadzović, E. Nakas-ićindić, E. Kučukalić-Selimović, N. Avdagić, Asija Začiragić

There is no clear evidence about the influence of programmed physical activity (training) on growth hormone (GH) response to acute physical exercise. The aim of this study was to estimate the relationship between the level of physical activity and the serum growth hormone concentration in response to acute physical exercise. The study was performed on 20, healthy male subjects. Based on the level of their physical activities they were divided in two groups of equal size: group 1, trained, and group 2, untrained subjects. All subjects performed one boot of exercise on cycle ergometer, lasting 30 minutes. Work intensity was approx. 65% of VO2 max, and the rate of cycling was 60/min. Serum GH concentrations were measured by IRMA (immunoradiometric assays) method in blood samples obtained in the period of rest, during exercise and in the recovery period. There were marked differences in the dynamics of changes in the serum GH concentrations during exercise period between the groups of various level of physical activity despite the lack of the significant differences in basal level and maximal level of serum GH concentration at the end of exercise. Untrained subjects showed faster increase in serum GH concentration than trained subjects, but in trained subjects the restoration of the basal values in the recovery period was faster. These results indicate that the level of physical activities in young, healthy male subjects has no influence on GH response to acute physical exercise.

E. Nakas-ićindić, Asija Začiragić, Almira Hadzović, N. Avdagić

Endothelin is a recently discovered peptide composed of 21 amino acids. There are three endothelin isomers: endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin- 3 (ET-3). In humans and animals levels of ET-1, ET-2, ET-3 and big endothelin in blood range from 0,3 to 3 pg/ml. ET-1, ET-2 and ET-3 act by binding to receptors. Two main types of the receptors for endothelins exist and they are referred to as A and B type receptors. Different factors can stimulate or inhibit production of endothelin by endothelial cells. Mechanical stimulation of endothelium, thrombin, calcium ions, epinephrine, angiotensin II, vasopressin, dopamine, cytokines, growth factors stimulate the production of endothelin whereas nitric oxide, cyclic guanosine monophosphate, atrial natriuretic peptide, prostacyclin, bradykinin inhibit its production. Endothelins have different physiological roles in human body but at the same time their actions are involved in the pathogenesis of many diseases. The aim of this review was to present some of, so far, the best studied physiological roles of endothelin and to summarize evidence supporting the potential role of ET in the pathogenesis of certain diseases.

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