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This study investigated whether serum C-reactive protein (CRP) concentration is increased in patients with type 1 diabetes mellitus with a normal body mass index (BMI) and whether BMI, glycated haemoglobin (HbA1c) and CRP are correlated in patients with type 1 diabetes. High-sensitivity CRP was determined by immunonephelometry and HbA1c by an immunoturbidimetric method in 30 patients with type 1 diabetes and 30 healthy individuals matched for age, sex and BMI. Median serum CRP concentration in patients with type 1 diabetes (1.34 mg/L) was significantly higher than healthy individuals (0.2 mg/L; p<0.0001). Positive correlation between CRP and BMI was observed (rho=0.598; p<0.0001), but no significant correlation was observed between CRP and HbA1c (rho=0.285; p=NS) in patients with type 1 diabetes. Increased CRP levels in type 1 diabetes patients do not appear to be associated with glycaemic control, and may reflect low-grade inflammation associated with atherosclerosis, as well as activation of innate immune activity. Br J Diabetes Vasc Dis 2011;11:249-252

M. Dilić, A. Nalbantić, A. Arslanagić, J. Huskic, Snežana Brdjanović, M. Kulić, E. Hodžić, S. Sokolovic et al.

This study evaluated brain natriuretic peptide (BNP) release in acute myocardial infarction (AMI), absolute values as well as pattern of its release. There are two different patterns of BNP release in AMI; monophasic pattern--concentration in the first measurement is higher than in the second one, and biphasic pattern--concentration in the first measurement is lower than in the second one. We observed significance of biphasic and monophasic pattern of BNP release related to diagnostic and prognostic value. We included in this prospective observational study total of 75 AMI patients, 52 males and 23 females, average age of 62.3 +/- 10.9 years with range of 42 to 79 years. BNP was measured and pattern of its release was evaluated. In AMI group BNP levels were significantly higher than in controls (462.88 pg/mL vs. 35.36 pg/mL, p < 0.001). We found statistically significant real negative correlation (p < 0.05) between BNP concentration and left ventricle ejection fraction (LVEF) with high correlation coefficient (r = -0.684). BNP concentrations were significantly higher among patients in Killip class II and III compared to Killip class I; Killip class I BNP = 226.18 pg/mL vs. Killip class II 622.51 pg/mL vs. Killip class III 1530.28 pg/mL, p < 0.001. BNP concentrations were significantly higher in patients with; (i) myocardial infarction vs. controls; (BNP 835.80 pg/mL vs. 243.03 pg/mL); (ii) in pts with positive major adverse cardiac events (MACE) vs. negative MACE (BNP 779.08 pg/mL vs. 242.28 pg/mL, p < 0.001); (iii) in pts with positive compared to negative left ventricle (LV) remodelling (BNP 840.77 pg/mL vs. 341.41 pg/mL, p < 0.001). Group with biphasic pattern of BNP release had significantly higher BNP concentration compared to monophasic pattern group. In biphasic pattern group we found significant presence of lower LVEF, Killip class II and III, LV remodelling and MACE. We found that BNP is strong marker of adverse cardiac events in patients presenting with a myocardial infarction. In our AMI group we found significant elevation of BNP and it is suspected that second peak secretion is not only due to systolic dysfunction and subsequent remodeling of LV but also due to impact of ischaemia. Patients with biphasic pattern probably have worse prognosis due to severe coronary heart disease. Besides its diagnostic role as a simple blood marker of systolic function, BNP is also important prognostic marker who helps making clinical decision about early invasive vs. conservative management.

AIM To examine coagulation factor VIII activity in plasma, as a risk factor for thrombosis, in the patients with diabetes mellitus (DM). Also, to assess its relationship with fibrinogen and fasting blood glucose concentrations and with body mass index. METHODS The plasma coagulation factor VIII activity, plasma levels of fibrinogen and blood glucose concentrations were measured in 30 patients with DM type 1, 30 patients with DM type 2 and in 30 healthy subjects. Body weight and body height were also measured and BMI was calculated. RESULTS The plasma factor VIII activity in patients with DM type 1 and patients with DM type 2 was significantly higher than the values measured in healthy subjects. There was no significant difference in the factor VIII activity between patients with DM type 1 and type 2. The concentrations of fibrinogen and blood glucose in both groups of patients were significantly higher than in the group of healthy subjects. Patients with DM type 2 had a significantly higher BMI compared to healthy subjects, as well as compared to patients with DM type 1. There was a significant positive correlation between plasma factor VIII activity and plasma level of fibrinogen and a significant negative correlation between factor VIII activity and BMI in patients with DM type 2. CONCLUSION Diabetic patients have the elevated plasma coagulation factor VIII activity and increased fibrinogen concentration thus an increased risk of thrombosis and vascular diseases.

Background and Aims: Hepatic steatosis seems to be a risk factor for poor response to interferon and ribavirin therapy in patients with chronic hepatitis C. The aim of this study was to determine presence of hepatic steatosis in chronic hepatitis C and its influence on early virological response in patients treated with combined antiviral therapy (pegylated interferon and ribavirin). Methods: We studied 96 patients treated at Gastroenterohepatology Department, in the period of four years (2005-2009). There were 71 males and 25 females enrolled in this study. 72 patients had genotype 1, 5 patients had genotype 2, 17 patients had genotype 3 and 2 patients had genotype 4. Liver histology was evaluated in order to establish presence of inflammation, fibrosis and steatosis. HCV RNA levels in sera were measured by real time PCR. Early virological response (EVR) was defined as negative serum HCV RNA at week 12. In order to measure the effect influence of steatosis on early response to therapy, as well as genotype and response to therapy, we calculated relative risk and the corresponding p-value after 12 and 48 weeks. Results: The overall rate of EVR was 70%. The rate was significantly lower in the group with steatosis, regardless of the presence of micro or macrosteatosis, amounting to 60%. Serum cholesterol level was significantly higher in females than in males (7.4±0.7 vs. 5.1±0.3 mg/mL). The values of relative risks (and p-values) for effect of steatosis on the response are RRS12=8.4615 (2.87E-05), and RRS48=0.9844 (0.7399), while the values for the effect of genotype to therapy were RRG12=1.3378 (0.7543), and RRG48=3.5862 (0.2709). Conclusions: Our findings suggested that hepatic steatosis may have a strong influence on interferon therapy response in the sence that it is eight times more probable to not respond in the presence of steatosis. The presence of steatosis was highly associated with progressive disease and failure to achieve the EVR; therefore it can be a predictor of poor response to antiviral therapy.

The role of ferritin in fibrogenesis of liver parenchyma in patients with alcoholic liver disease has been investigated in previous studies. Ferritin was shown to be an indirect marker of ferum deposition in liver parenchyma in alcohol liver disease. The aim of the present study was to examine the role of nitric oxide (NO) in the pathogenesis of alcoholic liver disease as well as the influence of NO on iron (ferritin) metabolism in patients with alcoholic liver disease. Serum concentrations of NO and iron markers (iron, total iron binding capacity, ferritin) were measured in 30 male patients (aged 20-60 years) with alcoholic liver disease, as well as from a control group (30 male patients (aged 20-60 years) without liver disease). NO concentration was detected by measuring production of nitrates and nitrites using classical colorimetric Griess reactions. There was a statistically significant increase in serum NO concentration in patients with alcoholic liver disease compared to the control group (mean +/- SEM; 41,2 +/- 25,3 vs. 28,9 +/- 12,3 mmol/dm3, respectively; p<0,03). Similarly, serum iron levels (18,7 +/- 8,2 vs. 13,2 +/- 10,2 g/100 cm3, respectively; p<0,03) and serum total iron binding capacity (51,3 +/- 13,9 vs. 41,4 +/- 11,4 micromol/dm3, respectively; p<0,005) were also significantly higher in patients with alcoholic liver disease compared to control patients. The serum concentration of ferritin was 27% higher in patients with alcoholic liver disease than in the control group; however this was not statistically significant (283,2 +/- 291,0 vs. 222,9 +/- 252,0 g, respectively; p<0,4). There was no correlation between NO and ferritin in the investigated groups. These results suggest a possible role of NO and iron in the pathogenesis of alcoholic liver disease. NO and iron may be used as non-invasive predictors of liver damage. Also the role of iron in sera, and its deposition in liver parenchyma, could be used in clinical practice, especially in regards to assessing the fibrogenesis of liver parenchyma induced by ferritin.

Th e role of ferritin in fi brogenesis of liver parenchyma in patients with alcoholic liver disease has been investigated in previous studies. Ferritin was shown to be an indirect marker of ferum deposition in liver parenchyma in alcohol liver disease. Th e aim of the present study was to examine the role of nitric oxide (NO) in the pathogenesis of alcoholic liver disease as well as the infl uence of NO on iron (ferritin) metabolism in patients with alcoholic liver disease. Serum concentrations of NO and iron markers (iron, total iron binding capacity, ferritin) were measured in  male patients (aged – years) with alcoholic liver disease, as well as from a control group ( male patients (aged – years) without liver disease). NO concentration was detected by measuring production of nitrates and nitrites using classical colorimetric Griess reactions. Th ere was a statistically signifi cant increase in serum NO concentration in patients with alcoholic liver disease compared to the control group (mean ± SEM; , ± , vs. , ± , mmol/dm, respectively; p<,). Similarly, serum iron levels (, ± , vs. , ± , g/ cm, respectively; p<,) and serum total iron binding capacity (, ± , vs. , ± , μmol/dm, respectively; p<,) were also signifi cantly higher in patients with alcoholic liver disease compared to control patients. Th e serum concentration of ferritin was  higher in patients with alcoholic liver disease than in the control group; however this was not statistically signifi cant (, ± , vs. , ± , g, respectively; p<,). Th ere was no correlation between NO and ferritin in the investigated groups. Th ese results suggest a possible role of NO and iron in the pathogenesis of alcoholic liver disease. NO and iron may be used as non-invasive predictors of liver damage. Also the role of iron in sera, and its deposition in liver parenchyma, could be used in clinical practice, especially in regards to assessing the fi brogenesis of liver parenchyma induced by ferritin.

Amela Matavulj, P. Kovačević, J. Huskic, S. Veljković, Z. Rajkovača, N. Ponorac, Z. Zagorac

Introduction: Nitric oxide (NO) plays an important role in a wide range of physiologic and pathophysiological processes. A major mediator of endothelial function, NO regulates vasodilatory and antithrombotic actions in the vasculature and plays a role in reproductive functions, bronchodilation, bone formation, memory, insulin sensitivity, and gastrointestinal relaxation. Impaired NO bioactivity is strongly associated with endothelial dysfunction. NO, an L-arginine derivative, also exerts a variety of renal and extrarenal physiological and pathophysiological effects. It seems that NO synthetic pathway could have a key role in mediating the complex hemodynamic and hemostatic disorders associated to the progression of renal disease. It remains unclear whether endogenous NO production is increased or decreased in patients with chronic renal failure. The objective of this study was to present the effect of different dialysis treatment on NO serum concentration in patients with chronic renal failure. Patients and Methods: To evaluate endogenous NO production in these patients we studied plasma NO2 and NO3 levels (determined with the Griess method) in patients who underwent regular continuous ambulatory peritoneal dialysis or repeated haemodialysis and in healthy subjects. The study included 51 patients suffering from chronic renal failure and 30 healthy subjects. Results: Our results show that patients with chronic renal failure had a significantly higher NO serum concentration than controls. These values did not differ between patients on haemodialysis and those on continuous ambulatory peritoneal dialysis. NO serum concentration did not differ between female and male independently of the patient’s treatment. Discussion and Conclusion: From obtained results we can concluded that uremia is associated with excessive systemic NO release independently of the patient’s treatment. Alter (increase) NO synthesis may help to explain some pathological changes seen in uraemia such as bleeding tendency, a well-known complication of uremia and hemodialysis hypotension.

J. Huskic, N. Mulabegović, F. Alendar, L. Ostojić, Z. Ostojić, D. Šimić, R. Milicevic, Mladenka Naletilić

Recent evidence suggests that the angiotensin converting enzyme (ACE) is present in skin. The real value of the determination of ACE activity as a clinical-biochemistry test for the diagnosis of psoriasis has not been attained. Serum and tissue ACE were measured in 60 patients with psoriasis, 20 patients with lichen planus, 20 patients with seborrhoic dermatitis and in 20 healthy individuals. The serum and tissue ACE activity was determined before and after therapy, using the spectrophotometric method and hippuryl-l-histidyl-l-leucine as a substrate. The results showed that serum ACE activity before therapy was significantly increased in both groups--patients with psoriasis (p < 0.001) and patients with lichen planus (p < 0.001) in comparison to healthy individuals. However, there were no significant differences in serum ACE activity among patients with seborrhoic dermatitis and healthy individuals. After therapy, serum ACE activity significantly decreased in both groups of patients with psoriasis and patients with lichen planus comparing it to the level found in the control group. The values in both were similar. The tissue ACE activity in altered skin was significantly increased only in the patients with psoriasis in comparison to uninvolved skin of these patients, as well as the skin of healthy individuals. After therapy, there were no significant differences in tissue ACE activity between the treated skin and the healthy skin. In conclusion, determination of tissue angiotensin converting enzyme activity can be used in the differential diagnostic of indistinct clinical forms of psoriasis.

P. Kovačević, Amela Matavulj, S. Veljković, Z. Rajkovača, N. Ponorac, J. Huskic

Uremic lung is different entity then oedema present in cardiovascular diseases or in adult respiratory distress syndrome as well. This state is one of the possible complications in patients with chronic renal failure (CRF) receiving regular hemodialysis (HD). There are several studies suggesting that in these patients in 30-40% cases pulmonary hypertension was developed. It is known that patients with primary pulmonary hypertension have peripheral airway obstruction The data also showed that primary as well secondary pulmonary hypertension are more often developed in females; even real reason is still unknown. The aim of the study was to estimate the ventilator function improvement in patients with CRF receiving regular HD related to sex differences. The study population consisted in 39 patients with CRF, with no cardiac and pulmonary diseases. These patients were treated by regular hemodialysis using bicarbonate or acetate mode, respectively. They were divided into two groups according to the sex. Spirometry parameters before and after onset of hemodialysis were recorded. The results were analyzed using Student t-test and presented as mean +/-SD. All p values <0,05 were considered significant. The result showed that ventilatory function in male patients is significantly improved, especially VC and FEV1, whereas in female patients improvement had not statistical significance. It can be concluded that one of the possible reasons for slight improvement of ventilator function in female patients is pulmonary hypertension.

J. Huskic, F. Culo, S. Dautović, N. Mulabegović

Angiotensin converting enzyme (ACE) and nitric oxide (NO) have been suggested to be involved in the regulation of fluid homeostasis. In the present investigation, ACE activity and NO levels were determined in serum of 20 patients (10 men and 10 women) with dehydration caused by gastroenterocolitis and 20 healthy individuals (10 men and 10 women). Serum and tissue ACE activity was determined by spectrophotometric method using hippuryl-l-histidyl-l-leucine (Hip-His-Leu) as a substrate. NO synthesis was determined by measuring the products of NO, nitrite and nitrate. The concentration of nitrites was determined by classic colorimetric method using Griess reagent. Nitrate concentration was determined indirectly by their reduction with elementary zinc into nitrite. Results have shown that serum ACE activity in patients with dehydration (36,46+/-2,74 U/L) is statistically higher then in healthy individuals (28,71+/-1,77 U/L, p<0,05). The average level of nitrites/nitrates in serum of patients with dehydration (30,57+/-1,05 microM; mean +/- SEM) is also statistically higher then in healthy individuals (12,44+/-0,60 microM, p<0,0001). There was no correlation between ACE activity and NO production. The results indicate that ACE and NO may participate in the regulation of the alteration in blood flow and in the regulation of the water balance in patients with dehydration.

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.

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