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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.

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.

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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