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  • Author: Dimce Zafirov x
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Background: Diabetic nephropaty (DN) occurs in approximately 40% of patients with diabetes mellitus, and is the most common cause of end-stage renal disease. The combination of ACE inhibitors with ARB could lead to a more effective inhibition of rennin angiotensin aldosterone system (RAAS).

Aim: The present study was undertaken to evaluate the effects of dual RAAS blockade with ARB (candesartan) and ACE inhibitor (perindopril) in streptozotocin induced diabetic nephropathy versus ACE-inhibitor or ARB alone.

Materials and Methods: Wistar rats (n=125), were used in this investigation. Diabetes was induced by streptozotocin (STZ) 60 mg/kg. The diabetic rats (n=100) were randomly assigned to receive vehicle, ARB-Candesartan (5 mg/kg/per d), ACE inhibitor-Perindopril (6 mg/kg/per d), or a combination of low dose Can+Per (2.5 mg/kg/per d and 3 mg/kg/per d) respectively, from weeks 4-12.

Results: Treatment with candesartan or perindopril as monotherapy, although significantly, only partially prevented the symptoms and signs of DN. Candesartan and perindopril were equally effective in treatment of DN. Combination therapy was more effective than monotherapy with either drug.

Conclusion: The results from this study demonstrate that combination treatment with both ACE and ARB in low doses may offer synergistic blockade of the RAAS, not obtainable with either drug alone.

Assessment of Three Inflammatory Markers of Cardiovascular Diseases with a Special Accent on C-Reactive Protein

Background: Elevated levels of CRP, myoglobin and creatine kinase are always associated with pathological changes and hence their values give useful information for exact diagnosis and therapy. They are helpful in monitoring the inflammatory processes and associated diseases.

Aim: The aim of this study was to determine the usefulness and practical value of application of CRP detection by comparing it with the results obtained for the classical enzymes - markers of myocardial damage, myoglobin and creatine kinase isoenzyme MB (CK-MB) in pts with acute coronary syndrome (ACS), pts with chronic coronary artery disease (CAD) and in healthy individuals.

Material and Methods: Sera were taken from a total of 152 individuals (78.9% males, 21.1% females, mean age 61.87 ± 10.32 years). The subjects were divided in three groups: 63 pts with ACS; 52 pts CAD and a group of 36 conditionally healthy individuals. Analysis of patients' sera for presence of markers for myocardial damage: myoglobin, CK-MB along with determination of CRP level was done on the Immulite system, DPC (Diagnostic Products Corporation), Los Angeles, USA.

Results: Comparison of examined biomarker's values in pts divided according to diagnosis showed statistically significant higher levels in patients with ACS vs. others. As for biomarker's cut-off values, out of all CK-MB ≥5.7 ng/mL was found in 34 (53.1%) pts with ACS with significant difference among the groups in favor of its higher values in pts with ACS (p=0.0001). Out of all, myoglobin ≥25 ng/mL was found in 54 (84.4%) pts with ACS without significant difference among the groups. As for CRP, value of ≥3 mg/L was found in 39 (60.9%) pts with ACS and there was significant difference among the groups in favor of higher values in pts with ACS (p=0.001). There was significant positive correlation among the levels of examined three biomarkers: CK-MB in correlation to myoglobin (r=0.460; p= 0.0001) and to CRP level (r=0.204; p= 0.009), as well as myoglobin to CRP level (r=0.218; p= 0.005).

Conclusion: We could conclude that determination of CRP levels is a valid test for detection of acute coronary artery disease in addition to the classical, standard markers for myocardial damage.


Salt sensitive hypertension is known to be a contributing factor for the progression of kidney disease. This study was undertaken to investigate the role of excessive dietary salt on renal function and to evaluate the effect of valsartan and amlodipin given as a combination therapy on blood pressure and parameters specific to the renal function in salt loaded SHR rats. 48 male SHR rats at age of 20 weeks and body weight ranging between 270-350 g were used. SHR rats were divided into 3 groups: control group of rats -SHRC (n = 16) given tab water ad libitum and two salt treated groups in which tab water was replaced with a solution of NaCl (1%) from age of 8 weeks given ad libitum: SHRVAL+AMLO group (n = 16) where investigated drugs were administered at a dose of 10 mg/kg/ b.w. (valsartan) and 5 mg/kg/ b.w. (amlodipin) by gavage and SHR NaCl group (n = 16) that received saline in the same volume and the same time intervals as the SHRVAL+AMLO group. For a period of 12 weeks we have investigated the effect of the VAL+AMLO drug combination on systolic blood pressure (SBP), body weight and renal function tests. Salt loading with 1% solution in the SHR NaCl group has lead to significant increase of blood pressure, proteinuria and decrease in creatinine clearance. Combined treatment with АТ1-receptor blocker and calcium antagonist has managed to control blood pressure and ameliorated renal damage.