Lina Mirić Kovačević
Name: dr. sc. MIRIĆ KOVAČEVIĆ LINA dr. med.
Thesis title: “DIFFERENCES IN EXPRESSION OF APOPTOSIS- AND PROLIFERATION-REGULATING PROTEINS BETWEEN HEALTHY SKIN AND SKIN IN PATIENTS WITH CHRONIC KIDNEY FAILURE AND PRURITUS“
Mentor: prof. dr. sc.PUIZINA IVIĆ NEIRA
Qualifying research publications:
Kovacevic LM, Puzina-Ivic N, Ljutic D i sur. Differences in epidermal thickness and expression of apoptosis regulatory protein int he skin of patients with chronic renal failure and pruritus. Acta Histochem 2013; 115: 144-50.
IF (JCR 2013) 1.760
Summary:
Chronic renal failure is often associated with skin itching (pruritus) in dialyzed patients. In order to investigate the possible causes of pruritus in those patients, the epidermis of the thigh of 12 dialyzed patients and 5 controls from patients without renal disease were examined. The sections of the epidermis were measured and statistically analyzed, and were immunohistochemically stained using antibodies to proliferation marker Ki-67, anti-apoptotic marker Bcl-2, and pro-apoptotic markers Bax and caspase-3, as well as TUNEL method. Proliferation index of epidermal cells was 10.8 % in normal skin, 11.3 % in the skin of patients after 3 years of dialysis and 12.5 % after 5 years of dialysis. An increased proliferation index characterized the skin of patients on dialysis, and accorded with duration of dialysis. After 3 years period on dialysis, a moderate increase of basal layer cell proliferation was noted in patient’s epidermis, while a significant decrease of proliferation in suprabasal layer of epidermis characterized patients after 5 years on dialysis. While the mean thickness of normal epidermis was 53 μm, in dialyzed patients it ranged between 23 and 34 μm during the 3–5 year period on dialysis. Compared to normal skin, the fine balance between the Bcl-2 and Bax proteins did not greatly change in the epidermis of dialyzed patients during the three years of dialysis. Following five-year dialysis, the epidermis displayed increased Bax and decreased Bcl-2 expression in the basal and intermediate epidermal layers, as well as the presence of apoptotic cells (TUNEL and caspase-3 positive) both in the superficial and intermediate epidermal layers. Our study demonstrated the predominant expression of cell death Bax proteins over cell survival Bcl-2 proteins, and apoptotic cells in the deeper layers of the epidermis in patients on long-term dialysis.
We speculate that the thinning of the epidermis might be associated with the appearance of dead cells in the deeper epidermal layers, while the changed internal milieu of epidermal cells could possibly affect the intra-epidermal nerve endings thus leading to the sensation of pruritus.
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