Manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with risk of early-onset prostate cancer.

Prostate cancer continues to be the most frequently diagnosed neoplasm, and the second leading cause of cancer-related mortality in men. Oxidative stress may enhance prostatic carcinogenesis. Manganese superoxide dismutase (MnSOD) is the only known superoxide scavenger in mitochondria. It plays a key role in antioxidant defense as mitochondria are important for oxidative metabolism coupled to the electron transport chain and oxidative phosphorylation and hence, ROS production. A T-->C single nucleotide substitution, resulting in a Val-->Ala change at position 9 (Ala-9Val), which alters the secondary structure of the protein, has been noted to affect transport of MnSOD into the mitochondria. We have determined the MnSOD genotype in 85 prostate cancer cases and 151 control subjects. Ala-9Val polymorphism was determined using real time polymerase chain reaction (PCR) amplification with fluorescently labeled primers. No significant difference was found in prostate cancer susceptibility in the subjects with Ala/Ala and Val/Ala genotype compared with Val/Val genotype (Odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.69-2.42; p = 0.416). We did not observe an association of the MnSOD genotype or allele frequency between subgroups of cases divided by disease status (aggressive vs. non-aggressive prostate cancer). However, in the analyses stratified by the age at diagnosis we have observed that men homozygous for Ala had a 5.2-fold increased risk of early-onset prostate cancer (under age of 65) compared to men homozygous for Val allele (p = 0.05). These data suggest that Ala/Ala MnSOD genotype in the Macedonian population could have an influence on early onset of prostate cancer, but no impact on the subsequent development of the disease.

Vascular calcification and atherosclerosis in hemodialysis patients: what can we learn from the routine clinical practice?

BACKGROUND: Hemodialysis (HD) patients are at increased risk for arterial intimal (AIC) and medial calcification (AMC). METHODS: In a cross-sectional study on 153 HD patients we evaluated the presence of AIC and AMC using plain radiography of the pelvis and the presence of atherosclerotic lesions using high-resolution B-mode ultrasonography of the common carotid arteries (CCA). RESULTS: The radiography of the pelvis confirmed the frequent presence of AIC (35.3%) and AMC (35.9%) in our HD patients. Arterial calcification was absent (non calcified-NC) in a minority of patients (28.8%). Patients with AIC had significantly higher prevalence of atherosclerotic plaques on CCA (78.6%) compared with both other groups and a higher number of documented atherosclerotic complications, such as cardiovascular (85.2%), cerebrovascular (33.3%) and peripheral arterial disease (38.9%) in comparison with the NC patients. According to the 1-year calculated data from patient records, there were no significant differences in the specific HD risks, such as the dose of prescribed calcium carbonate and vitamin D3, serum levels of calcium, phosphate, calcium-phosphate product and intact parathyroid hormone. All four bone metabolism markers within the range proposed by K/DOQI guidelines were achieved in 9.3%, 14.5% and 20.4% in the AIC, AMC and NC group, respectively. CONCLUSIONS: Patients with AIC and AMC are frequently found in the HD population. Screening for arterial calcifications in chronic kidney disease patients is suggested even in the early pre-dialysis period. The highest proportion of patients within the guidelines proposed range for bone and mineral metabolism markers was observed in the NC group. A longer period of data analysis is required in order to evaluate the possible role of some traditional and HD-specific risk factors for the development of arterial calcifications. The achievement of the K/DOQI guidelines is an important issue in the prevention of those conditions.

[The possible pathogenesis of AA type amyloidosis in a patient with ulcerative colitis and renal cell carcinoma]. / Sistemna amiloidoza tipa AA u bolesnika s ulceroznim kolitisom i bubreznim karcinomom.

A 43-year-old male with a two-month history of ulcerative colitis and nephrectomy due to a renal cell carcinoma performed a month before was admitted to University Department of Nephrology for nephrotic syndrome and chronic renal failure. Biopsy of the remnant kidney revealed secondary AA amyloidosis with deposits in the glomeruli and walls of intrarenal blood vessels. Re-evaluation of the nephrectomized kidney also showed amyloid deposits both in the renal tissue free from malignant cells and in tumor tissue. In this case the amyloid deposition may have been the result of two coexisting disorders, ulcerative colitis and renal cell carcinoma, both known to be stimulators of amyloid deposition. The remnant kidney function worsened during the follow up and the patients started chronic dialysis after 6 months.

Protocol for performing nephrological activity in the Republic of Macedonia.

The fast development of nephrology in the world, especially in the second half of the 20 th century demanded protocol (guidelines) for nephrological activity for all levels of medical care, of doctors and specialists. The International Society of Nephrology, the European Renal Association and other national associations created their own protocol (guidelines) for nephrological activity. The Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) proclaimed the First Protocol for Performing Nephrological Activity in the Republic of Macedonia at the First Congress of the MSNDTAO, held in Ohrid 1993, and it was published in the Macedonian Medical Review, 1994; Supplement 14: 397-406 [1]. The update of the Protocol for Performing Nephrological Activity in the Republic of Macedonia was proclaimed at the Fourth Congress of MSNDTAO, held in Ohrid 2012 and it presented in this text.

Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk.

Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low GPX activity or particular GPX1 polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations. Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20-0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90 subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may play an important role in prostate carcinogenesis.

Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

OBJECTIVES: The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). DESIGN AND METHODS: 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. RESULTS: A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. CONCLUSIONS: This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

The incidence of biopsy-proven primary glomerulonephritis in the Republic of Macedonia-long-term follow-up.

In order to define the type of renal disease, renal biopsy was performed in 1304 patients, aged 14-72 years. Their biopsies were processed for light and immunofluorescence microscopy, and electron microscopy in some cases. The diagnosis of primary glomerular disease was confirmed in 716 patients with the following incidence: minimal change nephrotic syndrome in 52 (7.2%), focal segmental glomerulosclerosis in 72 (9.9%), membranous nephropathy in 97 (13.5%), IgA nephropathy in 85 (11.8%), diffuse mesangial glomerulonephritis (GN) without IgA in 32 (4.4%), focal mesangial GN in 97 (13.5%), membranoproliferative GN in 59 (8.4%), acute GN in 88 (12.3%), crescentic GN in 53 (7.4%) and sclerosing GN in 46 patients (6.4%).