Balkan endemic nephropathy: role of ochratoxins A through biomarkers.

Several studies implicated mycotoxins, in endemic kidney disease geographically limited to Balkan region (Balkan endemic nephropathy (BEN)). In Bulgaria, much higher prevalence of ochratoxin A (OTA), exceeding 2 microg/L, was observed in the blood of affected population. OTA is found more often in the urine of people living in BEN-endemic villages. To confirm and quantify exposure to OTA in Vratza district, we followed up OTA intake for 1 month, OTA in blood and urine from healthy (20-30 years old) volunteers, from two villages with high risk for BEN disease. Food samples were collected daily, blood and urine at the beginning of each week. Relations between increasing OTA intake, blood concentration and elimination of OTA in urine have been studied in rats. Average weekly intake of OTA varies from 1.9 to 206 ng/kg body weight, twice tolerable weekly intake recommended by JECFA. OTA blood concentrations are in the same range as previously reported in this region with concentrations reaching 10 microg/L. Weekly OTA food intake is not directly correlated with blood and urine concentrations. Biomarkers of biological effects such as DNA adducts were detected in patients affected by urinary tract tumours (UTT) and in rat study. All these plead for the implication of OTA, in BEN and UTT.

Gemcitabine, epirubicin, and paclitaxel versus fluorouracil, epirubicin, and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: a Central European Cooperative Oncology Group International, multicenter, prospective, randomized phase III trial.

BACKGROUND: The objectives of this phase III trial were to compare the time to progressive disease (TtPD), overall response rate (ORR), overall survival, and toxicity of gemcitabine, epirubicin, and paclitaxel (GET) versus fluorouracil (FU), epirubicin, and cyclophosphamide (FEC) as first-line therapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Female patients aged 18 to 75 years with stage IV and measurable MBC were enrolled and randomly assigned to either gemcitabine (1,000 mg/m(2), days 1 and 4), epirubicin (90 mg/m(2), day 1), and paclitaxel (175 mg/m(2), day 1) or FU (500 mg/m(2), day 1), epirubicin (90 mg/m(2), day 1), and cyclophosphamide (500 mg/m(2), day 1). Both regimens were administered every 21 days for a maximum of eight cycles. RESULTS: Between October 1999 and November 2002, 259 patients (GET, n = 124; FEC, n = 135) were enrolled. Baseline characteristics were well balanced across treatment arms. After a median of 20.4 months of follow-up, median TtPD was 9.1 months and 9.0 months in the GET and FEC arms, respectively (P = .557). The ORR was 62.3% in the GET arm (n = 114) and 51.2% in the FEC arm (n = 129; P = .093). Grade 3 and 4 toxicities, including neutropenia, thrombocytopenia, anemia, stomatitis, neurosensory toxicity, and allergy, occurred significantly more often in the GET arm. CONCLUSION: No significant differences in terms of TtPD and ORR were observed between the two treatment arms. Treatment-related toxicity was higher in the GET arm.

Analysis of ochratoxin A in foods consumed by inhabitants from an area with balkan endemic nephropathy: a 1 month follow-up study.

In the 1950s, a series of publications from Bulgaria, Yugoslavia, and Romania locally described a kidney disease called Balkan Endemic Nephropathy (BEN). In Bulgaria, the exposure of populations to ochratoxin A (OTA) was supported by analysis of individual food items demonstrating a higher prevalence and higher levels of OTA in food from the high-incidence areas of BEN. In this work, food consumption from a series of individuals from two villages of the BEN area during 1 month was followed using the duplicate diet method. Meals consumed by volunteers from both villages showed uneven OTA contents, spreading from below the limit of quantification (<0.07 microg/kg) to 2.6 microg/kg. The average weekly intake of OTA varies from 1.86 to 92.7 ng/kg of body weight. Some of these levels approach the provisional tolerable weekly intake (PTWI) established by the JECFA at 100 ng/kg of body weight. These results confirm previous studies performed in the same area and demonstrate the high exposure of this population to OTA, thus strengthening the hypothesis of the involvement of this mycotoxin in BEN etiology.