A multi-gene panel study in hereditary breast and ovarian cancer in Colombia.

Germline mutations in BRCA1 and BRCA2 account for approximately 50% of inherited breast and ovarian cancers. Three founder mutations in BRCA1/2 have been reported in Colombia, but the pattern of mutations in other cancer susceptibility genes is unknown. This study describes the frequency and type of germline mutations in hereditary breast and/or ovarian cancer genes in a referral cancer center in Colombia. Eighty-five women referred to the oncogenetics unit of the Instituto de Cancerologia Las Americas in Medellin (Colombia), meeting testing criteria for hereditary breast and ovarian cancer syndrome (NCCN 2015), who had germline testing with a commercial 25-gene hereditary cancer panel, were included in the analysis. Nineteen patients (22.4%) carried a deleterious germline mutation in a cancer susceptibility gene: BRCA1 (7), BRCA2 (8), PALB2 (1), ATM (1), MSH2 (1) and PMS2 (1). The frequency of mutations in BRCA1/2 was 17.6%. One BRCA2 mutation (c.9246dupG) was recurrent in five non-related individuals and is not previously reported in the country. Seventeen mutation-carriers had a diagnosis of breast cancer (median age of diagnosis of 36 years) and two of ovarian cancer. All BRCA1 mutation-carriers with breast cancer had triple negative tumors (median age of diagnosis of 31 years). Variants of unknown significance were reported in 35% of test results. This is the first report of a multi-gene study for hereditary breast and/or ovarian cancer in a Latin American country. We found a high frequency and a wide spectrum of germline mutations in cancer susceptibility genes in Colombian patients, some of which were not previously reported in the country. We observed a very low frequency of known Colombian founder BRCA1/2 mutations (1.2%) and we found mutations in other genes such as PALB2, ATM, MSH2 and PMS2. Our results highlight the importance of performing multi-gene panel testing, including comprehensive BRCA1/2 analysis (full gene sequencing and large rearrangement analysis), in high-risk breast and/or ovarian cancer patients in Colombia.

Cytotoxicity study of plasma-sprayed hydroxyapatite coating on high nitrogen austenitic stainless steels.

Stainless steel has been frequently used for temporary implants but its use as permanent implants is restricted due to its low pitting corrosion resistance. Nitrogen additions to these steels improve both mechanical properties and corrosion resistance, particularly the pitting and crevice corrosion resistance. Many reports concerning allergic reactions caused by nickel led to the development of nickel free stainless steel; it has excellent mechanical properties and very high corrosion resistance. On the other hand, stainless steels are biologically tolerated and no chemical bonds are formed between the steel and the bone tissue. Hydroxyapatite coatings deposited on stainless steels improve osseointegration, due their capacity to form chemical bonds (bioactive fixation) with the bone tissue. In this work hydroxyapatite coatings were plasma-sprayed on three austenitic stainless steels: ASTM-F138, ASTM-F1586 and the nickel-free Böhler-P558. The coatings were analyzed by SEM and XDR. The cytotoxicity of the coatings/steels was studied using the neutral red uptake method by quantitative evaluation of cell viability. The three uncoated stainless steels and the hydroxyapatite coated Böhler-P558 did not have any toxic effect on the cell culture. The hydroxyapatite coated ASTM-F138 and ASTM-F1586 stainless steels presented cytotoxicity indexes (IC50%) lower than 50% and high nickel contents in the extracts.

[Hyperuricemia as a marker for anaerobic threshold in chronic cardiac failure]. / La hiperuricemia es un marcador del umbral anaeróbico en la insuficiencia cardíaca crónica.

BACKGROUND: Patients with chronic cardiac failure often have elevated plasma uric acid levels, that are associated to a dismal prognosis. AIM: To investigate possible metabolic mechanisms to explain elevated uric acid levels in these patients. PATIENTS AND METHODS: Eighteen patients with chronic cardiac failure aged 61 +/- 10 years old, without gout or renal failure and not using high doses of diuretics (equal or less than 80 mg/day furosemide or 50 mg/day hydrochlorothiazide) were studied. Plasma uric acid levels were correlated with anaerobic threshold, maximal oxygen uptake, plasma noradrenaline and creatinine and left ventricular ejection fraction, measured radioisotopically. RESULTS: Mean maximal oxygen uptake was 16.6 +/- 4.2 ml/kg/min. There was a negative correlation between uric acid levels and maximal oxygen uptake or maximal oxygen uptake/body surface area (r = 0.521 and -0.533 respectively, p < 0.05). Patients with uric acid levels over 7 mg/dl had a lower anaerobic threshold than patients with lower levels (9.81 +/- 2.41 and 13.08 +/- 3.28 ml/kg/min respectively, p < 0.05). No significant differences in maximal oxygen uptake were observed in these two groups of patients (15.5 +/- 4.24 and 18.08 +/- 3.86 ml/kg/min respectively). Uric acid levels did not correlate with plasma noradrenaline, creatinine or left ventricular ejection fraction. CONCLUSIONS: These results suggest that a defect in cellular oxygenation contributes to the elevation of plasma uric acid levels in patients with chronic cardiac failure.

Binding to phosphatidyl serine membranes causes a conformational change in the concave face of annexin I.

Recent studies have revealed that binding of annexin I to phospholipids induces the formation of a second phospholipid binding site. It is shown that the N terminus on the concave side of membrane-bound annexin I is cleaved much faster by trypsin or cathepsin than the N terminus of the free protein. The reactivity of the unique disulfide bond located near the concave face was similarly increased by membrane binding. These results demonstrate that Ca(2+)-dependent membrane binding induces a conformational change on the concave side of the annexin I molecule and support the notion that this face of the molecule may contribute to the formation of the secondary membrane-binding site.