Low-Molecular-Weight Hydrophilic and Lipophilic Antioxidants in Nonmelanoma Skin Carcinomas and Adjacent Normal-Looking Skin.

Low-molecular-weight antioxidants are some of the most efficient agents of the skin defense mechanism against environmental factors, such as cosmic rays, smoke, and pollutants. The total skin concentrations of hydrophilic ascorbic and uric acids, as well as lipophilic α-tocopherol, ß-carotene, and ubiquinol-10 antioxidants were determined by an HPLC-EC detector from 18 biopsies of human nonmelanoma skin carcinomas and 18 biopsies from skin areas adjacent to carcinomas. No significant differences in the concentrations of lipophilic antioxidants in both carcinomas and normal-looking skin areas adjacent to carcinomas were observed. On the contrary, ascorbic and uric acid concentrations were found to be 18 and 36% lower in carcinomas than in normal-looking skin areas, respectively. No statistical significance was observed between antioxidant concentrations and age, sex, phototype, profession, site of tumor, frequency, and time of UV light exposure either. Accordingly the antioxidant concentrations in both cancerous skin and adjacent normal-looking areas were found to be much higher than in normal skin, in contrast to literature data.

Impact of graded hypothermia on coagulation and fibrinolysis.

BACKGROUND: Hypothermia has a detrimental effect on hemostatic mechanism. The purpose of this experimental study was to investigate the effect of graded hypothermia on markers of the anticoagulant system (antithrombin III and protein C) and fibrinolytic system (plasminogen, α(2)-antiplasmin), and on vascular wall and other tissue specimens. MATERIALS AND METHODS: Ten New Zealand rabbits were subjected to mild and then moderate core hypothermia of 32 °C for 60 min. Blood samples were obtained at normothermic (T(1)), mild (T(2)), and moderate (T(3)) hypothermic conditions. Chromogenic assay methods were used to determine quantitatively (%) the activity of antithrombin III, protein C, plasminogen, and α(2)-antiplasmin. Hypothermic values were compared with the normothermic values. Tissue and vessel wall specimens were examined under light microscope. RESULTS: Reduction of activity (%) from normothermia (T(1)) to mild (T(2)) and moderate (T(3)) hypothermia was found for antithrombin III (103.40 ± 12.54, 87.40 ± 13.50, and 82.70 ± 20.78, respectively, with statistically significant difference between T(1)-T(3): P = 0.03), for protein C (70.1 ± 7.51, 56.30 ± 8.34, and 53.1 ± 7.34, with statistically significant difference between T(1)-T(2) and T(1)-T(3): P = 0.015 for both comparisons) and α(2)-antiplasmin (97 ± 9.63, 80.60 ± 11.73, and 83.70 ± 13.94, with statistically significant difference between T(1)-T(2): P = 0.006). Plasminogen activity was increased (14.50 ± 0.52, 16.30 ± 1.63, and 17.30 ± 2.45, with statistically significant difference between T(1)-T(2) and T(1)-T(3): P = 0.033 for both comparisons). Histologic examination revealed no significant lesions on tissue and vessel wall specimens. CONCLUSIONS: The results of our study suggest that even though the hypothermia period was relatively short, the processes of coagulation and fibrinolysis were altered with simultaneous changes.

Solution structure of the apo and copper(I)-loaded human metallochaperone HAH1.

The human metallochaperone HAH1 has been produced in Escherichia coli with four additional amino acids at the C-terminus and characterized in solution by NMR spectroscopy, both with and without copper(I). The solution structure of the apo-HAH1 monomer has a root-mean-square-deviation (RMSD) of 0.50 A for the coordinates of the backbone atoms and 0.96 A for all heavy atoms. These values compare, respectively, with 0.45 and 0.95 A for copper(I)-HAH1. There are only minor structural rearrangements upon copper(I) binding. In particular, the variation of interatomic interactions around the metal-binding region is limited to a movement of Lys60 toward the metal site. The protein structures are similar to those obtained by X-ray crystallography in a variety of derivatives, with backbone RMSD values below 1 A. In the holoprotein, copper(I) is confirmed to be two coordinated. If these data are compared with those of orthologue proteins, we learn that HAH1 has a lower tendency to change coordination number from two to three. Such a switch in coordination is a key step in copper transfer.