Paavo Pasanen

Oxidized LDL and thickness of carotid intima-media are associated with coronary atherosclerosis in middle-aged men: lower levels of oxidized LDL with statin therapy

We investigated the relation between serum lipids including oxidized LDL and the severity of coronary atherosclerosis. Serum lipids and oxidized LDL was measured in 62 men (33-66 years), who underwent diagnostic coronary angiography and sonography to measure the carotid intima-media thickness. LDL oxidation was found in chemical analyses to be due to conjugated fatty acids in cholesteryl esters and triglycerides. Regression analysis indicated that the carotid intima-media thickness and the ratio of LDL diene conjugation to LDL cholesterol (the ox-LDL:LDL ratio) were the only factors associated independently with the severity of coronary atherosclerosis. The patients with multi-vessel disease who did not use lipid lowering therapy had a 50% thicker carotid intima media (P = 0.030) and a 41% higher ox-LDL:LDL ratio (P = 0.020) than patients with normal vessels. Further, patients with multi-vessel disease on statin therapy had a 24% lower ox-LDL:LDL ratio than the subjects with multi-vessel disease who did not use lipid lowering drugs (P = 0.027), although the concentration of LDL cholesterol did not differ between the groups. This study supports the hypothesis that lipid oxidation plays a role in the development of atherosclerosis.

Establishment of a kinetic model for urocanic acid photoisomerization

Abstract The photoisomerization reactions of the E and Z isomers of urocanic acid (UCA), which are natural constituents of the mammalian epidermis, were studies by time-resolved flash photolysis and quantum yield determination in the pH range 3.0–10.0. A kinetic model for the processes is presented on the basis of the following observations: (1) the sum of the quantum yields for E → Z and Z → E reactions can be more than unity; (2) a kinetic component with almost equal rate parameters for both reactions is observed in flash photolysis; (3) fluorescence and (4) loss of material were not detected; (5) the quantum yield of formation of the isomerization product is represented by a short-lived decay component in the E → Z and by a long-lived component in the Z → E reaction. Correlations between the experimental data and possible molecular arrangements are examined.

Electrochemical synthesis and spectroscopic study of poly(3,4-methylenedioxythiophene)

Abstract Electropolymerization of a new thiophene derivative 3,4-methylenedioxythiophene was studied on indium tin oxide electrodes and platinum in different organic solvents (acetonitrile, propylene carbonate, and nitrobenzene). Electropolymerization potentiodynamically in anhydrous nitrobenzene resulted in best polymeric films, which were compact and tightly adhered to the substrate surface. The properties of these films were compared to those previously published for poly(3,4-ethylenedioxythiophene).

Stereospecific modulation of GABAA receptor function by urocanic acid isomers

A deamination product of histidine, urocanic acid, accumulates in the skin of mammals as trans-urocanic acid. Ultraviolet (UV) irradition converts it to the cis-isomer that is an important mediator in UV-induced immunosuppression. We have recently shown that urocanic acid interferes with the agonist binding to GABA(A) receptors. We now report that the effects of urocanic acid on binding of a convulsant ligand (t-butylbicyclo[35S]phosphorothionate) to GABA(A) receptors in brain membrane homogenates are dependent on pH of the incubation medium, the agonistic actions being enhanced at the normal pH of the skin (5.5). Using Xenopus laevis oocytes expressing recombinant rat alpha1beta1gamma2S GABA(A) receptors, the low pH potentiated the direct agonistic action of trans-urocanic acid under two-electrode voltage-clamp, whereas cis-urocanic acid retained its low efficacy both at pH 5.5 and 7.4. The results thus indicate clear differences between urocanic acid isomers in functional activity at one putative receptor site of immunosuppression, the GABA(A) receptor, the presence of which in the skin remains to be demonstrated.

Urocanic acid concentration and photoisomerization in Caucasian skin phototypes.

Abstract— To investigate the relationship between erythemal sensitivity of the skin to U V radiation and epidermal urocanic acid (UCA) concentration, 45 healthy volunteers of anamnestic skin phototypes (ASP) I‐IV were studied. In 16 of the subjects, we analyzed UCA photoisomerization after graded UVB exposures. The median and mean total UCA concentration in unirradiated skin was 22.4 and 35.3 nmol/cm2, and no statistically significant difference in total UCA concentrations was detectable either between ASP I through II and III through IV or between the phototested skin type (PSP) groups 1 through 2 and 3 through 4. The relative amount of the cis‐isomer varied between 3 and 35%, with median and mean values of 7 and 12%, respectively. No statistically significant difference in absolute or relative cis‐UCA concentrations was detectable between ASP I through II and III through IV, but a significantly lower absolute (P < 0.009) and relative (P < 0.002) cis‐UCA concentration in unirradiated skin was recorded in PSP groups 1 through 2, compared to types 3 through 4. In all tested subjects, an erythemally weighted dose of 1 mj/cm2sufficed to cause trans‐ to cis‐UCA isomerization. When comparing photosensitive (skin phototype I) and phototolerant (phototypes III and IV) individuals, who were irradiated with a reference 5 mJ/cm2UV dose or with fractions of 0.1‐1.0 of their individual minimal erythema dose values, no skin phototype‐dependent difference in ability to photoisomerize was discernible.