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Hypercholesterolemia has been suggested to have direct negative effects on myocardial function due to increased reactive oxygen species (ROS) generation and increased myocyte death. Mitochondrial permeability transition (MPT) is a significant mediator of cell death, which is enhanced by ROS generation and attenuated by exercise training. The purpose of this study was to investigate the effect of hypercholesterolemia on the MPT response of cardiac mitochondria. We tested the hypothesis that familial hypercholesterolemic (FH) pigs would have an enhanced MPT response and that exercise training could reverse this phenotype. MPT was assessed by mitochondrial swelling in response to 10-100 μM Ca(2+). FH pigs did show an increased MPT response to Ca(2+) that was associated with decreases in the expression of the putative MPT pore components mitochondrial phosphate carrier (PiC) and cyclophilin-D (CypD). FH also caused increased oxidative stress, depicted by increased protein nitrotyrosylation, as well as decreased levels of reduced GSH in cardiac mitochondria. Expression of the mitochondrial antioxidant enzymes manganese superoxide dismutase (MnSOD), thioredoxin-2 (Trx2), and peroxiredoxin-3 (Prx3) was greatly reduced in the FH pigs. In contrast, cytosolic catalase expression and activity were increased. However, chronic exercise training was able to normalize the MPT response in FH pigs, reduce mitochondrial oxidative stress, and return MnSOD, Trx2, Prx3, and catalase expression/activities to normal. We conclude that FH reduces mitochondrial antioxidants, increases mitochondrial oxidative stress, and enhances the MPT response in the porcine myocardium, and that exercise training can reverse these detrimental alterations.

The sunburn response is markedly reduced by dietary fish oil rich in omega-3 polyunsaturated fatty acids. Because prostaglandins mediate the vasodilatation, we examined the effect of fish oil on ultraviolet (UV) B-induced prostaglandin metabolism. In addition we assessed the potential photoprotective effect of fish oil in light-sensitive patients. Thirteen patients with polymorphic light eruption received dietary supplements of fish oil rich in omega-3 polyunsaturated fatty acids for 3 months. At baseline and 3 months, the minimal erythema dose of UVB irradiation was determined, and a graded UVA challenge given to a forearm to assess the threshold dose for papule provocation. Suction blisters were raised on the other forearm, on control skin, and on skin irradiated with four times the minimal erythema dose of UVB 24 h previously, and blister fluid prostaglandin E2 was measured by radioimmunoassay. Following 3 months of fish oil, the mean minimal erythema dose of UVB irradiation increased from 19.8 +/- 2.6 to 33.8 +/- 3.7 mJ/cm2 (mean +/- SEM), p < 0.01. The UVA provocation test was positive in 10 patients at baseline, and after 3 months nine of these showed reduced sensitivity to papule provocation, p < 0.001. Before fish oil, PGE2 increased from 8.6 (SEM 2.1) ng/ml in control skin to 27.2 (11) ng/ml after UVB, p < 0.01. Following 3 months of fish oil, PGE2 decreased to 4.1 (1) and 9.6 (2.4) ng/ml in control and irradiated skin, respectively, p < 0.05. Reduction of UV-induced inflammation by fish oil may be due, at least partially, to lowered prostaglandin E2 levels. The photoprotection against UVA-provocation of a papular response suggests a clinical application for fish oil in polymorphic light eruption.

Disturbances in the kynurenine pathway are present in pellagra and pellagroid syndromes. In 88 photodermatoses, the authors found increased urinary excretion of xanthurenic acid after oral load of tryptophan in a number of light-induced eruptions, i.e. benign summer photodermatosis (40%), polymorphous light eruptions (37%), and persistent light reactions (36%) as well as in patients with acute alcoholic intoxication. These biochemical abnormalities in the kynurenine pathway allow for a pathogenetic approach in some photodermatoses.

Urocanic acid was measured by means of high-performance liquid chromatography (HPLC) in the stratum corneum of a 3.5-year-old child suffering from hidroa vacciniformia. Compared to ten healthy children of equal age, the urocanic acid content of the stratum corneum was reduced significantly. In addition, there was an elevated level of some amino acids in the urine, particularly that of histidine and methylhistidine, which seems to be a very important finding. Urocanic acid acts as a natural sun protective agent, and the results are discussed with this in mind. It was not possible to elicit hidroa vacciniformia lesions in the patient by UV-A, as described by others.

The authors described three cases of Bazin's hydroa vacciniforme. Study of the history of the disease enables present nosological conceptions to be better understood. Diagnosis of hydroa vacciniforme is essentially clinical : appearance of the rash, periodicity and spontaneous improvement after puberty are characteristic. Hydroa vacciniforme has to be distinguished from porphyrias and polymorphous light sensitive eruptions. The etiology of this photodermatosis of child is unknown, but associated disturbances in tryptophan metabolism in some cases seem to be linked to a vitamin B6 deficiency.