One-time intrathecal triamcinolone acetonide application alters the redox potential in cerebrospinal fluid of progressive multiple sclerosis patients: a pilot study.

INTRODUCTION: Cerebrospinal fluid analysis may provide insight into the interplay between chronic inflammation and response to treatment. OBJECTIVES: To demonstrate the impact of one intrathecal triamcinolone injection on the redox potential and on ascorbyl radical appearance in the cerebrospinal fluid of chronic progressive multiple sclerosis patients. METHODS: A total of 16 patients received 40 mg triamcinolone. Electron-spin resonance spectroscopy measured the oxidation range after copper ion [Cu (II)] addition and ascorbyl-radical bioavailability. RESULTS: There was an increase of Cu (II) ion absorption, which reflects an augmented content of reduced proteins. Ascorbyl radicals were present in contrast to healthy controls according to the literature. CONCLUSION: Intrathecal steroid application alters the redox potential in cerebrospinal fluid. Our findings support the beneficial role of steroids on oxidative stress generally demonstrated by ascorbyl radical appearance. Reactive oxygen species decline is necessary for an upregulated production of reduced proteins.

Effects of water-filtered infrared-A and of heat on cell death, inflammation, antioxidative potential and of free radical formation in viable skin--first results.

The effects of water-filtered infrared-A (wIRA) and of convective heat on viability, inflammation, inducible free radicals and antioxidative power were investigated in natural and viable skin using the ex vivo Bovine Udder System (BUS) model. Therefore, skin samples from differently treated parts of the udder of a healthy cow were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, by prostaglandin E2 (PGE2) measurement and by electron spin resonance (ESR) spectroscopy. Neither cell viability, the inflammation status, the radical status or the antioxidative defence systems of the skin were significantly affected by wIRA applied within 30 min by using an irradiance of 1900 W m(-2) which is of relevance for clinical use, but which exceeded the maximum solar IR-A irradiance at the Earth's surface more than 5 times and which resulted in a skin surface temperature of about 45 °C without cooling and of about 37 °C with convective cooling by air ventilation. No significant effects on viability and on inflammation were detected when convective heat was applied alone under equivalent conditions in terms of the resulting skin surface temperatures and exposure time. As compared with untreated skin, free radical formation was almost doubled, whereas the antioxidative power was reduced to about 50% after convective heating to about 45 °C.

Reduction in the free radical status and clinical benefit of repeated intrathecal triamcinolone acetonide application in patients with progressive multiple sclerosis.

BACKGROUND: Previous open trials performed repeated intrathecal application of the sustained release steroid triamcinolone acetonide every third day in patients with progressive multiple sclerosis and described enhanced walking abilities. OBJECTIVES: The objectives of this study were to demonstrate the efficacy of 5 triamcinolone administrations every other day and to describe their effects on the amount of inducible free radicals in cerebrospinal fluid. SUBJECTS/METHODS: Clinical ratings, determinations of maximum walking distance, and execution of an instrumental peg insertion test were performed at baseline and on each day after a triamcinolone injection in 21 patients with progressive multiple sclerosis. Induction of free radicals was assessed in cerebrospinal fluid before each triamcinolone application by electron spin resonance spectroscopy. RESULTS: Scores for multiple sclerosis improved, walking distance increased, and necessary intervals for the peg insertion procedure were shortened. The amount of inducible free radicals decreased. CONCLUSIONS: Repeat triamcinolone application improves dysfunction of upper and lower extremities even when administered 5 times only and in series every other day. The declined potential for free radical synthesis may be caused by the anti-inflammatory effect of triamcinolone. It may contribute to suppress the smoldering, chronic inflammation, particularly in spinal lesions of patients with progressive multiple sclerosis. The enhanced arm function hypothetically reflects the effect on cervical and brain lesions due to the hypobaric features of triamcinolone.

The role of melanin as protector against free radicals in skin and its role as free radical indicator in hair.

Throughout the body, melanin is a homogenous biological polymer containing a population of intrinsic, semiquinone-like radicals. Additional extrinsic free radicals are reversibly photo-generated by UV and visible light. Melanin photochemistry, particularly the formation and decay of extrinsic radicals, has been the subject of numerous electron spin resonance (ESR) spectroscopy studies. Several melanin monomers exist, and the predominant monomer in a melanin polymer depends on its location within an organism. In skin and hair, melanin differs in content of eumelanin or pheomelanin. Its bioradical character and its susceptibility to UV irradiation makes melanin an excellent indicator for UV-related processes in both skin and hair. The existence of melanin in skin is strongly correlated with the prevention against free radicals/ROS generated by UV radiation. Especially in the skin melanin (mainly eumelanin) ensures the only natural UV protection by eliminating the generated free radicals/ROS. Melanin in hair can be used as a free radical detector for evaluating the efficacy of hair care products. The aim of this study was to investigate the suitability of melanin as protector of skin against UV generated free radicals and as free radical indicator in hair.

HPLC analysis of vitamin E isoforms in human epidermis: correlation with minimal erythema dose and free radical scavenging activity.

The content and composition of different vitamin E isoforms was analyzed in normal human skin. Interestingly the epidermis contained 1% alpha-tocotrienol, 3% gamma-tocotrienol, 87% alpha-tocopherol, and 9% gamma-tocopherol. Although the levels of tocotrienol in human epidermis appear to be considerably lower than reported in the hairless mouse, the presence of significant amounts of tocotrienol levels leads to speculation about the physiological function of tocotrienols in skin. Besides antioxidant activity and photoprotection, tocotrienols may have skin barrier and growth-modulating properties. A good correlation was found for epidermal alpha-tocopherol (r = 0.7909, p <.0003), gamma-tocopherol (r = 0.556, p <.025), and the total vitamin E content (r = 0.831, p <.0001) with the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging in epidermis, as assessed by electron paramagnetic resonance (EPR) spectroscopy. In human epidermis, alpha-tocopherol is quantitatively the most important vitamin E isoform present and comprises the bulk of first line free radical defense in the lipid compartment. Epidermal tocotrienol levels were not correlated with DPPH scavenging activity. The minimal erythema dose (MED), an individual measure for sun sensitivity and a crude indicator for skin cancer susceptibility, did not correlate with the epidermal content of the vitamin E isoforms. Hence it is concluded that vitamin E alone is not a determinant of individual photosensitivity in humans.

Kinetic measurements using EPR imaging with a modulated field gradient.

EPR imaging with modulated field gradient was applied for the investigation of fast diffusion processes. Three different imaging methods are possible: spectral-temporal, spatio-temporal, and spectral-spatial imaging. The time resolution is on the order of seconds and the spatial resolution is in the micrometer region. The efficiency of this imaging technique is demonstrated for the penetration of the spin probe Tempol in the skin of hairless mice biopsies. The skin is normally protected against the penetration of water soluble substances by the horny layer, a resistive thin lipophilic layer. Overcoming this horny layer for water soluble ingredients is one of the main practical problems for the topical application of pharmaceutics which could be investigated by EPR imaging. Different images represent the penetration behavior of the water soluble Tempol in the skin after treatment with the penetration enhancer DMSO (Dimethylsulfoxide) and after removing the horny layer.