Formation of DNA adducts in the skin of psoriasis patients, in human skin in organ culture, and in mouse skin and lung following topical application of coal-tar and juniper tar.

Preparations of coal-tar and juniper tar (cade oil) that are used in the treatment of psoriasis are known to contain numerous potentially carcinogenic polycyclic aromatic hydrocarbons (PAH). Evidence of covalent binding to DNA by components of these mixtures was sought in a) human skin biopsy samples from 12 psoriasis patients receiving therapy with these agents, b) human skin explants maintained in organ culture and treated topically with the tars, and c) the skin and lungs of mice treated with repeated doses of the formulations following the regimen used in the clinic. DNA was isolated from the human and mouse tissues and digested enzymically to mononucleotides. 32P-Post-labeling analysis revealed the presence of aromatic DNA adducts in the biopsy samples at levels of up to 0.4 fmol total adducts/microgram DNA. Treatment of human skin in organ culture produced similar levels of adducts, while treatment with dithranol, a non-mutagenic therapeutic agent, resulted in chromatograms indistinguishable from those from untreated controls. In mouse skin, coal-tar ointment and juniper tar gave similar DNA adduct levels, with a similar time-course of removal: maximum levels (0.5 fmol/microgram DNA) at 24 h after the final treatment declined rapidly to 0.05 fmol/microgram at 7 d, thereafter declining slowly over the succeeding 25 d. However, while coal-tar ointment produced only very low levels of adducts in mouse lung (less than 0.03 fmol/microgram DNA), juniper tar produced adducts at a high level (0.7 fmol/microgram DNA) that were persistent in this tissue. These results provide direct evidence for the formation of potentially carcinogenic DNA damage in human and mouse tissue by components of these therapeutic tar preparations.

Health status of copper refinery workers with specific reference to selenium exposure.

Copper refinery workers exposed to selenium were studied before, during, and after a shutdown period. Urine selenium levels were 83 +/- 30 mumol/mol creatinine and 69 +/- 27 mumol/mol creatinine when measured on two occasions during exposure compared with 56 +/- 17 mumol/mol creatinine when the workers had been free of exposure for 10 wk during a shutdown. The refinery workers reported more nose and eye irritation, indigestion, stomach pain, and fatigue than controls. "Garlic-like" breath odor was reported to be personally and socially offensive by many of the workers. Reporting of symptoms, pulmonary function indices, and laboratory test results did not change with exposure except for hemoglobin level, which rose during the shutdown. Hemoglobin levels were found to be inversely correlated with the urine selenium level, and there was a positive correlation noted for the interactive effect of urine selenium and urine arsenic levels on hemoglobin.

Modulation of chemically initiated and promoted skin tumorigenesis in CD-1 mice by dietary glucarate.

The efficacy of dietary calcium glucarate as a chemopreventative agent has been tested in the mouse skin tumorigenesis system. Skin tumorigenesis was initiated in mice of the CD-1 strain with 7,12-dimethylbenz(a)anthracene (DMBA), then promoted with twice weekly applications of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 13 weeks. The mice were fed a regular chow diet, or a chow diet fortified with calcium glucarate (128 mmol/kg diet), or with equimolar calcium as calcium gluconate (negative calcium control). When mice were fed calcium glucarate throughout both the initiation and promotion phases papilloma formation was inhibited by over 30%. Transfer of these DMBA-initiated, TPA promoted CD-1 mice to chow diet after 13 weeks on the calcium glucarate-supplemented diet, resulted in an increase in the number of skin papillomas within 3 weeks to the level of those seen in control animals maintained exclusively on the chow diet. When calcium glucarate feeding was restricted to either the initiation or promotion phases, papilloma formation was inhibited by 25%. Dietary calcium gluconate had no effect on papilloma formation in the CD-1 mouse system, but increased the calcium concentration in the skin to the same extent as that of calcium glucarate. The data indicate that the elevation of the normally low levels of glucarate in the body through supplementation, results in a marked alteration in the retention, activity and/or metabolism of xenobiotics.

[The change of the concentration of substance P in the rats "channel" "point" skin and plasma in the acupuncture analgesia].

Numerous reports indicated that substance p (SP) was a neurotransmitter involved in nociception, it also had analgesic effects in the most part of the central nervous system of all mammals, including man. The numbers of mast cell in human's some acupoint tissue were much higher than the non-acupoint tissue, there was connection between the nerves and mast cells which contained SP particles. Therefore, it is worth studying the change of the concentration of SP in the skin and plasma of rats during the process of acupuncture analgesia. 55 rats were divided into 8 groups; (1) Control group; (2) Heat stimulation group; (3) Electro-acupuncture group; (4) Morphine group; (5) Naloxone (NX) group; (6) NX plus electro-acupuncture group; (7) Non-acupoint electro-acupuncture group; (8) Normal saline solution group. The concentration of SP in the "channel" "acupoint" skin and plasma of rats were determined by radioimmunoassay (RIA). The results show that after acupuncture, the tail-flick threshold is increased, the concentration of SP in the skin and plasma is decreased significantly and the effect of electro-acupuncture is abolished by naloxone (i.p). The results suggest that SP is a transmitter relating to skin nociception and involves the process of pain regulation. Electro-acupuncture can inhibit SP release from the skin and the plasma of rats. There is a functional interaction between SP and endorphin in the effects of electro-acupuncture. That is the SP decreased induced by electro-acupuncture may depend upon the function of opiate receptors.

The effect of supplementation with selenium and vitamin E in psoriasis.

Since reduced concentrations of selenium in whole blood, plasma and white cells had previously been observed in psoriasis, 69 patients were supplemented daily with either 600 micrograms of selenium-enriched yeast, 600 micrograms of selenium-enriched yeast plus 600 IU of vitamin E or a placebo for 12 weeks. Before supplementation, the patients' mean concentrations of selenium in whole blood and plasma were reduced compared with those of matched healthy controls but their red cell glutathione peroxidase (GSH-Px) activity was normal. After 12 weeks supplementation the patients' mean whole blood, plasma and platelet selenium concentrations, platelet GSH-Px activity and plasma vitamin E concentration had risen significantly from the baseline values but their mean skin selenium concentration and red cell GSH-Px activity remained unchanged. The mean white cell selenium concentration rose only in the group receiving selenium alone. Neither supplementation regimen reduced the severity of psoriasis or produced side-effects. The increase in platelet GSH-Px activity suggests that the supplements were bioavailable and that the patients' selenium status may have been reduced prior to supplementation. The failure of the selenium content of the skin to increase may explain why the patients' psoriasis remained unchanged during supplementation.

Alterations in retinoid concentrations in several extrahepatic organs of rats by 3,4,3',4'-tetrachlorobiphenyl.

In this study, the effect of polychlorinated biphenyls on retinoid homeostasis was investigated in Sprague-Dawley rats, by analysing [3H]retinoid concentrations in peripheral organs, following exposure to 3,4,3',4'-tetrachlorobiphenyl (TCB). The rats were rendered retinoid-deficient through dietary restriction, followed by dietary supplementation with [3H]retinol for 14 days, in order to facilitate determination of retinoid concentrations in various tissues. At day 7 of [3H]retinol supplementation the rats were exposed to a single i.p. dose of 15 mg TCB dissolved in corn oil/kg body weight. In corn oil-treated control rats, the highest concentrations of [3H]retinoid radioactivity, consisting mainly of retinol and several retinylesters, were obtained in the liver (greater than 10(6) cpm/g,), followed by the kidney and the lung, while only minor concentrations were found in skin and heart. Exposure to TCB resulted in a significant reduction of both retinol and retinylester concentrations in the liver (to 25% of controls) and the lung (to 44% of controls), while in the heart a reduction of retinol to 35% of controls was observed. No significant alterations in retinoid concentrations were observed in the skin and kidney. It is suggested that the reductions in retinoid concentrations might contribute to the toxicological alterations reported in these organs upon exposure to TCB.

Noninvasive assessment of skin iron content in hemodialysis patients. An index of parenchymal tissue iron content?

Iron overload has been described in patients undergoing chronic hemodialysis. The present study was undertaken to evaluate a rapid, noninvasive method for determination of skin iron by the technique of diagnostic x-ray spectrometry (DXS). Thirty-five patients receiving chronic hemodialysis treatment entered the study and were compared with 25 normal controls. Since pathological skin iron deposition occurs mainly at the dermal-epidermal junction in the basal cells of the epidermis, measurements were made in the thenar eminence representing mainly epidermal tissue (FeE), and in the forearm representative mainly of dermis (FeD). The mean +/- SD FeE iron concentrations were equivalent to 14.5 +/- 8.8 and 18.2 +/- 10.2 parts per million wet weight tissue (ppm) and both were significantly higher than in normal controls in which they averaged 9.2 +/- 2.5 ppm (P less than 0.005) and 10.2 +/- 3.2 ppm (P less than 0.001), respectively. There was significant positive correlation between individual skin iron determinations with the total number of blood transfusions received, the rate of blood transfusion, and with serum ferritin levels. Bone marrow hemosiderin was examined in six patients and showed a similar trend. Despite correlation only with indirect indices of tissue iron, our findings suggest that DXS may serve as a reliable quick method for noninvasive estimation of nonreticuloendothelial tissue iron deposition in hemodialysis patients suspected of having transfusional iron overload. The method may be valuable in monitoring the effects of chelation therapy.

The effect of dietary fish oil supplementation on psoriasis. Improvement in a patient with pustular psoriasis.

An open study testing the effects of fish oil supplementation on psoriasis in 26 patients is described. None of the patients with plaque-type psoriasis vulgaris showed clinically significant improvement; however, a patient with generalized pustular psoriasis showed marked improvement with the fish oil supplementation. In this patient, scale leukotriene B4 levels were determined and shown to be significantly decreased after completion of the study, but the leukotriene B4 levels did not correlate with her clinical course. The results of our study are contrasted with those of a recent study that did show beneficial effects of fish oil supplementation on plaque-type psoriasis.

Electron probe analysis of human skin: element concentration profiles.

Concentration profiles for the major biological inorganic elements Na, P, S, Cl, and K were measured across human skin using electron probe analysis and analytical electron microscopy. Determinations were made within the cytoplasm of individual cells. Uniform element concentrations were present throughout the viable tissue, whereas element profiles in the stratum corneum were considerably diverse. Phosphorus was practically absent from the stratum corneum. Sulfur (per unit volume) continuously increased from the inner to the outer cell layers of the stratum corneum largely as a result of cytoplasmic water loss as cells migrate to the surface. Potassium was essentially excluded from the inner stratum corneum. Very large gradients for K, Na, and Cl occurred from the middle of the stratum corneum to its outer surface; these gradients are likely the result of the inward diffusion of salts from sweat and could play a variety of physiological roles. The paucity of K and P within the inner stratum corneum suggests these important intracellular solutes (and perhaps others, including water) are recycled within the viable tissue, thus providing a virtual nutrient supply immediately underneath the stratum corneum. Alterations in this recirculation could have a regulatory function in the physiology of this tissue.

Transcutaneous bilirubinometry. Effect of irradiation on the skin bilirubin index.

We studied the relation between irradiation and the percent decrease of skin and serum bilirubin during phototherapy. There was a significant positive correlation between the percent decrease of transcutaneous bilirubinometry readings at the sites exposed directly to light (chest) and irradiation (r = 0.593, p less than 0.001, n = 32). A significant positive correlation was also found between the percent decrease of serum bilirubin concentration and irradiation (r = 0.587, p less than 0.001, n = 32), and the percent decrease of skin bilirubin at exposed sites (chest) and the percent decrease of serum bilirubin concentration (r = 0.481, p less than 0.001, n = 32). Thus, light energy quantitatively affects skin and serum bilirubin. In order to determine the optimal effective wavelength and irradiation energy for phototherapy, it is necessary to examine skin bilirubin kinetics in detail during phototherapy.

Whole body hyperthermia (41-42 degrees C) induces interleukin-1 in vivo.

The role of endogenous mediated fever and exogenous hyperthermia as modulators of immunological processes against infection and neoplasms remains poorly understood. Hyperthermia appears to modulate the activity of a number of immunological cytokines including Interleukin-1 (IL-1). Using a recently developed Radiant Heat technology for safely producing 41-42 degrees C Whole Body Hyperthermia in mice, we have investigated the effect of 1 hour of 41 +/- 0.5 degrees C WBH on the production of cutaneous IL-1. After a transient fall in IL-1 production 4 hours post WBH, significant elevations (up to twice control levels) were noted with a peak at 16-20 hours post WBH. IL-1 levels remained elevated for 5-6 days post-WBH. The potential clinical significance of this finding is discussed with particular reference to human malignant melanoma.

[Comparison of lard-tallow mixture and bone fat in digestion and growth experiments in calves]. / Vergleich von Schmalz-Talg-Gemisch und Knochenfett im Verdauungs- und Wachstumsversuch mit Kälbern.

Male calves between 15 and 26 days old and with a live weight between 45 and 46 kg received dried skim milk dissolved in water plus fat concentration from lard--suet mixtures made with a synthetic emulsifier of the type ethoxylated partial ester with and without soybean lecithin supplement. One group received bone fat with an emulsifier as sole fat component. In the course of 9 experiment weeks the calves of the lard--suet group without lecithin reached an average daily weight gain of 710 g, which was not significantly better than the gains of 689 g of the lard--suet group with lecithin and of 674 g of the bone fat group. The calves of the lard--suet group with lecithin did not digest the feed fat significantly better than the calves in the other two groups. The quota of fatty acids in the feed distinctly influenced the composition of the fatty acids in the intestines, the kidneys and the hypodermis. With the example of suet the general relationship between the fatty acid patterns of the feed and body fats are recognizable, with the fatty acids C 16:0, C 18:2 and C 18:3 having a lower and C 16:1, C 18:0 and C 18:1 having a higher quota in the suet than in the feed fat. Due to the application of high amounts of bone fat, vegetable oil or sea animal fat there are deviations from this rule. There is a higher quota of linolenic acid in the suet of the calves than in butter fat but a lower quota than in foreign fat.

PIXE analysis in different stages of psoriatic skin.

Elemental distribution in psoriatic skin varies with the functional state of the keratinocytes, e.g., electrolytes influence cell metabolism and cell proliferation, and trace elements play a crucial role in a great number of enzymes. Elemental distribution in pinpoint lesions, old plaques, and uninvolved skin of 5 psoriatic patients and 4 healthy controls was studied by means of PIXE (proton-induced x-ray emission) analysis. This technique allows the simultaneous detection of elements with an atomic number greater than or equal to 14 along the epidermis and dermis in freeze-dried skin biopsies. Trace elements such as Fe, Cu, and Zn were determined down to a level of 1 ppm. In comparison with uninvolved skin, concentrations of P and K were elevated in psoriatic epidermis. In addition, increased levels of K were correlated with the stage of the psoriatic lesion. Zinc concentrations were significantly elevated in pinpoint lesions. The Zn concentration profiles within the epidermis and upper dermis showed high correlation to the P concentration profiles. Iron levels were decreased in old psoriatic plaques, whereas Cu concentrations varied considerably. In comparison to the controls, Cl concentrations were markedly decreased in the dermis of involved and uninvolved psoriatic skin, whereas epidermal Cl levels were unaffected. As high K levels prevent the Ca-induced differentiation of keratinocytes, high K levels may be the cause of the high cell differentiation in psoriatic skin. Elevated DNA- and RNA-polymerases might be the cause of elevated Zn levels in pinpoint lesions.

Effects of clonidine on the dermal inflammatory cell response of experimental toxic and allergic contact reactions and intradermal hypersensitivity.

In previous studies, the alpha 2-adrenoceptor agonist clonidine has been shown to suppress the wheal and flare reaction in guinea pigs sensitized to ovalbumin. This phenomenon has been further studied with special reference to effects on the dermal inflammatory cell infiltrate and mast cells. Clonidine lessens the degranulation of mast cells seen in control untreated immediate hypersensitivity reactions. Less neutrophils and eosinophils arrive to the treated reactions. Basophils and mononuclear cells (chiefly lymphocytes) which characterize the late phase of the wheal and flare reaction were not influenced by clonidine. Clonidine had a possible minimal effect on allergic contact (delayed hypersensitivity) reactions. The toxic contact reaction to croton oil (nonspecific cutaneous inflammation) was not affected.

Transcutaneous bilirubinometry. III. Dermal bilirubin kinetics under green and blue light phototherapy.

Using the transcutaneous bilirubinometer, we studied the response of cutaneous bilirubin to different colors of light during phototherapy. Three groups of ten infants were exposed to blue, green, and blue-green lights at a mean postnatal age ranging from 50 to 77 hours. Patched areas served as controls. Every 15 minutes during four hours of phototherapy, we obtained simultaneous measurements from exposed and covered areas. After the onset of phototherapy, transcutaneous bilirubinometer values from the covered areas in all groups remained stable. The overall rate of bleaching was lowest in the green light group and highest in the blue-green combination group. In this group of infants, green light appeared to enhance the effectiveness of blue light in reducing dermal bilirubin concentrations as measured by the transcutaneous bilirubinometer.

A potent factor in extracts of the skin of the Australian frog, Pseudophryne coriacea--III. Potentiation of contractions elicited in avian and mammalian isolated skeletal muscle preparations by direct and indirect electrical stimulation.

Extracts of the skin of the Australian frog Pseudophryne coriacea displayed a striking potentiating effect on contractions evoked in isolated skeletal muscle preparations of mammals (phrenic nerve diaphragm) and birds (chick biventer cervicis and semispinalis muscles) by indirect and direct electrical stimulation. There was both a conspicuous increase in the amplitude of the twitch, up to 10-fold, and a remarkable prolongation of the duration of the twitch. The effect was dose- and frequency-dependent. In the presence of the extract, fusion of twitches after tetanic stimulation occurred earlier. No tachyphylaxis upon repeated stimulation by the extract was observed and the response to large doses persisted, declining slowly, for hours. These effects must be ascribed to an alkaloid related in structure to pumiliotoxin B. Response to the extract of Pseudophryne coriacea by indirectly-stimulated preparations was potentiated by physostigmine and blocked by tubocurarine and alpha-bungarotoxin, demonstrating that in these preparations the extract acted pre-synaptically to facilitate the release of acetylcholine from motor nerve endings. However, the extract of Pseudophryne coriacea displayed equally potent effects in directly stimulated preparations, insensitive to physostigmine and to blockers of nicotinic acetylcholine receptors, indicating a direct action on the skeletal muscle. It is suggested that, like pumiliotoxin B, the Pseudophryne coriacea alkaloid may interfere in the regulation of calcium channels in both nerve and muscle fibres.