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RATIONALE: Several studies have shown that impulsive violent behavior is associated with reduced serotonin metabolism in the brain, but no data exist on possible alterations of the serotonin precursor (free L-tryptophan) levels among violent offenders. OBJECTIVES: To study free L-tryptophan and kynurenine plasma levels among antisocial violent offenders. METHODS: Free L-tryptophan and competing amino acid (CAA) plasma levels were measured among 19 male impulsive antisocial violent offenders and 19 age-matched healthy male controls. RESULTS: Mean free L-tryptophan/(CAA) plasma levels were 160% (95% CI 116%-204%) higher among offenders than controls (P=0.000). Seventeen of the 19 offenders (89.5%) had values of more than 2 SD above the mean value of controls. The levels of kynurenine, the major metabolite of tryptophan, were slightly increased in offenders. CONCLUSION: Free plasma L-tryptophan/CAA levels were markedly increased among antisocial violent offenders indicating a disturbed tryptophan metabolism.

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There is virtually no knowledge of the ingredients of cellulite creams in the dermatological literature. In the present study, the ingredients of cellulite creams, the frequency of their use and whether the ingredients have been reported to cause allergy were investigated. In the 32 products tested, 263 ingredients were used. On average each product contained 22 ingredients (range 4 to 31). Botanicals and emollients predominated; altogether 44 different botanicals and 39 different emollients were used in the 32 products. Caffeine, present in 14 products was the most common additive, apparently representing an "active" ingredient. In other respects the compositions of the products were similar to those of skin creams. All products contained fragrance. The creams were microbiologically pure. Concentrations of preservatives did not exceed limit values in the regulations. No formaldehyde was present (detection limit 10 ppm). The well-known allergens isothiazolinones or dibromoglutaronitril were declared only in a few products. In spite of the large number of substances used in cellulite creams, their safety seems acceptable for most users. Because, however, one fourth of the substances used have been shown to cause allergy, the risk of adverse effects should be taken into account when using cellulite creams.

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The regulations relating to cosmetic products give no limit values for toxic elements such as metals or arsenic occurring as impurities in cosmetic products. The present study of metals (lead, cobalt, nickel, chromium) and arsenic in eye shadows in 88 colors of 25 brands and 49 products provides a basis for assessing the safety of eye shadow. 66 out of 88 (75%) of the colors contained more than 5 ppm of at least one of the elements, and all 49 products contained more than one 1 ppm of at least 1 of the elements. In one color, the amount of all elements was less than 1 ppm. The highest levels of cobalt and nickel were 41 and 49 ppm, respectively. These levels were high enough to cause allergic symptoms in those previously sensitized. Furthermore, long-term exposure to such levels may probably sensitize. The concentrations of arsenic were extremely low, 2.3 ppm at most. The level of lead was less than 20 ppm in all products. Accordingly, the concentrations of arsenic and lead seemed to be safe. 9 colors had concentrations of water-soluble chromium exceeding 2 ppm, and a very high level, 318 ppm, was encountered in 1 case. The overall results indicate that eye-shadows probably have no significant systemic toxicological effects. The groups at greatest risk are those already sensitized to the allergenic elements. Such consumers will have difficulties in choosing suitable products, since these elements in the form of impurities are not declared in the list of ingredients. Manufacturers should demand certification that the raw materials they buy contain no toxic elements. Although some of the products studied were acceptable, many had excessive levels of the elements from the consumer's viewpoint.

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In this study, our previous finding that nicotinic acid activates tryptophan 2,3-dioxygenase as strongly as tryptophan was investigated in further detail. This study focused on the role of the adrenals in the activation process. Adrenalectomy abolished the activation due to nicotinic acid, but not the activation caused by tryptophan. The role of corticoids and/or adrenomedullary hormones in the enzyme activation was studied, by supplementing these hormones in adrenalectomized rats using minipumps implanted under the skin. The results showed that the enhanced activity of tryptophan 2,3-dioxygenase caused by nicotinic acid was partly restored by adrenaline following adrenalectomy but not by corticosterone supplementation. The results were supported by further experiments in which the rats were treated with adrenaline or corticosterone intraperitoneally before nicotinic acid administration. The conclusion that adrenaline participates in the regulation of tryptophan 2,3-dioxygenase should promote further study to determine whether adrenaline is a general modulator of this enzyme. This experimental model generated new information on the activation mechanism of tryptophan 2,3-dioxygenase by nicotinic acid.

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It has been known since the 1940s that nail polishes contain allergenic ingredients. The aim of this study was to clarify whether the nail polishes on the market today contain significant amounts of allergens, and what the solvents are. The following ingredients were determined: toluene, toluene sulfonamide formaldehyde resins, free formaldehyde, acrylates, methacrylates and certain organic solvents. The study comprised 20 brands and 42 samples. All the nail polishes analysed contained allergenic toluene sulfonamide formaldehyde resins (TSFR), in concentrations from 0.08 to 11.0%. The concentration of total formaldehyde varied from 0.02% to 0.5%. The more TSFR a nail polish contained, the higher was its formaldehyde content. Probably not only TSFR-allergic but also formaldehyde-allergic persons may get dermatitis from many of the nail polishes studied. The concentrations of acrylates and methacrylates were so small that they are of practical significance only to those previously sensitized to acrylates. Of the organic solvents, toluene was still widely used, whereas xylene was found in only 1 product. The nail polishes on the market today are not safe for all consumers. However, according to the regulations of the European Union, the packaging labeling of all cosmetic products must be supplied with a list of ingredients from the beginning of 1998. This will help the consumer to avoid allergenic products. A better alternative could, however, be to substitute the most allergenic ingredients with substances possessing minor allergy potency.

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Tryptophan is important both for protein synthesis and as a precursor of niacin, serotonin and other metabolites. Tryptophan is an unusual amino acid because of the complexity of its metabolism, the variety and importance of its metabolites, the number and diversity of the diseases it is involved in, and because of its use in purified form as a pharmacological agent. This review covers the metabolism of tryptophan, its presence in the diet, the disorders associated with low tryptophan levels due to low dietary intake, malabsorption, or high rates of metabolism, the therapeutic effects of tryptophan and the side effects of tryptophan when it is used as a drug including eosinophilia myalgia syndrome.

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The distribution of all-trans-retinoic acid (RA) was investigated using whole-body autoradiography of normal and partial vitamin A deficient (VAD) mice. Retinoic acid receptors (alpha, beta, and gamma) were also studied in normal mice using immunoblotting. Normal and VAD mice were injected with 5 muCi 14C RA. The distribution of RA was quantitatively studied using a computer-assisted image analysis system. 14C RA was incorporated 0.5 hr after RA administration in both normal and VAD mice, while the labelling peak was at 6 hr in most organs in normal and VAD mice. The most intense labeling was found in liver, kidney, intestine, lung, Harderian gland, and salivary gland at all time points. A band of M(r) 51K was found in all mouse tissues by immunoblotting using the polyclonal antibody RAR82 against total RARs or the RAR alpha-specific monoclonal antibody R alpha 13. In some tissue, an additional band of 55-58K was also found. Lung, large intestine, small intestine, testis, seminal vesicle, and spleen contained highest concentration of total RARs, while heart, lung, small intestine, spleen, salivary gland, and preputial gland had the highest concentration of RAR alpha. The uptake of labeled RA correlated well with RAR or RAR alpha concentration in the corresponding tissues.

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The present study summarizes information on toothpaste composition as supplied by the manufacturers. The survey covered 48 items, virtually all toothpastes offered for sale in Finland. It was concluded that the toothpastes are not entirely safe to use, because almost 50% of the products studied contained a total of some 30 compounds widely recognized as allergens. According to the literature, the most common allergens in toothpastes are flavours (e.g., cinnamic aldehyde, cinnamon oil and peppermint) and preservatives. Symptoms include stomatitis, cheilitis, glossitis, gingivitis, perioral dermatitis and immediate hypersensitivity.

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L-tryptophan is an essential amino acid in food, but is also widely used as a drug on the basis of several physiological actions. Lately, tryptophan's uses as a drug and as a food supplement have been discontinued in several countries due to its severe side-effects.In the present study, the distribution of tryptophan in mice was studied with special attention on the target organs, where the drug has been shown to have pathological or physiological effects.The results showed that several organs took up tryptophan and that glucose loading increased the accumulation. An interesting finding was that the highest concentration of tryptophan was found in the pancreas. The hypophysis and adrenal glands were also sites of accumulation. Within the brain the highest accumulation was found in the cerebrum. High concentrations were also seen in the gastrointestinal tract and bone marrow.The connection between the accumulation of tryptophan and its normal and pathophysiological effects is discussed.

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Alpha-fluoromethylhistidine (FMH), a histamine synthesis inhibitor, was infused into the lateral cerebral ventricle of male Long-Evans rats for 7 days at a dose of 60 mcg/day. During this period animals were housed in metabolic cages; water and food consumption were measured and urine samples were collected. FMH-treated rats ate significantly more than controls and had a significantly greater weight increase. Concomitantly, sodium and potassium excretion increased. On the seventh day, rats were injected i.p. with 6.67 ml/kg of either 5.8% NaCl or physiological saline. Animals were decapitated 1 h after injection and plasma vasopressin, corticosterone and posterior pituitary vasopressin levels were determined by radioimmunoassay. NaCl loading significantly increased plasma vasopressin in control rats but not in rats pretreated with FMH. FMH alone had no effect. There were no significant changes in pituitary vasopressin or plasma corticosterone. These results clearly suggest an inhibitory role for the histaminergic system in the regulation of food intake. They also agree with, although not proving, the stimulatory control of vasopressin release by the histaminergic system in rat brain.

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Whole-body autoradiography is an effective method for localizing labeled compounds in various organs. However, the technique is limited in its ability to quantify such material. Using tissue sections, this study investigated certain parameters involved in the quantitative estimation of labeled compounds by whole-body autoradiography. These included correlation between thickness of the section and radioactivity counted, the precision of such measurements, and the reproducibility of the autoradiographic films as tested by image analysis transmission. The precision of radioactivity measurements using tapes with a tissue section or a "punch biopsy" (punching off a piece of tissue from the section) was compared. The results revealed excellent linearity between the thickness of the section and the radioactivity counted (r = 0.97) when section thickness was 10-30 microns. The measurement precision using tapes was better than with the "punch specimen" method. The reproducibility of photographic films was good when transmission was measured by image analysis. It was concluded that a thickness of 30 micron is ideal for use in whole-body autoradiographic studies. It appeared that radioactivity measurement of tissue sections on tapes was superior to direct measurement from organs. Image analysis was employed and statistically evaluated for the first time in this study, and the promising findings suggest that it is likely to become the method of choice for future studies of this type.

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Tryptophan is one of the strongest activators of tryptophan 2,3-dioxygenase, the rate-limiting enzyme in the pathway which degrades tryptophan. One of the metabolites thus formed is nicotinic acid, widely administered as a drug--often at high doses--and a vitamin. This study determined whether nicotinic acid also has a potency to activate tryptophan 2,3-dioxygenase and, if so, by what mechanism, whether changes in plasma tryptophan result, and if such activation is permanent. The results showed that nicotinic acid activated the enzyme almost as strongly as tryptophan. The results confirmed the activation to be of the "substrate" type, i.e., at least partly due to increased tryptophan concentrations in the liver. In repeated nicotinic acid administration plasma tryptophan levels did not diminish, despite the high activation of tryptophan 2,3-dioxygenase (high flux of tryptophan through the kynurenine pathway). However, the activation disappeared after 11 days of treatment. The powerful and sustained activation of tryptophan 2,3-dioxygenase by nicotinic acid may at least partly explain some of its side effects, such as glucose intolerance. However, mental disturbance as a side effect of diminished brain levels of tryptophan is not supported by these findings.

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The mode of action of the highly toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is unknown. It was recently discovered that two strains of rat, Long-Evans (L-E) and Han/Wistar (H/W), differ widely in susceptibility to TCDD. Employing this strain divergence as a probe, the present study set out to assess the role of various biochemical and morphological effects in TCDD lethality. In the main experiment, the rats were treated once ip with 0,5,50, or (H/W) 500 micrograms/kg TCDD and killed 1 to 16 days postexposure. Several target organs were evaluated by light microscopy and a number of serum lipid and carbohydrate parameters as well as a few major regulatory hormones were analyzed. The results demonstrated that most alterations caused by TCDD were essentially similar in both strains. TCDD reduced circulating thyroxine to a slightly greater extent and more permanently in the sensitive L-E strain. Moreover, a highly significant interaction on thyroid-stimulating hormone was found among strain, dose, and time. Serum concentrations of corticosterone and free fatty acids were increased only in the L-E rats given 50 micrograms/kg TCDD, i.e., at an apparent LD100 dose level for this strain. Yet, the most striking interstrain difference was seen in the liver which was distinctly affected after Day 4 in L-E rats given 50 micrograms/kg TCDD but only marginally affected in rats from any H/W group. The lesion, while showing no necrotic cell changes, was suggestive of plasma membrane damage, possibly reflecting the production of free radicals. The relation of the findings to possible mechanisms of TCDD action is discussed.

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A radioimmunological method was developed for determining total and free corticosterone in rat plasma. This method was used to determine the dose-response curve of corticosterone and to measure the elimination and study the half-lives of total and free corticosterone in rat plasma with a dose of 5 mg/kg. The elimination with a dose of 5 mg/kg, when drawn on the half-logarithmic scale, formed a straight line. The half-lives for total and free corticosterone were 25 and 15 min, respectively.

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An analytical separation method for tryptophan and its seven metabolites of the kynurenine pathway by high-voltage paper electrophoresis is presented. Anthranilic acid, 3-hydroxyanthranilic acid, kynurenic acid, kynurenine, nicotinic acid, quinolinic acid, xanthurenic acid and unmetabolized tryptophan are measured in urine. Using radioactive labelling and scintillation counting as a quantification method, the relative standard deviation varied from 3.5% to 14.4%, corresponding to kynurenine and nicotinic acid, respectively. The recovery of labelled tryptophan added to urine was 95%. An advantage of the electrophoretic method is the minor tailing of spots and, hence, a good resolution of the components. For the monovalent anions of the kynurenine pathway metabolites, a linear correlation (r = 0.9996) was found between the experimental relative electrophoretic mobility and the quantity M-2/3, where M is the molecular mass of the anion.

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Plasma renin activity and the plasma concentrations of aldosterone, TSH, LH and beta-endorphin were radioimmunologically determined in rats after ip administration of 15 mg/kg of 6-methoxy-tetrahydro-beta-carboline (6-MeO-THBC, pinoline), a compound found to occur normally in mammalian and avian pineal gland. A 2.6-fold increase of plasma aldosterone concentration was found and it was preceded by increase of plasma renin activity. An increase was also found in beta-endorphin/beta-lipotrophin concentration while TSH and LH concentrations did not change significantly. The present results do not prove nor exclude the concept that 6-MeO-THBC is the 'adrenoglomerulotropin'. The effects of 6-MeO-THBC on plasma beta-endorphin/beta-lipotrophin levels may be mediated by the dopaminergic or 5-HT-neurones.

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