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Background: Neuropsychiatric symptoms are common complaints of elderly persons. Recent data suggest that chronic low-grade inflammation, a fundamental characteristic of aging, plays a role. Effects might rely on the influence of inflammation on the activity of two enzymatic pathways, the indoleamine-2,3-dioxygenase (IDO) and the guanosine-triphosphate-cyclohydrolase-1 (GTP-CH1) pathways, which are involved in the biosynthesis of monoamines. The present study assessed this possibility in 284 healthy elderly subjects drawn from the Three-City cohort., Methods: Assays included the measurement of serum interleukin-6 and C-reactive-protein, as inflammatory markers; tryptophan, kynurenine, and their ratio as index of IDO activity; and neopterin, phenylalanine, tyrosine, and nitrite, as markers of GTP-CH1 activity. In addition, structured assessments of depressive symptomatology, fatigue, and general behavioral/neurovegetative symptoms were performed., Results: As expected, age correlated significantly with concentrations of immune markers and neuropsychiatric symptoms. Increased inflammation was related to reduced tryptophan concentrations and increased kynurenine levels, suggestive of IDO-induced increased tryptophan catabolism. In addition, inflammation was associated with increases in neopterin and nitrite levels and in phenylalanine concentrations at the expense of tyrosine. Interestingly, increased tryptophan catabolism was associated with the depressive symptoms of lassitude, reduced motivation, anorexia, and pessimism. In contrast, variations in markers of GTP-CH1 activity correlated more with neurovegetative symptoms, including sleep disturbance, digestive symptoms, fatigue, sickness, and motor symptoms., Conclusions: These findings show that chronic low-grade inflammation in aging is associated with alterations in enzymatic pathways involved in monoamine metabolism and suggest that these alterations might participate in the pathophysiology of neuropsychiatric symptoms in elderly persons., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

In vivo assessment of the cellular impact of thyroid hormones on target tissues might be of help for physiological studies and to evaluate the consequences of various diseases of the thyroid gland in humans. Given the tenuous relationship between retinoid and tri-iodothyronine (T3) status and that retinoids have also intracellular roles, the aim of this study was to determine the effect of hypothyroidism on the expression of T3 nuclear receptors (TR) and retinoic acid nuclear receptors (RAR, RXR) in human peripheral blood mononuclear cells (PBMC). Using real time RT-PCR, we quantified the relative amount of mRNA of the thyroid (TR alpha and TR beta) and retinoid (RAR alpha, RAR gamma, and RXR alpha) nuclear receptors in PBMC of euthyroid (n = 22) compared with hypothyroid (n = 22) subjects. Classical plasma parameters (free T3 (FT3), free thyroxine (T4) (FT4), thyroid-stimulating hormone (TSH), retinol (ROH), retinol-binding protein (RBP) and transthyretin (TTR)) were also measured. In hypothyroid subjects, the concentration of TSH was elevated, and dramatically low T3 and T4 concentrations were associated with a decrease in the expression of TR beta. Expression of RAR alpha and RAR gamma significantly decreased in hypothyroid versus control subjects, while an increased concentration of ROH was emphasised by hypothyroidism. These results first indicated that primary hypothyroidism induces hypoactivation of the retinoid nuclear pathway in PBMC, which was not predicted by the plasma ROH level. Further investigations will be necessary to evaluate these parameters in very small changes in thyroid hormone production such as mild (subclinical) hypothyroidism.

Background: Chronic ethanol consumption induces disorders in the biosynthesis of retinoic acid, an active derivative of vitamin A. Recent evidence suggests that an alteration in the retinoic acid signaling pathway leads to impairments in learning and memory in adult mice. We have previously shown that chronic ethanol consumption in mice produces an increased expression of the brain retinoic acid receptor beta (RARbeta) mRNA. These results prompted us to examine whether suppressing the overexpression of retinoid receptors in alcohol-treated mice by RAR antagonist administration would reverse their cognitive impairment., Methods: After 10 months of ethanol consumption (12% v/v in drinking water), C57BL/6 mice were submitted to a working memory task in a T-maze. Then, mice of the control and the ethanol-treated groups received an RARbeta antagonist (CD2665 0.6 mg/kg) for 22 days. The behavioral effect of CD2665 administration was evaluated on a spontaneous alternation task and the neurochemical effect was measured by quantifying the mRNA expression of RARalpha, RARbeta, retinoid X receptor (RXRbeta/gamma) and tissue transglutaminase (tTG; a retinoic acid-target gene)., Results: Mice submitted to ethanol treatment exhibited a progressive decrease in spontaneous alternation rates over successive trials. Moreover, these mice displayed an increased expression of brain RARbeta and RXRbeta/gamma mRNA, together with an increased level of tTG mRNA and enzymatic activity. The administration of CD2665 to alcohol-treated mice totally reversed the working memory deficit and suppressed the overexpression of brain RARbeta, RXRbeta/gamma and tTG mRNA, whereas the same treatment in control mice decreased only the RARbeta mRNA level without affecting memory performance., Conclusion: These data point to the potential role of the retinoid signaling pathway in memory processes and suggest that the overexpression of brain RARbeta and RXRbeta/gamma could be responsible, at least in part, for some memory impairments observed during chronic ethanol consumption.

Objective: The "twinkling artifact" is a color-flow sonographic artifact described behind calcifications and presenting as a random color encoding in the region where shadowing would be expected on gray-scale images. Our purpose was to study the relationship between this twinkling artifact seen behind urinary stones on color-flow sonography and the morphology or biochemical composition of these urinary stones., Materials and Methods: Forty-seven urinary stones were studied in vitro with color-flow sonography. Transmit frequency, color gain, velocity range, color filters, focal depth, and depth of field were changed during scanning. The twinkling artifact was graded 0 when absent, 1 when present but occupying a portion of acoustic shadowing, and 2 when occupying the entire acoustic shadowing. Stones were studied under a binocular magnifying glass to characterize the surface, and infrared spectrophotometry was used to determine the chemical composition., Results: Calculi of calcium oxalate dihydrate and calcium phosphate always produced a grade 1 or grade 2 twinkling artifact. Absence of artifact was noted only for calcium oxalate monohydrate and urate stones. In 100% of grade 0 calcium oxalate stones, the monohydrate compound was predominant (>93%). In 100% of grade 2 calcium oxalate stones, the dihydrate compound was predominant (>75%). For calcium oxalate stones, the surface pattern was correlated with their composition. Sensitivity and specificity for absence of artifact, as indicative of calcium oxalate monohydrate, were 60% and 83%, respectively, for all stones and 56% and 100%, respectively, only for radiopaque stones., Conclusion: An in vitro relationship exists between the twinkling artifact and the morphology of urinary stones. Color-flow sonography could play a role in detecting dense calcium oxalate monohydrate calculi, which in turn may help predict fragmentability.

Many studies on anaesthetized animals and a few on awake animals have suggested that the cholinergic olivocochlear efferent feedback to outer hair cells can participate in the protection of the cochlea from acoustic overexposure. Lithium is known to stimulate acetylcholine synthesis and release in the brain and it is likely to act similarly at the level of the cochlear efferent synapses. We demonstrate here that, in the awake guinea-pig with a chronically implanted electrode on the round window of the cochlea, the temporary threshold shift induced by 1 minute exposure to different pure tones at around 90 dB sound pressure level (SPL) was reduced by as much as 40 dB, when exposure occurred after lithium treatment. The protection effect was not observed in anaesthetized animals. The effect was seen across the test frequency range of 6.4-12.5 kHz, suggesting that both 'fast' and 'slow' efferent effects are likely to be mediated by acetylcholine. Together our results provide new evidence that the olivocochlear efferents can provide a more efficient protection from acoustic overexposure when animals are awake.

The efficacy of an oral supplement of vitamins and trace elements during a longterm artificial parenteral and enteral nutrition was investigated for 3 months in patients with extensive burns. Thirty severely burned patients (22 male, 8 female, age 41 +/- 18 years, range 23-59 years, 33 +/- 12% total body surface area burn, 22% +/- 8 full thickness burn surface area) were included. Every 10 days, from day 10 until day 90, we determined serum levels of: *vitamins B1, B12, A, E, *folic acid, *copper, zinc, iron, *transferrin, albumin, prealbumin, total proteins, *fibronectin, retinol binding protein (RBP), *calcium, *phosphorus, *triglycerides, *total cholesterol, *C reactive protein (CRP), *erythrocyte folic acid. The mean daily nutritional support was 60 Kcals and 0.4 g N per kg of body weight, 70% enterally and 30% parenterally administered, with enteral vitamin and trace element supplementation. On day 10, there was a decrease of the serum level of 19/20 parameters. For 8 parameters (vitamin A, total cholesterol, iron, transferrin, fibronectin, phosphorus, RBP, total proteins), the level was lower than usual. Between day 10 and day 20, a significant normalization of 6 of them was noted, the average levels of transferrin and iron remaining below normal values until day 50. There was a significant decrease in C-reactive protein levels, however above normal limits. No deficiency in vitamins or trace elements was found. Cyclic variations of serum levels occurred which may be more related to volemic, hydroelectrolytic, endocrine and inflammatory disorders than to nutritional problems.

Properties of retinoic acid receptors and glucocorticoid receptors of rat liver were influenced by retinol status in a nonsimilar manner. The binding of the retinoic acid receptors which was lowered in vitamin A--deficient animals relative to controls was restored by a single dose (100 micrograms) of retinoic acid; in vitamin A--overloaded animals (40-fold the control intake) the binding was greater than in controls. The binding of the glucocorticoid receptor was higher in vitamin A--deficient rats than in controls and restored by retinoic acid supplementation, but did not differ from controls in the vitamin A--overloaded rats. The cellular actions of glucocorticoid hormone and retinoic acid were investigated by assaying the activity of some related enzymes. The activity of tyrosine aminotransferase reflected glucocorticoid receptor binding in vitamin A--deficient and vitamin A--restored rats. The decreased tyrosine amino transferase activity observed in vitamin A--overloaded rats could be related to the inhibition of expression of tyrosine amino transferase gene by retinoic acid. Alcohol dehydrogenase activity was unaffected or only slightly affected by vitamin A status. The known existence of glucocorticoid hormone- and retinoic acid--sensitive elements in the alcohol dehydrogenase gene could explain such observations. Furthermore, the changes in the binding of retinoic acid receptors and glucocorticoid receptors were often in opposite directions. These results provide new evidence for the mechanisms by which the amount of dietary vitamin A modulates hormonal status.

Two types of factors can theoretically modulate alcohol metabolism toward increased acetaldehyde production. These factors are the following: (a) individual, genetically determined isoenzymes with distinct catalytic properties, and (b) modifications of enzyme activity induced by alcohol itself or liver damage. To investigate the respective roles of these factors in white individuals, we studied the alcohol dehydrogenase phenotype, together with liver alcohol dehydrogenase and aldehyde dehydrogenase activities, in 161 patients. Patients with alcoholic cirrhosis (n = 31) were compared with three types of controls: patients with nonalcoholic cirrhosis (n = 25) and excessive (n = 62) and moderate drinkers (n = 43) without liver disease. No association between alcohol dehydrogenase-3 phenotype and alcoholic cirrhosis was found. The prevalence of atypical alcohol dehydrogenase in the four groups was less than 1%. Patients with cirrhosis, regardless of its cause, had significantly lower alcohol dehydrogenase activity than the patients without cirrhosis (p less than 0.05 and p less than 0.01 vs. excessive and moderate drinkers, respectively). Among the noncirrhotic patients, alcohol dehydrogenase activity was significantly lower in the excessive drinkers than in the moderate drinkers (p less than 0.001). Aldehyde dehydrogenase activity was not different between cirrhosis-free excessive and moderate drinkers; in contrast, compared with these two groups, it was significantly lower in the two cirrhosis groups (p less than 0.01). These results suggest that no phenotypic pattern of alcohol dehydrogenase-3 associated with alcoholic cirrhosis in white patients exists, that liver alcohol dehydrogenase activity falls as a consequence of both alcohol abuse and cirrhosis and that liver aldehyde dehydrogenase activity is unaffected by alcohol abuse and only falls after the onset of cirrhosis.

We developed a method for the enzymatic assay of glutathione which is easy to practice, rapid, specific, based on the reaction of the thiol group of glutathione with dithiobis-nitrobenzoic acid after the action of glutathione reductase in the presence of NADPH. This spectrophotometric technique allowed, on the one hand, the determination of total glutathione and on the other hand, that of oxidized glutathione (disulfide), after the blockage of reduced glutathione by 2-vinyl-pyridine. The improvements of the assay of blood glutathione concerned the sample preparation, the reaction sensitivity, thanks to a better definition of the optimal pH and a reduction ot the blockage time by 2-vinyl-pyridine in well defined operating conditions. We compared the performances of our technique with a fluorimetric method. We used our method for the determination of total and oxidized blood glutathione in a control population.

Etretinate (RO 10-9359) is a synthetic retinoid used instead of Vitamin A--toxic in large dose--during treatment of some skin diseases. In this work biological properties of Etretinate were studied by administration of this drug (2 mg/kg/day) in rats in a vitamin A-deficient state. Body growth, some seric parameters and some tissue enzymatic activities were studied. Results of this restitution experiment show that Etretinate corrects all parameters affected by vitamin A-deficiency testicular growth excepted. So Etretinate exhibits properties similar to that of retinoic acid.