Linear IgA dermatosis related to vancomycin.
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Humans↗
Biomedical subjects
C Jacquot
Publications and source records attributed to C Jacquot.
[Comparative pharmacodynamics of methadone, buprenorphine and codeine].
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Administration, Oral↗
Metabolism of 6-fluoro-DL-tryptophan and its specific effects on the rat brain serotoninergic pathway.
We administered 6-fluoro-DL-tryptophan (6F-Trp) to rats (50-200 mg/kg i.p.) and evaluated its neurochemical effects on central catechole and indole compounds; we also determined the time course of its action, together with its metabolism and kinetics in four rat brain areas. Neither norepinephrine nor dopamine and its major metabolites were affected by 6F-Trp. With regard to serotonin (5-HT), 6F-Trp induced a transient depletion in all the brain areas studied, with a maximum of about 60-65% obtained between 1 and 3 hr depending on the dose administered. After 6 hr, 5-HT levels generally returned to control values. 5-Hydroxyindolacetic acid (5-HIAA) levels were also reduced 3 hr after administration (-40 to -60%). A large dose-dependent increase in tryptophan (Trp) was observed in the four brain areas, possibly because of an inhibition of Trp incorporation into protein, as suggested by experiments with mouse neuroblastoma cells. The brain elimination half-life of 6F-Trp was estimated at 0.5-1 hr. Regarding 6F-Trp metabolism, three new compounds were detected in all four brain areas after 6F-Trp administration. They were identified by means of liquid chromatography with electrochemical detection and/or radioenzymology, in comparison with fluorinated standards, or after NSD 1015 or pargyline coadministration with 6F-Trp. The first two 6F-Trp metabolites detected were probably 6-fluoro-5-hydroxytryptophan and 6-fluoro-5-HIAA. The third, identified and quantified by means of the two analytical methods, was 6-fluoro-5-HT (6F-5-HT). These findings suggest that 6F-Trp could be used as the in vivo precursor of 6F-5-HT with a view to tracing neuronal serotoninergic pools, as has already been done with platelets.
Animals↗
Time course of brain serotonin metabolism after cessation of long-term fluoxetine treatment in the rat.
The effects of repeated fluoxetine (Flx) administration (5, 10, or 15 mg/kg i.p., twice daily for 21 days) on serotonin and 5-HIAA metabolism were examined in the hypothalamus, hippocampus, pons medulla and cerebral cortex of rats killed 1-28 days after the last dose. Dose-dependent weight loss was observed during treatment, followed by gradual and complete recovery of body weight over the following two weeks. Chronic Flx treatment caused a dose-dependent decrease in brain 5-HT levels (by between 10 and 50% depending on the region examined), lasting for 3-7 days after cessation of treatment with the lowest and intermediate doses, and for 7-14 days after cessation of the highest dose. 5-HIAA levels decreased more markedly (-20; -60% depending on the region examined) than those of 5-HT, and tended to overshoot during the recovery period. The prolonged reduction in brain 5-HT levels after chronic Flx treatment was similar to that seen in rats given very high doses of dexfenfluramine (d-fen), a drug which both blocks 5-HT uptake and increases its release. These data suggest that brain 5-HT and 5-HIAA depletion may reflect similar dose-related expressions of the drug's mechanisms of action.
Animals↗
Fasting affects more markedly neuropeptide Y than monoamines in the rat brain.
Monoamine turnover and neuropeptide Y (NPY) levels were evaluated in the CNS of 48- and 72-h-fasting adult, male rats in four brain areas: the hypothalamus, cortex, hippocampus, and striatum. In 48-h-fasted rats, NPY levels increased in the cortex and decreased in the striatum. The dopaminergic turnover increased in the hippocampus. The serotonergic turnover decreased in the hippocampus, striatum, and cortex and was still decreased after 72 h of fasting. In 72-h-fasted rats, an overall significant increase of NPY levels was observed except in the striatum, where it decreased significantly. No relationship appeared between NPY and monoamine levels, suggesting that NPY can act independently in feeding behavior and play, in different brain areas, an important role in its regulation.
Animals↗
Refeeding after 72 hour fasting alters neuropeptide Y and monoamines in various cerebral areas in the rat.
1. Monoamine turnover and neuropeptide Y (NPY) levels were evaluated in the CNS of adult male rats either after fasting (72 hr) or refeeding. 2. In the fasted group, an overall increase in NPY levels was observed except in the striatum where it was decreased. The serotoninergic turnover was decreased in the hippocampus, striatum and cortex. 3. After refeeding, NPY decreased in the hypothalamus and cortex but was further increased in the hippocampus and decreased in the striatum. The serotoninergic turnover was still decreased in the hippocampus and cortex. The norepinephrine levels and the dopaminergic turnover increased in the hippocampus and cortex. 4. No relationship appeared between NPY and monoamine changes suggesting that NPY can act independently in feeding behavior, and play, in different brain areas, an important role in its regulation.
Animals↗
Improved noninvasive diagnostic testing for malignant hyperthermia susceptibility from a combination of metabolites determined in vivo with 31P-magnetic resonance spectroscopy.
BACKGROUND: Phosphorus magnetic resonance spectroscopy (31P-MRS) in vivo has been suggested recently as a possible noninvasive diagnostic test in malignant hyperthermia (MH) susceptibility. However, differences between protocols and also within subjects may have led to inconsistent MRS abnormalities reported during and after exercise. The aim of the current study was to detect discriminant abnormalities in the leg muscles using in vivo 31P-MRS during the rest period. METHODS: Fourteen patients shown to be MH-susceptible and 22 patients MH-negative on the basis of in vitro caffeine/halothane contracture tests according to the European MH group protocol were compared to 36 control subjects using in vivo 31P-MRS during the rest period. A score of MRS combined abnormalities was calculated from a stepwise discriminant function analysis. RESULTS: The MH-susceptible group had a significantly (P < 0.01) higher inorganic phosphate (Pi) to phosphocreatine (PCr) (Pi/PCr) value (0.134 +/- 0.022) than either the MH-negative (0.097 +/- 0.016) or the control (0.101 +/- 0.017) group. The MH-susceptible group also exhibited a significantly (P < 0.01) higher phosphodiesters (PDE) to PCr (PDE/PCr) value (0.093 +/- 0.056) than either the MH-negative (0.034 +/- 0.021) or the control (0.029 +/- 0.019) group. Combining both MRS parameters, 13 of the 14 MH-susceptible patients demonstrated abnormal MRS test results (score value < 1.65). Conversely, 21 of the 22 MH-negative patients had normal MRS results (score value > or = 1.65). The sensitivity and specificity of this threshold value were 93 and 95%, respectively. CONCLUSIONS: This study confirms that 31P-MRS could be useful for distinguishing noninvasively between MH-susceptible and MH-negative patients if several MRS parameter are combined. Moreover, the present MRS approach appears to be more reliable and easier than that used during exercise.
Adolescent↗
Acute reversible renal failure with macroscopic haematuria in IgA nephropathy.
Macroscopic haematuria is common in IgA nephropathy, but its significance and influence on prognosis remains uncertain. We compared the clinical and pathological features of 11 adult patients with primary IgA nephropathy who had had a renal biopsy during or shortly after a bleeding episode. Six patients developed transient acute renal failure (ARF) (group 1) and five did not (group 2). Patients of group 1 had a higher percentage of tubular red-blood-cell (RBC) casts (P < 0.05) and of glomerular crescents (P < 0.001). However, crescents were focal and involved less than 50% of glomeruli. Acute tubular necrosis was only present in patients of group 1, and ARF was attributed to the acute tubular changes rather than to the glomerular lesions. Despite a prolonged duration of ARF (mean: 38 days), further outcome did not differ in patients of both groups. We suggest that acute tubular damage and/or tubular obstruction by RBC casts should be considered in any patient who develops ARF soon after a haematuric episode.
Acute Kidney Injury↗
Albumin binding and brain uptake of 6-fluoro-DL-tryptophan: competition with L-tryptophan.
We investigated potential competition between L-tryptophan (TRP) and 6-fluoro-DL-tryptophan (6-F-TRP) for binding to albumin and for passage through the blood-brain barrier (BBB). In experiments based on equilibrium dialysis, albumin (600 microM) bound about 80% of TRP and 50% of 6-F-TRP with affinity constants (Ka) of 3.7 +/- 0.04 x 10(4) and 0.62 +/- 0.01 x 10(4) M-1, respectively. Competitive inhibition was assessed as the decrease in the apparent Ka (K' a) of TRP in the presence of 6-F-TRP, with no modification of the N value. Competition between TRP, 6-F-TRP and L-valine (VAL) for passage across the BBB was demonstrated using two approaches. When administered concomitantly with TRP or 6-F-TRP to rats, VAL decreased brain uptake of TRP and 6-F-TRP and reversed their action on serotonin. In Oldendorf's model, 6-F-TRP and VAL decreased the brain uptake of TRP.
Animals↗
[Purpura during Listeria monocytogenes meningoencephalitis].
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Female↗
Striatal dopamine metabolism is differentially affected by insulin according to the genotype in Zucker rats: a microdialysis study.
The genetically obese Zucker rat presents several abnormalities related to insulin and brain monoamines, which may play a role in its impaired regulation of food intake and body weight. In a previous study, the possible insulin-monoamine interplay was investigated by measuring brain monoamine and metabolite levels in the three genotypes of the Zucker strain. In addition to the expected results, insulin had a particular effect on striatal dopamine (DA) release, regardless of ponderal status and genotype. We further investigated this point in the present study, using the brain microdialysis technique in the striatum. Lean homozygous Fa-Fa rats responded as expected to insulin with regard to striatal DA release, with increases in DA and 3-methoxy-tyramine levels and decreases in dihydroxyphenylacetic acid and homovanillic acid. Lean heterozygous Fa-fa rats showed a very specific response profile, with decreases in all dopaminergic parameters, suggestive of an effect on DA synthesis rather than DA release. This further emphasizes the marked differences between homozygous and heterozygous lean rats. The obese fa-fa rats clearly fell into two populations. The first showed a profile of response to insulin similar to that of the lean Fa-fa rats, in keeping with the disturbances related to the "fa" gene. The second showed an increase in all the dopaminergic parameters. This pattern of response was, however, different from that of the Fa-Fa rats. These opposing responses in the two obese populations did not reflect differences in the blood glucose response to insulin. One explanation is that 16 wk may be a critical transition period in the development of genetic obesity, with regard to brain monoamine disturbances and the response to insulin.
3,4-Dihydroxyphenylacetic Acid↗
In vivo evidence for carrier-mediated brain uptake of a new 2-amino-2-oxazoline (COR3224) via the purine transport system in rat.
We studied the brain uptake of a new 2-amino-2-oxazolamines derivative (COR3224) in the rat by means of the rapid intracarotid injection technique described by Oldendorf. The brain uptake index (BUI) of labelled COR3224 decreased progressively from 10% to 5% when concentrations of unlabelled compound were increased. The effect of various compounds indicated that COR3224 is transported into the brain by the purine carrier. The affinity of COR3224 for this carrier (Km = 5.68 microM) was higher than that of adenine.
Animals↗
Susceptibility to malignant hyperthermia detected non-invasively.
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Adult↗
Determination of a new 2-amino-2-oxazoline (COR 3224) in plasma and brain tissue of the rat by high-performance liquid chromatography with electrochemical detection.
A reversed-phase (CN as stationary phase) liquid chromatographic method with electrochemical detection is described for the quantitation of COR 3224, a new 2-amino-2-oxazoline in plasma and brain tissue of the rat. Extraction was performed with dichloromethane and detection was achieved at a working electrode potential of +0.85 V versus an Ag/AgCl reference electrode. The recovery of the method is about 80 and 60% for plasma and brain, respectively. The limit of detection was less than 10 ng/ml for both plasma and brain, five times lower than that with ultraviolet detection.
Animals↗
Effects of dexfenfluramine and opioid peptides, alone or in combination, on food intake and brain serotonin turnover in rats.
Dexfenfluramine (d-FF) and opiate agonists both act on food intake but in opposite ways. Serotonin is known to be involved in the pharmacological action of both d-FF and opiates, but not necessarily in the feeding effect of the latter. In order to test this hypothesis, the effects of three opioid agonists, beta-endorphin, dynorphin and D-Ser2-Leu-Enk-Thr6 (DSLET) and of an antagonist, naltrexone, were investigated individually and in combination with d-FF on food intake and brain serotonin turnover. The opioid agonist-d-FF combinations generally produced a similar anorectic effect to that of d-FF alone, with the exception of DSLET which showed a reciprocal antagonism. The serotonergic effects varied according to the opioid tested, alone or in combination with d-FF. This does not allow to highlight a general pattern of serotonin involvement in the feeding effects of these peptides. However, all the treatments which decreased feeding (d-FF, naltrexone and the combinations dynorphin-d-FF and beta-endorphin-d-FF) displayed similar trends in hypothalamic serotonergic variations. This study evidences a role of serotonin in the feeding effect of opiates, although not similar for all of them. The use of d-FF provides a tool for assessing this involvement.
Animals↗
Effects of insulin on brain monoamine metabolism in the Zucker rat: influence of genotype and age.
Disturbances of insulin or brain monoamine metabolism may play a role in the impaired regulation of food intake and body weight in the obese Zucker rat. We investigated a possible insulin-monoamine interaction by measuring monoamine levels in the hypothalamus and striatum of obese (fa-fa) and lean (Fa-Fa and Fa-fa) Zucker rats after peripheral insulin administration. The classically reported effects of insulin, i.e., increases in tryptophan, 5-hydroxy-indolacetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC) levels, were observed in the hypothalamus of Fa-Fa and Fa-fa rats, but not in obese fa-fa rats. Given the mechanism of action of insulin, this lack of effect in the obese rats may be related to the peripheral insulin resistance they exhibit. Furthermore, given the role of these monoaminergic systems, this reduced effect may be related to the impaired regulation of food intake and body weight. At 8 wk of age, however, insulin restored the decreased basal 5-HIAA levels observed in the obese rats. Increase in 5-HIAA levels following insulin administration appeared in the striatum of Fa-Fa rats only, suggesting that, as for brain insulin content, other central insulin-related disturbances may be related to the presence of the "fa" gene. In addition, certain effects of insulin on striatal dopamine release were observed in only the Fa-Fa and fa-fa rats, suggesting a particular disturbance related to the heterozygous character. This latter point calls for further investigations on the central dopaminergic effects of insulin.
3,4-Dihydroxyphenylacetic Acid↗
Biogenic amines and GABA in the larval and adult forms of the nematode Nippostrongylus brasiliensis.
1. Simultaneous detection (HPLC and electrochemical detection) of biological extracts of larval and adult stages of Nippostrongylus brasiliensis was performed in order to assay biogenic amines. 2. Gamma-amino-butyric acid was assayed in the same samples. 3. Tryptophan, 5-hydroxyindoleacetic acid were at the same level in adults and larvae. 4. 5-Hydroxytryptophan, serotonin, dihydroxyphenylalanine and dopamine were significantly higher in larvae in which gamma-amino-butyric acid was not detected.
Aging↗
Biogenic amine levels in the cockroach Blaberus craniifer Burm. nervous system.
1. Apart from octopamine, the same indolamines and catecholamines were detected in the whole nervous system of the cockroach Blaberus craniifer Burm., at the same time. 2. However, levels were found to depend on sex, age, and the anatomic region within the nervous system. 3. Although not established, it is thought that these substances act synchronously from the ganglia. 4. The differences in levels between males and females and between anatomical regions during imaginal life suggest, in this species of cockroach, the physiological importance of the metameric organization in metabolic pathways or functional aspects of biogenic amines.
Acetylation↗