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PubMed1986

Isolation of 2-hydroxycarboxylic acids with a boronate affinity gel.

Boric acid has been known to make a complex with 2-hydroxycarboxylic acids. Based on this principle, we have developed a new method for isolation of vanillylmandelic acid, p-hydroxymandelic acid, vanillyllactic acid, and p-hydroxyphenyllactic acid in urine. The technique involves two steps: extraction of lipophilic compounds from urine with n-butanol and selective isolation of 2-hydroxy acids in the n-butanol phase on a phenylboronate gel column. 2-Hydroxy acids were eluted from the column with 1.5 ml of 2% acetyl chloride in methanol with the recoveries of ca. 70%. According to analysis of urinary extract by gas chromatography--mass spectrometry, the mean excretion rates of the above four compounds in 12 healthy subjects were 3.68, 1.93, 0.091, and 1.08 mg/day, respectively.

Boronic Acids↗

PubMed2000

The quantitation of 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) in human urine specimens, a metabolite of LSD: comparative analysis using liquid chromatography-selected ion monitoring mass spectrometry and liquid chromatography-ion trap mass spectrometry.

This paper compares the potential forensic application of two sensitive and rapid procedures (liquid chromatography-mass spectrometry and liquid chromatography-ion trap mass spectrometry) for the detection and quantitation of 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) a major LSD metabolite. O-H-LSD calibration curves for both procedures were linear over the concentration range 0-8,000 pg/mL with correlation coefficients (r2) greater than 0.99. The observed limit of detection (LOD) and limit of quantitation (LOQ) for O-H-LSD in both procedures was 400 pg/mL. Sixty-eight human urine specimens that had previously been found to contain LSD by gas chromatography-mass spectrometry were reanalyzed by both procedures for LSD and O-H-LSD. These specimens contained a mean concentration of O-H-LSD approximately 16 times higher than the LSD concentration. Because both LC methods produce similar results, either procedure can be readily adapted to O-H-LSD analysis for use in high-volume drug-testing laboratories. In addition, the possibility of significantly increasing the LSD detection time window by targeting this major LSD metabolite for analysis may influence other drug-free workplace programs to test for LSD.

Chromatography, High Pressure Liquid↗

PubMed1998

Isolation and structure of a new galactolipid from oat seeds.

Seeds of oat (Avena sativa L.) were recently shown to contain significant quantities of a new hydroxy acid, (15 R)-hydroxy-(9Z),(12Z)-octadecadienoic acid (trivial name, avenoleic acid). In the present work, avenoleate was found to be mainly (63%) localized in the glycolipid fraction of oat seed lipids. Fractionation of the glycolipids by thin-layer chromatography and reversed-phase high-performance liquid chromatography revealed the presence of a main molecular species which accounted for 20% of the total avenoleate content of oat seeds. Structural studies by chemical methods and mass spectrometry demonstrated that the avenoleate-containing glycolipid was a galactolipid assembled of one molecule of avenoleic acid, two molecules of linoleic acid, two molecules of D-galactose, and one molecule of glycerol. Degradation of the new galactolipid by chemical and enzymatic methods demonstrated the localization of acyl chains, i.e., linoleate at sn-1 and linoleoylavenoleate at sn-2. Nuclear magnetic resonance spectroscopy gave independent support for this structure and also demonstrated that the two galactoses formed an alpha-D-galactopyranosyl-1-6-beta-D-galactopyranosyl moiety which was bound to the sn-3 position. Based on these experiments, the new galactolipid could be formulated as 1-[(9'Z),(12'Z)-octadecadienoyl]-2-[(15''R)-[(9'''Z),(12'''Z)-o ctadecadienoyloxy]-(9''Z),(12''Z)-octadecadienoyl]-3-(alpha-D-g alactopyranosyl-1-6-beta-D-galactopyranosyl)-glycerol. Quantitatively, the amount of the avenoleate-containing galactolipid was of the same order of magnitude as those of individual molecular species of digalactosyldiacylglycerol containing nonoxygenated acyl chains. The content of the new galactolipid in oat seeds was 0.5-0.6 mg per g of seed.

Avena↗

PubMed1985

Inhibition of class C beta-lactamases by (1'R,6R)-6-(1'-hydroxy)benzylpenicillanic acid SS-dioxide.

beta-Lactamases, enzymes that catalyse the hydrolysis of the beta-lactam ring in beta-lactam antibiotics, are divided into three classes, A, B and C, on the basis of the structures so far determined. There are relatively few effective inhibitors of class C beta-lactamases. A beta-lactam sulphone with a hydroxybenzyl side chain, namely (1'R,6R)-6-(1'-hydroxy)benzylpenicillanic acid SS-dioxide (I), has now been studied. The sulphone is a good mechanism-based inhibitor of class C beta-lactamases. At pH8, the inhibition of a Pseudomonas beta-lactamase is irreversible, and proceeds at a rate that is about one-tenth the rate of concurrent hydrolysis. The labelled enzyme has enhanced u.v. absorption and is probably an enamine. At a lower pH, however, inhibition is transitory.

Cephalosporins↗

PubMed1986

In vitro synthesis of 12-hydroxy-eicosatetraenoic acid is increased in uninvolved psoriatic epidermis.

Certain arachidonic acid (AA) metabolites have been detected in psoriatic skin lesions. In this study the capacity of normal epidermis and clinically uninvolved psoriatic epidermis to transform AA into lipoxygenase products was determined in vitro. After incubating homogenized epidermis with exogenous AA, the extracted lipids were isolated by reverse-phase high-performance liquid chromatography. Each chromatographic peak was characterized by its UV absorption spectrum and identified by its coelution with the appropriate authentic standard and by radioimmunoassay of its eluate fraction. Identified compounds were quantitated by integrated UV absorbance. Leukotriene B4 (LTB4) was also identified by neutrophil chemokinesis. Normal epidermis generated 15-hydroxy-eicosatetraenoic acid (15-HETE) and 12-HETE, the latter being more abundant. 5-Lipoxygenase products (LTB4, LTC4, and 5-HETE) were not detected. However, an unknown compound exhibiting a triplet UV absorbtion spectrum with maximum at 274 mm was formed. Its formation was inhibited by 5,8,11,14-eicosatetraynoic acid, but not by indomethacin or a specific 5-lipoxygenase inhibitor (REV 5901). These data suggest that a di-HETE with a triene structure is one possible candidate for the unknown compound. Compared with normal epidermis, the formation of 12-HETE and the unknown di-HETE by uninvolved psoriatic epidermis was increased by 54% and 63%, respectively. The formation of 12-HETE and the unknown di-HETE in uninvolved psoriatic epidermis was stimulated to the same degree in the presence of the phospholipase inhibitor quinacrine. These results indicate that uninvolved psoriatic epidermis has an increased capacity to metabolize free AA into 12-lipoxygenase products.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed2006

Routine clinical laboratory tests correspond to increased serum levels of 3-hydroxy fatty acids, markers of endotoxins, in cardiosurgery patients.

INTRODUCTION: Endotoxemia developing during cardiosurgery as elevated endotoxin concentrations in patient's serum may prevail over 24 h after operation. A major reason is thought to be increased gut permeability resulting in endotoxin and bacterial leakage. In this study we aimed to measure endotoxin levels on samples obtained during and after cardiovascular procedures and compare them with clinical observations and laboratory test results. MATERIALS AND METHODS: 3-Hydroxy fatty acids (3-OH FAs) of 10-18 carbon chain length, chemical markers of endotoxin (lipopolysaccharide), were determined in patient sera by gas chromatography-mass spectrometry-based analysis. RESULTS were compared with routine laboratory tests: blood morphology, urine, ALT, AST, bilirubin, kidney parameters, clotting parameters, and gasometry. RESULTS: Of a total of 16 patients, 5 patients (group I) showed increased serum 3-OH FA levels and 11 patients (group II) did not show any change in 3-OH FA levels 24 h after operation. All group I patients revealed leukocytosis, two developed post-operative anemia. Significantly different changes were observed: the initial, pre-operative 3-OH FA levels were similar for both groups, while group I patients showed increased levels of all the studied 3-OH FAs during the operation (p</=0.05), and 3-OH C14 and 3-OH C16 remained elevated 24 h after the operation. CONCLUSIONS: Cardiosurgery may strongly promote gut endotoxin translocation to the blood in some patients. Prolonged leukocytosis, deep anemia, and increased liver dysfunction markers may indicate the need for observation of possible endotoxemia development. It is recommended to monitor the endotoxin level and/or endotoxemia markers in cardiosurgery patients.

Biomarkers↗

PubMed1989

Lipid bilayer permeation by neutral aluminum citrate and by three alpha-hydroxy carboxylic acids.

Several groups have proposed that aluminum (Al) may permeate biological membranes as a neutral complex with citrate. We tested this hypothesis by measuring aluminum citrate flux across unilamellar phospholipid vesicles (liposomes). Results from two independent procedures show that lipid bilayer permeation by the neutral aluminum-citrate complex is slow (P approximately equal to 1 x 10(-11) cm.s-1). We then compared aluminum-citrate permeation with permeation by a series of alpha-hydroxy carboxylic acids and by trimethylcitrate. This comparison showed that the aluminum-citrate flux is limited by diffusion across the water/lipid interface. This is due to hydrogen bonding between water and the citrate carboxyl groups, and by hydration of the bound metal in the aqueous phase. By analogy with citric acid, steric hindrance of diffusion within the bilayer does not affect the permeation rate of aluminum citrate. Elevated tissue levels of Al in subjects fed a diet supplemented with citric acid and Al(OH)3 cannot be explained by lipid bilayer permeation of the neutral complex.

Aluminum↗

PubMed2005

Surface modification of interconnected porous scaffolds.

Surface properties of scaffolds play an important role in cell adhesion and growth. Biodegradable poly(alpha-hydroxy acids) have been widely used as scaffolding materials for tissue engineering; however, the lack of functional groups is a limitation. In this work, gelatin was successfully immobilized onto the surface of poly(alpha-hydroxy acids) films and porous scaffolds by a new entrapment process. The surface composition and properties were examined using attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectra (XPS), and contact angle measurements. Control over the amount of entrapped gelatin was achieved by varying the solvent composition, the duration of soaking, the concentration of gelatin in solution, and chemical crosslinking. The amount of entrapped gelatin increased with the ratio of dioxane/water in the solvent mixture used. Chemical crosslinking after physical entrapment considerably increased the amount of retained gelatin on the surface of poly(alpha-hydroxy acids). Osteoblasts were cultured on these films and scaffolds. The surface modification significantly improved cell attachment and proliferation. Cell numbers on the surface-modified films and scaffolds were significantly higher than those on controls 4 h and 1 day after cell seeding. The osteoblasts showed higher proliferation on surface-modified scaffolds than on the control during 4 weeks of in vitro cultivation. More collagen fibers and other cell secretions were deposited on the surface-modified scaffolds than on the control scaffolds. This novel surface treatment strategy provides a convenient and universal way to modify the surface properties of three-dimensional scaffolds and thus promote cell adhesion and proliferation for tissue engineering.

Biocompatible Materials↗

PubMed2004

An assessment of the genotoxicity and human health risk of topical use of kojic acid [5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one].

Kojic acid (KA), a natural substance produced by fungi or bacteria, such as Aspergillus, Penicillium or Acetobacter spp, is contained in traditional Japanese fermented foods and is used as a dermatological skin-lightening agent. High concentrations of KA (>or=1000 microg/plate) were mutagenic in S. typhimurium strains TA 98, TA 100, TA 1535, TA102 and E. coli WP2uvrA, but not in TA 1537. An Ames test following the "treat and plate" protocol was negative. A chromosome aberration test in V79 cells following a robust protocol showed only a marginal increase in chromosome aberrations at cytotoxic concentrations after prolonged (>or=18 h) exposure. No genotoxic activity was observed for hprt mutations either in mouse lymphoma or V79 cells, or in in vitro micronucleus tests in human keratinocytes or hepatocytes. All in vivo genotoxicity studies on KA doses were negative, including mouse bone marrow micronucleus tests after single or multiple doses, an in vivo/in vitro unscheduled DNA synthesis (UDS) test, or a study in the liver of the transgenic Muta(TM) Mouse. On the basis of pharmacokinetic studies in rats and in vitro absorption studies in human skin, the systemic exposure of KA in man following its topical application is estimated to be in the range of 0.03-0.06 mg/kg/day. Comparing these values with the NOAEL in oral subchronic animal studies (250 mg/kg/day), the calculated margin of safety would be 4200- to 8900-fold. Comparing human exposure with the doses that were negative for micronuclei, UDS and gene mutations in vivo, the margins of safety are 16000 to 26000-fold. In conclusion, the topical use of KA as a skin lightening agent results in minimal exposure that poses no or negligible risk of genotoxicity or toxicity to the consumer.

Administration, Topical↗

PubMed1989

Eicosanoids in acute and chronic psoriatic lesions: leukotriene B4, but not 12-hydroxy-eicosatetraenoic acid, is present in biologically active amounts in acute guttate lesions.

The biochemical changes underlying the clinical manifestations of psoriasis are unknown. Certain chemotactic eicosanoids derived from arachidonic acid metabolism have been suggested to play important roles in psoriasis, because of their presence in lesional psoriatic skin and their ability to elicit skin inflammation and to stimulate epidermal proliferation. The purpose of the present study was to elucidate which eicosanoids might be involved in the early phases of the inflammatory processes of psoriasis. Eicosanoids were analyzed in scale and in lesional skin without scale both in acute guttate and chronic plaque psoriatic lesions. Methods for identification of eicosanoids included reversed-phase high-performance liquid chromatography combined with radioimmunoassay. Leukotriene B4 was present in both acute guttate and chronic plaque skin lesions in biologically active amounts (acute guttate lesions: 18.7 +/- 7.1 ng/g wet tissue in scale and 3.2 +/- 1.5 ng/g wet tissue in lesional skin without scale; chronic plaque lesions: 33.1 +/- 9.7 ng/g wet tissue in scale and 5.3 +/- 2.0 ng/g wet tissue in lesional skin without scale). 12- and 15-hydroxy-eicosatetraenoic acid (HETE) reached biologically active concentrations only in scale of chronic plaque lesions (1,512 +/- 282 and 1,441 +/- 411 ng/g wet tissue, respectively). The level of prostaglandin E2 in chronic plaque lesions was similar to the level in normal skin, while the level in acute guttate lesions was increased twofold (71.0 +/- 14.8 ng/g wet tissue). These results demonstrate that leukotriene B4, but not 12-HETE, is present in acute guttate psoriatic skin lesions in concentrations able to exert biologic effects. Leukotriene B4 may therefore participate in inflammatory changes of acute psoriasis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1971

A convenient procedure for the synthesis of ceramides.

A procedure for the preparation of ceramides by direct coupling of long-chain bases and fatty acids in the presence of a mixed carbodiimide is described. This method has been used to prepare ceramides containing sphing-4-enine or sphinganine and various saturated and unsaturated fatty acids as well as saturated 2-hydroxy acids. Ceramides containing 4-hydroxy sphinganine and saturated nonhydroxy acids have also been prepared. The yields were 60-75%. The characterization of these compounds by gas-liquid chromatography-mass spectrometry as trimethylsilyl derivatives has been previously reported. Some of the ceramides are further characterized in this report by infrared spectroscopy and one compound, in addition, by elementary analysis. Use of racemic constituents for 2-hydroxy acid ceramide syntheses leads to the formation of diastereoisomers which separate by thin-layer chromatography. These were characterized by gas-liquid chromatography-mass spectrometry as the trimethylsilyl derivatives and by infrared spectroscopy. Their configurations were established by syntheses with optically active constituents.

Acylation↗

PubMed1979

Cytochemical localization of catalase and several hydrogen peroxide-producing oxidases in the nucleoids and matrix of rat liver peroxisomes.

The distribution of catalase, amino acid oxidase, alpha-hydroxy acid oxidase, urate oxidase and alcohol oxidase was studied cytochemically in rat hepatocytes. The presence of catalase was demonstrated with the conventional diaminobenzidine technique. Oxidase activities were visualized with methods based on the enzymatic or chemical trapping of the hydrogen peroxide produced by these enzymes during aerobic incubations. All enzymes investigated were found to be present in peroxisomes. Catalase activity was found in the peroxisomal matrix, but also associated with the nucleoid. After staining for oxidase activities the stain deposits occurred invariably in the peroxisomal matrix as well as in the nucleoids. In all experiments the activity of both catalase and the oxidases was confined to the peroxisomes. The presence of a hydrogen peroxide-producing alcohol oxidase was demonstrated for the first time in peroxisomes in liver cells. The results imply that the enzyme activity of the nucleoids of rat liver peroxisomes is not exclusively due to urate oxidase. The nucleoids obviously contain a variety of other enzymes that may be more or less loosely associated with the insoluble components of these structures.

3,3'-Diaminobenzidine↗

PubMed2003

Transformation of fatty acids catalyzed by cytochrome P450 monooxygenase enzymes of Candida tropicalis.

Candida tropicalis ATCC 20336 can grow on fatty acids or alkanes as its sole source of carbon and energy, but strains blocked in beta-oxidation convert these substrates to long-chain alpha,omega-dicarboxylic acids (diacids), compounds of potential commercial value (Picataggio et al., Biotechnology 10:894-898, 1992). The initial step in the formation of these diacids, which is thought to be rate limiting, is omega-hydroxylation by a cytochrome P450 (CYP) monooxygenase. C. tropicalis ATCC 20336 contains a family of CYP genes, and when ATCC 20336 or its derivatives are exposed to oleic acid (C(18:1)), two cytochrome P450s, CYP52A13 and CYP52A17, are consistently strongly induced (Craft et al., this issue). To determine the relative activity of each of these enzymes and their contribution to diacid formation, both cytochrome P450s were expressed separately in insect cells in conjunction with the C. tropicalis cytochrome P450 reductase (NCP). Microsomes prepared from these cells were analyzed for their ability to oxidize fatty acids. CYP52A13 preferentially oxidized oleic acid and other unsaturated acids to omega-hydroxy acids. CYP52A17 also oxidized oleic acid efficiently but converted shorter, saturated fatty acids such as myristic acid (C(14:0)) much more effectively. Both enzymes, in particular CYP52A17, also oxidized omega-hydroxy fatty acids, ultimately generating the alpha,omega-diacid. Consideration of these different specificities and selectivities will help determine which enzymes to amplify in strains blocked for beta-oxidation to enhance the production of dicarboxylic acids. The activity spectrum also identified other potential oxidation targets for commercial development.

Amino Acid Sequence↗

PubMed2000

Characterization and variability of endotoxin and 3-hydroxy fatty acids in an office building during a particle intervention study.

Air and dust samples were collected on two floors of an office building during a double-blind particle intervention study to examine spatial and temporal variability of airborne endotoxin over a period of weeks, and to characterize endotoxin activity and lipopolysaccharide (LPS) content in carpet and chair dust. Air samples were collected on multiple days within and across weeks. Dust samples were collected from carpets and chairs one day per week for three weeks. Endotoxin was measured using a Limulus assay. Dust samples were analyzed for LPS by determination of 3-hydroxy fatty acids (3-OHFAs) using gas chromatography-mass spectrometry. The geometric mean (geometric standard deviation) for 96 indoor air samples was 0.24 (1.6) EU/m3. Significant within-floor spatial variation of airborne endotoxin was found (P < 0.0001, n = 80). Temporal variability of airborne endotoxin was not significant across weeks. Mean (+/- SD) endotoxin levels in carpet dust (59 +/- 9.3 EU/mg dust, n = 12) and in chair dust (38 +/- 7.7 EU/mg dust, n = 10) were significantly different (P < 0.001). Carbon chain length-dependent differences in 3-OHFA levels by dust source and floor were found. Enhanced air filtration did not significantly affect airborne endotoxin (P = 0.62); however, total dust mass and total endotoxin in carpet dust samples increased significantly after enhanced surface cleaning (P < 0.01). These findings suggest that spatial variability, dust source, and surface cleaning may influence building occupant exposures to endotoxin.

Air Pollution, Indoor↗

PubMed1996

3-hydroxy fatty acids in a lipopolysaccharide-like material from Treponema denticola strain FM.

Treponemes are associated with major oral diseases such as apical and marginal periodontitis. Lipopolysaccharide (LPS) is regarded as an important virulence factor in these diseases. It is unclear whether LPS is present in oral treponemes. Therefore, the present study was undertaken to examine if a common oral treponeme-Treponema denticola-possesses LPS. A modified Westphal method (phenol water-ethanol-hexane extraction) was used to extract LPS-like material from T. denticola, reference strain FM. It was cultivated in prereduced anaerobically sterilized pectin medium. Gas chromatography and gas chromatography-mass spectrometry of the extract detected three hydroxy fatty acids: C3-OH-i-13:0, C3-OH-i-15:0, and C3-OH-16:0 which constituted 12% of its fatty acid content. These acids, commonly regarded as markers of LPS, suggested the presence of LPS in T. denticola.

Biomarkers↗

PubMed1994

Predominant role of the substituents on the hydroxyl groups of 3-hydroxy fatty acids of non-reducing glucosamine in lipid A for the endotoxic and antagonistic activity.

The synthetic disaccharide precursor of lipid A (406: identical to lipid IVA) was found to reduce its endotoxic activity in mice by an order of 10(5) or more, by replacing the hydroxyl groups with succinyl or acetyl residues. Both the succinylated and acetylated 406 were also found to antagonize the endotoxic mitogenicity on murine splenocytes. Previous studies demonstrated that the succinylated or acetylated synthetic complete lipid A preparations retained the whole endotoxic activity [1994, Infect. Immunol. 62, 1705]. The drastic contrast in all of these results suggests the importance of the substituents on the hydroxyl groups of 3-hydroxy fatty acids of non-reducing glucosamine of lipid A for the activity and for transformation to the antagonistic structure.

Acetylation↗

PubMed1996

Short contact 70% glycolic acid peels as a treatment for photodamaged skin. A pilot study.

BACKGROUND: Glycolic acid has been one of the more commonly used alpha hydroxy acids for the treatment of photodamaged skin. Its value as a quick "skin refreshing" peeling agent has been widely touted. This type of peel differs from a conventional therapeutic peel (eg, phenol, trichloroacetic acid, or a longer time exposure alpha hydroxy acid peel) in that there is little skin reaction and patients can go about their daily routine without concern. OBJECTIVE: To assess the potential value of glycolic acid-based refresher peels as a cosmetic procedure. METHODS: Twelve healthy subjects with at least a moderate degree of photodamage were treated with monthly serial 70% glycolic acid peels over a period of 4 months. In addition to the "peels," six subjects were randomized to a 10% glycolic acid-based moisturizer twice daily. Patients were evaluated monthly and graded on a clinical scale using objective measures. RESULTS: No conclusive differences were noted on histologic evaluation. Ninety percent (9/10) of patients felt that overall they noticed significant improvement, however, there was no distinction between the two treatment options. The improvement in fine wrinkling and pigmentation was primarily seen in the patients who additionally received 10% glycolic emollient twice daily. CONCLUSION: In this limited pilot study, no specific benefit could be assigned to the concomitant use of monthly glycolic acid refresher "peels" in the treatment of photodamaged skin.

Adult↗

PubMed2002

Serial cerebrospinal fluid tryptophan and 5-hydroxy indoleacetic acid concentrations in healthy human subjects.

The role of the serotonergic system in the pathogenesis of behavioral disorders such as depression, alcoholism, obsessive-compulsive disorder, and violence is not completely understood. Measurement of the concentration of neurotransmitters and their metabolites in cerebrospinal fluid (CSF) is considered among the most valid, albeit indirect, methods of assessing central nervous system function in man. However, most studies in humans have measured lumbar CSF concentrations only at single time points, thus not taking into account rhythmic or episodic variations in levels of neurotransmitters, precursors, or metabolites. We have continuously sampled lumbar CSF via subarachnoid catheter in 12 healthy volunteers, aged 20-65 years. One ml (every 10 min) CSF samples were collected at a rate of 0.1ml/min for 24-hour (h), and the levels of tryptophan (TRP) and 5-hydroxy indoleacetic acid (5-HIAA) were measured. Variability across all 12 subjects was significantly greater (P < 0.0001) than the variability seen in repeated analysis of a reference CSF sample for both 5-HIAA (32.0% vs 7.9%) and TRP (25.4% vs 7.0%), confirming the presence of significant biological variability during the 24-hr period examined. This variability could not be explained solely by meal related effects. Cosinor analysis of the 24-hr TRP concentrations from all subjects revealed a significant diurnal pattern in CSF TRP levels, whereas the 5-HIAA data were less consistent. These studies indicate that long-term serial CSF sampling reveals diurnal and biological variability not evident in studies based on single CSF samples.

Adult↗