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反式 -4-羟基- L -脯氨酸 ≥99%; CAS Number: 51-35-4; EC Number: 200-091-9; Synonyms: Hyp,(2S,4R)-4-羟基吡咯烷-2-羧酸; find Sigma-Aldrich-H54409 MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma-Aldrich

反式 -4-羟基- L -脯氨酸 ≥99% | Sigma-Aldrich

反式 -4-羟基- L -脯氨酸 &#8805;99%

<I>反式 </I>-4-羟基-<SC> L </SC>-脯氨酸

Notochordal cells (NCs) reside in the core of the healthy disc and produce soluble factors that can stimulate nucleus pulposus cells (NPCs). These NC-derived factors may be applied in intervertebral disc regeneration for treatment of low-back pain. However, identification of the active soluble factors is challenging. Therefore a novel approach to directly use porcine NC-rich NP matrix (NCM) is introduced. We explored porcine NCM's anabolic effects on bovine NPCs harvested from caudal discs of adolescent and adult (2-2.5 vs. 4-6 year old) cows. NC-conditioned medium (NCCM) and NCM were produced from porcine NC-rich NP tissue. Bovine NPCs were cultured in alginate beads for 4 weeks in base medium (BM), NCCM, and NCM to investigate NCM's regenerative potential. Porcine NCM increased glycosaminoglycan (GAG) content of both adolescent and adult bovine NPCs. This was through increased proliferation of adolescent bovine NPCs, whereas in adult bovine NPCs, it was mostly through increased GAG production per NPC. Furthermore, adolescent bovine NPCs were cultured in BM and porcine NCM treated with interleukin (IL)-1β to investigate NCM's potential in an inflammatory environment. Addition of IL-1β enhanced IL1β and CXCL8 (IL8) gene expression, while NCM diminished IL1β gene expression. IL-1β reduced GAG and DNA content, but the addition of NCM relative to BM improved GAG and DNA content. Altogether, porcine NCM exerts bovine NPC-age dependent effects, and NCM's anabolic effect on adult NPCs is stronger compared with NCCM. Furthermore, porcine NCM induced an anabolic response of bovine NPCs in an inflammatory environment and may have anti-inflammatory properties. Therefore, NCM has potential in a regenerative therapy for disc degeneration, and warrants additional in vivo studies.

Notochordal Cell Matrix As a Therapeutic Agent for Intervertebral Disc Regeneration.

Needle liver biopsy is essential for the diagnosis of liver fibrosis and cirrhosis. However, sampling variability has been reported by semiquantitative methods. The aim of the present study was to investigate quantitatively the sampling variability of needle liver biopsy on the assessment of liver fibrosis/cirrhosis. Liver samples of 12 patients undergoing autopsy, liver transplantation, or liver tumor resection were investigated. Nine to 10 liver biopsies at least 5 mm apart were taken from each of 12 removed human livers using Trucut needles. Hydroxyproline level of each liver core was determined. Sections >1 cm(2) and stained by Sirius red were used for the reference staging of liver fibrosis in each patient according to the METAVIR scoring system. Hydroxyproline levels for the three groups, F0-1, F2-3, and F4, were significantly elevated as the fibrosis score increased. There was a wide range of hydroxyproline contents for the 9-10 biopsy samples from each liver, the coefficient of variation being between 13% and 36% (mean, 23%). Several differences were noted between the amount of collagen present according to hydroxyproline measurement and the stages of fibrosis according to histology. Although increases in collagen content (by hydroxyproline) approximately paralleled increases in fibrosis stage (by histology), there was considerable overlap and some discrepancies. Much work remains to be done to clarify the significance of the apparent huge variations in fibrosis within diseased livers. It is advisable for clinicians to interpret staging diagnoses by histological staging with some caution.

Hydroxyproline content of needle biopsies as an objective measure of liver fibrosis: Emphasis on sampling variability.

In this work, we investigated the effects of lowered oxygen tension (20% and 5% O2) on the chondrogenesis and hypertrophy of articular chondrocytes (ACs), mesenchymal stem cells (MSCs) and their co-cultures with a 30:70 AC:MSC ratio. Cells were cultured for six weeks within porous scaffolds, and their cellularity, cartilaginous matrix production (collagen II/I expression ratio, hydroxyproline and GAG content) and hypertrophy markers (collagen X expression, ALP activity, calcium accumulation) were analyzed. After two weeks, hypoxic culture conditions had expedited chondrogenesis with all cell types by increasing collagen II/I expression ratio and matrix synthesis by ~2.5-11 and ~1.5-3.0 fold, respectively. At later times, hypoxia decreased cellularity but had little effect on matrix synthesis. ACs and co-cultures showed similarly high collagen II/I expression ratio and GAG rich matrix formation, whereas MSCs produced the least hyaline cartilage-like matrix and obtained a hypertrophic phenotype with eventual calcification. MSC hypertrophy was further emphasized in hypoxic conditions. We conclude that the most promising cell source for cartilage engineering was co-cultures, as they have a potential to decrease the need for primary chondrocyte harvest and expansion while obtaining a stable highly chondrogenic phenotype independent of the oxygen tension in the cultures.

The effect of hypoxia on the chondrogenic differentiation of co-cultured articular chondrocytes and mesenchymal stem cells in scaffolds.

The aldol reaction of acetone with aldehydes in aqueous medium under catalysis by zinc-proline (Zn(L-Pro)2) and secondary amines such as proline, (2S,4R)-4-hydroxyproline (Hyp) and (S)-(+)-1-(2-pyrrolidinomethyl)pyrrolidine (PMP) is shown to proceed by an enamine mechanism, as evidenced by reductive trapping of the iminium intermediate, while the aldol reaction of dihydroxyacetone (DHA) under catalysis by zinc-proline and by general bases such as N-methylmorpholine (NMM) is shown to occur under rate-limiting deprotonation of the alpha-carbon and formation of an enolate intermediate.

Dual mechanism of zinc-proline catalyzed aldol reactions in water.

It remains to be shown whether OA shares molecular similarities between different joints in humans. This study provides evidence for similarities in cartilage molecular damage in osteoarthritic (OA) joints. Articular cartilage from osteoarthritic hip joints were analysed and compared to non-OA controls regarding collagen, glycosaminoglycan and water content. Femoral heads from 16 osteoarthritic (OA) and 20 reference patients were obtained from hip replacement surgery due to OA and femoral neck fracture, respectively. Cartilage histological changes were assessed by Mankin grading and denatured collagen type II immunostaining and cartilage was extracted by α-chymotrypsin. Hydroxyproline and Alcian blue binding assays were used to measure collagen and glycosaminoglycan (GAG) content, respectively. Mankin and immunohistology scores were significantly higher in hip OA samples than in reference samples. Cartilage water content was 6% higher in OA samples than in references. 2.5 times more collagen was extracted from OA than from reference samples. There was a positive association between water content and percentage of extractable collagen pool (ECP) in both groups. The amounts of collagen per wet and dry weights did not differ statistically between OA and reference cartilage. % Extractable collagen was not related to collagen per dry weight in either group. However when collagen was expressed by wet weight there was a negative correlation between % extractable and collagen in OA cartilage. The amount of GAG per wet weight was similar in both groups but the amount of GAG per dry weight was higher in OA samples compared to reference samples, which suggests a capacity for GAG biosynthesis in hip OA cartilage. Neither of the studied parameters was related to age in either group. Increased collagen extractability and water content in human hip cartilage is associated with OA pathology and can be observed at early stages of the degenerative hip OA process. Our results suggest a common degradative pathway of collagen in articular cartilage of different joints. Furthermore, the study suggests that biochemical changes precede more overt OA changes and that chondrocytes may have a capability to compensate molecular loss in the early phase of OA.

Cartilage collagen damage in hip osteoarthritis similar to that seen in knee osteoarthritis; a case-control study of relationship between collagen, glycosaminoglycan and cartilage swelling.

Chronic ischemic heart disease is associated with myocardial hypoperfusion. The resulting hypoxia potentially inflicts damage upon the mitochondria, leading to a compromised energetic state. Furthermore, ischemic damage may cause excessive production of reactive oxygen species (ROS), producing mitochondrial damage, hereby reinforcing a vicious circle. Ischemic preconditioning has been proven protective in acute ischemia, but the subject of chronic ischemic preconditioning has not been explored in humans. We hypothesized that mitochondrial respiratory capacity would be diminished in chronic ischemic regions of human myocardium but that these mitochondria would be more resistant to ex vivo ischemia and, second, that ROS generation would be higher in ischemic myocardium. The aim of this study was to test mitochondrial respiratory capacity during hyperoxia and hypoxia, to investigate ROS production, and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared with nonischemic myocardium (P < 0.05), but the degree of coupling (respiratory control ratio) did not differ (P > 0.05). The presence of ex vivo hypoxia did not reveal any chronic ischemic preconditioning of the ischemic myocardial regions (P > 0.05). ROS production was higher in ischemic myocardium (P < 0.05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found.

Impaired mitochondrial function in chronically ischemic human heart.

Hydroxyproline (Hyp) O-arabinosylation is a post-translational modification that is prominent in extracellular glycoproteins in plants. Hyp O-arabinosylation is generally found in these glycoproteins in the form of linear oligoarabinoside chains and has a key role in their function by contributing to conformational stability. However, Hyp O-arabinosyltransferase (HPAT), a key enzyme that catalyzes the transfer of the L-arabinose to the hydroxyl group of Hyp residues, has remained undiscovered. Here, we purified and identified Arabidopsis HPAT as a Golgi-localized transmembrane protein that is structurally similar to the glycosyltransferase GT8 family. Loss-of-function mutations in HPAT-encoding genes cause pleiotropic phenotypes that include enhanced hypocotyl elongation, defects in cell wall thickening, early flowering, early senescence and impaired pollen tube growth. Our results indicate essential roles of Hyp O-arabinosylation in both vegetative and reproductive growth in plants.

Identification of three hydroxyproline O-arabinosyltransferases in Arabidopsis thaliana.

This study aimed to determine the effects of platelet-rich plasma (PRP) on the histologic, biochemical, and biomechanical properties of tissue-engineered cartilage. Chondrocytes isolated from bovine metacarpal-phalangeal articular cartilage were seeded on top of a porous ceramic substrate (calcium polyphosphate [CPP]). Cultures were supplemented with fetal bovine serum (FBS), PRP, or platelet-poor plasma (PPP) at 5%. On day 5, the concentration was increased to 20%. PRP and PPP were obtained through centrifugation of whole blood withdrawn from a mature cow. After 2 weeks, samples (n = 8) were analyzed histologically, biochemically, and biomechanically. Data were analyzed using the Wilcoxon test (significance, P < .05). Chondrocytes cultured in 20% PRP formed thicker cartilage tissue (1.6 ± 0.2 mm) than did cells grown in 20% FBS (0.7 ± 0.008 mm; P = .002) and 20% PPP (0.8 ± 0.2 mm; P = .03). Cartilage tissue generated in the presence of 20% PRP had a greater equilibrium modulus of 38.1 ± 3.6 kPa versus 15.6 ± 1.5 kPa (P = .0002) for 20% PPP and 20.4 ± 3.5 kPa (P = .007) for 20% FBS. Glycosaminoglycan (GAG) content was increased in tissues formed in 20% PRP (176 ± 18.8 μg GAG/mg) compared with those grown in 20% FBS (112 ± 10.6 μg GAG/mg; P = .01) or 20% PPP (131.5 ± 14.8 μg GAG/mg; P = .11). Hydroxyproline content was similar whether the media was supplemented with 20% PRP (8.7 ± 0.9 μg/mg), 20% FBS (7.6 ± 0.9 μg/mg; P = .37), or 20% PPP (6.4 ± 1 μg/mg; P = .28). DNA content was similar in all tissues whether formed in 20% PRP (11.9 ± 3.5 μg/mg), 20% FBS (9.3 ± 2.5 μg/mg; P = .99), or 20% PPP (7.2 ± 1.3 μg/mg; P = .78). Immunostained samples showed prevalence of type II collagen in tissues formed in the presence of 20% PRP. The presence of PRP in the culture media enhances the in vitro formation of cartilage, with increased GAG content and greater compressive mechanical properties, while maintaining characteristics of hyaline phenotype. Understanding the in vitro effects of PRP on tissue-engineered cartilage may lead to the creation of engineered cartilage tissue with enhanced properties suitable for cartilage repair.

Supplementation with platelet-rich plasma improves the in vitro formation of tissue-engineered cartilage with enhanced mechanical properties.

Fibrin sealants are used in pancreatic surgery to prevent leakage of pancreatic fluid and reduce associated complications. The efficacy of this approach is unclear. Fibrin clots were generated in vitro from two commercially available liquid fibrin sealants (Tissucol Duo® and Evicel®) and the carrier-bound fibrin sealant Tachosil®, and exposed to normal saline or human pancreatic fluid. Stability of the sealants was assessed by release of the fibrin and collagen degradation products, D-dimer and hydroxyproline. The effect of protease inhibitors on sealant breakdown was assessed. Clots generated from liquid fibrin sealants degraded rapidly in pancreatic fluid, but not in normal saline. D-dimer release from fibrin clots by pancreatic fluid was approximately 1700 µg/ml after 24 h and less than 20 µg/ml by saline. Pancreatic fluid, but not normal saline, degraded both the fibrin and collagen component of Tachosil®. After 6 h, mean(s.e.m.) D-dimer levels in pancreatic fluid exposed to Tachosil® were 850(183) ng/ml, compared with 60(6) ng/ml in normal saline. The mean(s.e.m.) hydroxyproline concentration in pancreatic fluid was 497(17) µg/ml after a 24-h exposure to Tachosil®, compared with 26(12) µg/ml in normal saline. Protease inhibitors significantly inhibited breakdown of liquid sealants (D-dimer levels less than 50 µg/ml after 24 h) and Tachosil® (D-dimer release 179(12) ng/ml at 6 h; hydroxyproline release 181(29) µg/ml at 24 h). Proteases in pancreatic juice effectively degrade both liquid and carrier-bound fibrin sealants in vitro. The use of these products in pancreatic surgery with the aim of preventing leakage of pancreatic fluid is not supported by this experimental study.

In vitro effects of proteases in human pancreatic juice on stability of liquid and carrier-bound fibrin sealants.

Non-steroid anti-inflammatory drugs such as the cyclooxygenase isoenzyme inhibitors diclofenac and naproxen are increasingly used for perioperative pain relief, while their potential effects on wound healing are scarcely investigated. In 104 male Wistar rats, an anastomosis was constructed in both colon and ileum. The rats were divided into groups who received diclofenac (4 mg kg(-1) day(-1)) or naproxen (10 mg kg(-1) day(-1)) daily from the day of surgery or from day 3 after surgery. Animals were killed on day 3 or 7 and analysed for signs of anastomotic dehiscence and wound strength of anastomoses and abdominal fascia. Anastomotic leakage in the ileum (p < 0.0001) and mortality rates (p = 0.001) were significantly increased in the diclofenac group. On day 7, the anastomotic bursting pressure in the ileum remained below that of the controls in the diclofenac- and naproxen-treated rats. When administration of diclofenac was postponed to day 3 after surgery, anastomotic dehiscence was almost absent. The colonic anastomosis and abdominal wall always remained unaffected. This study implies that immediate postoperative administration of diclofenac and, to a far lesser extent, naproxen can affect healing in the ileal anastomosis in the rat. This negative effect can be prevented by a short postoperative delay in administration. On steroid anti-inflammatory drugs such as the cyclooxygenase isoenzyme inhibitors diclofenac and naproxen are increasingly used for perioperative pain relief, while their potential effects on wound healing are scarcely investigated.

Diclofenac causes more leakage than naproxen in anastomoses in the small intestine of the rat.

Non-invasive imaging might assist in the clinical translation of tissue-engineered vascular grafts (TEVG). It can e.g. be used to facilitate the implantation of TEVG, to longitudinally monitor their localization and function, and to provide non-invasive and quantitative feedback on their remodeling and resorption. We here incorporated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles into polyvinylidene fluoride (PVDF)-based textile fibers, and used them to prepare imageable tissue-engineered vascular grafts (iTEVG). The USPIO-labeled scaffold materials were molded with a mixture of fibrin, fibroblasts and smooth muscle cells, and then endothelialized in a bioreactor under physiological flow conditions. The resulting grafts could be sensitively detected using T1-, T2- and T2*-weighted MRI, both during bioreactor cultivation and upon surgical implantation into sheep, in which they were used as an arteriovenous shunt between the carotid artery and the jugular vein. In vivo, the iTEVG were shown to be biocompatible and functional. Post-mortem ex vivo analyses provided evidence for efficient endothelialization and for endogenous neo-vascularization within the biohybrid vessel wall. These findings show that labeling polymer-based textile materials with MR contrast agents is straightforward and safe, and they indicate that such theranostic tissue engineering approaches might be highly useful for improving the production, performance, personalization and translation of biohybrid vascular grafts.

USPIO-labeled textile materials for non-invasive MR imaging of tissue-engineered vascular grafts.

Several studies have pointed to a release of drugs or protein-bound solutes from their binding sites during heparinization. The effect is attributed to the metabolism of triglycerides to free fatty acids (FFAs), which compete with drugs for protein binding sites. This study evaluated the impact of intradialytic heparin on the free concentration of the uremic toxin p-cresol and on FFAS: Blood samples from hemodialysis (HD) patients, before and during HD, were collected with selected anticoagulation strategies. We assessed the effects of standing time, temperature, pH, and the addition of a lipase inhibitor, tetrahydrolipstatin (THL) to blood samples on the free p-cresol concentration. p-Cresol was analyzed by HPLC with fluorescence detection. We measured FFAs by gas chromatography, and the free fractions of added valproic acid and phenytoin were evaluated by fluorescence polarization immunoassay. In blood samples (n = 22) not submitted to a specific treatment, free p-cresol increased from 9.9 +/- 5.1 to 31.9 +/- 22.3 micromol/L after 30 min of heparin HD (P < 0.001) and correlated significantly with FFAs (r = 0.80; P = 0.002; n = 12). There was no increase in free p-cresol during heparin-free HD (n = 6) and trisodium citrate HD (n = 9). In addition, p-cresol in ultrafiltrates (n = 3) did not correspond to the free p-cresol in heparinized blood, suggesting that the increase in free p-cresol was artifactual. The release of p-cresol in the test tube was enhanced by standing time (n = 6), sample temperature (n = 6), and alkaline pH (n = 6). Inhibition of lipase activity with THL prevented the increase of FFAs (n = 6) and the release of free p-cresol during HD (n = 22). These results were corroborated by the study of the free fraction of valproic acid (n = 6) and phenytoin (n = 6). The free concentrations of protein-bound solutes in plasma of heparinized patients are influenced by external factors that alter the lipase activity in the test tube. The free fraction does not increase during HD when lipase activity is neutralized at the time of blood sampling, so that previously reported increases are probably artifacts.

Heparin-induced release of protein-bound solutes during hemodialysis is an in vitro artifact.

The purpose of this study was to examine the effect of nocturnal hemodialysis (NHD) on serum amino acid (AA) profile. In a cross-over trial, we studied the AA profile in 11 patients who were switched from conventional hemodialysis to NHD. Plasma levels of AA were measured at monthly intervals for a period of 1 year. Concentrations of AA isoleucine, threonine, phenylalanine, valine, glycine, glutamine and taurine increased on switch to NHD. Total AA (2,907.2 +/- 542.2 vs. 3,870.2 +/- 715.2 micromol/l, p = 0.03), essential AA (EAA, 842.2 +/- 259.4 vs. 1,125. 8 +/- 235.3 micromol/l, p = 0.03), nonessential AA (NEAA, 2,307.2 +/- 399.1 vs. 2,879.5 +/- 581.2 micromol/l, p = 0.03), and branched chain AA (315.5 +/- 90.8 vs. 386.0 +/- 114.3 micromol/l, p = 0.05) concentrations were significantly higher on NHD. However, abnormalities in the ratios of EAA/NEAA, valine/glycine and tyrosine/phenylalanine persisted during NHD. NHD alleviated some abnormalities in the aminogram of uremia, but other metabolic derangements lingered.

Plasma amino acid profile on nocturnal hemodialysis.

Two chiral stationary phases containing a quinine- or a quinidine-based zwitterionic ion-exchanger as chiral selector were applied for the enantioseparation of 27 unusual cyclic secondary α-amino acids. The effects of the nature and concentration of the bulk solvent, the acid and base additives, the structures of the analytes and temperature on the enantioresolution were investigated. To study the effects of temperature and to obtain thermodynamic parameters, experiments were carried out at constant mobile phase compositions in the temperature range -5 to 55 °C. The thermodynamic parameters indicated that in most cases the separations were enthalpy-driven, but some entropy-driven separations were also observed. The sequence of elution of the enantiomers was determined in most cases.

Direct high-performance liquid chromatographic enantioseparation of secondary amino acids on Cinchona alkaloid-based chiral zwitterionic stationary phases. Unusual temperature behavior.

Metabolite profiling methods are important tools for measurement of metabolite pools in biological systems. While most metabolite profiling methods report relative intensities or depend on a few internal standards representing all metabolites, the ultimate requirement for a quantitative description of the metabolite pool in biological cells and fluids is absolute concentration determination. We report here a high-throughput and sensitive gas chromatography/tandem mass spectrometry (GC/MS/MS) targeted metabolite profiling method enabling absolute quantification of all detected metabolites. The method is based on methyl chloroformate derivatization and quantification by spiking samples with metabolite standards separately derivatized with deuterated derivatization reagents. The traditional electron impact ionization is replaced with positive chemical ionization since the latter to a much larger extent preserve the molecular ion and other high molecular weight fragments. This made it easier to select unique MS/MS transitions among the many coeluting metabolites. Currently, the novel GC/MS/MS method comprises 67 common primary metabolites of which most belong to the groups of amino and nonamino organic acids. We show the applicability of the method on urine and serum samples. The method is a significant improvement of present methodology for quantitative GC/MS metabolite profiling of amino acids and nonamino organic acids.

Highly sensitive GC/MS/MS method for quantitation of amino and nonamino organic acids.

There is evidence that increased blood concentrations of homocysteine may be a risk factor for Alzheimer's disease. (E)-4-hydroxy-2-nonenal (HNE) is a neurotoxic product of lipid peroxidation that is increased in the ventricular fluid and brains of patients with Alzheimer's disease. We measured the concentrations of homocysteine, HNE, vitamin B(12) and folate in the plasma of 27 patients with Alzheimer's disease and 25 control subjects. There was a statistically significant increase in the plasma concentration of homocysteine (P < 0.001) and HNE (P < 0.001) in the Alzheimer's disease patients compared to the control group. There was a significant decrease in the plasma concentration of vitamin B(12) (P < 0.001) and folate (P = 0.002) in the Alzheimer's group compared to the controls. There was a significant positive correlation between the plasma concentrations of homocysteine and HNE in the patients with Alzheimer's disease (r = 0.661, P < 0.001). A significant negative correlation was found between the plasma concentration of homocysteine and the plasma concentrations of vitamin B(12) (r = -0.605, P = 0.0006) and folate (r = 0.586, P = 0.001). We also measured the concentrations of homocysteine, HNE, vitamin B(12) and folate in the cerebrospinal fluid (CSF) of 8 patients with Alzheimer's disease compared to 6 control subjects. The concentrations of homocysteine (P = 0.032) and HNE (P = 0.001) were significantly higher in the CSF of Alzheimer's patients than in the control subjects. There were significant positive correlations between the CSF concentrations of homocysteine and HNE (r = 0.924, P = 0.001). There was also a significant positive correlation between the plasma concentration of homocysteine and the CSF concentrations of homocysteine (r = 0.850, P = 0.007) and HNE (r = 0.092, P = 0.002). These results demonstrate that there is a relationship between increased homocysteine concentrations and increased HNE concentrations in Alzheimer's disease.

The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease.

24S-Hydroxycholesterol (24OHC) and 27-hydroxycholesterol (27OHC) are two structurally similar oxysterols of different origins--the former almost exclusively formed in the brain and the latter formed to a lesser extent in the brain than in most other organs. HYPOTHESIS TO BE TESTED: Neuronal damage and/or demyelination causes increased flux of 24OHC from the brain into the cerebrospinal fluid (CSF), whereas a defect blood-brain barrier causes increased flux of 27OHC from the circulation into the CSF. Isotope dilution-mass spectrometry was used to assay the two oxysterols in CSF and plasma from more than 250 patients with different neurological and geriatric diseases. The CSF-levels of the two oxysterols were much more affected by the different diseases than the plasma levels. Patients with active demyelinating diseases had increased levels of 24OHC in CSF with a relatively high 24OHC/27OHC ratio. Patients with meningitis in general had high levels of both steroids with a low 24OHC/27OHC ratio. Patients with Alzheimer's disease had slightly increased levels of 24OHC in CSF with less increase in 27OHC. Patients with multiple sclerosis had a tendency to have higher levels of 24OHC during active periods with a high 24OHC/ 27OHC ratio. Measurements of the two oxysterols in CSF and plasma may add significantly to existing biochemical methods for evaluation of neurological diseases.

反式 -4-羟基- L -脯氨酸

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