n-acetyl aspartate creatine: Topics by WorldWideScience.org

Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder

Proton magnetic resonance spectroscopy (MRS) measures concentrations of metabolites in vivo and provides a powerful method for identifying tumours. MRS has not entered routine clinical use partly due to the difficulty of analysing the spectra. To create a straightforward method for interpreting short-echo-time MRS of childhood cerebellar tumours. Single-voxel MRS (1.5-T Siemens Symphony NUM4, TR/TE 1,500/30 ms) was performed at presentation in 30 children with cerebellar tumours. The MRS results were analysed for comparison with histological diagnosis. Peak heights for N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mIns) were determined and receiver operator characteristic curves used to select ratios that best discriminated between the tumour types. The method was implemented by a group of clinicians and scientists, blinded to the results. A total of 27 MRS studies met the quality control ...

2007-11-15

British Library Electronic Table of Contents (United Kingdom)

Singh MK, Spielman D, Libby A, Adams E, Acquaye T, Howe M, Kelley R, Reiss A, Chang KD. Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder.-Bipolar Disord 2011: 13: 189-197. 2011 The Authors.-Journal compilation 2011 John Wiley & Sons A/S. Objectives:- We aimed to compare concentrations of N-acetyl aspartate, myo-inositol, and other neurometabolites in the cerebellar vermis of offspring at risk for bipolar disorder (BD) and healthy controls to examine whether changes in these neuronal metabolite concentrations occur in at-risk offspring prior to the onset of mania. Methods:- A total of 22 children and adolescents aged 9-17-years with a familial risk for bipolar I or II disorder [at-risk offspring with non-bipolar I disorder mood symptoms (AR...

2011-01-01

Changes in N-acetyl-B-D-glucosaminidase and B-glucuronidase activities in milk during bovine mastitis.

Serum Creatine Phosphokinase Activity after Intramuscular ...

To determine the N-acetyl-B-D-glucosaminidase (NAGase) and B-glucuronidase (B-Gase) activities in mastitic milk, basic enzyme assay conditions, distribution of NAGase and B-Gase, comparison of their...Full Text Available

1987-01-01

Creatine and Phosphocreatine: A Review of Their Use in Exercise and Sport

... Title : Serum Creatine Phosphokinase Activity after Intramuscular Injection: The Effect of Dose, Concentration, and Volume. ...

1974-01-01

Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage

Objective: Creatine and phosphocreatine (PCr) are important compounds in the normal energy metabolism of muscle. Recently, it has been shown that dietary creatine (5 to 20 g/day)...Full Text Available

1997-01-01

N-acetyltransferase 2 slow acetylator genotype associated with adverse effects of sulfasalazine in the treatment of inflammatory bowel disease

Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional...Full Text Available

2011-06-01

THE CONTENT OF ADENINE NUCLEOTIDES AND ...

AIM:N-acetyltransferase 2 (NAT2) is an important enzyme catalyzing N-acetylation of sulfasalazine (SASP). The aim of the present study was to investigate...Full Text Available

2007-03-01

The Protective Effect of Antioxidants on Oxidative Stress in Rats Exposed to the 950 MHz Electromagnetic Field

... Accession Number : AD0262144. Title : THE CONTENT OF ADENINE NUCLEOTIDES AND CREATINE PHOSPHATE IN BRAIN. ...

1961-05-01

N"v"a"r"-"e"p"s"i"l"o"n-acetyl-#beta#-lysine: An osmolyte synthesized by mothanogenic archaebacteria

Studies have linked cell phone radiation to health problems such as headaches, high blood pressure, cancer and more. There is a latency period for most diseases and it may take years and more studies before the required weight of evidence is established. But the effects are cumulative and precautions should be taken now before it is too late. The aim of the present study was to investigate if supplementation with antioxidants would protect heart and liver tissues from harmful radiation emitted by cell phone. Thirty two male albino rats were randomly divided into four equal groups: I- Control, II- Antioxidants treated group, III- 950 MHz EMR, IV- 950 MHz EMR + antioxidants. A 950 MHz EMR radiation (217-Hz pulse rate, 2-W maximum peak power, SAR Specific Absorption Rate"1.6 W/Kg) was applied to groups III and IV 60 min/day, for 30 days using an experimental exposure device. Antioxidants supplement (Vitamins A, E and C + Se) was administered to rats daily, by gavages, during the period of ...

The impact of a repeated bout of eccentric exercise on muscular strength, muscle soreness and creatine kinase.

Methanosarcina thermophila, a nonmarine methanogenic archaebacterium, can grow in a range of saline concentrations. At less than 0.4 M NaCl, Ms. thermophila accumulated glutamate in response to increasing osmotic stress. At greater than 0.4 M NaCl, this organism synthesized a modified #beta#-amino acid that was identified as N"v"a"r"-"e"p"s"i"l"o"n-acetyl-#beta#-lysine by NMR spectroscopy and ion-exchange HPLC. This #beta#-amino acid derivative accumulated to high intracellular concentrations (up to 0.6 M) in Ms. thermophila and in another methanogen examined - Methanogenium cariaci, a marine species. The compound has features that are characteristic of a compatible solute: it is neutrally charged at physiological pH and it is highly soluble. When the cells were grown in the presence of exogenous glycine betaine, a physiological pH and it is highly soluble. When the cells were grown in the presence of exogenous glycine betaine, a physiological compatible solute, ...

Domain Bridging Interactions. A Necessary Contribution to the Function and Structure of 'Escherichia coli' Aspartate Transcarbamoylase

The purpose of this study was to determine if there were any beneficial or detrimental effects regarding delayed onset muscle soreness (DOMS), serum creatine kinase (CK), and maximum concentric strength...Full Text Available

1994-12-01

Surface structure recognized for covalent modification of the aspartate receptor in chemotaxis.

No abstract prepared.

2001-01-01

Cardiac Enzymes, Renal Failure and Renal Transplantation

The aspartate receptor involved in chemotaxis is modified by methyl esterification at four distinct glutamate residues during the adaptive response of this receptor. To explain the high degree of specificity...Full Text Available

1986-09-01

Evaluation of gels obtained from acetylation of chitosan in heterogeneous medium

Diagnostic accuracy of the currently available serum markers of cardiac injury, such as myoglobin, creatine kinase and its myocardial isoform, are altered in patients with renal failure. It is shown...Full Text Available

2006-03-01

Analysis by high-performance liquid chromatography of radioactively labeled carbohydrate components of proteoglycans

Chitosan was acetylated during 2, 5 and 10 h and physical gels were obtained at different polymer concentrations in N,N-dimethylacetamide containing 5% of LiCl. Acetylation was confirmed by infrared spectroscopy and "1"3C NMR, and degrees of acetylation in the range of 0.82-0.91 were determined by NMR. The O-acetylation degree (0.12-0.15) was exclusively determined by a volumetric method. Rheological studies showed that the storage modulus values were smaller for the more acetylated samples and increased with the temperature and the polymer concentration. All the gels presented storage modulus superior to loss modulus, evidencing more elastic than viscous characteristics. The results obtained in this work suggest a gelation process based on a balance between O and N-acetylation and intermolecular bonds. (author)

Effects of norepinephrine infusion on myocardial high-energy phosphate content and turnover in the living rat.

Methods were developed for the separation of radioactively labeled carbohydrate components of proteoglycans by isocratic ion-moderated partition HPLC. Neutral sugars were separated after hydrolysis in trifluoroacetic acid with baseline separation between glucose, xylose, galactose, fucose, and mannose. N-Acetylneuraminic acid, N-acetylated hexosamines, glucose, galactose, and xylitol were likewise well separated from each other under isocratic elution conditions. Glucuronic acid, iduronic acid, and their lactones were separated after hydrolysis in formic acid and sulfuric acid. Glucosamine, galactosamine, galactosaminitol, and glucosaminitol were separated by HPLC on a cation exchanger with neutral buffer after hydrolysis in hydrochloric acid. THe separation techniques also proved useful in fractionation of exoglycosidase digests of O- and N-linked oligosaccharides. Separations of aldoses, hexosamines, and uronic acids were adapted to sensitive photometric ...

1986-04-01

Use of Dimethyl Suberimidate, a Cross-Linking Reagent, in Studying the Subunit Structure of Oligomeric Proteins^*

Using 31P-nuclear magnetic resonance, we studied the relationship between myocardial high-energy phosphate content and flux values for the creatine kinase reaction in the living rat under inotropic...Full Text Available

1987-06-01

Transport of Arginine and Aspartic Acid into Isolated Barley Mesophyll Vacuoles ¹

Amidination of aldolase, glyceraldehyde-3-phosphate dehydrogenase, tryptophan synthetase B protein, L-arabinose isomerase, and the catalytic subunit of E. coli aspartate transcarbamylase...Full Text Available

1970-07-01

Dynamin-dependent NMDAR endocytosis during LTD and its dependence on synaptic state

The transport of arginine into isolated barley (Hordeum vulgare L.) mesophyll vacuoles was investigated. In the absence of ATP, arginine uptake was saturable with a K_m...Full Text Available

1991-10-01

Behavioral Responses of Phormia regina (Meigen) to Labellar Stimulation with Amino Acids

BackgroundThe N-methyl-D-aspartate (NMDA)-type glutamate receptor expressed at excitatory glutamatergic synapses is required for learning and memory and is critical for normal brain...Full Text Available

1 2 3

Aspartate Carbamyltransferase 1

Behavioral responses to labellar stimulation with 19 L-amino acids were predicted on the basis of electrophysiological responses of largest labellar hairs. With the exceptions alanine, aspartic...Full Text Available

1973-01-01

Comparison of secondary metabolite production by Penicillium crustosum strains, isolated from Arctic and other various ecological niches.

Lovatt et al. (1979 Plant Physiol 64: 562-569) have previously demonstrated that end-product inhibition functions as a mechanism regulating the activity of the orotic acid pathway in...Full Text Available

1984-07-01

"1H MR spectroscopy in pediatrics

Penicillium crustosum is common in food and feed both in subtropical and temperate regions. Recently, it has also been found occurring frequently in glacier ice, sea ice and sea water of Arctic regions of Svalbard. The aim of the study was to compare isolates of the same fungal species from widely different habitats and geographic regions to see if the nutritional physiology and the profile of secondary metabolites were consistent or depended on the isolation source. All 121 strains examined produced the following families of secondary metabolites: penitrems (100%), roquefortines (100%), terrestric acids (99.2%) and viridicatols (100%), whereas 81 of 83 Arctic isolates additionally produced andrastin A. However, only 8 of 38 non-Arctic isolates produced detectable andrastin A. The quantitative profiles of 96 strains were compared using cluster, principal component and correspondence analyses. There was no clear grouping of Arctic versus non-Arctic, creatine ...

2004-12-22

Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ beta chain.

Spectral appearance and concentrations of the most prominent metabolites are affected by brain development. This knowledge is essential for the detection of pathological changes in pediatric patients. This paper discusses specific conditions of MR spectroscopic examination of children and the effects of age on MR spectra quality and quantitation of the studied metabolites. Clinical examples show several diseases that are reflected in changes in "1H MR spectra due to pathological alterations in the biochemical pathways of the observed metabolites. Attention is given to the main metabolites such as N-acetylaspartate, creatine/phosphocreatine, cholines, lactate, inositol, etc.

2008-08-01

Effect of Exogenous Indole-3-Acetic Acid and Indole-3-Butyric Acid on Internal Levels of the Respective Auxins and Their Conjugation with Aspartic Acid during Adventitious Root Formation in Pea Cuttings

The presence of an amino acid other than aspartic acid at position 57 of the HLA-DQ beta chain (non-Asp-57) is highly associated with susceptibility to insulin-dependent diabetes mellitus (IDDM), whereas...Full Text Available

1990-10-01

Characterization of Auxin Conjugates in Arabidopsis. Low Steady-State Levels of Indole-3-Acetyl-Aspartate, Indole-3-Acetyl-Glutamate, and Indole-3-Acetyl-Glucose1

The influence of exogenous indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) on the internal levels of these auxins was studied during the first 4 days of adventitious root formation in cuttings...Full Text Available

1991-07-01

Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules

Amide-linked indole-3-acetic acid (IAA) conjugates constitute approximately 90% of the IAA pool in the dicot Arabidopsis, whereas ester-linked conjugates and free IAA account for approximately...Full Text Available

2000-06-01

The influence of amino acids on the biomineralization of hydroxyapatite in gelatin.

Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of {sup 125}I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10{sup 12} binding sites/mm{sup 2} ECM with an apparent k{sub D} of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 {mu}g/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 {mu}g/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the tetrasaccharide, released the ECM-bound FGF, but there ...

1989-02-21

Fluoride induced changes in protein metabolism in the tissues of freshwater crab Barytelphusa guerini.

The effects of pH on the calcium phosphate phase, of Tris and of amino acids, such as aspartic acid, glutamic acid, and serine on hydroxyapatite formation and morphology, were studied in double diffusion experiments. In this system, hydroxyapatite was only formed when the pH was around 7.4 or higher for the duration of the reaction. A decrease in pH resulted in the transformation of hydroxyapatite to octacalcium phosphate. Amino acids and Tris or the buffering capacity of Tris have an effect on the morphology of the synthetic hydroxyapatite. The presence of the additive results in spheres consisting of needles, blades or plates depending on the reaction system. PMID:12175941

2002-08-30

Stimulation of Erwinia sp. fumarase and aspartase synthesis by changing medium components.

Exposure of the freshwater field crab Barytelphusa guerini to a sublethal concentration of NaF (30 mg litre(-1)) caused significant alterations in protein metabolism. After an exposure time of 15 days, the crab was found to have a marked depletion of total protein and free amino acid content. A significant elevation in transaminases, Aspartate aminotransferase (AAT) and Alanine aminotransferase (ALAT), and Glutamate dehydrogenase (GDH) activities was reflected in the free amino acid levels of the tissues. PMID:15092215

1990-01-01

Kainate-enhanced release of D-(3H)aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital

The optimal concentrations of nutrient medium components, aeration conditions, and pH providing for maximum biomass yields, as well as fumarase and L-aspartase activities, during submerged cultivation of Erwinia sp. were determined. The data showed that different concentrations of carbon source (molasses) and pH of the nutrient medium were required to reach the maximum fumarase and L-aspartase activities. Calculations performed by application of the additive lattice model suggested that the combination of these optimized factors would result in 3.2-, 3.4-, and 3.8-fold increases as compared to the experimental means in Erwinia sp. biomass, and L-aspartase and fumarase activities, respectively. The conditions of the fumaric acid biotransformations into L-malic and L-aspartic acids were optimized on the basis of intact Erwinia sp. cells, a fumarase and L-aspartase producer. In the cases of fumarate transformation into L-malic acid and of fumarate transformation into ...

2005-05-01

Rapamycin (sirolimus) protects against hypoxic damage in primary heart cultures via Na^+/Ca^2^+ exchanger activation

A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-(2,3-3H)aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Subsequently, electrical stimulation of the slices evoked a Ca2+-dependent release of a portion of the D-ASP. Kainic acid (10(-5)-10(-3) M) produced a dose-dependent inhibition of D-ASP uptake. The electrically evoked release of D-ASP was increased 1.6-2.0 fold by 10(-5) and 10(-4)M kainic acid. The kainate-enlarged release was Ca2+-dependent. Dihydrokainic acid, an analogue of kainic acid with little excitatory or toxic action, did not increase D-ASP release but depressed D-ASP uptake. Attempts were made to block the action of kainic acid with baclofen and pentobarbital, compounds which depress the electrically evoked release of L-glutamate (L-GLU) and ...

1983-06-01

British Library Electronic Table of Contents (United Kingdom)

Aims: Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Rapamycin confers preconditioning-like protection against ischemic-reperfusion injury in isolated mouse heart cultures. Our aim was to further define the role of rapamycin in intracellular Ca^2^+ homeostasis and to investigate the mechanism by which rapamycin protects cardiomyocytes from hypoxic damage. Main methods: We demonstrate here that rapamycin protects rat heart cultures from hypoxic-reoxygenation (H/R) damage, as revealed by assays of lactate dehydrogenase (LDH) and creatine kinase (CK) leakage to the medium, by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-d...

2011-01-01

Pretargeted radioimmunotherapy in tumored mice using an in vivo {sup 212}Pb/{sup 212}Bi generator

Improved detection of myocardial infarction with technetium-99m stannous pyrophosphate and serum MB creatine phosphokinase

Objective: Pretargeting is the concept that combines optimal delivery of the antibody and rapid capture and elimination of the radioactivity. In this study, we evaluated the potential of antibody pretargeting to enable the tumor-targeting {sup 212}Pb for in vivo generation of {sup 212}Bi for {alpha} particle radiotherapy. Methods: The {sup 212}Pb/{sup 212}Bi chelate of DOTA-biotin, as well as their {gamma}-emitting analogues, {sup 203}Pb and {sup 205}Bi, was prepared and characterized. The radiolabeled compounds were injected in animals for evaluation of tumor targeting and normal tissue uptake and retention. In the pretargeting protocol, injection of 400 {mu}g of NR-LU-10 antibody-streptavidin conjugate was given at t=0 h, then 100 {mu}g of N-acetyl-galatosamine-biotin clearing agent was injected at t=20-24 h; finally, 1 {mu}g of {sup 212}Pb/{sup 212}Bi-DOTA-biotin was injected 6 h later. Results: Both {sup 203}Pb and {sup 205}Bi-DOTA-biotin were stable for at ...

2005-10-01

Targeting the kynurenine pathway as a potential strategy to prevent and treat Alzheimer's disease

The relative sensitivity and combined value of myocardial technetium-99m stannous pyrophosphate imaging and determinations of serum MB creatine phosphokinase (the ''myocardial'' CPK isoenzyme) in detecting acute myocardial infarction were evaluated in 41 patients with suspected infarction and 23 patients recovering from cardiac surgery. In the patients with suspected infarction, myocardial infarction was confirmed in 25 and was consistently associated with increased serum MB CPK. Abnormal radionuclide images were obtained in 23 of 25 patients (92%)) with definite myocardial infarction and in 2 of 16 patients without confirmed infarction. Although the localization of infarction by imaging correlated well with the localization by electrocardiogram, infarct size estimated by imaging did not correlate well with estimates based on peak total serum CPK activity or serial changes in CPK activity. Serum MB CPK activity increased after cardiac surgery in 6 patients ...

British Library Electronic Table of Contents (United Kingdom)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only...

2011-01-01

Assessment of oral toxicity and safety of 9-cis-UAB30, a potential chemopreventive agent, in rat and dog studies

British Library Electronic Table of Contents (United Kingdom)

9-cis-UAB30 is a potential chemopreventative agent that has been shown to be effective on many different types of tumors. The safety and toxicity of 9-cis-UAB30 had not been previously established. These studies were conducted to evaluate the potential toxicity and pharmacokinetics in a rodent and a nonrodent species for the purpose of investigational new drug submission. Oral gavage administration of 9-cis-UAB30 at the doses 0, 3, 15, and 100 ?mg/kg/day to CD? rats for 28 days showed a dose-dependent (although not dose-proportional) increase in plasma drug levels in week 4. The liver was the target organ for toxicity of 9-cis-UAB30. Hepatomegaly along with increases in serum aspartate-aminotransferase and alkaline-phosphatase levels were seen in rats. Moderate hypoalbuminemia and hyperglo...

2011-01-01

Proton magnetic resonance spectroscopy reflects cellular proliferative activity in astrocytomas

Vibrational spectroscopy of bacteriorhodopsin mutants: light-driven proton transport involves protonation changes of aspartic acid residues 85, 96, and 212

We examined whether proton magnetic resonance spectroscopy (MRS) could provide accurate information on histological grade and cell proliferation in astrocytomas. We studied 23 patients with astrocytomas: five grade II, 10 grade III and eight with grade IV (glioblastoma multiforme). We performed proton MRS and determined the Ki-67 labeling index (LI), a tumour proliferation marker, in the same areas of the astrocytomas, and examined the statistical relationship between proton MRS and Ki-67 LI. The N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline (Cho)-containing compound ratios were always significantly lower and the Cho/Cr ratios significantly higher than those for normal brain. The Cho/Cr ratio correlated positively and the NAA/Cho ratio inversely with Ki-67 LI. These findings suggest that the Cho signal in proton MRS reflects cellular proliferation. In Kaplan-Meier survival analysis, there was no significant difference between high (> 2.0, ...

2000-05-01

Synthesis, structural activity-relationships, and biological evaluation of novel amide-based allosteric binding site antagonists in NR1A/NR2B N-methyl-d-aspartate receptors

Fourier transform infrared (FTIR) difference spectra have been obtained for the bR----K, bR----L, and bR----M photoreactions in bacteriorhodopsin mutants in which Asp residues 85, 96, 115, and 212 have been replaced by Asn and by Glu. Difference peaks that had previously been attributed to Asp COOH groups on the basis of isotopic labeling were absent or shifted in these mutants. In general, each COOH peak was affected strongly by mutation at only one of the four residues. Thus, it was possible to assign each peak tentatively to a particular Asp. From these assignments, a model for the proton-pumping mechanism of bR is derived, which features proton transfers among Asp-85, -96, and -212, the chromophore Schiff base, and other ionizable groups within the protein. The model can explain the observed COOH peaks in the FTIR difference spectra of bR photointermediates and could also account for other recent results on site-directed mutants of bR.

1988-11-15

British Library Electronic Table of Contents (United Kingdom)

The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the...

2009-01-01

1 2 3

Mechanism of enzyme-catalyzed phospho group transfer

The Structure of the Amyloid-[beta] Peptide High-Affinity Copper II Binding Site in Alzheimer Disease

To understand more fully the mechanism of enzyme-catalyzed phospho group transfer, the stereochemical course at phosphorus of four enzymes has been determined. First, using adenosine (..gamma..-(S)-/sup 16/O, /sup 17/O, /sup 18/O)triphosphate as the substrate, the reaction catalyzed by creatine kinase has been found to proceed with overall inversion of configuration at phosphorus. Second, using adenosine (..beta..-(S)-/sup 16/O, /sup 17/O, /sup 18/O)diphosphate as the substrate, the reaction catalyzed by adenylate kinase has been found also to proceed with overall inversion. Third, the reaction catalyzed by phosphoenolpyruvate carboxylase has been studied using ((S/sub p/)-/sup 16/O, /sup 17/O)thiophospoenolpyruvate as the substrate in H/sub 2/ /sup 18/O. Fourth, using adenosine 5'-O-((..gamma..S/sub p/)-..beta gamma..-/sup 17/O,..gamma..-/sup 17/O,/sup 18/O)(3-thiotriphosphate) as the substrate, the reaction catalyzed by pyruvate carboxylase has been ...

1986-01-01

Involvement of a glutamergic mechanism in gamma-dendrotoxin-induced hippocampal neuronal cell loss in the rat.

Neurodegeneration observed in Alzheimer disease (AD) is believed to be related to the toxicity from reactive oxygen species (ROS) produced in the brain by the amyloid-{beta} (A{beta}) protein bound primarily to copper ions. The evidence for an oxidative stress role of A{beta}-Cu redox chemistry is still incomplete. Details of the copper binding site in A{beta} may be critical to the etiology of AD. Here we present the structure determined by combining x-ray absorption spectroscopy (XAS) and density functional theory analysis of A{beta} peptides complexed with Cu{sup 2+} in solution under a range of buffer conditions. Phosphate-buffered saline buffer salt (NaCl) concentration does not affect the high-affinity copper binding mode but alters the second coordination sphere. The XAS spectra for truncated and full-length A{beta}-Cu{sup 2+} peptides are similar. The novel distorted six-coordinated (3N3O) geometry around copper in the A{beta}-Cu{sup 2+} complexes include three histidines: ...

2008-11-03

Biomarkers of fibrosis and impaired liver function in chronic hepatitis C: how well do they predict clinical outcomes?

The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with CGP040116, a N-methyl-D-aspartate (NMDA) receptor antagonist, and in rats bearing a monolateral surgical lesion of the Schaffer collaterals whose terminals originate from CA3 pyramids and release glutamate in the CA1 hippocampal area. Administration of 35 pmol gamma-dendrotoxin elicited in all of the treated animals (n=8) bilateral EEG discharges and damage to the hippocampal formation. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1, CA3 and CA4 pyramidal cell layers. The lowest dose (0.35 pmol; n=4) of the toxin used did not affect EEG activity and failed to cause significant hippocampal cell loss whereas the 3.5 pmol (n=6) dose caused EEG seizures and hippocampal cell ...

2004-03-01

DEFF Research Database (Denmark)

PURPOSE OF REVIEW: To review the recent literature on the prognostic value of biomarkers of liver fibrosis and impaired liver function in patients with chronic hepatitis C with or without HIV coinfection. RECENT FINDINGS: A combination of standard blood tests seems to be useful in identifying patients at risk of liver-related complications. Findings from studies investigating the validity of the Model for End-Stage Liver Disease (MELD) score in HIV-infected liver transplant candidates are conflicting. Two large studies of HIV/hepatitis C virus (HCV) coinfected patients have shown that plasma levels of the fibrosis marker hyaluronic acid are a strong predictor of clinical complications. A smaller study found hyaluronic acid and two other fibrosis tests, aspartate aminotransferase-to-platelet ratio index (APRI) and Fib-4, to be independent predictors of mortality when included in models with the MELD or the Child-Pugh-Turcotte scores. SUMMARY: Although the data are ...

2010-01-01

Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

Developments of PET radioligands for NMDA receptors

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase ...

2009-08-15

Heated lipiodol as an embolization agent for transhepatic arterial embolization in VX2 rabbit liver cancer model

Aim: There has been a great demand for developments of the radioligands to visualize the N-methyl-D-aspartate (NMDA) receptors by PET/SPECT. We have recently synthesized two C-11 labeled antagonists for the glycine-binding site on NMDA receptors. The aim of this work is to examine for their in vitro and in vivo binding characteristics, and to evaluate their potentials as PET radioligands for the NMDA receptors. Materials and methods: Two C-11 labeled 4-hydroxy-2-quinolones (1 and 2) were synthesized by conventional methylation of the corresponding phenols with ["1"1C]methyl iodide. In vitro and ex vivo quantitative autoradiographs with imaging plate, as well as animal PET, were employed in order to evaluate their in vitro and in vivo binding to the NMDA receptors. Results: The compound 1 showed the specific binding to rat brain slices with higher localization in the hippocampus and cerebral cortex than in the cerebellum. Both glycine antagonists and agonists ...

2002-09-01