ABSTRACT
Our aim was to determine changes in free amino acid (FAA) and dipeptide (DP) concentrations in probable Alzheimer's disease (pAD) subjects compared with control (CT) subjects using liquid chromatography and electrospray ionization tandem mass spectrometry (LCMS2). We recruited gender- and age-matched study participants based on neurological and neuropsychological assessments. We measured FAAs and DPs in cerebrospinal fluid (CSF), plasma and urine using LCMS2 with selected reaction monitoring (SRM). Imidazole-containing FAAs (histidine, methyl-histidine), catecholamines (L-DOPA and dopamine), citrulline, ornithine, glycine and antioxidant DPs (carnosine and anserine) accounted for the major changes between CT and pAD. Carnosine levels were significantly lower in pAD (328.4 +/- 91.31 nmol/dl) than in CT plasma (654.23 +/- 100.61 nmol/dl). In contrast, L-DOPA levels were higher in pAD (1400.84 +/- 253.68) than CT (513.10 +/- 121.61 nmol/dl) plasma. These data underscore the importance of FAA and DP metabolism in the pathogenesis of AD. Since our data show changes in antioxidants, neurotransmitters and their precursors, or FAA associated with urea metabolism in pAD compared with CT, we propose that manipulation of these metabolic pathways may be important in preventing AD progression.
Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/urine , Amino Acids/blood , Amino Acids/cerebrospinal fluid , Amino Acids/urine , Dipeptides/blood , Dipeptides/cerebrospinal fluid , Dipeptides/urine , Aged , Antioxidants/chemistry , Carnosine/analysis , Chromatography, Liquid , Disease Progression , Female , Histidine/chemistry , Humans , Male , Middle Aged , Neuropsychological Tests , Spectrometry, Mass, Electrospray IonizationABSTRACT
Our aim was to develop a liquid chromatography and electrospray ionization tandem mass spectrometry (LCMS2) method to measure free amino acid (FAA) and dipeptide (DP) concentrations in biological fluids. We synthesized chloroformate derivatives of FAA and DP, identified the major precursor ions and used LCMS2 to obtain the most intense product ions. Using serial dilutions of unlabeled and labeled standards ([2H3]-L-Dopa, homoarginine, homophenylalanine, [15N]-Glutamine and [2H3]-methionine), we observed linear relationships in MS response that we used to calculate the amounts of FAA and DP in biological samples. This method is sensitive with a limit of detection (LOD) for most of the FAAs and DPs tested in the 0.05-1 pmol range and is linear over 3-5 orders of magnitude when many metabolites were measured simultaneously. Reproducibility and between run or daily variations were <10% for most FAAs and DPs. We applied this method to human samples and quantitatively measured 21 FAAs and 2 DPs in 200 microl CSF, 31 FAAs and 6 DPs in 100 microl plasma, and 23 FAAs and 5 DPs in 200 microl urine. These data demonstrate the potential for using LCMS2 to discover changes in FAA and DP metabolic pathways that occur during disease pathogenesis.
Subject(s)
Amino Acids/blood , Amino Acids/cerebrospinal fluid , Amino Acids/urine , Chromatography, Liquid/methods , Dipeptides/blood , Dipeptides/cerebrospinal fluid , Dipeptides/urine , Spectrometry, Mass, Electrospray Ionization/methods , Body Fluids/metabolism , Cerebrospinal Fluid/metabolism , Humans , Ions , Levodopa/pharmacology , Mass Spectrometry/methods , Reproducibility of Results , Sensitivity and Specificity , Time FactorsABSTRACT
The purpose of this study was to clarify the available literature and study the influence of ultrasound on the conduction velocity and amplitude of evoked sensory potentials in the median nerve. Thirteen subjects were assigned to either Experimental or Control Groups for ultrasound or placebo treatments. We compared sensory-nerve conduction velocity in the median nerve after 10 minutes of ultrasound treatment at three intensity levels (0.5, 1.0, and 1.5 W/cm2) with sensory-nerve conduction velocity in the median nerve after 10 minutes of placebo ultrasound treatment (0.0 W/cm2). No significant differences were noted between groups at any of the three ultrasound intensity levels, nor were the interaction effects significant. A hypothetical model, based on the available literature, proposes that ultrasound-induced changes in sensory-nerve conduction velocity may not progress in a direct linear fashion relative to the duration of treatment.
Subject(s)
Median Nerve/physiology , Neural Conduction , Ultrasonic Therapy , Adult , Electromyography , Evoked Potentials , Female , Humans , MaleABSTRACT
It has been suggested that the health care system might be best assessed by the patient's own attitudes concerning the quality of service rendered (Wood, 1974). The purpose of this study is to analyze the psychosocial quality of the health service/hospital system in the greater Iowa City, Iowa area, and the relative emotional stability of hospitalized patients in several local hospitals. Specifically, a survey of 20 questions has been developed to assess (1) patient's attitudes and psychosocial outlook, (2) patient's self-perception. (3) situation generated feelings and (4) family/support group generated feelings. The comparative results of this experiment may indicate (1) the overall emotional status of hospitalized patients relative to non-hospitalized individuals and (2) the general psychosocial effectiveness of the hospital system (in the greater Iowa City. Iowa area). This information may be useful to both the medical/allied-health student and the inexperienced clinician, relative to various preconceived notions concerning the emotional state of hospitalized patients, in general.
