Lang, Florian, Gillian L. Busch, Markus Ritter, Harald Volkl, Siegfried Waldegger, Erich Gulbins, and Dieter Haussinger. Functional Significance of Cell Volume Regulatory Mechanisms. Physiol. Rev. ...

Functional Significance of Cell Volume Regulatory Mechanisms

Proton NMR chemical shift and J-coupling values are presented for 35 metabolites that can be detected by in vivo or in vitro NMR studies of mammalian brain. Measurements were obtained using high-field NMR spectra of metabolites in solution, under conditions typical for normal physiological temperature and pH. This information is presented with an accuracy that is suitable for computer simulation of metabolite spectra to be used as basis functions of a parametric spectral analysis procedure. This procedure is verified by the analysis of a rat brain extract spectrum, using the measured spectral parameters. In addition, the metabolite structures and example spectra are presented, and clinical applications and MR spectroscopic measurements of these metabolites are reviewed.

http://pfeifer.phas.ubc.ca/refbase/files/Govindaraju-NMRBiomed-2000-13-129.pdf

Proton NMR chemical shifts and coupling constants for brain metabolites.

Muscle fatigue encompasses a class of acute effects that impair motor performance. The mechanisms that can produce fatigue involve all elements of the motor system, from a failure of the formulation of the descending drive provided by suprasegmental centers to a reduction in the activity of the contractile proteins. We propose four themes that provide a basis for the systematic evaluation of the neural and neuromuscular fatigue mechanisms: 1) task dependency to identify the conditions that activate the various mechanisms; 2) force-fatigability relationship to explore the interaction between the mechanisms that results in a hyperbolic relationship between force and endurance time; 3) muscle wisdom to examine the association among a concurrent decline in force, relaxation rate, and motor neuron discharge that results in an optimization of force; and 4) sense of effort to determine the role of effort in the impairment of performance. On the basis of this perspective with an emphasis on neural mechanisms, we suggest a number of experiments to advance our understanding of the neurobiology of muscle fatigue.

Neurobiology of muscle fatigue.

http://n-acetylaspartate.com/PDF%20files/NAA%20Review.pdf

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Alzheimer's disease is the most common cause of dementia in elderly people. Research into Alzheimer's disease therapy has been at least partly successful in terms of developing symptomatic treatments, but has also had several failures in terms of developing disease-modifying therapies. These successes and failures have led to debate about the potential deficiencies in our understanding of the pathogenesis of Alzheimer's disease and potential pitfalls in diagnosis, choice of therapeutic targets, development of drug candidates, and design of clinical trials. Many clinical and experimental studies are ongoing, but we need to acknowledge that a single cure for Alzheimer's disease is unlikely to be found and that the approach to drug development for this disorder needs to be reconsidered. Preclinical research is constantly providing us with new information on pieces of the complex Alzheimer's disease puzzle, and an analysis of this information might reveal patterns of pharmacological interactions instead of single potential drug targets. Several promising randomised controlled trials are ongoing, and the increased collaboration between pharmaceutical companies, basic researchers, and clinical researchers has the potential to bring us closer to developing an optimum pharmaceutical approach for the treatment of Alzheimer's disease.

/pdf/alzheimer-s-disease-clinical-trials-and-drug-development-46wp4j0jf2.pdf

Alzheimer's disease: clinical trials and drug development

Cerebral metabolite concentrations and water content were measured by means of localized proton magnetic resonance spectroscopy in 50 children, while metabolite peak ratios in short echo time spectra were evaluated in 173 examinations. Normative curves for normal development were established for two cerebral locations. The current report presents the first study of absolute metabolite concentrations and T1- and T2- relaxation as a function of age. Myo-inositol was found dominating the spectra at birth (12 mmoles/kg), while choline is responsible for the strongest peak in older infants (2.5 mmoles/kg). Creatine and N-acetyl groups are at significantly lower concentrations in the neonate than in the adult (Cr: 6, NA: 5 mmoles/kg). NA and Cr are determined by gestational age, whereas the concentration of ml correlates best with postnatal age. Quantitative 1H MRS is expected to be of particular value in diagnosis and monitoring of pathology in infants, since metabolite ratios are often misleading.

Development of the human brain: In vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy

Absolute Quantitation of Water and Metabolites in the Human Brain. II. Metabolite Concentrations

Absolute Quantitation of Water and Metabolites in the Human Brain. I. Compartments and Water

McARDLE'S syndrome,1 an inborn error of metabolism caused by a lack of glycogen phosphorylase activity in skeletal muscle, is a recessive condition of some rarity.2 Nevertheless, it poses a constan...

Brian D. Ross

Papers

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Development of the human brain: In vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy

Absolute Quantitation of Water and Metabolites in the Human Brain. II. Metabolite Concentrations

Absolute Quantitation of Water and Metabolites in the Human Brain. I. Compartments and Water

Examination of a Case of Suspected McArdle's Syndrome by 31P Nuclear Magnetic Resonance