The clinical use of nuclear magnetic resonance spectroscopy for studying human muscle metabolism.

Nuclear magnetic resonance (NMR) imaging has recently become an accepted technique in the medical practitioner's armory (38). NMR spectroscopy (44) is a subtly different application of the same physical principles underlying NMR imaging, but the clinical potential for this modality is currently still under evaluation. The most important application of clinical NMR spectroscopy is for the nonin-vasive monitoring of changes in metabolite levels and intracellular pH of intact tissues during physiological stress or in response to pharmacological agents or disease. The 31phosphorus (31P) nucleus has been the most commonly investigated in muscle disease (39) but the applications of proton (1H), (4,5,8) and 13carbon (13C), (2,7) are currently being explored

Modeling Electrically Active Viscoelastic Membranes

The membrane protein prestin is native to the cochlear outer hair cell that is crucial to the ear's amplification and frequency selectivity throughout the whole acoustic frequency range. The outer hair cell exhibits interrelated dimensional changes, force generation, and electric charge transfer. Cells transfected with prestin acquire unique active properties similar to those in the native cell that have also been useful in understanding the process. Here we propose a model describing the major electromechanical features of such active membranes. The model derived from thermodynamic principles is in the form of integral relationships between the history of voltage and membrane resultants as independent variables and the charge density and strains as dependent variables. The proposed model is applied to the analysis of an active force produced by the outer hair cell in response to a harmonic electric field. Our analysis reveals the mechanism of the outer hair cell active (isometric) force having an almost constant amplitude and phase up to 80 kHz. We found that the frequency-invariance of the force is a result of interplay between the electrical filtering associated with prestin and power law viscoelasticity of the surrounding membrane. Paradoxically, the membrane viscoelasticity boosts the force balancing the electrical filtering effect. We also consider various modes of electromechanical coupling in membrane with prestin associated with mechanical perturbations in the cell. We consider pressure or strains applied step-wise or at a constant rate and compute the time course of the resulting electric charge. The results obtained here are important for the analysis of electromechanical properties of membranes, cells, and biological materials as well as for a better understanding of the mechanism of hearing and the role of the protein prestin in this mechanism

Why pharmacokinetic differences among oral triptans have little clinical importance: a comment

Triptans, selective 5-HT1B/1D receptor agonists, are specific drugs for the acute treatment of migraine that have the same mechanism of action. Here, it is discussed why the differences among kinetic parameters of oral triptans have proved not to be very important in clinical practice. There are three main reasons: (1) the differences among the kinetic parameters of oral triptans are smaller than what appears from their average values; (2) there is a large inter-subject, gender-dependent, and intra-subject (outside/during the attack) variability of kinetic parameters related to the rate and extent of absorption, i.e., those which are considered as critical for the response; (3) no dose-concentration–response curves have been defined and it is, therefore, impossible both to compare the kinetics of triptans, and to verify the objective importance of kinetic differences; (4) the importance of kinetic differences is outweighed by non-kinetic factors of variability of response to triptans. If no oral formulations are found that can allow more predictable pharmacokinetics, the same problems will probably also arise with new classes of drugs for the acute treatment of migraine

Orientation and dynamics of transmembrane peptides: the power of simple models

In this review we discuss recent insights obtained from well-characterized model systems into the factors that determine the orientation and tilt angles of transmembrane peptides in lipid bilayers. We will compare tilt angles of synthetic peptides with those of natural peptides and proteins, and we will discuss how tilt can be modulated by hydrophobic mismatch between the thickness of the bilayer and the length of the membrane spanning part of the peptide or protein. In particular, we will focus on results obtained on tryptophan-flanked model peptides (WALP peptides) as a case study to illustrate possible consequences of hydrophobic mismatch in molecular detail and to highlight the importance of peptide dynamics for the experimental determination of tilt angles. We will conclude with discussing some future prospects and challenges concerning the use of simple peptide/lipid model systems as a tool to understand membrane structure and function

Photo-tautomerization of acetaldehyde as a photochemical source of formic acid in the troposphere

Organic acids play a key role in the troposphere, contributing to atmospheric aqueous-phase chemistry, aerosol formation, and precipitation acidity. Atmospheric models currently account for less than half the observed, globally averaged formic acid loading. Here we report that acetaldehyde photo-tautomerizes to vinyl alcohol under atmospherically relevant pressures of nitrogen, in the actinic wavelength range, λ = 300–330 nm, with measured quantum yields of 2–25%. Recent theoretical kinetics studies show hydroxyl-initiated oxidation of vinyl alcohol produces formic acid. Adding these pathways to an atmospheric chemistry box model (Master Chemical Mechanism) demonstrates increased formic acid concentrations by a factor of ~1.7 in the polluted troposphere and a factor of ~3 under pristine conditions. Incorporating this mechanism into the GEOS-Chem 3D global chemical transport model reveals an estimated 7% contribution to worldwide formic acid production, with up to 60% of the total modeled formic acid production over oceans arising from photo-tautomerization