Gastrointestinal Tolerability and Absorption of R- Versus R,S-Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial

We compared the gastrointestinal (GI) tolerability and assessed for bioequivalent absorption of R-lipoic acid (LA) in people with progressive multiple sclerosis (MS) in a single-center, double-blind, randomized crossover trial. Participants randomly assigned to formulation sequence took 600Â mg of R-LA or 1200Â mg of a 1:1 racemic R,S-LA mixture in single daily doses for 7 to 10 days, underwent a washout of at least 7 days, and then took the other form of LA for 7 to 10 days. At the end of each period on LA, GI symptoms were assessed with GI questions from the Monitoring of Side Effects Scale. Serum LA concentrations were measured before and 60, 90, 120, 180, and 240 minutes after the first and last day\u27s dose of each form of LA to derive an area under the plasma concentration-time curve (AUC) and maximum serum concentration (Cmax ). Twenty participants enrolled (12 women; 15 secondary progressive MS, 5 primary progressive MS; mean age, 59.6 years). Two withdrew early due to symptoms while taking R,S-LA, and one withdrew early while taking R-LA. The mean GI Monitoring of Side Effects Scale score was 1.7 points lower on R-LA than on R,S-LA (P = .069), and there were fewer reports of each GI side effect when taking the R-LA than the R,S-LA (31 vs 60; P = .025). The AUC and Cmax for R-LA were bioequivalent for the 2 formulations (90% confidence intervals 97.4% to 99.3% for AUC and 93.4% to 98.2% for Cmax ). This study supports that in people with progressive MS, there is better GI tolerability and bioequivalent serum absorption of R-LA when 600Â mg of R-LA is taken as R-LA alone than when taken in a 1:1 racemic R,S-LA mixture

Microearthquake seismicity at the intersection between the Kazerun fault and the Main Recent Fault (Zagros, Iran)

International audienceSeismicity and fault plane solutions of earthquakes at the intersection between the Main Recent Fault (a right-lateral strike-slip fault that bounds the Zagros to the NE) and the Kazerun Fault system (another right-lateral zone that crosses the Zagros) show slip to be partitioned into nearly pure strike-slip at shallow depths and nearly pure thrust slip below 12 km. Such slip partitioning is commonly observed where oblique convergence occurs, but in general faults of different styles lie adjacent to one another, not at different depths with one below the other. We provide evidence for this partitioning in a microearthquake study in which we deployed a temporary network of 29 seismographs for 7 weeks. We located no activity north of the Main Zagros Reverse Fault (MZRF), which separates the Zagros fold belt from Central Iran. Most earthquakes occurred between the northern termination of the Kazerun Fault and the MZRF, but not near to known major faults. Activity is limited to the upper crust, between 2 and 16 km. Most of the focal mechanisms show strike-slip faulting, dextral if the NS striking plane is the active plane, but a few for the deepest events show reverse faulting, distributed between the Kazerun Fault and the MZRF, with P-axis trending consistently ~NS. This partitioning of the deformation with depth suggests that the brittle upper crust deforms by slip on pre-existing faults that strike obliquely but that the lower crust accommodates the shortening by reverse faulting. We infer that the deformation in the upper part of the crust reflects a stiffer medium in which pre-existing faults localize the deformation. The largest event recorded during this experiment, located at the same place as the destructive 1977 Naghan earthquake (Mw ~5.9, 348 victims), shows reverse faulting, likely related to the Dopolan High Zagros Fault. The crustal thickness deduced from receiver function analysis does not show a marked difference across the Kazerun fault, which suggests a pure strike-slip motion on the fault

Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency

Genes have a major role in the control of high-density lipoprotein (HDL) cholesterol (HDL-C) levels. Here we have identified two Tangier disease (TD) families, confirmed 9q31 linkage and refined the disease locus to a limited genomic region containing the gene encoding the ATP-binding cassette transporter (ABC1). Familial HDL deficiency (FHA) is a more frequent cause of low HDL levels. On the basis of independent linkage and meiotic recombinants, we localized the FHA locus to the same genomic region as the TD locus. Mutations in ABC1 were detected in both TD and FHA, indicating that TD and FHA are allelic. This indicates that the protein encoded by ABC1 is a key gatekeeper influencing intracellular cholesterol transport, hence we have named it cholesterol efflux regulatory protein (CERP