Reduced MTR in the corticospinal tract and normal T2 in amyotrophic lateral sclerosis

The objective of this study was to test the hypothesis that magnetization transfer ratios (MTR) are decreased in the corticospinal tract of patients with amyotrophic lateral sclerosis (ALS); to determine if T2 is increased in corticospinal tract or reduced in motor cortex in ALS; to determine if corticospinal tract MTR correlates with a clinical measure of motor neuron function in ALS. Ten ALS patients and 17 age-matched controls were studied. Double spin echo MRI and 3D gradient echo MRI with and without off-resonance saturation were acquired on each subject. 3D data sets were coregistered and resliced to match the spin echo data set. MTR was calculated for corticospinal and non-corticospinal tract white matter. T2 was calculated for corticospinal and non-corticospinal tract white matter, motor cortex and non-motor cortex. MTR was reduced by 2.6% (p < .02) in corticospinal, but not in non-corticospinal, tract white matter in ALS. There was no difference in T2 in any brain region. The correlation between a clinical measure of motor neuron function and corticospinal tract MTR was statistically significant. These findings are consistent with the known pathology in ALS and suggest that MTR is more sensitive than T2 for detecting involvement of the corticospinal tract. Quantitative MTR of the corticospinal tract may be a useful, objective marker of upper motor neuron pathology in ALS.     

Aragonite Formation in the Chiton (Mollusca) Girdle

In the chitons (Polyplacophora, Mollusca), the body is not entirely protected by the shell. Mineralized spicules or scales often, but not always, decorate the exposed part of the girdle. Here, we report a study on the composition and ultrastructural organization of these mineralized skeletal parts in four different chiton species. In all specimens, the mineral component (97–98 wt‐%) is aragonite, and the organic matrix (2–3 wt‐%) consists of highly glycosylated proteins. X‐Ray diffraction and scanning electron microscopy show that the organic matrix fibers are aligned, morphologically and crystallographically, with the prismatic aragonite crystals. Matrix and mineral are thus clearly related. The matrix–mineral composite bundles are, however, assembled in the various skeletal parts examined with widely different degrees of alignment and order. In the same organism, the crystals are aligned within a range of ±15° in one type of spicule, while they are randomly oriented in another type. The wide heterogeneity in shape, density, and ultrastructure suggests that the girdle mineralized tissues do not fulfill a fundamental role necessary for the survival of the organism. This, together with the lack of chitin in the organic matrix, supports the hypothesis that they evolved separately from the other chiton mineralized tissues, namely the shell plates and teeth.     

Die Abtrennung von Chroms?ure mit Hilfe von Ionenaustauschern; Resistenzgrenzen

Zusammenfassung Die Abscheidung eines starken überschusses von ChromsÄure, die bei der Bestimmung anderer Kationen empfindlich stören würde, kann in sehr einfacher Weise mittels Ionenaustauscher erfolgen. Dazu müssen stark basische, chromsÄurebestÄndige Ionenaustauscher verwendet werden. Der Austauscher Amberlite IRA 410 erweist sich bis zu Konzentrationen von etwa 10 g CrO₃ im Liter als vollkommen bestÄndig. Auch bei stark verlangsamtem Durchlauf wird kein Angriff der ChromsÄure und Reduktion zu Cr³⁺ beobachtet. Bei lÄngerem Stehen des mit ChromsÄure beladenen Austauschers findet dagegen eine teilweise Reduktion des Chromates statt, so da\ es sich empfiehlt, den Austauscher jeweils unmittelbar nach Gebrauch wieder zu regenieren.     

An enzyme library approach to biocatalysis: development of nitrilases for enantioselective production of carboxylic acid derivatives

The discovery, from Nature, of a large and diverse set of nitrilases is reported. The utility of this nitrilase library for identifying enzymes that catalyze efficient production of valuable hydroxy carboxylic acid derivatives is demonstrated. Unprecedented enantioselectivity and substrate scope are highlighted for three newly discovered and distinct nitrilases. For example, a wide array of (R)-mandelic acid derivatives and analogues were produced with high rates, yields, and enantiomeric excesses (95-99% ee). We also have found nitrilases that provide direct access to (S)-phenyllactic acid and other aryllactic acid derivatives, again with high yields and enantioselectivities. Finally, different nitrilases have been discovered that catalyze enantiotopic hydrolysis of 3-hydroxyglutaronitrile to afford either enantiomer of 4-cyano-3-hydroxybutyric acid with high enantiomeric excesses (>95% ee). The first enzymes are reported that effect this transformation to furnish the (R)-4-cyano-3-hydroxybutyric acid which is a precursor to the blockbuster drug Lipitor.     

Method of analysis of the new cardiotonic agent, MDL 19,205, in plasma and urine and its application in a dog pharmacokinetic study

A high-performance liquid chromatographic method has been developed for the analysis of plasma and urine concentrations of a new cardiotonic agent, MDL 19,205 (I). This procedure was utilized to study the pharmacokinetics of I in beagle dogs. The results of the dog study show that the compound is completely and rapidly absorbed. Plasma concentrations fell in a monoexponential manner with a half-life of about 1.3 h which was unaffected by dose in the range 3-30 mg/kg. Urinary excretion of unchanged I accounts for about one-half of the dose and is essentially complete in 24-48 h.