Motoneurons require neurotrophic factors for their survival and axonal projection during development, as well as nerve regeneration. By using the axotomy-induced neuronal death paradigm and adenovirus-mediated gene transfer, we attempted to gain insight into the functional significances of major growth factor receptor downstream cascades, Ras-extracellular signalregulated kinase (Ras-ERK) pathway and phosphatidylinositol-3 kinase-Akt (PI3K-Akt) pathway. After neonatal hypoglossal nerve transection, the constitutively active Akt-overexpressing neurons could survive as well as those overexpressing Bcl-2, whereas the constitutively active ERK kinase (MEK)-overexpressing ones failed to survive. A dominant negative Akt experiment demonstrated that inhibition of Akt pathway hastened axotomy-induced neuronal death in the neonate. In addition, the dominant active Akt-overexpressing adult hypoglossal neurons showed accelerated axonal regeneration after axotomy. These results suggest that Akt plays dual roles in motoneuronal survival and nerve regeneration in vivo and that PI3K-Akt pathway is probably more vital in neuronal survival after injury than Ras-ERK pathway.

Hypoxia-inducible factor prolyl-hydroxylase inhibitors belong to a new class of orally administered drugs for treating anemia in patients with chronic kidney disease (CKD). The prevalence of hypothyroidism is disproportionately high in patients with CKD on hemodialysis. We report a rapid suppression of thyroid stimulating hormone (TSH) and decrease in free T3 and free T4 levels after switching from darbepoetin alfa to roxadustat in a hemodialysis patient with hypothyroidism on levothyroxine therapy. This was reversed after stopping roxadustat. Roxadustat has structural similarity with T3 and is a selective activating ligand for thyroid hormone receptor-β (THRβ) possibly suppressing TSH release.

Serum amino acid patterns in patients with different types of hepatic encephalopathy were investigated. Marked elevations in most of serum amino acids observed in untreated patients with acute type of fulminant hepatitis were not remarkable in the patients who have already treated; particularly branched chain amino acids (BCAA), phenylalanine and tyrosine were much lower in the latter group. However, elevation of serum methionine levels and lower ratio of BCAA/(phenylalanine + tyrosine) were similarly observed in both groups. In encephalopathic patients with decompensated cirrhosis, many amino acids such as phenylalanine, tyrosine and methionine were elevated with a slight depressed levels of serum BCAA. Highly significant decrease in serum BCAA levels and no elevation of phenylalanine and methionine with a minimal increase of tyrosine were observed in patients with chronic type of hepatic encephalopathy; other amino acids except for glutamine and arginine were much lower as compared to those in decompensated cirrhotics and even to the control values.

Therapy with 20 mg/day esomeprazole appears to be efficacious for improving disease-specific QOL and GERD symptoms in Japanese patients on maintenance hemodialysis.

SUMMARYNumerical analysis with the Boundary Element Method (BEM) has been used more and more in various engineering fields in recent years. In numerical techniques, however, there are some problems which have not been fully solved even now. The most essential one is the drop in the accuracy of results for internal points near the boundary of the structure, where the singularity of integrands in the boundary integral equation is too strong to be evaluated with the normal numerical method. For the boundary integral equation of stress, this problem became more serious, and the accuracy can be improved only partly, even though very refined boundary elements are used.In this paper, the boundary integral equation is newly formulated using a relative quantity of displacement. In this way, the singularity of boundary integrals is reduced by the order of l/r, and the accuracy of solution is improved significantly. Furthermore, in order to integrate it more accurately, two kinds of numerical integral methods are newly developed. By using these methods, both displacement and stress can be obtained with excellent accuracy at almost any point in the structure without any numerical difficulty, although the discretization may be comparatively coarse. The generality and practicability of the present formulation and integral methods are confirmed through some examples of three dimensional elastic problems.