比企 能之

Amyloid beta proteins (Aβ) in the brain are the main cause of Alzheimer's disease. Peripheral administration of Aβ-binding substances, which may act as a sink for Aβ from the brain, has been reported to reduce brain Aβ. We previously found C16-cellulose beads had high Aβ-removal activity in vitro. In this study, we investigated the optimum surface properties of adsorbents for removal of Aβ in vitro and in humans. Batch analysis was performed with porous cellulose beads or silica beads with or without 2-22 methylene groups. Aβ-removal activity of C16-cellulose beads increased with increasing alkyl chain length. In contrast, with cellulose the amount of Aβ removed by the silica beads decreased with increasing alkyl chain length. Cellulose beads with 16 or 22 methylene groups were best (over 99 % removal) among all the beads tested (p ≤ 0.01). The adsorbent surfaces were analyzed by near-infrared spectroscopy, which revealed that the optimum beads had a sufficiently hydrophobic surface with an appropriate amount of adsorbed water accessible on the surface. Aβ removal efficiency by C16-cellulose beads was investigated for 5 renal failure patients on hemodialysis, resulting in 51.1 ± 6.6 % for Aβ1-40 and 43.8 ± 4.5 % for Aβ1-42 (p ≤ 0.01). In conclusion, cellulose beads with 16 or 22 methylene groups and an appropriate amount of adsorbed water were the optimum Aβ adsorbents. The device with C16-cellulose beads had high Aβ removal activity in humans. These adsorbents might be useful for Alzheimer's disease therapy. © 2012 The Japanese Society for Artificial Organs.

To clarify the therapeutic impact of tonsillectomy and combined therapies of tonsillectomy plus steroid on the long-term prognosis of immunoglobulin A nephropathy (IgAN). A retrospective study was conducted on 208 patients with IgAN between 1986 and 2009. According to the strategies for treatments, patients were divided into four groups: tonsillectomy and steroid pulse (TSP, n = 47), tonsillectomy and oral steroid (TOS, n = 33), tonsillectomy alone (T, n = 56), and N group (no particular therapy, n = 72). Multivariate analysis based on the Cox's regression model was used to assess the relative risk of reaching the outcome of doubling creatinine based on the influence of baseline prognostic factors. The mean observation periods were 53.8 months in the TSP group, 122.0 months in the TOS group, 102.9 months in the T group, and 84.6 months in the N group. During an observation period, serum creatinine levels doubled as follows: one in the TSP group (2.1 %), two in the TOS group (6.1 %), five in the T group (8.9 %), histological severity, and 22 in the N group (30.6 %). The Cox's regression proportional hazard model showed that gender, age, histological activity, dialysis induction risk and therapy were associated with doubling creatinine levels. Hazard ratios (95 % CI) and (P value) in T, TOS, and TSP groups versus N were 0.314 (0.11-0.93, P = 0.037), 0.213 (0.04-1.10, P = 0.065), and 0.032 (0.00-0.28, P = 0.002), respectively. A combination therapy of tonsillectomy and steroid pulse had the most significant therapeutic impact compared to other therapies.

The pathological changes of Alzheimer's disease include the deposition of amyloid beta protein (A beta) as senile plaques in the brain. We hypothesized that the rapid removal of A beta s from the blood may act as a peripheral A beta drainage sink from the brain. In this study, the plasma A beta concentrations and the cognitive functions were investigated for in 57 patients on hemodailysis (69.4 +/- A 3.8 years), 26 renal-failure patients without hemodialysis (66.6 +/- 14.7 years), and 17 age-matched healthy controls (66.6 +/- 4.1 years). The concentrations of plasma A beta s increased along with the decline of renal functions. Moreover, the renal-failure patients without hemodialysis and with poorer renal functions showed lower cognitive functions. The plasma concentrations of A beta(1-42) correlated with serum creatinine (P < 0.001) and Mini-Mental-State Examination scores (P = 0.017). The dialyzers effectively removed A beta s in the blood during hemodialysis sessions. The plasma A beta concentrations showed steady or slightly decreasing along with duration of hemodialysis. The total amount of A beta s removed during a hemodialysis session was calculated to be comparable to the A beta s dissolved in the blood and the cerebrospinal fluid. The MMSE scores of the hemodialysis patients showed no clear decrease in longer hemodialysis duration. Therefore, the therapeutic approach for Alzheimer's disease by removing A beta s from the blood is worthy of further investigation, including whether or not A beta s in the brain decrease.

Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-gamma agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism.