Serum pro-hepcidin as an indicator of iron status in dialysis patients.

Hepcidin has recently been recognized as a hormone essential to the negative regulation of iron. Synthesis of hepcidin is increased by iron overload or inflammation, and decreased by iron deficiency, anemia and erythropoietin. Dialysis patients frequently suffer the effects of both hepcidin increasing and decreasing factors. In this study, we investigated, for the first time, pro-hepcidin in dialysis patients while minimizing or manipulating these factors. We measured the serum pro-hepcidin in 23 hemodialysis patients without inflammation (the HD group) and 10 age-matched healthy volunteers. Those patients in the HD group were assigned to an iron-deficiency group (the ID group) or a non-iron deficiency subgroup (non-ID group). The HD group was followed up for two months. Iron therapy was performed in the ID group during the follow-up period. At the end of this time we evaluated the influence of iron therapy. Pro-hepcidin was similar in the HD groups and the healthy controls (295.1 [241.9, 413.7] vs. 301.7 [280.5, 383.5] ng/mL; not significant) despite the presence of hepcidin-decreasing factors. Pro-hepcidin in the ID group was significantly lower than in the non-ID group (262.6 [233.1, 295.1] vs. 359.2 [282.3, 446.5] ng/mL; P < 0.05). In patients newly acquiring ID during follow-up without iron supplementation, pro-hepcidin fell significantly (from 444.7 [389.4, 470.1] to 299.8 [233.4, 330.4] ng/mL; P < 0.05). Pro-hepcidin also showed an increase after ID was treated with iron administration (from 246.9 [205.5, 329.1] to 344.6 [290.1, 377.9] ng/mL; not significant). Pro-hepcidin could serve as a marker for functional iron deficiency and disordered iron utilization in HD. Underlying mechanisms and improvements in measurement techniques will require additional investigation.

[Complete histological response in gastric cancer stage IV after neoadjuvant chemotherapy including S-1 combined with CDDP--report of a case].

A 60-year-old man complaining of black stool, body weight loss, and anemia, was examined and diagnosed with advanced gastric cancer (M, type 3, por 2, cT3, cN3, cH0, cP0, cM0, cStage IV). A poor prognosis was predicted, yet we tried neoadjuvant chemotherapy (NAC) expecting downstaging of the tumor. Considering the efficacy and safety, we chose S-1+CDDP as the NAC regimen. S-1 (120 mg/day) was administered orally for 21 days, followed by CDDP (75 mg/body) div on day 8. Distal partial gastrectomy and lymph node dissection (D2) were performed, with Billroth I reconstruction. Histological examination of the resected stomach and lymph nodes revealed no residual cancer cells, suggesting complete histological remission (grade 3) according to the Japanese classification of gastric carcinoma.

Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass.

The total mass of islets of Langerhans is reduced in individuals with type 2 diabetes, possibly contributing to the pathogenesis of this condition. Although the regulation of islet mass is complex, recent studies have suggested the importance of a signaling pathway that includes the insulin or insulin-like growth factor-1 receptors, insulin receptor substrate and phosphatidylinositol (PI) 3-kinase. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a serine-threonine kinase that mediates signaling downstream of PI 3-kinase. Here we show that mice that lack PDK1 specifically in pancreatic beta cells (betaPdk1-/- mice) develop progressive hyperglycemia as a result of a loss of islet mass. The mice show reductions in islet density as well as in the number and size of cells. Haploinsufficiency of the gene for the transcription factor Foxo1 resulted in a marked increase in the number, but not the size, of cells and resulted in the restoration of glucose homeostasis in betaPdk1-/- mice. These results suggest that PDK1 is important in maintenance of pancreatic cell mass and glucose homeostasis.