Interaction between Mitochondria and the Endoplasmic Reticulum: Implications for the Pathogenesis of Type 2 Diabetes Mellitus

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are closely associated with β-cell dysfunction and peripheral insulin resistance. Thus, each of these factors contributes to the development of type 2 diabetes mellitus (DM). The accumulated evidence reveals structural and functional communications between mitochondria and the ER. It is now well established that ER stress causes apoptotic cell death by disturbing mitochondrial Ca2+ homeostasis. In addition, recent studies have shown that mitochondrial dysfunction causes ER stress. In this paper, we summarize the roles that mitochondrial dysfunction and ER stress play in the pathogenesis of type 2 DM. Structural and functional communications between mitochondria and the ER are also discussed. Finally, we focus on recent findings supporting the hypothesis that mitochondrial dysfunction and the subsequent induction of ER stress play important roles in the pathogenesis of type 2 DM

Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan. Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance. Results. The IC50 values of simvastatin alone and irinotecan alone were 115.4±0.14 μM (r=0.98) and 62.5±0.18 μM (r=0.98) in HT-29 cells without resistance to irinotecan. The IC50 values of these two drugs were 221.9±0.22 μM (r=0.98) and 195.9±0.16 μM (r=0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at 2:1 molar ratio showed the best synergistic interaction. Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer

Volumetric analysis and indocyanine green retention rate at 15 min as predictors of post‐hepatectomy liver failure

AbstractObjectivesThe actual future liver remnant (aFLR) is calculated as the ratio of remnant liver volume (RLV) to total functional liver volume (TFLV). The standardized future liver remnant (sFLR) is calculated as the ratio of RLV to standard liver volume (SLV). The aims of this study were to compare the aFLR with the sFLR and to determine criteria for safe hepatectomy using computed tomography volumetry and indocyanine green retention rate at 15 min (ICG R15).MethodsMedical records and volumetric measurements were obtained retrospectively for 81 patients who underwent right hemi‐hepatectomy for malignant hepatic tumours from January 2010 to November 2013. The sFLR was compared with the aFLR, and a ratio of sFLR to ICG R15 as a predictor of postoperative hepatic function was established.ResultsIn patients without cirrhosis, the sFLR showed a stronger correlation with the total serum bilirubin level than the aFLR (R2 = 0.499 versus R2 = 0.239). Post‐hepatectomy liver failure developed only in the group with an sFLR of <25%, regardless of ICG R15. In patients with cirrhosis, the aFLR and sFLR had no correlation with postoperative total serum bilirubin. An sFLR : ICG R15 ratio of >1.9 showed 66.7% sensitivity and 100% specificity.ConclusionsRegardless of ICG R15, an sFLR of ≥25% in patients without cirrhosis, and an sFLR of ≥25% with an sFLR : ICG R15 ratio of >1.9 in patients with cirrhosis indicate acceptable levels of safety in major hepatectomy

Efficacy and Safety of Cabergoline as First Line Treatment for Invasive Giant Prolactinoma

Although cabergoline is effective in the treatment of micro- and macro-prolactinoma, little is known about its efficacy in the treatment of invasive giant prolactinoma. We investigated the efficacy and safety of cabergoline in 10 male patients with invasive giant prolactinoma. Before treatment, mean serum prolactin level was 11,426 ng/mL (range, 1,450-33,200 ng/mL) and mean maximum tumor diameter was 51 mm (range, 40-77 mm). Three months after initiation of cabergoline treatment, serum prolactin concentrations decreased more than 97% in 9 patients; at last follow-up (mean treatment duration, 19 months), the mean decrease in serum prolactin concentrations was 98%, with 5 patients having normal serum prolactin levels. At first MRI follow-up (3-12 months after initiation of cabergoline), the mean reduction in tumor size was 85±4% (range, 57-98%). Cabergoline treatment for more than 12 months caused a greater reduction in tumor size compared to the treatment for less than 12 months (97±1% vs. 78±7%, P<0.05). These findings indicate that cabergoline treatment led to a significant and rapid reduction in serum prolactin concentrations and tumor size in patients with giant prolactinoma. Therefore, cabergoline represents an effective and well-tolerated treatment for invasive giant prolactinoma

Splenic Artery Embolization for the Treatment of Gastric Variceal Bleeding Secondary to Splenic Vein Thrombosis Complicated by Necrotizing Pancreatitis: Report of a Case

Splenic vein thrombosis is a relatively common finding in pancreatitis. Gastric variceal bleeding is a life-threatening complication of splenic vein thrombosis, resulting from increased blood flow to short gastric vein. Traditionally, splenectomy is considered the treatment of choice. However, surgery in necrotizing pancreatitis is dangerous, because of severe inflammation, adhesion, and bleeding tendency. In the Warshaw operation, gastric variceal bleeding is rare, even though splenic vein is resected. Because the splenic artery is also resected, blood flow to short gastric vein is not increased problematically. Herein, we report a case of gastric variceal bleeding secondary to splenic vein thrombosis complicated by necrotizing pancreatitis successfully treated with splenic artery embolization. Splenic artery embolization could be the best treatment option for gastric variceal bleeding when splenectomy is difficult such as in case associated with severe acute pancreatitis or associated with severe adhesion or in patients with high operation risk

Lack of Mitochondrial DNA Sequence Divergence between Two Subspecies of the Siberian Weasel from Korea: Mustela sibirica coreanus from the Korean Peninsula and M. s. quelpartis from Jeju Island

The objective of this study was to determine the degree of mitochondrial DNA (mtDNA) divergence between two subspecies of Mustela sibirica from Korea (M. s. coreanus on the Korean Peninsula and M. s. quelpartis on Jeju Island) and to examine the taxonomic status of M. s. quelpartis. Thus, we obtained complete sequences of mtDNA cytochrome b gene (1,140 bp) from the two subspecies, and these sequences were compared to a corresponding haplotype of M. s. coreanus, downloaded from GenBank. From this analysis, it was observed that the sequences from monogenic M. s. quelpartis on Jeju Island were identical to the sequences of four M. s. coreanus from four locations across the Korean Peninsula, and that the two subspecies formed a single clade; the average nucleotide distance between the two subspecies was 0.26% (range, 0.00 to 0.53%). We found that the subspecies quelpartis is not genetically distinct from the subspecies coreanus, and that this cytochrome b sequencing result does not support the current classification, distinguishing these two subspecies by pelage color. Further systematic analyses using morphometric characters and other DNA markers are necessary to confirm the taxonomic status of M. s. quelpartis