Intra-Abdominal Venous Pressure During Laparoscopic Cholecystectomy

Superior vena cava (SVC) and inferior vena cava (IVC) pressures were measured serially during laparoscopic cholecystectomy in which the intra-abdominal pressure was maintained at 12mmHg. The influences of alteration of position from 15 degrees head-down to 15 degrees head-up and of the operative procedure of holding the gallbladder up to the right subphrenic space on SVC and IVC pressures were mild. IVC pressure was maintained almost equal to the intra-abdominal pressure during prolonged continuous pneumoperitoneum lasting longer than 60min, while SVC pressure did not change significantly during operation. The discrepancy between SVC and IVC pressures underwent no change during continuous pneumoperitoneum

Effects of Candidalysin Derived from Candida albicans on the Expression of Pro-Inflammatory Mediators in Human Gingival Fibroblasts

Candida albicans (Ca) is frequently detected in the peri-implant sulcus with peri-implantitis, a major postoperative complication after oral implant therapy. However, the involvement of Ca in the pathogenesis of peri-implantitis remains unclear. In this study, we aimed to clarify Ca prevalence in the peri-implant sulcus and investigated the effects of candidalysin (Clys), a toxin produced by Ca, on human gingival fibroblasts (HGFs). Peri-implant crevicular fluid (PICF) was cultured using CHROMagar and Ca colonization rate and colony numbers were calculated. The levels of interleukin (IL)-1β and soluble IL-6 receptor (sIL-6R) in PICF were quantified by enzyme-linked immunosorbent assay (ELISA). Pro-inflammatory mediator production and intracellular signaling pathway (MAPK) activation in HGFs were measured by ELISA and Western blotting, respectively. The Ca colonization rate and the average number of colonies in the peri-implantitis group tended to be higher than those in the healthy group. IL-1β and sIL-6R levels in the PICF were significantly higher in the peri-implantitis group than in the healthy group. Clys significantly induced IL-6 and pro-matrix metalloproteinase (MMP)-1 productions in HGFs, and co-stimulation with Clys and sIL-6R increased IL-6, pro-MMP-1, and IL-8 production levels in HGFs compared with Clys stimulation alone. These findings suggest that Clys from Ca plays a role in the pathogenesis of peri-implantitis by inducing pro-inflammatory mediators

Potential role of vacuolar H+–adenosine triphosphatase in neointimal formation in cultured human saphenous vein

AbstractObjective: Vacuolar H+–adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H+–adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. Methods and results: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A1, a selective inhibitor of vacuolar H+-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for α-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A1. Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A1. Detection of apoptotic cells by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A1. Conclusions: These results suggest that vacuolar H+–adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A1 may have potential therapeutic implications in the treatment for vein graft disease. (J Thorac Cardiovasc Surg 2000;119:998-1007

AGEs increase IL-6 and ICAM-1 expression

Background and Objectives: Diabetes mellitus (DM) is a risk factor for periodontal diseases and may exacerbate the progression of the pathogenesis of periodontitis. Advanced glycation end-products (AGEs) cause DM complications relative to levels of glycemic control and larger amounts accumulate in the periodontal tissues of patients with periodontitis and DM. In the present study, we investigated the effects of AGEs on the expression of inflammation-related factors in human gingival fibroblasts (HGFs) in order to elucidate the impact of AGEs on DM-associated periodontitis. Materials and Methods: HGFs were cultured with or without AGEs. Cell viability was examined, and RNA and protein fractions were isolated from AGE-treated cells. The expression of IL-6, ICAM-1, and the receptor for AGE (RAGE) was investigated using RT-PCR, quantitative real-time PCR, and ELISA, and reactive oxygen species (ROS) activity was measured using a kit with 2’,7’-dichlorofluorescin diacetate. Human monocytic cells (THP-1) labelled with a fluorescent reagent were co-cultured with HGFs treated with AGEs and IL-6 siRNA, and the adhesive activity of THP-1 cells to HGFs was assessed. The expression of IL-6 and ICAM-1 was examined when HGFs were pretreated with recombinant human IL-6 (rhIL-6), the siRNAs of RAGE and IL-6, and inhibitors of MAPK and NF-κB, and then cultured with and without AGEs. The phosphorylation of MAPK and NF-κB was assessed using Western blotting. Results: AGEs increased the mRNA and protein expressions of RAGE, IL-6, ICAM-1 and ROS activity in HGFs, and promoted the adhesion of THP-1 cells to HGFs, but had no effect on cell viability until 72 h. rhIL-6 increased ICAM-1 expression in HGFs, while the siRNAs of RAGE and IL-6 inhibited AGE-induced IL6 and ICAM1 mRNA expression, and IL-6 siRNA depressed AGE-induced THP-1 cell adhesion. AGEs increased the phosphorylation of p38 and ERK MAPKs, p65 NF-κB, and IκBα, while inhibitors of p38, ERK MAPKs, and NF-κB significantly decreased AGE-induced IL-6 and ICAM-1 expression. Conclusions: AGEs increase IL-6 and ICAM-1 expression via the RAGE, MAPK and NF-κB pathways in HGFs and may exacerbate the progression of the pathogenesis of periodontal diseases

Ablation of TSC2 Enhances Insulin Secretion by Increasing the Number of Mitochondria through Activation of mTORC1

) mice. The present study examines the effects of TSC2 ablation on insulin secretion from pancreatic beta cells. mice and TSC2 knockdown insulin 1 (INS-1) insulinoma cells treated with small interfering ribonucleic acid were used to investigate insulin secretion, ATP content and the expression of mitochondrial genes. mice exhibit hyperinsulinemia due to an increase in the number of mitochondria as well as enlargement of individual beta cells via activation of mTORC1.Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells

Pancreatic β Cell Mass Preserved in Heterozygous PDK1 Knockout Mice

We have demonstrated that 3-phosphoinositide-dependent protein kinase 1 (PDK1)contributes to signaling by insulin or insulin-like growth fctor-1 (IGF-1) that isresponsible for the regulation of both the number and size of pancreatic β cells in mice.Complete ablation of PDK1 in pancreatic β cells leads to progressive hyperglycemia asa result of loss of β cell mass. In this study, we generated heterozygous pancreatic βcell-specific PDK1 knockout (βPDK1+/–) mice and fed them a high-fat diet as a model ofhuman type 2 diabetes. The βPDK1+/– mice exhibited normal glucose tolerance even ona high-fat diet. Further, islet morphology and β cell mass were normal in βPDK1+/–mice, and haploinsufficiency of PDK1 did not impair the compensatory hyperplasia ofβ cells on a high-fat diet. The phosphorylation and expression of the molecules that areexpressed downstream of PDK1 were similar in the islets of the βPDK1+/– and controlmice. Eventually, we concluded that glucose homeostasis and islet mass weremaintained in βPDK1+/– mice