Efficacy of an artificial pancreas device for achieving tight perioperative glycemic control in living donor liver transplantation

Intraoperative hyperglycemia during liver transplantation can induce infectious bacterial complications after surgery. The aim of this study was to evaluate the efficacy of the artificial endocrine pancreas in achieving perioperative blood glucose control and preventing infection in patients undergoing living donor liver transplantation (LDLT). We compared 14 patients with an artificial endocrine pancreas device to 14 patients who underwent glycemic control using the sliding scale method with respect to perioperative blood glucose level and postoperative infection. In this study, we aimed to control the perioperative glucose levels consecutively for 24 hours from the induction of anesthesia. The average blood glucose level in the artificial pancreas group was significantly lower than that in the sliding scale group (118 vs. 141 mg/dL, P < 0.05). The postoperative bacterial infection rate of the artificial pancreas group was significantly lower than that of the sliding scale group within one month after LDLT (35.7% vs. 78.6%, P < 0.05). Multiple regression analysis showed non‐application of artificial endocrine pancreas as a significant risk factor of posttransplant infection. The artificial endocrine pancreas enabled the perioperative glucose level to be stably controlled without hypoglycemia. Artificial pancreas may reduce the incidence of postoperative infection after LDLT.     

Acarbose treatments improve arterial stiffness in patients with type 2 diabetes mellitus

Aims/Introduction: Although the improvement of postprandial hyperglycemia by an alpha‐glucosidase inhibitor (α‐GI) has been associated with a risk reduction of cardiovascular events, the relationship between postprandial hyperglycemia and arterial stiffness has not been well understood. We therefore examined whether ameliorating the postprandial state by α‐GI leads to an improvement in arterial stiffness. Materials and Methods: A total of 22 patients with type 2 diabetes mellitus were treated with acarbose. Cardio‐ankle vascular index (CAVI) as the arterial stiffness was measured by using a VaSera CAVI instrument before and 12 months after acarbose treatment. Serum high‐sensitivity C‐reactive protein (hs‐CRP), pentraxin‐3 (PTX3) and matrix metalloproteinase (MMP) ‐2, ‐9 were measured at the same time points. Furthermore, circulating peripheral blood mononuclear cells were examined for the frequencies of CD14 positive cells expressing membrane type‐1 MMP (MT1‐MMP) at the single cell level using flow cytometry. Results: After acarbose treatment, postprandial glucose and glycosylated hemoglobin (HbA_1c) were significantly decreased. Serum levels of hs‐CRP, PTX3, MMP‐2 and MMP‐9 were significantly decreased. CAVI showed a significant reduction, although the changes were not significant in blood pressure and heart rate. MT1‐MMP expression was significantly decreased by acarbose treatment. In multivariate analysis, improvement of blood glucose, decrease of PTX3 levels and MT1‐MMP expression were independent predictors of beneficial change in CAVI. Conclusions: The present study showed that the beneficial effects of acarbose on arterial stiffness are mediated by an improvement of postprandial hyperglycemia and vascular remodeling markers. In conclusion, acarbose treatment might reduce the risk of cardiovascular diseases by altering the arterial stiffness in postprandial hyperglycemic status. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00079.x , 2010)     

Nicotine does not affect stem cell properties requisite for suicide gene therapy against glioma

ABSTRACT

Objective: 

Glioblastoma is one of the most lethal tumors in adult central nervous system with a median survival of a year and half and effective therapeutic strategy is urgently needed. For that reason, stem cell-based suicide gene therapies have attracted much interest because of potent tumor tropism of stem cells and bystander effect. In this current clinical situation, stem cells are promising delivery tool of suicide genes for glioma therapy. Since habitual cigarette smoking still prevails worldwide, we investigated the effect of nicotine on stem cell tropism toward glioma and gap junctional intercellular communication (GJIC) function between glioma and stem cells, both of which are important for suicide gene therapies. Methods: Mouse induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) and human dental pulp mesenchymal stem cells (DPSCs) were used. The effect of nicotine on tumor tropism to glioma-conditioned medium (CM) at a non-cytotoxic concentration was assessed with Matrigel invasion assay. Nicotine effect on GJIC was assessed with the scrape loading/dye transfer (SL/DT) assay for co-culture of glioma and stem cells and the parachute assay among glioma cells using high-content analysis. Results: Tumor tropism of iPS-NSCs toward GL261-CM and DPSCs toward U251-CM was not affected by nicotine (0.1 and 1 µM). Nicotine at the concentrations equivalent to habitual smoking (1 µM) did not affect GJIC of iPS-NSC/GL261 and DPSC/U251 and GJIC among each glioma cells. Conclusions: The study demonstrated that non-cytotoxic concentrations of nicotine did not significantly change the stem cell properties requisite for stem cell-based suicide gene therapy.     

A case of postpartum fever caused by Mycoplasma hominis infection

A 26-year-old housewife was admitted to our hospital with a history of high fever after previous cesarean delivery. She had premature rupture of the membrane on the 41st week of pregnancy and the amniotic fluid was found to be cloudy on the fourth day after rupture. Therefore, cesarean delivery was performed. On the first day of operation, her body temperature increased up to 38 degrees C in spite of the treatment with Latamoxef (LMOX), 3 g/day. A sample of intrauterine material yielded M. hominis in pure culture. After administration of Minocycline (MINO) with antimycoplasmal activity, the clinical symptoms improved by the 11th day of operation. Sera obtained after the infection showed antibodies to M. hominis in ELISA study. These results suggested that the cause of this postpartum fever was M. hominis infection.     

Level of protein C determined by combined assays during disseminated intravascular coagulation and oral anticoagulation

We have developed a variation of the solid-phase enzyme-linked immunosorbent assay (ELISA) to enable measurement of the activity and antigen levels of protein C (PC) in human plasma. With this assay it is possible to do both tests with the same sample and same microtiter plate coated with anti-PC monoclonal antibody (MCA)JTC-4, which inhibited neither activation of PC nor activity of activated PC (APC). Even in patients undergoing heparin treatment for severe disseminated intravascular coagulation, there were no detectable differences between amidolytic activity and antigen levels of PC in patients' plasma. In addition, there was a strong correlation between the immunologic levels of PC in patients' plasma determined both by polyclonal ELISA using peroxidase-labeled immunopurified antiprotein C-IgG and those found with MCA ELISA using peroxidase-labeled MCAJTC-5, which does not bind to APC. In contrast, when oral anticoagulation therapy was started, immunologic levels of plasma PC estimated by peroxidase-labeled MCAJTC- 1, a MCA that recognizes a gamma-carboxyglutamic acid domain-related conformational change of PC induced by metal ions, decreased more rapidly than did either the PC level determined by polyclonal ELISA or the percent prothrombin time. This suggested that comparison of MCAJTC- 1-recognized PC levels and prothrombin time may be necessary at the beginning of oral anticoagulation therapy to treat patients safely.     

Cytotoxic Chemotherapy Successfully Induces Durable Complete Remission in 2 Patients with Mosquito Allergy Resulting from Epstein-Barr Virus-Associated T-/Natural Killer Cell Lymphoproliferative Disease

Recent findings indicate that Epstein-Barr virus (EBV)-infected T-/natural killer (NK) cells play an important role in the pathogenesis of mosquito allergy, and most patients with mosquito allergy die early in life if not properly treated. Over the last 7 years, we have been using combination chemotherapy and allogeneic stem cell transplantation for the treatment of EBV-associated T-/NK cell lymphoproliferative disease (LPD) in which chronic active EBV infection and mosquito allergy were included. As of this writing, we have successfully treated 2 patients with mosquito allergy with chemotherapy in which EBV-infected T-/NK cells were eradicated. The findings suggest the possible role of chemotherapy in the treatment of EBV-associated T-/NK cell LPD.     

Activated leukocytes and endothelial cells enhance retention of ultrasound contrast microspheres containing perfluoropropane in inflamed venules

PURPOSE: To characterize the flow dynamics of albumin ultrasound contrast microspheres containing perfluoropropane (PFP) in normal and inflamed microvasculature. MATERIALS AND METHODS: Mesenteric microvessels of rats were examined after an intravenous injection of fluorocein-labeled erythrocytes or PFP microspheres by fluorescence intravital microscopy with and without local application of 10(-8) M platelet activating factor (PAF) as an experimental form of inflammation. RESULTS: All the microspheres passed freely through arterioles and capillaries. Mean velocities of the microspheres in each vessel were closely correlated with those of erythrocytes. Only a minor fraction of the microspheres was retained in the venules (> or =0.1 s stoppage) by attachment to endothelial cells. The frequency of microsphere retention in venules was significantly enhanced by PAF (2.6+/-2.1%, P<0.01 vs. control), especially in regions with leukocyte adhesion. Treatment with a monoclonal antibody to intercellular adhesion molecule-1, P-selectin or the common leukocyte antigen inhibited PAF-induced microsphere retention in venules (P<0.05). In the inflamed microcirculation, a small subgroup of microspheres becomes attached to venular endothelial cells in regions with leukocyte adhesion via interaction among microspheres, activated leukocytes and endothelial cells via adhesion molecules. CONCLUSION: In inflamed microcirculation, a small subgroup of microspheres becomes attached to venular endothelial cells in regions with leukocyte adhesion via interaction among microspheres, activated leukocytes and endothelial cells via adhesion molecules. These results suggest that ultrasonography with microspheres has the potential to evaluate inflammatory site distribution as well as tissue perfusion.