Toshihiro Shinbo

X‐ray Radiation Causes Electromagnetic Interference in Implantable Cardiac Pacemakers

Background: X‐rays are not thought to cause electromagnetic interference (EMI) in implantable cardiac pacemakers. However, x‐ray radiation during computed tomography (CT) scanning has been reported to cause EMI in some implantable cardiac pacemakers. The objectives of this study were to identify the location within the pacemakers where x‐ray radiation causes EMI and to investigate the association of EMI with the x‐ray radiation conditions.

Bench study of auto-CPAP devices using a collapsible upper airway model with upstream resistance.

The aim of this study was to investigate the response of auto-CPAP devices to respiratory events (apnea, hypopnea, flow-limitation and snoring) on the same condition using a physiological upper airway model. The hypothesis of this study is that collapsibility of the flow-limiting collapsible segment of the airway is influenced by the upstream airway resistance. Five auto-CPAP devices, AutoSet T, AutoSet Spirit, Goodnight 420E, PV10i and REMstar Auto were evaluated. Apnea: all the devices increased the auto-CPAP level, while AutoSet T and AutoSet Spirit did not respond to apnea for 30s. Hypopnea: all the devices except the AutoSet T and Goodnight 420E increased pressure. Flow-limitation: all the devices except the PV10i and REMstar Auto increased pressure. Snoring: the snoring sounds disappeared when REMstar Auto and PV10i were used, and the Goodnight 420E lowered the level of snoring. In conclusion, the response of auto-CPAP devices to respiratory events differed. Collapsible upper airway model with upstream resistance is useful for the first-step assessment of auto-CPAP devices.

Hypoxia enhances the induction of human amniotic mesenchymal side population cells into vascular endothelial lineage

Human amniotic mesenchymal side population (hAM-SP) cells have pluripotency and weak immunogenicity, and have promising roles in the field GAPDH of regenerative medicine. The aim of the present study was to determine whether hypoxic conditions induce the differentiation of hAM-SP cells into the vascular endothelial lineage. Mesenchymal cells were isolated from enzyme-treated amniotic membranes and stained with Hoechst 33342. The hAM-SP cells were negatively sorted by FACS and cultured in induction medium containing vascular endothelial growth factor (VEGF) under normoxic (20% O2) or hypoxic (1% O2) conditions for 1 or 2 weeks. The expression of endothelial markers such as kinase domain region (KDR), fms-like tyrosine kinase (Flt)-1, von Willebrand factor (vWF), vascular endothelial (VE)-cadherin and human vascular cell adhesion molecule (VCAM) at the gene and protein level was evaluated by real-time PCR and fluorescent immunostaining, respectively. The gene expression of KDR, Flt-1, VE-cadherin and vWF peaked after 2 weeks of culture. The protein expression of KDR and VE-cadherin was also enhanced after 2 weeks of culture under hypoxic conditions. To confirm the involvement of hypoxia-inducible factor (HIF) in the induction under hypoxic conditions, the expression of genes which are known to be upregulated by HIF was analyzed by DNA microarray. The expression of these genes increased under hypoxic conditions. hAM-SP cells cultured under hypoxic conditions differentiated into the vascular endothelial lineage, probably due to upregulation of the gene expression associated with angiogenesis through activation of the HIF system.

Activation of platelets upon contact with a vitamin E-coated/non-coated surface

The purpose of this study was to determine the effects of a vitamin E-coated surface on platelet activation, focusing on the interactions among the vitamin E-coated surface, platelets and leukocytes. Platelet-rich plasma (PRP) or PRP containing leukocytes (LPRP) was used. No difference was observed in platelet activation between PRP and LPRP for a vitamin E-coated membrane, meaning that platelet activation triggered by leukocytes was suppressed in plasma coming in contact with a vitamin E-coated membrane, while the membrane itself directly induced platelet activation. The antioxidant capacity of the vitamin E-coated membrane in contact with PRP or LPRP was partially reduced, but sufficient residual capacity remained. The in vitro experiments using an oxidized vitamin E-coated surface revealed that P-selectin expression and superoxide anion production in the platelets and platelet adhesion were induced by contact with the oxidized vitamin E-coated surface. We conclude that contact with a vitamin E-coated surface reduces platelet activation mediated by superoxide anions, probably by reducing superoxide anions, but during the process of the reduction, the vitamin E-coated surface itself becomes oxidized, which again causes platelet activation. The beneficial effects of a vitamin E-coated dialyzer in respect of platelet activation were counteracted by the formation of oxidized vitamin E.

Urea concentrating ability of artificial renal tubule based on countercurrent multiplier system using electrodialysis, dialysis and filtration

Countercurrent multiplier systems have been found in various organs of various animal species. In a mammalian kidney, countercurrent multiplier system plays an important role in the process of urine concentration. An artificial renal tubule which can concentrate urea is one of the key elements to develop a wearable artificial kidney for the patients currently undergoing intermittent hemodialysis therapy. The objective of the present study was to develop a biomimetic artificial renal tubule based on the countercurrent multiplier system. We mimicked active transport of NaCl at ascending limbs of the Henle loop by electrodialysis and mimicked passive transport of the solute and water transport via water channel at descending limbs and collecting ducts by dialysis and filtration. The membranes used for electrodialysis, dialysis and filtration were placed parallel to each other to establish countercurrent configuration. We examined urea concentrating ability of the fabricated prototype module of artificial renal tubule based on the countercurrent multiplier system. The fabricated prototype module was capable of concentrating urea approximately 1.3 fold. These results indicate that the countercurrent multiplier system is useful to develop an artificial renal tubule.

The role of nitric oxide in reducing deformability of Lewis lung tumor cell stimulated by inflammatory cytokines

Highly metastatic cells, especially in the lungs, are known to be resistant to nitric oxide (NO)-mediated cytotoxicity, compared with poorly or non-metastatic cells. However, the precise mechanisms connecting NO and metastasis remain to be determined. To clarify the role of NO in the characteristic changes in NO-resistant cells in response to inflammatory cytokines, we used Lewis lung tumor (LLT) cells, which are known to be highly metastatic NO-resistant cells, and determined the changes in cell deformability and the gene expression profile after the cells were stimulated using cytokine mixture or an NO donor. Both exogenous NO and endogenous NO via inducible NO synthase produced by cytokines decreased cell deformability by enhancing actin polymerization. The expression of several genes associated with actin polymerization was changed so as to increase actin filaments in the cells by enhancing actin polymerization and by suppressing actin depolymerization, actin filament severing, and barbed-end actin filament capping. In conclusion, inflammatory cytokine stimulation reduces deformability of LLT cells and enhances actin polymerization which is mainly controlled by the same genes induced by NO.

Effects of Power Line Communication System on Medical Equipments

Power Line Communication (PLC) is an innovative system for carrying data through power line without conventional local area network cables. However, in hospitals the data signal from PLC system superimposed on the alternating power current possibly results in a power noise for medical equipments and thereby inducing hazardous malfunction of medical equipments. The purpose of this study was to investigate the effects of the PLC on medical equipments. We used three different types of PLC modems and their communication systems: HomePlug system, Universal Powerline Association (UPA) system and High Definition (HD)-PLC system. The frequency band of the data signal was 2~30 MHz. We investigated the effect of the data signal from PLC system superimposed on the alternating power current and voltage, and we also investigated the effect of the electromagnetic wave radiated from the power line of PLC modem on medical equipments. We evaluated thirty kinds of medical equipments, such as ventilators, telemeters, infusion pumps and so on. Malfunction did not occur in any medical equipment investigated by the data signal superimposed on the alternating power current. Although malfunction did occur in ultrasonic diagnostic equipment and external cardiac pacemaker when the power line was moved closer toward the medical equipments, the malfunction occurred in the distance less than 2 cm. In conclusion the effect of PLC on medical equipment investigated in this study was considered to be minor.

Synchronization between cardiac and respiratory rhythms in healthy subjects and patients.

Synchronization between cardiac and respiratory rhythms may be important for oxygen transport to tissues. The aim of this study was to investigate the synchronization between cardiac and respiratory rhythms. We evaluated the rhythms in 12 healthy males and 24 patients. The incidence rates of heart beats were obtained in each time interval relative to the initiation time point of inspiration. A simple index of timing variability of heart beats was defined. When the variability is large, the link between cardiac and respiratory rhythms was considered to be strong. The variability value of patients with disorder in the autonomic nervous system was larger than that of healthy subjects (p < 0.05). The variability of patients on controlled ventilation was lower than that of healthy subjects (p < 0.01), whereas the value on cardiac pacemaker did not differ from healthy subjects. In conclusion, the synchronization between cardiac and respiratory rhythms was confirmed, and it is suggested that the synchronization is enhanced when feed-back signals from respiratory movement to respiratory center were decreased.

Macrophages That Survive Hyperoxia Exposure Have Higher Superoxide Dismutase Activities in Their Mitochondria

Prolonged exposure to hyperoxia, which is routinely used in patients with severe respiratory failure, leads to the generation of excessive reactive oxygen species, resulting in lung injury. In the present study, we focused on macrophages and their survival, superoxide dismutase (SOD) activity in mitochondria (Mn-SOD activity), and mitochondrial DNA (mtDNA) mutation after exposure to hyperoxia. Macrophages were cultured under two different conditions: normoxia and intermittent hyperoxia. The number of cells exposed to intermittent hyperoxia for 3 weeks significantly decreased, compared with the number of cells exposed to normoxia. The Mn-SOD activity of the cells that survived intermittent hyperoxia exposure was significantly higher than that of the cells exposed to normoxia. Direct sequencing and a PCR-RFLP assay did not provide any evidence of mutation in the cells that survived intermittent hyperoxia exposure. In conclusion, an increase in the antioxidative activity of mitochondria is important for the survival of macrophages exposed to hyperoxia, and the increased activity level possibly enhances protective effects against mtDNA mutations in surviving cells.

Internal filtration induces severe concentration of blood cells inside hollow-fiber dialysis membrane at the start of postdilution hemodiafiltration

The hydraulic permeability of the dialysis membrane used for hemodiafiltration (HDF) is high, so that a large amount of internal filtration occurred in addition to ultrafiltration required for water removal and fluid replacement. Especially for the period immediately after the start of HDF, severe concentration of blood cells by internal filtration is likely to occur. The aims of this study was, using a mathematical simulation, to evaluate the amount of internal filtration and resulting blood cell concentration inside the hollow fiber and to develop a strategy to avoid the severe hemoconcentration during postdilution HDF. To this end, we calculated maximum internal filtration rate, and maximum hematocrit at varying blood flow rate, dialysate flow rate, and ultrafiltration rate. We found that at the start of the HDF, severe concentration of blood cells can occur where maximum hematocrit reached over 60%, even the dialyzer was designed to ensure minimal internal filtration. The hemoconcentration was not actually severe after membrane fouling occurred. To prevent the initial severe concentration of blood cells during HDF, at the start of the treatment the blood and dialysate flow rate should be below 100 ml/min and no ultrafiltration should be performed.