Gotaro Shirakami

A Model-Predictive Hypnosis Control System Under Total Intravenous Anesthesia

In ambulatory surgery, anesthetic drugs must be administered at a suitable rate to prevent adverse reactions after discharge from the hospital. To realize more appropriate anesthesia, we have developed a hypnosis control system, which administers propofol as an anesthetic drug to regulate the bispectral index (BIS), an electroencephalography (EEG)-derived index reflecting the hypnosis of a patient. This system consists of three functions: 1) a feedback controller using a model-predictive control method, which can adequately accommodate the effects of time delays; 2) a parameter estimation function of individual differences; and 3) a risk control function for preventing undesirable states such as drug overinfusion or intraoperative arousal. With the approval of the ethics committee of our institute, 79 clinical trials took place since July 2002. The results show that our system can reduce the total amount of propofol infusion and maintain the BIS more accurately than anesthesiologists manual adjustment.

Difference in abundance of blood and lymphatic capillaries in the murine epididymis

It is well known that the epididymis is responsible for the transportation, storage, and maturation of spermatozoa, and that it has four segments: i.e., initial segment, caput, corpus, and cauda. Previous studies revealed the presence of a very dense network of blood capillaries only in the initial segment; however, the relative distribution of blood and lymphatic capillaries has remained unknown. In the present study, we investigated the distribution of intraepididymal blood and lymphatic capillaries in mice by use of monoclonal antibodies against CD31 and lymph vessel endothelium HA-receptor 1, respectively. The results showed that lymphatic networks were quite scarce in the initial segment and strikingly abundant in the cauda compared with the other two regions. In sharp contrast, blood capillaries were abundant in both the initial segment and cauda but sparse in the other two regions. This observation suggests that the characteristic distribution of blood and lymphatic capillaries in the epididymis contributes to the different roles of each epididymal region.

Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats

Recovery from ischemic acute kidney injury requires the replacement of damaged tubular cells. This repair process involves epidermal growth factor (EGF) synthesized in medullary the thick ascending limbs (mTAL) of Henle. Atrial natriuretic peptide (ANP), a hormone synthesized by the cardiac atria, increases glomerular filtration rate and renal medullary blood flow. However, the effects of ANP on renal recovery after I/R-induced renal injury remain unclear. We therefore examined whether human ANP enhances recovery from I/R-induced renal injury by reducing damage to EGF-producing kidney cells in a rat model. Male Wistar rats weighing 200-240 g were observed for 48 h after reperfusion following 45-min renal ischemia. Rats were intravenously administered alpha-human ANP (alpha-hANP) at 0.2 microg/kg/min beginning immediately after ischemia and continuing for 2 h after reperfusion. Outer medullary blood flow (OMBF), EGF mRNA, serum blood urea nitrogen (BUN) and creatinine levels as indicators of glomerular function were measured, while urinary N-acetyl beta-D-glucosaminidase (NAG) was used as a specific indicator of proximal tubular function. OMBF was increased by alpha-hANP after reperfusion and maintained significantly higher mRNA level of EGF in the kidney 24 h after reperfusion. I/R-induced increases in serum concentrations of BUN and creatinine and urinary concentrations of NAG were also reduced by alpha-hANP, with improved histopathological changes, including acute tubular necrosis at 24-48 h after reperfusion. This report is the first to demonstrate that alpha-hANP accelerates recovery following renal ischemic insult by reducing the damage to EGF-producing kidney cells.

High ethanol and acetaldehyde impair spatial memory in mouse models: Opposite effects of aldehyde dehydrogenase 2 and apolipoprotein E on memory

Aldehyde dehydrogenase 2 deficiency may directly contribute to excess acetaldehyde (AcH) accumulation after ethanol (EtOH) drinking and AcH mediates some of the behavioral effects of EtOH. Apolipoprotein E has been suggested to be involved in the alteration of attention and memory. We have chosen Aldh2-knockout (Aldh2-KO), ApoE-KO, and their wild-type (WT) control mice to examine the effects of EtOH and AcH on spatial memory and to compare the possible relationship between genetic deficiency and memory using two behavioral assessments. Mice were trained for 4 days, with EtOH (0.5, 1.0, 2.0 g/kg) being given intraperitoneally on day 4. A probe trial was given on day 5 in the non-EtOH state in the Morris water maze (MWM). The results showed that 2.0 g/kg EtOH increased errors, indicating memory impairment on the eight-arm radial maze (RAM) for all the mice studied. One gram per kilogram EtOH impaired the performance of Aldh2-KO and ApoE-KO mice, but not WT mice. We found similar effects of EtOH on the MWM performance, with 2.0 g/kg EtOH increasing the latencies. One gram per kilogram EtOH increased the latencies of Aldh2-KO and WT mice, but not ApoE-KO mice. The 2.0 g/kg EtOH-induced memory impairment in Aldh2-KO mice was greater, suggesting an AcH effect. Furthermore, time spent on the probe trial was shorter in mice that had previously received 2.0 g/kg EtOH. ApoE-KO mice learned more slowly, while Aldh2-KO mice learned more quickly. Both the RAM and MWM results suggest that high EtOH and AcH impair spatial memory in mice, while lower doses do not have consistent memory effects. In addition, we conclude that genetic differences might underlie some of EtOHs effects on memory.

Effort-reward Imbalance and Low Back Pain among Eldercare Workers in Nursing Homes: A Cross-sectional Study in Kagawa Prefecture, Japan

Effort‐reward Imbalance and Low Back Pain among Eldercare Workers in Nursing Homes: A Cross‐sectional Study in Kagawa Prefecture, Japan; Katsunori YOKOYAMA, et al. Department of Anesthesiology, Graduate School of Medicine, Kagawa University—

Aldehyde dehydrogenase 2 deficiency increases resting-state glutamate and expression of the GluN1 subunit of N-methyl-D-aspartate receptor in the frontal cortex of mice

Our previous study showed that Aldh2-knockout (Aldh2-KO) mice, an animal model of inactive aldehyde dehydrogenase 2 (ALDH2), have better spatial memory when compared with wild-type (WT) mice. Given that the neurotransmitter glutamate has been associated with learning and memory, the goal of the present study was to investigate whether the strain-dependent difference in spatial memory was associated with changes in glutamate transmitter levels or receptor function in the frontal cortex of Aldh2-KO and WT mice. Thus, we first measured extracellular glutamate levels in free-moving mice using microdialysis. Second, we studied protein expression of the N-methyl-D-aspartate (NMDA) receptor (GluN1) subunit and the α-amino-3-hydroxy-5 methylisoxazole-4-propionic acid (AMPA) receptor (GluA1) subunit in lipid raft fractions using Western blot (WB). The samples were collected for WB, and lipid rafts were prepared from the insoluble fraction of homogenate tissue. Protein concentration was measured in the whole cell lysate (WCL) and in five separate lipid raft fractions. Cholesterol was also measured in all fractions 1-5. The microdialysis study revealed that basal glutamate concentration in the dialysates was approximately three-fold (0.27 ± 0.12 μM) higher in Aldh2-KO mice than in WT (0.10 ± 0.03 μM) mice. We also found an increase in the expression of GluN1 in Aldh2-KO mice compared with WT mice, both in the WCL and fraction 5, but GluA1 levels were unchanged as measured by WB. Our novel findings provide the first evidence for the role of ALDH2 in glutamate release and GluN1 protein expression in the frontal cortex. The observed strain differences in glutamate levels and GluN1 expression may suggest that enhanced glutamatergic function facilitates improved spatial memory in Aldh2-KO mice and such observation deserves further investigation.

Case of vascular air embolism during holmium laser enucleation of the prostate.

Vascular air embolism is a rare complication during transurethral surgery. A case of air embolism during holmium laser enucleation of the prostate in a 76‐year‐old man is presented. During the step of morcellation, the patients blood pressure suddenly oscillated up and down, and end‐tidal CO2 and arterial saturation decreased. Transesophageal and transthoracic echocardiography showed air collection in the right atrium. It was also discovered that incorrect assembly of the tube from the morcellator caused rapid entrainment of air into the vein. Computed tomography and abdominal X‐ray showed niveau formation in the femoral vein and air collection in the pelvic retroperitoneal space. The patient recovered with careful observation and was discharged 7 days after the operation with no sequelae. This report is presented to remind urologists of this unusual complication that can occur during holmium laser enucleation of the prostate procedures.

Hypnosis control based on the minimum concentration of anesthetic drug for maintaining appropriate hypnosis

This paper proposes a novel hypnosis control method using Auditory Evoked Potential Index (aepEX) as a hypnosis index. In order to avoid side effects of an anesthetic drug, it is desirable to reduce the amount of an anesthetic drug during surgery. For this purpose many studies of hypnosis control systems have been done. Most of them use Bispectral Index (BIS), another hypnosis index, but it has problems of dependence on anesthetic drugs and nonsmooth change near some particular values. On the other hand, aepEX has an ability of clear distinction between patient consciousness and unconsciousness and independence of anesthetic drugs. The control method proposed in this paper consists of two elements: estimating the minimum effect-site concentration for maintaining appropriate hypnosis and adjusting infusion rate of an anesthetic drug, propofol, using model predictive control. The minimum effect-site concentration is estimated utilizing the property of aepEX pharmacodynamics. The infusion rate of propofol is adjusted so that effect-site concentration of propofol may be kept near and always above the minimum effect-site concentration. Simulation results of hypnosis control using the proposed method show that the minimum concentration can be estimated appropriately and that the proposed control method can maintain hypnosis adequately and reduce the total infusion amount of propofol.

Effect of the volatile anesthetic agent isoflurane on lateral diffusion of cell membrane proteins

The volatile anesthetic isoflurane (ISO) has previously been shown to increase the fluidity of artificial lipid membranes, but very few studies have used biological cell membranes. Therefore, to investigate whether ISO affects the mobility of membrane proteins, fluorescence‐labeled transferrin receptor (TfR) and glycosylphosphatidylinositol (GPI)‐anchored protein were expressed in human embryonic kidney 293T cells and neural cells and lateral diffusion was examined using fluorescence recovery after photobleaching. Lateral diffusion of the TfR increased with ISO treatment. On the other hand, there was no effect on GPI‐anchored protein. We also used GC/MS to confirm that there was no change in the concentration of ISO due to vaporization during measurement. These results suggest that ISO affects the mobility of transmembrane protein molecules in living cells.

Sex differences in attachment to spouses among older Japanese couples.

Attachment among older adults can partially explain sex differences in bereavement outcomes, but there is currently little evidence regarding this. The aim was to quantify sex differences in the proportion of spouses as attachment figures among older couples.