Activation of Mitogen-Activated Protein Kinase in Descending Pain Modulatory System

The descending pain modulatory system is thought to undergo plastic changes following peripheral tissue injury and exerts bidirectional (facilitatory and inhibitory) influence on spinal nociceptive transmission. The mitogen-activated protein kinases (MAPKs) superfamily consists of four main members: the extracellular signal-regulated protein kinase1/2 (ERK1/2), the c-Jun N-terminal kinases (JNKs), the p38 MAPKs, and the ERK5. MAPKs not only regulate cell proliferation and survival but also play important roles in synaptic plasticity and memory formation. Recently, many studies have demonstrated that noxious stimuli activate MAPKs in several brain regions that are components of descending pain modulatory system. They are involved in pain perception and pain-related emotional responses. In addition, psychophysical stress also activates MAPKs in these brain structures. Greater appreciation of the convergence of mechanisms between noxious stimuli- and psychological stress-induced neuroplasticity is likely to lead to the identification of novel targets for a variety of pain syndromes

Clinical and genetic aspects of mild hypophosphatasia in Japanese patients

Background: Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from a dysfunctional tissue non-specific alkaline phosphatase enzyme (TNSALP). Although genotype-phenotype correlations have been described in HPP patients, only sparse information is currently available on the genetics of mild type HPP. Methods: We investigated 5 Japanese patients from 3 families with mild HPP (patients 1 and 2 are siblings; patient 4 is a daughter of patient 5) who were referred to Fujita Health University due to the premature loss of deciduous teeth. Physical and dental examinations, and blood, urine and bone density tests were conducted. Genetic analysis of the ALPL gene was performed in all patients with their informed consent. Results: After a detailed interview and examination, we found characteristic symptoms of HPP in some of the study cases. Mobile teeth or the loss of permanent teeth were observed in 2 patients, and 3 out of 5 patients had a history of asthma. The serum ALP levels of all patients were 30% below the lower limit of the age equivalent normal range. ALPL gene analysis revealed compound heterozygous mutations, including Ile395Val and Leu520Argfs in family 1, Val95Met and Gly491Arg in family 2, and a dominant missense mutation (Gly456Arg) in family 3. The 3D-modeling of human TNSALP revealed three mutations (Val95Met, Ile395Val and Gly456Arg) at the homodimer interface. Severe collisions between the side chains were predicted for the Gly456Arg variant. Discussion: One of the characteristic findings of this present study was a high prevalence of coexisting asthma and a high level serum IgE level. These characteristics may account for the fragility of tracheal tissues and a predisposition to asthma in patients with mild HPP. The genotypes of the five mild HPP patients in our present study series included 1) compound heterozygous for severe and hypomorphic mutations, and 2) dominant-negative mutations. All of these mutations were at the homodimer interface, but only the dominant-negative mutation was predicted to cause a severe collision effect between the side chains. This may account for varying mechanisms leading to different effects on TNSALP function

Combination Treatment of Perioperative Rehabilitation and Psychoeducation Undergoing Thoracic Surgery

Postoperative pulmonary complications are a risk associated with thoracic surgery. However, there have been few reports on cases at high risk of postoperative complications. Cancer patients often have negative automatic thoughts about illness, and these negative automatic thoughts are associated with reduced health behavior and physical activity. This case series demonstrates the successful combination treatment of perioperative rehabilitation and psychoeducation for negative automatic thoughts in two cancer patients who underwent thoracic surgery. One patient underwent pneumonectomy with laryngeal recurrent nerve paralysis; the other patient, who had a history of recurrent hepatic encephalopathy and dialysis, underwent S6 segmentectomy. Both patients had negative automatic thoughts about cancer-related stress and postoperative pain. The physical therapists conducted a perioperative rehabilitation program in which the patients were educated to replace their maladaptive thoughts with more adaptive thoughts. After rehabilitation, the patients had improved adaptive thoughts, increased physical activity, and favorable recovery without pulmonary complications. This indicates that the combination treatment of perioperative rehabilitation and psychoeducation was useful in two thoracic cancer surgery patients. The psychoeducational approach should be expanded to perioperative rehabilitation of patients with cancer

Computer-controlled closed-loop norepinephrine infusion system for automated control of mean arterial pressure in dogs under isoflurane-induced hypotension: a feasibility study

Introduction: Intra-operative hypotension is a common complication of surgery under general anesthesia in dogs and humans. Computer-controlled closed-loop infusion systems of norepinephrine (NE) have been developed and clinically applied for automated optimization of arterial pressure (AP) and prevention of intra-operative hypotension in humans. This study aimed to develop a simple computer-controlled closed-loop infusion system of NE for the automated control of the mean arterial pressure (MAP) in dogs with isoflurane-induced hypotension and to validate the control of MAP by the developed system. Methods: NE was administered via the cephalic vein, whereas MAP was measured invasively by placing a catheter in the dorsal pedal artery. The proportional-integral-derivative (PID) controller in the negative feedback loop of the developed system titrated the infusion rate of NE to maintain the MAP at the target value of 60 mmHg. The titration was updated every 2 s. The performance of the developed system was evaluated in six laboratory Beagle dogs under general anesthesia with isoflurane. Results: In the six dogs, when the concentration [median (interquartile range)] of inhaled isoflurane was increased from 1.5 (1.5-1.5)% to 4 (4-4)% without activating the system, the MAP was lowered from 95 (91-99) to 41 (37-42) mmHg. In contrast, when the concentration was increased from 1.5 (1.0-1.5)% to 4 (4-4.8)% for a 30-min period and the system was simultaneously activated, the MAP was temporarily lowered from 92 (89-95) to 47 (43-49) mmHg but recovered to 58 (57-58) mmHg owing to the system-controlled infusion of NE. If the acceptable target range for MAP was defined as target MAP ±5 mmHg (55 ≤ MAP ≤65 mmHg), the percentage of time wherein the MAP was maintained within the acceptable range was 96 (89-100)% in the six dogs during the second half of the 30-min period (from 15 to 30 min after system activation). The median performance error, median absolute performance error, wobble, and divergence were - 2.9 (-4.7 to 1.9)%, 2.9 (2.0-4.7)%, 1.3 (0.8-1.8)%, and - 0.24 (-0.34 to -0.11)%·min-1, respectively. No adverse events were observed during the study period, and all dogs were extubated uneventfully. Conclusion: This system was able to titrate the NE infusion rates in an accurate and stable manner to maintain the MAP within the predetermined target range in dogs with isoflurane-induced hypotension. This system can be a potential tool in daily clinical practice for the care of companion dogs

Visualization of oil-lubrication ball bearings at high rotational speeds

Deep-groove ball bearings for the eAxles of electric vehicles must adapt to higher rotational speed conditions because the speed of eAxle motors have been increasing as the size and weight of the motors decrease. Therefore, understanding the oil-lubricated conditions inside ball bearings at high rotational speeds is essential for optimizing their design for eAxles. To clarify the oil-lubricated conditions inside ball bearings at these high speeds, a new test apparatus was developed. This apparatus is capable of simultaneously measuring the friction torque of deep-groove ball bearings, the oil-film thickness on the rolling balls, and observing the oil distributions inside the bearings at rotational speeds up to 20,000 min-1. The oil-film thickness was measured using three-wavelength optical interferometry, and the oil distribution was observed using fluorescence. It was found that the oil-film thickness became constant at rotational speed conditions exceeding approximately 7,700 min-1. Oil starvations were observed on the raceway around the rolling ball, and these regions increased with increasing rotational speeds. Additionally, in the deep-groove ball bearing with a crown-shaped cage, the oil was mainly supplied to the rolling balls from the inner ring side through the space between the cage claws that held the ball. Moreover, the amount of mixed air tended to increase as the rotational speed increased to approximately 7,700 min-1. Those oil starvations and increasing air in oils were considered to be factors that prevent the increase in oil-film thickness. The findings of the reported study will contribute to the development of multibody dynamic technology for high-speed ball bearings necessary in electric vehicles

生態系における協調行動と個体群動態

博士(理学)doctoral創造科学技術大学院静岡大学甲第867号ET

Evaluation of harvest strategies for pelagic sharks taking ecological characteristics into consideration: an example for North Pacific blue shark

We have developed a population dynamics model that considers the spatial segregation by sex and ontogenetic stages of pelagic sharks. The model was used to evaluate the performance of harvest strategies based on ecological characteristics. We proposed five harvest strategies for longline fisheries based on the ecological characteristics of blue shark (Prionace glauca) in the North Pacific. Management objectives for depleted populations are to increase yield to the level that provides maximum sustainable yield (MSY) through increases in biomass without collapsing the fishery. Deterministic and stochastic analyses were undertaken. We determined that the harvest of male sharks was robust to uncertainty of environmental changes, reducing the likelihood of fishery collapse and stabilizing yield and mean biomass. The harvest of male sharks was also robust to the uncertainties of biological parameters such as natural mortality and steepness. These results suggested that, if there was no sperm limitation or impact on the mating behavior of the species, the harvest of males would be the most appropriate harvest strategy for blue shark in the North Pacific.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author