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Article ; Online: Depressive symptoms and overwork among physicians employed at a university hospital in Japan

Toru Maruyama

Journal of Health and Social Sciences, Vol 2, Iss 3, Pp 243-

2017 Volume 256

Abstract: Introduction: The excessive workload of Japanese hospital physicians is a serious social problem due to effects on their mental health status, as well as the potential for medical errors and lawsuits. The extent of overwork among resident physicians ... ...

Abstract	Introduction: The excessive workload of Japanese hospital physicians is a serious social problem due to effects on their mental health status, as well as the potential for medical errors and lawsuits. The extent of overwork among resident physicians employed at national university hospitals in Japan is unknown and needs to be investigated. Methods: This study used a questionnaire recommended by the Japanese Ministry of Health for hospital physicians working overtime, administered through an interview carried out by an occupational physician during the health surveillance to evaluate: 1) the severity of chronic fatigue; 2) the burden of work; 3) an overwork score derived from these two measures; and 4) presence of depressive symptoms. After the feasibility of the questionnaire was confirmed, both a cross-sectional and a longitudinal study were performed, while statistics analysis included multiple linear regression analysis and chi-square test set at P < 0.05. Results: Most of the overworked physicians were young medical staffs (48%), whereas postgraduate residents formed a small group (10%). In the cross-sectional study (n = 135; mean age 32.7 years ± 5.6), the histograms of scores for the four factors investigated showed a strong positive skewness, while overtime histograms showed a negative skewness at 4, 3, and 2 months prior to the interview with occupational physician, but positive skewness 1 month prior to the interview. The longitudinal study (n = 26) showed an increase or reduction of overtime respectively having a significant impact on exacerbation or improvement of the overwork score (P = 0.028) and depressive symptoms (P = 0.025). Discussion and Conclusions: A strong positive skewness of the histograms for items related to overwork might indicate fear of stigma of mental illness amongst young physicians. Physicians employed at Japanese national university hospitals should be protected by the institution, and the roles of occupational physician and health surveillance are crucial and should be ...
Keywords	Legislation;hospital ; Japan ; physicians ; preventive psychiatry ; psychology;industrial ; social stigma ; occupational health physicians ; overtime work ; Medicine (General) ; R5-920 ; Social sciences (General) ; H1-99
Subject code	360
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	Edizioni FS
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Advanced Oxidation Protein Products Contribute to Chronic-Kidney-Disease-Induced Adipose Inflammation through Macrophage Activation

Nanaka Arimura / Hiroshi Watanabe / Hiromasa Kato / Tadashi Imafuku / Takehiro Nakano / Miyu Sueyoshi / Mayuko Chikamatsu / Kai Tokumaru / Taisei Nagasaki / Hitoshi Maeda / Motoko Tanaka / Kazutaka Matsushita / Toru Maruyama

Toxins, Vol 15, Iss 179, p

2023 Volume 179

Abstract: Fat atrophy and adipose tissue inflammation can cause the pathogenesis of metabolic symptoms in chronic kidney disease (CKD). During CKD, the serum levels of advanced oxidation protein products (AOPPs) are elevated. However, the relationship between fat ... ...

Abstract	Fat atrophy and adipose tissue inflammation can cause the pathogenesis of metabolic symptoms in chronic kidney disease (CKD). During CKD, the serum levels of advanced oxidation protein products (AOPPs) are elevated. However, the relationship between fat atrophy/adipose tissue inflammation and AOPPs has remained unknown. The purpose of this study was to investigate the involvement of AOPPs, which are known as uremic toxins, in adipose tissue inflammation and to establish the underlying molecular mechanism. In vitro studies involved co-culturing mouse-derived adipocytes (differentiated 3T3-L1) and macrophages (RAW264.7). In vivo studies were performed using adenine-induced CKD mice and AOPP-overloaded mice. Fat atrophy, macrophage infiltration and increased AOPP activity in adipose tissue were identified in adenine-induced CKD mice. AOPPs induced MCP-1 expression in differentiated 3T3-L1 adipocytes via ROS production. However, AOPP-induced ROS production was suppressed by the presence of NADPH oxidase inhibitors and the scavengers of mitochondria-derived ROS. A co-culturing system showed AOPPs induced macrophage migration to adipocytes. AOPPs also up-regulated TNF-α expression by polarizing macrophages to an M1-type polarity, and then induced macrophage-mediated adipose inflammation. In vitro data was supported by experiments using AOPP-overloaded mice. AOPPs contribute to macrophage-mediated adipose inflammation and constitute a potential new therapeutic target for adipose inflammation associated with CKD.
Keywords	advanced oxidation protein products ; albumin ; chronic kidney disease ; adipose inflammation ; macrophage migration ; macrophage polarization ; Medicine ; R
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of the Pharmacokinetic Properties of Hemoglobin-Based Oxygen Carriers

Kazuaki Taguchi / Keishi Yamasaki / Toru Maruyama / Masaki Otagiri

Journal of Functional Biomaterials, Vol 8, Iss 1, p

2017 Volume 11

Abstract: Hemoglobin (Hb) is an ideal material for use in the development of an oxygen carrier in view of its innate biological properties. However, the vascular retention of free Hb is too short to permit a full therapeutic effect because Hb is rapidly cleared ... ...

Abstract	Hemoglobin (Hb) is an ideal material for use in the development of an oxygen carrier in view of its innate biological properties. However, the vascular retention of free Hb is too short to permit a full therapeutic effect because Hb is rapidly cleared from the kidney via glomerular filtration or from the liver via the haptogloblin-CD 163 pathway when free Hb is administered in the blood circulation. Attempts have been made to develop alternate acellular and cellular types of Hb based oxygen carriers (HBOCs), in which Hb is processed via various routes in order to regulate its pharmacokinetic properties. These HBOCs have been demonstrated to have superior pharmacokinetic properties including a longer half-life than the Hb molecule in preclinical and clinical trials. The present review summarizes and compares the pharmacokinetic properties of acellular and cellular type HBOCs that have been developed through different approaches, such as polymerization, PEGylation, cross-linking, and encapsulation.
Keywords	hemoglobin ; oxygen carrier ; liposome ; pharmacokinetic ; Biotechnology ; TP248.13-248.65 ; Medicine (General) ; R5-920
Language	English
Publishing date	2017-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: β2-adrenergic receptor agonist counteracts skeletal muscle atrophy and oxidative stress in uremic mice

Takaaki Higashihara / Hiroshi Nishi / Koji Takemura / Hiroshi Watanabe / Toru Maruyama / Reiko Inagi / Tetsuhiro Tanaka / Masaomi Nangaku

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 14

Abstract: Abstract In patients with chronic kidney disease, skeletal muscle dysfunction is associated with mortality. Uremic sarcopenia is caused by ageing, malnutrition, and chronic inflammation, but the molecular mechanism and potential therapeutics have not ... ...

Abstract	Abstract In patients with chronic kidney disease, skeletal muscle dysfunction is associated with mortality. Uremic sarcopenia is caused by ageing, malnutrition, and chronic inflammation, but the molecular mechanism and potential therapeutics have not been fully elucidated yet. We hypothesize that accumulated uremic toxins might exert a direct deteriorative effect on skeletal muscle and explore the pharmacological treatment in experimental animal and culture cell models. The mice intraperitoneally injected with indoxyl sulfate (IS) after unilateral nephrectomy displayed an elevation of IS concentration in skeletal muscle and a reduction of instantaneous muscle strength, along with the predominant loss of fast-twitch myofibers and intramuscular reactive oxygen species (ROS) generation. The addition of IS in the culture media decreased the size of fully differentiated mouse C2C12 myotubes as well. ROS accumulation and mitochondrial dysfunction were also noted. Next, the effect of the β2-adrenergic receptor (β2-AR) agonist, clenbuterol, was evaluated as a potential treatment for uremic sarcopenia. In mice injected with IS, clenbuterol treatment increased the muscle mass and restored the tissue ROS level but failed to improve muscle weakness. In C2C12 myotubes stimulated with IS, although β2-AR activation also attenuated myotube size reduction and ROS accumulation as did other anti-oxidant reagents, it failed to augment the mitochondrial membrane potential. In conclusion, IS provokes muscular strength loss (uremic dynapenia), ROS generation, and mitochondrial impairment. Although the β2-AR agonist can increase the muscular mass with ROS reduction, development of therapeutic interventions for restoring skeletal muscle function is still awaited.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Enrichment of bacteria and alginate lyase genes potentially involved in brown alga degradation in the gut of marine gastropods

Michihiro Ito / Kotaro Watanabe / Toru Maruyama / Tetsushi Mori / Kentaro Niwa / Seinen Chow / Haruko Takeyama

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 13

Abstract: Abstract Gut bacteria of phytophagous and omnivorous marine invertebrates often possess alginate lyases (ALGs), which are key enzymes for utilizing macroalgae as carbon neutral biomass. We hypothesized that the exclusive feeding of a target alga to ... ...

Abstract	Abstract Gut bacteria of phytophagous and omnivorous marine invertebrates often possess alginate lyases (ALGs), which are key enzymes for utilizing macroalgae as carbon neutral biomass. We hypothesized that the exclusive feeding of a target alga to marine invertebrates would shift the gut bacterial diversity suitable for degrading the algal components. To test this hypothesis, we reared sea hare (Dolabella auricularia) and sea snail (Batillus cornutus) for two to four weeks with exclusive feeding of a brown alga (Ecklonia cava). Pyrosequencing analysis of the gut bacterial 16S rRNA genes revealed shifts in the gut microbiota after rearing, mainly due to a decrease in the variety of bacterial members. Significant increases in six and four 16S rRNA gene phylotypes were observed in the reared sea hares and sea snails, respectively, and some of them were phylogenetically close to known alginate-degrading bacteria. Clone library analysis of PL7 family ALG genes using newly designed degenerate primer sets detected a total of 50 ALG gene phylotypes based on 90% amino acid identity. The number of ALG gene phylotypes increased in the reared sea hare but decreased in reared sea snail samples, and no phylotype was shared between them. Out of the 50 phylotypes, 15 were detected only after the feeding procedure. Thus, controlled feeding strategy may be valid and useful for the efficient screening of genes suitable for target alga fermentation.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A bioinspired carbon monoxide delivery system prevents acute kidney injury and the progression to chronic kidney disease

Taisei Nagasaki / Hitoshi Maeda / Kazuaki Taguchi / Hiroki Yanagisawa / Kento Nishida / Kazuki Kobayashi / Naoki Wada / Isamu Noguchi / Ryota Murata / Hiromi Sakai / Hiroaki Kitagishi / Junji Saruwatari / Hiroshi Watanabe / Masaki Otagiri / Toru Maruyama

Redox Biology, Vol 54, Iss , Pp 102371- (2022)

2022

Abstract: Renal ischemia-reperfusion (IR)-induced tissue hypoxia causes impaired energy metabolism and oxidative stress. These conditions lead to tubular cell damage, which is a cause of acute kidney injury (AKI) and AKI to chronic kidney disease (CKD). Three key ... ...

Abstract	Renal ischemia-reperfusion (IR)-induced tissue hypoxia causes impaired energy metabolism and oxidative stress. These conditions lead to tubular cell damage, which is a cause of acute kidney injury (AKI) and AKI to chronic kidney disease (CKD). Three key molecules, i.e., hypoxia-inducible factor-1α (HIF-1α), AMP-activated protein kinase (AMPK), and nuclear factor E2-related factor 2 (Nrf2), have the potential to protect tubular cells from these disorders. Although carbon monoxide (CO) can comprehensively induce these three molecules via the action of mitochondrial reactive oxygen species (mtROS), the issue of whether CO induces these molecules in tubular cells remains unclear. Herein, we report that CO-enriched red blood cells (CO-RBC) cell therapy, the inspiration for which is the in vivo CO delivery system, exerts a renoprotective effect on hypoxia-induced tubular cell damage via the upregulation of the above molecules. Experiments using a mitochondria-specific antioxidant provide evidence to show that CO-driven mtROS partially contributes to the upregulation of the aforementioned molecules in tubular cells. CO-RBC ameliorates the pathological conditions of IR-induced AKI model mice via activation of these molecules. CO-RBC also prevents renal fibrosis via the suppression of epithelial mesenchymal transition and transforming growth factor-β1 secretion in an IR-induced AKI to CKD model mice. In conclusion, our results confirm that the bioinspired CO delivery system prevents the pathological conditions of both AKI and AKI to CKD via the amelioration of hypoxia inducible tubular cell damage, thereby making it an effective cell therapy for treating the progression to CKD.
Keywords	Tubular cell damage ; Carbon monoxide ; Red blood cells ; Acute kidney injury ; Acute kidney injury to chronic kidney disease transition ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Response to “iPTH is not a significant factor influencing the tacrolimus C/D ratio”

Ryota Tanaka / Yosuke Suzuki / Hiroshi Watanabe / Takashi Fujioka / Kenshiro Hirata / Toshitaka Shin / Tadasuke Ando / Hiroyuki Ono / Ryosuke Tatsuta / Hiromitsu Mimata / Toru Maruyama / Hiroki Itoh

Clinical and Translational Science, Vol 15, Iss 4, Pp 807-

2022 Volume 808

Keywords	Therapeutics. Pharmacology ; RM1-950 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Metal-catalyzed oxidation of human serum albumin does not alter the interactive binding to the two principal drug binding sites

Keishi Yamasaki / Koji Nishi / Makoto Anraku / Kazuaki Taguchi / Toru Maruyama / Masaki Otagiri

Biochemistry and Biophysics Reports, Vol 14, Iss C, Pp 155-

2018 Volume 160

Abstract: It is well known that various physiological factors such as pH, endogenous substances or post-translational modifications can affect the conformational state of human serum albumin (HSA). In a previous study, we reported that both pH- and long chain ... ...

Abstract	It is well known that various physiological factors such as pH, endogenous substances or post-translational modifications can affect the conformational state of human serum albumin (HSA). In a previous study, we reported that both pH- and long chain fatty acid-induced conformational changes can alter the interactive binding of ligands to the two principal binding sites of HSA, namely, site I and site II. In the present study, the effect of metal-catalyzed oxidation (MCO) caused by ascorbate/oxygen/trace metals on HSA structure and the interactive binding between dansyl-L-asparagine (DNSA; a site I ligand) and ibuprofen (a site II ligand) at pH 6.5 was investigated. MCO was accompanied by a time-dependent increase in carbonyl content in HSA, suggesting that the HSA was being oxidized. In addition, The MCO of HSA was accompanied by a change in net charge to a more negative charge and a decrease in thermal stability. SDS-PAGE patterns and α-helical contents of the oxidized HSAs were similar to those of native HSA, indicating that the HSA had not been extensively structurally modified by MCO. MCO also caused a selective decrease in ibuprofen binding. In spite of the changes in the HSA structure and ligand that bind to site II, no change in the interactive binding between DNSA and ibuprofen was observed. These data indicated that amino acid residues in site II are preferentially oxidized by MCO, whereas the spatial relationship between sites I and II (e.g. the distance between sites), the flexibility or space of each binding site are not altered. The present findings provide insights into the structural characteristics of oxidized HSA, and drug binding and drug-drug interactions on oxidized HSA.
Keywords	Human serum albumin ; Metal-catalyzed oxidation ; Binding site ; Biology (General) ; QH301-705.5 ; Biochemistry ; QD415-436
Subject code	500
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Surgery for Idiopathic Scoliosis

Toru Maruyama / Katsushi Takeshita

Clinical Medicine: Pediatrics, Vol 3, Pp 39-

Currently Applied Techniques

2009 Volume 44

Abstract: This review discusses the basic knowledge and recent innovation of surgical treatment for scoliosis. Surgical treatment for scoliosis is indicated, in general, for a curve exceeding 45 to 50 degrees by the Cobb’s method on the basis that:1. Curves larger ...

Abstract	This review discusses the basic knowledge and recent innovation of surgical treatment for scoliosis. Surgical treatment for scoliosis is indicated, in general, for a curve exceeding 45 to 50 degrees by the Cobb’s method on the basis that:1. Curves larger than 50 degrees progress even after skeletal maturity.2. Curves larger than 60 degrees cause loss of pulmonary function, and much larger curves cause respiratory failure.3. Greater the curve progression, the more difficult it is to treat with surgery.Posterior fusion with instrumentation has been the standard form of surgical treatment for scoliosis. In modern instrumentation systems, more anchors are used to connect the rod and the spine, resulting in better correction and less frequent implant failures. Segmental pedicle screw constructs or hybrid constructs using pedicle screws, hooks, and wires are the trend of today. Anterior instrumentation surgery was once the choice of treatment for thoracolumbar and lumbar scoliosis because better correction could be obtained with shorter fusion levels. But in the recent times, superiority of anterior surgery for the thoracolumbar and lumbar scoliosis has been questioned. Initial enthusiasm for anterior instrumentation for the thoracic curve using video assisted thoracoscopy has faded out.
Keywords	scoliosis ; surgery ; instrumentation ; fusion ; fusionless ; Pediatrics ; RJ1-570 ; Medicine ; R ; DOAJ:Pediatrics ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2009-01-01T00:00:00Z
Publisher	Libertas Academica
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Association of CYP3A5 polymorphisms and parathyroid hormone with blood level of tacrolimus in patients with end‐stage renal disease

Ryota Tanaka / Yosuke Suzuki / Hiroshi Watanabe / Takashi Fujioka / Kenshiro Hirata / Toshitaka Shin / Tadasuke Ando / Hiroyuki Ono / Ryosuke Tatsuta / Hiromitsu Mimata / Toru Maruyama / Hiroki Itoh

Clinical and Translational Science, Vol 14, Iss 5, Pp 2034-

2021 Volume 2042

Abstract: Abstract Because tacrolimus is predominantly metabolized by CYP3A, the blood concentration/dose (C/D) ratio is affected by CYP3A5 polymorphism. Parathyroid hormone (PTH) expression increases in secondary hyperparathyroidism, which is frequently ... ...

Abstract	Abstract Because tacrolimus is predominantly metabolized by CYP3A, the blood concentration/dose (C/D) ratio is affected by CYP3A5 polymorphism. Parathyroid hormone (PTH) expression increases in secondary hyperparathyroidism, which is frequently associated with end‐stage renal disease. Recently, PTH has been shown to downregulate CYP3A expression at mRNA level. In this study, we examined the influence of CYP3A5 polymorphism on and association of serum intact‐PTH (iPTH) level with blood tacrolimus concentration in patients with end‐stage renal disease just before kidney transplantation. Forty‐eight patients who satisfied the selection criteria were analyzed. Subjects were classified into two phenotype subgroups: CYP3A5 expressor (CYP3A51/1 and 1/3; n = 15) and CYP3A5 nonexpressor (CYP3A53/3; n = 33). The blood tacrolimus C/D (per body weight) ratio was significantly lower in CYP3A5 expressors than that in CYP3A5 nonexpressors. A significant positive correlation was found between tacrolimus C/D and iPTH concentrations (r = 0.305, p = 0.035), and the correlation coefficient was higher after excluding 20 patients co‐administered CYP3A inhibitor or inducer (r = 0.428, p = 0.023). A multiple logistic regression analysis by stepwise selection identified CYP3A5 polymorphism and serum iPTH level as significant factors associated with tacrolimus C/D. These results may suggest the importance of dose design considering not only the CYP3A5 phenotype but also serum iPTH level when using tacrolimus in patients who undergo renal transplantation.
Keywords	Therapeutics. Pharmacology ; RM1-950 ; Public aspects of medicine ; RA1-1270
Subject code	610 ; 616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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