Publications by authors named "Kazuaki Okamoto"

15 Publications

  • Page 1 of 1

Risk factors of mFOLFOX6-induced hyperammonemia in patients with colorectal cancer: an observational study.

Int J Clin Oncol 2021 Aug 15;26(8):1477-1484. Epub 2021 May 15.

Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: FOLFOX therapy, a standard treatment for colorectal cancer (CRC), causes a rare, but serious adverse event, hyperammonemia. However, the risk factors of hyperammonemia remain unknown.

Methods: We examined 74 patients who received mFOLFOX6 therapy with or without biologics for CRC between April 2013 and March 2018 in Yaizu City Hospital. Clinicopathological factors were retrospectively reviewed in association with hyperammonemia, and risk factors of hyperammonemia during mFOLFOX6 therapy were analyzed in 32 patients with the available data.

Results: Seven patients developed hyperammonemia, with onset exclusively on day 2 or 3 in the first cycle of therapy. They were treated with branched chain amino acid administration and hydration; however, one patient with stage G4 chronic kidney disease (CKD) died. By multivariate analysis, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m was independently associated with hyperammonemia during FOLFOX therapy (odds ratio: 9.0, p = 0.040).

Conclusions: Reduced eGFR is considered a risk factor of developing hyperammonemia during FOLFOX therapy. Serum ammonia levels should be monitored especially during the first cycle of FOLFOX therapy in patients with CKD stage G3 or higher.
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http://dx.doi.org/10.1007/s10147-021-01932-wDOI Listing
August 2021

Extended Left Colectomy with Coloanal Anastomosis by Indocyanine Green-guided Deloyers Procedure: A Case Report.

J Anus Rectum Colon 2021 28;5(2):202-206. Epub 2021 Apr 28.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

The Deloyers procedure is performed after extended left colectomy, enabling the reach of the proximal colon to the rectum for anastomosis while preserving sufficient blood supply. We report a case of the Deloyers procedure performed safely under indocyanine green (ICG) fluorescence guidance. A 50-year-old man with obesity (body mass index, 35.7 kg/m) and a history of diabetes underwent an extended left hemicolectomy and ultralow anterior resection of the rectum as radical resection for transverse and sigmoid colon cancers and a lower rectal neuroendocrine tumor. Reconstruction was performed by the Deloyers procedure. A necessary length of the transverse colon with reduced blood flow was additionally resected under ICG fluorescence guidance, and a transanal hand-sewn coloanal anastomosis was performed. This is the first report in which the Deloyers procedure was performed successfully with the ICG fluorescence method. ICG fluorescence may be useful when combined with the Deloyers procedure.
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http://dx.doi.org/10.23922/jarc.2020-097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084531PMC
April 2021

Broad spectrum in vitro microbicidal activity of benzoyl peroxide against microorganisms related to cutaneous diseases.

J Dermatol 2021 Apr 28;48(4):551-555. Epub 2020 Dec 28.

Department of Microbiology and Infection Control Science, Kyoto Pharmaceutical University, Kyoto, Japan.

The in vitro microbicidal activity of benzoyl peroxide against Cutibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Malassezia furfur, Malassezia restricta, and Malassezia globosa was investigated. These strains were incubated for 1 h in the presence of 0.25, 0.5, 1, or 2 mmol/L benzoyl peroxide in phosphate buffered saline supplemented with 0.1% glycerol and 2% Tween 80. After exposure to benzoyl peroxide, counts of viable Gram-positive bacteria and fungi were markedly decreased, whereas counts of Gram-negative bacteria were unchanged. Transmission electron microscopy images showed a decrease in electron density and the destruction of C. acnes and M. restricta cell walls after exposure to 2 mmol/L benzoyl peroxide. In conclusion, this study showed that benzoyl peroxide has a potent and rapid microbicidal activity against Gram-positive bacteria and fungi that are associated with various cutaneous diseases. This suggests that the direct destruction of bacterial cell walls by benzoyl peroxide is an essential mechanism of its rapid and potent microbicidal activity against microorganisms.
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http://dx.doi.org/10.1111/1346-8138.15739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048985PMC
April 2021

Topologically Nontrivial Phase-Change Compound GeSbTe.

ACS Nano 2020 Jul 6;14(7):9059-9065. Epub 2020 Jul 6.

Department of Physical Sciences, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan.

Chalcogenide phase-change materials show strikingly contrasting optical and electrical properties, which has led to their extensive implementation in various memory devices. By performing spin-, time-, and angle-resolved photoemission spectroscopy combined with the first-principles calculation, we report the experimental results that the crystalline phase of GeSbTe is topologically nontrivial in the vicinity of the Dirac semimetal phase. The resulting linearly dispersive bulk Dirac-like bands that cross the Fermi level and are thus responsible for conductivity in the stable crystalline phase of GeSbTe can be viewed as a 3D analogue of graphene. Our finding provides us with the possibility of realizing inertia-free Dirac currents in phase-change materials.
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http://dx.doi.org/10.1021/acsnano.0c04145DOI Listing
July 2020

Anti-inflammatory effects of ozenoxacin, a topical quinolone antimicrobial agent.

J Antibiot (Tokyo) 2020 04 23;73(4):247-254. Epub 2020 Jan 23.

Maruho Co., Ltd, Kyoto R&D Center, Drug Development Laboratories, Kyoto Research Park, Bldg. #5, 93 Chudoji Awata-cho, Shimogyo-ku, Kyoto, 600-8815, Japan.

Ozenoxacin is a topical quinolone showing potent antimicrobial activities against Gram-negative and Gram-positive bacteria and is widely used for the treatment of inflammatory acne. However, the anti-inflammatory activities of ozenoxacin have not been examined so far. In the present study, we investigated the in vitro and in vivo anti-inflammatory effects of ozenoxacin. The production of interleukin (IL)-6 and IL-8 by human epidermal keratinocytes stimulated by heat-killed Cutibacterium acnes was significantly inhibited by ozenoxacin at concentrations from 1 to 30 μg ml. Likewise, the production of IL-6, IL-8, and tumor necrosis factor alpha by stimulated THP-1 cells, a human monocyte cell line, was inhibited by ozenoxacin at concentrations from 1 to 30 μg ml. The production of IL-1β by THP-1 was also inhibited by ozenoxacin at the concentration of 30 μg ml. Phosphorylation of the mitogen-activated protein kinases and degradation of IκB-α, an inhibitory factor of NF-κB in keratinocytes and THP-1 cells, was increased by stimulation with heat-killed C. acnes. Of these activated intracellular pathways, the p38 phosphorylation pathway was remarkably reduced by ozenoxacin in both keratinocytes and THP-1 cells. In addition, the application of 2% ozenoxacin suppressed the increase in the ear thickness of rats induced by an intracutaneous injection of heat-killed C. acnes. These findings suggest that ozenoxacin possesses an anti-inflammatory activity, which may contribute to its therapeutic effects on inflammatory acne.
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http://dx.doi.org/10.1038/s41429-020-0278-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056637PMC
April 2020

A case of pulmonary histoplasmosis diagnosed after lung lobectomy.

Surg Case Rep 2018 Dec 20;4(1):145. Epub 2018 Dec 20.

Department of Surgery, Yaizu City Hospital, 1000, Dobara, Yaizu, Shizuoka, Japan.

Background: Histoplasmosis is considered a fairly rare imported mycosis in Japan. Here we report a case of histoplasmosis describing the preoperative findings, histopathological findings, supposed infection route, and appropriate treatment, including the postoperative management.

Case Presentation: A healthy 65-year-old man was found at routine medical check-up to have an abnormal opacity on chest radiography. A chest computed tomography (CT) scan showed a nodular lesion in the posterior basal segment of the right lung, as well as two smaller nodules in the same lobe. This was highly suggestive of primary lung cancer with pulmonary metastases in the same lobe. We thus performed a right lower lobectomy with hilar and mediastinal lymph node dissection via thoracotomy. The lesions were diagnosed as pulmonary histoplasmosis on histopathology. At 6-month follow-up examination, the patient was free from fungal infection without any postoperative medication.

Conclusions: We describe a patient with pulmonary histoplasmosis diagnosed following surgical lobectomy. The possibility of pulmonary histoplasmosis should be considered in the differential diagnosis of pulmonary nodular lesions.
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http://dx.doi.org/10.1186/s40792-018-0554-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301901PMC
December 2018

Bactericidal activity and post-antibiotic effect of ozenoxacin against Propionibacterium acnes.

J Infect Chemother 2017 Jun 4;23(6):374-380. Epub 2017 Apr 4.

Department of Microbiology and Infection Control Science, Kyoto Pharmaceutical University, Japan.

Ozenoxacin, a novel non-fluorinated topical quinolone, is used for the treatment of acne vulgaris in Japan. We investigated bactericidal activity and post-antibiotic effect (PAE) of ozenoxacin against Propionibacterium acnes, a major causative bacterium of acne vulgaris. The minimum inhibitory concentrations (MICs) of ozenoxacin against 3 levofloxacin-susceptible strains (MIC of levofloxacin; ≤4 μg/mL) and 3 levofloxacin-resistant strains (MIC of levofloxacin; ≥8 μg/mL) ranged from 0.03 to 0.06 μg/mL and from 0.25 to 0.5 μg/mL, respectively. These MICs of ozenoxacin were almost the same or lower than nadifloxacin and clindamycin. The minimum bactericidal concentrations (MBCs) of ozenoxacin against the levofloxacin-susceptible and -resistant strains were from 0.06 to 8 μg/mL and from 0.5 to 4 μg/mL, respectively. These MBCs were lower than those of nadifloxacin and clindamycin. In time-kill assay, ozenoxacin at 1/4, 1 and 4 times the respective MIC against both levofloxacin-susceptible and -resistant strains showed a concentration-dependent bactericidal activity. Ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains showed more potent and more rapid onset of bactericidal activity compared to nadifloxacin and clindamycin at 4 times the respective MICs. The PAEs of ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains were from 3.3 to 17.1 h, which were almost the same or longer than nadifloxacin and clindamycin. In contrast, the PAEs were hardly induced by any antimicrobial agents against the levofloxacin-resistant strains. The present findings suggest that ozenoxacin has a potent bactericidal activity against both levofloxacin-susceptible and -resistant P. acnes, and a long-lasting PAE against levofloxacin-susceptible P. acnes.
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http://dx.doi.org/10.1016/j.jiac.2017.03.004DOI Listing
June 2017

Antimicrobial activities of ozenoxacin against isolates of propionibacteria and staphylococci from Japanese patients with acne vulgaris.

J Med Microbiol 2016 Aug 15;65(8):745-750. Epub 2016 Jun 15.

Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan.

Ozenoxacin, a novel non-fluorinated topical quinolone, was assessed for in vitro antimicrobial activity against clinical isolates of propionibacteria and staphylococci according to the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. The isolates used in this study were collected from Japanese patients with acne vulgaris during a period from 2012 to 2013. The MIC90s of ozenoxacin against Propionibacterium acnes (n=266), Propionibacterium granulosum (n=10), Staphylococcus aureus (n=23), Staphylococcus epidermidis (n=229) and other coagulase-negative staphylococci (n=82) were ≤0.06, ≤0.06, ≤0.06, 0.125 and ≤0.06 µg ml-1, respectively. The antimicrobial activity of ozenoxacin against the clinical isolates of propionibacteria and staphylococci was greater than that of five reference antimicrobial agents which have been used for the treatment of acne vulgaris. The MICs of ozenoxacin were correlated with those of nadifloxacin in P. acnes and S. epidermidis isolates. However, the MICs of ozenoxacin were 0.25-0.5 µg ml-1 and 0.5-8 µg ml-1 against nadifloxacin-resistant P. acnes (MIC: ≥8 µg ml-1; n=8) and S. epidermidis (MIC: ≥64 µg ml-1; n=10), respectively. These results indicated the potent antimicrobial activity against P. acnes and S. epidermidis isolates resistant to nadifloxacin. Topical ozenoxacin could represent an alternative therapeutic drug for acne vulgaris based on its potent antimicrobial activity against the isolates of propionibacteria and staphylococci from acne patients.
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http://dx.doi.org/10.1099/jmm.0.000293DOI Listing
August 2016

In vitro antimicrobial activity of ozenoxacin against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Streptococcus pyogenes isolated from clinical cutaneous specimens in Japan.

J Infect Chemother 2016 Oct 16;22(10):720-3. Epub 2016 Apr 16.

Clinical Trial Testing Department, LSI Medience Co., Japan.

Ozenoxacin, a novel non-fluorinated topical quinolone, was assessed for in vitro antimicrobial activity against each 50 isolates of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Streptococcus pyogenes according to the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. The isolates used in this study were recovered from cutaneous specimens of Japanese adult and pediatric patients who visited hospitals in 2014. The MIC90s of ozenoxacin against MSSA, MRSA and S. pyogenes isolates from adult patients were ≤0.06, 4 and ≤0.06 μg/mL, respectively. The MIC90s of ozenoxacin against MSSA and S. pyogenes isolates from pediatric patients were equal to those against the adult isolates. On the other hand, the MIC90s of ozenoxacin against the pediatric MRSA isolates was 0.12 μg/mL, and was 32 times lower than that against the adult isolates. The antimicrobial activity of ozenoxacin against MSSA, MRSA and S. pyogenes was equal to or greater than those of 7 reference antimicrobial agents had been used for the treatment of skin infections. The MICs of ozenoxacin was highly correlated with those of nadifloxacin and levofloxacin in the 50 MRSA isolates (r(2) = 0.906 and 0.833, respectively). However, ozenoxacin kept the potent antimicrobial activity with the MIC ranging from 1 to 4 μg/mL even against MRSA low susceptible (MIC: >64 μg/mL) to nadifloxacin or levofloxacin. Ozenoxacin could represent the first-in-class non-fluorinated quinolone for the topical treatment of various superficial skin infections caused by MSSA, MRSA and S. pyogenes.
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http://dx.doi.org/10.1016/j.jiac.2016.03.006DOI Listing
October 2016

In vitro antimicrobial activity of benzoyl peroxide against Propionibacterium acnes assessed by a novel susceptibility testing method.

J Infect Chemother 2016 Jun 21;22(6):426-9. Epub 2016 Jan 21.

Department of Dermatology, Tokyo Women's Medical University, Japan.

Benzoyl peroxide (BPO), a therapeutic agent for acne vulgaris, was assessed for in vitro antimicrobial activity against Propionibacterium acnes using a novel broth microdilution testing that improved BPO solubility. We searched for a suitable culture medium to measure the minimum inhibitory concentration (MIC) of BPO against P. acnes and finally found the Gifu anaerobic medium (GAM) broth supplemented with 0.1(v/v)% glycerol and 2(v/v)% Tween 80, in which BPO dissolved up to 1250 μg/mL and P. acnes grew well. The MICs and minimum bactericidal concentrations (MBCs) of BPO against 44 clinical isolates of P. acnes collected from Japanese patients with acne vulgaris were determined by our testing method using the supplemented GAM broth. The MICs of BPO were 128 or 256 μg/mL against all isolates of P. acnes regardless of susceptibility to nadifloxacin or clindamycin. The MBCs of BPO were also 128 or 256 μg/mL against the same isolates. Moreover, BPO at the MIC showed a rapid bactericidal activity against P. acnes ATCC11827 in time-kill assay. In conclusion, we could develop a novel assay for the MIC and MBC determinations of BPO against P. acnes, which is reliable and reproducible as a broth microdilution testing and the present results suggest that BPO has a potent bactericidal activity against P. acnes.
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http://dx.doi.org/10.1016/j.jiac.2015.12.010DOI Listing
June 2016

Perpendicular magnetic anisotropy with enhanced orbital moments of Fe adatoms on a topological surface of Bi2Se3.

J Phys Condens Matter 2013 Jun 14;25(23):232201. Epub 2013 May 14.

Hiroshima Synchrotron Radiation Center, Hiroshima University, 2-313 Kagamiyama, Higashi-Hiroshima, Japan.

We have found a perpendicular magnetic anisotropy of iron adatoms on a surface of the prototypical three-dimensional topological insulator Bi2Se3 by using x-ray magnetic circular dichroism measurements. The orbital magnetic moment of Fe is strongly enhanced at lower coverage, where angle-resolved photoemission spectroscopy shows coexistence of non-trivial topological states at the surface.
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http://dx.doi.org/10.1088/0953-8984/25/23/232201DOI Listing
June 2013

Involvement of hypothalamic periventricular GABAergic nerves in the central pressor response to clonidine in freely-moving conscious rats.

J Pharmacol Sci 2012 ;118(3):382-90

Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.

Microinjection of the α(2)-adrenoceptor agonist clonidine into the hypothalamic periventricular nuclei (PVN) induces the pressor response associated with bradycardia in freely-moving conscious rats. This study investigated the involvement of γ-aminobutyric acid nerves (GABAergic nerves) and glutamatergic nerves in the cardiovascular response to microinjection of clonidine in the PVN. Male Wistar rats were chronically implanted with a microinjection cannula into the PVN and an arterial catheter into the abdominal aorta through the femoral artery. Blood pressure and heart rate were measured under a conscious unrestrained state. PVN injection of clonidine induced a dose-dependent pressor response concomitant with bradycardia. PVN pretreatment with GABA, muscimol (GABA(A)-receptor agonist), or bicuculline (GABA(A)-receptor antagonist) significantly inhibited the pressor response to PVN-injected clonidine without affecting bradycardia. PVN pretreatment with baclofen (GABA(B)-receptor agonist), 2-hydroxysaclofen (GABA(B)-receptor antagonist), or kynurenic acid (non-selective NMDA-type glutamate-receptor and ionotropic glutamate-receptor antagonist) did not affect the pressor response to PVN-injected clonidine. These results suggest that clonidine induces a pressor response by stimulating the presynaptic α(2)-adrenoceptor of GABAergic nerves in the PVN, thereby inhibiting GABAergic nerve activity.
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http://dx.doi.org/10.1254/jphs.11233fpDOI Listing
September 2012

[Ameliorative effect of propolis on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats].

Yakugaku Zasshi 2010 Jun;130(6):833-40

Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.

Propolis is known to have abundant bioactive constituents and a variety of biological activities. To investigate the effect of Brazilian propolis on insulin resistance, 10-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a non-insulin-dependent type 2 diabetic model, were treated for 4 weeks with propolis (100 and 300 mg/kg, p.o.) or vehicle (control). Propolis treatment significantly decreased the plasma levels of insulin and insulin resistance index (Homeostasis Model Assessment-Insulin Resistance; HOM-IR), without affecting blood glucose levels and tended to lower systolic blood pressure compared with the control. In isolated and perfused mesenteric vascular beds of OLETF rats, propolis treatment resulted in significant reduction of sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and tended to increase calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS compared with in vehicle-treated OLETF rats. However, propolis treatment did not significantly affect the vasoconstrictor and vasodilator response to noradrenaline, CGRP, acetylcholine, and sodium nitroprusside. These results suggest that propolis could be an effective and functional food to prevent development of insulin resistance.
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http://dx.doi.org/10.1248/yakushi.130.833DOI Listing
June 2010

Separation of plastic mixtures using liquid-fluidized bed technology.

Chemosphere 2006 May 22;63(6):893-902. Epub 2005 Nov 22.

Nagoya Municipal Industrial Research Institute, 3-4-41 Rokuban, Atsuta-ku, Nagoya 456-0058, Japan.

Separation of heavier-than-water plastic mixtures had been investigated via the fluidization of their packed beds induced by an upward flow of water. The samples examined were resin pellets and crushed plastic products including PVC, PET and PBT. On the onset of a flow, a mixed bed was swelled to the state of fluidization and separated into layers of respective resins depending on their density. The effects of the flow rate, an amount of the samples and their density difference were examined on the separation of resin pellets. Under an appropriate condition, the process was completed within a few minutes, and satisfactory separation was attained when the density difference of the samples exceeded 0.05 g cm-3. By using a column equipped with several sample outlets sorted resins could be recovered with their purity intact by withdrawing each layer successively from above through a suitable outlet. Multi-stage separation was also found to be effective in treating close-density samples. Compared with uniform-sized resin pellets, size distribution of crushed plastic samples deteriorated the separation to some extent.
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http://dx.doi.org/10.1016/j.chemosphere.2005.09.068DOI Listing
May 2006

New poly(butylene succinate)/layered silicate nanocomposites: preparation and mechanical properties.

J Nanosci Nanotechnol 2002 Apr;2(2):171-6

Advanced Polymeric Materials Engineering, Graduate School of Engineering, Toyota Technological Institute, Hisakata 2-12-1, Tempaku, Nagoya 468 8511, Japan.

New poly(butylene succinate) (PBS)/layered silicate nanocomposites have been successfully prepared by simple melt extrusion of PBS and octadecylammonium modified montmorillonite (C18-mmt) at 150 degrees C. The d-spacing of both C18-mmt and intercalated nanocomposites was investigated by wide-angle X-ray diffraction analysis. Bright-field transmission electron microscopic study showed several stacked silicate layers with random orientation in the PBS matrix. The intercalated nanocomposites exhibited remarkable improvement of mechanical properties in both solid and melt states as compared with that of PBS matrix without clay.
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http://dx.doi.org/10.1166/jnn.2002.086DOI Listing
April 2002
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