Publications by authors named "Ayumi Ito"

35 Publications

Tumor Infiltrating Lymphocytes are Prognostic Factors and Can Be Markers of Sensitivity to Chemoradiotherapy in Head and Neck Squamous Cell Carcinoma.

Asian Pac J Cancer Prev 2022 Apr 1;23(4):1271-1278. Epub 2022 Apr 1.

Department of Molecular and Tumour Pathology, Akita University Graduate School of Medicine, Akita, 010-8543 Japan.

Background: Tumor-infiltrating lymphocytes (TILs) are assessed by the ratio of the area of lymphocytes infiltrating the stroma. TILs are important in breast cancer and malignant melanoma and are being established as a marker of prognosis and sensitivity to chemotherapy. This has resulted in various therapies being developed in fields such as breast cancer. However, the evaluation of TILs in head and neck squamous cell carcinoma (HNSCC) is not progressing, and the prognosis is still poor. Thus, investigating whether or not the evaluation of TILs is also effective in HNSCC and prognoses can be predicted with just biopsy samples alone is required.

Methods: This study included 153 patients who were diagnosed with HNSCC between January 2010 and December 2019, underwent treatment, and could be followed up thereafter at our institution.

Results: TILs, overall survival (OS), and progression-free survival (PFS) were evaluated in all patients, the chemoradiotherapy arm, and the surgery arm. The cut-off value for TILs was 50%. In all patients, OS was 69.8% and 40.2% (P = 0.01) and PFS was 58.4% and 31.6% (P = 0.003) in the high and low TIL groups, respectively. Multivariate analyses revealed that TILs independently predicted prognosis. In the chemoradiotherapy arm, OS was 70.8% and 31.6% (P = 0.012) and PFS was 63.4% and 20.3% (P = 0.001) in the high and low TIL groups, respectively. No significant differences were noted in the surgery arm.

Conclusions: In HNSCC, TILs can be used as a prognosis predictor and chemoradiotherapy biomarker. Assessments can be performed just with hematoxylin-eosin staining and is very simple. This will greatly contribute to report personalized therapy progress. Further evaluations and, thus, prospective clinical multicenter trials are needed to use TILs in clinical practice for HNSCC.
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http://dx.doi.org/10.31557/APJCP.2022.23.4.1271DOI Listing
April 2022

Degradation of the endocrine-disrupting 4-nonylphenol by ferrate(VI): biodegradability and toxicity evaluation.

Environ Sci Pollut Res Int 2022 Mar 27;29(13):18882-18890. Epub 2021 Oct 27.

Course of Civil and Environmental Engineering, Department of System Innovation Engineering, Faculty of Science and Engineering, Iwate University, Ueda 4-3-5, Morioka, 020-8551, Japan.

4-Nonylphenol (4-NP) is an endocrine-disrupting and persistent chemical and is partially degraded in conventional wastewater treatment processes. Ferrate(VI) can be used as an environment-friendly oxidizing agent to mediate 4-NP degradation. Thus, this paper evaluates the biodegradability of 4-NP and its degradation products after the addition of ferrate(VI). The biodegradability was examined using NP labeled with C as a tracer and activated sludge microorganisms as an inoculum. The addition of ferrate(VI) to the 4-NP solution spiked with the tracer resulted in no remarkable decrease in the concentration of C, indicating incomplete mineralization of 4-NP and formation of degradation products. The degradation products from 4-NP with Fe(VI) were estimated based on mass spectra, which detected a unique peak at m/z 223 at low intensity. Four hydrogen atoms might have been added to 4-NP by degradation with Fe(VI). In addition, the effect of ferrate(VI) concentration on the estrogenic activity of 4-NP in an aqueous solution was investigated using a yeast bioassay. The results show that estrogenic activity was significantly decreased at a mass ratio of Fe(VI) to 4-NP greater than or equal to 2.5.
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http://dx.doi.org/10.1007/s11356-021-17167-1DOI Listing
March 2022

Effect of dissolved soil organic matter on cesium adsorption by zeolite and illite.

J Environ Manage 2021 Jul 31;289:112477. Epub 2021 Mar 31.

Department of Systems Innovation Engineering, Faculty of Science and Engineering, Iwate University, 4-3-5 Ueda, Morioka, Iwate, 020-8551, Japan.

In controlled landfill sites, soil layers are installed around radioactive waste to prevent the leaching of radioactive cesium (Cs). The Cs retention capacity of soil has been reported to be enhanced by mixing clay minerals. However, several studies have indicated that dissolved soil organic matter (DSOM) inhibits the Cs sorption by clay minerals. Therefore, this study assesses the effect of DSOM on the Cs sorption by zeolite and illite. Excitation emission matrix fluorescence spectroscopy was used for DSOM in the soil solution before and after contact with clay minerals. The results show that DSOM sorption onto clay minerals, particularly fulvic acid, inhibited Cs sorption. Batch sorption tests were conducted to obtain the sorption isotherms using two sample solutions, namely, soil and ionic solutions. Soil solution, which contained DSOM, was prepared by mixing soil and ultrapure water and filtration using a 0.3-μm glass fiver filter. Ionic solution was prepared by removing DSOM larger than 500 Da from the soil solution using dialysis. The amount of sorbed Cs in the soil solution was lower than that in the ionic solution. Comparing the Freundlich coefficients (K) between the soil and ionic solutions, we found that the K values of zeolite and illite for the ionic solution accounted for 6.4- and 4.4-fold higher than that for the soil solution, respectively.
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http://dx.doi.org/10.1016/j.jenvman.2021.112477DOI Listing
July 2021

Clinical Characterization of Ulcerative Colitis in Patients with Primary Sclerosing Cholangitis.

Gastroenterol Res Pract 2020 7;2020:7969628. Epub 2020 Nov 7.

Department of Gastroenterology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.

Objectives: The clinical/colonoscopic features of ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC), the prognostic impact of UC, and the utility of UC screening in PSC patients are unknown. We characterized UC associated with PSC and assessed UC's impact on the prognosis of PSC and the importance of colonoscopic UC screening in PSC patients.

Methods: We retrospectively analyzed the cases of 77 patients treated for PSC at a single center (April 2000-July 2019). We reviewed the clinical/colonoscopic profiles of the concurrent UC patients and compared the clinical profiles, survival, and primary causes of death between the patients with/without UC ( = 35/ = 42). The details of all patients' colonoscopies were reviewed.

Results: The concurrent UC group: 17 men, 18 women, diagnosed with PSC at the mean (SD) age of 36 (17) years; 21 patients (60%) had no UC symptoms. Colonoscopy revealed pancolitis in all patients, predominantly affecting the right-sided colon in 30 patients (86%). Lesions were scattered. Backwash ileitis ( = 13, 37%) and rectal sparing ( = 18, 51%) were observed. Most patients had mild UC; some had moderate or more severe UC (median Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score 2; range, 1-5). Ludwig's stage determined by liver biopsy did not correlate with the Mayo endoscopic score for UC. The patients with UC were diagnosed with PSC at a significantly younger age than those without UC (mean (SD), 36 [17] years vs. 55 [19] years, < 0.0001) and had a significantly higher 5-year survival rate (97.1% vs. 70.5%, = 0.0028). UC was detected in 19 of 34 asymptomatic patients (56%) who underwent colonoscopy screening.

Conclusions: Our cohort's clinical/colonoscopic features of UC associated with PSC are more moderate or severe UC than previous cases. The coexistence of UC might affect the prognosis of PSC. In this regard, colonoscopy in PSC patients is an important examination for determining prognosis. There is also asymptomatic UC in patients with PSC. In this regard, screening for colonoscopy in PSC patients is essential. When a diagnosis of PSC is made, immediate colonoscopy is a priority with UC complications in mind.
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http://dx.doi.org/10.1155/2020/7969628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669346PMC
November 2020

The Efficacy of Medium- to Long-term Anti-TNF-α Antibody-based Maintenance Therapy in Behçet's Disease Patients with Intestinal Lesions.

Intern Med 2020 1;59(19):2343-2351. Epub 2020 Oct 1.

Institute of Gastroenterology, Tokyo Women's Medical University, Japan.

Objective Anti-tumor necrosis factor (TNF)-α antibody-based regimens are effective in Behçet's disease (BD) with intestinal lesions. We therefore evaluated the efficacy of medium- to long-term anti-TNF-α antibody-based maintenance therapy of BD intestinal and non-intestinal lesions. Methods In this retrospective study, the response to the treatment was assessed endoscopically and clinically. Treatment responders were transferred to maintenance therapy. We evaluated the sustain rate of maintenance therapy, reductions in the dose of prednisolone (PSL), and the presence of non-intestinal BD involvement before and after the start of anti-TNF-α antibody-based the maintenance therapy. Patients We assessed 20 BD patients with intestinal lesions who underwent anti-TNF-α antibody-based therapy. Results Treatment was discontinued in 3 patients (18%). Loss of response was noted in 1 (5.9%) patient. Maintenance therapy was continued in 13 (76%) patients. The cumulative sustain rates to maintenance therapy after 2, 4, and 6 years were 94%, 87%, and 72%, respectively. In the 13 patients with remission of intestinal lesions, the mean PSL dose decreased from 13.4±2.16 mg/day before treatment to 0.92±0.47 after treatment (p<0.0001). PSL was discontinued in 9 (69%) patients. Five of the 13 (38%) patients developed clinical features of non-intestinal BD during the remission-maintenance treatment. Conclusion Our results demonstrated the efficacy of medium- to long-term anti-TNF-α antibody-based maintenance treatment against BD intestinal lesions. Nevertheless, some cases with well-controlled intestinal lesions developed active non-intestinal BD symptoms. The results highlight the importance of a carefully planned treatment strategy for BD patients with intestinal involvement.
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http://dx.doi.org/10.2169/internalmedicine.5000-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644480PMC
November 2020

Relationship between mucosal healing by tacrolimus and relapse of refractory ulcerative colitis: a retrospective study.

BMC Gastroenterol 2020 Jun 26;20(1):203. Epub 2020 Jun 26.

Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan.

Background: Tacrolimus (TAC) is a powerful remission-inducing drug for refractory ulcerative colitis (UC). However, it is unclear whether mucosal healing (MH) influences relapse after completion of TAC.We investigated whether MH is related to relapse after TAC.

Patients: Among 109 patients treated with TAC, 86 patients achieved clinical remission and 55 of them underwent colonoscopy at the end of TAC. These 55 patients were investigated.

Methods: Patients with MH at the end of TAC were classified into the MH group (n = 41), while patients without MH were classified into the non-MH group (n = 14). These groups were compared with respect to 1) clinical characteristics before treatment, 2) clinical characteristics on completion of treatment, and 3) the relapse rate and adverse events rates. This is a retrospective study conducted at a single institution.

Results: 1) There was a significant difference in baseline age between the two groups before TAC therapy, but there were no significant differences in other clinical characteristics. The NMH group was younger (MH group: 48.1 (23-79) years, NMH group: 36.3 (18-58) years, P = 0.007). Endoscopic scores showed significant differences between the 2 groups at the end of TAC. There were also significant differences in the steroid-free rate after 24 weeks (MH group: 85.3%, NMH group 50%, P = 0.012). There was no significant difference in the relapse rate between the 2 groups at 100 days after remission, but a significant difference was noted at 300 days (17% vs. 43%), 500 days (17% vs. 75%), and 1000 days (17% vs. 81%) (all P < 0.05).

Conclusions: TAC is effective for refractory ulcerative colitis. However, even if clinical remission is achieved, relapse is frequent when colonoscopy shows that MH has not been achieved. It is important to evaluate the mucosal response by colonoscopy on completion of TAC.
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http://dx.doi.org/10.1186/s12876-020-01317-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320561PMC
June 2020

Safety and effectiveness of adalimumab in Japanese patients with juvenile idiopathic arthritis: Results from a real-world postmarketing study.

Mod Rheumatol 2021 Mar 18;31(2):421-430. Epub 2020 May 18.

Fuji Toranomon Orthopedic Hospital, Gotemba, Shizuoka, Japan.

Objectives: This study was conducted to assess the real-world safety and effectiveness of adalimumab in patients with juvenile idiopathic arthritis (JIA).

Methods: In this all-case, postmarketing surveillance study (NCT01412021) conducted in Japan, patients receiving adalimumab for JIA affecting multiple joints were observed for 24 weeks. The safety (adverse drug reactions [ADRs]/serious ADRs) and effectiveness (4-variable Disease Activity Score in 28 joints using erythrocyte sedimentation rate [DAS28-4/ESR] remission rate) were assessed.

Results: In the safety population ( = 356), 90.3% (65/72; weight, ≥15-<30 kg) of patients received adalimumab 20 mg every 2 weeks (q2w) and 98.3% (236/240; weight ≥30 kg) received 40 mg q2w. Incidence of ADRs and serious ADRs was 29.8% (106/356) and 3.4% (12/356), respectively. Incidence of ADRs was significantly higher in patients aged <15 years vs. ≥15 years (34.6% vs. 21.1%, = .0072), those with comorbidities vs. without (38.3% vs. 25.7%, = .0155), and those receiving dose <40 mg q2w vs. ≥40 mg q2w (38.8% vs. 26.9%, = .0418). DAS28-4/ESR remission rate improved from 21.7% (36/166) at baseline to 74.7% (112/150) at week 24.

Conclusions: Adalimumab was well tolerated and had acceptable safety and effectiveness in patients with JIA in the real-world setting.
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http://dx.doi.org/10.1080/14397595.2020.1761075DOI Listing
March 2021

Tylosin degradation during manure composting and the effect of the degradation byproducts on the growth of green algae.

Sci Total Environ 2020 May 13;718:137295. Epub 2020 Feb 13.

Faculty of Science and Engineering, Iwate University, Ueda 4-3-5, Morioka, Iwate 020-8551, Japan.

In this study, we investigate the tylosin degradation in sheep feces during composting. The sheep feces containing tylosin were composted using the laboratory-scale composting units. Tylosin was degraded during composting, and the half-life of tylosin degradation decreased with increasing temperature from 40 °C to 65 °C. The tylosin degradation in sheep feces can be attributed to the microorganisms in the feces and not to heating because tylosin did not degrade over a period of 48 h at temperatures of 0 °C-65 °C in sterilized water. The artificial rainwater solution extracted from the composted sample did not inhibit the growth of Raphidocelis subcapitata, a type of green alga. Our results indicate that composting the feces containing tylosin is effective in degrading tylosin, which may result in the preservation of agricultural fields as well as nearby aquatic environments.
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http://dx.doi.org/10.1016/j.scitotenv.2020.137295DOI Listing
May 2020

Association of trajectory of body mass index with knee pain risk in Japanese middle-aged women in a prospective cohort study: the Japan Nurses' Health Study.

BMJ Open 2020 02 6;10(2):e033853. Epub 2020 Feb 6.

Nagano University of Health and Medicine, Nagano, Japan.

Objectives: To investigate whether body mass index (BMI) trajectory, lifestyle and reproductive factors are associated with knee pain risk among middle-aged women.

Design: Prospective study of the Japan Nurses' Health Study (JNHS).

Setting: The JNHS investigates the health of female nurses in Japan. Biennial follow-up questionnaires are mailed to the participants.

Participants: The 7434 women aged over 40 years who responded to the 10-year self-administered follow-up questionnaire.

Primary Outcome Measure: Self-reported knee pain at the 10-year follow-up was the primary outcome. We analysed BMI (normal or overweight) trajectory data from a baseline survey to the 10-year follow-up survey using group-based trajectory modelling. Exposure measurements were BMI trajectory, BMI at age 18 years, lifestyle variables and reproductive history.

Results: BMI trajectories from baseline to the 10-year follow-up were divided into four groups: remained normal, remained overweight, gained weight or lost weight. At the 10-year follow-up, 1281 women (17.2%) reported knee pain. Multivariable logistic regression analysis revealed that compared with the remained normal group, multivariable-adjusted ORs (95% CI) of knee pain were 1.93 (1.60 to 2.33) for the remained overweight group, 1.60 (1.23 to 2.08) for the gained weight group and 1.40 (0.88 to 2.21) for the lost weight group. The attributable risk percent (95% CI) of the remained overweight group was 48.1% (37.3% to 57.0%) compared with the reference group of remained normal. Alcohol intake at baseline was significantly associated with knee pain.

Conclusions: The lost weight group had a lower risk than the remained overweight group and the gained weight group and did not carry statistically significant risks for knee pain. Weight reduction and maintaining a normal BMI in middle age was important for preventing knee pain in women.
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http://dx.doi.org/10.1136/bmjopen-2019-033853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045261PMC
February 2020

Incidence of postoperative nausea and vomiting is not increased by combination of low concentration sevoflurane and propofol compared with propofol alone in patients undergoing laparoscopic gynecological surgery.

JA Clin Rep 2019 Nov 2;5(1):70. Epub 2019 Nov 2.

Department of Anesthesiology, Hakodate Central General Hospital, 3-2, Honcho3, Hakodate, 040-8585, Japan.

Background: The incidence of postoperative nausea and vomiting (PONV) is higher in patients receiving volatile anesthetics than those receiving total intravenous anesthesia (TIVA) with propofol. However, it is unclear whether its incidence is increased when a low concentration of sevoflurane is used in combination with propofol.

Methods: This prospective, randomized, controlled trial enrolled women undergoing laparoscopic gynecological surgery. Patients were randomly assigned to receive general anesthesia either with propofol alone (group P) or with 0.8% sevoflurane and propofol (group SP, n = 36, each group) for maintenance of anesthesia. The incidence of PONV and the number of patients who required antiemetics were compared.

Results: There were no differences in the incidence of PONV and the number of patients who required antiemetics between the P and SP groups.

Conclusions: A combination of 0.8% sevoflurane and propofol to maintain anesthesia does not increase the incidence of PONV compared with TIVA with propofol.

Trial Registration: UMIN-CTR UMIN000023647 , registered 14 August 2016.
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http://dx.doi.org/10.1186/s40981-019-0292-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966744PMC
November 2019

Retrospective investigation of tacrolimus combined with an anti-tumor necrosis factorα antibody as remission induction therapy for refractory ulcerative colitis: Efficacy, safety, and relapse rate.

JGH Open 2019 Dec 5;3(6):525-531. Epub 2019 Jul 5.

Department of Gastroenterology Tokyo Women's Medical University Tokyo Japan.

Background And Aim: Combined therapy with tacrolimus (TAC) and an anti-tumor necrosis factorα (TNFα) antibody is used to induce remission in ulcerative colitis (UC) patients who have not responded to monotherapy with either drug. We evaluated the efficacy and safety of combined therapy, as well as the relapse rate.

Methods: Combined therapy was performed to induce remission in UC patients showing an inadequate response to monotherapy with TAC or an anti-TNFα antibody. The following items were assessed retrospectively: (i) clinical characteristics, (ii) the remission induction rate, (iii) the relapse rate, and (iv) adverse events.

Results: Combined therapy induced remission in 7 of the 12 patients (58.3%). There were no significant differences in clinical characteristics between the patients with and without the successful induction of remission. However, the number of female patients tended to be higher in the remission group than in the nonremission group. The remission group also showed trends of a lower clinical activity index (Lichtiger index; CAI) on admission and before combined therapy and a lower total dose of prednisolone during hospitalization. The 1-year relapse rate was 33.3%. Adverse events due to combined therapy included renal impairment ( = 2), tremors ( = 2), influenza ( = 1), and a positive cytomegalovirus antibody test ( = 3). None of these events were serious.

Conclusions: Combined therapy was effective in more than half of the patients with refractory UC who had not responded to monotherapy. Our findings suggest that combination therapy may be a new, third option for the treatment of refractory UC.
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http://dx.doi.org/10.1002/jgh3.12197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891029PMC
December 2019

Removal of nonylphenol and nonylphenol monoethoxylate from water and anaerobically digested sewage sludge by Ferrate(VI).

Chemosphere 2019 Dec 18;236:124399. Epub 2019 Jul 18.

Course of Civil and Environmental Engineering, Department of System Innovation Engineering, Faculty of Science and Engineering, Iwate University, Morioka, 020-8551, Japan.

Nonylphenol (NP) and nonylphenol monoethoxylate (NP1EO) have toxic and persistent characteristics, and are incompletely degraded in conventional wastewater treatment processes. These compounds are present in sewage sludge that can be reused as fertilizers or soil conditioners. Accordingly, NP and NP1EO should be properly removed before being discharged in the environment. In this study, potassium ferrate (KFeO) containing hexavalent iron (Fe(VI)) was used as an environment-friendly oxidizing agent to mediate NP and NP1EO degradation. The aim of this study was to investigate the effects of pH and Fe(VI) dosage on the degradation of NP and NP1EO in water and anaerobically digested sewage sludge samples. In water samples, under conditions examined in this study, maximum removal efficiencies for NP and NP1EO were 98% and 92%, respectively. For digested sewage sludge samples, the maximum removal efficiencies of NP and NP1EO were 58% and 96%, respectively. The results demonstrated that Fe(VI) can potentially degrade NP and NP1EO in water and digested sewage sludge samples. However, organic matter as a matrix in the sludge sample would inhibit the degradation of NP and NP1EO by Fe(VI). The pH values before and after adding KFeO to the samples had an obvious influence on the removal of NP and NP1EO.
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http://dx.doi.org/10.1016/j.chemosphere.2019.124399DOI Listing
December 2019

Comparison of Lewis Score and Capsule Endoscopy Crohn's Disease Activity Index in Patients with Crohn's Disease.

Dig Dis Sci 2020 04 20;65(4):1180-1188. Epub 2019 Sep 20.

Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Background/aims: Small bowel capsule endoscopy (SBCE) is used to visualize mucosal inflammatory changes in the small intestine of patients with Crohn's disease (CD). The Lewis score (LS) and Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) are used to evaluate the visualized images. We determined the score disagreement between LS and CECDAI in patients with CD.

Methods: We evaluated 184 SBCE procedures in 102 CD patients with small bowel lesions. Patients were classified according to the Montreal classification. LS and CECDAI were calculated, and cases with disagreement between the two scores were identified. We investigated the characteristics of disagreement, and analyzed the relationships with the Crohn's Disease Activity Index (CDAI) and C-reactive protein.

Results: LS (504 ± 1160) correlated strongly with CECDAI (6 ± 5.4) (Spearman's rank correlation coefficient ρ = 0.81, p < 0.0001). LS values of 135 and 790 were equivalent to CECDAI values of 4.9 and 6.9, respectively. The inflammatory changes by LS were significantly observed in several tertiles in the CECDAI discrepancy group (LS < 135, CECDAI ≥ 4.9) compared with the normal agreement group (LS < 135, CECDAI < 4.9) (p < 0.0001). In both groups, CDAI was also significantly different between Montreal L1 and L3 groups (p = 0.0232, p = 0.0196, respectively). LS inflammation score was 0 in six cases in the LS discrepancy group (LS ≥ 135, CECDAI ≤ 4.9, n = 10); the high LS scores were in patients with high stricture scores.

Conclusions: Discrepancies between the LS and CECDAI scores were observed in some patients. Cases with high CECDAI alone exhibited extensive inflammation and high disease activity (clinical symptoms and biomarker levels). CECDAI seems to better reflect active intestinal inflammation than LS.
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http://dx.doi.org/10.1007/s10620-019-05837-7DOI Listing
April 2020

Evaluation of Intestinal Patency with the Patency Capsule: The Twenty-Four Hour Assessment Method.

Digestion 2019 21;100(3):176-185. Epub 2018 Nov 21.

Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Introduction: Confirmation of intestinal patency using the patency capsule (PC) in 30-33 h may result in a complex testing schedule. The aim of this study was to perform and evaluate a 24-h PC procedure for potential use as a simple and easy-to-apply intestinal patency assessment method.

Subject And Methods: The study included 342 patients who were assessed 24 h after ingesting a PC for assessment of intestinal patency. The PC elimination rate and the distribution of elimination time were evaluated.

Results: Assessment of intestinal patency was conducted in 308 (90%) patients. Self-confirmed PC elimination within 24 h was possible in 104 (30.4%) patients. The PC was considered to have been already eliminated in 38 (11.1%) patients. Thus, the extracorporeal elimination rate was 41.5%. Among 200 patients with non-extracorporeal elimination, the PC reached the large intestine in 166 patients (48.5% of the total patients). Small-bowel capsule endoscopy (CE) was performed in all 308 patients, and the entire small bowel could be observed in 98.4%. Capsule retention was not observed in any of the patients.

Conclusion: The 24-h assessment method, in which the PC can be ingested using the same procedure as that for CE capsule, can be handled more easily and is more useful clinically.
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http://dx.doi.org/10.1159/000494717DOI Listing
February 2020

Tomosynthesis for colonic localization of patency capsules.

Arab J Gastroenterol 2018 Sep 24;19(3):134-135. Epub 2018 Sep 24.

Institute of Gastroenterology, Tokyo Women's Medical University, Japan.

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http://dx.doi.org/10.1016/j.ajg.2018.08.006DOI Listing
September 2018

Does the PillCam SB3 capsule endoscopy system improve image reading efficiency irrespective of experience? A pilot study.

Endosc Int Open 2018 Jun 25;6(6):E669-E675. Epub 2018 May 25.

Institute of Gastroenterology, Tokyo Women's University, Tokyo, Japan.

Background And Study Aims:  The aim of this study was tp compare the diagnostic efficiency of the PillCam SB3 capsule endoscopy (CE) system with the older system, PillCam SB2, taking into consideration the experience of the image reader.

Patients And Methods:  Small intestinal CE was conducted on 64 patients around May 2014 when the SB3 was introduced in our hospital. Data obtained from 20 patients (SB2: 10 and SB3: 10) based on transit time were assessed by junior (experience: 20 images), intermediate (> 50), and expert readers (> 600).

Results:  Reading time with the CE down to the end of the small intestine was shorter in the SB3 group for each reader (SB2 vs. SB3: junior, 40.2 ± 10.1 vs. 23.7 ± 6.7 [  = 0.0009]; intermediate, 21.4 ± 4.9 vs. 10.3 ± 2.9 [  = 0.0003]; expert, 23.2 ± 5.6 vs. 11.1 ± 2.9 min [  = 0.0002]). Interpretation agreement rates between the findings by junior and intermediate readers and those by the expert reader were 84.6 % and 92.3 %, respectively. For the junior reader, rates of agreement using the SB2 and SB3 systems with those by the expert reader were 85.7 % and 83.3 %, respectively; no significant difference was noted between the two systems. Similarly, for the intermediate reader, the respective agreement rates using the SB2 and SB3 systems were 85.7 % and 100 %, respectively.

Conclusions:  The PillCam SB3 reduces the time burden on readers irrespective of their experience.
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http://dx.doi.org/10.1055/a-0599-5852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979195PMC
June 2018

Efficacy and safety of granulocyte adsorption apheresis in elderly patients with ulcerative colitis.

J Clin Apher 2018 Aug 24;33(4):514-520. Epub 2018 Apr 24.

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

Background: Elderly ulcerative colitis (UC) is increasing. Elderly UC differ from younger UC with respect to the course of their disease. Granulocyte adsorption apheresis (CAP) is often used to treat elderly UC. We retrospectively analyzed the cases of elderly UC who underwent CAP for remission induction therapy in a comparison with younger UC.

Methods: 96 patients with UC underwent CAP. Patients who concurrently received tacrolimus, biological agents, or high-dose steroid therapy were excluded. The remaining 80 patients were evaluated. We divided them into an elderly group (aged ≥65 years) and a younger group, and then we compared the groups' (1) clinical characteristics, (2) the efficacy and adverse effects of CAP, and (3) the complications of PSL.

Results: The remission rate was 70.8% in the elderly group and 87.5% in the younger group. There were significant differences between the two groups with respect to the age at the onset of UC, the estimated glomerular filtration rate on admission, underlying diseases, and complications of PSL therapy. Adverse effects of CAP included headache, complications of blood reinfusion, heparin allergy, hypotension, and failure of blood removal. There were significant differences between the two groups with respect to the complications of PSL therapy (all P < .05).

Conclusions: Although the elderly group had longer durations of UC, a higher prevalence of underlying diseases, and a higher frequency of adverse events due to PSL therapy. No serious adverse effects of CAP occurred in either group. Thus, CAP was safe and effective in both younger and elderly UC.
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http://dx.doi.org/10.1002/jca.21631DOI Listing
August 2018

Determination of tylosin excretion from sheep to assess tylosin spread to agricultural fields by manure application.

Sci Total Environ 2018 Aug 28;633:399-404. Epub 2018 Mar 28.

Faculty of Science and Engineering, Iwate University, Ueda 4-3-5, Morioka, Iwate 020-8551, Japan.

Antibiotics administered to livestock are partly excreted with urine and feces. As livestock excrement is used as manure on agricultural fields, soil may be contaminated by excreted antibiotics, potentially resulting in the development of antibiotic-resistant bacteria. Therefore, it is necessary to determine the amount of antibiotic administered to livestock that could spread to agricultural fields through manure application. This study reveals the excretion ratio of tylosin from sheep. After developing an analysis procedure for tylosin in urine and feces from sheep, a tylosin excretion study was performed with two sheep. Tylosin was excreted in urine and feces for four days, after which its concentrations dropped below the limits of quantification (urine: 0.5μg/kg, feces: 2.4μg/kg). The total excretion ratio was 11% on average. The results of our study can provide useful knowledge for treating excrement in order to prevent the spread of antibiotics to agricultural fields through manure application.
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http://dx.doi.org/10.1016/j.scitotenv.2018.03.216DOI Listing
August 2018

Relationship between the Clinical Course of Ulcerative Colitis during Pregnancy and the Outcomes of Pregnancy: A Retrospective Evaluation.

Intern Med 2018 Jan 16;57(2):159-164. Epub 2017 Oct 16.

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

Objective Little information is available on the relationship between the clinical course of ulcerative colitis (UC) and the outcomes of pregnancy and delivery in pregnant Japanese women. The aim of this retrospective study was to determine the factors that influence pregnancy and childbirth in middle-aged UC patients. Methods We studied 53 pregnancies in 45 pregnant women with UC who delivered at our department. They included 41 pregnancies that started while in UC remission and 12 pregnancies that started in the UC active phase. The following factors were evaluated: 1) the clinical course of UC; 2) the frequency and details of abnormal pregnancy/abnormal delivery; and 3) the course of pregnancy/delivery. We compared the clinical features, course of UC, and details of treatment between women with a normal pregnancy/delivery and those with an abnormal delivery. Results A comparison of the remission and acute groups showed lower clinical activity indices (CAIs) during pregnancy in the remission group and significantly higher rates of recurrence/exacerbation in the active group (75%) than in the remission group (7.3%). The respective CAIs in the first, second, and third trimesters were 3 and 6, 3 and 5, and 3 and 4, in the remission and active groups, respectively. Live infants were delivered in 51 (96%) pregnancies, with 7 (17%) abnormal pregnancies in the remission group and 4 (33.3%) in the active group (p>0.05). Abnormal delivery occurred in 16 of 53 (30.1%) pregnancies, and the rate was higher in the remission group than in the active group (p>0.05). In both groups, the most common abnormal event during pregnancy was delivery of low-birth-weight infants. Delivery was normal in 37 cases and abnormal in 16 cases. A multivariate analysis showed that a shorter UC disease duration (odds ratio=1.16) and higher CAI in the first trimester (odds ratio=1.49) were associated with an increased risk of abnormal pregnancy. Conclusion Our findings demonstrated that the clinical course of UC, as evaluated by the CAI, during pregnancy influenced the outcome of pregnancy and delivery.
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http://dx.doi.org/10.2169/internalmedicine.8550-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820031PMC
January 2018

Development and Improvement of Simple Colonic Mucosal Ulcer during Treatment of Severe Ulcerative Colitis with Tacrolimus.

Case Rep Gastroenterol 2017 Jan-Apr;11(1):168-177. Epub 2017 Mar 21.

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

Diarrhea, melena, and lower abdominal pain developed in a male in his 20s and colonoscopy showed pancolitis-type severe ulcerative colitis (UC). Treatment was initiated with 4,000 mg of 5-aminosalicylic acid and 60 mg/day of prednisolone, but the symptoms and inflammatory reaction worsened with prednisolone dose reduction. Tacrolimus was added to the treatment, which subsequently induced remission. Serial colonoscopies during the treatment showed improvement in ulcer and mucosal edema throughout the entire large intestine, but a new solitary round ulcer appeared at the end of the ileum. Since no signs of Behçet's disease were noted, it was considered as a simple ulcer, a complication of UC. Tacrolimus treatment was continued based on continued improvement in clinical features and colonic mucosa, excluding the end of the ileum. Colonoscopy at 6 months after initiation of tacrolimus showed healing of the large intestinal mucosa, although mild congestion was still noted. The solitary round ulcer at the end of the ileum improved to a small erosion. We report the improvement of a simple ulcer that developed during tacrolimus treatment.
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http://dx.doi.org/10.1159/000456605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465708PMC
March 2017

A case of gastrojejunocolic fistula with steatohepatitis.

Clin J Gastroenterol 2017 Feb 19;10(1):23-31. Epub 2016 Dec 19.

Institute of Gastroenterology Internal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

A man in his 30s, who had undergone retrocolic Billroth II reconstruction for perforated duodenal ulcer, presented with watery diarrhea for 2 years and suspected fatty liver. He was referred to our hospital for management of chronic diarrhea, weight loss, hepatopathy and hypoalbuminemia. Initial upper and lower gastrointestinal endoscopies were negative. Since a small bowel lesion was suspected, peroral single-balloon enteroscopy was performed, which identified feces-like residue near the Billroth II anastomotic site and a connection to the colon separate from the afferent and efferent loops. Transanal single-balloon enteroscopy identified a fistula between the gastrojejunal anastomosis and transverse colon, with the scope reaching the stomach transanally. Barium enema confirmed flow of contrast medium from the transverse colon through the fistula to the anastomotic site, allowing the diagnosis of gastrojejunocolic fistula. Liver biopsy showed relatively severe steatohepatitis (Brunt's classification: stage 2-3, grade 3). Resection of the anastomotic site and partial transverse colectomy were performed to remove the fistula, followed by Roux-en-Y reconstruction. Postoperatively, watery diarrhea resolved and the stools became normal. Hepatopathy and hypoproteinemia improved. One year later, liver biopsy showed marked improvement of steatosis. This case demonstrated marked improvement of both diarrhea/nutritional status and steatohepatitis after treatment of gastrojejunocolic fistula, suggesting that the fistula caused non-alcoholic steatohepatitis.
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http://dx.doi.org/10.1007/s12328-016-0703-2DOI Listing
February 2017

Cesium and strontium loads into a combined sewer system from rainwater runoff.

J Environ Manage 2016 Dec 28;183(Pt 3):1041-1049. Epub 2016 Sep 28.

Dept. of Science and Engineering, Iwate University, Ueda 4-3-5, Morioka, Iwate, 020-8551, Japan.

In this study, combined sewage samples were taken with time in several rain events and sanitary sewage samples were taken with time in dry weather to calculate Cs and Sr loads to sewers from rainwater runoff. Cs and Sr in rainwater were present as particulate forms at first flush and the particulate Cs and Sr were mainly bound with inorganic suspended solids such as clay minerals in combined sewage samples. In addition, multiple linear regression analysis showed Cs and Sr loads from rainwater runoff could be estimated by the total amount of rainfall and antecedent dry weather days. The variation of the Sr load from rainwater to sewers was more sensitive to total amount of rainfall and antecedent dry weather days than that of the Cs load.
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http://dx.doi.org/10.1016/j.jenvman.2016.09.067DOI Listing
December 2016

Tacrolimus for Remission Induction and Maintenance Therapy in Patients with Ulcerative Colitis: A Retrospective Evaluation Study.

Gastroenterol Res Pract 2016 16;2016:5956316. Epub 2016 Jun 16.

Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1, shinjuku-ku, Tokyo 162-8666, Japan.

Background. In this retrospective study, we compared the efficacy of tacrolimus (TAC) or prednisolone (PSL) for maintenance therapy in patients with ulcerative colitis (UC) at remission. Methods. The study patients were followed up for at least one year after induction of remission with either PSL (n = 55, between April 2004 and March 2014) or TAC (n = 40, between April 2009 and March 2014). The clinical features and relapse rates were compared in the two groups. Maintenance therapy in the TAC group included TAC alone, AZA alone, and TAC plus AZA. Results. The recurrence rates at 1500 days after remission were 61% and 46% for the PSL and TAC groups, respectively (P < 0.05). The recurrence rates at 600 days for TAC, AZA, and TAC + AZA maintenance groups were 24%, 49%, and 55%, respectively. Nephrotoxicity developed in 16 patients on TAC maintenance therapy. Conclusions. TAC monotherapy is a potential alternative especially for PSL nonresponders or those intolerant to AZA. However, patients on TAC therapy should be regularly monitored for adverse effects including nephrotoxicity.
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http://dx.doi.org/10.1155/2016/5956316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927944PMC
July 2016

Removal of steroid estrogens from municipal wastewater in a pilot scale expanded granular sludge blanket reactor and anaerobic membrane bioreactor.

Environ Technol 2016 7;37(3):415-21. Epub 2015 Sep 7.

a Cranfield Water Science Institute, School of Energy, Environmental Technology and Agrifood , Cranfield University , Bedfordshire MK43 0AL , UK.

Anaerobic treatment of municipal wastewater offers the prospect of a new paradigm by reducing aeration costs and minimizing sludge production. It has been successfully applied in warm climates, but does not always achieve the desired outcomes in temperate climates at the biochemical oxygen demand (BOD) values of municipal crude wastewater. Recently the concept of 'fortification' has been proposed to increase organic strength and has been demonstrated at the laboratory and pilot scale treating municipal wastewater at temperatures of 10-17°C. The process treats a proportion of the flow anaerobically by combining it with primary sludge from the residual flow and then polishing it to a high effluent standard aerobically. Energy consumption is reduced as is sludge production. However, no new treatment process is viable if it only addresses the problems of traditional pollutants (suspended solids - SS, BOD, nitrogen - N and phosphorus - P); it must also treat hazardous substances. This study compared three potential municipal anaerobic treatment regimes, crude wastewater in an expanded granular sludge blanket (EGSB) reactor, fortified crude wastewater in an EGSB and crude wastewater in an anaerobic membrane bioreactor. The benefits of fortification were demonstrated for the removal of SS, BOD, N and P. These three systems were further challenged with the removal of steroid estrogens at environmental concentrations from natural indigenous sources. All three systems removed these compounds to a significant degree, confirming that estrogen removal is not restricted to highly aerobic autotrophs, or aerobic heterotrophs, but is also a faculty of anaerobic bacteria.
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http://dx.doi.org/10.1080/09593330.2015.1070922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062038PMC
September 2016

Activation of apoptosis by caspase-3-dependent specific RelB cleavage in anticancer agent-treated cancer cells: involvement of positive feedback mechanism.

Biochem Biophys Res Commun 2015 Jan 13;456(3):810-4. Epub 2014 Dec 13.

Department of Molecular Target Medicine, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute 480-1195, Japan. Electronic address:

DTCM-glutarimide (DTCM-G) is a newly found anti-inflammatory agent. In the course of experiments with lymphoma cells, we found that DTCM-G induced specific RelB cleavage. Anticancer agent vinblastine also induced the specific RelB cleavage in human fibrosarcoma HT1080 cells. The site-directed mutagenesis analysis revealed that the Asp205 site in RelB was specifically cleaved possibly by caspase-3 in vinblastine-treated HT1080 cells. Moreover, the cells stably overexpressing RelB Asp205Ala were resistant to vinblastine-induced apoptosis. Thus, the specific Asp205 cleavage of RelB by caspase-3 would be involved in the apoptosis induction by anticancer agents, which would provide the positive feedback mechanism.
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http://dx.doi.org/10.1016/j.bbrc.2014.12.024DOI Listing
January 2015

Tongue pressure during swallowing in adults with down syndrome and its relationship with palatal morphology.

Dysphagia 2014 Aug 21;29(4):509-18. Epub 2014 May 21.

Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan,

In individuals with Down syndrome, hypotonicity of the tongue and an underdeveloped maxilla may lead to poor oral motor coordination, which adversely affects the oral phase of swallowing. This study aimed to evaluate the characteristics of pressure produced by the tongue against the hard palate during swallowing in individuals with Down syndrome. In addition, the relationship between tongue pressure and palatal morphology was examined. We studied nine adults with Down syndrome and ten healthy adults as controls. Tongue pressure while swallowing 5 mL water was recorded by a sensor sheet system with five measuring points attached to the hard palate. Palatal length, depth, width, curvature, and slope were measured by three-dimensional digital maxillary imaging. The order of onset of tongue pressure on the median line of the hard palate was the same in all participants, except for three with Down syndrome. The duration and maximal magnitude of tongue pressure on the median line in nine participants with Down syndrome were significantly shorter and lower than those of controls. In participants with Down syndrome, significant positive correlations were observed between the duration of tongue pressure at the mid-median part of the hard palate and palatal depth and width, and between the duration and maximal magnitude of tongue pressure at the posterior-median part and palatal length. These findings suggest that impaired tongue activity, poor tongue control, and constrained tongue motion due to a short and narrow palate contribute to swallowing difficulty in individuals with Down syndrome.
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http://dx.doi.org/10.1007/s00455-014-9538-5DOI Listing
August 2014

Fate of radiocesium in sewage treatment process released by the nuclear accident at Fukushima.

Chemosphere 2013 Oct 6;93(4):689-94. Epub 2013 Jul 6.

Department of Civil and Environmental Engineering, Iwate University, Ueda 4-3-5, Morioka, Iwate 020-8551, Japan. Electronic address:

The nuclear accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP) which occurred after the Great East Japan Earthquake on March 11, 2011 resulted in releases of radionuclides such as (134)Cs (half-life:T1/2=2.06 yr), (137)Cs (T1/2=30.04 yr) and (131)I (T1/2=8.05 d) to the environment. For this paper, we observed the monthly variations of radiocesium ((134)Cs and (137)Cs) and stable Cs concentrations in influent, effluent, sewage sludge, and sludge ash collected from a sewage treatment plant 280 km north of the FDNPP from July to December, 2011. Using the stable Cs results, we concluded the mass balance of Cs in the sewage treatment plant showed that about 10% of the Cs entering the sewage treatment plant would be transferred to the sewage sludge, and then Cs in the sewage sludge was totally recovered in the sludge ash. The behavior of Cs was similar to that of Rb, but it was not similar to that of K in the sewage treatment process.
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http://dx.doi.org/10.1016/j.chemosphere.2013.06.012DOI Listing
October 2013

Fate of stable strontium in the sewage treatment process as an analog for radiostrontium released by nuclear accidents.

J Hazard Mater 2013 Sep 29;260:420-4. Epub 2013 May 29.

Department of Civil and Environmental Engineering, Iwate University, Ueda 4-3-5, Morioka, Iwate 020-8551, Japan.

Radionuclides were widely released into the environment due to the nuclear accident at the Fukushima Daiichi Nuclear Power Plant. Some of these radionuclides have flowed into municipal sewage treatment plants through sewer systems. We have observed the fate of stable Sr in the sewage treatment process as a means to predict the fate of radiostrontium. Concentrations of stable Sr were determined in sewage influent, effluent, dewatered sludge, and incinerated sewage sludge ash collected from a sewage treatment plant once a month from July to December 2011. In the mass balance of Sr in the sewage treatment plant, 76% of the Sr entering the plant was discharged to the receiving water on average. Additionally, 14% of the Sr flowing through the plant was transferred to the sewage sludge and then concentrated in the sludge ash without being released to the atmosphere. We also investigated Sr sorption by activated sludge in a batch experiment. Measurements at 3 and 6h after the contact showed Sr was sorbed in the activated sludge; however, the measurements indicated Sr desorption from activated sludge occurred 48 h after the contact.
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http://dx.doi.org/10.1016/j.jhazmat.2013.05.038DOI Listing
September 2013

Increased oxidative stress biomarkers in the saliva of Down syndrome patients.

Arch Oral Biol 2013 Sep 25;58(9):1246-50. Epub 2013 May 25.

Division of Dentistry for Special Patients, Department of Clinical Care Medicine, Kanagawa Dental College, Yokosuka, Kanagawa, Japan.

Objective: The DNA oxidation byproduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a well-known biomarker used to evaluate oxidative stress. We previously reported that the generation of reactive oxygen species (ROS) is increased in cultured gingival fibroblasts (GF) from patients with Down syndrome (DS). Thus, the aim of this study was to evaluate 8-OHdG as a marker of oxidative stress in saliva of DS patients.

Materials And Methods: The study group consisted of DS patients (66 patients; age range 1-62 years) and systemically healthy control subjects (71 subjects; age range 4-58 years). Periodontal status was judged based on standard measurements of probing depth (PD) and gingival index (GI). The salivary levels of 8-OHdG were determined using an enzyme-linked immunosorbent assay.

Results: The mean of PD and GI values were not significantly different between young (1-12 years) patients with DS (DS-1) and controls (C-1) or between adult (30-62 years) patients with DS (DS-2) and controls (C-2). There were statistically significant positive correlations between the salivary 8-OHdG levels and GI in the DS-1, DS-2 and C-2 groups, but not in the C-1. There were also statistically significant positive correlations between salivary 8-OHdG levels and PD in the DS-2 and C-2 groups, but not in the DS-1 or C-1 groups. The salivary levels of 8-OHdG of DS-1 and DS-2 groups were significantly higher than in the C-l and C-2 groups, respectively.

Conclusions: These results suggest that progressive oxidative stress occurred in DS patients. Oxidative stress may contribute to the clinical features of DS, particularly to the progressive periodontitis characteristic of early ageing.
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http://dx.doi.org/10.1016/j.archoralbio.2013.03.017DOI Listing
September 2013

Inhibition of NO-induced β-cell death by novel NF-κB inhibitor (-)-DHMEQ via activation of Nrf2-ARE pathway.

Biochem Biophys Res Commun 2013 Apr 26;433(2):181-7. Epub 2013 Feb 26.

Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan.

Excessive nitric oxide (NO) plays a pivotal role in the progression of β-cell apoptosis in type 1 diabetes mellitus. We used mouse insulinoma Min6 cells as a model of β cells in this research. We found that (-)-DHMEQ, an NF-κB inhibitor, rescued β cells from NO-induced apoptosis, and then studied the mechanism of apoptosis inhibition. (-)-DHMEQ activated Nrf2 and induced transcription of Nrf2-target genes following the increase of antioxidant response element (ARE) reporter activity. Similarly, tert-butyl hydroquinone (tBHQ), a known activator of Nrf2, inhibited NO-induced cell death along with the transcriptional activation of ARE. RNAi-mediated knockdown of Nrf2 lowered the cytoprotective effect of (-)-DHMEQ against NO, suggesting that (-)-DHMEQ inhibited NO-induced cell death via Nrf2 activation. Furthermore, overexpression of Nrf2 rendered cells to be more resistant to NO, indicating that Nrf2 activation provides critical defense function against NO in Min6 cells. Taken together, we conclude that (-)-DHMEQ may be a useful therapeutic agent for type 1 diabetes mellitus in the onset of disease by protecting β cells from apoptosis.
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http://dx.doi.org/10.1016/j.bbrc.2013.02.062DOI Listing
April 2013
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