Publications by authors named "Hiroshi Yoshino"

62 Publications

Prominent Hyperproinsulinemia in a Middle Age Patient.

Clin Med Insights Case Rep 2021 1;14:11795476211042241. Epub 2021 Sep 1.

Center for Diabetes, Shin-suma General Hospital, Kobe, Japan.

Introduction: Insulin is synthesized in the β-cells from preproinsulin. Preproinsulin becomes proinsulin after leaving the signal peptide. Proinsulin is separated into C-peptide and insulin by 2 enzymes. Hyperproinsulinemia is suspected to be a pancreatic β-cell defect that is augmented by the increased demand placed on the β-cell by hyperglycemia.

Case Presentation: A 39-year-old Japanese man visited to Shin-suma hospital in May 2013. Liver dysfunction, dyslipidemia, and hyperuricemia had been found in medical checkups in his workplace. Therefore, he visited Shin-suma hospital in order to receive intensive examination. Diet and exercise therapy were initiated. In November 2013, intact proinsulin and proinsulin per insulin (PI/I) ratio were evaluated as part of an ongoing study. His intact proinsulin level and PI/I ratio were markedly elevated. A 75 g oral OGTT revealed that his glucose tolerance was impaired. His glycosylated hemoglobin was 6.9%. He was diagnosed as having type 2 diabetes mellitus. Although, diet and exercise therapy continued, his hyperproinslinemia and diabetes mellitus remained. Therefore, aloguliptin was started in order to recover insulin secretion in November 2014. Thereafter, pioglitazone was added to improve insulin resistance. Finally, luseogliflozin was commenced to expect glucose-lowering effects. His HbA1c was stabilized. To the best of our knowledge, there have been few reports of patients with hyperproinsulinemia.

Conclusion: When the physicians face treatment resistance in diabetes mellitus, we emphasize that evaluation of proinsulin should be considered as one of the methods.
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http://dx.doi.org/10.1177/11795476211042241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414601PMC
September 2021

Impact of indoor temperature instability on diurnal and day-by-day variability of home blood pressure in winter: a nationwide Smart Wellness Housing survey in Japan.

Hypertens Res 2021 Jul 29. Epub 2021 Jul 29.

Institute for Building Environment and Energy Conservation, Kojimachi, Chiyoda-ku, Tokyo, Japan.

Home blood pressure (HBP) variability is an important factor for cardiovascular events. While several studies have examined the effects of individual attributes and lifestyle factors on reducing HBP variability, the effects of living environment remain unknown. We hypothesized that a stable home thermal environment contributes to reducing HBP variability. We conducted an epidemiological survey on HBP and indoor temperature in 3785 participants (2162 households) planning to have their houses retrofitted with insulation. HBP was measured twice in the morning and evening for 2 weeks in winter. Indoor temperature was recorded with each HBP observation. We calculated the morning-evening (ME) difference as an index of diurnal variability and the standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM) as indices of day-by-day variability. The association between BP variability and temperature instability was analyzed using multiple linear regression models. The mean ME difference in indoor/outdoor temperature (a decrease in temperature overnight) was 3.2/1.5 °C, and the mean SD of indoor/outdoor temperature was 1.6/2.5 °C. Linear regression analyses showed that the ME difference in indoor temperature was closely correlated with the ME difference in systolic BP (0.85 mmHg/°C, p < 0.001). The SD of indoor temperature was also associated with the SD of systolic BP (0.61 mmHg/°C, p < 0.001). The CV, ARV, and VIM showed similar trends as the SD of BP. In contrast, outdoor temperature instability was not associated with either diurnal or day-by-day HBP variability. Therefore, residents should keep the indoor temperature stable to reduce BP variability.
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http://dx.doi.org/10.1038/s41440-021-00699-xDOI Listing
July 2021

Indoor Fungal Contamination in Temporary Housing after the East Japan Great Earthquake Disaster.

Int J Environ Res Public Health 2021 03 23;18(6). Epub 2021 Mar 23.

Division of Microbiology, National Institute of Health Sciences, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.

To understand fungal contamination in the indoor environment of the disaster region, a field survey was performed to measure the number of fungal counts and identify isolates in the indoor air of prefabricated temporary housing, privately independent-housing, and rented apartments flooded by the East Japan Great Earthquake disaster tsunami. As a result, the period with the highest detected fungal count was from the rainy season to summer in independent-housing and rented apartments. Moreover, in the temporary housing, the fungal number increased further in winter as indicated by the maximum fungal-number throughout the measurement period. The detection frequency of species was relatively higher in the indoor air of temporary housing than in typical housing in the non-disaster area. Since is known as an allergenic genus, it requires careful attention to the health risk for residents. The extremely high level of fungal condensation in indoor air possibly occurred due to high relative humidity and loss of heat insulation in the building attics. It is suggested that this problem commonly happened in the cold region including the entire disaster region of the East Japan Great Earthquake.
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http://dx.doi.org/10.3390/ijerph18063296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004879PMC
March 2021

Influences of COVID-19 in a dementia outpatient clinic: experience from the Fujita-Health University Hospital in Aichi, Japan.

Psychogeriatrics 2021 05 18;21(3):438-439. Epub 2021 Mar 18.

Department of Geriatrics and Cognitive Disorders, Fujita-Health University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/psyg.12684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251064PMC
May 2021

Long-term follow-up of insulin autoimmune syndrome in an elderly patient.

Clin Case Rep 2020 Dec 14;8(12):2941-2944. Epub 2020 Sep 14.

Department of Geriatrics and Cognitive Disorders Fujita Health University School of Medicine Toyoake Japan.

An 84-year-old man was admitted to our hospital. His blood glucose level was 20 mg/dL. Since laboratory tests showed high titers of insulin antibodies, insulin autoimmune syndrome (IAS) was diagnosed. In order to avoid hypoglycemia, steroids can be effective in the long-term management of IAS in elderly patients.
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http://dx.doi.org/10.1002/ccr3.3150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752643PMC
December 2020

Usefulness of CogEvo, a computerized cognitive assessment and training tool, for distinguishing patients with mild Alzheimer's disease and mild cognitive impairment from cognitively normal older people.

Geriatr Gerontol Int 2021 Feb 17;21(2):192-196. Epub 2020 Dec 17.

Department of Geriatrics and Cognitive Disorders, Fujita Health University School of Medicine, Toyoake, Japan.

Aim: This study aimed to assess whether CogEvo, a computerized cognitive assessment and training tool, could distinguish patients with mild Alzheimer's disease and mild cognitive impairment from cognitively normal older people.

Methods: This cross-sectional study enrolled 166 participants with Alzheimer's disease, mild cognitive impairment and cognitively normal older people. In CogEvo, five types of cognitive tasks were carried out, and the z-scores were used as a composite score. Logistic regression and receiver operating characteristics analyses were then carried out to evaluate the usefulness of CogEvo in distinguishing between the three groups.

Results: CogEvo and Mini-Mental State Examination scores showed excellent correlation, and could significantly differentiate between the Alzheimer's disease, mild cognitive impairment and cognitively normal older people groups (Mini-Mental State Examination 20.4 ± 3.5, 25.5 ± 1.6 and 27.6 ± 2.0, respectively; CogEvo: -1.9 ± 0.9, -0.8 ± 0.8 and 0.0 ± 1.0, respectively; both P < 0.001 by analysis of variance). Logistic regression analysis adjusted for age, sex and years of education significantly differentiated the mild cognitive dysfunction group (mild cognitive impairment plus mild Alzheimer's disease; n = 78) from the cognitively normal group (n = 88) (P < 0.001), whereas receiver operating characteristics analysis showed moderate accuracy (area under the receiver operating characteristic curve 0.830).

Conclusions: These results suggest that CogEvo, a computerized cognitive assessment tool, is useful for evaluating early-stage cognitive impairment. Further studies are required to assess its effectiveness as a combination assessment and training tool. Geriatr Gerontol Int 2021; 21: 192-196.
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http://dx.doi.org/10.1111/ggi.14110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898622PMC
February 2021

Eight months observation of check-up system 'Kobe dementia model' of dementia in Kobe City.

Psychogeriatrics 2021 03 14;21(2):246-248. Epub 2020 Dec 14.

Department of Geriatrics and Cognitive Disorders, Fujita Health University School of Medicine, Toyoake, Japan.

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http://dx.doi.org/10.1111/psyg.12649DOI Listing
March 2021

Disparities of indoor temperature in winter: A cross-sectional analysis of the Nationwide Smart Wellness Housing Survey in Japan.

Indoor Air 2020 11 6;30(6):1317-1328. Epub 2020 Jul 6.

Institute for Building Environment and Energy Conservation, Chiyoda-ku, Tokyo, Japan.

The WHO Housing and health guidelines recommend a minimum indoor temperature of 18°C to prevent cold-related diseases. In Japan, indoor temperatures appear lower than in Euro-American countries because of low insulation standards and use of partial intermittent heating. This study investigated the actual status of indoor temperatures in Japan and the common characteristics of residents who live in cold homes. We conducted a nationwide real-world survey on indoor temperature for 2 weeks in winter. Cross-sectional analyses involving 2190 houses showed that average living room, changing room, and bedroom temperatures were 16.8°C, 13.0°C, and 12.8°C, respectively. Comparison of average living room temperature between prefectures revealed a maximum difference of 6.7°C (Hokkaido: 19.8°C, Kagawa: 13.1°C). Compared to the high-income group, the odds ratio for living room temperature falling below 18°C was 1.38 (95% CI: 1.04-1.84) and 2.07 (95% CI: 1.28-3.33) for the middle- and low-income groups. The odds ratio was 1.96 (95% CI: 1.19-3.22) for single-person households, compared to households living with housemates. Furthermore, lower room temperature was correlated with local heating device use and a larger amount of clothes. These results will be useful in the development of prevention strategies for residents who live in cold homes.
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http://dx.doi.org/10.1111/ina.12708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689703PMC
November 2020

Intervention study of the effect of insulation retrofitting on home blood pressure in winter: a nationwide Smart Wellness Housing survey.

J Hypertens 2020 12;38(12):2510-2518

Institute for Building Environment and Energy Conservation, Tokyo, Japan.

Objective: The WHO's Housing and health guidelines (2018) listed 'low indoor temperatures and insulation' as one of five priority areas, and indicated insulation retrofitting to help mitigate the effect of low indoor temperatures on health. However, there is still not enough evidence for the effect of insulation retrofitting based on an objective index.

Methods: We conducted a nonrandomized controlled trial comparing home blood pressure (HBP) between insulation retrofitting (942 households and 1578 participants) and noninsulation retrofitting groups (67 households and 107 participants). HBP and indoor temperature were measured for 2 weeks before and after the intervention in winter. To examine the influence of insulation retrofitting on HBP, we used multiple linear regression analysis.

Results: The analyses showed that indoor temperature in the morning rose by 1.4°C after insulation retrofitting, despite a slight decrease in outdoor temperature by 0.2°C. Insulation retrofitting significantly reduced morning home SBP (HSBP) by 3.1 mmHg [95% confidence interval (95% CI): 1.5-4.6], morning home DBP (HDBP) by 2.1 mmHg (95% CI: 1.1-3.2), evening HSBP by 1.8 mmHg (95% CI: 0.2-3.4) and evening HDBP by 1.5 mmHg (95% CI: 0.4-2.6). In addition, there was a dose-response relationship between indoor temperature and HBP, indicating the effectiveness of a significant improvement in the indoor thermal environment. Furthermore, there was heterogeneity in the effect of insulation retrofitting on morning HSBP in hypertensive patients compared with normotensive occupants (-7.7 versus -2.2 mmHg, P for interaction = 0.043).

Conclusion: Insulation retrofitting significantly reduced HBP and was more beneficial for reducing the morning HSBP of hypertensive patients.
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http://dx.doi.org/10.1097/HJH.0000000000002535DOI Listing
December 2020

Impact of immunophenotypic characteristics on genetic subgrouping in childhood acute lymphoblastic leukemia: Tokyo Children's Cancer Study Group (TCCSG) study L04-16.

Genes Chromosomes Cancer 2020 10 16;59(10):551-561. Epub 2020 Jul 16.

Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development (Research Institute, National Center for Child Health and Development, NCCHD), Tokyo, Japan.

Immunophenotyping was performed in 1044 consecutive childhood acute lymphoblastic leukemia (ALL) patients enrolled in the Tokyo Children's Cancer Study Group L04-16 trial, revealing novel findings associated with genetic abnormalities. In addition to TCF3-PBX1 and MEF2D fusions, the CD10 subtype of KMT2A-MLLT3-positive ALL frequently exhibited the cytoplasmic-μ pre-B ALL immunophenotype. Although ETV6-RUNX1 was significantly correlated with myeloid antigen expression, more than half of patients expressed neither CD33 nor CD13, while the CD27 /CD44 immunophenotype was maintained. Expression of CD117 and CD56 in B-cell precursor-ALL was limited to certain subtypes including ETV6-RUNX1 and KMT2A-MLLT3. Besides BCR-ABL1, CRLF2, hyperdiploidy, and hypodiploidy, CD66c was also expressed in Ph-like kinase fusion-, PAX5 fusion-, and DUX4 fusion-positive ALL, but not in MEF2D fusion-positive ALL, indicating constant selectivity of CD66c expression. In T-ALL, SIL-TAL1-positive patients were likely to exhibit a more mature immunophenotype. Expression of CD21 and CD10 was not rare in T-ALL, while lack of CD28 was an additional feature of early T-cell precursor-ALL. Considering the immunophenotype as a prognostic maker, MEF2D fusion-positive ALL with CD5 expression may be associated with a poorer prognosis in comparison with those lacking CD5 expression. In cases with characteristic marker expression, the presence of certain fusion transcripts could be predicted accurately.
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http://dx.doi.org/10.1002/gcc.22858DOI Listing
October 2020

Functional characterization of a germline ETV6 variant associated with inherited thrombocytopenia, acute lymphoblastic leukemia, and salivary gland carcinoma in childhood.

Int J Hematol 2020 Aug 4;112(2):217-222. Epub 2020 May 4.

Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), 113-8519 Yushima 1-5-45, Bukyo-ku, Tokyo, Japan.

Germline pathogenic ETV6 variants have been discovered in families with inherited thrombocytopenia and predisposition to hematological and solid malignancies. We present a patient with short stature who was initially diagnosed with chronic immune thrombocytopenia. Subsequently, the patient developed acute lymphoblastic leukemia, followed by mammary analog secretory carcinoma. Sequencing analysis identified an ETV6 c.641C > T (p.Pro214Leu) germline variant. The variant protein exhibited attenuated nuclear localization, increased protein degradation, and reduced transcription repression function. Our findings suggest that the ETV6 gene should be sequenced in patients with inherited thrombocytopenia and malignancy, and emphasize the importance of careful follow-up to identify secondary cancer in patients with pathogenic ETV6 variants.
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http://dx.doi.org/10.1007/s12185-020-02885-yDOI Listing
August 2020

Author Correction: Exposure to paternal tobacco smoking increased child hospitalization for lower respiratory infections but not for other diseases in Vietnam.

Sci Rep 2020 Apr 6;10(1):6162. Epub 2020 Apr 6.

Department of Clinical Tropical Medicine, Institute of Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-62383-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136198PMC
April 2020

Dementia Cafés as Hubs to Promote Community-Integrated Care for Dementia through Enhancement of the Competence of Citizen Volunteer Staff Using a New Assessment Tool.

Dement Geriatr Cogn Disord 2019 4;48(5-6):271-280. Epub 2020 Mar 4.

Nagoya City Dementia Support Center, Nagoya, Japan.

Introduction: Dementia cafés have recently been attracting attention. The increased involvement of citizen volunteers and the competence of dementia café staff could enhance the potential of dementia cafés. The aim of the present study was to examine enhancement of the competence of citizen volunteers using a new assessment tool.

Methods: This cross-sectional analysis included 433 dementia café staff members, including medical and care professionals and citizen volunteers. A 20-item dementia café staff self-assessment (DCSA) instrument was newly developed. After confirmation of the reliability and validity of the instrument, DCSA scores among citizen volunteers were evaluated.

Results: DCSA showed very good psychometric properties. The mean (±SD) DCSA score was significantly higher for café staff with a medical and care professional background (n = 267) than for citizen volunteers (n = 166) (2.2±0.5 vs. 1.7±0.7, respectively; p < 0.001). The DCSA scores of citizen volunteers became significantly higher with increasing attendance (minimum: n = 24; 1.3±0.7; intermediate: n = 65; 1.6±0.6; and frequent: n = 77; 1.8±0.7; p < 0.01).

Conclusion: Assessment of the competence of dementia café staff using the DCSA revealed the potential of citizen volunteers. This tool could also enhance the potential of dementia cafés.
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http://dx.doi.org/10.1159/000505871DOI Listing
July 2020

Successful Treatment of Amiodarone-induced Thyrotoxicosis Type 1 in Combination with Methimazole and Potassium Iodide in a Patient with Hashimoto's Thyroiditis.

Intern Med 2020 Feb 26;59(3):383-388. Epub 2019 Sep 26.

Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Japan.

A patient with underlying Hashimoto's thyroiditis developed amiodarone-induced thyrotoxicosis type 1 that was successfully treated using methimazole in combination with potassium iodide. A 35-year-old woman admitted for perinatal care of twin-to-twin transfusion syndrome was given amiodarone for 7 days for paroxysmal ventricular contraction following pulseless ventricular tachycardia 1 day after delivery. She developed thyrotoxicosis one month after the discontinuation of amiodarone therapy and was negative for thyroid-stimulating hormone receptor antibody. An increased peak velocity of the superior thyroid artery suggested amiodarone-induced thyrotoxicosis type 1. Her thyroid function recovered after combination therapy with methimazole and potassium iodide.
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http://dx.doi.org/10.2169/internalmedicine.2179-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028412PMC
February 2020

Cross-Sectional Analysis of the Relationship Between Home Blood Pressure and Indoor Temperature in Winter: A Nationwide Smart Wellness Housing Survey in Japan.

Hypertension 2019 10 26;74(4):756-766. Epub 2019 Aug 26.

Institute for Building Environment and Energy Conservation, Tokyo, Japan (S.M.).

Mortality due to cardiovascular disease rises sharply in winter. Known as excess winter mortality, this phenomenon is partially explained by cold exposure-induced high blood pressure. Home blood pressure, especially in the morning, is closely associated with cardiovascular disease risk. We conducted the first large nationwide survey on home blood pressure and indoor temperature in 3775 participants (2095 households) who intended to conduct insulation retrofitting and were recruited by construction companies. Home blood pressure was measured twice in the morning and evening for 2 weeks. The relationship between home blood pressure and indoor temperature in winter was analyzed using a multilevel model with 3 levels: repeatedly measured day-level variables (eg, indoor ambient temperature and quality of sleep), nested within individual-level (eg, age and sex), and nested within household level. Cross-sectional analyses involving about 2900 participants (1840 households) showed that systolic blood pressure in the morning had significantly higher sensitivity to changes in indoor temperature (8.2 mm Hg increase/10°C decrease) than that in the evening (6.5 mm Hg increase/10°C decrease) in participants aged 57 years (mean age in this survey). We also found a nonlinear relationship between morning systolic blood pressure and indoor temperature, suggesting that the effect of indoor temperature on blood pressure varied depending on room temperature range. Interaction terms between age/women and indoor temperature were significant, indicating that systolic blood pressure in older residents and women was vulnerable to indoor temperature change. We expect that these results will be useful in determining optimum home temperature recommendations for men and women of each age group. Clinical Trial Registration- URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000030601.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12914DOI Listing
October 2019

Participants in a randomized controlled trial had longer overall survival than non-participants: a prospective cohort study.

Breast Cancer Res Treat 2019 Aug 21;176(3):631-635. Epub 2019 May 21.

Department of Integrated Science and Engineering, Chuo University, Tokyo, Japan.

Purpose: While some studies show improved outcomes in clinical trial participants as compared to non-participants, existence of such a trial effect has not been proved precisely.

Methods: This was a prospective cohort study to compare the prognoses for participants in the randomized controlled trial (SELECT BC) and non-participants. SELECT BC compared S-1 and taxane as first-line treatment for metastatic breast cancer. Non-participants were all patients who met the eligibility criteria of SELECT BC and who had been requested to participate in that trial by attending doctors and declined. The study aimed to compare the prognoses between participants and non-participants. The primary endpoint was median overall survival.

Results: The median OS in participants was significantly superior to that in non-participants with a statistically significant difference (36.8 months vs. 25.2 months. HR 1.48, p = 0.022). A similar result was obtained when only patients who received the same chemotherapy (S-1 or taxane) used in SELECT BC after declining participation were assumed as non-participants (36.8 months vs. 22.0 months. HR 2.03, p = 0.006).

Conclusions: This study may suggest the existence of a trial effect, in which, for a given treatment, participation in a clinical trial is associated with a better outcome.
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http://dx.doi.org/10.1007/s10549-019-05276-yDOI Listing
August 2019

Sustained fasting glucose oxidation and postprandial lipid oxidation associated with reduced insulin dose in type 2 diabetes with sodium-glucose cotransporter 2 inhibitor: A randomized, open-label, prospective study.

J Diabetes Investig 2019 Jul 19;10(4):1022-1031. Epub 2019 Feb 19.

Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.

Aims/introduction: Hyperglycemia impairs energy substrate oxidation as a result of glucotoxicity. We examined whether the reduction of plasma glucose using a sodium-glucose cotransporter 2 inhibitor, in inpatient diabetes management, has any effect on: (i) treatment period and basal-bolus dosage of insulin that achieve euglycemia; (ii) fasting/postprandial energy expenditure (EE); and (iii) energy substrate oxidation.

Materials And Methods: This was a randomized, open-label, 7-day prospective study. Participants were type 2 diabetes patients with hyperglycemia, aged >20 years, with glycated hemoglobin >10%, daily mean preprandial blood glucose >11 mmol/L (200 mg/dL) and no previous antidiabetic medication. A total of 18 type 2 diabetes patients were randomized (1:1) to basal-bolus insulin titration algorithm (INS) alone or INS + dapagliflozin 5 mg/day (INS/DAPA). The main outcome measures were total daily insulin dose to achieve euglycemia, as well as EE and respiratory quotient during fasting and postprandial states, measured by indirect calorimetry.

Results: The rate of euglycemia was higher in the INS/DAPA compared with INS group (100 vs 55.6%, P = 0.04), whereas the total daily dose of insulin was 19% lower and was accompanied by a decreased basal-bolus ratio (P = 0.02). Fasting and postprandial EE elevation were similar in both groups. The post-treatment fasting respiratory quotient significantly increased in the INS/DAPA group (0.72 ± 0.05 vs 0.79 ± 0.08, P = 0.04), and the postprandial respiratory quotient elevation was abolished; the opposite trend was observed in the INS group (P < 0.02).

Conclusions: INS/DAPA sustained fasting carbohydrate oxidation, postprandial lipid-derived EE (failed to increase carbohydrate-derived EE) and reduced basal insulin requirement might be related to further bodyweight loss.

Clinical Trial Registry: National University Hospital Medical Information Network UMIN000018997.
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http://dx.doi.org/10.1111/jdi.12994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626995PMC
July 2019

Comprehensive Evaluation of Combination Therapy with Basal Insulin and Either Lixisenatide or Vildagliptin in Japanese Patients with Type 2 Diabetes: A Randomized, Open-Label, Parallel-Group, Multicenter Study.

Diabetes Ther 2018 Oct 11;9(5):2067-2079. Epub 2018 Sep 11.

Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Introduction: We comprehensively evaluated the effects of combination therapy with insulin glargine and the incretin-based drugs lixisenatide or vildagliptin in Japanese patients with type 2 diabetes.

Methods: In this 12-week, randomized, open-label, parallel-group, multicenter study (GLP-ONE Kobe), the incretin-based drug sitagliptin was randomly switched to lixisenatide (20 μg/day, n = 18) or vildagliptin (100 mg/day, n = 20) in patients with inadequate glycemic control despite combination therapy with insulin glargine and sitagliptin. The dose of insulin glargine was titrated after the switch to maintain fasting blood glucose at approximately 110 mg/dL. The primary end points of the study were the change in glycosylated hemoglobin (HbA) level between before and 12 weeks after the treatment switch, the proportion of patients achieving an HbA level below 7.0%, and the postprandial increase in glucose concentration as assessed by self-monitoring of blood glucose.

Results: The change in HbA level from baseline to 12 weeks did not differ significantly between the lixisenatide and vildagliptin groups (- 0.6 ± 0.7% and - 0.6 ± 1.2%, respectively, P = 0.920). Neither the proportion of patients achieving an HbA level below 7.0% nor the postprandial increase in glucose concentration was different between two groups. Body weight and serum low density lipoprotein (LDL) cholesterol level decreased significantly in the lixisenatide and vildagliptin groups, respectively. Both drugs were associated with mild gastrointestinal symptoms but not with severe hypoglycemia. Vildagliptin was associated with elevation of serum aspartate transaminase. Treatment satisfaction as assessed with the Diabetes Treatment Satisfaction Questionnaire did not differ significantly between the two groups.

Conclusion: The combinations of basal insulin and either lixisenatide or vildagliptin have similar efficacies with regard to improvement of glycemic control.

Trial Registration: This trial has been registered with UMIN (No. 000010769).
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http://dx.doi.org/10.1007/s13300-018-0505-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167300PMC
October 2018

Efficacy of intermittent empagliflozin supplementation on dietary self-management and glycaemic control in patients with poorly controlled type 2 diabetes: A 24-week randomized controlled trial.

Diabetes Obes Metab 2019 02 5;21(2):303-311. Epub 2018 Oct 5.

Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.

Aims: To explore the effects of intermittent use of empagliflozin, a sodium-glucose co-transporter-2 inhibitor, on dietary self-management and glycaemic control in patients with inadequately controlled type 2 diabetes.

Materials And Methods: We conducted a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative clinical trial of 50 patients with type 2 diabetes, treated with no more than three oral antidiabetic drugs (glycated haemoglobin [HbA1c] ≥52 mmol/mol but <86 mmol/mol). The participants were randomized to take 10 mg/d empagliflozin either every day (regular group, n = 25) or on the day on which they considered they had overeaten (intermittent group, n = 25) for 24 weeks. We limited empagliflozin prescription to half of the required period in the intermittent group. The primary endpoint was change in HbA1c at the end of the 24-week treatment period relative to baseline. The secondary outcomes included changes in body weight, daily energy intake and diabetes treatment-related quality of life (QoL). Energy intake was assessed using a diet-specific validated questionnaire rather than actual assessments of food intake.

Results: The intake rate of empagliflozin was 96.7 ± 7.2% for the regular group and 45.7 ± 7.0% for the intermittent group. Interestingly, ΔHbA1c was identical in the two groups (-0.64 ± 0.19% and - 0.65 ± 0.17%, respectively). Body weight decreased (-2.72 ± 0.52 and - 1.50 ± 0.45 kg, respectively) and diabetes treatment-related QoL increased significantly from baseline in both groups. Energy intake, however, decreased significantly only in the intermittent group (-221.0 ± 108.3 kcal/d).

Conclusions: Intermittent empagliflozin supplementation is a useful therapeutic option that empowers dietary self-management, improves glycaemic control and is accompanied by body weight loss and an increase in diabetes treatment-related QoL in patients with inadequately controlled type 2 diabetes.
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http://dx.doi.org/10.1111/dom.13524DOI Listing
February 2019

Common SVOCs in house dust from urban dwellings with schoolchildren in six typical cities of China and associated non-dietary exposure and health risk assessment.

Environ Int 2018 11 20;120:431-442. Epub 2018 Aug 20.

Beijing Key Laboratory of Green Built Environment and Energy Efficient Technology, Beijing University of Technology, Beijing 100124, China.

This paper presents concentrations of common SVOCs in house dusts from urban dwellings with schoolchildren in six typical Chinese cities in winter and summer. Among the detected SVOCs, DBP and DEHP have a higher detection rate. The levels of these two substances contribute an average proportion of over 90% of the total SVOCs' levels, and show a significant correlation in most cities. Based on measured concentrations, schoolchildren's non-dietary exposures to DBP and DEHP at homes are estimated. Due to a longer time spent in child's bedrooms, children's non-dietary exposures to phthalates in child's bedrooms are greatly higher than that in living rooms. As for DBP non-dietary exposure, the most significant pathway is dermal absorption from air, accounting for >70%, whereas, the most predominant pathway for DEHP non-dietary exposure is dust ingestion, contributing from 61.5% to 91.9%. Based on estimated exposure doses, child-specific reproductive and cancer risk are assessed by comparing the exposure doses with DBP and DEHP benchmarks specified in California's Proposition 65. Owing to the high DBP exposure, nearly all of target schoolchildren appear to have a severe reproductive risk, although only non-dietary exposures at home are considered in this study. The average risk quotient of DBP exposure for child-specific MADL in all cities is 31.27 in winter and 10.35 in summer. Also, some schoolchildren are confronted with potential carcinogenic risk, because DEHP exposure exceeds child-specific NSRLs. The maximum DEHP exposure exceeds the cancer benchmark by over 6 times. These results also indicate that controlling indoor phthalates pollution at home is urgent to ensure the healthy development of children in China.
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http://dx.doi.org/10.1016/j.envint.2018.08.031DOI Listing
November 2018

[New Scientific Evidence-based Public Health Guidelines and Practical Manual for Prevention of Sick House Syndrome].

Nihon Eiseigaku Zasshi 2018 ;73(2):116-129

Hokkaido University Center for Environmental and Health Sciences.

Recently, we have published a book containing evidence-based public health guidelines and a practical manual for the prevention of sick house syndrome. The manual is available through the homepage of the Ministry of Health, Labour and Welfare (http://www.mhlw.go.jp/file/06-Seisakujouhou-11130500-Shokuhinanzenbu/0000155147.pdf). It is an almost completely revised version of the 2009 version. The coauthors are 13 specialists in environmental epidemiology, exposure sciences, architecture, and risk communication. Since the 1970s, health problems caused by indoor chemicals, biological pollution, poor temperature control, humidity, and others in office buildings have been recognized as sick building syndrome (SBS) in Western countries, but in Japan it was not until the 1990s that people living in new or renovated homes started to describe a variety of nonspecific subjective symptoms such as eye, nose, and throat irritation, headache, and general fatigue. These symptoms resembled SBS and were designated "sick house syndrome (SHS)." To determine the strategy for prevention of SHS, we conducted a nationwide epidemiological study in six cities from 2003-2013 by randomly sampling 5,709 newly built houses. As a result 1,479 residents in 425 households agreed to environmental monitoring for indoor aldehydes and volatile organic compounds (VOCs). After adjustment for possible risk factors, some VOCs and formaldehyde were dose-dependently shown to be significant risk factors. We also studied the dampness of the houses, fungi, allergies, and others. This book is fully based on the scientific evidence collected through these studies and other newly obtained information, especially from the aspect of architectural engineering. In addition to SHS, we included chapters on recent information about "multi-chemical sensitivity."
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http://dx.doi.org/10.1265/jjh.73.116DOI Listing
August 2018

Age-related changes of proinsulin processing in diabetic and non-diabetic Japanese individuals.

Geriatr Gerontol Int 2018 Jul 17;18(7):1046-1050. Epub 2018 Apr 17.

Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.

Aim: The present study was carried out to examine whether the insulin secretory mechanism deteriorates during the aging process using the new intact proinsulin assay system in non-diabetic and diabetic individuals.

Methods: A total of 172 participants were separated into four groups according to their age (<64 years and >65 years) and an association of type 2 diabetes; that is, 46 older diabetics (mean age 74.5 ± 6.2 years, glycated hemoglobin [National Glycohemoglobin Standardization Program] 7.5 ± 1.3%), 27 older non-diabetics (mean age 76.9 ± 7.5 years), 48 middle-aged diabetics (mean age 50.8 ± 10.4, glycated hemoglobin 7.8 ± 1.5%) and 51 middle aged non-diabetics (mean age 46.6 ± 13.0 years) participants were enrolled.

Results: The proinsulin/insulin (PI/I) ratio of the diabetic group was higher than that of the non-diabetic group in the older group (0.19 ± 0.12 vs 0.11 ± 0.06, P = 0.002). In the middle-aged groups, the PI/I ratio of the diabetic group was higher than that of the non-diabetic group (0.16 ± 0.15 vs 0.09 ± 0.09, P = 0.003). Simple regression analysis showed that male sex (95% CI 0.02-0.01, P = 0.004), age (95% CI 0.00-0.002, P = 0.03), lower body mass index (95% CI -0.06 to 0.00, P = 0.02) and the presence of diabetes mellitus (95% CI 0.04-0.012, P < 0.0001) were significantly associated with the increase in the PI/I ratio. Multivariate regression analysis showed that male sex and age were the independent factors determining the increase in the PI/I ratio in the non-diabetic group. After adjusted for body mass index, the PI/I ratio correlated significantly with age only in the non-diabetic group (r = 0.5, P = 0.004).

Conclusions: The proinsulin processing system might deteriorate not only in diabetics, but also in non-diabetic Japanese individuals with age. Also, sex-related hormones can be protective for the proinsulin processing system. Geriatr Gerontol Int 2018; 18: 1046-1050.
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http://dx.doi.org/10.1111/ggi.13303DOI Listing
July 2018

Giant Cavernous Hemangioma of the Adrenal Gland in an Elderly Patient.

Intern Med 2018 May 27;57(9):1317-1319. Epub 2017 Dec 27.

Department of Internal Medicine. Division of Diabetes, Metabolism and Endocrinology, Japan.

Cavernous hemangioma is a rare, non-functional, benign adrenal tumor. Adrenal cavernous hemangioma is often diagnosed after surgery with a histologic examination. A 70-year-old man complaining of appetite loss was admitted to our hospital. An incidental large left adrenal mass was found by computed tomography (CT). There were no clinical signs of adrenogenital syndrome, Cushing's syndrome or primary aldosteronism. Total resection was carried out. The pathological diagnosis was cavernous hemangioma. The differentiation of adrenal tumor is necessary in cases of large tumors, and resection is desirable given the risks of hemorrhaging and rupture.
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http://dx.doi.org/10.2169/internalmedicine.9711-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980818PMC
May 2018

A case of idiopathic normal pressure hydrocephalus in an elder diabetic patient.

Nihon Ronen Igakkai Zasshi 2017 ;54(2):186-190

Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine (Omori), Toho University School of Medicine.

The clinical entity idiopathic normal pressure hydrocephalus (iNPH) is characterized by dementia, urinary incontinence, gait ataxia. An 80-year old man with a past history of Type 2 diabetes mellitus admitted to our hospital. Combination of twice Aspart and Aspart premixed30/70 insulin were used. Although, he was unable to inject insulin by himself recently. On physical examination, he walked in a mildly wide based manner. According to his family, urinary incontinence was existed. Laboratory data were as follows: Postrandial blood glucose 243 mg/dl and glycated hemoglobin 8.0% (NGSP). Brain magnetic resonance imaging (MRI) scans showed thinning of the corpus callosum with enlargement of the lateral ventricles on a colonal image. Evan's ratio was 0.29. The revised version of Hasegawa's Dementia scale (HDS-R) was 10. The patient showed no evidence a related antecedent event, such as head trauma, intracerebral hemorrhage and meningitis. Thus, he was diagnosed as having possible Idiopathic normal pressure hydrocephalus (iNPH). The following several psychological tests and walking test were applied. Before and after the tap, he was evaluated using the HDS-R, Mini mental state examination (MMSE), Timed Up and Go test (TUG). Insulin was replaced by glargine, and Sitagliptin was added. On the 31 day, the patient underwent Ventriculo-perioneal shunt. Laboratoly data and memory impairment were also improved. 8 month's later, HbA1c was 7.5%. iNPH occurs in the elderly and is characterized by a clinical triad of gait disturbance, urinary incontinence and dementia. In the present case, thinning of the corpus callosum with enlargement of the lateral ventricles was detected by MRI. 49% of iNPH patients had Diabetes mellitus. However, we were unable to detect a relationship iNPH and Diabetes mellitus. Cognitive impairment may interfere with the insulin therapy. In the present case, failure of insulin self-injection was the first clinical sign to appear. We were able to reduce dose of insulin. We conclude that iNPH is a treatable disorder, especially when treatment is started early in the course of the disease.
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http://dx.doi.org/10.3143/geriatrics.54.186DOI Listing
May 2018

Glycemic Variability in Type 1 Diabetes Compared with Degludec and Glargine on the Morning Injection: An Open-label Randomized Controlled Trial.

Diabetes Ther 2017 Aug 25;8(4):783-792. Epub 2017 May 25.

Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.

Introduction: Optimal adjustment of basal insulin to overcome hypoglycemia and glycemic variability (GV) depends on its duration of action and peak-less profile. Owing to the ability of long-acting basal insulin to avoid hypoglycemia, we titrated pre-meal glucose to normal fasting blood glucose, 80-110 mg/dL (4.5-6.1 mmol/L), and post-meal glucose to 80-140 mg/dL (4.5-7.8 mmol/L). The purpose of this study was to evaluate two basal insulin analogues degludec (IDeg) and glargine (IGlar), injected in the morning, for GV using continuous glucose monitoring (CGM) in type 1 diabetes (T1DM).

Methods: In this crossover study, 20 Japanese patients with T1DM (age 54 ± 16 years, disease duration 16 ± 8 years, BMI 24 ± 4 kg/m, HbA1c 7.4 ± 0.8%) were randomized into one of two different starting regimens, and CGM was conducted on three consecutive days during the last week of each 12-week titration period. Treatment satisfaction was assessed at the end of each treatment period using the Diabetes Therapy-Related Quality of Life Questionnaire (DTR-QOL).

Results: There were no differences in HbA1c, total insulin dosage, body weight changes, and basal to bolus ratio between the IDeg and IGlar arms. The day-to-day variability in fasting interstitial GV on the CGM curves was significantly less in the IDeg than IGlar treatment period (25.9 ± 22.0 vs. 43.8 ± 30.1 mg/dl, p = 0.04). Other markers of GV, calculated by the EasyGV software, including mean amplitude of glycemic excursions (MAGE), J-index, total and nocturnal hypoglycemia were not different between the two treatment periods. The score of "satisfaction with treatment", a subdomain of the DTR-QOL system, was higher in the IDeg period.

Conclusion: Thus, the morning injection of the two long-acting insulin analogues seemed similar with regard to the magnitude of hypoglycemia in T1DM, but treatment with IDeg was associated with lower day-to-day variation in glucose level. These results suggest that IDeg is safe with minimal morning GV in patients with T1DM.

Clinical Trial Registration: Japanese Clinical Trials Registry, UMIN000012358.
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http://dx.doi.org/10.1007/s13300-017-0269-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544606PMC
August 2017

Acute suppurative thyroiditis in infected thyroid cyst in an adult patient under hemodialysis.

Clin Case Rep 2017 05 15;5(5):570-573. Epub 2017 Mar 15.

Division of Diabetes, Metabolism and Endocrinology Department of Internal Medicine Toho University School of Medicine 6-11-1 Omori-nishi Ota-ku Tokyo 143-8541 Japan.

Acute suppurative thyroiditis (AST) accompanied by an abscess is a rare clinical case. Hemodialysis patients are at risk for infections. Sepsis mortality was from 100 to 300 times higher for chronic dialysis patients than that for the general public. Thus, special care should be taken against infection in patients under hemodialysis.
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http://dx.doi.org/10.1002/ccr3.861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412757PMC
May 2017

Exposure to paternal tobacco smoking increased child hospitalization for lower respiratory infections but not for other diseases in Vietnam.

Sci Rep 2017 03 31;7:45481. Epub 2017 Mar 31.

Department of Clinical Tropical Medicine, Institute of Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

Exposure to environmental tobacco smoke (ETS) is an important modifiable risk factor for child hospitalization, although its contribution is not well documented in countries where ETS due to maternal tobacco smoking is negligible. We conducted a birth cohort study of 1999 neonates between May 2009 and May 2010 in Nha Trang, Vietnam, to evaluate paternal tobacco smoking as a risk factor for infectious and non-infectious diseases. Hospitalizations during a 24-month observation period were identified using hospital records. The effect of paternal exposure during pregnancy and infancy on infectious disease incidence was evaluated using Poisson regression models. In total, 35.6% of 1624 children who attended follow-up visits required at least one hospitalization by 2 years of age, and the most common reason for hospitalization was lower respiratory tract infection (LRTI). Paternal tobacco smoking independently increased the risk of LRTI 1.76-fold (95% CI: 1.24-2.51) after adjusting for possible confounders but was not associated with any other cause of hospitalization. The population attributable fraction indicated that effective interventions to prevent paternal smoking in the presence of children would reduce LRTI-related hospitalizations by 14.8% in this epidemiological setting.
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http://dx.doi.org/10.1038/srep45481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374438PMC
March 2017

High glycated albumin (GA) levels and the GA/HbA1c ratio in patients with insulin autoimmune syndrome.

Diabetol Int 2017 Jun 4;8(2):199-204. Epub 2016 Nov 4.

7Diabetes Center, Toyonaka Municipal Hospital, Osaka, Japan.

Insulin autoimmune syndrome (IAS) involves not only fasting hypoglycemia, but also postprandial hyperglycemia. In the present study, we hypothesized that glycated albumin (GA) levels and the GA/HbA1c ratio, which reflect fluctuations in plasma glucose levels, are elevated in IAS patients. Four IAS patients were enrolled in the present study. Thirty-two non-diabetic subjects matched for gender, age, and BMI were used as the control group. The fasting plasma glucose levels in the IAS patients were significantly lower than in the control group. However, the oral glucose tolerance test (OGTT) revealed impaired glucose tolerance or diabetes mellitus in all the IAS patients, and thus the OGTT 2-h plasma glucose levels were significantly higher than in the control group. The GA levels and the GA/HbA1c ratio in the IAS patients were significantly higher than in the control group, despite no significant difference in the HbA1c levels between the two groups. In one case in which IAS spontaneously went into remission, there was a significant correlation between anti-insulin antibodies and GA, but not HbA1c. Improvement in glucose fluctuations was observed by continuous glucose monitoring in another patient along with improvement in the clinical symptoms. Furthermore, anti-insulin antibodies, GA, and the GA/HbA1c ratio decreased, but HbA1c did not change significantly in three IAS patients along with the improvement in clinical symptoms. These results suggest that GA and the GA/HbA1c ratio are useful indicators for determining the level of disease activity in IAS patients.
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http://dx.doi.org/10.1007/s13340-016-0294-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224948PMC
June 2017

Case of anal fistula with Fournier's gangrene in an obese type 2 diabetes mellitus patient.

J Diabetes Investig 2016 Mar 31;7(2):276-8. Epub 2015 Jul 31.

Department of Surgery Shin-suma General Hospital Kobe Japan.

A 64-year-old man was admitted to Shin-suma General Hospital, Kobe, Japan, complaining of a 3-day history of scrotal swelling and high fever. He had type 2 diabetes mellitus. On examination, his body temperature had risen to 38.5 °C. Examination of the scrotum showed abnormal enlargement. Laboratory data were as follows: white cell count 35,400/μL and glycated hemoglobin 9.6%. Anal fistula was found in an endorectal ultrasound. Computed tomography scan showed a relatively high density of subcutaneous tissue and elevated air density. Thus, he was diagnosed with Fournier's gangrene. On the fourth hospital day, the patient underwent debridement of gangrenous tissue. Seton surgery was carried out for anal fistula on the 34th hospital day. He responded to the treatment very well. He was discharged on the 33rd postoperative day. Once Fournier's gangrene has been diagnosed, considering the association of anal fistula and perianal abscess is important.
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http://dx.doi.org/10.1111/jdi.12355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773667PMC
March 2016

The toxic effects of indoor atmospheric fine particulate matter collected from allergic and non-allergic families in Wuhan on mouse peritoneal macrophages.

J Appl Toxicol 2016 Apr 24;36(4):596-608. Epub 2015 Aug 24.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei, China.

Recent studies have shown that fine particulate matter (PM2.5) is associated with multiple adverse health outcomes and PM2.5-induced oxidative stress is now commonly known as a proposed mechanism of PM2.5-mediated toxicity. However, the association between allergic symptoms in children and exposure to PM2.5 has not been fully elucidated, particularly the role of PM2.5 on the indoor environment involved in allergy or non-allergy is unknown. The aim of the present study was to explore whether indoor PM2.5 from the homes of children with allergic symptoms had more increased risks of allergy than that of healthy ones and then compare the toxicity and inflammatory response of them. In this study, indoor PM2.5 was collected from the homes of schoolchildren with allergic symptoms and those of healthy ones respectively, and components of PM2.5 were analyzed. PM2.5-mediated oxidative damage and inflammatory response were further evaluated in mouse peritoneal macrophages based on its effects on the levels of reactive oxygen species accumulation, lipid peroxidation, DNA damage or cytokine production. It seems that oxidative stress may contribute to PM2.5-induced toxicity, and PM2.5 from the allergic indoor environment produced more serious toxic effects and an inflammatory response on mouse peritoneal macrophages than that from a non-allergic indoor environment.
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http://dx.doi.org/10.1002/jat.3217DOI Listing
April 2016
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