Publications by authors named "Yusuke Miyazaki"

88 Publications

A Sulfonyl Azide-Based Sulfide Scavenger Rescues Mice from Lethal Hydrogen Sulfide Intoxication.

Toxicol Sci 2021 Jul 16. Epub 2021 Jul 16.

Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA.

Exposure to hydrogen sulfide (H2S) can cause neurotoxicity and cardiopulmonary arrest. Resuscitating victims of sulfide intoxication is extremely difficult, and survivors often exhibit persistent neurological deficits. However, no specific antidote is available for sulfide intoxication. The objective of this study was to examine whether administration of a sulfonyl azide-based sulfide-specific scavenger, SS20, would rescue mice in models of H2S intoxication: ongoing exposure and post-cardiopulmonary arrest. In the ongoing exposure model, SS20 (1,250 µmol/kg) or vehicle was administered to awake CD-1 mice intraperitoneally at 10 minutes after breathing 790 ppm of H2S followed by another 30 minutes of H2S inhalation. Effects of SS20 on survival was assessed. In the post-cardiopulmonary arrest model, cardiopulmonary arrest was induced by an intraperitoneal administration of sodium sulfide nonahydrate (125 mg/kg) in anesthetized mice. After 1 minute of cardiopulmonary arrest, mice were resuscitated with intravenous administration of SS20 (250 µmol/kg) or vehicle. Effects of SS20 on survival, neurological outcomes, and plasma H2S levels were evaluated. Administration of SS20 during ongoing H2S inhalation improved 24-hour survival (6/6 [100%] in SS20 versus 1/6 [17%] in vehicle; P = 0.0043). Post-arrest administration of SS20 improved 7-day survival (4/10 [40%] in SS20 versus 0/10 [0%] in vehicle; P = 0.0038) and neurological outcomes after resuscitation. SS20 decreased plasma H2S levels to pre-arrest baseline immediately after reperfusion and shortened the time to return of spontaneous circulation and respiration. The current results suggest that SS20 is an effective antidote against lethal H2S intoxication, even when administered after cardiopulmonary arrest.
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http://dx.doi.org/10.1093/toxsci/kfab088DOI Listing
July 2021

AgDD System: A Chemical Controllable Protein Aggregates in Cells.

Authors:
Yusuke Miyazaki

Methods Mol Biol 2021 ;2312:277-285

ANRI, Tokyo, Japan.

There are increasing evidence and growing interest in the relationship between protein aggregates/phase separation and various human diseases, especially neurodegenerative diseases. However, we do not entirely comprehend how aggregates generate or the clearance network of chaperones, proteasomes, ubiquitin ligases, and other factors interact with aggregates. Here, we describe chemically controllable systems compose with a genetically engineered cell and a small drug that enables us to rapidly induce protein aggregates' formation by withdrawing the small molecule. This trigger does not activate global stress responses induced by stimuli, such as proteasome inhibitors or heat shock. This method can produce aggregates in a specific compartment and diverse experimental systems, including live animals.
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http://dx.doi.org/10.1007/978-1-0716-1441-9_16DOI Listing
January 2021

Neutrophil/lymphocyte ratio is correlated with levels of inflammatory markers and is significantly reduced by smoking cessation.

J Int Med Res 2021 Jun;49(6):3000605211019223

Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.

Previous studies have reported that the neutrophil to lymphocyte ratio (NLR) is associated with onset and prognosis of cardiovascular disease (CVD). Smoking is a major risk factor for CVD and smoking cessation significantly reduces CVD risk. However, the effects of smoking cessation on the NLR remain unknown. Among smokers visiting our smoking cessation clinics, we examined changes in the NLR and CVD biomarkers before and after smoking cessation. A total of 389 individuals (301 men and 88 women) were enrolled in the study. The median NLR was significantly reduced after successful smoking cessation (before: 1.8, interquartile range [IQR] 1.5, 2.5; after: 1.7, IQR 1.3, 2.4). In a linear regression model adjusted for sex, percent change in NLR comparing before and after smoking cessation was significantly and positively correlated with percent changes in C-reactive protein (β = 0.260), α1-antitrypsin-low density lipoprotein (β = 0.151,  < 0.05), and serum amyloid A-low density lipoprotein (β = 0.325). Our study demonstrated for the first time that smoking cessation significantly reduces the NLR in tandem with markers of inflammation and oxidative stress.
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http://dx.doi.org/10.1177/03000605211019223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258763PMC
June 2021

Serum TNFα levels at 24 h after certolizumab pegol predict effectiveness at week 12 in patients with rheumatoid arthritis from TSUBAME study.

Arthritis Res Ther 2021 06 1;23(1):154. Epub 2021 Jun 1.

The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu, 807-8555, Japan.

Objective: To estimate the relationship between serum TNFα, IL-6, and serum CZP levels and the clinical response to CZP in RA patients in the TSUBAME study.

Methods: One hundred patients with RA who received CZP were enrolled and multiple clinical parameters, serum TNFα, IL-6, and CZP levels, were assessed at 0, 24, and 48 h and 12 weeks after first administration of CZP.

Results: The CZP therapy significantly improved the DAS28(ESR) at 12 weeks. Serum TNFα and IL-6 levels significantly decreased from baseline at 24 h after the first administration of CZP. Serum TNFα levels at baseline were not related to clinical parameters at baseline and improvement in DAS28(ESR) at week 12 of the CZP therapy. However, serum levels of CZP at 24 h were strongly and negatively correlated with TNFα levels at 24 h, which were negatively correlated with improved rate in DAS28(ESR) at week 12. Only serum levels of TNFα, but not IL-6, at 24 h had a negative correlation with achievement of DAS28(ESR)<2.6 at week 12 by the multivariate analysis (odds ratio 0.01, 95% confidence interval 0.04e-2-0.22, p < 0.01). A receiver operating characteristic analysis was conducted to estimate the achievement of DAS28(ESR)<2.6 at week 12 after the CZP therapy and cut-off value of 0.76 pg/ml for serum levels of TNFα at 24 h was yielded (area under the curve=0.75). DAS28(ESR)<2.6 was achieved at week 12 significantly more patients with lower serum TNF levels (≦0.76 pg/ml) at 24 h than those with higher TNF levels.

Conclusions: CZP was highly effective in RA patients who had low serum TNFα levels at 24 h after the initial administration of CZP. Therefore, we propose that serum TNFα levels at 24 h could serve as a biomarker predicting effectiveness to CZP at week 12 in patients with RA.

Trial Registration: Clinical trial registration number: UMIN ID:000022831.
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http://dx.doi.org/10.1186/s13075-021-02547-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167961PMC
June 2021

Sulfide catabolism ameliorates hypoxic brain injury.

Nat Commun 2021 05 25;12(1):3108. Epub 2021 May 25.

Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.

The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain's sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.
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http://dx.doi.org/10.1038/s41467-021-23363-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149856PMC
May 2021

Sepsis Induces Physical and Mental Impairments in a Mouse Model of Post-Intensive Care Syndrome.

J Clin Med 2021 Apr 9;10(8). Epub 2021 Apr 9.

Department of Disaster and Emergency and Critical Care Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.

Post-intensive care syndrome (PICS) is a physical, cognitive, and mental impairment observed in intensive care unit (ICU) survivors. Although this is an emerging problem in the ICU, how sepsis induces the characteristic symptoms of PICS remains unclear. To develop a model of PICS, we induced sepsis in male C57/B6 mice via sublethal cecum slurry injection and subsequently treated them using ICU-like interventions. At 1-2 weeks post-sepsis induction, we simultaneously evaluated the abilities of the surviving mice using the following behavioral tests: (1) a grip strength test (GST) and a treadmill test for physical assessment, (2) a novel object recognition test (NORT) for cognitive assessment, and (3) an open field test (OFT) and a marble burying test (MBT) for mental assessment. The surviving mice showed a range of deficits, including muscle weakness with significantly decreased grip strength in the GST; decreased total mileage during the treadmill test; anxiety and decreased activity, with significantly decreased time in the central area, and increased duration of immobility in the OFT; and an increased number of buried marbles in the MBT. Given these physical and mental impairments in the surviving mice, our model has the potential to elucidate mechanistic insights and to discover therapeutic targets and new interventions for PICS.
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http://dx.doi.org/10.3390/jcm10081593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068824PMC
April 2021

Efficacy and safety of tofacitinib versus baricitinib in patients with rheumatoid arthritis in real clinical practice: analyses with propensity score-based inverse probability of treatment weighting.

Ann Rheum Dis 2021 Apr 7. Epub 2021 Apr 7.

The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan

Objectives: The differences of efficacy between each Janus kinase (JAK) inhibitors have not been clarified in the patients with rheumatoid arthritis (RA) in clinical practice. Here, we compared the efficacy between tofacitinib (TOFA) and baricitinib (BARI) in clinical practice.

Methods: The efficacy of TOFA (n=156) in patients with RA was compared with BARI (n=138). Selection bias was reduced to a minimum using propensity score-based inverse probability of treatment weighting (IPTW). The Clinical Disease Activity Index (CDAI) trajectory for patients who started TOFA or BARI was analysed using growth mixture modelling (GMM).

Results: No significant difference was observed in patient characteristics between the TOFA and BARI groups in after adjustment by propensity score-based IPTW. The BARI group had a significantly higher rate of CDAI remission at week 24 after the introduction of JAK inhibitors than the TOFA group. The treatment-resistant group defined by GMM, comprising patients who did not achieve low disease activity at week 24, was more likely to include those who had received many biological disease-modifying antirheumatic drugs (bDMARDs) before the introduction of JAK inhibitors and those who received TOFA. Among patients with RA who received TOFA, those who had received ≥4 bDMARDs before the introduction of TOFA were more likely to be classified into the treatment-resistant group.

Conclusions: BARI showed a similar safety profile and better clinical outcome when compared with TOFA after reduction to a minimum of selection bias. However, these were observed in a small population. Accordingly, further investigation is required in an accurately powered head-to-head trial.
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http://dx.doi.org/10.1136/annrheumdis-2020-219699DOI Listing
April 2021

Hypoxia ameliorates brain hyperoxia and NAD deficiency in a murine model of Leigh syndrome.

Mol Genet Metab 2021 05 11;133(1):83-93. Epub 2021 Mar 11.

Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

Leigh syndrome is a severe mitochondrial neurodegenerative disease with no effective treatment. In the Ndufs4 mouse model of Leigh syndrome, continuously breathing 11% O (hypoxia) prevents neurodegeneration and leads to a dramatic extension (~5-fold) in lifespan. We investigated the effect of hypoxia on the brain metabolism of Ndufs4 mice by studying blood gas tensions and metabolite levels in simultaneously sampled arterial and cerebral internal jugular venous (IJV) blood. Relatively healthy Ndufs4 and wildtype (WT) mice breathing air until postnatal age ~38 d were compared to Ndufs4 and WT mice breathing air until ~38 days old followed by 4-weeks of breathing 11% O. Compared to WT control mice, Ndufs4 mice breathing air have reduced brain O consumption as evidenced by an elevated partial pressure of O in IJV blood (PO) despite a normal PO in arterial blood, and higher lactate/pyruvate (L/P) ratios in IJV plasma revealed by metabolic profiling. In Ndufs4 mice, hypoxia treatment normalized the cerebral venous PO and L/P ratios, and decreased levels of nicotinate in IJV plasma. Brain concentrations of nicotinamide adenine dinucleotide (NAD) were lower in Ndufs4 mice breathing air than in WT mice, but preserved at WT levels with hypoxia treatment. Although mild hypoxia (17% O) has been shown to be an ineffective therapy for Ndufs4 mice, we find that when combined with nicotinic acid supplementation it provides a modest improvement in neurodegeneration and lifespan. Therapies targeting both brain hyperoxia and NAD deficiency may hold promise for treating Leigh syndrome.
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http://dx.doi.org/10.1016/j.ymgme.2021.03.005DOI Listing
May 2021

Effectiveness and safety of mepolizumab in combination with corticosteroids in patients with eosinophilic granulomatosis with polyangiitis.

Arthritis Res Ther 2021 03 16;23(1):86. Epub 2021 Mar 16.

The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Kitakyushu, 807-8555, Japan.

Background: Mepolizumab (MPZ), an anti-interleukin-5 antibody, is effective for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). However, its effectiveness has not been adequately evaluated in real-world clinical practice. In this study, we assessed the effectiveness and safety of MPZ (300 mg) for relapsing/refractory EGPA resistant to corticosteroids (CS) for 1 year in real-world settings.

Methods: We administered MPZ (300 mg) to 16 patients with relapsing/refractory EGPA resistant to CS (Post-MPZ). We also retrospectively collected data from the same patients for the 12 months before the administration of MPZ (Pre-MPZ). The primary endpoint was the 12-month remission rate after MPZ administration and the secondary endpoints were the Birmingham vasculitis activity score (BVAS), vasculitis damage index (VDI), eosinophil counts, changes in concomitant CS doses/concomitant immunosuppressant use, MPZ retention rate, and incidence of adverse events. The clinical course was compared between Pre-MPZ and Post-MPZ.

Results: The 12-month remission rate after the initiation of MPZ was 75%. No change was observed in BVAS, eosinophil count, or concomitant CS dose over time in the Pre-MPZ group, whereas all these parameters were significantly decreased over time in the Post-MPZ group. The number of patients using concomitant immunosuppressant also decreased over time in the Post-MPZ group. VDI did not increase in either group. The MPZ retention rate was 100% and only three patients (18.8%) had infections. Changes in BVAS, eosinophil count, and cumulative concomitant CS dose were significantly lower in the Post-MPZ group than in the Pre-MPZ group. There was no significant difference in the changes in VDI between the groups.

Conclusion: This study demonstrated that MPZ is effective and safe for EGPA. Furthermore, MPZ decreases disease activity, increases remission rate, and has a CS-sparing effect.
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http://dx.doi.org/10.1186/s13075-021-02462-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962235PMC
March 2021

Histone Acetylation Domains Are Differentially Induced during Development of Heart Failure in Dahl Salt-Sensitive Rats.

Int J Mol Sci 2021 Feb 10;22(4). Epub 2021 Feb 10.

Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Japan.

Histone acetylation by epigenetic regulators has been shown to activate the transcription of hypertrophic response genes, which subsequently leads to the development and progression of heart failure. However, nothing is known about the acetylation of the histone tail and globular domains in left ventricular hypertrophy or in heart failure. The acetylation of H3K9 on the promoter of the hypertrophic response gene was significantly increased in the left ventricular hypertrophy stage, whereas the acetylation of H3K122 did not increase in the left ventricular hypertrophy stage but did significantly increase in the heart failure stage. Interestingly, the interaction between the chromatin remodeling factor BRG1 and p300 was significantly increased in the heart failure stage, but not in the left ventricular hypertrophy stage. This study demonstrates that stage-specific acetylation of the histone tail and globular domains occurs during the development and progression of heart failure, providing novel insights into the epigenetic regulatory mechanism governing transcriptional activity in these processes.
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http://dx.doi.org/10.3390/ijms22041771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916721PMC
February 2021

Urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of colitis-associated colorectal cancer in mice.

PLoS One 2021 27;16(1):e0245292. Epub 2021 Jan 27.

Department of Animal Radiology and Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Early diagnosis of colorectal cancer is needed to reduce the mortal consequence by cancer. Lipid mediators play critical role in progression of colitis and colitis-associated colon cancer (CAC) and some of their metabolites are excreted in urine. Here, we attempted to find novel biomarkers in urinary lipid metabolite of a murine model of CAC. Mice were received single administration of azoxymethane (AOM) and repeated administration of dextran sulfate sodium (DSS). Lipid metabolites in their urine was measured by liquid chromatography mass spectrometry and their colon was collected to perform morphological study. AOM and DSS caused inflammation and tumor formation in mouse colon. Liquid chromatography mass spectrometry-based comprehensive analysis of lipid metabolites showed that cyclooxygenase-mediated arachidonic acid (AA) metabolites, prostaglandins, and reactive oxygen species (ROS)-mediated AA metabolites, isoprostanes, were predominantly increased in the urine of tumor-bearing mice. Among that, urinary prostaglandin (PG)E2 metabolite tetranor-PGEM and PGD2 metabolite tetranor-PGDM were significantly increased in both of urine collected at the acute phase of colitis and the carcinogenesis phase. On the other hand, two F2 isoprostanes (F2-IsoPs), 8-iso PGF2α and 2,3-dinor-8-iso PGF2α, were significantly increased only in the carcinogenesis phase. Morphological study showed that infiltrated monocytes into tumor mass strongly expressed ROS generator NADPH (p22phox). These observations suggest that urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of CAC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245292PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840041PMC
May 2021

Enhanced Fatty Acid Synthesis Leads to Subset Imbalance and IFN-γ Overproduction in T Helper 1 Cells.

Front Immunol 2020 30;11:593103. Epub 2020 Nov 30.

The First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health, Kitakyushu, Japan.

Recent reports have shown the importance of IFN-γ and T-bet B cells in the pathology of SLE, suggesting the involvement of IFN-γ-producing T-bet CD4 cells, i.e., Th1 cells. This study determined the changes in Th1 subsets with metabolic shift and their potential as therapeutic targets in SLE. Compared with healthy donors, patients with SLE had higher numbers of T-betCXCR3 effector cells and T-betFoxp3 non-suppressive cells, which excessively produce IFN-γ, and lower number of non-IFN-γ-producing T-betFoxp3 activated-T cells. These changes were considered to be involved in treatment resistance. The differentiation mechanism of Th1 subsets was investigated using memory CD4 cells obtained from healthy donors and patients with SLE. In memory CD4 cells of healthy donors, both rapamycin and 2-deoxy-D-glucose (2DG) suppressed T-betFoxp3 cells, and induced T-betFoxp3 cells. Rapamycin induced IFN-γ-producing T-betFoxp3 cells accompanied with enhanced lipid metabolism, whereas 2DG induced IFN-γ-non-producing T-betFoxp3 cells. In memory CD4 cells of SLE patients, inhibition of fatty acid synthesis, but not β-oxidation, suppressed IFN-γ production, and up-regulated of Foxp3 expression in T-betFoxp3 cells. Metabolic regulators such as fatty acid synthesis inhibitors may improve the pathological status by correcting Th1 subset imbalance and overproduction of IFN-γ in SLE.
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http://dx.doi.org/10.3389/fimmu.2020.593103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734283PMC
June 2021

Complete Republication: Fall Injury while the Parent Is Operating a Bicycle with an Infant in a Baby Carrier.

JMA J 2020 Oct 30;3(4):330-339. Epub 2020 Sep 30.

Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.

Introduction: Pediatric emergency physicians commonly experience cases of infantile trauma as a result of a child falling from the arms or the back of a parent while the parent is operating a bicycle.

Methods: 1. We conducted a retrospective case-series study which included children younger than 1 year who were injured after falling from the arms or the back of the parent while the latter was operating a bicycle. 2. We conducted a dynamics experiment by recreating the circumstances of the accident using dummies representing a 6-month-old infant being carried on the back of the mother. We assessed the score of the Head Injury Criterion (HIC) and the maximum impact load on the head of the dummy infant.

Results: 1. We found eight injured patients, two of whom required intensive care. One of the latter experienced neurological sequelae. 2. The HIC score and the maximum impact load varied from 7.7 to 17.0 and 2.26 to 3.47 times the reference values for 6-month-old infants, respectively.

Conclusions: Our study revealed that a strong impact on an infant's head can result in severe head trauma due to the mechanics of the injury type studied. Preventive strategies for the safe transportation of infants are needed.
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http://dx.doi.org/10.31662/jmaj.2020-0032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676997PMC
October 2020

Short-term Changes in Self-rating Depression Scale Scores after Smoking Cessation in Neurotic Patients.

Intern Med 2021 Apr 14;60(8):1175-1181. Epub 2020 Oct 14.

Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Japan.

Objective The psychological status is a key factor in smoking continuance. However, details on short-term changes in mild depressive states after smoking cessation (SC) are still unknown. The purpose of the present study was to investigate these short-term changes. Methods A total of 989 patients who visited our SC Clinic were assessed using the Zung Self-Rating-Depression-Scale (SDS), an official instrument to measure depressive tendencies. The participants were classified into normal and neurotic groups based on their SDS scores during their initial visit; they were assessed again 2, 4, 8, and 12 weeks thereafter. Results The majority of patients in the neurotic group were women. These patients were also younger, with a higher nicotine dependence, and presented with a lower successful SC rate than the patients in the normal group. A decrease in SDS scores after starting the SC treatment was observed only in the neurotic group, especially during the first two weeks. In patients who continued to smoke, no improvement in depressive tendencies was noted in this period. Conclusion Depressive tendencies of patients with neurosis improve in the initial stages of the SC treatment (i.e., within two weeks after starting the treatment). This finding fills the mentioned knowledge gap regarding the effects of SC on mild depressive states in the short term.
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http://dx.doi.org/10.2169/internalmedicine.4868-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112982PMC
April 2021

High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19).

Obstet Gynecol 2020 12;136(6):1109-1113

Department of Anesthesia, the Department of Pediatrics, the Respiratory Care Department, the Department of Obstetrics and Gynecology, and the Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; and the Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking.

Method: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160-200 ppm) nitric oxide by mask twice daily and report on their clinical response.

Experience: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission.

Conclusion: Nitric oxide at 160-200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.
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http://dx.doi.org/10.1097/AOG.0000000000004128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673637PMC
December 2020

Effectiveness of an Educational Video in Maternity Wards to Prevent Self-Reported Shaking and Smothering during the First Week of Age: A Cluster Randomized Controlled Trial.

Prev Sci 2020 11;21(8):1028-1036

Department of Obstetrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.

This study aimed to investigate whether watching an educational video on infant crying and the dangers of shaking and smothering within 1 week after delivery at maternity wards reduces self-reported shaking and smothering, at a 1-month health checkup. A cluster randomized controlled trial, stratified by area and hospital function, was employed in 45 obstetrics hospitals/clinics in Osaka Prefecture, Japan. In the intervention group, mothers watched an educational video on infant crying and the dangers of shaking and smothering an infant, within 1 week of age, during hospitalization at maternity wards, without blinding on group allocation. Control group received usual care. A total of 4722 (N = 2350 and 2372 for intervention and control group, respectively) mothers who delivered their babies (still birth and gestational age < 22 weeks were excluded) between October 1, 2014, and January 31 were recruited. Outcomes were self-reported shaking and smothering behaviors, knowledge on infant crying and shaking, and behaviors to cope with infant crying, assessed via a questionnaire at a 1-month health checkup. In all, 2718 (N = 1078 and 1640) responded to the questionnaire (response rate: 58.3%), and analytic sample size was 2655 (N = 1058 and 1597 for intervention and control group, respectively). Multilevel analysis was used to adjust for correlation within the cluster. Prevalence of shaking was significantly lower in the intervention group (0.19%) than in the control group (1.69%). Intention-to-treat analysis showed an 89% reduction in the reported prevalence of self-reported shaking (OR: 0.11, 95% CI: 0.02-0.53) due to watching the educational video. However, self-reported smothering behavior showed no significant reduction (OR: 0.66, 95% CI: 0.27-1.60). No side effects were reported. Watching an educational video on infant crying and the dangers of shaking and smothering within 1 week after delivery at maternity wards reduced self-reported shaking at 1 month of age. UMIN Clinical Trial Registry UMIN000015558.
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http://dx.doi.org/10.1007/s11121-020-01145-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569084PMC
November 2020

Cacao Bean Polyphenols Inhibit Cardiac Hypertrophy and Systolic Dysfunction in Pressure Overload-induced Heart Failure Model Mice.

Planta Med 2020 Nov 9;86(17):1304-1312. Epub 2020 Jul 9.

Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

Pathological stresses such as pressure overload and myocardial infarction induce cardiac hypertrophy, which increases the risk of heart failure. Cacao bean polyphenols have recently gained considerable attention for their beneficial effects on cardiovascular diseases. This study investigated the effect of cacao bean polyphenols on the development of cardiac hypertrophy and heart failure. Cardiomyocytes from neonatal rats were pre-treated with cacao bean polyphenols and then stimulated with 30 µM phenylephrine. C57BL/6j male mice were subjected to sham or transverse aortic constriction surgery and then orally administered with vehicle or cacao bean polyphenols. Cardiac hypertrophy and function were examined by echocardiography. In cardiomyocytes, cacao bean polyphenols significantly suppressed phenylephrine-induced cardiomyocyte hypertrophy and hypertrophic gene transcription. Extracellular signal-regulated kinase 1/2 and GATA binding protein 4 phosphorylation induced by phenylephrine was inhibited by cacao bean polyphenols treatment in the cardiomyocytes. Cacao bean polyphenols treatment at 1200 mg/kg significantly ameliorated left ventricular posterior wall thickness, fractional shortening, hypertrophic gene transcription, cardiac hypertrophy, cardiac fibrosis, and extracellular signal-regulated kinase 1/2 phosphorylation induced by pressure overload. In conclusion, these findings suggest that cacao bean polyphenols prevent pressure overload-induced cardiac hypertrophy and systolic dysfunction by inhibiting the extracellular signal-regulated kinase 1/2-GATA binding protein 4 pathway in cardiomyocytes. Thus, cacao bean polyphenols may be useful for heart failure therapy in humans.
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http://dx.doi.org/10.1055/a-1191-7970DOI Listing
November 2020

The profile of lipid metabolites in urine of marmoset wasting syndrome.

PLoS One 2020 23;15(6):e0234634. Epub 2020 Jun 23.

Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Marmoset wasting syndrome (MWS) is clinically characterized by progressive weight loss. Although morbidity and mortality of MWS are relatively high in captive marmosets, its causes remain unknown. Lipid mediators are bioactive metabolites which are produced from polyunsaturated fatty acids, such as arachidonic acid (AA) and eicosapentaenoic acid. These lipid metabolites regulate a wide range of inflammatory responses and they are excreted into the urine. As urinary lipid profiles reflect systemic inflammatory conditions, we comprehensively measured the levels of 141 types of lipid metabolites in the urines obtained from healthy common marmoset (Callithrix jacchus) (N = 7) or marmosets with MWS (N = 7). We found that 41 types of metabolites were detected in all urine samples of both groups. Among them, AA-derived metabolites accounted for 63% (26/41 types) of all detected metabolites. Notably, the levels of AA-derived prostaglandin (PG) E2, PGF2α, thromboxane (TX) B2 and F2-isoprostanes significantly increased in the urine samples of marmosets with MWS. In this study, we found some urinary lipid metabolites which may be involved in the development of MWS. Although the cause of MWS remains unclear, our findings may provide some insight into understanding the mechanisms of development of MWS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234634PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310677PMC
August 2020

Favorable efficacy of rituximab in ANCA-associated vasculitis patients with excessive B cell differentiation.

Arthritis Res Ther 2020 06 15;22(1):141. Epub 2020 Jun 15.

School of Medicine, University of Occupational & Environmental Health, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu, Fukuoka, 807-8555, Japan.

Objectives: B cell depletion by rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, peripheral B cell phenotypes and the selection criteria for RTX therapy in AAV remain unclear.

Methods: Phenotypic characterization of circulating B cells was performed by 8-color flow cytometric analysis in 54 newly diagnosed AAV patients (20 granulomatosis with polyangiitis and 34 microscopic polyangiitis). Patients were considered eligible to receive intravenous cyclophosphamide pulse (IV-CY) or RTX. All patients also received high-dose glucocorticoids (GC). We assessed circulating B cell phenotypes and evaluated the efficacy after 6 months of treatment.

Results: There were no significant differences in the rate of clinical improvement, relapses, or serious adverse events between patients receiving RTX and IV-CY. The rate of Birmingham Vasculitis Activity Score (BVAS) improvement at 6 months tended to be higher in the RTX group than in the IV-CY group. The proportion of effector or class-switched memory B cells increased in 24 out of 54 patients (44%). The proportions of peripheral T and B cell phenotypes did not correlate with BVAS at baseline. However, among peripheral B cells, the proportion of class-switched memory B cells negatively correlated with the rate of improvement in BVAS at 6 months after treatment initiation (r = - 0.28, p = 0.04). Patients with excessive B cell differentiation were defined as those in whom the proportion of class-switched memory B cells or IgDCD27 B cells among all B cells was > 2 SDs higher than the mean in the HCs. The rate of BVAS remission in patients with excessive B cell differentiation was significantly lower than that in patients without. In patients with excessive B cell differentiation, the survival rate, the rate of BVAS-remission, and dose reduction of GC were significantly improved in the RTX group compared to those in the IV-CY group after 6 months of treatment.

Conclusions: The presence of excessive B cell differentiation was associated with treatment resistance. However, in patients with circulating B cell abnormality, RTX was effective and increased survival compared to IV-CY. The results suggest that multi-color flow cytometry may be useful to determine the selection criteria for RTX therapy in AAV patients.
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http://dx.doi.org/10.1186/s13075-020-02215-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294638PMC
June 2020

Nitric Oxide in Post-cardiac Arrest Syndrome.

J Cardiovasc Pharmacol 2020 06;75(6):508-515

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Sudden cardiac arrest is a leading cause of death worldwide. Although the methods of cardiopulmonary resuscitation have been improved, mortality is still unacceptably high, and many survivors suffer from lasting neurological deficits due to the post-cardiac arrest syndrome (PCAS). Pathophysiologically, generalized vascular endothelial dysfunction accompanied by platelet activation and systemic inflammation has been implicated in the pathogenesis of PCAS. Because endothelial-derived nitric oxide (NO) plays a central role in maintaining vascular homeostasis, the role of NO-dependent signaling has been a focus of the intense investigation. Recent preclinical studies showed that therapeutic interventions that increase vascular NO bioavailability may improve outcomes after cardiac arrest complicated with PCAS. In particular, NO inhalation therapy has been shown to improve neurological outcomes and survival in multiple species. Clinical studies examining the safety and efficacy of inhaled NO in patients sustaining PCAS are warranted.
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http://dx.doi.org/10.1097/FJC.0000000000000765DOI Listing
June 2020

The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice.

Sci Rep 2020 04 28;10(1):7172. Epub 2020 Apr 28.

Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.

Curcumin is a naturally occurring p300-histone acetyltransferase (p300-HAT) inhibitor that suppresses cardiomyocyte hypertrophy and the development of heart failure in experimental animal models. To enhance the therapeutic potential of curcumin against heart failure, we produced a series of synthetic curcumin analogues and investigated their inhibitory activity against p300-HAT. The compound with the strongest activity was further evaluated to determine its effects on cardiomyocyte hypertrophy and pressure overload-induced heart failure in mice. We synthesised five synthetic curcumin analogues and found that a compound we have named GO-Y030 most strongly inhibited p300-HAT activity. Furthermore, 1 μM GO-Y030, in a manner equivalent to 10 µM curcumin, suppressed phenylephrine-induced hypertrophic responses in cultured cardiomyocytes. In mice undergoing transverse aortic constriction surgery, administration of GO-Y030 at a mere 1% of an equivalently-effective dose of curcumin significantly attenuated cardiac hypertrophy and systolic dysfunction. In addition, this low dose of GO-Y030 almost completely blocked histone H3K9 acetylation and eliminated left ventricular fibrosis. A low dose of the synthetic curcumin analogue GO-Y030 effectively inhibits p300-HAT activity and markedly suppresses the development of heart failure in mice.
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http://dx.doi.org/10.1038/s41598-020-64207-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188884PMC
April 2020

Kosen-cha, a Polymerized Catechin-Rich Green Tea, as a Potential Functional Beverage for the Reduction of Body Weight and Cardiovascular Risk Factors: A Pilot Study in Obese Patients.

Biol Pharm Bull 2020 ;43(4):675-681

Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka.

Previous studies have shown that green tea catechins (GTCs) have beneficial effects on obesity and metabolic syndromes. In this study, we prepared kosen-cha from green tea using high pressure extraction, to reduce the astringent taste of the green tea. We identified a large quantity of polymerized GTCs in kosen-cha. To investigate the effects of kosen-cha containing polymerized GTCs in obese Japanese patients, we designed an open-label pilot study in which 6 obese subjects (body mass index (BMI) >25 kg/m) were administered kosen-cha (5 g/L/d) for 12 weeks. Body composition, serum lipids, insulin resistance, vascular functions, and cardiac hypertrophy were measured before and 12 weeks after kosen-cha administration. Kosen-cha showed no significant adverse effects on the patients. Body weights, BMI, waist circumferences, serum triglyceride (TG) levels, and homeostasis model assessment as an index of insulin resistance (HOMA-IR) levels were significantly decreased after the 12 weeks of administration. Flow-mediated dilation (FMD) (p = 0.0214), brachial-ankle pulse wave velocity (baPWV)(p = 0.0141), left ventricular mass indexes (p = 0.0120), and plasma brain natriuretic peptide (BNP) (p = 0.0144) were significantly improved. Overall, kosen-cha reduced obesity and improved insulin resistance, vascular function, and cardiac hypertrophy, indicating its preventive potential in obesity and metabolic syndrome.
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http://dx.doi.org/10.1248/bpb.b19-00921DOI Listing
November 2020

Fulminant Type 1 Diabetes with Diversity in Peripheral Blood Lymphocytes: A Case Report.

J UOEH 2020 ;42(1):57-62

First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan.

A 29-year-old woman was admitted to our hospital for treatment of fulminant type 1 diabetes (FT1D) with diabetic ketoacidosis. The phenotype of peripheral blood lymphocytes was analyzed using an 8-color flow cytometer. An analysis of the CD4-positive T cells showed a tendency for higher proportions of effector and central memory T cells and a normal proportion of regulatory T (Treg) cells, compared to healthy control. An analysis of B cell differentiation showed higher proportions of switched memory B cells and plasmablasts. The differences in lymphocyte phenotypes between our case and previously reported cases suggest a diversity of FT1D pathology.
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http://dx.doi.org/10.7888/juoeh.42.57DOI Listing
August 2020

Nickel-Catalyzed Asymmetric Friedel-Crafts Propargylation of 3-Substituted Indoles with Propargylic Carbonates Bearing an Internal Alkyne Group.

Org Lett 2020 Mar 19;22(5):2049-2053. Epub 2020 Feb 19.

Department of Chemistry, College of Humanities & Sciences, Nihon University, Sakurajosui, Setagaya-ku, Tokyo 156-8550, Japan.

The nickel-catalyzed highly enantioselective Friedel-Crafts propargylation of 3-substituted indoles with propargylic carbonates bearing an internal alkyne group was developed. A wide array of the propargylic carbonates as well as 3-substituted indoles can be applicable to the asymmetric nickel catalysis, providing the corresponding chiral C-3 propargylated indolenine derivatives bearing two vicinal chiral centers in up to 89% yield with up to >99% ee and 94:6 dr (24 examples).
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http://dx.doi.org/10.1021/acs.orglett.0c00465DOI Listing
March 2020

The additive effects of hydroxychloroquine to maintenance therapy with standard of care in patients with systemic lupus erythematosus.

Int J Rheum Dis 2020 Apr 5;23(4):549-558. Epub 2020 Feb 5.

The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.

Aim: In this retrospective study, the effect of hydroxychloroquine (HCQ) added to maintenance therapy according to the standard of care (SoC) was evaluated for 1 year in 101 patients with systemic lupus erythematosus (SLE).

Methods: The primary endpoint was the SLE Disease Activity Index (SLEDAI). The secondary endpoints were the British Isles Lupus Assessment Group index, serum complement activity (CH50) levels, anti-double-stranded DNA (dsDNA) antibody titer, concomitant corticosteroid (CS) dose, and Systemic Lupus International Collaborating Clinics (SLICC) damage index. These variables were compared between the SoC + HCQ (n = 42) and SoC (n = 59) groups.

Results: The SLEDAI improved from 2 (0, 6) to 0 (0, 4) in the SoC + HCQ group (P = .038) but significantly deteriorated from 1 (0, 4) to 2 (0, 8) in the SoC group (P = .033). CH50, anti-dsDNA antibody titer, concomitant CS dose, and SLICC damage index did not significantly change. The increase in the SLEDAI and concomitant CS dose after 1 year were all significantly greater in the SoC group, and the proportion of patients with SLEDAI flare was significantly lower in the SoC + HCQ group (SoC + HCQ: 4.76% vs SoC: 25.4%, P = .006). Univariate logistic regression analyses identified HCQ as a predictive factor for no SLEDAI flare (P = .003, odds ratio 6.81, 95% confidence interval 1.77-45.00).

Conclusions: The use of HCQ effectively improved SLEDAI scores and was a predictive factor for the prevention of SLEDAI flare. Therefore, HCQ may be considered a potential mainstay of maintenance therapy.
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http://dx.doi.org/10.1111/1756-185X.13792DOI Listing
April 2020

Fish rubbings, 'gyotaku', as a source of historical biodiversity data.

Zookeys 2020 16;904:89-101. Epub 2020 Jan 16.

Nobeoka Marine Science Station, Field Science Center, University of Miyazaki, 376-6 Akamizu, Nobeoka, Miyazaki 889-0517, Japan.

Methods for obtaining historical biodiversity information are mostly limited to examining museum specimens or surveying past literature. Such materials are sometimes time limited due to degradation, discarding, or other loss. The Japanese cultural art of 'gyotaku', which means "fish impression" or "fish rubbing" in English, captures accurate images of fish specimens, and has been used by recreational fishermen and artists since the Edo Period (the oldest known 'gyotaku' was made in 1839). 'Gyotaku' images often include distributional information, i.e., locality and sampling date. To determine the extent and usefulness of these data, field and questionnaire surveys targeting leisure fishing and boating stores were conducted in the following regions where threatened or extinct fishing targets exist (four regions including the northernmost to the southernmost regions). As a result, 261 'gyotaku' rubbings were digitally copied with their owners' consents. From these, distributional data were extracted for 218 individuals, which roughly represented regional fish faunas and common fishing targets. The peak number of 'gyotaku' stocked at the surveyed shops was made in 2002, while ones made before 1985 were much fewer. The number of 'gyotaku' rubbings made in recent years shows a recovery trend after 2011-2012. The present study demonstrates the validity of examining 'gyotaku' for historical biodiversity information.
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http://dx.doi.org/10.3897/zookeys.904.47721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983646PMC
January 2020

Effectiveness of using an educational video simulating the anatomical mechanism of shaking and smothering in a home-visit program to prevent self-reported infant abuse: A population-based quasi-experimental study in Japan.

Child Abuse Negl 2020 03 13;101:104359. Epub 2020 Jan 13.

Department of Systems and Control Engineering, Tokyo Institute of Technology, Tokyo, Japan.

Background: A video that simulates the anatomical mechanism of shaking the infant head, which may have a stronger impact on the viewer, and a tool to prevent self-reported smothering in response to crying, has never been investigated.

Objective: To investigate whether watching an educational video at home visit at 2 months postpartum on infant crying and the dangers of shaking and smothering reduces self-reported shaking and smothering behaviors at 4 months postpartum.

Method: In a quasi-experimental study in A city in Japan, the video intervention was implemented at home visits by a midwife, public health nurse or trained volunteers when babies were 2 months old. At the 4-month health checkup, participants received a questionnaire about the video, self-reported shaking and smothering behaviors and other covariates. The impacts of watching the video and self-reported shaking or smothering were analyzed using multiple logistic regression.

Results: In total, 5961 caregivers provided valid response for this study (valid response rate: 73.8 %). In the adjusted model, those who watched the video were 74 % less likely to shake their infants (odds ratio (OR): 0.36, 95 % confidence interval (CI): 0.21-0.64), 43 % were less likely to smother their infants (OR: 0.57, 95 % CI: 0.37-0.89), 52 % were less likely to shake or smother (OR: 0.48, 95 % CI: 0.33-0.69) their infants.

Conclusion: The educational video on infant crying and the dangers of shaking and smothering, with anatomical mechanism of shaking, may halve the risk of self-reported shaking and smothering at 4 months of age.
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http://dx.doi.org/10.1016/j.chiabu.2020.104359DOI Listing
March 2020

An engineered enzyme that targets circulating lactate to alleviate intracellular NADH:NAD imbalance.

Nat Biotechnol 2020 03 13;38(3):309-313. Epub 2020 Jan 13.

Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.

An elevated intracellular NADH:NAD ratio, or 'reductive stress', has been associated with multiple diseases, including disorders of the mitochondrial electron transport chain. As the intracellular NADH:NAD ratio can be in near equilibrium with the circulating lactate:pyruvate ratio, we hypothesized that reductive stress could be alleviated by oxidizing extracellular lactate to pyruvate. We engineered LOXCAT, a fusion of bacterial lactate oxidase (LOX) and catalase (CAT), which irreversibly converts lactate and oxygen to pyruvate and water. Addition of purified LOXCAT to the medium of cultured human cells with a defective electron transport chain decreased the extracellular lactate:pyruvate ratio, normalized the intracellular NADH:NAD ratio, upregulated glycolytic ATP production and restored cellular proliferation. In mice, tail-vein-injected LOXCAT lowered the circulating lactate:pyruvate ratio, blunted a metformin-induced rise in blood lactate:pyruvate ratio and improved NADH:NAD balance in the heart and brain. Our study lays the groundwork for a class of injectable therapeutic enzymes that alleviates intracellular redox imbalances by directly targeting circulating redox-coupled metabolites.
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http://dx.doi.org/10.1038/s41587-019-0377-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135927PMC
March 2020

Effects of Highly Absorbable Curcumin in Patients with Impaired Glucose Tolerance and Non-Insulin-Dependent Diabetes Mellitus.

J Diabetes Res 2019 23;2019:8208237. Epub 2019 Nov 23.

Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.

Oxidative stress is enhanced by various mechanisms. Serum oxidized low-density lipoprotein (LDL) is a useful prognostic marker in diabetic patients with coronary artery disease. To examine the effects of Theracurmin®, a highly absorbable curcumin preparation, on glucose tolerance, adipocytokines, and oxidized LDL, we conducted a double-blind placebo-controlled parallel group randomized trial in patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus. We randomly divided the patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus and stable individuals into the placebo group and the Theracurmin® (180 mg daily for 6 months) group. Of the 33 patients analyzed, 18 (14 males and 4 females) were administered placebo and 15 (9 males and 6 females) were administered Theracurmin®. The patient characteristics did not differ between the two groups. The primary endpoint, HbA1c, did not differ significantly between the two groups. However, the level of 1-antitrypsin-low-density lipoprotein (AT-LDL), the oxidized LDL, significantly increased ( = 0.024) in the placebo group from the beginning of the trial up to 6 months, although there was no such change in the Theracurmin® group. The percentage change in BMI from the beginning of the trial up to 6 months tended to be higher in the Theracurmin® group than in the placebo group. Patients in the Theracurmin® group tended to have a larger percentage change in adiponectin and LDL-C than those in the placebo group. Patients in the Theracurmin® group showed a smaller percentage change in AT-LDL than those in the placebo group. This study suggests that the highly absorbable curcumin could potentially inhibit a rise in oxidized LDL in patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus. This trial is registered with UMIN000007361.
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http://dx.doi.org/10.1155/2019/8208237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906884PMC
June 2020
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