Publications by authors named "Takashi Sakakibara"

35 Publications

Comparison between biodegradable- and durable-polymer everolimus-eluting stents in hemodialysis patients with coronary artery disease.

Cardiovasc Interv Ther 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

To investigate the clinical outcomes after biodegradable-polymer (BP) and durable-polymer (DP) everolimus-eluting stent (EES) implantation in hemodialysis (HD) patients with coronary artery disease. We enrolled 221 consecutive HD patients successfully treated with EES implantation for coronary lesions. Over the following 2 years, we assessed the incidence of target lesion revascularization (TLR) and major adverse cardiac event (MACE), defined as the composite endpoint of TLR, all-cause mortality, or myocardial infarction. We performed a propensity-score matching analysis and collected follow-up coronary angiography data. There were 91 patients in the BP-EES group and 130 in the DP-EES group. Male sex and diabetes rates were significantly lower in the BP-EES group than in the DP-EES group. A debulking device was less frequently used in the BP-EES group than in the DP-EES group (7.6% vs. 21.5%, p = 0.006). TLR occurred in 38 patients, while stent thrombosis was observed in 3 patients; 19 patients died. TLR and MACE rates at 2 years were comparable between the two groups (19.2% in the BP-EES group vs. 20.4% in the DP-EES group, p = 0.73 and 26.9% vs. 34.2%, p = 0.93, respectively). In the propensity-score-matched cohort, TLR and MACE rates were similar between the two groups (19.2% in the BP-EES group vs. 18.1% in the DP-EES group, p = 0.69, and 26.9% vs. 30.2%, p = 0.66, respectively). Restenosis rates at follow-up angiography were similar between the two groups (p = 0.79). In hemodialysis patients, BP-EES and DP-EES showed similar 2-year clinical outcomes.
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http://dx.doi.org/10.1007/s12928-021-00827-xDOI Listing
November 2021

Satisfaction Survey on Antipsychotic Formulations by Schizophrenia Patients in Japan.

Clin Psychopharmacol Neurosci 2021 Nov;19(4):610-617

Departments of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.

Objective: To identify factors affecting adherence to medication, a subjective questionnaire survey was administered to schizophrenia patients regarding the prescribed antipsychotic formulations.

Methods: We evaluated the patients' satisfaction and dissatisfaction with prescribed antipsychotic formulations, and patients answered the Drug Attitude Inventory-10 Questionnaire (DAI-10). Inclusion criteria for patients are as follows: age between 20 and 75 years and taking antipsychotic agents containing the same ingredients and formulations, for at least 1 month.

Results: In total, 301 patients answered the questionnaire survey. Tablets were found to be the most commonly used antipsychotic formulations among schizophrenia patients (n = 174, 57.8%), followed by long-acting injections (LAIs, n = 93, 30.9%). No significant differences in the formulation satisfaction level and DAI-10 scores were observed between all formulations. Formulations, except for LAI, were selected by physicians in more than half of the patients. Patients who answered "Decided by consultation with physicians" had significantly higher satisfaction levels and DAI-10 scores compared to those who answered "Decided by physicians" (4.11 ± 0.77 vs. 3.80 ± 1.00, = 0.0073 and 6.20 ± 3.51 vs. 4.39 ± 4.56, < 0.001, respectively). Satisfaction levels moderately correlated with DAI-10 scores (r = 0.48, < 0.001).

Conclusion: No formulation had a high satisfaction level in all patients, and it is important to be reflect the patients' individual preferences in pharmacotherapy. Shared decision-making in the selection of the formulations is seen to be useful for improving medication adherence.
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http://dx.doi.org/10.9758/cpn.2021.19.4.610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553540PMC
November 2021

A novel gene associated with small bowel bleeding in patients taking low-dose aspirin.

Dig Liver Dis 2021 Jul 28;53(7):841-845. Epub 2021 May 28.

Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan.

Objective: We have previously revealed the clinical factors and genetic polymorphisms associated with gastrointestinal mucosal injury and bleeding, induced by low-dose aspirin (LDA). After performing genome-wide analysis of single nucleotide polymorphisms (SNPs) using the Drug Metabolizing Enzymes and Transporters (DMET) system among drug metabolism and transporter genes, certain SNPs were found to increase the risk for LDA-induced small bowel bleeding. The aim of this study was to identify the SNPs involved in LDA-induced small bowel bleeding.

Subjects And Methods: Subjects were patients taking LDA, with small bowel bleeding diagnosed using capsule endoscopy. We investigated the clinical characteristics and the previously identified SNPs, that were examined by the DNA direct sequence method.

Results: 56 patients with bleeding and 410 controls taking LDA were enrolled. The risk factors associated with small bowel bleeding included smoking, cerebrovascular diseases, chronic renal failure, non-steroidal anti-inflammatory drug (NSAID) or anticoagulants combination, and two SNPs (CYP4F11 20043G>A (D446N) rs1060463, GSTP1 313A>G rs1695). After propensity score matching, GSTP1 rs1695 was significantly associated with small bowel bleeding.

Conclusion: The GSTP1 SNP may be a predictive marker for small bowel bleeding among patients taking LDA.
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http://dx.doi.org/10.1016/j.dld.2021.04.038DOI Listing
July 2021

Outcomes after drug-coated balloon interventions for de novo coronary lesions in the patients on chronic hemodialysis.

Heart Vessels 2021 Nov 25;36(11):1646-1652. Epub 2021 Apr 25.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

The impact of drug-coated balloon (DCB) on hemodialysis (HD) patients with coronary lesions remains unclear. This study aimed to compare outcomes after DCB treatment between HD and non-HD patients with de novo coronary lesions. A total of 235 consecutive patients who electively underwent DCB treatment for de novo coronary lesions were included (HD group: n = 100; non-HD group: n = 135). Angiographic follow-up was performed 6 months after the procedure. Patients were clinically followed up for 2 years. The incidence rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE) were investigated. Diabetes and a history of coronary bypass grafting were more frequent in the HD group than in the non-HD group (69.0% vs. 50.7%, p = 0.007, and 24.0% vs 9.1%, p = 0.013, respectively). The reference diameter and pre-procedural diameter stenosis were greater in the HD group than in the non-HD group (2.49 mm vs. 2.24 mm, p = 0.007, and 65.9% vs. 59.6%, p = 0.015, respectively). Calcification was observed in 65.5% of all lesions, and rotational atherectomy was performed in 30.2% patients. The average diameter of the DCB was 2.51 mm (2.57 mm, HD group vs. 2.47 mm, non-HD group, p = 0.14). Although post-procedural diameter stenosis was similar between the groups, late lumen loss on follow-up angiography was larger in HD patients than in non-HD patients (0.27 mm vs. - 0.03 mm, p = 0.0009). The 2-year rates of freedom from TLR and MACE were lower in HD patients than in non-HD patients [79.3% vs. 91.7%, hazard ratio (HR) 2.76, 95% confidence interval (CI) 1.23-6.77, p = 0.014; and 61.6% vs. 89.4%, HR 4.60, 95% CI 2.30-10.2, p < 0.001, respectively]. In conclusion, the rates of TLR and MACE after DCB treatment were higher in HD patients than in non-HD patients.
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http://dx.doi.org/10.1007/s00380-021-01858-3DOI Listing
November 2021

Impact of the Antithrombotic Effects of Prasugrel on Mid-Term Vascular Healing in Acute Coronary Syndrome vs. Stable Coronary Artery Disease.

Circ J 2021 05 8;85(6):808-816. Epub 2021 Jan 8.

Kobe University Graduate School of Medicine.

Background: The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD).Methods and Results:We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Yreaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009).

Conclusions: In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.
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http://dx.doi.org/10.1253/circj.CJ-20-0872DOI Listing
May 2021

Fentanyl compared to buprenorphine for atrial fibrillation ablation analgesia and sedation: a retrospective cross-sectional study.

J Pharm Health Care Sci 2021 Jan 4;7(1). Epub 2021 Jan 4.

Department of Pharmacy, Kariya Toyota General Hospital, 5-15, Sumiyoshi-cho, Kariya City, Aichi Prefecture, 448-8505, Japan.

Background: The effects of general anesthesia with deep sedation and conscious sedation have been compared for sedation management in the perioperative period for radiofrequency catheter ablation of the heart to treat atrial fibrillation. However, there is no consensus as to which drug to use for conscious sedation. This study aimed to investigate analgesic and sedative drugs suitable for perioperative ablation.

Methods: We retrospectively examined 93 patients who underwent atrial fibrillation ablation at Kariya Toyoda General Hospital between December 2017 and April 2019 and investigated differences in the outcomes, such as depth of sedation and postoperative adverse events between the buprenorphine hydrochloride (n = 46) and fentanyl citrate (n = 47) groups.

Results: The depth of sedation was similar between the two groups, without significant between-group differences in postoperative vomiting. The number of additional injections of thiamylal sodium to manage discomfort and pain during ablation were significantly lower in the fentanyl group. Additionally, the cumulative area product, cumulative total air kerma, 1-year postoperative atrial fibrillation recurrence rate, and postoperative complications were not significantly different between the two groups.

Conclusions: Although there were no significant differences in the efficacy or safety between buprenorphine hydrochloride and fentanyl citrate as analgesics used during atrial fibrillation ablation, intraoperative body movements and patient discomfort could be reduced to a greater extent with the use of fentanyl.
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http://dx.doi.org/10.1186/s40780-020-00184-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784385PMC
January 2021

Long-term clinical outcomes after self-expandable bare nitinol stent implantation for femoropopliteal occlusive disease in hemodialysis patients.

Catheter Cardiovasc Interv 2021 02 12;97(2):318-324. Epub 2020 Nov 12.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives: To compare the long-term clinical outcomes after self-expandable bare nitinol stent (BNS) implantation between hemodialysis (HD) and non-HD patients with femoropopliteal (FP) disease.

Background: Although a BNS has been commonly used in patients with FP disease, the long-term efficacy of BNSs in HD patients remains unknown.

Methods: In total, 427 HD patients treated with a BNS for FP disease were enrolled, along with 157 non-HD patients as a control group. Over the following 5 years, the incidence of target lesion revascularization (TLR), major amputation and mortality was investigated. We also performed propensity-score matching analysis.

Results: The 5-year TLR rate (45.2 vs. 32.5%, p = .013) and mortality rate (39.3 vs. 14.0%, p = .0002) were significantly higher in the HD group than in the non-HD group. The major amputation rate was comparable between the groups (7.2% in the HD group vs. 2.8% in the non-HD group, p = .16). In the propensity-score-matched cohort, the TLR rate, and mortality rate were remained higher in the HD group than in the non-HD group (48.9 vs. 34.1%, hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.30-3.49, p = .0024, and 47.9 vs. 12.0%, HR 3.38, 95% CI 1.86-6.56, p < .0001, respectively). The adjusted amputation rate was consistently similar between the groups (1.7% in the HD group vs. 2.7% in the non-HD group, HR 0.90, 95% CI 0.26-2.99, p = .86).

Conclusions: The TLR rate and mortality at 5 years post BNS implantation for FP disease were significantly higher in HD patients than in non-HD patients, though the limb salvage rate was similar.
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http://dx.doi.org/10.1002/ccd.29372DOI Listing
February 2021

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

Heart Vessels 2019 Jun 1;34(6):936-947. Epub 2019 Jan 1.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.
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http://dx.doi.org/10.1007/s00380-018-1322-2DOI Listing
June 2019

Colonic endoscopic mucosal resection in patients taking anticoagulants: Is heparin bridging therapy necessary?

J Dig Dis 2018 May 27;19(5):288-294. Epub 2018 May 27.

Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.

Objective: Heparin bridging therapy (HBT) reportedly increases the risk of post-procedural bleeding, and its safety during endoscopic interventions remains unclear. We aimed to evaluate the effects of peri-procedural HBT in patients taking anticoagulants who underwent colonic endoscopic mucosal resection (EMR) for polyps.

Methods: Patients who underwent colonic EMR while taking a single anticoagulant agent were enrolled in this study. Anticoagulants were temporarily ceased in all patients either without (the non-HBT group, prospectively enrolled) or with HBT (the HBT group, retrospectively enrolled). The incidences of post-procedural bleeding and anemia exacerbation and their length of hospitalization were evaluated and compared.

Results: There were altogether 43 consecutive adult patients (30 men; mean age 72.2 ± 7.4 years) in the non-HBT group and 41 sex- and age-matched adults (32 men; mean age 72.9 ± 8.3 years) in the HBT group. There were no significant differences in the location, number or size of resected polyps between the two groups. The percentage of patients with post-procedural bleeding within 2 weeks after colonic EMR in the non-HBT group was lower than that in the HBT group (2.3% vs 9.8%, P = 0.15), although the frequency of anemia exacerbation was not significantly different between the two groups. The total hospitalization length was shorter in the non-HBT compared with the HBT group (4.5 days vs 6.0 days, P < 0.001).

Conclusions: No patient in either group developed embolism during hospitalization. Colonic EMR with the temporary cessation of anticoagulants without HBT may be acceptable and beneficial for patients taking anticoagulants.
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http://dx.doi.org/10.1111/1751-2980.12598DOI Listing
May 2018

Long-term clinical outcomes after coronary artery bypass graft versus everolimus-eluting stent implantation in chronic hemodialysis patients.

Coron Artery Dis 2018 09;29(6):489-494

Department of Cardiology, Nagoya University Graduate School of Medicine.

Background: It remains controversial whether coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) should be optimized to treat coronary artery disease in patients on chronic hemodialysis (HD). Recently, further refinement of drug-eluting stents, such as the everolimus-eluting stent (EES), has led to marked development in this field. We compared long-term clinical outcomes after CABG versus PCI with EES implantation in patients on chronic HD.

Patients And Methods: We compared 138 patients undergoing CABG and 187 patients treated with EES implantation. The endpoint was major adverse cardiac events (MACE) as a composite outcome, including any revascularization, nonfatal myocardial infarction, or mortality. To reduce the selection bias for the two procedures, propensity score-matching was performed.

Results: During the follow-up period (43 months), 95 (29.2%) MACEs, including 43 (13.2%) revascularizations, 14 (4.3%) nonfatal myocardial infarctions, and 63 (19.4%) deaths, occurred. The freedom rate from MACE and mortality at 5 years were comparable between groups (69.7 vs. 66.7%, P=0.82 and 75.0 vs. 80.6%, P=0.10, respectively); however, those from revascularization at 5 years was higher in the CABG group than the EES group (89.4 vs. 81.0%, P=0.030). In propensity score-matched patients (n=92), the freedom rate from revascularization at 5 years was still higher in the CABG group than in the EES group (93.4 vs. 79.1%, P=0.013). Similarly, the freedom rates from MACE and mortality were comparable (70.0 vs. 66.3%, P=0.69 and 73.8 vs. 79.7%, P=0.30, respectively).

Conclusion: Even in the second-generation drug-eluting stent era, CABG is still superior for preventing revascularization in patients on chronic HD. However, PCI with EES implantation might not have disadvantages compared with CABG in terms of MACE.
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http://dx.doi.org/10.1097/MCA.0000000000000628DOI Listing
September 2018

Clinical Outcomes after Isolated Infrapopliteal Revascularization in Hemodialysis Patients with Critical Limb Ischemia: Endovascular Therapy versus Bypass Surgery.

J Atheroscler Thromb 2018 Sep 23;25(9):799-807. Epub 2018 Jan 23.

Department of Cardiology, Nagoya University Graduate School of Medicine.

Aim: To investigate the long-term clinical outcome of endovascular therapy (EVT) or bypass surgery in patients on hemodialysis (HD) with critical limb ischemia due to isolated infrapopliteal disease.

Methods: We enrolled 254 consecutive HD patients successfully undergoing infrapopliteal revascularization by EVT (126 patients) and bypass surgery (128 patients). They were followed up for five years. Amputation-free survival (AFS) and incidence of any re-intervention were evaluated. A propensity score from all baseline variables was incorporated into Cox analysis.

Results: In the EVT group, age was higher (p=0.039), diabetes and coronary artery disease were more frequent (p=0.004 and p=0.0052, respectively), and tissue loss was more rarely observed (p< 0.0001) than in the bypass group. During the follow-up period, 21 major amputations and 64 deaths occurred. The propensity score-adjusted AFS rate at 5 years was comparable between groups (61.0% in EVT group vs. 55.1% in the bypass group, adjusted hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.52-1.42, p=0.58). The adjusted survival rates were also similar between groups for amputation and all-cause mortality. However, freedom from any re-intervention was markedly lower in the EVT than in the bypass group (48.6% vs. 84.6%, adjusted-HR, 3.56, 95% CI 1.95-6.75, p< 0.0001).

Conclusions: The rate of AFS was broadly comparable between the two strategies, although compared with bypass surgery, EVT had much higher rates for re-intervention.
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http://dx.doi.org/10.5551/jat.42648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143781PMC
September 2018

Hypergastrinemia in Long-Term Use of Proton Pump Inhibitors.

Digestion 2018 8;97(2):154-162. Epub 2018 Jan 8.

Department of Gastroenterology, Sakakibara Heart Institute of Okayama, Okayama, Japan.

Background/aim: The use of proton pump inhibitors (PPIs) is known to lead to hypergastrinemia; however, the data in patients with atrophic gastritis is still lacking. The aim of this study was to investigate the effects of long-term PPIs use on the gastrin levels in patients with atrophic gastritis and to determine factors affecting hypergastrinemia in long-term users of PPIs.

Methods: Serum Helicobacter pylori IgG, gastrin and pepsinogen levels were measured. Atrophic gastritis was assessed by upper gastrointestinal endoscopies based on the Kimura-Takemoto classification and pepsinogen levels. CYP2C19 polymorphisms were assessed using DNA extracted from peripheral blood.

Results: A total number of 382 patients (275 men and 107 women) were enrolled. Median serum gastrin levels were higher in PPI users than in non- users (234 vs. 113 pg/mL, p < 0.001) and in women than in men (252 vs. 155 pg/mL, p = 0.006). Gastrin levels were significantly associated with corpus atrophy only in the subgroup of non-users of PPIs. Multivariate analysis revealed that hypergastrinemia (over 150 pg/mL) was significantly associated with PPI use (OR 5.30; 95% CI 3.32-8.47), women (OR 2.22; 95% CI 1.33-3.72) and corpus atrophy (OR 1.82; 95% CI 1.14-2.90).

Conclusion: PPI use, women and corpus atrophy were risk factors for hypergastrinemia. Gender, but not corpus atrophy, affected the gastrin levels in long-term users of PPIs.
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http://dx.doi.org/10.1159/000484688DOI Listing
August 2018

The Association of Ankle Brachial Index, Protein-Energy Wasting, and Inflammation Status with Cardiovascular Mortality in Patients on Chronic Hemodialysis.

Nutrients 2017 Apr 21;9(4). Epub 2017 Apr 21.

Department of Cardiology, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

Protein-energy wasting (PEW) is highly prevalent in hemodialysis (HD) patients. We investigated the association of abnormal ankle brachial index (ABI), PEW, and chronic inflammation status with clinical prognosis in HD patients. A total of 973 HD patients were enrolled and were followed-up for 8 years. As a marker of the PEW, geriatric nutritional risk index (GNRI) was used. Cut-off levels were 91.2 for GNRI defined from previous studies and 1.9 mg/L for C-reactive protein (CRP) as median value, respectively. Abnormal ABI was seen in 332 (34.1%) patients. Declined GNRI and elevated CRP levels were independently associated with abnormal ABI (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99, = 0.0009 and OR 1.40, 95% CI 1.07-1.83, = 0.013, respectively). GNRI levels were also independently correlated with CRP levels (β = -0.126, < 0.0001). During follow-up period, 283 (29.1%) patients died, including 123 (12.6%) due to cardiovascular disease (CVD). Abnormal ABI (adjusted hazard ratio (HR) 1.62, 95% CI 1.13-2.32, = 0.0096), GNRI < 91.2 (adjusted HR 1.57, 95% CI 1.06-2.33, = 0.023) and CRP > 1.9 mg/L (adjusted HR 1.89, 95% CI 1.31-2.77, = 0.0007) independently predicted mortality due to CVD, respectively. In conclusion, abnormal ABI, GNRI, and CRP levels were closely associated with each other, and the combination of these variables increase their predictive values for the risk of mortality due to CVD and all-cause mortality in HD patients.
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http://dx.doi.org/10.3390/nu9040416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409755PMC
April 2017

Reverse association of omega-3/omega-6 polyunsaturated fatty acids ratios with carotid atherosclerosis in patients on hemodialysis.

Atherosclerosis 2016 06 1;249:65-9. Epub 2016 Apr 1.

Cardiolovascular Center, Nagoya Kyoritsu Hospital, Nagoya, Japan.

Background And Aims: Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are widely recognized to have beneficial effects against cardiovascular disease. We investigated the association of n-3 PUFAs levels with carotid atherosclerosis in patients on hemodialysis (HD), who are at high risk for cardiovascular events.

Methods: Carotid ultra-sound was performed in a total of 461 patients on HD (male 67%, age 67 ± 12years, diabetes rate 46%). Intima-media thickness (IMT) and the plaque score (PS) in carotid arteries were measured. Carotid atherosclerosis was defined as IMT >1.2 mm and/or PS > 5.0. The levels of n-6 PUFAs [dihomo-gamma-linolenic acid (DHLA) and arachidonic acid (AA)] and n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] were also measured prior to carotid ultra-sound.

Results: Carotid atherosclerosis was observed in 94 patients (20.4%). Individual PUFAs levels were comparable between patients with and without carotid atherosclerosis. However, the ratio of EPA/AA and that of n-3/n-6 PUFAs were significantly lower in patients with carotid atherosclerosis compared to those without (median 0.36 vs. 0.41, p = 0.031 and 0.85 vs. 0.93, p = 0.041, respectively]. After adjustment for other confounders, the ratio of EPA/AA (OR 0.30, 95% CI 0.12-0.70, p = 0.0055) and the ratio of n-3/n-6 PUFAs (OR 0.45, 95% CI 0.25-0.80, p = 0.0066) showed an independent reverse association with carotid atherosclerosis. In addition, the area under receiver-operating characteristic curves for carotid atherosclerosis was significantly greater in an established risk model with EPA/AA and n-3/n-6 ratios than in the established risk model alone.

Conclusions: These data suggest that low ratios of both EPA/AA ratio and n-3/n-6 PUFAs were closely associated with carotid atherosclerosis in patients on HD.
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http://dx.doi.org/10.1016/j.atherosclerosis.2016.03.037DOI Listing
June 2016

Histopathological evaluation of the ocular-irritation potential of shampoos, make-up removers and cleansing foams in the bovine corneal opacity and permeability assay.

J Toxicol Pathol 2015 Oct 31;28(4):243-8. Epub 2015 Jul 31.

Safety Research Institute for Chemical Compounds Co., Ltd., 363-24 Shin-ei, Kiyota-ku, Sapporo, Hokkaido 004-0839, Japan.

The bovine corneal opacity and permeability (BCOP) assay is an alternative method to the in vivo Draize eye test in rabbits for evaluating eye irritation in vitro. Here, we compared the numerical results of the BCOP assay with the corresponding histopathology for three different corneas for each test substance, including commercially available shampoos, make-up removers and cleansing foams that contained surfactants and other ingredients. The histopathological score was defined based on the severity of lesions in the corneal epithelium. The histopathological findings and scores of the three sections for each test substance were comparable. The in vitro irritancy score (IVIS) generally corresponds to the corneal irritant potential of the test substances assigned on the basis of the histopathological findings in this study. In the present study, we characterized the histopathology of the corneal epithelium and stroma and especially showed that the corneal epithelial injury caused by test substances might be important in assessment of test substances that are mild eye irritants (category 2B) as classified by the United Nations (UN) Globally Harmonized System of Classification and Labelling of Chemicals (GHS), as corneal lesions suggestive of classification into category 2B were localized on the border between the corneal epithelium and stroma, which contained cell elements related to assessment of prognosis of an in vivo eye injury. Histopathological assessment might be useful in predicting in vivo ocular irritation, particularly for test substances with an IVIS >3.1 but ≤25 that are classified as mild irritants (category 2B) according to the UN GHS.
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http://dx.doi.org/10.1293/tox.2015-0022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604136PMC
October 2015

Treatment with cilostazol improves clinical outcome after endovascular therapy in hemodialysis patients with peripheral artery disease.

J Cardiol 2016 Feb 11;67(2):199-204. Epub 2015 Jun 11.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Cilostazol has been reported to prevent atherosclerotic events in the general population. However, data have been limited whether there are beneficial effects of cilostazol use on long-term clinical outcomes after endovascular therapy in hemodialysis (HD) patients with peripheral artery disease (PAD).

Methods And Results: This study consisted of 595 HD patients undergoing endovascular therapy for a clinical diagnosis of PAD. They were divided into two groups: patients receiving 100mg cilostazol twice daily in conjunction with standard therapy (n=249 patients, cilostazol group) and those not administered cilostazol (n=346 patients, control group). A propensity score analysis was performed to adjust for baseline differences between the two groups. The propensity score-adjusted 10-year event-free survival rate from major adverse cardiovascular events (MACE) was significantly higher in the cilostazol group than in the control group [58.6% vs. 43.7%, hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.41-0.79; p=0.0010]. Notably, the adjusted stroke-free rate was significantly higher in the cilostazol group than in the control group (81.6% vs. 74.7%; HR=0.48; 95% CI, 0.25-0.92, p=0.028). Even after adjusting for other confounders, treatment with cilostazol was an independent predictor for prevention of MACE and stroke (p=0.0028 and p=0.039, respectively).

Conclusions: Cilostazol administration improves long-term clinical outcomes including prevention of MACE and stroke after endovascular therapy in HD patients with PAD.
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http://dx.doi.org/10.1016/j.jjcc.2015.05.003DOI Listing
February 2016

Single nucleotide polymorphism markers for low-dose aspirin-associated peptic ulcer and ulcer bleeding.

J Gastroenterol Hepatol 2014 Dec;29 Suppl 4:47-52

Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Matsushima Kurashiki, Okayama Prefecture, Japan.

Background And Aim: In our previous study, the SLCO1B1 521TT genotype and the SLCO1B1*1b haplotype were significantly associated with the risk of peptic ulcer in patients taking low-dose aspirin (LDA). The aim of the present study was to investigate pharmacogenomic profile of LDA-induced peptic ulcer and ulcer bleeding.

Methods: Patients taking 100 mg of enteric-coated aspirin for cardiovascular diseases and with a peptic ulcer or ulcer bleeding and patients who also participated in endoscopic surveillance were studied. Genome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DME Plus Premier Pack. SLCO1B1*1b haplotype and candidate genotypes of genes associated with ulcer bleeding or small bowel bleeding identified by genome-wide analysis were determined using TaqMan SNP Genotyping Assay kits, polymerase chain reaction-restriction fragment length polymorphism, and direct sequencing.

Results: Of 593 patients enrolled, 111 patients had a peptic ulcer and 45 had ulcer bleeding. The frequencies of the SLCO1B1*1b haplotype and CHST2 2082 T allele were significantly greater in patients with peptic ulcer and ulcer bleeding compared to the controls. After adjustment for significant factors, the SLCO1B1*1b haplotype was associated with peptic ulcer (OR 2.20, 95% CI 1.24-3.89) and CHST2 2082 T allele with ulcer bleeding (2.57, 1.07-6.17).

Conclusion: The CHST2 2082 T allele as well as SLCO1B1*1b haplotype may identify patients at increased risk for aspirin-induced peptic ulcer or ulcer bleeding.
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http://dx.doi.org/10.1111/jgh.12770DOI Listing
December 2014

Long-term clinical outcome after surgical or percutaneous coronary revascularization in hemodialysis patients.

Circ J 2014 14;78(4):986-92. Epub 2014 Feb 14.

Department of Cardiovascular Surgery, Matsunami General Hospital.

Background:  Although revascularization via coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) has been widely performed, there are limited data on which procedure is best in hemodialysis (HD) patients.

Methods And Results:  This 10-year follow-up study consisted of 997 HD patients electively undergoing coronary revascularization (CABG, n=210; PCI, n=787). With an adjustment for propensity scores with all baseline covariates, the incidence of major adverse cardiac events (MACE) was evaluated as a composite endpoint including all-cause death, non-fatal myocardial infarction (MI) and any revascularization. During the follow-up period, 465 MACE (death, n=325; non-fatal MI, n=45; revascularization, n=274) occurred. The 10-year freedom from MACE was higher in the CABG group compared to the PCI group (51.0% vs. 34.8%, adjusted hazard ratio [HR], 0.64; 95% confidence interval [CI]: 0.49-0.82, P=0.0003). On landmark analysis, adjusted HR of death was higher during the first 6 months after CABG compared to PCI (1.72; 95% CI: 1.04-2.79, P=0.036), but lower from 6 months onward (0.69; 95% CI: 0.48-0.97, P=0.033). When compared to patients treated with drug-eluting stent alone (n=345) in the PCI group, the CABG group still had an advantage for any revascularization (adjusted HR, 0.38; 95% CI: 0.22-0.62, P<0.0001), but not for MACE (adjusted HR, 0.86; 95% CI: 0.64-1.15, P=0.33).

Conclusions:  CABG was totally clinically advantageous compared to PCI in HD patients.
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http://dx.doi.org/10.1253/circj.cj-13-1357DOI Listing
October 2014

Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding.

PLoS One 2013 18;8(12):e84244. Epub 2013 Dec 18.

Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan.

Background: Aspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established.

Aim: To investigate pharmacogenomic profile of low dose aspirin (LDA)-induced small bowel bleeding.

Methods: Genome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate genes associated with small bowel bleeding were determined using TaqMan SNP Genotyping Assay kits and direct sequencing.

Results: In the validation study in overall 37 patients with small bowel bleeding and 400 controls, 4 of 27 identified SNPs: CYP4F11 (rs1060463) GG (p=0.003), CYP2D6 (rs28360521) GG (p=0.02), CYP24A1 (rs4809957) T allele (p=0.04), and GSTP1 (rs1695) G allele (p=0.04) were significantly more frequent in the small bowel bleeding group compared to the controls. After adjustment for significant factors, CYP2D6 (rs28360521) GG (OR 4.11, 95% CI. 1.62 -10.4) was associated with small bowel bleeding.

Conclusions: CYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084244PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867469PMC
October 2014

Fertilization recovery after defective sperm cell release in Arabidopsis.

Curr Biol 2012 Jun 17;22(12):1084-9. Epub 2012 May 17.

Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan.

In animal fertilization, multiple sperms typically arrive at an egg cell to "win the race" for fertilization. However, in flowering plants, only one of many pollen tubes, conveying plant sperm cells, usually arrives at each ovule that harbors an egg cell. Plant fertilization has thus been thought to depend on the fertility of a single pollen tube. Here we report a fertilization recovery phenomenon in flowering plants that actively rescues the failure of fertilization of the first mutant pollen tube by attracting a second, functional pollen tube. Wild-type (WT) ovules of Arabidopsis thaliana frequently (∼80%) accepted two pollen tubes when entered by mutant pollen defective in gamete fertility. In typical flowering plants, two synergid cells on the side of the egg cell attract pollen tubes, one of which degenerates upon pollen tube discharge. By semi-in vitro live-cell imaging we observed that fertilization was rescued when the second synergid cell accepted a WT pollen tube. Our results suggest that flowering plants precisely control the number of pollen tubes that arrive at each ovule and employ a fertilization recovery mechanism to maximize the likelihood of successful seed set.
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http://dx.doi.org/10.1016/j.cub.2012.03.069DOI Listing
June 2012

Risk and preventive factors of low-dose aspirin-induced gastroduodenal injuries: a comprehensive review.

J Gastroenterol Hepatol 2012 Apr;27 Suppl 3:8-12

Department of Internal Medicine, Kawasaki Medical School, Kurashiki City, Okayama Prefecture, Japan.

The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1β (IL-1β)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1β and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA.
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http://dx.doi.org/10.1111/j.1440-1746.2012.07071.xDOI Listing
April 2012

Sirolimus-eluting stent vs. everolimus-eluting stent for coronary intervention in patients on chronic hemodialysis.

Circ J 2012 30;76(2):351-5. Epub 2011 Nov 30.

Cardiovascular Center, Nagoya Kyoritsu Hospital, Nagoya, Japan.

Background: Even in the drug-eluting stent era, adverse cardiac events, including restenosis after percutaneous coronary intervention (PCI), have been more frequently seen in patients on hemodialysis (HD) than in non-HD patients. The objective of this study was to compare the sirolimus-eluting stent (SES) and everolimus-eluting stent (EES) for prevention of adverse cardiac events, including restenosis, in HD patients.

Methods And Results: A total of 100 consecutive patients on HD who underwent PCI were enrolled and randomly assigned to receive SES or EES. Although there was no difference between the 2 groups in baseline patient and lesion characteristics, the angiographic restenosis rate at 8-month follow-up was 21.2% in the SES group and 8.7% in the EES group (P = 0.041). Significant differences were also seen in % diameter stenosis (%DS), minimal lumen diameter, and late lumen loss at 8-month follow-up (P = 0.0024, P = 0.0040, and P = 0.033, respectively). During the 1-year follow-up, major adverse cardiac events occurred in 11 (22.0%) patients in the SES group and in 5 (10.0%) patients in the EES group (P = 0.10).

Conclusions: The use of EES was as safe as that of SES. Moreover, EES significantly prevented restenosis in patients on maintenance HD compared with SES.
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http://dx.doi.org/10.1253/circj.cj-11-0814DOI Listing
May 2012

Association of SLCO1B1 1b with peptic ulcer amongst Japanese patients taking low-dose aspirin.

Dig Liver Dis 2012 Mar 15;44(3):201-5. Epub 2011 Nov 15.

Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.

Background: In the recent case-control study, we showed an inverse association between peptic ulcer and angiotensin type 1 receptor (AT1R) blockers (ARBs) or HMG-Co A reductase inhibitors (statins). The aim was to evaluate whether the genotypes of uptake and efflux transporters of ARBs and statins relate to the presence of peptic ulcer and/or ulcer bleeding associated with aspirin use.

Methods: Patients taking 100mg of enteric-coated aspirin for cardiovascular diseases who also participated in endoscopic surveillance were studied. SLCO1B, ABCC2, ABCG2, and MDR1 genotypes were determined by PCR or PCR-RFLP.

Results: 492 patients enrolled including 78 with peptic ulcer. The frequencies of the SLCO1B1 521TT genotype were significantly higher in the ulcer group (p=0.006) compared to the controls. After adjustment for significant factors, the SLCO1B1 1b haplotype was significantly associated with peptic ulcer (OR, 3.64; 95% CI, 1.81-7.29).

Conclusions: SLCO1B1 1b haplotype may identify patients at increased risk for aspirin-induced peptic ulcer.
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http://dx.doi.org/10.1016/j.dld.2011.10.005DOI Listing
March 2012

Combination of low-dose aspirin and thienopyridine exacerbates small bowel injury.

Scand J Gastroenterol 2011 Mar 7;46(3):281-6. Epub 2010 Dec 7.

Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima Kurashiki City, Okayama Prefecture, Japan.

Objective: Antithrombotics is increasingly being used for cardiovascular prevention. In more recent studies, small bowel injury and enteropathy associated with low-dose aspirin are increasingly being recognized. Aim of this study was to evaluate small bowel injury using video capsule endoscopy (VCE) in obscure gastrointestinal bleeding (OGIB) patients taking low-dose aspirin including other antithrombotics.

Material And Methods: This is a retrospective review of chronic users of antithrombotics who underwent VCE for suspected small bowel bleeding. Small bowel mucosal injury was evaluated using VCE findings.

Results: Fifty-four OGIB patients (36 men and 18 women, mean age 72.4 years) underwent VCE from January 2007 to May 2009. Twenty-two patients were taking 100 mg of enteric-coated aspirin (aspirin group), 8 taking thienopyridine, (ticlopidine or clopidogrel, thienopyridine group), 13 taking aspirin combined with thienopyridine (combined group), and 11 taking warfarin (warfarin group). The mucosal injury, especially ulcers were most frequently detected in the combined group (46.2%, p = 0.01) among the four groups. The median number of redness lesions in the combined group was the highest among the four groups and was significantly higher than that in the warfarin group. The lesions of redness or small erosions in the aspirin and the combined groups tended to exist in the proximal part of small bowel.

Conclusions: Combination of low-dose aspirin therapy and thienopyridine may exacerbate small bowel injury, and the preventive strategies should be established.
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http://dx.doi.org/10.3109/00365521.2010.533381DOI Listing
March 2011

Renin-angiotensin system associated with risk of upper GI mucosal injury induced by low dose aspirin: renin angiotensin system genes' polymorphism.

Dig Dis Sci 2011 Feb 8;56(2):465-71. Epub 2010 Sep 8.

Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.

Background: We have previously shown that co-treatment of angiotensin type 1 receptor (AT1R) blocker (ARB) or angiotensin converting enzyme (ACE) inhibitor seem to reduce peptic ulcer among patients taking low dose aspirin. It is reported that a series of renin-angiotensin system (RAS) gene polymorphisms significantly influence the rate of the gene transcription.

Aim: The aim of this study was to examine the genotypes of RAS genes related to the risk of peptic ulcer and ulcer bleeding among patients taking low dose aspirin.

Methods: Patients taking 100 mg of aspirin who were planning to undergo endoscopy for surveillance or who had history of recent upper GI ulcer bleeding were included. ACE (Ins/Del), angiotensinogen (AGT; G-217A, A-20C, A-6G, T174 M, M235T), and AT1R (T-713G, C-521T, A1166C) genotypes were determined by PCR or PCR-RFLP.

Results: Four hundred twenty-five patients were enrolled including 68 patients with peptic ulcer and 20 patients with ulcer bleeding. Co-treatment of ARB was significantly associated with peptic ulcer and ulcer bleeding. AGT-20 CC (adjusted OR 4.94, 95% CI 1.21-20.2) was significantly associated with ulcer bleeding. The CC genotype of AT1R-521 was significantly associated with peptic ulcer only in the subgroup taking neither ACE inhibitor nor ARB.

Conclusions: Co-treatment of ARB reduces peptic ulcer and bleeding among patients taking low dose aspirin. RAS may play an important role in the development of upper GI mucosal injury induced by low dose aspirin.
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http://dx.doi.org/10.1007/s10620-010-1382-3DOI Listing
February 2011

Aspirin-induced peptic ulcer and genetic polymorphisms.

J Gastroenterol Hepatol 2010 May;25 Suppl 1:S31-4

Department of Internal Medicine, Kawasaki Medical School, Matsushima Kurashiki City, Okayama, Japan.

There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.
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http://dx.doi.org/10.1111/j.1440-1746.2009.06212.xDOI Listing
May 2010

[Multicenter investigation of preventive measures against FOLFOX-induced neurotoxicity-a project of the 4th Chapter of the Oncology Research Group, Aichi Prefectural Society of Hospital Pharmacists].

Gan To Kagaku Ryoho 2009 Aug;36(8):1315-20

The 4th Chapter of the Oncology Research Group of Aichi Prefectural Society of Hospital Pharmacists.

FOLFOX therapy is associated with a high incidence of neurotoxicity that is specific to oxaliplatin and liable to lead to marked deterioration in the patient's quality of life (QOL). Therefore, we conducted a survey on whether any prophylactic measures were taken to guard against the development of such neurotoxicity, and we investigated the incidence of the neurotoxicity and the efficacy of glutathione and Ca/Mg administration. The results of the survey indicated that 5 among 17 medical facilities engaged in prophylactic measures. The timing of the initial development of neurotoxicity was after 2.9 courses of FOLFOX therapy for those without prophylaxis, after 7.5 courses for those treated with glutathione, and 6.4 courses for those on Ca/Mg treatment. The glutathione or Ca/Mg treatment significantly delayed development of the neurotoxicity. The mean total number of cycles that had been given by the completion of FOLFOX therapy was 5, 9, 11.3 and 8.5, respectively, for no prophylactic treatment, treatment with glutathione and Ca/Mg, indicating that these prophylactic measures allow increases in the number of cycles of FOLFOX therapy given. It was concluded that glutathione or Ca/Mg administered with FOLFOX therapy can delay the development of neurotoxicity, thus contributing to an improvement in the patient's QOL.
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August 2009

The preventive factors for aspirin-induced peptic ulcer: aspirin ulcer and corpus atrophy.

J Gastroenterol 2009 16;44(7):717-25. Epub 2009 May 16.

Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan.

Purpose: Interleukin-1beta (IL-1beta) polymorphisms are associated with peptic ulcer and atrophic gastritis. This study aimed to examine effects of corpus atrophy and the genotypes of genes related to peptic ulcer, including IL-1beta, on risk of aspirin ulcer.

Methods: 232 patients taking 100 mg of aspirin for cardiovascular diseases, of whom 40 had peptic ulcer, were enrolled. IL1beta, interleukin-1 receptor antagonist (IL-1RN), tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-1, cytochrome p450 2C9 (CYP2C9), UDP-glucuronosyltransferase (UGT1A6) genotypes were determined, and serum pepsinogen levels were measured.

Results: The polymorphisms of IL-1beta-511/-31 were significantly associated with peptic ulcer, but other genotypes were not. Serum pepsinogen I and II levels and I/II ratio were significantly higher in the ulcer group than in the non-ulcer group. Taking PPI [adjusted odds ratio (OR), 0.09; 95% confidence interval (CI), 0.02-0.39], pepsinogen I of less than 50 ng/ml (OR, 0.24; 95% CI, 0.10-0.56) and IL-1beta-511 T carrier (OR, 0.42; 95% CI, 0.18-0.93) were significantly associated with peptic ulcer.

Conclusions: Hypoacidity related to corpus atrophy as well as taking PPI seems to be preventively associated with development of peptic ulcer among low dose aspirin users.
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http://dx.doi.org/10.1007/s00535-009-0068-0DOI Listing
August 2009

Defensin-like polypeptide LUREs are pollen tube attractants secreted from synergid cells.

Nature 2009 Mar;458(7236):357-61

Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan.

For more than 140 years, pollen tube guidance in flowering plants has been thought to be mediated by chemoattractants derived from target ovules. However, there has been no convincing evidence of any particular molecule being the true attractant that actually controls the navigation of pollen tubes towards ovules. Emerging data indicate that two synergid cells on the side of the egg cell emit a diffusible, species-specific signal to attract the pollen tube at the last step of pollen tube guidance. Here we report that secreted, cysteine-rich polypeptides (CRPs) in a subgroup of defensin-like proteins are attractants derived from the synergid cells. We isolated synergid cells of Torenia fournieri, a unique plant with a protruding embryo sac, to identify transcripts encoding secreted proteins as candidate molecules for the chemoattractant(s). We found two CRPs, abundantly and predominantly expressed in the synergid cell, which are secreted to the surface of the egg apparatus. Moreover, they showed activity in vitro to attract competent pollen tubes of their own species and were named as LUREs. Injection of morpholino antisense oligomers against the LUREs impaired pollen tube attraction, supporting the finding that LUREs are the attractants derived from the synergid cells of T. fournieri.
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http://dx.doi.org/10.1038/nature07882DOI Listing
March 2009
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