Patients with cholestatic liver diseases, such as primary biliary cirrhosis, usually suffer from pruritus. However, the pathogenesis of cholestatic pruritus is unclear, and there is no current ...effective treatment for it. In order to find a treatment for the condition, an appropriate mouse model should be developed. Therefore, here, we established a surgically-induced mouse model of cholestatic pruritus. The bile duct was ligated in order to block bile secretion from the anterior, right, and left lobes, with the exception of the caudate lobe. Serum levels of total bile acid increased after bile duct ligation (BDL). The spontaneous hind paw scratching was also increased in BDL mice. Spontaneous scratching was reduced in BDL mice by naloxone (µ-opioid receptor antagonist), U-50,488H (κ-opioid receptor agonist), and clonidine (α2-adrenoceptor agonist). Azelastine (H1 receptor antagonist with membrane-stabilizing activity) slightly reduced scratching. However, terfenadine (H1 receptor antagonist), methysergide (serotonin (5-HT)2 receptor antagonist), ondansetron (5-HT3 receptor antagonist), proteinase-activated receptor 2-neutralizing antibody, fluvoxamine (selective serotonin reuptake inhibitor), milnacipran (serotonin-noradrenalin reuptake inhibitor), and cyproheptadine (H1 and 5-HT2 receptor antagonist) did not affect scratching. These results suggested that partial obstruction of bile secretion in mice induced anti-histamine-resistant itching and that central opioid system is involved in cholestatic itching.
Ruthenium oxide powders were produced by the reaction of an RuCl3 solution with H2O2, followed by heating of the resulting precursor at a temperature between 200°C and 600°C in air. Pb-based anodes ...containing these heated products of 1.0 mass% were prepared by the powder-rolling method, and the effect of the heated product as an electrode catalyst on lowering the anode potential was investigated in order to develop an energy-saving insoluble anode for Zn electrowinning. Based on XPS results, RuO2 with a signifi cant amount of RuO2･nH2O was produced by heating the precursor at 250°C or lower. The ratio of RuO2 to RuO2･nH2O increased remarkably above 300°C and the potential of the Pb-based anode decreased in inverse proportion to the RuO2 content of the heated product. The lowest anode potential of 1.72 V vs. NHE, which was about 360 mV lower than that of the anode with the unheated precursor, was observed for the Pb-based anode containing the product heated at 400°C. However, the anode potential of the Pb-based anode increased again when the heating temperature was 500°C or higher. The subsequent increase in the anode potential was probably caused by a decrease in the active sites of the oxygen evolution reaction, that is, the grain growth of the heated product decreased the effective reaction area of the RuO2 catalyst.
Background: Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes complicated by hypercholesterolemia. Aim: To examine the mechanism by which colestimide ...decreases plasma glucose levels in the above patients. Methods: A total of 16 inpatients with type 2 diabetes complicated by hypercholesterolemia received colestimide for 1 week after their plasma glucose levels stabilized. We measured plasma glucose, serum immunoreactive insulin (IRI), serum lipid, plasma glucagon, and plasma glucagon-like peptide-1 (GLP-1) levels. These variables at baseline and 1 week of colestimide administration were compared. Results: Preprandial plasma glucose levels (baseline: 132 ± 33 mg/dL vs. completion: 118 ± 43 mg/dL, P=0.073) tended to decrease after colestimide administration, while 1-hr postprandial plasma glucose levels (baseline: 208 ± 49 mg/dL vs. completion: 166 ± 30 mg/dL, P<0.001) and 2-hr postprandial plasma glucose levels (baseline: 209 ± 56 mg/dL vs. completion: 178 ± 39 mg/dL, P=0.015) decreased significantly at 1 week of colestimide administration. The 2-hr postprandial plasma GLP-1 level was significantly (P=0.015) higher at 1 week of colestimide administration as compared with the baseline level, while there were no significant changes in preprandial and 1-hr postprandial plasma GLP-1 levels. Conclusions: The GLP-1-increasing activity of colestimide may explain, at least in part, the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes complicated by hypercholesterolemia.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Aim
To establish prehospital triage in accordance with the new guidelines for endovascular therapy, we retrospectively analyzed the monitoring data of the city‐wide transportation system using the ...Maria Prehospital Stroke Scale (MPSS), a novel prehospital stroke scale for emergency medical technicians (EMTs) to predict the likelihood of thrombolytic therapy after transportation.
Methods
Kawasaki City, Japan, has six comprehensive stroke centers (CSCs) and six primary stroke centers (PSCs). In CSCs, endovascular therapy can be carried out 24 h a day, 7 days a week, but not in PSCs. There is no “drip and ship” protocol for further endovascular therapy from PSCs to CSCs. We determined the predictive value of MPSS scoring by the EMTs for the performance of endovascular therapy after transportation.
Results
There were 2031 patients (mean age, 71.1 ± 13.3 years) registered from April 2012 to March 2015. Multivariate logistic regression analysis indicated that the MPSS score and type of stroke center were independent predictors for performance of endovascular therapy. In particular, the odds ratio (OR) for endovascular therapy was significant for MPSS score 3 (OR, 2.914; 95% confidence interval (CI), 1.152–7.372; P = 0.024), MPSS score 4 (OR, 5.474; 95%CI, 2.300–13.029; P = 0.000), and MPSS score 5 (OR, 11.459; 95%CI, 4.334–30.296; P = 0.000) when MPSS score 1 was set as a reference. The diagnostic accuracy of the MPSS score evaluated by EMTs was 0.689 (95%CI, 0.627–0.751).
Conclusions
Prehospital triage using MPSS scores evaluated by EMTs can predict the likelihood of performance of endovascular therapy after transportation, and may become a tool offering a flexible solution for designing a new transportation protocol.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Previous studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. ...We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals.
Thirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading.
Percentage decreases from FMD0 to FMD60 were significantly greater in the TM group (-21.19% ± 17.90%; P < 0.001) and the OG group (-17.59% ± 26.64%) than in the control group (6.46% ± 9.17%; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group (-18.91% ± 16.58%) than in the control group (6.78% ± 11.43%; P < 0.001) or the TM group (5.22% ± 37.22%; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = -0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = -0.462; P < 0.05) and the AUC of IRI (r = -0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables.
Differences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is no prehospital stratification tool specifically for predicting thrombolytic therapy after transportation. We developed a new prehospital scale named the Maria Prehospital Stroke Scale (MPSS) ...by modifying the Cincinnati Prehospital Stroke Scale. Our objective is to evaluate its utility in a citywide bypass transportation protocol for intravenous (IV) tissue plasminogen activator (tPA). In the MPSS, facial droop, arm drift, and speech disturbance are tested by emergency medical technicians (EMTs). Facial droop is graded as normal (0) or abnormal (1), and the other 2 items are graded in 3 levels as normal (0), not severe (1), and severe (2). Thus, the total MPSS score ranges from 0 to 5. The predictive value of MPSS for thrombolytic therapy after bypass transportation was evaluated in 1057 patients. The MPSS scored by EMTs was significantly correlated with the National Institutes of Health Stroke Scale score in the emergency room (Spearman rho = .67, P = .000). The onset-to-door time was significantly longer with a low MPSS score (analysis of variance, F5,4.21 = .001). The rate of thrombolytic therapy was increased when the MPSS score increased from 0 to 5: 0%, 4.1%, 8.8%, 13.0%, 20.3%, and 31.5%, respectively. The areas under the receiver operating characteristic curve for the correct diagnosis of stroke and prediction of IV tPA therapy were calculated as .737 (95% confidence interval CI: .688-.786) and .689 (95% CI: .645-.732), respectively. Multivariate logistic regression analysis showed that the MPSS score and the detection-to-door time were independent predictors of tPA use after transportation. The MPSS is a novel prehospital stratification tool for the prediction of thrombolytic therapy after transportation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of this study was to evaluate the relationship between postprandial glucose level and atherosclerosis in patients without diabetes and cardiovascular disease by determining carotid ...ultrasonographic variables and serum levels of 1,5-anhydroglucitol (1,5-AG).
The subjects were 72 patients without diabetes and cardiovascular disease being treated for hypertension or dyslipidemia. The clinical characteristics of all subjects, including the serum level of 1,5-AG, which appears to be well suited for monitoring postprandial hyperglycemia, were evaluated after an overnight fast. The average intima-media thickness (IMT) and the average pulsatility index (PI) of the right and left common carotid arteries were determined with high-resolution ultrasonography and used as ultrasonographic variables. The subjects were divided into a lower 1,5-AG group (n = 36) and a higher 1,5-AG group (n = 36). We evaluated the relationship between clinical characteristics and ultrasonographic variables of the carotid artery in both groups.
The average PI in the Lower 1,5-AG group was significantly higher than that in the Higher 1,5-AG group, but the average IMT did not differ between the groups. Linear regression analysis, with the ultrasonographic variables as the dependent variables, with 1,5-AG as the independent variable, and adjusted for other clinical characteristics, showed significant correlation between 1,5-AG and the PI but not between 1,5-AG and IMT.
Our results suggest that postprandial hyperglycemia increases carotid artery stiffness, but not morphological change, in patients without diabetes or cardiovascular disease.
Cu electrolysis was performed using low-grade copper anode with purity 78.7 mass% at a anode current density of 200 A・m-2 in an unagitated sulfate solution containing 0.596 mol・dm-3 of Ni2+ ions as ...impurity at 60 ℃, and the structure of anode slime before and after passivation was analyzed. The highly-concentrated Sb, Pb and Ag were dispersed in copper anode before electrolysis. The passivation occurred at short time of 17.7 hours in the case of low-grade copper anode, and it occurred at shorter time of 11.4 hours in the solution containing Ni2+ ions as impurity. At normal dissolution of copper anode, copper parent phase dissolved in the form of dendrite and the framework of anode slime was composed of remained Cu-Ni-Sb-Sn-As compound. Cu2S and single phase of Ag and Pb were observed around this framework. At passivation, Cu, Ni and Sn dissolved from the slime framework composed of Cu-Ni-Sb-Sn-As compound, resulting in formation of Sb condensed phase. These Cu-Ni-Sb-Sn-As compound, Sb condensed phase, Cu2S compound around the slime framework, Ag and needle-shaped PbO dotted in the whole slime suppressed the diffusion of Cu2+ ions, as a result, CuSO4 was formed at interface between the slime and copper substrate. The passivation occurred at slime thickness of approximately 500μm in Ni2+-free solution, while it occurred at slime thickness of approximately 300μm in solution containing Ni2+ ions. This indicates that the passivation do not depend on only the thickness of slime. The thickness of CuSO4 formed at passivation in Ni2+-free solution was almost identical with that from the solution containing Ni2+ ions. In solution containing Ni2+ ions, the passivation occurred at less thickness of slime, showing that CuSO4 is easy to be formed in the vicinity of copper substrate due to decrease in solubility of CuSO4 and diffusion coefficient of Cu2+ ions.
Aims: This study aimed to evaluate the relationship between aortic arch calcification (AAC) detectable on chest X-ray films and plasma diacron-reactive oxygen metabolites (d-ROMs) in patients with ...type 2 diabetes but without cardiovascular disease. Methods: Forty-nine patients with type 2 diabetes but without cardiovascular disease were evaluated with chest X-ray examinations and divided into those with AAC (n=26) and those without AAC (n=23). Biochemical variables, including plasma levels of d-ROMS, high-sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) (Lp(a)), were evaluated after an overnight fast. The relationships of AAC with both inflammation and oxidative-stress variables were evaluated. Results: The plasma level of d-ROMs in subjects with AAC was significantly higher than that in subjects without AAC, whereas plasma levels of hsCRP, PAI-1, and Lp(a) in subjects with AAC were higher, but not significantly so, than those in subjects without AAC. Multivariate linear regression analysis with AAC grade as the dependent variable and plasma levels of d-ROMs, hsCRP, PAI-1, or Lp(a) as independent variables demonstrated a significant association of AAC grade with plasma levels of d-ROMs but not with plasma levels of hsCRP, PAI-1, or Lp(a). Conclusions: The plasma level of d-ROMs is associated with AAC in patients with type 2 diabetes but without cardiovascular disease. Hence, the results of the present study suggest that AAC in these patients is strongly associated with oxidative stress. Furthermore, patients with type 2 diabetes and AAC may be at high risk for the development and progression of various diabetic complications induced by oxidative stress.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background Stroke-bypass transportation to the stroke center by paramedics is important to maximize the efficiency of intravenous tissue plasminogen activator (iv-tPA) therapy. To improve access to ...stroke thrombolysis, a citywide protocol was launched on January 2007 in Kawasaki City (population 1.4 million) using the Maria Prehospital Stroke Scale (MPSS), and quality assurance monitoring has been performed every 6 months. The aim was to identify whether the citywide quality assurance monitoring improves the process and outcome of iv-tPA therapy. Methods All of the MPSS-based transportation data prospectively recorded by the Kawasaki City Fire Department and the associated clinical data in the 11 hospitals that accept stroke-bypass transfers were merged every 6 months for the quality assurance monitoring. Clinical indicators such as ambulance call-to-door time, onset-to-needle time, door-to-needle time, frequency of thrombolytic use, and outcome of thrombolytic therapy were analyzed. These clinical indicators were also compared between patients transferred on weekdays and on weekends. Results A total of 2049 patients was registered from April 2009 to March 2013. Their mean age was 70.4 ± 13.2 (range, 24-98) years, and 64.3% were male. Ambulance call-to-door time decreased gradually from 37.5 ± 12.5 minutes to 33.9 ± 11.7 minutes over 4 years ( P = .000, analysis of variance with the post hoc Dunnett test). Onset-to-needle time and door-to-needle time were similar over the 4 years. Good outcome (modified Rankin Scale score <2) after iv-tPA therapy increased from 24.1% to 35.3% ( P = .045, 2010 vs. 2012). No deleterious effect of weekend admission was observed based on these clinical indicators. Conclusions A citywide MPSS-based transportation protocol significantly decreased the delay in the ambulance call-to-door time. The implementation of standardized cross-institutional quality assurance programs for acute stroke therapy may improve the process and outcome of iv-tPA therapy in the community.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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