48 research outputs found

    Site-specific and linkage analyses of fucosylated N-glycans on haptoglobin in sera of patients with various types of cancer: possible implication for the differential diagnosis of cancer: possible implication for the differential diagnosis of cancer

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    Fucosylation is an important type of glycosylation involved in cancer, and fucosylated proteins could be employed as cancer biomarkers. Previously, we reported that fucosylated N-glycans on haptoglobin in the sera of patients with pancreatic cancer were increased by lectin-ELISA and mass spectrometry analyses. However, an increase in fucosylated haptoglobin has been reported observed in various types of cancer. To ascertain if characteristic fucosylation is observed in each cancer type, we undertook site-specific analyses of N-glycans on haptoglobin in the sera of patients with five types of operable gastroenterological cancer (esophageal, gastric, colon, gallbladder, pancreatic), a non-gastroenterological cancer (prostate cancer) and normal controls using ODS column LC-ESI MS. Haptoglobin has four potential glycosylation sites (Asn184, Asn207, Asn211, Asn241). In all cancer samples, monofucosylated N-glycans were significantly increased at all glycosylation sites. Moreover, difucosylated N-glycans were detected at Asn 184, Asn207 and Asn241 in only cancer samples. Remarkable differences in N-glycan structure among cancer types were not observed. We next analyzed N-glycan alditols released from haptoglobin using graphitized carbon column LC-ESI MS to identify the linkage of fucosylation. Lewis-type and core-type fucosylated N-glycans were increased in gastroenterological cancer samples, but only core-type fucosylated N-glycan was relatively increased in prostate cancer samples. In metastatic prostate cancer, Lewis-type fucosylated N-glycan was also increased. These data suggest that the original tissue/cell producing fucosylated haptoglobin is different in each cancer type and linkage of fucosylation might be a clue of primary lesion, thereby enabling a differential diagnosis between gastroenterological cancers and non-gastroenterological cancers

    Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

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    Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

    Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment

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    Dyslipidemia is a major risk factor for cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in type 2 diabetes (T2DM). Statins have played a crucial role in its management, but residual risk remains since many patients cannot achieve their desired low-density lipoprotein cholesterol (LDL-C) level and up to 20% of patients are statin-intolerant, experiencing adverse events perceived to be caused by statins, most commonly muscle symptoms. Recently, great advances have been made in nonstatin treatment with ezetimibe, a cholesterol absorption inhibitor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), all showing a proven benefit with an excellent safety profile in cardiovascular outcome trials. This review summarizes the key aspects and the evolving role of these agents in the management of dyslipidemia in patients with T2DM, along with a brief introduction of novel drugs currently in development

    A geochemical clogging model with carbonate precipitation rates under hydrothermal conditions

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    A step-wise numerical calculation method was developed to provide predictions of when and where carbonate deposits might be found through reservoirs during CO2 sequestration. Flow experiments through porous media using a supersaturated carbonate fluid were also performed in order to observe flow rates. In order to evaluate precipitation rates and permeability change in the formation, calculated flow rates based on the proposed geochemical clogging model were compared with the experimentally observed data. Both high and low temperature cases were studied to understand how hydrothermal conditions can affect precipitation rates of carbonate. According to chemical kinetics, growth rates of minerals are generally proportional to the saturation index (S.I.) that depends on temperature. Thus, a supersaturated fluid has the advantage of improving the filtration and the amount of C fixation (σ). However, when the ratio of filtration coefficient (λ) to pore fluid velocity (u) increases, the permeability around the injection point tends to be significantly reduced by carbonate accumulation, and thus, this might result in insufficient injection of CO2. Therefore, it is essential to understand how to control both λ and u so that the precipitation of carbonate can be located as far away from the inlet as possible

    Efficacy and safety of switching to insulin glargine 300 U/mL from 100 U/mL in Japanese patients with type 2 diabetes: A 12-month retrospective analysis

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    Aims: To evaluate the efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) from insulin glargine 100 U/mL (Gla-100) in Japanese patients with type 2 diabetes (T2DM). Methods: This was a 12-month retrospective study comprising 109 patients. Primary endpoint was glycated hemoglobin (HbA1c) level at month 12. Secondary endpoints were hypoglycemia for the overall study period as well as body weight and insulin dose at month 12. Results: Similar glycemic control was achieved with mean (standard deviation) HbA1c level of 7.7 (1.1)% (61 [12] mmol/mol) at baseline and 7.7 (1.3)% (61 [14] mmol/mol) at month 12. Fewer confirmed (<3.0 mmol/L [< 54 mg/dL]) or severe hypoglycemic events were observed (0.52 vs. 0.85 events per patient-year; rate ratio 0.61; 95% confidence interval 0.38–0.97; p = 0.037), but the percent of patients experiencing ≥1 hypoglycemic event did not differ. There was no difference in confirmed (≤3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemia and nocturnal hypoglycemia. Conclusions: In Japanese patients with T2DM who switched to Gla-300 from Gla-100, similar glycemic control was achieved with fewer confirmed (<3.0 mmol/L [< 54 mg/dL]) or severe hypoglycemic events over a 12-month period, although the absolute benefit was marginal
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