Relationship between coronary flow reserve evaluated by phase-contrast cine cardiovascular magnetic resonance and serum eicosapentaenoic acid.

BACKGROUND: Long-term intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs), especially eicosapentaenoic acid (EPA) is associated with a low risk for cardiovascular disease. Phase-contrast cine cardiovascular magnetic resonance (PC cine CMR) can assess coronary flow reserve (CFR). The present study investigates the relationship between CFR evaluated by PC cine CMR and the serum EPA. METHODS: We studied 127 patients (male, 116 (91%); mean age, 72.2 ± 7.4 years) with known or suspected coronary artery disease (CAD). X-ray coronary angiography revealed no significant coronary arterial stenoses (defined as luminal diameter reduction ≥ 50% on quantitative coronary angiogram (QCA) analysis) in all study participants. Breath-hold PC cine CMR images of the coronary sinus (CS) were acquired to assess blood flow of the CS both at rest and during adenosine triphosphate (ATP) infusion. We calculated CFR as CS blood flow during ATP infusion divided by that at rest. Patients were allocated to groups according to whether they had high (n = 64, EPA ≥ 75.8 µg/mL) or low (n = 63, EPA < 75.8 µg/mL) median serum EPA. RESULTS: CFR was significantly lower in the low, than in the high EPA group (2.54 ± 1.00 vs. 2.91 ± 0.98, p = 0.038). Serum EPA positively correlated with CFR (R = 0.35, p < 0.001). We defined preserved CFR as > 2.5, which is the previously reported lower limit of normal flow reserve without obstructive CAD. Multivariate analysis revealed that EPA is an independent predictor of CFR > 2.5 (odds ratio, 1.01; 95% confidence interval, 1.00 - 1.02, p = 0.008). CONCLUSIONS: The serum EPA is significantly correlated with CFR in CAD patients without significant coronary artery stenosis.

Glucose-lowering effect of colestimide is associated with baseline HbA1c in type 2 diabetic patients with hypercholesterolemia.

We previously reported that colestimide, an anion exchange resin, improved glycemic control in patients with type 2 diabetes. However, the factors associated with the decrease of HbA1c remain unclear. In present study, we retrospectively compared glycemic control between groups receiving colestimide (n=71), atorvastatin (n=99), pravastatin (n=85), and pitavastatin (n=95) until 3 months after the start of treatment. In the colestimide group, fasting plasma glucose decreased significantly from 169 ± 59 to 138 ± 29 mg/dL after 3 months (P<0.01), and glycated hemoglobin (HbA1c) declined from 8.1 ± 1.0% to 7.4 ± 0.8% (an 8% reduction, P<0.01). Fasting plasma glucose and HbA1c did not change in the pravastatin and pitavastatin groups. On the other hand, both parameters increased significantly in the atorvastatin group. Multivariate analysis revealed that baseline HbA1c was the main determinant of the decrease of HbA1c in the colestimide group while age, sex, BMI, and baseline lipid levels were not correlated with the effect of colestimide treatment. The decrease of HbA1c showed a positive correlation with baseline HbA1c (r=0.60, P<0.0001), and patients with a larger change of HbA1c (>8.4%) displayed a better response to colestimide. In conclusion, since patients with type 2 diabetes often have hyperlipidemia as well, colestimide therapy may have a clinically useful dual action in such patients. Baseline HbA1c has the most important independent influence on the glucose-lowering effect of colestimide.

Effect of Caloric Intake 25 or 30 kcal/kg/day on the Glycemic Control in Obese Patients With Type 2 Diabetes.

BACKGROUND: The recommended total dietary energy intake prescribed medical nutrition therapy for obese or overweight patients with type 2 diabetes in Japan is often set at 25 kcal/kg ideal body weight (IBW)/day. This study was conducted to determine the impact of the total dietary energy intake (25 or 30 kcal/kg IBW/day) on the glycemic control, lipid profile, and satisfaction level in overweight patients with type 2 diabetes. METHODS: We performed interview and a designed prospective, randomized, controlled, multicenter study trial. Recruitment for interview for doctors and hospitalization of the obese or overweight patients with type 2 diabetes began from September 2008 and continued until June 2010. The subjects were randomly assigned to 25 kcal/kg IBW/day group (25 kcal group) or 30 kcal/kg IBW/day group (30 kcal group). The primary endpoint was the body weight of the subjects at the time of hospitalization, at the time of discharge from the hospital, and at 3, 6 and 12 months after discharge from the hospital. RESULTS: The glycemic control, lipid control and body weight were similar between the 25 and 30 kcal groups during the 12-month follow-up, and the degree of satisfaction in respect of the medical treatment was significantly higher in the 30 kcal group than in the 25 kcal group at 1 year after discharge. CONCLUSIONS: It is considered to be preferable for the caloric intake to be set at 30kcal/kg IBW/day rather than at 25 kcal/kg IBW/day for obese or overweight patients with type 2 diabetes.

Three T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen antigens, retain their immunogenicity and tolerogenicity in a linked peptide.

It has been demonstrated in detail that administration of a dominant T-cell determinant to animals induces activation or immunological tolerance of T cells. However, it has not been determined whether multiple T-cell determinants, when integrated into a single peptide, retain their potential to induce T-cell activation and tolerance. We prepared a synthetic peptide comprising three T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen antigens, and investigated the immunogenicity and tolerogenicity of each T-cell determinant in the linked peptide by means of lymph node cell proliferation assays using mice. Lymph node cells from mice immunized with each of the three T-cell determinants proliferated against the linked peptide in a dose-dependent manner, similar to that of the immunized peptide. Lymph node cells from mice immunized with the linked peptide proliferated against all of the three T-cell determinants. In addition, the degree of proliferation against the three T-cell determinants occurred according to their original immunogenicity, as observed in the native protein antigens. Oral administration of the linked peptide to mice before they were immunized with Cry j 1 and Cry j 2 inhibited lymph node cell proliferation against the three T-cell determinants, depending on the dose of the linked peptide administered. In conclusion, it was demonstrated that three T-cell determinants retain their original immunogenicity and tolerogenicity in a linked peptide comprising them.

Identification of 2'-phosphodiesterase, which plays a role in the 2-5A system regulated by interferon.

The 2-5A system is one of the major pathways for antiviral and antitumor functions that can be induced by interferons (IFNs). The 2-5A system is modulated by 5'-triphosphorylated, 2',5'-phosphodiester-linked oligoadenylates (2-5A), which are synthesized by 2',5'-oligoadenylate synthetases (2',5'-OASs), inactivated by 5'-phosphatase and completely degraded by 2'-phosphodiesterase (2'-PDE). Generated 2-5A activates 2-5A-dependent endoribonuclease, RNase L, which induces RNA degradation in cells and finally apoptosis. Although 2',5'-OASs and RNase L have been molecularly cloned and studied well, the identification of 2'-PDE has remained elusive. Here, we describe the first identification of 2'-PDE, the third key enzyme of the 2-5A system. We found a putative 2'-PDE band on SDS-PAGE by successive six-step chromatographies from ammonium sulfate precipitates of bovine liver and identified a partial amino acid sequence of the human 2'-PDE by mass spectrometry. Based on the full-length sequence of the human 2'-PDE obtained by in silico expressed sequence tag assembly, the gene was cloned by reverse transcription-PCR. The recombinant human 2'-PDE expressed in mammalian cells certainly cleaved the 2',5'-phosphodiester bond of 2-5A trimer and 2-5A analogs. Because no sequences with high homology to this human 2'-PDE were found, the human 2'-PDE was considered to be a unique enzyme without isoform. Suppression of 2'-PDE by a small interfering RNA and a 2'-PDE inhibitor resulted in significant reduction of viral replication, whereas overexpression of 2'-PDE protected cells from IFN-induced antiproliferative activity. These observations identify 2'-PDE as a key regulator of the 2-5A system and as a potential novel target for antiviral and antitumor treatments.