Michiyasu Yoshitsugu

Significant Increase in Prostaglandin E-Main Urinary Metabolite by Laxative Administration: Comparison with Ulcerative Colitis

Objective: To assess the production of prostaglandin E2, an important chemical mediator in diarrhea induced by laxative administration, a prostaglandin E-main urinary metabolite (7α-hydroxy-5,11-diketotetranor-prosta-1,16-dioic acid, PGE-MUM) was measured in healthy volunteers and compared with the values of patients with ulcerative colitis. Methods: PGE-MUM was determined by a simplified immunoassay of bicyclic PGE-MUM and analyzed for the influence of laxative administration and active/remission phases of ulcerative colitis. Results: Administration of laxatives induced a significant increase in PGE-MUM in healthy volunteers. A significant elevation was also found in the active as compared with the remission phase of ulcerative colitis. The PGE-MUM levels were significantly correlated with our modified Talstad scores, clinical disease activity indices in ulcerative colitis. It was confirmed by time course studies of individual patients that changes in PGE-MUM correlated well with colitis activity. Conclusion: Laxative administration induces production of prostaglandin E2 as one of the chemical mediators, although its production grade is relatively low as compared with ulcerative colitis in the active phase.

Comparison between sitagliptin and nateglinide on postprandial lipid levels: The STANDARD study

AIM To assess the effects of sitagliptin and nateglinide on lipid metabolism. METHODS In a parallel group comparative open trial, patients with type 2 diabetes mellitus under treatment at the Japanese Red Cross Medical Center were randomly assigned to receive either sitagliptin (50 mg once daily) or nateglinide (90 mg three times daily before meals). Eligible patients met the following criteria: age ≥ 20 years; hemoglobin A1c (HbA1c) > 6.5% despite diet and exercise; HbA1c between 6.5% and 8.0%; fasting glucose < 7.77 mmol/L; diet and exercise therapy for more than 3 mo; and ability to read and understand the information for written informed consent. Exclusion criteria were contraindications to sitagliptin, contraindications to nateglinide, pregnancy or possible pregnancy, and severe liver/renal failure. Patients who were considered to be unsuitable by the attending physician for other reasons were also excluded. Blood samples were collected at one and three hours after intake of a test meal. The primary outcome measure was the area under the curve (AUC) of apolipoprotein (Apo) B48 at three hours postprandially. RESULTS Twenty patients were randomly assigned to the sitagliptin group and sixteen patients were randomized to the nateglinide group. All 36 patients took the medication as directed by the physician in both groups, and they all were analyzed. Apart from antidiabetic drugs, there was no difference between the two groups with respect to the frequency of combined use of lipid-lowering, antihypertensive, and/or antiplatelet drugs. The doses of these medications were maintained during 12 wk of treatment. Detailed dietary advice, together with adequate exercise therapy, was given to the patients so that other factors apart from the two test drugs were similar in the two groups. There were no significant differences of the baseline characteristics between the two groups, except for body mass index (the sitagliptin group: 25.14 ± 3.05 kg/m(2); the nateglinide group: 21.39 ± 2.24 kg/m(2)). Fasting levels of HbA1c, glycated albumin, 1.5-anhydroglucitol, and blood glucose, as well as the blood glucose levels at one and three hours postprandially, improved in both groups after 12 wk of treatment, and there were no significant differences between the two groups. However, the glucagon level at one hour postprandially (P = 0.040) and the diastolic blood pressure (P < 0.01) only showed a significant decrease in the sitagliptin group. In the nateglinide group, there was no significant change in the AUC of Apo B48, the glucagon level at one hour postprandially, the fasting triglyceride level, or the diastolic blood pressure. Body weight was unchanged in both groups. However, the AUC of Apo B48 at three hours postprandially showed a significant decrease in the sitagliptin group from 2.48 ± 0.11 at baseline to 1.94 ± 0.78 g/L per hour after 12 wk (P = 0.019). The fasting triglyceride level also decreased significantly in the sitagliptin group (P = 0.035). With regard to lipid-related markers other than Apo B48 and fasting triglycerides, no significant changes were observed with respect to Apo A1, Apo B, or Apo C3 in either group. No adverse events occurred in either group. CONCLUSION Sitagliptin significantly improves some lipid parameters while having a comparable effect on blood glucose to nateglinide. A large-scale prospective study of sitagliptin therapy is warranted.

Lack of predictive power of plasma lipids or lipoproteins for gestational diabetes mellitus in Japanese women.

To determine the diagnostic potential of plasma lipids and apolipoproteins in gestational diabetes mellitus (GDM), we carried out a retrospective cohort study of 1,161 Japanese women at 20–28 weeks of gestation who underwent a glucose challenge test (GCT).

Periportal Stellate Cells in Subjects with Chronic Hepatitis C with a Varied Serum Alanine Aminotransferase Level

Recently it has been reported that HCV-related cirrhotic patients with persistently high serum levels of alanine aminotransferase (ALT) activity have higher risk of development of hepatocellular carcinoma (HCC) than those with persistently low levels of ALT activity [1]. Vitamin A has been demonstrated to have many biological functions in regulation of growth and differentiation of normal and cancer cells. Hepatic stellate cells (SCs) are the main storage site of vitamin A and regulate homeostasis of vitamin A. To analyze cellular and molecular mechanism in the relationship between persistent high serum level of ALT and HCC development from the viewpoint of vitamin A handling, this study was performed.