Metabolic changes induced by dapagliflozin, an SGLT2 inhibitor, in Japanese patients with type 2 diabetes treated by oral anti-diabetic agents: A randomized, clinical trial.

AIM: We aimed to determine whether SGLT2 inhibitor dapagliflozin treatment affects body composition and amino acid (AA) metabolism. METHODS: Fifty-two overweight patients treated by oral antidiabetic agents were randomly assigned to dapagliflozin (Dapa) or a standard treatment (Con) and followed for 24 weeks. The primary outcome was the change in body mass (BM) between baseline and week 24. Body composition, intrahepatic triglyceride (IHTG) content, and plasma AA concentrations were examined as secondary outcomes. RESULTS: The change in BM was significantly larger in the Dapa than in the Con group, with a difference in the mean change of -1.72 kg (95 %CI: -2.85, -0.59; P = 0.004) between the groups. Total fat mass was reduced by dapagliflozin treatment, but fat-free mass was maintained. IHTG content was significantly reduced in the Dapa than in the Con (P = 0.033). Changes in AAs showed small differences between the groups, but only serine concentrations were significantly reduced in the Dapa. Intra-group analysis showed that positive associations were observed between changes in branched chain AA concentrations and body composition only in the Dapa. CONCLUSIONS: Dapagliflozin treatment causes a reduction in BM mainly by reducing fat mass. AA metabolism shows subtle changes with dapagliflozin treatment.

[Plasma platinum concentration and anti-tumor effects after intra-arterial infusion of lipiodol-CDDP suspension evaluation with VX 2 rabbit liver cancer model and 7.0 Tesla MRI system].

To evaluate the usefulness of combination chemotherapy with cisplatin powder, which was newly designed for intra-arterial infusion (IA CALL) and lipiodol, for the VX 2 liver cancer model of the rabbit, sequential change of the plasma platinum concentration within the first 24 hours, as well as the tissue platinum concentration at 24 hours was measured after intra-arterial infusion of IA CALL. The infused materials were either IA CALL alone (C) or the combination of lipiodol+IA CALL (CL). In addition,the reduction rate of the VX 2 tumor was calculated among four therapeutic groups (C, CL, lipiodol alone (L), and saline alone (S)) after one week of intra-arterial infusion on the basis of 7.0 Tesla MR images. Total plasma platinum concentrations within the first 24 hours were kept low in group CL. No increase in the tissue platinum concentration in group CL was observed. On the other hand, the tumor reduction rate tended to be higher in group CL (group CL>group L=group C>group S). These results suggested that the intra-arterial infusion of IA CALL with lipiodol is more effective than that of IA CALL alone.

Defining thresholds for changes in size of simulated T2-hyperintense brain lesions on the basis of qualitative comparisons.

OBJECTIVE: Our purpose was to define thresholds below which trained reviewers cannot detect changes in the size of T2-hyperintense brain lesions. MATERIALS AND METHODS: We generated T2-weighted brain MR images (TR/TE, 4000/80) with simulated hyperintense lesions derived from a real multiple sclerosis plaque. The size of the original multiple sclerosis lesion was varied by scaling up or down the lesion using a bicubic interpolation method. Three hundred seventy-eight composite images, in which two T2-weighted images containing lesions were paired, were presented to three equally trained neuroradiologists to define thresholds below which changes in original lesion size could not be detected. Stepwise logistic regression was used to evaluate the dependency of size thresholds on the original size of the lesion. RESULTS: Thresholds ranged from a 5% to 15% increase in the original lesion diameter. For increases greater than 15%, all three reviewers detected the change in lesion size irrespective of the diameter of the original lesion. There was a dependency of the threshold on the diameter of the original lesion (p = 0.02). CONCLUSION: Using an MR simulator, we can define thresholds below which changes in original lesion size cannot be reliably detected. These results may guide the design of clinical trials that rely on trained reviewers to assess change in lesion burden.

Proton MR spectroscopic and diffusion tensor brain MR imaging in X-linked adrenoleukodystrophy: initial experience.

PURPOSE: To compare conventional magnetic resonance (MR) imaging, proton MR spectroscopic imaging, and diffusion tensor (DT) MR imaging findings in patients with X chromosome-linked adrenoleukodystrophy (X-ALD). MATERIALS AND METHODS: Multisection proton MR spectroscopy and DT imaging were performed in 11 patients with X-ALD and in 11 healthy control subjects. Quantitative measures of N-acetylaspartate (NAA), choline, and creatine values and of isotropic apparent diffusion coefficient (IADC) and fractional anisotropy (FA) were obtained from coregistered regions of interest. DT imaging and metabolic parameters were compared by using regression analysis. In addition, differences in DT imaging and metabolite measurements between normal- and abnormal-appearing white matter on conventional MR images were evaluated by using a nonparametric (Mann-Whitney) test. RESULTS: A strong logarithmic relationship between NAA value and FA (r = 0.64, P <.001) and an inverse logarithmic relationship were found between NAA value and IADC (r = -0.69, P <.001). Creatine and choline values correlated poorly with IADC and FA. In the normal-appearing white matter of asymptomatic patients, the NAA value was 17% lower than that in the healthy control subjects (P =.016), whereas no significant difference in DT imaging measures was seen in these regions. CONCLUSION: In patients with X-ALD, MR spectroscopic imaging can depict abnormalities in white matter that have a normal appearance on both conventional MR and DT images; this finding suggests that it may be the most sensitive technique for detecting early abnormalities of demyelination or axonal loss in patients with X-ALD.