Background and purpose: The effects of statins on diabetes mellitus (DM) are controversial, and their effects on pancreatic fibrosis are poorly defined. We investigated the effect of long‐ and ...short‐term treatments with pravastatin on the development of DM and pancreatic fibrosis in DM‐prone Otsuka–Long–Evans–Tokushima Fatty (OLETF) rats.
Experimental approach: Male OLETF rats were divided into four groups at 12 weeks of age. The first group received a standard rat diet until the end of the experimental period at age 80 weeks. The second group was given a diet containing 0.05% pravastatin from 12 weeks of age, before the onset of DM and pancreatic fibrosis, and the third group was given the same pravastatin diet from 28 weeks of age, after the onset of DM and pancreatic fibrosis, until age 80 weeks. The fourth group received the same pravastatin diet only for 16 weeks, from 12 to 28 weeks of age, and switched to a standard diet. Progressions of DM and pancreatic fibrosis were evaluated.
Key results: Long‐term treatments with pravastatin, either from 12 or 28 weeks of age, decreased serum glucose concentration and fibrotic area, elevated superoxide dismutase activity and down‐regulated transforming growth factor‐β1 mRNA in the pancreas. In contrast, after a short‐term treatment with pravastatin, these parameters markedly deteriorated after its cessation.
Conclusions and implications: The results suggest that long‐term treatment with pravastatin improves DM and pancreatic fibrosis via anti‐oxidative and anti‐fibrotic properties, whereas cessation of pravastatin abolishes these beneficial effects, and accelerates DM and pancreatic fibrosis.
The short-circuit failure mechanism of 1200 V trench gate field-stop insulated gate bipolar transistor (IGBT) has been investigated in this paper. Experimental testing shows that most of the devices ...failed during the blocking state after a few hundred microseconds of the short-circuit turn-off condition. This unusual failure mode was analyzed both with experimental and numerical investigation. It has been determined that due to significantly large leakage current, thermal run-away can occur causing device failure after short circuit turn-off. Due to the smaller heat capacity of the FS-IGBT structure, the device temperature after the turn-off becomes so high that the local heating produced by the high temperature leakage current results in the thermal run-away.
Introduction
Treatment-related quality of life (QOL) is an important aspect of diabetes management. We evaluated the influence of a sodium-glucose cotransporter 2 (SGLT2) inhibitor, tofogliflozin, on ...treatment-related QOL in Japanese patients with type 2 diabetes mellitus (T2DM).
Methods
This is the prespecified subanalysis study of the “Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)” trial. Treatment-related QOL was evaluated at baseline, week 26, week 52, and week 104 after the initiation of the study using the Diabetes Therapy-Related QOL questionnaire (DTR-QOL). Among the 340 patients in the original UTOPIA study, a total of 252 patients (127, tofogliflozin group; 125, conventional treatment group) who completed the DTR-QOL questionnaire at baseline were the study subjects of the current subanalysis.
Results
The tofogliflozin and conventional treatment groups exhibited almost comparable baseline clinical characteristics, while the use of antihypertensive drugs and lipid-lowering agents was significantly lower in the tofogliflozin treatment group than in the conventional treatment group. Tofogliflozin treatment increased the total score of DTR-QOL7 from baseline (
P
< 0.001), while conventional treatment did not change it. There were statistically significant differences in delta change in the total DTR-QOL7 score and DTR-QOL7 Q4, Q5, Q6, and Q7 scores from the baseline to week 104 between the treatment groups. Delta changes in HbA1c (Spearman’s correlation coefficient,
ρ
= − 0.30,
P
< 0.001), fasting blood glucose (
ρ
= − 0.16,
P
= 0.031), BMI (
ρ
= − 0.19,
P
= 0.008), and waist circumference (
ρ
= − 0.17,
P
= 0.024) at week 104 were negatively associated with delta change in the total QOL7 score.
Conclusions
Our data indicated that tofogliflozin treatment improved treatment-related QOL compared to conventional treatment in Japanese patients with T2DM, in accordance with the improvement of major cardiovascular risk factors.
Trial registration:
UMIN000017607
Unified description on the long-time tail of velocity autocorrelation function (VACF) and the algebraic decays of the equal-time spatial correlation functions for nearly elastic and uniformly sheared ...granular liquids is developed based on the generalized fluctuating hydrodynamics. We predict that the cross-over of the long-time tail of VACF from t
−3/2
to t
−5/2
with the time t regardless of the density. We also demonstrate the existence of algebraic tails of the equal-time spatial density correlation function and the equal-time spatial velocity correlation function which respectively satisfy r
−11/3
and r
−5/3
for large distance r.
We study the protocol dependence of the mechanical properties of granular media by means of computer simulations. We control a protocol of realizing disk packings in a systematic manner. In 2D, by ...keeping material properties of the constituents identical, we carry out compaction with various strain rates. The disk packings exhibit the strain rate dependence of the critical packing fraction above which the pressure becomes non-zero. The observed behavior contrasts with the well-studied jamming transitions for frictionless disk packings. We also observe that the elastic moduli of the disk packings depend on the strain rate logarithmically. Our results suggest that there exists a time-dependent state variable to describe macroscopic material properties of disk packings, which depend on its protocol.
Aim
To evaluate the influence of reduced glutathione (GSH) application on 2‐hydroxyethylmethacrylate (HEMA) cytotoxicity on rat pulpal cells and evaluate the effect of etched‐dentine treatment with ...GSH on the immediate microtensile bond strength (μTBS) of etch‐and‐rinse adhesive.
Methodology
The cytotoxicity of 10 mmol L−1 HEMA, 10 mmol L−1 HEMA + 1 mmol L−1 GSH, 10 mmol L−1 HEMA + 5 mmol L−1 GSH and 10 mmol L−1 HEMA + 10 mmol L−1 GSH was compared (6 h and 24 h). Cells viability was measured by means of 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, followed by morphological observation of cells. Etched‐dentine surfaces were rinsed and treated with one of the following solutions: 2% GSH, 5% GSH or 10% GSH, bonded with Adper Single Bond Plus (3M, ESPE, St. Paul, MN, USA) and restored with resin composite. The control group received no GSH treatment. After 1 day of water‐storage at 37 °C, the specimens were subjected to μTBS testing. Cytotoxicity and μTBS data were analysed by one‐way anova and Tukey post hoc tests (P < 0.05).
Results
There were significant differences between the groups. HEMA elicited a remarkable toxic effect. 10 mmol L−1 GSH prevented HEMA‐induced damage at both exposure times. Whilst 5 mmol L−1 GSH lost its protective effect at 24‐h exposure time and 1 mmol L−1 GSH showed no protective effect at both exposure times, GSH had no significant effect on the immediate μTBS; however, 5% GSH had higher bond strength value when compared to 10% GSH (P = 0.003).
Conclusion
Controlled concentrations of GSH had a protective effect against HEMA cytotoxicity. GSH had neither positive nor negative influence on μTBS.
This paper presents the new gate structure concept in trench gate IGBTs in order to have extended performance in faster switching without penalties on the on-state voltage drop (Von). The combination ...of the trench gate and adjacent emitter-connected trench achieves the dramatic Miller capacitance reduction while maintaining the enough Injection Enhancement (IE) effect. The experimental demonstration achieved as much as 37% of reduction in the total switching loss.
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