Rationale and Design of the Multicenter Trial on Japan Working Group on the Effects of Angiotensin Receptor Blockers Selection (Azilsartan vs. Candesartan) on Diastolic Function in the Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE Trial

Background

Previous studies suggest that the pathophysiology of heart failure with preserved ejection fraction (HFpEF) is characterized not only by high ventricular stiffness, but also by vascular stiffness. Azilsartan has higher vascular affinity compared with other angiotensin II receptor blockers (ARBs), which were proven to have no beneficial effects on clinical outcomes in patients with HFpEF in earlier clinical trials. We aimed to test the hypothesis that azilsartan may improve left ventricular diastolic function in HFpEF patients with hypertension in this trial.

Methods

The Effects of Angiotensin Receptor Blockers on Diastolic Function in Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE trial is a multicenter, randomized, open-labeled, and assessor(s)-blinded, active controlled using candesartan, parallel-group clinical trial, to compare changes in left ventricular (LV) diastolic dysfunction between HFpEF patients with hypertension who have received candesartan or azilsartan for 48 weeks. The primary endpoint is the change in early diastolic wave height/early diastolic mitral annulus velocity (E/e’) assessed by echocardiography from the baseline to the end of the study (48 weeks). A total of 190 patients will be recruited into the study.

Conclusions

The design of the J-TASTE trial will provide data on whether differences between the effects of the two tested drugs on LV diastolic function exist in HFpEF patients with hypertension and will improve understanding of the pathophysiological role of vascular stiffness on diastolic function.

     

Physiological and pathological age-associated changes in diurnal rhythm of energy expenditure in rats

Although the idea that energy metabolism of rats decreases with age has been widely accepted, few studies with regard to the diurnal rhythm of energy expenditure have been reported. Whether age alone altered the diurnal rhythm of energy expenditure was examined in Sprague-Dawley (SD) rats. The same determination was conducted in Otsuka Long Evans Tokushima Fatty (OLETF) rats to examine the effect of insulin resistance and diabetes. OLETF rats were developed as a model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity. The characteristic features of OLETF rats are late onset of hyperglycemia at about 18 weeks of age, followed by insulin deficiency at about 65 weeks. Age-associated changes in diurnal rhythm of energy expenditure were not observed in SD rats. In OLETF rats, the diurnal rhythm of energy expenditure with two peaks was observed at 8 weeks of age, while these two peaks disappeared at 24 weeks of age (with NIDDM). Then, the pattern of diurnal rhythm at 44 weeks of age (with advanced NIDDM) was resembled to that of 62 weeks of age (with insulin deficiency). In conclusion, we clarified the changes in diurnal rhythm of energy expenditure associated with the progress of diabetes, while age alone did not alter the diurnal rhythm.     

Serum DJ-1 level is positively associated with improvements in some aspects of metabolic syndrome in Japanese women through lifestyle intervention

DJ-1 is a protein that is associated with Parkinson disease and cancer, and the reduction of DJ-1 function and expression is also thought to be a cause of diabetes and hypertension. However, little is known about the association between the plasma concentration of DJ-1 and risk of metabolic syndrome. We hypothesized that a lifestyle intervention would increase serum DJ-1 and that up-regulated DJ-1 functions will result in the prevention of metabolic syndrome. The objective of our study is to examine whether the level of serum DJ-1 is associated with the risk of metabolic syndrome. Therefore, to reveal the association between DJ-1 and metabolic syndrome, this study investigated lifestyle intervention in a control group (n = 37) and intervention group (n = 45). The results showed that body mass index, body fat ratio, waist-hip ratio, waist circumference, blood pressure, and plasma glucose level were improved in the intervention group, as compared with those in the control group. Furthermore, serum levels of DJ-1 were increased in the intervention group, when compared with those in the control group. These results suggest that serum DJ-1 is increased by lifestyle intervention and that increased serum DJ-1 prevents metabolic syndrome. Thus, the level of serum DJ-1 will become one of the indexes for the risk of metabolic syndrome.     

Application of X-ray grating interferometry for the imaging of joint structures

Conventional X-ray absorption contrast imaging does not depict soft tissues, such as cartilage, in sufficient detail. For visualization of the soft tissues, X-ray phase-contrast imaging is more sensitive than absorption-contrast imaging. The basic concept of the X-ray phase-contrast imaging used in this study is similar to that of differential interference contrast (Nomarski) microscopy. We applied Talbot–Lau X-ray interferometry to visualize the joint structures in the right hand and knee of a donated cadaver. This imaging system simultaneously produced three different types of images: an absorption image, a differential phase image, and a visibility image. The interface between the articular cartilage of the metacarpo-phalangeal joint and fluid or the bony cortex was clearly demonstrated on the differential phase image, whereas this interface was unclear on the absorption image. Within the knee joint, the surface of the articular cartilage was demonstrated both on the differential phase and visibility images; the medial collateral ligament and medial meniscus were also visualized successfully. These results are clinically significant for the diagnosis and therapeutic estimation of rheumatoid arthritis and related joint diseases. This feasibility study on the clinical application of this imaging tool was a collaborative effort of researchers in the fields of physics, radiology, and gross anatomy.     

Effects of alkaloids from Corydalis decumbens on contraction and electrophysiology of cardiac myocytes

The chloroform extract of Corydalis decumbens significantly increased the beating amplitude of cultured myocardial cell sheets. Chemical analysis led to the isolation of isoquinoline and protopine alkaloids. Of these isolated alkaloids, corlumidine and (+)-adlumidine increased the beating amplitude, but (+)-egenine decreased the beating rate and beating amplitude while protopine did not show any activity. We also studied the effects of (+)-egenine and corlumidine on contractile responses and Ca²⁺ currents in single bullfrog atrial cells using the voltage-clamp method. (+)-Egenine inhibited Ca²⁺ current by 68% of the control in single cell of bullfrog atrium, while corlumidine increased Ca²⁺ current to 60% at a concentration of 0.03 mM.