LC–MS analysis of saponins of Achyranthes root in the Japanese market

Journal of Natural Medicines - LC–MS analyses of saponin fractions of Achyranthes roots in the Japanese market revealed that there were three patterns for the saponin fraction of their water...     

Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation Chloride Transporters

Upon activation by with-no-lysine kinases, STE20/SPS1-related proline–alanine-rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such as the Na⁺-Cl⁻ cotransporter (NCC) and Na⁺-K⁺-2Cl⁻ cotransporter type 1 (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable and display hypotension with decreased activity (phosphorylation) of NCC and NKCC1 in the kidneys and aorta, respectively. Therefore, agents that inhibit SPAK activity could be a new class of antihypertensive drugs with dual actions (i.e., NaCl diuresis and vasodilation). In this study, we developed a new ELISA-based screening system to find novel SPAK inhibitors and screened >20,000 small-molecule compounds. Furthermore, we used a drug repositioning strategy to identify existing drugs that inhibit SPAK activity. As a result, we discovered one small-molecule compound (Stock 1S-14279) and an antiparasitic agent (Closantel) that inhibited SPAK-regulated phosphorylation and activation of NCC and NKCC1 in vitro and in mice. Notably, these compounds had structural similarity and inhibited SPAK in an ATP-insensitive manner. We propose that the two compounds found in this study may have great potential as novel antihypertensive drugs.     

Accurate and Easy Measurement of Sliding Distance of Intramedullary Nail in Trochanteric Fracture

Background

In daily clinical practice, it is essential to properly evaluate the postoperative sliding distance of various femoral head fixation devices (HFD) for trochanteric fractures. Although it is necessary to develop an accurate and reproducible method that is unaffected by inconsistent postoperative limb position on radiography, few studies have examined which method is optimal. Therefore, the purpose of this study is to prospectively compare the accuracy and reproducibility of our four original methods in the measurement of sliding distance of the HFD.

Methods

Radiographs of plastic simulated bone implanted with Japanese proximal femoral nail antirotation were taken in five limb postures: neutral, flexion, minute internal rotation, greater external rotation, and flexion with external rotation. Orthopedic surgeons performed five measurements of the sliding distance of the HFD in each of the flowing four methods: nail axis reference (NAR), modified NAR, inner edge reference, and nail tip reference. We also assessed two clinical cases by using these methods and evaluated the intraclass correlation coefficients.

Results

The measured values were consistent in the NAR method regardless of limb posture, with an even smaller error when using the modified NAR method. The standard deviation (SD) was high in the nail tip reference method and extremely low in the modified NAR method. In the two clinical cases, the SD was the lowest in the modified NAR method, similar to the results using plastic simulated bone. The intraclass correlation coefficients showed the highest value in the modified NAR method.

Conclusions

We conclude that the modified NAR method should be the most recommended based on its accuracy, reproducibility, and usefulness.