Walkerwomble7615

Worldwide, calcific aortic valve disease is one of the leading causes of morbidity and mortality among patients with cardiac abnormalities. Aortic valve mineralization and calcification are the key events of adult calcific aortic valve disease manifestation and functional insufficiency. Due to heavy mineralization and calcification, adult aortic valvular cusps show disorganized and dispersed stratification concomitant with deposition of calcific nodules with severely compromised adult valve function. Interestingly, shared gene regulatory pathways are identified between bone-forming cells and heart valve cells during development. Asporin, a small leucine-rich proteoglycan (43 kDa), acts to inhibit mineralization in periodontal ligament cells and is also detected in normal murine adult aortic valve leaflets with unknown function. Therefore, to understand the Asporin function in aortic cusp mineralization and calcification, adult avian aortic valvular interstitial cell culture system is established and osteogenesis has been induced in these cells successfully. Upon induction of osteogenesis, reduced expression of Asporin mRNA and increased expression of bone and osteogenesis markers are detected compared to cells maintained without osteogenic induction. Importantly, treatment with human recombinant Asporin protein reduces the mineralization level in osteogenic media-induced aortic valvular interstitial cells with the concomitant decreased level of Wnt/β-catenin signaling. Overall, all these data are highly indicative that Asporin might be a novel biomolecular target to treat patients of calcific aortic valve disease over current cusp replacement surgery. Copyright © 2020 Anisha Polley et al.Low-dose thiazide and thiazide-like diuretics are widely used as first-line therapy for hypertension. Chlorthalidone, a monosulfamyl diuretic, is frequently prescribed in cases of hypertension and congestive heart failure. In this research paper, an improved reverse-phase HPLC method was developed for the simultaneous identification and quantitation of pharmacopoeia-listed and in-house process- and degradation-related impurities of chlorthalidone in bulk drug and formulations. Chromatographic separation was carried out on a C8 column (250 × 4.6 mm; '5 μm particle size) at a flow rate of 1.4 mL/min with a 220 nm detection wavelength. Mobile phase A consisted of buffer solution (diammonium hydrogen orthophosphate (10 mM, pH 5.5)) and methanol at a 65  35 ratio (v/v), and mobile phase B consisted of buffer solution and methanol at a 50  50 ratio (v/v). The API and formulation were subjected to stress conditions such as acid, alkali, oxidation, thermal, and photolytic conditions. Validation studies for the in-house process impurities were performed for specificity, limit of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy, and robustness. Thus, an improved RP-HPLC method capable of good separation of all known and unknown impurities with acceptable resolution and tailing factor was developed. Copyright © 2020 Chaitali Kharat et al.Evodiamine (Evo) is an indole alkaloid extracted from the traditional Chinese medicinal herb Evodia rutaecarpa. Evo may regulate gastrointestinal motility, but the evidence is insufficient, and the mechanisms remain unknown. The aim of this study was to investigate the effect of Evo on colonic motility of rats and the underlying mechanisms in vitro. Rat colonic muscle was exposed to Evo (10 and 100 μM) followed by immunohistochemistry of cholecystokinin receptor 1 (CCK1R). β-Nicotinamide Muscle contractions were studied in an organ bath system to determine whether CCK1R, nitric oxide (NO), and enteric neurons are involved in the relaxant effect of Evo. Whole-cell patch-clamp was used to detect L-type calcium currents (I Ca,L) in isolated colonic smooth muscle cells (SMCs). CCK1R was observed in SMCs, intermuscular neurons, and mucosa of rat colon. Evo could inhibit spontaneous muscle contractions; NO synthase, inhibitor L-NAME CCK1R antagonist, could partly block this effect, while the enteric neurons may not play a major role. Evo inhibited the peak I Ca,L in colonic SMCs at a membrane potential of 0 mV. The current-voltage (I-V) relationship of L-type calcium channels was modified by Evo, while the peak of the I-V curve remained at 0 mV. Furthermore, Evo inhibited the activation of L-type calcium channels and decreased the peak I Ca,L. The relaxant effect of Evo on colonic muscle is associated with the inhibition of L-type calcium channels. The enteric neurons, NO, and CCK1R may be partly related to the inhibitory effect of Evo on colonic motility. This study provides the first evidence that evodiamine can regulate colonic motility in rats by mediating calcium homeostasis in smooth muscle cells. These data form a theoretical basis for the clinical application of evodiamine for treatment of gastrointestinal motility diseases. Copyright © 2020 Guo-xiang Wang et al.Objective Studies comparing magnetic resonance enterography (MRE) and capsule endoscopy (CE) for the assessment of small bowel (SB) Crohn's disease (CD) are scarce in Korea. In addition, there is no Korean experience of patency capsule (PC) examination prior to CE. The primary aim of this study was to compare diagnostic yields of MRE and CE for the assessment of SB CD. Secondary objectives were to compare the detection rate of proximal SB lesions by each modality in the Montreal classification and evaluate the safety and feasibility of PC in Korean CD patients. Methods MRE was performed as the first examination to assess SB CD. PC examination and CE were then performed. Diagnostic yields of active SB disease by MRE and CE were then analyzed. Results Disintegration of the patency capsule was shown in 5 patients out of 26 patients, who did not undergo CE. These 5 patients were accounted as negative CE findings. Overall, MRE and CE detected 80.8% and 65.4% of active SB lesions of CD in 26 patients, respectively (P = 0.212). MRE and CE detected 0% (0/26) and 19.2% (5/26) (P = 0.051) of jejunal lesions, 30.8% (8/26) and 42.3% (11/26) (P = 0.388) of proximal ileal lesions, and 80.8% (21/26) and 53.8% (14/26) (P = 0.039) of terminal ileal lesions, respectively. According to the Montreal classification, MRE and CE independently detected proximal disease (L4) in 30.8% (8/26) and 53.8% (14/26) (P = 0.092), respectively. Conclusions The diagnostic yields of MRE and CE for the assessment of SB CD including proximal SB lesions were similar. MRE is a more objective tool for detecting clinically relevant stricture than PC although PC examination could be performed safely before CE to prove the patency of SB. This trial is registered with KCT0004305. Copyright © 2020 Hyun Seok Lee et al.