An Angiotensin II Type 1 Receptor Blocker Prevents Renal Injury via Inhibition of the Notch Pathway in Ins2 Akita Diabetic Mice

Recently, it has been reported that the Notch pathway is involved in the pathogenesis of diabetic nephropathy. In this study, we investigated the activation of the Notch pathway in Ins2 Akita diabetic mouse (Akita mouse) and the effects of telmisartan, an angiotensin II type1 receptor blocker, on the Notch pathway. The intracellular domain of Notch1 (ICN1) is proteolytically cleaved from the cell plasma membrane in the course of Notch activation. The expression of ICN1 and its ligand, Jagged1, were increased in the glomeruli of Akita mice, especially in the podocytes. Administration of telmisartan significantly ameliorated the expression of ICN1 and Jagged1. Telmisartan inhibited the angiotensin II-induced increased expression of transforming growth factor β and vascular endothelial growth factor A which could directly activate the Notch signaling pathway in cultured podocytes. Our results indicate that the telmisartan prevents diabetic nephropathy through the inhibition of the Notch pathway

Fully gapped superconductivity with no sign change in the prototypical heavy-fermion CeCu2Si2

In exotic superconductors including high-$T_c$ copper-oxides, the interactions mediating electron Cooper-pairing are widely considered to have a magnetic rather than the conventional electron-phonon origin. Interest in such exotic pairing was initiated by the 1979 discovery of heavy-fermion superconductivity in CeCu$_2$Si$_2$, which exhibits strong antiferromagnetic fluctuations. A hallmark of unconventional pairing by anisotropic repulsive interactions is that the superconducting energy gap changes sign as a function of the electron momentum, often leading to nodes where the gap goes to zero. Here, we report low-temperature specific heat, thermal conductivity and magnetic penetration depth measurements in CeCu$_2$Si$_2$, demonstrating the absence of gap nodes at any point on the Fermi surface. Moreover, electron-irradiation experiments reveal that the superconductivity survives even when the electron mean free path becomes substantially shorter than the superconducting coherence length. This indicates that superconductivity is robust against impurities, implying that there is no sign change in the gap function. These results show that, contrary to long-standing belief, heavy electrons with extremely strong Coulomb repulsions can condense into a fully-gapped s-wave superconducting state, which has an on-site attractive pairing interaction.Comment: 8 pages, 5 figures + Supplement (3 pages, 5 figures

Iron overload may be critical for liver dysfunction in anorexia nervosa, and the role of haematocrit-adjusted albumin in assessing nutritional status: a case report

Abstract Background Anorexia nervosa (AN) is frequently associated with liver dysfunction, but the precise mechanism remains undefined. Since the nutritional marker albumin has a low correlation with changes in body weight in AN, and patients with AN often have dehydration as a complication, we also examined whether haematocrit (HCT)-adjusted serum albumin could be a better nutritional marker in AN. Case presentation We describe a 15-year-old girl with severe weight loss and liver damage whose liver enzymes normalized after 1.5 months of hospitalization and weight gain. We found a significant correlation between body weight (BW) and HCT-adjusted serum albumin (Spearman’s rank correlation coefficient (rs) = 0.66, P = 5.28 × 10−3) and between BW and alanine aminotransferase (ALT) (rs = -0.825, P = 8.45 × 10−5). After division by HCT, correlations between serum albumin and ALT (rs = -0.835, P = 5.24 × 10−5) and between the iron-storage protein ferritin and the liver enzyme gamma-glutamyl transferase (rs = 1.0, P = 0.017) were also statistically significant. Conclusion These results suggest that improvement of the nutritional status in AN could relieve liver dysfunction and facilitate iron transport. Since a decrease in the iron-transport protein transferrin presumably increases labile non-transferrin-bound iron, resulting in excess reactive oxygen species production, a defect in iron transport due to malnutrition could be one of the causes of liver injury in AN. In addition, HCT-adjusted albumin could be a better marker than its raw data to assess changes in nutritional status in AN

Persistent Hemarthrosis of the Knee after Arthroscopic Meniscal Repair

Introduction. In this case report, we report a patient with complicated with persistent hemarthrosis following arthroscopic meniscal repair. Case Presentation. A 41-year-old male patient presented with persistent swelling of the knee 6 months after arthroscopic meniscal repair and partial meniscectomy performed for lateral discoid meniscal tear. The initial surgery was performed at another hospital. Four months after the surgery, swelling of the knee was noted when he resumed running. At his initial visit to our hospital, intra-articular blood accumulation was revealed via joint aspiration. A second arthroscopic examination performed 7 months after the initial procedure showed healing of the meniscal repair site and synovial proliferation. The suture materials identified during the arthroscopy were removed. Histological examination of the resected synovial tissue showed inflammatory cell infiltration and neovascularization. In addition, a multinucleated giant cell was identified in the superficial layer. After the second arthroscopic surgery, the hemarthrosis did not recur, and the patient was able to resume running without symptom one and a half years post-surgery. Conclusion. Bleeding from the proliferated synovia at or near the periphery of the lateral meniscus was thought to be the cause of the hemarthrosis as a rare complication following arthroscopic meniscal repair

Clinical outcome of meniscus repair for isolated meniscus tear in athletes

Objective: To examine the clinical and functional outcomes for a series of patients who underwent meniscal repair for isolated meniscal tears focusing the study population on athletes. Methods: This study represents a case series of 46 athletes who underwent repair of isolated meniscal lesions of the knee from 2010 to 2015. Cases of discoid meniscal lesions and combined ligament injuries were excluded. The mean age of the patients was 22.9 years ranging from 12 to 50 years. Arthroscopic inside-out repair was primarily a procedure of option. For repair of tears with degeneration and inferior vascularity, autogenous fibrin clot was implanted to the repair site for healing enhancement. The mean follow-up period of all patients was 19.8 ± 6.8 months (range; 12 months–33 months). Results: In total, 37 of 46 patients (80%) could go back to their original sports activities. During the follow-up period, re-tear was encountered in 4 of 46 knees (8.7%). No significant differences in clinical/functional outcomes and re-tear rate were detected between the medial and lateral meniscal repairs. Conclusion: In our expanded repair indication for isolated meniscus repair for athletes, the rate of satisfactory return to sports was 91.3% in total (88.9% for the medial meniscus group; 92.9% for the lateral meniscus group). During the follow-up period ranging from 12 to 33 months (mean, 19.8 months), re-tear of the repaired site was encountered in 4 of the 46 knees (8.7%)

Transanal total mesorectal excision for primary rectovaginal carcinosarcoma: A case report and literature review.

We report a case of rectovaginal septum carcinosarcoma successfully treated with surgical excision via transanal total mesorectal excision following platinum-based neoadjuvant chemotherapy. A 48-year-old woman presented with a 3-week defecation pain preceding the visit. Pelvic imaging showed an 8-cm sized lesion in the lower rectovaginal septum. Transvaginal biopsy and immunohistochemical analysis were performed. After three courses of carboplatin-paclitaxel-bevacizumab therapy, the mass reduced by half. Subsequently, laparoscopic excision with transanal total mesorectal excision, and radical hysterectomy were performed. The anus was preserved, and dysuria improved within a month. The final histopathological diagnosis was carcinosarcoma of the rectovaginal septum from an uncertain origin, presumably endometriotic or mesonephric. Twelve months following surgery, solitary liver metastasis was confirmed; however, there was no evidence of local recurrence. Total mesorectal excision following platinum-based neoadjuvant chemotherapy may be an ideal treatment for gynecological malignancies in the rectovaginal septum, especially for large tumors localized deep into the pelvis

Motion of left atrial appendage as a determinant of thrombus formation in patients with a low CHADS2 score receiving warfarin for persistent nonvalvular atrial fibrillation

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to define the independent determinants of left atrial appendage (LAA) thrombus among various echocardiographic parameters measured by Velocity Vector Imaging (VVI) in patients with nonvalvular atrial fibrillation (AF) receiving warfarin, particularly in patients with a low CHADS2 score.</p> <p>Methods</p> <p>LAA emptying fraction (EF) and LAA peak longitudinal strain were measured by VVI using transesophageal echocardiography in 260 consecutive patients with nonvalvular persistent AF receiving warfarin. The patients were divided into two groups according to the presence (n=43) or absence (n=217) of LAA thrombus. Moreover, the patients within each group were further divided into subgroups according to a CHADS2 score ≤1.</p> <p>Results</p> <p>Multivariate logistic regression analysis showed that LAAEF was an independent determinant of LAA thrombus in the subgroup of 140 with a low CHADS2 score. Receiver operating characteristics curve analysis showed that an LAAEF of 21% was the optimal cutoff value for predicting LAA thrombus.</p> <p>Conclusions</p> <p>LAA thrombus formation depended on LAA contractility. AF patients with reduced LAA contractile fraction (LAAEF ≤21%) require strong anticoagulant therapy to avoid thromboembolic events regardless of a low CHADS2 score (≤1).</p