Characterization of Urate Transport System in JAR and JEG-3 Cells, Human Trophoblast-derived Cell Lines

Urate (uric acid) is the major inert end product of purine metabolism in humans. Since it is water soluble, it requires a membranous protein called transporter for its permeation across the plasma membrane. Increased blood urate level is often seen in preeclampsia, but its precise mechanism remains unknown. Syncytiotrophoblasts function as a barrier between maternal blood and fetal one so called “blood-placental barrier”. So far, the expression of several urate transporters was identified in these cells, but it is still unclear about their contribution to urate handling in blood-placental barrier. In this study, we investigated the expression of urate transporters and the properties of ［14C］urate transport in both JAR and JEG-3, human choriocarcinoma cells as a model of human placenta. Conventional PCR analysis revealed that both JAR and JEG-3 cells express strongly breast cancer resistance protein (BCRP/ABCG2) mRNA. Uptake of ［14C］urate by these cells is time-dependent with Na＋- and Cl－-independent and voltage-insensitive manner and is not inhibited by benzbromarone, a representative renal urate transport inhibitor. Then, we focused on BCRP which shows strong mRNA expression and found that these cells have urate efflux property that is sensitive to fumitremorgin C (FMC), a BCRP inhibitor. These results suggest that BCRP is one of the important components for urate handling in human placenta in pathophysiological condition such as preeclampsia

Corneal Endothelial Cell Loss after Ciliary Sulcus Placement of Ahmed Glaucoma Valve in Patients with Noninfectious Uveitic Glaucoma

This study was performed to investigate the corneal endothelial cell density (CECD) reduction and treatment efficacy in patients with uveitic glaucoma treated by the ciliary sulcus placement of the Ahmed glaucoma valve (AGV). This retrospective study included 27 eyes of 27 patients with noninfectious uveitis who underwent the sulcus placement of the AGV. Each patient underwent a clinical assessment including a CECD measurement before surgery and at 3, 6, 9, and 12 months after surgery. The mean CECD was 2431.4 ± 367.5 cells/mm2 at preoperative baseline and 2360.5 ± 391.3 cells/mm2 at 12 months (p = 0.074), with a reduction rate of 2.73 ± 9.29%. The CECD reduction was significantly greater in patients with unilateral uveitis than that with bilateral uveitis. The rate of successful intraocular pressure control was 88% at 12 months, and the number of intraocular pressure-lowering medications was significantly reduced (p < 0.001). The current study showed that the implantation of an Ahmed tube into the ciliary sulcus provided stable intraocular pressure control in patients with glaucoma secondary to noninfectious uveitis, and CECD reduction was moderate in most patients at 12 months

Prognostic significance of inflammatory parameters and nutritional index in clinical stage IVB endometrial carcinomas

Recently, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) or prognostic nutritional index (PNI) have been investigated as prognostic parameters in various malignancies. Herein, we detail how we have investigated the prognostic significance of NLR, PLR and PNI together with the other clinicopathological factors for International Federation of Gynaecology and Obstetrics stage IVB endometrial carcinoma. Thirty-two patients with clinical stage IVB disease were enrolled. The relationship between clinicopathological factors, NLR, PLR or PNI and overall survival (OS) rates was investigated. The 5-year OS rate was 9.7%, and the median survival time was 9 months. In univariate analysis, PS 0–1, G1–2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. In multivariate analysis, only a histology (G1–2 endometrioid carcinoma) was identified as an independent favourable prognostic factor. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma.Impact Statement What is already known on this subject? Several parameters representing the systemic inflammatory response (e.g. neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR)) or the nutritional condition (e.g. prognostic nutritional index (PNI)) have been investigated as prognostic parameters in various malignancies, whereas they have not been thoroughly investigated in endometrial carcinoma. What the results of this study add? In univariate analysis of various factors for overall survival, the performance status (PS) 0–1, grade 1–2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. However, in a multivariate analysis, only the histology (grade 1–2 endometrioid carcinoma) was identified as an independent favourable prognostic factor. What the implications are of these findings for clinical practice and/or further research? This retrospective study identified that neither inflammatory parameters nor the nutritional index were revealed to be independent prognostic factors by multivariate analyses. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma to improve the poor prognosis of this disease

Liposarcoma of the uterine corpus: A case report and literature review

Liposarcoma of the uterine corpus is extremely rare. We performed a laparotomy on a 55-year-old woman with the complaints of abdominal distension and genital bleeding who was found to have a uterine tumor, 17 × 16 cm in diameter. The preoperative diagnosis was a lipoma or lipoleiomyoma of the uterine corpus. However, pathological examination revealed proliferation of mature adipocytes and lipoblast-like atypical cells with small, weakly pleomorphic nuclei and foamy or vacuolated cytoplasm present within a fibrous septum. Immunohistochemistry showed that the tumor cells were focally positive for mouse double minute 2 homolog (MDM2). The final pathological diagnosis was a well-differentiated liposarcoma of International Federation of Gynecology and Obstetrics (FIGO) stage IB (pT1bNxM0). On magnetic resonance imaging (MRI), T1 -weighted and fat-saturated images showed high and low intensity in the tumor, respectively, suggesting that this tumor contained a fat component. The septum inside the tumor had a contrast enhancement on T1-weighted, gadolinium-enhanced imaging. The septum was nonuniformly thickened and partially nodular. In hindsight, these findings may have suggested a well-differentiated liposarcoma in the uterine corpus rather than a lipoma or lipoleiomyoma. Clinicians should be aware of the possibility of a liposarcoma of the uterine corpus when a neoplasm contains adipose tissue and a nonuniformly thickened or partially nodular septum on MRI. Keywords: Liposarcoma, MDM2, MRI, uterine corpus, well-differentiated typ

A multicenter phase II study on the safety of rho-kinase inhibitor (ripasudil) with needling for the patients after trabeculectomy

Background: There is no established method of maintaining or reducing intra ocular pressure after the needling procedure for failing blebs post trabeculectomy. Regarding newer antihypertensive medications, ripasudil, which is a rho-associated protein kinase inhibitor ophthalmic solution, was able to prevent excessive scarring in vitro. This study aims to evaluate the safety of glaucoma patients submitted to the needling procedure and administered ripasudil for preventing scarring after the procedure. We also investigate the efficacy of ripasudil after needling for bleb failure through suppression of fibrosis to the bleb. Methods: This study is a multicenter, open-label, single-arm, phase II trial to evaluate the safety and efficacy of ripasudil in glaucoma patients after the needling procedure. Forty patients who will undergo needling at least 3 months after trabeculectomy will be recruited in Hiroshima university hospital and Hiroshima eye clinic. All the patients will instill ripasudil two times per day for three months after the needling procedure. The primary endpoint is the safety of ripasudil. Conclusions: We plan to establish the safety of ripasudil and to collect information involving the efficacy of ripasudil widely in this study