Improvement in Quality of Life Following Celiprolol Hydrochloride Administration in a Patient with Vascular Ehlers-Danlos Syndrome: A Case Report.

A 40-year-old female, who underwent transcatheter arterial embolization due to acute bleeding from an iliolumbar artery, was subsequently genetically diagnosed with vascular Ehlers-Danlos syndrome. She experienced chronic anemia for many years due to the easy bruising of her whole body. The bruising improved with oral administration of celiprolol hydrochloride. There were no cardiac or vascular events during the 7 years following the transcatheter arterial embolization. Vascular Ehlers-Danlos syndrome requires specialized treatment that is scientifically proven to prevent a major vascular event. Proactive genetic diagnosis is recommended in patients suspected of having vascular Ehlers-Danlos syndrome after careful patient interview.

Radiological features of human papillomavirus-related multiphenotypic sinonasal carcinoma: systematic review and case series.

PURPOSE: To comprehensively summarize the radiological characteristics of human papillomavirus (HPV)-related multiphenotypic sinonasal carcinomas (HMSCs). METHODS: We reviewed the findings for patients with HMSCs who underwent computed tomography (CT) and/or magnetic resonance imaging (MRI) and included nine cases from nine publications that were identified through a systematic review and three cases from our institution. Two board-certified radiologists reviewed and evaluated the radiological images. RESULTS: The locations in almost all cases included the nasal cavity (11/12, 91.7%). The involved paranasal sinuses included the ethmoid sinus (6/12, 50.0%) and maxillary sinus (3/12, 25.0%). The mean long diameter of the tumors was 46.3 mm. The margins in 91.7% (11/12) of the cases were well-defined and smooth. Heterogeneous enhancement on contrast-enhanced CT, heterogeneous high signal intensities on T2-weighted images and heterogeneous enhancement on gadolinium-enhanced T1-weighted images were noted in 2/2, 5/5, and 8/8 cases, respectively. Mean apparent diffusion coefficient values in two cases of our institution were 1.17 and 1.09 × 10-3 mm2/s. Compressive changes in the surrounding structures were common (75%, 9/12). Few cases showed intraorbital or intracranial extension. None of the cases showed a perineural spread, neck lymph node metastasis, or remote lesions. CONCLUSIONS: We summarized the CT and MRI findings of HMSCs. Knowledge of such characteristics is expected to facilitate prompt diagnosis and appropriate management.

Risk factors for abdominal wall pseudohernia after percutaneous cryoablation of renal cell carcinoma.

INTRODUCTION: Percutaneous cryoablation (PCA) is increasingly recognized as a feasible minimally invasive, nephron-sparing treatment for renal cell carcinomas, with comparable efficacy to nephrectomy. The development of abdominal wall pseudohernia (AWP) is a rare complication of PCA for renal masses, which can negatively impact patients' quality of life. AIM: To retrospectively evaluate the risk factors and prognosis for AWP after PCA and, based on these results, to discuss strategies to lower the risk of AWP associated with image-guided PCA for renal masses. MATERIAL AND METHODS: We retrospectively studied 117 PCAs performed for renal masses in 92 patients, between 2016 and 2019, at our hospital. We compared the following clinical characteristics (age, sex, body mass index, tumour diameter, RENAL nephrometry score, procedural details, transcatheter arterial embolization, dissection techniques, number of cryoneedles used, location of needles, and location of ice ball) between those who developed AWP and those who did not. RESULTS: Of the 117 PCAs (92 patients) included in our study group, AWP complications were observed in 6 (5.1%) procedures. Puncture through the erector spinae muscle (p < 0.01) and non-use of hydro- or pneumo-dissection (p = 0.01) were identified as risk factors for AWP. CONCLUSIONS: Although PCA is relatively safe to perform and the occurrence of an associated AWP is a rare and infrequent complication, the risk for AWP could be further decreased by avoiding punctures through the erector spinae muscle and using hydro- or pneumo-dissection.

The Gαs-protein-mediated pathway may be steadily stimulated by prostanoid EP2 receptors, but not by EP4 receptors.

EP2 and EP4 prostanoid receptors have long been considered to have similar roles, since they are known to couple with Gαs-protein and activate cAMP-mediated signaling pathways. In this study, we re-evaluated the results of cAMP assays with or without phosphodiesterase (PDE) inhibitor pretreatment. Here, we show that in the absence of PDE inhibitor pretreatment, prostaglandin E2 causes accumulation of cAMP in EP2 receptors, whereas markedly low levels of cAMP accumulated in EP4 receptors. By applying the Black/Leff operational model calculation, we found that EP2 receptors have a biased ability to intrinsically activate the Gαs-protein-mediated pathway, whereas EP4 receptors have strong biased activity for the Gαi-protein-mediated pathway. Thus, EP2 and EP4 receptors may not be similar Gαs-coupled receptors but instead substantially different receptors with distinct roles.

Short chain fatty acid butyrate uptake reduces expressions of prostanoid EP4 receptors and their mediation of cyclooxygenase-2 induction in HCA-7 human colon cancer cells.

Microbiota produce short chain fatty acids (SCFAs), which are known to maintain gut homeostasis, by the fermentation of dietary fiber in the human colon. Among SCFAs, butyrate has been considered as the most physiologically effective SCFA in colorectal epithelial cells for growth and differentiation. Here we show that the E-type prostanoid 4 (EP4) receptor expression level is regulated by different concentrations of butyrate, but not by other SCFAs, in human colon cancer HCA-7 cells, through sodium-coupled monocarboxylate transporter-1 (SMCT-1)-mediated uptake followed by the activation of histone acetyltransferase: cAMP response element binding protein-binding protein/p300. Of particular interest, the prostanoid EP4 receptors are known to be expressed in normal colorectal crypt epithelial cells and maintain intestinal homeostasis by preserving mucosal integrity, while they are also known to be involved in the early stage of carcinogenesis. Thus, the links between butyrate and the expression of prostanoid EP4 receptors are both important factors for maintaining homeostasis. Based on in silico analysis, almost half of colorectal cancer tissues have lost the expression of SMCT-1 mRNA when compared with healthy corresponding tissues. Therefore, with the collapse of homeostasis systems such as a decrease in the concentration of butyrate in colorectal tissues, or reduced butyrate uptake, there is a possibility of early stage colorectal cancer development; the transformation of normal cells to the cancerous phenotype may be due to the overexpression of prostanoid EP4 receptors followed by excessive cyclooxygenase-2 induction, which are caused by a reduced amount of butyrate and/or its uptake, in/around colorectal epithelial cells.

Cellular density-dependent increases in HIF-1α compete with c-Myc to down-regulate human EP4 receptor promoter activity through Sp-1-binding region.

The up-regulated expression of E-type prostanoid (EP) 4 receptors has been implicated in carcinogenesis; however, the expression of EP4 receptors has also been reported to be weaker in tumor tissues than in normal tissues. Indeed, EP4 receptors have been suggested to play a role in the maintenance of colorectal homeostasis. This study aimed to examine the underlying mechanisms/reasons for why inconsistent findings have been reported regarding EP4 receptor expression levels in homeostasis and carcinogenesis by focusing on cellular densities. Thus, the human colon cancer HCA-7 cells, which retain some functional features of normal epithelia, and luciferase reporter genes containing wild-type or mutated EP4 receptor promoters were used for elucidating the cellular density-dependent mechanisms about the regulation of EP4 receptor expression. In silico analysis was also utilized for confirming the relevance of the findings with respect to colon cancer development. We here demonstrated that the expression of EP4 receptors was up-regulated by c-Myc by binding to Sp-1 under low cellular density conditions, but was down-regulated under high cellular density conditions via the increase in the expression levels of HIF-1α protein, which may pull out c-Myc and Sp-1 from DNA-binding. The tightly regulated EP4 receptor expression mechanism may be a critical system for maintaining homeostasis in normal colorectal epithelial cells. Therefore, once the system is altered, possibly due to the transient overexpression of EP4 receptors, it may result in aberrant cellular proliferation and transformation to cancerous phenotypes. However, at the point, EP4 receptors themselves and their mediated homeostasis would be no longer required.

Digestive Tract Complications of Renal Cryoablation.

We report a case each of duodenorenal and colorenal fistula that arose after computed tomography-guided percutaneous cryoablation (PCA) for renal cell carcinoma and use imaging and endoscopic findings to analyze their causes and mechanisms. Both complications occurred though the edge of the iceball did not touch the intestinal wall, and patients' symptoms and fistula formation occurred several days after the PCA procedure. Based on imaging and endoscopy findings, we suspected the colorenal fistula resulted from bowel injury caused by ischemia from the occlusion of small vessels at the procedure's low temperature. Both cases were resolved conservatively without surgical intervention.

Prostaglandin E2-stimulated prostanoid EP4 receptors induce prolonged de novo prostaglandin E2 synthesis through biphasic phosphorylation of extracellular signal-regulated kinases mediated by activation of protein kinase A in HCA-7 human colon cancer cells.

Approximately two decades have passed since E-type prostanoid 4 (EP4) receptors were cloned, and the signaling pathways mediated by these receptors have since been implicated in cancer development through the alliance of Gαi-protein/phosphatidylinositol 3-kinase (PI3K)/extracellular signal-regulated kinases (ERKs) activation. Although prostanoid EP4 receptors were initially identified as Gαs-coupled receptors, the specific/distinctive role(s) of prostanoid EP4 receptor-induced cAMP/protein kinase A (PKA) pathways in cancer development have not yet been elucidated in detail. We previously reported using HCA-7 human colon cancer cells that prostaglandin E2 (PGE2)-stimulated prostanoid EP4 receptors induced cyclooxygenase-2 (COX-2) as an initiating event in development of colon cancer. Moreover, this induction of COX-2 was mediated by transactivation of epidermal growth factor (EGF) receptors. However, direct activation of EGF receptors by EGF also induced similar amounts of COX-2 in this cell line. Thus, the emergence of unique role(s) for prostanoid EP4 receptors is expected by clarifying the different signaling mechanisms between PGE2-stimulated prostanoid EP4 receptors and EGF-stimulated EGF receptors to induce COX-2 and produce PGE2. We here demonstrated that prostanoid EP4 receptor activation by PGE2 in HCA-7 cells led to PKA-dependent re-activation of ERKs, which resulted in prolonged de novo synthesis of PGE2. Although EGF-stimulated EGF receptors in cells also induced COX-2 and the de novo synthesis of PGE2, the activation of this pathway was transient and not mediated by PKA. Therefore, the novel mechanism underlying prolonged de novo synthesis of PGE2 has provided an insight into the importance of prostanoid EP4 receptor-mediated Gαs-protein/cAMP/PKA pathway in development of colon cancer.

A successful case of liver biopsy via the right femoral vein using the Quick-Core biopsy needle.

A 35-year-old male with ascites and coagulopathy underwent transjugular liver biopsy (TJLB) for severe hepatic dysfunction. However, the acute angle of the inferior vena cava and hepatic veins (HVs) prevented insertion of a 14-gauge inner stiffening metallic cannula into the HV. He then underwent successful liver biopsy by right femoral vein access (transfemoral liver biopsy) using a TJLB device without complications and was pathologically diagnosed with nonalcoholic steatohepatitis.

Reaction of an oxaruthenacycle with DMAD. Stoichiometric transformations of 2,6-xylenol to allylic phenols and benzopyrans via sp(3) C-H bond cleavage reaction.

Insertion of a dimethyl acetylenedicarboxylate (DMAD) into the Ru-C bond in a cycloruthenated complex Ru[OC(6)H(3)(2-CH(2))(6-Me)-kappa(2)O,C](PMe(3))(4) () has been achieved to give a seven-membered oxaruthenacycle Ru[OC(6)H(3){2-CH(2)C(CO(2)Me)[double bond, length as m-dash]C(CO(2)Me)}(6-Me)-kappa(2)O,C](PMe(3))(3) () in 47% yield. The molecular structure of by X-ray analysis shows an agostic interaction between the ruthenium and one of the benzylic methylene protons. Complex shows fluxional behaviour in solution and the variable temperature NMR studies suggest this fluxionality to be responsible for the turnstile rotation of three PMe(3) ligands and the rotation of the alpha-methoxycarbonyl group. Heating of a toluene solution of at 100 degrees C for 2 h results in the 1,3-H shift reaction in to give a kappa(1)O,eta(3)-C,C',C'' allylic complex Ru[OC(6)H(3){2-CHC(CO(2)Me)CH(CO(2)Me)}(6-Me)-kappa(1)O,eta(3)C,C',C''](PMe(3))(3) () (80-90%), whose molecular structure is revealed by X-ray analysis. Acidolyses of and give 2-[(Z)-2',3'-bis(methoxycarbonyl)allyl]-6-methylphenol () (88%) and 2-[(Z)-2',3'-bis(methoxycarbonyl)propenyl]-6-methylphenol () (47%), respectively, and iodolyses of and produce 2,3-bis(methoxycarbonyl)-8-methyl-4H-benzopyran () (24%) and 2,3-bis(methoxycarbonyl)-8-methyl-2H-benzopyran () (48%), respectively.