Eicosapentaenoic acid protects endothelial cells against anoikis through restoration of cFLIP

Dietary supplementation with eicosapentaenoic acid (EPA) improves the prognosis of chronic inflammatory diseases, including atherosclerosis. The mechanism underlying these beneficial effects, however, remains to be elucidated. Here we show that EPA protects endothelial cells from anoikis through upregulation of the cellular FLICE (Fas-associating protein with death domain-like interleukin-1-converting enzyme)-inhibitory protein (cFLIP), an endogenous inhibitor of caspase-8. EPA-induced upregulation of cFLIP expression was partially suppressed by the phosphatidylinositol-3-kinase inhibitor wortmannin. Conversely, treatment with insulinlike growth factor-1 (IGF-1), an activator of phosphatidylinositol-3-kinase/Akt signaling, or infection with an adenoviral construct expressing the constitutively active Akt gene induced upregulation of cFLIP expression. In addition, pretreatment of endothelial cells with either EPA or IGF-1 protected them from anoikis, suggesting that EPA-induced protection against anoikis is partially mediated through activation of Akt. On the other hand, when endothelial cells were already detached, treatment of these cells with EPA but not with IGF-1 protected them against anoikis. Importantly, EPA restored cFLIP expression without activating Akt signaling in detached endothelial cells, whereas IGF-1 had no effect. Additionally, exogenously restored expression of cFLIP by the tetracycline-regulated adenovirus system protected endothelial cells against anoikis. Furthermore, EPA was protective against the loss of endothelium in an organ culture of rat aortas. These findings suggest that EPA protects against endothelial cell anoikis through restoration of cFLIP expression, which might contribute to the mechanism underlying the beneficial effects of EPA in patients with hypertension.     

Retrospective multicenter study of surgical treatments for osteoporotic vertebral fractures

Background  

Although many surgical procedures are available for treating osteoporotic vertebral fractures, there have been no comprehensive multicenter surveys in Japan focusing on surgical treatments for these fractures. This study aimed at (1) conducting a retrospective multicenter study to survey surgical treatments performed at referral center hospitals in various regions in Japan and (2) analyzing situations and problems related to the surgical treatments of osteoporotic vertebral fractures in Japanese hospitals.     

Determining circulating endothelial cells using CellSearch system during preoperative systemic chemotherapy in breast cancer patients

Background

Circulating endothelial cells (CECs) have been studied as a biomarker for tumour progression and monitoring therapeutic effects. The CellSearch system is a semi-automated system that allows standardised analysis of CECs. This study assessed the clinical implications of CECs determined by the CellSearch system in breast cancer patients.

Methods

Seventy-six consecutive breast cancer patients (53 operable and 23 metastatic or recurrent) were enrolled for the study. Thirty-five patients with operable breast cancer received preoperative chemotherapy with a regimen based on anthracycline and/or taxane. CECs are defined as CD146⁺CD105⁺CD45⁻DAPI⁺ cells in the system. CD34 expression was examined using the additional channel in the system.

Results

A majority (4539 of 5183 cells, 88%) of CECs from patients with operable breast cancer were CD34-positive. Triple-negative cancers showed higher baseline CEC and CD34⁺CEC counts than the other types (P = 0.0387 and 0.0377, respectively). Low baseline CEC and CD34⁺CEC counts, and a low CD34 positive rate were associated with pathological complete response (pCR) of preoperative chemotherapy in patients with primary breast cancer (P = 0.046, 0.027 and 0.01, respectively). In multivariate analyses, the CD34 positive rate was significant for pCR (P = 0.021). During preoperative chemotherapy, CEC and CD34⁺CEC counts before each cycle of chemotherapy increased with taxane-based regimens (P = 0.0018 and 0.0008, respectively) but not with anthracycline-based regimens.

Conclusions

Baseline CEC, in particular CD34⁺CEC, counts and the CD34 positive rate might be useful for the prediction of treatment response of preoperative chemotherapy in patients with operable breast cancer.     

Asymptomatic extra-adrenal paraganglioma masquerading as retroperitoneal sarcoma

A 41-year-old man without clinical symptoms was referred for treatment of an enlarging retroperitoneal tumor. Enhanced computed tomography showed a well-defined and heterogeneously enhanced tumor, 4 cm in size, in the dorsal portion of the pancreas. A low-density nodule was detected in the left adrenal gland, 10 mm in diameter. Retroperitoneal sarcoma and nonfunctional left adrenal tumor were suspected, and surgical treatment was performed. During excision of the retroperitoneal tumor, blood pressure was extremely elevated when the tumor was compressed. Blood pressure normalized after excision of the tumor; thus, a diagnosis of paraganglioma was favored over that of retroperitoneal sarcoma. The left adrenal gland was resected together with the adrenal tumor. Microscopically, the tumor cells of the retroperitoneum had round to oval nuclei, and abundant granular amphophilic cytoplasm proliferated in nest-like fashion. Extra-adrenal retroperitoneal paraganglioma was considered, and the adrenal tumor was diagnosed as cortical adenoma. In patients with retroperitoneal tumor, even in the absence of clinical symptoms, we should keep in mind the possibility of extra-adrenal paraganglioma.     

Trauma and diverse child populations

It has been estimated that as many as two-thirds of American youth experience a potentially life-threatening event before 18 years of age and that half have experienced multiple potentially traumatic events. Race, ethnicity, and culture influence the frequency and nature of these traumas and also the ways in which children react to traumatic events. The authors discuss the varied influences of cultural background on these reactions to trauma, the varying presentations of diverse children experiencing troubling reactions, and the need to provide treatment to children and their families in a fashion that is culturally sensitive and acceptable to diverse families.     

Impact of network time-delay and force feedback on tele-surgery

Object

We have developed a robotic minimally invasive surgical system within a tele-surgery capability and conducted several times of tele-surgery experiments including Japan–Thailand and Japan–Korea tele-surgery experiments by using conventional network infrastructures. In these experiments, laparoscopic cholecystectomies have been successfully performed on pigs. On the other hand, repetitive task evaluation studies are also crucial for further studies on tele-surgery applications. Nowadays, task evaluations of tele-robotic system within network time-delay have been studied in past years by many researchers. These experiments have been mostly focused on simplified tasks such as a peg-in-hole task. However, most of surgical procedures in minimally invasive surgery are based on medical specific skills such as anatomical knowledge and past experiences of surgeons. From these perspectives, a trial experiment within two tasks including surgery oriented manipulations was conducted to study the impact of network time-delay and force feedback on tele-surgery.

Materials and methods

The experiment was conducted by using the minimally invasive surgical system. As the experimental setup, a research and development Internet, JGN2 (Japan Gigabit Network 2) was used as a network infrastructure, and two tasks were performed by 15 subjects including 5 medical doctors. The trial conditions were given by changing time-delay (on the both tasks) and force feedback (on the first task). The first task was configured to test a simple surgical procedure, which is commonly performed in a laparoscopy as translational motions of surgical tools. The subjects were instructed to touch four columns located on points of a square. The second task was configured to test integrated surgical procedures. The subjects were instructed to perform a part of suturing procedures by using the robotic bending forceps.

Results

In the first task, the completion time was increased approximately 50% by time-delay. By using force feedback, the applied force was decreased. However, the effectiveness of force feedback was not strongly shown in MD group. On the other hand, the effectiveness of the force feedback was strongly shown in the applied force on the tip of surgical tool in both MD and non-MD groups. In the second task, the adverse impact of time-delay was not strongly shown in MD group. From the analysis of the motion records found that a skill of experienced surgeons on “occlusion problem” could be related in the results. These results indicate that skilful operators on surgical procedures can overcome the adverse impact of time-delay by introducing their skills depending on required surgical tasks. However, the drawback of time-delay still remains concerning on safety issues. The effectiveness of the force feedback was strongly shown in the first task in terms of the applied force on the surrounding environment.

Conclusions

Force feedback is an essential technology for further applications of tele-surgery. In addition, the force feedback technology can be partially used for compensating the drawback of time-delay.     

Edge-to-edge tricuspid valve repair in hypoplastic left heart syndrome

Tricuspid regurgitation (TR) is known to be a risk factor for mortality in the surgical management of patients with hypoplastic left heart syndrome (HLHS). Concomitant repair for TR should be considered when the TR is moderate to severe to achieve successful Fontan completion. The present case was a 20-month-old girl who was diagnosed with HLHS (mitral atresia and aortic atresia). She underwent a Norwood procedure as the first palliation followed by a Glenn procedure. After that, she gradually developed TR, which progressed to a severe state at the time of the Fontan procedure. An edge-to-edge tricuspid valve repair, in which the anterior and septal leaflets were sutured together, was performed simultaneously with the extracardiac Fontan procedure. Discharge echocardiography revealed that the degree of TR was less than mild. The technique is simple, not time-consuming, and may be an effective adjunct for successful completion of the Fontan procedure in these patients.     

Transporter-mediated hepatic uptake of ulifloxacin, an active metabolite of a prodrug-type new quinolone antibiotic prulifloxacin, in rats

Prulifloxacin (PUFX) is a prodrug-type new quinolone antibiotic and immediately converted to an active metabolite, ulifloxacin (UFX). It has been previously reported that UFX is highly excreted into the bile, although the hepatic uptake process of UFX has not been investigated yet. In this study, we attempted to characterize the mechanism of hepatic uptake of UFX in rats. The hepatic uptake in vivo was evaluated by integration plot analysis. Furthermore, the uptake of [(14)C]-UFX by isolated rat hepatocytes was measured, and the effects of several transporter inhibitors and other quinolone antibiotics on the uptake were examined. The hepatic uptake clearance of UFX (1 mg/kg) was calculated to be 37.7 mL/min/kg, which was larger than those at doses of 5 and 25 mg/kg and was decreased by co-administration of cyclosporine A (CysA; 30 mg/kg). The uptake of [(14)C]-UFX by isolated rat hepatocytes linearly increased up to 1 min and also inhibited by CysA. Other quinolone antibiotics inhibited the [(14)C]-UFX uptake in a concentration-dependent manner, whereas taurocholate and estrone-3-sulfate partially inhibited the [(14)C]-UFX uptake. These results demonstrate that a carrier-mediated transport system which is common to the quinolone antibiotics is involved in the uptake of UFX in the rat liver.