Aldosterone-induced kidney injury is mediated by NFκB activation

Background  

Aldosterone induces inflammation and fibrosis in the kidney, while nuclear factor κB (NFκB) plays key roles in inflammation mediated by various cytokines. Here, we determined the roles of NFκB activation in aldosterone-induced kidney injury.     

The prevalence of congenitally missing permanent teeth in Japanese children: A survey conducted in south-west area of Kanto district

AimThe purpose of this study was to investigate the prevalence of congenitally missing permanent teeth in Japanese children residing in south-west area of Kanto district in recent years.MethodsPanoramic radiographs taken for dental treatment between 1990 and 2007 were used to evaluate the congenitally missing permanent teeth excluding the third molar. The participants of this study consisted of 2,125 children aged between 7 and 20 years.ResultsThe congenitally missing teeth were observed in 251 participants (11.8%). The majority of the participants (114) presented with only one tooth missing, and there was a general tendency that the number of participants gradually decreased as the number of missing teeth increased. A total of 539 teeth were congenitally missing, and mandibular second premolar was the most frequently missing tooth (153 teeth), followed by mandibular lateral incisor (86 teeth), maxillary second premolar (71 teeth), maxillary lateral incisor (61 teeth). Only one missing tooth (114 participants) was found most frequently in mandibular lateral incisor (30 participants), followed by mandibular second premolar (28 participants). There was a tendency that congenitally missing teeth occurred symmetrically; especially most of the participants who had two missing teeth (80 in 88 participants) were symmetrically missing.ConclusionThe prevalence of congenitally missing permanent teeth in this study was 11.8% and it was comparable to those reported in previous studies of Japanese population evaluated using panoramic radiographs.     

Endoscopy-assisted anastomosis: a modified technique for laparoscopic side-to-side esophagojejunostomy following a total gastrectomy

Introduction: Esophagojejunostomy with a circular stapling device is sometimes difficult to perform in a laparoscopic setting. On the other hand, a side‐to‐side anastomosis with a linear stapling device is technically challenging. Methods: Between June 2002 and March 2008, 10 consecutive patients underwent a laparoscopy‐assisted total gastrectomy using a side‐to‐side anastomosis technique. Of these patients, four underwent a laparoscopy‐assisted total gastrectomy with a modified anastomosis technique. A small wound was created on the antimesenteric side of the jejunum 5 cm distal to the resected portion and then in the lower esophagus. A peroral endoscope was advanced to the hole, and the cartridge fork was introduced into the lower esophagus under endoscopic guidance. The device (45 mm, blue) was fired to create an antiperistaltic side‐to‐side anastomosis. The common entry hole was closed by transecting the jejunum and the esophagus with another linear stapler and by using an endoscope as a stent. Results: Four patients underwent the modified procedure and did not require an open procedure. One patient developed a pancreatic fistula, which was treated conservatively. The average operative time, reconstruction time and blood loss were 483 ± 133 minutes, 139 ± 31 minutes, and 199 ± 121 mL, respectively. An introduction of the stapler into the lower esophagus and a closure of the common entry hole were performed safely without any stress. Conclusion: Although several techniques must be compared to determine the ideal procedure for laparoscopic esophagojejunostomy, the modified side‐to‐side anastomosis technique may be useful in clinical settings.     

Crucial role of c-Myc in the generation of induced pluripotent stem cells

c-Myc transduction has been considered previously to be nonessential for induced pluripotent stem cell (iPSC) generation. In this study, we investigated the effects of c-Myc transduction on the generation of iPSCs from an inbred mouse strain using a genome integration-free vector to exclude the effects of the genetic background and the genomic integration of exogenous genes. Our findings reveal a clear difference between iPSCs generated using the four defined factors including c-Myc (4F-iPSCs) and those produced without c-Myc (3F-iPSCs). Molecular and cellular analyses did not reveal any differences between 3F-iPSCs and 4F-iPSCs, as reported previously. However, a chimeric mice formation test indicated clear differences, whereby few highly chimeric mice and no germline transmission was observed using 3F-iPSCs. Similar differences were also observed in the mouse line that has been widely used in iPSC studies. Furthermore, the defect in 3F-iPSCs was considerably improved by trichostatin A, a histone deacetyl transferase inhibitor, indicating that c-Myc plays a crucial role in iPSC generation through the control of histone acetylation. Indeed, low levels of histone acetylation were observed in 3F-iPSCs. Our results shed new light on iPSC generation mechanisms and strongly recommend c-Myc transduction for preparing high-quality iPSCs.     

Effects of ad libitum ingestion of monosodium glutamate on weight gain in C57BL6/J mice

Although the umami compound monosodium glutamate (MSG) is a widely used flavor enhancer, controversy still persists regarding the effects of MSG intake on body weight. It has been claimed, in particular, that chronic MSG intake may result in excessive body weight gain and obesity. In this study we assessed the effects of chronic (16 weeks) ad libitum MSG on body weight and metabolism of C57BL6/J mice. Adult male mice were divided in four experimental groups and fed with either a low-fat (LF) or high-fat (HF) diet and with either two bottles of plain water or one bottle containing 1% MSG and another one containing water according to a factorial design. Mice were monitored weekly for body weight and food/fluid intake for 15 weeks. At the end of the experiments, the circulating levels of leptin, insulin, total protein, total cholesterol, triglyceride, blood urea nitrogen, and non-esterified fatty acids were also analyzed. Our results show that MSG intake did not influence body weight in either LF or HF groups. Interestingly, although animals overall displayed strong preferences for MSG against water, preferences were relatively higher in LF compared to HF group. Consistent with the body weight data, while significant differences in leptin, insulin, total cholesterol, and non-esterified fatty acids were found between HF and LF groups, such an effect was not influenced by MSG intake. Finally, indirect calorimetry measurements revealed similar energy expenditure levels between animals being presented water only and MSG only. In summary, our data does not support the notion that ad libitum MSG intake should trigger the development of obesity or other metabolic abnormalities.     

Proteomic analysis of rat brains in a model of neuropathic pain following exposure to electroconvulsive stimulation

Some reports have shown that electroconvulsive shock therapy is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. This study analyzes changes in protein expression in the brainstems of neuropathic pain model rats with or without electroconvulsive stimulation (ECS). A neuropathic pain model rat is produced by chronic constrictive injury (CCI) of the sciatic nerve. An ECS was administered to rodents once daily for 6 days after the CCI operation. After ECS, the latency to withdrawal from thermal stimulation was significantly increased. The expression of several proteins was changed after CCI. Ten proteins that increased after CCI then had decreased expression levels (close to control) after ECS, and 8 proteins that decreased after CCI then had increased expression levels (close to control) after ECS. In conclusion, ECS improved thermal hypersensitivity in a rat CCI model. Proteomic analysis showed that altered expression levels of proteins in the brainstem of CCI model rats returned to close to control levels after ECS, including many proteins associated with pain. This trend suggests an association of ECS with improved hypersensitivity, and these results may help elucidate the mechanism of this effect.     

Long-term outcomes and prognostic factors of patients with advanced gastric cancer treated with S-1 plus cisplatin combination chemotherapy as a first-line treatment

Background

The long-term outcomes of advanced gastric cancer (AGC) patients treated with S-1 plus cisplatin (SP) combination chemotherapy remain unclear. Therefore, we sought to evaluate these outcomes to identify the prognostic factors affecting patient survival.

Methods

We retrospectively analyzed 153 AGC patients treated with SP at a single institution between January 2005 and July 2011.

Results

Median overall survival (OS) was 15.0 months [95 % confidence interval (CI), 12.5–17.9 months]. Three independent prognostic factors affecting poor survival were identified: performance status (PS) ≥ 1 [hazard ratio (HR) = 2.39, 95 % CI, 1.58–3.62); >1 metastatic site (HR = 1.57, 95 % CI, 1.10–2.26], and elevated alkaline phosphatase levels (HR = 1.70, 95 % CI, 1.16–2.49). A simple prognostic index was generated using three risk groups: good (no risk factor), moderate (one or two risk factors), and poor (three risk factors). The median OS for good-, moderate-, and poor-risk groups was 28.6, 14.8, and 7.3 months, respectively (log-rank test; P < 0.0001). Among the twelve 3-year survivors, 9 (75 %) had a PS of 0 and 8 (67 %) had only one metastatic site.

Conclusions

Three prognostic factors were identified in AGC patients treated with SP. Using a simple prognostic index, the patients were divided into three risk groups, in which the survival differences were markedly significant, suggesting that patients with good PS and only one metastatic site may have a higher chance of long-term survival than those with poor PS and multiple metastatic sites.