Evaluation of flexible ureteroscope with an omni-directional bending tip, using a JOYSTICK unit (URF-Y0016): an ex-vivo study.

PURPOSE: To compare the range of reach of our newly designed omni-directional ureteroscope (URF-Y0016), compared to the commonly used URF-P6, FlexX2s, and LithoVue™ scopes, in the upper, middle, and lower calyces in an ex-vivo pyelocaliceal model. METHODS: We fabricated a three-dimensional pyelocaliceal model of the upper, middle, and lower pole calyces using urethane and acrylic resin. The inner surface of the dome of each calyx was engraved with reference lines along eight directions, set at 10° of latitude from the top to the base of the dome, and at angles of 0-90°, to precisely determine the range of reach of each scope. The main feature of the URF-Y0016 scope is the omni-directional bending of the tip of the flexible ureteroscope, with the control of these four directions integrated into a handgun-type control unit with a joystick. The range of reach within each calyx was measured by four expert surgeons. RESULTS: The URF-Y0016 scope provided a greater range of reach along all directions in the lower pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p < 0.001), particularly along the anterior-posterior direction in the lower lobe calyx. However, the URF-Y0016 scope did not influence the improvement of reach range in the upper and middle pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p = 0.08, p = 0.296). CONCLUSION: The novel design of the URF-Y0016 could improve treatment outcomes for calyceal stones in the lower pole in practice.

A prospective study on symptom generation according to spicy food intake and TRPV1 genotypes in functional dyspepsia patients.

BACKGROUND: Capsaicin is an ingredient of red peppers that binds to transient receptor potential vanilloid subtype 1 (TRPV1), and Koreans eat more capsaicin-rich food than do Japanese. This study aimed to compare symptom generation according to TRPV1 genotypes and the intake of spicy foods. METHODS: Consecutive functional dyspepsia (FD) patients who were evaluated at Konkuk University Medical Centre (Korea) and Keio University Hospital (Japan) were included. Questionnaires on spicy food intake, patient assessment of gastrointestinal symptoms (PAGI-SYM), patient assessment of quality of life, and hospital anxiety and depression scale were provided. Blood was sampled for the detection of TRPV1 polymorphisms, and upper gastrointestinal endoscopy was performed with biopsies. KEY RESULTS: Of 121 included subjects, 35 and 28 carried the TRPV1 CC and GG genotypes, respectively, with the prevalence rates not differing between Japan and Korea. The prevalence of FD subtypes did not differ with the spicy food intake, TRPV1 genotypes, or Helicobacter pylori infection. Neither TRPV1 polymorphisms nor H. pylori infections were related to scores on the PAGI-SYM questionnaires, but spicy food intake was positively correlated with the scores for stomach fullness (p = 0.001) and retching (p = 0.001). Using the linear regression analysis, stomach fullness was associated with spicy food intake (p = 0.007), whereas retching was related to younger age (p < 0.001) and female gender (p = 0.014). CONCLUSIONS & INFERENCES: Upper gastrointestinal symptoms are more common in subjects with a higher consumption of spicy foods, younger age and female gender, regardless of TRPV1 genotypes and the H. pylori infection status. Capsaicin-rich foods may induce stomach fullness.

Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints.

T-cell trafficking at vascular sites has emerged as a key step in antitumour immunity. Chemokines are credited with guiding the multistep recruitment of CD8(+) T cells across tumour vessels. However, the multiplicity of chemokines within tumours has obscured the contributions of individual chemokine receptor/chemokine pairs to this process. Moreover, recent studies have challenged whether T cells require chemokine receptor signalling at effector sites. Here we investigate the hierarchy of chemokine receptor requirements during T-cell trafficking to murine and human melanoma. These studies reveal a non-redundant role for Gαi-coupled CXCR3 in stabilizing intravascular adhesion and extravasation of adoptively transferred CD8(+) effectors that is indispensable for therapeutic efficacy. In contrast, functional CCR2 and CCR5 on CD8(+) effectors fail to support trafficking despite the presence of intratumoral cognate chemokines. Taken together, these studies identify CXCR3-mediated trafficking at the tumour vascular interface as a critical checkpoint to effective T-cell-based cancer immunotherapy.

Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia--a multicenter, double-blind, randomized, placebo-controlled study.

BACKGROUND: Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large-scale, randomized, placebo-controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). METHODS: FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo-controlled, parallel-group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. KEY RESULTS: Two hundred forty-seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori-infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori-uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori-positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. CONCLUSIONS & INFERENCES: Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954).

Greater loss of productivity among Japanese workers with gastro-esophageal reflux disease (GERD) symptoms that persist vs resolve on medical therapy.

BACKGROUND: Gastro-esophageal reflux disease (GERD) impairs quality of life; however, the association between GERD and work productivity has not been well investigated in Japan. This study was designed to compare the impact of GERD on productivity between Japanese workers with GERD symptoms that persisted vs resolved on medical therapy. METHODS: A cross-sectional Web-based survey was conducted in workers. The impact of GERD on work and daily productivity was evaluated using a Web-reported Work Productivity and Activity Impairment Questionnaire for patients with GERD and a GERD symptom severity Questionnaire. Demographic information, clinical history, and satisfaction with GERD medication were also ascertained. KEY RESULTS: A total of 20 000 subjects were invited to the survey. After the exclusion of patients with a history of gastrointestinal (GI) malignancy, peptic ulcer, upper GI surgery, and unemployment, 650 participants were included in the analysis. Participants with persistent GERD symptoms reported a significantly greater losses of work productivity (11.4 ± 13.4 h/week), absenteeism (0.7 ± 3.1 h/week), presenteeism (10.7 ± 12.6 h/week), costs (20 100 ± 26 800 JPY/week), and lower daily productivity (71.3% [95% confidence interval, 69.0-73.7]) than those whose symptoms were alleviated with medications. The level of dissatisfaction with GERD medications among participants with persistent GERD symptoms was significantly correlated with loss of work and daily productivity (p < 0.001). CONCLUSIONS & INFERENCES: GERD places a significant burden on work and daily productivity despite medical therapy. Ineffective GERD therapy is associated with greater productivity loss.

CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence.

BACKGROUND: Multiple early gastric cancers (EGCs) may develop in 6-14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence. METHODS: Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed. RESULTS: The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71-83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30-18.8). CONCLUSION: CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.

Successful endovascular therapy of a penetrating zone III jugular bulb injury. A case report.

Penetrating venous injuries via Zone III of the neck extended over jugular bulb are rare. The optimal strategies for these venous injuries are currently unknown because many of the vital structures in this region are poorly accessible to the surgeon and therefore it is difficult to control bleeding. A 76-year-old man got drunk and fell down onto a paper door. The wooden framework of the paper door was broken and got stuck deep in the right side of his neck. Enhanced computed tomography showed the wood stick had penetrated through the right jugular foramen and injured the jugular bulb. We successfully performed right sigmoid and jugular vein occlusion via an endovascular approach using Guglielmi detachable coils at first and then to draw out the wood stick in order to avoid venous bleeding. To our best knowledge, these venous injuries have reported in only four cases. Only one case was performed by endovascular approach using n-butyl cyanoacrylate (NBCA). Coil embolization is much better than NBCA in the light of reducing complications due to adhesion to the inserted wood stick and embolization of unintended vessels. Venous occlusion using coil embolization is the best way to treat a penetrating jugular bulb injury via zone III because of reducing the hemorrhage and air embolism.

High frequency of overlap between functional dyspepsia and overactive bladder.

BACKGROUND: Overactive bladder syndrome (OAB) is defined as a symptom complex comprising urgency, with or without urge incontinence, and usually frequency and nocturia. The association between irritable bowel syndrome (IBS) and bladder symptoms has been reported. This study is designed to investigate whether functional dyspepsia (FD), like IBS, is associated with OAB. METHODS: A web surveys containing questions about OAB, FD, IBS, and demographics were completed by 5494 public individuals (2302 men and 3192 women) who have no history of severe illness. The prevalence and overlap of OAB, FD, and IBS were examined. KEY RESULTS: Among participants with FD, 20.5% could also be diagnosed with OAB (odds ratio [OR]: 2.85; 95% confidence interval [CI]: 2.21-3.67). Although concomitant FD and IBS were more strongly associated with OAB (OR: 4.34; 95% CI: 2.81-6.73), OAB was also highly prevalent among participants with FD but without IBS (OR: 3.09; 95% CI: 2.29-4.18). Among participants with FD, an overlapping OAB condition was more prevalent in those with both postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) (OR: 3.75; 95% CI: 2.48-5.67) than in those with PDS or EPS alone. Among participants with OAB, the severity of bladder symptoms was greater in participants with dyspeptic symptoms than without them. CONCLUSIONS & INFERENCES: Overactive bladder syndrome is common among FD patients, even if they do not have IBS. To improve FD patients' quality of life, it will be important to provide management for OAB.

Classification of functional dyspepsia based on concomitant bowel symptoms.

BACKGROUND: Functional dyspepsia (FD) is a heterogeneous disease, and categorized into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). However, many FD patients have overlap of both PDS and EPS. The present study was designed to examine whether FD could be categorized based on the presence of concomitant gastrointestinal symptoms. METHODS: A web survey comprised of the Gastrointestinal Symptom Rating Scale (GSRS), Rome III criteria of FD, and demographic information was sent to public participants who have no history of severe illness. Factor and cluster analyses were conducted to identify sub-categories of FD based on GSRS. KEY RESULTS: A total of 8038 participants completed the survey. A total of 563 participants met the criteria for FD, whereas 6635 participants did not have dyspepsia symptoms. The remainder had either organic disease (377) or uninvestigated dyspepsia (463). The cluster analysis categorized participants as constipation predominant (cluster C), diarrhea predominant (cluster D), or having neither diarrhea nor constipation (cluster nCnD). Cluster C and D were significantly associated with the presence of FD [odds ratio (OR) 2.57, 95% confidence interval (CI) 2.06-3.21; OR 2.80; 95% CI 2.27-3.45, respectively]. In FD, especially in PDS cases, the scores of upper gastrointestinal symptoms were higher in cluster C or D than in cluster nCnD. CONCLUSIONS & INFERENCES: The severity of dyspepsia symptoms is associated with the presence of bowel symptoms especially in PDS. This novel categorization of FD based on concomitant constipation or diarrhea may improve classification of patients.

Serum lipid levels are positively associated with non-erosive reflux disease, but not with functional heartburn.

BACKGROUND: Metabolic syndrome and obesity are known risk factors for gastro-esophageal reflux disease (GERD), especially for erosive esophagitis. Although non-erosive reflux disease (NERD) is probably associated with obesity or other metabolic syndrome, there is little direct evidence to support this assertion. METHODS: Workers in Keio University who underwent a general health examination between September 2006 and August 2007 were enrolled. Reflux symptom questionnaires were administered and metabolic parameters were obtained. The severity of gastro-esophageal reflux (GER) was scored using a validated scale of videoesophagography. KEY RESULTS: Two hundred and eighty-three subjects (243 men and 40 women; mean age 49.8 +/- 6.9 years) with no radiographic evidence of erosive esophagitis were enrolled. The severity of GER was worse among men than among women, whereas the severity of reflux symptoms was worse among women. The severity of GER was associated with age and serum triglyceride levels in men, and with the serum low-density lipoprotein cholesterol levels in women. The severity of reflux symptoms, however, was not associated with metabolic parameters. There were more women than men with reflux symptoms but without GER ('presumed' functional heartburn group), compared with subjects with neither GER nor reflux symptoms. In men, the presence of both reflux symptoms and GER ('presumed' NERD group) was associated with the serum triglyceride levels. CONCLUSIONS & INFERENCES: While NERD is associated with serum lipid levels, functional heartburn is not. The prevalence of GER was greater among men; conversely, the prevalence of functional heartburn was greater among women.

Delayed gastric emptying and disruption of the interstitial cells of Cajal network after gastric ischaemia and reperfusion.

BACKGROUND: Gastrointestinal tract is one of the most susceptible organ systems to ischaemia. Not only mucosal injury but also alterations of the intestinal motility and loss of interstitial cells of Cajal (ICC) have been reported in response to ischaemia and reperfusion (I/R). However, there are few reports on the changes in the gastric motility after gastric I/R. The present study was designed to investigate the alterations in gastric emptying, the ICC and enteric nerves that regulate smooth muscle function in response to gastric I/R. METHODS: Seven-week-old male Wistar rats were exposed to gastric I/R, and the gastric emptying rates at 12 and 48 h after I/R were evaluated by the phenol red method. Expressions of gene product of c-kit receptor tyrosine kinase (c-Kit), a marker of ICC, and of neuronal proteins were also examined. KEY RESULTS: Gastric emptying was transiently delayed at 12 h after I/R, but returned to normal by 48 h. Expression of c-Kit protein as assessed by Western blotting and immunofluorescent staining of the smooth muscle layer, as well as expression of the mRNA of stem cell factor, the ligand for c-Kit, were reduced at both 12 and 48 h after I/R. The expression of neuronal nitric oxide synthase (nNOS) protein as assessed by Western blotting and immunofluorescent staining was also decreased at 12 h after I/R, but was restored to normal by 48 h. CONCLUSIONS & INFERENCES: Gastric I/R evokes transient gastroparesis with delayed gastric emptying, associated with disruption of the ICC network and nNOS-positive neurons.

Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells.

Epigenetic therapy using DNA methylation inhibitors and histone deacetylase (HDAC) inhibitors has clinical promise for the treatment of human malignancies. To investigate roles of microRNAs (miRNAs) on epigenetic therapy of gastric cancer, the miRNA expression profile was analysed in human gastric cancer cells treated with 5-aza-2'-deoxycytidine (5-Aza-CdR) and 4-phenylbutyric acid (PBA). miRNA microarray analysis shows that most of miRNAs activated by 5-Aza-CdR and PBA in gastric cancer cells are located at Alu repeats on chromosome 19. Analyses of chromatin modification show that DNA demethylation and HDAC inhibition at Alu repeats activates silenced miR-512-5p by RNA polymerase II. In addition, activation of miR-512-5p by epigenetic treatment induces suppression of Mcl-1, resulting in apoptosis of gastric cancer cells. These results suggest that chromatin remodeling at Alu repeats plays critical roles in the regulation of miRNA expression and that epigenetic activation of silenced Alu-associated miRNAs could be a novel therapeutic approach for gastric cancer.

Post-secretion neutralization of transgene-derived effect: soluble erythropoietin receptor/IgG1Fc expressed in liver neutralizes erythropoietin produced in muscle.

BACKGROUND: The regulation of transgene expression is a key issue for the development of safe gene therapy. Various strategies have been used to regulate protein production at the levels of transgene expression, transcription, translation, and secretion. Neutralization following secretion is another important backup system to prevent super-therapeutic levels of a protein from being expressed by gene transfer. METHODS: We tested whether the soluble human erythropoietin receptor (EpoR)/IgG(1)Fc could neutralize the rat Epo at the post-secretory level and suppress erythrocytosis. RESULTS: To assess whether soluble human EpoR could bind rat Epo in vitro, we used the Epo-dependent human leukemic cell line, AS-E2. EpoR/IgG(1)Fc significantly inhibited the growth of AS-E2 cells in Epo-containing medium. To test this neutralization effect of EpoR/IgG(1)Fc in vivo, we first transferred pCAGGS-Epo into rat muscle by in vivo electroporation, confirmed erythropoiesis for 3 weeks, and then delivered EpoR/IgG(1)Fc by liver-targeted gene transfer via tail-vein injection with hydrodynamics-based transfection. Reticulocyte counts and hematocrit levels in rats that received pCAGGS-EpoR/IgG(1)Fc injections were significantly lower than in rats that received pCAGGS-EpoR, pCAGGS-IgG(1)Fc, or no injection. CONCLUSIONS: These results demonstrate that liver-targeted pCAGGS-EpoR/IgG(1)Fc transfer by tail-vein injection with hydrodynamics-based transfection is useful for neutralizing Epo delivered by in vivo electroporation. This backup strategy at the level of post-secretion could facilitate the clinical application of gene therapy in the future.

[Evaluation of usefulness of urinary nuclear matrix protein 22 (NMP22) in the detection of urothelial transitional cell carcinoma].

We evaluated the usefulness of urinary nuclear matrix protein 22 (NMP22) compared to urinary cytology in the detection of urothelial transitional cell carcinoma (TCC). Between July 1999 and March 2000, 227 patients complaining of microscopic or gross hematuria were analyzed. Twenty-four patients (10.6%) had urothelial TCC. The urinary NMP22 level was significantly higher in the patients with urinary TCC compared to the other patients. The sensitivity and specificity of the results obtained with urinary NMP22 were 58.3% and 84.2%, respectively, and those obtained by urinary cytology were 45.8% and 98.0%, respectively. False-positive results were obtained with urinary NMP22 in the patients with urinary diversion using intestine, bladder invasion from other cancers, urinary tract infection, and urolithiasis. The urinary NMP22 level was significantly associated with tumor stage, suggesting its usefulness for detection of urothelial TCC. However, although urinary NMP22 showed equal sensitivity for the detection of TCC, it was not superior to urinary cytology.

Inflammatory responses to lipopolysaccharide are suppressed in 40% energy-restricted mice.

To elucidate the suppressive effects of energy restriction on the inflammatory responses to lipopolysaccharide (LPS), mice were divided into a control group (fed 5.0 g diet/d; 71 kJ/d) and a 40% energy-restricted group (fed 3.0 g diet/d; 43 kJ/d) at 8-wk of age. Four weeks later, 25 microg of LPS was intraperitoneally injected. After the LPS injection, interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha were elevated in serums in the 40% energy-restricted mice and in the controls, but the extent of the elevation was significantly lower in the restricted group. The LPS-induced expression of inducible nitric oxide synthase in the liver was significantly suppressed by the energy restriction. In addition, the LPS-induced elevations of serum aspartate and alanine aminotransferase activities, which are indexes of hepatic injury, were also significantly attenuated in the restricted group. Moreover, the extent of LPS-induced alterations in hepatic structure was less in the restricted mice than in controls. Serum corticosterone level in the restricted mice was higher than that in the controls before LPS treatment (P < 0.05). Furthermore, after LPS injection, the significantly higher level of corticosterone was maintained in the restricted mice, although the LPS treatment significantly enhanced the level even in the control group. These results suggest that the extreme inflammatory responses to endotoxin are prevented in the 40% energy-restricted mice, and corticosterone participates in the preventive effects.

[Clinicopathological study of influential factors on prognosis in patients with renal cell carcinoma].

Between January 1986 and August 1996, 120 patients were diagnosed with renal cell carcinoma (RCC) at Kanagawa Cancer Center. In this study, we analyzed these patients in view of the clinicopathological factors, which affect the prognosis of these patients with univariate and multivariate analysis using Cox's proportional hazard model. Of these 120 patients, 40 patients (33%) died of RCC during this period. The cause specific survival rate was 65% after 5 years and 57% after 10 years. Univariate analysis showed some factors, performance status, symptoms, tumor size, histological grade, local invasion (pT), venous involvement (pV), lung metastasis, lymph-node metastasis, and bone metastasis, affected the prognosis. Furthermore, multivariate analysis using Cox's proportional hazard model showed that performance status, pT, pV, lung metastasis, lymphnode metastasis, and bone metastasis independently affected the prognosis. In summary, TMN factors and performance status importantly affect the prognosis of RCC patients.

[A survey of radical surgery without neoadjuvant therapy for patients with stage B and C prostatic carcinoma].

There has been much controversy regarding radical surgery for both localized and locally extensive carcinoma of the prostate. We analyzed the outcome of radical prostatectomy and the preoperative evaluation in order to assess the indication of radical prostatectomy. Fifty-six patients with clinical stage B or C prostate cancer were treated by radical prostatectomy without neoadjuvant therapy. Endocrine therapy was added to the non-curative cases postoperatively. Preoperative evaluation was compared with pathological results and survival, and furthermore the usefulness of the preoperative PSA and PSA half-life were investigated. The mean follow-up period was 44.5 months. The accuracy of the grade and the clinical stage were 58.9% and 23.2%, respectively. Organ-confined disease was seen in patients with an initial PSA level less than 30 ng/ml. Postoperative PSA half-life is significantly prolonged in cases with poorly differentiated adenocarcinoma or lymph node involvement and may be a predictor of PSA failure. The cause-specific 5-year survival rates were 92.7% on the whole, 92.9% for well differentiated, 96.7% for moderately differentiated, 85.7% for poorly differentiated, 100% for stage B1, 95.0% for stage B2 and 86.8% for stage C. These results indicated that patients with an initial PSA level of less than 30 ng/ml will benefit from radical prostatectomy.

Beneficial effects of immediate enteral nutrition after esophageal cancer surgery.

This study was conducted to determine the effects of immediate enteral nutrition (EN) on nutritional status, immunological competence, and the suppression of excessive inflammatory responses in patients following esophageal cancer surgery. Twenty-four patients who underwent the same elective operation for thoracic esophageal carcinoma were randomized into an immediate enteral nutrition (IEN) group who received EN from postoperative day (POD) 1 and a parenteral nutrition (PAN) group. Both groups received comparable volumes and calories on the same POD. Laboratory studies were carried out preoperatively and on PODs 1-7. Other nutritional and immunological assessments were repeated on PODs 1 and 7. Plasma concentrations of nitrate and nitrite were also measured. All of the patients in the IEN group tolerated enteral feeding well. There were no significant differences in the results of nutritional assessments, lymphocyte function, or plasma nitrate and nitrite levels between the two groups. The IEN group showed a significantly earlier recovery of the total lymphocyte count. The serum levels of total bilirubin and C-reactive protein were significantly attenuated in the IEN group. These results indicate that immediate EN may have beneficial effects on immunological competence and the suppression of excessive inflammatory responses in patients following esophagectomy. Patients undergoing radical esophageal surgery who are subjected to severe surgical stress might benefit the most from early EN.

Increases in gastric histidine decarboxylase activity and plasma gastrin level in streptozotocin-induced type 1 diabetic rats.

When type 1 diabetes mellitus was induced in rats by injecting streptozotocin, histidine decarboxylase expression was abnormally up-regulated in a transcriptional level, and 7 d after the injection, the enzyme activity was increased about 3-fold over the control (p < 0.05). When the diabetic rats were administered with insulin for 3 d, the increased histidine decarboxylase activity returned to a normal level in addition to normalization of the plasma glucose level. The plasma gastrin level in the fasting state was also significantly elevated in the diabetic rats, and the insulin treatment normalized the level. In the diabetic rats, fasting gastric acid output increased significantly and gastric pH was lowered. These results suggest that the gastric histidine decarboxylase activity and plasma gastrin level are increased in connection with the depletion of insulin in streptozotocin-induced diabetic rats, and gastric acid secretion is stimulated at a basal level, presumably due to increases in the concentrations of histamine and gastrin in oxyntic mucosa.

Interleukin-6 family of cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes.

This study was designed to investigate whether angiotensin II induces the interleukin (IL)-6 family of cytokines in cardiac fibroblasts and, if so, whether these cytokines can augment cardiac hypertrophy. Angiotensin II increased IL-6, leukemia inhibitory factor (LIF) and cardiotrophin-1 mRNA by 6.5-, 10.2-, and 2.0-fold, respectively, but did not affect IL-11, ciliary neurotrophic factor, or oncostatin M in cardiac fibroblasts. Enzyme-linked immunosorbent assay revealed that angiotensin II-stimulated conditioned medium from cardiac fibroblasts contained 9.3 ng/ml IL-6 at 24 h, which was 24-fold higher than the control. It phosphorylated gp130 and STAT3 in cardiomyocytes, which was reduced with RX435 (anti-gp130 blocking antibody). It increased [(3)H]phenylalanine uptake and cell area by 44% and 86% in cardiomyocytes compared with mock medium. RX435 suppressed these increases by 26% and 38%, while TAK044 (endothelin-A/B-R blocker) suppressed them by 52% and 52%, respectively. Antisense oligonucleotides against LIF and cardiotrophin-1 blocked their up-regulation, and attenuated the conditioned medium-induced increase in [(3)H]phenylalanine uptake by 21% and 13%, respectively. The combination of antisense oligonucleotides to LIF and cardiotrophin-1 decreased their uptake by 33%. These results indicated that angiotensin II induced IL-6, LIF, and cardiotrophin-1 in cardiac fibroblasts, and that these cytokines, particularly LIF and cardiotrophin-1, activated gp130-linked signaling and contributed to angiotensin II-induced cardiomyocyte hypertrophy.