Febrile Urinary Tract Infection after Radical Cystectomy and Ileal Neobladder in Patients with Bladder Cancer.

PubMed

Kim, Kwang Hyun; Yoon, Hyun Suk; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Lee, Dong Hyeon

2016-07-01

Urinary tract infection (UTI) is one of the most common complications after radical cystectomy and orthotopic neobladder reconstruction. This study investigated the incidence and implicated pathogen of febrile UTI after ileal neobladder reconstruction and identify clinical and urodynamic parameters associated with febrile UTI. From January 2001 to May 2015, 236 patients who underwent radical cystectomy and ileal neobladder were included in this study. Fifty-five episodes of febrile UTI were identified in 46 patients (19.4%). The probability of febrile UTI was 17.6% and 19.8% at 6 months and 24 months after surgery, respectively. While, Escherichia coli was the most common implicated pathogen (22/55, 40.0%), Enterococcus spp. were the most common pathogen during the first month after surgery (18/33, 54.5%). In multivariate logistic regression analysis, ureteral stricture was an independent risk factor associated with febrile UTI (OR 5.93, P = 0.023). However, ureteral stricture accounted for only 6 episodes (10.9%, 6/55) of febrile UTI. Most episodes of febrile UTI occurred within 6 months after surgery. Thus, to identify risk factors associated with febrile UTI in the initial postoperative period, we assessed videourodynamics within 6 months after surgery in 38 patients. On videourodyamic examination, vesicoureteral reflux (VUR) was identified in 16 patients (42.1%). The rate of VUR presence in patients who had febrile UTI was not significantly different from those in patients without febrile UTI (50% vs. 39.3%, P = 0.556). Patients with febrile UTI had significantly larger residual urine volume (212.0 ± 193.7 vs. 90.5 ± 148.2, P = 0.048) than those without. E. coli and Enterococcus spp. are common pathogens and ureteral stricture and residual urine are risk factors for UTI after ileal neobladder reconstruction.

Newly Designed Y-configured Single-Catheter Stenting for the Treatment of Hilar-Type Nonanastomotic Biliary Strictures After Orthotopic Liver Transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Changming; Li Xuan, E-mail: lixuanbysy@163.com; Song Shibing

2012-02-15

Purpose: This study was designed to introduce our novel technique of percutaneous single catheter placement into the hilar bile ducts strictures while fulfilling the purpose of bilateral biliary drainage and stenting. We investigated the efficacy and safety of the technique for the treatment of hilar nonanastomotic biliary strictures. Methods: Ten patients who were post-orthotopic liver transplantation between July 2000 and July 2010 were enrolled in this study. Percutaneous Y-configured single-catheter stenting for bilateral bile ducts combined with balloon dilation was designed as the main treatment approach. Technical success rate, clinical indicators, complications, and recurrent rate were analyzed. Results: Technical successmore » rate was 100%. Nine of the ten patients had biochemical normalization, cholangiographic improvement, and clinical symptoms relief. None of them experienced recurrence in a median follow-up of 26 months after completion of therapy and removal of all catheters. Complications were minor and limited to two patients. The one treatment failure underwent a second liver transplantation but died of multiple system organ failure. Conclusions: Percutaneous transhepatic Y-configured single-catheter stenting into the hilar bile ducts is technically feasible. The preliminary trial of this technique combined with traditional PTCD or choledochoscopy for the treatment of hilar biliary strictures after orthotopic liver transplantation appeared to be effective and safe. Yet, further investigation is needed.« less

Orthotopic neo- bladder in women.

PubMed

Schettini, Manlio

2010-12-01

Radical cystectomy is the most effective treatment madality for high grade urinary bladder carcinoma and orthotopic reconstruction is the better urinary diversion modality also in women. From 2002 to 2007 we performed 14 radical cystectomies followed by orthotopic reconstruction in women aged between 47 and 68 years (mean age 56) affected by urinary bladder carcinoma. Our reconstructive technique requires the preparation of two strips of the recti muscles fascia, the sectioning of the bladder neck and, when the uterus is present, hysteroannessiectomy and cystectomy en block leaving intact the lateral and inferior vaginal walls. The pelvic floor is stabilized by a colposacropexis with a prosthesis and placing an omental flap over the prosthesis. The orthotopic reconstruction is achieved via a neobladder according to the Padovana technique. The ureters are anastomized to the neobladder and splinted with single J stents. The pathological examination demonstrated in all patients the presence of a high grade carcinoma (G3): more specifically 4 patients had a full thickness intramural infiltration (T2), 2 patients had involvment of the perivescical fat (T3) ad 8 patients were in T1 stage. Lymphnodes were negative for tumour (NO). In 8 patients blood transfusions were necessary to treat post surgical anemia. No significant intra-, peri- or post operative complications were noted. The mean follow-up was 45 months: a patient died for diffuse metastatic disease after 11 months. The remaining patients are still alive and report normal lifestyle: 10 with normal micturition and 4 with urinary retention treated with intermittent self-catetherization. Two patients report nocturnal incontinence treated with hourly micturition and one pad. The five patients who had normal preoperative sexual intercourse resumed a normal sexual activity. The possibility to orthotopically recontruct the female urinary bladder has been established long time after the introduction of orthotopic

Postoperative gastrointestinal bleeding after an orthotopic liver transplant: a single-center experience.

PubMed

Fidan, Cihan; Kırnap, Mahir; Akdur, Aydıncan; Özçay, Figen; Selçuk, Haldun; Arslan, Gülnaz; Moray, Gökhan; Haberal, Mehmet

2014-03-01

The overall incidence, causes, and treatment of posttransplant gastrointestinal bleeding, have been previously described. In this study, we examined the causes and treatment of postoperative gastrointestinal bleeding after orthotopic liver transplant. Clinical data of 335 patients who underwent an orthotopic liver transplant at our institution between September 2001 and December 2012 were analyzed retrospectively. The diagnosis and treatment of postoperative gastrointestinal bleeding after an orthotopic liver transplant were reviewed. Gastrointestinal bleeding occurred in 13 patients (3.8%) after an orthotopic liver transplant. Five patients (38.4%) were adult and 8 patients (61.6%) were pediatric. The sites of the bleeding were Roux-en-Y anastomosis bleeding in 5 cases, peptic ulcer in 3 cases, erosive gastritis in 3 cases, gastric and esophageal varices in 1 case, and hemobilia in 1 case. These 13 patients with gastrointestinal bleeding were managed with conservative treatment, endoscopic treatment, radiologic interventional embolism, or exploratory laparotomy. No patients died because of gastro--intestinal bleeding. During follow-up, 4 patients died because of sepsis and 1 patient died of recurrence of hepatocellular carcinoma. Gastrointestinal bleeding after liver transplant and its incidence, causes, and treatment are not well-described in the literature. Diagnosis and management of gastrointestinal bleeding requires a multidisciplinary approach involving surgeons, hepatologists, advanced and experienced endoscopists, and interventional radiologists.

Ileal conduit vs orthotopic neobladder: Which one offers the best health-related quality of life in patients undergoing radical cystectomy? A systematic review of literature and meta-analysis.

PubMed

Ziouziou, I; Irani, J; Wei, J T; Karmouni, T; El Khader, K; Koutani, A; Iben Attya Andaloussi, A

2018-04-01

Orthotopic neobladder (ONB) and ileal conduit (IC) are the most commonly practiced techniques of urinary diversion (UD) after radical cystectomy (RC) in bladder cancer patients. Data in the literature is still discordant regarding which UD technique offers the best HR-QoL. The objective was to compare HR-QoL in patients undergoing ONB and IC after RC, through a systematic review of the literature and meta-analysis. We performed a literature search of PubMed, ScienceDirect, CochraneLibrary and ClinicalTrials.Gov in September 2017 according to the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes. The studies were evaluated according to the "Oxford Center for Evidence-Based Medicine" criteria. The outcome measures evaluated were subdomains' scores of Bladder Cancer Index BCI: urinary function (UF), urinary bother (UB), bowel function (BF), bowel bother (BB), sexual function (SF) and sexual bother (SB). Continuous outcomes were compared using weighted means differences, with 95% confidence intervals. The presence of publication bias was examined by funnel plots. Four studies met the inclusion criteria. The pooled results demonstrated better UF and UB scores in IC patients: differences were -18.17 (95% CI: -27.49, -8.84, P=0.0001) and -3.72 (95% CI: -6.66, -0.79, P=0.01) respectively. There was no significant difference between IC and ONB patients in terms of BF and BB. SF was significantly better in ONB patients: the difference was 12.7 (95% CI, 6.32, 19.08, P<0.0001). However no significant difference was observed regarding SB. This meta-analysis of non-randomized studies demonstrated a better HR-QoL in urinary outcomes in IC patients compared with ONB patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Ileal brake activation: macronutrient-specific effects on eating behavior?

PubMed

van Avesaat, M; Troost, F J; Ripken, D; Hendriks, H F; Masclee, A A M

2015-02-01

Activation of the ileal brake, by infusing lipid directly into the distal part of the small intestine, alters gastrointestinal (GI) motility and inhibits food intake. The ileal brake effect on eating behavior of the other macronutrients is currently unknown. The objective of this study was to investigate the effects of ileal infusion of sucrose and casein on food intake, release of GI peptides, gastric emptying rate and small-bowel transit time with safflower oil as positive control. This randomized, single-blind, crossover study was performed in 13 healthy subjects (6 male; mean age 26.4±2.9 years; mean body mass index 22.8±0.4 kg m(-2)) who were intubated with a naso-ileal catheter. Thirty minutes after the intake of a standardized breakfast, participants received an ileal infusion, containing control ((C) saline), safflower oil ((HL) 51.7 kcal), low-dose casein ((LP) 17.2 kcal) or high-dose casein ((HP) 51.7 kcal), low-dose sucrose ((LC) 17.2 kcal) and high-dose sucrose ((HC) 51.7 kcal), over a period of 90 min. Food intake was determined during an ad libitum meal. Visual analogue score questionnaires for hunger and satiety and blood samples were collected at regular intervals. Ileal infusion of lipid, protein and carbohydrate resulted in a significant reduction in food intake compared with control (HL: 464.3±90.7 kcal, P<0.001; HP: 458.0±78.6 kcal, P<0.005; HC: 399.0±57.0 kcal, P<0.0001 vs control: 586.7±70.2 kcal, P<0.001, respectively). A reduction in energy intake was still apparent when the caloric amount of infused nutrients was added to the amount eaten during the ad libitum meal.Secretion of cholecystokinin and peptide YY but not of glucagon-like peptide-1 (7-36) was increased during ileal perfusion of fat, carbohydrates and protein. During ileal perfusion of all macronutrients, a delay in gastric emptying and intestinal transit was observed, but differences were not significant compared with control. Apart from lipids, also

Health information quality on the internet for bladder cancer and urinary diversion: a multi-lingual analysis.

PubMed

Corfield, Julia M; Abouassaly, Robert; Lawrentschuk, Nathan

2018-04-01

Bladder cancer patients undergoing radical cystectomy and urinary diversion are faced with difficult decisions regarding mode of urinary diversion. Although these patients may use the Internet as a guide to diagnosis and treatment options, online resources remain largely unregulated leading to a great variation in quality of medical information. Further variation in quality is seen between languages. Fortunately, tools such as an automated toolbar developed by the World Health Organization Health on the Net (HON) Foundation exist to assist physicians in recommending quality online health information to patients. We set out to compare and assess the quality of bladder cancer, ileal conduit and orthotopic neobladder web sites in 2016 on the basis of the HON principles for English language. The Google search engine imbedded with the HON toolbar was used to assess 1350 Web sites using the keywords "bladder cancer", "ileal conduit" and "orthotopic neobladder" in English, Italian and Spanish. The first 150 results of each search were identified and screened. A further analysis was completed comparing results between 2009 and 2016. Less than 20% of English, Italian and Spanish "bladder cancer" and urinary diversion ("ileal conduit" and "orthotopic neobladder") web sites are HON-accredited. HON-accredited web sites featured preferentially in the first 50 search results for bladder cancer (P=0.0001) and ileal conduit (P=0.03) web sites. Comparing 2016 results to 2009, percentage of HON-accreditation has not shown statistically significant change (-13%, P=0.23), while overall number of search results has increased (+44%). A lack of validation of bladder cancer sites is present, which is consistent across modes of urinary diversion (orthotopic neobladder and ileal conduit) and languages. It is important that physicians involved in the care of bladder cancer patients undergoing radical cystectomy and urinary diversion participate in the development of informative, ethical, and

The influence of copper concentration and source on ileal microbiota.

PubMed

Pang, Y; Patterson, J A; Applegate, T J

2009-03-01

Copper is normally supplemented in poultry diets as a growth promotant and antimicrobial. However, there are conflicting reports about the growth benefits and little information about how Cu affects the microbiota in the intestinal tract of poultry. Therefore, in vitro and in vivo experiments were conducted with broilers to determine the effects of Cu source and supplementation on ileal microbiota. The influence of Cu on growth of lactobacilli and Escherichia coli in media inoculated with ileal contents was determined in the first study. When Cu sulfate pentahydrate was supplemented to the cultures, quadratic increases in lactobacilli to graded concentrations of Cu up to 125 mg/kg and quadratic decreases in E. coli up to 250 mg/kg of Cu were observed after 24 h of incubation at 37 degrees C. However, when tribasic Cu chloride (TBCC) was supplemented, neither linear nor quadratic responses to graded concentrations of dietary Cu were observed on number of lactobacilli or number of E. coli. The effects of Cu and Cu source on ileal microbiota and growth performance in broiler chickens were determined in the second study. Bird performance was not affected by Cu source or concentration. The bacterial culture enumeration results revealed that supplementation with 187.5 mg/kg of Cu from Cu sulfate pentahydrate and TBCC had no effect on number of ileal lactobacilli of birds. The denaturing gradient gel electrophoresis analyses of ileal microbial communities revealed that neither Cu supplementation nor source had effects on the number of bacterial species predominant in the ileal digesta or associated with the ileal mucosa. Supplementation with TBCC supplementation significantly increased the similarity coefficients of microbiota in the ileal mucosa compared with cross-products of all individuals. This suggests that TBCC may alter the intestinal microbiota, yet this shift had no effect on bird performance.

SeHCAT absorption: a simple test of ileal dysfunction.

PubMed

Fagan, E A; Chadwick, V S; Baird, I M

1983-01-01

A new selenium-labelled synthetic bile salt SeHCAT (taurine conjugate of 23-[75Se]-25-homocholic acid) was assessed as a test of ileal dysfunction in 20 patients with inflammatory bowel disease (IBD). Whole body retention of SeHCAT was compared with tests of vitamin B12 absorption (Schilling test and whole body retention) and the cholylglycine-1-14C breath test and faecal isotope excretion. Clear differentiation, with no overlap was obtained between 10 normal subjects and patients with ileal disease/resection in the SeHCAT 7-day retention results. The Schilling test was more sensitive; enabling discrimination between patients with limited and extensive ileal disease/resection. An unexpected rise in SeHCAT retention was observed in patients with colonic IBD. The 7-day SeHCAT retention is a safe, simple screening test for ileal dysfunction and has practical advantages compared with the Schilling test.

Cluster analysis identifies three urodynamic patterns in patients with orthotopic neobladder reconstruction.

PubMed

Kim, Kwang Hyun; Yoon, Hyun Suk; Song, Wan; Choo, Hee Jung; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Lee, Dong Hyeon

2017-01-01

To classify patients with orthotopic neobladder based on urodynamic parameters using cluster analysis and to characterize the voiding function of each group. From January 2012 to November 2015, 142 patients with bladder cancer underwent radical cystectomy and Studer neobladder reconstruction at our institute. Of the 142 patients, 103 with complete urodynamic data and information on urinary functional outcomes were included in this study. K-means clustering was performed with urodynamic parameters which included maximal cystometric capacity, residual volume, maximal flow rate, compliance, and detrusor pressure at maximum flow rate. Three groups emerged by cluster analysis. Urodynamic parameters and urinary function outcomes were compared between three groups. Group 1 (n = 44) had ideal urodynamic parameters with a mean maximal bladder capacity of 513.3 ml and mean residual urine volume of 33.1 ml. Group 2 (n = 42) was characterized by small bladder capacity with low compliance. Patients in group 2 had higher rates of daytime incontinence and nighttime incontinence than patients in group 1. Group 3 (n = 17) was characterized by large residual urine volume with high compliance. When we examined gender differences in urodynamics and functional outcomes, residual urine volume and the rate of daytime incontinence were only marginally significant. However, females were significantly more likely to belong to group 2 or 3 (P = 0.003). In multivariate analysis to identify factors associated with group 1 which has the most ideal urodynamic pattern, age (OR 0.95, P = 0.017) and male gender (OR 7.57, P = 0.003) were identified as significant factors. While patients with ileal neobladder present with various voiding symptoms, three urodynamic patterns were identified by cluster analysis. Approximately half of patients had ideal urodynamic parameters. The other two groups were characterized by large residual urine and small capacity bladder with low compliance. Young age and male

Our Experiences with Robot-Assisted Laparoscopic Radical Cystectomy: Orthotopic Neobladder by the Suprapubic Incision Method

PubMed Central

Cho, Byung Chul; Jung, Ha Bum; Cho, Sung Tae; Kim, Ki Kyung; Han, Jun Hyun; Lee, Yong Seong

2012-01-01

Purpose To report our technique for and experience with robot-assisted laparoscopic radical cystectomy (RARC) with orthotopic neobladder (ON) formation in a cohort of bladder cancer patients. Materials and Methods Between December 2007 and December 2011, a total of 35 patients underwent RARC. The patients' mean age was 63.3 years and their mean body mass index was 23.7 kg/m2. Thirty patients had a clinical stage of T2 or higher. Postoperative mean follow-up duration was 25.5 months. In 5 patients, a 4-cm midline infraumbilical skin incision was made for an ileal conduit (IC) and the stoma formation was similar to the open procedure. In 30 patients undergoing the ON procedure, the skin for specimen removal and extracorporeal enterocystoplasty was incised infraumbilically in the early 5 cases with redocking (ON-I) and suprapubically in the latter 25 cases without redocking (ON-S). Results The mean operative times of the IC, ON-I, and ON-S groups were 442.5, 646.0, and 531.3 minutes, respectively (p=0.001). Mean console and lymph node dissection time were not significantly different between the groups. Mean urinary diversion times in each group were 68.8, 125.0, and 118.8 minutes, respectively (p=0.001). In the comparison between the ON-I and ON-S group, only operative time was significant. Four patients required a blood transfusion. We had no cases of intraabdominal organ injury or open conversion. Thiry-three patients (94.2%) had a pathologic stage of T2 or higher. Two patients (5.7%) had lymph node-positive disease. Postoperative complications included ileus (n=4), stricture in the uretero-ileal junction (n=2), and vesicovaginal fistula (n=1). Conclusions Our robotic neobladder-suprapubic incision without redocking procedure is easier and more rapid than that of infraumbilical incision with redocking. PMID:23185668

Under pressure: a contribution to the pathogenesis of acquired ileal atresia

PubMed Central

Houben, C H; Lo, A W I; Tsui, S Y; Chan, K W

2013-01-01

An acquired ileal atresia is a rare occurrence. A 3-week-old neonate is presented, who developed postnatally a type 2 ileal atresia and an ileal stenosis within a pre-existing internal hernia secondary to an adhesion band. The literature reports a total of eight cases (4 females) with acquired ileal atresia in babies ranging in age from 3 weeks to 2 years (median 4 months). Mechanical forces (eg, adhesion band, intussusception and volvulus) onto the intestine are most frequently (75%) implicated as the primary event. The distal ileum is most often affected and a type 3A atresia is identified in six of eight (75%) cases. PMID:24225736

Inclusion of dietary β-mannanase improves performance and ileal digestibility and reduces ileal digesta viscosity of broilers fed corn-soybean meal based diet.

PubMed

Balasubramanian, B; Ingale, S L; Park, J Hong; Rathi, P C; Shanmugam, S; Kim, I H

2018-05-16

This study was aimed to evaluate the influence of dietary β-mannanase inclusion on growth performance, apparent ileal digestibility, digesta viscosity, blood metabolites and excreta noxious gas emissions in broilers fed corn-soybean meal based diet. A total of 600 conventional healthy 1-d-old ROSS 308 broilers with body weight 45 ± 0.50 g (mean ± SD) were randomly assigned to 4 dietary treatments with 10 replicates cages, with 15 broilers in each and fed basal diet supplemented to corn-SBM based diets with 0, 2400, 4800, and 7200 MNU β-mannanase/kg for 35 d feeding trial period. Significant results were observed on improved average daily gain and reduced feed conversion ratio during trial period and also reduced ileal digesta viscosity and improved apparent ileal digestibility of dry matter, nitrogen and energy. However, no significant effects were found on blood urea nitrogen and creatinine, excreta noxious gas emissions. In conclusion, the inclusion of dietary β-mannanase had potential to improve daily gain and feed efficiency and apparent ileal digestibility while decreasing digesta viscosity of broiler.

⁶⁸Ga-DOTA-TOC-PET/CT detects heart metastases from ileal neuroendocrine tumors.

PubMed

Calissendorff, Jan; Sundin, Anders; Falhammar, Henrik

2014-09-01

Metastases from ileal neuroendocrine tumors (NETs) to the myocardium are rare and generally seen in patients with widespread metastatic NET disease. The objectives of this investigation were to describe the frequency of intracardiac metastases in ileal NET patients examined by (68)Ga-DOTA-TOC-PET/CT and to describe the cases in detail. All (68)Ga-DOTA-TOC-PET/CT examinations performed at the Karolinska University Hospital since 2010 until April 2012 were reviewed. In all, 128 out of 337 examinations were in patients with ileal NETs. Four patients had seven myocardiac metastases, yielding a frequency of 4.3 % in patients with ileal NETs. One patient had cardiac surgery while three were treated with somatostatin analogs. The cardiac metastases did not affect the patients' activity of daily life. (68)Ga-DOTA-TOC-PET/CT is an established imaging modality in identifying cardiac metastases in ileal NETs. Prospective studies are needed to confirm the true clinical value of (68)Ga-DOTA-TOC-PET/CT in detecting cardiac metastases in both ileal and non-ileal NETs.

True ileal amino acid digestibility and endogenous ileal amino acid losses in growing pigs fed wheat shorts- or casein-based diets.

PubMed

Libao-Mercado, A J; Yin, Y; van Eys, J; de Lange, C F M

2006-06-01

Use of dietary AA in growing pigs reflects digestion and use of digested AA for various body functions. Before evaluating dietary effects on use of digestible AA intake for body protein deposition, a digestibility study was conducted to investigate true ileal AA digestibility and endogenous ileal AA losses in growing pigs fed graded levels of wheat shorts (WS) or casein (CS; control). A casein-based basal diet (basal) was formulated to contain 0.27 g of standardized ileal digestible (SID) Lys per MJ of DE, to which extra Lys was added from WS (WS2, +0.10 g of SID Lys per MJ of DE; WS3, +0.20 g of SID Lys per MJ of DE) or casein (CS3, +0.20 g of SID Lys per MJ of DE). A fifth diet was formulated to be similar in CP level and source as CS3 but in which 6% pectin, a source of soluble non-starch polysaccharides (NSP), was included at the expense of cornstarch (CS3 + pectin). Five Yorkshire barrows (17.5 +/- 1.5 kg of BW) were fitted with a T-cannula at the distal ileum and randomly assigned to 1 of the 5 experimental diets in a 5 x 5 Latin Square design. Apparent ileal digestibility (AID), true ileal digestibility (TID), and endogenous ileal protein losses (EPL) were determined using the homoarginine method. Diet CS level did not influence (P > or = 0.10) TID of most essential AA or EPL (10.4 g/kg of DM intake). Including pectin in the diet did not influence TID of AA (P > or = 0.10) but increased EPL (15.6 g/kg of DM intake; P > or = 0.01). Inclusion of WS in the diet reduced TID of most essential AA (P < 0.01). The TID values for most essential AA, however, were the same (P > or = 0.10) for both dietary WS levels, except for Lys and Met, which were further reduced at the greatest dietary WS level. Increased EPL (P < 0.01) was only observed for WS3 (16 g/kg of DMI). We concluded that (1) the effects of dietary protein source on AID of AA can be attributed both to reduced TID of AA and increased EPL, (2) the impact of dietary WS level on TID of AA and EPL does not seem

Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

PubMed

Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G

2018-01-01

Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

Microbiota-derived butyrate suppresses group 3 innate lymphoid cells in terminal ileal Peyer's patches.

PubMed

Kim, Sae-Hae; Cho, Byeol-Hee; Kiyono, Hiroshi; Jang, Yong-Suk

2017-06-21

The regional specialization of intestinal immune cells is affected by the longitudinal heterogeneity of environmental factors. Although the distribution of group 3 innate lymphoid cells (ILC3s) is well characterized in the lamina propria, it is poorly defined in Peyer's patches (PPs) along the intestine. Given that PP ILC3s are closely associated with mucosal immune regulation, it is important to characterize the regulatory mechanism of ILC3s. Here, we found that terminal ileal PPs of specific pathogen-free (SPF) mice have fewer NKp46 + ILC3s than jejunal PPs, while there was no difference in NKp46 + ILC3 numbers between terminal ileal and jejunal PPs in antibiotics (ABX)-treated mice. We also found that butyrate levels in the terminal ileal PPs of SPF mice were higher than those in the jejunal PPs of SPF mice and terminal ileal PPs of ABX-treated mice. The reduced number of NKp46 + ILC3s in terminal ileal PPs resulted in a decrease in Csf2 expression and, in turn, resulted in reduced regulatory T cells and enhanced antigen-specific T-cell proliferation. Thus, we suggest that NKp46 + ILC3s are negatively regulated by microbiota-derived butyrate in terminal ileal PPs and the reduced ILC3 frequency is closely associated with antigen-specific immune induction in terminal ileal PPs.

Two-dimensional networks of brominated Y-shaped molecules on Au(111)

NASA Astrophysics Data System (ADS)

Jeon, Un Seung; Chang, Min Hui; Jang, Won-Jun; Lee, Soon-Hyung; Han, Seungwu; Kahng, Se-Jong

2018-02-01

In the design of supramolecular structures, Y-shaped molecules are useful to expand the structures in three different directions. The supramolecular structures of Y-shaped molecules with three halogen-ligands on surfaces have been extensively studied, but much less are done for those with six halogen-ligands. Here, we report on the intermolecular interactions of a Y-shaped molecule, 1,3,5-Tris(3,5-dibromophenyl)benzene, with six Br-ligands studied using scanning tunneling microscopy (STM). Honeycomb-like structures were observed on Au(111), and could be explained with chiral triple-nodes made of three Br···Br halogen bonds. Molecular models were proposed based on STM images and reproduced with density-functional theory calculations. Although the molecule has six Br-ligands, only three of them form Br···Br halogen bonds because of geometrical restrictions. Our study shows that halogenated Y-shaped molecules will be useful components for building supramolecular structures.

Quality of life after Brooke ileostomy and ileal pouch-anal anastomosis. Comparison of performance status.

PubMed Central

Pemberton, J H; Phillips, S F; Ready, R R; Zinsmeister, A R; Beahrs, O H

1989-01-01

Although the clinical results of Brooke ileostomy are good, patients are permanently incontinent of stool and gas. Alternative operations designed to restore enteric continence, such as ileal pouch-anal anastomosis, must not only be as safe and effective as Brooke ileostomy, but should provide an improved quality of life in order to establish long-term acceptability. Ileal pouch-anal anastomosis has been performed safely and good functional results have been reported. The quality of life after ileal pouch-anal anastomosis, however, has not been documented. Two hundred ninety-eight ileal pouch patients and 406 Brooke ileostomy patients who had the operations performed for chronic ulcerative colitis or familial adenomatous polyposis formed the basis of the study. After adjusting for age, diagnosis, and reoperation rate, logistic regression analysis of performance scores in seven different categories was used to discriminate between operations. Median follow-up was longer in Brooke ileostomy patients than in ileal pouch patients (104 months vs. 47 months, respectively), and Brooke ileostomy patients were slightly older (38 years vs. 32 years). A great majority of patients in each group were satisfied (93% Brooke ileostomy; 95% ileal pouch-anal anastomosis). Thirty-nine per cent of Brooke ileostomy patients, however, desired a change in the type of ileostomy they had. At 47 months, ileal pouch patients had a median of 5 stools per day and 1 at night, 77% did not experience any daytime incontinence, while 22% reported occasional spotting. In each performance category, the performance score discriminated between operations, with the probability of having had an ileal pouch-anal anastomosis operation increasing with improvement in performance scores (p less than 0.05). We concluded that after ileal pouch-anal anastomosis, patients experienced significant advantages in performing daily activities compared to patients with Brooke ileostomy and thus may experience a better

Venous outflow obstruction and portopulmonary hypertension after orthotopic liver transplantation

PubMed Central

Aguirre-Avalos, Guadalupe; Covarrubias-Velasco, Marco Antonio; Rojas-Sánchez, Antonio Gerardo

2013-01-01

Patient: Female, 54 Final Diagnosis: Suprahepatic inferior vena cava anastomosis stricture Symptoms: Ascites • fatigue • lower limb edema • hepatomegaly Medication: — Clinical Procedure: — Specialty: Transplantology • Critical Care Medicine Objective: Unusual clinical course Background: Suprahepatic inferior vena cava anastomosis stricture is an unusual vascular complication after orthotopic liver transplantation with the “piggyback” technique. Clinical manifestations are dependent upon the severity of the stenosis. Portopulmonary hypertension after orthotopic liver transplantation is a complication that carries high mortality due to cardiopulmonary dysfunction. The pathogenesis of pulmonary vascular disorders after orthotopic liver transplantation remains uncertain. Case Report: We report a case of acute right heart pressure overload after surgical correction of the suprahepatic inferior vena cava anastomotic stricture in a 54-year-old woman who had preexisting pulmonary arterial hypertension associated with portal hypertension after orthotopic liver transplantation. Twenty months posttransplantation, she developed fatigue and progressive ascites. On admission, the patient had hepatomegaly, ascites, and lower limb edema. Symptoms in the patient developed gradually over time. Conclusions: Recurrent portal hypertension by vascular complications is a cause of pulmonary arterial hypertension after orthotopic liver transplantation. Clinical manifestations of suprahepatic inferior vena cava anastomotic stenosis are dependent upon their severity. Sildenafil is an effective drug for treatment of pulmonary arterial hyper-tension after portal hypertension by vascular complications. PMID:24046802

Prevalence, Cause, and Treatment of Respiratory Insufficiency After Orthotopic Heart Transplant.

PubMed

Savaş Bozbaş, Şerife; Ulubay, Gaye; Öner Eyüboğlu, Füsun; Sezgin, Atilla; Haberal, Mehmet

2015-11-01

Heart transplant is the best treatment for end-stage heart failure. Respiratory insufficiency after heart transplant is a potentially serious complication. Pulmonary complications, pulmonary hypertension, allograft failure or rejection, and structural heart defects in the donor heart are among the causes of hypoxemia after transplant. In this study, we evaluated the prevalence of hypoxemia and respiratory insufficiency in patients with orthotopic heart transplant during the early postoperative period. We retrospectively evaluated the medical records of 45 patients who had received orthotopic heart transplant at our center. Clinical and demographic variables and laboratory data were noted. Oxygen saturation values from patients in the first week and the first month after transplant were analyzed. We also documented the cause of respiratory insufficiency and the type of treatment. Mean age was 35.3 ± 15.3 years (range, 12-61 y), with males comprising 32 of 45 patients (71.1%). Two patients had mild chronic obstructive pulmonary disease and 1 had asthma. Twenty-five patients (55.6%) had a history of smoking. Respiratory insufficiency was noted in 9 patients (20%) during the first postoperative week. Regarding cause, 5 of these patients (11.1%) had pleural effusion, 2 (4.4%) had atelectasis, 1 (2.2%) had pneumonia, and 1 (2.2%) had acute renal failure. Therapies administered to patients with respiratory insufficiency were as follows: 5 patients had oxygen therapy with nasal canula/mask, 3 patients had continuous positive airway pressure, and 1 patient had mechanical ventilation. One month after transplant, 2 patients (4.4%) had respiratory insufficiency 1 (2.2%) due to pleural effusion and 1 (2.2%) due to atelectasis. Respiratory insufficiency is a common complication in the first week after orthotopic heart transplant. Identification of the underlying cause is an important indicator for therapy. With appropriate care, respiratory insufficiency can be treated

Infections After Orthotopic Liver Transplantation

PubMed Central

Pedersen, Mark; Seetharam, Anil

2014-01-01

Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. PMID:25755581

[Prevention of side effects and complications after operation for partial ileal bypass].

PubMed

Mirchuk, K K; Sedletskiĭ, Iu I

2014-01-01

Side effects and complications of the application of partial ileal bypass used for dislipidemia were analyzed in 162 patients with atherosclerosis. It was shown, that the partial ileal bypass operation could lead to the development of series of undesirable side effects such as diarrhea, hypovitaminosis B12, off-state intestine enteritis. The application of modification of partial ileal bypass such as formation of ileo-ileoanastomosis 5-6 cm long near ileocecal valve with the maintenance of its functions disposed the diarrhea and minimized the risk of the development of hypovitaminosis B12 after operation. It is possible to prevent the development of enteritis of off-state loop of the small intestine by using microanastomosis between off-state and functioning iliac intestine. The partial ileal bypass operation didn't influence on body weight, wouldn't increase the risk of stone formation in the gallbladder and kidneys. The risk of the development of hypovitaminosis B12 is minimal after operation.

A rare case of ileal metastasis from cervical cancer.

PubMed

Iliescu, L; David, L; Orban, C; Herlea, V; Toma, L

2014-01-01

We present the case of a 70-year-old woman, with a history of radiation-treated and surgically- resected cervical cancer, who was admitted to our clinic for intermittent sub occlusive symptoms. CT scan revealed a liver nodule and intestinal obstruction. The patient underwent surgery for excision of suspected liver metastasis and resolution of intestinal obstruction.Intraoperatively an ileal tumour was found to be the cause of the obstruction. Anatomo-pathological findings were consistent with an ileal metastasis from the cervical cancer.The liver nodule was only an area of focal steatosis. Celsius.

Total intracorporeal robot-assisted laparoscopic ileal conduit (Bricker) urinary diversion: technique and outcomes.

PubMed

Rehman, Jamil; Sangalli, Mattia N; Guru, Khurshid; de Naeyer, Geert; Schatteman, Peter; Carpentier, Paul; Mottrie, Alexander

2011-02-01

Several recent preliminary reports have demonstrated that Robot-Assisted Cystectomy with total intracorporeal Ileal Conduit (RACIC) is a feasible option over the open technique. We report our stepwise surgical procedure of robotic total intracorporeal ileal conduit urinary diversion, technical consideration, development, refinements and initial experience. Only the ileal conduit urinary diversion is described with no emphasis on the cystectomy's steps. Between February 2008 and September 2009, nine patients underwent RACIC for muscle invasive transitional cell carcinoma (TCC). The entire procedure, including radical cystoprostatectomy, extended pelvic node dissection (ePLND), ileal conduit urinary diversion (Bricker) including isolation of the ileal loop (20 cm ileal segment) 15 cm away from the ileocecal junction, restoration of bowel continuity with stapled side-to-side ileo-ileal anastomosis, retroperitoneal transfer of the left ureter to the right side, and bilateral stented (8 F feeding tube) ileo-ureteral anastomoses in a Wallace faction were all performed exclusively intracorporeally using the da Vinci Si surgical robot and finally the conduit stoma was fashioned. The RACIC was technically successful in all nine patients (three females and six males. Mean age 74.1; 57 to 87) without open conversion. The mean operative time including extended pelvic lymphadenectomy and urinary diversion was 346.2 minutes (210 to 480). Mean operative time of diversion is 72 minutes (52-113) mean estimated blood loss 258 mL (200 to 500) and the median hospital stay were 14 days (10 to 27). In all three female patients, the specimen was extracted through the vagina. There were no intraoperative complications and only one major postoperative complication: one postoperative iatrogenous necrosis of the ileal conduit caused by uncareful retraction of the organ bag and thereby probably injuring the conduit pedicle, as the ileal conduit was well vascularised at the end of the

Impaired absorption of marked oligopeptide Glycine-I Tyrosine-Glycine after successful autologous-allotopic ileal mucosa transplantation in beagles.

PubMed

Beiler, H A; Steinorth, J; Witt, A; Mier, W; Mohammed, A; Waag, K L; Zachariou, Z

2004-10-01

After establishing a method for ileal mucosa transplantation in an animal model, the authors investigated the absorptive capacity for oligopeptides of the transplanted mucosa. In 14 beagle dogs the authors transplanted ileal mucosa in a vascularized demucosed segment of the transverse colon. The colonic wall-ileal mucosa complex then was integrated in the ileal continuity. Six animals were lost owing to operative complications. Absorptive capacity for oligopeptides was measured in the remaining 8 animals with the iodine 131 (131I)-marked tripeptide glycine-tyrosine-glycine before and 4 weeks after transplantation. The results were compared and analyzed with the Student's t test for matched pairs. Blood concentrations of the marked tripeptide with P value less than .05 were considered as a significant reduction in the absorptive capacity of the transplanted ileal mucosa. After fixation with glutaraldehyd graft, uptake of the colonic wall-ileal mucosa complex was evaluated histologically in 8 animals. In all 8 animals, a 100% graft uptake was verified in all sections. Fifteen minutes after application of 15 MBc Glycine-131I-Tyrosine-Glycine there was no significant difference in the absorption between normal and transplanted ileal mucosa. After 30 minutes, the absorption of the transplanted ileal mucosa showed a tendency (P < .1) for an impaired uptake of the marked tripeptide. However, 60 minutes after application the difference in the absorptive capacity of the transplanted ileal mucosa was significant (P < .05). Autologous allotopic ileal mucosa transplantation is feasible; however, an impaired absorption of oligopeptides of the transplanted mucosa 4 weeks after transplantation could be observed.

Silencing Intersectin 1 Slows Orthotopic Neuroblastoma Growth in Mice.

PubMed

Harris, Jamie; Herrero-Garcia, Erika; Russo, Angela; Kajdacsy-Balla, Andre; O'Bryan, John P; Chiu, Bill

2017-11-01

Neuroblastoma accounts for 15% of all pediatric cancer deaths. Intersectin 1 (ITSN1), a scaffold protein involved in phosphoinositide 3-kinase (PI3K) signaling, regulates neuroblastoma cells independent of MYCN status. We hypothesize that by silencing ITSN1 in neuroblastoma cells, tumor growth will be decreased in an orthotopic mouse tumor model. SK-N-AS neuroblastoma cells transfected with empty vector (pSR), vectors expressing scrambled shRNA (pSCR), or shRNAs targeting ITSN1 (sh#1 and sh#2) were used to create orthotopic neuroblastoma tumors in mice. Volume was monitored weekly with ultrasound. End-point was tumor volume >1000 mm. Tumor cell lysates were analyzed with anti-ITSN1 antibody by Western blot. Orthotopic tumors were created in all cell lines. Twenty-five days post injection, pSR tumor size was 917.6±247.7 mm, pSCR was 1180±159.9 mm, sh#1 was 526.3±212.8 mm, and sh#2 was 589.2±74.91 mm. sh#1-tumors and sh#2-tumors were smaller than pSCR (P=0.02), no difference between sh#1 and sh#2. Survival was superior in sh#2-tumors (P=0.02), trended towards improved survival in sh#1-tumors (P=0.09), compared with pSCR-tumors, no difference in pSR tumors. Western blot showed decreased ITSN1 expression in sh#1 and sh#2 compared with pSR and pSCR. Silencing ITSN1 in neuroblastoma cells led to decreased tumor growth in an orthotopic mouse model. Orthotopic animal models can provide insight into the role of ITSN1 pathways in neuroblastoma tumorigenesis.

Fracture Property of Y-Shaped Cracks of Brittle Materials under Compression

PubMed Central

Zhang, Xiaoyan; Zhu, Zheming; Liu, Hongjie

2014-01-01

In order to investigate the properties of Y-shaped cracks of brittle materials under compression, compression tests by using square cement mortar specimens with Y-shaped crack were conducted. A true triaxial loading device was applied in the tests, and the major principle stresses or the critical stresses were measured. The results show that as the branch angle θ between the branch crack and the stem crack is 75°, the cracked specimen has the lowest strength. In order to explain the test results, numerical models of Y-shaped cracks by using ABAQUS code were established, and the J-integral method was applied in calculating crack tip stress intensity factor (SIF). The results show that when the branch angle θ increases, the SIF K I of the branch crack increases from negative to positive and the absolute value K II of the branch crack first increases, and as θ is 50°, it is the maximum, and then it decreases. Finally, in order to further investigate the stress distribution around Y-shaped cracks, photoelastic tests were conducted, and the test results generally agree with the compressive test results. PMID:25013846

Impact of a multicarbohydrase containing α-galactosidase and xylanase on ileal digestible energy, crude protein digestibility, and ileal amino acid digestibility in broiler chickens.

PubMed

Jasek, A; Latham, R E; Mañón, A; Llamas-Moya, S; Adhikari, R; Poureslami, R; Lee, J T

2018-06-08

Exogenous enzymatic supplementation of poultry feeds, including α-galactosidase and xylanase, has been shown to increase metabolically available energy, although little information has been published on the impact on amino acid digestibility. An experiment was conducted to investigate a multicarbohydrase containing α-galactosidase and xylanase on amino acid digestibility, ileal digestible energy (IDE), and CP in male broiler chicks. The experiment was a 2 × 2 (diet × enzyme) factorial arrangement with 15 replicates of 8 male broilers per replicate raised for 21 d in a battery setting. The 2 dietary treatments included a positive control (PC) and a negative control (NC) diet formulated to contain 2.5% less calculated AME and digestible amino acids. Each of these diets was fed with and without enzyme. Broilers were fed a starter diet from 0-14 d (crumble) and a grower from 14-21 d (pellet). Birds were sampled on day 21 to determine ileal amino acid digestibility, IDE, and CP digestibility. Titanium dioxide (TiO2) was used as an indigestible marker for the determination of digestibility coefficients. Total ileal amino acid digestibility was increased (P = 0.008) by 3.80% with the inclusion of enzyme. Methionine and lysine digestibility was improved (P < 0.05) with the inclusion of enzyme by 3.37% and 2.61%, respectively. Enzyme inclusion increased (P = 0.001) cysteine digestibility by 9.3%. Diet-influenced ileal amino acid digestibility with tryptophan, threonine, isoleucine, and valine digestibility being increased (P < 0.05) in the PC when compared to the NC. IDE was decreased (P = 0.037) in broilers fed the NC diet by 100 kcal/kg feed when compared to broilers fed the PC diet. Enzyme inclusion increased (P = 0.047) IDE value by 90 kcal/kg. Crude protein digestibility was not influenced by diet; however, similar improvements in CP digestibility with enzyme inclusion were observed as with energy. These data support the benefits of a multicarbohydrase containing �

Paradoxical Impact of Ileal Pouch-Anal Anastomosis on Male and Female Fertility in Patients With Ulcerative Colitis.

PubMed

Pachler, Frederik R; Brandsborg, Søren B; Laurberg, Søren

2017-06-01

Birth rates in males with ulcerative colitis and ileal pouch-anal anastomosis have not been studied. This study aimed to estimate birth rates in males and females with ulcerative colitis and study the impact of ileal pouch-anal anastomosis. This was a retrospective registry-based cohort study that was performed over a 30-year period. Records for parenting a child from the same period were cross-linked with patient records, and birth rates were calculated using 15 through 49 years as age limits. All data were prospectively registered. All patients with ulcerative colitis and ulcerative colitis with ileal pouch-anal anastomosis between 1980 and 2010 were identified in Danish national databases. The primary outcomes measured were birth rates in females and males with ulcerative colitis and ulcerative colitis with ileal pouch-anal anastomosis. We included 27,379 patients with ulcerative colitis (12,812 males and 14,567 females); 1544 had ileal pouch-anal anastomosis (792 males and 752 females). Patients with ulcerative colitis have slightly reduced birth rates (males at 40.8 children/1000 years, background population 43.2, females at 46.2 children/1000 years, background population 49.1). After ileal pouch-anal anastomosis, males had increased birth rates at 47.8 children/1000 years in comparison with males with ulcerative colitis without ileal pouch-anal anastomosis (40.5 children/1000 years), whereas females had reduced birth rates at 27.6 children/1000 years in comparison with females with ulcerative colitis without ileal pouch-anal anastomosis (46.8 children/1000 years). Only birth rates were investigated and not fecundability. Furthermore, there is a question about misattributed paternity, but this has previously been shown to be less than 5%. Ulcerative colitis per se has little impact on birth rates in both sexes, but ileal pouch-anal anastomosis surgery leads to a reduction in birth rates in females and an increase in birth rates in males. This has clinical

[Astigmatism after keratoplasty: influence of orthotopic transplantation].

PubMed

Feuerstacke, J; Hellwinkel, O; Naydis, I; Linke, S; Klemm, M

2014-09-01

Patients undergoing corneal transplantation often suffer from postoperative reduced vision due to high astigmatism. This retrospective study analyzed the influence of heterotopic or orthotopic transplantation on astigmatism and visual outcome. In this study 373 eyes of 334 patients were analyzed. Group 1 (OT) contained 186 eyes, which underwent orthotopic transplantation (side of recipient and donor corresponded), whereas group 2 (HT) included 187 heterotopic keratoplasties (donor cornea placed in the recipient's contralateral side). After 1, 3, 6, 12 and 24 months the median of keratometric astigmatism, objective astigmatism, topographic astigmatism and best corrected visual acuity (BCVA) were assessed and compared between groups. The long-term results showed no statistically significant differences regarding keratometric and objective astigmatism, whereas topographic astigmatism differed significantly (p = 0.04) after 3 months. We observed a lower astigmatism of 5.7 dpt (range 3.08-7.78 dpt) in group OT than in the group HT with 7.1 dpt (range 3.9-10.7 dpt). No differences were found at the other time points. The BCVA showed a significantly better effect after 1 month (p = 0.01) in the OT group of 0.2 (0.1-0.3) than in HT group of 0.1 (0.05/0.25). In the postoperative course no additional significant dissimilarities were documented. Heterotopic and orthotopic keratoplasty show no significant long-term differences in astigmatism and visual outcom.

Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hewitson, Laura; Thissen, James B.; Gardner, Shea N.

In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technologymore » was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae , Bacteroidaceae , and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.« less

Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

DOE PAGES

Hewitson, Laura; Thissen, James B.; Gardner, Shea N.; ...

2014-01-01

In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technologymore » was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae , Bacteroidaceae , and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.« less

Prolapse of inverted ileal loops through a patent vitellointestinal duct

PubMed Central

Pathak, Ashish; Agarwal, Nitin; Singh, Poonam; Dhaneria, Mamta

2015-01-01

We report a case of a prolapsed patent vitellointestinal duct (PVID) in a 2-month-old girl child who presented with sudden increase in size of a polypoidal lesion into a large, ‘Y’-shaped reddish, prolapsing lesion, discharging gaseous and faecal matter at her umbilicus. The lesion was diagnosed as a prolapse of inverted ileal loops through the PVID. The child had no associated congenital anomalies. A transumbilical exploration was performed, followed by wedge resection and anastomosis. The child tolerated the procedure well and the postoperative course was uneventful. If the omphalomesenteric duct fails to obliterate a range of congenital defects related to the umbilicus, it can become clinically apparent. Meckel's diverticulum is the commonest of these defects but is most often asymptomatic. PVID is the most common symptomatic anomaly of the patent omphalomesenteric duct and requires prompt surgical correction to avoid complications. PMID:26494719

Measurement of true ileal phosphorus digestibility in meat and bone meal for broiler chickens.

PubMed

Mutucumarana, R K; Ravindran, V; Ravindran, G; Cowieson, A J

2015-07-01

An experiment was conducted to estimate true ileal phosphorus (P:) digestibility of 3 meat and bone meal samples (MBM-1, MBM-2: , and MBM-3:) for broiler chickens. Four semipurified diets were formulated from each sample to contain graded concentrations of P. The experiment was conducted as a completely randomized design with 6 replicates (6 birds per replicate) per dietary treatment. A total of 432 Ross 308 broilers were assigned at 21 d of age to the 12 test diets. The apparent ileal digestibility coefficient of P was determined by the indicator method, and the linear regression method was used to determine the true P digestibility coefficient. The apparent ileal digestibility coefficient of P in birds fed diets containing MBM-1 and MBM-2 was unaffected by increasing dietary concentrations of P (P > 0.05). The apparent ileal digestibility coefficient of P in birds fed the MBM-3 diets decreased with increasing P concentrations (linear, P < 0.001; quadratic, P < 0. 01). In birds fed the MBM-1 and MBM-2 diets, ileal endogenous P losses were estimated to be 0.049 and 0.142 g/kg DM intake (DMI:), respectively. In birds fed the MBM-3 diets, endogenous P loss was estimated to be negative (-0.370 g/kg DMI). True ileal P digestibility of MBM-1, MBM-2, and MBM-3 was determined to be 0.693, 0.608, and 0.420, respectively. True ileal P digestibility coefficients determined for MBM-1 and MBM-2 were similar (P < 0.05), but were higher (P < 0.05) than that for MBM-3. Total P and true digestible P contents of MBM-1, MBM-2, and MBM-3 were determined to be 37.5 and 26.0; 60.2 and 36.6; and 59.8 and 25.1 g/kg, respectively, on an as-fed basis. © 2015 Poultry Science Association Inc.

Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

PubMed Central

2013-01-01

Background Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. Methods We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. Results TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. Conclusions We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies. PMID:23937707

Role of airway epithelial injury in murine orthotopic tracheal allograft rejection.

PubMed

Kuo, Elbert; Bharat, Ankit; Shih, Jennifer; Street, Tyler; Norris, Jenyi; Liu, Wei; Parks, William; Walter, Michael; Patterson, G Alexander; Mohanakumar, T

2006-10-01

Murine tracheal transplantation is a model used to study bronchiolitis obliterans syndrome, a major cause of morbidity and mortality after lung transplantation. Unlike murine heterotopic tracheal transplants, orthotopic transplantation does not cause luminal obliteration despite major histocompatibility antigen mismatch. Repopulation of the tracheal allografts with recipient-derived epithelium confers protection against luminal obliteration. The purpose of this study was to determine whether (1) orthotopic tracheal transplantation showed signs of allograft rejection, and (2) airway epithelial cell injury promoted orthotopic tracheal allograft rejection. Forty isogeneic (C57BL/6 to C57BL/6) and 40 allogeneic (BALB/c to C57BL/6) orthotopic tracheal transplants were performed. Damage to airway epithelial cells was induced by Sendai viral (SdV) infection and tracheal transplantation into non-reepithelializing matrix metalloproteinase-7 knockout (MMP7-KO) recipient mice. Percent fibrosis and lamina propria to cartilage ratio were calculated with computer assistance on harvested allografts. Allografts showed significantly more intramural fibrosis compared with isografts at 30, 60, and 180 days after transplant without luminal occlusion. Tracheal allografts infected with SdV showed an increase in fibrosis and lamina propria to cartilage ratio compared with noninfected controls. Allografts retrieved from MMP7-KO recipients also showed a significant increase in fibrosis and lamina propria to cartilage ratio. Although orthotopic tracheal transplantation does not cause luminal obliteration, it results in increased fibrosis in allografts. Damage to the respiratory epithelium by viral infection or defective reepithelialization after transplant as seen in MMP7-KO recipient mice leads to changes consistent with chronic allograft rejection, suggesting a role for epithelial injury in bronchiolitis obliterans syndrome development.

Robot-assisted intracorporeal ileal conduit: Marionette technique and initial experience at Roswell Park Cancer Institute.

PubMed

Guru, Khurshid; Seixas-Mikelus, Stéfanie A; Hussain, Abid; Blumenfeld, Aaron J; Nyquist, John; Chandrasekhar, Rameela; Wilding, Gregory E

2010-10-01

To present our technique and initial experience with patients who underwent robot-assisted intracorporeal creation of ileal conduit and to compare them with patients who underwent extracorporeal ileal diversion after robot-assisted radical cystectomy. Twenty-six patients diagnosed with invasive transitional cell carcinoma of the bladder underwent a robot-assisted radical cystectomy with bilateral extended pelvic lymphadenectomy with ileal conduit diversion. Total intracorporeal ileal conduit creation was performed in the last 13 patients. Operative data and short-term outcomes between the 2 groups were assessed. The novel surgical technique for intracorporeal ileal conduit will be presented. The intracorporeal group (IC) included 2 female and 11 male patients (mean age 71 years). The extracorporeal group (EC) included 4 female and 9 male patients (mean age 66 years). No significant differences were noted between the groups in terms of patient age, BMI, sex, prior surgery, or pathologic stage. Overall operative time and intraoperative complications were similar. No significant differences were noted between the 2 groups in terms of diversion time or estimated blood loss. There were 4 complications recorded in IC patients, including nonspecific colitis, small bowel obstruction requiring exploratory laparotomy with lysis of adhesions, a urine leak that eventually resolved but required a temporary nephrostomy tube, and a fever of unknown origin that resolved without intervention. Robot-assisted intracorporeal ileal conduit can be accomplished safely with acceptable operative times even during early experience. Larger series with favorable results will be required to add this new paradigm to minimally invasive surgery for bladder cancer. Copyright © 2010 Elsevier Inc. All rights reserved.

Establishment of a patient-derived orthotopic osteosarcoma mouse model.

PubMed

Blattmann, Claudia; Thiemann, Markus; Stenzinger, Albrecht; Roth, Eva K; Dittmar, Anne; Witt, Hendrik; Lehner, Burkhard; Renker, Eva; Jugold, Manfred; Eichwald, Viktoria; Weichert, Wilko; Huber, Peter E; Kulozik, Andreas E

2015-04-30

Osteosarcoma (OS) is the most common pediatric primary malignant bone tumor. As the prognosis for patients following standard treatment did not improve for almost three decades, functional preclinical models that closely reflect important clinical cancer characteristics are urgently needed to develop and evaluate new treatment strategies. The objective of this study was to establish an orthotopic xenotransplanted mouse model using patient-derived tumor tissue. Fresh tumor tissue from an adolescent female patient with osteosarcoma after relapse was surgically xenografted into the right tibia of 6 immunodeficient BALB/c Nu/Nu mice as well as cultured into medium. Tumor growth was serially assessed by palpation and with magnetic resonance imaging (MRI). In parallel, a primary cell line of the same tumor was established. Histology and high-resolution array-based comparative genomic hybridization (aCGH) were used to investigate both phenotypic and genotypic characteristics of different passages of human xenografts and the cell line compared to the tissue of origin. A primary OS cell line and a primary patient-derived orthotopic xenotranplanted mouse model were established. MRI analyses and histopathology demonstrated an identical architecture in the primary tumor and in the xenografts. Array-CGH analyses of the cell line and all xenografts showed highly comparable patterns of genomic progression. So far, three further primary patient-derived orthotopic xenotranplanted mouse models could be established. We report the first orthotopic OS mouse model generated by transplantation of tumor fragments directly harvested from the patient. This model represents the morphologic and genomic identity of the primary tumor and provides a preclinical platform to evaluate new treatment strategies in OS.

[Intestinal intussusception due to ileal gastrointestinal stromal tumor--a case report].

PubMed

Andrei, S; Andrei, A; Tonea, A; Andronesi, D; Preda, C; Herlea, V; Popescu, I

2011-01-01

Intestinal occlusion due to intussusception produced by intestinal tumors is a very rare condition. Gastrointestinal stromal tumors are also rare digestive neopasias, with an impredictable malignant behavior, which are usually growing outside the intestinal wall, being rarely the initiators of an intestinal intussusception. We present the case of a 59 years old female, admitted in our hospital to elucidate the etiology of her iron deficient anaemia, which developed an intestinal occlusion at the intestinal preparation for colonoscopy. The abdominal CT scan performed in emergency conditions highlighted occlusive intestinal tumor complicated with intestinal intussusception. We performed an emergency laparotomy that revealed intestinal occlusion due to ileo-ileal intussusception produced by an ileal tumor. The surgical intervention consisted in segmental ileal enterectomy including the tumor with latero-lateral entero-enteral anastomosis. The patient recovered without complications. The histopathological and immunohisto-chemical examinations established the diagnose of gastro-intestinal stromal tumor with high risk malignant behavior, therefore the patient was guided in the oncological department for specific treatment and oncological surveillance.

Orthotopic heart transplant versus left ventricular assist device: A national comparison of cost and survival

PubMed Central

Mulloy, Daniel P.; Bhamidipati, Castigliano M.; Stone, Matthew L.; Ailawadi, Gorav; Kron, Irving L.; Kern, John A.

2012-01-01

Objectives Orthotopic heart transplantation is the standard of care for end-stage heart disease. Left ventricular assist device implantation offers an alternative treatment approach. Left ventricular assist device practice has changed dramatically since the 2008 Food and Drug Administration approval of the HeartMate II (Thoratec, Pleasanton, Calif), but at what societal cost? The present study examined the cost and efficacy of both treatments over time. Methods All patients who underwent either orthotopic heart transplantation (n = 9369) or placement of an implantable left ventricular assist device (n = 6414) from 2005 to 2009 in the Nationwide Inpatient Sample were selected. The trends in treatment use, mortality, and cost were analyzed. Results The incidence of orthotopic heart transplantation increased marginally within a 5-year period. In contrast, the annual left ventricular assist device implantation rates nearly tripled. In-hospital mortality from left ventricular assist device implantation decreased precipitously, from 42% to 17%. In-hospital mortality for orthotopic heart transplantation remained relatively stable (range, 3.8%–6.5%). The mean cost per patient increased for both orthotopic heart transplantation and left ventricular assist device placement (40% and 17%, respectively). With the observed increase in both device usage and cost per patient, the cumulative Left ventricular assist device cost increased 232% within 5 years (from $143 million to $479 million). By 2009, Medicare and Medicaid were the primary payers for nearly one half of all patients (orthotopic heart transplantation, 45%; left ventricular assist device, 51%). Conclusions Since Food and Drug Administration approval of the HeartMate II, mortality after left ventricular assist device implantation has decreased rapidly, yet has remained greater than that after orthotopic heart transplantation. The left ventricular assist device costs have continued to increase and have been

Primary Segmental Volvulus Mimicking Ileal Atresia

PubMed Central

Rao, Sadashiva; B Shetty, Kishan

2013-01-01

Neonatal intestinal volvulus in the absence of malrotation is a rare occurrence and rarer still is the intestinal volvulus in absence of any other predisposing factors. Primary segmental volvulus in neonates is very rare entity, which can have catastrophic outcome if not intervened at appropriate time. We report two such cases, which were preoperatively diagnosed as ileal atresia and intraoperatively revealed to be primary segmental volvulus of the ileum. PMID:26023426

Gross and true ileal digestible amino acid contents of several animal body proteins and their hydrolysates.

PubMed

Cui, J; Chong, B; Rutherfurd, S M; Wilkinson, B; Singh, H; Moughan, P J

2013-07-01

Amino acid compositions of ovine muscle, ovine myofibrillar protein, ovine spleen, ovine liver, bovine blood plasma, bovine blood globulins and bovine serum albumin and the amino acid compositions and in vivo (laboratory rat) true ileal amino acid digestibilities of hydrolysates (sequential hydrolysis with Neutrase, Alcalase and Flavourzyme) of these protein sources were determined. True ileal amino acid digestibility differed (P<0.05) among the seven protein hydrolysates. The ovine myofibrillar protein and liver hydrolysates were the most digestible, with a mean true ileal digestibility across all amino acids of 99%. The least digestible protein hydrolysate was bovine serum albumin with a comparable mean true ileal digestibility of 93%. When the digestible amino acid contents were expressed as proportions relative to lysine, considerable differences, across the diverse protein sources, were found in the pattern of predicted absorbed amino acids. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ileal inflammatory fibroid polyp causing chronic ileocolic intussusception and mimicking cecal carcinoma

PubMed Central

Gara, Naveen; Falzarano, John S; Limm, Whitney ML; Namiki, Thomas S; Tom, Laurie KS

2009-01-01

Inflammatory fibroid polyp (IFP) is a rare, idiopathic pseudotumorous lesion of the gastrointestinal tract. While mostly reported as solitary gastric lesions, multiple cases of small bowel IFPs are also reported. It is a documented cause of intussusception in adults. In the case reports of ileal inflammatory fibroid polyps with intussusception, an emergent presentation with small bowel obstruction has been most often described. Here we depict a case of ileal inflammatory fibroid polyp presenting with chronic intermittent ileocolic intussusception, anemia and weight loss with an endoscopic appearance mimicking necrotic cecal carcinoma. PMID:21160780

Development of an In Vivo and In Vitro Ileal Fermentation Method in a Growing Pig Model.

PubMed

Montoya, Carlos A; de Haas, Edward S; Moughan, Paul J

2018-02-01

Substantial microbial fermentation may occur mainly in the lower small intestine (SI) of human adults, but there is no established methodology to determine this. The study aimed to develop a combined in vivo and in vitro methodology for ileal fermentation based on the pig as an animal model for digestion in human adults. Several aspects of a combined in vivo/in vitro ileal fermentation assay were evaluated. Male 9-wk-old pigs (n = 30; mean ± SD body weight: 23 ± 1.6 kg) were fed a human-type diet (143, 508, 45, 49, and 116 g/kg dry matter diet of crude protein, starch, total lipid, ash, and total dietary fiber) for 15 d. On day 15, pigs were killed, and the last third of the SI was collected to prepare an ileal digesta-based inoculum. Terminal jejunal digesta (last 50 cm of the second third of the SI) were collected as substrate for the assay to test the form of substrate (fresh or freeze-dried), origin (location in jejunum or SI) of the substrate, storage of the inoculum, incubation time (1.2-6.8 h), pH of the medium, and inoculum concentration (6-26 mg inoculum/100 mg substrate). The group of donor pigs used to prepare the inoculum, form of the substrate, origin of the substrate, origin of the inoculum (location in the SI), storage of the inoculum, incubation time, and inoculum concentration did not influence the in vitro ileal organic matter (OM) fermentability (P > 0.05). The in vitro ileal OM fermentability decreased when the pH of the medium increased from 5.5 to 7.5 (31% to 28%; P ≤ 0.05). Predicted (in vivo/in vitro) apparent ileal OM digestibility was similar to the value measured in vivo. Thirty-percent of the terminal jejunal digesta OM was fermented in the ileum. Fiber fermentation in the ileum can be studied using the optimized in vivo/in vitro ileal fermentation method.

Laparoscopic proctocolectomy with ileal j-pouch anal anastomosis in children.

PubMed

Ateş, Ufuk; Ergün, Ergun; Göllü, Gülnur; Küçük, Gönül; Yağmurlu, Aydın

2017-09-01

We aimed to evaluate postoperative fecal incontinence scales of children who underwent laparoscopic proctocolectomy and ileal J-pouch anastomosis for familial adenomateous polyposis (FAP) and inflammatory bowel disease (IBD). Fecal incontinence scores were collected at 3 months post-surgery. A retrospective chart review was also performed to obtain the demographic data and operative technical details. The postoperative Wexner Fecal Incontinence Score was 0 in 9 of 11 patients and satisfactory in the remaining two. None of the children had a major complication. Even though the presented study does not have any comparable data, it seems that laparoscopic total proctocolectomy with ileal J-pouch anal anastomosis (TP IPAA) might be the best choice of surgery because it provides good continence with low complication rates.

Study of the effect of ileal distension on the motor activity of the jejunum, and of jejunal distension on the motor activity of the ileum.

PubMed

Shafik, Ahmed; Shafik, Ali A; El, Sibai Olfat; Shafik, Ismail A

2007-01-01

The effect of ileal distension on the jejunal motor activity and ofjejunal distension on the ileal motility have been poorly addressed in the literature. We investigated the hypothesis that distension of either ileum or jejunum would affect the motile activity of the other. Response of jejunal pressure to ileal balloon distension and of ileal pressure to jejunal distension in increments of 2 mL of normal saline were recorded in 18 dogs. The test was performed after individual local anesthetization of the ileum and jejunum and was repeated using saline instead of lidocaine. Ileal distension with 2, 4, and 6mL of saline produced no jejunal pressure response (p >0.05), while 8- and up to 12-mL distension effected jejunal pressure decrease (p<0.05). Jejunal distension up to 6mL did not change ileal pressure (p>0.05); distension with 8, 10, and 12 mL reduced it (p<0.05). Jejunal or ileal pressure responses were maintained as long as ileal or jejunal distension was continued. Distension of the anesthetized ileum or jejunum did not produce significant pressure changes in either. Jejunal or ileal pressure decrease and presumably hypotonia upon large-volume ileal or jejunal, respectively, distension postulate reflex relationship which we call 'ileal-jejunal and jejuno-ileal inhibitory reflex'. These reflexes appear to regulate chyme flow in small intestine by creating a balance of chyme delivery between the jejunum and ileum. Reflex derangement in neurogenic and myogenic diseases may result in gastrointestinal disorders, a point that needs to be investigated.

Successful Embolization of Bleeding Ileal Varices with N-butyl Cyanoacrylate via a Recanalized Paraumbilical Vein.

PubMed

Onishi, Yasuyuki; Kimura, Hiroyuki; Kanagaki, Mitsunori; Oka, Shojiro; Fukumoto, Genki; Otani, Tomoaki; Matsubara, Naoko; Kawabata, Kazuna; Namikawa, Mio; Matsumura, Takeshi; Kimura, Toshiyuki

2018-04-23

A 48-year-old woman with alcoholic liver cirrhosis was admitted to our hospital because of hematochezia and severe anemia. She had been hospitalized many times over the past year for hematochezia of unknown etiology. Contrast-enhanced CT demonstrated ileal varices, which were fed by several ileal veins. These feeding veins were selectively embolized with N-butyl cyanoacrylate (NBCA) via a recanalized paraumbilical vein. The paraumbilical vein instead of the portal vein was punctured to decrease the risk of bleeding complications because she had coagulopathy and ascites. We consider antegrade embolization of ileal varices with NBCA to be a feasible and effective treatment. Access via a paraumbilical vein is an alternative to the transhepatic approach.Level of Evidence Level V, case report.

Ileal Varices Treated with Balloon-Occluded Retrograde Transvenous Obliteration.

PubMed

Sato, Takahiro; Yamazaki, Katsu; Toyota, Jouji; Karino, Yoshiyasu; Ohmura, Takumi; Akaike, Jun

2009-04-01

A 55-year-old man with hepatitis B virus antigen-positive liver cirrhosis was admitted to our hospital with anal bleeding. Colonoscopy revealed blood retention in the entire colon, but no bleeding lesion was found. Computed tomography images showed that vessels in the ileum were connected to the right testicular vein, and we suspected ileal varices to be the most probable cause of bleeding. We immediately performed double balloon enteroscopy, but failed to find any site of bleeding owing to the difficulty of fiberscope insertion with sever adhesion. Using a balloon catheter during retrograde transvenous venography, we found ileal varices communicating with the right testicular vein (efferent vein) with the superior mesenteric vein branch as the afferent vein of these varices. We performed balloon occluded retrograde transvenous obliteration by way of the efferent vein of the varices and have detected no further bleeding in this patient one year after treatment.

Incidence and Patient Outcomes in Renal Replacement Therapy After Orthotopic Liver Transplant.

PubMed

Ayhan, Asude; Ersoy, Zeynep; Ulas, Aydin; Zeyneloglu, Pinar; Pirat, Arash; Haberal, Mehmet

2017-02-01

Our objective was to evaluate the incidence of renal replacement therapy after orthotopic liver transplant and to evaluate and analyze patient outcomes. We performed a retrospective analysis of 177 consecutive patients at a tertiary care unit who underwent orthotopic liver transplant between January 2010 and June 2016. Patients who were admitted to the intensive care unit after orthotopic liver transplant and who required renal replacement therapy were included. A total of 177 (79 adult, 98 pediatric) orthotopic liver transplants were performed during the study period. Of these, 35 patients (19%) required renal replacement therapy during the early posttransplantation period. After excluding 5 patients with previous chronic renal failure, 30 patients (17%; 20 adult [25% ], 10 pediatric [10% ]) with acute kidney injury required renal replacement therapy. The mean patient age was 31.1 ± 20.0 years, with a mean Model for End-stage Liver Disease score of 16.7 ± 12.3. Of the patients with acute kidney injury who underwent renal replacement therapy, in-hospital mortality was 23.3% (7 of 30 patients), and 40% remained on dialysis. No significant difference was seen in mortality between early versus delayed initiation of renal replacement therapy in patients with stage 3 acute kidney injury (P = .17). Of liver transplant recipients who present with acute kidney injury, 19% require renal replacement therapy, and in-hospital mortality is 20% in the early postoperative period.

Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

PubMed Central

ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

2015-01-01

Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

Ferret lung transplant: an orthotopic model of obliterative bronchiolitis.

PubMed

Sui, H; Olivier, A K; Klesney-Tait, J A; Brooks, L; Tyler, S R; Sun, X; Skopec, A; Kline, J; Sanchez, P G; Meyerholz, D K; Zavazava, N; Iannettoni, M; Engelhardt, J F; Parekh, K R

2013-02-01

Obliterative bronchiolitis (OB) is the primary cause of late morbidity and mortality following lung transplantation. Current animal models do not reliably develop OB pathology. Given the similarities between ferret and human lung biology, we hypothesized an orthotopic ferret lung allograft would develop OB. Orthotopic left lower lobe transplants were successfully performed in 22 outbred domestic ferrets in the absence of immunosuppression (IS; n = 5) and presence of varying IS protocols (n = 17). CT scans were performed to evaluate the allografts. At intervals between 3-6 months the allografts were examined histologically for evidence of acute/chronic rejection. IS protects allografts from acute rejection and early graft loss. Reduction of IS dosage by 50% allowed development of controlled rejection. Allografts developed infiltrates on CT and classic histologic acute rejection and lymphocytic bronchiolitis. Cycling of IS, to induce repeated episodes of controlled rejection, promoted classic histologic hallmarks of OB including fibrosis-associated occlusion of the bronchiolar airways in all allografts of long-term survivors. In conclusion, we have developed an orthotopic lung transplant model in the ferret with documented long-term functional allograft survival. Allografts develop acute rejection and lymphocytic bronchiolitis, similar to humans. Long-term survivors develop histologic changes in the allografts that are hallmarks of OB. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Measurement of true ileal digestibility of phosphorus in some feed ingredients for broiler chickens.

PubMed

Mutucumarana, R K; Ravindran, V; Ravindran, G; Cowieson, A J

2014-12-01

An experiment was conducted to estimate the true ileal digestibility of P in wheat, sorghum, soybean meal, and corn distiller's dried grains with solubles (DDGS) in broiler chickens. Four semipurified diets were formulated from each ingredient (wheat and sorghum: 236.5, 473, 709.5, and 946 g/kg; soybean meal and corn DDGS: 135, 270, 405, and 540 g/kg) to contain graded concentrations of nonphytate P. The experiment was conducted as a randomized complete block design with 4 weight blocks of 16 cages each (5 birds per cage). A total of 320 21-d-old broilers (Ross 308) were assigned to the 16 test diets with 4 replicates per diet. Apparent ileal digestibility coefficients of P were determined by the indicator method and the linear regression method was used to determine the true P digestibility coefficients. The results showed that the apparent ileal P digestibility coefficients of wheat-based diets were not influenced (P>0.05) by increasing dietary P concentrations, whereas those of diets based on sorghum, soybean meal, and corn DDGS differed (P<0.05) at different P concentrations. Apparent ileal P digestibility in broilers fed diets with soybean meal and corn DDGS linearly (P<0.001) increased with increasing P concentrations. True ileal P digestibility coefficients of wheat, sorghum, soybean meal, and corn DDGS were determined to be 0.464, 0.331, 0.798, and 0.727, respectively. Ileal endogenous P losses in birds fed diets with wheat, soybean meal, and corn DDGS were estimated to be 0.080, 0.609, and 0.418 g/kg DMI, respectively. In birds fed sorghum-based diets, endogenous P losses were estimated to be negative (-0.087 g/kg DMI). True digestible P contents of wheat, sorghum, soybean meal, and corn DDGS were determined to be 1.49, 0.78, 5.16, and 5.94 g/kg, respectively. The corresponding nonphytate P contents in wheat, sorghum, soybean meal, and corn DDGS were 1.11, 0.55, 2.15, and 4.36 g/kg, respectively. These differences between digestible P and nonphytate P

Infections Complicating Orthotopic Liver Transplantation

PubMed Central

Schröter, Gerhard P. J.; Hoelscher, Manfred; Putnam, Charles W.; Porter, Kendrick A.; Hansbrough, John F.; Starzl, Thomas E.

2011-01-01

In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant. PMID:793568

Postnatal development and lymphocyte production of jejunal and ileal Peyer's patches in normal and gnotobiotic pigs.

PubMed Central

Pabst, R; Geist, M; Rothkötter, H J; Fritz, F J

1988-01-01

The development of the number, size, structure and proliferative capacity of Peyer's patches (PP) in the jejunum and ileum has been studied during the early postnatal period of conventional and germ-free pigs. A mean of 15 discrete PP in the jejunum and upper ileum (jejPP) were counted at birth, and the number increased only gradually. A continuous PP is located in the terminal ileum (ileal PP). The length of both jejPP and ileal PP increased with age due to the increase in follicle size and in the number of follicles in the ileal PP. In older pigs, only the ileal PP regressed to small scattered follicles. In germ-free piglets at 39 and 59 days of age, longer PP were found than in normal new-born piglets, but they were significantly shorter than in age-matched controls. Lymphocyte production was studied by the metaphase-arrest technique using vincristine. Lymphocyte production in follicles increased dramatically with age, while in other compartments, such as the inter-follicular and dome area, a low age-independent production of lymphocytes was found. There were no differences in lymphocytopoiesis between jejPP and ileal PP. The present data show major differences in the development, structure and function of PP in pigs in comparison to other species. These species-specific aspects are important for future studies on the immunological function of PP. Images Figure 1 Figure 5 PMID:3410497

[Comparative study on laparoscopic vaginoplasty using pedicled ileal and sigmoid colon segment transfer].

PubMed

Zhang, Dawei; Zhang, Jun; Wang, Huanying; Li, Bin; Zhu, Xiaoxing; Wang, Liying; Wu, Jixiang

2014-03-01

To study the clinical effect of laparoscopic vaginoplasty using pedicled ileal and sigmoid colon segment. From January 2004 to December 2009, 105 cases undergoing laparoscope-assisted vaginoplasty using a vascularized pedicled intestinal flap were studied retrospectively. Operation time, blood loss in operating, bowel movement after operation, postoperation hospital duration, side effect, and artificial vagina were compared between two surgical management. The vaginoplasty were preformed successfully in all 105 cases. There were 48 patients treated by aparoscope-assisted ileal vaginoplasty and 57 patients treated by laparoscope-assisted sigmoid colon vaginoplasty. The values of the operation time [(141 ± 22) minutes versus (159 ± 18) minutes, P = 0.000], blood loss in operating [(42 ± 6) ml versus (83 ± 14) ml, P = 0.000], bowel movement after operation (36 ± 9) hours versus (68 ± 8) hours(P = 0.000), and postoperation hospital duration [(9.8 ± 2.0) days versus (11.1 ± 1.3) days, P = 0.004] in the sigmoid colon vaginoplasty group were longer or higher than those in ileal vaginoplasty group (P < 0.05).No intraoprative complication occurred. There were four postoperative complications: 2 cases with intestinal obstruction in sigmoid colon vaginoplasty group, 1 case with urethral orifice stenosis and 1 case with vaginal-rectal fistula in ileal vaginoplasty group. At follow-up of 6-62 months, all artificial vaginas had a capacity of over two fingers in wideness and 12-15 cm in length. Vaginal discharges resembled a milky white water or mucus without odour. Fifty-five patients with sexual intercourse reported satisfactory results.Six patients complained vaginal stenosis:5 patients in ileal vaginoplasty group and 1 patient in sigmoid colon vaginoplasty group. Laparoscope-assisted vaginoplasty using pedicled ileum or sigmoid colon segment are both the effective ways in forming vagina. The latter management takes more time and blood loss while operating, yet the

Ileal Varices Treated with Balloon-Occluded Retrograde Transvenous Obliteration

PubMed Central

Sato, Takahiro; Yamazaki, Katsu; Toyota, Jouji; Karino, Yoshiyasu; Ohmura, Takumi; Akaike, Jun

2009-01-01

A 55-year-old man with hepatitis B virus antigen-positive liver cirrhosis was admitted to our hospital with anal bleeding. Colonoscopy revealed blood retention in the entire colon, but no bleeding lesion was found. Computed tomography images showed that vessels in the ileum were connected to the right testicular vein, and we suspected ileal varices to be the most probable cause of bleeding. We immediately performed double balloon enteroscopy, but failed to find any site of bleeding owing to the difficulty of fiberscope insertion with sever adhesion. Using a balloon catheter during retrograde transvenous venography, we found ileal varices communicating with the right testicular vein (efferent vein) with the superior mesenteric vein branch as the afferent vein of these varices. We performed balloon occluded retrograde transvenous obliteration by way of the efferent vein of the varices and have detected no further bleeding in this patient one year after treatment. PMID:27956966

OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models

PubMed Central

Shi, Jun; Wei, Pin-Kang; Zhang, Shen; Qin, Zhi-Feng; Li, Jun; Sun, Da-Zhi; Xiao, Yan; Yu, Zhi-Hong; Lin, Hui-Ming; Zheng, Guo-Jing; Su, Xiao-Mei; Chen, Ya-Lin; Liu, Yan-Fang; Xu, Ling

2008-01-01

AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS: Using OB glue paste technique, orthotopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS: The success rates of orthotopic transplan-tation of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION: OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors. PMID:18720543

EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

PubMed

Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

2011-03-01

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

The influence of soy oligosaccharides on apparent and true ileal amino acid digestibilities and fecal consistency in growing pigs.

PubMed

Smiricky, M R; Grieshop, C M; Albin, D M; Wubben, J E; Gabert, V M; Fahey, G C

2002-09-01

Fourteen ileally cannulated pigs (BW = 35 +/- 2 kg) were randomly allotted to a replicated 7 x 7 Latin square design experiment to evaluate the influence of the soybean oligosaccharides (OS), raffinose and stachyose, on ileal nutrient digestibility and fecal consistency. Semipurified diets containing soy protein concentrate (SPC) or soybean meal (SBM) as the sole protein sources were fed. Soy solubles (SS), a by-product of SBM processing containing 3.5% raffinose and 11.5% stachyose, were used to increase dietary raffinose and stachyose concentrations. The seven dietary treatments were SPC, SPC + 9% SS, SBM, SBM + 9% SS, SBM + 18% SS, SBM + 24,000 U alpha-galactosidase enzyme preparation/kg diet, and a low-protein casein (LPC) diet used to calculate true digestibility. Diets, with the exception of the LPC diet, were formulated to contain 17% CP. All diets contained 0.5% chromic oxide as a marker for ileal digestibility determination. The experimental periods were divided into a 5-d diet adaptation followed by 2-d of ileal digesta collection. Diets and digesta were analyzed for DM, N, Cr, amino acids (AA), raffinose, and stachyose. Fecal consistency was determined on d 6 and 7 of each experimental period. The apparent and true ileal AA digestibilities were not different (P < 0.05) for the SPC and SBM control diets. When SS was added to the SPC diet, apparent and true N and AA digestibilities were depressed (P < 0.05) with the exception of Trp and Pro. The apparent and true ileal N and AA digestibilities were not different (P > 0.05) between the SBM control and SBM + 9% SS diets with the exception of Glu. There was a linear decrease (P < 0.05) in apparent and true DM, Val, Gly, and Tyr digestibilities when increasing levels of SS were added to the SBM diet. The addition of alpha-galactosidase did not improve apparent or true ileal N or AA digestibilities except for apparent and true Val and Tyr. Ileal raffinose digestibility was improved (P < 0.05) by addition of a

Ileal transposition surgery produces ileal length-dependent changes in food intake, body weight, gut hormones and glucose metabolism in rats.

PubMed

Ramzy, A R; Nausheen, S; Chelikani, P K

2014-03-01

Enhanced stimulation of the lower gut is hypothesized to play a key role in the weight loss and resolution of diabetes following bariatric surgeries. Ileal transposition (IT) permits study of the effects of direct lower gut stimulation on body weight, glucose homeostasis and other metabolic adaptations without the confounds of gastric restriction or foregut exclusion. However, the underlying mechanisms and the length of the ileum sufficient to produce metabolic benefits following IT surgery remain largely unknown. To determine the effects of transposing varying lengths of the ileum to upper jejunum on food intake, body weight, glucose tolerance and lower gut hormones, and the expression of key markers of glucose and lipid metabolism in skeletal muscle and adipose tissue in rats. Adult male Sprague-Dawley rats (n=9/group) were subjected to IT surgery with translocation of 5, 10 or 20 cm of the ileal segment to proximal jejunum or sham manipulations. Daily food intake and body weight were recorded, and an intraperitoneal glucose tolerance test was performed. Blood samples were assayed for hormones and tissue samples for mRNA (RT-qPCR) and/or protein abundance (immunoblotting) of regulatory metabolic markers. We demonstrate that IT surgery exerts ileal length-dependent effects on multiple parameters including: (1) decreased food intake and weight gain, (2) improved glucose tolerance, (3) increased tissue expression and plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and decreased leptin concentrations and (4) upregulation of key markers of glucose metabolism (glucose transporter-4 (GLUT-4), insulin receptor substrate 1 (IRS-1), adenosine monophosphate-activated protein kinase (AMPK), hexokinase (HK) and phosphofructokinase (PFK)) together with a downregulation of lipogenic markers (fatty acid synthase (FAS)) in muscle and adipose tissue. Together, our data demonstrate that the reduction in food intake and weight gain, increase in lower

Study of the effect of jejuno-ileal distension on the motor activity of the stomach with evidence of "entero-gastric inhibitory reflex".

PubMed

Shafik, Ahmed; Shafik, Ali A; el-Sibai, Olfat

2003-01-01

In chronic constipation due to delayed colonic transit, stasis of the ileal contents with resulting ileal distension may occur. The current study investigated the effect of ileal and jejunal distension on the gastric motility, aiming at elucidating the possible existence of a relationship and its role in the flow through the gut. The response of the gastric pressure to ileal and jejunal balloon distension in increments of 2 mL of saline was recorded in 12 mongrel dogs. The test was repeated after separate local anesthetization of the ileum, jejunum and stomach. 2- and 4-mL ileal balloon distension produced no significant gastric pressure response, while 6- and up to 10-mL distension effected decrease of the antral and corporeal pressures (p < 0.05, p < 0.05, respectively). Jejunal distension produced a gastric pressure decline (p < 0.05) with 4 and up to 10 mL of saline. The gastric pressure decrease did not show significant changes with the various distending volumes. It was maintained as long as ileal or jejunal distension was continued. Distension of the anesthetized ileum or jejunum caused no gastric pressure changes, nor did ileal or jejunal distension produce pressure changes in the anesthetized stomach. The gastric pressure decline and presumably hypotonia upon ileal or jejunal distension with big volumes postulate a reflex relationship which we call "entero-gastric inhibitory reflex". The small intestine is suggested to slow down gastric emptying through this reflex. A balance is thus created between chyme delivery from the stomach and chyme processing by the small intestine. Reflex derangement in neurogenic and myogenic diseases may result in gastrointestinal disorders, a point that needs to be investigated.

Disseminated histoplasmosis presenting with ileal perforation in a renal transplant recipient.

PubMed

Zainudin, B M; Kassim, F; Annuar, N M; Lim, C S; Ghazali, A K; Murad, Z

1992-08-01

A renal transplant patient presented with ileal perforation due to histoplasmosis 3 years after transplantation. Mesenteric lymph nodes and lungs were also affected by the disease. She was successfully treated with amphotericin B followed by ketoconazole.

Effects of feeding corn naturally contaminated with aflatoxin on growth performance, apparent ileal digestibility, serum hormones levels and gene expression of Na+, K+-ATPase in ducklings.

PubMed

Abbasi, Farzana; Liu, Jingbo; Zhang, Hongfu; Shen, Xiaoyun; Luo, Xuegang

2018-01-01

A 14-d trial was conducted to determine the effects of feeding corn naturally contaminated with aflatoxin B 1 (AFB 1 ) on growth performance, apparent ileal digestibility, serum hormones levels and gene expression of Na + , K + -ATPase in ducklings. A total of 704 ducklings were blocked on the basis of sex and body weight (BW), and then allocated randomly to one of the following two treatments: i) CON, basal diet and ii) AFB 1 , diets with 100% of normal corn replaced with AFB 1 contaminated corn. There were 22 pens per treatment and 16 birds per pen. The concentration of AFB 1 was 195.4 and 124.35 μg/kg in the contaminated corn and AFB 1 diet, respectively. The AFB 1 decreased average daily gain, average daily feed intake, d 7 BW, final BW in the whole trial, and feed conversion ratio (FCR) during d 8 to 14 and d 1 to 14 by 10% to 47% (p<0.05), while FCR during d 1 to 7 was increased (p<0.05). AFB 1 did not affect mortality to 7 d of age, and then increased to 5.8% from 8 to 14 d of age (p<0.01). Apparent ileal gross energy digestibility was reduced by AFB 1 , whereas apparent ileal digestibility of dry matter, nitrogen, and amino acid was improved (p<0.01). Feeding AFB 1 diets increased serum concentration of leptin and insulin-like growth factors-1 (IGF-1) (p<0.05), but had no effect on neuropeptide Y, ghrelin, cholecystokinin-8 or insulin (p>0.05). Dietary treatments did not influence relative expression of jejunal Na + , K + -ATPase gene (p>0.05). Taken together, feeding corn naturally contaminated with AFB 1 reduced growth performance, improved apparent ileal digestibility, and affected serum leptin and IGF-1 in ducklings from d 1 to 14.

Impact of intraoperative factor concentrates on blood product transfusions during orthotopic liver transplantation.

PubMed

Colavecchia, A Carmine; Cohen, David A; Harris, Jesse E; Thomas, Jeena M; Lindberg, Scott; Leveque, Christopher; Salazar, Eric

2017-12-01

Major bleeding in orthotopic liver transplantation is associated with significant morbidity and mortality. Limited literature exists regarding comparative effectiveness of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation on blood product utilization. This retrospective, single-institution study evaluated the impact of prothrombin complex concentrate and fibrinogen concentrate on blood product utilization during orthotopic liver transplantation from December 2013 to April 2016. This study included patients age 18 years or older and excluded patients who received simultaneous heart or lung transplantation or did not meet documentation criteria. A propensity score matching technique was used to match patients who were exposed to prothrombin complex concentrate with unexposed patients, at a 2 to 1 ratio, to control for selection bias. During this study, 212 patients received orthotopic liver transplantation with 39 prothrombin complex concentrate exposures. The matched study population included 39 patients who were exposed to prothrombin complex concentrate and 78 unexposed patients. Overall, 84.6% of patients who were exposed to prothrombin complex concentrate also received concomitant fibrinogen concentrate, whereas only 2% of patients in the control group received fibrinogen concentrate. After propensity score matching, no other factors that were included in the model differed significantly or had a standardized mean difference of 0.11 or greater. There was no statistical difference in the utilization of red blood cells or fresh frozen plasma for the exposed group versus the unexposed group after matching (mean ± standard deviation: red blood cell units, 12.4 ± 8.0 units vs. 9.7 ± 5.6 units [p = 0.058]; fresh-frozen plasma units, 10.0 ± 6.3 vs. 12.7 ± 9.7 units [p = 0.119], respectively). The intraoperative use of prothrombin complex concentrate and fibrinogen concentrate during

Orthotopic tumorgrafts in nude mice: A new method to study human prostate cancer.

PubMed

Saar, Matthias; Körbel, Christina; Linxweiler, Johannes; Jung, Volker; Kamradt, Jörn; Hasenfus, Andrea; Stöckle, Michael; Unteregger, Gerhard; Menger, Michael D

2015-10-01

In vivo model systems in prostate cancer research that authentically reproduce tumor growth are still sparse. While orthotopic implantation is technically difficult, particularly in the mouse, most models favor subcutaneous tumor growth. This however provides little information about natural tumor growth behavior and tumor stroma interaction. Furthermore, established prostate cancer cell lines grown as in vivo xenografts are not able to reflect the variety of tumor specific growth patterns and growth behavior in men. Primary cell cultures are difficult to handle and an induction of orthotopic tumors has not been successful yet. Therefore, a tumorgraft model using tumor tissue from prostatectomy specimens was developed. Balb/c nude mice were used to graft fresh prostate tumor tissue by renal subcapsular and orthotopic implantation. Testosterone propionate was supplemented. Animals were tracked by means of 30 MHz ultrasound to monitor tumor engraftment and growth. Autopsy, histology, PSA measurements as well as immunostaining and PCR for human tissue were performed to confirm orthotopic tumor growth. Renal subcapsular engraftment was seen in 2 of 3 mice. Orthotopic engraftment was observed in 7 of 11 animals (63.6%) with an overall engraftment of 5 out of 9 patient specimens (55.6%). Ultrasound confirmed the tumor growth over time. Of interest, the tumorgrafts not only retained essential features of the parental tumors, but also stained positive for tumor specific markers such as AR, PSA, and AMACR. Tumor positive animals showed highly elevated serum PSA levels with confirmation of a human specific PCR sequence and a human endothelial cell lining in the tumor vessels. Standardized implantation of fresh tumor tissue in nude mice prostates generates tumorgrafts with histological properties of organ-confined prostate cancer. These tumorgrafts display a new approach for an optimized in vivo model of prostate cancer and will allow further investigations on specific

Sulfasalazine in Prevention of Pouchitis After Proctocolectomy with Ileal Pouch-Anal Anastomosis for Ulcerative Colitis.

PubMed

Scaioli, Eleonora; Sartini, Alessandro; Liverani, Elisa; Digby, Richard John; Ugolini, Giampaolo; Rosati, Giancarlo; Poggioli, Gilberto; Festi, Davide; Bazzoli, Franco; Belluzzi, Andrea

2017-04-01

Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for refractory ulcerative colitis. A non-standardized preventative treatment exists. Sulfasalazine has proved effective in acute pouchitis therapy. The aim of this study was to retrospectively evaluate the effect of sulfasalazine in primary prophylaxis of pouchitis after proctocolectomy with ileal pouch-anal anastomosis. Data files of patients who underwent total proctocolectomy with ileal pouch-anal anastomosis for refractory ulcerative colitis and/or dysplasia from January 2007 to December 2014, with a follow-up until August 2015, were analyzed. After closure of loop ileostomy, on a voluntary basis, patients received a primary prophylaxis of pouchitis with sulfasalazine (2000 mg per day) continually until acute pouchitis flare and/or drop out due to side effects. Follow-up data were available for 51 of the 55 surgical patients. Median follow-up time was 68 months (range 10-104). Thirty postoperative complications occurred in 25 patients. 45% of patients developed pouchitis. Sulfasalazine prophylaxis was administered in 39.2% of patients; 15% of the these developed pouchitis versus 64.5% (20/31) of the non-sulfasalazine patients (p < 0.001). Pouchitis-free survival curves were 90.55 months in sulfasalazine patients and 44.46 in non-sulfasalazine patients (log-rank test p = 0.001, Breslow p = 0.001). Sulfasalazine may be potentially administered in pouchitis prophylaxis after proctocolectomy with ileal pouch-anal anastomosis, but large prospectively controlled trials are needed.

Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn's disease.

PubMed

Craven, Melanie; Egan, Charlotte E; Dowd, Scot E; McDonough, Sean P; Dogan, Belgin; Denkers, Eric Y; Bowman, Dwight; Scherl, Ellen J; Simpson, Kenneth W

2012-01-01

Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn's Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis. We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI; 0.1 mg/mouse), or high dose indomethacin (HDI; 1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype. Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from >95% gram + Firmicutes to >95% gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the dysbiosis of ileal CD. In contrast, dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2(-/-), and reduced dysbiosis in ileitis-resistant CCR2(-/-) mice. Abrogating inflammation with the CD therapeutic anti-TNF-α-mAb tempered dysbiosis and bacterial invasion. Acute ileitis induces dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal dysbiosis are of high relevance to developing effective therapies for CD.

A true orthotopic gastric cancer murine model using electrocoagulation.

PubMed

Bhullar, Jasneet Singh; Makarawo, Tafadzwa; Subhas, Gokulakkrishna; Alomari, Ahmed; Silberberg, Boris; Tilak, Jacqueline; Decker, Milessa; Mittal, Vijay K

2013-07-01

Orthotopic mouse models of human gastric cancer represent an important in vivo tool for testing chemotherapeutic agents and for studying intraluminal factors. Currently, orthotopic mouse models of gastric cancer require an operative procedure involving either injection or implantation of tumor cells in stomach layers. The resultant tumor does not grow from the stomach's mucosal surface, so it does not mimic the human disease process. A low-dose gastric mucosal coagulation was done transorally in the body of stomach using a specially designed polyethylene catheter in 16 female severe combined immunodeficient mice. This was followed by the instillation of SNU-16 human gastric cancer tumor cells (1 × 10(6) cells). Five mice each were euthanized at 1 and 2 months, and 6 mice were euthanized at 3 months. Three control mice underwent electrocoagulation alone and 3 mice underwent cell line instillation alone. Tumors were detected in 11 of 16 experimental mice, but not in the control mice. Tumors were noted in mice at 1 month. Over time, there was an increase in tumor growth and metastasis to lymph nodes and surrounding organs. Histopathologic evaluation showed that the tumors grew from the gastric mucosa. Our model is easy to create and overcomes the limitations of the existing models, as the tumor arises from the stomach's mucosal layer and mimics the human disease in terms of morphology and biologic behavior. This is the first report of a true orthotopic gastric cancer murine model. This model opens new doors for additional studies that were not possible earlier. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Zinc Oxide Nanoparticles Influence Microflora in Ileal Digesta and Correlate Well with Blood Metabolites.

PubMed

Feng, Yanni; Min, Lingjiang; Zhang, Weidong; Liu, Jing; Hou, Zhumei; Chu, Meiqiang; Li, Lan; Shen, Wei; Zhao, Yong; Zhang, Hongfu

2017-01-01

Zinc oxide nanoparticles (ZnO NPs) are used widely in consumer and industrial products, however, their influence on gut microbiota and metabolism and their mutual interactions are not fully understood. In this study, the effects of ZnO NPs on ileal bacterial communities, plasma metabolites, and correlations between them were investigated. Hens were fed with different concentrations of ZnO NPs [based on Zn; 0 mg/kg (control), 25 mg/kg, 50 mg/kg, and 100 mg/kg] for 9 weeks. Subsequently, ileal digesta and blood plasma were collected for analysis of microflora and metabolites, respectively. The V3-V4 region of the 16S rRNA gene of ileal digesta microbiota was sequenced using the Illumina HiSeq 2500 platform. The predominant bacterial community in the ileum belongs to the phylum Firmicutes. The richness of the bacterial community was negatively correlated with increasing amounts of ZnO NPs ( r = -0.636, P < 0.01); when ZnO NP levels were at 100 mg/kg, microbiota diversity was significantly decreased ( P < 0.05). The community structure determined by LEfSe analysis indicated that Bacilli, Fusobacteria, and Proteobacteria were changed, and Lactobacillus was reduced by ZnO NPs. Moreover, metabolism as analyzed by nuclear magnetic resonance (NMR) indicated that glucose, some amino acids, and other metabolites were changed by ZnO NPs. Choline, lactate, and methionine were positively correlated with bacterial richness. In summary, ZnO NPs could influence the levels of microflora in ileal digesta, particularly Lactobacillus . Furthermore, the richness of the microbiota was related to changes in choline, lactate, and methionine metabolism.

Real-time Non-invasive Spectral Imaging of Orthotopic Red Fluorescent Protein-expressing Lung Tumor Growth in Nude Mice.

PubMed

Zhang, Yong; Zhang, Nan; Zhao, Ming; Hoffman, Robert M

2015-07-01

Orthotopic implantation of cancer allows metastasis to occur. The most patient-like metastatic orthotopic models are developed with surgical orthotopic implantation using intact tissue in order to preserve the natural tissue structure of the tumor which contains both cancer cells and stroma. In the present study, we performed a simple thoracotomy by making an intercostal incision between the fourth and fifth ribs on the left side of the chest of nude mice. Lung tumor fragments expressing red fluorescent protein were then implanted on the left lung. It was possible to monitor tumor formation in the lung non-invasively by spectral imaging using the Maestro system with a liquid tunable filter. The model described here has high tumorigenicity in the lung (100%) and a low mortality rate (5%). This imageable nude mouse model using surgical orthotopic implantation of lung cancer will be useful for all types of longitudinal studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Inhibition of ileal bile acid transporter: An emerging therapeutic strategy for chronic idiopathic constipation.

PubMed

Mosińska, Paula; Fichna, Jakub; Storr, Martin

2015-06-28

Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation.

In-situ observation of switchable nanoscale topography for y-shaped binary brushes in fluids.

PubMed

Lin, Yen-Hsi; Teng, Jing; Zubarev, Eugene R; Shulha, Hennady; Tsukruk, Vladimir V

2005-03-01

Direct, in-fluid observation of the surface morphology and nanomechanical properties of the mixed brushes composed of Y-shaped binary molecules PS-PAA revealed nanoscale network-like surface topography formed by coexisting stretched soluble PAA arms and collapsed insoluble PS chains in water. Placement of Y-shaped brushes in different fluids resulted in dramatic reorganization ranging from soft repellent layer covered by swollen PS arms in toluene to an adhesive, mixed layer composed of coexisting swollen PAA and collapsed PS arms in water. These binary layers with the overall nanoscale thickness can serve as adaptive nanocoatings with stimuli-responsive properties.

Linking ileal digestible phosphorus and bone mineralization in broiler chickens fed diets supplemented with phytase and highly soluble calcium.

PubMed

Adeola, O; Walk, C L

2013-08-01

The objectives of this study were to determine the ileal digestibility of P in potassium phosphate, phytase-related ileal digestible P release, bone-mineralization-based ileal digestible P equivalency of phytase, and phytase-related efficiency of ileal digestible P utilization for bone mineralization in broiler chickens at 2 dietary concentrations of highly soluble Ca (HSC). Birds were sorted by BW at d 15 posthatch and assigned to 8 cages per diet with 8 birds per cage. Twelve diets were arranged in a 2 × 6 factorial of HSC at 5 or 6 g/kg and P supply treatment at 6 levels consisting of 4 added P levels (P from KH2PO4 added at 0, 0.7, 1.4, or 2.1 g/kg of diet) or 2 added phytase levels (500 or 1,000 phytase units). On d 24 posthatch, ileal digesta were collected for ileal P digestibility (IPD) determination and the left tibia was collected from the 4 heaviest birds in each cage for bone ash determination. Weight gain, G:F, and tibia ash were higher (P < 0.05) at 5 than at 6 g of HSC/kg. Added P from KH2PO4 or added phytase linearly increased (P < 0.001) weight gain, G:F, tibia ash, and IPD. The IPD of KH2PO4 derived from multiple linear regressions of digestible on total P intake for the diets without added phytase showed a reduction (P < 0.05) from 89.5 to 84.5% with increased HSC from 5 to 6 g/kg. Polynomial regressions of digestible P intake on phytase intake indicated that 1,000 units of added phytase released 1.701 or 1.561 g of digestible P in diets containing 5 or 6 g of added HSC/kg, respectively. Polynomial regressions of tibia ash on digestible P or phytase intake in diets containing 5 or 6 g of added HSC/kg at 1,000 phytase units gave digestible P equivalency of 1.487 or 1.448 g, respectively. Thus, phytase-related efficiency of ileal digestible P utilization for bone mineralization was 87.4 and 92.8% in diets containing 5 or 6 g of added HSC/kg, respectively.

Multicolor spectral karyotype analysis of a transplantable human ileal carcinoid.

PubMed

Sjögren, H; Nilsson, O; Behrendt, M; Kölby, L; Jacobsen Levin, A M; Ahlman, H; Stenman, G

2000-12-01

In this report we present the results of a combined cytogenetic and multicolor spectral karyotype (SKY) analysis of a transplantable human ileal carcinoid (GOT1). By using SKY it was possible to identify the origin and organization of all clonal marker chromosomes and to identify cryptic translocations not detectable by conventional chromosome banding. The stemline karyotype of low passage GOT1 cells was interpreted as 43,XX, der(1)del(1)(?), inv(2)(p25q13), del(3)(p21), del(5)(q13q31), del(6)(q13), -9, -13, -15, del(16) (q22). Analysis of the GOT1 cells after about 2.5 years of propagation in nude mice allowed us to follow the in vivo progression of this tumor. Relatively few additional rearrangements had occurred during this period, indicating that the GOT1 cells are genetically stable. Most of the abnormalities detected result in loss of whole or parts of chromosomes, suggesting that loss of multiple chromosomal regions, presumably containing tumor suppressor genes, might be important genetic events in ileal carcinoids.

Analysis of kidney-shaped indentation cracks in 4Y-PSZ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pajares, A.; Guiberteau, F.; Cumbrera, F.L.

1996-11-01

Vickers indentation cracks in zirconia containing ceramics very often exhibit two non-connected mirror symmetric branches with kidney-shaped morphology. Kidney cracks, generated with different indentation loads (98--490 N) in 4 mol.% yttria-partially-stabilized-zirconia (4Y-PSZ), are described and analyzed by proposing a model which combines the observed geometrical features with residual stress considerations. The crack shape is affected by a radial decreasing hydrostatic stress field originating in the plastic deformation zone underneath the impression and with its center at a certain depth from the surface. The hydrostatic stresses modify the generally assumed point force residual stress field. The model provides a self-similar descriptionmore » of the residual stress intensity factor for kidney cracks from different indentation loads. Furthermore, the experimental observation that one single half-penny crack rather than the two kidney cracks forms at higher indentation loads is explained by the model. For 4Y-PSZ a reasonably good agreement between the theoretically calculated and the experimentally observed critical transition load from kidney to half-penny geometry, P*, is obtained. The transition load varies with toughness, K{sub R} and hardness, H, according to P* {approximately} K{sub R}{sup 4}/H{sup 3}, indicating the relative influence of deformation and fracture characteristics on crack morphology. It must be concluded that the kidney-shaped contour is the dominant geometry of elastic/plastic contact cracks in tough zirconia-containing ceramics.« less

Inflammation Drives Dysbiosis and Bacterial Invasion in Murine Models of Ileal Crohn’s Disease

PubMed Central

Craven, Melanie; Egan, Charlotte E.; Dowd, Scot E.; McDonough, Sean P.; Dogan, Belgin; Denkers, Eric Y.; Bowman, Dwight; Scherl, Ellen J.; Simpson, Kenneth W.

2012-01-01

Background and Aims Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn’s Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis. Methods We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI;0.1 mg/mouse), or high dose indomethacin (HDI;1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype. Results Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from >95% Gram + Firmicutes to >95% Gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the dysbiosis of ileal CD. In contrast, dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2−/−, and reduced dysbiosis in ileitis-resistant CCR2−/− mice. Abrogating inflammation with the CD therapeutic anti-TNF-α-mAb tempered dysbiosis and bacterial invasion. Conclusions Acute ileitis induces dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal dysbiosis are of high relevance to developing effective therapies for CD. PMID:22848538

Ileal Crohn disease: mural microvascularity quantified with contrast-enhanced US correlates with disease activity.

PubMed

De Franco, Antonio; Di Veronica, Alessandra; Armuzzi, Alessandro; Roberto, Italia; Marzo, Manuela; De Pascalis, Barbara; De Vitis, Italo; Papa, Alfredo; Bock, Enrico; Danza, Francesco M; Bonomo, Lorenzo; Guidi, Luisa

2012-02-01

To quantitatively assess microvascular activation in the thickened ileal walls of patients with Crohn disease (CD) by using contrast-enhanced ultrasonography (US) and evaluate its correlation with widely used indexes of CD activity. This prospective study was approved by the ethics committee, and written informed consent was obtained from all patients. The authors examined 54 consecutively enrolled patients (mean age, 35.29 years; age range, 18-69 years; 39 men, 15 women) with endoscopically confirmed CD of the terminal ileum. Ileal wall segments thicker than 3 mm were examined with low-mechanical-index contrast-enhanced US and a second-generation US contrast agent. The authors analyzed software-plotted time-enhancement intensity curves to determine the maximum peak intensity (MPI) and wash-in slope coefficient (β) and evaluated their correlation with (a) the composite index of CD activity (CICDA), (b) the CD activity index (CDAI), and (c) the simplified endoscopic score for CD (SES-CD, evaluated in 37 patients) for the terminal ileum. Statistical analysis was performed with the Mann-Whitney test, Spearman rank test, and receiver operating characteristic (ROC) analysis. MPI and β coefficients were significantly increased in the 36 patients with a CICDA indicative of active disease (P<.0001 for both), the 33 patients with a CDAI of at least 150 (P<.032 and P<.0074, respectively), and the 26 patients with an SES-CD of at least 1 (P<.0001 and P<.002, respectively). ROC analysis revealed accurate identification (compared with CICDA) of active CD with an MPI threshold of 24 video intensity (VI) (sensitivity, 97%; specificity, 83%) and a β coefficient of 4.5 VI/sec (sensitivity, 86%; specificity, 83%). Contrast-enhanced US of the ileal wall is a promising method for objective, reproducible assessment of disease activity in patients with ileal CD. © RSNA, 2011

Bombesin functionalized 64Cu-copper sulfide nanoparticles for targeted imaging of orthotopic prostate cancer.

PubMed

Cai, Huawei; Xie, Fang; Mulgaonkar, Aditi; Chen, Lihong; Sun, Xiankai; Hsieh, Jer-Tsong; Peng, Fangyu; Tian, Rong; Li, Lin; Wu, Changqiang; Ai, Hua

2018-05-22

To synthesize and evaluate the imaging potential of Bom-PEG-[ 64 Cu]CuS nanoparticles (NPs) in orothotopic prostate tumor. [ 64 Cu]CuS NPs were synthesized in aqueous solution by 64 CuCl 2 and Na 2 S reaction. Then PEG linker with or without bombesin peptide were conjugated to the surface of [ 64 Cu]CuS NPs to produce Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs. These two kinds of NPs were used for testing specific uptake in prostate cancer cells in vitro and imaging of orthotopic prostate tumor in vivo. Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs were successfully synthesized with core diameter of approximately 5 nm. Radioactive cellular uptake revealed that Bom-PEG-[ 64 Cu]CuS was able to specifically bind to prostate cancer cells, and the microPET-CT imaging indicated clear visualization of orthotopic prostate tumors. Radiolabeled Bom-PEG-[ 64 Cu]CuS NPs have potential as an ideal agent for orthotopic prostate tumor imaging by microPET-CT.

The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis.

PubMed

Derakhshani, Hooman; De Buck, Jeroen; Mortier, Rienske; Barkema, Herman W; Krause, Denis O; Khafipour, Ehsan

2016-01-01

Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that

The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis

PubMed Central

Derakhshani, Hooman; De Buck, Jeroen; Mortier, Rienske; Barkema, Herman W.; Krause, Denis O.; Khafipour, Ehsan

2016-01-01

Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that

Early Transcriptomic Changes in the Ileal Pouch Provide Insight into the Molecular Pathogenesis of Pouchitis and Ulcerative Colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Yong; Dalal, Sushila; Antonopoulos, Dionysios

Background: Ulcerative colitis (UC) only involves the colonic mucosa. Yet, nearly 50% of patients with UC who undergo total proctocolectomy with ileal pouch anal anastomosis develop UC-like inflammation of the ileal pouch (pouchitis). By contrast, patients with familial adenomatous polyposis (FAP) with ileal pouch anal anastomosis develop pouchitis far less frequently. We hypothesized that pathogenic events associated with the development of UC are recapitulated by colonic-metaplastic transcriptomic reprogramming of the UC pouch. Methods: We prospectively sampled pouch and prepouch ileum mucosal biopsies in patients with UC with ileal pouch anal anastomosis 4, 8, and 12 months after their pouch wasmore » in continuity. Mucosal samples were also obtained from patients with FAP. Transcriptional profiles of the UC and FAP pouch and prepouch ileum were investigated via RNA sequencing and compared with data from a previously published microarray study. Results: Unlike patients with FAP, subjects with UC exhibited a large set of differentially expressed genes between the pouch and prepouch ileum as early as 4 months after pouch functionalization. Functional pathway analysis of differentially expressed genes in the UC pouch revealed an enhanced state of immune/inflammatory response and extracellular matrix remodeling. Moreover, >70% of differentially expressed genes mapped to published inflammatory bowel diseases microarray data sets displayed directional changes consistent with active UC but not with Crohn's disease. Conclusions: The UC pouch, well before histologic inflammation, already displays a systems-level gain of colon-associated genes and loss of ileum-associated genes. Patients with UC exhibit a unique transcriptomic response to ileal pouch creation that can be observed well before disease and may in part explain their susceptibility to the development of pouchitis.« less

Taeniasis: A possible cause of ileal bleeding.

PubMed

Settesoldi, Alessia; Tozzi, Alessandro; Tarantino, Ottaviano

2017-12-16

Taenia spp. are flatworms of the class Cestoda, whose definitive hosts are humans and primates. Human infestation (taeniasis) results from the ingestion of raw meat contaminated with encysted larval tapeworms and is considered relatively harmless and mostly asymptomatic. Anemia is not recognized as a possible sign of taeniasis and taeniasis-induced hemorrhage is not described in medical books. Its therapy is based on anthelmintics such praziquantel, niclosamide or albendazole. Here we describe a case of acute ileal bleeding in an Italian man affected with both Taenia spp. infestation resistant to albendazole and Helicobacter pylori -associated duodenal ulcers.

Predictors of the use of orthotopic bladder reconstruction after radical cystectomy for bladder cancer: data from a pilot study of 1756 cases 2004-2011.

PubMed

Hounsome, Luke S; Abel, Gary A; Verne, Julia; Neal, David E; Lyratzopoulos, Georgios

2013-06-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: How often orthotopic reconstruction should be used after radical cystectomy is uncertain. Male sex, younger age, affluence, white ethnicity and treatment in specialist hospitals may be associated with more frequent use. More evidence about the level and likely variation in the use of orthotopic surgery is needed to establish whether there are inequalities and unmet need. In England during the study period orthotopic bladder reconstruction was likely to be used in about one in 15 patients treated by radical cystectomy. This is lower than previously reported in US series or European studies. Men and younger patients were more likely to be treated by orthotopic reconstruction, as were more affluent patients and those with less advanced disease. Whether clinical reasons or patient choice can explain some of this variation is unclear. There was no evidence for variation between different English cancer networks. A specific procedure code to allow routine analysis of population-based nationwide data would be invaluable for ongoing monitoring of potential inequalities and unmet need. To examine variation in the use of orthotopic bladder reconstruction. Variability in the use of orthotopic reconstruction may indicate potential for quality improvement. We analysed data from the British Association of Urological Surgeons Cancer Registry Complex Operations data set and Hospital Episode Statistics, covering the period 2004-2011. Three-level (patient, consultant and cancer network) mixed effect logistic regression models were used to examine sociodemographic and organizational variation in use of orthotopic reconstruction. The primary outcome was the odds ratio for use of orthotopic reconstruction for different patient groups. The final analysis sample included 1756 patients with bladder cancer who were treated by cystectomy by 121 consultants in 17 cancer networks. Of these, 120 (6.8%) were treated by orthotopic

Ileal Amino Acid Digestibility of Broken Rice Fed to Postweaned Piglets with or without Multicarbohydrase and Phytase Supplementation.

PubMed

Dadalt, J C; Gallardo, C; Polycarpo, G V; Budiño, F E L; Rogiewicz, A; Berto, D A; Trindade Neto, M A

2016-10-01

Most of amino acid (AA) digestibility values for feed ingredients are obtained using pigs cannulated in the distal ileum. The ileal-cannulated pig model uses pigs older than six weeks due to difficulties related to implanting the T-cannula in distal ileum of younger pigs and complications during the post-surgical recovery. However, to properly formulate the diet of weaned pigs, the nutritive value of feed ingredients should be determined with younger pigs. Thus, 25 weaned pigs were used to determine the apparent total tract digestibility (ATTD) of nutrients, energy, and apparent ileal digestibility (AID) and standardized ileal digestibility (SID) ileal AA digestibility of broken rice (BR), with or without multicarbohydrase (MC) and phytase (Phy) supplementation. Piglets were weaned at 23 d of age and individually housed in digestibility cages until 45 d of age. The trial consisted of 7 d of adaptation to the experimental diets and 3 d of excreta (feces and urine) collection. Ileal digesta was collected at slaughter (about 6 weeks of age). A completely randomized experimental design was used to determine the effects of MC and Phy. Reference diets (RD, 5% casein) was replaced by 30% of BR with or without MC, Phy, or MC+Phy. The RD was used to quantify endogenous AA losses. BR with Phy supplied had increased the ATTD of dry matter (p<0.05) and SID of histidine (p = 0.05), arginine, leucine, lysine, valine, alanine, and proline (p<0.05). BR with MC had been increased digestible energy and protein and SID for histidine (p<0.05). There was no interaction between Phy and MC on the BR nutrient digestibilities. Standardized amino acid digestibilities of BR, without enzymes, were lower than those values reported in the literature. The MC and Phy improved the digestibility of some nutrients and energy of BR in post-weaned piglet diets.

[A finite element analysis of petal-shaped poly-axial locking plate fixation in treatment of Y-shaped patellar fracture].

PubMed

Meng, Depeng; Ouyang, Yueping; Hou, Chunlin

2017-12-01

To establish the finite element model of Y-shaped patellar fracture fixed with titanium-alloy petal-shaped poly-axial locking plate and to implement the finite element mechanical analysis. The three-dimensional model was created by software Mimics 19.0, Rhino 5.0, and 3-Matic 11.0. The finite element analysis was implemented by ANSYS Workbench 16.0 to calculate the Von-Mises stress and displacement. Before calculated, the upper and lower poles of the patella were constrained. The 2.0, 3.5, and 4.4 MPa compressive stresses were applied to the 1/3 patellofemoral joint surface of the lower, middle, and upper part of the patella respectively, and to simulated the force upon patella when knee flexion of 20, 45, and 90°. The number of nodes and elements of the finite element model obtained was 456 839 and 245 449, respectively. The max value of Von-Mises stress of all the three conditions simulated was 151.48 MPa under condition simulating the knee flexion of 90°, which was lower than the yield strength value of the titanium-alloy and patella. The max total displacement value was 0.092 8 mm under condition simulating knee flexion of 45°, which was acceptable according to clinical criterion. The stress concentrated around the non-vertical fracture line and near the area where the screws were sparse. The titanium-alloy petal-shaped poly-axial locking plate have enough biomechanical stiffness to fix the Y-shaped patellar fracture, but the result need to be proved in future.

Bile acid malabsorption after continent urinary diversion with an ileal reservoir.

PubMed

Olofsson, G; Fjälling, M; Kilander, A; Ung, K A; Jonsson, O

1998-09-01

We determine the effect of urinary diversion with a Kock ileal reservoir on bile acid absorption and bowel habits. We asked 96 patients with a Kock ileal urinary reservoir to record bowel habits and abdominal symptoms for 1 week. Data on 75 patients were further analyzed. Bile acid absorption was determined in 29 healthy control subjects, in 17 before and 6 months after continent urinary diversion, and in 21, 2 to 14 years postoperatively. Bile acid absorption was considered pathological when retention of less than 10% of an oral capsule containing selenium-75 labeled tauroselcholic acid (SeHCAT) was noted after 1 week. Mean number of defecations plus or minus standard deviation was 9.4 +/- 6.1 (75 cases). Of the patients 13% had 15 or more stools per week and 15% complained of always having loose stools. Mean value for the SeHCAT test was 32 +/- 19% preoperatively and 17 +/- 16% 6 months postoperatively (p = 0.0023). The corresponding value for healthy controls was 39 +/- 18%. Significant relationships were found between the results of the SeHCAT test postoperatively, and the number of stools per week and consistency of the feces. All patients with more than 10 defecations per week had a pathological SeHCAT test. Most patients with an ileal urinary reservoir have fairly normal bowel habits. Bile acid absorption is significantly reduced postoperatively and approximately a third of the patients have a pathological SeHCAT test. Preoperative investigation of bowel habits is recommended and a SeHCAT test should be performed in patients with frequent, loose defecations. Other types of diversion should be offered when preoperative retention is below 10 to 20% especially in patients with impaired anal control.

Target-induced Catalytic Assembly of Y-Shaped DNA and Its Application for In Situ Imaging of MicroRNAs.

PubMed

Xue, Chang; Zhang, Shu-Xin; Ouyang, Chang-He; Chang, Dingran; Salena, Bruno J; Li, Yingfu; Wu, Zai-Sheng

2018-06-14

DNA is a highly programmable material that can be configured into unique high-order structures, such as DNA branched junctions containing multiple helical arms converging at a center. Herein we show that DNA programmability can deliver in situ growth of a 3-way junction-based DNA structure (denoted Y-shaped DNA) with the use of three hairpin-shaped DNA molecules as precursors, a specific microRNA target as a recyclable trigger, and a DNA polymerase as a driver. We demonstrate that the Y-shaped configuration comes with the benefit of restricted freedom of movement in confined cellular environment, which makes the approach ideally suited for in situ imaging of small RNA targets, such as microRNAs. Comparative analysis illustrates that the proposed imaging technique is superior to both the classic fluorescence in situ hybridization (FISH) method and an analogous amplified imaging method via programmed growth of a double-stranded DNA (rather than Y-shaped DNA) product. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laparoscopic management of terminal ileal volvulus caused by Meckel's diverticulum.

PubMed

Xanthis, A; Hakeem, A; Safranek, P

2015-04-01

Complications from a Meckel's diverticulum include diverticulitis, bleeding, intussusception, bowel obstruction, a volvulus, a vesicodiverticular fistula, perforation or very rarely as a tumour. We report a case where a Meckel's diverticulum presented with a terminal ileal volvulus in a 32-year-old man without the presence of a typical vitelline band or axial torsion of the diverticulum causing the volvulus. It was successfully managed laparoscopically.

Magnetic Resonance Imaging Predicts Histopathological Composition of Ileal Crohn's Disease.

PubMed

Wagner, Mathilde; Ko, Huaibin Mabel; Chatterji, Manjil; Besa, Cecilia; Torres, Joana; Zhang, Xiaofei; Panchal, Hinaben; Hectors, Stefanie; Cho, Judy; Colombel, Jean-Frederic; Harpaz, Noam; Taouli, Bachir

2018-05-25

Recently, smooth muscle hypertrophy has been suggested to be a contributor to small bowel lesions secondary to Crohn's disease [CD], in addition to inflammation and fibrosis. Here, we assess the value of magnetic resonance imaging [MRI] for the characterisation of histopathological tissue composition of small bowel CD, including inflammation, fibrosis, and smooth muscle hypertrophy. A total of 35 consecutive patients [male/female 17/18, mean age 33 years] with ileal CD, who underwent small bowel resection and a preoperative contrast-enhanced MRI examination within 1 month before surgery, were retrospectively included. Image assessment included qualitative [pattern/degree of enhancement, presence of ulcerations/fistulas/abscesses] and quantitative parameters [wall thickness on T2/T1-weighted images [WI], enhancement ratios, apparent diffusion coefficient [ADC], Clermont and Magnetic Resonance Index of Activity [MaRIA] scores). MRI parameters were compared with histopathological findings including active inflammation, collagen deposition, and muscle hypertrophy using chi square/Fisher or Mann-Whitney tests and univariate/multivariate logistic/linear regression analyses. Forty ileal segments were analysed in 35 patients. Layered pattern at early-post-contrast phase was more prevalent (odds ratio [OR] = 8; p = 0.008), ADC was significantly lower [OR = 0.005; p = 0.022], and MaRIA score was significantly higher [OR = 1.125; p = 0.022] in inflammation grades 2-3 compared with grade 1. Wall thickness on T2WI was significantly increased [OR = 1.688; p = 0.043], and fistulas [OR = 14.5; p = 0.017] were more prevalent in segments with disproportionately increased muscle hypertrophy versus those with disproportionately increased fibrosis. MaRIA/Clermont scores, wall thickness on T1WI and T2WI, and ADC were all significantly correlated with degree of muscular hypertrophy. MRI predicts the degree of inflammation, and can distinguish prominent muscle hypertrophy from prominent

Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ.

PubMed

Joo, Kyeung Min; Kim, Jinkuk; Jin, Juyoun; Kim, Misuk; Seol, Ho Jun; Muradov, Johongir; Yang, Heekyoung; Choi, Yoon-La; Park, Woong-Yang; Kong, Doo-Sik; Lee, Jung-Il; Ko, Young-Hyeh; Woo, Hyun Goo; Lee, Jeongwu; Kim, Sunghoon; Nam, Do-Hyun

2013-01-31

Frequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable "patient tumor's phenocopy" that represents molecular and functional heterogeneity of GBMs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats

PubMed Central

Shi, Yaoping; Zhang, Feng; Bai, Zhibin; Wang, Jianfeng; Qiu, Longhua; Li, Yonggang; Meng, Yanfeng; Valji, Karim

2017-01-01

Purpose To determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance local chemotherapy in a rat model with orthotopic esophageal squamous cancers. Materials and Methods The animal protocol was approved by the institutional animal care and use committee and the institutional review board. Human esophageal squamous cancer cells were transduced with luciferase lentiviral particles. Cancer cells, mice with subcutaneous cancer esophageal xenografts, and nude rats with orthotopic esophageal cancers in four study groups of six animals per group were treated with (a) combination therapy of magnetic resonance imaging heating guidewire–mediated RF hyperthermia (42°C) plus local chemotherapy (cisplatin and 5-fluorouracil), (b) chemotherapy alone, (c) RF hyperthermia alone, and (d) phosphate-buffered saline. Bioluminescent optical imaging and transcutaneous ultrasonographic imaging were used to observe bioluminescence signal and changes in tumor size among the groups over 2 weeks, which were correlated with subsequent histologic results. The nonparametric Mann-Whitney U test was used for comparisons of variables. Results Compared with chemotherapy alone, RF hyperthermia alone, and phosphate-buffered saline, combination therapy with RF hyperthermia and chemotherapy induced the lowest cell proliferation (relative absorbance of formazan: 23.4% ± 7, 44.6% ± 7.5, 95.8% ± 2, 100%, respectively; P < .0001), rendered the smallest relative tumor volume (0.65 mm3 ± 0.15, P < .0001) and relative bioluminescence optical imaging photon signal (0.57 × 107 photons per second per square millimeter ± 0.15, P < .001) of mice with esophageal cancer xenografts, as well as the smallest relative tumor volume (0.68 mm3 ± 0.13, P < .05) and relative photon signal (0.56 × 107 photons per second per square millimeter ± 0.11. P < .001) of rat orthotopic esophageal cancers. Conclusion Intraesophageal RF hyperthermia can enhance the effect of chemotherapy

Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging.

PubMed

Murakami, Takashi; Zhang, Yong; Wang, Xiaoen; Hiroshima, Yukihiko; Kasashima, Hiroaki; Yashiro, Masakazu; Hirakawa, Kosei; Miwa, Atsushi; Kiyuna, Tasuku; Matsuyama, Ryusei; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2016-05-01

Orthotopic (literally "correct place") implantation of cancer in nude mice has long been known to be superior to subcutaneous transplantation because the orthotopic tumor can metastasize. We reported previously on surgical orthotopic implantation (SOI) of gastric cancer tissue in nude mice resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject gastric cancer cells orthotopically, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of orthotopically implanting intact tissue to allow full expression of metastatic potential. However, the different behavior of tumors implanted orthotopically by the two methods has not been visualized in real time. OCUM-2MD3 human gastric cancer cells labeled with the fluorescent protein Azami-Green were implanted orthotopically as cells or tissue in nude mice. Orthotopic implantation of cells resulted in local spread on the stomach. In contrast, SOI of tumor tissue of OCUM-2MD3 resulted in vessel spread of the Azami-Green-expressing cancer cells. Metastasis was also observed in the left lobe of the liver after SOI. These results demonstrate the physiological importance of intact cancer tissue for orthotopic implantation in order for tumors to properly grow and express their metastatic potential. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Alterations of the Ileal and Colonic Mucosal Microbiota in Canine Chronic Enteropathies

PubMed Central

Cassmann, Eric; White, Robin; Atherly, Todd; Wang, Chong; Sun, Yaxuan; Khoda, Samir; Mosher, Curtis; Ackermann, Mark; Jergens, Albert

2016-01-01

Background The intestinal microbiota is increasingly linked to the pathogenesis of chronic enteropathies (CE) in dogs. While imbalances in duodenal and fecal microbial communities have been associated with mucosal inflammation, relatively little is known about alterations in mucosal bacteria seen with CE involving the ileum and colon. Aim To investigate the composition and spatial organization of mucosal microbiota in dogs with CE and controls. Methods Tissue sections from endoscopic biopsies of the ileum and colon from 19 dogs with inflammatory bowel disease (IBD), 6 dogs with granulomatous colitis (GC), 12 dogs with intestinal neoplasia, and 15 controls were studied by fluorescence in situ hybridization (FISH) on a quantifiable basis. Results The ileal and colonic mucosa of healthy dogs and dogs with CE is predominantly colonized by bacteria localized to free and adherent mucus compartments. CE dogs harbored more (P < 0.05) mucosal bacteria belonging to the Clostridium-coccoides/Eubacterium rectale group, Bacteroides, Enterobacteriaceae, and Escherichia coli versus controls. Within the CE group, IBD dogs had increased (P < 0.05) Enterobacteriaceae and E. coli bacteria attached onto surface epithelia or invading within the intestinal mucosa. Bacterial invasion with E. coli was observed in the ileal and colonic mucosa of dogs with GC (P < 0.05). Dogs with intestinal neoplasia had increased (P < 0.05) adherent (total bacteria, Enterobacteriaceae, E. coli) and invasive (Enterobacteriaceae, E. coli, and Bacteroides) bacteria in biopsy specimens. Increased numbers of total bacteria adherent to the colonic mucosa were associated with clinical disease severity in IBD dogs (P < 0.05). Conclusion Pathogenic events in canine CE are associated with different populations of the ileal and colonic mucosal microbiota. PMID:26840462

Orthotopic Liver Transplantation for Urea Cycle Enzyme Deficiency

PubMed Central

Todo, Satoru; Starzl, Thomas E.; Tzakis, Andreas; Benkov, Keith J.; Kalousek, Frantisek; Saheki, Takeyori; Tanikawa, Kyuichi; Fenton, Wayne A.

2010-01-01

Hyperammonemia, abnormalities in plasma amino acids and abnormalities of standard liver functions were corrected by orthotopic liver transplantation in a 14-day-old boy with carbamyl phosphate synthetase-I deficiency and in a 35-yr-old man with argininosuccinic acid synthetase deficiency. The first patient had high plasma glutamine levels and no measureable citrulline, whereas citrulline values were markedly increased in Patient 2. Enzyme analysis of the original livers showed undetectable activity of carbamyl phosphate synthetase-I in Patient 1 and arginosuccinic acid synthetase in Patient 2. Both patients were comatose before surgery. Intellectual recovery of patient 1 has been slightly retarded because of a brain abscess caused by Aspergillus infection after surgery. Both patients are well at 34 and 40 mo, respectively, after surgery. Our experience has shown that orthotopic liver transplantation corrects the life-threatening metabolic abnormalities caused by deficiencies in the urea cycle enzymes carbamyl phosphate synthetase-I and arginosuccinic acid synthetase. Seven other patients–six with ornithine transcarbamylase deficiency and another with carbamyl phosphate synthetase-I deficiency–are known to have been treated elsewhere with liver transplantation 1½ yr or longer ago. Four of these seven recipients also are well, with follow-ups of 1½ to 5 yr. Thus liver transplantation corrects the metabolic abnormalities of three of the six urea cycle enzyme deficiencies, and presumably would correct all. PMID:1544622

Optimization of an idealized Y-Shaped Extracardiac Fontan Baffle

NASA Astrophysics Data System (ADS)

Yang, Weiguang; Feinstein, Jeffrey; Mohan Reddy, V.; Marsden, Alison

2008-11-01

Research has showed that vascular geometries can significantly impact hemodynamic performance, particularly in pediatric cardiology, where anatomy varies from one patient to another. In this study we optimize a newly proposed design for the Fontan procedure, a surgery used to treat single ventricle heart patients. The current Fontan procedure connects the inferior vena cava (IVC) to the pulmonary arteries (PA's) via a straight Gore-Tex tube, forming a T-shaped junction. In the Y-graft design, the IVC is connected to the left and right PAs by two branches. Initial studies on the Y-graft design showed an increase in efficiency and improvement in flow distribution compared to traditional designs in a single patient-specific model. We now optimize an idealized Y-graft model to refine the design prior to patient testing. A derivate-free optimization algorithm using Kriging surrogate functions and mesh adaptive direct search is coupled to a 3-D finite element Navier-Stokes solver. We will present optimization results for rest and exercise conditions and examine the influence of energy efficiency, wall shear stress, pulsatile flow, and flow distribution on the optimal design.

Measurement of true ileal calcium digestibility in meat and bone meal for broiler chickens using the direct method.

PubMed

Anwar, M N; Ravindran, V; Morel, P C H; Ravindran, G; Cowieson, A J

2016-01-01

The objective of the study that is presented herein was to determine the true ileal calcium (Ca) digestibility in meat and bone meal (MBM) for broiler chickens using the direct method. Four MBM samples (coded as MBM-1, MBM-2, MBM-3 and MBM-4) were obtained and analyzed for nutrient composition, particle size distribution and bone to soft tissue ratio. The Ca concentrations of MBM-1, MBM-2, MBM-3 and MBM-4 were determined to be 71, 118, 114 and 81 g/kg, respectively. The corresponding geometric mean particle diameters and bone to soft tissue ratios were 0.866, 0.622, 0.875 and 0.781 mm, and 1:1.49, 1:0.98, 1:0.92 and 1:1.35, respectively. Five experimental diets, including four diets with similar Ca concentration (8.3 g/kg) from each MBM and a Ca and phosphorus-free diet, were developed. Meat and bone meal served as the sole source of Ca in the MBM diets. Titanium dioxide (3 g/kg) was incorporated in all diets as an indigestible marker. Each experimental diet was randomly allotted to six replicate cages (eight birds per cage) and offered from d 28 to 31 post-hatch. Apparent ileal Ca digestibility was calculated by the indicator method and corrected for ileal endogenous Ca losses to determine the true ileal Ca digestibility. Ileal endogenous Ca losses were determined to be 88 mg/kg dry matter intake. True ileal Ca digestibility coefficients of MBM-1, MBM-2, MBM-3 and MBM-4 were determined to be 0.560, 0.446, 0.517 and 0.413, respectively. True Ca digestibility of MBM-1 was higher (P < 0.05) than MBM-2 and MBM-4 but similar (P > 0.05) to that of MBM-3. True Ca digestibility of MBM-2 was similar (P > 0.05) to MBM-3 and MBM-4, while that of MBM-3 was higher (P < 0.05) than MBM-4. These results demonstrated that the direct method can be used for the determination of true Ca digestibility in feed ingredients and that Ca in MBM is not highly available as often assumed. The variability in true Ca digestibility of MBM samples could not be attributed to Ca content, percentage

Spin splitting generated in a Y-shaped semiconductor nanostructure with a quantum point contact

NASA Astrophysics Data System (ADS)

Wójcik, P.; Adamowski, J.; Wołoszyn, M.; Spisak, B. J.

2015-07-01

We have studied the spin splitting of the current in the Y-shaped semiconductor nanostructure with a quantum point contact (QPC) in a perpendicular magnetic field. Our calculations show that the appropriate tuning of the QPC potential and the external magnetic field leads to an almost perfect separation of the spin-polarized currents: electrons with opposite spins flow out through different output branches. The spin splitting results from the joint effect of the QPC, the spin Zeeman splitting, and the electron transport through the edge states formed in the nanowire at the sufficiently high magnetic field. The Y-shaped nanostructure can be used to split the unpolarized current into two spin currents with opposite spins as well as to detect the flow of the spin current. We have found that the separation of the spin currents is only slightly affected by the Rashba spin-orbit coupling. The spin-splitter device is an analogue of the optical device—the birefractive crystal that splits the unpolarized light into two beams with perpendicular polarizations. In the magnetic-field range, in which the current is carried through the edges states, the spin splitting is robust against the spin-independent scattering. This feature opens up a possibility of the application of the Y-shaped nanostructure as a non-ballistic spin-splitter device in spintronics.

Spin splitting generated in a Y-shaped semiconductor nanostructure with a quantum point contact

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wójcik, P., E-mail: pawel.wojcik@fis.agh.edu.pl; Adamowski, J., E-mail: janusz.adamowski@fis.agh.edu.pl; Wołoszyn, M.

2015-07-07

We have studied the spin splitting of the current in the Y-shaped semiconductor nanostructure with a quantum point contact (QPC) in a perpendicular magnetic field. Our calculations show that the appropriate tuning of the QPC potential and the external magnetic field leads to an almost perfect separation of the spin-polarized currents: electrons with opposite spins flow out through different output branches. The spin splitting results from the joint effect of the QPC, the spin Zeeman splitting, and the electron transport through the edge states formed in the nanowire at the sufficiently high magnetic field. The Y-shaped nanostructure can be usedmore » to split the unpolarized current into two spin currents with opposite spins as well as to detect the flow of the spin current. We have found that the separation of the spin currents is only slightly affected by the Rashba spin-orbit coupling. The spin-splitter device is an analogue of the optical device—the birefractive crystal that splits the unpolarized light into two beams with perpendicular polarizations. In the magnetic-field range, in which the current is carried through the edges states, the spin splitting is robust against the spin-independent scattering. This feature opens up a possibility of the application of the Y-shaped nanostructure as a non-ballistic spin-splitter device in spintronics.« less

[Establishment of a nude mouse model of highly metastatic gastric lymphoma constructed with orthotopic transplantation of surgical specimen].

PubMed

Yang, Bo; Tuo, Shuai; Tuo, Chao-wei; Zhang, Ning; Liu, Qiu-zhen

2010-06-01

To construct a mouse model of highly metastatic gastric lymphoma with orthotopic transplantation of human primary gastric lymphoma specimen. A fresh surgical specimen of primary gastric lymphoma was obtained intraoperatively and implanted into the submucosa of stomach in nude mice. Tumor formation, invasion, metastasis, morphological characteristics under light microscopy and electron microscopy, immunohistochemistry,and the karyotype of orthotopically transplanted tumor cells were studied. An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice(HGBL-0305) was successfully established. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. CD19, CD20, CD22 and CD79alpha were positive, while CD3 and CD7 were negative. The number of chromosome ranged from 56 to 69. DNA index(DI) was 1.47+/-0.12(i.e. heteroploid). Until now, HGBL-0305 model has been maintained for 45 generations by orthotopic passage for almost 4 years in nude mice. A total of 156 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumor cells were both 100%. The autonomic growth of the transplanted tumor cells invaded and destructed all the layers of the nude mice stomach. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 69.5%, 55.6%, 45.7%, and 30.5%, respectively. An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice is successfully established. HGBL-0305 model may simulate the natural course of primary gastric lymphoma in human and provides an ideal animal model for studies on pathogenesis, metastasis biology and anti-metastatic therapies of primary gastric lymphoma.

Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model.

PubMed

Abe, Shinji; Kaneko, Mika Kato; Tsuchihashi, Yuki; Izumi, Toshihiro; Ogasawara, Satoshi; Okada, Naoto; Sato, Chiemi; Tobiume, Makoto; Otsuka, Kenji; Miyamoto, Licht; Tsuchiya, Koichiro; Kawazoe, Kazuyoshi; Kato, Yukinari; Nishioka, Yasuhiko

2016-09-01

Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Orthotopic lung cancer murine model by nonoperative transbronchial approach.

PubMed

Nakajima, Takahiro; Anayama, Takashi; Matsuda, Yasushi; Hwang, David M; McVeigh, Patrick Z; Wilson, Brian C; Zheng, Gang; Keshavjee, Shaf; Yasufuku, Kazuhiro

2014-05-01

The aim of this work was to establish a novel orthotopic human non-small cell lung cancer (NSCLC) murine xenograft model by a nonsurgical, transbronchial approach. Male athymic nude mice and human NSCLC cell lines, including A549, H460, and H520 were used. Under direct visualization of the vocal cords, a 23-gauge blunt-tip slightly curved metal catheter was introduced into the trachea to the bronchus, and 2.5×10(5) tumor cells mixed with Matrigel (BD Biosciences, Mississauga, Ontario, Canada) were administered into the lung. Mice were monitored using weekly microcomputed tomography scans for tumor formation. When the tumor size reached more than 4 mm in diameter, the animals were euthanized, and the tumor tissue was evaluated histopathologically. Of 37 mice studied, 34 were confirmed to have tumor formation: 29 developed solitary tumors and 5 had multifocal lesions. There was no evidence of extrapleural dissemination or effusion. Transbronchial delivery of tumor cells enabled the establishment of a novel orthotopic human NSCLC murine xenograft model. This clinically relevant preclinical model bearing a solitary nodule is of value for a variety of in vivo research studies. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Disentangling the role of the Y(4260) in e+e- →D*Dbar* and Ds* Dbars* via line shape studies

NASA Astrophysics Data System (ADS)

Xue, Si-Run; Jing, Hao-Jie; Guo, Feng-Kun; Zhao, Qiang

2018-04-01

Whether the Y (4260) can couple to open charm channels has been a crucial issue for understanding its nature. The available experimental data suggest that the cross section line shapes of exclusive processes in e+e- annihilations have nontrivial structures around the mass region of the Y (4260). As part of a series of studies of the Y (4260) as mainly a D bar D1 (2420) + c . c . molecular state, we show that the partial widths of the Y (4260) to the two-body open charm channels of e+e- →D*Dbar* and Ds* D bars* are much smaller than that to D bar D* π + c . c . . The line shapes measured by the Belle Collaboration for these two channels can be well described by the vector charmonium states ψ (4040), ψ (4160) and ψ (4415) together with the Y (4260). It turns out that the interference of the Y (4260) with the other charmonia produces a dip around 4.22 GeV in the e+e- →D*Dbar* cross section line shape. The data also show an evidence for the strong coupling of the Y (4260) to the DDbar1 (2420), in line with the expectation in the hadronic molecular scenario for the Y (4260).

Effects of high ambient temperature on the community structure and composition of ileal microbiome of broilers.

PubMed

Wang, X J; Feng, J H; Zhang, M H; Li, X M; Ma, D D; Chang, S S

2018-06-01

The intestinal microbiome has been shown to influence animal nutrient metabolism and immune homeostasis. The present study aimed to examine the effect of heat stress on the intestinal microbiome of broilers using pyrosequencing technologies. Ninety-six Arbor Acres broiler chicks were allocated to thermoneutral control (TC; 21 ± 1°C) and high ambient temperature (HT; 31 ± 1°C) groups (6 cages of 8 birds per group), respectively, and raised in 2 controlled climate chambers from 28 to 42 d old. Genomic DNA was extracted from ileal contents isolated from 6 male broiler chicks of each group at 42 d old, and then amplified based on the V3-4 hyper-variable region of 16S rRNA. High temperature had no significant effects, but tended to influence the relative abundance of major phyla and orders in the broilers' ileal microbiota. Analysis of linear effect size feature selection identified 9 discriminative features (genus level, linear discriminant analysis score > 3). Clostridium XIVb, Streptophyta, Faecalibacterium, Rothia, Alistipes, Azospirillum, and Oscillibacter were enriched, while Coprococcus and Streptococcus were reduced in heat-stressed broilers. High temperature significantly influenced the alpha diversity, with higher observed species (P = 0.004), whole-tree phylogenetic diversity (P = 0.002), and Chao 1 (P = 0.002), but the Pielou, Shannon, and Simpson indices were unaltered (P > 0.05), indicating that high temperature increased the ileal microbiota species richness. Based on unweighted UniFrac distance metric matrices, principal component analysis showed that the HT group formed a distinct cluster clearly set apart from the TC group. Analysis of similarity also indicated that samples within groups were more similar to each other than to any samples from other groups (R = 0.626; P = 0.004). In conclusion, high temperature influenced the bacterial composition and community structure of the ileal microbiota of broilers, specifically by increasing the species

Mechanism of ultrasonic energy-assisted formation of V-, Y-shaped nano-structures in conjugated polymers.

PubMed

Majumdar, D; Maiti, R P; Basu, S; Saha, S K

2009-12-01

Recently, hydrocarbon-nanostructures from organic solvent using ultrasonic energy were reported. However, their formation-dynamics remained unexplored. Here, we describe a new technique to synthesize controlled nanostructures (V-, Y-shape) from nanorods of conducting polyaniline applying ultrasonic energy. To characterize the conducting state (emaraldine) of these polyaniline nanorods, electrical measurements have been carried out from which it is seen that there is a crossover from metallic to semiconductor as temperature increases. The observed crossover has been explained by the core-shell structure of the nanorods with core resistivity much higher than the shell resistivity. The nonlinear current-voltage behavior is attributed to the formation of alternate ordered/disordered chain segments along the length of the nanorods. We also propose a model to explore the mechanism of formation of these V-, Y-shaped nanostructures. It is believed that bubble-formation occurs in liquid due to ultrasonic vibration; and asymmetry in the bubble is created when formed near the solid surface leading to jet formation. Liquid jets of collapsing bubble move with incredible velocity (400 km/h); collide with the nanorod to cause fragmentations followed by V-, Y-shaped structure formation when the imparted kinetic energy of jets is comparable with elastic energy of fragments.

Atraumatic splenic rupture and ileal volvulus following cocaine abuse.

PubMed

Ballard, David H; Smith, J Patrick; Samra, Navdeep S

2015-01-01

We present the case of a 38-year-old male with an atraumatic splenic rupture, hemoperitoneum, and ileal volvulus following acute cocaine intoxication. Computed tomography showed a "whirl sign", a subcapsular splenic hematoma with suspected peripheral laceration, and diffuse hemoperitoneum. At laparotomy, the spleen was confirmed to be the source of bleeding and was removed. A nonreducible volvulus was found at the distal ileum, and this segment of small bowel was removed. The patient had an uneventful postoperative recovery. Copyright © 2015 Elsevier Inc. All rights reserved.

Characteristics of lipid substances activating the ileal brake in the rat.

PubMed Central

Brown, N J; Read, N W; Richardson, A; Rumsey, R D; Bogentoft, C

1990-01-01

Studies were carried out in 36 adult male rats to determine the characteristics of lipid substances which, after infusion into the ileum, slow the stomach to caecum transit time of the head of a bean meal in the rat. Stomach to caecum transit time was measured by environmental hydrogen analysis. Ileal infusion of a range of free fatty acids including petroselinic, oleic, myristoleic, erucic, linoleic, and linolenic all significantly slowed stomach to caecum transit time, as did the detergents (sodium bis (2-ethyl hexyl) sulphosuccinate and sodium linoleyl sulphate), the triglyceride corn oil, and the phospholipid lecithin. Although the lipid soluble deconjugated bile acid deoxycholic acid slowed stomach to caecum transit time, the water soluble conjugated bile acid taurocholic acid accelerated it. Infusion of the lipid alcohol oleyl alcohol and the calcium chelating agent disodium edetate (EDTA) into the ileum did not delay the passage of the meal through the stomach and small intestine. The diversity of lipid substances activating the ileal brake suggest a nonspecific effect by lipid soluble substances that can penetrate cell membranes. The lack of effect of EDTA suggested that calcium binding was not important. PMID:2128071

[Orthotopic cartilage transplantation. Morphologic, angiography and histochemical studies of the vitality of free septum transplants].

PubMed

Gubisch, W; Donath, K

1999-11-01

Orthotopic cartilage transplantation is a technique frequently used in modern septal surgery. The prerequisite for a stable long-term result is viability of the transplanted cartilage. Therefore, we studied the healing process histologically, angiographically, and histochemically. We found a characteristic picture. Due to chondronal structure of the cartilage, the healing process varied in time and location. Reintegration took place by chondroneogenesis, commencing at the inner perichondrium. Reintegration depended directly on the distance of the cartilage cells to the surrounding vessels. Histochemically, we found an intact respiratory chain in the mitochondria and thus, we were able to demonstrate the preservation of viability in orthotopic transplanted cartilage.

Early feed restriction of lambs modifies ileal epimural microbiota and affects immunity parameters during the fattening period.

PubMed

Frutos, J; Andrés, S; Yáñez-Ruiz, D R; Benavides, J; López, S; Santos, A; Martínez-Valladares, M; Rozada, F; Giráldez, F J

2018-04-22

Bacteria firmly attached to the gastrointestinal epithelium during the pre-weaning phase may show a significant impact on nutrient processing, immunity parameters, health and feed efficiency of lambs during post-weaning phases. Thus, the aim of this study was to describe the differences in the ileal epimural microbiota (e.g. total bacteria, Prevotella spp., Bifidobacterium spp. and Lactobacillus spp.) of fattening lambs promoted by early feed restriction during the suckling phase trying to elucidate some of the underlying mechanisms behind changes in feed efficiency during the fattening period. A total of 24 Merino lambs (average BW 4.81±0.256 kg) were used, 12 of them (ad libitum, ADL) kept permanently in individual pens with their mothers, whereas the other 12 lambs were separated from their dams for 9 h each day to be exposed to milk restriction (RES). After weaning (BW=15 kg) all the animals were penned individually, offered the same complete pelleted diet (35 g/kg BW per day) and slaughtered at a BW of 27 kg. During the fattening period, reduced gain : feed ratio (0.320 v. 0.261, P<0.001) was observed for the RES group. Moreover, increments of Prevotella spp. were detected in the ileal epimural microbiota of RES lambs (P<0.05). There were also higher numbers of infiltrated lymphocytes (T and B cells) in the ileal lamina propria (P<0.05), a higher M-cell labelling intensity in ileal Peyer's patches domes (P<0.05) and a trend towards a thickening of the submucosa layer when compared with the ADL group (P=0.057). Some other immunological parameters, such as an increased immunoglobulin A (IgA) production (pg IgA/µg total protein) and increments in CD45+ cells were also observed in the ileum of RES group (P<0.05), whereas transforming growth factor β and toll-like receptor gene expression was reduced (P<0.05). In conclusion, early feed restriction during the suckling phase promoted changes in ileal epimural microbiota and several immunity parameters that could

Pathogenesis of tropical sprue: A pilot study of antroduodenal manometry, duodenocaecal transit time & fat-induced ileal brake

PubMed Central

Ghoshal, Uday C.; Kumar, Sunil; Misra, Asha; Choudhuri, Gourdas

2013-01-01

Background & objectives: Small intestinal bacterial overgrowth (SIBO) due to ileal brake-induced hypomotility may cause tropical sprue (TS). We evaluated effect of infusion of fat or placebo in duodenum randomly in patients with TS and healthy controls on antroduodenal manometry (ADM) and mediators of ileal brake, and duodenocaecal transit time (DCTT). Methods: ADM and DCTT (lactulose hydrogen breath test, HBT) were evaluated with placebo and fat in eight controls and 13 patients with TS (diagnostic criteria: tests showing malabsorption of two unrelated substances, abnormal duodenal histology, absence of other causes, response to antibiotics and folate). Results: Patients with TS (6 had SIBO by glucose HBT) were similar in age and gender with controls. After fat infusion, proximal gut motility index (MI) was reduced compared to fasting state in TS, and DCTT was longer in TS than controls (200 min, 120-380 vs. 130, 70-160, P=0.001), though comparable after placebo (70 min, 30-140 vs. 60, 40-90). TS patients had higher PYY and neurotensin than controls after fat infusion. DCTT after fat infusion correlated with plasma level of PYY in TS but not in controls. Post-fat PYY and neurotensin levels were higher in TS with lower BMI (<16 kg/m2) than those with higher BMI. Parameters of ileal brake (post-fat DCTT, PYY and neurotensin) were higher in patients with than without SIBO. Interpretation & conclusions: Fat infusion reduced proximal gut MI, increased DCTT, PYY, and neurotensin among patients with TS. Malabsorbed fat might cause exaggerated ileal brake reducing gut motility, promoting SIBO and bacterial colonization and malabsorption in TS. PMID:23481053

Colonic Crohn's Disease Is Associated with Less Aggressive Disease Course Than Ileal or Ileocolonic Disease.

PubMed

Arora, Umang; Kedia, Saurabh; Garg, Prerna; Bopanna, Sawan; Jain, Saransh; Yadav, Dawesh P; Goyal, Sandeep; Gupta, Vipin; Sahni, Peush; Pal, Sujoy; Dash, Nihar Ranjan; Madhusudhan, Kumble Seetharama; Sharma, Raju; Makharia, Govind; Ahuja, Vineet

2018-06-01

The literature on disease characteristics of colonic Crohn's disease (CD) is sparse, especially from Asia, where the burden of inflammatory bowel disease is on the rise. The present study aims to describe the disease characteristics of colonic CD, and compare it with that of ileal/ileocolonic disease. This retrospective study included adult patients of CD (diagnosed by standard criteria, follow-up duration > 6 months) on follow-up between August 2004 and January 2016. The disease location was classified by Montreal classification. The data were recorded on demographic characteristics, smoking status, disease phenotype, disease course, treatment received, hospitalization and surgeries. Of 406 CD patients, 123 had colonic [mean age (at onset) 30.4 ± 13.2 years, 59.3% males] and 265 had ileal/ileocolonic disease [mean age (at onset) 32.9 ± 13.8 years, 61.5% males] while 18 patients had isolated upper GI disease. The frequency of inflammatory behavior (B1 phenotype; 61.8 vs. 46.4%, p = 0.003), perianal disease (23.6 vs. 4.5%, p < 0.001), and extra-intestinal manifestation (42.3 vs. 30.2%, p = 0.019) was higher in colonic than ileal/ileocolonic CD. Though not statistically significant, requirement of atleast one course of steroid was lower in colonic CD (72.7 vs. 84.2%, p = 0.098). Although there was no difference in the frequency of hospitalization (30.1 vs. 27.1%, p = 0.45), the overall requirement for surgery was significantly lower in colonic CD (17.1 vs. 26.1%, p = 0.032) and patients with colonic disease had a lower cumulative probability of first surgery in the first 10 years of follow-up [Hazard ratio 0.556 (95% CI 0.313-0.985), p = 0.045]. Colonic CD was associated with less aggressive disease behavior and lower requirement of surgery as compared to ileal/ileocolonic CD.

Thoracic stomach-right main bronchus fistula treated with dual Y-shaped covered airway stents.

PubMed

Li, Z-M; Lu, H-B; Ren, K-W; Han, X-W; Wu, G; Jiao, D-C

2017-06-01

To determine the efficacy of dual Y-shaped covered airway stents to treat thoracic stomach-right main bronchus fistulae. Fifteen patients who developed thoracic stomach-right main bronchus fistula after oesophageal cancer resection and postoperative irradiation were retrospectively analysed. All fistulae were close to the right upper lobe bronchus. Two Y-shaped covered airway stents were designed for each patient. Under radiographic guidance, one stent was placed from the right main bronchus into the bifurcation of upper lobe and intermediate bronchus, the other was placed from the trachea into both main bronchi. All fistulae were closed immediately after stenting. All patients could eat a semi-solid diet. The symptom of coughing while lying down resolved in all patients, and no complications, such as airway bleeding or pneumothorax, occurred. The average survival time was 26.65 months (range 2-40 months, 11 patients were still alive at the study end). Two patients died of tumour recurrence. Another two patients died of pulmonary infections. In one of these patients, there was a long delay between symptom onset and stenting. In the other patient, a small rupture occurred in the silicone membrane covering the stent, which allowed the leakage of gastric contents into the lung. Dual Y-shaped covered airway stent placement is feasible and safe to treat thoracic stomach-right main bronchus fistulae. Improvements to the material covering the stents is required. Copyright © 2017. Published by Elsevier Ltd.

Acquired toxoplasmosis after orthotopic heart transplantation in a sulfonamide-allergic patient.

PubMed

Sanchez Mejia, Aura; Debrunner, Mark; Cox, Elaine; Caldwell, Randall

2011-01-01

We report the case of a young adult with a history of an allergic reaction to a sulfonamide antibiotic who developed toxoplasmosis after his second orthotopic heart transplant. As a result of this drug allergy, the patient did not receive prophylaxis with trimethoprim and sulfamethoxazole. He was successfully treated with clindamycin, pyrimethamine, and folic acid.

Effects of corn gluten feed inclusion at graded levels in a corn-soybean diet on the ileal and fecal digestibility of growing pigs

PubMed Central

2014-01-01

Background This study aimed to determine the effect of the inclusion of corn gluten feed (CGF) on the apparent and standardized ileal digestibility of protein and amino acids and the apparent ileal and total tract digestibility of energy in growing pigs. The study was performed using 16 barrows (weight, 45.3 ± 4.5 kg) that were fitted with a T cannula at the terminal ileum. There were four treatments: a corn-soybean diet without CGF and three corn-soybean diets containing increasing levels of CGF (65, 130, and 195 g/kg). Data were analyzed according to a randomized complete block design, four blocks with four pigs each (one pig per treatment). The trend of the response (linear or quadratic) was determined using orthogonal contrasts, and when a linear effect was determined, a linear equation was obtained. Results The results showed that the inclusion up to 195 g/kg of CGF in the corn-soybean diet did not diminish the ileal digestibility (apparent and standardized) of protein and amino acids (P > 0.05), except that of phenylalanine, cystine, and proline. A linear decrease (P < 0.05) per gram of CGF added to the diet in the apparent and standardized ileal digestibility of phenylalanine (0.011 and 0.015 percentage units, respectively), cystine (0.048 and 0.043 percentage units, respectively), and proline (0.045 and 0.047 percentage units, respectively) was noted. Similarly, ileal digestibility of dry matter and energy were adversely affected (reduced by 0.028 and 0.025 percentage units, respectively, per gram of CGF increment in the diet). A significant (P < 0.05) linear reduction in total tract digestibility with increase in CGF amount in the diet was observed for energy (0.027 percentage units), dry matter (0.027 percentage units), crude protein (0.020 percentage units), and neutral detergent fiber (0.041 percentage units) per gram of CGF added to the diet. Conclusion CGF did not affect the ileal digestibility of protein and most amino acids but

A case report of modified laparoscopic keyhole plus repair for parastomal hernia following ileal conduit

PubMed Central

Rajapandian, S.; Jankar, Samrat V.; Dey, Sumanta; Annamaneni, Vikram; Sabnis, Sandeep C.; Sathiymurthy, S.; Parthsarathi, R.; Raj, P. Praveen; Senthilnathan, P.; Palanivelu, C.

2017-01-01

Parastomal hernia is one of the most common but challenging complication after stoma formation. Modified Sugarbaker technique is the recommended procedure for repair parastomal hernia, however, keyhole repair technique had also been used in certain instances. In cases of parastomal hernia following ileal conduit procedure, the Sugarbaker technique is been described, although with associated theoretical risk of conduit failure. We are reporting a case of post-radical cystectomy with ileal conduit presented with symptomatic large parastomal hernia. Laparoscopic modified keyhole plus repair has been done successfully in this patient with no recurrence in 2 years of follow-up. The purpose of our case report is to describe our novel modification of the laparoscopic keyhole technique which can be a feasible and acceptable alternative surgical method in these types of patients. PMID:28695881

Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer.

PubMed

Okumura, Masaki; Ichihara, Hideaki; Matsumoto, Yoko

2018-11-01

Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.

Laparoscopic Repair of Ileal Conduit Parastomal Hernia Using the Sling Technique

PubMed Central

Chand, Bipan

2008-01-01

Laparoscopic parastomal hernia repair has become a viable option to overcome the challenges that face the hernia surgeon. Multiple techniques have been described over the last 5 years, one of which is the lateralizing “sling” technique, first described by Sugarbaker in1980. In this study, we report the technique and our early results with the laparoscopic modified Sugarbaker repair of parastomal hernias after ileal conduit. PMID:18435893

Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT.

PubMed

Liu, Xiang; Liu, Jun; Guan, Yubao; Li, Huiling; Huang, Liyan; Tang, Hailing; He, Jianxing

2012-04-01

To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT. A549 cells (5×10(6) mL(-1)) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice. The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner. The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically.

Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT

PubMed Central

Liu, Xiang; Liu, Jun; Guan, Yubao; Li, Huiling; Huang, Liyan; Tang, Hailing

2012-01-01

Objective To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT. Methods A549 cells (5×106 mL-1) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice. Results The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner. Conclusions The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically. PMID:22833819

Factors affecting choice between ureterostomy, ileal conduit and continent reservoir after radical cystectomy: Japanese series.

PubMed

Sugihara, Toru; Yasunaga, Hideo; Horiguchi, Hiromasa; Fujimura, Tetsuya; Fushimi, Kiyohide; Yu, Changhong; Kattan, Michael W; Homma, Yukio

2014-12-01

Little is known about the disparity of choices between three urinary diversions after radical cystectomy, focusing on patient and institutional factors. We identified urothelial carcinoma patients who received radical cystectomy with cutaneous ureterostomy, ileal conduit or continent reservoir using the Japanese Diagnosis Procedure Combination database from 2007 to 2012. Data comprised age, sex, comorbidities (converted into the Charlson index), TNM classification (converted into oncological stage), hospitals' academic status, hospital volume, bed volume and geographical region. Multivariate ordinal logistic regression analyses fitted with the proportional odds model were performed to analyze factors affecting urinary diversion choices. For dependent variables, the three diversions were converted into an ordinal variable in order of complexity: cutaneous ureterostomy (reference), ileal conduit and continent reservoir. Geographical variations were also examined by multivariate logistic regression models. A total of 4790 patients (1131 cutaneous ureterostomies [23.6 %], 2970 ileal conduits [62.0 %] and 689 continent reservoirs [14.4 %]) were included. Ordinal logistic regression analyses showed that male sex, lower age, lower Charlson index, early tumor stage, higher hospital volume (≥3.4 cases/year) and larger bed volume (≥450 beds) were significantly associated with the preference of more complex urinary diversion. Significant geographical disparity was also found. Good patient condition and early oncological status, as well as institutional factors, including high hospital volume, large bed volume and specific geographical regions, are independently related to the likelihood of choosing complex diversions. Recognizing this disparity would help reinforce the need for clinical practice uniformity.

Progression of Neurovisceral Storage Disease With Supranuclear Ophthalmoplegia Following Orthotopic Liver Transplantation

PubMed Central

Gartner, J. Carlton; Bergman, Ira; Malatack, J. Jeffrey; Zitelli, Basil J.; Jaffe, Ronald; Watkins, John B.; Shaw, Byers W.; Iwatsuki, Shunzaburo; Starzl, Thomas E.

2011-01-01

A 7-year-old girl with progressive ataxia, spasticity, supranuclear ophthalmoplegia, and sea-blue histiocytes in her bone marrow underwent orthotopic liver transplantation for hepatocellular carcinoma. After an initial period of stabilization, she has shown progression of neurologic symptoms with recurrence of storage material in the transplanted liver. PMID:2999691

[A novel method based on Y-shaped cotton-polyester thread microfluidic channel].

PubMed

Wang, Lu; Shi, Yan-ru; Yan, Hong-tao

2014-08-01

A novel method based on Y-shaped microfluidic channel was firstly proposed in this study. The microfluidic channel was made of two cotton-polyester threads based on the capillary effect of cotton-polyester threads for the determination solutions. A special device was developed to fix the Y-shaped microfluidic channel by ourselves, through which the length and the tilt angle of the channel can be adjusted as requested. The spectrophotometry was compared with Scan-Adobe Photoshop software processing method. The former had a lower detection limit while the latter showed advantages in both convenience and fast operations and lower amount of samples. The proposed method was applied to the determination of nitrite. The linear ranges and detection limits are 1.0-70 micromol x L(-1), 0.66 micromol x L(-1) (spectrophotometry) and 50-450 micromol x L(-1), 45.10 micromol x L(-1) (Scan-Adobe Photoshop software processing method) respectively. This method has been successfully used to the determination of nitrite in soil samples and moat water with recoveries between 96.7% and 104%. It was proved that the proposed method was a low-cost, rapid and convenient analytical method with extensive application prospect.

Parastomal hernias after radical cystectomy and ileal conduit diversion

PubMed Central

Donahue, Timothy F.

2016-01-01

Parastomal hernia, defined as an "incisional hernia related to an abdominal wall stoma", is a frequent complication after conduit urinary diversion that can negatively impact quality of life and present a clinically significant problem for many patients. Parastomal hernia (PH) rates may be as high as 65% and while many patients are asymptomatic, in some series up to 30% of patients require surgical intervention due to pain, leakage, ostomy appliance problems, urinary obstruction, and rarely bowel obstruction or strangulation. Local tissue repair, stoma relocation, and mesh repairs have been performed to correct PH, however, long-term results have been disappointing with recurrence rates of 30%–76% reported after these techniques. Due to high recurrence rates and the potential morbidity of PH repair, efforts have been made to prevent PH development at the time of the initial surgery. Randomized trials of circumstomal prophylactic mesh placement at the time of colostomy and ileostomy stoma formation have shown significant reductions in PH rates with acceptably low complication profiles. We have placed prophylactic mesh at the time of ileal conduit creation in patients at high risk for PH development and found it to be safe and effective in reducing the PH rates over the short-term. In this review, we describe the clinical and radiographic definitions of PH, the clinical impact and risk factors associated with its development, and the use of prophylactic mesh placement for patients undergoing ileal conduit urinary diversion with the intent of reducing PH rates. PMID:27437533

Comparative estimation of inevitable endogenous ileal flow of amino acids in Pekin ducks under varying dietary or physiological conditions and their significance to nutritional requirements for amino acids.

PubMed

Akinde, D O

2017-10-01

In 2 experiments in Pekin ducks the inevitable endogenous ileal flow (IEIF) of AA was estimated at changing intake and source of crude fiber (CF) or soybean oil (SO) level. Also the roles of dry matter intake (DMI) and BW or age as well as the proportion of IEIF in the dietary requirement for AA were studied. In experiment 1 three basal CP (20, 60, or 100 g/kg) diets were formulated containing a low CF (LCF, 30 g/kg) or high (HCF, 80 g/kg) level; achieved with cellulose supplementation. All diets were similar in every other respect including having SO content of 40 g/kg. Four floor pens of eight 85-day-old ducks were randomly allocated to each diet. Similar diets were mixed in experiment 2 but corn cob meal replaced cellulose as the fiber source. A high SO (HSO) series was also formed by increasing the SO level from 40 g/kg in the basal series to 100 g/kg. Thus the LCF series was concurrently classified as low SO (LSO) series to control SO effect. Each of the eventual 9 diets were fed to 5 floor pens of ten 65-day-old ducks. Ileal AA flow was measured after a 5 day feeding period in both experiments. Linear regression was calculated between ileal flow and dietary intake of individual AA. The IEIF interpreted as the y-intercept of each linear function responded neither to elevated ingestion of each CF type nor to SO level. Age and DMI had no effect on IEIF computed in relation to BW, but wide discrepancies resulted when related to DMI. Overall IEIF of AA varied between 14.3 to 129.8 mg/kg BW d-1. These flows were established in model computations to account for 10 to 64% of the recommended intake of limiting AA. In conclusion the ileal inevitable flow is constant within the dietary/age conditions investigated. However it is modulated by feed intake and accounts for a significant portion of total amino acid requirement. © 2017 Poultry Science Association Inc.

Safe and effective treatment of early suprahepatic inferior vena caval outflow compromise following orthotopic liver transplantation using percutaneous transluminal angioplasty and stent placement.

PubMed

Tasse, Jordan; Borge, Marc; Pierce, Kenneth; Brems, John

2011-01-01

To describe the safety and efficacy of percutaneous transluminal angioplasty and stent placement in patients presenting with suprahepatic inferior vena cava (IVC) outflow compromise in the early postoperative period following orthotopic liver transplantation. Between October 2002 and April 2009, 3 patients presented with IVC outflow compromise in the first 2 months following orthotopic liver transplantation. All 3 underwent percutaneous transluminal angioplasty and stent placement without complication and showed significant clinical improvement at short and intermediate term follow-up. Percutaneous transluminal angioplasty and Gianturco stent placement is a safe and effective treatment for IVC outflow compromise in the early postoperative period following orthotopic liver transplantation.

Risk of in-hospital complications after radical cystectomy for urinary bladder carcinoma: population-based follow-up study of 7608 patients

PubMed Central

Hemelrijck, Mieke; Thorstenson, Andreas; Smith, Philip; Adolfsson, Jan; Akre, Olof

2013-01-01

Objective To evaluate the risk of different in-hospital complications for patients undergoing a radical cystectomy (RC), as limited nationwide population data on short- and long-term complications after RC is available, despite it being the standard treatment for localised muscle-invasive urinary bladder cancer (UBC). Patients and Methods In all, 7608 persons underwent a RC after UBC diagnosis, as registered in the Swedish National Patient Register between 1964 and 2008. We estimated the frequency and incidences and calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards models. Results Urinary tract infection/septicaemia was the most common complication following radical cystectomy, with an incidence of 90.4 per 1,000 person years. There was a higher risk of urinary tract infection among patients who had a continent cutaneous reservoir (HR: 1.11 (0.94–1.30) or orthotopic neobladder 1.21 (1.05–1.39) than among those with ileal conduit. Similarly, continent cutaneous reservoir and orthotopic neobladder were associated with increased risks for wound and abdominal wall hernias, stones in the urinary tract, hydronephrosis and nephrostomy tube treatment, and kidney failure. In contrast, risk of bowel obstruction was lower among those with orthotopic neobladder than those with ileal conduit (HR: 0.64 (0.50–0.81)) and those with continent cutaneous reservoir (HR: 0.92 (0.73–1.16). Conclusions In-hospital complications after RC are numerous and continue to accumulate for many years after surgery, indicating the need for life-long follow-up of these patients. Comparison between different types of diversion should, however, be made with care because of potential confounding by indication. PMID:23906011

[Intrarenal Bacillus Calmette-Guerin perfusion therapy was effective for carcinoma in situ of the upper urinary tract after ileal conduit replacement : a case report].

PubMed

Hayashi, Takuji; Yamanaka, Yohei; Kinjo, Takanori; Katayama, Kinzo; Kamoto, Akihito; Mori, Naoki; Yoshioka, Toshiaki

2014-04-01

A 63-year-old man who had undergone radical cystectomy and ileal conduit formation for invasive bladder cancer 3 years before presented with continuous positive urinary cytology in the ileal conduit. His diagnosis was carcinoma in situ (CIS) of the left upper urinary tract. He was treated with Bacillus Calmette-Guérin (BCG) perfusion therapy using a single-J ureteric stent. BCG (80 mg) in 100 ml saline was instilled in a one-hour period weekly for 6 weeks. Usage of another catheter was effective for continuing the therapy. Urinary cytology in the left upper urinary tract and the ileal conduit became negative after the therapy. There was no evidence of recurrence or metastasis of urothelial carcinoma 6 months after the therapy.

Alteration of the ileal microbiota of weanling piglets by the growth-promoting antibiotic chlortetracycline.

PubMed

Rettedal, Elizabeth; Vilain, Sébastien; Lindblom, Stacy; Lehnert, Kelly; Scofield, Clay; George, Sajan; Clay, Sharon; Kaushik, Radhey S; Rosa, Artur J M; Francis, David; Brözel, Volker S

2009-09-01

Antibiotics such as chlortetracycline (CTC) have been used to promote growth of pigs for decades, but concerns over increased antibiotic-resistant infections in humans have prompted the development of alternative strategies. Developing alternatives to antibiotic growth promoters (AGPs) could be informed by information on the mechanisms of growth promotion, notably, how AGPs affect the microbial populations of the gastrointestinal tract. Pigs from three sows were aseptically delivered by cesarean section. Six piglets were distributed to each of two foster mothers until weaning, when piglets were fed a diet with or without 50 mg/kg CTC for 2 weeks. The ileal bacterial microbiota was characterized by using a cultivation-independent approach based on DNA extraction, PCR amplification, cloning, and sequencing of the 16S rRNA gene pool. The ileal and mucosal communities of these growing pigs were dominated by Lactobacillus bacteria, various members of the family Clostridiaceae, and members of the poorly known genus Turicibacter. Overall, CTC treatment resulted in three shifts: a decrease in Lactobacillus johnsonii, an increase in L. amylovorus, and a decrease in Turicibacter phylotypes. The composition of the microbiota varied considerably between individual pigs, as revealed by shared operational taxonomic units (OTUs) and similarity (SONS) analysis (theta(YC) values). While the observed variation between untreated pigs obscured the possible effect of CTC, integral-LIBSHUFF and SONS analyses of pooled libraries indicated a significant shift due to CTC in both the lumen and the mucosa, with some OTUs unique to either treated or control ileum. DOTUR analysis revealed little overlap between control and treated communities at the 3% difference level, indicating unique ileal communities in the presence of CTC.

Inhibiting platelet-derived growth factor beta reduces Ewing's sarcoma growth and metastasis in a novel orthotopic human xenograft model.

PubMed

Wang, Yong Xin; Mandal, Deendayal; Wang, Suizhau; Hughes, Dennis; Pollock, Raphael E; Lev, Dina; Kleinerman, Eugenie; Hayes-Jordan, Andrea

2009-01-01

Despite aggressive therapy, Ewing's sarcoma (ES) patients have a poor five-year overall survival of only 20-40%. Pulmonary metastasis is the most common form of demise in these patients. The pathogenesis of pulmonary metastasis is poorly understood and few orthotopic models exist that allow study of spontaneous pulmonary metastasis in ES. We have developed a novel orthotopic xenograft model in which spontaneous pulmonary metastases develop. While the underlying biology of ES is incompletely understood, in addition to the EWS-FLI-1 mutation, it is known that platelet-derived growth factor receptor beta (PDGFR-beta) is highly expressed in ES. Hypothesizing that PDGFR-beta expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-beta inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model. Silencing PDGFR-beta reduced spontaneous growth and metastasis in ES. Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.

Postoperative Pleural Effusions After Orthotopic Heart Transplant: Cause, Clinical Manifestations, and Course.

PubMed

Ulubay, Gaye; Küpeli, Elif; Er Dedekargınoğlu, Balam; Savaş Bozbaş, Şerife; Alekberov, Mahal; Salman Sever, Özlem; Sezgin, Atilla

2016-11-01

Postoperative pleural effusions are common in patients who undergo cardiac surgery and orthotopic heart transplant. Postoperative pleural effusions may also occur as postcardiac injury syndrome. Most of these effusions are nonspecific and develop as a harmless complication of the surgical procedure itself and generally have a benign course. Here, we investigated the cause and clinical and laboratory features of postoperative early and late pleural effusions in orthotopic heart transplant patients. We retrospectively reviewed the medical records of 50 patients who underwent orthotopic heart transplant between 2004 and 2015 at Baskent University. Patient demographics and clinical and laboratory data, including cause of heart failure, presence of pleural effusions at chest radiography in the first year after transplant, timing of onset, microbiologic and biochemical analyses of pleural effusions, and treatment strategies were noted. Mean age of patients was 39.22 ± 13.83 years (39 men, 11 women). Reason for heart failure was dilated cardiomyopathy in most patients (76%). Nineteen patients (38%) had postoperative pleural effusions, with 15 patients (78.9%) with pleural effusion during the first week after transplant. Of these, 4 patients had recurrent pleural effusion. A diagnostic thoracentesis was performed in 10 patients, with 4 showing transudative effusion and 6 showing exudative effusion secondary to infection (2 patients), postcardiac injury syndrome (1 patient), and hemothorax (3 patients). Aspergillus fumigatus was detected by quantitative culture from pleural effusion in 1 patient. Tube thoracoscopy drainage was performed in 10 patients (25%), and 2 patients received antibiotic therapy. Pleural effusions are frequent after cardiac transplant. Complications may occur in a small portion of patients, with most effusions being nonspecific and having a benign course with spontaneous resolution. Early diagnostic thoracentesis could improve postoperative outcomes

Temozolomide combined with PD-1 Antibody therapy for mouse orthotopic glioma model.

PubMed

Dai, Bailing; Qi, Na; Li, Junchao; Zhang, Guilong

2018-07-02

Temozolomide (TMZ) is the most frequent adjuvant chemotherapy drug in gliomas. PDL1 expresses on various tumors, including gliomas, and anti-PD-1 antibodies have been approved for treating some tumors by FDA. This study was to evaluate the therapeutical potential of combined TMZ with anti-PD-1 antibody therapy for mouse orthotopic glioma model. We performed C57BL/6 mouse orthotopic glioma model by stereotactic intracranial implantation of glioma cell line GL261, mice were randomly divided into four groups: (1) control group; (2) TMZ group; (3) anti-PD-1 antibody group; (4) TMZ combined with anti-PD-1 antibody group. Then the volume or size of tumor was assessed by 7.0 T MRI and immunohistochemistry, and the number of CD4 and CD8 infiltrating cells in brain tumor and spleen was evaluated by immunohistochemistry. Western blot was used to evaluate the expression of PDL1. Furthermore, Overall survival of each group mice was also evaluated. Overall survival was significantly improved in combined group compared to other groups (χ2 = 32.043, p < 0.01). The volume or size of tumor was significantly decreased in combined group compared with other groups (F = 42.771, P < 0.01). And the number of CD4 and CD8 infiltrating cells in brain tumor was also obviously increased in combined group (CD4 F = 45.67, P < 0.01; CD8 F = 53.75, P < 0.01). Anti-PD1 antibody combined with TMZ therapy for orthotopic mouse glioma model could significantly improve the survival time of tumor-bear mice. Thus, this study provides the effective preclinical evidence for support clinical chemotherapy combined with immunotherapy for glioma patients. Copyright © 2018 Elsevier Inc. All rights reserved.

[Stress urinary incontinence after radical cystectomy: neobladder construction and placement of the functional retrourethral sling].

PubMed

Mayer, M; Bauer, R M; Walther, S; Becker, A J; Stief, C G; Bastian, P J; Gozzi, C

2009-06-01

Stress urinary incontinence (SUI) following radical cystectomy and orthotopic ileal neobladder construction represents a challenging problem. The incidence of incontinence following this surgery is reported to be 30-60% and is - despite a better understanding of the male (and female) pelvic anatomy - still regarded as an adverse outcome of this surgery.Therapeutic options have been limited up until now and include pharmacological agents, surgical treatment and pelvic floor training with only moderate amelioration of the symptoms and often unacceptable side effects. Nevertheless, urinary continence is probably the most important key to patient satisfaction. Here we introduce the perineal approach of the functional retrourethral mesh as a new and innovative sling suspension based on a non-obstructive procedure in a patient with urinary stress incontinence after ileal neobladder. The sling adjusts the changed anatomy after radical cystectomy returning it to the former preoperative position and thus continence can be achieved again. The approach of the sling in a patient with ileal neobladder is safe and the good result concerning continence is promising.

Retrograde Endourological Management of Upper Urinary Tract Abnormalities in Patients with Ileal Conduit Urinary Diversion: A Dual-Center Experience.

PubMed

Olson, Louise; Satherley, Hywel; Cleaveland, Paul; Zelhof, Bachar; Mokete, Max; Neilson, Donald; Srirangam, Shalom

2017-09-01

Patients with ileal conduit urinary diversions are at an increased risk of long-term upper urinary tract (UUT) complications, including anastomotic strictures, infections, and urolithiasis. The reconstructed urinary system poses challenges for endoscopic manipulation. We present and describe our dual-center experience in performing retrograde ureteroscopy to treat or diagnose UUT abnormalities in patients with ileal conduit incontinent diversion. We performed a retrospective analysis of medical records for all patients with previous urinary diversion who underwent retrograde ureteroscopic procedures via the ileal loop in our institutions over a 9 year period (between June 2007 and August 2016). Fifty-four procedures were performed in 36 patients. Mean age was 61 (28-90) years. Average time from diversion to ureteroscopic procedure was 13.0 (0.08-53) years. Stone disease was the most common indication for intervention in 35.2% (19/54) of cases, with a stone-free rate of 78.9% (15/19). Other indications included surveillance of transitional-cell carcinoma in 22.2% (12/54), diagnostic flexible ureteroscopy (fURS) in 20.4% (11/54), stricture management in 11.1% (6/54), removal of encrusted stent/nephrostomy in 7.4% (4/54), urine leak after diversion in 1.9% (1/54), and miscellaneous in 1.9% (1/54). Successful retrograde access was possible in 74% (40/54) of cases. A long and tortuous ileal segment, too difficult to negotiate, was the most common cause of failure to access the UUT. In 13 out of 54 (24.1%) cases, retrograde fURS was combined with simultaneous percutaneous antegrade access. Six patients (11.1%) developed postprocedural pyrexia requiring additional antibiotic therapy, and one (1.9%) patient required embolization of the renal artery for ongoing bleeding. Median length of stay was 1 day (0-55), with 13 (24%) being performed as day-case procedures. Retrograde ureteroscopy in patients with ileal conduits can be technically challenging due to distorted anatomy

Effects of viscosity and fermentability of dietary fibre on nutrient digestibility and digesta characteristics in ileal-cannulated grower pigs.

PubMed

Hooda, Seema; Metzler-Zebeli, Barbara U; Vasanthan, Thavaratnam; Zijlstra, Ruurd T

2011-09-01

Relative contributions of two functional properties, viscosity and fermentability of dietary fibre, on apparent ileal digestibility (AID), apparent total tract digestibility (ATTD), digesta passage rate, N retention and SCFA concentration have not been established. Thus, eight ileal-cannulated pigs randomised in a double 4 × 4 Latin square were fed four diets based on maize starch and casein supplemented with 5 % of actual fibre in a 2 × 2 factorial arrangement: low-fermentable, low-viscous cellulose (CEL); low-fermentable, high-viscous carboxymethylcellulose (CMC); high-fermentable, low-viscous oat β-glucan (LBG); high-fermentable, high-viscous oat β-glucan (HBG). Viscosity and fermentability interacted to affect (P < 0·001) digesta viscosity and AID and ATTD of nutrients. These properties tended to interact to affect (P < 0·10) digesta passage rate and butyrate. Pigs fed the CMC diet had the lowest (P < 0·05) digesta passage rate and the highest (P < 0·001) AID of energy, crude protein and DM, and ATTD of energy and DM. Post-ileal DM digestibility was highest (P < 0·001) for pigs fed the CEL and HBG diets. Post-ileal DM digestibility had a negative, curvilinear relationship with the AID of energy and crude protein (R2 0·85 and 0·72, respectively; P < 0·001). Digesta viscosity had a less strong relationship with the AID of energy and crude protein (R2 0·45 and 0·36, respectively; P < 0·001). In conclusion, high-viscous, low-fermentable dietary fibre increases the proportion of a diet that is digested in the small intestine by reducing digesta passage rate.

CETUXIMAB AND IRINOTECAN INTERACT SYNERGISTICALLY TO INHIBIT THE GROWTH OF ORTHOTOPIC ANAPLASTIC THYROID CARCINOMA XENOGRAFTS IN NUDE MICE

PubMed Central

Kim, Seungwon; Prichard, Christopher N.; Younes, Maher N.; Yazici, Yasemin D.; Jasser, Samar A.; Bekele, B. Nebiyou; Myers, Jeffrey N.

2006-01-01

Objective Anaplastic thyroid carcinoma (ATC) remains one of the most lethal known human cancers. Targeted molecular therapy with cetuximab, a monoclonal antibody against EGFR, offers new treatment potentials for patient with ATC. Cetuximab has also been reported to have synergistic effects when combined with irinotecan, a topoisomerase inhibitor. Therefore, we hypothesized that cetuximab and irinotecan would be effective in inhibiting the growth and progression of ATC in a murine orthotopic model. Design The in vitro anti-proliferative effects of cetuximab and irinotecan on ATC cell line ARO were examined. We also studied the in vivo effects of cetuximab and irinotecan on the growth, invasion, and metastasis of orthotopic ATC tumors in nude mice. The in vivo antitumor efficacy of cetuximab/irinotecan combination was also compared with that of doxorubicin. Results Cetuximab alone did not show any anti-proliferative or pro-apoptotic effect on this cell line. However, when combined with irinotecan, cetuximab potentiated the in vitro anti-proliferative and pro-apoptotic effect of irinotecan. Cetuximab, irinotecan, and cetuximab/irinotecan combination resulted in 77%, 79%, and 93% in vivo inhibition of tumor growth, respectively. Incidences of lymph node metastasis, laryngeal invasion, and tumor microvessel density were also significantly decreased in these treatment groups. Furthermore, the cetuximab/irinotecan combination was significantly more effective than doxorubicin in inhibiting the growth of orthotopic ATC xenografts. Conclusions Combination therapy with cetuximab/irinotecan inhibits the growth and progression of orthotopic ATC xenografts in nude mice. Given the lack of curative options for patients with ATC, combination therapy with cetuximab and irinotecan treatment warrants further study. PMID:16428506

Characterization of thyroid cancer cell lines in murine orthotopic and intracardiac metastasis models.

PubMed

Morrison, Jennifer A; Pike, Laura A; Lund, Greg; Zhou, Qiong; Kessler, Brittelle E; Bauerle, Kevin T; Sams, Sharon B; Haugen, Bryan R; Schweppe, Rebecca E

2015-06-01

Thyroid cancer incidence has been increasing over time, and it is estimated that ∼1950 advanced thyroid cancer patients will die of their disease in 2015. To combat this disease, an enhanced understanding of thyroid cancer development and progression as well as the development of efficacious, targeted therapies are needed. In vitro and in vivo studies utilizing thyroid cancer cell lines and animal models are critically important to these research efforts. In this report, we detail our studies with a panel of authenticated human anaplastic and papillary thyroid cancer (ATC and PTC) cell lines engineered to express firefly luciferase in two in vivo murine cancer models-an orthotopic thyroid cancer model as well as an intracardiac injection metastasis model. In these models, primary tumor growth in the orthotopic model and the establishment and growth of metastases in the intracardiac injection model are followed in vivo using an IVIS imaging system. In the orthotopic model, the ATC cell lines 8505C and T238 and the PTC cell lines K1/GLAG-66 and BCPAP had take rates >90 % with final tumor volumes ranging 84-214 mm(3) over 4-5 weeks. In the intracardiac model, metastasis establishment was successful in the ATC cell lines HTh74, HTh7, 8505C, THJ-16T, and Cal62 with take rates ≥70 %. Only one of the PTC cell lines tested (BCPAP) was successful in the intracardiac model with a take rate of 30 %. These data will be beneficial to inform the choice of cell line and model system for the design of future thyroid cancer studies.

In Vitro Selective Growth-Inhibitory Effect of 8-Hydroxyquinoline on Clostridium perfringens versus Bifidobacteria in a Medium Containing Chicken Ileal Digesta.

PubMed

Skrivanova, Eva; Van Immerseel, Filip; Hovorkova, Petra; Kokoska, Ladislav

2016-01-01

Clostridium perfringens-induced necrotic enteritis is generally controlled by antibiotics. However, because of increasing antibiotic resistance, other antibacterial agents are required, preferably ones that do not affect the beneficial intestinal microbiota of the host. This study evaluated the in vitro selective growth-inhibitory effect of 8-hydroxyquinoline (8HQ) on C. perfringens vs. bifidobacteria in a medium containing chicken ileal digesta. Prior to the experiments, the minimum inhibitory concentrations of 8HQ and penicillin G were determined by broth microdilution assay. The minimum inhibitory concentration values of 8HQ for C. perfringens were 16-32 times lower than the values for bifidobacteria. Treatment of autoclaved and non-autoclaved chicken ileal digesta with 8HQ showed a selective anticlostridial effect. After incubation of C. perfringens with autoclaved ileal digesta for 3 h, all 8HQ concentrations tested (32-2048 μg/mL) significantly reduced C. perfringens bacterial count. In contrast, the same treatment had no or only a slight effect on bifidobacteria counts. Unlike 8HQ, penicillin G did not exhibit any selectivity. Similar results were obtained after incubation for 24 h. In non-autoclaved ileal digesta, all 8HQ concentrations tested significantly reduced C. perfringens bacterial counts after incubation for 30 min and 3 h, while no effect was observed on bifidobacteria. These results suggest that 8HQ may serve as a prospective veterinary compound for use against necrotic enteritis in poultry.

High True Ileal Digestibility but Not Postprandial Utilization of Nitrogen from Bovine Meat Protein in Humans Is Moderately Decreased by High-Temperature, Long-Duration Cooking.

PubMed

Oberli, Marion; Marsset-Baglieri, Agnès; Airinei, Gheorghe; Santé-Lhoutellier, Véronique; Khodorova, Nadezda; Rémond, Didier; Foucault-Simonin, Angélique; Piedcoq, Julien; Tomé, Daniel; Fromentin, Gilles; Benamouzig, Robert; Gaudichon, Claire

2015-10-01

Meat protein digestibility can be impaired because of indigestible protein aggregates that form during cooking. When the aggregates are subsequently fermented by the microbiota, they can generate potentially harmful compounds for the colonic mucosa. This study evaluated the quantity of bovine meat protein escaping digestion in the human small intestine and the metabolic fate of exogenous nitrogen, depending on cooking processes. Sixteen volunteers (5 women and 11 men; aged 28 ± 8 y) were equipped with a double lumen intestinal tube positioned at the ileal level. They received a test meal exclusively composed of 120 g of intrinsically (15)N-labeled bovine meat, cooked either at 55°C for 5 min (n = 8) or at 90°C for 30 min (n = 8). Ileal effluents and blood and urine samples were collected over an 8-h period after the meal ingestion, and (15)N enrichments were measured to assess the digestibility of meat proteins and the transfer of dietary nitrogen into the metabolic pools. Proteins tended to be less digestible for the meat cooked at 90°C for 30 min than at 55°C for 5 min (90.1% ± 2.1% vs. 94.1% ± 0.7% of ingested N; P = 0.08). However, the particle number and size in ileal digesta did not differ between groups. The appearance of variable amounts of intact fibers was observed by microscopy. The kinetics of (15)N appearance in plasma proteins, amino acids, and urea were similar between groups. The amount of exogenous nitrogen lost through deamination did not differ between groups (21.2% ± 0.8% of ingested N). Cooking bovine meat at a high temperature for a long time can moderately decrease protein digestibility compared with cooking at a lower temperature for a short time and does not affect postprandial exogenous protein metabolism in young adults. The study was registered at www.clinicaltrials.gov as NCT01685307. © 2015 American Society for Nutrition.

Effect of feeding level on ileal and total tract digestibility of nutrients and energy from soybean meal-based diets for piglets.

PubMed

Goerke, M; Mosenthin, R; Jezierny, D; Sauer, N; Piepho, H-P; Messerschmidt, U; Eklund, M

2014-12-01

A total of 36 piglets with an initial body weight (BW) of 5.6 ± 0.7 kg, fitted with simple T-cannulas at the distal ileum, were used to evaluate the effect of three graded feeding levels (50, 75 or 100 g/kg BW(0.75) day) on apparent ileal digestibility (AID) and total tract digestibility (ATTD) of dry matter (DM), nitrogen (N) and energy, and on ATTD of organic matter (OM), ether extracts (EE), neutral detergent fibre (NDF), acid detergent fibre (ADF) and digestible (DE), metabolisable (ME) and net energy (NE) content in soybean meal (SBM)-casein-cornstarch-based diets. The AID of DM, N and energy and ATTD of NDF, ADF and EE in the diets were not affected (p > 0.05) by the feed intake (FI) level. There was a small decrease in ATTD of DM, N (CP), OM, ash and energy, and in DE, ME and NE content in the diets (p < 0.05) with increasing FI level. The net disappearance in the large intestine (in % of ileal recovery) decreased for DM, N and energy (p < 0.05) with increasing FI level. The design of the study allowed for estimating ileal endogenous loss of N and total tract endogenous loss of ash, N and EE, for estimating corresponding true ileal and total tract digestibility values, and for estimating urinary endogenous N loss. High variability in estimates of ileal endogenous N loss and total tract endogenous losses of N, EE and ash reflects great variation in individual endogenous losses between animals. Estimation of true total tract digestibility of N, EE and ash by regression analysis was affected by their decrease in ATTD with increasing FI level, as estimates for true digestibility were lower compared to their apparent values. The present results suggest that FI level can affect both apparent and true total tract nutrient digestibility in piglets. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Furosemide suppresses ileal and colonic contractility via interactions with GABA-A receptor in mice.

PubMed

Kaewsaro, Kannaree; Nualplub, Suparp; Bumrungsri, Sara; Khuituan, Pissared

2017-11-01

The loop diuretic furosemide has an action to inhibit Na + -K + -2Cl - co-transporter at the thick ascending limb of Henle's loop resulting in diuresis. Furosemide also has the non-diuretic effects by binding to GABA-A receptor which may involve the gastrointestinal tract. The aim of this study was to investigate the effects of furosemide on smooth muscle contractions in mice ileum and proximal colon. Each intestinal segment suspended in an organ bath was connected to a force transducer. Signal output of mechanical activity was amplified and recorded for analysis using PowerLab System. After equilibration, the intestine was directly exposed to furosemide, GABA, GABA-A receptor agonist (muscimol), or muscarinic receptor antagonist (atropine). Furosemide (50, 100 and 500 μmol L -1 ) acutely reduced the amplitude of ileal and colonic contraction. In the ileum, 1 mmol L -1 GABA and 10-60 μmol L -1 muscimol significantly increased the amplitude, whereas in the colon, 50-100 mmol L -1 GABA and 60 μmol L -1 muscimol decreased the contractions. The contractions were also significantly suppressed by atropine. To investigate the mechanisms underlying the inhibiting effect of furosemide, furosemide was added to the organ bath prior to the addition of muscimol or atropine. A comparison of furosemide combined with muscimol or atropine group and furosemide group showed no significant difference of the ileal contraction, but the amplitude of colonic contraction significantly decreased when compared to adding furosemide alone. These results suggest that furosemide can reduce the ileal and proximal colonic contraction mediated by blocking and supporting of GABA-A receptor, respectively, resulting in decreased acetylcholine release. © 2017 John Wiley & Sons Australia, Ltd.

New waveguide shape for low loss and high uniformity y-branch optical splitter

NASA Astrophysics Data System (ADS)

Burtscher, Catalina; Seyringer, Dana; Lucki, Michal; Kohler, Linda

2017-02-01

The most common application of optical Y-splitters is their use in FTTx networks. It allows several customers to share the same physical medium, bringing high-speed networking, digital television and telephone services to residences using fiber-optic cables. The task of the optical splitters in such FTTH networks is to split one optical signal in many identical signals bringing for example the same TV signal in different households. Of course, the more buildings can be served by one optical splitter the lower are the installation costs. Therefore, the special attention is paid mainly to the design of high channel optical splitters presenting the serious challenge for the professional designers. In this paper a new Y-branch shape is proposed for 1×32 Y-branch splitter ensuring better splitting properties compared to the one recommended by ITU, in terms of their performance in transmission systems using wavelength division multiplexing.

Effects of dietary inclusion of silymarin on performance, intestinal morphology and ileal bacterial count in aflatoxin-challenged broiler chicks.

PubMed

Jahanian, E; Mahdavi, A H; Asgary, S; Jahanian, R

2017-10-01

This study was conducted to investigate the effect of dietary supplementation of silymarin on performance, jejunal morphology and ileal bacterial population in broiler chicks intoxicated with a mix of aflatoxins. A total of three hundred thirty six 7-day-old Ross broiler chicks were randomly distributed between seven experimental groups with four replicates of 12 birds each. Experimental treatments consisted of a control group (unchallenged), and a 2 × 3 factorial arrangement, including two aflatoxin levels (0.5 and 2 ppm) and three levels of silymarin (0, 500 and 1000 ppm). Birds were challenged with a mix of aflatoxins from 7 to 28 days of age. Results showed that increasing aflatoxin level resulted in decreased average daily feed intake (ADFI) and weight gain (ADWG), consequently impaired feed conversion ratio (FCR) throughout the trial period. Dietary supplementation of silymarin resulted in the marked increases in ADFI and ADWG, and improved FCR values in aflatoxin-challenged chicks. Ileal bacterial populations at days 28 and 42 of age were increased by incremental levels of aflatoxins. On the other hand, dietary silymarin supplementation suppressed ileal populations of Escherichia coli, Salmonella, Klebsiella and total negative bacteria in aflatoxicated birds. Increase in dietary aflatoxin level resulted in the decreased villi height, villi height-to-crypt depth ratio (VH:CD), villi surface area and apparent villi absorptive area, while it increased crypt depth, goblet cell count and lymphoid follicular diameter. Feeding silymarin at the level of 1000 ppm increased villi height and VH:CD in aflatoxicated birds. Present results indicate that dietary inclusion of silymarin could improve performance by suppressing ileal bacteria and enhancing absorptive surface area in aflatoxin-challenged broiler chicks. Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.

Salinomycin nanoparticles interfere with tumor cell growth and the tumor microenvironment in an orthotopic model of pancreatic cancer.

PubMed

Daman, Zahra; Faghihi, Homa; Montazeri, Hamed

2018-05-02

Recently, salinomycin (SAL) has been reported to inhibit proliferation and induce apoptosis in various tumors. The aim of this study was to deliver SAL to orthotopic model of pancreatic cancer by the aid of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The NPs were physico-chemically characterized and evaluated for cytotoxicity on luciferase-transduced AsPC-1 cells in vitro as well as implanted orthotopically into the pancreas of nude mice. SAL (3.5 mg/kg every other day) blocked tumor growth by 52% compared to the control group after 3 weeks of therapy. Western blotting of tumor protein extracts indicated that SAL treatment leads to up-regulation of E-cadherin, β-catenin, and transforming growth factor beta receptor (TGFβR) expressions in AsPC-1 orthotopic tumor. Noteworthy, immunofluorescence staining of adjacent tumor sections showed that treatment with SAL NPs cause significant apoptosis in the tumor cells rather than the stroma. Further investigations also revealed that TGFβR2 over-expression was induced in stroma cells after treatment with SAL NPs. These results highlight SAL-loaded PLGA NPs as a promising system for pancreatic cancer treatment, while the mechanistic questions need to be subsequently tested.

Adenocarcinoma in the anal transitional zone after ileal pouch for ulcerative colitis: report of a case.

PubMed

Bell, Stephen W; Parry, B; Neill, M

2003-08-01

This article reports the seventh known case of adenocarcinoma arising in or adjacent to an ileal pouch after proctocolectomy for ulcerative colitis. It is the second reported case of adenocarcinoma in the anal transitional zone in this setting. A literature review is presented of the six previous cases published, and on the wider subject of how to best manage the anal transitional zone. It is concluded that this is a rare, but catastrophic, event with a potentially poor prognosis and can occur late (more than a decade) after the original surgery. All ileal pouches performed for ulcerative colitis should be followed for extended periods. The development of dysplasia necessitates close follow-up, including regular biopsies, and local excision and pouch advancement can manage persistent dysplasia. When operating for dysplasia or cancer, biopsies of the anal transitional zone should be performed or consideration given to mandatory mucosectomy.

A case of staghorn stones in a kidney with an ileal ureter treated by percutaneous nephrolithotomy.

PubMed

Gao, Xiaofeng; Zhou, Tie; Li, Jinyi; Sun, Yinghao

2008-12-01

A 59-year-old man was admitted to hospital for investigation of a 1-year history of intermittent hematuria. He had undergone ileal ureteral replacement for left renal stones 36 years earlier. Renal ultrasonography, physical examination, abdominal plain radiography, intravenous urography, CT urography, measurement of serum levels of creatinine, urea and electrolytes, renal scintigraphy, urinalysis and urine culture. Staghorn calculi in the left kidney, with a high-lying anastomosis between the renal pelvis and the proximal ileal segment. The patient underwent percutaneous nephrolithotomy via a middle-calyx access for the large staghorn stones. After surgery, no residual calculi were found and the patient was discharged with an uneventful postoperative course. At 1 month, renal scintigraphy showed normal bilateral kidney function. The patient received potassium citrate supplementation and was followed up with 6-monthly imaging studies. At the last report, he had been stone-free for 7 months.

[To the issue of postreperfusion syndrome predictors in orthotopic liver transplantation (OLT)].

PubMed

Kiseleva, E A; Ushakova, I A; Kim, E F; Matveev, G P; Biriulina, N Iu; Vabishchevich, A V

2012-01-01

The aim of the study is revelation of postperfusion syndrome (pPS) predictors in orthotopic liver transplantation (OLT). Was conducted a retrospective analysis of anesthesia maintainance protocols during orthotopic liver transplantation in 261 patients aged from 6 months to 60 years. Investigated the effect of various factors on the development of PPS by the application of methods of non-parametric statistics. Significantly more frequent development of the PPS is noted in the age group from 3 to 18 years (up to 30% of patients). In recipients older than 18 years the frequency of the development of the PPS does not depend on age, with an average of 14%. The development of the PPS does not depend on the recipient sex, the nature of the pathology which served as an indication to the OTP, the initial severity of the state, type of OTP (living related donor or cadaveric transplantation, primary or re-transplantation), the transplant warm ischemia duration, use, or the lack of venous-venous bypass, metabolic status of the patient. The obtained results do not contradict to the data of foreign publications. Among parameters available for screening, predictor of PPS was not detected.

Perfluorocarbon emulsions radiosensitise brain tumors in carbogen breathing mice with orthotopic GL261 gliomas

PubMed Central

Feldman, Lisa A.; Fabre, Marie-Sophie; Grasso, Carole; Reid, Dana; Broaddus, William C.; Lanza, Gregory M.; Spiess, Bruce D.; Garbow, Joel R.; McConnell, Melanie J.

2017-01-01

Background Tumour hypoxia limits the effectiveness of radiation therapy. Delivering normobaric or hyperbaric oxygen therapy elevates pO2 in both tumour and normal brain tissue. However, pO2 levels return to baseline within 15 minutes of stopping therapy. Aim To investigate the effect of perfluorocarbon (PFC) emulsions on hypoxia in subcutaneous and intracranial mouse gliomas and their radiosensitising effect in orthotopic gliomas in mice breathing carbogen (95%O2 and 5%CO2). Results PFC emulsions completely abrogated hypoxia in both subcutaneous and intracranial GL261 models and conferred a significant survival advantage orthotopically (Mantel Cox: p = 0.048) in carbogen breathing mice injected intravenously (IV) with PFC emulsions before radiation versus mice receiving radiation alone. Carbogen alone decreased hypoxia levels substantially and conferred a smaller but not statistically significant survival advantage over and above radiation alone. Conclusion IV injections of PFC emulsions followed by 1h carbogen breathing, radiosensitises GL261 intracranial tumors. PMID:28873460

One-step solvothermal synthesis, a worm-shaped morphology and luminescence properties of green-emitting Y2O2S:Tb3+ nanophosphors

NASA Astrophysics Data System (ADS)

Liu, Fan; Lian, Jingbao; Wu, Nianchu; He, Jiao; Zhang, Xue; Liu, Feng

2018-02-01

The worm-shaped Y2O2S:Tb3+ nanophosphors have been successfully prepared via one-step solvothermal synthesis, using ethanediamine as the main solvent and sublimed sulfur powder as the source of sulfur without adding additional structure-directing reagents. XRD, FT-IR, FESEM, PL and CIE chromaticity diagram were used to characterize the obtained products. XRD results demonstrate that all diffraction peaks of the sample can be well indexed to pure hexagonal phase of Y2O2S with optimal condition, i.e. the molar ration of S/Y3+m = 10, solvothermal temperature T = 220 °C and synthetic time t = 24 h. When t varies from 2 h to 24 h, the morphology of Y2O2S transforms from cauliflower-like structure to worm-shaped nanoparticles with the length of ∼80 nm. The formation mechanism depending on t has also been proposed. Upon 250 nm ultraviolet (UV) light excitation, the worm-shaped Y2O2S:Tb3+ nanophosphors exhibit green emissions, corresponding to the 5D4 → 7FJ (J = 6, 5, 4, 3) transitions of Tb3+ions. The quenching concentration is 7% and its corresponding lifetime is 1216 μs. The CIE chromaticity coordinates show the tuneable emission shifting from yellow green to yellowish green with increasing concentration of Tb3+ions from 1% to 7%. Those results suggest that the worm-shaped Y2O2S:Tb3+ nanophosphors may have potential applications in X-ray intensifying screens, fluorescence and biomedical fields.

Orthotopic Transplantation of Achilles Tendon Allograft in Rats

PubMed Central

Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

2018-01-01

The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at −80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

Anesthetic management in pediatric orthotopic liver transplant for fulminant hepatic failure and end-stage liver disease.

PubMed

Camkıran, Aynur; Araz, Coşkun; Seyhan Ballı, Sevgi; Torgay, Adnan; Moray, Gökhan; Pirat, Arash; Arslan, Gülnaz; Haberal, Mehmet

2014-03-01

We assessed the anesthetic management and short-term morbidity and mortality in pediatrics patients who underwent an orthotopic liver transplant for fulminant hepatic failure or end-stage liver disease in a university hospital. We retrospectively analyzed the records of children who underwent orthotopic liver transplant from May 2002 to May 2012. Patients were categorized into 2 groups: group fulminant hepatic failure (n=22) and group end-stage liver disease (n=19). Perioperative data related to anesthetic management and intraoperative events were collected along with information related to postoperative course and survival to hospital discharge. Mean age and weight for groups fulminant hepatic failure and end-stage liver disease were 8.6 ± 2.7 years and 10.8 ± 3.8 years (P = .04) and 29.2 ± 11.9 kg and 33.7 ± 16.9 kg (P = .46). There were no differences between the groups regarding length of anhepatic phase (65 ± 21 min vs 73 ± 18 min, P = .13) and operation time (9.1 ± 1.6 h vs 9.5 ± 1.8 h, P = .23). When compared with the patients in group fulminant hepatic failure, those in group end-stage liver disease more commonly had a Glasgow Coma score of 7 or less (32% vs 6%, P = .04). Compared with patients in group fulminant hepatic failure, those in group end-stage liver disease were more frequently extubated in the operating room (31.8% versus 89.5% P < .001). Postoperative duration of mechanical ventilation (2.78 ± 4.02 d vs 2.85 ± 10.21 d, P = .05), and the mortality rates at 1 year after orthotopic liver transplant (7.3% vs 0%, P = .09) were similar between the groups. During pediatric orthotopic liver transplant, those children with fulminant hepatic failure require more intraoperative fluids and more frequent perioperative mechanical ventilation than those with end-stage liver disease.

Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature.

PubMed

Haberman, Yael; Tickle, Timothy L; Dexheimer, Phillip J; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N; Noe, Joshua D; Rosh, Joel; Markowitz, James; Heyman, Melvin B; Griffiths, Anne M; Crandall, Wallace V; Mack, David R; Baker, Susan S; Huttenhower, Curtis; Keljo, David J; Hyams, Jeffrey S; Kugathasan, Subra; Walters, Thomas D; Aronow, Bruce; Xavier, Ramnik J; Gevers, Dirk; Denson, Lee A

2014-08-01

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.

Standardized Ileal Amino Acid Digestibility of Corn, Corn Distillers' Dried Grains with Solubles, Wheat Middlings, and Bakery By-Products in Broilers and Laying Hens.

PubMed

Adedokun, S A; Jaynes, P; Payne, R L; Applegate, T J

2015-10-01

Standardized ileal amino acid digestibility (SIAAD) of 5 samples of corn distillers dried grain with solubles (DDGS), 5 samples of bakery by-products (BBP), 3 samples of corn, and 1 sample of wheat middlings (WM) were evaluated in broilers and laying hens. Diets containing each of the 14 feed ingredients were evaluated in 21 day-old broiler chickens. The DDGS and BBP containing diets were fed to 30-week-old laying hens, while corn and wheat middling were evaluated in 50-week-old laying hens. All the diets were semi-purified with each feed ingredient being the only source of amino acid (AA). To obtain SIAAD values, apparent ileal AA digestibility was corrected for basal ileal endogenous AA losses using values generated from broilers and laying hens fed a nitrogen-free diet. Ileal crude protein digestibility for the 5 DDGS samples was higher (P < 0.05) in broilers than in laying hens. Broilers had higher SIAAD for DDGS 2, 3, 4, and 5 while there was no difference for DDGS 1 except for 4 AA where broilers had higher (P < 0.05) SIAAD values. Standardized ileal AA digestibility values for broilers were higher (P < 0.05) for BBP 1 and 4. Ileal CP digestibility for corn 1 was higher (P < 0.05) for broilers compared to laying hens, and SIAAD values for the 16 AA (9 indispensable and 7 dispensable) evaluated in this study were higher (P < 0.05) in broilers. Broilers had higher (P < 0.05) SIAAD values for 4 (histidine, leucine, phenylalanine, and valine) and 6 (histidine, leucine, methionine, phenylalanine, threonine, and valine) indispensable and 3 (cysteine, glutamic acid, and proline) and 4 (cysteine, glutamic acid, proline, and serine) dispensable AA for corn 2 and corn 3, respectively. No difference in SIAAD between broilers and laying hens was observed for WM. Results from this study confirm that high variability in digestibility exists between different samples of DDGS. Differences in SIAAD between broilers and laying hens were observed in some samples of

Ionic liquid-assisted preparation of square-shaped Y{sub 2}O{sub 3} nanoplates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lei; Fang, Hao; Xu, Hualan

Highlights: • Y{sub 4}O(OH){sub 9}(NO{sub 3}) nanosheets were prepared by an ionic liquid-assisted mixed solvothermal route. • Y{sub 2}O{sub 3} nanosheets were obtained after calcining the Y{sub 4}O(OH){sub 9}(NO{sub 3}) nanosheets. • The Y{sub 2}O{sub 3} nanosheets are with length of about 300 nm and thickness of several nanometers. - Abstract: Uniform square-shaped Y{sub 4}O(OH){sub 9}(NO{sub 3}) nanoplates with side length of about 300 nm and thickness of tens of nanometers have been successfully prepared by an ionic liquid-assisted mixed solvothermal route. Y{sub 2}O{sub 3} nanoplates with similar size were obtained after calcining the Y{sub 4}O(OH){sub 9}(NO{sub 3}) nanoplates atmore » 800 °C. The products were analyzed by powder X-ray diffraction (XRD), thermogravimetric analysis (TG), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high resolution TEM (HRTEM), and electron diffraction (ED). The effects of reaction time, composition of solvents, and the molar ratio of reagents on the morphology of the products have been investigated. The possible formation mechanism of the Y{sub 4}O(OH){sub 9}(NO{sub 3}) nanoplates was also discussed. Y{sub 2}O{sub 3}:Eu{sup 3+} nanoplates were also synthesized and their photoluminescent properties were examined.« less

An alternative technique for orthotopic cardiac transplantation, with preservation of the normal anatomy of the right atrium.

PubMed

Sievers, H H; Weyand, M; Kraatz, E G; Bernhard, A

1991-04-01

The standard technique for orthotopic cardiac transplantation implies large atrial anastomoses which do not preserve the anatomical integrity of the donor atria. This may become a potential source of electrophysiological and mechanical atrial dysfunction, especially in the right atrium with the sinus node and the sensitive low-pressure atrioventricular valve. As an improvement we suggest an alternative technique which we have recently developed for orthotopic cardiac transplantation; it combines the simple, convenient left atrial connection of the standard technique with individual anastomoses of the superior and inferior venae cavae, preserving the right atrium of the donated heart intact. This technique and our first results in two cases are described. Postoperatively, no arrhythmias and no signs of tricuspid insufficiency were observed.

Application of Y-shaped, coated self-expandable metallic stents for anastomotic stenosis after gastrojejunostomy (Billroth II).

PubMed

Li, Teng-Fei; Wu, Gang; Han, Xin-Wei; Shui, Shao-Feng; Ren, Jian-Zhuang; Li, Zhen; Ren, Ke-Wei

2017-01-01

Anastomotic stenosis is an infrequent but life-threatening complication after gastrojejunostomy (Billroth II). Tubular or single tubular stents have limited efficacy due to the particular anatomy. To assess the feasibility of a Y-shaped, fully-coated, self-expandable, metallic stent (SEMS) for anastomotic stenosis after gastrojejunostomy (Billroth II). Between January 2008 and August 2014, 14 patients (10 with gastric carcinoma and four with duodenal ulcers) had anastomotic stenoses following Billroth II reconstructions. Eight patients with gastric cancer had tumor recurrence near the anastomosis; two had benign strictures. The four duodenal ulcer patients had benign stenoses. An integrated Y-shaped, fully coated SEMS was designed to accord with the anatomy of residual gastrojejunal anastomotic strictures. Fourteen stents were inserted under fluoroscopic control. Follow-up was at 1, 3, 9, and 12 months, and then annually. All 14 stents were inserted successfully at the first attempt with a technical success rate of 100%. After stenting, abdominal symptoms resolved in all patients. All patients were followed up for 4-27 months (mean, 13.9 months). One of the eight recurrent cases died of multiple tumor metastases and liver failure after 7 months, without obstruction symptoms. In all six patients with benign anastomotic stenosis, the stents were removed successfully without complication and with no evidence of restenosis based on clinical evaluation and imaging. A Y-shaped, fully-coated SEMS proved to be a feasible and minimally invasive procedure for treating anastomotic stenosis after gastrojejunostomy (Billroth II). © The Foundation Acta Radiologica 2016.

Sex-dependent selection differentially shapes genetic variation on and off the guppy Y chromosome.

PubMed

Postma, Erik; Spyrou, Nicolle; Rollins, Lee Ann; Brooks, Robert C

2011-08-01

Because selection is often sex-dependent, alleles can have positive effects on fitness in one sex and negative effects in the other, resulting in intralocus sexual conflict. Evolutionary theory predicts that intralocus sexual conflict can drive the evolution of sex limitation, sex-linkage, and sex chromosome differentiation. However, evidence that sex-dependent selection results in sex-linkage is limited. Here, we formally partition the contribution of Y-linked and non-Y-linked quantitative genetic variation in coloration, tail, and body size of male guppies (Poecilia reticulata)-traits previously implicated as sexually antagonistic. We show that these traits are strongly genetically correlated, both on and off the Y chromosome, but that these correlations differ in sign and magnitude between both parts of the genome. As predicted, variation in attractiveness was found to be associated with the Y-linked, rather than with the non-Y-linked component of genetic variation in male ornamentation. These findings show how the evolution of Y-linkage may be able to resolve sexual conflict. More generally, they provide unique insight into how sex-specific selection has the potential to differentially shape the genetic architecture of fitness traits across different parts of the genome. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

[The application of Y-shaped self-expandable covered metal stents in the thoracostomach-airway fistula: a single center, 11 years experience].

PubMed

Fang, Yi; Li, Tengfei; Han, Xinwei; Wu, Gang; Ren, Jianzhuang; Ren, Kewei; Lu, Huibin; Zhang, Quanhui; Li, Zongming

2015-08-01

To investigate the clinical feasibility and efficacy of Y-shaped self-expandable covered metal stents (Y-stents) in the management of thoracostomach-airway fistula. Retrospective analysis was performed for 108 patients treated for thoracostomach-airway fistula with Y-shaped self-expandable coated metal stents between April 2003 and October 2014. Y-stents were designed based on the dimensions of trachea and bronchus and sites of the fistula and then were inserted under DSA monitoring. There were 65 cases with single big Y-stent placement, 26 cases with single small Y-stent placement, 23 cases with double Y-stents placement, and 1 case with 3 Y-stents placement. Stent implantation was successfully accomplished with single manipulation in all patients. Complete occlusion of the fistula was obtained in 104 patients after the primary manipulation, and 4 patients required a secondary manipulation where a double Y-stents was inserted because of failure of primary manipulate. Ninety-two patients completed the follow-up , while 16 were lost. Fifty-nine patients died while 33 were alive with marked improvement in their quality of life. The placement of Y-stents can effectively occlude the thoracostomach-airway fistula in patients who had had the esophageal tumors resected. The technique is not only feasible but reliable to improve the quality of life of the patients.

Y-type urethral duplication: an unusual variant of a rare anomaly.

PubMed

Kumaravel, S; Senthilnathan, R; Sankkarabarathi, C; Bagdi, R K; Soundararajan, S; Prasad, N

2004-12-01

Urethral duplications are rare anomalies. We present a 3-year-old continent boy passing urine since birth per anus while voiding from penis. Micturating cystourethrogram, retrograde urethrogram and cystoscopy revealed a Y connection between the posterior urethra and anal canal. The accessory channel was excised by a perineal approach. Histopathology revealed that the tract was lined by transitional epithelium, proving that it was indeed a case of urethral duplication; hence, we suggest that all urethroanal fistulas are not variants of anorectal malformations. Certain of these fistulas should be considered as variants of Y-type urethral duplication even if the orthotopic urethra is normal.

Examining the effect of dietary electrolyte balance, energy source, and length of feeding of nitrogen-free diets on ileal endogenous amino acid losses in broilers.

PubMed

Adedokun, S A; Pescatore, A J; Ford, M J; Jacob, J P; Helmbrecht, A

2017-09-01

The effect of dietary electrolyte balance (DEB), energy source (ES), and length of feeding of nitrogen-free diet (NFD) on ileal endogenous amino acid (EAA) loss in mg/kg dry matter intake (DMI) was evaluated in broiler chickens. In Experiment 1, 720 chickens consisting of 15 replicate cages with 6 chickens/replicate were used. Treatments were arranged in a 2 × 2 × 2 factorial and consisted of 4 NFD with 2 levels (low or high) of DEB and 2 ES [corn starch (CS) or dextrose (DX)], and 2 sampling time-points (diets were fed for either 72 h (d 16 to 19) or 120 h (d 16 to 21). Experiment 2 used 360 chickens in a 2 × 2 factorial arrangement of treatments with 2 levels (low or high) of DEB and 2 ES (CS or DX). Diets were fed for 72 h (d 18 to 21). All birds had access to feed and water on an ad libitum basis. Data were analyzed using the GLM procedure of SAS appropriate for a completely randomized design for a factorial arrangement of treatments. For Experiment 1, there were interactions (P < 0.05) between the 3 main factors for nitrogen and all the AA except Trp. Broilers that were fed DX-based NFD with high DEB for 72 h had the highest (P < 0.05) EAA losses. In Experiment 2, there was no interaction between DEB and ES except for His and Lys. When ileal EAA losses from birds fed the low DEB, CS-based NFD were used to standardize apparent ileal digestibility values from a previous study, there was no effect of length of feeding on standardized ileal AA digestibility values. In conclusion, DX-based NFD with high DEB increased endogenous AA loses. Despite differences in ileal EAA losses from CS-based NFD, standardized ileal AA digestibility values were not influenced by the length of feeding of NFD. Based on the results from these studies, NFD could be fed for 72 h without influencing SIAAD values. © 2017 Poultry Science Association Inc.

Ureteric catheterization via an ileal conduit: technique and retrieval of a JJ stent.

PubMed

Wah, T M; Kellett, M J

2004-11-01

Retrograde ureteric catheterization of a patient with an ileal conduit is difficult, because guide wires and catheters coil in the conduit. A modified loopogram, using a Foley catheter as a fulcrum through which catheters can be advanced to the ureteric anastomosis, is described. This technique was used to remove a JJ stent, which had been inserted previously across a stricture in one ureter, the stent crossing from one kidney to the other.

Effectiveness of a cranberry (Vaccinium macrocarpon) preparation in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty.

PubMed

Botto, Henry; Neuzillet, Yann

2010-04-01

Bacteriuria is a usual complication of enterocystoplasty following cystectomy. Cranberry products may decrease the number of urinary tract infections because of a non-dialysable compound, a condensed tannin, the proanthocyanidin (PAC) type A. This study determined the effectiveness of treatment with a cranberry preparation highly dosed in proanthocyanidin A in prevention of repeated bacteriuria in patients with an ileal enterocystoplasty. Between November 2004 and November 2009, a controlled study was open to patients seen in consultation for follow-up after a radical cystectomy and ileal cystoplasty. Patients had a history of repeated urinary infection and/or bacteriuria during the pretreatment phase. During the treatment phase, patients received a cranberry (Vaccinium macrocarpon) preparation highly dosed in proanthocyanidin A (36 mg measured by the dimethylaminocinnamaldehyde method), one capsule a day. The primary endpoint was the absence of bacteria in urine culture. The secondary endpoints were the presence or absence of symptoms (pain, fever), continence status and upper excretory tract enlargement. Each patient was his or her own historical control. Fifteen patients were included. The median duration of the period without treatment with cranberry compound was 18.5 (1-93) months. The median duration of the period with treatment with cranberry compound was 32.8 (13-60) months. There was a significant decrease in the number of positive urine cultures during cranberry compound treatment. Treatment with a cranberry compound seems to be effective in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty. These results need to be validated by further double-blind randomized studies.

Malignant Hilar Biliary Obstruction: Treatment by Means of Placement of a Newly Designed Y-Shaped Branched Covered Stent.

PubMed

Yun, Jong Hyouk; Jung, Gyoo-Sik; Park, Jung Gu; Kang, Byung Chul; Shin, Dong-Hoon; Yun, Byung Chul; Lee, Sang Uk

2016-04-01

To evaluate the technical feasibility and clinical efficacy of placement of a newly designed Y-shaped branched covered stent for palliative treatment of malignant hilar biliary obstruction. From June 2011 to September 2014, 34 consecutive patients with malignant hilar biliary obstruction underwent percutaneous placement of a Y-shaped branched covered stent for palliative treatment. Technical and clinical success, complications, cumulative patient survival, and stent patency were evaluated. Stent placement was technically successful in all patients. All patients showed adequate biliary drainage on the follow-up cholangiogram. Mean serum bilirubin level (10.9 mg/dl) decreased significantly 1 week (5.7 mg/dl) and 1 month (2.6 mg/dl) after stent placement (p < 0.01). Complications associated with the procedure included hemobilia (n = 3) and biloma (n = 1). During the mean follow-up period of 225 (range 12-820) days, nine patients (26.5%) developed stent occlusion caused by tumor overgrowth (n = 8) and sludge (n = 1). Two of them underwent coaxial placement of a second stent with good results. The median survival time was 281 days and median primary stent patency was 337 days. There were no significant differences in the patient survival and stent patency rates in relation to age, sex, or Bismuth type. Percutaneous placement of the Y-shaped branched covered stent seems to be technically feasible and clinically effective for palliative treatment of malignant hilar biliary obstruction.

Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer.

PubMed

Kochall, Susan; Thepkaysone, May-Linn; García, Sebastián A; Betzler, Alexander M; Weitz, Jürgen; Reissfelder, Christoph; Schölch, Sebastian

2017-07-18

Despite the advantages of easy applicability and cost-effectiveness, subcutaneous mouse models have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Orthotopic mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in hollow organs such as the large bowel. In order to produce uniform tumors which reliably grow and metastasize, standardized techniques of tumor cell preparation and injection are critical. We have developed an orthotopic mouse model of colorectal cancer (CRC) which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials. Tumor cells from either primary tumors, 2-dimensional (2D) cell lines or 3-dimensional (3D) organoids are injected into the cecum and, depending on the metastatic potential of the injected tumor cells, form highly metastatic tumors. In addition, CTCs can be found regularly. We here describe the technique of tumor cell preparation from both 2D cell lines and 3D organoids as well as primary tumor tissue, the surgical and injection techniques as well as the isolation of CTCs from the tumor-bearing mice, and present tips for troubleshooting.

Periosteum tissue engineering in an orthotopic in vivo platform.

PubMed

Baldwin, J G; Wagner, F; Martine, L C; Holzapfel, B M; Theodoropoulos, C; Bas, O; Savi, F M; Werner, C; De-Juan-Pardo, E M; Hutmacher, D W

2017-03-01

The periosteum plays a critical role in bone homeostasis and regeneration. It contains a vascular component that provides vital blood supply to the cortical bone and an osteogenic niche that acts as a source of bone-forming cells. Periosteal grafts have shown promise in the regeneration of critical size defects, however their limited availability restricts their widespread clinical application. Only a small number of tissue-engineered periosteum constructs (TEPCs) have been reported in the literature. A current challenge in the development of appropriate TEPCs is a lack of pre-clinical models in which they can reliably be evaluated. In this study, we present a novel periosteum tissue engineering concept utilizing a multiphasic scaffold design in combination with different human cell types for periosteal regeneration in an orthotopic in vivo platform. Human endothelial and bone marrow mesenchymal stem cells (BM-MSCs) were used to mirror both the vascular and osteogenic niche respectively. Immunohistochemistry showed that the BM-MSCs maintained their undifferentiated phenotype. The human endothelial cells developed into mature vessels and connected to host vasculature. The addition of an in vitro engineered endothelial network increased vascularization in comparison to cell-free constructs. Altogether, the results showed that the human TEPC (hTEPC) successfully recapitulated the osteogenic and vascular niche of native periosteum, and that the presented orthotopic xenograft model provides a suitable in vivo environment for evaluating scaffold-based tissue engineering concepts exploiting human cells. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

A 20-year period of orthotopic liver transplantation activity in a single center: a time series analysis performed using the R Statistical Software.

PubMed

Santori, G; Andorno, E; Morelli, N; Casaccia, M; Bottino, G; Di Domenico, S; Valente, U

2009-05-01

In many Western countries a "minimum volume rule" policy has been adopted as a quality measure for complex surgical procedures. In Italy, the National Transplant Centre set the minimum number of orthotopic liver transplantation (OLT) procedures/y at 25/center. OLT procedures performed in a single center for a reasonably large period may be treated as a time series to evaluate trend, seasonal cycles, and nonsystematic fluctuations. Between January 1, 1987 and December 31, 2006, we performed 563 cadaveric donor OLTs to adult recipients. During 2007, there were another 28 procedures. The greatest numbers of OLTs/y were performed in 2001 (n = 51), 2005 (n = 50), and 2004 (n = 49). A time series analysis performed using R Statistical Software (Foundation for Statistical Computing, Vienna, Austria), a free software environment for statistical computing and graphics, showed an incremental trend after exponential smoothing as well as after seasonal decomposition. The predicted OLT/mo for 2007 calculated with the Holt-Winters exponential smoothing applied to the previous period 1987-2006 helped to identify the months where there was a major difference between predicted and performed procedures. The time series approach may be helpful to establish a minimum volume/y at a single-center level.

Evaluation of dried vegetables residues for poultry: II. Effects of feeding cabbage leaf residues on broiler performance, ileal digestibility and total tract nutrient digestibility.

PubMed

Mustafa, A F; Baurhoo, B

2017-03-01

A study was conducted to investigate the effects of partial replacing corn and soybean meal with dried cabbage leaf residues (DCR) on broiler growth performance, apparent ileal nutrient digestibility, and apparent total tract nutrient utilization. Dietary treatments include 4 levels of DCR (0, 3, 6, and 9%). Two hundred and twenty-four day-old male broilers were randomly assigned to one of 4 groups (8 cage replicates; 7 birds/cage) and grown over a 35-d experimental period. Results showed that feeding DCR had no effects on daily body weigh gain (average 53.4 g/d), daily feed intake (average 94.9 g/d), and feed conversion ratio (average 1.78 g of feed/g of gain). Inclusion of DCR reduced apparent ileal DM (quadratic effect, P < 0.001), OM (linear effect, P = 0.012), and CP (quadratic effect, P = 0.001) digestibility of younger birds (d 21) while incremental levels of DCR had no effect on apparent ileal nutrient digestibilities of older birds (d 35). Apparent total tract digestibility of DM, OM, and CP increased (linear effect, P < 0.001) as the level of DCR increased. It was concluded that the inclusion of DCR in broiler diets up to 9% had no negative impact on bird performance and apparent ileal digestibility of older birds and improved apparent total tract nutrient digestibility. © 2016 Poultry Science Association Inc.

Orthotopic Patient-Derived Pancreatic Cancer Xenografts Engraft Into the Pancreatic Parenchyma, Metastasize, and Induce Muscle Wasting to Recapitulate the Human Disease.

PubMed

Go, Kristina L; Delitto, Daniel; Judge, Sarah M; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Judge, Andrew R; Trevino, Jose G

2017-07-01

Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer (PC). In an effort to develop more reliable preclinical models, we have recently established a subcutaneous patient-derived xenograft (PDX) model. However, critical aspects of PC responsible for its highly lethal nature, such as the development of distant metastasis and cancer cachexia, remain underrepresented in the flank PDX model. The purpose of this study was to evaluate the degree to which an orthotopic PDX model of PC recapitulates these aspects of the human disease. Human PDX-derived PC tumors were implanted directly into the pancreas of NOD.Cg-Prkdc Il2rg/SzJ mice. Tumor growth, metastasis, and muscle wasting were then evaluated. Orthotopically implanted PDX-derived tumors consistently incorporated into the murine pancreatic parenchyma, metastasized to both the liver and lungs and induced muscle wasting directly proportional to the size of the tumor, consistent of the cancer cachexia syndrome. Through the orthotopic implantation technique described, we demonstrate a highly reproducible model that recapitulates both local and systemic aspects of human PC.

Highly Effective Auger-Electron Therapy in an Orthotopic Glioblastoma Xenograft Model using Convection-Enhanced Delivery

PubMed Central

Thisgaard, Helge; Halle, Bo; Aaberg-Jessen, Charlotte; Olsen, Birgitte Brinkmann; Therkelsen, Anne Sofie Nautrup; Dam, Johan Hygum; Langkjær, Niels; Munthe, Sune; Någren, Kjell; Høilund-Carlsen, Poul Flemming; Kristensen, Bjarne Winther

2016-01-01

Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [125I]5-Iodo-2'-deoxyuridine (125I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED). Moreover, we aimed to determine if the therapeutic effect could be enhanced when combining 125I-UdR therapy with the currently used first-line chemotherapeutic agent temozolomide. 125I-UdR significantly decreased glioblastoma cell viability and migration in vitro and the cell viability was further decreased by co-treatment with methotrexate and/or temozolomide. Intratumoral CED of methotrexate and 125I-UdR with and without concomitant systemic temozolomide chemotherapy significantly reduced the tumor burden in orthotopically xenografted glioblastoma-bearing nude rats. Thus, 100% (8/8) of the animals survived the entire observation period of 180 days when subjected to the combined Auger-chemotherapy while 57% (4/7) survived after the Auger-therapy alone. No animals (0/8) treated with temozolomide alone survived longer than 50 days. Blood samples and post-mortem histology showed no signs of dose-limiting adverse effects. In conclusion, the multidrug approach consisting of CED of methotrexate and 125I-UdR with concomitant systemic temozolomide was safe and very effective leading to 100% survival in an orthotopic xenograft glioblastoma model. Therefore, this therapeutic strategy may be a promising option for future glioblastoma therapy. PMID:27924163

Highly Effective Auger-Electron Therapy in an Orthotopic Glioblastoma Xenograft Model using Convection-Enhanced Delivery.

PubMed

Thisgaard, Helge; Halle, Bo; Aaberg-Jessen, Charlotte; Olsen, Birgitte Brinkmann; Therkelsen, Anne Sofie Nautrup; Dam, Johan Hygum; Langkjær, Niels; Munthe, Sune; Någren, Kjell; Høilund-Carlsen, Poul Flemming; Kristensen, Bjarne Winther

2016-01-01

Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [ 125 I]5-Iodo-2'-deoxyuridine ( 125 I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED). Moreover, we aimed to determine if the therapeutic effect could be enhanced when combining 125 I-UdR therapy with the currently used first-line chemotherapeutic agent temozolomide. 125 I-UdR significantly decreased glioblastoma cell viability and migration in vitro and the cell viability was further decreased by co-treatment with methotrexate and/or temozolomide. Intratumoral CED of methotrexate and 125 I-UdR with and without concomitant systemic temozolomide chemotherapy significantly reduced the tumor burden in orthotopically xenografted glioblastoma-bearing nude rats. Thus, 100% (8/8) of the animals survived the entire observation period of 180 days when subjected to the combined Auger-chemotherapy while 57% (4/7) survived after the Auger-therapy alone. No animals (0/8) treated with temozolomide alone survived longer than 50 days. Blood samples and post-mortem histology showed no signs of dose-limiting adverse effects. In conclusion, the multidrug approach consisting of CED of methotrexate and 125 I-UdR with concomitant systemic temozolomide was safe and very effective leading to 100% survival in an orthotopic xenograft glioblastoma model. Therefore, this therapeutic strategy may be a promising option for future glioblastoma therapy.

Post-operative infection and prophylactic antibiotic administration after radical cystectomy with orthotopic neobladder urinary diversion.

PubMed

Shigemura, Katsumi; Tanaka, Kazushi; Matsumoto, Minori; Nakano, Yuzo; Shirakawa, Toshiro; Miyata, Masahiro; Yamashita, Masuo; Arakawa, Soichi; Fujisawa, Masato

2012-08-01

The purpose of this study was to investigate the association between prophylactic antibiotic administration (PAA) and post-operative infection in radical cystectomy with orthotopic neobladder urinary diversion carried out for patients with bladder cancer. Fifty-seven consecutive cases were analyzed retrospectively. Post-operative infections were categorized as urinary tract, wound, and remote infections. We used the antibiotics tazobactam/piperacillin (TAZ/PIPC), sulbactam/ampicillin (SBT/ABPC), flomoxef (FMOX), cefazolin (CEZ), cefotiam (CTM), and cefmetazole (CMZ). Twenty-five (43.9%) patients had post-operative infections. Five of these (8.77%) patients had wound infections, 22 (38.6%) patients had urinary tract infections, and 2 (3.51%) had remote infections. Our statistical analysis demonstrated that the patients with TAZ/PIPC used for PAA (5/18: 27.8%) had a significantly lower post-operative infection rate than patients with other antibiotics (24/39: 61.5%) (p = 0.0442). In addition, the patients with a shorter-duration PAA (within 72 h after the operation (48-72 h)) had a significantly lower rate of post-operative infections (12/33: 36.4%) than those with longer-duration PAA (longer than 72-96 h after the operation) (16/24: 66.7%) (p = 0.0239). Taken together, these results suggest that TAZ/PIPC with shorter PAA duration (within 72 h) might lead to a lower rate of post-operative infections. In conclusion, our data showed that PAA with TAZ/PIPC with a shorter duration PAA (within 72 h) might be recommended for radical cystectomy with orthotopic neobladder reconstruction. A prospective study based on our data is desirable to establish or revise guidelines for prophylactic medication for preventing post-operative infection after radical cystectomy with orthotopic neobladder urinary diversion.

In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

PubMed

Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

2017-03-01

Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub

Effect of limestone particle size and calcium to non-phytate phosphorus ratio on true ileal calcium digestibility of limestone for broiler chickens.

PubMed

Anwar, M N; Ravindran, V; Morel, P C H; Ravindran, G; Cowieson, A J

2016-10-01

The purpose of this study was to determine the effect of limestone particle size and calcium (Ca) to non-phytate phosphorus (P) ratio on the true ileal Ca digestibility of limestone for broiler chickens. A limestone sample was passed through a set of sieves and separated into fine (<0.5 mm) and coarse (1-2 mm) particles. The analysed Ca concentration of both particle sizes was similar (420 g/kg). Six experimental diets were developed using each particle size with Ca:non-phytate P ratios of 1.5:1, 2.0:1 and 2.5:1, with ratios being adjusted by manipulating the dietary Ca concentrations. A Ca-free diet was also developed to determine the basal ileal endogenous Ca losses. Titanium dioxide (3 g/kg) was incorporated in all diets as an indigestible marker. Each experimental diet was randomly allotted to 6 replicate cages (8 birds per cage) and fed from d 21 to 24 post hatch. Apparent ileal digestibility of Ca was calculated using the indicator method and corrected for basal endogenous losses to determine the true Ca digestibility. The basal ileal endogenous Ca losses were determined to be 127 mg/kg of dry matter intake. Increasing Ca:non-phytate P ratios reduced the true Ca digestibility of limestone. The true Ca digestibility coefficients of limestone with Ca:non-phytate P ratios of 1.5, 2.0 and 2.5 were 0.65, 0.57 and 0.49, respectively. Particle size of limestone had a marked effect on the Ca digestibility, with the digestibility being higher in coarse particles (0.71 vs. 0.43).

Estimation of endogenous protein and amino acid ileal losses in weaned piglets by regression analysis using diets with graded levels of casein

PubMed Central

2013-01-01

Background Many studies have investigated endogenous loss of proteins and amino acids (AAs) at the ileal level in growing pigs. However, only a few studies have researched this subject in piglets. Knowledge regarding AA ileal digestibility in piglets would be helpful during the formulation of diets for weaning piglets, rather than just using coefficients obtained in growing pigs. Therefore, in this study, we sought to estimate endogenous protein and AA ileal losses in piglets. Furthermore, apparent and true ileal digestibility (AID and TID) of protein and AAs from casein were measured. Results The average flow of protein was 20.8 g/kg of dry matter intake (DMI). Basal protein loss, as estimated by regression, was 16.9 g/kg DMI. Glutamic acid, arginine, and aspartic acid (2.2, 1.4, and 1.2 g/kg DMI, respectively) were the AAs for which greater losses were seen. The AID of protein and AAs increased as the protein level in the diet increased. A higher increment in AID was observed between diets with 80 and160 g CP/kg of feed; this finding was mainly attributable to increases in glycine and arginine (46.1% and 18%, respectively). The TID of protein was 97.8, and the TID of AAs varied from 93.9 for histidine to 100.2 for phenylalanine. Conclusions The basal endogenous protein loss in piglets was 16.9 g/kg DMI. Endogenous protein was rich in glutamic acid, aspartic acid, and arginine, which represented 32.7% of endogenous protein loss in weaning piglets. The TID of casein was high and varied from 93.0 for histidine to 100.2 for phenylalanine. PMID:24053636

Development of Y-shaped peptide for constructing nanoparticle systems targeting tumor-associated macrophages in vitro and in vivo

NASA Astrophysics Data System (ADS)

Yan, Lu; Gao, Yunxiang; Pierce, Ryan; Dai, Liming; Kim, Julian; Zhang, Mei

2014-04-01

Tumor-associated macrophage (TAM) is increasingly being viewed as a target of great interest in tumor microenvironment due to its important role in the progression and metastasis of cancers. It has been shown that TAM indeed overexpresses unique surface marker legumain. In this study, we designed and synthesized a Y-shaped legumain-targeting peptide (Y-Leg) with functional groups allowing for further conjugation with imaging and therapeutic moieties (vide infra). The in vitro cell experiments using FITC-conjugated Y-Leg revealed its specific and selective interaction with M2-polarized macrophages (i.e., TAMs) with preference to M1 macrophages, and that the interaction was not interfered with by conjugating FITC to its functional group. Further, we constructed a nanotube system by grafting Y-Leg onto oxidized carbon nanotubes (OCNTs) loaded with paramagnetic Fe3O4 nanoparticles. The intravenous injection of the resultant Y-Leg-OCNT/Fe3O4 nanotubes to 4T1 mammary tumor-bearing mouse led to the magnetic resonance imaging (MRI) of TAM-infiltrated tumor microenvironment, revealing the targeting specificity of Y-Leg-conjugated nanotubes in vivo. The Y shape of peptide and its functional groups containing amines and imidazole can protonate at different pHs, contributing to the in vitro and in vivo targeting specificity. This study represents the first development of novel peptide and peptide-grafted nanotube system targeting M2-polarized TAMs in vivo. The methodology developed in this study is applicable to the construction of various multifunctional nanoparticle systems for selectively targeting, imaging and manipulating of TAMs for the diagnosis and treatment of cancers and inflammatory diseases identified with macrophage-infiltrated disease tissue.

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

PubMed

Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P < 0.05) and higher than in middle and remote paraneoplastic tissue (P < 0.01). There was no statistically significant difference between the expression of these genes in middle and proximal paraneoplastic tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

The effect of microbial phytase on ileal phosphorus and amino acid digestibility in the broiler chicken.

PubMed

Rutherfurd, S M; Chung, T K; Moughan, P J

2002-09-01

1. The study aimed to assess the effect of a commercially available microbial phytase on phytate phosphorus and total phosphorus content at the terminal ileum as well as true ileal amino acid digestibility. 2. Five diets, each containing a different plant-based feedstuff, were supplemented with microbial phytase and fed, along with a non-supplemented corresponding diet, to 28-d-old broiler chickens, Chromic oxide was used as an indigestible marker. Ileal contents were collected and analysed, along with the diets, for total phosphorus, phytate phosphorus and amino acids. 3. Endogenous phosphorus determined at the terminal ileum was 272 +/- 108 mg/kg food dry matter (mean +/- SE). Endogenous ileal amino acid flows ranged from 58 +/- 10 mg/kg food dry matter for methionine to 568 +/- 47 mg/kg food dry matter for glutamic acid. 4. Supplementation with microbial phytase resulted in a significantly greater phytate P disappearance from the terminal ileum for rice bran (17% units), but not for soyabean meal, maize, wheat or rapeseed meal. Similarly total phosphorus digestibility was significantly (P < 0.05) higher when microbial phytase was added to the rice-bran-based diet but not for any of the other feedstuffs. 5. Amino acid digestibility was significantly greater in the presence of microbial phytase for all the amino acids examined in wheat, for several of the amino acids each in maize and rapeseed meal and for one amino acid in rice bran and soyabean meal. The average increase in amino acid digestibility for those amino acids affected, was 13, 6, 10, 7 and 12% units for wheat, maize, rapeseed meal, rice bran and soyabean meal, respectively. 6. It appears that microbial phytase improves phosphorus digestibility and amino acid digestibility for certain plant-based feedstuffs.

Sonographic diagnosis of fetal intestinal volvulus with ileal atresia: a case report.

PubMed

Yu, Wang; Ailu, Cai; Bing, Wang

2013-05-01

Fetal intestinal volvulus is a rare life-threatening condition usually manifesting after birth with most cases being associated with intestinal malrotation. It appears on prenatal sonography (US) as a twisting of the bowel loops around the mesenteric artery, leading to mechanical obstruction and ischemic necrosis of the bowel. We report a case of intrauterine intestinal volvulus with ileal atresia, suspected when US revealed a typical "whirlpool" sign at 37 weeks' gestation, with a segment of markedly distended bowel loops and small amount of fetal ascites. Copyright © 2012 Wiley Periodicals, Inc.

Orthotopic liver transplantation in an adult with cholesterol ester storage disease.

PubMed

Ambler, Graeme K; Hoare, Matthew; Brais, Rebecca; Shaw, Ashley; Butler, Andrew; Flynn, Paul; Deegan, Patrick; Griffiths, William J H

2013-01-01

Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit.

The axon guidance molecule semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors

PubMed Central

Vercherat, Cécile; Blanc, Martine; Lepinasse, Florian; Gadot, Nicolas; Couderc, Christophe; Poncet, Gilles; Walter, Thomas; Joly, Marie-Odile; Hervieu, Valérie; Scoazec, Jean-Yves; Roche, Colette

2015-01-01

Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidance molecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs. SEMA3F expression was detected in normal neuroendocrine cells but was lost in most of human primary tumors and all their metastases. SEMA3F loss of expression was associated with promoter gene methylation. After increasing endogenous SEMA3F levels through stable transfection, enteroendocrine cell lines STC-1 and GluTag showed a reduced proliferation rate in vitro. In two different xenograft mouse models, SEMA3F-overexpressing cells exhibited a reduced ability to form tumors and a hampered liver dissemination potential in vivo. This resulted, at least in part, from the inhibition of mTOR and MAPK signaling pathways. This study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy. PMID:26447612

Estimation of the standardized ileal digestible valine to lysine ratio in 13- to 32-kilogram pigs

USDA-ARS?s Scientific Manuscript database

Three experiments were conducted to determine the optimum standardized ileal digestible Val to Lys (SID Val:Lys) ratio for 13 to 32 kg pigs. In Exp. 1, a Val deficient basal diet containing 0.60% L-Lys•HCl, 1.21% SID Lys, and 0.68% SID Val was developed (0.56 SID Val:Lys). Performance of pigs fed th...

Prospective study of the impact on quality of life of cystectomy with ileal conduit urinary diversion for neurogenic bladder dysfunction.

PubMed

Guillotreau, Julien; Castel-Lacanal, Evelyne; Roumiguié, Mathieu; Bordier, Benoit; Doumerc, Nicolas; De Boissezon, Xavier; Malavaud, Bernard; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2011-11-01

Neurogenic bladder dysfunction has a negative impact on the patient's quality of life (QoL). Cystectomy with ileal conduit urinary diversion is a treatment option in patients in failure after conservative management. The objective of this study was to evaluate the impact of ileal conduit urinary diversion on the QoL of patients with neurogenic bladder dysfunction. From March 2004 to November 2010, 48 patients (36 women and 12 men with a mean age of 50.6  ±  11.8 years) treated by cystectomy with ileal conduit urinary diversion for neurogenic bladder dysfunction, prospectively completed, before and after surgery, two self-administered QoL questionnaires. Neurological diseases were multiple sclerosis in 38 cases, spinal cord injury in 7 cases, and other neurological disease in 3 cases. Cystectomy was performed by laparoscopy in all patients. QoL was measured by using two self-administered questionnaires, one questionnaire specific for urinary disorders validated in neurological patients, Qualiveen®, and the generic SF36-v2® questionnaire. Data were compared by Student's t test. Comparison of the Qualiveen® self-administered questionnaire scores and indices before and after surgery showed that, after surgery, patients presented a significant reduction of limitations (0.57 ± 0.64 vs. 1.55 ± 1.35, P < 0.001), constraints (2.12  ±  0.83 vs. 2.64  ±  1.12, P = 0.046) scores and the SIUP index (1.29 ± 0.65 vs. 1.79 ± 0.95, P = 0.015). No significant change in SF36-v2® scores was observed postoperatively. Ileal conduit urinary diversion improves the urinary QoL of patients with neurogenic bladder dysfunction by decreasing limitations and constraints induced by urinary disorders, but has no impact on general QoL. Copyright © 2011 Wiley Periodicals, Inc.

[A simple and efficient method for establishing a mouse model of orthotopic MB49 bladder cancer].

PubMed

Liang, Zhong-kun; Zhang, Lin; Hu, Zhi-ming; Chen, Zhong; Huang, Xin; Shi, Xiang-hua; Tan, Wan-long; Gao, Ji-min

2009-04-01

To establish a simple and efficient method for establishing a mouse model of orthotopic superficial bladder cancer. C57BL/6 mice were anesthetized with sodium pentobarbital and catheterized with modified IV catheter (24 G). The mice were intravesically pretreated with HCl and then with NaOH, and after washing the bladders with phosphate-buffered saline (PBS), 100 microl (1 x 10(7)) MB49 cells were infused and allowed to incubate in the bladder for 2 h followed intravesical mitomycin C (MMC) administration. The tumor formation rate, survival, gross hematuria, and bladder weight were determined as the outcome variables, and the pathology of the bladders was observed. Instillation of MB49 tumor cells resulted in a tumor formation rates of 100% in all the pretreated groups while 0% in the control group without pretreatment. MMC significantly reduced the bladder weight as compared to PBS. We have successfully established a stable, reproducible, and reliable orthotopic bladder cancer model in mice.

The effect of drying method temperature, collection method, and marker type on apparent ileal amino acid digestibility in 21-day-old broilers fed corn-soybean meal-barley based diet.

PubMed

Olojede, O C; Ford, M J; Jacob, J P; Ao, T; Pescatore, A J; Adedokun, S A

2018-06-01

For accurate estimation of nutrient digestibility, an ideal drying and sampling method is required to preserve the quality of the digesta. A standard corn-soybean meal (corn-SBM) broiler starter diet was fed from d 0 to 10 before birds were placed on the experimental diets until d 21. One hundred and sixty-eight male Cobb 500 broiler chicks were used to evaluate the effect of two drying methods (freeze-dryer vs. forced air-oven) and two drying temperatures (40 vs. 55°C) (Exp 1), while ninety-six chicks were used to evaluate the effect of flushing and squeezing as well as marker types (titanium vs. chromium) on apparent ileal DM, N, Ca, P, and AA digestibility (Exp 2). There were seven (Exp 1) or eight (Exp 2) replicate cages per treatment with 6 birds/cage. Digesta from the distal two thirds of the ileum was obtained from birds following euthanasia on d 21 by squeezing (Exp 1) and squeezing or flushing (Exp 2). Samples collected were stored in the freezer at -20°C until they were either freeze-dried (FD) or oven-dried (OD) at 40 or 55°C. There were no interactions between the drying methods and drying temperatures (Exp 1) on apparent ileal DM, N, and AA digestibility. Met had the highest (92.3%) while Cys had the lowest (73.8%) digestibility value. In Exp 2, no interaction between sampling methods and marker types was observed. The effect of sampling methods was not significant except for Arg and Met where squeezing resulted in higher (P < 0.05) digestibility values. Furthermore, apparent ileal His, Ile, Cys, Ser, and Tyr digestibility tended to be higher (P < 0.1) in squeezed digesta compared to the flushed digesta. Results from these studies showed that OD ileal digesta at 40 or 55°C had no negative effect on apparent ileal AA digestibility. Likewise, marker type did not influence apparent ileal AA digestibility values.

Effect of Bacillus subtilis and Bacillus licheniformis supplementation in diets with low- and high-protein content on ileal crude protein and amino acid digestibility and intestinal microbiota composition of growing pigs.

PubMed

Kaewtapee, Chanwit; Burbach, Katharina; Tomforde, Georgina; Hartinger, Thomas; Camarinha-Silva, Amélia; Heinritz, Sonja; Seifert, Jana; Wiltafsky, Markus; Mosenthin, Rainer; Rosenfelder-Kuon, Pia

2017-01-01

Bacillus spp. seem to be an alternative to antimicrobial growth promoters for improving animals' health and performance. However, there is little information on the effect of Bacillus spp. in combination with different dietary crude protein (CP) levels on the ileal digestibility and microbiota composition. Therefore, the objective of this study was to determine the effect of Bacillus spp. supplementation to low- (LP) and high-protein diets (HP) on ileal CP and amino acid (AA) digestibility and intestinal microbiota composition. Eight ileally cannulated pigs with an initial body weight of 28.5 kg were randomly allocated to a row-column design with 8 pigs and 3 periods of 16 d each. The assay diets were based on wheat-barley-soybean meal with two protein levels: LP (14% CP, as-fed) and HP diet (18% CP, as-fed). The LP and HP diets were supplemented with or without Bacillus spp. at a level of 0.04% (as-fed). The apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of CP and AA was determined. Bacterial community composition from ileal digesta was analyzed by Illumina amplicon sequencing and quantitative real-time PCR. Data were analyzed as a 2 × 2 factorial design using the GLIMMIX procedures of SAS. The supplementation with Bacillus spp. did not affect both AID and SID of CP and AA in growing pigs. Moreover, there was no difference in AID of CP and AA between HP and LP diets, but SID of cystine, glutamic acid, glycine, and proline was lower ( P  < 0.05) in pigs fed the HP diets. The HP diets increased abundance of Bifidobacterium spp. and Lactobacillus spp., ( P  < 0.05) and by amplicon sequencing the latter was identified as predominant genus in microbiota from HP with Bacillus spp., whereas dietary supplementation of Bacillus spp. increased ( P  < 0.05) abundance of Roseburia spp.. The HP diet increased abundance of Lactobacillus spp. and Bifidobacterium spp.. The supplementation of Bacillus spp. resulted in a higher

Y-shaped Folic Acid-Conjugated PEG-PCL Copolymeric Micelles for Delivery of Curcumin.

PubMed

Feng, Runliang; Zhu, Wenxia; Chu, Wei; Teng, Fangfang; Meng, Ning; Deng, Peizong; Song, Zhimei

2017-01-01

Curcumin is a natural hydrophobic product showing anticancer activity. Many studies show its potential use in the field of cancer treatment due to its safety and efficiency. However, its application is limited due to its low water-solubility and poor selective delivery to cancer. A Y-shaped folic acid-modified poly (ethylene glycol)-b-poly (ε-caprolactone)2 copolymer was prepared to improve curcumin solubility and realize its selective delivery to cancer. The copolymer was synthesized through selective acylation reaction of folic acid with α- monoamino poly(ethylene glycol)-b-poly(ε-caprolactone)2. Curcumin was encapsulated into the copolymeric micelles with 93.71% of encapsulation efficiency and 11.94 % of loading capacity. The results from confocal microscopy and cellular uptake tests showed that folic acid-modified copolymeric micelles could improve cellular uptake of curcumin in Hela and HepG2 cells compared with folic acid-unmodified micelles. In vitro cytotoxicity assay showed that folic acid-modified micelles improved anticancer activity against Hela and HepG2 cells in comparison to folic acidunmodified micelles. Meanwhile, both drug-loaded micelles demonstrated higher activity against Hela cell lines than HepG2. The research results suggested that the folic acid-modified Y-shaped copolymeric micelles should be used to enhance hydrophobic anticancer drugs' solubility and their specific delivery to folic acid receptors-overexpressed cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Porphyrin lipid nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model

NASA Astrophysics Data System (ADS)

MacLaughlin, Christina M.; Ding, Lili; Jin, Cheng; Cao, Pingjiang; Siddiqui, Iram; Hwang, David M.; Chen, Juan; Wilson, Brian C.; Zheng, Gang; Hedley, David W.

2016-03-01

Local disease control is a major problem in the treatment of pancreatic cancer, because curative-intent surgery is only possible in a minority of patients, and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for ablation of pancreatic tumors, this approach remains under investigated. Using photothermal sensitizers in combination with laser light for PTT can result in more efficient conversion of light energy to heat, and confinement of thermal destruction to the tumor, thus sparing adjacent organs and vasculature. Porphyrins have been previously employed as photosensitizers for PDT and PTT, however their incorporation in to "porphysomes", lipid-based nanoparticles each containing ~80,000 porphyrins through conjugation of pyropheophorbide to phospholipids, carries two distinct advantages: 1) high-density porphyrin packing imparts the nanoparticles with enhanced photonic properties for imaging and phototherapy; 2) the enhanced permeability and retention effect may be exploited for optimal delivery of porphysomes to the tumor region thus high payload porphyrin delivery. The feasibility of porphysome-enhanced PTT for pancreatic cancer treatment was investigated using a patient-derived orthotopic pancreas xenograft tumor model. Uptake of porphysomes at the orthotopic tumor site was validated using ex vivo fluorescence imaging of intact organs of interest. The accumulation of porphysomes in orthotopic tumor microstructure was also confirmed by fluorescence imaging of excised tissue slices. PTT progress was monitored as changes in tumor surface temperature using IR optical imaging. Histological analyses were conducted to examine microstructure changes in tissue morphology, and the viability of remaining tumor tissues following exposure to heat. These studies may also provide insight as to the contribution of heat sink in application of thermal therapies to highly vascularized pancreatic tumors.

The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

PubMed Central

Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler

2014-01-01

Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WT and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This

Antitumor immune activity by chemokine CX3CL1 in an orthotopic implantation of lung cancer model in vivo.

PubMed

Kee, Ji-Ye; Arita, Yoshihisa; Shinohara, Kanna; Ohashi, Yasukata; Sakurai, Hiroaki; Saiki, Ikuo; Koizumi, Keiichi

2013-01-01

Due to their chemoattractant properties stimulating the accumulation of infiltrating immune cells in tumors, chemokines are known to have antitumor effects. Fractalkine, a unique CX3C chemokine, is expressed in activated endothelial cells, while its receptor, CX3CR1, is expressed in cytolytic immune cells, such as natural killer cells, monocytes and some CD8 + T cells. The biological properties of cancer cells are affected by the implantation organ and differences in immune systems, requiring cancer implantation in orthotopic organs in an in vivo experiment. To develop new therapy strategies for lung cancer, an animal model reflecting the clinical features of lung cancer was previously established. This study aimed to determine whether CX3CL1-induced biological functions should be used for immune cell-based gene therapy of lung cancer in the orthotopic implantation model. An orthotopic intrapulmonary implantation of CX3CL1-stable expression in mouse lung cancer (LLC-CX3CL1) was performed to analyze growth. Results showed a significant decrease in tumor growth in the lung compared to the control cells (LLC-mock). Furthermore, the antitumor effects of CX3CL1 were derived from natural killer cell activities in the depletion experiment in vivo . Therefore, CX3CL1 has the potential of a useful therapeutic target in lung cancer.

Comparative ileal amino acid digestibility of distillers' grains for growing pigs.

PubMed

Adeola, Olayiwola; Ragland, Darryl

2016-12-01

The objective of the experiment reported here was to investigate and compare the amino acid (AA) digestibility of distillers' dried grains (DDG), distillers' dried grains with solubles (DDGS), high protein distillers' dried grains (HP-DDG), and high protein distillers' dried grains with solubles (HP-DDGS) in growing pigs. Five semi-purified diets consisting of DDG, DDGS, HP-DDG, HP-DDGS, and nitrogen-free diet (NFD) were fed to pigs fitted with simple T-cannula for 5 observations per diet. Endogenous losses of AA at the terminal ileum of pigs that received the NFD were used to calculate standardized ileal digestibility (SID) of AA from apparent ileal digestibility (AID) of AA. The AID of Lys in DDGS was lower ( P  < 0.05) than that in DDG, which was also lower ( P  < 0.05) than that in HP-DDG. There were no differences in AID of Met among DDG, DDGS and HP-DDGS, but was greater ( P  < 0.05) in HP-DDG than in DDG or DDGS. The AID of Thr in HP-DDG was greater ( P  < 0.05) than that in DDGS but not different from that in DDG or HP-DDGS. The branched-chain AA Ile and Leu had greater ( P  < 0.05) AID in HP-DDG than in DDG, DDGS or HP-DDGS, and there was no difference among DDG, DDGS, and HP-DDGS. The AID of Trp in DDG and DDGS or HP-DDG and HP-DDGS were not different, but the AID of Trp in HP-DDGS was greater ( P  < 0.05) than that of DDGS. The greatest SID of the indispensable AA was in HP-DDG. Except for Arg and Lys in which DDG had greater ( P  < 0.05) digestibility, there was no difference between DDG and DDGS in the SID of the indispensable AA. The SID of Lys in DDG was greater ( P  < 0.05) than that of DDGS but there was no difference between that of DDG and HP-DDGS. Only His, Ile, and Met had lower ( P  < 0.05) SID in HP-DDGS than HP-DDG within the indispensable AA. The SID of Ala, Asp, Cys, Glu, Gly, Ser and Tyr were lower ( P  < 0.05) in DDGS than in HP-DDG. There SID of dispensable AA in DDG was not different from that of HP-DDGS. The

Technical note: assessment of recovery site of mobile nylon bags for measuring ileal digestibility of starch in dairy cows.

PubMed

Norberg, E; Volden, H; Harstad, O M

2007-01-01

The objective of this study was to evaluate recovery site of mobile nylon bags for measuring ileal digestibility of ruminally undegraded starch in dairy cows. Eight feed samples of untreated and treated concentrates were examined. Three lactating cows equipped with rumen fistula and duodenal and ileal cannulas were used in the experiment. The mobile nylon bags containing intact feeds or residues after a 12-h ruminal incubation were pretreated using a 2-step procedure to simulate abomasal digestion before insertion through the duodenal cannula. To assess the effect of hindgut fermentation on starch digestibility, approximately half of the bags were collected from the ileum and half from the feces. The results indicate that feed samples should be preincubated in rumen before insertion into duodenum, and that samples with relatively high fractions of rumen-undigestible starch should be collected from the ileum instead of from feces.

Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation.

PubMed

Kuo, Elbert; Bharat, Ankit; Goers, Trudie; Chapman, Will; Yan, Le; Street, Tyler; Lu, Wei; Walter, Michael; Patterson, Alexander; Mohanakumar, Thalachallour

2006-09-01

The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-gamma ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-gamma producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

Malignant Hilar Biliary Obstruction: Treatment by Means of Placement of a Newly Designed Y-Shaped Branched Covered Stent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yun, Jong Hyouk, E-mail: xell1015@naver.com; Jung, Gyoo-Sik, E-mail: gsjung@medimail.co.kr; Park, Jung Gu

PurposeTo evaluate the technical feasibility and clinical efficacy of placement of a newly designed Y-shaped branched covered stent for palliative treatment of malignant hilar biliary obstruction.MethodsFrom June 2011 to September 2014, 34 consecutive patients with malignant hilar biliary obstruction underwent percutaneous placement of a Y-shaped branched covered stent for palliative treatment. Technical and clinical success, complications, cumulative patient survival, and stent patency were evaluated.ResultsStent placement was technically successful in all patients. All patients showed adequate biliary drainage on the follow-up cholangiogram. Mean serum bilirubin level (10.9 mg/dl) decreased significantly 1 week (5.7 mg/dl) and 1 month (2.6 mg/dl) after stent placement (p < 0.01). Complications associated withmore » the procedure included hemobilia (n = 3) and biloma (n = 1). During the mean follow-up period of 225 (range 12–820) days, nine patients (26.5 %) developed stent occlusion caused by tumor overgrowth (n = 8) and sludge (n = 1). Two of them underwent coaxial placement of a second stent with good results. The median survival time was 281 days and median primary stent patency was 337 days. There were no significant differences in the patient survival and stent patency rates in relation to age, sex, or Bismuth type.ConclusionPercutaneous placement of the Y-shaped branched covered stent seems to be technically feasible and clinically effective for palliative treatment of malignant hilar biliary obstruction.« less

Numerical Modeling of Surface and Volumetric Cooling using Optimal T- and Y-shaped Flow Channels

NASA Astrophysics Data System (ADS)

Kosaraju, Srinivas

2017-11-01

The layout of T- and V-shaped flow channel networks on a surface can be optimized for minimum pressure drop and pumping power. The results of the optimization are in the form of geometric parameters such as length and diameter ratios of the stem and branch sections. While these flow channels are optimized for minimum pressure drop, they can also be used for surface and volumetric cooling applications such as heat exchangers, air conditioning and electronics cooling. In this paper, an effort has been made to study the heat transfer characteristics of multiple T- and Y-shaped flow channel configurations using numerical simulations. All configurations are subjected to same input parameters and heat generation constraints. Comparisons are made with similar results published in literature.

Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model

NASA Astrophysics Data System (ADS)

Schwartz, Jon A.; Shetty, Anil M.; Price, Roger E.; Stafford, R. Jason; Wang, James C.; Uthamanthil, Rajesh K.; Pham, Kevin; McNichols, Roger J.; Coleman, Chris L.; Payne, J. Donald

2009-02-01

We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8+/-4.1ºC. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of 48.6+/-1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

Orthotopic bladder substitution in men revisited: identification of continence predictors.

PubMed

Koraitim, M M; Atta, M A; Foda, M K

2006-11-01

We determined the impact of the functional characteristics of the neobladder and urethral sphincter on continence results, and determined the most significant predictors of continence. A total of 88 male patients 29 to 70 years old underwent orthotopic bladder substitution with tubularized ileocecal segment (40) and detubularized sigmoid (25) or ileum (23). Uroflowmetry, cystometry and urethral pressure profilometry were performed at 13 to 36 months (mean 19) postoperatively. The correlation between urinary continence and 28 urodynamic variables was assessed. Parameters that correlated significantly with continence were entered into a multivariate analysis using a logistic regression model to determine the most significant predictors of continence. Maximum urethral closure pressure was the only parameter that showed a statistically significant correlation with diurnal continence. Nocturnal continence had not only a statistically significant positive correlation with maximum urethral closure pressure, but also statistically significant negative correlations with maximum contraction amplitude, and baseline pressure at mid and maximum capacity. Three of these 4 parameters, including maximum urethral closure pressure, maximum contraction amplitude and baseline pressure at mid capacity, proved to be significant predictors of continence on multivariate analysis. While daytime continence is determined by maximum urethral closure pressure, during the night it is the net result of 2 forces that have about equal influence but in opposite directions, that is maximum urethral closure pressure vs maximum contraction amplitude plus baseline pressure at mid capacity. Two equations were derived from the logistic regression model to predict the probability of continence after orthotopic bladder substitution, including Z1 (diurnal) = 0.605 + 0.0085 maximum urethral closure pressure and Z2 (nocturnal) = 0.841 + 0.01 [maximum urethral closure pressure - (maximum contraction amplitude

The Role of Lymphangiogenesis in Orthotopic Prostatic Tumor-Environment on Regional and Systemic Metastasis

DTIC Science & Technology

2008-01-01

expressing Renilla luciferase and VEGF-C shRNA or irrelevant firefly luciferase shRNA (Ctrl) were implanted orthotopically as before. To determine the...on metastasis in Pten knockout model (Month 10-24): a) Generate Ubc/sVEGFR-3 and Ubc/ Renilla luciferase (RL) lentiviral vectors by subcloning...progression (month 10-12) c) Monitor efficiency of Ubc/lentiviral transduction and expression in Pten (-/-) prostate using optical imaging of Renilla

Surgical treatment of ulcerative colitis: ileorectal vs ileal pouch-anal anastomosis.

PubMed

Scoglio, Daniele; Ahmed Ali, Usama; Fichera, Alessandro

2014-10-07

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the current gold standard in the surgical treatment of ulcerative colitis (UC) refractory to medical management. A procedure of significant magnitude carries its own risks including anastomotic failure, pelvic sepsis and a low rate of neoplastic degeneration overtime. Recent studies have shown that total colectomy with ileorectal anastomosis (IRA) has been associated with good long-term functional results in a selected group of UC patients amenable to undergo a strict surveillance for the relatively high risk of cancer in the rectum. This manuscript will review and compare the most recent literature on IRA and IPAA as it pertains to postoperative morbidity and mortality, failure rates, functional outcomes and cancer risk.

Combination radiotherapy in an orthotopic mouse brain tumor model.

PubMed

Kramp, Tamalee R; Camphausen, Kevin

2012-03-06

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 μl every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without

Y-shaped biotin-conjugated poly (ethylene glycol)-poly (epsilon-caprolactone) copolymer for the targeted delivery of curcumin.

PubMed

Zhu, Wenxia; Song, Zhimei; Wei, Peng; Meng, Ning; Teng, Fangfang; Yang, Fengying; Liu, Na; Feng, Runliang

2015-04-01

In order to improve curcumin's low water-solubility and selective delivery to cancer, we reported ligand-mediated micelles based on a Y-shaped biotin-poly (ethylene glycol)-poly (epsilon-caprolactone)2 (biotin-PEG-PCL2) copolymer. Its structure was characterized by (1)H NMR. The blank and drug-loaded micelles obtained by way of thin-film hydration were characterized by dynamic light scattering, X-ray diffraction, infrared spectroscopy and hemolytic test. Curcumin was loaded into micelles with a high encapsulating efficiency (93.83%). Curcumin's water-solubility was enhanced 170,400 times higher than free curcumin. Biotin-PEG-PCL2 micelles showed slower drug release in vitro than H2N-PEG-PCL2 micelles. In vitro cellular uptake and cytotoxicity tests showed that higher dosage of curcumin might overcome the effect of slow release on cytotoxicities because of its higher uptake induced by biotin, resulting in higher anticancer activities against MDA-MB-436 cells. In brief, Y-shaped biotin-PEG-PCL2 is a promising delivery carrier for anticancer drug. Copyright © 2014 Elsevier Inc. All rights reserved.

Radiation Dose Uncertainty and Correction for a Mouse Orthotopic and Xenograft Irradiation Model

PubMed Central

Gan, Gregory N.; Altunbas, Cem; Morton, John J.; Eagles, Justin; Backus, Jennifer; Dzingle, Wayne; Raben, David; Jimeno, Antonio

2016-01-01

Purpose In animal irradiation models, reported dose can vary significantly from the actual doses delivered. We describe an effective method for in vivo dose verification. Materials and Methods Mice bearing commercially-available cell line or patient-derived tumor cell orthotopic or flank xenografts were irradiated using a 160 kVp, 25 mA X-ray source. Entrance dose was evaluated using optically-stimulated luminescence dosimeters (OSLD) and exit dose was assessed using radiochromic film dosimetry. Results Tumor position within the irradiation field was validated using external fiducial markers. The average entrance dose in orthotopic tumors from 10 OSLDs placed on 2 different animal irradiation days was 514±37 cGy (range: 437–545). Exit dose measurements taken from 7 radiochromic films on two separate days were 341±21 cGy (a 34% attenuation). Flank tumor irradiation doses measured by OSLD were 368±9 cGy compared to exit doses of 330 cGy measured by radiochromic film. Conclusion Variations related to the irradiation model can lead to significant under or over- dosing in vivo which can affect tumor control and/or biologic endpoints that are dose dependent. We recommend that dose measurements be determined empirically based on the mouse model and irradiator used and dose compensation adjustments performed to ensure correct and appropriate doses. PMID:26689828

Radiation dose uncertainty and correction for a mouse orthotopic and xenograft irradiation model.

PubMed

Gan, Gregory N; Altunbas, Cem; Morton, John J; Eagles, Justin; Backus, Jennifer; Dzingle, Wayne; Raben, David; Jimeno, Antonio

2016-01-01

In animal irradiation models, reported dose can vary significantly from the actual doses delivered. We describe an effective method for in vivo dose verification. Mice bearing commercially-available cell line or patient-derived tumor cell orthotopic or flank xenografts were irradiated using a 160 kVp, 25 mA X-ray source. Entrance dose was evaluated using optically-stimulated luminescence dosimeters (OSLD) and exit dose was assessed using radiochromic film dosimetry. Tumor position within the irradiation field was validated using external fiducial markers. The average entrance dose in orthotopic tumors from 10 OSLDs placed on two different animal irradiation days was 514 ± 37 cGy (range: 437-545). Exit dose measurements taken from seven radiochromic films on two separate days were 341 ± 21 cGy (a 34% attenuation). Flank tumor irradiation doses measured by OSLD were 368 ± 9 cGy compared to exit doses of 330 cGy measured by radiochromic film. Variations related to the irradiation model can lead to significant under or overdosing in vivo which can affect tumor control and/or biologic endpoints that are dose-dependent. We recommend that dose measurements be determined empirically based on the mouse model and irradiator used and dose compensation adjustments performed to ensure correct and appropriate doses.

Phosphorus utilization and characterization of ileal digesta and excreta from broiler chickens fed diets varying in cereal grain, phosphorus level, and phytase addition.

PubMed

Leytem, A B; Widyaratne, G P; Thacker, P A

2008-12-01

Both intrinsic and exogenous phytase in poultry feeds can alter phytate utilization and the solubility of P excreted. This experiment determined the effects of feeding diets varying in cereal grain, P concentration and phytase addition on phytate and P utilization and P characterization of ileal digesta and excreta. Twelve treatments, consisting of diets based on corn, wheat, barley, or high fat-low lignin oat and 3 P treatments (low P with 0.30% nonphytate P; low P + 1,000 phytase units of phytase; high P with 0.45% nonphytate P), were fed to 300 broilers using a factorial design. Fresh excreta were collected at 20 and 21 d and ileal digesta was collected at 21 d. Ileal digesta and excreta were analyzed for total P, phytate P and Ca, with P composition determined by solution (31)P nuclear magnetic resonance spectroscopy. Excreta samples were also analyzed for water soluble P (WSP). Apparent ileal digestibility coefficients for phytate P and total P ranged from 0.03 to 0.42 and 0.56 to 0.71, respectively. Diets supplemented with phytase had greater phytate P hydrolysis than unsupplemented diets. Apparent total tract digestibility coefficients for phytate P and total P ranged from 0.10 to 0.73 and 0.43 to 0.61, respectively. Across cereal grains, there was almost a 3-fold increase in total tract phytate P hydrolysis with phytase supplementation. The P composition of ileal digesta was predominantly phytate P (70 to 88% of total P), whereas excreta phytate P ranged from 26 to 76% of total P. Excreta WSP ranged from 3.2 to 7.5 g kg(-1) and was least for the barley diets. There was a 25% reduction in excreta WSP from the high P to the low P + phytase diets and a 37% reduction from the high P to the low P diets. As cereal grain had little influence on phytate digestibility, it is unlikely that intrinsic phytase in grain has much influence on phytate utilization by poultry. Both total P and WSP in excreta were reduced by the low P diet and the low P + phytase diet

[Highly metastatic nude mouse model of human primary gastric lymphoma constructed by surgical orthotopic transplantation and in vivo continuous screening method].

PubMed

Yang, Bo; Tuo, Shuai; Tuo, Chao-wei; Zhang, Ning; Liu, Qiu-zhen

2010-02-09

To develop a series of high metastatic models of human gastric malignant lymphoma in nude mice by orthotopic transplantation. Two histologically intact primary and hepatic metastatic fragments derived from surgical specimen of a patient with primary gastric lymphoma were implanted into the submucosa of stomach in nude mice. Highly metastatic and specific organ metastatic models were screened by selective orthotopic passage in nude mice. Transplantability, invasion, metastasis, morphological characteristics (light microscopy, electron microscopy and immunohistochemistry), karyotypic analysis and DNA content of orthotopically transplanted tumors were studied. Primary and hepatic metastatic fragments of primary gastric lymphoma were successfully transplanted in nude mice. Two nude mouse models of human primary gastric lymphoma, termed HGBL-0304 (hepatic metastasis model) and HGBL-0305 (high metastasis model), were developed, exhibiting different metastasis biology. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. Two models have been maintained for 45 generations by orthotopic passage in nude mice. A total of 419 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumors were both 100%. Significant difference in metastasis biology was exhibited in four aspects of metastasis time, organ metastatic rate, the extent of hepatic metastasis and survival of cancer-bearing mice. The metastatic rates of liver, spleen, lymph nodes and peritoneal seeding in HGBL-0304 and HGBL-0305 models were 100% and 69.5%, 94.3% and 55.6%, 62.6% and 45.7%, and 43.5% and 30.5%. The onset time for metastases of liver, spleen, lymph nodes and peritoneal seeding was 2 w and 5 w, 3 w and 6 w, 2 w and 3 w, 3 w and 6 w respectively. The extent of hepatic metastasis in HGBL-0304 and HGBL-0305 models displayed diffuse involvement of the whole liver and mainly right lobe invasion of

Antibiotic inclusion in the diet did not alter the standardized ileal digestible tryptophan to lysine ratio for growing pigs

USDA-ARS?s Scientific Manuscript database

Two 21-d experiments were conducted to determine the optimum standard ileal digestible (SID) Trp:Lys ratio in growing pigs fed diets supplemented with or without an antibiotic. The primary response variables in both experiments were ADG, ADFI, G:F and plasma urea N (PUN) concentrations with the opti...

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer.

PubMed

Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-Pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

2016-01-01

Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections. The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery.

An unusual case of Y-shaped right renal vein.

PubMed

Lavy, M; Martin, L; Eouzan, D; Turco, C; Heyd, B; Mantion, G; Parratte, B; Tatu, L

2015-01-01

Vascular renal anomalies are frequent, multiple and well described and result from errors in vessel embryogenesis between the 6th and 10th week of gestation. Historically, variations are described in anatomic dissection and currently mostly in image interpretation. We report an anatomic variation concerning the right renal vein which, to our knowledge, has never been described in the literature either by dissection or by radiological examination. This variation was discovered during the routine dissection of an embalmed male body. It consists of a Y-shaped right renal vein and is associated with multiple retroperitoneal variations: a bilateral accessory renal artery, a trident ending of the right renal artery and a left testicular vein variation. Venous and arterial renal anatomy and its variations are fundamentally important in renal surgery, especially concerning living donor renal grafts. These variations may be diagnosed thanks to injected tomodensitometry which has a good sensitivity and specificity for anomalies. Preoperative diagnosis of an anatomic vascular renal variation may reduce morbidity during surgery, which is why precise examination of injected tomography should be mandatory.

Ileal absorption of bile acids in patients with chronic cholestasis: SeHCAT test results and effect of ursodeoxycholic acid (UDCA).

PubMed

Chazouillères, O; Marteau, P; Haniche, M; Jian, R; Poupon, R

1996-12-01

The effect of cholestasis on ileal bile acid absorption is controversial in animal models (up- or down-regulation) and unknown in humans. We therefore studied values of the selena homotaurocholic acid (SeHCAT) test before and after long-term administration (>3 months, 13-15 mg/kg/day) of ursodeoxycholic acid (UDCA) in 27 patients with chronic cholestatic liver diseases (24 women, 3 men; mean age, 50 years; 24 primary biliary cirrhosis, 2 secondary biliary cirrhosis, 2 others). The control group consisted of 14 healthy volunteers. Seven-day SeHCAT percentage retention was identical in the 12 untreated cholestatic patients (serum bilirubin, 75+/-42 micromol/L, alkaline phosphatase, 4.2+/-1.0 N; mean+/-SEM) and in the control group (43.6+/-2.9 and 43.8+/-4.2%, respectively). In the 22 patients treated by UDCA for 38+/-8 months, SeHCAT percentage retention was 20.3+/-3.0%. In the seven patients with the SeHCAT test done before and after UDCA treatment (16+/-5 months), SeHCAT percentage retention decreased significantly under UDCA therapy (42.0+/-4.4 vs 19.4+/-4.1%; P < 0.02). We conclude that, in patients with chronic cholestasis (1) SeHCAT percentage retention is not altered-taken together with the known defect of biliary excretion, this lack of increase in SeHCAT percentage retention argues against up-regulation of bile acid ileal transport; and (2) UDCA treatment induces a decrease in the SeHCAT percentage retention-this effect may be related primarily to a decreased bile acid ileal absorption.

Determination of additivity of apparent and standardized ileal digestibility of amino acids in diets containing multiple protein sources fed to growing pigs.

PubMed

Xue, P C; Ragland, D; Adeola, O

2014-09-01

An experiment was conducted in growing pigs to investigate the additivity of apparent ileal digestibility (AID) or standardized ileal digestibility (SID) of CP and AA in mixed diets containing multiple protein sources. Using the determined AID or SID for CP and AA in corn, soybean meal (SBM), corn distillers' dried grains with solubles (DDGS), or canola meal (CM), the AID or SID for 4 mixed diets based on corn-SBM, corn-SBM-DDGS, corn-SBM-CM, or corn-SBM-DDGS-CM were predicted and compared with determined AID or SID, respectively. Eighteen growing pigs (initial BW = 61.3 ± 5.5 kg) were surgically fitted with T-cannulas and assigned to a duplicated 9 × 4 incomplete Latin square design with 9 diets and 4 periods. The 9 experimental diets consisted of a nitrogen-free diet (NFD) to estimate basal ileal endogenous loss (BEL) of AA, 4 semipurified diets to determine the AID and SID of CP and AA in the 4 ingredients, and 4 mixed diets to test the additivity of AID and SID. Chromic oxide was added as an indigestible marker. Pigs were fed 1 of the 9 diets during each 7-d period, and ileal digesta were collected on d 6 and 7, from 0800 to 1800 h. The analyzed AA levels for the mixed diets were close to the calculated values based on the AA composition of each ingredient. The results revealed that the predicted SID were consistent with determined values, except for Leu, Thr, Asp, Cys, Pro, and Ser in the corn-SBM diet and Met and Cys in the corn-SBM-DDGS diet. The determined AID for total AA and Arg, His, Trp, Gly, and Pro in the corn-SBM diet were greater (P < 0.05) than predicted. For the corn-SBM-DDGS diet, the determined AID were greater (P < 0.05) than predicted AID for CP, total AA, and all AA except for Arg, Leu, and Pro. In the corn-SBM-CM diet, the determined AID were greater (P < 0.05) than predicted AID for Arg, Cys, and Gly. When compared with determined values, predicted AID in the corn-SBM-DDGS-CM diet were lower (P < 0.05) for total AA and Arg, Met, Cys, and

Management of ileal perforation due to typhoid fever.

PubMed Central

Kim, J P; Oh, S K; Jarrett, F

1975-01-01

The results of the surgical management of 161 cases of ileal perforation due to typhoid fever are presented. Most were seen after an illness of 2-4 weeks, and because of delays in seeking hospital admission, more than half were explored more than 24 hours after their perforation occurred. All patients were prepared for operation with nasogastric suction, intravenous fluids, and antibiotics. At laparotomy, 80% had considerable quantities of pus and small bowel contents in the peritoneal cavity and the remainder had localized abscesses; there were no instances of localization of the perforation. One hundred three of these patients underwent simple closure of their perforations, while 43 underwent small bowel resection, usually because of multiple perforations. Exteriorization or drainage were performed only in patients too sick to tolerate a more appropriate procedure. The overall mortality was 9.9%. The authors believe that typhoid perforations can best be dealt with at operation. Delay in operative intervention adversely affects the survival rate after surgery. Chloramphenicol is used as the drug of choice. PMID:1119873

Low-protein diets affect ileal amino acid digestibility and gene expression of digestive enzymes in growing and finishing pigs.

PubMed

He, Liuqin; Wu, Li; Xu, Zhiqi; Li, Tiejun; Yao, Kang; Cui, Zhijie; Yin, Yulong; Wu, Guoyao

2016-01-01

The objective of this study was to evaluate effects of dietary crude protein (CP) intake on ileal amino acid digestibilities and expression of genes for digestive enzymes in growing and finishing pigs. In Experiment 1, 18 growing pigs (average initial BW = 36.5 kg) were assigned randomly into one of three treatments (n = 6/treatment group) representing normal (18 % CP), low (15 % CP), and very low (12 % CP) protein intake. In Experiment 2, 18 finishing pigs (average initial BW = 62.3 kg) were allotted randomly into one of three treatments (n = 6/treatment group), representing normal (16 % CP), low (13 % CP) and very low (10 % CP) protein intake. In both experiments, diets with low and very low CP were supplemented with crystalline amino acids to achieve equal content of standardized ileal digestible Lys, Met, Thr, and Trp, and were provided to pigs ad libitum. Daily feed intake, BW, and feed/gain ratios were determined. At the end of each experiment, all pigs were slaughtered to collect pancreas, small-intestine samples, and terminal ileal chymes. Samples were used for determining expression of genes for digestive enzymes and ileal amino acid digestibilities. Growing pigs fed the 12 % CP and 15 % CP diets had lower final body weight (P < 0.01) and ADG (P < 0.0001) when compared with pigs fed the 18 % dietary CP diet. Growing pigs fed with the 12 % CP diet showed higher digestibilities for CP (P < 0.05), DM (P < 0.05), Lys (P < 0.0001), Met (P < 0.01), Cys (P < 0.01), Thr (P < 0.01), Trp (P < 0.05), Val (P < 0.05), Phe (P < 0.05), Ala (P < 0.05), Cys (P < 0.01), and Gly (P < 0.05) than those fed the 18 % CP diet. Finishing pigs fed the 16 % CP diet had a higher (P < 0.01) final body weight than those fed the 10 % CP diet. mRNA levels for digestive enzymes (trypsinogen, chymotrypsin B, and dipeptidases-II and III) differed among the three groups of pigs (P < 0.05), and no difference was noted in the genes expression between control group and lower CP group. These

Surgical treatment of ulcerative colitis: Ileorectal vs ileal pouch-anal anastomosis

PubMed Central

Scoglio, Daniele; Ahmed Ali, Usama; Fichera, Alessandro

2014-01-01

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the current gold standard in the surgical treatment of ulcerative colitis (UC) refractory to medical management. A procedure of significant magnitude carries its own risks including anastomotic failure, pelvic sepsis and a low rate of neoplastic degeneration overtime. Recent studies have shown that total colectomy with ileorectal anastomosis (IRA) has been associated with good long-term functional results in a selected group of UC patients amenable to undergo a strict surveillance for the relatively high risk of cancer in the rectum. This manuscript will review and compare the most recent literature on IRA and IPAA as it pertains to postoperative morbidity and mortality, failure rates, functional outcomes and cancer risk. PMID:25309058

Potential of SeHCAT retention as an indicator of terminal ileal involvement in inflammatory bowel disease.

PubMed

Holdstock, G; Phillips, G; Hames, T K; Condon, B R; Fleming, J S; Smith, C L; Ackery, D M

1985-01-01

The absorption of 75Se-23-selena-25-homotaurocholate (SeHCAT) was compared with vitamin-B12 absorption and conventional radiography in 44 patients with inflammatory bowel disease. The retention of SeHCAT was normal in 11 patients with ulcerative colitis but was abnormally low in 9 patients with terminal-ileal resection, 9 out of 14 patients with small-bowel Crohn's disease and in 2 out of 10 patients with Crohn's colitis. The 5 patients with small-bowel Crohn's disease and normal retention had either inactive disease or no radiological evidence of terminal ileal involvement. Measurements of the absorption of vitamin B12 did not discriminate between these groups, and there was very poor correlation between B12 and SeHCAT absorption (r = 0.506, P less than 0.05). There was extremely good correlation of SeHCAT retention measured using a wholebody counter with that measured using an uncollimated gamma camera (r = 0.96, P less than 0.001). The results suggest that SeHCAT retention may prove complementary to conventional methods of assessing small-bowel disease in patients with inflammatory bowel disease. As measurement by gamma camera is feasible, this test can be used in most departments of nuclear medicine.

Experimental evaluation of ileal patch in delayed primary repair of penetrating colon injuries: An animal study.

PubMed

Abbasi, Hamid Reza; Bolandparvaz, Shahram; Yarmohammadi, Hooman; Geramizadeh, Bita; Tanideh, Nader; Paydar, Shahram; Hosseini, Seyed Vahid

2006-10-01

Primary repair of traumatic colonic perforation is progressively gaining acceptance as the best method of management. However, when delayed, the risk of infection-related complications may increase. Here, we present a new method of repairing colon perforation in the presence of peritonitis. Acute colon injury was simulated in 22 German shepherd dogs. The dogs were randomly divided into two groups of 11 and after 24 hours they were operated on. The perforations were repaired by subserosal suture technique. In the first group (group A), ileal patch was used. In the other group (group B), the colon was closed by debridement and anastomosis. After 6 weeks, the repairs were assessed on the basis of survival, gross and histological assessments. Nine (82%) dogs in group A and six (56%) in group B survived. Ileal patch utilization significantly decreased the mortality rate (p < 0.05). The cause of death in two group A dogs and five group B dogs was peritonitis and intra-abdominal abscess formation. None of the surviving dogs showed evidence of anastomotic leakage or breakdown. Small bowel patch used in primary repair of colon injury in the presence of peritonitis may decrease the risk of postoperative infection-related complications and the mortality rate.

Pregnancy after orthotopic continent urinary diversion.

PubMed

Kennedy, W A; Hensle, T W; Reiley, E A; Fox, H E; Haus, T

1993-10-01

Continent urinary diversion has become a common form of bladder management for the female exstrophy patient in whom primary reconstruction has failed. Reported are the results of successful pregnancies in four young adult females, who had previously undergone a flap vaginoplasty as part of earlier management and more recently a continent right colonic urinary reservoir with a perineal stoma (Indiana pouch). Pregnancy in each of these patients was characterized by several urinary tract infections, cervical prolapse and mild to severe maternal hydronephrosis. All of the patients had some degree of difficulty with clean intermittent catheterization. One patient required an indwelling catheter with prolonged bed rest. Maternal hydronephrosis resolved after delivery in all instances. All four patients delivered their infants by way of cesarean section, either emergently for maternal or fetal distress or electively. Cervical prolapse did not resolve in three patients and will require surgical repair. After delivery, all patients returned to their previous pattern of clean intermittent catheterization without loss of continence. All the infants delivered were healthy with appropriate weights and high Apgar scores (more than 8). Orthotopic (perineal stoma) continent urinary diversion is not a contraindication to pregnancy. However, our experience mandates delivery by cesarean section with close monitoring for maternal or fetal distress during gestation.

Novel prototype sewing device, EndoSew®, for minimally invasive surgery: an extracorporeal ileal conduit construction pilot study in 10 patients.

PubMed

Roth, Beat; Birkhäuser, Frédéric D; Thalmann, George N; Zehnder, Pascal

2013-11-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The EndoSew(®) prototype was first tested in a porcine model several years ago. The investigators found it both simple to master and reliable, its greatest advantage being a 2.4-fold time saving compared with straight laparoscopic suturing. In addition to that publication, there is a single case report describing the performance of an open EndoSew(®) suture to close parts (16 cm) of an ileal neobladder. The time for suturing the 16 cm ileum was 25 min, which is in line with our experience. The knowledge on this subject is limited to these two publications. We report on the first consecutive series of ileal conduits performed in humans using the novel prototype sewing device EndoSew(®). The study shows that the beginning and the end of the suture process represent the critical procedural steps. It also shows that, overall, the prototype sewing machine has the potential to facilitate the intracorporeal suturing required in reconstructive urology for construction of urinary diversions. To evaluate the feasibility and safety of the novel prototype sewing device EndoSew(®) in placing an extracorporeal resorbable running suture for ileal conduits. We conducted a prospective single-centre pilot study of 10 consecutive patients undergoing ileal conduit, in whom the proximal end of the ileal conduit was closed extracorporeally using an EndoSew(®) running suture. The primary endpoint was the safety of the device and the feasibility of the sewing procedure which was defined as a complete watertight running suture line accomplished by EndoSew(®) only. Watertightness was assessed using methylene blue intraoperatively and by loopography on postoperative days 7 and 14. Secondary endpoints were the time requirements and complications ≤30 days after surgery. A complete EndoSew(®) running suture was feasible in nine patients; the suture had to be abandoned in one patient because of mechanical failure. In three

BK virus associated pronounced hemorrhagic cystoureteritis after bone marrow transplantation.

PubMed

Haab, Alexander C; Keller, Isabelle S; Padevit, Christian; John, Hubert

2015-10-01

Ureteral stenosis due to reactivation of the BK virus (BKV) in a state of immunodeficiency is very rare. More common is the appearance of a hemorrhagic cystitis. This report not only shows bilateral ureteral stenosis after bone marrow transplantation, but also presents severe complications as chronic pelvic pain and impaired kidney function as well as irreparable damage to the whole urinary tract leading to nephroureterectomy, subtrigonal cystectomy and orthotopic ileal neobladder. Finally renal transplantation was required. To our knowledge this is the first case in the literature where such a severe course of BKV associated hemorrhagic cystoureteritis is described.

Long-term functional outcomes after radical cystectomy with ileal bladder substitute: does the definition of continence matter?

PubMed

Liedberg, Fredrik; Ahlgren, Göran; Baseckas, Gediminas; Gudjonsson, Sigurdur; Håkansson, Ulf; Lindquist, Sara; Löfgren, Annica; Patschan, Oliver; Siller, Carina; Sjödahl, Gottfrid

2017-02-01

Functional outcomes after ileal bladder substitution reflect the expectations of future patients at a particular centre. The aim of this study was to use validated questionnaires and a pad-weighing test to investigate functional outcomes after neobladder reconstruction at long-term follow-up in patients at a single centre. During 2005 - 2015, 75 patients received a Studer ileal bladder substitute at the Department of Urology, Malmö. Forty-six of these patients were alive for follow-up and were evaluated using the pad-weighing test and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF). Five of 37 evaluable patients (14%) were considered fully continent, reporting a pad-weighing test result of 0 g and an ICIQ-UI-SF score of 0. The median ICIQ-UI-SF score was 8 [interquartile range (IQR) 3-11], and seven patients (17%) were continent according to the ICIQ-UI-SF score only. In the pad-weighing test, 28 out of 37 patients (76%) reported 0 g day-time leakage whereas only 12 out of 37 patients (32%) reported 0 g night-time leakage. At follow-up, nine out of 39 (23%) of evaluable male patients were potent. The median ICIQ-UI-SF score was significantly lower during the second half of the study period [4 (IQR 0-8) vs 10 (IQR 6-14); p = .003]. The inverse applied to the median IIEF score [5 (IQR 3-12) vs 2 (IQR 1-4); p = .02]. Functional outcomes at long-term follow-up after radical cystectomy and Studer ileal bladder substitute were at best modest in this series. Better outcomes during the second half of the study period might be explained by improved patient selection and a refined surgical technique, but possibly also by longer follow-up of patients during the first half of the period resulting in a more pronounced time-dependent decline in functional outcomes.

Relationship between in vitro assays and standardized ileal amino acid digestibility of animal protein meals in broilers.

PubMed

Rochell, S J; Kuhlers, D L; Dozier, W A

2013-01-01

Two identical trials were conducted to determine the relationship of a novel digestive enzyme assay, Poultry Complete IDEA (PC IDEA), and the pepsin digestibility assay with standardized ileal amino acid digestibility (SIAAD) of 20 animal protein meals (APM) fed to broilers from 25 to 30 d of age. Animal protein meals included 10 meat and bone meals (MBM) consisting of bovine, porcine, or mixed bovine and porcine raw materials (BP), and 10 animal protein blends containing animal proteins from various species. Treatments consisted of 20 semi-purified diets containing 1 APM as the sole source of dietary amino acids (AA), and 1 N-free diet to determine endogenous ileal AA flow. With the exception of the N-free diet, diets were formulated to contain 20% CP. In each trial, 756 Ross × Ross 708 male broilers were housed in battery cages and randomly assigned to 21 dietary treatments on d 25 (12 birds per cage; 3 replicate cages), and ileal digesta were collected on d 30 for determination of SIAAD. Pepsin digestibility and PC IDEA were determined for APM samples from each experimental diet (3 replicates per trial; 6 total replicates). Pepsin digestibility and PC IDEA were both correlated (P < 0.001) with SIAAD for each AA. Multiple linear regression of PC IDEA and pepsin digestibility on SIAAD resulted in the following equations: % Lys SIAAD = [-9.65 + (0.38 × % PC IDEA predicted Lys digestibility) + (0.69 × % pepsin digestibility)], % Met SIAAD = [-35.95 + (0.62 × % PC IDEA predicted Met digestibility) + (0.75 × % pepsin digestibility)], % Thr SIAAD = [-77.5 + (0.39 × % PC IDEA predicted Thr digestibility) + (1.37 × % pepsin digestibility)]. Values of R(2) were 0.46, 0.47, and 0.55 for Lys, Met, and Thr, respectively. The relatively low R(2) values may have been due to the limited range in SIAAD observed for the 20 APM, and additional data on APM varying in SIAAD are needed.

A deimmunized bispecific ligand directed toxin that shows an impressive anti-pancreatic cancer effect in a systemic nude mouse orthotopic model

PubMed Central

Oh, Seunguk; Todhunter, Deborah A.; Panoskaltsis-Mortari, Angela; Buchsbaum, Donald J.; Toma, Shoko; Vallera, Daniel A.

2011-01-01

Objective The objective was to test a bispecific ligand directed toxin (BLT), with reduced immunogenicity for enhanced efficacy in targeting orthotopic pancreatic cancer in vivo. Method A new BLT was created in which both human EGF and IL-4 cytokines were cloned onto the same single chain molecule with deimmunized pseudomonas exotoxin (dEGF4KDEL). Key amino acids dictating B cell generation of neutralizing anti-toxin antibodies were mutated. Bioassays were used to determine whether mutation reduced potency, and ELISA studies were performed to determine whether anti-toxin antibodies were reduced. A genetically altered luciferase MIA PaCa-2 xenograft model was used to image in real time and determine affects on systemic malignant human cancer. BLTs targeting B cells were used as specificity controls. Results dEGF4KDEL was significantly effective following systemic injection against established orthotopic MIA PaCa-2 pancreatic cancer and selectively prevented metastasis. Mutagenesis significantly reduced anti-toxin levels in vivo with no apparent activity loss in vitro. The drug was effective against three human pancreatic cancer lines in vitro, MIA PaCa-2, SW1990, and S2VP10. Conclusions Despite the metastatic nature of the MIA PaCa-2 orthotopic tumor xenografted in nude mice, high percentages of tumors responded to extended dEGFKDEL treatment resulting in significant anti-cancer effects and disease-free survivors. PMID:22258068

Luminally-polarized mural and vascular remodeling in ileal strictures of Crohn's Disease.

PubMed

Zhang, Xiaofei; Ko, Huaibin Mabel; Torres, Joana; Panchal, Hinaben J; Cai, Zhenjian; Wagner, Mathilde; Sands, Bruce E; Colombel, Jean-Frederic; Cho, Judy; Taouli, Bachir; Harpaz, Noam

2018-03-16

Intestinal stricture, a major complication of Crohn's disease (CD), results from fibromuscular remodeling and expansion of the intestinal wall. The corresponding microanatomical alterations have not been fully described, hindering progress toward understanding their pathogenesis and devising appropriate treatments. We used tissue-specific staining and quantitative digital histomorphometry for this purpose. Serial histological sections from 37 surgically-resected ileal strictures and adjacent non-strictured controls from patients with CD were evaluated after staining for smooth muscle actin, collagen (Sirius red) and collagen types I, III and V. Overall mural thickening in strictures was increased 2.4±0.3-fold compared with non-strictured regions of the same specimens. The muscular layer most altered was the muscularis mucosae (MM). Compared with the inner and outer layers of the MP which were expanded 2.1±0.2- and 1.4±0.1-fold, respectively, the MM was expanded 22.1±3.6-fold, reflecting the combined effects of architectural disarray, an 11.6±1.4-fold increase smooth muscle content, and elaboration of pericellular type V collagen. In contrast, the architecture of the MP was preserved and pericellular collagen was virtually absent; rather, fibrosis in this layer was limited to expansion of the intramuscular septa by collagen types I and III. The muscular arteries and veins within the strictured submucosa frequently exhibited eccentric, luminally-oriented adventitial mantles comprising hyperplastic myocytes and extracellular type V collagen. We conclude that the fibromuscular remodeling which results in CD-associated ileal strictures predominantly involves the MM and submucosal vasculature in a luminally-polarized fashion and suggests that mucosal-based factors may contribute to stricture pathogenesis. Copyright © 2018. Published by Elsevier Inc.

Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumors in patients

PubMed Central

Grisanzio, Chiara; Seeley, Apryle; Chang, Michelle; Collins, Michael; Di Napoli, Arianna; Cheng, Su-Chun; Percy, Andrew; Beroukhim, Rameen; Signoretti, Sabina

2013-01-01

Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumor tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphologic, phenotypic, and genetic characteristics of the kidney tumor tissues before and after implantation. Twenty kidney tumors were transplanted into mice. Successful tumor growth was detected in 19 cases (95%). The histopathologic and immunophenotypic features of the xenografts and those of the original tumors largely overlapped in all the cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumors and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6 of 10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing, and for deeper understanding of kidney carcinogenesis. PMID:21710693

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer

PubMed Central

Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

2016-01-01

Background Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. Methods CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections Results The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Conclusion Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery. PMID:27584018

A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts.

PubMed

Hoover, Malachia; Adamian, Yvess; Brown, Mark; Maawy, Ali; Chang, Alexander; Lee, Jacqueline; Gharibi, Armen; Katz, Matthew H; Fleming, Jason; Hoffman, Robert M; Bouvet, Michael; Doebler, Robert; Kelber, Jonathan A

2017-01-24

Next-generation sequencing (NGS) can identify and validate new biomarkers of cancer onset, progression and therapy resistance. Substantial archives of formalin-fixed, paraffin-embedded (FFPE) cancer samples from patients represent a rich resource for linking molecular signatures to clinical data. However, performing NGS on FFPE samples is limited by poor RNA purification methods. To address this hurdle, we developed an improved methodology for extracting high-quality RNA from FFPE samples. By briefly integrating a newly-designed micro-homogenizing (mH) tool with commercially available FFPE RNA extraction protocols, RNA recovery is increased by approximately 3-fold while maintaining standard A260/A280 ratios and RNA quality index (RQI) values. Furthermore, we demonstrate that the mH-purified FFPE RNAs are longer and of higher integrity. Previous studies have suggested that pancreatic ductal adenocarcinoma (PDAC) gene expression signatures vary significantly under in vitro versus in vivo and in vivo subcutaneous versus orthotopic conditions. By using our improved mH-based method, we were able to preserve established expression patterns of KRas-dependency genes within these three unique microenvironments. Finally, expression analysis of novel biomarkers in KRas mutant PDAC samples revealed that PEAK1 decreases and MST1R increases by over 100-fold in orthotopic versus subcutaneous microenvironments. Interestingly, however, only PEAK1 levels remain elevated in orthotopically grown KRas wild-type PDAC cells. These results demonstrate the critical nature of the orthotopic tumor microenvironment when evaluating the clinical relevance of new biomarkers in cells or patient-derived samples. Furthermore, this new mH-based FFPE RNA extraction method has the potential to enhance and expand future FFPE-RNA-NGS cancer biomarker studies.

Facile preparation of well-defined AB2 Y-shaped miktoarm star polypeptide copolymer via the combination of ring-opening polymerization and click chemistry.

PubMed

Rao, Jingyi; Zhang, Yanfeng; Zhang, Jingyan; Liu, Shiyong

2008-10-01

Well-defined AB2 Y-shaped miktoarm star polypeptide copolymer, PZLL-b-(PBLG)2, was synthesized via a combination of ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydride (NCA) and click chemistry, where PZLL is poly(epsilon-benzyloxycarbonyl-L-lysine) and PBLG is poly(gamma-benzyl-L-glutamate). First, two types of primary-amine-containing initiators, N-aminoethyl 3,5-bis(propargyloxyl)-benzamide and 3-azidopropylamine, were synthesized and employed for the ROP of NCA, leading to the formation of dialkynyl-terminated PZLL and azide-terminated PBLG, dialkynyl-PZLL and PBLG-N3, respectively. The subsequent copper(I)-catalyzed cycloaddition reaction between dialkynyl-PZLL and slightly excess PBLG-N3 led to facile preparation of PZLL-b-(PBLG)2 Y-shaped miktoarm star polypeptide copolymer. The excess PBLG-N3 was scavenged off by reacting with alkynyl-functionalized Wang resin. The obtained Y-shaped miktoarm star polypeptide copolymer was characterized by gel permeation chromatograph (GPC), Fourier transform-infrared spectroscopy (FT-IR), and (1)H NMR. Moreover, after the hydrolysis of protecting benzyl and benzyloxycarbonyl groups of PZLL-b-(PBLG)2, water-soluble pH-responsive Y-shaped miktoarm star polypeptide copolymer, PLL-b-(PLGA)2, was obtained, where PLL is poly(L-lysine) and PLGA is poly(L-glutamic acid). It can self-assemble into PLGA-core micelles at acidic pH and PLL-core micelles at alkaline pH, accompanied with the coil-to-helix transition of PLGA and PLL sequences, respectively. The spontaneous pH-responsive supramolecular assembly of PLL-b-(PLGA)2 miktoarm star polypeptide copolymer has been investigated via a combination of (1)H NMR, laser light scattering (LLS), transmission electron microscopy (TEM), and circular dichroism (CD) spectroscopy.

Impact of PRRSV infection and dietary soybean meal on ileal amino acid digestibility and endogenous amino acid losses in growing pigs

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant disease in the swine industry and increasing soybean meal (SBM) during this disease challenge may improve performance. Our objectives were to determine the impact of SBM level on apparent total tract (ATTD) and ileal (AID) ...

Lactobacillus acidophilus alleviates pouchitis after ileal pouch-anal anastomosis in rats.

PubMed

Xu, Yan-Yan; Zhang, Ying-Ying; He, An-Qi; Li, Kai-Yu; Gao, Sen-Yang; Liu, Gang

2017-07-14

To assess the therapeutic potential of Lactobacillus acidophilus (LA) for the treatment of pouchitis in a rat model. Sprague Dawley rats underwent proctocolectomy and ileal pouch-anal anastomosis followed by administration of dextran sulfate sodium (DSS) to induce pouchitis. Rats with pouchitis were randomly divided into three groups: no intervention (NI), normal saline (NS, 3 mL/d normal saline for 7 d), and LA (3 mL/d LA at 1× 10 10 colony-forming units for 7 d). General body condition was recorded and pouch specimens were obtained for histological examination. mRNA expression levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were determined by RT-PCR. Zonula occludens protein 1 (ZO-1) levels were measured by immunohistochemistry. LA reduced weight loss associated with pouchitis ( P < 0.05) and improved the symptoms of pouchitis in rats. Compared with the NI and NS groups, rats in the LA group showed earlier disappearance of hematochezia (6.17 ± 0.75, 6.50 ± 0.55, 3.17 ± 0.75, P < 0.05) and higher fecal scores (2.67 ± 0.48, 2.50 ± 0.51, 4.42 ± 0.50, respectively, P < 0.05). Histological scores were also lower in the LA group compared with the other two groups (7.17 ± 0.98, 8.00 ± 0.89, 4.00 ± 0.89, respectively, P < 0.05). mRNA expression levels of IL-1β, IL-6, and tumor necrosis factor-α were significantly reduced, while IL-10 mRNA levels were significantly increased in the LA group ( P < 0.05, respectively). ZO-1 protein levels were also significantly increased after administration of LA ( P < 0.05). LA alleviates pouchitis induced by DSS after ileal pouch-anal anastomosis by decreasing pro-inflammatory factors and increasing anti-inflammatory factors, and restoring ZO-1 expression in the mucosa.

Lentinan diminishes apoptotic bodies in the ileal crypts associated with S-1 administration.

PubMed

Suga, Yasuyo; Takehana, Kenji

2017-09-01

S-1 is an oral agent containing tegafur (a prodrug of 5-fluorouracil) that is used to treat various cancers, but adverse effects are frequent. Two pilot clinical studies have suggested that lentinan (LNT; β-1,3-glucan) may reduce the incidence of adverse effects caused by S-1 therapy. In this study, we established a murine model for assessment of gastrointestinal toxicity associated with S-1 and studied the effect of LNT. S-1 was administered orally to BALB/c mice at the effective dose (8.3mg/kg, as tegafur equivalent) once daily (5days per week) for 3weeks. Stool consistency and intestinal specimens were examined. We investigated the effect of combined intravenous administration of LNT at 0.1mg, which is an effective dose in murine tumor models. We also investigated the effect of a single administration of S-1. During long-term administration of S-1, some mice had loose stools and an increase in apoptotic bodies was observed in the ileal crypts. An increase in apoptotic bodies was also noted after a single administration of S-1 (15mg/kg). Prior or concomitant administration of LNT inhibited the increase in apoptotic bodies in both settings. Administration of LNT also increased the accumulation of CD11b + TIM-4 + cells in the ileum, while depletion of these cells by liposomal clodronate diminished the inhibitory effect of LNT on S-1 toxicity. Combined administration of LNT with S-1 led to a decrease in apoptotic bodies in the ileal crypts, possibly because LNT promoted phagocytosis of damaged cells by CD11b + TIM-4 + cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

PubMed

Miller, Amy; Burson, Hannah; Söling, Ariane; Roughan, Johnny

2016-01-01

Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP) testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg) and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking) was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an effective method of

Effect of dietary nutrients on ileal endogenous losses of threonine, cysteine, methionine, lysine, leucine and protein in broiler chicks.

PubMed

Cerrate, S; Vignale, S K; Ekmay, R; England, J; Coon, C

2018-04-01

An isotope dose technique was utilized (i) to determine endogenous amino acid (AA) and protein losses and (ii) to propose adjusted values for AA requirements. The endogenous flow rate was calculated from the pool of enrichment in plasma AA, assuming similitude to enrichment of endogenous AA. In experiment 1, chicks were orally administered D4-lysine at 2% of estimated lysine intake from 16 to 24 days to find the isotopic steady state of the atom percent excess (APE) of lysine for plasma and jejunal and ileal digesta. The APE of D4-lysine in plasma, jejunal digesta and ileal digesta reached the isotopic steady state at 5.5, 3.4 and 2.0 days, respectively, by using the broken-line model. It was assumed that the isotopic steady state at 5 days identified for D4-lysine is also representative for the 15N-labeled AA. In experiment 2, chicks were fed diets from 1 to 21 days with increasing levels of fat (6%, 8%, 12%, 13% extract ether), protein (26%, 28.5%, 31% CP) or fiber (14%, 16%, 18% NDF) by adding poultry fat, soybean meal, blended animal protein or barley. Chicks were orally administered 15N-threonine, 15N-cysteine, 15N-methionine, 15N-lysine and 15N-leucine at 2% of estimated daily intake for 5 days from 17 to 21 days of age. Dietary nutrients influenced endogenous losses (EL), where dietary fat stimulated EL of lysine (P=0.06), leucine and protein (P=0.07); dietary protein enhanced EL of leucine and protein; and finally the dietary fiber increased EL of leucine. Dietary nutrients also affected apparent ileal digestibility (AID). Dietary fat increased AID of cysteine but decreased AID of lysine. Dietary protein reduced AID of protein, threonine, lysine and leucine, and similarly dietary fiber decreased AID of protein, threonine, methionine, lysine and leucine. In contrast, dietary fat or protein did not affect real ileal digestibility (RID) of protein and AA except threonine and leucine. The dietary fiber reduced the RID of protein, threonine and leucine. This

Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willing, B.; Halfvarson, J.; Dicksved, J.

2008-08-15

Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. Themore » microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.« less

Using Dual Fluorescence Reporting Genes to Establish an In Vivo Imaging Model of Orthotopic Lung Adenocarcinoma in Mice.

PubMed

Lai, Cheng-Wei; Chen, Hsiao-Ling; Yen, Chih-Ching; Wang, Jiun-Long; Yang, Shang-Hsun; Chen, Chuan-Mu

2016-12-01

Lung adenocarcinoma is characterized by a poor prognosis and high mortality worldwide. In this study, we purposed to use the live imaging techniques and a reporter gene that generates highly penetrative near-infrared (NIR) fluorescence to establish a preclinical animal model that allows in vivo monitoring of lung cancer development and provides a non-invasive tool for the research on lung cancer pathogenesis and therapeutic efficacy. A human lung adenocarcinoma cell line (A549), which stably expressed the dual fluorescence reporting gene (pCAG-iRFP-2A-Venus), was used to generate subcutaneous or orthotopic lung cancer in nude mice. Cancer development was evaluated by live imaging via the NIR fluorescent signals from iRFP, and the signals were verified ex vivo by the green fluorescence of Venus from the gross lung. The tumor-bearing mice received miR-16 nucleic acid therapy by intranasal administration to demonstrate therapeutic efficacy in this live imaging system. For the subcutaneous xenografts, the detection of iRFP fluorescent signals revealed delicate changes occurring during tumor growth that are not distinguishable by conventional methods of tumor measurement. For the orthotopic xenografts, the positive correlation between the in vivo iRFP signal from mice chests and the ex vivo green fluorescent signal from gross lung tumors and the results of the suppressed tumorigenesis by miR-16 treatment indicated that lung tumor size can be accurately quantified by the emission of NIR fluorescence. In addition, orthotopic lung tumor localization can be accurately visualized using iRFP fluorescence tomography in vivo, thus revealing the trafficking of lung tumor cells. We introduced a novel dual fluorescence lung cancer model that provides a non-invasive option for preclinical research via the use of NIR fluorescence in live imaging of lung.

Comprehensive investigation of noble metal nanoparticles shape, size and material on the optical response of optimal plasmonic Y-splitter waveguides

NASA Astrophysics Data System (ADS)

Ahmadivand, Arash; Golmohammadi, Saeed

2014-01-01

With the purpose of guiding and splitting of optical power at C-band spectrum, we studied Y-shape splitters based on various shapes of nanoparticles as a plasmon waveguide. We applied different configurations of Gold (Au) and Silver (Ag) nanoparticles including spheres, rods and rings, to optimize the efficiency and losses of two and four-branch splitters. The best performance in light transportation specifically at telecom wavelength (λ≈1550 nm) is achieved by nanorings, due to an extra degree of freedom in their geometrical components. In addition, comparisons of several values for offset distance (doffset) of examined structures shows that Au nanoring splitters with feasible lower doffset have high quality in guiding and splitting of light through the structure. Finally, we studied four-branch Y-splitters based on Au and Ag nanorings with least possible offset distances to optimize the splitter performance. The power transmission as a key element is calculated for examined structures.

Liver Stiffness Measurements Using Acoustic Radiation Force Impulse in Recipients of Living-Donor and Deceased-Donor Orthotopic Liver Transplant.

PubMed

Haberal, Kemal Murat; Turnaoğlu, Hale; Özdemir, Adnan; Uslu, Nihal; Haberal Reyhan, Asuman Nihan; Moray, Gökhan; Haberal, Mehmet

2017-08-24

The aim of this study was to evaluate the diagnostic efficiency of the acoustic radiation force impulse (Siemens Medical Solutions, Erlangen, Germany) elastography in assessment of fibrosis in orthotopic liver transplant patients. We enrolled 28 orthotopic liver transplant patients (deceased and living donors), whose biopsy decision had been prospectively given clinically. Ten acoustic radiation force impulse elastographic measurements were applied before the biopsy or within 3 days after the biopsy by 2 radiologists. After the core tissue needle biopsy, specimens of all patients were analyzed according to the modified Ishak scoring system. Measurements of acoustic radiation force impulse elastography and pathology specimen results were compared. From 28 biopsies, fibrosis scores of 4 biopsies were evaluated as F0 (14.3%), 16 as F1 (57.1%), 4 as F2 (14.3%), and 4 as F3 (14.3%). Mean results of acoustic radiation force impulse measurements were calculated as 1.4 ± 0.07 in F0, 1.74 ± 0.57 in F1, 2.19 ± 0.7 in F2, and 2.18 ± 0.35 in F3. There were no significant correlations of mean acoustic radiation force impulse values between the F0 versus F1 (P = .956) and F0 versus F2 stages (P = .234). A statistically significant correlation of mean acoustic radiation force impulse values was found between the F0 and F3 fibrosis stages (P = .046). Acoustic radiation force impulse imaging is a promising screening test for detecting significant liver fibrosis (≥ F3 in modified Ishak) in living-donor or deceased-donor orthotopic liver transplant recipients.

Development of a novel preclinical pancreatic cancer research model: bioluminescence image-guided focal irradiation and tumor monitoring of orthotopic xenografts.

PubMed

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; Deweese, Theodore L; Herman, Joseph M

2012-04-01

We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response.

Analysis of Stroma Labeling During Multiple Passage of a Sarcoma Imageable Patient-Derived Orthotopic Xenograft (iPDOX) in Red Fluorescent Protein Transgenic Nude Mice.

PubMed

Kiyuna, Tasuku; Murakami, Takashi; Tome, Yasunori; Kawaguchi, Kei; Igarashi, Kentaro; Miyake, Kentaro; Kanaya, Fuminori; Singh, Arun; Eilber, Fritz C; Hoffman, Robert M

2017-10-01

A patient-derived orthotopic xenograft (PDOX) model of undifferentiated pleomorphic sarcoma (UPS) was previously established that acquired red fluorescent protein (RFP)-expressing stroma by growth in an RFP transgenic nude mouse. In the present study, an imageable PDOX model (iPDOX) of UPS was established by orthotopic implantation in the biceps femoris of transgenic RFP nude mice. After the tumors grew to a diameter of 10 mm, they were harvested and the brightest portion of the tumors were subsequently orthotopically transplanted to both RFP and non-colored nude mice. The UPS PDOX tumor was again transplanted to RFP transgenic and non-colored nude mice, and finally a 3rd passage was made in the same manner. Five UPS tumors from each passage in both RFP and non-colored mouse models were harvested. The FV1,000 confocal microscope was used to visualize and quantitate the RFP area of the resected tumors. The average percent fluorescent area in the first passage of RFP mice was 34 ± 22%; in the second passage, 34 ± 20%; and 36 ± 11% in the third passage of RFP transgenic nude mice. The average tumor RFP area in the first passage from RFP mice to non-colored mice was 20 ± 7%; in the second passage, 28 ± 11%; in the third passage was 27 ± 13%. The present results demonstrate the extensive and stable acquisition of stroma by the UPS-tumor growing orthotopically in transgenic RFP nude mice (iPDOX). This model can be used for screening for effective drugs for individual patients and drug discovery. J. Cell. Biochem. 118: 3367-3371, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

PubMed

Schwartz, Anthony L; Custis, James T; Harmon, Joseph F; Powers, Barbara E; Chubb, Laura S; LaRue, Susan M; Ehrhart, Nicole P; Ryan, Stewart D

2013-03-01

To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. 26 athymic nude rats. 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

Virotherapy of the Malignant U87 Human Glioblastoma in the Orthotopic Xenotransplantation Mouse SCID Model.

PubMed

Shchelkunov, S N; Razumov, I A; Kolosova, I V; Romashchenko, A V; Zavjalov, E L

2018-01-01

The possibility of glioblastoma virotherapy at intravenous injection of the LIVP-GFP recombinant virus was studied in experimental model of orthotopic xenotransplantation of human glioblastoma cell line U87 to SCID laboratory mice. The LIVP-GFP recombinant virus deficient for thymidine kinase exhibited a significantly greater oncolytic capacity than the original LIVP virus, and an intravenous injection of LIVP-GFP at the early stages of tumorigenesis in mouse brain in most cases resulted in the lysis of the tumor.

Mandibular second molar exhibiting a unique "Y-" and "J-" "shaped" root canal anatomy diagnosed using cone-beam computed tomographic scanning: A case report.

PubMed

Parashar, Saumya-Rajesh; Kowsky, R Dinesh; Natanasabapathy, Velmurugan

2017-01-01

This article aims to report a unique case with aberrant root canal anatomy exhibiting "Y-" and "J"-shaped canal pattern in a mandibular second molar. Anatomic complexities may pose challenges for endodontic treatment. Before performing endodontic treatment, the clinician should be aware of the internal anatomy of the tooth being treated and should recognize anatomic aberrations if present. Presence of unusual anatomy may call for modifications in treatment planning. This report describes in detail about a mandibular second molar tooth associated with two paramolar tubercles having a peculiar "Y-" and "J-"shaped canal anatomy detected with the aid of cone beam computed tomography, which has never been reported in the dental literature. The proposed treatment protocol for the endodontic management of the same has also been discussed.

Successful Pregnancies in Two Orthotopic Liver Transplant (OLT) Recipients in Iran; Two Case Reports.

PubMed

Zahra, Tayebi; Seyyed Alireza, Taqhavi; Shirin, Shahbazi

2009-10-01

Pregnancy and parenting have been part of human life throughout history and liver transplant recipients are not any exception. This paper reports successful pregnancies in two liver transplant recipients in Iran. The first case was a 34-year old woman who had undergone orthotopic liver transplantation (OLT) at Shiraz Namazi Educational Hospital in 2002. She decided to get pregnant seven years after the operation. During pregnancy, immunosuppressive therapy continued, except Mycophenolate Mofetil which has an absolute contra-indication in pregnancy. The patient was followed up during pregnancy by the transplant team as well as a gynecologist. She faced no significant complications and the liver function was stable during pregnancy. She later underwent a Cesarean section in the 38(th) week of gestation and the newborn was a healthy girl weighing 2480g with an Apgar score of 8 at the time of birth. There were no evidences of prematurity or structural abnormalities in the newborn. The second case was a 31-year old primipara who had received an orthotopic liver transplant (OLT) in Shiraz in 2002. She had a smooth pregnancy without any complications and the newborn was a boy weighing 3100g with Apgar scores of 8 and 10 at the time of birth and 5 minutes thereafter, respectively. As the number of transplant recipients is growing along with the number of recipients who are in their fertility years, it is vital to ensure a proper medical care by a coordinated multidisciplinary team during pregnancy.

Digestibility marker and ileal amino acid digestibility in phytase-supplemented soybean or canola meals for growing pigs.

PubMed

Favero, A; Ragland, D; Vieira, S L; Owusu-Asiedu, A; Adeola, O

2014-12-01

Two experiments using soybean meal (SBM) or canola meal (CM) were conducted to investigate whether the choice of digestibility marker influenced the apparent ileal digestibility (AID) or standardized ileal digestibility (SID) of N and AA in diets supplemented with phytase. In each experiment, 18 barrows fitted with T-cannulas at the ileocecal junction were assigned to 3 diets consisting of a N-free diet to determine endogenous losses of N and AA, a semipurified diet (SBM in Exp. 1 or CM in Exp. 2), and the semipurified diet supplemented with phytase at 1,000 phytase units/kg. Three digestibility markers including acid-insoluble ash (AIA), chromic oxide (Cr2O3), and titanium dioxide (TiO2) were added to each diet at 3 g/kg. Each diet was fed for 7 d, consisting of a 5-d adjustment and a 2-d collection of ileal digesta. In both studies, basal ileal endogenous losses determined with Cr2O3 as a digestibility marker were lower (P<0.01) than with those determined with AIA or TiO2 digestibility markers. Using SBM as the protein source in Exp. 1, there was no interaction between phytase and digestibility marker on AID or SID of AA. The AID of N and AA in SBM using AIA as a digestibility marker tended to be lower (P<0.1) compared with Cr2O3 or TiO2 digestibility markers. Phytase supplementation increased (P<0.001) the AID of Ca and P. The use of AIA or Cr2O3 digestibility marker tended to be associated with lower (P<0.1) SID values compared with TiO2. Phytase did not affect the SID of N or any AA in SBM except for Met, for which there was an increase (P<0.05) with phytase supplementation. Using CM as the protein source in Exp. 2, there were significant interactions between digestibility marker and phytase. Phytase supplementation had effects (P<0.01) on AID or SID when Cr2O3 or TiO2 was used as the digestibility marker. With Cr2O3 or TiO2 as the digestibility marker in the CM diets, phytase supplementation increased (P<0.05) the SID of N and all AA (except Trp). There was

Inflammation-induced synergetic enhancement of nanoparticle treatments with DOXIL® and 90Y-Lactosome for orthotopic mammary tumor

NASA Astrophysics Data System (ADS)

Kurihara, Kensuke; Ueda, Motoki; Hara, Isao; Hara, Eri; Sano, Kohei; Makino, Akira; Ozeki, Eiichi; Yamamoto, Fumihiko; Saji, Hideo; Togashi, Kaori; Kimura, Shunsaku

2016-05-01

Polymeric micelles (Lactosome) in the size of 20-30 nm were labeled with radionuclides of 111In (111In-DOTA-Lactosome) for SPECT imaging and 90Y (90Y-DOTA-Lactosome) for β-ray irradiation for mammary tumor in mice. The tumor site at the femoral right leg grafted with 4T1 cells was clearly imaged at 24 h after the intravenous injection. Biodistribution revealed that the half-life time of 111In-DOTA-Lactosome was 11 h, which enabled the nanoparticle selectively accumulated in tumor site due to the enhanced permeability and retention (EPR) effect. The anti-tumor therapeutic effect of 90Y-DOTA-Lactosome was observed depending on the dose frequency and amount. Under the condition of the percutaneous ethanol injection treatment, the therapeutic effect of 90Y-DOTA-Lactosome was enhanced due to the super EPR effect. Owing to the super EPR effect, co-administration of 90Y-DOTA-Lactosome and DOXIL® inhibited the tumor growth during 15 days with their administrations.

Percutaneous Transluminal Angioplasty of Hepatic Artery Stenosis in Patients After Orthotopic Liver Transplantation: Mid-term Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarmila, Lastovickova, E-mail: jala@ikem.cz; Jan, Peregrin

2011-12-15

Purpose: This study was designed to present our experience with percutaneous treatment of hepatic artery stenosis in orthotopic liver transplant patients and to evaluate the efficacy, technical outcomes, and mid-term clinical results of the procedure. Methods: Twenty-two percutaneous transluminal angioplasties (PTAs) were performed in 19 liver transplant recipients at our institution between 1998 and 2010. Stents were placed into the hepatic/celiac artery in 16 PTAs, but balloon dilatation alone was performed in 6 because of the anatomical condition of the vessel. PTA/stenting was indicated in 17 patients because of elevated liver enzymes; 2 patients were asymptomatic. The objective of treatingmore » stenosis was prevention of long-term complications, including thrombosis. Results: Technical success was achieved in all patients. There was only one complication: dissection of the treated artery without any subsequent adverse effects. In all patients, elevated liver enzyme levels improved after treatment. No restenosis was observed in any patient during a mean follow-up of 2.6 years (1 month to 5.5 years). Conclusions: Percutaneous angioplasty/stent placement is a safe method for the treatment of hepatic artery stenosis after orthotopic liver transplantation, with a high technical success rate and promising mid-term results.« less

Dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation in humans

PubMed Central

Weng, Xiao-chuan; Zhou, Liang; Fu, Yin-yan; Zhu, Sheng-mei; He, Hui-liang; Wu, Jian

2005-01-01

Objective: To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation (OLT) in humans. Methods: Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve was monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain T1/Tc ratio of 2%~10%. The total dose of each drug given during each of the three phases of OLT was recorded. Results: Rocuronium requirement, which were (0.468±0.167) mg/(kg·h) during the paleohepatic phase, decreased significantly during the anhepatic phase to (0.303±0.134) mg/(kg·h) and returned to the initial values at the neohepatic period ((0.429±0.130) mg/(kg·h)); whereas atracuruim requirements remained unchanged during orthotopic liver transplantation. Conclusions: This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed, which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT. PMID:16130187

Effects of feed additives on ileal mucosa-associated microbiota composition of broiler chickens.

PubMed

Ruiz, R; Peinado, M J; Aranda-Olmedo, I; Abecia, L; Suárez-Pereira, E; Ortiz Mellet, C; García Fernández, J M; Rubio, L A

2015-07-01

The effects of dietary supplementation with 2 recently developed feed additives on the composition of the mucosa-associated microbiota of the ileum were studied in growing broiler chickens. A total of 48 male 1-d-old broiler chickens of the Cobb 500 strain were distributed in 4 treatments with 2 replicates of 6 birds each. The 2 additives tested were a di-d-fructose dianhydride–enriched caramel (FC) and the garlic derivative propyl propane thiosulfonate (PTS-O). Dietary treatments were a control (commercial diet with no additive), INU (20 g inulin/kg diet), CAR (20 g FC/kg diet), and GAR (90 mgPTS-O/kg diet). As a result of this study, inulin supplementation resulted in lower (P < 0.05) and FC feeding resulted in higher (P < 0.05) Blautia coccoides/Eubacterium rectale log10 number of copies respect to controls. Higher (P < 0.05) bifidobacteria log10 number of copies with respect to the controls was determined in the ileal mucosa of birds fed the PTS-O–supplemented diet. Denaturing gradient gel electrophoresis and PCR analysis on Bifidobacterium spp. revealed the presence of Bifidobacterium longum, Bifidobacterium pseudolongum, and Bifidobacterium pseudocatenulatum in samples from chickens fed the control and the PTS-O–supplemented diet. Bifidobacterium longum was exclusively found in poultry fed the control diet, whereas B. pseudocatenulatum was found only in poultry fed the PTS-O–supplemented diet. This study showed that both PTS-O and FC were able to modulate the composition of the ileal mucosa-associated microbiota of growing broiler chickens. Finally, in addition to B. pseudolongum, the presence of B. longum and B. pseudocatenulatum, species not previously described in intestinal samples of broilers, was also demonstrated.

Laparoscopic restorative proctocolectomy ileal pouch anal anastomosis: How I do it?

PubMed Central

Madnani, Manish A; Mistry, Jitendra H; Soni, Harshad N; Shah, Atul J; Patel, Kantilal S; Haribhakti, Sanjiv P

2015-01-01

Surgery for ulcerative colitis is a major and complex colorectal surgery. Laparoscopy benefits these patients with better outcomes in context of cosmesis, pain and early recovery, especially in young patients. For surgeons, it is a better tool for improving vision and magnification in deep cavities. This is not the simple extension of the laparoscopy training. Starting from preoperative preparation to post operative care there are wide variations as compared to open surgery. There are also many variations in steps of laparoscopic surgery. It involves left colon, right colon and rectal mobilisation, low division of rectum, pouch creation and anastomosis of pouch to rectum. Over many years after standardisation of this technique, it takes same operative time as open surgery at our centre. So we present our standardized technique of laparoscopic assisted restorative proctocolectomy and ileal pouch anal anastomosis (IPAA). PMID:26195886

Laparoscopic restorative proctocolectomy ileal pouch anal anastomosis: How I do it?

PubMed

Madnani, Manish A; Mistry, Jitendra H; Soni, Harshad N; Shah, Atul J; Patel, Kantilal S; Haribhakti, Sanjiv P

2015-01-01

Surgery for ulcerative colitis is a major and complex colorectal surgery. Laparoscopy benefits these patients with better outcomes in context of cosmesis, pain and early recovery, especially in young patients. For surgeons, it is a better tool for improving vision and magnification in deep cavities. This is not the simple extension of the laparoscopy training. Starting from preoperative preparation to post operative care there are wide variations as compared to open surgery. There are also many variations in steps of laparoscopic surgery. It involves left colon, right colon and rectal mobilisation, low division of rectum, pouch creation and anastomosis of pouch to rectum. Over many years after standardisation of this technique, it takes same operative time as open surgery at our centre. So we present our standardized technique of laparoscopic assisted restorative proctocolectomy and ileal pouch anal anastomosis (IPAA).

Paediatric Crohn disease patients with stricturing behaviour exhibit ileal granulocyte–macrophage colony-stimulating factor (GM-CSF) autoantibody production and reduced neutrophil bacterial killing and GM-CSF bioactivity

PubMed Central

Jurickova, I; Collins, M H; Chalk, C; Seese, A; Bezold, R; Lake, K; Allmen, D; Frischer, J S; Falcone, R A; Trapnell, B C; Denson, L A

2013-01-01

Granulocyte–macrophage colony-stimulating factor (GM-CSF) autoantibodies are associated with stricturing behaviour in Crohn disease (CD). We hypothesized that CD ileal lamina propria mononuclear cells (LPMC) would produce GM-CSF autoantibodies and peripheral blood (PB) samples would contain GM-CSF neutralizing capacity (NC). Paediatric CD and control PBMC and ileal biopsies or LPMC were isolated and cultured and GM-CSF, immunoglobulin (Ig)G and GM-CSF autoantibodies production were measured by enzyme-linked immunosorbent assay (ELISA). Basal and GM-CSF-primed neutrophil bacterial killing and signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation (pSTAT5) were measured by flow cytometry. GM-CSF autoantibodies were enriched within total IgG for LPMC isolated from CD ileal strictures and proximal margins compared to control ileum. Neutrophil bacterial killing was reduced in CD patients compared to controls. Within CD, neutrophil GM-CSF-dependent STAT5 activation and bacterial killing were reduced as GM-CSF autoantibodies increased. GM-CSF stimulation of pSTAT5 did not vary between controls and CD patients in washed PB granulocytes in which serum was removed. However, GM-CSF stimulation of pSTAT5 was reduced in whole PB samples from CD patients. These data were used to calculate the GM-CSF NC. CD patients with GM-CSF NC greater than 25% exhibited a fourfold higher rate of stricturing behaviour and surgery. The likelihood ratio (95% confidence interval) for stricturing behaviour for patients with elevation in both GM-CSF autoantibodies and GM-CSF NC was equal to 5 (2, 11). GM-CSF autoantibodies are produced by LPMC isolated from CD ileal resection specimens and are associated with reduced neutrophil bacterial killing. CD peripheral blood contains GM-CSF NC, which is associated with increased rates of stricturing behaviour. PMID:23600834

Y-shaped bilateral self-expandable metallic stent placement for malignant hilar biliary obstruction: data from a referral center for palliative care.

PubMed

Di Mitri, R; Mocciaro, F

2014-01-01

Malignant hilar strictures are a clinical challenge because of the current therapeutic approach and the poor prognosis. In recent years, self-expandable metallic stents have proven more effective than plastic stents for palliation of malignant hilar strictures, with the bilateral stent-in-stent technique registering a high success rate. We report our experience with Y-shaped endoscopic self-expandable metallic stents placement for treatment of advanced malignant hilar strictures. From April 2009 to August 2012, we prospectively collected data on patients treated with Y-shaped SEMS placement for advanced malignant hilar carcinoma. Data on technical success, clinical success, and complications were collected. Twenty patients (9 males) were treated (mean age 64.2 ± 15.3 years). The grade of malignant hilar strictures according to the Bismuth classification was II in 5 patients (25%), IIIa in 1 (5%), and IV in 14 (70%). The mean bilirubin level was 14.7 ± 4.9 mg/dL. Technical success was achieved in all patients, with a significant reduction in bilirubin levels (2.9 ± 1.7 mg/dL). One patient experienced cholangitis as early complication, while in 2 patients stent ingrowth was observed. No stents migration was recorded. There was no procedure-related mortality. At the end of the follow-up (7.1 ± 3.1 months), 13 of the 20 patients (65%) had died. Our experience confirms endoscopic bilateral self-expandable metallic stents placement with stent-in-stent technique (Y-shaped configuration) as a feasible, effective, and safe procedure for palliation of unresectable malignant hilar strictures.

Ileal loop ureteroileostomy in patients with neurogenic bladder. Personal experience with 54 patients.

PubMed

Kambouris, A A; Allaben, R D; Carpenter, W S; Shumaker, E J

1976-02-01

(1) In a six year experience with ileal loops in patients with neurogenic bladder, 49% of the patients were paralyzed, 30% had multiple sclerosis, and 91% had recurrent or persistent urinary tract infection. Reflux, incontinence, retention, and bladder calculi were additional indications for supravesical urinary diversions. (2) All loops were performed in a similar manner, most of them placed retroperitoneally, and a vigorous program of postoperative care was followed. There were no postoperative deaths, and a moderate number of complications occurred in 51.8% of the patients. (3) The participation of the enterostomal therapist is the preparation of the patient and in the immediate and long-term stomal care has been invaluable and is strongly recommended.

Morphologic and Biochemical Changes in Dogs After Portacaval Shunt Plus Bile Fistula or Ileal Bypass: Failure of Bile Fistula or Ileal Bypass to Prevent Hepatocyte Atrophy

PubMed Central

Thompson, Jon S.; Porter, Kendrick A.; Hayashida, Nobuo; McNamara, Donald J.; Parker, Thomas S.; Russell, William J. I.; Francavilla, Antonio; Starzl, Thomas E.

2010-01-01

External biliary fistula (BF) or ileal bypass (IB) was performed in dogs at the time of or 2 weeks after portacaval shunt (PCS). The pathologic changes in the dog livers 2 to 4 weeks later were compared to those caused by PCS alone. Histopathologic differences between PCS alone vs. PCS plus BF or IB could not be found. Thus, the experiments did not confirm recent observations by others in rats that BF prevents or reverses the hepatic injury of PCS. As estimated by plasma mevalonic acid determinations, the increase in hepatic cholesterol synthesis that is characteristic after BF or IB was suppressed in animals with PCS. BF and IB reduced but did not eliminate the postprandial elevation in serum bile acid that occurs after PCS. The findings have possible relevance in planning the treatment of patients with familial hypercholesterolemia with the combined use of PCS and IB. PMID:6862371

High-fiber rye diet increases ileal excretion of energy and macronutrients compared with low-fiber wheat diet independent of meal frequency in ileostomy subjects

PubMed Central

Isaksson, Hanna; Landberg, Rikard; Sundberg, Birgitta; Lundin, Eva; Hallmans, Göran; Zhang, Jie-Xian; Tidehag, Per; Erik Bach Knudsen, Knud; Moazzami, Ali A.; Åman, Per

2013-01-01

Background Whole-grain foods and cereal dietary fiber intake is associated with lower body weight. This may partly result from lower energy utilization of high-fiber diets. Objective In the present study, the impact on ileal excretion of energy and macronutrients in response to a rye bread high-fiber diet compared to a refined wheat low-fiber diet was investigated. Furthermore, the effect of meal frequency on apparent absorption of nutrients was studied for the first time. Design Ten participants that had undergone ileostomy consumed standardized iso-caloric diets, including low-fiber wheat bread (20 g dietary fiber per day) for 2 weeks followed by high-fiber rye bread (52 g dietary fiber per day) for 2 weeks. The diets were consumed in an ordinary (three meals per day) and a nibbling (seven meals per day) meal frequency in a cross-over design. Ileal effluents were collected during 24 h at the third day of each of the four dietary periods and analyzed for gross energy and nutrient contents. Results The results showed that intake of rye bread high-fiber diet compared to the refined wheat low-fiber diet caused an increase in ileal excretion of energy and macronutrients. The effect was independent of meal frequency. This suggests that a high intake of rye may result in lower availability of macronutrients for small intestinal digestion and absorption. A regular intake of rye may therefore have implications for weight management. PMID:24358035

High-fiber rye diet increases ileal excretion of energy and macronutrients compared with low-fiber wheat diet independent of meal frequency in ileostomy subjects.

PubMed

Isaksson, Hanna; Landberg, Rikard; Sundberg, Birgitta; Lundin, Eva; Hallmans, Göran; Zhang, Jie-Xian; Tidehag, Per; Erik Bach Knudsen, Knud; Moazzami, Ali A; Aman, Per

2013-01-01

Whole-grain foods and cereal dietary fiber intake is associated with lower body weight. This may partly result from lower energy utilization of high-fiber diets. In the present study, the impact on ileal excretion of energy and macronutrients in response to a rye bread high-fiber diet compared to a refined wheat low-fiber diet was investigated. Furthermore, the effect of meal frequency on apparent absorption of nutrients was studied for the first time. Ten participants that had undergone ileostomy consumed standardized iso-caloric diets, including low-fiber wheat bread (20 g dietary fiber per day) for 2 weeks followed by high-fiber rye bread (52 g dietary fiber per day) for 2 weeks. The diets were consumed in an ordinary (three meals per day) and a nibbling (seven meals per day) meal frequency in a cross-over design. Ileal effluents were collected during 24 h at the third day of each of the four dietary periods and analyzed for gross energy and nutrient contents. The results showed that intake of rye bread high-fiber diet compared to the refined wheat low-fiber diet caused an increase in ileal excretion of energy and macronutrients. The effect was independent of meal frequency. This suggests that a high intake of rye may result in lower availability of macronutrients for small intestinal digestion and absorption. A regular intake of rye may therefore have implications for weight management.

Orthotopic mouse models for the preclinical and translational study of targeted therapies against metastatic human thyroid carcinoma with BRAFV600E or wild-type BRAF

PubMed Central

Antonello, ZA; Nucera, C

2015-01-01

Molecular signature of advanced and metastatic thyroid carcinoma involves deregulation of multiple fundamental pathways activated in the tumor microenvironment. They include BRAFV600E and AKT that affect tumor initiation, progression and metastasis. Human thyroid cancer orthotopic mouse models are based on human cell lines that generally harbor genetic alterations found in human thyroid cancers. They can reproduce in vivo and in situ (into the thyroid) many features of aggressive and refractory human advanced thyroid carcinomas, including local invasion and metastasis. Humanized orthotopic mouse models seem to be ideal and commonly used for preclinical and translational studies of compounds and therapies not only because they may mimic key aspects of human diseases (e.g. metastasis), but also for their reproducibility. In addition, they might provide the possibility to evaluate systemic effects of treatments. So far, human thyroid cancer in vivo models were mainly used to test single compounds, non selective and selective. Despite the greater antitumor activity and lower toxicity obtained with different selective drugs in respect to non-selective ones, most of them are only able to delay disease progression, which ultimately could restart with similar aggressive behavior. Aggressive thyroid tumors (for example, anaplastic or poorly differentiated thyroid carcinoma) carry several complex genetic alterations that are likely cooperating to promote disease progression and might confer resistance to single-compound approaches. Orthotopic models of human thyroid cancer also hold the potential to be good models for testing novel combinatorial therapies. In this article, we will summarize results on preclinical testing of selective and nonselective single compounds in orthotopic mouse models based on validated human thyroid cancer cell lines harboring the BRAFV600E mutation or with wild-type BRAF. Furthermore, we will discuss the potential use of this model also for

Phytase modulates ileal microbiota and enhances growth performance of the broiler chickens.

PubMed

Ptak, Anna; Bedford, Michael R; Świątkiewicz, Sylwester; Żyła, Krzysztof; Józefiak, Damian

2015-01-01

Phytase is well studied and explored, however, little is known about its effects on the microbial ecology of the gastrointestinal tract. In total, 400 one-day-old female Ross 308 chicks were randomly distributed to four experimental groups. The dietary treatments were arranged as a 2 × 2 complete factorial design, with the factors being adequate (PC) or insufficient calcium (Ca) and digestible phosphor (dP)(NC) and with or without 5000 phytase units (FTU)/kg of Escherichia coli 6-phytase. The gastrointestinal tract pH values, ileal microbial communities and short-chain fatty acid concentrations in the digesta were determined. The reduction in Ca and dP concentration significantly affected pH in the crop and caeca, and addition of phytase to the NC resulted in a pH increase in the ileum. The reduction in Ca and dP concentration significantly lowered, while phytase supplementation increased ileal total bacterial counts. Additionally, the deficient diet reduced butyrate- but increased lactate-producing bacteria. The addition of phytase increased Lactobacillus sp./Enterococcus sp. whereas in case of Clostridium leptum subgroup, Clostridium coccoides-Eubacterium rectale cluster, Bifidobacterium sp. and Streptococcus/Lactococcus counts, a significant Ca and dP level x phytase interaction was found. However, the recorded interactions indicated that the effects of phytase and Ca and dP levels were not consistent. Furthermore, the reduction of Ca and dP level lowered Clostridium perfringens and Enterobacteriaceae counts. The analysis of fermentation products showed that reducing the Ca and dP content in the diet reduced total SCFA, DL-lactate, and acetic acid in the ileum whereas phytase increased concentrations of these acids in the NC group. This suggests that P is a factor which limits fermentation in the ileum. It may be concluded that phytase plays a role in modulating the gut microbiota of chicken, however, this is clearly linked with the levels of P and Ca in a diet.

Phytase Modulates Ileal Microbiota and Enhances Growth Performance of the Broiler Chickens

PubMed Central

Ptak, Anna; Bedford, Michael R.; Świątkiewicz, Sylwester; Żyła, Krzysztof; Józefiak, Damian

2015-01-01

Phytase is well studied and explored, however, little is known about its effects on the microbial ecology of the gastrointestinal tract. In total, 400 one-day-old female Ross 308 chicks were randomly distributed to four experimental groups. The dietary treatments were arranged as a 2 × 2 complete factorial design, with the factors being adequate (PC) or insufficient calcium (Ca) and digestible phosphor (dP)(NC) and with or without 5000 phytase units (FTU)/kg of Escherichia coli 6-phytase. The gastrointestinal tract pH values, ileal microbial communities and short-chain fatty acid concentrations in the digesta were determined. The reduction in Ca and dP concentration significantly affected pH in the crop and caeca, and addition of phytase to the NC resulted in a pH increase in the ileum. The reduction in Ca and dP concentration significantly lowered, while phytase supplementation increased ileal total bacterial counts. Additionally, the deficient diet reduced butyrate- but increased lactate-producing bacteria. The addition of phytase increased Lactobacillus sp./Enterococcus sp. whereas in case of Clostridium leptum subgroup, Clostridium coccoides - Eubacterium rectale cluster, Bifidobacterium sp. and Streptococcus/Lactococcus counts, a significant Ca and dP level x phytase interaction was found. However, the recorded interactions indicated that the effects of phytase and Ca and dP levels were not consistent. Furthermore, the reduction of Ca and dP level lowered Clostridium perfringens and Enterobacteriaceae counts. The analysis of fermentation products showed that reducing the Ca and dP content in the diet reduced total SCFA, DL-lactate, and acetic acid in the ileum whereas phytase increased concentrations of these acids in the NC group. This suggests that P is a factor which limits fermentation in the ileum. It may be concluded that phytase plays a role in modulating the gut microbiota of chicken, however, this is clearly linked with the levels of P and Ca in a

Efficacy of PARP inhibitor rucaparib in orthotopic glioblastoma xenografts is limited by ineffective drug penetration into the central nervous system

PubMed Central

Parrish, Karen E.; Cen, Ling; Murray, James; Calligaris, David; Kizilbash, Sani; Mittapalli, Rajendar K.; Carlson, Brett L.; Schroeder, Mark A.; Sludden, Julieann; Boddy, Alan V.; Agar, Nathalie Y.R.; Curtin, Nicola J.; Elmquist, William F.; Sarkaria, Jann N.

2015-01-01

Poly (ADP-ribose) polymerase (PARP) inhibition can enhance the efficacy of temozolomide (TMZ) and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with TMZ and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient-derived GBM xenograft models. The combination of rucaparib with TMZ was highly effective in vitro in short-term explant cultures derived from GBM12, and similarly, the combination of rucaparib and TMZ (dosed for 5 days every 28 days × 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts. In contrast, the addition of rucaparib had no impact on the efficacy of TMZ in GBM12 or GBM39 orthotopic models. Using Madin-Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1, cell accumulation studies demonstrated that rucaparib is transported by both transporters. Consistent with the influence of these efflux pumps on central nervous system drug distribution, Mdr1a/b−/−Bcrp1−/− knockout mice had a significantly higher brain to plasma ratio for rucaparib (1.61 ± 0.25) than wild-type mice (0.11 ± 0.08). A pharmacokinetic and pharmacodynamic evaluation after a single dose confirmed limited accumulation of rucaparib in the brain associated with substantial residual PARP enzymatic activity. Similarly, matrix-assisted laser desorption/ionization mass spectrometric imaging demonstrated significantly enhanced accumulation of drug in flank tumor compared to normal brain or orthotopic tumors. Collectively, these results suggest that limited drug delivery into brain tumors may significantly limit the efficacy of rucaparib combined with TMZ in GBM. PMID:26438157

Efficacy of PARP Inhibitor Rucaparib in Orthotopic Glioblastoma Xenografts Is Limited by Ineffective Drug Penetration into the Central Nervous System.

PubMed

Parrish, Karen E; Cen, Ling; Murray, James; Calligaris, David; Kizilbash, Sani; Mittapalli, Rajendar K; Carlson, Brett L; Schroeder, Mark A; Sludden, Julieann; Boddy, Alan V; Agar, Nathalie Y R; Curtin, Nicola J; Elmquist, William F; Sarkaria, Jann N

2015-12-01

PARP inhibition can enhance the efficacy of temozolomide and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with temozolomide and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient-derived GBM xenograft models. The combination of rucaparib with temozolomide was highly effective in vitro in short-term explant cultures derived from GBM12, and, similarly, the combination of rucaparib and temozolomide (dosed for 5 days every 28 days for 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts. In contrast, the addition of rucaparib had no impact on the efficacy of temozolomide in GBM12 or GBM39 orthotopic models. Using Madin-Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1, cell accumulation studies demonstrated that rucaparib is transported by both transporters. Consistent with the influence of these efflux pumps on central nervous system drug distribution, Mdr1a/b(-/-)Bcrp1(-/-) knockout mice had a significantly higher brain to plasma ratio for rucaparib (1.61 ± 0.25) than wild-type mice (0.11 ± 0.08). A pharmacokinetic and pharmacodynamic evaluation after a single dose confirmed limited accumulation of rucaparib in the brain is associated with substantial residual PARP enzymatic activity. Similarly, matrix-assisted laser desorption/ionization mass spectrometric imaging demonstrated significantly enhanced accumulation of drug in flank tumor compared with normal brain or orthotopic tumors. Collectively, these results suggest that limited drug delivery into brain tumors may significantly limit the efficacy of rucaparib combined with temozolomide in GBM. ©2015 American Association for Cancer Research.

Noninvasive PET quantitative myocardial blood flow with regadenoson for assessing cardiac allograft vasculopathy in orthotopic heart transplantation patients

PubMed Central

Pampaloni, Miguel Hernandez; Shrestha, Uttam M.; Sciammarella, Maria; Seo, Youngho; Gullberg, Grant T.; Botvinick, Elias H.

2016-01-01

Background Risk stratification and early detection of cardiac allograft vasculopathy (CAV) is essential in orthotopic heart transplantation (OHT) patients. This study assesses the changes in myocardial blood flow (MBF) noninvasively in OHT patients using quantitative cardiac PET with regadenoson. Methods Twelve patients (Group 1) (8 males, 4 females, mean age 55 ± 7 y) with no history of post OHT myocardial ischemia were enrolled after 5.4± 2.0 y after OHT. Fifteen patients (Group 2) (9 males, 6 females, mean age 71 ± 9 y) with intermediate pretest probability but not documented evidence for coronary artery disease (CAD) were also included to serve as control. Global and regional MBFs were assessed using dynamic 13N-NH3 PET at rest and during regadenoson-induced hyperemia. The coronary flow reserve (CFR) was also calculated as the ratio of hyperemic to resting MBF. Results Mean regadenoson-induced rate-pressure products were similar in both groups, while there was an increase in resting rate-pressure product in Group 1 patients. Both mean and median values of resting MBF were higher in Group 1 than Group 2 patients (1.33±0.31 and 1.01±0.21 mL/min/g for Groups 1 and 2, respectively, P<.001), while mean hyperemic MBF values were similar in both Groups (2.68±0.84 and 2.64±0.94 mL/min/g, P=NS) but median hyperemic MBF values were lower in Group 1 than Group 2 patients (2.0 vs. 2.60 mL/min/g, P=.018). Both mean and median CFR values demonstrated a significant reduction toward the Group 1 compared to Group 2 patients (2.07±0.74 vs. 2.63±0.48, P = .025). Conclusions This study suggests that the MBF in OHT patients may be abnormal at resting state with diminished CFR. This hints that the epicardial and microvascular coronary subsystem may be exacerbated after OHT leading to the gradual progression of CAV. PMID:28138813

Quality of Life in Patients with Bladder Cancer Undergoing Ileal Conduit: A Comparison of Women Versus Men

PubMed Central

SIRACUSANO, SALVATORE; D’ELIA, CAROLINA; CERRUTO, MARIA ANGELA; SALEH, OMAR; SERNI, SERGIO; GACCI, MAURO; CICILIATO, STEFANO; SIMONATO, ALCHIEDE; PORCARO, ANTONIO; DE MARCO, VINCENZO; TALAMINI, RENATO; TOFFOLI, LAURA; VISALLI, FRANCESCO; NIERO, MAURO; LONARDI, CRISTINA; IMBIMBO, CIRO; VERZE, PAOLO; MIRONE, VINCENZO; RACIOPPI, MARCO; IAFRATE, MASSIMO; CACCIAMANI, GIOVANNI; DE MARCHI, DAVIDE; BASSI, PIERFRANCESCO; ARTIBANI, WALTER

2018-01-01

Background/Aim: Studies comparing health-related quality of life (HR-QoL) between patients who underwent radical cystectomy (RC) and those who underwent a different form of urinary diversion has not reached yet univocal and reliable conclusions. The aim of our study was to evaluate bladder-specific long-term HR-QoL after radical cystectomy and ileal conduit. Patients and Methods: A multicenter study was carried out on 145 consecutive patients (112 males and 33 females) undergoing RC and ileal conduit (IC). HR-QoL assessment was conducted using Italian versions of European Organisation for Research and Treatment of Cancer QLQ-C30 and EORTC BLM-30 questionnaires. Results: Our data showed that women who underwent IC presented greater problems than men in cognitive functioning (mean score±SD: 77.3±27.9 vs. 87.8±18.6) as well in future perspective (score: 42.4±34.4 vs. 21.9±24.6). Nevertheless, men undergoing IC had more problems in sexual functioning than women (score: 23.3±24.5 vs. 7.0±20.3) (all p<0.05). Conclusion: In our series, female patients presented a greater burden than male patients in cognitive functioning as well in future perspective, but lower concerns with regard to sexual function. PMID:29275311

Quality of Life in Patients with Bladder Cancer Undergoing Ileal Conduit: A Comparison of Women Versus Men.

PubMed

Siracusano, Salvatore; D'Elia, Carolina; Cerruto, Maria Angela; Saleh, Omar; Serni, Sergio; Gacci, Mauro; Ciciliato, Stefano; Simonato, Alchiede; Porcaro, Antonio; DE Marco, Vincenzo; Talamini, Renato; Toffoli, Laura; Visalli, Francesco; Niero, Mauro; Lonardi, Cristina; Imbimbo, Ciro; Verze, Paolo; Mirone, Vincenzo; Racioppi, Marco; Iafrate, Massimo; Cacciamani, Giovanni; DE Marchi, Davide; Bassi, Pierfrancesco; Artibani, Walter

2018-01-01

Studies comparing health-related quality of life (HR-QoL) between patients who underwent radical cystectomy (RC) and those who underwent a different form of urinary diversion has not reached yet univocal and reliable conclusions. The aim of our study was to evaluate bladder-specific long-term HR-QoL after radical cystectomy and ileal conduit. A multicenter study was carried out on 145 consecutive patients (112 males and 33 females) undergoing RC and ileal conduit (IC). HR-QoL assessment was conducted using Italian versions of European Organisation for Research and Treatment of Cancer QLQ-C30 and EORTC BLM-30 questionnaires. Our data showed that women who underwent IC presented greater problems than men in cognitive functioning (mean score±SD: 77.3±27.9 vs. 87.8±18.6) as well in future perspective (score: 42.4±34.4 vs. 21.9±24.6). Nevertheless, men undergoing IC had more problems in sexual functioning than women (score: 23.3±24.5 vs. 7.0±20.3) (all p<0.05). In our series, female patients presented a greater burden than male patients in cognitive functioning as well in future perspective, but lower concerns with regard to sexual function. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Preconditioning methods influence tumor property in an orthotopic bladder urothelial carcinoma rat model

PubMed Central

MIYAZAKI, KOZO; MORIMOTO, YUJI; NISHIYAMA, NOBUHIRO; SATOH, HIROYUKI; TANAKA, MASAMITSU; SHINOMIYA, NARIYOSHI; ITO, KEIICHI

2014-01-01

Urothelial carcinoma (UC) is an extremely common type of cancer that occurs in the bladder. It has a particularly high rate of recurrence. Therefore, preclinical studies using animal models are essential to determine effective forms of treatment. In the present study, in order to establish an orthotopic bladder UC animal model with clinical relevance, the effects of preconditioning methods on properties of the developed tumor were evaluated. The bladder cavity was pretreated with phosphate-buffered saline (PBS), acid-base, trypsin (TRY) or poly (L-lysine) (PLL) and then rat UC cells (AY-27) (4×106 cells) were inoculated. The results demonstrated that, two weeks later, the tumorigenic rate (88%) and tumor count (2.3 per rat) were not significantly different among the preconditioning methods, whereas tumor volume and invasion depth into bladder tissue were significantly different. Average tumor volumes were >50 mm3 in the PBS and acid-base-treated groups and <10 mm3 in the TRY- and PLL-treated groups. The percentage of invasive tumors (T2 or more advanced stage) was ∼75% of total tumors in the PBS- and acid-base-treated groups, whereas the percentages were reduced in the TRY- and PLL-treated groups (58 and 32%, respectively). Non-invasive tumors (Ta or T1) accounted for 54% of tumors in the PLL-treated group, which was 2-5-fold higher than the percentages in the remaining groups. Properties of the developed tumor in the rat orthotopic UC model were different depending on preconditioning methods. Therefore, different animal models suitable for a discrete preclinical examination may be established by using the appropriate preconditioning condition. PMID:24649309

Ischaemia-reperfusion injury in orthotopic mouse lung transplants - a scanning electron microscopy study.

PubMed

Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

2011-02-01

Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin-eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

NASA Astrophysics Data System (ADS)

Maawy, Ali A.; Hiroshima, Yukihiko; Kaushal, Sharmeela; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

2013-12-01

The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); 550-nm group (Alexa Fluor 555 or DyLight 550); 650-nm group (Alexa Fluor 660 or DyLight 650), or the 750-nm group (Alexa Fluor 750 or DyLight 755). After 24 h, the Olympus OV100 small-animal imaging system was used for noninvasive and intravital fluorescence imaging of mice. Dyes were compared with respect to depth of imaging, resolution, tumor-to-background ratio (TBR), photobleaching, and hemoglobin quenching. The longer wavelength dyes had increased depth of penetration and ability to detect the smallest tumor deposits and provided the highest TBRs, resistance to hemoglobin quenching, and specificity. The shorter wavelength dyes were more photostable. This study showed unique advantages of each dye for specific cancer imaging in a clinically relevant orthotopic model.

A liver-metastatic model of human primary gastric lymphoma in nude mice orthotopically constructed by using histologically intact patient specimens.

PubMed

Yang, Bo; Tuo, Shuai; Tuo, Chao-Wei; Zhang, Ning; Liu, Qiu-Zhen

2010-06-01

In recent years, incidence and mortality of lymphoma are markedly increasing worldwide. However, the pathogenesis and mechanism of invasion and metastasis for lymphoma are not yet fully clarified. It is mainly due to the lack of ideal animal models, which can precisely simulate the invasion and metastasis of lymphoma in the human body. So, it is very necessary to establish a highly metastatic nude mouse model of human lymphoma. This study developed a liver-metastatic model of primary gastric lymphoma in nude mice by using orthotopic surgical implantation of histologically intact patient specimens into the corresponding organs of the recipient small animals. A histologically intact fragment of liver metastasis derived from a surgical specimen of a patient with primary gastric lymphoma was implanted into the submucosa of the stomach in nude mice. Tumorigenicity, invasion, metastasis, morphologic characteristics (via light microscopy, electron microscopy, and immunohistochemistry), karyotype analysis, and DNA content of the orthotopically transplanted tumors were studied. An orthotopic liver metastatic model of human primary gastric lymphoma in nude mice (termed HGBL-0304) was successfully established. The histopathology of the transplanted tumors showed primary gastric diffuse large B-cell lymphoma. CD19, CD20, CD22, and CD79alpha were positive, but CD3 and CD7 were negative. The serum level of lactate dehydrogenase (LDH) was elevated [(1010.56+/-200.85) U/L]. The number of chromosomes ranged from 75 to 89. The DNA index (DI) was 1.45+/-0.25 (that is, heteroploid). So far, the HGBL-0304 model has been passed on for 45 generations of nude mice. A total of 263 nude mice were used for the transplantation. Both the growth and resuscitation rates of liquid nitrogen cryopreservation of the transplanted tumors were 100%. The transplanted tumors autonomically invasively grew and damaged a whole layer in the stomach of nude mice. The metastasis rates of liver, spleen, lymph

Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer.

PubMed

Yao, Jun; Zhang, Lu-Lin; Huang, Xu-Mei; Li, Wen-Yao; Gao, She-Gan

2017-06-07

To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. The expression rates of PTN and N-syndecan proteins were 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI ( P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites ( P = 0.009), liver metastasis ( P = 0.035), and decreased survival time ( P = 0.022). N-syndecan expression was significantly associated with tumor size ( P = 0.025), but not with survival time ( P = 0.539). High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer.

Biological characterization of preclinical Bioluminescent Osteosarcoma Orthotopic Mouse (BOOM) model: A multi-modality approach

PubMed Central

Garimella, Rama; Eskew, Jeff; Bhamidi, Priyanka; Vielhauer, George; Hong, Yan; Anderson, H. Clarke; Tawfik, Ossama; Rowe, Peter

2013-01-01

Osteosarcoma (OS) is a bone malignancy that affects children and adolescents. It is a highly aggressive tumor and typically metastasizes to lungs. Despite aggressive chemotherapy and surgical treatments, the current 5 year survival rate is 60–70%. Clinically relevant models are needed to understand OS pathobiology, metastatic progression from bones to lungs, and ultimately, to develop more efficacious treatment strategies and improve survival rates in OS patients with metastasis. The main goal of this study was to develop and characterize an in vivo OS model that will allow non-invasive tracking of tumor progression in real time, and aid in studying OS pathobiology, and screening of potential therapeutic agents against OS. In this study, we have used a multi-modality approach using bioluminescent imaging, electron microscopy, micro-computed tomography, and histopathology to develop and characterize a preclinical Bioluminescent Osteosarcoma Orthotopic Mouse (BOOM) model, using 143B human OS cell line. The results of this study clearly demonstrate that the BOOM model represents the clinical disease as evidenced by a spectrum of changes associated with tumor establishment, progression and metastasis, and detection of known OS biomarkers in the primary and metastatic tumor tissue. Key novel findings of this study include: (a) multimodality approach for extensive characterization of the BOOM model using 143B human OS cell line; (b) evidence of renal metastasis in OS orthotopic model using 143B cells; (c) evidence of Runx2 expression in the metastatic lung tissue; and (d) evidence of the presence of extracellular membrane vesicles and myofibroblasts in the BOOM model. PMID:25688332

Ischaemia-reperfusion injury in orthotopic mouse lung transplants – a scanning electron microscopy study

PubMed Central

Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

2011-01-01

Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin–eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. PMID:21272104

Comparison of amino acid digestibility of feedstuffs determined with the precision-fed cecectomized rooster assay and the standardized ileal amino acid digestibility assay

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate and compare amino acid digestibility of several feedstuffs using 2 commonly accepted methods: the precision-fed cecectomized rooster assay (PFR) and the standardized ileal amino acid assay (SIAAD). Six corn, 6 corn distillers dried grains with or without s...

Rod-shaped cavitation bubble structure in ultrasonic field.

PubMed

Bai, Lixin; Wu, Pengfei; Liu, Huiyu; Yan, Jiuchun; Su, Chang; Li, Chao

2018-06-01

Rod-shaped cavitation bubble structure in thin liquid layers in ultrasonic field is investigated experimentally. It is found that cavitation structure successively experiences several stages with the change of the thickness of the thin liquid layer. Rod-shaped structure is a stable structure of the boundary between the cavitation cloud region and the non-cavitation liquid region, which can be formed in two different ways. Cavitation bubbles in a thin liquid layer have a distribution in the thickness direction. The rod-shaped structures tend to crosslink with each other to form stable Y-branch structures. The angle of the Y-branch structure is Gauss distribution with mathematical expectation μ = 119.93. A special rod-shaped cavitation structure with source is also investigated in detail. Due to the pressure gradient in the normal direction, the primary Bjerknes force causes the bubbles in the rod-shaped structure on both sides to converge to the axis. The secondary Bjerknes forces between the bubbles also make the cluster converge, so the large bubbles which are attached to the radiating surface tend to align themselves along the central line. According to the formula deduced in this paper, the variation of curvature of curved rod-shaped structure is qualitatively analyzed. The Y-branch structure of cavitation cloud and Plateau boundary of soap bubbles are compared. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of calcium feeding strategy on true ileal phosphorus digestibility and true phosphorus retention determined with growing broilers.

PubMed

Perryman, K R; Masey O'Neill, H V; Bedford, M R; Dozier, W A

2016-05-01

An experiment utilizing 960 Ross × Ross 708 male broilers was conducted to determine the effects of Ca feeding strategy on true ileal (prececal) P digestibility (TIPD) and true P retention (TPR) of corn. Experimental diets were formulated with 1 of 3 dietary Ca feeding strategies (0.95%, 0.13%, or variable Ca concentrations to maintain a 2.1:1 Ca:P ratio) and contain 0, 25, 50, or 75% corn. A practical corn-soybean meal diet (1.4:1 Ca:P ratio) was fed as a control. After receiving a common starter diet, experimental diets were fed from 19 to 26 d of age. After a 48-h dietary adaptation period, a 48-h retention assay was conducted. At 25 and 26 d of age, ileal digesta were collected from 8 birds per cage. Broilers consuming the control diet had higher (P<0.001) BW gain, feed intake, digesta P, and excreta P than broilers consuming the corn titration diets. Digesta and excreta P increased (linear, P<0.05) with graded increases of corn. True ileal P digestibility and TPR were highest (P<0.05) for diets with 0.13% Ca (57.3 and 69.5%, respectively) compared with diets formulated with a 2.1:1 Ca:P ratio (41.2 and 37.8%, respectively) or 0.95% Ca (25.4 and 39.0%, respectively). Values for TPR were higher (P<0.05) than those for TIPD except when the dietary Ca:P ratio was fixed. Additionally, negative endogenous P losses were predicted by regression equations when TPR was estimated for birds fed titration diets with the fixed Ca:P ratio. Changing the Ca concentration of the diets to maintain a fixed Ca:P ratio influenced (P<0.001) apparent P retention, which affected the estimate for TPR due to the prediction of negative endogenous P losses. These data demonstrated that regression analysis may have limitations when estimating the TIPD or TPR of corn when formulating diets with different Ca feeding strategies. More research is necessary to elucidate the factors that contributed to regression equations predicting negative endogenous P losses. © 2016 Poultry Science

Acute surgical abdomen due to phytobezoar-induced ileal obstruction.

PubMed

Salemis, Nikolaos S; Panagiotopoulos, Nikolaos; Sdoukos, Nikolaos; Niakas, Evangelos

2013-01-01

Phytobezoar-induced small bowel obstruction is an uncommon clinical entity accounting for 2-4.8% of all mechanical intestinal obstructions. In addition, presentation with features of acute surgical abdomen is extremely rare, accounting for only 1% of the patients. The aim of this report is to present a very rare case of a phytobezoar-induced small bowel obstruction in a male patient who presented with acute surgical abdomen. A correct preoperative diagnosis was made based on the patient's history and characteristic imaging features on the emergency computed tomography (CT) scan. A 55-year-old man with previous gastrectomy presented with typical manifestations of acute abdomen. CT scan demonstrated dilatated small bowel loops and an intraluminal ileal mass with a mottled appearance. At exploratory laparotomy, a phytobezoar was found impacted in the terminal ileum and was removed through an enterotomy. Phytobezoar should be considered in patients with previous gastric outlet surgery who present with bowel obstruction and features of acute surgical abdomen. The presence of a well-defined intraluminal mass with a mottled gas pattern on emergency CT scan is suggestive of an intestinal phytobezoar. Copyright © 2013 Elsevier Inc. All rights reserved.

Intravital imaging of a spheroid-based orthotopic model of melanoma in the mouse ear skin

PubMed Central

Chan, Keefe T.; Jones, Stephen W.; Brighton, Hailey E.; Bo, Tao; Cochran, Shelly D.; Sharpless, Norman E.; Bear, James E.

2017-01-01

Multiphoton microscopy is a powerful tool that enables the visualization of fluorescently tagged tumor cells and their stromal interactions within tissues in vivo. We have developed an orthotopic model of implanting multicellular melanoma tumor spheroids into the dermis of the mouse ear skin without the requirement for invasive surgery. Here, we demonstrate the utility of this approach to observe the primary tumor, single cell actin dynamics, and tumor-associated vasculature. These methods can be broadly applied to investigate an array of biological questions regarding tumor cell behavior in vivo. PMID:28748125

Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts1

PubMed Central

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; DeWeese, Theodore L; Herman, Joseph M

2012-01-01

PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. RESULTS: Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. CONCLUSIONS: We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response. PMID:22496923

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity

PubMed Central

Garcia, Emmanuel; Becker, Veronika G. C.; McCullough, Danielle J.; Stabley, John N.; Gittemeier, Elizabeth M.; Opoku-Acheampong, Alexander B.; Sieman, Dietmar W.

2016-01-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10−9 to 10−4 M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. PMID:27125846

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

PubMed

Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

2016-07-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. Copyright © 2016 the American Physiological Society.

Orthotopic heart transplantation in the prince sultan cardiac center.

PubMed

Al Fagih, M R

1996-01-01

In this report we attempt to demonstrate the efforts involved in establishing and organizing the heart transplant program at the Armed Forces Hospital in Riyadh, Saudi Arabia. From 1986 to date, 25 orthotopic heart transplants were performed at this center. Patient age ranged from 22 months to 57 years; 4 patients were below 12 years of age and 4 aged 50 years and above. The incidations for transplantation were cardiomyopathy in 15 patients, ischemic heart disease in 6 patients, and valvular heart disease in 4 patients. Fourteen recipients have died. Three of them were classified as hospital deaths, occuring before the patient could be discharged after the procedure; the reminder died from rejection and associated problems. Eight patients of them died within the first year. The longest survival period was almost 8 years. The overall 8 years survival rate was 45%, which is comparable to the international figures. Shortage of donors may affect the future of the transplant programs. Increasing the awareness of the public about the importance of organ donation and transplantation is crucial in this regard.

Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

PubMed

Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

2012-10-01

It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

Immunome differences between porcine ileal and jejunal Peyer's patches revealed by global transcriptome sequencing of gut-associated lymphoid tissues.

PubMed

Maroilley, T; Berri, M; Lemonnier, G; Esquerré, D; Chevaleyre, C; Mélo, S; Meurens, F; Coville, J L; Leplat, J J; Rau, A; Bed'hom, B; Vincent-Naulleau, S; Mercat, M J; Billon, Y; Lepage, P; Rogel-Gaillard, C; Estellé, J

2018-06-13

The epithelium of the intestinal mucosa and the gut-associated lymphoid tissues (GALT) constitute an essential physical and immunological barrier against pathogens. In order to study the specificities of the GALT transcriptome in pigs, we compared the transcriptome profiles of jejunal and ileal Peyer's patches (PPs), mesenteric lymph nodes (MLNs) and peripheral blood (PB) of four male piglets by RNA-Seq. We identified 1,103 differentially expressed (DE) genes between ileal PPs (IPPs) and jejunal PPs (JPPs), and six times more DE genes between PPs and MLNs. The master regulator genes FOXP3, GATA3, STAT4, TBX21 and RORC were less expressed in IPPs compared to JPPs, whereas the transcription factor BCL6 was found more expressed in IPPs. In comparison between IPPs and JPPs, our analyses revealed predominant differential expression related to the differentiation of T cells into Th1, Th2, Th17 and iTreg in JPPs. Our results were consistent with previous reports regarding a higher T/B cells ratio in JPPs compared to IPPs. We found antisense transcription for respectively 24%, 22% and 14% of the transcripts detected in MLNs, PPs and PB, and significant positive correlations between PB and GALT transcriptomes. Allele-specific expression analyses revealed both shared and tissue-specific cis-genetic control of gene expression.

Ileal Digesta Nondietary Substrates from Cannulated Pigs Are Major Contributors to In Vitro Human Hindgut Short-Chain Fatty Acid Production.

PubMed

Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

2017-02-01

It has been assumed that short-chain fatty acids (SCFAs) in the colon originate mainly from dietary fiber fermentation. However, SCFAs in the colon are also produced from the fermentation of nondietary material. We aimed to predict the relative contributions of dietary and nondietary substrates in the production of SCFAs with the use of a human fecal inoculum for diets containing kiwifruit as a model fiber. Terminal ileal digesta were collected from ileal-cannulated male pigs [n = 7; mean ± SD: 41.4 ± 2.98 kg body weight] adapted (44-d feeding) to diets containing either 25 g/kg dry matter (DM) of kiwifruit fiber (KFf) (25 KFf) or 50 g/kg DM of KFf (50 KFf) and then again after receiving a fiber-free diet (n = 14) for a further 7 d. Pigs were used as a model for adult humans for digestion in the upper digestive tract (mouth to the terminal ileum). The ileal digesta (either unfractionated or fractionated into crude mucin and microbial fractions) were fermented in vitro for 24 h with the use of a fresh human fecal inoculum to predict SCFA production in the human hindgut. SCFAs of nondietary origin were the main source (65%) of total SCFAs predicted to be produced in the human hindgut. The contribution of SCFAs from KFf was only 26% of the total SCFAs, and that from total dietary material was 35%. The higher contribution of nondietary material to total predicted SCFA production was observed at both dietary fiber concentrations. Predicted SCFA intake from dietary fiber was 76 and 105 mmol/kg diet DM intake for the diets containing 25 KFf and 50 KFf, respectively, and from the nondietary substrates it was 178 and 280 mmol/kg diet DM intake, respectively. A considerable proportion of the SCFAs produced in the human hindgut seems to be derived from the fermentation of nondietary substrates. © 2017 American Society for Nutrition.

Societal reintegration following cadaveric orthotopic liver transplantation.

PubMed

Kelly, Ryan; Hurton, Scott; Ayloo, Subhashini; Cwinn, Mathew; De Coutere-Bosse, Sarah; Molinari, Michele

2016-06-01

Studies on patients' societal reintegration following orthotopic liver transplantation (OLT) are scarce. Between September 2006 and January 2008, all adults who were alive after 3 years post OLT were included in this prospective cohort study. Validated questionnaires were administered to all candidates with the primary aim of investigating the rate of their social re-integration following OLT and potential barriers they might have encountered. Among 157 eligible patients 110 (70%) participated. Mean participants' age was 57 years (SD 11.4) and 43% were females. Prior to OLT, 75% of patients were married and 6% were divorced. Following OLT there was no significant difference in marital status. Employment rate fell from 72% to 30% post-OLT. Patients who had been employed in either low-skill or advanced-skill jobs were less likely to return to work. After OLT, personal income fell an average of 4,363 Canadian dollars (CAN$) (SD 20,733) (P=0.03) but the majority of recipients (80%) reported high levels of satisfaction for their role in society. Although patients' satisfaction post-OLT is high, employment status is likely to be negatively affected for individuals who are not self-employed. Strategies to assist recipients in returning to their pre-OLT jobs should be developed to improve patients' economical status and societal ability to recoup resources committed for OLT.

ILEAL HERNIATION THROUGH THE FORAMEN OF WINSLOW: OVEREATING AS A RISK FACTOR FOR INTERNAL HERNIATION.

PubMed

Kirigin, Lora Stanka; Nikolić, Marko; Kruljac, Ivan; Marjan, Domagoj; Penavić, Ivan; Ljubicić, Neven; Budimir, Ivan; Vrkljan, Milan

2016-03-01

Internal hernias have an overall incidence of less than 1% and are difficult to diagnose clinically due to their nonspecific presentation. Most internal hernias present as strangulating closed-loop obstruction and delay in surgical intervention is responsible for a high mortality rate (49%). We present a case of ileal herniation through the foramen of Winslow. A 29-year-old previously healthy female presented with acute onset right upper quadrant pain, abdominal fullness, and nausea. The pain was sudden in onset and began shortly after a dinner party where she consumed larger portions of food. Laboratory investigations revealed mild leukocytosis with left shift. Dual-phase multi-detector computed tomography disclosed herniation of the small bowel into the lesser sac. The patient underwent an emergency median laparotomy that revealed ileal herniation through the foramen of Winslow. Adhesiolysis and manual reduction of the bowel was performed, and the reduced bowel showed only congestive changes. The postoperative recovery was uneventful and the patient was discharged on the third postoperative day. Risk factors for internal herniation still remain unclear, although excessively mobile bowel loops and an enlarged foramen of Winslow have been described. Our case demonstrated that overeating could be an additional risk factor for internal herniation. We describe our clinical and radiology findings, as well as surgical management. Due to the high rates of morbidity and mortality, it is imperative that clinicians be aware of the possible risks factors for internal herniation. Internal hernias should be included in the differential diagnosis of small bowel obstruction so that appropriate steps can be made in the work-up of these patients, followed by timely surgical intervention.

AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models

PubMed Central

Pohling, Christoph; Natarajan, Arutselvan; Witney, Timothy H.; Kaur, Jasdeep; Xu, Lingyun; Gowrishankar, Gayatri; D’Souza, Aloma L; Murty, Surya; Schick, Sophie; Chen, Liyin; Wu, Nicholas; Khaw, Phoo; Mischel, Paul; Abbasi, Taher; Usmani, Shahabuddin; Mallick, Parag

2017-01-01

Glioblastoma multiforme (GBM) is an aggressive, malignant cancer Johnson and O’Neill (J Neurooncol 107: 359–364, 2012). An extract from the winter cherry plant (Withania somnifera), AshwaMAX, is concentrated (4.3 %) for Withaferin A; a steroidal lactone that inhibits cancer cells Vanden Berghe et al. (Cancer Epidemiol Biomark Prev 23: 1985–1996, 2014). We hypothesized that AshwaMAX could treat GBM and that bioluminescence imaging (BLI) could track oral therapy in orthotopic murine models of glioblastoma. Human parietal-cortical glioblastoma cells (GBM2, GBM39) were isolated from primary tumors while U87-MG was obtained commercially. GBM2 was transduced with lentiviral vectors that express Green Fluorescent Protein (GFP)/firefly luciferase fusion proteins. Mutational, expression and proliferative status of GBMs were studied. Intracranial xenografts of glioblastomas were grown in the right frontal regions of female, nude mice (n = 3–5 per experiment). Tumor growth was followed through BLI. Neurosphere cultures (U87-MG, GBM2 and GBM39) were inhibited by AshwaMAX at IC50 of 1.4, 0.19 and 0.22 μM equivalent respectively and by Withaferin A with IC50 of 0.31, 0.28 and 0.25 μM respectively. Oral gavage, every other day, of AshwaMAX (40 mg/kg per day) significantly reduced bioluminescence signal (n = 3 mice, p < 0.02, four parameter non-linear regression analysis) in preclinical models. After 30 days of treatment, bioluminescent signal increased suggesting onset of resistance. BLI signal for control, vehicle-treated mice increased and then plateaued. Bioluminescent imaging revealed diffuse growth of GBM2 xenografts. With AshwaMAX, GBM neurospheres collapsed at nanomolar concentrations. Oral treatment studies on murine models confirmed that AshwaMAX is effective against orthotopic GBM. AshwaMAX is thus a promising candidate for future clinical translation in patients with GBM. PMID:26650066

AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models.

PubMed

Chang, Edwin; Pohling, Christoph; Natarajan, Arutselvan; Witney, Timothy H; Kaur, Jasdeep; Xu, Lingyun; Gowrishankar, Gayatri; D'Souza, Aloma L; Murty, Surya; Schick, Sophie; Chen, Liyin; Wu, Nicholas; Khaw, Phoo; Mischel, Paul; Abbasi, Taher; Usmani, Shahabuddin; Mallick, Parag; Gambhir, Sanjiv S

2016-01-01

Glioblastoma multiforme (GBM) is an aggressive, malignant cancer Johnson and O'Neill (J Neurooncol 107: 359-364, 2012). An extract from the winter cherry plant (Withania somnifera ), AshwaMAX, is concentrated (4.3 %) for Withaferin A; a steroidal lactone that inhibits cancer cells Vanden Berghe et al. (Cancer Epidemiol Biomark Prev 23: 1985-1996, 2014). We hypothesized that AshwaMAX could treat GBM and that bioluminescence imaging (BLI) could track oral therapy in orthotopic murine models of glioblastoma. Human parietal-cortical glioblastoma cells (GBM2, GBM39) were isolated from primary tumors while U87-MG was obtained commercially. GBM2 was transduced with lentiviral vectors that express Green Fluorescent Protein (GFP)/firefly luciferase fusion proteins. Mutational, expression and proliferative status of GBMs were studied. Intracranial xenografts of glioblastomas were grown in the right frontal regions of female, nude mice (n = 3-5 per experiment). Tumor growth was followed through BLI. Neurosphere cultures (U87-MG, GBM2 and GBM39) were inhibited by AshwaMAX at IC50 of 1.4, 0.19 and 0.22 µM equivalent respectively and by Withaferin A with IC50 of 0.31, 0.28 and 0.25 µM respectively. Oral gavage, every other day, of AshwaMAX (40 mg/kg per day) significantly reduced bioluminescence signal (n = 3 mice, p < 0.02, four parameter non-linear regression analysis) in preclinical models. After 30 days of treatment, bioluminescent signal increased suggesting onset of resistance. BLI signal for control, vehicle-treated mice increased and then plateaued. Bioluminescent imaging revealed diffuse growth of GBM2 xenografts. With AshwaMAX, GBM neurospheres collapsed at nanomolar concentrations. Oral treatment studies on murine models confirmed that AshwaMAX is effective against orthotopic GBM. AshwaMAX is thus a promising candidate for future clinical translation in patients with GBM.

Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

PubMed Central

Sjöqvist, Sebastian; Jungebluth, Philipp; Ling Lim, Mei; Haag, Johannes C.; Gustafsson, Ylva; Lemon, Greg; Baiguera, Silvia; Angel Burguillos, Miguel; Del Gaudio, Costantino; Rodríguez, Antonio Beltrán; Sotnichenko, Alexander; Kublickiene, Karolina; Ullman, Henrik; Kielstein, Heike; Damberg, Peter; Bianco, Alessandra; Heuchel, Rainer; Zhao, Ying; Ribatti, Domenico; Ibarra, Cristián; Joseph, Bertrand; Taylor, Doris A.; Macchiarini, Paolo

2014-01-01

A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi. PMID:24736316

Standardized ileal digestibility of proteins and amino acids in sesame expeller and soya bean meal in weaning piglets.

PubMed

Aguilera, A; Reis de Souza, T C; Mariscal-Landín, G; Escobar, K; Montaño, S; Bernal, M G

2015-08-01

Apparent ileal digestibility (AID) of diets containing sesame expeller (SE) and soya bean meal (SBM) was determined using 15 piglets (Genetiporc(®)), weaned at 17 ± 0.4 days with average body weight of 6.4 ± 0.7 kg (Fertilis 20 × G Performance, Genetiporc(®), PIC México, Querétaro, México). Piglets were randomly assigned to three treatments: (i) a reference diet with casein as the sole protein source; (ii) a mixed diet of casein-SE; and (iii) a mixed diet of casein-SBM. The chemical composition of SE and SBM was determined, and AID and standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AAs) were determined for each protein source. SE contained greater quantities of ether extract, neutral detergent fibre, phytic acid, methionine and arginine than SBM. Lysine and proline contents and trypsin inhibitor activity were higher in SBM than in SE. The AID and SID of CP and AA (except for lysine and proline) were similar in SE and SBM. The AID of lysine and proline was higher in SBM than in SE (p < 0.05), and the SID of proline was higher in SE than in SBM (p < 0.05). These findings indicate that SE is an appropriate alternative protein source for early weaned pigs. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Molecularly Targeted Dose-Enhancement Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model

DTIC Science & Technology

2013-10-01

cell lines, such as cervix cancer cell line (HeLa) and breast cancer cell line (MDA-MB-231), were also employed. The experiments with other cell lines...breast cancer cell line (MDA-MB- 231), and cervix cancer cell line (HeLa). Different from our hypothesis, prostate cancer cell lines did not present...Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model PRINCIPAL INVESTIGATOR: Kwang Song

Assessment of ileal function by abdominal counting of the retention of a gamma emitting bile acid analogue.

PubMed Central

Thaysen, E H; Orholm, M; Arnfred, T; Carl, J; Rødbro, P

1982-01-01

In eight patients without gastrointestinal complaints and 30 patients with various gastrointestinal disorders ileal bile acid conservation was assessed by oral administration of 75Se 23-selena-25-homocholic acid (SeHCAT) followed by abdominal gamma counting (SeHCAT-test). The results of the test correlated fairly well with the clinical features and with the [1-14C]-cholylglycine breath test including faecal 14C measurements (breath test). Of the two bile acid absorption tests the new is perhaps the more sensitive and is the one most easily performed. PMID:7117906

MR-CBCT image-guided system for radiotherapy of orthotopic rat prostate tumors.

PubMed

Chiu, Tsuicheng D; Arai, Tatsuya J; Campbell Iii, James; Jiang, Steve B; Mason, Ralph P; Stojadinovic, Strahinja

2018-01-01

Multi-modality image-guided radiotherapy is the standard of care in contemporary cancer management; however, it is not common in preclinical settings due to both hardware and software limitations. Soft tissue lesions, such as orthotopic prostate tumors, are difficult to identify using cone beam computed tomography (CBCT) imaging alone. In this study, we characterized a research magnetic resonance (MR) scanner for preclinical studies and created a protocol for combined MR-CBCT image-guided small animal radiotherapy. Two in-house dual-modality, MR and CBCT compatible, phantoms were designed and manufactured using 3D printing technology. The phantoms were used for quality assurance tests and to facilitate end-to-end testing for combined preclinical MR and CBCT based treatment planning. MR and CBCT images of the phantoms were acquired utilizing a Varian 4.7 T scanner and XRad-225Cx irradiator, respectively. The geometry distortion was assessed by comparing MR images to phantom blueprints and CBCT. The corrected MR scans were co-registered with CBCT and subsequently used for treatment planning. The fidelity of 3D printed phantoms compared to the blueprint design yielded favorable agreement as verified with the CBCT measurements. The geometric distortion, which varied between -5% and 11% throughout the scanning volume, was substantially reduced to within 0.4% after correction. The distortion free MR images were co-registered with the corresponding CBCT images and imported into a commercial treatment planning software SmART Plan. The planning target volume (PTV) was on average 19% smaller when contoured on the corrected MR-CBCT images relative to raw images without distortion correction. An MR-CBCT based preclinical workflow was successfully designed and implemented for small animal radiotherapy. Combined MR-CBCT image-guided radiotherapy for preclinical research potentially delivers enhanced relevance to human radiotherapy for various disease sites. This novel protocol

Isolation and (111)In-Oxine Labeling of Murine NK Cells for Assessment of Cell Trafficking in Orthotopic Lung Tumor Model.

PubMed

Malviya, Gaurav; Nayak, Tapan; Gerdes, Christian; Dierckx, Rudi A J O; Signore, Alberto; de Vries, Erik F J

2016-04-04

A noninvasive in vivo imaging method for NK cell trafficking is essential to gain further understanding of the pathogenesis of NK cell mediated immune response to the novel cancer treatment strategies, and to discover the homing sites and physiological distribution of NK cells. Although human NK cells can be labeled for in vivo imaging, little is known about the murine NK cell labeling and its application in animal models. This study describes the isolation and ex vivo radiolabeling of murine NK cells for the evaluation of cell trafficking in an orthotopic model of human lung cancer in mice. Scid-Tg(FCGR3A)Blt transgenic SCID mice were used to isolate NK cells from mouse splenocytes using the CD49b (DX5) MicroBeads positive selection method. The purity and viability of the isolated NK cells were confirmed by FACS analysis. Different labeling buffers and incubation times were evaluated to optimize (111)In-oxine labeling conditions. Functionality of the radiolabeled NK cell was assessed by (51)Cr-release assay. We evaluated physiological distribution of (111)In-oxine labeled murine NK cells in normal SCID mice and biodistribution in irradiated and nonirradiated SCID mice with orthotopic A549 human lung tumor lesions. Imaging findings were confirmed by histology. Results showed that incubation with 0.011 MBq of (111)In-oxine per million murine NK cells in PBS (pH 7.4) for 20 min is the best condition that provides optimum labeling efficiency without affecting cell viability and functionality. Physiological distribution in normal SCID mice demonstrated NK cells homing mainly in the spleen, while (111)In released from NK cells was excreted via kidneys into urine. Biodistribution studies demonstrated a higher lung uptake in orthotopic lung tumor-bearing mice than control mice. In irradiated mice, lung tumor uptake of radiolabeled murine NK cells decreased between 24 h and 72 h postinjection (p.i.), which was accompanied by tumor regression, while in nonirradiated mice

Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer

PubMed Central

Yao, Jun; Zhang, Lu-Lin; Huang, Xu-Mei; Li, Wen-Yao; Gao, She-Gan

2017-01-01

AIM To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). METHODS An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. RESULTS The expression rates of PTN and N-syndecan proteins were 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI (P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites (P = 0.009), liver metastasis (P = 0.035), and decreased survival time (P = 0.022). N-syndecan expression was significantly associated with tumor size (P = 0.025), but not with survival time (P = 0.539). CONCLUSION High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer. PMID:28638231

Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

PubMed Central

Bermueller, Christian; Elsaesser, Alexander F.; Sewing, Judith; Baur, Nina; von Bomhard, Achim; Scheithauer, Marc; Notbohm, Holger; Rotter, Nicole

2013-01-01

Autologous grafts are frequently needed for nasal septum reconstruction. Because they are only available in limited amounts, there is a need for new cartilage replacement strategies. Tissue engineering based on the use of autologous chondrocytes and resorbable matrices might be a suitable option. So far, an optimal material for nasal septum reconstruction has not been identified. The aim of our study was to provide the first evaluation of marine collagen for use in nasal cartilage repair. First, we studied the suitability of marine collagen as a cartilage replacement matrix in the context of in vitro three dimensional cultures by analyzing cell migration, cytotoxicity, and extracellular matrix formation using human and rat nasal septal chondrocytes. Second, we worked toward developing a suitable orthotopic animal model for nasal septum repair, while simultaneously evaluating the biocompatibility of marine collagen. Seeded and unseeded scaffolds were transplanted into nasal septum defects in an orthotopic rat model for 1, 4, and 12 weeks. Explanted scaffolds were histologically and immunohistochemically evaluated. Scaffolds did not induce any cytotoxic reactions in vitro. Chondrocytes were able to adhere to marine collagen and produce cartilaginous matrix proteins, such as collagen type II. Treating septal cartilage defects in vivo with seeded and unseeded scaffolds led to a significant reduction in the number of nasal septum perforations compared to no replacement. In summary, we demonstrated that marine collagen matrices provide excellent properties for cartilage tissue engineering. Marine collagen scaffolds are able to prevent septal perforations in an autologous, orthotopic rat model. This newly described experimental surgical procedure is a suitable way to evaluate new scaffold materials for their applicability in the context of nasal cartilage repair. PMID:23621795

The Effect of Rod-Shaped Long-Period Stacking Ordered Phases Evolution on Corrosion Behavior of Mg95.33Zn2Y2.67 Alloy

PubMed Central

Wang, Jingfeng; Jiang, Weiyan; Li, Yang; Ma, Yao

2018-01-01

The morphology evolution of long-period stacking ordered (LPSO) phases on corrosion behavior of Mg95.33Zn2Y2.67 alloy is investigated systematically during as-cast, pre-extrusion heat-treated, as-extruded and post-extrusion heat-treated conditions. The second phases in the as-cast alloy are only LPSO phases with a few Y particles. The pre-extrusion heat treatment changed LPSO phases from blocks into a rudimentary rod shape with lamellar structure, subsequently into fine fragments by extrusion, and then into a regular rod shape with lamellar structure followed by post-extrusion heat treatment. Immersion tests and electrochemical measurements in 3.5 wt % NaCl solution reveal that the post-extrusion heat-treated alloy has the best corrosion resistance with the lowest corrosion rate. This is attributed to the rod-shaped LPSO phases, which could hinder corrosion proceeding, and result in corrosion orientated along the direction of rods and forming relatively dense long-strip corrosion products. Our findings demonstrate that the improved corrosion resistance of magnesium alloys with LPSO phases can be tailored effectively by the proceeding technology and post-heat treatment. PMID:29772721

Introduction of a Simple Experiment for the Undergraduate Organic Chemistry Laboratory Demonstrating the Lewis Acid and Shape-Selective Properties of Zeolite Na-Y

ERIC Educational Resources Information Center

Maloney, Vincent; Szczepanski, Zach

2017-01-01

A simple, inexpensive, discovery-based experiment for undergraduate organic laboratories has been developed that demonstrates the Lewis acid and shape-selective properties of zeolites. Calcined zeolite Na-Y promotes the electrophilic aromatic bromination of toluene with a significantly higher para/ortho ratio than observed under conventional…

Retrograde exchange of heavily encrusted ureteric stents via the ileal conduit: a technical report.

PubMed

Tapping, Charles Ross; Boardman, Phil

2014-02-01

We describe two cases of retrograde ureteric stent exchange of heavily encrusted ureteric stents (JJ) via tortuous ileal conduits. The blocked ureteric stents were snared from inside the conduit so they could be accessed and a wire inserted. The lumens of the stents were unblocked with a wire but the stents could not be withdrawn due to heavy encrustation of the ureteric stent in the renal pelvis. A stiff wire was inserted to provide support and a 9 French peel away sheath was used to remove the encrustations allowing the stents to be withdrawn and exchanged. This is a safe and successful technique allowing ureteric stents to be removed when heavily encrusted. © 2013 The Royal Australian and New Zealand College of Radiologists.

Fecal Calprotectin in Ileal Crohn's Disease: Relationship with Magnetic Resonance Enterography and a Pathology Score.

PubMed

Cerrillo, Elena; Beltrán, Belén; Pous, Salvador; Echarri, Ana; Gallego, Jose Carlos; Iborra, Marisa; Pamies, Jose; Nos, Pilar

2015-07-01

Magnetic resonance enterography (MRE) is an effective method of assessing small bowel Crohn's disease (CD). Fecal calprotectin (FC) correlates well with endoscopic disease activity. We aimed to evaluate the correlation between FC and disease activity according to MRE and surgical pathology in small bowel CD. One hundred twenty consecutive patients with ileal CD who underwent MRE assessment were included. Clinical data, C-reactive protein and FC, radiological and histological variables were obtained. Clinical activity was evaluated by the Harvey-Bradshaw Index and FC by enzyme-linked immunosorbent assay. MRE activity was assessed by means of the Magnetic Resonance Index of Activity score. Chiorean's score was used to grade pathological inflammation in surgical specimens. Seventy-five patients (62.5%) were in clinical remission (Harvey-Bradshaw Index < 5) and 45 (37.5%) had active disease (Harvey-Bradshaw Index ≥ 5). The Magnetic Resonance Index of Activity score was significantly associated with FC levels (P < 0.01), with a moderate overall correlation (Spearman's r = 0.56, P < 0.001). FC reflected MRE inflammatory activity with an area under the receiver operating characteristic curve of 0.914 (confidence interval, 0.849-0.958; P < 0.001). A cutoff value of 166.50 μg/g had 90% sensitivity, 74% specificity, 89% positive predictive value, and 76% negative predictive value for diagnosis of inflammation. Twenty-eight of 120 patients were operated. Surgical pathology showed a good agreement with FC for moderate (P = 0.03) and severe (P = 0.01) Chiorean's index. No relationship was detected for C-reactive protein. FC correlates with the degree of MRE inflammatory activity and with surgical pathology damage in ileal CD. Thus, FC could be a surrogate marker of disease control used to select patients for MRE assessment and therapeutic adjustment.

Therapeutic Cell-Cycle-Decoy Efficacy of a Telomerase-Dependent Adenovirus in an Orthotopic Model of Chemotherapy-Resistant Human Stomach Carcinomatosis Peritonitis Visualized With FUCCI Imaging.

PubMed

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-11-01

We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. Human MKN45 poorly-differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination-based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra-peritoneal tumors and ascites contained mostly quiescent G 1 /G o cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G 0 /G 1 , visualized by FUCCI red. In contrast, OBP-301 telomerase-dependent adenovirus-treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G 2 phases in the early-stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP-301 significantly reduced the size of tumors (P < 0.01) and ascites even in a late-stage carcinomatosis peritonitis model. These results suggest that quiescent peritoneally-disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP-301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. J. Cell. Biochem. 118: 3635-3642, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Distribution of mucosal pathology and an assessment of colonic phenotypic change in the pelvic ileal reservoir.

PubMed Central

Shepherd, N A; Healey, C J; Warren, B F; Richman, P I; Thomson, W H; Wilkinson, S P

1993-01-01

The mucosa of the pelvic ileal reservoir undergoes adaptive changes--inflammatory, architectural, and metaplastic--on exposure to the faecal stream. Twenty three quadruple loop ileal pouches constructed for ulcerative colitis (20 patients) and familial adenomatous polyposis (FAP) (three patients) were studied. No patient fulfilled clinical, endoscopic, or histopathological criteria for pouchitis. Standard duplicate biopsy specimens were taken from the proximal limb, the anterior wall, the posterior wall, and the body of the reservoir. An established scoring system was used and showed a highly significant increase in inflammatory scores in posterior wall biopsy specimens compared with those from the anterior wall. These results suggest that the adaptive changes are the direct result of contact with static faecal contents. One patient only showed significant inflammation in the proximal limb. There was no evidence of mucosal prolapse in any anterior wall biopsy specimen. Patients with colitis showed substantially more inflammatory and architectural changes than those with FAP. Ninety six per cent of pouches showed some colonic phenotypic expression as defined by mucin histochemical and PR 3A5 immunohistochemical studies. Our results suggest, however, that there may not be complete colonic metaplasia and that the mucin changes and other phenotypic alterations may represent a non-specific response to pouch inflammation and not a prerequisite for the development of pouchitis. The focal nature of the inflammatory and architectural changes, which may be the result of direct contact with static faecal residue, are clearly shown. A single random biopsy specimen of pouch mucosa is of limited value in assessing pathological changes and screening for potential neoplastic change within the reservoir. Images Figure 2 Figure 4 PMID:8381756

Apparent and true ileal and total tract digestibility of fat in canola press-cake or canola oil and effects of increasing dietary fat on amino acid and energy digestibility in growing pigs.

PubMed

Zhou, X; Beltranena, E; Zijlstra, R T

2017-06-01

Digestibility of remaining oil in canola press-cake (CPC) may be lower than that of extracted, liquid canola oil (CO) because oil may be partly entrapped in the CPC matrix. To determine true digestibility of fat in ingredients, endogenous fat losses should be estimated. Dietary fat may interact with digestion of other dietary components. To test these hypotheses, 10 ileal-cannulated pigs (initial BW, 25.4 kg) were fed 10 diets for 8 periods in a 10 × 8 Youden square. A basal diet was formulated based on wheat, barley, and canola meal. The 4 CPC and 4 CO test diets were prepared by replacing identical portion of basal diet with 10%, 20%, 30%, or 40% CPC, or 1.5%, 3.0%, 4.5%, or 6.0% CO, respectively, to match the fat content of CPC diet with CO diet at each fat level. An N-free diet based on corn starch was prepared to measure basal endogenous losses of AA. Apparent total tract digestibility (ATTD) and apparent ileal digestibility (AID) of acid-hydrolyzed ether extract (AEE) were calculated for each diet. True ileal digestibility (TID) and true total tract (TTTD) digestibility of AEE in CPC and CO, and total endogenous losses of AEE were estimated by regressing apparent digestible AEE (g/kg of DMI) against dietary AEE intake (g/kg of DM) at the total tract and distal ileum, respectively. The mean AID and ATTD of AEE in CPC diets were 78.9% and 61.5%, which were lower ( < 0.01) than 81.9% and 63.4% in CO diets. Apparent ileal and total tract digestible AEE content in CPC and CO diets increased linearly ( < 0.01) with increasing AEE intake. Endogenous losses of AEE were greater ( < 0.05) for the total tract than for the ileum (23.4 vs. 9.4 g/kg of DMI). Dietary fat source did not affect ( > 0.05) total tract or ileal endogenous losses of AEE. The TID and TTTD of AEE in CPC were 92.3% and 94.5%, respectively, lower ( < 0.01) than 96.5% and 100% in CO. Increasing dietary inclusion of CO linearly increased ( < 0.001) standardized ileal digestibility (SID) of CP, Lys

Shape Distribution of Fragments from Microsatellite Impact Tests

NASA Technical Reports Server (NTRS)

Liou, J.C.; Hanada, T.

2009-01-01

Fragment shape is an important factor for conducting reliable orbital debris damage assessments for critical space assets, such as the International Space Station. To date, seven microsatellite impact tests have been completed as part of an ongoing collaboration between Kyushu University and the NASA Orbital Debris Program Office. The target satellites ranged in size from 15 cm 15 cm 15 cm to 20 cm 20 cm 20 cm. Each target satellite was equipped with fully functional electronics, including circuits, battery, and transmitter. Solar panels and multi-layer insulation (MLI) were added to the target satellites of the last two tests. The impact tests were carried out with projectiles of different sizes and impact speeds. All fragments down to about 2 mm in size were collected and analyzed based on their three orthogonal dimensions, x, y, and z, where x is the longest dimension, y is the longest dimension in the plane perpendicular to x, and z is the longest dimension perpendicular to both x and y. Each fragment was also photographed and classified by shape and material composition. This data set serves as the basis of our effort to develop a fragment shape distribution. Two distinct groups can be observed in the x/y versus y/z distribution of the fragments. Objects in the first group typically have large x/y values. Many of them are needle-like objects originating from the fragmentation of carbon fiber reinforced plastic materials used to construct the satellites. Objects in the second group tend to have small x/y values, and many of them are box-like or plate-like objects, depending on their y/z values. Each group forms the corresponding peak in the x/y distribution. However, only one peak can be observed in the y/z distribution. These distributions and how they vary with size, material type, and impact parameters will be described in detail within the paper.

Heterogeneous Binding and Central Nervous System Distribution of the Multitargeted Kinase Inhibitor Ponatinib Restrict Orthotopic Efficacy in a Patient-Derived Xenograft Model of Glioblastoma.

PubMed

Laramy, Janice K; Kim, Minjee; Gupta, Shiv K; Parrish, Karen E; Zhang, Shuangling; Bakken, Katrina K; Carlson, Brett L; Mladek, Ann C; Ma, Daniel J; Sarkaria, Jann N; Elmquist, William F

2017-11-01

This study investigated how differences in drug distribution and free fraction at different tumor and tissue sites influence the efficacy of the multikinase inhibitor ponatinib in a patient-derived xenograft model of glioblastoma (GBM). Efficacy studies in GBM6 flank (heterotopic) and intracranial (orthotopic) models showed that ponatinib is effective in the flank but not in the intracranial model, despite a relatively high brain-to-plasma ratio. In vitro binding studies indicated that flank tumor had a higher free (unbound) drug fraction than normal brain. The total and free drug concentrations, along with the tissue-to-plasma ratio (Kp) and its unbound derivative (Kp,uu), were consistently higher in the flank tumor than the normal brain at 1 and 6 hours after a single dose in GBM6 flank xenografts. In the orthotopic xenografts, the intracranial tumor core displayed higher Kp and Kp,uu values compared with the brain-around-tumor (BAT). The free fractions and the total drug concentrations, hence free drug concentrations, were consistently higher in the core than in the BAT at 1 and 6 hours postdose. The delivery disadvantages in the brain and BAT were further evidenced by the low total drug concentrations in these areas that did not consistently exceed the in vitro cytotoxic concentration (IC 50 ). Taken together, the regional differences in free drug exposure across the intracranial tumor may be responsible for compromising efficacy of ponatinib in orthotopic GBM6. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

[Orthotopic renal transplant: our experience].

PubMed

De Gracia, R; Jiménez, C; Gil, F; Escuin, F; Tabernero, A; Sanz, A; Hidalgo, L

2007-01-01

Orthotopic renal transplant (ORT) is useful in cases of severe atherosclerosis, heterotopic bilateral transplant, unsuitable pelvic vessels and in aortic thrombosis, but it is not available in all the institutions and it is only realized of exceptional form. To review the indication, surgical technique and outcome of the ORT at our hospital. The studied included five cases between January 1990 and December 2005. We analyzed several variables: demographic characteristics, characteristics of the donor, ischemia times, evolution of renal function and morbi-mortality associated. Left ORT was performed in three men and two women. Mean patient age was 52+/-5 years, all the patients received kidneys from cadaveric donors. Mean creatinine and urea one month postoperative were 2.2+/-0.72 mg/dl and 103+/-17.2 mg/dl and at 6 months postoperative were 1.8+/-0.59 mg/dl and 78+/-14 mg/dl respectively. Immediately all patients received prophylaxis with low molecular weight heparin but it was indicated antiaggregation to two patients when they left the hospital, anticoagulation to two patients and to one of them was decided to anticoagulation nor antiagregation for history of bled digestive. A patient died for bleeding episode at level of the renal graft six months after the transplant, she was in treatment with dicumarinics, they were indicated by venous deep thrombosis in right leg. The survival a year is 80 % of the graft and the patient. Only two patients returned to hospital later, one of them for presenting an episode of diverticulitis and the other one for renal obstructive failure that needed laying of catheter pig-tail. Four patients presented stenosis of renal native vassels detected in control magnetic nuclear resonance, not symptomatic. There are two patients who take more than three years transplanted with renal stable function (creatinina 1.3 mg/dl and 1.4 mg/dl respectively). ORT is an excellent option in patients with co-morbidity increased for atherosclerosis and

Diagnostic Accuracy of CT Enterography for Active Inflammatory Terminal Ileal Crohn Disease: Comparison of Full-Dose and Half-Dose Images Reconstructed with FBP and Half-Dose Images with SAFIRE.

PubMed

Gandhi, Namita S; Baker, Mark E; Goenka, Ajit H; Bullen, Jennifer A; Obuchowski, Nancy A; Remer, Erick M; Coppa, Christopher P; Einstein, David; Feldman, Myra K; Kanmaniraja, Devaraju; Purysko, Andrei S; Vahdat, Noushin; Primak, Andrew N; Karim, Wadih; Herts, Brian R

2016-08-01

Purpose To compare the diagnostic accuracy and image quality of computed tomographic (CT) enterographic images obtained at half dose and reconstructed with filtered back projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) with those of full-dose CT enterographic images reconstructed with FBP for active inflammatory terminal or neoterminal ileal Crohn disease. Materials and Methods This retrospective study was compliant with HIPAA and approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety subjects (45 with active terminal ileal Crohn disease and 45 without Crohn disease) underwent CT enterography with a dual-source CT unit. The reference standard for confirmation of active Crohn disease was active terminal ileal Crohn disease based on ileocolonoscopy or established Crohn disease and imaging features of active terminal ileal Crohn disease. Data from both tubes were reconstructed with FBP (100% exposure); data from the primary tube (50% exposure) were reconstructed with FBP and SAFIRE strengths 3 and 4, yielding four datasets per CT enterographic examination. The mean volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE) at full dose were 13.1 mGy (median, 7.36 mGy) and 15.9 mGy (median, 13.06 mGy), respectively, and those at half dose were 6.55 mGy (median, 3.68 mGy) and 7.95 mGy (median, 6.5 mGy). Images were subjectively evaluated by eight radiologists for quality and diagnostic confidence for Crohn disease. Areas under the receiver operating characteristic curves (AUCs) were estimated, and the multireader, multicase analysis of variance method was used to compare reconstruction methods on the basis of a noninferiority margin of 0.05. Results The mean AUCs with half-dose scans (FBP, 0.908; SAFIRE 3, 0.935; SAFIRE 4, 0.924) were noninferior to the mean AUC with full-dose FBP scans (0.908; P < .003). The proportion of images with inferior quality was significantly higher with all

Self-assembled morphologies of an amphiphilic Y-shaped weak polyelectrolyte in a thin film.

PubMed

Mu, Dan; Li, Jian-Quan; Feng, Sheng-Yu

2017-11-29

Different from the self-assembly of neutral polymers, polyelectrolytes self-assemble into smaller aggregates with a more loosely assembled structure, which results from the repulsive forces acting between similar electrical compositions with the introduction of ions. The Y-shaped weak polyelectrolytes self-assemble into a core-shell type cylindrical structure with a hexagonal arrangement in a thin film, whose thickness is smaller than the gyration radius of the polymer chain. The corresponding formation mechanism consists of enrichment of the same components, adjustment of the shape of the aggregate, and the subsequent separation into individual aggregates. With the increase in the thickness of the thin film until it exceeds the gyration radius of the polymer chain, combined with the greater freedom of movement along the direction of thin film thickness, the self-assembled structure changes into a micellar structure. Under confinement, the repulsive force to the polymeric components is weakened by the repulsive forces among polyelectrolyte components with like charges, and this helps in generating aggregates with more uniform size and density distribution. In particular, when the repulsive force between the walls and the core forming components is greater than that between the walls and the shell forming components, such asymmetric confinement produces a crossed-cylindrical structure with nearly perpendicular arrangement of two cylinder arrays. Similarly, a novel three-crossed cylinder morphology is self-assembled upon removal of confinement.

White light supercontinuum generation in a Y-shaped microstructured tapered fiber pumped at 1064 nm.

PubMed

Cascante-Vindas, J; Díez, A; Cruz, J L; Andrés, M V

2010-07-05

We report the generation of supercontinuum in a Ge-doped Y-shape tapered fiber pumped at 1064 nm in the ns pump regime. The taper was designed to have long taper transitions and a taper waist with a core diameter of 0.9 mum. The large air-filling fraction and diameter of the air-hole microstructure reduces the confinement loss at long wavelengths so, enabling the extension of the spectrum to longer wavelengths. Along the taper transition the zero-dispersion wavelength decreases as the diameter of the taper becomes smaller. The spectral components generated along the taper transition pump the taper waist, enhancing the generation of short wavelengths. A flat spectrum spanning from 420 nm to 1850 nm is reported.

Porcine intestinal microbiota is shaped by diet composition based on rye or triticale.

PubMed

Burbach, K; Strang, E J P; Mosenthin, R; Camarinha-Silva, A; Seifert, J

2017-12-01

The present study aimed to compare the microbiota composition from pigs fed different cereal grain types, either rye or triticale, as sole energy source. Ileal digesta and faeces were sampled from eight pigs of each experiment. Illumina amplicon sequencing of the 16S rRNA gene was used to analyse the microbiota. Concentrations of short-chain fatty acids and ammonia were determined from faecal samples. The grain type revealed significant alterations in the overall microbiota structure. The rye-based diet was associated with an increased abundance of Lactobacillus in ileal digesta and Streptococcus in faeces and significantly higher concentrations of faecal short-chain fatty acids and ammonia compared to triticale. However, triticale significantly promoted the abundance of Streptococcus in ileal digesta and Clostridium sensu stricto in faeces. Diets based on rye or triticale affect varying intestinal microbiota, both of taxonomical and metabolic structure, with rye indicating an enhanced saccharolytic potential and triticale a more cellulolytic potential. Nutrient composition of rye and triticale are attractive for porcine nutrition. Both cereal grains show varying stimuli on the microbiota composition and microbial products of the ileum and faeces. © 2017 The Society for Applied Microbiology.

SYMPATHETIC INNERVATION, NOREPINEPHRINE CONTENT, AND NOREPINEPHRINE TURNOVER IN ORTHOTOPIC AND SPONTANEOUS MODELS OF BREAST CANCER

PubMed Central

Dawes, Ryan P.; Madden, Kelley S.

2016-01-01

Activation of the sympathetic nervous system (SNS) drives breast cancer progression in preclinical breast cancer models, but it has yet to be established if neoplastic and stromal cells residing in the tumor are directly targeted by locally released norepinephrine (NE). In murine orthotopic and spontaneous mammary tumors, tyrosine hydroxylase (TH)+ sympathetic nerves were limited to the periphery of the tumor. No TH+ staining was detected deeper within these tumors, even in regions with a high density of blood vessels. NE concentration was much lower in tumors compared to the more densely innervated spleen, reflecting the relative paucity of tumor TH+ innervation. Tumor and spleen NE concentration decreased with increased tissue mass. In mice treated with the neurotoxin 6-hydroxydopamine (6-OHDA) to selectively destroy sympathetic nerves, tumor NE concentration was reduced approximately 50%, suggesting that the majority of tumor NE is derived from local sympathetic nerves. To evaluate NE utilization, NE turnover in orthotopic 4T1 mammary tumors was compared to spleen under baseline and stress conditions. In non-stressed mice, NE turnover was equivalent between tumor and spleen. In mice exposed to a stressor, tumor NE turnover was increased compared to spleen NE turnover, and compared to non-stressed tumor NE turnover. Together, these results demonstrate that NE in mammary tumors is derived from local sympathetic nerves that synthesize and metabolize NE. However, differences between spleen and tumor NE turnover with stressor exposure suggest that sympathetic NE release is regulated differently within the tumor microenvironment compared to the spleen. Local mammary tumor sympathetic innervation, despite its limited distribution, is responsive to stressor exposure and therefore can contribute to stress-induced tumor progression. PMID:26718447

The customization of APACHE II for patients receiving orthotopic liver transplants

PubMed Central

Moreno, Rui

2002-01-01

General outcome prediction models developed for use with large, multicenter databases of critically ill patients may not correctly estimate mortality if applied to a particular group of patients that was under-represented in the original database. The development of new diagnostic weights has been proposed as a method of adapting the general model – the Acute Physiology and Chronic Health Evaluation (APACHE) II in this case – to a new group of patients. Such customization must be empirically tested, because the original model cannot contain an appropriate set of predictive variables for the particular group. In this issue of Critical Care, Arabi and co-workers present the results of the validation of a modified model of the APACHE II system for patients receiving orthotopic liver transplants. The use of a highly heterogeneous database for which not all important variables were taken into account and of a sample too small to use the Hosmer–Lemeshow goodness-of-fit test appropriately makes their conclusions uncertain. PMID:12133174

Targeting Hypoxia-Inducible Factor 1α in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment.

PubMed

Nigim, Fares; Cavanaugh, Jill; Patel, Anoop P; Curry, William T; Esaki, Shin-ichi; Kasper, Ekkehard M; Chi, Andrew S; Louis, David N; Martuza, Robert L; Rabkin, Samuel D; Wakimoto, Hiroaki

2015-07-01

Tissue hypoxia and necrosis represent pathophysiologic and histologic hallmarks of glioblastoma (GBM). Although hypoxia inducible factor 1α (HIF-1α) plays crucial roles in the malignant phenotypes of GBM, developing HIF-1α-targeted agents has been hampered by the lack of a suitable preclinical model that recapitulates the complex biology of clinical GBM. We present a new GBM model, MGG123, which was established from a recurrent human GBM. Orthotopic xenografting of stem-like MGG123 cells reproducibly generated lethal tumors that were characterized by foci of palisading necrosis, hypervascularity, and robust stem cell marker expression. Perinecrotic neoplastic cells distinctively express HIF-1α and are proliferative in both xenografts and the patient tissue. The xenografts contain scattered hypoxic foci that were consistently greater than 50 μm distant from blood vessels, indicating intratumoral heterogeneity of oxygenation. Hypoxia enhanced HIF-1α expression in cultured MGG123 cells, which was abrogated by the HIF-1α inhibitors digoxin or ouabain. In vivo, treatment of orthotopic MGG123 xenografts with digoxin decreased HIF-1α expression, vascular endothelial growth factor mRNA levels, and CD34-positive vasculature within the tumors, and extended survival of mice bearing the aggressive MGG123 GBM. This preclinical tumor model faithfully recapitulates the GBM-relevant hypoxic microenvironment and stemness and is a suitable platform for studying disease biology and developing hypoxia-targeted agents.

Lanthanum induced B-to-Z transition in self-assembled Y-shaped branched DNA structure

PubMed Central

Nayak, Ashok K.; Mishra, Aseem; Jena, Bhabani S.; Mishra, Barada K.; Subudhi, Umakanta

2016-01-01

Controlled conversion of right-handed B-DNA to left-handed Z-DNA is one of the greatest conformational transitions in biology. Recently, the B-Z transition has been explored from nanotechnological points of view and used as the driving machinery of many nanomechanical devices. Using a combination of CD spectroscopy, fluorescence spectroscopy, and PAGE, we demonstrate that low concentration of lanthanum chloride can mediate B-to-Z transition in self-assembled Y-shaped branched DNA (bDNA) structure. The transition is sensitive to the sequence and structure of the bDNA. Thermal melting and competitive dye binding experiments suggest that La3+ ions are loaded to the major and minor grooves of DNA and stabilize the Z-conformation. Our studies also show that EDTA and EtBr play an active role in reversing the transition from Z-to-B DNA. PMID:27241949

Lanthanum induced B-to-Z transition in self-assembled Y-shaped branched DNA structure

NASA Astrophysics Data System (ADS)

Nayak, Ashok K.; Mishra, Aseem; Jena, Bhabani S.; Mishra, Barada K.; Subudhi, Umakanta

2016-05-01

Controlled conversion of right-handed B-DNA to left-handed Z-DNA is one of the greatest conformational transitions in biology. Recently, the B-Z transition has been explored from nanotechnological points of view and used as the driving machinery of many nanomechanical devices. Using a combination of CD spectroscopy, fluorescence spectroscopy, and PAGE, we demonstrate that low concentration of lanthanum chloride can mediate B-to-Z transition in self-assembled Y-shaped branched DNA (bDNA) structure. The transition is sensitive to the sequence and structure of the bDNA. Thermal melting and competitive dye binding experiments suggest that La3+ ions are loaded to the major and minor grooves of DNA and stabilize the Z-conformation. Our studies also show that EDTA and EtBr play an active role in reversing the transition from Z-to-B DNA.

Nanoparticle-enabled, image-guided treatment planning of target specific RNAi therapeutics in an orthotopic prostate cancer model.

PubMed

Lin, Qiaoya; Jin, Cheng S; Huang, Huang; Ding, Lili; Zhang, Zhihong; Chen, Juan; Zheng, Gang

2014-08-13

The abilities to deliver siRNA to its intended action site and assess the delivery efficiency are challenges for current RNAi therapy, where effective siRNA delivery will join force with patient genetic profiling to achieve optimal treatment outcome. Imaging could become a critical enabler to maximize RNAi efficacy in the context of tracking siRNA delivery, rational dosimetry and treatment planning. Several imaging modalities have been used to visualize nanoparticle-based siRNA delivery but rarely did they guide treatment planning. We report a multimodal theranostic lipid-nanoparticle, HPPS(NIR)-chol-siRNA, which has a near-infrared (NIR) fluorescent core, enveloped by phospholipid monolayer, intercalated with siRNA payloads, and constrained by apoA-I mimetic peptides to give ultra-small particle size (<30 nm). Using fluorescence imaging, we demonstrated its cytosolic delivery capability for both NIR-core and dye-labeled siRNAs and its structural integrity in mice through intravenous administration, validating the usefulness of NIR-core as imaging surrogate for non-labeled therapeutic siRNAs. Next, we validated the targeting specificity of HPPS(NIR)-chol-siRNA to orthotopic tumor using sequential four-steps (in vivo, in situ, ex vivo and frozen-tissue) fluorescence imaging. The image co-registration of computed tomography and fluorescence molecular tomography enabled non-invasive assessment and treatment planning of siRNA delivery into the orthotopic tumor, achieving efficacious RNAi therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Contribution of protein, starch, and fat to the apparent ileal digestible energy of corn- and wheat-based broiler diets in response to exogenous xylanase and amylase without or with protease.

PubMed

Romero, L F; Sands, J S; Indrakumar, S E; Plumstead, P W; Dalsgaard, S; Ravindran, V

2014-10-01

The ileal energy contribution of protein, starch, and fat in response to 2 exogenous enzyme combinations was studied in 2 digestibility assays with 21- (experiment 1; 432 birds) and 42-d-old (experiment 2; 288 birds) Ross 308 broiler chickens. A 2 × 2 × 3 factorial arrangement of treatments with 2 base grains (corn or wheat), without or with high fiber ingredients (corn distillers dried grains with solubles and canola meal), and 3 enzyme treatments was implemented. Enzyme treatments, fed from 12 to 21 d or 32 to 42 d, were 1) without enzymes, 2) with xylanase from Trichoderma ressei (2,000 U/kg) and amylase from Bacillus licheniformis (200 U/kg; XA), or 3) with XA plus protease from Bacillus subtilis (4,000 U/kg; XAP). All diets contained Escherichia coli phytase (500 FTU/kg). Apparent ileal digestibility (AID) of protein, starch, and fat, as well as the apparent ileal digestible energy, were determined using titanium dioxide as inert marker. A generalized mixed model was used to test main effects and 2-way interactions at P < 0.05. An enzyme × grain interaction was detected for AID of starch at 21 and 42 d, and AID of fat at 21 d, with greater effects of enzymes in wheat-based compared with corn-based diets, but significant increments due to enzymes compared with controls in both diet types. Apparent ileal digestibility of fat at 42 d increased with enzyme supplementation compared with the control treatments. The XA and XAP treatments gradually (P < 0.05) increased AID of protein at 21 d, but only XAP increased AID of protein compared with the control at 42 d. Compared with the controls, XA increased AID energy by 52 or 87 kcal, and XAP by 104 or 152 kcal/kg of DM at 21 or 42 d, respectively. The caloric contribution of starch, fat, and protein were affected differentially by base grain and the presence of fibrous ingredients at 21 and 42 d of age. ©2014 Poultry Science Association Inc.

Carbachol regulation of rabbit ileal brush border Na+–H+ exchanger 3 (NHE3) occurs through changes in NHE3 trafficking and complex formation and is Src dependent

PubMed Central

Li, Xuhang; Zhang, Huiping; Cheong, Alice; Yueping Chen, Sharon Leu; Elowsky, Christian G; Donowitz, Mark

2004-01-01

The epithelial brush border membrane (BBM) Na+–H+ exchanger 3 (NHE3) is the major transport protein responsible for ileal electroneutral Na+ absorption. We have previously shown that ileal BBM NHE3 activity is rapidly inhibited by carbachol, an agonist that mimics cholinergic activation in digestion. In this study, we investigated the mechanisms involved in this NHE3 inhibition. Carbachol decreased the amount of ileal Na+ absorptive cell BBM NHE3 within 10 min of exposure. Based on OptiPrep gradient centrifugation, carbachol increased the amount of NHE3 in early endosomes and decreased the amount of NHE3 in BBM, consistent with effects on NHE3 trafficking. The decrease in BBM NHE3 occurred in the detergent-soluble BBM fraction with no change in the amount of NHE3 in the BBM detergent-resistant membranes. The size of BBM NHE3 complexes increased in carbachol-exposed ileum, as studied with sucrose gradient centrifugation. The NHE3 complex size increased in the total BBM, but did not change in the detergent-soluble fraction. This suggests that carbachol treatment enhanced the association of proteins with NHE3 complexes specifically in the detergent-resistant fraction of ileal BBM. NHERF2, α-actinin-4 and protein kinase C were among those NHE3-associated proteins because they were more efficiently coimmunoprecipitated from total BBM after carbachol treatment. Moreover, Src was involved in the carbachol-mediated inhibition since: (1) c-Src was rapidly activated in the detergent-resistant membranes by carbachol; and (2) carbachol inhibition of ileal Na+ absorption was completely abolished by the Src family inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2). Moreover, the carbachol-induced increase in the size of NHE3-containing complexes was reversed by PP2. These data demonstrate that regulation of NHE3 activity by carbachol can be achieved at several interrelated levels: (1) the subcellular level, at which NHE3 is rapidly endocytosed

Rare Coexistance of Ileal Diverticulosis, Crohn's Disease and Small Bowel Adenocarcinoma: Report of a Case.

PubMed

Spartalis, Eleftherios; Garmpis, Nikolaos; Spartalis, Michael; Damaskos, Christos; Moris, Demetrios; Athanasiou, Antonios; Gkolfakis, Paraskevas; Korkolopoulou, Penelope; Dimitroulis, Dimitrios; Mantas, Dimitrios

2018-01-01

Adenocarcinoma is one of the most common malignant tumors of the small intestine complicating Crohn's disease. However, the coexistence of both conditions with diverticulosis of small bowel in young age makes this coincidence rare and clinical diagnosis very difficult. We report a case of a woman admitted to our Department with acute abdominal pain and fever. The surgical and histological investigation, revealed a rare coexistence that has never been mentioned in the published medical literature. Ileal diverticulosis is not frequent and often asymptomatic as well as adenocarcinoma of the small bowel. In this case, those diseases along with Crohn's disease led the patient to acute symptoms. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Marked elevation of hepatic transaminases in recipients of an orthotopic liver transplant from a brain-dead donor receiving extracorporeal membrane oxygenation.

PubMed

Teng-Wei, Chen; Chung-Bao, Hsieh; Chan, De-Chuan; Yu, Jyh-Cherng; Kuo, Shih-Ming; Tsai, Chien-Sung; Fan, Hsiu-Lung

2014-12-29

Hemodynamic instability can lead to failure of donor organ procurement in brain-dead donors. Extracorporeal membrane oxygenation (ECMO) has been used in non-heart-beating donors to increase the donor pool, but the use of ECMO to salvage donor organs has been rarely used. We aimed to analyze postoperative liver function test results in patients receiving orthotopic liver transplants from ECMO-supported brain-dead donors. We retrospectively reviewed the records of 43 recipients of orthotopic liver transplantation from May 2009 to June 2012. Six recipients received liver grafts from ECMO-maintained donors designated as the ECMO group (n=6). The remaining patients were assigned to the non-ECMO group (n=37). Complication and mortality rates and liver function test results on postoperative days 1, 3, 5, 7, and 14 were compared between the 2 groups. Serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase levels were significantly elevated on postoperative Day 1 in the ECMO group. There were no significant differences in the complication and overall survival rates between the 2 groups (P=0.411). Although serum transaminases markedly elevated on postoperative Day 1, ECMO successfully preserved potential liver grafts in hemodynamically unstable brain-dead donors.

Significance of the antireflux valve for upper urinary tract pressure. An experimental study in patients with urinary diversion via a continent ileal reservoir.

PubMed

Berglund, B; Brevinge, H; Akerlund, S; Kock, N G

1992-01-01

When bladder substitution is required, a low pressure receptacle and an antireflux valve with low resistance to flow is essential for preservation of the upper urinary tract. The aim of this study was to evaluate whether these criteria are attained in the continent ileal reservoir used for urinary diversion. The investigations were performed in six patients more than one year after supravesical urinary diversion via a continent ileal reservoir. The pressure was recorded simultaneously both in the afferent loop and in the reservoir during filling of the reservoir. There was a slow parallel increase in the basal pressure in the reservoir and the afferent loop. Pressure waves appeared sometimes simultaneously and sometimes in only one compartment at a time. Only during short periods of time did the pressure exceed 25 cm of water. The frequency of pressure waves increased with increased filling of the reservoir. The "total pressure" was larger in the reservoir than in the afferent loop. It is the antireflux valve which prevents pressure rises in the reservoir from being conveyed to the upper urinary tract. The resistance to urinary flow was moderate.

Effects of dietary fiber on the ideal standardized ileal digestible threonine:lysine ratio for twenty-five to fifty kilogram growing gilts.

PubMed

Mathai, J K; Htoo, J K; Thomson, J E; Touchette, K J; Stein, H H

2016-10-01

Four experiments were conducted to determine effects of fiber on the ideal Thr:Lys ratio for 25- to 50-kg gilts. In Exp. 1, the objective was to determine the requirement for standardized ileal digestible Lys for gilts from 25 to 50 kg BW. Seventy gilts (24.54 ± 3.28 kg BW) were used in a growth assay with 2 pigs per pen, 5 diets, and 7 replicate pens per diet. The 5 diets were based on corn and soybean meal and contained between 0.80 and 1.32% SID Lys. Results indicated that 1.09% SID Lys was needed to optimize ADG and G:F. In Exp. 2, the objective was to determine the standardized ileal digestibility of AA in corn, soybean meal, field peas, fish meal, and soybean hulls. Six ileal-cannulated gilts (26.5 ± 0.74 kg BW) were allotted to a 6 × 6 Latin square design with 6 diets and 6 periods. Values for standardized ileal digestibility of AA were calculated for all ingredients. In Exp. 3, the objective was to determine the effect of fiber on the ideal SID Thr:Lys ratio for gilts from 25 to 50 kg BW. A total of 192 gilts (26.29 ± 4.64 kg BW) were used in a growth assay with 2 pigs per pen and 8 replicate pens per treatment. Six low-fiber diets and 6 high-fiber diets were formulated using the same batches of ingredients as in Exp. 2. Within each level of fiber, diets with SID Thr:Lys ratios ranging from 45:100 to 90:100 were formulated using the SID values calculated in Exp. 2. In both types of diets, ADG and G:F linearly and quadratically ( < 0.05) increased as the Thr:Lys ratio increased. Regression analysis estimated the ideal SID Thr:Lys ratio at 0.66 and 0.63 for ADG and G:F, respectively, for pigs fed low-fiber diets and at 0.71 and 0.63, respectively, for pigs fed high-fiber diets. In Exp. 4, the objective was to determine the N balance in pigs fed low-fiber or high-fiber diets that were formulated to have SID Thr:Lys ratios of 45:100 or 60:100. The 4 diets were formulated using the same batches of ingredients as in Exp. 2, and the SID values determined in

Rare Coexistance of Ileal Diverticulosis, Crohn’s Disease and Small Bowel Adenocarcinoma: Report of a Case

PubMed Central

SPARTALIS, ELEFTHERIOS; GARMPIS, NIKOLAOS; SPARTALIS, MICHAEL; DAMASKOS, CHRISTOS; MORIS, DEMETRIOS; ATHANASIOU, ANTONIOS; GKOLFAKIS, PARASKEVAS; KORKOLOPOULOU, PENELOPE; DIMITROULIS, DIMITRIOS; MANTAS, DIMITRIOS

2018-01-01

Background/Aim: Adenocarcinoma is one of the most common malignant tumors of the small intestine complicating Crohn’s disease. However, the coexistence of both conditions with diverticulosis of small bowel in young age makes this coincidence rare and clinical diagnosis very difficult. Case Report: We report a case of a woman admitted to our Department with acute abdominal pain and fever. The surgical and histological investigation, revealed a rare coexistence that has never been mentioned in the published medical literature. Conclusion: Ileal diverticulosis is not frequent and often asymptomatic as well as adenocarcinoma of the small bowel. In this case, those diseases along with Crohn’s disease led the patient to acute symptoms. PMID:29275319

Impact of complications and bladder cancer stage on quality of life in patients with different types of urinary diversions.

PubMed

Prcic, Alden; Aganovic, Damir; Hadziosmanovic, Osman

2013-12-01

Determine correlation between complications and stage of the disease and their impact on quality of life in patients with different types of ileal urinary derivation after radical cystectomy, and upon estimation of acquired results, to suggest the most acceptable type of urinary diversion. In five year period a prospective clinical study was performed on 106 patients, to whom a radical cystectomy was performed due to bladder cancer. Patients were divided into two groups, 66 patients with ileal conduit derivation and 40 patients with orthotopic derivation, whereby in each group a comparison between reflux and anti-reflux technique of orthotopic bladder was made. All patients from both groups filled the Sickness Impact Profile score six months after the operation. All patients had CT urography or Intravenous urography performed, as well as standard laboratory, vitamin B12 blood values, in order to evaluate early (ileus or subileus, wound dehiscence, bladder fistula, rupture of orthotopic bladder, urine extravazation) and late complications (VUR, urethral stricture, ureter stenosis, metabolic acidosis, mineral dis-balance, hypovitaminosis of vitamin B12, increased resorption of bone calcium, urinary infection, kidney damage, relapse of primary disease), so as disease stage and it's impact on quality of life. From gained results we observe that each category of SIP score correlates with different rate of correlation with the type of operation, group, T, N, and R grade, except work category. Average value of SIP score rises depending on the type of operation and T stage. It is notable that there is no difference in T1 stage, no matter the type of operation. So the average value of SIP score in T1 stage for conduit was 20.3, for Abol-Enein and Ghoneim 17.25 and Hautmann 18.75 respectively. Average value of SIP score in T2 stage for conduit was 31, for Abol-Enein and Ghoneim 19.1 and Hautmann 17.8. Average value of SIP score in T3 stage for conduit was 38.03, for Abol

Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced In Vivo Imaging

PubMed Central

Batey, Michael A.; Almeida, Gilberto S.; Wilson, Ian; Dildey, Petra; Sharma, Abhishek; Blair, Helen; Hide, I. Geoff; Heidenreich, Olaf; Vormoor, Josef; Maxwell, Ross J.; Bacon, Chris M.

2014-01-01

Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2−/−/γc−/− mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000–5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised “malignant” bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which

Contribution of protein, starch, and fat to the apparent ileal digestible energy of corn- and wheat-based broiler diets in response to exogenous xylanase and amylase without or with protease1

PubMed Central

Romero, L. F.; Sands, J. S.; Indrakumar, S. E.; Plumstead, P. W.; Dalsgaard, S.; Ravindran, V.

2014-01-01

The ileal energy contribution of protein, starch, and fat in response to 2 exogenous enzyme combinations was studied in 2 digestibility assays with 21- (experiment 1; 432 birds) and 42-d-old (experiment 2; 288 birds) Ross 308 broiler chickens. A 2 × 2 × 3 factorial arrangement of treatments with 2 base grains (corn or wheat), without or with high fiber ingredients (corn distillers dried grains with solubles and canola meal), and 3 enzyme treatments was implemented. Enzyme treatments, fed from 12 to 21 d or 32 to 42 d, were 1) without enzymes, 2) with xylanase from Trichoderma ressei (2,000 U/kg) and amylase from Bacillus licheniformis (200 U/kg; XA), or 3) with XA plus protease from Bacillus subtilis (4,000 U/kg; XAP). All diets contained Escherichia coli phytase (500 FTU/kg). Apparent ileal digestibility (AID) of protein, starch, and fat, as well as the apparent ileal digestible energy, were determined using titanium dioxide as inert marker. A generalized mixed model was used to test main effects and 2-way interactions at P < 0.05. An enzyme × grain interaction was detected for AID of starch at 21 and 42 d, and AID of fat at 21 d, with greater effects of enzymes in wheat-based compared with corn-based diets, but significant increments due to enzymes compared with controls in both diet types. Apparent ileal digestibility of fat at 42 d increased with enzyme supplementation compared with the control treatments. The XA and XAP treatments gradually (P < 0.05) increased AID of protein at 21 d, but only XAP increased AID of protein compared with the control at 42 d. Compared with the controls, XA increased AID energy by 52 or 87 kcal, and XAP by 104 or 152 kcal/kg of DM at 21 or 42 d, respectively. The caloric contribution of starch, fat, and protein were affected differentially by base grain and the presence of fibrous ingredients at 21 and 42 d of age. PMID:25071229

Ileal pouch-anal anastomosis: the Australasian experience.

PubMed

Rickard, M J F X; Young, C J; Bissett, I P; Stitz, R; Solomon, M J

2007-02-01

The aim of this project was to establish and maintain an internet-based database of all ileal pouch procedures performed in major centres in Australasia. The initial three colorectal units contributing data are Auckland, northern Brisbane and Central Sydney Area Health Service. A web-based database was designed. The data collection method was tested on a subgroup of 20 patients to ensure functionality. Data were collected in five main categories: patient demographics, preoperative data, operative details, postoperative complications and functional results. Initial data are presented for 516 patients [363 J, (70%), 133 W (26%), 16 S pouches (3%)]. There were two deaths within 30 days (0.4%). The anastomotic leak rate overall, in handsewn (HSA) and stapled anastomoses (SA) respectively was 5.0%, 8.5% and 3.3% (P=0.02 for difference HSA vs SA). Incidence of pouchitis was 20% (ulcerative colitis 23%, Crohn's disease 20%, indeterminate colitis 22%, familial adenomatous polyposis 9%). Incidence of anal stricture requiring intervention (11% overall) was significantly greater in HSAs than in SAs (16%vs 9%, P=0.02). Incidence of small bowel obstruction at any time postoperatively was 16%. Functional data were available for 234 patients. The median frequency of bowel actions during waking hours was significantly less in W pouches than in J pouches (four vs five, P=0.0005). A national web-based database has been developed for access by all Australasian colorectal units. Initial Australasian data compare favourably with other international studies. Pouchitis continues to be a long-term problem. The leak rate and rate of late anal stricture requiring a procedure are higher if the anastomosis is handsewn rather than stapled. Functional results are better with the W pouch than with the J pouch.

Color-Coded Imaging of Syngeneic Orthotopic Malignant Lymphoma Interacting with Host Stromal Cells During Metastasis.

PubMed

Matsumoto, Takuro; Suetsugu, Atsushi; Hasegawa, Kosuke; Nakamura, Miki; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

2016-04-01

The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. In a previous study, EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were established and injected into the tail vein of C57/BL6 green fluorescent protein (GFP) transgenic mice. Metastasis was observed at multiple sites which were also enriched with host GFP-expressing stromal cells. In the present study, our aim was to establish an orthotopic model of EL4-RFP. In the present study, EL4-RFP lymphoma cells were injected in the spleen of C57/BL6 GFP transgenic mice as an orthotopic model of lymphoma. Resultant primary tumor and metastases were imaged with the Olympus FV1000 scanning laser confocal microscope. EL4-RFP metastasis was observed 21 days later. EL4-RFP tumors in the spleen (primary injection site), liver, supra-mediastinum lymph nodes, abdominal lymph nodes, bone marrow, and lung were visualized by color-coded imaging. EL4-RFP metastases in the liver, lymph nodes, and bone marrow in C57/BL6 GFP mice were rich in GFP stromal cells such as macrophages, fibroblasts, dendritic cells, and normal lymphocytes derived from the host animal. Small tumors were observed in the spleen, which were rich in host stromal cells. In the lung, no mass formation of lymphoma cells occurred, but lymphoma cells circulated in lung peripheral blood vessels. Phagocytosis of EL4-RFP lymphoma cells by macrophages, as well as dendritic cells and fibroblasts, were observed in culture. Color-coded imaging of the lymphoma microenvironment suggests an important role of stromal cells in lymphoma progression and metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Ultrasound-Accelerated, Catheter-Directed Thrombolysis for Inferior Vena Cava Thrombosis After an Orthotopic Liver Transplant

PubMed Central

Latchana, Nicholas; Dowell, Joshua D.; Taani, Jamal Al; Michaels, Anthony; Elkhammas, Elmadhi; Black, Sylvester M.

2015-01-01

Inferior vena cava thrombosis is a rare occurrence after an orthotopic liver transplant that is associated with a high rate of retransplant and mortality. There is no consensus regarding the optimal therapeutic strategy. Surgical management, including thrombectomy with revision of the cavocaval anastomosis, has been described. With the use of endovascular therapies, several minimally invasive approaches are available that are effective and avoid the high morbidity associated with reoperative surgery. We describe our successful experience using an approach after a liver transplant in which the inferior vena cava thrombosis in a patient presenting with acute renal failure, anorexia, weight loss, and fatigue using an ultrasound-accelerated, catheter-directed thrombolysis platform in conjunction with systemic anticoagulation. PMID:24918871

Preclinical evaluation of transcriptional targeting strategy for human hepatocellular carcinoma in an orthotopic xenograft mouse model.

PubMed

Sia, Kian Chuan; Huynh, Hung; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Hui, Kam Man; Lam, Paula Yeng Po

2013-08-01

Gene regulation of many key cell-cycle players in S-, G(2) phase, and mitosis results from transcriptional repression in their respective promoter regions during the G(0) and G(1) phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma.

Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3

PubMed Central

Subramaniam, Aruljothi; Shanmugam, Muthu K; Ong, Tina H; Li, Feng; Perumal, Ekambaram; Chen, Luxi; Vali, Shireen; Abbasi, Taher; Kapoor, Shweta; Ahn, Kwang Seok; Kumar, Alan Prem; Hui, Kam M; Sethi, Gautam

2013-01-01

BACKGROUND AND PURPOSE Aberrant activation of STAT3 is frequently encountered and promotes proliferation, survival, metastasis and angiogenesis in hepatocellular carcinoma (HCC). Here, we have investigated whether emodin mediates its effect through interference with the STAT3 activation pathway in HCC. EXPERIMENTAL APPROACH The effect of emodin on STAT3 activation, associated protein kinases and apoptosis was investigated using various HCC cell lines. Additionally, we also used a predictive tumour technology to analyse the effects of emodin. The in vivo effects of emodin were assessed in an orthotopic mouse model of HCC. KEY RESULTS Emodin suppressed STAT3 activation in a dose- and time-dependent manner in HCC cells, mediated by the modulation of activation of upstream kinases c-Src, JAK1 and JAK2. Vanadate treatment reversed emodin-induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase and emodin induced the expression of the tyrosine phosphatase SHP-1 that correlated with the down-regulation of constitutive STAT3 activation. Interestingly, silencing of the SHP-1 gene by siRNA abolished the ability of emodin to inhibit STAT3 activation. Finally, when administered i.p., emodin inhibited the growth of human HCC orthotopic tumours in male athymic nu/nu mice and STAT3 activation in tumour tissues. CONCLUSIONS AND IMPLICATIONS Emodin mediated its effects predominantly through inhibition of the STAT3 signalling cascade and thus has a particular potential for the treatment of cancers expressing constitutively activated STAT3. PMID:23848338

Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease

PubMed Central

Gathungu, Grace; Zhang, Yuanhao; Tian, Xinyu; Bonkowski, Erin; Rowehl, Leahana; Krumsiek, Julia; Nix, Billy; Chalk, Claudia; Trapnell, Bruce; Zhu, Wei; Newberry, Rodney; Denson, Lee; Li, Ellen

2018-01-01

AIM To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn’s disease (CD). METHODS We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA IgG and IgA, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence. RESULTS Ninety six percent of patients underwent initial ileocecal resection (ICR) or ileal resection (IR) and subsequently 40% of patients required a second ICR/IR for CD. GM-CSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio (HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine (HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators (HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking (HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16L1 (HR = 0.65, 95%CI: 0.49-0.88, P = 0.006). CONCLUSION GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior. PMID:29434451

Structure optimization and preliminary bioactivity evaluation of N-hydroxybenzamide-based HDAC inhibitors with Y-shaped cap.

PubMed

Yu, Chenggong; He, Feng; Qu, Ying; Zhang, Qiuqiong; Lv, Jiahui; Zhang, Xiangna; Xu, Ana; Miao, Pannan; Wu, Jingde

2018-05-01

Histone deacetylase inhibitors (HDACIs) are effective small molecules in the treatment of human cancers. In our continuing efforts to develop novel N-hydroxyterephthalamide-based HDACIs, herein we report the design and development of a new class of N-hydroxybenzamide-based HDACIs. In this new class of analogs, we inserted an ethylene moiety in the linker and used indole as a part of the Y-shaped cap group. Biological characterization identified compounds 4o, 4p, 4q and 4t to show improved HDAC inhibition, while no isoform selectivity for HDACs was observed. These compounds also exhibited improved anti-proliferative activity against multiple cancer cell lines when compared to their parent compound and positive control SAHA. Copyright © 2018 Elsevier Ltd. All rights reserved.

Orthotopic transplantation of LH receptor knockout and wild-type ovaries.

PubMed

Chudgar, Daksha; Lei, Zhenmin; Rao, Ch V

2005-10-07

Luteinizing hormone (LH) receptor knockout animals have an ovarian failure due to an arrest in folliculogenesis at the antral stage. As a result, the animals have an infertility phenotype. The present study was undertaken to determine whether this phenotype could be reversed by orthotopic transplantation of wild-type ovaries. The results revealed that transplanting wild-type ovaries into null animals did not result in resumption of estrus cycles. Although the number of different types of follicles increased, none progressed to ovulation. The serum hormone profiles improved, reflecting the ovarian changes. The wild-type animals with null ovaries also failed to cycle and their ovaries and serum hormone levels were more like null animals with their own ovaries. Although the lack of rescue of null ovaries placed into wild-type animals was predicted, the failure of wild-type ovaries placed in null animals was not, which could be due to chronic exposure of transplanted tissue to high circulating LH levels and also possibly due to altered internal milieu in null animals. These findings may have implications for potential future considerations of grafting normal donor ovaries into women who have an ovarian failure resulting from inactivating LH receptor mutations.

A method to calculate fission-fragment yields Y(Z,N) versus proton and neutron number in the Brownian shape-motion model

DOE PAGES

Moller, Peter; Ichikawa, Takatoshi

2015-12-23

In this study, we propose a method to calculate the two-dimensional (2D) fission-fragment yield Y(Z,N) versus both proton and neutron number, with inclusion of odd-even staggering effects in both variables. The approach is to use the Brownian shape-motion on a macroscopic-microscopic potential-energy surface which, for a particular compound system is calculated versus four shape variables: elongation (quadrupole moment Q 2), neck d, left nascent fragment spheroidal deformation ϵ f1, right nascent fragment deformation ϵ f2 and two asymmetry variables, namely proton and neutron numbers in each of the two fragments. The extension of previous models 1) introduces a method tomore » calculate this generalized potential-energy function and 2) allows the correlated transfer of nucleon pairs in one step, in addition to sequential transfer. In the previous version the potential energy was calculated as a function of Z and N of the compound system and its shape, including the asymmetry of the shape. We outline here how to generalize the model from the “compound-system” model to a model where the emerging fragment proton and neutron numbers also enter, over and above the compound system composition.« less

Different surgical strategies in the treatment of familial adenomatous polyposis: what's the role of the ileal pouch-anal anastomosis?

PubMed

Leonard, D; Wolthuis, A; D'Hoore, A; Bruyninx, L; Van De Stadt, J; Van Cutsem, E; Kartheuser, A

2011-09-01

Restorative coloproctectomy (RCP) with ileal pouch-anal anastomosis (IPAA), is one of the surgical responses to the crucial question of prophylactic treatment in familial adenomatous polyposis (FAP). No consensus has been reached, until now, to choose between IPAA and ileo-rectal anastomosis (IRA), the rectal sparing prophylactic colectomy. This paper aims to review the latest issues related to IPAA and highlights its specificities compared to IRA. PubMed database was searched using the following search items: familial adenomatous polyposis, surgery, ileal pouch-anal anastomosis, ileo-rectal anastomosis. Papers published between 1978 and 2010 were selected. Absence of mortality, acceptable morbidity and good functional results combined to high quality of life have promoted the IPAA technique. New technical issues such as the double stapled technique, mesenteric lengthening, omission of temporary protective stoma can be addressed almost systematically for these patients. A laparoscopic approach, lessening the body image impact, has proven to be as effective and safe as the open approach to perform IPAA. Further advantages of laparoscopic IPAA rely on the lower adhesion formation resulting in less small bowel occlusion. Sexuality, fertility and childbirth are important functional issues often cited as threatened by the pelvic manoeuvres of the IPAA technique which can be prevented by close rectal wall dissection and a laparoscopic approach. IPAA offers the best available prophylaxis in FAP patients. Technical enhancements in IPAA will most probably decrease the functional risks. Thus IPAA remains the alternative to IRA for the prophylactic treatment of FAP.Nevertheless, based on the latest evidence, the choice between both procedures is still matter of debate.

[Laparoscopic cystectomy and ileal conduit urinary diversion for neurogenic bladders and related conditions. Morbidity and better quality of life].

PubMed

Sakhri, R; Seigle-Murandi, F; Jacqmin, D; Lang, H; Saussine, C

2015-05-01

To assess morbidity and functional consequences of laparoscopic cystectomy with ileal conduit urinary diversion: in neurologic patients. We reviewed the records of forty-two patients (ten men and thirty-two women) who underwent surgery between August 2007 and October 2013. The median age of the patient was 54 years old (range between 21-79 years). A laparoscopic cystectomy was performed followed by a short laparotomy to perform the ileal conduit urinary diversion. Records were reviewed to retrieve the indications and describe the postoperative and functional course. Patients and GPs were interviewed during phone calls to appreciate the quality of life by the PGII scale in order to assess the functional outcome. The operation was performed on 42 patients, of whom 18 had multiple sclerosis, nine a post-traumatic neurogenic bladder. Among the total population, 10 patients (23.81%) required a transfusion of at least one packed red blood cells (1-7). The overall rate of early complications was 35.71%. Belated complications were seen in 52.38% of the population. The median duration of hospital stay was 16 days (range between 9-70 days). The median follow up was 34 months (range between 1-76 months). For patients, the PGII scale rating had a median value of 6 (2-7). All referring physicians described a better functional status. The laparoscopic cystectomy can make postoperative course smoother for the neurological patients. However, the surgeon must weigh individually the benefit of performing the operation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Effect of novel fiber ingredients on ileal and total tract digestibility of energy and nutrients in semi-purified diets fed to growing pigs.

PubMed

Cervantes-Pahm, Sarah K; Liu, Yanhong; Evans, Annette; Stein, Hans H

2014-05-01

Consumption of different dietary fibers may influence the digestibility of carbohydrates and other nutrients. Therefore the objectives of this experiment were to determine the effect of novel fiber ingredients on the apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of gross energy (GE), dry matter (DM), crude protein (CP) and total dietary fiber (TDF) in pigs and to calculate the standardized digestibility of analyzed TDF in four novel fiber ingredients. The AID of DM and GE in diets containing novel fiber ingredients was less (P < 0.05) than in a maltodextrin diet. Addition of cellulose or pullulan, but not resistant starch (RS) 60, RS 75 or soluble corn fiber 70, reduced (P < 0.05) the AID of CP. The average ileal and total tract endogenous losses of analyzed TDF were calculated at 25.25 and 42.87 g kg⁻¹ DM intake, respectively. Addition of novel fiber ingredients to a maltodextrin-based diet had different effects on the AID of DM, CP, GE and TDF. Measurements of the standardized digestibility of analyzed TDF may be a better indicator of TDF fermentability than measurements of AID and ATTD of TDF, because some endogenous metabolites may be analyzed as TDF. © 2013 Society of Chemical Industry.

A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: The CAR-OLT score.

PubMed

VanWagner, Lisa B; Ning, Hongyan; Whitsett, Maureen; Levitsky, Josh; Uttal, Sarah; Wilkins, John T; Abecassis, Michael M; Ladner, Daniela P; Skaro, Anton I; Lloyd-Jones, Donald M

2017-12-01

Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979). © 2017 by the American Association for the Study of Liver

Evidence for the role of shape in mental representations of similes.

PubMed

van Weelden, Lisanne; Schilperoord, Joost; Maes, Alfons

2014-03-01

People mentally represent the shapes of objects. For instance, the mental representation of an eagle is different when one thinks about a flying or resting eagle. This study examined the role of shape in mental representations of similes (i.e., metaphoric comparisons). We tested the prediction that when people process a simile they will mentally represent the entities of the comparison as having a similar shape. We conducted two experiments in which participants read sentences that either did (experimental sentences) or did not (control sentences) invite comparing two entities. For the experimental sentences, the ground of the comparison was explicit in Experiment 1 ("X has the ability to Z, just like Y") and implicit in Experiment 2 ("X is like Y"). After having read the sentence, participants were presented with line drawings of the two objects, which were either similarly or dissimilarly shaped. They judged whether both objects were mentioned in the preceding sentence. For the experimental sentences, recognition latencies were shorter for similarly shaped objects than for dissimilarly shaped objects. For the control sentences, we did not find such an effect of similarity in shape. These findings suggest that a perceptual symbol of shape is activated when processing similes. © 2013 Cognitive Science Society, Inc.

A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors.

PubMed

El Meskini, Rajaa; Iacovelli, Anthony J; Kulaga, Alan; Gumprecht, Michelle; Martin, Philip L; Baran, Maureen; Householder, Deborah B; Van Dyke, Terry; Weaver Ohler, Zoë

2015-01-01

Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Previous work describes a genetically engineered mouse (GEM) model that contains perturbations in the most frequently dysregulated networks in GBM (driven by RB, KRAS and/or PI3K signaling and PTEN) that induce development of Grade IV astrocytoma with properties of the human disease. Here, we developed and characterized an orthotopic mouse model derived from the GEM that retains the features of the GEM model in an immunocompetent background; however, this model is also tractable and efficient for preclinical evaluation of candidate therapeutic regimens. Orthotopic brain tumors are highly proliferative, invasive and vascular, and express histology markers characteristic of human GBM. Primary tumor cells were examined for sensitivity to chemotherapeutics and targeted drugs. PI3K and MAPK pathway inhibitors, when used as single agents, inhibited cell proliferation but did not result in significant apoptosis. However, in combination, these inhibitors resulted in a substantial increase in cell death. Moreover, these findings translated into the in vivo orthotopic model: PI3K or MAPK inhibitor treatment regimens resulted in incomplete pathway suppression and feedback loops, whereas dual treatment delayed tumor growth through increased apoptosis and decreased tumor cell proliferation. Analysis of downstream pathway components revealed a cooperative effect on target downregulation. These concordant results, together with the morphologic similarities to the human GBM disease characteristics of the model, validate it as a new platform for the evaluation of GBM treatment. © 2015. Published by The Company of Biologists Ltd.

A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors

PubMed Central

El Meskini, Rajaa; Iacovelli, Anthony J.; Kulaga, Alan; Gumprecht, Michelle; Martin, Philip L.; Baran, Maureen; Householder, Deborah B.; Van Dyke, Terry; Weaver Ohler, Zoë

2015-01-01

Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Previous work describes a genetically engineered mouse (GEM) model that contains perturbations in the most frequently dysregulated networks in GBM (driven by RB, KRAS and/or PI3K signaling and PTEN) that induce development of Grade IV astrocytoma with properties of the human disease. Here, we developed and characterized an orthotopic mouse model derived from the GEM that retains the features of the GEM model in an immunocompetent background; however, this model is also tractable and efficient for preclinical evaluation of candidate therapeutic regimens. Orthotopic brain tumors are highly proliferative, invasive and vascular, and express histology markers characteristic of human GBM. Primary tumor cells were examined for sensitivity to chemotherapeutics and targeted drugs. PI3K and MAPK pathway inhibitors, when used as single agents, inhibited cell proliferation but did not result in significant apoptosis. However, in combination, these inhibitors resulted in a substantial increase in cell death. Moreover, these findings translated into the in vivo orthotopic model: PI3K or MAPK inhibitor treatment regimens resulted in incomplete pathway suppression and feedback loops, whereas dual treatment delayed tumor growth through increased apoptosis and decreased tumor cell proliferation. Analysis of downstream pathway components revealed a cooperative effect on target downregulation. These concordant results, together with the morphologic similarities to the human GBM disease characteristics of the model, validate it as a new platform for the evaluation of GBM treatment. PMID:25431423

Influence of in vivo growth on human glioma cell line gene expression: Convergent profiles under orthotopic conditions

PubMed Central

Camphausen, Kevin; Purow, Benjamin; Sproull, Mary; Scott, Tamalee; Ozawa, Tomoko; Deen, Dennis F.; Tofilon, Philip J.

2005-01-01

Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown in vitro or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype of the in situ tumor cell. To begin addressing this issue, we have used microarray analysis to define the gene expression profile of two human glioma cell lines (U251 and U87) when grown in vitro and in vivo as s.c. or as intracerebral (i.c.) xenografts. For each cell line, the gene expression profile generated from tissue culture was significantly different from that generated from the s.c. tumor, which was significantly different from those grown i.c. The disparity between the i.c gene expression profiles and those generated from s.c. xenografts suggests that whereas an in vivo growth environment modulates gene expression, orthotopic growth conditions induce a different set of modifications. In this study the U251 and U87 gene expression profiles generated under the three growth conditions were also compared. As expected, the profiles of the two glioma cell lines were significantly different when grown as monolayer cultures. However, the glioma cell lines had similar gene expression profiles when grown i.c. These results suggest that tumor cell gene expression, and thus phenotype, as defined in vitro is affected not only by in vivo growth but also by orthotopic growth, which may have implications regarding the identification of relevant targets for cancer therapy. PMID:15928080

In growing pigs, the true ileal and total tract digestibility of acid hydrolyzed ether extract in extracted corn oil is greater than in intact sources of corn oil or soybean oil.

PubMed

Kim, B G; Kil, D Y; Stein, H H

2013-02-01

An experiment was conducted to determine the true ileal digestibility (TID) and the true total tract digestibility (TTTD) of acid-hydrolyzed ether extract (AEE) in extracted corn oil, high-oil corn, distillers dried grains with solubles (DDGS), corn germ, and high protein distillers dried grains (HP DDG) and to compare these values to the TID and TTTD of AEE in full-fat soybeans. Nineteen barrows with an initial BW of 52.2 kg (SD = 3.8) were fitted with a T-cannula in the distal ileum and allotted to a 19 × 11 Youden square design with 19 diets and 11 periods. A basal diet based on cornstarch, casein, sucrose, and corn bran was formulated. Eighteen additional diets were formulated by adding 3 levels of extracted corn oil, high-oil corn, DDGS, corn germ, HP DDG, or full-fat soybeans to the basal diet. The apparent ileal and the apparent total tract digestibility of AEE were calculated for each diet. The endogenous flow of AEE associated with each ingredient and values for TID and TTTD were calculated using the regression procedure. Results indicated that digested AEE in ileal digesta and feces linearly increased as AEE intake increased regardless of ingredient (P < 0.001) and the regression of ileal and fecal AEE output against AEE intake was significant for all ingredients (P < 0.001; r(2) > 0.77). However, the ileal and fecal endogenous losses of AEE were different (P < 0.05) from 0 only for extracted corn oil, HP DDG, and full-fat soybeans. The TID of AEE was greater (P < 0.05) for extracted corn oil (95.4%) than for all other ingredients. The TID of AEE in HP DDG (76.5%) was not different from the TID of AEE in full-fat soybeans (85.2%) but greater (P < 0.05) than high-oil corn, DDGS, and corn germ (53.0, 62.1, and 50.1%, respectively). The TTTD of AEE was greater (P < 0.05) for extracted corn oil (94.3%) than for all other ingredients, and the TTTD in full-fat soybeans (79.7%) was greater (P < 0.05) than the TTTD of AEE in high-oil corn, DDGS, corn germ, and

Photoelectron spectroscopy and density functional theory study of TiAlO(y) (-) (y=1-3) and TiAl(2)O(y) (-) (y=2-3) clusters.

PubMed

Zhang, Zeng-Guang; Xu, Hong-Guang; Zhao, Yuchao; Zheng, Weijun

2010-10-21

Small titanium-aluminum oxide clusters, TiAlO(y) (-) (y=1-3) and TiAl(2)O(y) (-) (y=2-3), were studied by using anion photoelectron spectroscopy. The adiabatic detachment energies of TiAlO(y) (-) (y=1-3) were estimated to be 1.11±0.05, 1.70±0.08, and 2.47±0.08eV based on their photoelectron spectra; those of TiAl(2)O(2) (-) and TiAl(2)O(3) (-) were estimated to be 1.17±0.08 and 2.2±0.1eV, respectively. The structures of these clusters were determined by comparison of density functional calculations with the experimental results. The structure of TiAlO(-) is nearly linear with the O atom in the middle. That of TiAlO(2) (-) is a kite-shaped structure. TiAlO(3) (-) has a kite-shaped TiAlO(2) unit with the third O atom attaching to the Ti atom. TiAl(2)O(2) (-) has two nearly degenerate Al-O-Ti-O-Al chain structures that can be considered as cis and trans forms. TiAl(2)O(3) (-) has two low-lying isomers, kite structure and book structure. The structures of these clusters indicate that the Ti atom tends to bind to more O atoms.

Case report of primary intestinal lymphangiectasia diagnosed in an octogenarian by ileal intubation and by push enteroscopy after missed diagnosis by standard colonoscopy and EGD

PubMed Central

Cappell, Mitchell S.; Edhi, Ahmed; Amin, Mitual

2018-01-01

Abstract Rationale: Primary intestinal lymphangiectasia (PIL) is a rare, presumably congenital lesion that is usually diagnosed in patients < 3 years old, is rarely first diagnosed in adulthood, and when first diagnosed in adulthood typically presents with symptoms for many years. Although PIL is often identified by endoscopic abnormalities, it must be emphasized that the jejunoileum/distal duodenum must be intubated for diagnosis because the lesions are present in these regions. This work demonstrates that 1)-PIL can occur in an octogenarian; 2)-shows that the characteristic endoscopic findings are not found at colonoscopy without terminal ileal intubation; and 3)-may be missed at standard EGD without distal duodenal intubation. Diagnoses: A patient initially presented at age 83 with symptoms of watery diarrhea, abdominal distention, 5-Kg-weight-gain, and weakness for one month, and had typical clinical findings of PIL including chylous ascites, pleural effusions, bilateral pitting leg edema, hypoalbuminemia, borderline lymphopenia, hypovitaminosis-D, and hypocalcemia. Protein-losing-enteropathy was demonstrated by positive stool tests for alpha-1-antitrypsin. Standard colonoscopy revealed no significant lesions, but terminal ileal intubation during colonoscopy demonstrated creamy-white, punctate, mucosal lesions in terminal ileum, characteristic of lymphangiectasia. EGD with intubation to mid-descending duodenum revealed no significant lesions, but subsequent enteroscopy demonstrated lesions in distal duodenum/proximal jejunum similar to those in terminal ileum characteristic of lymphangiectasia. Histopathologic analysis of lesions of terminal ileum/distal duodenum demonstrated dilated mucosal vessels, confirmed as lymphatic vessels by immunohistochemistry. PIL was diagnosed after excluding secondary causes of intestinal lymphangiectasia. Interventions/Outcomes: Patient placed on standard PIL diet: oral supplements of medium-chain triglycerides, a high protein

Antimetastatic Efficacy of the Combination of Caffeine and Valproic Acid on an Orthotopic Human Osteosarcoma Cell Line Model in Nude Mice.

PubMed

Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Murakami, Takashi; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Hoffman, Robert M

2017-03-01

We have previously reported that caffeine can enhance chemotherapy efficacy of bone and soft tissue sarcoma via cell-cycle perturbation. Valproic acid has histone deacetylase (HDAC) inhibitory activity. We have also reported the anti-tumor efficacy of combination treatment with caffeine and valproic acid against osteosarcoma primary tumors in a cell-line orthotopic mouse model. In this study, we performed combination treatment of caffeine and valproic acid on osteosarcoma cell lines in vitro and in spontaneous and experimental lung metastasis mouse models of osteosarcoma. Survival of 143B-RFP human osteosarcoma cells after exposure to caffeine and valproic acid for 72 hours was determined using the WST-8 assay. IC 50 values and combination indices were calculated. Mouse models of primary osteosarcoma and spontaneous lung metastasis were obtained by orthotopic intra-tibial injection of 143B-RFP cells. Valproic acid, caffeine, and combination of both drugs were administered from day 7, five times a week, for four weeks. Six weeks after orthotopic injection, lung samples were excised and observed with a fluorescence imaging system. A mouse model of experimental lung metastasis was obtained by tail vein injection of 143B-RFP cells. The mice were treated with these agents from day 0, five times a week for four weeks. Both caffeine and valproic acid caused concentration-dependent cell kill in vitro. Synergistic efficacy of the combination treatment was observed. In the spontaneous lung-metastasis model, the number of lung metastasis was 9.0±2.6 in the untreated group (G1); 10.8±2.9 in the caffeine group (G2); 10.0±3.1 in the valproic-acid group (G3); and 3.0±1.1 in the combination group (G4); (p=6.78E-5 control vs. combination; p=0.006 valproic acid vs. combination; p=0.003 caffeine vs. combination). In the experimental lung-metastasis model, the combination group significantly reduced lung metastases and improved overall survival (p=0.0005). Efficacy of the

The confining baryonic Y-strings on the lattice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakry, Ahmed S.; Chen, Xurong; Zhang, Peng-Ming

2016-01-22

In a string picture, the nucleon is conjectured as consisting of a Y-shaped gluonic string ended by constituent quarks. In this proceeding, we summarize our results on revealing the signature of the confining Y-bosonic string in the gluonic profile due to a system of three static quarks on the lattice at finite temperature. The analysis of the action density unveils a background of a filled-Δ distribution. However, we found that these Δ-shaped profiles are comprised of three Y-shaped Gaussian-like flux tubes. The length of the revealed Y-string-like distribution is maximum near the deconfinement point and approaches the geometrical minimal nearmore » the end of the QCD plateau. The action density width profile returns good fits to a baryonic string model for the junction fluctuations at large quark source separation.« less

Barrier dysfunction and bacterial uptake in the follicle-associated epithelium of ileal Crohn's disease.

PubMed

Keita, Asa V; Söderholm, Johan D

2012-07-01

The ability to control uptake across the mucosa and protect from harmful substances in the gut lumen is defined as intestinal barrier function. The etiology of Crohn's disease is unknown, but genetic, environmental, and immunological factors all contribute. The frontline between these factors lies in the intestinal barrier. The most important inflammation-driving environmental factor in Crohn's disease is the microbiota, where Esherichia coli strains have been assigned a key role. The first observable signs of Crohn's disease are small aphtoid ulcers over Peyer's patches and lymphoid follicles. The overlaying follicle-associated epithelium (FAE) is specialized for luminal sampling and is an entry site for antigens and bacteria. We have demonstrated increased E. coli uptake across the FAE in Crohn's disease, which may initiate inflammation. This short review will discuss barrier dysfunction and bacteria in the context of ileal Crohn's disease, and how the FAE might be the site of initial inflammation. © 2012 New York Academy of Sciences.

Flow field and oscillatory shear stress in a tuning-fork-shaped model of the average human carotid bifurcation.

PubMed

Ding, Z; Wang, K; Li, J; Cong, X

2001-12-01

The oscillatory shear index (OSI) was developed based on the hypothesis that intimal hyperplasia was correlated with oscillatory shear stresses. However, the validity of the OSI was in question since the correlation between intimal thickness and the OSI at the side walls of the sinus in the Y-shaped model of the average human carotid bifurcation (Y-AHCB) was weak. The objectives of this paper are to examine whether the reason for the weak correlation lies in the deviation in geometry of Y-AHCB from real human carotid bifurcation, and whether this correlation is clearly improved in the tuning-fork-shaped model of the average human carotid bifurcation (TF-AHCB). The geometry of the TF-AHCB model was based on observation and statistical analysis of specimens from 74 cadavers. The flow fields in both models were studied and compared by using flow visualization methods under steady flow conditions and by using laser Doppler anemometer (LDA) under pulsatile flow conditions. The TF-shaped geometry leads to a more complex flow field than the Y-shaped geometry. This added complexity includes strengthened helical movements in the sinus, new flow separation zone, and directional changes in the secondary flow patterns. The results show that the OSI-values at the side walls of the sinus in the TF-shaped model were more than two times as large as those in the Y-shaped model. This study confirmed the stronger correlation between the OSI and intimal thickness in the tuning-fork geometry of human carotid bifurcation, and the TF-AHCB model is a significant improvement over the traditional Y-shaped model.

Airfoil shape for a turbine bucket

DOEpatents

Hyde, Susan Marie; By, Robert Romany; Tressler, Judd Dodge; Schaeffer, Jon Conrad; Sims, Calvin Levy

2005-06-28

Third stage turbine buckets have airfoil profiles substantially in accordance with Cartesian coordinate values of X, Y and Z set forth Table I wherein X and Y values are in inches and the Z values are non-dimensional values from 0 to 0.938 convertible to Z distances in inches by multiplying the Z values by the height of the airfoil in inches. The X and Y values are distances which, when connected by smooth continuing arcs, define airfoil profile sections at each distance Z. The profile sections at each distance Z are joined smoothly to one another to form a complete airfoil shape. The X and Y distances may be scalable as a function of the same constant or number to provide a scaled up or scaled down airfoil section for the bucket. The nominal airfoil given by the X, Y and Z distances lies within an envelop of .+-.0.150 inches in directions normal to the surface of the airfoil.

Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model

PubMed Central

Igarashi, Kentaro; Kawaguchi, Kei; Li, Shukuan; Han, Qinghong; Tan, Yuying; Gainor, Emily; Kiyuna, Tasuku; Miyake, Kentaro; Miyake, Masuyo; Higuchi, Takashi; Oshiro, Hiromichi; Singh, Arun S.; Eckardt, Mark A.; Nelson, Scott D.; Russell, Tara A.; Dry, Sarah M.; Li, Yunfeng; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Eilber, Fritz C.; Hoffman, Robert M.

2018-01-01

Synovial sarcoma (SS) is a recalcitrant subgroup of soft tissue sarcoma (STS). A tumor from a patient with high grade SS from a lower extremity was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) mouse model. The PDOX mice were randomized into the following groups when tumor volume reached approximately 100 mm3: G1, control without treatment; G2, doxorubicin (DOX) (3 mg/kg, intraperitoneal [i.p.] injection, weekly, for 2 weeks; G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G4 DOX (3mg/kg), i.p. weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks). On day 14 after treatment initiation, all therapies significantly inhibited tumor growth compared to untreated control, except DOX: (DOX: p = 0.48; rMETase: p < 0.005; DOX combined with rMETase < 0.0001). DOX combined with rMETase was significantly more effective than both DOX alone (p < 0.001) and rMETase alone (p < 0.05). The relative body weight on day 14 compared with day 0 did not significantly differ between any treatment group or untreated control. The results indicate that r-METase can overcome DOX-resistance in this recalcitrant disease. PMID:29721200

Selective efficacy of zoledronic acid on metastasis in a patient-derived orthotopic xenograph (PDOX) nude-mouse model of human pancreatic cancer.

PubMed

Hiroshima, Yukihiko; Maawy, Ali A; Katz, Matthew H G; Fleming, Jason B; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2015-03-01

Patient-derived orthotopic xenograft (PDOX) nude-mouse models replicate the behavior of clinical cancer, including metastasis. The objective of the study was to determine the efficacy of zoledronic acid (ZA) on metastasis of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of pancreatic cancer. In the present study, we examined the efficacy of ZA on pancreatic cancer growth and metastasis in a PDOX nude-mouse model. ZA monotherapy did not significantly suppress primary tumor growth. However, the primary tumor weight of gemcitabine (GEM) and combination GEM + ZA-treated mice was significantly decreased compared to the control group (GEM: P = 0.003; GEM + ZA: P = 0.002). The primary tumor weight of GEM + ZA-treated mice was significantly decreased compared to GEM-treated mice (P = 0.016). The metastasis weight decreased in ZA- or GEM-treated mice compared to the control group (ZA: P = 0.009; GEM: P = 0.007. No metastasis was detected in combination GEM + ZA-treated mice compared to the control group (GEM + ZA; P = 0.005). The results of the present study indicate that ZA can selectively target metastasis in a pancreatic cancer PDOX model and that the combination of ZA and GEM should be evaluated clinically in the near future for this highly treatment-resistant disease. © 2014 Wiley Periodicals, Inc.

Integrated self-assembling drug delivery system possessing dual responsive and active targeting for orthotopic ovarian cancer theranostics.

PubMed

Lin, Chun-Jui; Kuan, Chen-Hsiang; Wang, Li-Wen; Wu, Hsi-Chin; Chen, Yunching; Chang, Chien-Wen; Huang, Rih-Yang; Wang, Tzu-Wei

2016-06-01

Ovarian cancers are the leading cause for mortality among gynecologic malignancies with five-year survival rate less than 30%. The purpose of this study is to develop a redox and pH-sensitive self-assembling hyaluronic acid nanoparticle with active targeting peptide for anticancer drug delivery. Anti-cancer drug is grafted onto hyaluronic acid (HA) via cis-aconityl linkage and disulfide bond to possess pH sensitivity and redox property, respectively. This conjugate is amphiphilic and can self-assemble into nanoparticle (NP) in aqueous solution. The results show that the nanoconjugate is successfully developed and the grafting ratio of cystamine (cys) is 17.8% with drug loading amount about 6.2% calculated by (1)H NMR spectra. The particle size is approximately 229.0 nm using dynamic light scatting measurement, and the morphology of nanoparticles is observed as spherical shape by transmission electron microscope. The pH and redox sensitivities are evaluated by changing either pH value or concentration of dithiothreitol in the medium. It is proved that the drug carrier is capable of achieving sustained controlled release of anti-cancer drug to 95% within 150 h. The intracellular uptake is observed by fluorescent microscope and the images show that conjugating luteinizing hormone-releasing hormone (LHRH) peptide can enhance specific uptake of nanoparticles by OVCAR-3 cancer cells; thus, resulting in inhibitory cell growth to less than 20% in 72 h in vitro. Orthotopic ovarian tumor model is also established to evaluate the therapeutic and diagnostic efficacy using non-invasive in vivo imaging system. The representative results demonstrate that LHRH-conjugated NPs possess a preferable tumor imaging capability and an excellent antitumor ability to almost 30% of original size in 20 days. Copyright © 2016 Elsevier Ltd. All rights reserved.

Petal Thicknesses and Shape Transformations in Blooming Lilies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Portet, Thomas; Holmes, Peter N.; Bowden, Mark E.

2013-01-29

During blooming, flower petals undergo significant shape changes. For lilies, various different mechanisms responsible for the change have been suggested [1,2]. One is that cell growth along the edge of a petal, or, more generally, a tepal, drives a transition from a cup shape (within a bud) to a saddle shape (within a bloom). This mechanism has been previously considered for tepals modeled as shallow elliptical shells whose thickness from the center, t, falls off at least as fast as t = t0 (1 - x2/a2 - y2/b2 ) [1]. Here t0 is the maximum thickness of the shell, amore » and b are the semimajor and semiminoraxes, x and y are the coordinates along the longitudinal and lateral axes. By measuring tepal thicknesses from images collected by x-ray tomography of intact buds and by photography of microtomed buds, we find that this condition is indeed met for both Lilium casablanca and Lilium lancifolium. [1] Liang and Mahadevan. Growth, geometry, and mechanics of a blooming lily.« less

Responses of dietary ileal amino acid digestibility to consumption of different cultivars of potatoes and conventional fibers in grower pigs fed a high-fat basal diet.

PubMed

Wang, Q; Yang, X; Leonard, S; Archbold, T; Sullivan, J A; Duncan, A M; Ma, W D L; Bizimungu, B; Murphy, A; Htoo, J K; Fan, M Z

2012-12-01

Whereas dietary fibers are well recognized for nutritional management of human health issues, fiber is also known to be one of the dietary factors potentially affecting digestive use of dietary proteins. As a staple food, potato (Solanum tuberosum) may be a significant dietary fiber source. The objective of this study was to examine effects of dietary supplementation of six potato cultivar-genotype samples that differ in soluble fiber content and two conventional fiber components (i.e., cellulose and guar gum) on the apparent ileal AA digestibility in pigs fed a high-fat basal diet. The basal diet was formulated as a zero-fiber negative control (NC) to contain 41.5% poultry meal, 4% casein, 15% animal fat-oil blend, 2.8% sucrose, 31% corn (Zea mays) starch, 0.50% salt, and 0.40% trace mineral-vitamin supplement with fat contributing to 47% of the dietary GE. The two fiber diets were formulated by respectively diluting the basal diet with 10% guar gum and 10% cellulose at the expense of corn starch. Six other test diets were formulated by including 8.5% guar gum and further diluting the basal diet with 25.1% one of the six cultivar-genotype samples of dehydrated potato tuber powder to contain about 10% total dietary fiber at the expense of corn starch. Eighty-one 25-kg barrows were fitted with a simple T-cannula at the distal ileum and fed the diets according to a completely randomized block design with each block lasting 28 d. Compared with the NC, the ileal digestibility of Ala, Gly, and Pro were decreased (P < 0.05) by 10% guar gum whereas the digestibility of Gly was reduced (P < 0.05) by 10% cellulose. The ileal digestibility of several AA was decreased (P < 0.05) by the test potatoes plus 8.5% guar gum compared with the NC. Our results suggest that dietary inclusion of fiber at 10% from guar gum and cellulose and contributed by potatoes may adversely affect digestive use of dietary protein.

Piggyback technique in adult orthotopic liver transplantation: an analysis of 1067 liver transplants at a single center

PubMed Central

Nakamura, Noboru; Vaidya, Anil; Levi, David M.; Kato, Tomoaki; Nery, Jose R.; Madariaga, Juan R.; Molina, Enrique; Ruiz, Phillip; Gyamfi, Anthony; Tzakis, Andreas G.

2006-01-01

Background. Orthotopic liver transplantation (OLT) in adult patients has traditionally been performed using conventional caval reconstruction technique (CV) with veno-venous bypass. Recently, the piggyback technique (PB) without veno-venous bypass has begun to be widely used. The aim of this study was to assess the effect of routine use of PB on OLTs in adult patients. Patients and methods. A retrospective analysis was undertaken of 1067 orthotopic cadaveric whole liver transplantations in adult patients treated between June 1994 and July 2001. PB was used as the routine procedure. Patient demographics, factors including cold ischemia time (CIT), warm ischemia time (WIT), operative time, transfusions, blood loss, and postoperative results were assessed. The effects of clinical factors on graft survival were assessed by univariate and multivariate analyses.In all, 918 transplantations (86%) were performed with PB. Blood transfusion, WIT, and usage of veno-venous bypass were less with PB. Seventy-five (8.3%) cases with PB had refractory ascites following OLT (p=NS). Five venous outflow stenosis cases (0.54%) with PB were noted (p=NS). The liver and renal function during the postoperative periods was similar. Overall 1-, 3-, and 5-year patient survival rates were 85%, 78%, and 72% with PB. Univariate analysis showed that cava reconstruction method, CIT, WIT, amount of transfusion, length of hospital stay, donor age, and tumor presence were significant factors influencing graft survival. Multivariate analysis further reinforced the fact that CIT, donor age, amount of transfusion, and hospital stay were prognostic factors for graft survival. Conclusions. PB can be performed safely in the majority of adult OLTs. Results of OLT with PB are as same as for CV. Liver function, renal function, morbidity, mortality, and patient and graft survival are similar to CV. However, amount of transfusion, WIT, and use of veno-venous bypass are less with PB. PMID:18333273

Use of Panitumumab-IRDye800 to Image Microscopic Head and Neck Cancer in an Orthotopic Surgical Model

PubMed Central

Heath, C. Hope; Deep, Nicholas L.; Sweeny, Larissa; Zinn, Kurt R; Rosenthal, Eben L.

2013-01-01

Background Fluorescence imaging hardware (SPY) has recently been developed for intraoperative assessment of blood flow via detection of probes emitting in the near-infrared (NIR) spectrum. This study sought to determine if this imaging system was capable of detecting micrometastatic head and neck squamous cell carcinoma (HNSCC) in preclinical models. Methods A NIR fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody targeting EGFR (panitumumab) or non-specific IgG. HNSCC flank (SCC-1) and orthotopic (FADU and OSC19) xenografts were imaged 48-96hrs following systemic injection of labeled panitumumab or IgG. The primary tumor and regional lymph nodes were dissected using fluorescence guidance with the SPY system and grossly assessed with a charge-coupled NIR system (Pearl). Histologic slides were also imaged with a NIR charged-coupled device (Odyssey) and fluorescence intensity was correlated with pathologic confirmation of disease. Results Orthotopic tongue tumors were clearly delineated from normal tissue with tumor-to-background ratios of 2.9(Pearl) and 2.3(SPY). Disease detection was significantly improved with panitumumab-IRDye compared to IgG-IRDye800 (P<0.05). Tissue biopsies (average size=3.7mm) positive for fluorescence were confirmed for pathologic disease by histology and immunohistochemistry (n=25/25). Biopsies of non-fluorescent tissue were proven to be negative for malignancy (n=28/28). The SPY was able to detect regional lymph node metastasis (<1.0mm) and microscopic areas of disease. Standard histological assessment in both frozen and paraffin-embedded histologic specimens was augmented using the Odyssey. Conclusions Panitumumab-IRDye800 may have clinical utility in detection and removal of microscopic HNSCC using existing intraoperative optical imaging hardware and may augment analysis of frozen and permanent pathology. PMID:22669455

Orthotopic Transplantation of Achilles Tendon Allograft in Rats: With or without Incorporation of Autologous Mesenchymal Stem Cells.

PubMed

Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

2018-02-01

The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at -80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs).

PubMed

Shevtsov, Maxim; Nikolaev, Boris; Marchenko, Yaroslav; Yakovleva, Ludmila; Skvortsov, Nikita; Mazur, Anton; Tolstoy, Peter; Ryzhov, Vyacheslav; Multhoff, Gabriele

2018-01-01

Glioblastoma is the most devastating primary brain tumor of the central nervous system in adults. Magnetic nanocarriers may help not only for a targeted delivery of chemotherapeutic agents into the tumor site but also provide contrast enhancing properties for diagnostics using magnetic resonance imaging (MRI). Synthesized hybrid chitosan-dextran superparamagnetic nanoparticles (CS-DX-SPIONs) were characterized using transmission electron microscopy (TEM) and relaxometry studies. Nonlinear magnetic response measurements were employed for confirming the superparamagnetic state of particles. Following in vitro analysis of nanoparticles cellular uptake tumor targeting was assessed in the model of the orthotopic glioma in rodents. CS-DX-SPIONs nanoparticles showed a uniform diameter of 55 nm under TEM and superparamagentic characteristics as determined by T 1 (spin-lattice relaxation time) and T 2 (spin-spin relaxation time) proton relaxation times. Application of the chitosan increased the charge from +8.9 to +19.3 mV of the dextran-based SPIONs. The nonlinear magnetic response at second harmonic of CS-DX-SPIONs following the slow change of stationary magnetic fields with very low hysteresis evidenced superparamagnetic state of particles at ambient temperatures. Confocal microscopy and flow cytometry studies showed an enhanced internalization of the chitosan-based nanoparticles in U87, C6 glioma and HeLa cells as compared to dextran-coated particles. Cytotoxicity assay demonstrated acceptable toxicity profile of the synthesized nanoparticles up to a concentration of 10 μg/ml. Intravenously administered CS-DX-SPIONs in orthotopic C6 gliomas in rats accumulated in the tumor site as shown by high-resolution MRI (11.0 T). Retention of nanoparticles resulted in a significant contrast enhancement of the tumor image that was accompanied with a dramatic drop in T 2 values ( P <0.001). Subsequent histological studies proved the accumulation of the nanoparticles inside

Intracranial AAV-sTRAIL combined with lanatoside C prolongs survival in an orthotopic xenograft mouse model of invasive glioblastoma.

PubMed

Crommentuijn, Matheus H W; Maguire, Casey A; Niers, Johanna M; Vandertop, W Peter; Badr, Christian E; Würdinger, Thomas; Tannous, Bakhos A

2016-04-01

Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of secreted, soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) to GBM tumors in mice and combined it with the TRAIL-sensitizing cardiac glycoside, lanatoside C (lan C). We applied this combined therapy to two different GBM models using human U87 glioma cells and primary patient-derived GBM neural spheres in culture and in orthotopic GBM xenograft models in mice. In U87 cells, conditioned medium from AAV2-sTRAIL expressing cells combined with lan C induced 80% cell death. Similarly, lan C sensitized primary GBM spheres to sTRAIL causing over 90% cell death. In mice bearing intracranial U87 tumors treated with AAVrh.8-sTRAIL, administration of lan C caused a decrease in tumor-associated Fluc signal, while tumor size increased within days of stopping the treatment. Another round of lan C treatment re-sensitized GBM tumor to sTRAIL-induced cell death. AAVrh.8-sTRAIL treatment alone and combined with lanatoside C resulted in a significant decrease in tumor growth and longer survival of mice bearing orthotopic invasive GBM brain tumors. In summary, AAV-sTRAIL combined with lanatoside C induced cell death in U87 glioma cells and patient-derived GBM neural spheres in culture and in vivo leading to an increased in overall mice survival. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The Antineoplastic Activity of Photothermal Ablative Therapy with Targeted Gold Nanorods in an Orthotopic Urinary Bladder Cancer Model.

PubMed

Yang, Xiaoping; Su, Lih-Jen; La Rosa, Francisco G; Smith, Elizabeth Erin; Schlaepfer, Isabel R; Cho, Suehyun K; Kavanagh, Brian; Park, Wounjhang; Flaig, Thomas W

2017-07-27

Gold nanoparticles treated with near infrared (NIR) light can be heated preferentially, allowing for thermal ablation of targeted cells. The use of novel intravesical nanoparticle-directed therapy in conjunction with laser irradiation via a fiber optic cystoscope, represents a potential ablative treatment approach in patients with superficial bladder cancer. To examine the thermal ablative effect of epidermal growth factor receptor (EGFR)-directed gold nanorods irradiated with NIR light in an orthotopic urinary bladder cancer model. Gold nanorods linked to an anti-EGFR antibody (Conjugated gold NanoRods - CNR) were instilled into the bladder cavity of an orthotopic murine xenograft model with T24 bladder cancer cells expressing luciferase. NIR light was externally administered via an 808 nm diode laser. This treatment was repeated weekly for 4 weeks. The anti-cancer effect was monitored by an in vivo imaging system in a non-invasive manner, which was the primary outcome of our study. The optimal approach for an individual treatment was 2.1 W/cm 2 laser power for 30 seconds. Using this in vivo model, NIR light combined with CNR demonstrated a statistically significant reduction in tumor-associated bioluminescent activity ( n  = 16) compared to mice treated with laser alone ( n  = 14) at the end of the study ( p  = 0.035). Furthermore, the CNR+NIR light treatment significantly abrogated bioluminescence signals over a 6-week observation period, compared to pre-treatment levels ( p  = 0.045). Photothermal tumor ablation with EGFR-directed gold nanorods and NIR light proved effective and well tolerated in a murine in vivo model of urinary bladder cancer.

Methodology affects measures of phosphorus availability in growing broilers: Effects of calcium feeding strategy and dietary adaptation period length on true ileal phosphorus digestibility and predicted endogenous phosphorus losses1.

PubMed

Perryman, K R; Masey O'Neill, H V; Bedford, M R; Dozier, W A

2017-03-01

An experiment was conducted to determine the effects of Ca feeding strategy and dietary adaptation period length (DAPL) on the apparent ileal P digestibility (AIPD) and apparent ileal myo-inositol 1,2,3,4,5,6 hexakis dihydrogen phosphate (IP6) hydrolysis (AIIP6H) of corn titration diets. Nine hundred sixty Ross × Ross 708 male broiler chicks were placed into 80 battery cages. Broilers received a common starter diet until 18 d of age and then were fed one of 10 experimental treatments from 19 to 21 d of age. Nine diets were formulated to evaluate 5 corn inclusion concentrations (15, 30, 45, 60, or 75%) and 2 Ca feeding strategies (fixed at 0.35% or 1.4:1 Ca:P) after 3 DAPL (zero, 24, and 48 h). As a control for DAPL, one treatment group received the common starter diet for the duration of the experiment. Broilers consuming the control diet had higher (P < 0.001) BW gain and feed intake than broilers fed the corn titration diets. Apparent ileal P digestibility of the control diet was affected (P = 0.038) by DAPL. For diets formulated with a 1.4:1 Ca:P ratio, negative linear effects (P < 0.05) on AIPD and AIIP6H were observed with increasing corn. Conversely, for diets formulated with 0.35% Ca, positive linear effects (P < 0.05) were measured for AIPD after a 48 DAPL while no linear or quadratic effects (P > 0.05) were measured for AIPD or AIIP6H for other DAPL. Broilers fed diets formulated with 1.4:1 Ca:P had variable (P < 0.05) true ileal P digestibility (TIPD; 32.2, 15.1, and 35.4%) and negative endogenous P losses (EPL; -190, -499, and -262 mg/kg DM intake) for zero, 24, and 48 h DAPL, respectively. Conversely, TIPD values (41.2, 39.1, and 47.3%) were similar (P > 0.05) and EPL were positive (102, 197, and 154 mg/kg DM intake), regardless of DAPL, for broilers fed diets formulated with 0.35% Ca. These data demonstrated that formulating diets with a 1.4:1 Ca:P ratio affected AIPD of the titration diets, shifting the regression line and predicted

Effects of multi-carbohydrase and phytase on standardized ileal digestibility of amino acids and apparent metabolizable energy in canola meal fed to broiler chicks.

PubMed

Gallardo, C; Dadalt, J C; Kiarie, E; Trindade Neto, M A

2017-09-01

Two assays were conducted to evaluate nutritive value of canola meal (CM) fed to broiler chicks without or with a multi-carbohydrase (MC) preparation (700 U α-galactosidase, 2,200 U galactomannanase, 30,000 U xylanase, and 22,000 U β-glucanase per kg of diet) and phytase (Phy, 500 FTU per kg of diet). Assay 1 determined apparent total tract digestibility (ATTD) of nutrients and metabolizable energy (AME) by the difference method. Assay 2 determined apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of amino acids by the index method. Two reference diets (RD) - an 85% corn based and a 5% casein-cornstarch diet fortified with vitamins and minerals - were made for assays 1 and 2, respectively. For each assay, the test diets were made by mixing RD and CM 7:3 wt/wt basis and fed without or with MC or Phy or combination. A total of 245 day-old male broilers (Cobb 500) was allocated to 5 treatments to give 7 replicates (7 birds/cage). The birds were fed a commercial diet from day zero to 10 followed by assay 1 fed from d 11 to 18 and assay 2 fed from d 19 to 21. Excreta samples were collected on d 15 to18, and all birds were slaughtered on d 21 for ileal digesta. There was an interaction (P < 0.05) between MC and Phy on ATTD of DM, N, and P. There was no interaction (P > 0.05) between MC and Phy on AMEn; however, MC and Phy individually improved AMEn retention. Enzymes interacted (P < 0.05) on SID of Arg, His, Leu, Met, Thr, Ala, Asp, Gln, and Gly. In this context, feeding a combination of MC and Phy resulted in higher (P < 0.05) SID of Arg, His, Met, and Thr relative to single activity or control. Both enzymes improved (P < 0.05) SID of Lys independently. The combination of carbohydrase and Phy may be an effective strategy to improve amino acid utilization in CM for poultry. © 2017 Poultry Science Association Inc.

Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation†

PubMed Central

Casino, Carmela; Lilli, Daniela; Rivanera, Daniela; Comanducci, Antonella; Rossi, Massimo; Casciaro, Giovanni; Pecorella, Irene; Alfani, Dario; Mancini, Carlo

1999-01-01

The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation. PMID:10405433

Action on ileal smooth muscle of synthetic detergents and pardaxin.

PubMed

Primor, N

1986-01-01

Pardaxin (PX), a toxic and repellent substance isolated from the Red Sea flatfish, causes a sharp ball-like profile of drop of saline placed on a hydrophobic film to turn into a flattened one. This effect results with a decrease of the contact angle (theta) from 96 degrees to a maximum of 42 degrees at 10(-4) M of PX. The action of sodium dodecyl sulphate (SDS), a synthetic anionic detergent, benzalkonium chloride (BAC) cationic detergent and pardaxin (PX) a toxic protein with detergent properties, were studied in the ileal guinea-pig longitudinal smooth muscle preparation. SDS (4 X 10(-4) M) and PX (5 X 10(-6) M) diminished the muscle contractile response to field stimulation (0.1 Hz, 1 msec) and to acetylcholine (Ach) and to histamine and elicited a prolonged (4-6 min) TTX-insensitive muscle contraction. The dose dependence of muscle contraction to SDS and PX was found to be sigmoidal and occurred over a narrow range of concentrations. The SDS- but not PX-induced muscle contraction could be reduced by diphenhydramine (H1 antihistamine). BAC (10(-5)-10(-4) M) suppressed the muscle's contractile response to electrical stimulation (0.1 Hz, 1 msec), to Ach, histamine and 5-hydroxytryptamine but did not produce muscle contraction. PX at concentrations higher than 5 X 10(-6) M is a potent detergent and at this concentration shares several pharmacological similarities with SDS.

Standardized ileal digestibility of amino acids in European soya bean and rapeseed products fed to growing pigs.

PubMed

Kaewtapee, C; Mosenthin, R; Nenning, S; Wiltafsky, M; Schäffler, M; Eklund, M; Rosenfelder-Kuon, P

2018-04-01

This study was conducted to determine the chemical composition and standardized ileal digestibility coefficients (SID) of crude protein (CP) and amino acids (AA) of European soya bean and rapeseed products in pigs. Six soya bean and two rapeseed products were used as the sole dietary source of CP and AA, including raw (FFSB) and roasted full-fat soya beans (FFSB R oasted ), soya bean (SBC) and rapeseed cake (RSC), and rapeseed meal (RSM) from Bavaria (Germany), soya bean meal (SBM) from the Danube region (Austria; SBM A ustria ), a commercially available standard SBM (SBM S td ) and an imported genetically modified organism-free SBM (SBM GMO -free ). Eight ileal- cannulated pigs with an initial body weight of 32 ± 2 kg were allotted to a row-column design with eight diets and six periods of seven days each. Trypsin inhibitor activity (TIA) ranged from 1.8 in SBM S td to 24.5 mg/g DM in FFSB. The SID of CP and all AA in FFSB R oasted were greater than in FFSB, but lower when compared to SBC and SBM A ustria (p < .05). The SID of CP and all AA (except glutamic acid) were not different between SBC and SBM A ustria , but the SID of CP and all AA (except methionine) were greater (p < .05) in SBC than in SBM GMO -free . Furthermore, the SID of CP and most AA showed a quadratic response with decreasing TIA, and there exists a quadratic response in SID of CP and all AA with increasing lysine to CP ratio and neutral detergent insoluble nitrogen (p < .05). In conclusion, variation in chemical composition and SID of CP and AA was observed in different European soya bean and rapeseed products as influenced by differences in processing conditions. European SBC and SBM A ustria can be used as alternative to imported SBM GMO -free and SBM S td in diets for growing pigs. © 2017 Blackwell Verlag GmbH.

Thermal inactivation of ileal loop-reactive Clostridium perfringens type A strains in phosphate buffer and beef gravy.

PubMed

Bradshaw, J G; Peeler, J T; Twedt, R M

1977-09-01

The thermal resistance of spore crops produced from each of two ileal loop-reactive strains of Clostridium perfringens type A was determined in two suspending vehicles consisting of 0.067 M (pH 7.0) phosphate buffer and a commercial beef gravy. D115.6 values obtained in buffer and enumerated after pretreatment with sodium ethylenediaminetetraacetate and recovery in plating medium containing lysozyme were two- to threefold greater than those obtained without this treatment. D115.6 values obtained with beef gravy were less than those obtained in buffer with or without lysozyme; however, the D98.9 and D104.4 values were 1.3 to 2 times greater than those obtained in buffer with lysozyme. The z values were within the ranges reported by previous investigators.

Thermal inactivation of ileal loop-reactive Clostridium perfringens type A strains in phosphate buffer and beef gravy.

PubMed Central

Bradshaw, J G; Peeler, J T; Twedt, R M

1977-01-01

The thermal resistance of spore crops produced from each of two ileal loop-reactive strains of Clostridium perfringens type A was determined in two suspending vehicles consisting of 0.067 M (pH 7.0) phosphate buffer and a commercial beef gravy. D115.6 values obtained in buffer and enumerated after pretreatment with sodium ethylenediaminetetraacetate and recovery in plating medium containing lysozyme were two- to threefold greater than those obtained without this treatment. D115.6 values obtained with beef gravy were less than those obtained in buffer with or without lysozyme; however, the D98.9 and D104.4 values were 1.3 to 2 times greater than those obtained in buffer with lysozyme. The z values were within the ranges reported by previous investigators. PMID:199113

Tall oil fatty acid inclusion in the diet improves performance and increases ileal density of lactobacilli in broiler chickens.

PubMed

Vienola, K; Jurgens, G; Vuorenmaa, J; Apajalahti, J

2018-04-20

1. Studies were conducted with tall oil fatty acids (TOFA) to determine their effect on broiler chicken performance and ileal microbiota. TOFA, a product originating from coniferous trees and recovered by fractional distillation of side-streams from pulp production, mainly comprises free long-chain fatty acids (~90%) and resin acids (~8%). Conjugated linolenic acids and pinolenic acid are characteristic fatty acid components of TOFA. 2. TOFA products at 750 mg/kg feed were tested in two 35-day broiler chicken trials, each using a wheat soya-based diet and with 12 replicate pens per treatment. In both trials, TOFA improved body weight gain at all time points (P < 0.001) and feed conversion efficiency during the first 21 days (P < 0.01). Two different dry TOFA formulations (silica carrier and palm oil coating) were tested and showed performance effects similar to liquid TOFA. 3. Ileal digesta of the broiler chickens was analysed for total eubacteria, Lactobacillus spp., Enterococcus spp., Escherichia coli and Clostridium perfringens on days 14 and 35. TOFA significantly increased total eubacteria and lactobacilli density on day 14 (P < 0.05). There was a significant positive correlation between these bacterial groups and broiler body weight on day 14 (P < 0.01). 4. A numerical reduction in C. perfringens was observed. In vitro growth inhibition studies showed that C. perfringens was strongly inhibited by 10 mg/l TOFA (P < 0.001), while common lactobacilli were resistant to >250 mg/l. The in vitro results were thus in line with in vivo observations. 5. The mechanisms behind the bacterial shifts and their role in performance improvement are unknown. Further purification of TOFA components is needed to identify the effective agents.

Multidetector-row computed tomography enterographic assessment of the ileal-anal pouch: descriptive radiologic analysis with endoscopic and pathologic correlation.

PubMed

Liszewski, Mark C; Sahni, V Anik; Shyn, Paul B; Friedman, Sonia; Hornick, Jason L; Erturk, Sukru M; Mortele, Koenraad J

2012-01-01

To describe the multidetector-row computed tomography enterographic (MD-CTE) features of the ileal-anal pouch after ileal pouch anal anastomosis (IPAA) surgery and correlate them with pouch endoscopy and histopathologic findings. All MD-CTE examinations performed on patients who underwent IPAA from July 1, 2005 to December 1, 2010 (n = 35; 16 [45.7%] men; mean age, 37.7 years; age range, 22-72 years) were retrospectively evaluated in consensus by 2 radiologists. All studies were evaluated for the presence of multiple imaging features. Two radiographic scores were then calculated: a total radiographic score and a radiographic active inflammation score. In patients who underwent MD-CTE, pouch endoscopy, and biopsy within 30 days (n = 13), both scores were correlated with findings on pouch endoscopy and histopathology. Of the 35 patients, 33 (94%) had at least one MD-CTE finding of active or chronic pouch inflammation and 27 patients (77%) had at least one MD-CTE finding of active pouch inflammation. Of the 13 patients who underwent endoscopy and biopsy, the total radiographic score demonstrated a strong positive correlation with endoscopic score (r = 0.81; P = 0.001) and a moderate positive correlation with histopathologic score (r = 0.56; P = 0.047). The radiographic active inflammation score demonstrated a strong positive correlation with endoscopic score (r = 0.83; P = 0.0004), but only a weak nonsignificant positive correlation with histopathologic score (r = 0.492, P = 0.087). In patients who had IPAA surgery, findings on MD-CTE correlate positively with findings on pouch endoscopy and histopathology and are sensitive measures for pouch inflammation with high positive predictive value. Thus, MD-CTE can be a useful noninvasive test in the early evaluation of symptomatic patients.

Inorganic Nanovehicle Targets Tumor in an Orthotopic Breast Cancer Model

NASA Astrophysics Data System (ADS)

Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

2014-03-01

The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

Inorganic nanovehicle targets tumor in an orthotopic breast cancer model.

PubMed

Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

2014-03-21

The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

Influence of source and micronization of soya bean meal on growth performance, nutrient digestibility and ileal mucosal morphology of Iberian piglets.

PubMed

Berrocoso, J D; Cámara, L; Rebollar, P G; Guzmán, P; Mateos, G G

2014-04-01

The effects of inclusion in the diet of different sources of soya bean meal (SBM) on growth performance, total tract apparent digestibility (TTAD) and apparent ileal digestibility (AID) of major dietary components and mucosal ileum morphology were studied in Iberian pigs weaned at 30 days of age. From 30 to 51 days of age (phase I), there was a control diet based on regular soya bean meal (R-SBM; 44% CP) of Argentina (ARG) origin and five extra diets in which a high-protein soya bean meal (HP-SBM; 49% CP) of the USA or ARG origin, either ground (990 μm) or micronized (60 μm), or a soya protein concentrate (SPC; 65% CP) substituted the R-SBM. From 51 to 61 days of age (phase II), all pigs were fed a common commercial diet in mash form. The following pre-planned orthogonal contrasts were conducted: (1) R-SBM v. all the other diets, (2) SPC v. all the HP-SBM diets, (3) micronized HP-SBM v. ground HP-SBM, (4) HP-SBM of ARG origin v. HP-SBM of US origin and (5) interaction between source and the degree of grinding of the HP-SBM. Dietary treatment did not affect growth performance of the pigs at any age but from 30 to 51 days of age, post weaning diarrhoea (PWD) was higher (P<0.001) and the TTAD and AID of all nutrients were lower for pigs fed the R-SBM diet than for pigs fed the HP-SBM or the SPC diets. However, no differences between the HP-SBM and the SPC containing diets were detected for any trait. The TTAD of organic matter (P=0.07) and gross energy (GE) (P=0.05) tended to be higher for the micronized HP-SBM than for the ground HP-SBM and that of GE was higher (P<0.05) for US meal than for the ARG meal. Pigs fed R-SBM had lower villus height (P<0.01) than pigs fed HP-SBM or SPC but no differences in ileal mucosal morphology were detected between SPC and HP-SBM containing diets. It is concluded that feeding the HP-SBM or SPC-reduced PWD and improved nutrient digestibility and ileal morphology as compared with feeding the R-SBM, but had no effect on pig performance

Analysis of an ethanol precipitate from ileal digesta: evaluation of a method to determine mucin.

PubMed

Miner-Williams, Warren M; Moughan, Paul J; Fuller, Malcolm F

2013-11-06

The precipitation of mucin using high concentrations of ethanol has been used by many researchers while others have questioned the validity of the technique. In this study, analysis of an ethanol precipitate, from the soluble fraction of ileal digesta from pigs was undertaken using molecular weight profiling and polyacrylamide gel electrophoresis. The precipitate contained 201 mg·g⁻¹ protein, 87% of which had a molecular weight >20 KDa. Polyacrylamide gel electrophoresis stained with Coomassie blue and periodic acid/Schiff, revealed that most glycoprotein had a molecular weight between 37-100 KDa. The molecular weight of glycoprotein in the precipitate was therefore lower than that of intact mucin. These observations indicated that the glycoprotein in the ethanol precipitate was significantly degraded. The large amount of protein and carbohydrate in the supernatant from ethanol precipitation indicated that the precipitation of glycoprotein was incomplete. As a method for determining the concentration of mucin in digesta, ethanol precipitation is unreliable.

Reduction of production rate in Y-shaped microreactors in the presence of viscoelasticity.

PubMed

Helisaz, Hamed; Saidi, Mohammad Hassan; Sadeghi, Arman

2017-10-16

The viscoelasticity effects on the reaction-diffusion rates in a Y-shaped microreactor are studied utilizing the PTT rheological model. The flow is assumed to be fully developed and considered to be created under a combined action of electroosmotic and pressure forces. In general, finite-volume-based numerical simulations are conducted to handle the problem; however, analytical solutions based on the depthwise averaging approach are also obtained for the case for which there is no reaction between the inlet components. The analytical solutions are found to predict accurate results when the width to height ratio is at least 10 and acceptable results for lower aspect ratios. An investigation of the viscoelasticity effect reveals that it is accompanied by a significant reduction of the production rate and the production efficiency, defined as the ratio of the average product concentration to the inlet concentration of the limiting reactant. In addition, this effect gives rise to a more uniform transport with more symmetric concentration distributions. The pressure effects on the reaction-diffusion rates are also pronounced in the presence of viscoelasticity. Finally, the influences of the product diffusivity are investigated for the first time revealing that the lower it is the thinner the area of significant production becomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Case report of primary intestinal lymphangiectasia diagnosed in an octogenarian by ileal intubation and by push enteroscopy after missed diagnosis by standard colonoscopy and EGD.

PubMed

Cappell, Mitchell S; Edhi, Ahmed; Amin, Mitual

2018-01-01

Primary intestinal lymphangiectasia (PIL) is a rare, presumably congenital lesion that is usually diagnosed in patients < 3 years old, is rarely first diagnosed in adulthood, and when first diagnosed in adulthood typically presents with symptoms for many years. Although PIL is often identified by endoscopic abnormalities, it must be emphasized that the jejunoileum/distal duodenum must be intubated for diagnosis because the lesions are present in these regions. This work demonstrates that 1)-PIL can occur in an octogenarian; 2)-shows that the characteristic endoscopic findings are not found at colonoscopy without terminal ileal intubation; and 3)-may be missed at standard EGD without distal duodenal intubation. A patient initially presented at age 83 with symptoms of watery diarrhea, abdominal distention, 5-Kg-weight-gain, and weakness for one month, and had typical clinical findings of PIL including chylous ascites, pleural effusions, bilateral pitting leg edema, hypoalbuminemia, borderline lymphopenia, hypovitaminosis-D, and hypocalcemia. Protein-losing-enteropathy was demonstrated by positive stool tests for alpha-1-antitrypsin. Standard colonoscopy revealed no significant lesions, but terminal ileal intubation during colonoscopy demonstrated creamy-white, punctate, mucosal lesions in terminal ileum, characteristic of lymphangiectasia. EGD with intubation to mid-descending duodenum revealed no significant lesions, but subsequent enteroscopy demonstrated lesions in distal duodenum/proximal jejunum similar to those in terminal ileum characteristic of lymphangiectasia. Histopathologic analysis of lesions of terminal ileum/distal duodenum demonstrated dilated mucosal vessels, confirmed as lymphatic vessels by immunohistochemistry. PIL was diagnosed after excluding secondary causes of intestinal lymphangiectasia. Patient placed on standard PIL diet: oral supplements of medium-chain triglycerides, a high protein diet, supplements of fat-soluble vitamins, and avoiding

Ethanolic Extract of Traditional Chinese Medicine (TCM) Gamboge Inhibits Colon Cancer via the Wnt/Beta-Catenin Signaling Pathway in an Orthotopic Mouse Model.

PubMed

Wang, Wei; Li, Youran; Chen, Yiqi; Chen, Hongjin; Zhu, Ping; Xu, Minmin; Wang, Hao; Wu, Minna; Yang, Zhijian; Hoffman, Robert M; Gu, Yunfei

2018-04-01

The aim of the present study was to investigate the efficacy of an ethanolic extract of gamboge (EEG), a traditional Chinese medicine (TCM), both in vitro on colon cancer cells and in vivo in an orthotopic mouse model of human colon cancer. The in vitro cytotoxicity of EEG on colon cancer cells was determined with the CCK8 proliferation assay and the Annexin V-PE/7-AAD apoptosis assay. Efficacy of EEG in vivo was evaluated in an orthotopic mouse model of human colon cancer implated with the green fluorescent protein-expressing human colon cancer cell line SW480-GFP. The tumor-bearing mice were treated with vehicle (0.2 ml/dose normal saline, po, daily), irinotecan (50 mg/kg/dose, ip, twice a week), 5-FU (15 mg/kg/dose, ip, every other day) as positive controls or EEG at doses of 12.5, 25 and 50 mg/kg/dose, po, daily. Real-time fluorescence imaging was performed to determine tumor inhibition in each treated group compared to the untreated controls. The protein expression of β-catenin, MMP-7, cyclin D1 and E-cadherin in the tumors was analyzed by immunohistochemistry. EEG significantly induced proliferation inhibition and apoptosis of SW480 colon cancer cells in vitro in a dose-dependent manner. Tumor growth in the colon-cancer orthotopic model was significantly inhibited by irinotecan, 5-FU and all three doses of EEG. The efficacy of EEG was comparable to irinotecan and 5-FU. Irinotecan, 5-FU and 50 mg/kg EEG significantly decreased the protein expression of β-catenin and MMP-7. Cyclin D1 expression was decreased and E-cadherin expression was increased by irinotecan, 5-FU and all three doses of EEG. The present study demonstrates anti-tumor efficacy of EEG on colon cancer both in vitro and in vivo through inducing proliferation inhibition and apoptosis of SW480 colon cancer cells and inhibiting tumor growth, respectively. EEG exerts anti-tumor activity at least partly via down-regulation of the Wnt/β-catenin signaling pathway. Copyright© 2018, International

Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption

PubMed Central

Montagnani, Marco; Abrahamsson, Anna; Gälman, Cecilia; Eggertsen, Gösta; Marschall, Hanns-Ulrich; Ravaioli, Elisa; Einarsson, Curt; Dawson, Paul A

2006-01-01

The etiology of most cases of idiopathic bile acid malabsorption (IBAM) is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR) and peroxisome proliferator activated receptor alpha (PPARα). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine (SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7α-hydroxy-4-cholesten-3-one (C4). The ASBT, FXR, and PPARα genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARα genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM. PMID:17171805

Intravesical Toll-like receptor 7 agonist R-837: Optimization of its formulation in an orthotopic mouse model of bladder cancer

PubMed Central

Hayashi, Tomoko; Crain, Brian; Corr, Maripat; Chan, Michael; Cottam, Howard B; Maj, Roberto; Barberis, Alcide; Leoni, Lorenzo; Carson, Dennis A

2013-01-01

Objective To study the immune response caused by the intravesical administration of the immunomodulator R-837 in various formulations and to estimate its therapeutic potential for bladder cancer. Methods Female C57BL/6 mice were intravesically treated with different formulations of R-837, a Toll-like receptor 7 agonist used for treating genital warts and skin malignancy. The tested formulation mixtures contained different ratios of lactic acid, a thermosensitive poloxamer polymer (Lutrol F127) and 2-(hydroxypropyl)-β-cyclodextrin (HPβCD). Induction of tumor necrosis factor α (TNFα) and keratinocyte-derived chemokine (KC) was analyzed by Luminex microbeads assay. The therapeutic potential of intravesical administration of R-837 was assessed in an orthotopic, syngeneic mouse model of bladder cancer using MB49 cells. Results Intravesical administration of R-837 in lactic acid alone induced systemic and bladder TNFα and KC in a dose-dependent manner. Formulations including poloxamer decreased systemic absorption of R-837 and significantly reduced systemic and local induction of KC. Addition of HPβCD in the poloxamer formulation particularly reversed levels of systemic and local levels of TNFα and KC. Histological examination showed that poloxamer-HPβCD formulation allowed infiltration of mononuclear cells into urothelium and lamina propria. In studies using orthotopic mouse bladder cancer, the tumor loads in R-837-treated mice were significantly lower than those in vehicle-treated or non-treated mice. Conclusion The optimized poloxamer-HPβCD formulation of R-837 shows therapeutic potential for bladder cancer while avoiding adverse side-effects. PMID:20337728

Zyflamend Suppresses Growth and Sensitizes Human Pancreatic Tumors to Gemcitabine in an Orthotopic Mouse Model Through Modulation of Multiple Targets

PubMed Central

Kunnumakkara, Ajaikumar B.; Sung, Bokyung; Ravindran, Jayaraj; Diagaradjane, Parmeswaran; Deorukhkar, Amit; Dey, Sanjit; Koca, Cemile; Tong, Zhimin; Gelovani, Juri G.; Guha, Sushovan; Krishnan, Sunil; Aggarwal, Bharat B.

2011-01-01

Agents that can potentiate the efficacy of standard chemotherapy against pancreatic cancer are of great interest. Because of their low cost and safety, patients commonly use a variety of dietary supplements, although evidence of their efficacy is often lacking. One such commonly used food supplement, Zyflamend, is a polyherbal preparation with potent anti-inflammatory activities, and preclinical efficacy against prostate and oral cancer. Whether Zyflamend has any efficacy against human pancreatic cancer alone or in combination with gemcitibine, a commonly used agent, was examined in cell cultures and in an orthotopic mouse model. In vitro, Zyflamend inhibited the proliferation of pancreatic cancer cell lines regardless of p53 status and also enhanced gemcitabine-induced apoptosis. This finding correlated with inhibition of NF-κB activation by Zyflamend and suppression of cyclin D1, c-myc, COX-2, Bcl-2, IAP, survivin, VEGF, ICAM-1, and CXCR4. In nude mice, oral administration of Zyflamend alone significantly inhibited the growth of orthotopically transplanted human pancreatic tumors, and when combined with gemcitabine, further enhanced the antitumor effects. Immunohistochemical and Western blot analyses of tumor tissue showed that the suppression of pancreatic cancer growth correlated with inhibition of proliferation index marker (Ki-67), COX-2, MMP-9, NF-κB, and VEGF. Overall, these results suggest that the concentrated multiherb product Zyflamend alone can inhibit the growth of human pancreatic tumors and, in addition, can sensitize pancreatic cancers to gemcitabine through the suppression of multiple targets linked to tumorigenesis. PMID:21935918

Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer.

PubMed

Jackson, Amanda L; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M; Gilliam, Timothy P; Zhou, Chunxiao; Bae-Jump, Victoria L

2017-11-21

Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease.

Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer

PubMed Central

Jackson, Amanda L.; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M.; Gilliam, Timothy P.; Zhou, Chunxiao; Bae-Jump, Victoria L.

2017-01-01

Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease. PMID:29245964

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

PubMed Central

Spiller, R C; Trotman, I F; Adrian, T E; Bloom, S R; Misiewicz, J J; Silk, D B

1988-01-01

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary

Usefulness for Predicting Cardiac Events After Orthotopic Liver Transplantation of Myocardial Perfusion Imaging and Dobutamine Stress Echocardiography Preoperatively.

PubMed

Snipelisky, David; Ray, Jordan; Vallabhajosyula, Saraschandra; Matcha, Gautam; Squier, Samuel; Lewis, Jacob; Holliday, Rex; Aggarwal, Niti; Askew, J Wells; Shapiro, Brian; Anavekar, Nandan

2017-04-01

Patients undergoing orthotopic liver transplantation have high rates of cardiac morbidity and mortality. Although guidelines recommend noninvasive stress testing as part of the preoperative evaluation, little data have evaluated clinical outcomes following orthotopic liver transplantation. A retrospective study at 2 high-volume liver transplantation centers was performed. All patients undergoing noninvasive stress testing (myocardial perfusion imaging [MPI] or dobutamine stress echocardiography [DSE]) over a 5-year period were included. Descriptive analyses, including clinical outcomes and perioperative and postoperative ischemic events, were performed. Comparisons were made between subsets of patients within each stress modality based on abnormal versus normal results. A total of 506 patients were included, of which 343 underwent DSE and 163 MPI. Few patients had abnormal results, with 19 (5.5%) in the DSE group and 13 (8%) in the MPI group. Perioperative and postoperative cardiac complications were low (n = 20, 5.8% and n = 3, 0.9% in DSE group and n = 15, 9.2% and n = 3, 1.8% in MPI group). Comparisons between abnormal versus normal findings showed a trend toward periprocedural cardiac complications in the abnormal DSE group (n = 3, 15.8% vs n = 17, 5.25%; p = 0.09) with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 0.9%; p = 1.0). In the MPI group, a trend toward periprocedural ischemic complications (n = 3, 23.1% vs n = 12, 8%; p = 0.1) was noted with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 2%; p = 1.0). In conclusion, our study found a significantly lower than reported cardiac event rate. In addition, it demonstrated that ischemic cardiac events are uncommon in patients with normal stress testing. Copyright © 2017 Elsevier Inc. All rights reserved.

MicroPET/CT Imaging of an Orthotopic Model of Human Glioblastoma Multiforme and Evaluation of Pulsed Low-Dose Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Sean S.; Chunta, John L.; Robertson, John M.

2011-07-01

Purpose: Glioblastoma multiforme (GBM) is an aggressive tumor that typically causes death due to local progression. To assess a novel low-dose radiotherapy regimen for treating GBM, we developed an orthotopic murine model of human GBM and evaluated in vivo treatment efficacy using micro-positron-emission tomography/computed tomography (microPET/CT) tumor imaging. Methods: Orthotopic GBM xenografts were established in nude mice and treated with standard 2-Gy fractionation or 10 0.2-Gy pulses with 3-min interpulse intervals, for 7 consecutive days, for a total dose of 14 Gy. Tumor growth was quantified weekly using the Flex Triumph (GE Healthcare/Gamma Medica-Ideas, Waukesha, WI) combined PET-single-photon emission CTmore » (SPECT)-CT imaging system and necropsy histopathology. Normal tissue damage was assessed by counting dead neural cells in tissue sections from irradiated fields. Results: Tumor engraftment efficiency for U87MG cells was 86%. Implanting 0.5 x 10{sup 6} cells produced a 50- to 70-mm{sup 3} tumor in 10 to 14 days. A significant correlation was seen between CT-derived tumor volume and histopathology-measured volume (p = 0.018). The low-dose 0.2-Gy pulsed regimen produced a significantly longer tumor growth delay than standard 2-Gy fractionation (p = 0.045). Less normal neuronal cell death was observed after the pulsed delivery method (p = 0.004). Conclusion: This study successfully demonstrated the feasibility of in vivo brain tumor imaging and longitudinal assessment of tumor growth and treatment response with microPET/CT. Pulsed radiation treatment was more efficacious than the standard fractionated treatment and was associated with less normal tissue damage.« less

MicroPET/CT imaging of an orthotopic model of human glioblastoma multiforme and evaluation of pulsed low-dose irradiation.

PubMed

Park, Sean S; Chunta, John L; Robertson, John M; Martinez, Alvaro A; Oliver Wong, Ching-Yee; Amin, Mitual; Wilson, George D; Marples, Brian

2011-07-01

Glioblastoma multiforme (GBM) is an aggressive tumor that typically causes death due to local progression. To assess a novel low-dose radiotherapy regimen for treating GBM, we developed an orthotopic murine model of human GBM and evaluated in vivo treatment efficacy using micro-positron-emission tomography/computed tomography (microPET/CT) tumor imaging. Orthotopic GBM xenografts were established in nude mice and treated with standard 2-Gy fractionation or 10 0.2-Gy pulses with 3-min interpulse intervals, for 7 consecutive days, for a total dose of 14 Gy. Tumor growth was quantified weekly using the Flex Triumph (GE Healthcare/Gamma Medica-Ideas, Waukesha, WI) combined PET-single-photon emission CT (SPECT)-CT imaging system and necropsy histopathology. Normal tissue damage was assessed by counting dead neural cells in tissue sections from irradiated fields. Tumor engraftment efficiency for U87MG cells was 86%. Implanting 0.5 × 10(6) cells produced a 50- to 70-mm(3) tumor in 10 to 14 days. A significant correlation was seen between CT-derived tumor volume and histopathology-measured volume (p = 0.018). The low-dose 0.2-Gy pulsed regimen produced a significantly longer tumor growth delay than standard 2-Gy fractionation (p = 0.045). Less normal neuronal cell death was observed after the pulsed delivery method (p = 0.004). This study successfully demonstrated the feasibility of in vivo brain tumor imaging and longitudinal assessment of tumor growth and treatment response with microPET/CT. Pulsed radiation treatment was more efficacious than the standard fractionated treatment and was associated with less normal tissue damage. Copyright © 2011 Elsevier Inc. All rights reserved.

Indocyanine green plasma disappearance rate during the anhepatic phase of orthotopic liver transplantation.

PubMed

Bruegger, Lukas; Studer, Peter; Schmid, Stefan W; Pestel, Gunther; Reichen, Juerg; Seiler, Christian; Candinas, Daniel; Inderbitzin, Daniel

2008-01-01

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI]=0.8-2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account.

Macroscopic shape change of melt-processed YBa{sub 2}Cu{sub 3}O{sub x-}Y{sub 2}BaCuO{sub 5} bulk superconductors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diko, P.; Goretta, K. C.; Energy Technology

A macroscopic change in the shape of five-domain melt-processed YBa{sub 2}Cu{sub 3}O{sub x}/Y{sub 2}BaCuO{sub 5} bulk superconductors is reported and explained. The change, a distortion from circular cross-section, is attributed to liquid transport from a slower growth front in an a-axis direction to a faster growth front in a c-axis direction at the edge between the a- and c-growth fronts, a phenomenon that we call the edge melt distribution (EMD) effect. Formation of bands of higher Y{sub 2}BaCuO{sub 5} particle density along the a/c growth boundaries, which nearly coincide with {l_brace}110{r_brace}-type planes, is explained by the EMD effect.

Effect of dietary lignocellulose on ileal and total tract digestibility of fat and fatty acids in broiler chickens.

PubMed

Bogusławska-Tryk, M; Piotrowska, A; Szymeczko, R; Burlikowska, K

2016-12-01

The study was conducted to determine the effect of a lignocellulose supplemented diet on apparent ileal and total tract digestibility of fat and fatty acids (FA) in broiler chickens. A total of 48 21-day-old male Ross 308 chickens were divided into four treatment groups (n = 12) with six replicates per treatment. From 21 to 42 days of age, the broilers were fed experimental diets varied in the amount of lignocellulose: 0%, 0.25%, 0.5% and 1%. Total excreta were gathered during the last 3 days of the feeding trial and digesta was collected from the ileum at 42 days of the bird age. Digestibility was determined by the indicator method. The ether extract content in diet/digesta/excreta was determined by the gravimetric method, and fatty acid methyl esters were analysed by gas chromatography-mass spectrometry. Fat digestibility measured to the end of the small intestine and in the whole gastrointestinal tract in birds was high and exceeded 90% and 87% respectively. Addition of lignocellulose (1%) increased (p < 0.05) ileal fat digestibility but had no significant effect on total tract fat digestion. Absorption of total fatty acids (TFA) as well as myristic (C14:0), palmitoleic (C16:1) and α-linolenic (C18:3n-3) acids, estimated by both methods, was significantly higher in birds fed the diets supplemented with lignocellulose, especially at a dose of 1%. Total tract absorption of some dietary polyunsaturated fatty acids (PUFA) (C20:2, C20:4n-6) was significantly lower from diet supplemented with 0.5% and 0.25% lignocellulose. There was observed a decrease in apparent digestibility of fat and most examined fatty acids, when measured between terminal ileum and total gastrointestinal tract. The results suggest that lignocellulose can affect digestion and FA absorption in broilers but, as the effect of lignocellulose was not studied previously, further investigations are necessary to confirm the results of the present experiment. Journal of Animal Physiology and Animal

The influence of narrow-leafed lupin seed fermentation on their chemical composition and ileal digestibility and microbiota in growing pigs.

PubMed

Zaworska, Anita; Frankiewicz, Andrzej; Kasprowicz-Potocka, Małgorzata

2017-08-01

The aims of this study were to provide a controlled fermentation process of blue lupin seeds (Lupinus angustifolius, cv. Neptun), monitor the changes in seed composition and determine the influence of the fermentation on the apparent ileal digestibility (AID) of crude protein (CP) and amino acids in growing pigs, compared with raw lupin seeds. The fermentation with bacteria and yeast was conducted for 24 h at 25ºC under aerobic conditions. Seed fermentation increased the contents of CP, fibre, fat and ash and most of the analysed amino acids but reduced the levels of the nitrogen-free extractives. Furthermore, fermentation decreased the contents of raffinose family oligosaccharides and phytic acids but increased the alkaloid content. The AID was estimated on three barrows (mean initial body weight 25 kg), surgically fitted with a T-cannula in the distal ileum. The pigs received three diets, each for 6 d, within three experimental periods (3 × 3 Latin Square design). The diets contained soybean meal (Group SBM), raw lupin seeds (Group RL) or fermented lupin seeds (Group FL) as solely protein sources. Fermentation had a positive impact on the AID of CP and methionine, cysteine, isoleucine, leucine, phenylalanine and valine (p < 0.05). Feeding raw or fermented lupin seeds did not affect the microbial status of the ileal digesta. Moreover, ammonia content in the caecal digesta did not differ between Groups RL and FL, although it was significantly higher than in Group SBM. It can be concluded that the fermentation process modified the chemical composition of nutrients in seeds, which can influence the digestibility and utilisation of the fermentation product in animal diets compared to raw seeds.

Shape-Controlled Synthesis of Isotopic Yttrium-90-Labeled Rare Earth Fluoride Nanocrystals for Multimodal Imaging.

PubMed

Paik, Taejong; Chacko, Ann-Marie; Mikitsh, John L; Friedberg, Joseph S; Pryma, Daniel A; Murray, Christopher B

2015-09-22

Isotopically labeled nanomaterials have recently attracted much attention in biomedical research, environmental health studies, and clinical medicine because radioactive probes allow the elucidation of in vitro and in vivo cellular transport mechanisms, as well as the unambiguous distribution and localization of nanomaterials in vivo. In addition, nanocrystal-based inorganic materials have a unique capability of customizing size, shape, and composition; with the potential to be designed as multimodal imaging probes. Size and shape of nanocrystals can directly influence interactions with biological systems, hence it is important to develop synthetic methods to design radiolabeled nanocrystals with precise control of size and shape. Here, we report size- and shape-controlled synthesis of rare earth fluoride nanocrystals doped with the β-emitting radioisotope yttrium-90 ((90)Y). Size and shape of nanocrystals are tailored via tight control of reaction parameters and the type of rare earth hosts (e.g., Gd or Y) employed. Radiolabeled nanocrystals are synthesized in high radiochemical yield and purity as well as excellent radiolabel stability in the face of surface modification with different polymeric ligands. We demonstrate the Cerenkov radioluminescence imaging and magnetic resonance imaging capabilities of (90)Y-doped GdF3 nanoplates, which offer unique opportunities as a promising platform for multimodal imaging and targeted therapy.

Effects of a 6-phytase on the apparent ileal digestibility of minerals and amino acids in ileorectal anastomosed pigs fed on a corn-soybean meal-barley diet.

PubMed

Guggenbuhl, P; Waché, Y; Simoes Nunes, C; Fru, F

2012-12-01

Phosphorus of plant-based feedstuffs for monogastric animals is mainly in the form of phytic P, which has a very low bioavailability. The nondigested phytic P may contribute to P pollution. Furthermore, phytic acid may reduce digestibility of other minerals and protein. This study evaluated effects of the microbial 6-phytase RONOZYME HiPhos on apparent ileal digestibility of P, phytic acid, Ca, CP, energy, and AA in six 60-d-old ileorectal anastomosed pigs. In a duplicated 3 × 3 Latin square design, pigs had free access to alternatively a corn (Zea mays)-soybean (Glycine max) meal-barley (Hordeum vulgare)-based diet or this diet supplemented with RONOZYME HiPhos at either 500 units/kg (RH500) or 1000 units/kg (RH1000). Pigs fed diets supplemented with RH500 or RH1000 increased (P < 0.05) digestibility of P, Ca, and Lys. Pigs fed diet RH1000 increased (P < 0.05) digestibility of CP, total AA, indispensable AA, Glu + Gln, His, Gly, Ala, Tyr, Leu, Phe, and Met. Similar to growth trials with increased total tract digestibility of P and Ca, phytase increased apparent ileal digestibility of these indispensable minerals and phytate. The phytase increased digestibility of CP and indispensable AA indicating a better availability of plant-based proteins.

Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models.

PubMed

Jandial, Rahul; Neman, Josh; Lim, Punnajit P; Tamae, Daniel; Kowolik, Claudia M; Wuenschell, Gerald E; Shuck, Sarah C; Ciminera, Alexandra K; De Jesus, Luis R; Ouyang, Ching; Chen, Mike Y; Termini, John

2018-01-30

Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1) to detoxify the toxic glycolytic byproduct methylglyoxal (MG) and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs). Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM), the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA) approaches. Inhibition of GLO1 with S -( p -bromobenzyl) glutathione dicyclopentyl ester ( p- BrBzGSH(Cp)₂) increased levels of the DNA-AGE N ²-1-(carboxyethyl)-2'-deoxyguanosine (CEdG), a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE); and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p -BrBzGSH(Cp)₂ exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors.

Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models

PubMed Central

Jandial, Rahul; Neman, Josh; Tamae, Daniel; Kowolik, Claudia M.; Wuenschell, Gerald E.; Ciminera, Alexandra K.; De Jesus, Luis R.; Ouyang, Ching; Chen, Mike Y.

2018-01-01

Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1) to detoxify the toxic glycolytic byproduct methylglyoxal (MG) and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs). Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM), the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA) approaches. Inhibition of GLO1 with S-(p-bromobenzyl) glutathione dicyclopentyl ester (p-BrBzGSH(Cp)2) increased levels of the DNA-AGE N2-1-(carboxyethyl)-2′-deoxyguanosine (CEdG), a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE); and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p-BrBzGSH(Cp)2 exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors. PMID:29385725

Ancient Male Recombination Shaped Genetic Diversity of Neo-Y Chromosome in Drosophila albomicans.

PubMed

Satomura, Kazuhiro; Tamura, Koichiro

2016-02-01

Researchers studying Y chromosome evolution have drawn attention to neo-Y chromosomes in Drosophila species due to their resembling the initial stage of Y chromosome evolution. In the studies of neo-Y chromosome of Drosophila miranda, the extremely low genetic diversity observed suggested various modes of natural selection acting on the nonrecombining genome. However, alternative possibility may come from its peculiar origin from a single chromosomal fusion event with male achiasmy, which potentially caused and maintained the low genetic diversity of the neo-Y chromosome. Here, we report a real case where a neo-Y chromosome is in transition from an autosome to a typical Y chromosome. The neo-Y chromosome of Drosophila albomicans harbored a rich genetic diversity comparable to its gametologous neo-X chromosome and an autosome in the same genome. Analyzing sequence variations in 53 genes and measuring recombination rates between pairs of loci by cross experiments, we elucidated the evolutionary scenario of the neo-Y chromosome of D. albomicans having high genetic diversity without assuming selective force, i.e., it originated from a single chromosomal fusion event, experienced meiotic recombination during the initial stage of evolution and diverged from neo-X chromosome by the suppression of recombination tens or a few hundreds of thousand years ago. Consequently, the observed high genetic diversity on the neo-Y chromosome suggested a strong effect of meiotic recombination to introduce genetic variations into the newly arisen sex chromosome. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

In Vitro and In Vivo Comparison of Gemcitabine and the Gemcitabine Analog 1-(2'-deoxy-2'-fluoroarabinofuranosyl) Cytosine (FAC) in Human Orthotopic and Genetically Modified Mouse Pancreatic Cancer Models.

PubMed

Russell, James; Pillarsetty, Nagavarakishore; Kramer, Robin M; Romesser, Paul B; Desai, Pooja; Haimovitz-Friedman, Adriana; Lowery, Maeve A; Humm, John L

2017-12-01

Although gemcitabine is a mainstay of pancreatic cancer therapy, it is only moderately effective, and it would be desirable to measure drug uptake in patients. 1-(2'-deoxy-2'-fluoroarabinofuranosyl) cytosine (FAC), is an analog of gemcitabine, and when labeled with F-18, it may be a potential surrogate PET tracer for the drug. [ 18 F]FAC was synthesized to a radiochemical purity of >96 %. The human tumor lines AsPC1, BxPC3, Capan-1, Panc1, and MiaPaca2 were grown orthotopically in nude mice. KPC mice that conditionally express oncogenic K-ras and p53 mutations in pancreatic tissue were also used. The intra-tumoral distributions of [ 14 C]gemcitabine and [ 18 F]FAC were mapped with autoradiography. The inter-tumor correlation between [ 14 C]gemcitabine and [ 18 F]FAC was established in the orthotopic tumors. Expression of the equilibrative and concentrative nucleoside transporters (ENT, CNT) in vitro was detected by western blotting. Drug uptake was characterized in vitro using [ 3 H]gemcitabine and the effect of transporter inhibition on gemcitabine and FAC uptake was investigated. The relative affinity of cells for gemcitabine and FAC was tested in competition assays. The cell lines differed in sensitivity to transport inhibitors and in competition studies. There was a good in vivo correlation between the total uptake of [ 18 F]FAC and [ 14 C]gemcitabine, measured across all orthotopic tumors. Using the KPC and BxPC3 models, we found that [ 14 C]gemcitabine and [ 18 F]FAC were largely co-localized. In the lines examined here, [ 18 F]FAC uptake correlates well with gemcitabine in vivo, supporting the notion that [ 18 F]FAC can serve as a PET radiotracer surrogate to determine the uptake and distribution of gemcitabine within pancreatic tumors.

Precipitation Hardenable High Temperature Shape Memory Alloy

NASA Technical Reports Server (NTRS)

Noebe, Ronald Dean (Inventor); Draper, Susan L. (Inventor); Nathal, Michael V. (Inventor); Crombie, Edwin A. (Inventor)

2010-01-01

A composition of the invention is a high temperature shape memory alloy having high work output, and is made from (Ni+Pt+Y),Ti(100-x) wherein x is present in a total amount of 49-55 atomic % Pt is present in a total amount of 10-30 atomic %, Y is one or more of Au, Pd. and Cu and is present in a total amount of 0 to 10 atomic %. The alloy has a matrix phase wherein the total concentration of Ni, Pt, and the one or more of Pd. Au, and Cu is greater than 50 atomic %.

Unusual binding of ursodeoxycholic acid to ileal bile acid binding protein: role in activation of FXRα.

PubMed

Fang, Changming; Filipp, Fabian V; Smith, Jeffrey W

2012-04-01

Ursodeoxycholic acid (UDCA, ursodiol) is used to prevent damage to the liver in patients with primary biliary cirrhosis. The drug also prevents the progression of colorectal cancer and the recurrence of high-grade colonic dysplasia. However, the molecular mechanism by which UDCA elicits its beneficial effects is not entirely understood. The aim of this study was to determine whether ileal bile acid binding protein (IBABP) has a role in mediating the effects of UDCA. We find that UDCA binds to a single site on IBABP and increases the affinity for major human bile acids at a second binding site. As UDCA occupies one of the bile acid binding sites on IBABP, it reduces the cooperative binding that is often observed for the major human bile acids. Furthermore, IBABP is necessary for the full activation of farnesoid X receptor α (FXRα) by bile acids, including UDCA. These observations suggest that IBABP may have a role in mediating some of the intestinal effects of UDCA.

Orthotopic Transplantation of Cryopreserved Mouse Ovaries and Gonadotrophin Releasing Hormone Analogues in the Restoration of Function following Chemotherapy-Induced Ovarian Damage

PubMed Central

Li, Qing; Szatmary, Peter; Liu, Yanyang; Ding, Zhenyu; Zhou, Jin; Sun, Yi; Luo, Feng

2015-01-01

Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients’ quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I); cyclophosphamide only (group II); cyclophosphamide plus GnRHa (group III); cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV). Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide. PMID:25811681

Characteristics and Outcomes of Neutropenia after Orthotopic Liver Transplantation

PubMed Central

Alraddadi, B; Nierenberg, NE; Price, LL; Chow, JKL; Poutsiaka, DD; Rohrer, RJ; Cooper, JT; Freeman, RB; Snydman, DR

2015-01-01

Neutropenia after orthotopic liver transplantation (LT) is relatively common but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] less than or equal to 1000/mm3) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, blood stream infection (BSI), invasive fungal infection (IFI), Cytomegalovirus (CMV) disease and graft rejection within the first year of LT. Of the 304 LT recipients, 73 (24%) developed neutropenia, 5 (7%) of whom had grade 4 neutropenia (ANC less than 500/mm3). The following were independent predictors for neutropenia: Child-Turcotte-Pugh score (HR 1.15; 95% CI 1.02, 1.28; p=0.02), BSI (HR 2.89; 95% CI 1.64, 5.11; p=<0.001), CMV disease (HR 4.28; 95% CI 1.55, 11.8; p=0.005), baseline tacrolimus trough level (HR 1.02; 95% CI 1.01, 1.03; p=0.007) and later era LT (2004–2009 versus 1999–2003) (HR 2.28; 95% CI 1.43, 3.65; p=<0.001). Moreover, neutropenia was found to be an independent predictor for mortality within the first year of LT (HR 3.76; 95% CI 1.84, 7.68; p= <0.001). Conclusion Our data suggest that neutropenia within a year after LT is not unusual and is an important predictor of mortality. PMID:26336061

Improved therapeutic outcomes of thermal ablation on rat orthotopic liver allograft sarcoma models by radioiodinated hypericin induced necrosis targeted radiotherapy

PubMed Central

Gao, Long; Zhang, Jian; Ma, Tengchuang; Yao, Nan; Gao, Meng; Shan, Xin; Ni, Yicheng; Shao, Haibo; Xu, Ke

2016-01-01

Residual tumor resulting in tumor recurrence after various anticancer therapies is an unmet challenge in current clinical oncology. This study aimed to investigate the hypothesis that radioiodinated hypericin (131I-Hyp) may inhibit residual tumor recurrence after microwave ablation (MWA) on rat orthotopic liver allograft sarcoma models. Thirty Sprague-Dawley (SD) rats with hepatic tumors were divided into three groups: Group A received laparotomy MWA and sequential intravenous injection (i.v.) of 131I labelled hypericin (131I-Hyp) in a time interval of 24 h; Group B received only laparotomy MWA; Group C was a blank control. Tumor inhibitory effects were monitored with in vivo magnetic resonance imaging (MRI) and these findings were compared to histopathology data before (baseline, day 0) and 1, 4, and 8 days after MWA. In addition, biodistribution of 131I-Hyp was assessed with in vivo single-photon emission computed tomography-computed tomography (SPECT-CT) imaging, in vitro autoradiography, fluorescent microscopy, and gamma counting. A fast clearance of 131I-Hyp and increasing deposit in necrotic tumors appeared over time, with a significantly higher radioactivity than other organs (0.9169 ± 1.1138 % ID/g, P < 0.01) on day 9. Tumor growth was significantly slowed down in group A compared to group B and C according to MRI images and corresponding tumor doubling time (12.13 ± 1.99, 4.09 ± 0.97, 3.36 ± 0.72 days respectively). The crescent tagerability of 131I-Hyp to necrosis was visualized consistently by autoradiography and fluorescence microscopy. In conclusion, 131I-Hyp induced necrosis targeted radiotherapy improved therapeutic outcomes of MWA on rat orthotopic liver allograft sarcoma models. PMID:27285983

Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.

PubMed

Ota, Shinichi; Geschwind, Jean-Francois H; Buijs, Manon; Wijlemans, Joost W; Kwak, Byung Kook; Ganapathy-Kanniappan, Shanmugasundaram

2013-06-01

Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer.

Using PEGylated iron oxide nanoparticles with ultrahigh relaxivity for MR imaging of an orthotopic model of human hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Wang, Ruizhi; Hu, Yong; Yang, Yuchan; Xu, Wei; Yao, Mingrong; Gao, Dongmei; Zhao, Yan; Zhan, Songhua; Shi, Xiangyang; Wang, Xiaolin

2017-02-01

Hepatocellular carcinoma (HCC) is the most common type of liver malignant tumor, which is often diagnosed in advanced stages, resulting in low survival rate. The sensitive diagnosis of early HCC presents a great interest. Herein, a novel superparamagnetic contrast agent composed of iron oxide nanoparticles is reported. Firstly, polyethyleneimine-coated iron oxide (Fe3O4@PEI) nanoparticles (NPs) were synthesized via a mild reduction route, followed by their modification of polyethylene glycol monomethyl ether ( mPEG-COOH) via 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride coupling chemistry. After acetylation of the remaining PEI amines, the PEGylated Fe3O4 (Fe3O4@PEI.Ac- mPEG-COOH) NPs were successively characterized via different techniques. The Fe3O4@PEI.Ac- mPEG-COOH probes with an Fe3O4 NP size of 9 nm are water dispersible and cytocompatible within the given concentration range. The percentages of PEI and m-PEG-COOH on the particles surface are calculated to be 15.5 and 7.2%, respectively. Prior to the administration of Fe3O4@PEI.Ac- mPEG-COOH NPs of ultrahigh r 2 relaxivity (461.29 mM-1 s-1) via tail intravenous injection for MR imaging of HCC, the orthotopic model of HCC was established in the nude mice by surgical transplantation with HCCLM3 cells. The analysis of MR signal intensity (SI) in the orthotopic tumor model demonstrated that the developed Fe3O4@PEI.Ac- mPEG-COOH NPs were able to infiltrate into the tumor area through the enhanced permeability and retention (EPR) effect reaching the bottom at 2 h postinjection. The developed Fe3O4@PEI.Ac- mPEG-COOH NPs may be further applied for theranostics of different diseases through combing various therapeutic agents.

Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

PubMed

Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

2014-04-01

The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

Mid-term 4-Year Outcomes with Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy Surgery at a Single US Center.

PubMed

Zaveri, Hinali; Surve, Amit; Cottam, Daniel; Cottam, Austin; Medlin, Walter; Richards, Christina; Belnap, LeGrand; Cottam, Samuel; Horsley, Benjamin

2018-06-16

Single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is a modification of Roux-en-Y duodenal switch (RYDS). Long-term data on this operation is lacking in the literature. We reviewed our mid-term data of this RYDS modification. To analyze the outcomes with SADI-S at 4 years. Data from patients who underwent a primary SADI-S procedure performed by three surgeons at a single institution from June 2013 through February 2018 were retrospectively reviewed. All revision bariatric surgeries were excluded. Regression analyses were performed for all follow-up weight loss data. There were 437 patients in our database. The pre-operative mean body mass index (BMI) was 49.8 ± 8.8 kg/m 2 . The 30-day complication rate was 7.7%. The 30-day readmission, reoperation, and mortality rates were 1.8, 1.3, and 0.2%, respectively. The long-term complication rate was 10.9%. Seventy-nine patients were 4 years post SADI-S surgery and follow-up was possible for 44 patients (55.7%). At 4 years, patients had an average change in BMI of 18.1 ± 6 units with an excess weight loss (EWL) of 85.7 ± 27.3%. At 4 years, 97.6% patients were able to maintain HbA1c < 6% with or without the use of diabetic medication. There was a statistically significant difference between most of the pre-operative and post-operative nutritional data. SADI-S is a safe and effective procedure in both short- and mid-term data points. Diabetes resolution and weight loss appear similar to traditional RYDS and better than RYGB.

Replacement of the ureter by an ileal loop. Quantitative aspects of long-term morphological alterations in minipigs.

PubMed

Pabst, R; Kamran, D

1983-06-01

In minipigs 1 ureter was replaced by a loop of the terminal ileum and the contralateral kidney removed. After 2.5 to 3 years the morphology of the replaced ureter was compared with the normal ileum. Independent of the 3 different operative techniques used, in about half of the pigs there was loss or flattening of the villi. In the other pigs the morphometrically determined number of intraepithelial lymphocytes, the cell density in the lamina propria and the length of the villi did not differ significantly compared with the normal ileum. There was no increase in goblet cells in the crypts. The transitional epithelium covered only a short distance at the anastomotic junctions. Peyer's patches of normal age-related size were found in the replaced ureter. Despite the long-term contact with urine instead of gut contents, in many pigs a normal amount of lymphocytes remained in the "ileal ureter".

In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers

PubMed Central

Li, Di; Ding, Jian Xun; Tang, Zhao Hui; Sun, Hai; Zhuang, Xiu Li; Xu, Jing Zhe; Chen, Xue Si

2012-01-01

Four monomethoxy poly(ethylene glycol)-poly(L-lactide-co-glycolide)2 (mPEG-P( LA-co-GA)2) copolymers were synthesized by ring-opening polymerization of L-lactide and glycolide with double hydroxyl functionalized mPEG (mPEG-(OH)2) as macroinitiator and stannous octoate as catalyst. The copolymers self-assembled into nanoscale micellar/vesicular aggregations in phosphate buffer at pH 7.4. Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into the micellar/vesicular nanoparticles, yielding micellar/vesicular nanomedicines. The in vitro release behaviors could be adjusted by content of hydrophobic polyester and pH of the release medium. In vitro cell experiments showed that the intracellular DOX release could be adjusted by content of P(LA-co-GA), and the nanomedicines displayed effective proliferation inhibition against Henrietta Lacks’s cells with different culture times. Hemolysis tests indicated that the copolymers were hemocompatible, and the presence of copolymers could reduce the hemolysis ratio of DOX significantly. These results suggested that the novel anticancer nanomedicines based on DOX and amphiphilic Y-shaped copolymers were attractive candidates as tumor tissular and intracellular targeting drug delivery systems in vivo, with enhanced stability during circulation and accelerated drug release at the target sites. PMID:22701317

Irrigation of continent catheterizable ileal pouches: tap water can replace sterile solutions because it is safe, easy, and economical.

PubMed

Birkhäuser, Frédéric D; Zehnder, Pascal; Roth, Beat; Schürch, Leander; Ochsner, Katharina; Willener, Rita; Thalmann, George N; Burkhard, Fiona C; Studer, Urs E

2011-04-01

Continent catheterizable ileal pouches require regular irrigations to reduce the risk of bacteriuria and urinary tract infections (UTIs). Our aim was to compare the UTI rate, patient friendliness, and costs of standard sterile irrigation versus irrigation with tap water. Twenty-three patients participated in a prospective randomized two-arm crossover single-center trial. Aseptic intermittent self-catheterization (ISC) combined with sterile sodium chloride (NaCl) 0.9% irrigation was compared with clean ISC and irrigation with tap water (H(2)O) during two study periods of 90 d each. Patients underwent daily pouch irrigations with NaCl 0.9% solution or tap water. Urine nitrite dipstick tests were evaluated daily; urine culture (UC) and patient friendliness were evaluated monthly. Costs were documented. A total of 3916 study days with nitrite testing and irrigation were analyzed, 1876 (48%) in the NaCl arm and 2040 (52%) in the H(2)O arm. In the NaCl arm, 418 study days (22%) with nitrite-positive dipsticks were recorded, 219 d (11%) in the H(2)O arm, significantly fewer (p=0.01). Of the 149 UCs, 96 (64%) were positive, 48 in each arm, revealing a total of 16 different germs. All patients preferred the H(2)O method. Monthly costs were up to 20 times lower in the H(2)O arm. Pouch irrigation with sterile NaCl 0.9% solution and tap water had comparable rates of positive UC. Irrigation with tap water significantly lowered the incidence of nitrite-positive study days and was substantially less costly and more patient friendly than NaCl irrigation. We therefore recommend the use of tap water (or bottled water) instead of sterile NaCl 0.9% solution for daily irrigation of continent catheterizable ileal pouches. Australian New Zealand Clinical Trials Registry, ACTRN12610000618055, http://www.ANZCTR.org.au/ACTRN12610000618055.aspx. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Blood-plasma separation in Y-shaped bifurcating microfluidic channels: A dissipative particle dynamics simulation study

PubMed Central

Li, Xuejin; Popel, Aleksander S.; Karniadakis, George Em

2012-01-01

The motion of a suspension of red blood cells (RBCs) flowing in a Y-shaped bifurcating microfluidic channel is investigated using a validated low-dimensional RBC (LD-RBC) model based on dissipative particle dynamics (DPD). Specifically, the RBC is represented as a closed torus-like ring of ten colloidal particles, which leads to efficient simulations of blood flow in microcirculation over a wide range of hematocrits. Adaptive no-slip wall boundary conditions were implemented to model hydrodynamic flow within a specific wall structure of diverging 3D microfluidic channels, paying attention to controlling density fluctuations. Plasma skimming and the all-or-nothing phenomenon of RBCs in a bifurcating microfluidic channel have been investigated in our simulations for healthy and diseased blood, including the size of cell-free layer on the daughter branches. The feed hematocrit level in the parent channel has considerable influence on blood-plasma separation. Compared to the blood-plasma separation efficiencies of healthy RBCs, malaria-infected stiff RBCs (iRBCs) have a tendency to travel into the low flowrate daughter branch because of their different initial distribution in the parent channel. Our simulation results are consistent with previously published experimental results and theoretical predictions. PMID:22476709

Pendant Allyl Crosslinking as a Tunable Shape Memory Actuator for Vascular Applications

PubMed Central

Zachman, Angela L.; Lee, Sue Hyun; Balikov, Daniel A.; Kim, Kwangho; Bellan, Leon M.; Sung, Hak-Joon

2015-01-01

Thermo-responsive shape memory polymers (SMPs) can be fit into small-bore incisions and recover their functional shape upon deployment in the body. This property is of significant interest for developing the next generation of minimally-invasive medical devices. To be used in such applications, SMPs should exhibit adequate mechanical strengths that minimize adverse compliance mismatch-induced host responses (e.g. thrombosis, hyperplasia), be biodegradable, and demonstrate switch-like shape recovery near body temperature with favorable biocompatibility. Combinatorial approaches are essential in optimizing SMP material properties for a particular application. In this study, a new class of thermo-responsive SMPs with pendant, photocrosslinkable allyl groups, x%poly( -caprolactone)-co-y%( -allyl carboxylate -caprolactone) (x%PCL-y%ACPCL), are created in a robust, facile manner with readily tunable material properties. Thermomechanical and shape memory properties can be drastically altered through subtle changes in allyl composition. Molecular weight and gel content can also be altered in this combinatorial format to fine-tune material properties. Materials exhibit high elastic, switch-like shape recovery near 37 °C. Endothelial compatibility is comparable to tissue culture polystyrene (TCPS) and 100%PCL in vitro and vascular compatibility is demonstrated in vivo in a murine model of hindlimb ischemia, indicating promising suitability for vascular applications. PMID:26072363

N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation

PubMed Central

Taut, F J H; Schmidt, H; Zapletal, C M; Thies, J C; Grube, C; Motsch, J; Klar, E; Martin, E

2001-01-01

In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P ≤ 0·02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment. PMID:11422213

Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT-2 pancreatic cancer mouse model

PubMed Central

Higuchi, Tamami; Yokobori, Takehiko; Naito, Tomoharu; Kakinuma, Chihaya; Hagiwara, Shinji; Nishiyama, Masahiko; Asao, Takayuki

2018-01-01

Prognosis of pancreatic cancer is poor, thus the development of novel therapeutic drugs is necessary. During preclinical studies, appropriate models are essential for evaluating drug efficacy. The present study sought to determine the ideal pancreatic cancer mouse model for reliable preclinical testing. Such a model could accurately reflect human pancreatic cancer phenotypes and predict future clinical trial results. Systemic pathology analysis was performed in an orthotopic transplantation model to prepare model mice for use in preclinical studies, mimicking the progress of human pancreatic cancer. The location and the timing of inoculated cancer cell metastases, pathogenesis and cause of fatality were analyzed. Furthermore, the efficacy of gemcitabine, a key pancreatic cancer drug, was evaluated in this model where liver metastasis and peritoneal dissemination occur. Results indicated that the SUIT-2 orthotopic pancreatic cancer model was similar to the phenotypic sequential progression of human pancreatic cancer, with extra-pancreatic invasion, intra-peritoneal dissemination and other hematogenous organ metastases. Notably, survival was prolonged by administering gemcitabine to mice with metastasized pancreatic cancer. Furthermore, the detailed effects of gemcitabine on the primary tumor and metastatic tumor lesions were pathologically evaluated in mice. The present study indicated the model accurately depicted pancreatic cancer development and metastasis. Furthermore, the detailed effects of pancreatic cancer drugs on the primary tumor and on metastatic tumor lesions. We present this model as a potential new standard for new drug development in pancreatic cancer. PMID:29435042

Risk factors for alcohol relapse following orthotopic liver transplantation: a systematic review.

PubMed

Rustad, James K; Stern, Theodore A; Prabhakar, Maithri; Musselman, Dominique

2015-01-01

Each year, 5000-6000 individuals undergo orthotopic liver transplantation (OLT) in the United States, and of these, nearly 18% have alcoholic liver disease. Relapse to alcohol occurs in more than 40% of patients with OLT for alcoholic liver disease. We sought to identify factors that predict relapse to alcohol or medication nonadherence following OLT in patients with alcoholic liver disease and to review what randomized clinical interventions have addressed these factors following OLT. Our hypothesis was that there would be factors before and after OLT that predict relapse to alcohol following OLT, and that these, if targeted, might improve sobriety and associated outcomes of adherence with medications and appointments. We performed a review (focusing on articles published since 2004) with PubMed and MEDLINE searches using the following search terms: liver transplantation, recidivism, alcohol relapse, and predictors of alcohol relapse. We supplemented the online searches with manual reviews of article reference lists and selected relevant articles for further review by author consensus. In largely white populations, prospective studies document that shorter length of pretransplantation sobriety is a significant predictor of time to first drink and time to binge use. Presence of psychiatric comorbidity, high score on standardized High-risk Alcoholism Relapse Scale, and diagnosis of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) alcohol dependence are predictive of posttransplantation alcohol relapse. Pretransplantation alcohol use history variables (e.g., family history of alcoholism) reliably discriminate between complete abstainers and those who drink, while medical and psychosocial characteristics at early post-liver transplantation period (e.g., more bodily pain) maximally discriminate patterns of alcohol use. Alcoholic individuals with early-onset, rapidly accelerating moderate use and early-onset, continuously increasing heavy use have

[Inhibitory effect of Xiaotan Sanjie Recipe on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice].

PubMed

Ye, Min; Sun, Da-Zhi; Wei, Pin-kang

2014-05-01

To study the inhibitory effect of Xiaotan Sanjie Recipe (XSR) on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice. The 3rd passage subcutaneous transplantation tumor was taken as the origin of the model by using MKN-45 human gastric cancer cell lines. MKN-45 human gastric cancer nude mouse model was established using OB glue adhesive method. Then 30 nude mice were divided into the model group, the XSR group, and the chemotherapy group. Mice in the XSR group were intragastrically given XSR at the daily dose of 0.4 mL. Mice in the chemotherapy group were intragastrically given Fluorouracil at the daily dose of 0.4 mL. No intervention was given to mice in the model group. After 6 weeks of medication, the tumor weight was measured, and the tumor inhibition rate calculated. The size, the peak height, and the peak area of 5 microsatellite instability sites were detected. The tumor inhibition rate was 40. 84% in the XSR group. The tumor weight was significantly lower in the XSR group than in the model group (P < 0.01), showing no statistical difference when compared with the chemotherapy group (P >0.05). The incidence of high microsatellite instability (MSI-H) in the model group was 70%, and the incidence of low microsatellite instability (MSI-L) was 30%. Microsatellite stable site tended be stable after 6 weeks of XSR treatment. XSR showed inhibition on microsatellite instable orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice.

The impact of the fecal stream and stasis on immunologic reactions in ileal pouch after restorative proctocolectomy for ulcerative colitis: a prospective, pilot study.

PubMed

Yamamoto, Takayuki; Umegae, Satoru; Kitagawa, Tatsushi; Matsumoto, Koichi

2005-10-01

The etiology of pouch inflammation after restorative proctocolectomy is unknown. The fecal stream and immunological reactions are potential pathological factors. This study was performed to examine the impact of the fecal stream and stasis on immunological reactions in the pouch. Patients who underwent a restorative proctocolectomy with a covering ileostomy for ulcerative colitis were studied. Mucosal biopsy specimens were obtained from both the pouch and the proximal ileum at the time of ileostomy closure, and 3, 6, and 12 months after ileostomy closure. As a control group, normal ileal biopsies were obtained from patients with colonic polyps. At the time of ileostomy closure, mucosal interleukin-1beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha levels in the pouch and the proximal ileum were not significantly different from those in the normal control group. At 3 months after ileostomy closure, the mucosal cytokine levels in the pouch increased significantly compared with those at ileostomy closure, and their levels were significantly higher than those in the proximal ileum. At 6 and 12 months after ileostomy closure, the mucosal cytokine levels in the pouch did not change significantly compared with those at 3 months after ileostomy closure. The mucosal cytokine levels in the proximal ileum did not change significantly during the entire study. The immunological reactions in the pouch occurred soon after ileostomy closure, and continued for at least 1 yr. The fecal stream and stasis play an important part in the pathogenesis of immunological reactions in the ileal pouch.

Studer orthotopic ileal bladder substitute construction - surgical technique and complication management: one-center and 12-year experience.

PubMed

Wyczółkowski, M; Juszczak, K; Rzepecki, M; Drewniak, T; Klima, W

2010-01-01

We have performed Studer neobladder creation in 61 patients (53 male and 8 female). The aims of this study were to evaluate the clinical outcomes, to review the surgical technique modification, postoperative complications management and metabolic disturbances. All patients were retrospectively studied and followed-up. The follow-up: 12 years to 2 months. 44 patients (41 male and 3 female) returned for a control visit. All completed IIQ-7 questionnaire. Continence was analysed. Kidney ultrasound, post void residual and uroflowmetry, blood tests (electrolytes, kidney markers, acid-base balance) were performed. All patients were divided into two groups: I (with Zuber mineral water intake) and group II (without Zuber mineral water intake) for acid-base balance analysis. Early complications occurred in 13.1% (enterocolitis, neobladder-urethral anastomosis leakage, pyelonephritis, and lymphorrhoea). Late complications occurred in 14.0% (stricture of the neobladder-urethra anastomosis, urosepsis secondarily to bilateral hydronephrosis, stone formation, and pyonephrosis). In the follow-up 88.6% of patients revealed normal continence. The nocturnal incontinence, nocturia, and external or indwelling catheter were reported in 9, 6 and 5 patients, respectively). In IIQ-7 the mean negative impact of continence level on patients quality of life was 10.08% ± 14.47%. The mean Qmax., Qave., post void residual were 15.8 ± 4.9 ml/s, 7.9 ± 3.0 ml/s, and 151.2 ± 139.2 ml, respectively. Patients who regularly intake the Zuber present significant decrease of BE deficiency as compared to patient without Zuber usage. The Studer neobladder is the alternative urinary diversion. This is the difficult, skill demanding procedure, nevertheless gaining experience with self modifications resulted in decrease of complications. The Zuber mineral water intake ameliorates the base excess deficiency after Studer creation.

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model.

PubMed

Fu, Yilong; Ong, Lai-Chun; Ranganath, Sudhir H; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K H; Wang, Chi-Hwa

2016-01-01

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model

PubMed Central

Ranganath, Sudhir H.; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K. H.; Wang, Chi-Hwa

2016-01-01

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. PMID:26844770

An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis.

PubMed

Paschall, Amy V; Liu, Kebin

2016-08-14

Metastasis is the primary cause of mortality of breast cancer patients. The mechanism underlying cancer cell metastasis, including breast cancer metastasis, is largely unknown and is a focus in cancer research. Various breast cancer spontaneous metastasis mouse models have been established. Here, we report a simplified procedure to establish orthotopic transplanted breast cancer primary tumor and resultant spontaneous metastasis that mimic human breast cancer metastasis. Combined with the bioluminescence live tumor imaging, this mouse model allows tumor growth and progression kinetics to be monitored and quantified. In this model, a low dose (1 x 10(4) cells) of 4T1-Luc breast cancer cells was injected into BALB/c mouse mammary fat pad using a tuberculin syringe. Mice were injected with luciferin and imaged at various time points using a bioluminescent imaging system. When the primary tumors grew to the size limit as in the IACUC-approved protocol (approximately 30 days), mice were anesthetized under constant flow of 2% isoflurane and oxygen. The tumor area was sterilized with 70% ethanol. The mouse skin around the tumor was excised to expose the tumor which was removed with a pair of sterile scissors. Removal of the primary tumor extends the survival of the 4T-1 tumor-bearing mice for one month. The mice were then repeatedly imaged for metastatic tumor spreading to distant organs. Therapeutic agents can be administered to suppress tumor metastasis at this point. This model is simple and yet sensitive in quantifying breast cancer cell growth in the primary site and progression kinetics to distant organs, and thus is an excellent model for studying breast cancer growth and progression, and for testing anti-metastasis therapeutic and immunotherapeutic agents in vivo.

Sodium-reduced continuous venovenous hemodiafiltration (CVVHDF) for the prevention of central pontine myelinolysis (CPM) in hyponatremic patients scheduled for orthotopic liver transplantation.

PubMed

Lenk, Marcus R; Kaspar, Michael

2012-08-01

Two patients in end-stage hepatic failure presented for orthotopic liver transplantation with longstanding severe hyponatremia (121 and 122 mmol/L). Both patients underwent liver transplantation with the concomitant use of continuous venovenous hemodiafiltration. Replacement and dialysate solutions were prepared individually to contain a sodium level that was individually considered safe with regard to the development of central pontine myelinolysis. The sodium increase in both patients was within the expected and planned limits despite a situation of mass transfusion. Both patients did well postoperatively and neither patient suffered neurological deficits. Copyright © 2012 Elsevier Inc. All rights reserved.

In Vitro and In Vivo Comparison of Gemcitabine and the Gemcitabine Analog 1-(2′-deoxy-2′-fluoroarabinofuranosyl) Cytosine (FAC) in Human Orthotopic and Genetically Modified Mouse Pancreatic Cancer Models

PubMed Central

Russell, James; Pillarsetty, Nagavarakishore; Kramer, Robin M; Romesser, Paul B; Desai, Pooja; Haimovitz-Friedman, Adriana; Lowery, Maeve A; Humm, John L

2017-01-01

Purpose Although gemcitabine is a mainstay of pancreatic cancer therapy, it is only moderately effective, and it would be desirable to measure drug uptake in patients. 1-(2′-deoxy-2′-fluoroarabinofuranosyl) cytosine (FAC), is an analog of gemcitabine, and when labeled with F-18, it may be a potential surrogate PET tracer for the drug. Procedures [18F]FAC was synthesized to a radiochemical purity of >96 %. The human tumor lines AsPC1, BxPC3, Capan-1, Panc1, and MiaPaca2 were grown orthotopically in nude mice. KPC mice that conditionally express oncogenic K-ras and p53 mutations in pancreatic tissue were also used. The intra-tumoral distributions of [14C]gemcitabine and [18F]FAC were mapped with autoradiography. The inter-tumor correlation between [14C]gemcitabine and [18F]FAC was established in the orthotopic tumors. Expression of the equilibrative and concentrative nucleoside transporters (ENT, CNT) in vitro was detected by western blotting. Drug uptake was characterized in vitro using [3H]gemcitabine and the effect of transporter inhibition on gemcitabine and FAC uptake was investigated. The relative affinity of cells for gemcitabine and FAC was tested in competition assays. The cell lines differed in sensitivity to transport inhibitors and in competition studies. There was a good in vivo correlation between the total uptake of [18F]FAC and [14C]gemcitabine, measured across all orthotopic tumors. Using the KPC and BxPC3 models, we found that [14C]gemcitabine and [18F]FAC were largely co-localized. Conclusions In the lines examined here, [18F]FAC uptake correlates well with gemcitabine in vivo, supporting the notion that [18F]FAC can serve as a PET radiotracer surrogate to determine the uptake and distribution of gemcitabine within pancreatic tumors. PMID:28349292

Unusual binding of ursodeoxycholic acid to ileal bile acid binding protein: role in activation of FXRα[S

PubMed Central

Fang, Changming; Filipp, Fabian V.; Smith, Jeffrey W.

2012-01-01

Ursodeoxycholic acid (UDCA, ursodiol) is used to prevent damage to the liver in patients with primary biliary cirrhosis. The drug also prevents the progression of colorectal cancer and the recurrence of high-grade colonic dysplasia. However, the molecular mechanism by which UDCA elicits its beneficial effects is not entirely understood. The aim of this study was to determine whether ileal bile acid binding protein (IBABP) has a role in mediating the effects of UDCA. We find that UDCA binds to a single site on IBABP and increases the affinity for major human bile acids at a second binding site. As UDCA occupies one of the bile acid binding sites on IBABP, it reduces the cooperative binding that is often observed for the major human bile acids. Furthermore, IBABP is necessary for the full activation of farnesoid X receptor α (FXRα) by bile acids, including UDCA. These observations suggest that IBABP may have a role in mediating some of the intestinal effects of UDCA. PMID:22223860

Duodenal and ileal glucose infusions differentially alter gastrointestinal peptides, appetite response, and food intake: a tube feeding study.

PubMed

Poppitt, Sally D; Shin, Hyun Sang; McGill, Anne-Thea; Budgett, Stephanie C; Lo, Kim; Pahl, Malcolm; Duxfield, Janice; Lane, Mark; Ingram, John R

2017-09-01

Background: Activation of the ileal brake through the delivery of nutrients into the distal small intestine to promote satiety and suppress food intake provides a new target for weight loss. Evidence is limited, with support from naso-ileal lipid infusion studies. Objective: The objective of the study was to investigate whether glucose infused into the duodenum and ileum differentially alters appetite response, food intake, and secretion of satiety-related gastrointestinal peptides. Design: Fourteen healthy male participants were randomly assigned to a blinded 4-treatment crossover, with each treatment of single-day duration. On the day before the intervention (day 0), a 380-cm multilumen tube (1.75-mm diameter) with independent port access to the duodenum and ileum was inserted, and position was confirmed by X-ray. Subsequently (days 1-4), a standardized breakfast meal was followed midmorning by a 90-min infusion of isotonic glucose (15 g, 235 kJ) or saline to the duodenum or ileum. Appetite ratings were assessed with the use of visual analog scales (VASs), blood samples collected, and ad libitum energy intake (EI) measured at lunch, afternoon snack, and dinner. Results: Thirteen participants completed the 4 infusion days. There was a significant effect of nutrient infused and site (treatment × time, P < 0.05) such that glucose-to-ileum altered VAS-rated fullness, satisfaction, and thoughts of food compared with saline-to-ileum (Tukey's post hoc, P < 0.05); decreased ad libitum EI at lunch compared with glucose-to-duodenum [-22%, -988 ± 379 kJ (mean ± SEM), Tukey's post hoc, P < 0.05]; and increased glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) compared with all other treatments (Tukey's post hoc, P < 0.05). Conclusions: Macronutrient delivery to the proximal and distal small intestine elicits different outcomes. Glucose infusion to the ileum increased GLP-1 and PYY secretion, suppressed aspects of VAS-rated appetite, and decreased ad libitum EI at a

Micro-positron emission tomography/contrast-enhanced computed tomography imaging of orthotopic pancreatic tumor-bearing mice using the αvβ₃ integrin tracer ⁶⁴Cu-labeled cyclam-RAFT-c(-RGDfK-)₄.

PubMed

Aung, Winn; Jin, Zhao-Hui; Furukawa, Takako; Claron, Michael; Boturyn, Didier; Sogawa, Chizuru; Tsuji, Atsushi B; Wakizaka, Hidekatsu; Fukumura, Toshimitsu; Fujibayashi, Yasuhisa; Dumy, Pascal; Saga, Tsuneo

2013-09-01

The purpose of this study was to develop a clinically relevant orthotopic xenotransplantation model of pancreatic cancer and to perform a preclinical evaluation of a new positron emission tomography (PET) imaging probe, ⁶⁴Cu-labeled cyclam-RAFT-c(-RGDfK-)₄ peptide (⁶⁴Cu-RAFT-RGD), using this model. Varying degrees of αvβ₃ integrin expression in several human pancreatic cancer cell lines were examined by flow cytometry and Western blotting. The cell line BxPC-3, which is stably transfected with a red fluorescence protein (RFP), was used for surgical orthotopic implantation. Orthotopic xenograft was established in the pancreas of recipient nude mice. An in vivo probe biodistribution and receptor blocking study, preclinical PET imaging coregistered with contrast-enhanced computed tomography (CECT) comparing ⁶⁴Cu-RAFT-RGD and ¹⁸F-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) accumulation in tumor, postimaging autoradiography, and histologic and immunohistochemical examinations were done. Biodistribution evaluation with a blocking study confirmed that efficient binding of probe to tumor is highly αvβ₃ integrin specific. ⁶⁴Cu-RAFT-RGD PET combined with CECT provided for precise and easy detection of cancer lesions. Autoradiography, histologic, and immunohistochemical examinations confirmed the accumulation of ⁶⁴Cu-RAFT-RGD in tumor versus nontumor tissues. In comparative PET studies, ⁶⁴Cu-RAFT-RGD accumulation provided better tumor contrast to background than ¹⁸F-FDG. Our results suggest that ⁶⁴Cu-RAFT-RGD PET imaging is potentially applicable for the diagnosis of αvβ₃ integrin-expressing pancreatic tumors.

Female sexual function and fertility after ileal pouch-anal anastomosis.

PubMed

Hor, Thevy; Lefevre, Jeremie H; Shields, Conor; Chafai, Najim; Tiret, Emmanuel; Parc, Yann

2016-03-01

A potential complication in women after ileal pouch-anal anastomosis (IPAA) is sexual impairment and reduced fertility. The aim was to evaluate sexual function and fertility after IPAA. All female patients who underwent an IPAA between 2004 and 2013 were retrospectively included. Sexual function, fertility, and continence were explored by the female sexual function index (FSFI), telephonic interview, and Wexner's score. Among 127 women included, 93 responded to the questionnaires (73.2%). Seventy five were sexually active, and 48 (64%) had normal sexual function (FSFI > 26). In univariate analysis, there was a significant relationship between ulcerative colitis (p = 0.0161), age > 40 years (p = 0.01311), number of bowel movements (p = 0.0238), nocturnal pouch activity (p = 0.0094), use of loperamide (p = 0.0283), and existence of sexual dysfunction. After multivariate analysis, age and nocturnal pouch activity were associated with a worse sexual function (p = 0.0235, OR = 3.3 (1.2-9.9) and p = 0.0094, OR = 4.1 (1.4-13.5)). Of 16 patients who wished to have children, 10 (63%) became pregnant without recourse to in vitro fertilization, of whom 3 had two or more pregnancies. In total, there were 13 children born after IPAA. The mean time between the first pregnancy and surgery was 24.8 ± 22 months. At 12 and 24 months after cessation of contraception, 57 and 67% had at least one pregnancy. While sexual function is impaired in a limited number of patients, the impact of surgery can be regarded as modest. Age and nocturnal pouch activity were some independent factors of worse sexual function. The risk of infertility should not preclude consideration of IPAA as a treatment option.

[Effects of Rhizoma kaempferiae volatile oil on tumor growth and cell cycle of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice].

PubMed

Xiao, Yan; Wei, Pin-Kang; Li, Jun; Shi, Jun; Yu, Zhi-Hong; Lin, Hui-Ming

2006-07-01

To evaluate the effects of Rhizoma kaempferiae volatile oil on tumor growth and cell cycle of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice. One hundred and five nude mice orthotopically transplanted with MKN-45 human gastric cancer cells were randomly divided into seven groups: untreated group, normal saline-treated group, dissolvant-treated group, cyclophosphamide (CTX)-treated group and high-, medium-, and low-dose Rhizoma kaempferiae volatile oil-treated groups. Corresponding interventions were implemented in each group except the untreated group. The antitumor effects in vivo were evaluated. Cell cycle distribution and apoptosis of MKN-45 human gastric cancer cells were determined by using flow cytometry (FCM). The ultrastructure of MKN-45 gastric cancer cells was observed by a transmission electron microscope. In the high-, medium-, and low-dose Rhizoma kaempferiae volatile oil-treated groups, the growth inhibition rates of gastric cancer were 57.2%, 28.0% and 5.0% respectively, and the gastric cancer cells were arrested at G(0)/G(1) phase. This antitumor effect was dose-dependent. The apoptotic cells occurred more frequently in the high-dose Rhizoma kaempferiae volatile oil-treated group and the CTX-treated group than those in the medium- and low-dose Rhizoma kaempferiae volatile oil-treated groups. The Rhizoma kaempferiae volatile oil is an effective composition for growth inhibition of gastric cancer, and its mechanism may be related to regulating the cell cycle and inducing apoptosis.

Structure of IgG and IgY molecules in ribosome-antibody complexes as studied by electron microscopy.

PubMed

Noll, F; Lutsch, G; Bielka, H

1982-03-01

The overall shape and dimensions of IgG (rabbit) and IgY (chicken) antibodies against ribosomal proteins have been studied in electron micrographs of ribosome-antibody complexes. The antibodies appear as Y-shaped molecules with an angle of about 90 degrees between their Fab arms. The length of one Fab arm amounts to about 10 nm. No differences between the IgG and IgY molecules could be detected electron microscopically. The data obtained on the shape of IgG and IgY correlate with those of earlier electron microscopic studies while the determined size of the Fab arms is in the range found by scattering methods.

Isoflurane: An Ideal Anesthetic for Rodent Orthotopic Liver Transplantation Surgery?

PubMed

Cao, D; Liu, Y; Li, J; Gong, J

2016-10-01

Because the choice of anesthetic affects the rodent orthotopic liver transplantation (OLT) model, we compared the effects of isoflurane, ketamine, chloral hydrate, and pentobarbital on the OLT model. OLT was performed using the two-cuff technique. Two hundred male rats were randomly divided into five groups: control, isoflurane, ketamine, chloral hydrate, and pentobarbital groups. Rectal temperatures, respiratory rates, arterial blood values (pH, PaCO 2 , PaO 2 , and SatO 2 ), liver function tests and histopathology, recovery times, and anhepatic stage mortality rates were assessed. Compared with controls, respiratory rates decreased by 20% in the isoflurane group, and decreased by 40%-50% in the ketamine, chloral hydrate, and pentobarbital groups. The PaO 2 , SatO 2 , and pH levels in the ketamine, chloral hydrate, and pentobarbital groups were significantly lower than those in the isoflurane and control groups (P < .05). Only the pentobarbital group displayed significant liver histopathologic changes along with significantly higher levels of serum alanine aminotransferase and total bilirubin, but a significantly lower level of serum albumin, compared with the control group (P < .05). The isoflurane group had a 0% anhepatic stage mortality rate compared with rates of 30%-40% in the other anesthetic groups. Isoflurane should be the preferred anesthetic for rodent OLT surgery due to its minimal respiratory and hepatic physiological effects as well as its low anhepatic phase mortality rate. Secondary to isoflurane, ketamine and chloral hydrate may be administered as donor anesthetics. Pentobarbital use should be avoided entirely in rodent OLT surgery due to its significant hepatotoxic effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlation between urodynamic function and 3D cat scan anatomy in neobladders: does it exist?

PubMed

Crivellaro, S; Mami, E; Wald, C; Smith, J J; Kocjancic, E; Stoffel, J; Bresette, J; Libertino, J A

2009-01-01

We compared the functional and anatomical differences among three different orthotopic neobladders, utilizing video urodynamics and 3D CT to determine what parameters, if any, correlate to function. Thirty-four patients were able to participate in the evaluation of their neobladder by 3D CT and video urodynamics. Three different orthotopic neobladders were identified (12 ileal, 7 ileocecal, 15 sigmoid). Multiple measurements, observations and functional data have been obtained. Statistical analysis for this study employed a linear regression test and an odds ratio calculation (using StatSoft V. 5.1). In comparing three different neobladders, no significant differences were noted. Looking at the entire population, the following association was statistically significant in linear correlation: the maximal capacity and the neobladder volume; the pressure at the maximal capacity and the distance from the symphysis, the pressure at maximal flow and both the distance from the symphysis and the thickness of the neobladder. The distance from the left femoral head was directly correlated with the post void residual and inversely correlated with the maximal flow. The Odds ratio calculation revealed (with significant P < 0.05) that the further the center of the neobladder is from the right femoral head, the higher risk of incontinence. The study seems to show no significant anatomical or functional difference among the three different types of neobladders. A possible correlation between the position of the neobladder and urinary incontinence is suggested, recognizing further study in a larger population is required.

Novel model of orthotopic U-87 MG glioblastoma resection in athymic nude mice.

PubMed

Bianco, John; Bastiancich, Chiara; Joudiou, Nicolas; Gallez, Bernard; des Rieux, Anne; Danhier, Fabienne

2017-06-01

In vitro and in vivo models of experimental glioma are useful tools to gain a better understanding of glioblastoma (GBM) and to investigate novel treatment strategies. However, the majority of preclinical models focus on treating solid intracranial tumours, despite surgical resection being the mainstay in the standard care of patients with GBM today. The lack of resection and recurrence models therefore has undermined efforts in finding a treatment for this disease. Here we present a novel orthotopic tumour resection and recurrence model that has potential for the investigation of local delivery strategies in the treatment of GBM. The model presented is simple to achieve through the use of a biopsy punch, is reproducible, does not require specific or expensive equipment, and results in a resection cavity suitable for local drug delivery systems, such as the implantation or injection of hydrogels. We show that tumour resection is well tolerated, does not induce deleterious neurological deficits, and significantly prolongs survival of mice bearing U-87 MG GBM tumours. In addition, the resulting cavity could accommodate adequate amounts of hydrogels for local delivery of chemotherapeutic agents to eliminate residual tumour cells that can induce tumour recurrence. Copyright © 2017 Elsevier B.V. All rights reserved.

Liquid mixing enhanced by pulse width modulation in a Y-shaped jet configuration

NASA Astrophysics Data System (ADS)

Xia, Qingfeng; Zhong, Shan

2013-04-01

In this paper, mixing between two fluid streams, which are injected into a planar mixing channel via a Y-shaped confluence section at the same volume flow rate, is studied experimentally. The injection of the two fluid streams is controlled by two separate solenoid valves, which are operated with a phase difference of 180°, using pulse width modulation. The experiments are conducted using water at a mean Reynolds number between 83 and 250, a range of pulsation frequencies and two duty cycles (25 and 50%). Both particle-image velocimetry and planar laser-induced fluorescence technique are used to visualize the flow patterns and to quantify the mixing degree in the mixing channel. This experiment shows that the pulsation of each jet produces vortical structures, which promotes mixing via vortex entrainment and vortex breakup, and at the same time the mixing is also greatly enhanced by sequential segmentation produced by a 180° out-of-phase pulsation of the two jets. This mixing enhancement method is effective at a Reynolds number greater than 125 with a mixing degree of 0.9 being achieved. For the Reynolds numbers studied in the present experiments, an optimal frequency exists, which corresponds to a Strouhal number in the range of 0.5-2. Furthermore, at a given mean Reynolds number a lower duty cycle is found to produce a better mixing due to the resultant higher instantaneous Reynolds number in the jet flow. It is also found that pulsation of only one jet can produce a similar mixing effect.

Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

PubMed

Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

2018-04-02

Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The role of the AMOP domain in MUC4/Y-promoted tumour angiogenesis and metastasis in pancreatic cancer.

PubMed

Tang, Jie; Zhu, Yi; Xie, Kunling; Zhang, Xiaoyu; Zhi, Xiaofei; Wang, Weizhi; Li, Zheng; Zhang, Qun; Wang, Linjun; Wang, Jiwei; Xu, Zekuan

2016-06-10

MUC4 is a high molecular weight membrane protein that is overexpressed in pancreatic cancer (PC) and is associated with the development and progression of this disease. However, the exact mechanisms through which MUC4 domains promote these biological processes have rarely been studied, partly because of its high molecular weight, difficulty to overexpress it. Here, we use MUC4/Y, one of the MUC4 transcript variants, as a model molecule to investigate the AMOP-domain of MUC4(MUC/Y). We used cell proliferation, migration, invasion and tube formation assays in vitro to explore the abilities of AMOP domain in PC. In vivo, the matrigel plug assay, orthotopic implantation and Kaplan-Meier survival curves were used to check the results we observed in vitro. Finally, we discovered the underlying mechanism through western blot and immunofluorescence. We found that MUC4/Y overexpression could enhance the angiogenic and metastatic properties of PC cells, both in vitro and in vivo. However, the deletion of AMOP domain could cutback these phenomena. Additionally, Kaplan-Meier survival curves showed that mice injected with MUC4/Y overexpressed cells had shorter survival time, compared with empty-vector-transfected cells (MUC4/Y-EV), or cells expressing MUC4/Y without the AMOP domain (MUC4/Y-AMOP(△)). Our data also showed that overexpression of MUC4/Y could activate NOTCH3 signaling, increasing the expression of downstream genes: VEGF-A, MMP-9 and ANG-2. The AMOP domain had an important role in MUC4/Y (MUC4)-mediated tumour angiogenesis and metastasis of PC cells; and the NOTCH3 signaling was involved. These findings provided new insights into PC therapies. Our study also supplies a new method to study other high molecular membrane proteins.

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model.

PubMed

Huang, Feng-Yun J; Lee, Te-Wei; Chang, Chih-Hsien; Chen, Liang-Cheng; Hsu, Wei-Hsin; Chang, Chien-Wen; Lo, Jem-Mau

2015-01-01

In this study, the (188)Re-labeled PEGylated nanoliposome ((188)Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. The reporter cell line, F98(luc) was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of (188)Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered (188)Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the (188)Re-liposome-treated rats. By using bioluminescent imaging, the well-established reporter cell line (F98(luc)) showed a high relationship between cell number and its bioluminescent intensity (R(2)=0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of (188)Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the (188)Re-liposome-treated group than the control group (P<0.05). As a result, the lifespan of glioma-bearing rats treated with (188)Re-liposome was prolonged 10.67% compared to the control group. The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting (188)Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma

Ovarian Tumor-Stroma Interactions in an In Vivo Orthotopic Model

DTIC Science & Technology

2012-08-01

32. 7. Zheng X, Cui XX, Avila GE, Huang MT, Liu Y, Patel J, Kong AN, Paulino R, Shih WJ, Lin Y, Rabson AB, Reddy BS, Conney AH. Atorvastatin and...Shih WJ, Huang MT, Liu Y, Rabson A, Reddy B, Yang CS, Conney AH. Atorvastatin and celecoxib in combination inhibits the progression of androgen

Establishment and characterization of in vivo orthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice.

PubMed

Marques da Costa, Maria Eugenia; Daudigeos-Dubus, Estelle; Gomez-Brouchet, Anne; Bawa, Olivia; Rouffiac, Valerie; Serra, Massimo; Scotlandi, Katia; Santos, Conceição; Geoerger, Birgit; Gaspar, Nathalie

2018-03-01

Osteosarcoma is one of the most common primary bone tumors in childhood and adolescence. Metastases occurrence at diagnosis or during disease evolution is the main therapeutic challenge. New drug evaluation to improve patient survival requires the development of various preclinical models mimicking at best the complexity of the disease and its metastatic potential. We describe here the development and characteristics of two orthotopic bioluminescent (Luc/mKate2) cell-derived xenograft (CDX) models, Saos-2-B-Luc/mKate2-CDX and HOS-Luc/mKate2-CDX, in different immune (nude and NSG mouse strains) and bone (intratibial and paratibial with periosteum activation) contexts. IVIS SpectrumCT system allowed both longitudinal computed tomography (CT) and bioluminescence real-time follow-up of primary tumor growth and metastatic spread, which was confirmed by histology. The murine immune context influenced tumor engraftment, primary tumor growth, and metastatic spread to lungs, bone, and spleen (an unusual localization in humans). Engraftment in NSG mice was found superior to that found in nude mice and intratibial bone environment more favorable to engraftment compared to paratibial injection. The genetic background of the two CDX models also led to distinct primary tumor behavior observed on CT scan. Saos-2-B-Luc/mKate2-CDX showed osteocondensed, HOS-Luc/mKate2-CDX osteolytic morphology. Bioluminescence defined a faster growth of the primary tumor and metastases in Saos-2-B-Luc/mKate2-CDX than in HOS-Luc/mKate2-CDX. The early detection of primary tumor growth and metastatic spread by bioluminescence allows an improved exploration of osteosarcoma disease at tumor progression, and metastatic spread, as well as the evaluations of anticancer treatments. Our orthotopic models with metastatic spread bring complementary information to other types of existing osteosarcoma models. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth

PubMed Central

WANG, TING-AN; ZHANG, XIAO-DONG; GUO, XING-YU; XIAN, SHU-LIN; LU, YUN-FEI

2016-01-01

Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT. PMID:26708213

3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

PubMed

Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

2016-03-01

Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT.

Curative potential of GM-CSF-secreting tumor cell vaccines on established orthotopic liver tumors: mechanisms for the superior antitumor activity of live tumor cell vaccines.

PubMed

Tai, Kuo-Feng; Chen, Ding-Shinn; Hwang, Lih-Hwa

2004-01-01

In preclinical studies, tumor cells genetically engineered to secrete cytokines, hereafter referred to as tumor cell vaccines, can often generate systemic antitumor immunity. This study investigated the therapeutic effects of live or irradiated tumor cell vaccines that secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) on established orthotopic liver tumors. Experimental results indicated that two doses (3 x 10(7) cells per dose) of irradiated tumor cell vaccines were therapeutically ineffective, whereas one dose (3 x 10(6) cells) of live tumor cell vaccines caused complete tumor regression. In vivo depletion of CD8+ T cells, but not natural killer cells, restored tumor formation in the live vaccine-treated animals. Additionally, the treatment of cells with live vaccine induced markedly higher levels of cytotoxic T lymphocyte activity than the irradiated vaccines in the draining lymph nodes. The higher levels of cytokine and antigen loads could partly explain the superior antitumor activity of live tumor cell vaccines, but other unidentified mechanisms could also play a role in the early T cell activation in the lymph nodes. A protocol using multiple and higher dosages of irradiated tumor cell vaccines also caused significant regression of liver tumors. These results suggest that the GM-CSF-secreting tumor cell vaccines are highly promising for orthotopic liver tumors if higher levels of immune responses are elicited during early tumor development. Copyright 2004 National Science Council, ROC and S. Karger AG, Basel

Enhanced detection of intracellular organism of swine proliferative enteritis, ileal symbiont intracellularis, in feces by polymerase chain reaction.

PubMed Central

Jones, G F; Ward, G E; Murtaugh, M P; Lin, G; Gebhart, C J

1993-01-01

A sensitive assay based on amplification of a 319-bp DNA fragment of the intracellular bacterium of swine proliferative enteritis was developed for the detection of the organism in the feces of swine. A vernacular name, ileal symbiont intracellularis (IS-intracellularis), has recently been published for the intracellular bacterium, which was formerly known as a Campylobacter-like organism (C.J. Gebhart, S.M. Barnes, S. McOrist, G.F. Lin, and G.H.K. Larson, Int. J. Syst. Bacteriol. 43:533-538, 1993). As few as 10(1) IS-intracellularis organisms purified from intestinal mucosa, or 10(3) IS-intracellularis per g of feces, were detected. No amplification product was produced from a polymerase chain reaction performed on DNA extracted from the feces of healthy pigs. A 319-bp DNA fragment specific for IS-intracellularis was produced on amplification of DNA from the feces of pigs with experimental and naturally occurring proliferative enteritis. Images PMID:8253956

Ileal metastasis of breast cancer in a patient with a BRCA2 gene mutation: report of a case.

PubMed

Cho, Dong Hui; Jeon, Young San; Choi, Min-Young; Lee, Se Kyung; Kim, Sang Min; Hur, Sung Mo; Koo, Min Young; Bae, Soo Youn; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo; Nam, Seok Jin; Yang, Jung-Hyun; Lee, Jeong Eon

2011-12-01

Breast cancer is the most common malignancy in females. Common sites of metastases include the liver, lung, bone, and brain, while metastases to the extrahepatic digestive system are very rare. This report presents a patient diagnosed with breast carcinoma metastasis in the terminal ileum. The patient underwent breast-conserving surgery on both breasts because of breast cancer at the age of 46 years. Both breast cancers were consistent with stage I invasive ductal carcinomas. Colonoscopy during an investigation for hematochezia revealed a 2-cm ulceration in the terminal ileum 22 months later, and microscopic examination of a biopsy specimen of the ulceration revealed a poorly differentiated mass that was strongly suggestive of metastatic adenocarcinoma with endolymphatic tumor emboli. She underwent hand-assisted laparoscopic ileocecectomy because of ileal metastasis. She had a family history of breast cancer (sister) and colon cancer (brother). She exhibited HER2/neu discordance and carried the BRCA2 gene mutation. Surgeons should remain aware that breast cancer can metastasize to the gastrointestinal tract.

Symptomatic osteonecrosis of the femoral head after adult orthotopic liver transplantation.

PubMed

Li, Hua; Zhang, Jian; He, Ji-Wen; Wang, Kun; Wang, Gen-Shu; Jiang, Nan; Fu, Bin-Sheng; Wang, Guo-Ying; Yang, Yang; Chen, Gui-Hua

2012-07-01

With the increase of survival in liver transplantation recipients, more patients are at a high risk of developing osteonecrosis, especially in the femoral head, due to immunosuppressive treatment. The purpose of this study was to report the incidence, possible risk factors, and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China. A retrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008. The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months. The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported. The incidence of ONFH was 1.33% in patients after OLT. ONFH occurred at a mean of (14 ± 6) months (range, 10 - 21 months) after transplantation. Male patients more often presented with osteonecrosis as a complication than female patients. The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH. Patients were treated either pharmacologically or surgically. All patients showed a nice curative effect without major complications during the 18 - 63 months post-treatment follow up. The symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.

The effects and mechanism of action of methane on ileal motor function.

PubMed

Park, Y M; Lee, Y J; Hussain, Z; Lee, Y H; Park, H

2017-09-01

Methane has been associated with constipation-predominant irritable bowel syndrome, slowing intestinal transit time by augmenting contractile activity. However, the precise mechanism underlying this effect remains unclear. Therefore, we investigated the mechanisms underlying the effect of methane on contractile activity, and whether such effects are mediated by nerve impulses or muscular contraction. We connected guinea pig ileal muscle strips to a force/tension transducer and measured amplitudes of contraction in response to electrical field stimulation (EFS; 1, 2, 8, 16 Hz) following methane infusion in the presence of tetradotoxin (TTX), atropine, guanethidine, or GR 113808. We then performed calcium imaging using Oregon Green 488 BAPTA-1 AM in order to visualize changes in calcium fluorescence in response to EFS following methane infusion in the presence of TTX, atropine, or a high K + solution. Methane significantly increased amplitudes of contraction (P<.05), while treatment with TTX abolished such contraction. Methane-induced increases in amplitude were inhibited when lower-frequency (1, 2 Hz) EFS was applied following atropine infusion (P<.05). Neither guanethidine nor GR 113808 significantly altered contraction amplitudes. Methane significantly increased calcium fluorescence, while this increase was attenuated following atropine infusion (P<.05). Although calcium fluorescence was increased by the high K + solution under pretreatment with TTX, the intensity of fluorescence remained unchanged after methane infusion. The actions of methane on the intestine are influenced by the cholinergic pathway of the enteric nervous system. Our findings support the classification of methane as a gasotransmitter. © 2017 John Wiley & Sons Ltd.

High strength, light weight Ti-Y composites and method of making same

DOEpatents

Verhoeven, John D.; Ellis, Timothy W.; Russell, Alan M.; Jones, Lawrence L.

1993-04-06

A high strength, light weight "in-situ" Ti-Y composite is produced by deformation processing a cast body having Ti and Y phase components distributed therein. The composite comprises elongated, ribbon-shaped Ti and Y phase components aligned along an axis of the deformed body.

High strength, light weight Ti-Y composites and method of making same

DOEpatents

Verhoeven, J.D.; Ellis, T.W.; Russell, A.M.; Jones, L.L.

1993-04-06

A high strength, light weight in-situ'' Ti-Y composite is produced by deformation processing a cast body having Ti and Y phase components distributed therein. The composite comprises elongated, ribbon-shaped Ti and Y phase components aligned along an axis of the deformed body.

Tumor-Targeting Salmonella typhimurium A1-R Promotes Tumoricidal CD8+ T Cell Tumor Infiltration and Arrests Growth and Metastasis in a Syngeneic Pancreatic-Cancer Orthotopic Mouse Model.

PubMed

Murakami, Takashi; Hiroshima, Yukihiko; Zhang, Yong; Zhao, Ming; Kiyuna, Tasuku; Hwang, Ho Kyoung; Miyake, Kentaro; Homma, Yuki; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Ichikawa, Yasushi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2018-01-01

The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8 + tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic-cancer orthotopic mouse model. The effect of tumor-targeting S. typhimurium A1-R on CD8 + TILs was determined on the Pan02 murine pancreatic-adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n = 8); and G2: S. typhimurium A1-R-treatment group (n = 8, 1 × 10 7 colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor-volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1-R-treated group (G2) (3.0 ± 2.8) than the untreated control (G1) (39.9 ± 30.7, P < 0.01). Hematoxylin and easin (H&E) staining on tumor sections was performed to evaluate tumor destruction which was classified according to the Evans grading system and found to be much greater in the S. typhimurium A1-R-treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P < 0.01). Immunohistochemical staining with anti-mouse CD8 + antibody was performed in order to detect TILs determined by calculating the average number of CD8 + cells in three high power fields (200×) in the treated and untreated tumors. The TIL score was significantly higher in G2 (133.5 ± 32.2) than G1 (45.1 ± 19.4, P < 0.001). The present study demonstrates that S. typhimurium A1-R promotes CD8 + T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634-639, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Alendronate decreases orthotopic PC-3 prostate tumor growth and metastasis to prostate-draining lymph nodes in nude mice

PubMed Central

Tuomela, Johanna M; Valta, Maija P; Väänänen, Kalervo; Härkönen, Pirkko L

2008-01-01

Background Metastatic prostate cancer is associated with a high morbidity and mortality but the spreading mechanisms are still poorly understood. The aminobisphosphonate alendronate, used to reduce bone loss, has also been shown to inhibit the invasion and migration of prostate cancer cells in vitro. We used a modified orthotopic PC-3 nude mouse tumor model of human prostate cancer to study whether alendronate affects prostate tumor growth and metastasis. Methods PC-3 cells (5 × 105) were implanted in the prostates of nude mice and the mice were treated with alendronate (0.5 mg/kg/day in PBS, s.c.) or vehicle for 4 weeks. After sacrifice, the sizes of tumor-bearing prostates were measured and the tumors and prostate-draining regional iliac and sacral lymph nodes were excised for studies on markers of proliferation, apoptosis, angiogenesis and lymphangiogenesis, using histomorphometry and immunohistochemistry. Results Tumor occurrence in the prostate was 73% in the alendronate-treated group and 81% in the control group. Mean tumor size (218 mm3, range: 96–485 mm3, n = 11) in the alendronate-treated mice was 41% of that in the control mice (513 mm3, range: 209–1350 mm3, n = 13) (p < 0.05). In the iliac and sacral lymph nodes of alendronate-treated mice, the proportion of metastatic area was only about 10% of that in control mice (p < 0.001). Immunohistochemical staining of tumor sections showed that alendronate treatment caused a marked decrease in the number of CD34-positive endothelial cells in tumors (p < 0.001) and an increase in that of ISEL positive apoptotic cells in tumors as well as in lymph node metastases (p < 0.05) compared with those in the vehicle-treated mice. The density of m-LYVE-1-stained lymphatic capillaries was not changed. Conclusion Our results demonstrate that alendronate treatment opposes growth of orthotopic PC-3 tumors and decreases tumor metastasis to prostate-draining lymph nodes. This effect could be at least partly explained by

Laparoscopic kidney orthotopic transplant: preclinical study in the pig model.

PubMed

He, B; Musk, G C; Mou, L; Waneck, G L; Delriviere, L

2013-06-01

Laparoscopic surgery has rapidly expanded in clinical practice replacing conventional open surgery over the last three decades. Laparoscopic donor nephrectomy has been favored due to its multiple benefits. The aim of this study was to explore the safety and feasibility of kidney transplantation by a laparoscopic technique in a pig model. The study was approved by the university animal ethics committee. Eight female pigs (Sus Scrofra, weighing 45-50 kg) were divided into 2 groups: group I included 4 animals that underwent laparoscopic kidney orthotopic transplantation on the left side. The right kidney was remained functional in situ. The pigs recovered and were observed for 1 week. In the 4 hosts group II pigs underwent a laparoscopic kidney transplantation on the left side. With simultaneous clipping of the right ureter. After recovery, the pigs were observed for 4 weeks. A laparotomy for examination was performed prior to euthanasia. All 4 group I pigs survived for 1 week. The laparotomy showed normal graft perfusion with wall patent renal artery and vein as well as satisfactory urine output upon transection of ureter in 3 hosts. Renal artery stenosis occurred in one pig. In The Immediate kidney graft function was achieved in 3 group II pigs. The fourth died following extubation due to laryngospasm despite a functional graft. The average creatinine levels were 195.5 μmol/L on day 3; 224.5 μmol/L at week 1; 127 μmol/L at week 2; 182.7 umol/L at week 3; and 154.7 umol/L at week 4. Laparoscopic kidney transplantation was feasible and safe in a pig model with immediate graft function. This study will provide further evidence to support application of laparoscopic technique to human kidney transplant. Copyright © 2013 Elsevier Inc. All rights reserved.

Optimization of Glioblastoma Mouse Orthotopic Xenograft Models for Translational Research.

PubMed

Irtenkauf, Susan M; Sobiechowski, Susan; Hasselbach, Laura A; Nelson, Kevin K; Transou, Andrea D; Carlton, Enoch T; Mikkelsen, Tom; deCarvalho, Ana C

2017-08-01

Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panel of patient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex. Glioblastoma CSC from 4 patients and a glioblastoma nonstem-cell line were then implanted by using the same coordinates for evaluation of tumor location, growth rate, and morphologic and histologic features. Dye injections into one of the defined locations resulted in dye dissemination throughout the ventricles, whereas tumor cell implantation at the same location resulted in a much higher percentage of small multifocal ventricular tumors than did the other 3 locations tested. Ventricular tumors were associated with a lower tumor growth rate, as measured by in vivo bioluminescence imaging, and decreased survival in 4 of 5 cell lines. In addition, tissue oxygenation, vasculature, and the expression of astrocytic markers were altered in ventricular tumors compared with nonventricular tumors. Based on this information, we identified an optimal implantation location that avoided the ventricles and favored cortical tumor growth. To assess the effects of stress from oral drug administration, mice that underwent daily gavage were compared with stress-positive and -negative control groups. Oral gavage procedures did not significantly affect the survival of the implanted mice or physiologic measurements of stress. Our findings document the importance of optimization of the implantation site for

Optimization of Glioblastoma Mouse Orthotopic Xenograft Models for Translational Research

PubMed Central

Irtenkauf, Susan M; Sobiechowski, Susan; Hasselbach, Laura A; Nelson, Kevin K; Transou, Andrea D; Carlton, Enoch T; Mikkelsen, Tom; deCarvalho, Ana C

2017-01-01

Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panel of patient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex. Glioblastoma CSC from 4 patients and a glioblastoma nonstem-cell line were then implanted by using the same coordinates for evaluation of tumor location, growth rate, and morphologic and histologic features. Dye injections into one of the defined locations resulted in dye dissemination throughout the ventricles, whereas tumor cell implantation at the same location resulted in a much higher percentage of small multifocal ventricular tumors than did the other 3 locations tested. Ventricular tumors were associated with a lower tumor growth rate, as measured by in vivo bioluminescence imaging, and decreased survival in 4 of 5 cell lines. In addition, tissue oxygenation, vasculature, and the expression of astrocytic markers were altered in ventricular tumors compared with nonventricular tumors. Based on this information, we identified an optimal implantation location that avoided the ventricles and favored cortical tumor growth. To assess the effects of stress from oral drug administration, mice that underwent daily gavage were compared with stress-positive and ‑negative control groups. Oral gavage procedures did not significantly affect the survival of the implanted mice or physiologic measurements of stress. Our findings document the importance of optimization of the implantation site for

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

PubMed

Wakefield, A J; Murch, S H; Anthony, A; Linnell, J; Casson, D M; Malik, M; Berelowitz, M; Dhillon, A P; Thomson, M A; Harvey, P; Valentine, A; Davies, S E; Walker-Smith, J A

1998-02-28

We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

Laparoscopic Restorative Total Proctocolectomy With Ileal Pouch Anal Anastomosis for Familial Adenomatous Polyposis

PubMed Central

Palanivelu, C.; Sendhilkumar, K.; Parthasarathi, R.; Senthilnathan, P.; Maheshkumar, G.

2008-01-01

Background: Familial adenomatous polyposis is a hereditary disease characterized by the presence of thousands of colonic adenomas, which, if untreated, invariably undergo malignant transformation. Because this disease manifests at a young age, the laparoscopic approach to perform surgery would be desirable due to its cosmetic benefits. We describe our experience with this procedure and review the literature on the topic. Methods: This is a case series of 15 patients who underwent restorative proctocolectomy with ileo-anal pouch anastomosis for familial adenomatous polyposis between 2000 and 2007. The salient operative steps are described. Results: There were 9 males and 6 females, 32 to 52 years of age, with an average age of 44.8 years. The median body mass index was 21.5 (range, 17 to 28). Rectal cancer was already present in 4 patients at the time of diagnosis. The median operating time was 225 minutes. Mean blood loss was 60mL, with none of the patients requiring perioperative blood transfusion. None of the surgeries required conversion to the open approach. Bowel function resumed on the second postoperative day in 12 patients and on the third postoperative day in 3 patients. The median hospital stay was 8 days. Postoperatively, there was no mortality and no serious morbidity. Conclusion: Laparoscopic restorative proctocolectomy with ileal pouch anal anastomosis is a feasible surgery for familial adenomatous polyposis, and considering its cosmetic benefit, is a desirable option for this group of predominantly young patients. PMID:18765048

Laparoscopic restorative total proctocolectomy with ileal pouch anal anastomosis for familial adenomatous polyposis.

PubMed

Palanivelu, C; Jani, Kalpesh; Sendhilkumar, K; Parthasarathi, R; Senthilnathan, P; Maheshkumar, G

2008-01-01

Familial adenomatous polyposis is a hereditary disease characterized by the presence of thousands of colonic adenomas, which, if untreated, invariably undergo malignant transformation. Because this disease manifests at a young age, the laparoscopic approach to perform surgery would be desirable due to its cosmetic benefits. We describe our experience with this procedure and review the literature on the topic. This is a case series of 15 patients who underwent restorative proctocolectomy with ileo-anal pouch anastomosis for familial adenomatous polyposis between 2000 and 2007. The salient operative steps are described. There were 9 males and 6 females, 32 to 52 years of age, with an average age of 44.8 years. The median body mass index was 21.5 (range, 17 to 28). Rectal cancer was already present in 4 patients at the time of diagnosis. The median operating time was 225 minutes. Mean blood loss was 60 mL, with none of the patients requiring perioperative blood transfusion. None of the surgeries required conversion to the open approach. Bowel function resumed on the second postoperative day in 12 patients and on the third postoperative day in 3 patients. The median hospital stay was 8 days. Postoperatively, there was no mortality and no serious morbidity. Laparoscopic restorative proctocolectomy with ileal pouch anal anastomosis is a feasible surgery for familial adenomatous polyposis, and considering its cosmetic benefit, is a desirable option for this group of predominantly young patients.

Perioperative management in orthotopic liver transplantation: results of an Italian national survey.

PubMed

Biancofiore, G; Della Rocca, G

2012-06-01

No data are available on the perioperative approach during orthotopic liver transplantation (OLT) in Italy, apart from sporadically single center studies. The Department of Anesthesia cooperating with each Italian licensed OLT center received a questionnaire regarding preoperative evaluation, intraoperative anesthesia management, anesthetic drugs, blood components therapy, perioperative monitoring, supportive therapies, postoperative care, staff and organization. Twenty-two centers were surveyed and 17 returned the questionnaire. Center specific protocols for OLT anesthesia exist in 12 centers. Balanced anesthesia (volatile anesthetic agents and continuous infusion of opioids) is the standard anesthetic method. In 14 cases a thromboelastogram is available; one center reported not to have a rapid infusion device available. Pulmonary artery catheterization with a continuous cardiac output device is the most used hemodynamic monitoring system; in case of hemodynamic instability, the combination of dopamine/noradrenaline resulted the first choice before vascular clamping whereas noradrenaline alone after graft's reperfusion. No difference about which intraoperative phase is mostly characterized by the use of blood components was reported. Postoperative care is provided on anesthesiological-guided Intensive Care Units (ICU) in all the surveyed centers and in three centers the ICU is dedicated only to transplant patients. The results of this survey show that in Italy the perioperative management of patients undergoing OLT is not homogeneous. This database allows to debate on the best practices and pathways for perioperative management of these patients, and to stimulate future clinical trials aimed to assess the different component and steps forwards of the whole process.

Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants.

PubMed

Okazaki, Mikio; Gelman, Andrew E; Tietjens, Jeremy R; Ibricevic, Aida; Kornfeld, Christopher G; Huang, Howard J; Richardson, Steven B; Lai, Jiaming; Garbow, Joel R; Patterson, G Alexander; Krupnick, Alexander S; Brody, Steven L; Kreisel, Daniel

2007-12-01

Lung transplantation remains the only therapeutic option for many patients suffering from end-stage pulmonary disease. Long-term success after lung transplantation is severely limited by the development of bronchiolitis obliterans. The murine heterotopic tracheal transplantation model has been widely used for studies investigating pathogenesis of obliterative airway disease and immunosuppressive strategies to prevent its development. Despite its utility, this model employs proximal airway that lacks airflow and is not vascularized. We have developed a novel model of orthotopic vascularized lung transplantation in the mouse, which leads to severe vascular rejection in allogeneic strain combinations. Here we characterize differences in the fate of airway epithelial cells in nonimmunosuppressed heterotopic tracheal and vascularized lung allograft models over 28 days. Up-regulation of growth factors that are thought to be critical for the development of airway fibrosis and interstitial collagen deposition were similar in both models. However, while loss of airway epithelial cells occurred in the tracheal model, airway epithelium remained intact and fully differentiated in lung allografts, despite profound vascular rejection. Moreover, we demonstrate expression of the anti-apoptotic protein Bcl-2 in airway epithelial cells of acutely rejected lung allografts. These findings suggest that in addition to alloimmune responses, other stimuli may be required for the destruction of airway epithelial cells. Thus, the model of vascularized mouse lung transplantation may provide a new and more physiologic experimental tool to study the interaction between immune and nonimmune mechanisms affecting airway pathology in lung allografts.

Early Therapy Evaluation of Combined Anti-DR5 Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts by Diffusion Weighted Magnetic Resonance Imaging

PubMed Central

Kim, Hyunki; Morgan, Desiree E.; Buchsbaum, Donald J.; Zeng, Huadong; Grizzle, William E.; Warram, Jason M.; Stockard, Cecil R.; McNally, Lacey R.; Long, Joshua W.; Sellers, Jeffrey C.; Forero, Andres; Zinn, Kurt R.

2008-01-01

Early therapeutic efficacy of anti-DR5 antibody (TRA-8) combined with gemcitabine was measured using diffusion-weighted magnetic resonance imaging (DWI) in an orthotopic pancreatic tumor model. Groups 1–4 of SCID mice (n=5–7/group) bearing orthotopically implanted, luciferase-positive human pancreatic tumors (MIA PaCa-2) were subsequently (4–5 weeks thereafter) injected with saline (control), gemcitabine (120mg/kg), TRA-8 (200μg), or TRA-8 combined with gemcitabine, respectively, on day 0. DWI, anatomical MRI, and bioluminescence imaging were performed on days 0, 1, 2, and 3 after treatment. Three tumors from each group were collected randomly on day 3 after imaging, and TUNEL staining was performed to quantify apoptotic cellularity. At just 1 day after starting therapy, the changes of apparent diffusion coefficient (ADC) in tumor regions for groups 3 (TRA-8) and 4 (TRA-8/Gem) were 21±9% (mean±SE) and 27±3%, respectively, significantly higher (p <0.05) than those of groups 1 (−1±5%) and 2 (−2±4%). There was no statistical difference in tumor volumes for the groups at this time. The mean ADC values of groups 2–4 gradually increased over 3 days, which were concurrent with tumor-volume regressions and bioluminescence-signal decreases. Apoptotic-cell densities of tumors in groups 1–4 were 0.7±0.4%, 0.6±0.2%, 3.1±0.9%, and 4.7±1.0%, respectively, linearly proportional to the ADC changes on day 1. Further, the ADC changes were highly correlated with the previously reported mean survival times of animals treated with the same agents and doses. This study supports the clinical use of DWI for pancreatic tumor patients for early assessment of drug efficacy. PMID:18922909

Geometric morphometrics reveals sex-differential shape allometry in a spider.

PubMed

Fernández-Montraveta, Carmen; Marugán-Lobón, Jesús

2017-01-01

Common scientific wisdom assumes that spider sexual dimorphism (SD) mostly results from sexual selection operating on males. However, testing predictions from this hypothesis, particularly male size hyperallometry, has been restricted by methodological constraints. Here, using geometric morphometrics (GMM) we studied for the first time sex-differential shape allometry in a spider ( Donacosa merlini , Araneae: Lycosidae) known to exhibit the reverse pattern (i.e., male-biased) of spider sexual size dimorphism. GMM reveals previously undetected sex-differential shape allometry and sex-related shape differences that are size independent (i.e., associated to the y-intercept, and not to size scaling). Sexual shape dimorphism affects both the relative carapace-to-opisthosoma size and the carapace geometry, arguably resulting from sex differences in both reproductive roles (female egg load and male competition) and life styles (wandering males and burrowing females). Our results demonstrate that body portions may vary modularly in response to different selection pressures, giving rise to sex differences in shape, which reconciles previously considered mutually exclusive interpretations about the origins of spider SD.

Artemisia supplementation differentially affects the mucosal and luminal ileal microbiota of diet-induced obese mice

PubMed Central

Shawna, Wicks; M., Taylor Christopher; Meng, Luo; Eugene, Blanchard IV; David, Ribnicky; T., Cefalu William; L., Mynatt Randall; A., Welsh David

2014-01-01

Objective The gut microbiome has been implicated in obesity and metabolic syndrome; however, most studies have focused on fecal or colonic samples. Several species of Artemisia have been reported to ameliorate insulin signaling both in vitro and in vivo. The aim of this study was to characterize the mucosal and luminal bacterial populations in the terminal ileum with or without supplementation with Artemisia extracts. Materials/Methods Following 4 weeks of supplementation with different Artemisia extracts (PMI 5011, Santa or Scopa), diet-induced obese mice were sacrificed and luminal and mucosal samples of terminal ileum were used to evaluate microbial community composition by pyrosequencing of 16S rDNA hypervariable regions. Results Significant differences in community structure and membership were observed between luminal and mucosal samples, irrespective of diet group. All Artemisia extracts increased the Bacteroidetes:Firmicutes ratio in mucosal samples. This effect was not observed in the luminal compartment. There was high inter-individual variability in the phylogenetic assessments of the ileal microbiota, limiting the statistical power of this pilot investigation. Conclusions Marked differences in bacterial communities exist dependent upon the biogeographic compartment in the terminal ileum. Future studies testing the effects of Artemisia or other botanical supplements require larger sample sizes for adequate statistical power. PMID:24985102

Effects of a protease and essential oils on growth performance, blood cell profiles, nutrient retention, ileal microbiota, excreta gas emission, and breast meat quality in broiler chicks.

PubMed

Park, J H; Kim, I H

2018-05-19

A total of 360 Ross male broiler chicks (39.8 ± 1.8 g) were used in a five week experiment to determine the effect of a protease and essential oils (EO) on growth performance, blood cell profile, nutrient retention, ileal microbiota, excreta gas emission, and breast meat quality in broiler chicks. Broiler chicks were randomly allotted to four dietary treatments with 15 birds/cage and six cages/treatment. Experimental treatments were arranged as a 2 × 2 factorial with two levels of protease (0 and 0.02%) and two levels of EO (0 and 0.03%). For days 8 to 21 and overall, body weight gain and the feed conversion ratio were better in broilers fed diets supplemented with protease (P < 0.05) than in those fed diets without protease supplementation. Protease and/or EO increased (P < 0.05) the total tract retention of dry matter, nitrogen, or gross energy, and decreased the excreta ammonia gas emission. In addition, there was a significant interaction between the protease and EO on total tract retention of nitrogen and excreta ammonia gas emission (P < 0.05). The density of ileal Lactobacillus increased and Escherichia coli decreased in broilers (P < 0.05) by the addition of EO to the diet. There were no significant differences in the measurements of breast meat quality and organ weight of broilers fed diets with protease or EO. In conclusion, diets with a combination of a protease and EO improved total tract retention of nitrogen and excreta ammonia gas emission in growing broiler chicks.

Telomerase inhibition improves tumor response to radiotherapy in a murine orthotopic model of human glioblastoma.

PubMed

Ferrandon, Sylvain; Malleval, Céline; El Hamdani, Badia; Battiston-Montagne, Priscillia; Bolbos, Radu; Langlois, Jean-Baptiste; Manas, Patrick; Gryaznov, Sergei M; Alphonse, Gersende; Honnorat, Jérôme; Rodriguez-Lafrasse, Claire; Poncet, Delphine

2015-07-17

Glioblastoma (GBM) is the most frequent and aggressive type of adult brain tumor. Most GBMs express telomerase; a high level of intra-tumoral telomerase activity (TA) is predictive of poor prognosis. Thus, telomerase inhibitors are promising options to treat GBM. These inhibitors increase the response to radiotherapy (RT), in vitro as well as in vivo. Since typical treatments for GBM include RT, our objective was to evaluate the efficiency of Imetelstat (TA inhibitor) combined with RT. We used a murine orthotopic model of human GBM (N = 8 to11 mice per group) and μMRI imaging to evaluate the efficacy of Imetelstat (delivered by intra-peritoneal injection) alone and combined with RT. Using a clinically established protocol, we demonstrated that Imetelstat significantly: (i) inhibited the TA in the very center of the tumor, (ii) reduced tumor volume as a proportion of TA inhibition, and (iii) increased the response to RT, in terms of tumor volume regression and survival increase. Imetelstat is currently evaluated in refractory brain tumors in young patients (without RT). Our results support its clinical evaluation combined with RT to treat GBM.

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer.

PubMed

Fonseca-Filho, V C N; Katayama, M L H; Lyra, E C; Maria, D A; Basso, R A; Nonogaki, S; Guerra, J M; Maistro, S; Góes, J C G S; Folgueira, M A A K

2017-11-01

Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3) highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly proliferative tumor samples. Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.

Effects of sleeve gastrectomy with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats

PubMed Central

Zhong, Ming-Wei; Liu, Shao-Zhuang; Zhang, Guang-Yong; Zhang, Xiang; Hu, San-Yuan

2016-01-01

AIM To explore the effect of sleeve gastrectomy (SG) with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats. METHODS Diabetic rats, which were induced by high-fat diet (HFD), nicotinamide and low-dose streptozotocin, underwent sham operations, SG, SG with jejuno-ileal loop (SG-JI) and SG with jejuno-jejunal loop (SG-JJ) followed by postoperative HFD. Then, at the time points of baseline and 2, 12 and 24 wk postoperatively, we determined and compared several variables, including the area under the curve for the results of oral glucose tolerance test (AUCOGTT), serum levels of triglyceride, cholesterol and ghrelin in fasting state, homeostasis model assessment of insulin resistance (HOMA-IR), body weight, calorie intake, glucagon-like peptide (GLP)-1 and insulin secretions after glucose gavage at dose of 1 g/kg. RESULTS At 2 wk postoperatively, rats that underwent SG, SG-JJ and SG-JI, compared with sham-operated (SHAM) rats, demonstrated lower body weight, calorie intake and ghrelin (P < 0.05 vs SHAM), enhanced secretion of insulin and GLP-1 after glucose gavage (P < 0.05 vs SHAM), improved AUCOGTT, HOMA-IR, fasting serum triglyceride and cholesterol (AUCOGTT: 1616.9 ± 83.2, 837.4 ± 83.7, 874.9 ± 97.2 and 812.6 ± 81.9, P < 0.05 vs SHAM; HOMA-IR: 4.31 ± 0.54, 2.94 ± 0.22, 3.17 ± 0.37 and 3.41 ± 0.22, P < 0.05 vs SHAM; Triglyceride: 2.35 ± 0.17, 1.87 ± 0.23, 1.98 ± 0.30 and 2.04 ± 0.21 mmol/L, P < 0.05 vs SHAM; Cholesterol: 1.84 ± 0.21, 1.53 ± 0.20, 1.52 ± 0.20 and 1.46 ± 0.23 mmol/L). At 12 wk postoperatively, rats receiving SG-JJ and SG-JI had lower body weight, reduced levels of triglyceride and cholesterol and elevated level of GLP-1 compared to those receiving SG (P < 0.05 vs SG). At 24 wk after surgery, compared with SG, the advantage of SG-JJ and SG-JI for glucolipid metabolism was still evident (P < 0.05 vs SG). SG-JI had a better performance in lipid metabolism and GLP-1 secretion of rats than did SG-JJ. CONCLUSION

Theoretical study on third-order nonlinear optical properties in hexagonal graphene nanoflakes: Edge shape effect

NASA Astrophysics Data System (ADS)

Nagai, Hiroshi; Nakano, Masayoshi; Yoneda, Kyohei; Fukui, Hitoshi; Minami, Takuya; Bonness, Sean; Kishi, Ryohei; Takahashi, Hideaki; Kubo, Takashi; Kamada, Kenji; Ohta, Koji; Champagne, Benoît; Botek, Edith

2009-08-01

Using hybrid density functional theory methods, we investigate the second hyperpolarizabilities ( γ) of hexagonal shaped finite graphene fragments, which are referred to as hexagonal graphene nanoflakes (HGNFs), with two types of edge shapes: zigzag (Z) and armchair (A) edges. It is found that Z-HGNF, which gives intermediate diradical characters ( y), exhibits about 3.3 times larger orthogonal components of γ ( γ xxxx = γ yyyy in this case) than A-HGNF, which gives zero y value (closed-shell system). The γ density analysis reveals that this enhancement originates in the significant contribution of γ densities on edge regions in Z-HGNF. These observations strongly indicate that Z-HGNF is a promising candidate of open-shell singlet NLO systems.

Meiotic activity in orthotopic xenografts derived from human postpubertal testicular tissue.

PubMed

Van Saen, D; Goossens, E; Bourgain, C; Ferster, A; Tournaye, H

2011-02-01

Grafting of frozen-thawed testicular tissue has been suggested as a novel fertility preservation method for patients undergoing gonadotoxic treatments. However, this technique still needs further optimization before any clinical application. So far, grafting of human testicular tissue has only been performed to the back skin of nude mice and has shown spermatogonial stem-cell survival and occasionally differentiation up to primary spermatocytes. In this study, orthotopic grafting to mouse testes was evaluated as an alternative, and the effect of freezing and the donor's age was studied. Human testicular tissue was obtained from two prepubertal (aged 3 and 5) and two postpubertal (aged 12 and 13) boys. Both fresh and frozen-thawed testicular tissue was grafted to the testis of immuno-deficient nude mice. Four and nine months after transplantation, testes were analyzed by histology and immunohistochemistry. Four and nine months after transplantation, spermatogonial stem cells were observed in all tissue grafts. Germ cell survival was found to be higher in xenografts from the older boys when compared with that from younger donors. Furthermore, no differentiation was observed in the xenografts from younger patients, but the grafts of two older donors showed differentiation up to the primary spermatocyte level, with the presence of secondary spermatocytes in the oldest donor 9 months after transplantation. This xenografting study shows that intratesticular grafting results in high germ cell survival. In grafts derived from the older boys, meiotic activity was maintained in the xenografts for at least 9 months. Although difficult to conduct due to the scarcity of the tissue, more comparative research is needed to elucidate an optimal grafting strategy.

Phase transitions in a system of hard Y-shaped particles on the triangular lattice

NASA Astrophysics Data System (ADS)

Mandal, Dipanjan; Nath, Trisha; Rajesh, R.

2018-03-01

We study the different phases and the phase transitions in a system of Y-shaped particles, examples of which include immunoglobulin-G and trinaphthylene molecules, on a triangular lattice interacting exclusively through excluded volume interactions. Each particle consists of a central site and three of its six nearest neighbors chosen alternately, such that there are two types of particles which are mirror images of each other. We study the equilibrium properties of the system using grand canonical Monte Carlo simulations that implement an algorithm with cluster moves that is able to equilibrate the system at densities close to full packing. We show that, with increasing density, the system undergoes two entropy-driven phase transitions with two broken-symmetry phases. At low densities, the system is in a disordered phase. As intermediate phases, there is a solidlike sublattice phase in which one type of particle is preferred over the other and the particles preferentially occupy one of four sublattices, thus breaking both particle symmetry as well as translational invariance. At even higher densities, the phase is a columnar phase, where the particle symmetry is restored, and the particles preferentially occupy even or odd rows along one of the three directions. This phase has translational order in only one direction, and breaks rotational invariance. From finite-size scaling, we demonstrate that both the transitions are first order in nature. We also show that the simpler system with only one type of particle undergoes a single discontinuous phase transition from a disordered phase to a solidlike sublattice phase with an increasing density of particles.

Ultra-wideband surface plasmonic Y-splitter.

PubMed

Gao, Xi; Zhou, Liang; Yu, Xing Yang; Cao, Wei Ping; Li, Hai Ou; Ma, Hui Feng; Cui, Tie Jun

2015-09-07

We present an ultra-wideband Y-splitter based on planar THz plasmonic metamaterials, which consists of a straight waveguide with composite H-shaped structure and two branch waveguides with H-shaped structure. The spoof surface plasmonic polaritons (SSPPs) supported by the straight waveguide occupy the similar dispersion relation and mode characteristic to the ones confined by the branch waveguides. Attributing to these features, the two branch waveguides can equally separate the SSPPs wave propagating along the straight plasmonic waveguide to form a 3dB power divider in an ultra-wideband frequency range. To verify the functionality and performance of the proposed Y-splitter, we scaled down the working frequency to microwave and implemented microwave experiments. The tested device performances have clearly validated the functionality of our designs. It is believed to be applicable for future plasmonic circuit in microwave and THz ranges.

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

PubMed Central

Huang, Feng-Yun J; Lee, Te-Wei; Chang, Chih-Hsien; Chen, Liang-Cheng; Hsu, Wei-Hsin; Chang, Chien-Wen; Lo, Jem-Mau

2015-01-01

Purpose In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. Materials and methods The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats. Results By using bioluminescent imaging, the well-established reporter cell line (F98luc) showed a high relationship between cell number and its bioluminescent intensity (R2=0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P<0.05). As a result, the lifespan of glioma-bearing rats treated with 188Re-liposome was prolonged 10.67% compared to the control group. Conclusion The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting 188Re-liposome via systemic administration can significantly prolong the

Hepatic gas gangrene following orthotopic liver transplantation: three cases treated with re-transplantation and a review of the literature.

PubMed

Doblecki-Lewis, S; Palaios, E; Bejarano, P A; Tzakis, A G; Selvaggi, G; Morris, M I

2008-07-01

Gas gangrene is a rare and devastating infectious process that can occur after liver transplantation, most often following hepatic artery thrombosis. We here report 3 cases of gas gangrene following orthotopic liver transplantation. Blood cultures were positive for Clostridium clostridiiforme in one case. In 2 other cases liver tissue from explanted specimens was positive for Enterobacter cloacae. Ultrasound demonstrated hepatic artery thrombosis and computed tomography imaging revealed diffuse liver necrosis with gas formation in each case. All 3 patients were successfully treated with a combination of antibiotics and emergent re-transplantation. We review previously published cases of gas gangrene after liver transplant and emphasize the importance of hepatic artery thrombosis in the development of this syndrome as well as the frequent involvement of non-clostridial organisms. Early diagnosis and aggressive combined medical and surgical treatment including re-transplantation are essential for successful treatment of these rare and catastrophic infections.

Donor age does not influence 12-month outcome after orthotopic liver transplantation.

PubMed

Faber, W; Seehofer, D; Puhl, G; Guckelberger, O; Bertram, C; Neuhaus, P; Bahra, M

2011-12-01

Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease to date. The discrepancy between the numbers of donor livers and recipients has become a significant problem, resulting in a high patient mortality on the waiting list. Due to this, an expansion of the donor pool is necessary, for example, by accepting donor grafts from elderly donors. The aim of this study was to investigate the outcome after OLT depending on donor age. We retrospectively evaluated the outcome of 272 full-size cadaveric initial single OLTs within 12 months after OLT. The outcome was analyzed by dividing the collective into four donor age categories: donor age under 50, between 50 and 59, between 60 and 69, and 70 years or above. The outcome after OLT in these patients was retrospectively reviewed by using a prospective database. Patients positive for hepatitis C were excluded from the analysis. No increase of initial nonfunction was observed. Furthermore, no significant differences with regard to surgical complications and serum liver parameter were observed between the groups. Neither patient mortality rates nor rejection rates were different between the groups. However, ischemic-type biliary lesion rates increased significantly with donor age over 70 years (P<.05). The acceptance of liver grafts from older donors is a possible alternative to narrow the gap between donated and required organs. Safe use under optimal protocols is necessary to avoid a deterioration of post-OLT results. Copyright © 2011 Elsevier Inc. All rights reserved.

[Ursolic acid inhibits corneal graft rejection following orthotopic allograft transplantation in rats].

PubMed

Wang, Bo; Wu, Jing; Ma, Ming; Li, Ping-Ping; Yu, Jian

2015-04-01

To investigate the effects of ursolic acid on corneal graft rejection in a rat model of othotopic corneal allograft transplantation. Forty-eight recipient Wistar rats were divided into normal control group with saline treatment (group A), autograft group with saline treatment (group B), SD rat allograft group with saline treatment (group C), and SD rat allograft group with intraperitoneal ursolic acid (UA) treatment group (group D). The rats received saline or UC (20 mg·kg(-1)·d(-1)) treatment for 12 days following othotopic graft transplantation. The grafts were evaluated using the Larkin corneal rejection rating system, and the graft survival was assessed with Kaplan-Meier analysis. On day 14, the grafts were harvested for histological examination, Western blotting, and assessment of expressions of interlukin-2 (IL-2), interferon-γ (IFN-γ), nuclear transcription factor-κB (NF-κB) p65, vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1). The allograft survival was significantly longer in group D than in group C (29.12±9.58 vs 9.67±2.16 days, P<0.05). UC treatment obviously reduced the expression levels of IL-2, IFN-γ, NF-κBp65, ICAM-1 and VEGF and increased inhibitory kappa B alpha (IκB-α) expression in the grafts, where no obvious inflammatory cell infiltration or corneal neovascularization was found. As a NF-κB inhibitor, ursolic acid can prevent corneal neovascularization and corneal allograft rejection to promote graft survival in rats following orthotopic corneal allograft transplantation.

Elastic collisions of low-energy electrons with SiY4 (Y = Cl, Br, I) molecules

NASA Astrophysics Data System (ADS)

Bettega, M. H. F.

2011-11-01

We employed the Schwinger multichannel method to compute elastic integral, differential, and momentum transfer cross sections for low-energy electron collisions with SiY4 (Y = Cl, Br, I) molecules. The calculations were carried out in the static-exchange and static-exchange plus polarization approximations for energies up to 10 eV. The elastic integral cross section for SiCl4 and SiBr4, computed in the static-exchange plus polarization approximation, shows two shape resonances belonging to the T2 and E symmetries of the Td group, and for SiI4 shows one shape resonance belonging to the E symmetry of the Td group. The present results agree well in shape with experimental total cross sections. The positions of the resonances observed in the calculated integral cross sections are also in agreement with the experimental positions. We have found the presence of a virtual state for SiCl4 and a Ramsauer-Townsend minimum for SiI4 at 0.5 eV. The present results show that the proper inclusion of polarization effects is crucial in order to correctly describe the resonance spectra of these molecules and also to identify a Ramsauer-Townsend minimum for SiI4 and a virtual state for SiCl4.

Robotic radical cystectomy and intracorporeal urinary diversion: The USC technique.

PubMed

Abreu, Andre Luis de Castro; Chopra, Sameer; Azhar, Raed A; Berger, Andre K; Miranda, Gus; Cai, Jie; Gill, Inderbir S; Aron, Monish; Desai, Mihir M

2014-07-01

Radical cystectomy is the gold-standard treatment for muscle-invasive and refractory nonmuscle-invasive bladder cancer. We describe our technique for robotic radical cystectomy (RRC) and intracorporeal urinary diversion (ICUD), that replicates open surgical principles, and present our preliminary results. Specific descriptions for preoperative planning, surgical technique, and postoperative care are provided. Demographics, perioperative and 30-day complications data were collected prospectively and retrospectively analyzed. Learning curve trends were analyzed individually for ileal conduits (IC) and neobladders (NB). SAS(®) Software Version 9.3 was used for statistical analyses with statistical significance set at P < 0.05. Between July 2010 and September 2013, RRC and lymph node dissection with ICUD were performed in 103 consecutive patients (orthotopic NB=46, IC 57). All procedures were completed robotically replicating the open surgical principles. The learning curve trends showed a significant reduction in hospital stay for both IC (11 vs. 6-day, P < 0.01) and orthotopic NB (13 vs. 7.5-day, P < 0.01) when comparing the first third of the cohort with the rest of the group. Overall median (range) operative time and estimated blood loss was 7 h (4.8-13) and 200 mL (50-1200), respectively. Within 30-day postoperatively, complications occurred in 61 (59%) patients, with the majority being low grade (n = 43), and no patient died. Median (range) nodes yield was 36 (0-106) and 4 (3.9%) specimens had positive surgical margins. Robotic radical cystectomy with totally ICUD is safe and feasible. It can be performed using the established open surgical principles with encouraging perioperative outcomes.

SHAPE Selection (SHAPES) enrich for RNA structure signal in SHAPE sequencing-based probing data

PubMed Central

Poulsen, Line Dahl; Kielpinski, Lukasz Jan; Salama, Sofie R.; Krogh, Anders; Vinther, Jeppe

2015-01-01

Selective 2′ Hydroxyl Acylation analyzed by Primer Extension (SHAPE) is an accurate method for probing of RNA secondary structure. In existing SHAPE methods, the SHAPE probing signal is normalized to a no-reagent control to correct for the background caused by premature termination of the reverse transcriptase. Here, we introduce a SHAPE Selection (SHAPES) reagent, N-propanone isatoic anhydride (NPIA), which retains the ability of SHAPE reagents to accurately probe RNA structure, but also allows covalent coupling between the SHAPES reagent and a biotin molecule. We demonstrate that SHAPES-based selection of cDNA–RNA hybrids on streptavidin beads effectively removes the large majority of background signal present in SHAPE probing data and that sequencing-based SHAPES data contain the same amount of RNA structure data as regular sequencing-based SHAPE data obtained through normalization to a no-reagent control. Moreover, the selection efficiently enriches for probed RNAs, suggesting that the SHAPES strategy will be useful for applications with high-background and low-probing signal such as in vivo RNA structure probing. PMID:25805860

Cost-effectiveness of quantitative fecal lactoferrin assay for diagnosis of symptomatic patients with ileal pouch-anal anastomosis.

PubMed

Parsi, Mansour A; Ellis, Jeffrey J; Lashner, Bret A

2008-08-01

To assess cost-effectiveness of fecal lactoferrin (FL) as the initial diagnostic approach to symptomatic patients with ileal pouch-anal anastomosis (IPAA). Four competing strategies [empiric metronidazole therapy (txMTZ), initial pouch endoscopy with biopsy (testBiop), initial FL assay followed by metronidazole therapy (testFL+MTZ), and initial FL assay followed by pouch endoscopy and biopsy (testFL+Biop)] were modeled in a decision tree. In the base-case, the average cost per patient was $241 for testFL+MTZ, $251 for txMTZ, $405 for testFL+Biop, and $431 for testBiop. The testBiop strategy had greater effectiveness compared with txMTZ but at an incremental cost of $158 per day. The txMTZ strategy was slightly more costly and minimally more effective than testFL+MTZ with an incremental cost effectiveness of just over $12 per day. However, the testFL+MTZ strategy was associated with a 31% absolute reduction in antibiotic exposure compared with the txMTZ strategy. Compared with empiric metronidazole therapy, FL before treatment with metronidazole is less costly with less exposure to antibiotics and less need for endoscopy, with only marginal decrease in effectiveness.

Growth, nutrient digestibility, ileal digesta viscosity, and energy metabolizability of growing turkeys fed diets containing malted sorghum sprouts supplemented with enzyme or yeast.

PubMed

Oke, F O; Oso, A O; Oduguwa, O O; Jegede, A V; Südekum, K-H; Fafiolu, A O; Pirgozliev, V

2017-06-01

Growth, apparent nutrient digestibility, ileal digesta viscosity, and energy metabolizability of growing turkeys fed diets containing malted sorghum sprouts (MSP) supplemented with enzyme or yeast were investigated using 120, 28-day-old male turkeys. Six treatments were laid out in a 3 × 2 factorial arrangement of treatments with three dietary inclusion levels of MSP (0, 50, and 100 g/kg) and supplemented with 200 mg/kg yeast (Saccharomyces cerevisiae) or 200 mg/kg of a commercial enzyme. The experiment lasted for the starter (day 28-56) and grower phases (day 57-84) of the birds. Each treatment group consisted of 20 turkeys replicated four times with five birds each. Data were analysed using analysis of variance while polynomial contrast was used to determine the trends (linear and quadratic) of MSP inclusion levels. Irrespective of dietary supplementation with enzyme or yeast, final body weight (BW), total BW gain, and feed intake for turkey poults from day 29-56 was reduced (p < 0.05) with increasing inclusion level of MSP. Dietary supplementation with yeast resulted in increased (p < 0.05) feed intake while enzyme supplementation improved (p < 0.05) feed conversion ratio of the poults. Turkeys fed enzyme-supplemented MSP diets had higher (p < 0.05) BW gain than their counterparts fed yeast-supplemented MSP diets. Apparent ash digestibility reduced linearly (p < 0.05) with increasing inclusion levels of MSP. Apparent metabolizable energy (AME) did not vary significantly (p > 0.05) with MSP inclusion levels. Enzyme supplementation reduced (p < 0.05) ileal viscosity but had no effect (p > 0.05) on AME. Inclusion of MSP resulted in poor growth performance. This confirms earlier studies that utilization of MSP by poultry is rather poor. Supplementation with enzyme or yeast did not lead to any appreciable improvement in performance of turkeys in this study. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

In vitro smooth muscle contractility before and after relief of experimental obstruction in the rat: application to the surgical management of ileal dilatation.

PubMed

Haraux, Elodie; Canarelli, Jean-Pierre; Khorsi, Hafida; Delanaud, Stéphane; Bach, Véronique; Gay-Quéheillard, Jérome

2014-03-01

Bowel dilatation occurs proximal to an obstruction and predisposes to intestinal dysmotility. The present study sought to determine whether or not changes in smooth muscle contractility and the thickness of the proximal, dilated bowel wall can be reversed following relief of the obstruction. Three groups of seven male Wistar rats were studied. In 8-week-old animals in a control group and a sham-operated group, a small segment of bowel (designated as R1 for controls and R2 for shams) was resected 5.0 cm from the cecum. In the third (operated) group, a narrow, isoperistaltic intestinal loop was created proximal to an end-to-end anastomosis of the ileum in 4-week-old animals. When these animals were 6 weeks old, the loop was re-anastomosed to the distal small bowel (after resection of the loop's distal portion, referred to as R3). Two weeks later, a small segment of bowel was resected proximal to the anastomosis (R4). We evaluated the thickness of the smooth muscle layers and the in vitro contractile responses of circular smooth muscle ileal strips (R1-R4) to electrical stimulation and pharmacological stimulation (with KCl, acetylcholine (ACh), substance P, N(G)-nitro-l-arginine methyl ester (L-NAME) and histamine). The amplitudes of contraction in response to electrical and Ach-mediated stimulation were higher for R3 than for R4 (P<0.001), R1 and R2 (both P<0.05). Compared with R1 and R2, the smooth muscle layer was three times as thick in R3 (P<0.001) and 2.5 times as thick in R4 (P<0.01). Our study provides evidence of the possible recovery of intestinal motility (in response to neurotransmitters involved in gut function) after the relief of an obstruction. If ileal motility can conceivably return to normal values, conservative surgical procedures in pediatric patients should be preferred (in order to leave a sufficient length of bowel and avoid short bowel syndrome). © 2013 Elsevier Inc. All rights reserved.

Freeze-thaw and high-voltage discharge allow macromolecule uptake into ileal brush-border vesicles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donowitz, M.; Emmer, E.; McCullen, J.

1987-06-01

High-voltage discharge or one cycle of freeze-thawing are shown to transiently permeabilize rabbit ileal brush-border membrane vesicles to macromolecules. Uptake of the radiolabeled macromolecule dextran, mol wt 70,000, used as a marker for vesicle permeability, was determined by a rapid filtration technique, with uptake defined as substrate associated with the vesicle and releasable after incubation of vesicles with 0.1% saponin. Dextran added immediately after electric shock (2000 V) or at the beginning of one cycle of freeze-thawing was taken up approximately eightfold compared with control. ATP also was taken up into freeze-thawed vesicles, whereas there was no significant uptake intomore » control vesicles. The increase in vesicle permeability was reversible, based on Na-dependent D-glucose uptake being decreased when studied 5 but not 15 min after electric shock, and was not significantly decreased after completion of one cycle of freeze-thawing. In addition, adenosine 3',5'-cyclic monophosphate and Ca/sup 2 +/-calmodulin-dependent protein kinase activity were similar in control vesicles and vesicles exposed to high-voltage discharge or freeze-thawing. Also, vesicles freeze-thawed with (/sup 32/P)ATP demonstrated increased phosphorylation compared with nonfrozen vesicles, while freeze-thawing did not alter vesicle protein as judged by Coomassie blue staining. These techniques should allow intestinal membrane vesicles to be used for studies of intracellular control of transport processes, for instance, studies of protein kinase regulation of transport.« less

Literature Review: Double-Barrelled Wet Colostomy (One Stoma) versus Ileal Conduit with Colostomy (Two Stomas).

PubMed

Gan, Jason; Hamid, Rizwan

2017-01-01

The aim of this literature review was to analyse the advantages and disadvantages of a traditional ileal conduit (IC) with separate colostomy technique compared to the outcomes of a double-barrelled wet colostomy (DBWC) technique. The former technique results in the formation of two stomas, and the latter results in the formation of one stoma. PubMed was searched electronically for articles on DBWC. Fifteen articles were retrieved and of them 13 were included in the literature review (350 patients). Of the articles, 3 directly compared DBWC to IC with colostomy. Review of 13 DBWC articles demonstrated perioperative mortality ranging between 0 and 11.1% and postoperative complications ranging from 0 to 100%. Three of the studies directly compared DBWC to IC with colostomy; median operating times and length of stay were shorter in DBWC patients (p < 0.001); 30-day morbidity was reported to either be lower in the DBWC group (p < 0.043) or to have no statistically significant difference. Rates of mortality, pyelonephritis, electrolyte disturbances and urinary anastomotic problems did not differ between the 2 groups. The DBWC technique inherently has a benefit over the IC with colostomy technique, as it requires only one stoma. This literature review supports the use of the technically less challenging DBWC technique as a viable alternative to the traditional IC with colostomy technique. © 2016 S. Karger AG, Basel.

Effects of Inclusion Levels of Wheat Bran and Body Weight on Ileal and Fecal Digestibility in Growing Pigs

PubMed Central

Huang, Q.; Su, Y. B.; Li, D. F.; Liu, L.; Huang, C. F.; Zhu, Z. P.; Lai, C. H.

2015-01-01

The objective of this study was to determine the effects of graded inclusions of wheat bran (0%, 9.65%, 48.25% wheat bran) and two growth stages (from 32.5 to 47.2 kg and 59.4 to 78.7 kg, respectively) on the apparent ileal digestibility (AID), apparent total tract digestibility (ATTD) and hindgut fermentation of nutrients and energy in growing pigs. Six light pigs (initial body weight [BW] 32.5±2.1 kg) and six heavy pigs (initial BW 59.4±3.2 kg) were surgically prepared with a T-cannula in the distal ileum. A difference method was used to calculate the nutrient and energy digestibility of wheat bran by means of comparison with a basal diet consisting of corn-soybean meal (0% wheat bran). Two additional diets were formulated by replacing 9.65% and 48.25% wheat bran by the basal diet, respectively. Each group of pigs was allotted to a 6×3 Youden square design, and pigs were fed to three experimental diets during three 11-d periods. Hindgut fermentation values were calculated as the differences between ATTD and AID values. For the wheat bran diets, the AID and ATTD of dry matter (DM), ash, organic matter (OM), carbohydrates (CHO), gross energy (GE), and digestible energy (DE) decreased with increasing inclusion levels of wheat bran (p<0.05). While only AID of CHO and ATTD of DM, ash, OM, CHO, GE, and DE content differed (p<0.05) when considering the BW effect. For the wheat bran ingredient, there was a wider variation effect (p<0.01) on the nutrient and energy digestibility of wheat bran in 9.65% inclusion level due to the coefficient of variation (CV) of the nutrient and energy digestibility being higher at 9.65% compared to 48.25% inclusion level of wheat bran. Digestible energy content of wheat bran at 48.25% inclusion level (4.8 and 6.7 MJ/kg of DM, respectively) fermented by hindgut was significantly higher (p<0.05) than that in 9.65% wheat bran inclusion level (2.56 and 2.12 MJ/kg of DM, respectively), which was also affected (p<0.05) by two growth stages

In vivo testing of Renilla luciferase substrate analogs in an orthotopic murine model of human glioblastoma.

PubMed

Otto-Duessel, Maya; Khankaldyyan, Vazgen; Gonzalez-Gomez, Ignacio; Jensen, Michael C; Laug, Walter E; Rosol, Michael

2006-01-01

In vivo bioluminescent imaging using cells expressing Renilla luciferase is becoming increasingly common. Hindrances to the more widespread use of Renilla luciferase are the high autoluminescence of its natural substrate, coelenterazine, in plasma, the relatively high absorbance by tissue of the light emitted by the enzyme-substrate reaction; rapid clearance of the substrate; and significant cost. These factors, save for the cost, which has its own limiting effect on use, can combine to reduce the sensitivity of in vivo assays utilizing this reporter system, and methods of increasing light output or decreasing autoluminescence could be of great benefit. A number of analogs of coelenterazine are being investigated may accomplish one or both of these goals. In this study that we report on the testing of two new substrate analogs, EnduRen and ViViren, manufactured by Promega Corporation, in an orthotopic murine model of human glioblastoma expressing Renilla luciferase. We have tested these analogs in this cell line both in vitro and in vivo, and find that the substrate viviren results in significantly greater light output than the natural substrate or the other analog EnduRen. This new substrate could be valuable for studies where greater sensitivity is important.

Evolving experience with prevention and treatment of splenic artery syndrome after orthotopic liver transplantation.

PubMed

Mogl, Martina T; Nüssler, Natascha C; Presser, Sabine J; Podrabsky, Petr; Denecke, Timm; Grieser, Christian; Neuhaus, Peter; Guckelberger, Olaf

2010-08-01

Impaired hepatic arterial perfusion after orthotopic liver transplantation (OLT) may lead to ischemic biliary tract lesions and graft-loss. Hampered hepatic arterial blood flow is observed in patients with hypersplenism, often described as arterial steal syndrome (ASS). However, arterial and portal perfusions are directly linked via the hepatic arterial buffer response (HABR). Recently, the term 'splenic artery syndrome' (SAS) was coined to describe the effect of portal hyperperfusion leading to diminished hepatic arterial blood flow. We retrospectively analyzed 650 transplantations in 585 patients. According to preoperative imaging, 78 patients underwent prophylactic intraoperative ligation of the splenic artery. In case of postoperative SAS, coil-embolization of the splenic artery was performed. After exclusion of 14 2nd and 3rd retransplantations and 83 procedures with arterial interposition grafts, SAS was diagnosed in 28 of 553 transplantations (5.1%). Twenty-six patients were treated with coil-embolization, leading to improved liver function, but requiring postinterventional splenectomy in two patients. Additionally, two patients with SAS underwent splenectomy or retransplantation without preceding embolization. Prophylactic ligation could not prevent SAS entirely (n = 2), but resulted in a significantly lower rate of complications than postoperative coil-embolization. We recommend prophylactic ligation of the splenic artery for patients at risk of developing SAS. Post-transplant coil-embolization of the splenic artery corrected hemodynamic changes of SAS, but was associated with a significant morbidity.

The use of TMZ embedded hydrogels for the treatment of orthotopic human glioma xenografts.

PubMed

Adhikari, Bandita; Li, Jie; Brandel, Michael G; Futalan, Diahnn; Akers, Johnny; Deming, Timothy; Chen, Clark C; Carter, Bob S

2017-11-01

The current treatment of glioblastoma multiforme (GBM) is limited by the restricted arsenal of agents which effectively cross the blood brain barrier (BBB). For example, only a fraction of temozolomide (TMZ) administered systemically is available for therapeutic effect because of the BBB and the instability of TMZ under physiologic conditions. A novel approach to overcome this obstacle is to bypass the BBB and locally deliver chemotherapeutic agents directly to the tumor mass. We have explored the loading of TMZ into a novel hydrogel matrix, which can be delivered in liquid form and then solidifies in situ and releases chemotherapy as the matrix dissolves. Here, we tested the effect of amphiphilic diblock copolypeptide hydrogels (DCHs) of 180-poly-lysine and 20-poly-leucine (K 180 L 20 ) on TMZ using Glioblastoma models. In both the in vitro model, which involved treatment of a human glioblastoma GSC line suspended as neurospheres, and in vivo using an orthotopic glioma xenograft mouse model, we found that K 180 L 20 could safely enhance the efficacy of TMZ. This technique may offer the opportunity to 'coat' the inner lining of the cavity following glioma resection with a slow-release TMZ and potentially decrease recurrence. Future studies in larger animals are needed to delineate this effect. Copyright © 2017. Published by Elsevier Ltd.

Superordinate Shape Classification Using Natural Shape Statistics

ERIC Educational Resources Information Center

Wilder, John; Feldman, Jacob; Singh, Manish

2011-01-01

This paper investigates the classification of shapes into broad natural categories such as "animal" or "leaf". We asked whether such coarse classifications can be achieved by a simple statistical classification of the shape skeleton. We surveyed databases of natural shapes, extracting shape skeletons and tabulating their…

Metformin Improves Ileal Epithelial Barrier Function in Interleukin-10 Deficient Mice

PubMed Central

Xue, Yansong; Zhang, Hanying; Sun, Xiaofei; Zhu, Mei-Jun

2016-01-01

Background and aims The impairment of intestinal epithelial barrier is the main etiologic factor of inflammatory bowel disease. The proper intestinal epithelial proliferation and differentiation is crucial for maintaining intestinal integrity. Metformin is a common anti-diabetic drug. The objective is to evaluate the protective effects of metformin on ileal epithelial barrier integrity using interleukin-10 deficient (IL10KO) mice. Methods Wild-type and IL10KO mice were fed with/without metformin for 6 weeks and then ileum was collected for analyses. The mediatory role of AMP-activated protein kinase (AMPK) was further examined by gain and loss of function study in vitro. Results Compared to wild-type mice, IL10KO mice had increased proliferation, reduced goblet cell and Paneth cell lineage differentiation in the ileum tissue, which was accompanied with increased crypt expansion. Metformin supplementation mitigated intestinal cell proliferation, restored villus/crypt ratio, increased goblet cell and Paneth cell differentiation and improved barrier function. In addition, metformin supplementation in IL10KO mice suppressed macrophage pro-inflammatory activity as indicated by reduced M1 macrophage abundance and decreased pro-inflammatory cytokine IL-1β, TNF-α and IFN-γ expressions. As a target of metformin, AMPK phosphorylation was enhanced in mice treated with metformin, regardless of mouse genotypes. In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin. Consistently, in Caco-2 cells, metformin promoted claudin-3 and E-cadherin assembly and mitigated TNF-α-induced fragmentation of tight junction proteins. Gain and loss of function assay also demonstrated AMPK was correlated with epithelial differentiation and proliferation. Conclusions Metformin supplementation promotes