bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroprotective Effect of Orexin-A Is Mediated by an Increase of Hypoxia-inducible Factor-1 Activity in Rat
Authors: Yuan Li-bang , Dong Hai-long , Zhang Hao-Peng , Zhao Rui-ni , Gong Gu , Chen Xiao-mei , Zhang Li-na , Xiong Lize 
Published: January 2011

Background
Recent studies suggest that the novel neuropeptide orexin-A may play an essential role during neuronal damage. However, the function of orexin-A during brain ischemia remains unclear. Recently, hypoxia-inducible factor-1α (HIF-1α) was shown to be activated by orexin-A. The aim of the current study is to test the hypothesis that administration of exogenous orexin-A can attenuate ischemia-reperfusion injury through the facilitation of HIF-1α expression.

Methods
Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 120 min. Rats were treated with different doses of orexin-A or vehicle before the ischemia and at the onset of reperfusion. To investigate the action of HIF-1α in the neuroprotective effects of orexin-A, the HIF-1α inhibitor YC-1 was used alone or combined with orexin-A. Neurologic deficit scores and infarct volume were assessed. Brains were harvested for immunohistochemical staining and western blot analysis.

Results
Orexin-A significantly ameliorated neurologic deficit scores and reduced infarct volume after cerebral ischemia reperfusion. Administration of 30 μg/kg orexin-A showed optimal neuroprotective effects. This effect was still present 7 days after reperfusion. Furthermore, orexin-A decreased the number of apoptotic cells and significantly enhanced HIF-1α expression after cerebral ischemia reperfusion. Moreover, the facilitation of HIF-1α expression was accompanied with inhibition of von Hippel-Lindau expression. Administration of HIF-1α inhibitor suppressed the increase of HIF-1α and reversed the neuroprotective effects of orexin-A.

Conclusions
Orexin-A has a neuroprotective effect against cerebral ischemia-reperfusion injury. These effects may be mediated through the HIF-1α pathway.
A Biopsy Is Not Always Necessary to Diagnose Celiac Disease
Authors: Mubarak Amani , Wolters Victorien M , Gerritsen Susan AM , Gmelig‐Meyling Frits HJ , Ten Kate Fiebo JW , Houwen Roderick HJ 
Published: January 2011

AbstractObjectives:Small intestinal histology is the criterion standard for the diagnosis of celiac disease (CD). However, results of serological tests such as anti‐endomysium antibodies and anti‐tissue transglutaminase antibodies (tTGA) are becoming increasingly reliable. This raises the question of whether a small intestinal biopsy is always necessary. The aim of the present study was, therefore, to investigate whether a small intestinal biopsy can be avoided in a selected group of patients.Patients and Methods:Serology and histological slides obtained from 283 pediatric patients suspected of having CD were examined retrospectively. The response to a gluten‐free diet (GFD) in patients with a tTGA level ≥100 U/mL was investigated.Results:A tTGA level ≥100 U/mL was found in 128 of the 283 patients. Upon microscopic examination of the small intestinal epithelium, villous atrophy was found in 124 of these patients, confirming the presence of CD. Three patients had crypt hyperplasia or an increased number of intraepithelial lymphocytes. In 1 patient no histological abnormalities were found. This patient did not respond to a GFD.Conclusions:Pediatric patients with a tTGA level ≥100 U/mL in whom symptoms improve upon consuming a GFD may not need a small intestinal biopsy to confirm CD.
Colonic Hyperactivity Results in Frequent Fecal Soiling in a Subset of Children After Surgery for Hirschsprung Disease
Authors: Kaul Ajay , Garza Jose M , Connor Frances L , Cocjin Jose T , Flores Alejandro F , Hyman Paul E , Di Lorenzo Carlo 
Published: January 2011

ABSTRACTBackground and Aim:Fecal soiling is a challenging problem in some children after pull‐through surgery for Hirschsprung disease (HSCR). The prevailing perception is that soiling results from overflow incontinence; however, its treatment with laxatives yields mixed results. Colonic manometry studies are reported to be normal in most patients in this population. The interpretation of these findings does not support the physiology of fecal overflow incontinence in these children. The aim of the present study was to define the physiology underlying daily, frequent fecal soiling in children after surgery for HSCR using manometric techniques.Patients and Methods:Four pediatric motility centers in the United States participated in the study; medical records and manometric tracings (anorectal and colonic) of children (n = 59; 6.5 years; 48 boys) who had pull‐through surgery for HSCR and presented with daily, frequent fecal soiling were examined. Children referred for evaluation of constipation who had normal colonic manometry served as controls (n = 25; 6.7 years; 12 boys). The patients with HSCR were divided into 2 groups (Hirschsprung disease groups 1 and 2 [HD1, HD2]) based on the absence or presence of high‐amplitude propagated contractions (HAPCs). A control group that included children with chronic constipation was also studied. We compared the mean HAPC frequency between the HD2 and control groups.Results:HD1 included 21 patients who had no HAPCs in fasting or postprandial periods. HD2 included 38 patients who had an average of 0.07 HPACs/min while fasting and 0.13/min in the postprandial state. In this subset the number of HAPCs in the fasting state (P = 0.04) and the postprandial state (P < 0.001) was greater when compared with controls. Additionally, there was a significant increase in HAPCs/min from the fasting to the postprandial state (P = 0.01). In the HD2 group 40% had colonic hyperactivity.Conclusions:Daily, frequent fecal soiling after pull‐through surgery for HSCR may be due to colonic hyperactivity in some children. It is imperative that this unique subset be identified because the management strategy would include avoidance of laxatives, contrary to standard current practice.
Evaluations of Psychological Preparation for Children Undergoing Endoscopy
Authors: Tanaka Kyoko , Oikawa Nao , Terao Rieko , Negishi Yoshie , Fujii Toru , Kudo Takahiro , Shimizu Toshiaki 
Published: January 2011

ABSTRACTWe provided psychological preparation to children who were hospitalized for endoscopy. We performed a multifaceted evaluation of the effects of the preparation to identify appropriate methods for individual children. The subjects were 20 children, ages 4 to 15 years (average 9.9 years), who were divided into 3 groups according to the preparation methods. From our study, we suggest that it is important to discuss the preparation methods for medical procedures using methods appropriate to the level of cognitive development of each individual child.
Optimisation of the Reflux‐symptom Association Statistics for Use in Infants Being Investigated by 24‐hour pH impedance
Authors: Omari Taher I , Schwarzer Andrea , vanWijk Michiel P , Benninga Marc A , McCall Lisa , Kritas Stamatiki , Koletzko Sibylle , Davidson Geoffrey P 
Published: January 2011

ABSTRACTBackground and Aim:pH‐impedance monitoring is used to diagnose symptomatic gastroesophageal reflux (GER) based on symptom association probability (SAP). Current criteria for calculation of SAP are optimised for heartburn in adults. Infants, however, demonstrate a different symptom profile. The aim of the present study was to optimise criteria for calculation of SAP in infants with GER disease.Patients and Methods:Ten infants referred for investigation of symptomatic reflux were enrolled. GER episodes were recorded using a pH‐impedance probe, which remained in place for 48 hours. During the test, cough, crying, and regurgitation were marked. Impedance recordings were analysed for the occurrence of bolus reflux episodes. SAP for behaviors following reflux episodes was separately calculated for day 1 and day 2 using automated reporting software, which enabled the time window used for SAP calculations to be modified from 15 to 600 seconds. Day‐to‐day agreement of SAP was assessed by calculating the 95% limits of agreement (mean difference ± 1.96 standard deviations of differences) and their confidence intervals.Results:The number of bolus GER episodes and symptom episodes reported did not differ from day to day. The best agreement in SAP between the 2 days was found using time intervals of 2 minutes for cough, 5 minutes for crying, and 15 seconds and/or 2 to 5 minutes for regurgitation.Conclusions:We conclude that the standard 2‐minute time interval is appropriate for the investigation of cough and regurgitation symptoms. The day‐to‐day agreement of SAP for crying was poor using standard criteria, and our results suggest increasing the reflux‐symptom association time interval to 5 minutes.
Early High Calcium and Phosphorus Intake by Parenteral Nutrition Prevents Short‐term Bone Strength Decline in Preterm Infants
Authors: Pereira‐da‐Silva L , Costa AB , Pereira L , Filipe AF , Virella D , Leal E , Moreira AC , Rosa ML , Mendes L , Serelha M 
Published: January 2011

ABSTRACTBackground and Aim:Very premature newborns have an increased risk of low bone mass and metabolic bone disease. Most longitudinal studies report a significant decline in bone strength in the first weeks after birth. The aim of the study was to evaluate whether higher early calcium (Ca) and phosphorus (P) intake delivered by parenteral nutrition (PN) can prevent bone strength decline in preterm infants, within the first weeks after birth.Patients and Methods:This was a randomized controlled trial of consecutively admitted neonates born with ≤33 weeks of gestational age, assigned to receive either Ca 45 mg · kg−1 · day−1 (low dose [LD]) or Ca 75 mg · kg−1 · day−1 (high dose [HD]) by PN. P was added to the PN solutions at a fixed Ca:P ratio (mg) of 1.7:1. Bone strength was assessed by the speed of sound (SOS) using the quantitative ultrasound method. Measurements were performed weekly from birth until discharge. Low bone strength (SOS <10th centile of reference values) was the main outcome.Results:Eighty‐six infants were enrolled, 40 assigned to LD group and 46 to HD group. Mean (standard error) gestational age was 29.6 weeks (2.1) and birth weight was 1262 g (0.356). In the HD group, the SOS values never fell below those recorded at birth and, up to the sixth week of life, low bone strength was significantly less frequent as compared with that in the LD group, in spite of progressive reduction in parenteral mineral intake and/or establishment of full enteral feeding.Conclusions:Early assigned parenteral intake of Ca 75 mg · kg−1 · day−1 and P 44 mg · kg−1 · day−1 significantly contributed to preventing short‐term bone strength decline in preterm infants.
Acetaminophen Pharmacokinetics in Children With Nonalcoholic Fatty Liver Disease
Authors: Barshop Nicole J , Capparelli Edmund V , Sirlin Claude B , Schwimmer Jeffrey B , Lavine Joel E 
Published: January 2011

ABSTRACTObjectives:The aim of the study was to evaluate UDP‐glucuronyltransferase activity and the pharmacokinetics of a single oral dose of acetaminophen (APAP) in children with nonalcoholic fatty liver disease (NAFLD).Patients and Methods:Twelve boys 10 to 17 years old with biopsy‐proven NAFLD and 12 age‐ and sex‐matched controls without NAFLD were recruited. Following administration of a single oral dose of APAP (5 mg/kg, maximum 325 mg), APAP and its glucuronide metabolite (APAP‐G) were measured in plasma, urine, and sputum at various intervals up to 24 hours. The activity of UDP‐glucuronyltransferase was estimated by the plasma ratio of APAP‐G to APAP at 4 hours.Results:Following administration of APAP, children with NAFLD had significantly higher concentrations of APAP‐G in serum (P= 0.0071) and urine (P= 0.0210) compared with controls. No significant differences in APAP pharmacokinetics parameters were observed between the 2 groups.Conclusions:APAP glucuronidation is altered in children with fatty liver disease. Despite the altered disposition of this metabolite, the pharmacokinetics of a single 5 mg/kg dose of APAP is the same in children with NAFLD as in children with normal liver function.
Relations of Steatosis Type, Grade, and Zonality to Histological Features in Pediatric Nonalcoholic Fatty Liver Disease
Authors: Carter‐Kent Christine , Brunt Elizabeth M , Yerian Lisa M , Alkhouri Naim , Angulo Paul , Kohli Rohit , Ling Simon C , Xanthakos Stavra A , Whitington Peter F , Charatcharoenwitthaya Phunchai , Yap Jason , Lopez Rocio , McCullough Arthur J , Feldstein Ariel E 
Published: January 2011

ABSTRACTBackground:The relations between hepatic steatosis and histological features of hepatocyte injury in children with nonalcoholic fatty liver disease have yet to be examined. The aims of the present study were to establish associations between steatosis amount, type, and distribution in a well‐characterized group of children with biopsy‐proven nonalcoholic fatty liver disease (NAFLD).Patients and Methods:One hundred eight children with NAFLD seen in 5 centers were studied. Clinical and laboratory data were collected. Hematoxylin‐eosin and Masson trichrome stains were evaluated by 2 expert liver pathologists. Steatosis grade (0–3), type (macrovesicular, microvesicular, or mixed), and zone (1, 3, azonal, or panacinar) were determined. The NAFLD activity score and fibrosis stage were determined.Results:Median patient age was 12 years and median body mass index was 31 kg/m2. Fibrosis was present in 87%. The median NAFLD activity score was 4. Mild, moderate, and severe steatosis were present in 42%, 34%, and 24% of biopsies, respectively. Macrovesicular steatosis was present in 81% and mixed steatosis was present in 19%. Panacinar distribution of steatosis was most frequent (40%), followed by azonal (27%). Steatosis grade positively correlated with portal inflammation (P = 0.018). Azonal distribution positively correlated with presence of hepatocyte ballooning (P = 0.03). Biopsies with mixed steatosis were approximately 20 times more likely to have megamitochondria than those with macrovesicular steatosis alone (95% confidence interval 2.3–204.9). There was no relation between steatosis amount, type, or distribution to fibrosis stage.Conclusions:Specific histological patterns of steatosis in children are associated with histological markers of steatohepatitis. Ballooning and portal inflammation correlated well with features of steatosis.
Addition of Polydextrose and Galactooligosaccharide to Formula Does Not Affect Bacterial Translocation in the Neonatal Piglet
Authors: Monaco Marcia H , Kashtanov Dimitri O , Wang Mei , Walker D Carey , Rai Deshanie , Jouni Zeina E , Miller Michael J , Donovan Sharon M 
Published: January 2011

ABSTRACTObjectives:The aim of the study was to determine the effect of polydextrose (PDX) and galactooligosaccharide (GOS) on bacterial translocation (BT) in neonatal piglets.Materials and Methods:Piglets (n = 36) were randomized 12 hours after birth to receive total enteral nutrition (TEN) as formula; TEN + GOS (4 g/L), TEN + PDX (4 g/L), or TEN + GOS + PDX (2 g/L each) for 7 days or were supported by total parenteral nutrition (TPN) as a positive control for BT (n = 8). Blood, spleen, liver, and mesenteric lymph node (MLN) samples were cultured for aerobic and anaerobic bacteria. Colon microbiota 16S rDNA was measured by polymerase chain reaction. Myeloperoxidase activity and tumor necrosis factor‐α expression were measured in ileum and ascending colon.Results:Among the enterally fed groups, no difference was seen in the Lactobacillus and Bacteroides 16S rDNA copies per gram of colonic contents, yet total bacterial levels were lower (P < 0.05) in the TEN + GOS group compared with TEN alone. Bacteria were detected in the blood, liver spleen, and MLN of TPN piglets. In contrast, bacterial counts were predominantly detected in the MLN of TEN piglets, at much lower levels than in TPN, and levels were not affected by GOS and PDX addition. TPN piglets had elevated (P < 0.05) ileal myeloperoxidase activity and a trend in elevated ascending colon tumor necrosis factor‐α expression (P = 0.1).Conclusions:PDX and GOS added to formula do not induce BT in healthy piglets. Low levels of bacteria in MLN of healthy neonatal piglets may reflect mucosal sampling rather than pathological BT.
Esophageal Impedance Monitoring for Gastroesophageal Reflux
Authors: Mousa Hayat M , Rosen Rachel , Woodley Frederick W , Orsi Marina , Armas Daneila , Faure Christophe , Fortunato John , O'Connor Judith , Skaggs Beth , Nurko Samuel 
Published: January 2011

ABSTRACTDual pH‐multichannel intraluminal impedance (pH‐MII) is a sensitive tool for evaluating overall gastroesophageal reflux disease, and particularly for permitting detection of nonacid reflux events. pH‐MII technology is especially useful in the postprandial period or at other times when gastric contents are nonacidic.pH‐MII was recently recognized by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition as being superior to pH monitoring alone for evaluation of the temporal relation between symptoms and gastroesophageal reflux. In children, pH‐MII is useful to correlate symptoms with reflux (particularly nonacid reflux), to quantify reflux during tube feedings and the postprandial period, and to assess efficacy of antireflux therapy. This clinical review is simply an evidence‐based overview addressing the indications, limitations, and recommended protocol for the clinical use of pH‐MII in children.
Ileal Immune Dysregulation in Necrotizing Enterocolitis: Role of CD40/CD40L in the Pathogenesis of Disease
Authors: Xu Jiliu , Treem William R , Roman Christopher , Anderson Virginia , Rubenstein Richard , Schwarz Steven M 
Published: January 2011

AbstractObjectives:CD40, a co‐stimulatory molecule, plays a critical role in coordinating enteric inflammatory immune responses. In necrotizing enterocolitis (NEC), upregulation of IL‐10, a CD40‐modulated cytokine, has been described, but the role of the IL‐10 receptor (IL‐10Rβ), CD40, and its ligand CD40L in disease pathogenesis is unknown. The study herein investigates ileal expression of CD40, CD40L, and IL‐10R in a rat model of NEC.Subjects and Methods:NEC was induced in newborn rats using established methods of formula feeding, asphyxia, and cold stress. Expression of CD40, CD40L, IL‐10Rβ, and other proinflammatory molecules, including Toll‐like receptor‐4 (TLR‐4) and IL‐18, was assessed by immunoblotting. Tissue infiltration by macrophages, monocytes, and T cells was examined by confocal immunohistochemistry.Results:Ileum from rat pups with NEC showed increased expression of TLR‐4, IL‐18, and IL‐10Rβ. Sections from both NEC and control pups demonstrated preservation of ileal cells expressing CD40/CD40L. The distal ileum of controls expressed both CD40 and CD40L; conversely, neither molecule was detected in ileal tissue from NEC pups. Additional studies showed that treatment with epidermal growth factor (EGF), previously shown to ameliorate the severity of NEC in an animal model, did not restore CD40 expression.Conclusions:Ileal cytokine dysregulation, manifested by decreased CD40/CD40L and increased IL‐10Rβ expression, may be involved in the pathogenesis of NEC. Dampened CD40 signaling may be related to enhanced IL‐10 expression and a suppressed T‐cell response to injury. We speculate that augmenting CD40‐CD40L interactions may achieve a protective effect in this NEC model.
Identification and Characterization of Thioredoxin h Isoforms Differentially Expressed in Germinating Seeds of the Model Legume Medicago truncatula
Authors: Renard Michelle , Alkhalfioui Fatima , Schmitt-Keichinger Corinne , Ritzenthaler Christophe , Montrichard Françoise 
Published: January 2011

Abstract
Thioredoxins (Trxs) h, small disulfide reductases, and NADP-thioredoxin reductases (NTRs) have been shown to accumulate in seeds of different plant species and play important roles in seed physiology. However, little is known about the identity, properties, and subcellular location of Trx h isoforms that are abundant in legume seeds. To fill this gap, in this work, we characterized the Trx h family of Medicago truncatula, a model legume, and then explored the activity and localization of Trx h isoforms accumulating in seeds. Twelve Trx h isoforms were identified in M. truncatula. They belong to the groups previously described: h1 to h3 (group I), h4 to h7 (group II), and h8 to h12 (group III). Isoforms of groups I and II were found to be reduced by M. truncatula NTRA, but with different efficiencies, Trxs of group II being more efficiently reduced than Trxs of group I. In contrast, their insulin disulfide-reducing activity varies greatly and independently of the group to which they belong. Furthermore, Trxs h1, h2, and h6 were found to be present in dry and germinating seeds. Trxs h1 and, to a lesser extent, h2 are abundant in both embryonic axes and cotyledons, while Trx h6 is mainly present in cotyledons. Thus, M. truncatula seeds contain distinct isoforms of Trx h that differ in spatial distribution and kinetic properties, suggesting that they play different roles. Because we show that Trx h6 is targeted to the tonoplast, the possible role of this isoform during germination is finally discussed.
Glutathione-Indole-3-Acetonitrile Is Required for Camalexin Biosynthesis in Arabidopsis thaliana
Authors: Su Tongbing , Xu Juan , Li Yuan , Lei Lei , Zhao Luo , Yang Hailian , Feng Jidong , Liu Guoqin , Ren Dongtao 
Published: January 2011

Abstract
Camalexin, a major phytoalexin in Arabidopsis thaliana, consists of an indole ring and a thiazole ring. The indole ring is produced from Trp, which is converted to indole-3-acetonitrile (IAN) by CYP79B2/CYP79B3 and CYP71A13. Conversion of Cys(IAN) to dihydrocamalexic acid and subsequently to camalexin is catalyzed by CYP71B15. Recent studies proposed that Cys derivative, not Cys itself, is the precursor of the thiazole ring that conjugates with IAN. The nature of the Cys derivative and how it conjugates to IAN and subsequently forms Cys(IAN) remain obscure. We found that protein accumulation of multiple glutathione S-transferases (GSTs), elevation of GST activity, and consumption of glutathione (GSH) coincided with camalexin production. GSTF6 overexpression increased and GSTF6-knockout reduced camalexin production. Arabidopsis GSTF6 expressed in yeast cells catalyzed GSH(IAN) formation. GSH(IAN), (IAN)CysGly, and γGluCys(IAN) were determined to be intermediates within the camalexin biosynthetic pathway. Inhibitor treatments and mutant analyses revealed the involvement of γ-glutamyl transpeptidases (GGTs) and phytochelatin synthase (PCS) in the catabolism of GSH(IAN). The expression of GSTF6, GGT1, GGT2, and PCS1 was coordinately upregulated during camalexin biosynthesis. These results suggest that GSH is the Cys derivative used during camalexin biosynthesis, that the conjugation of GSH with IAN is catalyzed by GSTF6, and that GGTs and PCS are involved in camalexin biosynthesis.