bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Parenteral Amino Acid Administration to Extremely Low‐Birth‐Weight Infants During Early Postnatal Life
Authors: Porcelli Peter J. , Sisk Paula M. 
Published: January 2024

ABSTRACTBackgroundEarly administration of parenteral amino acids to infants with extremely low birth weight (birth weight ≤1,000 g) has been encouraged to foster growth. However, excessive intravenous intake of amino acids may cause metabolic acidosis and uremia in extremely low birth weight infants. The hypothesis for this study was that extremely low birth weight infants would tolerate slightly increased early postnatal parenteral amino acid administration and benefit.MethodsThe peak daily parenteral amino acid dosage was increased from 3 g/kg (standard group) to 4 g/kg (modified group). The corrected parenteral amino acid dosage was computed to account for enteral protein intake and keep the combined daily intravenous amino acid and enteral protein intake at or below 3 g · kg−1 · d−1 in the standard group and 4 g · kg−1 · d−1 in the modified group. The primary outcome measure was plasma bicarbonate concentration as an indicator of acid–base status. Data were collected for patient demographics, nutritional intake, serum bicarbonate and serum urea nitrogen concentrations, and outcome.ResultsThe corrected parenteral amino acid intake of the modified group was 16% greater at postnatal week 1 (3.30 ± 0.83 g · kg−1 · d−1; mean, ±1 SD) and 18% greater (3.86 ± 0.94 g · kg−1 · d−1) at postnatal week 2 than the parenteral amino acid intake of the standard group. In the modified group, the mean serum bicarbonate concentration was 19.1 ± 1.8 mEq/dL at week 1 and 23.9 ± 2.9 mEq/dL at week 2, with no difference between the groups. At week 1, serum urea nitrogen concentrations were the same in both groups. The mean serum urea nitrogen concentration of the modified group at postnatal week 2 (18.2 ± 8.8 mg/dL) was unchanged from postnatal week 1, but was greater than that of the standard group at postnatal week 2. Weight gain was the same in both groups. Corrected parenteral amino acid intake at postnatal week 1 correlated directly with weight gain from birth to postnatal week 2 (P < 0.03) in both groups.ConclusionsInfants with extremely low birth weight tolerated parenteral amino acid intake of approximately 4 g · kg−1 · d−1. Mild increases of mean serum urea nitrogen concentration and mean weight gain were associated with increased parenteral amino acid administration without significant acidosis.
Diet‐Related Adaptation of the Small Intestine at Weaning in Pigs Is Functional Rather Than Structural
Authors: Boudry Gaëlle , Lallès Jean Paul , Malbert Charles Henri , Bobillier Eric , Sève Bernard 
Published: January 2024

ABSTRACTBackgroundIncidence of diarrhea at weaning in commercial pigs is an important problem, and diet is thought to be a predisposing factor. The aim of this study was to determine the impact of switching from milk‐based to cereal‐based diets on the morphology and function of the small intestine of piglets using a model of delayed weaning to isolate the influence of the diet from that of environmental and social factors.MethodsForty‐five piglets received a milk‐based diet for 5 weeks after weaning. Thirty piglets were then switched from milk‐based to wheat‐ or barley‐based diets, mimicking the dietary change that occurs at weaning. The last 15 piglets remained on the milk‐based diet. Piglets were killed 4 days after the dietary switch. Jejunal mucosa morphometry and enzyme activities were measured. Ussing chambers were used to measure intestinal permeability to macromolecules, basal electrical properties, glucose absorption, and induced chloride‐secretion.ResultsAlkaline phosphatase– and sucrase‐specific activities were higher in both groups of cereal‐fed piglets than in milk‐fed piglets. Dipeptidylpeptidase IV activity was higher in wheat‐fed piglets than in the other groups. Na+‐dependent glucose absorption was 1.7‐fold higher in cereals‐fed piglets than in milk‐fed piglets. Serotonin‐induced and vasoactive intestinal polypeptide–induced chloride secretion was doubled in cereals‐fed piglets. Dietary transition did not influence the other parameters.ConclusionsThese results indicate that switching from milk to cereals increased some mucosal enzyme activities, intestinal Na+–dependent glucose absorption, and response to secretagogues. This supports the hypothesis that dietary factors could initiate diarrhea in the presence of other aggravating factors, such as pathogens or environmental stress.
Dosage‐Related Bifidogenic Effects of Galacto‐ and Fructooligosaccharides in Formula‐Fed Term Infants
Authors: Moro G. , Minoli I. , Mosca M. , Fanaro S. , Jelinek J. , Stahl B. , Boehm G. 
Published: January 2024

ABSTRACTBackgroundHuman milk oligosaccharides have been shown to stimulate selectively the growth of Bifidobacteria and Lactobacilli in the intestine. In this study, the bifidogenic effect of an experimental prebiotic oligosaccharide mixture consisting of low‐molecular‐weight galactooligosaccharides and high‐molecular‐weight fructooligosaccharides was analyzed in 90 term infants.MethodsTwo test formulas were supplemented with either 0.4 g/dL or with 0.8 g/dL oligosaccharides. In the control formula, maltodextrin was used as placebo. At study day 1 and study day 28, the fecal species, colony forming units (cfu) and pH were measured and stool characteristics, growth, and side effects were recorded.ResultsAt study day 1, the median number of Bifidobacteria did not differ among the groups (0.4 g/dL group, mean [interquartile range] 8.5 [1.9] cfu/g; 0.8 g/dL group, 7.7 [6.1] cfu/g; and the placebo group, 8.8 [6.1] cfu/g) (figures in square brackets are interquartile range). At the end of the 28‐day feeding period, the number of Bifidobacteria was significantly increased for both groups receiving supplemented formulas (the 0.4 g/dL group, 9.3 [4.9] cfu/g; the 0.8 g/dL group, 9.7 [0.8] cfu/g) versus the placebo group (7.2 [4.9] cfu/g, P < 0.001). This effect was dose dependent (0.4 g/dL versus 0.8 g/dL, P < 0.01). The number of Lactobacilli also increased significantly in both groups fed the supplemented formulas (versus placebo, P < 0.001), but there was no statistically significant difference between the group fed formula with 0.4 g/dL oligosaccharides and the group fed formula with 0.8 g/dL oligosaccharides. The dosage of supplement significantly influenced the change in fecal pH (P < 0.05) (placebo, pH 5.5–6.1; 0.4 g/dL formula, pH 5.48–5.44; 0.8 g/dL formula, pH 5.54–5.19). Slight changes in the stool frequency resulted in a significant difference between the placebo group and the group fed the 0.8 g/dL formula at day 28 (P < 0.01). Supplementation had a significant dose‐dependent influence on stool consistency (0.8 g/dL versus placebo, P < 0.0001; 0.8 g/dL versus 0.4 g/dL, P < 0.01). Supplementation had no influence on the incidence of side effects (crying, regurgitation, vomiting) or growth.ConclusionsThese data indicate that supplementation of a term infant's formula with a mixture of galacto‐ and fructooligosaccharides has a dose‐dependent stimulating effect on the growth of Bifidobacteria and Lactobacilli in the intestine and results in softer stool with increasing dosage of supplementation.
Reactive Nitrogen Species Modulate the Effects of Rhein, an Active Component of Senna Laxatives, on Human Epithelium In Vitro
Authors: Raimondi Francesco , Santoro Pasquale , Maiuri Luigi , Londei Marco , Annunziata Simona , Ciccimarra Filippo , Rubino Armido 
Published: January 2024

ABSTRACTBackgroundSenna laxatives are used worldwide. However, their misuse can lead to chronic mucosal inflammation with the accumulation of pigment‐laden leukocytes and may cause colon cells to undergo apoptosis. This study explores the mechanisms by which rhein, an active component of senna, acts on a human intestinal cell line to induce ion secretion, apoptosis, and indirect chemotaxis of polymorphonuclear leukocytes.MethodsHuman colonic adenocarcinoma (CaCo‐2) monolayer cells, in the presence or in the absence of rhein, were used to monitor the production of reactive nitrogen species using the Griess reaction. Modified Ussing chambers were used to study electrolyte secretion. The capacity to recruit human polymorphonuclear leukocytes was evaluated using masked well chemotaxis chambers. Rhein‐induced apoptosis was investigated by counting apoptotic nuclei stained with Hoechst 33258 dye.ResultsRhein caused a dose‐dependent increase in short‐circuit current that was abolished in chloride‐free bathing buffer or by preincubating with 100 μmol/L NG‐nitro‐L‐arginine (L‐NAME) methyl ester. The concentration that maximally stimulated intestinal secretion, 50 μmol/L rhein, induced nitrate production. Supernatants obtained from CaCo‐2 cultures after incubation with 50 μmol/L rhein stimulated a time‐dependent polymorphonuclear leukocytes chemotaxis that was significantly decreased with 100 μmol/L L‐NAME, whereas rhein per se was not active. Neutralizing antibodies anti–interleukin‐8 (IL‐8) and anti‐ENA78 also inhibited chemotaxis. Overnight rhein incubation produced an increased number of apoptotic cells in the culture supernatant that was significantly decreased by preincubation with 100 μmol/L L‐NAME. Light‐degraded rhein had no effects on CaCo‐2 monolayers.ConclusionsThe integrity of rhein is crucial to generating nitric oxide, which mediates, with different time courses, ion secretion, chemotaxis, and apoptosis of human‐derived cells.
Management of Esophageal Strictures in Children With Recessive Dystrophic Epidermolysis Bullosa
Authors: Castillo Ricardo O. , Davies Yinka K. , Lin Yuan‐Chi , Garcia Manuel , Young Harvey 
Published: January 2024

ABSTRACTBackgroundRecessive dystrophic epidermolysis bullosa is a rare, genetically transmitted skin disorder characterized by blister formation and scarring in response to minor trauma. One of the most debilitating features of the disease is the development of esophageal strictures, which produces profound dysphagia, exacerbating an already highly compromised nutritional status common to these patients. Due to the extreme fragility of epithelial surfaces, the optimal therapeutic approach to esophageal strictures in this setting has not been established.MethodsWe have developed an approach to treatment of esophageal strictures in children with epidermolysis bullosa combining upper endoscopy using small caliber endoscopes, endotracheal intubation, and fluoroscopically assisted balloon dilatation. We report our experience using this technique in 22 children who have undergone a total of 109 dilatations.ResultsUpper endoscopy, endotracheal intubation, and balloon dilatation were well tolerated by even very young children with epidermolysis bullosa. Dysphagia was markedly reduced post‐procedure, permitting resumption of normal diet for age, including solids, within six hours of the procedure. Post‐procedure recovery has been rapid and does not require admission to the hospital. Complications have been infrequent, minor, and limited to the first year of our experience. The mean interval between dilatations for all children is 11 months. All children have gained weight, and have not required steroids or phenytoin.ConclusionsBalloon dilatation is a safe and effective therapy for esophageal strictures in children with recessive dystrophic epidermolysis bullosa. Limited upper endoscopy and endotracheal intubation are well tolerated by these children. This approach should be considered as primary therapy in this clinical setting.
Neonatal Hypoxia in the Rat: Effects on Exocrine Pancreatic Development
Authors: Lee Ping C. , Struve Mark , Lewis Suzan M. , Raff Hershel 
Published: January 2024

ABSTRACTBackgroundGlucocorticoids profoundly affect pancreatic development during the suckling period. Increases in circulating glucocorticoids during exposure to hypoxia may alter the normal pattern of pancreatic enzyme development.MethodsRats were exposed to hypoxia from birth to 7 days (suckling) or from 28 to 35 days of age (weaned at day 21).ResultsHypoxia in neonatal rats (0–7 days) led to decreased pancreatic weight, and trypsin, lipase, and amylase activity compared with normoxic controls. In contrast, rats exposed to hypoxia from 28 to 35 days of age had decreased lipase activity but no change in other pancreatic parameters. Two weeks after hypoxia (0–7 days) pups were returned to normoxia, and their body weights remained smaller than the age‐matched, previously normoxic controls. Pancreatic enzyme activities were decreased in the group recovering from hypoxia compared with controls. Recovery of enzyme activities was observed 3 weeks after hypoxic rats were returned to normoxia. Normoxic pups were given dexamethasone to simulate the hyperglucocorticoid state in hypoxia at 7‐day olds. Dexamethasone administration led to decreased body weight, but increased pancreatic weight and enzyme activity compared with normoxic, age‐matched controls.ConclusionsHypoxia in newborn rats delays the maturation of pancreatic exocrine enzymes. The mechanism is not related to increased serum glucocorticoids.
Helicobacter pylori Infection in Asymptomatic Children: Impact of Epidemiologic Factors on Accuracy of Diagnostic Tests
Authors: Malaty Hoda M. , Haveman Teresa , Graham David Y. , Fraley J. Kennard 
Published: January 2024

ABSTRACTBackgroundChildhood is a time of high risk for acquiring H. pylori infection. Accurate information on the epidemiology of the infection requires accurate diagnostic tests.ObjectiveTo study the epidemiologic factors that influence the accuracy of diagnostic tests among asymptomatic children.MethodsTwo rapid, noninvasive assays (FlexSure® whole‐blood test and OraSure® saliva test) were evaluated using the 13C‐urea breath test (13C‐UBT) as the gold standard. The three diagnostic tests were conducted in children from 10 licensed day care centers from various locations in Houston, Texas. Demographic information and socioeconomic factors evaluated included age, gender, ethnicity, and crowded living conditions in each center. The three tests were conducted on each child on the same day. We examined the effect of epidemiologic factors on the sensitivity, the specificity, and the positive and negative predictive values of both tests.ResultsThirty‐two percent of the 243 asymptomatic children who participated in the study tested positive for H. pylori using 13C‐UBT. Among all the children, the sensitivities of FlexSure and OraSure were 47% (95% confidence interval, 35–57%) and 65% (95% confidence interval, 54–73%), respectively. Both tests had greater than 95% specificity. Positive and negative predictive values for FlexSure were 86% and 80%, respectively, and 98% and 86% for OraSure. Among children attending the more crowded day care centers, the sensitivities of FlexSure and OraSure were 40% and 63%, respectively, compared with 100% sensitivity for FlexSure and 80% sensitivity for OraSure among children attending the less‐crowded centers. FlexSure and OraSure tests had the highest sensitivities among the 6‐to 10‐year‐olds. Ethnicity had no effect on the sensitivity or the specificity of either test.ConclusionEpidemiologic factors influenced the accuracy of serologic tests for diagnosing H. pylori infection in children. The lowest sensitivities of both tests were among children who attended the more crowded centers and among the youngest and oldest age groups, reflecting an increased proportion of recent infections. The strategy for choosing a diagnostic test for H. pylori infection in children varies based on the epidemiologic characteristics of the studied population.
Tyrosinemia I, A Model For Human Diseases Mediated By 2‐Oxoacid‐Utilizing Dioxygenases: Hepatotoxin Suppression By NTBC Does Not Normalize Hepatic Collagen Metabolism
Authors: Hanauske‐Abel Hartmut M. , Popowicz Anthony , Remotti Helen , Newfield Ron S. , Levy Joseph 
Published: January 2024

ABSTRACTObjectivesMedical treatment of tyrosinemia I relies on the herbicide NTBC [Orfadin™ 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐cyclohexane‐1,3‐dione], an inhibitor of plant and mammalian 2‐oxoacid‐utilizing dioxygenases with a collective catalytic cycle (`HAG' mechanism). We hypothesize that NTBC‐treated tyrosinemia I is a human model for the pathogenic role of two major enzymes in this class, 4‐hydroxyphenylpyruvate dioxygenase (4‐HPPD; EC 1.13.11.27) and prolyl 4‐hydroxylase (P4‐H; E.C. 1.14.11.2), essential for tyrosine and collagen metabolism, respectively.MethodsIn a patient with established tyrosinemia I, we monitored the in vivo activities of 4‐HPPD and P4‐H via five biomarkers before and during NTBC medication. Hypothesis testing at the molecular level was performed by computational modeling of NTBC binding to the crystal structure‐derived active site of 4‐HPPD, and then relating these findings to our experimental results and to known P4‐H data.ResultsNTBC rapidly normalized the biomarkers for 4‐HPPD activity. However, those for P4‐H activity remained uniformly elevated after one hundred days on NTBC, the PIIINP biomarker even increasing above its grossly abnormal, initial level. This selective enzyme inhibition despite a collective catalytic cycle is attributed to the conformation of NTBC, which only fits the active site of 4‐HPPD, as confirmed by its crystal structure.ConclusionsNormalization of hepatic collagen formation, highly desirable in all fibrotic liver diseases, is not achieved by NTBC in tyrosinemia I. By establishing the molecular cause for this failure, our results also establish a rational approach to identify inhibitors that achieve that goal, either by joint 4‐HPPD / P‐4H inhibition, or by inhibition of only P‐4H.
Mechanisms of Gastroesophageal Reflux and Gastroesophageal Reflux Disease
Authors: Vandenplas Yvan , Hassall Eric 
Published: January 2024

ABSTRACTGastroesophageal reflux is a physiological phenomenon, occurring with different severity and duration in different individuals. Reflux disease occurs when this normal event results in the occurrence of symptoms/signs or complications. The pathophysiology of gastroesophageal reflux is complex and diverse, since it is influenced by factors that are genetic, environmental (e.g., diet smoking), anatomic, hormonal, and neurogenic. However, many mechanisms remain incompletely understood. Future research should focus on a better understanding of the physiology of the upper and lower esophageal sphincters, and of gastric motility. The afferent and efferent neural pathways and neuropharmacologic mediators of transient lower esophageal sphincter relaxations and gastric dysmotility require further study. The role of anatomic malformations such as hiatal hernia in children has been underestimated.While therapeutic possibilities are greater in number and largely improved, the outcomes of some treatments are far from satisfactory in many cases. In addition to development of new forms of treatment, research should address better use of currently available medical and surgical treatments.
Esophageal Acid Clearance: More Volume‐Dependent Than Motility‐Dependent in Healthy Piglets
Authors: Vicente Yvone , da Rocha Cecilia , Hernandez‐Peredo Guillermo , Madero Rosario , Tovar Juan A. 
Published: January 2024

ABSTRACTBackground/aimsThe present study investigates manometrically in healthy piglets whether esophageal clearance after distension with different volumes of acid is volume‐dependent.MethodsSedated, non‐intubated piglets (n = 22) underwent stationary manometry of the esophagus with a 4‐probe perfused assembly after successive injection of 1, 2, and 3 mL of saline and acid. Simultaneous pH metering allowed assessment of acid clearance. Wave features and clearance times after saline and acid were compared by paired non‐parametric tests and Friedman analysis of variance. The linearity of the relationships between the clearance times and the volumes of acid infused were tested after square root transformations by one‐way ANOVA repeated measures. The significance level was set atP< 0.05.ResultsThe motor response was identical after distension with saline and acid except for the largest amount of acid used, which elicited more waves during the first 5 minutes after infusion. Time elapsed until regaining pH4 was longer after higher amounts of acid, but not significantly, whereas that necessary to regain baseline pH was significantly longer after such challenge. Esophageal motility was practically identical after 1 and 2 mL of acid, but it was slightly less effective in the first minute after the 3 mL challenge. There was a linear correlation between clearance times and volumes of acid infused.ConclusionsUp to a certain volume, the motor responses of the healthy esophagus to distension with neutral or acid fluids were similar. Acid clearance was more a function of the amount of acid present than of the motor response elicited by its presence. Only when the amount of acid was large, esophageal motor response was worse than that elicited after equivalent volumes of neutral fluid. The present evidence suggests that long episodes of reflux in pH tracings might reflect large volumes of refluxate as well as disturbed motor function.
Parenteral Amino Acids Increase Albumin and Skeletal Muscle Protein Fractional Synthetic Rates in Premature Newborn Minipigs
Authors: Hellstern Gerald , Kaempf‐Rotzoll Daisy , Linderkamp Otwin , Langhans Klaus‐Dieter , Rating Dietz 
Published: January 2024

ABSTRACTObjectivesEarly administration of parenteral amino acids increases whole body nitrogen retention in premature infants. Tracer kinetic studies suggest an increase in whole body protein synthesis as a possible mechanism for this increase in nitrogen retention. However, the effect of early parenteral amino acids on synthesis of specific proteins remains uncertain. Using premature newborn minipigs as a model for human premature newborns, we investigated the effects of parenterally administered amino acids on albumin and skeletal muscle protein fractional synthetic rates.MethodsFifteen Yucatan minipigs were delivered by cesarean section 6 days before the mean expected delivery date (day 106 of gestation; expected gestation, 111–113 days) and randomized to two groups immediately after birth: 7 piglets received a mixture of amino acids (0.4 g · kg−1 · h−1) and glucose (0.8 g · kg−1 · h−1) for 5 hours, and 8 piglets (control group) received glucose only. All piglets received a continuous primed infusion of 1‐[13C]valine. Arterial plasma free 13C‐valine enrichment was measured by gas chromatography/mass spectrometry, and protein synthetic rates were determined by measuring incorporation of 13C‐valine into albumin and skeletal muscle protein using gas chromatography/combustion/isotope ratio mass spectrometry.ResultsAdministration of amino acids increased albumin (87.0% ± 42.1% [mean ± SD] vs. 37.6% ± 6.8% per 24 hours;P < 0.05) and skeletal muscle fractional synthetic rates (11.60% ± 6.9% vs. 6.5% ± 1.5% per 24 hours;P < 0.05).ConclusionWe conclude that parenteral amino acids increase albumin and skeletal muscle fractional synthetic rates in premature piglets on the first day of life.