Nutritional support in children with end-stage liver disease : a randomized crossover trial of a branched-chain amino acid supplement

Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formulation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD. and are deserving of wider application and study.

The bentiromide test using plasma p-aminobenzoic acid for diagnosing pancreatic insufficiency in young children. The effect of two different doses and a liquid meal

The bentiromide test was evaluated using plasma p-aminobenzoic acid as an indirect test of pancreatic insufficiency in young children between 2 months and 4 years of age. To determine the optimal test method, the following were examined: (a) the best dose of bentiromide (15 mg/kg or 30 mg/kg); (b) the optimal sampling time for plasma p-aminobenzoic acid, and; (c) the effect of coadministration of a liquid meal. Sixty-nine children (1.6 ± 1.0 years) were studied, including 34 controls with normal fat absorption and 35 patients (34 with cystic fibrosis) with fat maldigestion due to pancreatic insufficiency. Control and pancreatic insufficient subjects were studied in three age-matched groups: (a) low-dose bentiromide (15 mg/kg) with clear fluids; (b) high-dose bentiromide (30 mg/kg) with clear fluids, and; (c) high-dose bentiromide with a liquid meal. Plasma p-aminobenzoic acid was determined at 0, 30, 60, and 90 minutes then hourly for 6 hours. The dose effect of bentiromide with clear liquids was evaluated. High-dose bentiromide best discriminated control and pancreatic insufficient subjects, due to a higher peak plasma p-aminobenzoic acid level in controls, but poor sensitivity and specificity remained. High-dose bentiromide with a liquid meal produced a delayed increase in plasma p-aminobenzoic acid in the control subjects probably caused by retarded gastric emptying. However, in the pancreatic insufficient subjects, use of a liquid meal resulted in significantly lower plasma p-aminobenzoic acid levels at all time points; plasma p-aminobenzoic acid at 2 and 3 hours completely discriminated between control and pancreatic insufficient patients. Evaluation of the data by area under the time-concentration curve failed to improve test results. In conclusion, the bentiromide test is a simple, clinically useful means of detecting pancreatic insufficiency in young children, but a higher dose administered with a liquid meal is recommended.

Structure of the K12 capsule containing 5,7-di-N-acetylacinetaminic acid from Acinetobacter baumannii isolate D36

The repeat unit of the K12 capsular polysaccharide isolated from the Acinetobacter baumannii global clone 1 clinical isolate, D36, was elucidated by means of chemical and spectroscopical methods. The structure was shown to contain N-acetyl-D-galactosamine (D-GalpNAc), N-acetyl-D-fucosamine and N-acetyl-L-fucosamine linked together in the main chain, with the novel sugar, 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-L-altro-non-2-ulosonic acid (5,7-di-N-acetylacinetaminic acid or Aci5Ac7Ac), attached to D-GalpNAc as a side branch. This matched the sugar composition of the K12 capsule and the genetic content of the KL12 capsule gene cluster reported previously. D-FucpNAc was predicted to be the substrate for the initiating transferase, ItrB3, with the Wzy polymerase making a α-D-FucpNAc-(1 → 3)-D-GalpNAc linkage between the repeat units. The three glycosyltransferases encoded by KL12 are all retaining glycosyltransferases and were predicted to form specific linkages between the sugars in the K12 repeat unit.

Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2x10(-201)), ABCG2 (p = 3.1x10(-26)), SLC17A1 (p = 3.0x10(-14)), SLC22A11 (p = 6.7x10(-14)), SLC22A12 (p = 2.0x10(-9)), SLC16A9 (p = 1.1x10(-8)), GCKR (p = 1.4x10(-9)), LRRC16A (p = 8.5x10(-9)), and near PDZK1 (p = 2.7x10(-9)). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0x10(-26)) and propionyl-L-carnitine (p = 5.0x10(-8)) concentrations, which in turn were associated with serum UA levels (p = 1.4x10(-57) and p = 8.1x10(-54), respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.

Factors influencing kinetic and equilibrium behaviour of sodium ion exchange with strong acid cation resin

This study reports an investigation of the ion exchange treatment of sodium chloride solutions in relation to use of resin technology for applications such as desalination of brackish water. In particular, a strong acid cation (SAC) resin (DOW Marathon C) was studied to determine its capacity for sodium uptake and to evaluate the fundamentals of the ion exchange process involved. Key questions to answer included: impact of resin identity; best models to simulate the kinetics and equilibrium exchange behaviour of sodium ions; difference between using linear least squares (LLS) and non-linear least squares (NLLS) methods for data interpretation; and, effect of changing the type of anion in solution which accompanied the sodium species. Kinetic studies suggested that the exchange process was best described by a pseudo first order rate expression based upon non-linear least squares analysis of the test data. Application of the Langmuir Vageler isotherm model was recommended as it allowed confirmation that experimental conditions were sufficient for maximum loading of sodium ions to occur. The Freundlich expression best fitted the equilibrium data when analysing the information by a NLLS approach. In contrast, LLS methods suggested that the Langmuir model was optimal for describing the equilibrium process. The Competitive Langmuir model which considered the stoichiometric nature of ion exchange process, estimated the maximum loading of sodium ions to be 64.7 g Na/kg resin. This latter value was comparable to sodium ion capacities for SAC resin published previously. Inherent discrepancies involved when using linearized versions of kinetic and isotherm equations were illustrated, and despite their widespread use, the value of this latter approach was questionable. The equilibrium behaviour of sodium ions form sodium fluoride solution revealed that the sodium ions were now more preferred by the resin compared to the situation with sodium chloride. The solution chemistry of hydrofluoric acid was suggested as promoting the affinity of the sodium ions to the resin.

Positive associations of serum Perfluoroalkyl substances with uric acid and hyperuricemia in children from Taiwan

To investigate the risk of hyperuricemia in relation to Perfluoroalkyl substances (PFASs) in children from Taiwan, 225 Taiwanese children aged 12-15 years were recruited from 2009 to 2010. Linear and logistic regression models were employed to examine the influence of PFASs on serum uric acid levels. Findings revealed that eight of ten PFASs analyses were detected in > 94% of the participants' serum samples. Multivariate linear regression models revealed that perfluorooctanic acid (PFOA) was positively associated with serum uric acid levels (β=0.1463, p<0.05). Of all the PFASs analyses, only PFOA showed a significant effect on elevated levels of hyperuricemia (aOR=2.16, 95%CI: 1.29-3.61). When stratified by gender, the association between serum PFOA and uric acid levels was only evident among boys (aOR=2.76, 95%CI: 1.37-5.56). In conclusion, PFOA was found to be associated with elevated serum levels of uric acid in Taiwanese children, especially boys. Further research is needed to elucidate these links.

Starch composites with aconitic acid

The aim of this project is to examine the effectiveness of using aconitic acid (AcA), a tricarboxylic acid which contains a carbon/carbon double bond (C=C), to enhance the properties of starch-based films. Starch/glycerol cast films were prepared with 0, 2, 5, 10 and 15 wt% AcA (starch wt% basis) and the properties analysed. It was shown that AcA acted as both a cross-linking agent and also a strong plasticising agent. The 5 wt% AcA derived starch films were the most effectively cross-linked having the lowest solubility (28 wt%) and decreased swelling coefficient (35 vol.%) by approximately 3 times and 2.4 times respectively compared to the control film submerged in water (23 °C). There was also a significant increase in the film elongation at break by approximately 35 times (compared to the control) with the addition of 15 wt% AcA, emphasising the plasticising effect of AcA. However, generally there was a reduced tensile strength, softening of the film, and reduced thermal stability with increased amounts of AcA.

Can current force fields reproduce ring puckering in 2-O-sulfo-α-l-iduronic acid? A molecular dynamics simulation study

The monosaccharide 2-O-sulfo-α-l-iduronic acid (IdoA2S) is one of the major components of glycosaminoglycans. The ability of molecular mechanics force fields to reproduce ring-puckering conformational equilibrium is important for the successful prediction of the free energies of interaction of these carbohydrates with proteins. Here we report unconstrained molecular dynamics simulations of IdoA2S monosaccharide that were carried out to investigate the ability of commonly used force fields to reproduce its ring conformational flexibility in aqueous solution. In particular, the distribution of ring conformer populations of IdoA2S was determined. The GROMOS96 force field with the SPC/E water potential can predict successfully the dominant skew-boat to chair conformational transition of the IdoA2S monosaccharide in aqueous solution. On the other hand, the GLYCAM06 force field with the TIP3P water potential sampled transitional conformations between the boat and chair forms. Simulations using the GROMOS96 force field showed no pseudorotational equilibrium fluctuations and hence no inter-conversion between the boat and twist boat ring conformers. Calculations of theoretical proton NMR coupling constants showed that the GROMOS96 force field can predict the skew-boat to chair conformational ratio in good agreement with the experiment, whereas GLYCAM06 shows worse agreement. The omega rotamer distribution about the C5–C6 bond was predicted by both force fields to have torsions around 10°, 190°, and 360°.

Facile synthesis, ex-vivo and in vitro screening of 3-sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716) a potent CB1 receptor antagonist

Facile synthesis of biaryl pyrazole sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716, 1) and an investigation of the effect of replacement of the –CO group in the compound 1 by the –SO2 group in the aminopiperidine region is reported. Primary ex-vivo pharmacological testing and in vitro screening of sulfonamide derivative 2 showed the loss of CB1 receptor antagonism.

Diaryl dihydropyrazole-3-carboxamides with significant in vivo antiobesity activity related to CB1 receptor antagonism: Synthesis, biological evaluation, and molecular modeling in the homology model

A number of analogues of diaryl dihydropyrazole-3-carboxamides have been synthesized. Their activities were evaluated for appetite suppression and body weight reduction in animal models. Depending on the chemical modification of the selected dihydropyrazole scaffold, the lead compoundsthe bisulfate salt of (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 26 and the bisulfate salt of (−)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 30showed significant body weight reduction in vivo, which is attributed to their CB1 antagonistic activity and exhibited a favorable pharmacokinetic profile. The molecular modeling studies also showed interactions of two isomers of (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 9 with CB1 receptor in the homology model similar to those of N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (rimonabant) 1 and 4S-(−)-3-(4-chlorophenyl)-N-methyl-N‘-[(4-chlorophenyl)-sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamidine (SLV-319) 2.

Ion exchange of sodium chloride and sodium bicarbonate solutions using strong acid cation resins in relation to coal seam water treatment

Coal seam gas production has resulted in the production of large volumes of associated water which contains dissolved salts dominated by sodium chloride and sodium bicarbonate. Ion exchange using synthetic resins has been proposed as a method for desalination of coal seam water to make it suitable for various beneficial reuse options. This study investigated the behaviour of solutions of sodium chloride and sodium bicarbonate with respect to exchange with Lanxess S108H strong acid cation (SAC) resin. Equilibrium isotherms were created for solutions of NaCl and NaHCO3 and an actual sample of coal seam water from the Surat Basin in southern Queensland. The exchange of sodium ions arising from sodium bicarbonate was found to be considerably more favourable than exchange of sodium ions from sodium chloride solutions. This latter behaviour was attributed to the secondary decomposition of bicarbonate species under acidic conditions which resulted in the evolution of carbon dioxide and formation of water. The isotherm profiles could not be satisfactorily fitted by a single isotherm model such as the Langmuir expression. Instead, two Langmuir equations had to be simultaneously applied in order to fit the sections of the isotherm attributable to sodium ion exchange from sodium bicarbonate and sodium chloride. The shape of the isotherm profile was dependent upon the ratio of sodium chloride to sodium bicarbonate in solution and there was a high degree of correlation between simulated and actual coal seam water solutions.

Associations of serum perfluoroalkyl acid levels with T-helper cell-specific cytokines in children: By gender and asthma status

Perfluoroalkyl acids (PFAAs) are a group of common chemicals that ubiquitously exist in wildlife and humans. Experimental data suggest that they may alter T-lymphocyte functioning in situ by preferentially enhancing the development of T-helper 2 (TH2)- and inhibiting TH1-lymphocyte development and might increase allergic inflammation, but few human studies have been conducted. To evaluate the association between serum PFAAs concentrations and T-lymphocyte-related immunological markers of asthma in children, and further to assess whether gender modified this association, 231 asthmatic children and 225 non-asthmatic control children from Northern Taiwan were recruited into the Genetic and Biomarker study for Childhood Asthma. Serum concentrations of ten PFAAs and levels of TH1 [interferon (IFN)-γ, interleukin (IL)-2] and TH2 (IL-4 and IL-5) cytokines were measured. The results showed that asthmatics had significantly higher serum PFAAs concentrations compared with the healthy controls. When stratified by gender, a greater number of significant associations between PFAAs and asthma outcomeswere found in males than in females. Among males, adjusted odds ratios for asthma among those with the highest versus lowest quartile of PFAAs exposure ranged from 2.59 (95% CI: 1.14, 5.87) for the perfluorobutanesulfonate (PFBS) to 4.38 (95% CI: 2.02, 9.50) for perfluorooctanesulfonate (PFOS); and serum PFAAs were associated positively with TH2 cytokines and inversely with TH1 cytokines among male asthmatics. Among females, no significant associations between PFAAs and TH2 cytokines could be detected. In conclusion, increased serum PFAAs levels may promote TH cell dysregulation and alter the availability of key TH1 and TH2 cytokines, ultimately contributing to the development of asthma that may differentially impact males to a greater degree than females. These results have potential relevance in asthma prevention.

Polydimethylsiloxane (PDMS) modulates CD38 expression, absorbs retinoic acid and may perturb retinoid signalling

Polydimethylsiloxane (PDMS) is the most commonly used material in the manufacture of customized cell culture devices. While there is concern that uncured PDMS oligomers may leach into culture medium and/or hydrophobic molecules may be absorbed into PDMS structures, there is no consensus on how or if PDMS influences cell behaviour. We observed that human umbilical cord blood (CB)-derived CD34+ cells expanded in standard culture medium on PDMS exhibit reduced CD38 surface expression, relative to cells cultured on tissue culture polystyrene (TCP). All-trans retinoic acid (ATRA) induces CD38 expression, and we reasoned that this hydrophobic molecule might be absorbed by PDMS. Through a series of experiments we demonstrated that ATRA-mediated CD38 expression was attenuated when cultures were maintained on PDMS. Medium pre-incubated on PDMS for extended durations resulted in a time-dependant reduction of ATRA in the medium and increasingly attenuated CD38 expression. This indicated a time-dependent absorption of ATRA into the PDMS. To better understand how PDMS might generally influence cell behaviour, Ingenuity Pathway Analysis (IPA) was used to identify potential upstream regulators. This analysis was performed for differentially expressed genes in primary cells including CD34+ haematopoietic progenitor cells, mesenchymal stromal cells (MSC), and keratinocytes, and cell lines including prostate cancer epithelial cells (LNCaP), breast cancer epithelial cells (MCF-7), and myeloid leukaemia cells (KG1a). IPA predicted that the most likely common upstream regulator of perturbed pathways was ATRA. We demonstrate here that ATRA is absorbed by PDMS in a time-dependent manner and results in the concomitant reduced expression of CD38 on the cell surface of CB-derived CD34+ cells.

BDST modelling of sodium ion exchange column behaviour with strong acid cation resin in relation to coal seam water treatment

Reverse osmosis is the dominant technology utilized for desalination of saline water produced during the extraction of coal seam gas. Alternatively, ion exchange is of interest due to potential cost advantages. However, there is limited information regarding the column performance of strong acid cation resin for removal of sodium ions from both model and actual coal seam water samples. In particular, the impact of bed depth, flow rate, and regeneration was not clear. Consequently, this study applied Bed Depth Service Time (BDST) models to reveal that increasing sodium ion concentration and flow rates diminished the time required for breakthrough to occur. The loading of sodium ions on fresh resin was calculated to be ca. 71.1 g Na/kg resin. Difficulties in regeneration of the resin using hydrochloric acid solutions were discovered, with 86% recovery of exchange sites observed. The maximum concentration of sodium ions in the regenerant brine was found to be 47,400 mg/L under the conditions employed. The volume of regenerant waste formed was 6.2% of the total volume of water treated. A coal seam water sample was found to load the resin with only 53.5 g Na/kg resin, which was consistent with not only the co-presence of more favoured ions such as calcium, magnesium, barium and strontium, but also inefficient regeneration of the resin prior to the coal seam water test.

Pilot-scale cellulosic ethanol production using eucalyptus biomass pre-treated by dilute acid and steam explosion

The widespread deployment of commercial-scale cellulosic ethanol currently hinges on developing and evaluating scalable processes whilst broadening feedstock options. This study investigates whole Eucalyptus grandis trees as a potential feedstock and demonstrates dilute acid pre-treatment (with steam explosion) followed by pre-saccharification simultaneous saccharification fermentation process (PSSF) as a suitable, scalable strategy for the production of bioethanol. Biomass was pre-treated in dilute H2SO4 at laboratory scale (0.1 kg) and pilot scale (10 kg) to evaluate the effect of combined severity factor (CSF) on pre-treatment effectiveness. Subsequently, pilot-scale pre-treated residues (15 wt.%) were converted to ethanol in a PSSF process at 2 L and 300 L scales. Good polynomial correlations (n = 2) of CSF with hemicellulose removal and glucan digestibility with a minimum R2 of 0.91 were recorded. The laboratory-scale 72 h glucan digestibility and glucose yield was 68.0% and 51.3%, respectively, from biomass pre-treated at 190 °C /15 min/ 4.8 wt.% H2SO4. Pilot-scale pre-treatment (180 °C/ 15 min/2.4 wt.% H2SO4 followed by steam explosion) delivered higher glucan digestibility (71.8%) and glucose yield (63.6%). However, the ethanol yields using PSSF were calculated at 82.5 and 113 kg/ton of dry biomass for the pilot and the laboratory scales, respectively. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd