Dietary Oxalate and Its Intestinal Absorption

Dietary oxalate is currently believed to make only a minor contribution (\u3c 20%) to urinary oxalate excretion. A recent prospective study of stone disease suggested that dietary oxalate may be a significant risk factor. This observation led us to re-evaluate the contribution of dietary oxalate to urinary oxalate excretion. Previous studies have been hampered by inaccurate food composition tables for oxalate and inadequate methods for studying intestinal oxalate absorption. This evidence as well as factors that modify oxalate absorption are reviewed. New approaches to measure food oxalate and intestinal oxalate absorption have been examined. Capillary electrophoresis appears to be well suited for the analysis of the oxalate content of food. Two individuals consumed an oxalate-free formula diet for 7 days. This diet decreased urinary oxalate excretion by an average of 67% (18.6 mg per 24 hours) compared to oxalate excretion on self-selected diets. The absence of detectable oxalate in feces by day 6 of the diet suggested that the intestinal absorption was minimal. However, an effect of the formula diet on endogenous oxalate synthesis cannot be excluded. Restoring oxalate to the formula diet increased urinary oxalate excretion and illustrates that this experimental protocol may be well-suited for studying oxalate absorption and factors that modify it. Our results suggest that the intestinal absorption of dietary oxalate makes a substantial contribution to urinary oxalate excretion and that this absorption can be modified by decreasing oxalate intake or increasing the intakes of calcium, magnesium, and fiber

Glyoxal Formation and Its Role in Endogenous Oxalate Synthesis

Calcium oxalate kidney stones are a common condition affecting many people in the United States. The concentration of oxalate in urine is a major risk factor for stone formation. There is evidence that glyoxal metabolism may be an important contributor to urinary oxalate excretion. Endogenous sources of glyoxal include the catabolism of carbohydrates, proteins, and fats. Here, we review all the known sources of glyoxal as well as its relationship to oxalate synthesis and crystal formation

Structural and Biochemical Studies of Human 4-hydroxy-2-oxoglutarate Aldolase: Implications for Hydroxyproline Metabolism in Primary Hyperoxaluria

4-hydroxy-2-oxoglutarate (HOG) aldolase is a unique enzyme in the hydroxyproline degradation pathway catalyzing the cleavage of HOG to pyruvate and glyoxylate. Mutations in this enzyme are believed to be associated with the excessive production of oxalate in primary hyperoxaluria type 3 (PH3), although no experimental data is available to support this hypothesis. Moreover, the identity, oligomeric state, enzymatic activity, and crystal structure of human HOGA have not been experimentally determined.In this study human HOGA (hHOGA) was identified by mass spectrometry of the mitochondrial enzyme purified from bovine kidney. hHOGA performs a retro-aldol cleavage reaction reminiscent of the trimeric 2-keto-3-deoxy-6-phosphogluconate aldolases. Sequence comparisons, however, show that HOGA is related to the tetrameric, bacterial dihydrodipicolinate synthases, but the reaction direction is reversed. The 1.97 Å resolution crystal structure of hHOGA bound to pyruvate was determined and enabled the modeling of the HOG-Schiff base intermediate and the identification of active site residues. Kinetic analyses of site-directed mutants support the importance of Lys196 as the nucleophile, Tyr168 and Ser77 as components of a proton relay, and Asn78 and Ser198 as unique residues that facilitate substrate binding.The biochemical and structural data presented support that hHOGA utilizes a type I aldolase reaction mechanism, but employs novel residue interactions for substrate binding. A mapping of the PH3 mutations identifies potential rearrangements in either the active site or the tetrameric assembly that would likely cause a loss in activity. Altogether, these data establish a foundation to assess mutant forms of hHOGA and how their activity could be pharmacologically restored

Going places

Journeys. We all make them. Often they take us to exotic places. Sometimes they take us even further. They might take us through time. Or they might take us into a new way of life. There are times too, when we go all over the world and back again only to find that home is, after all, where it’s all happening. This book contains stories about many different types of journey. We hope you will enjoy travelling into it and finding a world that suits you

Accuracy of Nonexercise Prediction Equations for Assessing Longitudinal Changes to Cardiorespiratory Fitness in Apparently Healthy Adults: BALL ST Cohort

Background Repeated assessment of cardiorespiratory fitness (CRF) improves mortality risk predictions in apparently healthy adults. Accordingly, the American Heart Association suggests routine clinical assessment of CRF using, at a minimum, nonexercise prediction equations. However, the accuracy of nonexercise prediction equations over time is unknown. Therefore, we compared the ability of nonexercise prediction equations to detect changes in directly measured CRF. Methods and Results The sample included 987 apparently healthy adults from the BALL ST (Ball State Adult Fitness Longitudinal Lifestyle Study) cohort (33% women; average age, 43.1±10.4 years) who completed 2 cardiopulmonary exercise tests ≥3 months apart (3.2±5.4 years of follow-up). The change in estimated CRF (eCRF) from 27 distinct nonexercise prediction equations was compared with the change in directly measured CRF. Analysis included Pearson product moment correlations, SEE values, intraclass correlation coefficient values, Cohen\u27s κ coefficients, γ coefficients, and the Benjamini-Hochberg procedure to compare eCRF with directly measured CRF. The change in eCRF from 26 of 27 equations was significantly associated to the change in directly measured CRF (P\u3c0.001), with intraclass correlation coefficient values ranging from 0.06 to 0.63. For 16 of the 27 equations, the change in eCRF was significantly different from the change in directly measured CRF. The median percentage of participants correctly classified as having increased, decreased, or no change in CRF was 56% (range, 39%-61%). Conclusions Variability was observed in the accuracy between nonexercise prediction equations and the ability of equations to detect changes in CRF. Considering the appreciable error that prediction equations had with detecting even directional changes in CRF, these results suggest eCRF may have limited clinical utility

Banking from Leeds, not London: regional strategy and structure at the Yorkshire Bank, 1859–1952

Industrial philanthropist Edward Akroyd created the Yorkshire Penny Savings Bank in 1859. Despite competition from the Post Office Savings Bank after 1861 and a serious reserve problem in 1911, it sustained his overall strategy to become a successful regional bank. Using archival and contemporary sources to build on recent scholarship illustrating how savings banks were integrated into local economies and the complementary roles of philanthropy and paternalism, we analyse an English regional bank's strategy, including an assessment of strategic innovation, ownership changes and management structure. This will demonstrate that the founder's vision continued, even though the 1911 crisis radically altered both strategy and structure

Variability in urinary oxalate measurements between six international laboratories

Background. Hyperoxaluria is a major risk factor for kidney stone formation. Although urinary oxalate measurement is part of all basic stone risk assessment, there is no standardized method for this measurement. Methods. Urine samples from 24-h urine collection covering a broad range of oxalate concentrations were aliquoted and sent, in duplicates, to six blinded international laboratories for oxalate, sodium and creatinine measurement. In a second set of experiments, ten pairs of native urine and urine spiked with 10 mg/L of oxalate were sent for oxalate measurement. Three laboratories used a commercially available oxalate oxidase kit, two laboratories used a high-performance liquid chromatography (HPLC)-based method and one laboratory used both methods. Results. Intra-laboratory reliability for oxalate measurement expressed as intraclass correlation coefficient (ICC) varied between 0.808 [95% confidence interval (CI): 0.427-0.948] and 0.998 (95% CI: 0.994-1.000), with lower values for HPLC-based methods. Acidification of urine samples prior to analysis led to significantly higher oxalate concentrations. ICC for inter-laboratory reliability varied between 0.745 (95% CI: 0.468-0.890) and 0.986 (95% CI: 0.967-0.995). Recovery of the 10 mg/L oxalate-spiked samples varied between 8.7 ± 2.3 and 10.7 ± 0.5 mg/L. Overall, HPLC-based methods showed more variability compared to the oxalate oxidase kit-based methods. Conclusions. Significant variability was noted in the quantification of urinary oxalate concentration by different laboratories, which may partially explain the differences of hyperoxaluria prevalence reported in the literature. Our data stress the need for a standardization of the method of oxalate measuremen

Structural Phase Transition at High Temperatures in Solid Molecular Hydrogen and Deuterium

We study the effect of temperature up to 1000K on the structure of dense molecular para-hydrogen and ortho-deuterium, using the path-integral Monte Carlo method. We find a structural phase transition from orientationally disordered hexagonal close packed (hcp) to an orthorhombic structure of Cmca symmetry before melting. The transition is basically induced by thermal fluctuations, but quantum fluctuations of protons (deuterons) are important in determining the transition temperature through effectively hardening the intermolecular interaction. We estimate the phase line between hcp and Cmca phases as well as the melting line of the Cmca solid.Comment: 8 pages, 7 figures; accepted in Phys. Rev.

Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total

Imaging learned fear circuitry in awake mice using fMRI

Functional magnetic resonance imaging (fMRI) of learned behaviour in ‘awake rodents’ provides the opportunity for translational preclinical studies into the influence of pharmacological and genetic manipulations on brain function. fMRI has recently been employed to investigate learned behaviour in awake rats. Here, this methodology is translated to mice, so that future fMRI studies may exploit the vast number of genetically modified mouse lines that are available. One group of mice was conditioned to associate a flashing light (conditioned stimulus, CS) with foot shock (PG; paired group), and another group of mice received foot shock and flashing light explicitly unpaired (UG; unpaired group). The blood oxygen level-dependent signal (proxy for neuronal activation) in response to the CS was measured 24 h later in awake mice from the PG and UG using fMRI. The amygdala, implicated in fear processing, was activated to a greater degree in the PG than in the UG in response to the CS. Additionally, the nucleus accumbens was activated in the UG in response to the CS. Because the CS signalled an absence of foot shock in the UG, it is possible that this region is involved in processing the safety aspect of the CS. To conclude, the first use of fMRI to visualise brain activation in awake mice that are completing a learned emotional task is reported. This work paves the way for future preclinical fMRI studies to investigate genetic and environmental influences on brain function in transgenic mouse models of disease and aging