Acid inhibition on the first day of dosing : comparison of four proton pump inhibitors

RESUME Introduction: Les inhibiteurs de la pompe à protons sont actuellement considérés comme les médicaments de choix pour le traitement des affections peptiques comme l'ulcère gastroduodénal et l'oesophagite de reflux. La rapidité, ainsi que le degré d'inhibition de la sécrétion gastrique acide sont importants pour le contrôle optimal des symptômes ainsi que pour le traitement de ces affections. But : Le but principal de cette étude a été de comparer, chez les sujets asymptomatiques non infectés par H. pylori, par pH-métrie intragastrique de 24 heures, la rapidité et la durée de l'action antisécrétoire de doses uniques de rabéprazole 20 mg, d'oméprazole capsule 20 mg, d'oméprazole en comprimé MUPS (« Multiple Unit Pellet System ») 20 mg, de pantoprazole 40 mg et de lansoprazole 30 mg, respectivement. Matériel et méthodes : Cette étude, effectuée en double aveugle et randomisée, a été conduite de manière croisée chez 18 sujets H. pylori-négatifs. Une pH-métrie de 24 heures a été effectuée le jour de l'administration du médicament (dose unique de rabéprazole 20 mg, de lansoprazole 30mg, de pantoprazole 40 mg, d'oméprazole capsule 20 mg, d'oméprazole MUPS comprimé 20mg, ou de placebo). Résultats : Le pH intragastrique médian (3.4 vs. 2.9, 2.2, 1.9 et 1.8, respectivement; p≤ 0.03) et le temps avec un pH supérieur à 4 pendant les 24 heures suivant la prise du médicament (8.0 heures vs. 7.4, 4.9, 2.9, et 3.0, respectivement; p≤ 0.003) ont été statistiquement plus élevés avec le rabéprazole qu'avec le lansoprazole, le pantoprazole, l'oméprazole capsule, l'oméprazole comprimé MUPS, ou le placebo. Les valeurs du pH pendant les périodes diurnes et nocturnes étaient plus hautes avec le rabeprazole et le lansoprazole qu'avec le pantoprazole, l'oméprazole capsule, et l'oméprazole comprimé MUPS (p≤0.04). Conclusion : Le rabéprazole s'est montré le plus efficace de tous les inhibiteurs de pompe à protons étudiés durant le premier jour de l'administration du médicament. SUMMARY Background: Rapid and consistent acid suppression on the first day of dosing may be important in treating acid-related disorders. Aim: To compare the antisecretory activity and onset of action of single doses of rabeprazole, lansoprazole, pantoprazole, omeprazole capsule, omeprazole multiple unit pellet system (MUPS) tablet and placebo in healthy Helicobacter pylori-negative subjects. Methods: This cross-over, double-blind, randomized study was performed in 18 H. pylori-negative subjects. Twenty-four-hour intragastric pH monitoring was performed on the day of treatment (once-daily dose of rabeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, omeprazole capsule 20 mg, omeprazole MUPS tablet 20 mg or placebo). Results: The intragastric pH (3.4) and time at pH > 4 during the 24 h post-dose (8.0 h) were significantly greater with rabeprazole than with lansoprazole, pantoprazole, omeprazole capsule, omeprazole MUPS tablet or placebo (P ≤ 0.04 for rabeprazole vs. the others). Daytime and night-time pH values were higher with rabeprazole and lansoprazole than with pantoprazole, omeprazole capsule and omeprazole MUPS tablet (P ≤ 0.04). Conclusion: Rabeprazole was the most potent acid inhibitor of all the proton pump inhibitors tested during the first day of dosing.

Sensitive determination of D-lactic acid and L-lactic acid in urine by high-performance liquid chromatography-tandem mass spectrometry.

D-lactic acid in urine originates mainly from bacterial production in the intestinal tract. Increased D-lactate excretion as observed in patients affected by short bowel syndrome or necrotizing enterocolitis reflects D-lactic overproduction. Therefore, there is a need for a reliable and sensitive method able to detect D-lactic acid even at subclinical elevation levels. A new and highly sensitive method for the simultaneous determination of L- and D-lactic acid by a two-step procedure has been developed. This method is based on the concentration of lactic acid enantiomers from urine by supported liquid extraction followed by high-performance liquid chromatography-tandem mass spectrometry. The separation was achieved by the use of an Astec Chirobiotic? R chiral column under isocratic conditions. The calibration curves were linear over the ranges of 2-400 and 0.5-100 µmol/L respectively for L- and D-lactic acid. The limit of detection of D-lactic acid was 0.125 µmol/L and its limit of quantification was 0.5 µmol/L. The overall accuracy and precision were well within 10% of the nominal values. The developed method is suitable for production of reference values in children and could be applied for accurate routine analysis.

Gas-chromatography mass-spectrometry determination of phthalic acid in human urine as a biomarker of folpet exposure.

Agricultural workers are exposed to folpet, but biomonitoring data are limited. Phthalimide (PI), phthalamic acid (PAA), and phthalic acid (PA) are the ring metabolites of this fungicide according to animal studies, but they have not yet been measured in human urine as metabolites of folpet, only PA as a metabolite of phthalates. The objective of this study was thus to develop a reliable gas chromatography-tandem mass spectrometry (GC-MS) method to quantify the sum of PI, PAA, and PA ring-metabolites of folpet in human urine. Briefly, the method consisted of adding p-methylhippuric acid as an internal standard, performing an acid hydrolysis at 100 °C to convert ring-metabolites into PA, purifying samples by ethyl acetate extraction, and derivatizing with N,O-bis(trimethylsilyl)trifluoro acetamide prior to GC-MS analysis. The method had a detection limit of 60.2 nmol/L (10 ng/mL); it was found to be accurate (mean recovery, 97%), precise (inter- and intra-day percentage relative standard deviations <13%), and with a good linearity (R (2) > 0.98). Validation was conducted using unexposed peoples urine spiked at concentrations ranging from 4.0 to 16.1 μmol/L, along with urine samples of volunteers dosed with folpet, and of exposed workers. The method proved to be (1) suitable and accurate to determine the kinetic profile of PA equivalents in the urine of volunteers orally and dermally administered folpet and (2) relevant for the biomonitoring of exposure in workers.

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices.

BACKGROUND: The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K+, Ca2+ and Na2+ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field. RESULTS: In this study, four P-type II ATPase sub-families have been isolated from three AMF species. We show that, contrary to previous predictions, P-type IIC ATPases are present in all basal fungal taxa. Additionally, P-Type IIE ATPases should no longer be considered as exclusive to the Ascomycota and the Basidiomycota, since we also demonstrate their presence in the Zygomycota. Finally, a comparison of homologous sequences encoding P-type IID ATPases showed unexpectedly that indel mutations among coding regions, as well as specific gene duplications occur among AMF individuals within the same field. CONCLUSION: On the basis of these results we suggest that the diversification of P-Type IIC and E ATPases followed the diversification of the extant fungal phyla with independent events of gene gains and losses. Consistent with recent findings on the human genome, but at a much smaller geographic scale, we provided evidence that structural genomic changes, such as exonic indel mutations and gene duplications are less rare than previously thought and that these also occur within fungal populations.

Effect of abscisic acid on maize root gravireaction

Primary roots of intact maize seedlings (cv. LG11) were pretreated when kept vertically (1 or 2 in the dark) with a droplet of buffer solution containing ABA (at different concentrations) applied to the root tip. Then, apical root segments were prepared and placed horizontally in both light and darkness. The downward curvature was measured. In the light, curvature was greater than in darkness and ABA (5×10−5 mol·dm−3) significantly enhanced the curvature in both darkness and light. The amplitude of the increase in the gravireaction was found to be dependent on the ABA concentration and the duration of the pretreatment.

Sucrose metabolizing enzymes in cell suspension cultures of Bauhinia forficata, Curcuma zedoaria and Phaseolus vulgaris

The objective of this work was to study the activity of sucrose metabolizing enzymes in extracts of cell suspension cultures of Bauhinia forficata Link, Curcuma zedoaria Roscoe and Phaseolus vulgaris L. Invertase pathway was identified in the three studied species. Sucrose synthase pathway was also responsible for sucrose metabolism in Curcuma zedoaria and Phaseolus vulgaris cells. Activity values higher than 300 nmol min-1 mg-1 of protein were found for acid and neutral invertases, UDPglucose pyrophosphorylase and phosphoglucomutase in the cell extract of the three plant species. Sucrose synthase showed low activity in Bauhinia forficata cells. As sucrose concentration in the culture medium decreased, sucrose synthase activity increased in C. zedoaria and P. vulgaris cells. The glycolytic enzymes activity gradually reduced at the end of the culture period, when carbohydrate was limited.

Dietary effects on muscle fatty acid composition of finished heifers

The effects of diet on Longissimus muscle fatty acid composition was determined using 24 crossbred heifers of Simmental vs. Nelore and Limousin vs. Nelore. The experimental diets were: 1) corn and yeast (CY); 2) corn, cottonseed meal + meat and bones meal (CMB); 3) cassava hull and yeast (CHY); 4) cassava hull, cottonseed meal + meat and bones meal (CHMB). Feeding CHMB diets resulted in lower lipid and higher cholesterol contents (P<0.05) for both crosses. Most of the identified fatty acids were monounsaturated, and the highest percentage was found to oleic acid (C18:1w9), with values ranging from 32.54 to 46.42%. Among the saturated fatty acids the palmitic acid (C16:0) showed the highest percentage, with its contents ranging between 19.40 and 32.44%. The highest polyunsaturated/saturated fatty acid ratio was of 0.30, and the lowest was of 0.08. Feeding CY diets resulted in lower cholesterol and higher polyunsaturated fatty acid contents of the Longissimus muscle.

Deoxyribonucleic acid content as an indicator of progression of squamous cell carcinogenesis in the esophagus: comparative analysis on imprint-cytospin and tissue section preparation.

BACKGROUND: The purpose of this study was to explore the potential use of image analysis on tissue sections preparation as a predictive marker of early malignant changes during squamous cell (SC) carcinogenesis in the esophagus. Results of DNA ploidy quantification on formalin-fixed, paraffin-embedded tissue using two different techniques were compared: imprint-cytospin and 6 microm thick tissue sections preparation. METHODS: This retrospective study included 26 surgical specimens of squamous cell carcinoma (SCC) from patients who underwent surgery alone at the Department of Surgery in CHUV Hospital in Lausanne between January 1993 and December 2000. We analyzed 53 samples of healthy tissue, 43 tumors and 7 lymph node metastases. RESULTS: Diploid DNA histogram patterns were observed in all histologically healthy tissues, either distant or proximal to the lesion. Aneuploidy was observed in 34 (79%) of 43 carcinomas, namely 24 (75%) of 32 early squamous cell carcinomas and 10 (91%) of 11 advanced carcinomas. DNA content was similar in the different tumor stages, whether patients presented with single or multiple synchronous tumors. All lymph node metastases had similar DNA content as their primary tumor. CONCLUSIONS: Early malignant changes in the esophagus are associated with alteration in DNA content, and aneuploidy tends to correlate with progression of invasive SCC. A very good correlation between imprint-cytospin and tissue section analysis was observed. Although each method used here showed advantages and disadvantages; tissue sections preparation provided useful information on aberrant cell-cycle regulation and helped select the optimal treatment for the individual patient along with consideration of other clinical parameters.

Assessment of high hydrostatic pressure and starter culture on the quality properties of low-acid fermented sausages

The addition of starter culture and high pressure processing after ripening improved the microbial quality of low-acid fermented sausages (fuet and chorizo). The use of Lactobacillus sakei CTC6626 and Staphylococcus xylosus CTC6013 as starter culture significantly reduced Enterobacteriaceae and Enterococcus levels in the finished sausages. Moreover, the addition of starter culture produced sausages of similar quality to traditional low-acid fermented sausages. Slightly lower pH values and higher cohesiveness were obtained for both fuet and chorizo with starter culture. Sensory analysis showed no differences between lots of chorizo whereas starter fuet was more acid and gummy. High pressure induced an additional reduction of Enterobacteriaceae in non-starter sausages. An increase of textural properties was observed after pressurization. No other differences were observed between non-treated and pressurized sausages.

Pitfalls in aminoacid and organic acid analysis: 3-hydroxypropionic aciduria.

Pitfalls in organic acid analysis can originate from inadequate methodology, analytical interferences, in vivo interactions and from pre-analytical conditions which often are unknown to the specialized analytical laboratory. Among the latter, ingested food and additives, metabolites of food processing or medications have to be considered. Bacterial metabolites from the gastrointestinal or urogenital system or formed after sample collection can lead to pitfalls as well. An example of such a patient whose urinary metabolites mimic at first glance inherited propionic aciduria is described.

Characterization of rapeseed (Brassica napus) oils by bulk C, O, H, and fatty acid C stable isotope analyses

Rapeseed (Brassica napus) oils differing in cultivar, sites of growth, and harvest year were characterized by fatty acid concentrations and carbon, hydrogen, and oxygen stable isotope analyses of bulk oils (delta(13)C(bulk), delta(2)H(bulk), delta(18)O(bulk) values) and individual fatty acids (delta(13)C(FA)). The delta(13)C(bulk), delta(2)H(bulk), and delta(18)O(bulk) values were determined by continuous flow combustion and high-temperature conversion elemental analyzer isotope ratio mass spectrometry (EA/IRMS, TC-EA/IRMS). The delta(13)C(FA) values were determined using gas chromatography-combustion isotope ratio mass spectrometry (GC/C/IRMS). For comparison, other C(3) vegetable oils rich in linolenic acid (flax and false flax oils) and rich in linoleic acid (poppy, sunflower, and safflower oils) were submitted to the same chemical and isotopic analyses. The bulk and molecular delta(13)C values were typical for C(3) plants. The delta(13)C value of palmitic acid (delta(13)C(16:0)) and n-3 alpha-linolenic acid (delta(13)C(18:3n-3)) differed (p < 0.001) between rape, flax, and poppy oils. Also within species, significant differences of delta(13)C(FA) were observed (p < 0.01). The hydrogen and oxygen isotope compositions of rape oil differed between cultivars (p < 0.05). Major differences in the individual delta(13)C(FA) values were found. A plant-specific carbon isotope fractionation occurs during the biosynthesis of the fatty acids and particularly during desaturation of C(18) acids in rape and flax. Bulk oil and specific fatty acid stable isotope analysis might be useful in tracing dietary lipids differing in their origin.

Auxin response factors ARF6 and ARF8 promote jasmonic acid production and flower maturation.

Pollination in flowering plants requires that anthers release pollen when the gynoecium is competent to support fertilization. We show that in Arabidopsis thaliana, two paralogous auxin response transcription factors, ARF6 and ARF8, regulate both stamen and gynoecium maturation. arf6 arf8 double-null mutant flowers arrested as infertile closed buds with short petals, short stamen filaments, undehisced anthers that did not release pollen and immature gynoecia. Numerous developmentally regulated genes failed to be induced. ARF6 and ARF8 thus coordinate the transition from immature to mature fertile flowers. Jasmonic acid (JA) measurements and JA feeding experiments showed that decreased jasmonate production caused the block in pollen release, but not the gynoecium arrest. The double mutant had altered auxin responsive gene expression. However, whole flower auxin levels did not change during flower maturation, suggesting that auxin might regulate flower maturation only under specific environmental conditions, or in localized organs or tissues of flowers. arf6 and arf8 single mutants and sesquimutants (homozygous for one mutation and heterozygous for the other) had delayed stamen development and decreased fecundity, indicating that ARF6 and ARF8 gene dosage affects timing of flower maturation quantitatively.

Uric acid and cardio-metabolic risk factors : an epidemiological approach

The role of serum uric acid (SUA) in cardio-metabolic conditions has long been contentious. It is still unclear if SUA is an independent risk factor or marker of cardio-metabolic conditions and most observed associations are not necessarily causal. This study aimed to further understand and explore the causal role of SUA in cardio-metabolic conditions using genetic and non-genetic epidemiological methods in population-based data. In the first part of this study, we found moderate to high heritability estimates for SUA and fractional excretion of urate (FEUA) suggesting the role of genetic factors in the etiology of hyperuricemia. With regards to the role of SUA on inflammatory markers (IMs), a strong positive association of SUA with C-reactive protein (CRP) and a weaker positive association with tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was observed, which was in part mediated by body mass index (BMI). These findings suggest that SUA may have a role in sterile inflammation. In view of the inconsistency surrounding the causal nature and direction of the relation between SUA and adiposity, we applied a bidirectional Mendelian randomization approach using genetic variants to decipher the association. The finding that elevated SUA is a consequence rather than a cause of adiposity was not totally unexpected and is compatible with the hypothesis that hyperinsulinemia, accompanying obesity, enhances renal proximal tubular reabsorption of uric acid. The fourth part of this study examined the relationship between SUA and blood pressure (BP) in young adults. The association between SUA and BP, significant only in females, was strongly attenuated upon adjustment for BMI. The possibility that BMI lies in the causal pathway may explain the attenuation observed in the associations of SUA with BP and IMs. Finally, a significant hockey-stick shaped association of SUA with social phobia in our data suggests a protective effect of SUA only up to a certain concentration. Although our study findings have shed some light on the uncertainty underlying the pathophysiology of SUA, more compelling evidence using longitudinal designs, randomized controlled trials and the use of robust genetic tools is warranted to increase our understanding of the clinical significance of SUA.