Absolute pH Research Articles

UniChem – Unifying Concepts for Acid-Base- and Redox-Chemistry: Development, Validation and Application of Absolute pH and pe Scales Culminating in the Protoelectric Potential Map PPM – ERC

UniChem – Unifying Concepts for Acid-Base- and Redox-Chemistry: Development, Validation and Application of Absolute pH and pe Scales Culminating in the Protoelectric Potential Map PPM – ERC

Measurement of Autolysosomal pH by Dual-Wavelength Ratio Imaging.

Cellular components sequestered by autophagosomes during macroautophagy must be degraded and their components recycled in order to maintain homeostasis. To this end cells orchestrate the fusion of autophagosomes with lysosomes, degradative organelles that are rich in hydrolases. Most of the lysosomal enzymes function optimally at low pH, and products of macromolecular catabolism are cotransported with protons across the autolysosomal membrane. These functions are facilitated by the ability of lysosomes to pump protons inward, acidifying their lumen. Clearly, proper homeostasis of the luminal pH is crucial for autolysosomal function. We describe a method for the measurement of the absolute pH of individual autolysosomes in live cells. This technique involves measurement of the fluorescence of a pH-sensitive probe initially delivered to lysosomes and subsequently determined to have reached autolysosomes. By measuring the fluorescence at two separate wavelengths and calculating their ratio, potential artifacts introduced by photobleaching or by changes in autolysosome size, shape, or positioning are minimized. Combining such ratio determinations with an in situ calibration procedure enables absolute measurements of pH, which are superior to the qualitative estimates obtained with fluorescent weak bases such as LysoTracker.

An Impedance-Based Mold Sensor with on-Chip Optical Reference.

A new miniaturized sensor system with an internal optical reference for the detection of mold growth is presented. The sensor chip comprises a reaction chamber provided with a culture medium that promotes the growth of mold species from mold spores. The mold detection is performed by measuring impedance changes with integrated electrodes fabricated inside the reaction chamber. The impedance change in the culture medium is caused by shifts in the pH (i.e., from 5.5 to 8) as the mold grows. In order to determine the absolute pH value without the need for calibration, a methyl red indicator dye has been added to the culture medium. It changes the color of the medium as the pH passes specific values. This colorimetric principle now acts as a reference measurement. It also allows the sensitivity of the impedance sensor to be established in terms of impedance change per pH unit. Major mold species that are involved in the contamination of food, paper and indoor environments, like Fusarium oxysporum, Fusarium incarnatum, Eurotium amstelodami, Aspergillus penicillioides and Aspergillus restrictus, have been successfully analyzed on-chip.

Oxidized (non)-regenerated cellulose affects fundamental cellular processes of wound healing.

In this study we investigated how hemostats such as oxidized regenerated cellulose (ORC, TABOTAMP) and oxidized non-regenerated cellulose (ONRC, RESORBA CELL) influence local cellular behavior and contraction of the extracellular matrix (ECM). Human stromal fibroblasts were inoculated in vitro with ORC and ONRC. Cell proliferation was assayed over time, and migration was evaluated by Live Cell imaging microscopy. Fibroblasts grown in collagen-gels were treated with ORC or ONRC, and ECM contraction was measured utilizing a contraction assay. An absolute pH decline was observed with both ORC and ONRC after 1 hour. Mean daily cell proliferation, migration and matrix contraction were more strongly inhibited by ONRC when compared with ORC (p < 0.05). When control media was pH-lowered to match the lower pH values typically seen with ORC and ONRC, significant differences in cell proliferation and migration were still observed between ONRC and ORC (p < 0.05). However, in these pH conditions, inhibition of matrix contraction was only significant for ONRC (p < 0.05). We find that ORC and ONRC inhibit fibroblast proliferation, migration and matrix contraction, and stronger inhibition of these essential cellular processes of wound healing were observed for ONRC when compared with ORC. These results will require further validation in future in vivo experiments to clarify the clinical implications for hemostat use in post-surgical wound healing.

Navigational choice between reversal and curve during acidic pH avoidance behavior in Caenorhabditis elegans.

BackgroundUnder experimental conditions, virtually all behaviors of Caenorhabditis elegans are achieved by combinations of simple locomotion, including forward, reversal movement, turning by deep body bending, and gradual shallow turning. To study how worms regulate these locomotion in response to sensory information, acidic pH avoidance behavior was analyzed by using worm tracking system.ResultsIn the acidic pH avoidance, we characterized two types of behavioral maneuvers that have similar behavioral sequences in chemotaxis and thermotaxis. A stereotypic reversal-turn-forward sequence of reversal avoidance caused an abrupt random reorientation, and a shallow gradual turn in curve avoidance caused non-random reorientation in a less acidic direction to avoid the acidic pH. Our results suggest that these two maneuvers were each triggered by a distinct threshold pH. A simulation study using the two-distinct-threshold model reproduced the avoidance behavior of the real worm, supporting the presence of the threshold. Threshold pH for both reversal and curve avoidance was altered in mutants with reduced or enhanced glutamatergic signaling from acid-sensing neurons.ConclusionsC. elegans employ two behavioral maneuvers, reversal (klinokinesis) and curve (klinotaxis) to avoid acidic pH. Unlike the chemotaxis in C. elegans, reversal and curve avoidances were triggered by absolute pH rather than temporal derivative of stimulus concentration in this behavior. The pH threshold is different between reversal and curve avoidance. Mutant studies suggested that the difference results from a differential amount of glutamate released from ASH and ASK chemosensory neurons.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-015-0220-0) contains supplementary material, which is available to authorized users.

Microfabricated Collector-Generator Electrode Sensor for Measuring Absolute pH and Oxygen Concentrations.

Fast-scan cyclic voltammetry (FSCV) has attracted attention for studying in vivo neurotransmission due to its subsecond temporal resolution, selectivity, and sensitivity. Traditional FSCV measurements use background subtraction to isolate changes in the local electrochemical environment, providing detailed information on fluctuations in the concentration of electroactive species. This background subtraction removes information about constant or slowly changing concentrations. However, determination of background concentrations is still important for understanding functioning brain tissue. For example, neural activity is known to consume oxygen and produce carbon dioxide which affects local levels of oxygen and pH. Here, we present a microfabricated microelectrode array which uses FSCV to detect the absolute levels of oxygen and pH in vitro. The sensor is a collector-generator electrode array with carbon microelectrodes spaced 5 μm apart. In this work, a periodic potential step is applied at the generator producing transient local changes in the electrochemical environment. The collector electrode continuously performs FSCV enabling these induced changes in concentration to be recorded with the sensitivity and selectivity of FSCV. A negative potential step applied at the generator produces a transient local pH shift at the collector. The generator-induced pH signal is detected using FSCV at the collector and correlated to absolute solution pH by postcalibration of the anodic peak position. In addition, in oxygenated solutions a negative potential step at the generator produces hydrogen peroxide by reducing oxygen. Hydrogen peroxide is detected with FSCV at the collector electrode, and the magnitude of the oxidative peak is proportional to absolute oxygen concentrations. Oxygen interference on the pH signal is minimal and can be accounted for with a postcalibration.

Photomechanically Controlled Encapsulation and Release from pH-Responsive and Photoresponsive Microcapsules.

Poly(acrylic acid)/azobenzene microcapsules were obtained through distillation precipitation polymerization and the selective removal of silica templates by hydrofluoric acid etching. The uniform, robust, and monodisperse microcapsules, confirmed by transmission electron microscopy and scanning electron microscopy, had reversible photoisomerization under ultraviolet (UV) and visible light. Under UV irradiation, azobenzene cross-linking sites in the main chain transformed from the trans to cis isomer, which induced the shrinkage of microcapsules. These photomechanical effects of azobenzene moieties were applied to the encapsulation and release of model molecules. After loading with rhodamine B (RhB), the release behaviors were completely distinct. Under steady UV irradiation, the shrinkage adjusted the permeability of the capsule, providing a novel way to encapsulate RhB molecules. Under alternate UV/visible light irradiation, a maximal release amount was reached due to the continual movement of shell networks by cyclic trans-cis photoisomerization. Also, microcapsules had absolute pH responsiveness. The diffusion rate and the final release percentage of RhB both increased with pH. The release behaviors under different irradiation modes and pH values were in excellent agreement with the Baker-Lonsdale model, indicating a diffusion-controlled release behavior. Important applications are expected in the development of photocontrolled encapsulation and release systems as well as in pH-sensitive materials and membranes.

Cerenkov-specific contrast agents for detection of pH in vivo.

We report the design, testing, and in vivo application of pH-sensitive contrast agents designed specifically for Cerenkov imaging. Radioisotopes used for PET emit photons via Cerenkov radiation. The multispectral emission of Cerenkov radiation allows for selective bandwidth quenching, in which a band of photons is quenched by absorption by a functional dye. Under acidic conditions, (18)F-labeled derivatives emit the full spectrum of Cerenkov light. Under basic conditions, the dyes change color and a wavelength-dependent quenching of Cerenkov emission is observed. Mono- and di-(18)F-labeled derivatives of phenolsulfonphthalein (phenol red) and meta-cresolsulfonphthalein (cresol purple) were synthesized by electrophilic fluorination. Cerenkov emission was measured at different wavelengths as a function of pH in vitro. Intramolecular response was measured in fluorinated probes and intermolecular quenching by mixing phenolphthalein with (18)F-FDG. Monofluorocresol purple (MFCP) was tested in mice treated with acetazolamide to cause urinary alkalinization, and Cerenkov images were compared with PET images. Fluorinated pH indicators were produced with radiochemical yields of 4%-11% at greater than 90% purity. Selective Cerenkov quenching was observed intramolecularly with difluorophenol red or monofluorocresol purple and intermolecularly in phenolphthalein (18)F-FDG mixtures. The probes were selectively quenched in the bandwidth closest to the indicator's absorption maximum (λmax) at pHs above the indicator pKa (the negative logarithm of the acid dissociation constant). Addition of acid or base to the probes resulted in reversible switching from unquenched to quenched emission. In vivo, the bladders of acetazolamide-treated mice exhibited a wavelength-dependent quenching in Cerenkov emission, with the greatest reduction occurring near the λmax. Ratiometric imaging at 2 wavelengths showed significant decreases in Cerenkov emission at basic pH and allowed the estimation of absolute pH in vivo. We have created contrast agents that selectively quench photons emitted during Cerenkov radiation within a given bandwidth. In the presence of a functional dye, such as a pH indicator, this selective quenching allows for a functional determination of pH in vitro and in vivo. This method can be used to obtain functional information from radiolabeled probes using multimodal imaging. This approach allows for the imaging of nonfluorescent chromophores and is generalizable to any functional dye that absorbs at suitable wavelengths.

Impact of Ph+ Stem Cell Burden on Clinical Findings and Molecular Responses to First-Line Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia: The Results from the Interim Analysis of N-Road, Multi-Center a Phase II Study

Background: Second generation tyrosine kinase inhibitors (2G-TKIs) are more potent than imatinib against chronic myeloid leukemia in chronic phase (CML-CP) as a first-line therapy, and the majority of patients (pts) on 2G-TKIs could achieve favorable molecular responces over MR3.0 by 24 M (Saglio G, et al. Blood 2011, Kantarjian HM, et al. Blood 2012). It is also likey that molecular response at 3 M will predict outcome for CML-CP pts on imatinib. Furthermore, Mustjoki S, et al. showed that Ph+ stem cell burden at diagnosis is a prognostic marker of molecular responses at 3-9 M on dasatinib or imatinib (Leukemia 2013). Thus, early prognostic marker of outcome is feasible for CML-CP on TKIs.Methods: We are conducting a phase II study (N-road) for newly diagnosed CML-CP pts, in which nilotinib 300mg BID is given for 24 M and is to be escalated to 400mg BID if no optimal response at any check points. The primary endpoint is CMR rate by 24 M, and secondary endpoints include MR3.0/MR4.0 by 12 M and exploring prognostic factors. In this setting, the impact of initial Ph+ stem cell burden on clinical findings and therapeutic responses has been investigated in a sub-study. By July 2014, 48 pts were enrolled and BM CD34+ cell fractions could be evaluated by FACS-FISH analysis at diagnosis in 43 pts, among those 35 pts passed 3 M, 34 pts 6 M and 15 pts 12 M, respectively.Results: MR3.0 rate was 8/35 at 3M, 23/34 at 6M and 10/15 at 12M. When 43 pts were classified into two groups (higher: H, lower: L) according to the mean CD34+ cell counts at diagnosis (5995/mL of BM aspirates), there were significant differences (p<0.05) in BCR-ABL transcripts indicated as IS (77.66 vs 64.03 %, p=0.030) and WBC count (81.3 vs 22.3 /mL, p=0.012), but no differences in molecular responses at 3, 6 and 12 M between the two groups. There was a positive correlation between CD34+ cell count and WBC count (r=0.328, p=0.035).The median percentage of Ph+ cells, as measured by FISH (~1000 cells analyzed), in CD34+CD38- fraction at diagnosis was 97.1% (range 2-100%) compared to 98.6% (range 28.2-99.8%) in CD34+CD38+ fraction. The proportion of Ph+ cells in CD34+CD38- fraction correlated with PLT count (r=0.394, p=0.014) but inversely with RBC count (r=-0.474, p=0.003), Hb (r=-0.587, p=0.0001) and Ht (r=-0.475, p=0.003), respectively. Between the two groups divided by the median percentage, there were significant differences in RBC count (406 vs 460 x104/mL, p=0.046), Hb (11.7 vs 14.5 g/dL, p=0.009) and Hct (38.8 vs 44.7%, p=0.040). There were no significant differences in molecular responses at any check points. On the other hand, when divided by the mean percentage (81.1%), there was only a significant difference in PLT count (48.1 vs 27.2 /mL, p=0.028).Absolute Ph+ cell counts in CD34+CD38- fraction were estimated in each patient by combining 3 parameters of CD34 cell counts/mL of BM aspirates, proportion of CD38- fraction and percentage of Ph+ cells. Ph+CD34+CD38- cell counts siginificantly correlated with WBC count (r=0.365, p=0.021) and inversely with RBC count (r=-0.361, p=0.002), Hb (r=-0.409, p=0.009) and percentage of lymphocytes (r=-0.339, p=0.032). Between the 2 groups divided by the median cell counts (256/mL), there were significant differences in RBC (406.5 vs 472.0 x104/mL, p=0.005), Hb (11.8 vs 14.3 g/dL, p=0.004), Hct (39.0 vs 44.6 %, p=0.024). Although we could not find significant difference in molecular responses at any check points, patients with lower number of Ph+CD34+CD38- cells tend to achieve MR3.0 faster than those with higher number of cells (p=0.059) (Figure 1). When divided by the mean cell counts (578/mL), there was a significant difference in WBC count (94.45 vs 22.44 /mL, p=0.016).Conclusion: increased Ph+ stem cell burden apparently affects the level of leukocytosis and anemia at diagnosis, but not MR3.0/MR4.0 rate by 12 M on nilotinib, although it is likely to extend time to achieve MR3.0. [Display omitted] DisclosuresNishiwaki:Novartis: Research Funding. Sugimoto:Novartis: Speakers Bureau. Shimizu:Novartis: Speakers Bureau. Wakita:Novartis: Speakers Bureau. Tojo:Novartis: Research Funding, Speakers Bureau.

The Protoelectric Potential Map (PPM): The Two-Dimensional Plot of Absolute Redox Potentials and Absolute pH Values

We recently introduced a unified Brønsted acidity scale on the basis of the chemical potential of the proton in any medium allowing the comparison of pH values of different media and a precise definition of superacidic media. For this purpose we defined the reference state of maximum acidity as the standard chemical potential µ abs°(H+, g) of the proton in the gas phase (ideal H+ gas at 1 bar and 298.15 K), which is arbitrarily set to 0 kJ mol–1. The acidity and hence the chemical potential of the gaseous proton H+(g) is lowered by the interaction with any type of a medium, i.e. complexation of H+ in the gas phase, solution, or in the solid state. In this way the defined absolute pH value pHabs depends in a simple manner on the absolute potential of the proton in the media of interest. [1]Analogously to the definition of the pHabs value we define an absolute redox potential (peabs) scale on the basis of the absolute chemical potential of the electron with the ideal electron gas at 1 bar and 298.15 K as reference state (µ abs°(e–, g) = 0 kJ mol–1). This scale establishes the possibility of direct comparison of the reduction power (which we term “reducity”) of any redox system in any medium. [2]Above all, both scales are combined to the Protoelectric Potential Map (PPM, peabs vs. pHabs, see fig.) as the Hydrogen Evolution Reaction (HER) correlates the pH scale to the redox scale. [2] The thermodynamics of any redox, acid-base or combined system in any medium can be represented and related to any other. For example, the pH-dependency of a redox system can be easily read off by the slope of the line representing the redox system in the whole pH range of the solvent under consideration. Thermodynamic stabilities of solvents can be clearly displayed and even predictions of reactions become possible at a glance, please compare with K. Pütz who presents that silver is a non-noble metal in the acidic IL HmimBr at this conference.Figure: The Protoelectric Potential Map (PPM).[1] a) D. Himmel, S.K. Goll, I. Leito, I. Krossing, Angew. Chem., Int. Ed. Engl. 2010, 49, 6885-6888; b) VIP-Paper: D. Himmel, S.K. Goll, I. Leito, I. Krossing, Chem. Eur. J. 2011, 17, 5808 – 5826.[2] V. Radtke, D. Himmel, K. Pütz, S. Goll, I. Krossing, Chem. Eur. J., 2014, DOI: 10.1002/chem.201302473

Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI.

Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading to irreversible cellular damage. Chemical exchange saturation transfer (CEST) effects can be used to generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been used to delineate the ischemic penumbra after ischemic stroke. In the current study, a novel MRI ratiometric technique is presented to measure absolute pH using the ratio of CEST-mediated contrast from amine and amide protons: amine/amide concentration-independent detection (AACID). Effects of CEST were observed at 2.75 parts per million (p.p.m.) for amine protons and at 3.50 p.p.m. for amide protons downfield (i.e., higher frequency) from bulk water. Using numerical simulations and in vitro MRI experiments, we showed that pH measured using AACID was independent of tissue relaxation time constants, macromolecular magnetization transfer effects, protein concentration, and temperature within the physiologic range. After in vivo pH calibration using phosphorus ((31)P) magnetic resonance spectroscopy ((31)P-MRS), local acidosis is detected in mouse brain after focal permanent middle cerebral artery occlusion. In summary, our results suggest that AACID represents a noninvasive method to directly measure the spatial distribution of absolute pH in vivo using CEST MRI.

Tu2078 The Effect of Lubiprostone on Regional Alimentary Tract Transit Times Measured by Wireless Motility Capsule in Patients With Chronic Constipation

Introduction: Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces a chloride-rich intestinal fluid secretion which diminishes viscoelasticity of luminal contents and increases lubrication. These effects have led to increased stool frequency and relief of symptoms in patients with chronic constipation (CC). While radionuclide studies have indicated acceleration in colon transit, the impact of lubiprostone on transit times in specific regions of the gut has not been clarified. These measurements can now be achieved by the novel wireless motility capsule (WMC) technology in patients with CC. Our aim was to investigate the effects of lubiprostone on gastric emptying (GET), small bowel (SBTT), colon (CTT) and small/large bowel (SLBTT) transit times assessed by WMC in CC (Rome III) patients. Methods: Twenty nine female patients with CC, mean age 38 (19-64) mean weight 167 lbs (111-305) were tested with WMC before treatment and on day number 8 after receiving 24 mcg BID of lubiprostone. GET was calculated from the time WMC was ingested until the point at which there was an abrupt and sustained increase in pH of more than 2 units from the gastric pH to an absolute pH of .6.0. SBTT was defined as the elapsed time from capsule leaving the stomach until capsule arrived at the cecum. This was determined by a sudden drop of pH.1 unit, for longer than 1 h, which was preceded by a gradual, sustained rise in pH as the capsule passes through the distal small bowel. CTT was defined as the time interval between the point of entry into the cecum and the exit of WMC from the body. SLBTT includes SBTT and CTT. Statistical analysis, using Mann-Whitney Rank Sum Test was performed using Sigma-Stat software. Results are presented as Median with 25-75 percentiles range. Results: After administration of lubiprostone gastric emptying was slowed by 14.5% to 4.02h (2.27-8.82) versus 3.51h (2.38-12.83) at baseline (P=0.913); SBTT was significantly accelerated by 12.2% to 4.03h (3.13-4.49) when compared with 4.59 h (4.00-6.32) at baseline (P=0.010) and CTT was accelerated by 10.1% to 35.1h (22.66-47.99) vs 39.05h (22.61-63.39) before treatment ( P=0.328). The comparison of SLBTT before and after therapy with lubiprostone showed 18.9% reduction of this regional transit time with median being 46.24h (30.97-80.47) at baseline and 37.55h (24.49-54.21) while on medication (P=0.128). Conclusions: 1) During treatment with lubiprostone the acceleration of SBTT is more pronounced that colon transit in CC patients. 2) This implies that type 2 chloride channel activation within the small bowel does affect small intestine motility patterns in patients with chronic constipation. 3) The very modest delay in gastric emptying was not accompanied by clinically relevant nausea and is unlikely to explain the nausea side effect profile of lubiprostone.

Superacidic or Not…︁? Synthesis, Characterisation, and Acidity of the Room‐Temperature Ionic Liquid [C(CH3)3]+ [Al2Br7]−

The room-temperature ionic liquid (RT-IL) [C(CH(3))(3)](+)[Al(2)Br(7)](-) (m.p. 2 °C) was generated by bromide abstraction from tert-butyl bromide with the Lewis acid aluminum bromide in the absence of solvent. The crystal structure of the tert-butyl cation salt was determined by X-ray diffraction. NMR, IR, and Raman spectroscopy, as well as quantum-chemical and thermodynamic calculations, confirm the composition of this RT-IL. Thus, one may consider this RT-IL to be a readily accessible (and on a large scale) cationic Brønsted acid (protonated isobutene) with the potential for further reactivity. Based on the new absolute Brønsted acidity scale, we calculated an absolute pH(abs) value of 171 for liquid bulk [C(CH(3))(3)](+)[Al(2)Br(7)](-). This value is about as acidic as 100 % sulfuric acid (pH(abs) = 171) and, thus, on the edge of superacidity.

Su1102 Juice Test: A Simple Way to Predict Esophageal Clearance and Acid Exposure During Esophageal pH Monitoring

Background: Acidification of esophageal lumen either after gastroesophageal reflux (GER) or consumption of acidic beverages is followed by pH recovery which depends mainly of esophageal motility and saliva swallowing. Compromised esophageal clearance may favor a longer contact of gastric juice after GER episodes. In the light of this, swallowing orange juice during esophageal pH monitoring might be used as a simple test to predict esophageal clearance and acid exposure. Aims: To assess whether a juice test can predict esophageal clearance and acid exposure in patients who were referred for esophageal pH monitoring. Methods: Patients referred for GERD investigation with standard pH monitoring were invited to perform a juice test in the beginning of the procedure. After positioning a pH sensor in the distal esophagus, patients in sitting position were instructed to swallow orange juice (pH 2.5) as follows: an initial swallow of 10 ml with simultaneous monitoring of pH drop, followed by five rapid multiple swallows of juice after recovery of pH to 5 from the initial swallow. In the following day the pH catheter was removed and tracings analyzed. Esophageal pH drop after multiple swallows of juice was analyzed to calculate (1) delta5 in mol.s.dm3, i.e. area above the curve between pH drop from 5 to pH recovery to 5; (2) absolute pH drop; and (3) duration in seconds from pH drop to recovery to 5. Results: The juice test was well tolerated by all patients. Among 59 patients, 5 (8%) were excluded due to the occurrence of acid GER during pH recovery after multiple swallows. Fifty-four patients composed the final study population (40.2 ± 15 years old, 61% women). After analysis of pH monitoring, there were 29 patients (54%) with increased total acid exposure (> 4.2%) and 25 patients with normal acid exposure. Baseline pH before multiple swallows did not differ between these groups (5.1 ± 0.6 vs. 5 ± 0.5; P = 0.612). Delta5 was higher in patients with increased acid exposure (33.5 ± 20.9 vs. 17.2 ± 8.2; P < 0.001). These patients also showed higher values for absolute pH drop (2.2 ± 0.6 vs. 1.7 ± 0.6; P = 0.030) and delayed pH recovery [median (IQR25-75%): 270 sec (207-550) vs. 200 (127-310); P = 0.044] than those with normal acid exposure. Conclusions: Our data suggest that a juice test with calculation of delta5 can be a simple way to predict esophageal clearance and acid exposure in patients investigated for GERD with esophageal pH monitoring. Further studies using impedance-pH technology are needed to evaluate the performance of juice test in the prediction of pathological GER.

Diagnosis of supra-esophageal gastric reflux: correlation of oropharyngeal pH with esophageal impedance monitoring for gastro-esophageal reflux

Oropharyngeal (OP) pH monitoring has been developed as a new way to diagnose supra-esophageal gastric reflux (SEGR), but has not been well validated. Our aim was to determine the correlation between OP pH and gastro-esophageal reflux (GER) events detected by multichannel intraluminal impedance-pH (MII-pH). Fifteen patients (11 males, median age 10.8 years) with suspected GER were prospectively evaluated with ambulatory 24-h OP pH monitoring (positioned at the level of the uvula) and concomitant esophageal MII-pH monitoring. Potential OP events were identified by the conventional pH threshold of <4 and by the following alternative criteria: (i) relative pH drop >10% from 15-min baseline and (ii) absolute pH drop below thresholds of <5.5, 5.0, and 4.5. The 2-min window preceding each OP event was analyzed for correlation with an episode of GER detected by MII-pH. A total of 926 GER events were detected by MII-pH. Application of alternative pH criteria increased the identification of potential OP pH events; however, a higher proportion of OP events had no temporal correlation with GER (45-81%), compared with the conventional definition of pH < 4 (40%). A total of 306 full-column acid reflux episodes were detected by MII-pH, of which 10 (3.3%) were also identified by OP pH monitoring. Use of extended pH criteria increased the detection of potential SEGR events, but the majority of decreases in OP pH were not temporally correlated with GER. Oropharyngeal pH monitoring without concurrent esophageal measurements may overestimate the presence of SEGR in children.

Quantum chemical calculations on a unified pH scale for all phases

One for all – a unified Bronsted acidity scale...! On the basis of the absolute chemical potential of the proton a unified absolute pH scale universally applicable in the gas phase, in solution and the solid state is introduced [1]. This scale allows to directly compare acidities in different media and to give a thermodynamically meaningful definition of superacidity and can be used in all areas where proton activity changes during use, e.g. in proton-induced catalytic reactions, hydrocarbon processing, fuel cells, in the biological proton pump, and others. For calculating acidities we developed and applied several models based on quantum chemistry (modified G3, MP2/def2-QZVPP, MP2-extrapolated CCSD(T)/aug’-cc-pVDZ®QZ, COSMO@BP86/defTZVP, etc.). Our investigations also point out the inadequateness of the established GA scale, which in contrast to our unified acidity scale does not take into account the pressure dependent speciation in the gas phase. Below the accessible absolute Bronsted acidities given by their μabs(H+) or so-called pHabs values in different media as expressed by the width of their protochemical window (= pKAP) are illustrated (Figure 1). Author details Institute for Inorganic and Analytical Chemistry and Freiburger Materialforschungszentrum FMF, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany. Institute of Chemistry, University of Tartu, Tartu, 50411, Estonia.

Noninvasive pH measurement to monitor changes during suboptimal storage of platelet concentrates

Noninvasive pH measurement of platelet concentrates (PCs) was evaluated as a tool for the quality control of PC storage by simulating worst-case conditions. PCs from pooling four buffy coats in 70% PAS-3M were both stored in bags wrapped to impair gas permeability and agitated or not until Day 9 of storage. pH values measured both in samples (electrode, blood gas analyzer) and noninvasively by fluorimetry (BCSI pH1000, Blood Cell Storage, Inc.) were compared groupwise and to changes in platelet (PLT) size and biochemical variables. The noninvasive pH measurements agreed well with the results from each of the two reference methods (R(2) >0.9) in a wide range of pH values between 6.4 and 7.5. Changes of the pH of PCs (n=64) by all interventions (agitation or resting plus occlusion by 0, 25, 50, or 100%; n=8/group) were subtle but already significant after 20 to 24 hours of treatment in comparison to the controls. A steady state after Day 6 and reductions up to a mean pH of approximately 6.5 were observed. The extent of manipulation determined both the absolute pH differences to the controls and the interindividual variation of pH changes. Termination of the agitation significantly enhanced pH reduction by surface blockade. Significant changes were also observed for the mean PLT volume, β-thromboglobulin, and soluble P-selectin. Noninvasive pH measurement in PCs using this technique reliably detects pH changes of 0.1 or more. Storage of PLTs in buffered additive solution requires profound impairment of gas exchange to trigger a substantial decline in pH.

Survey of Tuber pH Variation in Potato (Solanum) Species

Variation in tuber pH has been previously reported in cultivated potato and shown to be associated with economic traits. We here report a broad survey of potato germplasm for tuber pH, including wild Solanum species. Cultivar pH ranged from about 5.5 to 6.2, while six wild species were significantly lower. Solanum microdontum had the lowest pH average of the wild species examined at 5.17 with the lowest observed reading of 4.99. This species also exhibited a strong environmental effect, in which field tubers (5.28) were much lower than greenhouse tubers (5.63). Long storage generally did not have a significant effect on wild species tubers, except for S. jamesii, which reduced from 5.78 to 5.54. Various types of sampling were tested. Skins were generally lower than flesh, with a high correlation between the tissues. Samples that were frozen, cooked, or reconstituted from dried powder had different absolute pH values, but these were highly correlated, so germplasm would be ranked for pH similarly regardless of method. Although not tested here, physiological links between pH and economic traits like disease resistance, nutrition and tuber quality are plausible. If so, pH testing might serve as a rapid and inexpensive screening tool in breeding programs. The association of pH and useful traits might also provide clues for exploring underlying genetic and physiological mechanisms in potatoes.

Absolute hodograph winding number and planar PH quintic splines

We present a new semi-topological quantity, called the absolute hodograph winding number, that measures how close the quintic PH spline interpolating a given sequence of points is to the cubic spline interpolating the same sequence. This quantity then naturally leads into a new criterion of determining the best quintic PH spline interpolant. This seems to work favorably compared with the elastic bending energy criterion developed by Farouki [Farouki, R.T., 1996. The elastic bending energy of Pythagorean-hodograph curves. Comput. Aided Geom. Design 13 (3), 227–241]. We also present a fast method that is a modification of the method of Albrecht, Farouki, Kuspa, Manni, and Sestini [Albrecht, G., Farouki, R.T., 1996. Construction of C 2 Pythagorean-hodograph interpolating splines by the homotopy method. Adv. Comput. Math. 5 (4), 417–442; Farouki, R.T., Kuspa, B.K., Manni, C., Sestini, A., 2001. Efficient solution of the complex quadratic tridiagonal system for C 2 PH quintic splines. Numer. Algorithms 27 (1), 35–60]. While the basic scheme of our approach is essentially the same as theirs, ours differs in that the underlying space in which the Newton–Raphson method is applied is the double covering space of the hodograph space, whereas theirs is the hodograph space itself. This difference, however, seems to produce more favorable results, when viewed from the above mentioned semi-topological criterion.

Acid−Base Equilibria in Nonpolar Media. Absolute pKa Scale of Bases in Tetrahydrofuran

The acidity constants (pKa) of 11 bases (amines, anilines, pyridines, pyrrolidines, and iminophosphoranes) have been determined in tetrahydrofuran by potentiometry, complemented by conductometric measurements. The pK(a) values of the studied bases cover a wide absolute pH range of acidity in tetrahydrofuran, from 7.4 to 21.7. From the pK(a) values obtained, a scale of absolute acidity in tetrahydrofuran has been established, which has allowed calculation of the absolute pKa values of 77 bases from literature relative pK(a) data.