Severe systemic adverse reaction to proton pump inhibitors in an infant

Episodes of respiratory distress with chest retraction and wheezing, sometimes associated with facial edema, were noted after administering the proton pump inhibitors omeprazole and esomeprazole in an infant with gastroesophageal reflux. The disturbances relieved dramatically after withdrawing the proton pump inhibitor.

Brain metabolism in Alzheimer disease and vascular dementia assessed by in vivo proton magnetic resonance spectroscopy

Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimer's disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification.

DtpB (YhiP) and DtpA (TppB, YdgR) are prototypical proton-dependent peptide transporters of Escherichia coli

The genome of Escherichia coli contains four genes assigned to the peptide transporter (PTR) family. Of these, only tppB (ydgR) has been characterized, and named tripeptide permease, whereas protein functions encoded by the yhiP, ybgH and yjdL genes have remained unknown. Here we describe the overexpression of yhiP as a His-tagged fusion protein in E. coli and show saturable transport of glycyl-sarcosine (Gly-Sar) with an apparent affinity constant of 6.5 mm. Overexpression of the gene also increased the susceptibility of cells to the toxic dipeptide alafosfalin. Transport was strongly decreased in the presence of a protonophore but unaffected by sodium depletion, suggesting H(+)-dependence. This was confirmed by purification of YhiP and TppB by nickel affinity chromatography and reconstitution into liposomes. Both transporters showed Gly-Sar influx in the presence of an artificial proton gradient and generated transport currents on a chip-based sensor. Competition experiments established that YhiP transported dipeptides and tripeptides. Western blot analysis revealed an apparent mass of YhiP of 40 kDa. Taken together, these findings show that yhiP encodes a protein that mediates proton-dependent electrogenic transport of dipeptides and tripeptides with similarities to mammalian PEPT1. On the basis of our results, we propose to rename YhiP as DtpB (dipeptide and tripeptide permease B), by analogy with the nomenclature in other bacteria. We also propose to rename TppB as DtpA, to better describe its function as the first protein of the PTR family characterized in E. coli.

Characterization Of Porous Media In Proton Exchange Membrane Fuel Cell Based on Percolation Studies

Water management in the porous media of proton exchange membrane (PEM) fuel cells, catalyst layer and porous transport layers (PTL) is confronted by two issues, flooding and dry out, both of which result in improper functioning of the fuel cell and lead to poor performance and degradation. The data that has been reported about water percolation and wettability within a fuel cell catalyst layer is limited to porosimetry. A new method and apparatus for measuring the percolation pressure in the catalyst layer has been developed. The experimental setup is similar to a Hele-Shaw experiment where samples are compressed and a fluid is injected into the sample. Pressure-Wetted Volume plots as well as Permeability plots for the catalyst layers were generated from the percolation testing. PTL samples were also characterizes using a Hele-Shaw method. Characterization for the PTLs was completed for the three states: new, conditioned and aged. This is represented in a Ce-t* plots, which show a large offset between new and aged samples.

The effectiveness and safety of proton radiation therapy for indications of the eye : a systematic review

BACKGROUND AND PURPOSE: : Proton radiation has been used for the treatment of uveal melanoma since 1975, but few studies have been conducted to assess its efficacy and safety. This paper aims to systematically review the effects and side effects of proton therapy for any indication of the eye. MATERIAL AND METHODS: : A range of databases were searched from inception to 2007. All studies that included at least ten patients and that assessed the efficacy or safety of proton therapy for any indication of the eye were included. RESULTS: : The search generated 2,385 references, of which 37 met the inclusion criteria. Five controlled trials, two comparative studies and 30 case series were found, most often reporting on uveal melanoma, choroidal melanoma and age-related macular degeneration (AMD). Methodological quality of these studies was poor. Studies were characterized by large differences in radiation techniques applied within the studies, and by variation in patient characteristics within and between studies. Results for uveal melanoma and choroidal melanoma suggest favorable survival, with, however, significant rates of side effects. Results for choroidal hemangioma and AMD did not reveal beneficial effects from proton radiation. CONCLUSION: : There is limited evidence on the effectiveness and safety of proton radiation due to the lack of well-designed and well-reported studies. There is a need to lift evidence on proton therapy to a higher level by performing dose-finding randomized controlled trials (RCTs), comparative studies of proton radiation versus standard given alternatives and prospective case studies enrolling only patients treated with up-to-date techniques, allowing extrapolation of results to similar patient groups.

Proton-coupled oligopeptide transporter family SLC15: physiological, pharmacological and pathological implications

Mammalian members of the proton-coupled oligopeptide transporter family (SLC15) are integral membrane proteins that mediate the cellular uptake of di/tripeptides and peptide-like drugs. The driving force for uphill electrogenic symport is the chemical gradient and membrane potential which favors proton uptake into the cell along with the peptide/mimetic substrate. The peptide transporters are responsible for the absorption and conservation of dietary protein digestion products in the intestine and kidney, respectively, and in maintaining homeostasis of neuropeptides in the brain. They are also responsible for the absorption and disposition of a number of pharmacologically important compounds including some aminocephalosporins, angiotensin-converting enzyme inhibitors, antiviral prodrugs, and others. In this review, we provide updated information on the structure-function of PepT1 (SLC15A1), PepT2 (SLC15A2), PhT1 (SLC15A4) and PhT2 (SLC15A3), and their expression and localization in key tissues. Moreover, mammalian peptide transporters are discussed in regard to pharmacogenomic and regulatory implications on host pharmacology and disease, and as potential targets for drug delivery. Significant emphasis is placed on the evolving role of these peptide transporters as elucidated by studies using genetically modified animals. Whenever possible, the relevance of drug-drug interactions and regulatory mechanisms are evaluated using in vivo studies.

Proton diffusion tensor spectroscopy of metabolites in human muscle in vivo

PURPOSE To study the apparent diffusivity and its directionality for metabolites of skeletal muscle in humans in vivo by (1) H magnetic resonance spectroscopy. METHODS The diffusion tensors were determined on a 3 Tesla MR system using optimized acquisition and processing methods including an adapted STEAM sequence with orientation-dependent diffusion weighting, pulse-triggering with individually adapted delays, eddy-current correction schemes, median filtering, and simultaneous prior-knowledge fitting of all related spectra. RESULTS The average apparent diffusivities, as well as the fractional anisotropies of taurine (ADCav  = 0.74 × 10(-3) s/mm(2) , FA = 0.46), creatine (ADCav  = 0.41 × 10(-3)  s/mm(2) , FA = 0.33), trimethylammonium compounds (ADCav  = 0.48 × 10(-3)  s/mm(2) , FA = 0.34), carnosine (ADCav  = 0.46 × 10(-3)  s/mm(2) , FA = 0.47), and water (ADCav  = 1.5 × 10(-3)  s/mm(2) , FA = 0.36) were estimated. The diffusivities of most metabolites and water were significantly different from each other. Diffusion was found to be anisotropic and the diffusion tensors showed tensor correlation coefficients close to 1 and were hence found to be essentially coaligned. The magnitudes of apparent metabolite diffusivities were largely ordered according to molecular weight, with taurine as the smallest molecule diffusing fastest, both along and across the fiber direction. CONCLUSION Diffusivities, directional dependence of diffusion and fractional anisotropies of (1) H MRS-visible muscle metabolites were presented. It was shown that metabolites share diffusion directionality with water and have similar fractional anisotropies, hinting at similar diffusion barriers. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Clinical Proton MR Spectroscopy in Central Nervous System Disorders.

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units. © RSNA, 2014 Online supplemental material is available for this article.