Low Surface pH Research Articles

Ethylene Electrosynthesis via Selective CO2 Reduction: Fundamental Considerations, Strategies, and Challenges

AbstractThe electrochemical carbon dioxide reduction reaction (CO2RR) is a promising approach for reducing atmospheric carbon dioxide (CO2) emissions, allowing harmful CO2 to be converted into more valuable carbon‐based products. On one hand, single carbon (C1) products have been obtained with high efficiency and show great promise for industrial CO2 capture. However, multi‐carbon (C2+) products possess high market value and have demonstrated significant promise as potential products for CO2RR. Due to CO2RR's multiple pathways with similar equilibrium potentials, the extended reaction mechanisms necessary to form C2+ products continue to reduce the overall selectivity of CO2‐to‐C2+ electroconversion. Meanwhile, CO2RR as a whole faces many challenges relating to system optimization, owing to an intolerance for low surface pH, systemic stability and utilization issues, and a competing side reaction in the form of the H2 evolution reaction (HER). Ethylene (C2H4) remains incredibly valuable within the chemical industry; however, the current established method for producing ethylene (steam cracking) contributes to the emission of CO2 into the atmosphere. Thus, strategies to significantly increase the efficiency of this technology are essential. This review will discuss the vital factors influencing CO2RR in forming C2H4 products and summarize the recent advancements in ethylene electrosynthesis.

Reduced surface pH and upregulated AE2 anion exchange in SLC26A3-deleted polarized intestinal epithelial cells.

Loss of function mutations in the SLC26A3 gene cause chloride-losing diarrhea in mice and humans. Although systemic adaptive changes have been documented in these patients and in the corresponding knockout mice, how colonic enterocytes adapt to loss of this highly expressed and highly regulated luminal membrane anion exchanger remains unclear. To address this question, SLC26A3 was deleted in the self-differentiating Caco2BBe colonic cell line by the CRISPR/Cas9 technique. We selected a clone with loss of SLC26A3 protein expression and morphological features indistinguishable from those of the native cell line. Neither growth curves nor development of transepithelial electrical resistance (TEER) differed between wild-type (WT) and SLC26A3 knockout (KO) cells. Real-time qPCR and Western analysis in SLC26A3-KO cells revealed an increase in AE2 expression without significant change in NHE3 expression or localization. Steady-state pHi and apical and basolateral Cl-/HCO3- exchange activities were assessed fluorometrically in a dual perfusion chamber with independent perfusion of luminal and serosal baths. Apical Cl-/HCO3- exchange rates were strongly reduced in SLC26A3-KO cells, accompanied by a surface pH more acidic than that of WT cells. Steady-state pHi was not significantly different from that of WT cells, but basolateral Cl-/HCO3- exchange rates were higher in SLC26A3-KO than in WT cells. The data show that CRISPR/Cas9-mediated SLC26A3 deletion strongly reduced apical Cl-/HCO3- exchange rate and apical surface pH, but sustained a normal steady-state pHi due to increased expression and function of basolateral AE2. The low apical surface pH resulted in functional inhibition of NHE-mediated fluid absorption despite normal expression of NHE3 polypeptide.NEW & NOTEWORTHY SLC26A3 gene mutations cause chloride-losing diarrhea. To understand how colonic enterocytes adapt, SLC26A3 was deleted in Caco2BBe cells using CRISPR/Cas9. In comparison to the wild-type cells, SLC26A3 knockout cells showed similar growth and transepithelial resistance but substantially reduced apical Cl-/HCO3- exchange rates, and an acidic surface pH. Steady-state intracellular pH was comparable between the WT and KO cells due to increased basolateral AE2 expression and function.

Effects of pH alteration on respiratory syncytial virus in human airway epithelial cells.

Respiratory syncytial virus (RSV) is a leading cause of respiratory distress and hospitalisation in the paediatric population. Low airway surface pH impairs antimicrobial host defence and worsens airway inflammation. Inhaled Optate safely raises airway surface pH in humans and raises intracellular pH in primary human airway epithelial cells (HAECs) in vitro. We aimed to determine whether raising intracellular pH with Optate would decrease infection and replication of RSV in primary HAECs. We cultured HAECs from healthy subjects in both air-liquid interface and submerged conditions. We infected HAECs with green fluorescent protein-labelled RSV (GFP-RSV; multiplicity of infection=1) and treated them with Optate or PBS control. We collected supernatant after a 4-h incubation and then every 24 h. We used fluorescence intensity, fluorescent particle counts, plaque assays, Western blots and ELISA to quantitate infection. In submerged culture, fluorescence intensity decreased in Optate-treated cells (48 h p=0.0174, 72 h p≤0.001). Similarly, Optate treatment resulted in decreased fluorescent particle count (48 h p=0.0178, 72 h p=0.0019) and plaque-forming units (48 h p=0.0011, 72 h p=0.0148) from cell culture supernatant. In differentiated HAECs cultured at ALI, Optate treatment decreased fluorescence intensity (p≤0.01), GFP via Western blot and ELISA (p<0.0001), and RSV-fusion protein via ELISA (p=0.001). Additionally, RSV infection decreased as Optate concentration increased in a dose-dependent manner (p<0.001). Optate inhibits RSV infection in primary HAECs in a dose-dependent manner. These findings suggest that Optate may have potential as an inhaled therapeutic for patients with RSV.

Protective Barriers Provided by the Epidermis.

The skin is the largest organ of the body and consists of an epidermis, dermis and subcutaneous adipose tissue. The skin surface area is often stated to be about 1.8 to 2 m2 and represents our interface with the environment; however, when one considers that microorganisms live in the hair follicles and can enter sweat ducts, the area that interacts with this aspect of the environment becomes about 25-30 m2. Although all layers of the skin, including the adipose tissue, participate in antimicrobial defense, this review will focus mainly on the role of the antimicrobial factors in the epidermis and at the skin surface. The outermost layer of the epidermis, the stratum corneum, is physically tough and chemically inert which protects against numerous environmental stresses. It provides a permeability barrier which is attributable to lipids in the intercellular spaces between the corneocytes. In addition to the permeability barrier, there is an innate antimicrobial barrier at the skin surface which involves antimicrobial lipids, peptides and proteins. The skin surface has a low surface pH and is poor in certain nutrients, which limits the range of microorganisms that can survive there. Melanin and trans-urocanic acid provide protection from UV radiation, and Langerhans cells in the epidermis are poised to monitor the local environment and to trigger an immune response as needed. Each of these protective barriers will be discussed.

PHLIP Peptides Target Acidity in Activated Macrophages.

Acidity can be a useful alternative biomarker for the targeting of metabolically active cells in certain diseased tissues, as in acute inflammation or aggressive tumors. We investigated the targeting of activated macrophages by pH low insertion peptides (pHLIPs), an established technology for targeting cell-surface acidity. The uptake of fluorescent pHLIPs by activated macrophages was studied in cell cultures, in a mouse model of lung inflammation, and in a mouse tumor model. Fluorescence microscopy, whole-body and organ imaging, immunohistochemistry, and FACS analysis were employed. We find that cultured, activated macrophages readily internalize pHLIPs. The uptake is higher in glycolytic macrophages activated by LPS and INF-γ compared to macrophages activated by IL-4/IL-13. Fluorescent pHLIPs target LPS-induced lung inflammation in mice. In addition to marking cancer cells within the tumor microenvironment, fluorescent pHLIPs target CD45+, CD11b+, F4/80+, and CD206+ tumor-associated macrophages with no significant targeting of other immune cells. Also, fluorescent pHLIPs target CD206-positive cells found in the inguinal lymph nodes of animals inoculated with breast cancer cells in mammary fat pads. pHLIP peptides sense low cell surface pH, which triggers their insertion into the cell membrane. Unlike cancerous cells, activated macrophages do not retain inserted pHLIPs on their surfaces, instead their highly active membrane recycling moves the pHLIPs into endosomes. Targeting activated macrophages in diseased tissues may enable clinical visualization and therapeutic opportunities.

Mutations in 3β-hydroxysteroid-δ8, δ7-isomerase paradoxically benefit epidermal permeability barrier homeostasis in mice.

Inherited or acquired blockade of distal steps in the cholesterol synthetic pathway results in ichthyosis, due to reduced cholesterol production and/or the accumulation of toxic metabolic precursors, while inhibition of epidermal cholesterol synthesis compromises epidermal permeability barrier homeostasis. We showed here that 3β-hydroxysteroid-δ8, δ7-isomerase-deficient mice (TD), an analog for CHILD syndrome in humans, exhibited not only lower basal transepidermal water loss rates, but also accelerated permeability barrier recovery despite the lower expression levels of mRNA for epidermal differentiation marker-related proteins and lipid synthetic enzymes. Moreover, TD mice displayed low skin surface pH, paralleled by increased expression levels of mRNA for sodium/hydrogen exchanger 1 (NHE1) and increased antimicrobial peptide expression, compared with wild-type (WT) mice, which may compensate for the decreased differentiation and lipid synthesis. Additionally, in comparison with WT controls, TD mice showed a significant reduction in ear thickness following challenges with either phorbol ester or oxazolone. However, TD mice exhibited growth retardation. Together, these results demonstrate that 3β-hydroxysteroid-δ8, δ7-isomerase deficiency does not compromise epidermal permeability barrier in mice, suggesting that alterations in epidermal function depend on which step of the cholesterol synthetic pathway is interrupted. But whether these findings in mice could be mirrored in humans remains to be determined.

A Treatment to Eliminate SARS-CoV-2 Replication in Human Airway Epithelial Cells Is Safe for Inhalation as an Aerosol in Healthy Human Subjects.

Low airway surface pH is associated with many airway diseases, impairs antimicrobial host defense, and worsens airway inflammation. Inhaled Optate is designed to safely raise airway surface pH and is well tolerated in humans. Raising intracellular pH partially prevents activation of SARS-CoV-2 in primary normal human airway epithelial (NHAE) cells, decreasing viral replication by several mechanisms. We grew primary NHAE cells from healthy subjects, infected them with SARS-CoV-2 (isolate USA-WA1/2020), and used clinical Optate at concentrations used in humans in vivo to determine whether Optate would prevent viral infection and replication. Cells were pretreated with Optate or placebo prior to infection (multiplicity of infection = 1), and viral replication was determined with plaque assay and nucleocapsid (N) protein levels. Healthy human subjects also inhaled Optate as part of a Phase 2a safety trial. Optate almost completely prevented viral replication at each time point between 24 h and 120 h, relative to placebo, on both plaque assay and N protein expression (P < .001). Mechanistically, Optate inhibited expression of major endosomal trafficking genes and raised NHAE intracellular pH. Optate had no effect on NHAE cell viability at any time point. Inhaled Optate was well tolerated in 10 normal subjects, with no change in lung function, vital signs, or oxygenation. Inhaled Optate may be well suited for a clinical trial in patients with pulmonary SARS-CoV-2 infection. However, it is vitally important for patient safety that formulations designed for inhalation with regard to pH, isotonicity, and osmolality be used. An inhalational treatment that safely prevents SARS-CoV-2 viral replication could be helpful for treating patients with pulmonary SARS-CoV-2 infection.

Low Surface Energy and pH Effect on SnO₂ Nanoparticles Formation for Supercapacitor Applications.

The SnO₂ nanoparticles formation by hydrothermal method at different experimental conditions such as temperature, pH, reaction time, and capping agent (cetyltrimethylammonium bromide), was studied. X-ray diffraction results confirmed regular rutile crystal structure of SnO₂. The characteristic Raman peak observed at 635 cm-1 corresponded to A1g modes of Sn-O vibrations. The study of optical property using photoluminescence confirmed the emissive spectra of SnO₂. The infrared peak observed at 618 cm-1 corresponded to Eu modes of Sn-O vibrations of TO phonon because of E⊥ to c-axis. Scanning electron microscope images clearly revealed the formation of complete SnO₂ nanoparticles. The unique SnO₂ nanoparticles stacked together to form microspheres at pH-5 showed high specific capacitance of 274.8 F/g at a current density of 0.5 A/g. The observed results confirmed the feasibility of SnO₂ nanoparticles being used as appropriate positive electrode candidate for supercapacitor applications.

Biomass derived activated carbon cathode performance for sustainable power generation from Microbial Fuel Cells

Significant amount of wastewater is generated from Sewage, and treating this wastewater consumes huge amount of energy. Microbial Fuel Cells can be used to treat this wastewater and generate electricity in the process. Traditionally, Platinum catalyst on Carbon Cloth is used as the cathode for oxygen reduction. In this work, an advanced cathode material in the form of an activated carbon derived from biomass sources was evaluated in terms of cathode performance, stability of operation and cost. For activated carbon cathode, an open circuit voltage of 580 ± 30 mV was achieved between fed-batch cycles. Constant external load produced a peak current density and power density of 0.40 mA/m2 and 110 ± 6.58 mW/m2 respectively. Further polarization curves reveal system stability with varying resistances with a change in COD for the wastewater from 780 ± 20 mg/l to 260 ± 30 mg/l over two weeks of operation, achieving a removal efficiency of around 64%, the BOD content of the wastewater also reduced from 520 ± 20 mg/l to 165 ± 25 mg/l with a dissolved solutes removal efficiency of 51% during time of operation. Activated carbon derived from biomass sources is a promising alternative to expensive platinum; further it has a low surface pH, lacks any acidic surface functional group, and can be regenerated to more than 85% of its initial performance with dilute acid wash as compared to platinum which cannot be reused once fouled, thus implicating a sustainable solution.

Identification of Bernalite Transformation and Tridentate Arsenate Complex at Nano-goethite under Effects of Drying, pH and Surface Loading

The structural configuration of arsenate on iron (hydr)oxide determines its leachability and bioavailability in the soil environment. It is important to understand how the stability of iron hydroxide and the structural configuration of arsenate complexes vary in response to changes in environmental conditions. Therefore, we investigated the effects of drying, pH and surface loadings on the stability of goethite and the structural configuration of arsenate through batch experiments and TEM and XAS measurements with DFT calculation. As a result, we observed no significant transformation of goethite under most conditions, but TEM confirmed the partial formation of bernalite in the presence of arsenate at a pH of 10, and the bernalite showed 2.18 times higher arsenate sorption than the goethite. The linear combination fitting of the EXAFS spectra with DFT calculations revealed that tridentate and bidentate complexes were dominant under low surface loading and pH conditions in the sedimented samples, while monodentate complexes were abundant under high surface loading and pH conditions. Based on our results, we conclude that the formation of arsenic-rich colloids could account for mobilization in the soil environment, and the density of available sorption sites combined with the concentration of solute could cause the change in structural configuration.

The influence of pH on thein vitropermeation of rhodium through human skin

Workers in precious metals refineries are at risk of exposure to salt compounds of the platinum group metals through inhalation, as well as through the skin. Rhodium salt permeation through the skin has previously been proven using rhodium trichloride (RhCl3) dissolved in synthetic sweat at a pH of 6.5. However, the skin surface pH of refinery workers may be lower than 6.5. The aim of this study was to investigate the influence of pH 6.5 and 4.5 on the in vitro permeation of rhodium through intact Caucasian skin using Franz diffusion cells. A concentration of 0.3 mg mL-1 rhodium was used and analyses were performed using inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry. Results indicated a cumulative increase in permeation over 24 h. Rhodium permeation after 12 h was significantly greater at pH 4.5 (1.56 ± 0.24 ng cm-2) than at 6.5 (0.85 ± 0.13 ng cm-2; p = 0.02). At both pH levels, there was a highly significant difference ( p < 0.01) between the mass of rhodium remaining in the skin (1428.68 ± 224.67 ng cm-2 at pH 4.5 and 1029.90 ± 115.96 ng cm-2 at pH 6.5) and the mass that diffused through (0.88 ± 0.17 ng cm-2 at pH 4.5 and 0.62 ± 0.10 ng cm-2 at pH 6.5). From these findings, it is evident that an acidic working environment or low skin surface pH may enhance permeation of rhodium salts, contributing to sensitization and adverse health effects.

Tu1846 SLC26A3 (DRA)-Deficient Mice Display Dramatically Low Surface pH, Normal Mucus Secretion but Loss of Firmly Adherent Mucus Layer, Altered Colonic Microbiome and Low Grade Intestinal Inflammation

Tu1846 SLC26A3 (DRA)-Deficient Mice Display Dramatically Low Surface pH, Normal Mucus Secretion but Loss of Firmly Adherent Mucus Layer, Altered Colonic Microbiome and Low Grade Intestinal Inflammation

Tu1847 RNA-Binding Protein HuR Regulates Intestinal Mucosal Repair by Altering CDC42 Translation

BODY: Background: Patients with congenital chloride diarrhea (CLD), caused by loss of function mutations of SLC26a3 (DRA), display a propensity for acute and chronic intestinal inflammation. Conversely, patients with intestinal inflammation, as well as murine inflamed colon, display a defect in surface cell anion exchange, luminal alkalinisation rates, and a decrease in DRA mRNA and protein expression. Aim: In this study, we investigated the effect of genetic ablation of Slc26a3 (DRA) on the surface pH and the dynamics of mucus layer buildup in vivo by two photon microscopy, on the intestinal microbiome by 16S rRNA sequencing, and on the inflammatory state of the mucosa by qPCR and immunohistochemistry, under nonchallenged, specific pathogen-free conditions. Methods and Results: DRA-deficient mice, an animal model for congenital Cldiarrhea (CLD), had a strongly abnormal low surface pH and loss of fluid absorption in the mid-distal colon, but a virtually normal mucus layer buildup rate. However, they lacked a firmly adherent mucus layer. In addition, they displayed altered microbiota composition in the caecum as S-918 AGA Abstracts well as in the proximal and distal colon. In all three gut sections, operative taxonomic units (OTUs) with differential abundance between DRA-deficient andWTmice could be. However, only the distal colon, which displays the thickest mucus layer and the highest DRA expression levels in WT mice, showed evidence for inflammation in the DRA KO mice, indicated by an increase in infiltrating mononuclear cells and increased TNF-alpha expression. Conclusions: Apart from absorbing Cl-, the anion exchanger Scl26a3 (DRA) is intimately involved in the maintenance of intestinal barrier properties such as high colonic surface pH, firmly adherent mucus layer, and the composition of the microbiome. Because the microbiota composition was different from WT in all parts of the DRA-deficient colon, but inflammation was seen only in the mid-distal colon, we speculate that the reason for inflammation is a combination of weakened barrier properties with a more aggressive microbiota in the absence of DRA expression. Intestinal inflammation is thus both a consequence of, and a cause for, disregulated ileocolonic HCO3 transport.

Targeting diseased tissues by pHLIP insertion at low cell surface pH

The discovery of the pH Low Insertion Peptides (pHLIPs®) provides an opportunity to develop imaging and drug delivery agents targeting extracellular acidity. Extracellular acidity is associated with many pathological states, such as those in cancer, ischemic stroke, neurotrauma, infection, lacerations, and others. The metabolism of cells in injured or diseased tissues often results in the acidification of the extracellular environment, so acidosis might be useful as a general marker for the imaging and treatment of diseased states if an effective targeting method can be developed. The molecular mechanism of a pHLIP peptide is based on pH-dependent membrane-associated folding. pHLIPs, being moderately hydrophobic peptides, have high affinities for cellular membranes at normal pH, but fold and insert across membranes at low pH, allowing them to sense pH at the surfaces of cells in diseased tissues, where it is the lowest. Here we discuss the main principles of pHLIP interactions with membrane lipid bilayers at neutral and low pHs, the possibility of tuning the folding and insertion pH by peptide sequence variation, and potential applications of pHLIPs for imaging, therapy and image-guided interventions.

Investigation of Chromate Coordination on Ferrihydrite by in Situ ATR-FTIR Spectroscopy and Theoretical Frequency Calculations

Chromate mobility, reactivity, and bioavailability in soil environments are affected by adsorption reactions on iron oxide minerals, but the adsorption mechanisms remain controversial. In this study, we employed in situ attenuated total reflectance Fourier transform infrared spectroscopy and theoretical frequency calculations to characterize chromate adsorption on 2-line ferrihydrite. The effects of pH, aqueous chromate concentration, ionic strength, and deuterium exchange were investigated. Results suggest the formation of monodentate and bidentate surface complexes. It was determined that monodentate complexes are dominant at low surface coverage and pH ≥ 6.5 and that bidentate complexes form at high surface coverage and pH < 6. Deuterium exchange experiments indicated that the inner-sphere complexes are not protonated. Difference spectra revealed that monodentate complexes are particularly susceptible to ionic strength effects under acidic conditions.

Does a low-pH microenvironment around phototrophic FeII-oxidizing bacteria prevent cell encrustation by FeIII minerals?

Neutrophilic Fe(II) -oxidizing bacteria precipitate positively charged Fe(III) minerals that are expected to sorb to the negatively charged cell surface, leading to encrustation and thus limiting the cells' accessibility to substrates and nutrients. However, electron-microscopy analysis of phototrophic iron-oxidizing Thiodictyon sp. strain F4 cells showed no encrustation, but mineral precipitation at a distance from the cell surface. In situ fluorescence microscopy analysis of F4 cells using a pH-sensitive fluorescent dye revealed a low cell surface pH (6.0 ± 0.1) in contrast to the bulk pH (6.6 ± 0.1). Biogeochemical modeling showed that the pH difference reduces Fe(III) sorption and Fe(III) precipitation rates at the cell surface, therefore directing mineral formation away from the cells. The results from this study therefore suggest that the establishment of a low cell surface pH could provide a mechanism for photoferrotrophs to successfully prevent Fe(III) mineral precipitation on the cell surface.

The effect of methods of preparation on the performance of cupric chloride-impregnated sorbents for the removal of mercury from flue gases

Cupric chloride-impregnated carbon sorbents (CuCl 2-ACs) showed comparable performance in elemental mercury (Hg 0) oxidation and adsorption to a brominated activated carbon sorbent (Darco Hg-LH) in our previously reported experimental studies using fixed-bed and entrained-flow systems. This study tested several CuCl 2-ACs prepared in different solvents to investigate the effects of solvents on the Hg 0 removal capability of CuCl 2-ACs and find the most efficient and economical method of sorbent preparation. The performance of CuCl 2-ACs prepared in different solvents was also examined with respect to surface tension and pH of solvents. As a result, the sorbents prepared in isopropyl alcohol and acetone showed the best performance in these tests, but low surface tension and pH of isopropyl alcohol and acetone were not found to be critical factors.

Surface pH of resin-modified glass polyalkenoate (ionomer) cements

The recently developed group of materials known as light-activated, or resin-modified, glass polyalkenoate (ionomer) cements have been produced in response to clinical demands for a command set cavity base material. This study monitored the surface pH of three commercially available resin-modified glass ionomer cements over a 60-min period following either mixing alone or mixing followed by a 30-s exposure to a curing lamp. The results indicate that each material behaves in a unique manner. For all materials and conditions the pH reached after a 60-min period was significantly ( P < 0.001) higher than the initial value. Light curing the materials significantly increased ( P < 0.01) the surface pH of two of the materials (Baseline VLC and Vitrebond) as compared to the same materials in the uncured state. In the case of XR-Ionomer, however, no significant ( P > 0.05) effect of light curing upon the surface pH was apparent. The precise clinical consequences of a low surface pH are unclear but may be an aetiological factor in postoperative pulpal sensitivity. It is therefore recommended that a sublining of a proprietary calcium hydroxide lining material should be placed routinely beneath these materials and every effort made to ensure effective light curing.

Effect of lipid surface charges on the purple-to-blue transition of bacteriorhodopsin.

Purple membrane (lambda max = 568 nm) can be converted to blue membrane (lambda max = 605 nm) by either acid titration or deionization. Partially delipidated purple membrane, containing only 25% of the initial lipid phosphorus, could be converted to a blue form by acid titration but not by deionization. This reversible transition of delipidated membrane did not require the presence of other cations, and the pK of the color change that in native membrane under similar conditions is between 3.0 and 4.0 was shifted to 1.4. We conclude that the purple-to-blue transition is controlled by proton concentration only and that, in native membranes, the cations act only by raising the low surface pH generated by the acidic groups of the lipids. The observation that extraction of lipids from deionized native membrane converts its color from blue to purple further confirms this conclusion. The two states of the membrane probably reflect two preferred conformations of bacteriorhodopsin, which are controlled by protonation changes at the surface of the membrane and differ slightly in the spatial distribution of charges around the chromophore.

Determination of acid surface pH in vivo in rat proximal jejunum.

Surface pH of rat intestine was measured in vivo in exteriorised loops using pH-electrodes. Surface pH was approximately 6.1 in Krebs-phosphate buffer in proximal jejunum and was significantly more acid (p less than 0.01) than the bulk medium pH of 7.2. Values for the midgut were approximately 6.5, yet the distal ileum gave values of 7.3, which was marginally more alkaline than the buffer. These results agree with the known acidification phenomenon in the jejunum and the alkalinisation process in the ileum. No difference in surface pH was detected when bicarbonate buffer was used, nor when glucose was included in the buffer. The acid surface pH was almost completely inhibited when jejunal loops were made anoxic by completely occluding the blood supply, showing that the low surface pH is not itself a consequence of preparative anoxia. If glucose was included in the buffer, allowing glucose access from the luminal surface, surface pH was not significantly altered after occlusion. This indicates that previously reported in vitro results in the presence of glucose are similar to the present in vivo findings. The present experiments confirm the existence in vivo of the 'acid-microclimate' proposed to alter the absorption profiles of some dissociable drugs.