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Seminars in Nephrology Jul 2019Although students initially learn of ionic buffering in basic chemistry, buffering and acid-base transport in biology often is relegated to specialized classes,... (Review)
Review
Although students initially learn of ionic buffering in basic chemistry, buffering and acid-base transport in biology often is relegated to specialized classes, discussions, or situations. That said, for physiology, nephrology, pulmonology, and anesthesiology, these basic principles often are critically important for mechanistic understanding, medical treatments, and assessing therapy effectiveness. This short introductory perspective focuses on basic chemistry and transport of buffers and acid-base equivalents, provides an outline of basic science acid-base concepts, tools used to monitor intracellular pH, model cellular responses to pH buffer changes, and the more recent development and use of genetically encoded pH-indicators. Examples of newer genetically encoded pH-indicators (pHerry and pHire) are provided, and their use for in vitro, ex vivo, and in vivo experiments are described. The continued use and development of these basic tools provide increasing opportunities for both basic and potentially clinical investigations.
Topics: Acid-Base Equilibrium; Animals; Biological Transport; Buffers; Humans; Hydrogen; Hydrogen-Ion Concentration; Intracellular Fluid
PubMed: 31300088
DOI: 10.1016/j.semnephrol.2019.04.002 -
Physiological Reviews Oct 2023Calcium signaling underlies much of physiology. Almost all the Ca in the cytoplasm is bound to buffers, with typically only ∼1% being freely ionized at resting levels... (Review)
Review
Calcium signaling underlies much of physiology. Almost all the Ca in the cytoplasm is bound to buffers, with typically only ∼1% being freely ionized at resting levels in most cells. Physiological Ca buffers include small molecules and proteins, and experimentally Ca indicators will also buffer calcium. The chemistry of interactions between Ca and buffers determines the extent and speed of Ca binding. The physiological effects of Ca buffers are determined by the kinetics with which they bind Ca and their mobility within the cell. The degree of buffering depends on factors such as the affinity for Ca, the Ca concentration, and whether Ca ions bind cooperatively. Buffering affects both the amplitude and time course of cytoplasmic Ca signals as well as changes of Ca concentration in organelles. It can also facilitate Ca diffusion inside the cell. Ca buffering affects synaptic transmission, muscle contraction, Ca transport across epithelia, and the killing of bacteria. Saturation of buffers leads to synaptic facilitation and tetanic contraction in skeletal muscle and may play a role in inotropy in the heart. This review focuses on the link between buffer chemistry and function and how Ca buffering affects normal physiology and the consequences of changes in disease. As well as summarizing what is known, we point out the many areas where further work is required.
Topics: Humans; Calcium; Buffers; Cytoplasm; Heart; Synaptic Transmission; Calcium Signaling
PubMed: 37326298
DOI: 10.1152/physrev.00042.2022 -
Management of acute metabolic acidosis in the ICU: sodium bicarbonate and renal replacement therapy.Critical Care (London, England) Aug 2021This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at... (Review)
Review
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .
Topics: Acidosis; Buffers; Humans; Intensive Care Units; Renal Replacement Therapy; Sodium Bicarbonate
PubMed: 34461963
DOI: 10.1186/s13054-021-03677-4 -
Anesthesiology May 2021
Review
Topics: Acidosis; Acute Kidney Injury; Buffers; Critical Care; Critical Illness; Humans; Sodium Bicarbonate
PubMed: 33721887
DOI: 10.1097/ALN.0000000000003733 -
Molecular Pharmaceutics Nov 2022Lipid nanoparticles containing messenger RNA (mRNA-LNPs) have launched to the forefront of nonviral delivery systems with their realized potential during the COVID-19...
Lipid nanoparticles containing messenger RNA (mRNA-LNPs) have launched to the forefront of nonviral delivery systems with their realized potential during the COVID-19 pandemic. Here, we investigate the impact of commonly used biological buffers on the performance and durability of mRNA-LNPs. We tested the compatibility of three common buffers─HEPES, Tris, and phosphate-buffered saline─with a DLin-MC3-DMA mRNA-LNP formulation before and after a single controlled freeze-thaw cycle. We hypothesized that buffer composition would affect lipid-aqueous phase separation. Indeed, the buffers imposed structural changes in LNP morphology as indicated by electron microscopy, differential scanning calorimetry, and membrane fluidity assays. We employed in vitro and in vivo models to measure mRNA transfection and found that Tris or HEPES-buffered LNPs yielded better cryoprotection and transfection efficiency compared to PBS. Understanding the effects of various buffers on LNP morphology and efficacy provides valuable insights into maintaining the stability of LNPs after long-term storage.
Topics: Humans; RNA, Messenger; Lipids; Pandemics; COVID-19; Nanoparticles; Liposomes; RNA, Small Interfering
PubMed: 36129254
DOI: 10.1021/acs.molpharmaceut.2c00587 -
Reviews of Geophysics (Washington, D.C.... Sep 2020Alkalinity, the excess of proton acceptors over donors, plays a major role in ocean chemistry, in buffering and in calcium carbonate precipitation and dissolution.... (Review)
Review
Alkalinity, the excess of proton acceptors over donors, plays a major role in ocean chemistry, in buffering and in calcium carbonate precipitation and dissolution. Understanding alkalinity dynamics is pivotal to quantify ocean carbon dioxide uptake during times of global change. Here we review ocean alkalinity and its role in ocean buffering as well as the biogeochemical processes governing alkalinity and pH in the ocean. We show that it is important to distinguish between measurable titration alkalinity and charge balance alkalinity that is used to quantify calcification and carbonate dissolution and needed to understand the impact of biogeochemical processes on components of the carbon dioxide system. A general treatment of ocean buffering and quantification via sensitivity factors is presented and used to link existing buffer and sensitivity factors. The impact of individual biogeochemical processes on ocean alkalinity and pH is discussed and quantified using these sensitivity factors. Processes governing ocean alkalinity on longer time scales such as carbonate compensation, (reversed) silicate weathering, and anaerobic mineralization are discussed and used to derive a close-to-balance ocean alkalinity budget for the modern ocean.
PubMed: 32879922
DOI: 10.1029/2019RG000681 -
Journal of Oleo Science 2021Monoammonium glycyrrhizinate is produced by the neutralization of glycyrrhizic acid from plant licorice with ammonia. In this study, the physicochemical properties of...
Monoammonium glycyrrhizinate is produced by the neutralization of glycyrrhizic acid from plant licorice with ammonia. In this study, the physicochemical properties of aqueous monoammonium glycyrrhizinate were investigated from the viewpoint of surface chemistry. The structure of the amphiphilic molecule is bola type, comprising two glucuronic acid moieties having two carboxylic acids groups and an aglycone part having a carboxylic acid at the opposite end of the molecule from the glucuronic acids. We found that the physicochemical properties of aqueous monoammonium glycyrrhizinate are dependent on the ionization of the carboxylic acid groups. The solubility of monoammonium glycyrrhizinate gradually increased above pH 4 in the buffer solution. The critical micelle concentration (CMC) and surface tension at the CMC (γ) of monoammonium glycyrrhizinate were determined by the surface tension method to be 1.5 mmol L and 50 mN m in pH 5 buffer and 3.7 mmol L and 51 mN m in pH 6 buffer, respectively. The surface tension gradually decreased with increasing concentration of monoammonium glycyrrhizinate in the pH 7 buffer, but the CMC was not defined by the curve. Light scattering measurements also did not reveal a clear CMC in the pH 7 buffer. The ionization of the carboxylic acid groups in the bola-type amphiphilic molecule with increasing pH is disadvantageous for micelle formation. Cryo-transmission electron microscopy showed that monoammonium glycyrrhizinate forms rod-like micelles in pH 5 buffer, and small angle X-ray scattering experiments confirmed that the average micellar structure was rod-like in pH 5 buffer. Thus, it was found that monoammonium glycyrrhizinate can form micelles only in weakly acidic aqueous solutions.
Topics: Buffers; Glycyrrhizic Acid; Hydrogen-Ion Concentration; Micelles; Solubility; Surface Tension
PubMed: 34193668
DOI: 10.5650/jos.ess21046 -
Cancer Metastasis Reviews Jun 2019The extracellular pH of solid tumors is unequivocally acidic due to a combination of high rates of lactic acid production (a consequence of fermentative glycolytic... (Review)
Review
The extracellular pH of solid tumors is unequivocally acidic due to a combination of high rates of lactic acid production (a consequence of fermentative glycolytic metabolism) and poor perfusion. This has been documented by us and others in a wide variety of solid tumor models, primarily using magnetic resonance spectroscopic imaging (MRSI). This acidity contributes to tumor progression by inducing genome instability, promoting local invasion and metastases, inhibiting anti-tumor immunity, and conferring resistance to chemo- and radio-therapies. Systemic buffer therapies can neutralize tumor acidity and has been shown to inhibit local invasion and metastasis and improve immune surveillance in a variety of cancer model systems. This review will revisit the causes and consequences of acidosis by summarizing strategies used by cancer cells to adapt to acidosis, and how this acidity associated with carcinogenesis, metastasis, and immune function. Finally, this review will discuss how neutralization of acidity can be used to inhibit carcinogenesis and metastasis and improve anti-cancer immunotherapy.
Topics: Acidosis; Animals; Buffers; Humans; Hydrogen-Ion Concentration; Neoplasms; Sodium Bicarbonate
PubMed: 30806853
DOI: 10.1007/s10555-019-09787-4 -
Dental Materials : Official Publication... Nov 2022The aim of this study was to investigate the degradation of inert glass fillers which are commonly used in conventional resin-based composites to provide radiopacity,...
OBJECTIVES
The aim of this study was to investigate the degradation of inert glass fillers which are commonly used in conventional resin-based composites to provide radiopacity, reduce the polymerization shrinkage and improve the mechanical properties.
METHODS
75 mg of five different glass powders (1 µm) was immersed separately into 50 mL of acetic acid (pH 4) and tris buffer (pH 7.4) for up to 4 weeks. At each time point the glass powder was filtered and dried for characterization using ATR-FTIR and XRD to assess the degradation behavior and crystallization. ICP-OES, ISE and pH measurements were performed on the supernatant solutions to monitor the pH and ion release.
RESULTS
Although FTIR and XRD analysis showed no significant glass degradation or crystallization upon immersion, there was a substantial release of ions from the inert fillers, especially from BABFG and CDL. Barium release for these fillers were 270 and 165 ppm respectively. G018-373 glass presented the lowest ion release followed by GM27884 and BABG. The ion release was more pronounced in acidic conditions compared to neutral conditions apart from the fluoride release.
SIGNIFICANCE
Inert glasses are not as inert as previously thought. This may result in leaching of ions, potentially causing toxicity, reduction in mechanical properties, increased wear and subsequent failure of the composite material. The ions released from the inert glass may interfere with other glass fillers such as bioactive glass fillers, inhibiting degradation of the bioactive glass, beneficial ion release from the bioactive glass, pH neutralization and apatite formation.
Topics: Apatites; Barium; Fluorides; Glass; Materials Testing; Powders; Tromethamine
PubMed: 36154969
DOI: 10.1016/j.dental.2022.09.004