Continuous renal replacement therapy (CRRT) is a form of dialysis prescribed to severely ill patients who cannot tolerate regular hemodialysis. However, as the patients are typically very ill to begin with, there is always uncertainty whether they will survive during or after CRRT treatment. Because of outcome uncertainty, a large percentage of patients treated with CRRT do not survive, utilizing scarce resources and raising false hope in patients and their families.
View Article and Find Full Text PDFThe SLC4 family of secondary bicarbonate transporters is responsible for the transport of HCO, CO, Cl, Na, K, NH, and H, which are necessary for regulation of pH and ion homeostasis. They are widely expressed in numerous tissues throughout the body and function in different cell types with different membrane properties. Potential lipid roles in SLC4 function have been reported in experimental studies, focusing mostly on two members of the family: AE1 (Cl/HCO exchanger) and NBCe1 (Na-COcotransporter).
View Article and Find Full Text PDFContinuous renal replacement therapy (CRRT) is a form of dialysis prescribed to severely ill patients who cannot tolerate regular hemodialysis. However, as the patients are typically very ill to begin with, there is always uncertainty as to whether they will survive during or after CRRT treatment. Because of outcome uncertainty, a large percentage of patients treated with CRRT do not survive, utilizing scarce resources and raising false hope in patients and their families.
View Article and Find Full Text PDFBiocompatibility and the ability to mediate the appropriate flux of ions, urea, and uremic toxins between blood and dialysate components are key parameters for membranes used in dialysis. Oxone-mediated TEMPO-oxidized cellulose nanomaterials have been demonstrated to be excellent additives in the production and tunability of ultrafiltration and dialysis membranes. In the present study, nanocellulose ionic liquid membranes (NC-ILMs) were tested in vitro and ex vivo.
View Article and Find Full Text PDFUnlabelled: The SLC4 family of secondary bicarbonate transporters is responsible for the transport of HCO -, CO , Cl , Na , K , NH and H necessary for regulation of pH and ion homeostasis. They are widely expressed in numerous tissues throughout the body and function in different cell types with different membrane properties. Potential lipid roles in SLC4 function have been reported in experimental studies, focusing mostly on two members of the family: AE1 (Cl /HCO exchanger) and NBCe1 (Na -CO cotransporter).
View Article and Find Full Text PDFAcidification of the cellular lysosome is an important factor in infection of mammalian cells by SARS-CoV-2. Therefore, raising the pH of the lysosome would theoretically be beneficial in prevention or treatment of SARS-CoV-2 infection. Sodium bicarbonate, carbicarb, and THAM are buffers that can be used clinically to provide base to patients.
View Article and Find Full Text PDFH+ or base transporters and channels in the mammalian genome play important roles in the maintenance of numerous cellular biochemical and physiologic processes throughout the body. Among the known base transporters, those within the SLC4 and SLC26 gene families are involved in cell, transepithelial, and whole organ function. Whether the functional properties of these transporters involve HCO3-, CO32-, or HCO3-/CO32- stimulated H+ (or OH-) transport has not received widespread attention in the literature.
View Article and Find Full Text PDFAnion exchanger 1 (AE1, band 3) is a major membrane protein of red blood cells and plays a key role in acid-base homeostasis, urine acidification, red blood cell shape regulation, and removal of carbon dioxide during respiration. Though structures of the transmembrane domain (TMD) of three SLC4 transporters, including AE1, have been resolved previously in their outward-facing (OF) state, no mammalian SLC4 structure has been reported in the inward-facing (IF) conformation. Here we present the cryoEM structures of full-length bovine AE1 with its TMD captured in both IF and OF conformations.
View Article and Find Full Text PDFCalcium is a key ion involved in cardiac and skeletal muscle contractility, nerve function, and skeletal structure. Global calcium balance is affected by parathyroid hormone and vitamin D, and calcium is shuttled between the extracellular space and the bone matrix compartment dynamically. The kidney plays an important role in whole-body calcium balance.
View Article and Find Full Text PDFPurpose Of Review: Nearly 20 years ago, vascular endothelial growth factor (VEGF)inhibitors (VEGFi) were adapted from systemic use from antiangiogenesis roles to intravitreal uses. Initially bevacizumab a murine immunoglobulin was injected 'off label' as a treatment for diabetic macular edema and age-related macular degeneration. Throughout the following decade aflibercept and finally ranibizumab were adapted and obtained Food and Drug Administration approval for intravitreal use.
View Article and Find Full Text PDFIntravitreal vascular endothelial growth factor (VEGF) receptor blockade is used for a variety of retinal pathologies. These include age-related macular degeneration (AMD), diabetic macular edema (DME) and central retinal vein obstruction. Reports of absorption of intravitreal agents into systemic circulation have increased in number and confirmation of depletion of VEGF has been confirmed.
View Article and Find Full Text PDFSLC4 transporters play significant roles in pH regulation and cellular sodium transport. The previously solved structures of the outward facing (OF) conformation for AE1 (SLC4A1) and NBCe1 (SLC4A4) transporters revealed an identical overall fold despite their different transport modes (chloride/bicarbonate exchange versus sodium-carbonate cotransport). However, the exact mechanism determining the different transport modes in the SLC4 family remains unknown.
View Article and Find Full Text PDFSystemic vascular endothelial growth factor (VEGF) inhibitions can induce worsening hypertension, proteinuria and glomerular diseases of various types. These agents can also be used to treat ophthalmic diseases like proliferative diabetic retinopathy, diabetic macular edema, central retinal vein occlusion and age-related macular degeneration. Recently, pharmacokinetic studies confirmed that these agents are absorbed at levels that result in biologically significant suppression of intravascular VEGF levels.
View Article and Find Full Text PDFVascular endothelial growth factor (VEGF) inhibition can cause worsening hypertension, proteinuria, chronic kidney injury, and glomerular disease. Thrombotic microangiopathy (TMA) and other nephrotic disorders have been reported with systemic VEGF blockade. These same agents are given intravitreally for age-related macular degeneration (AMD) and diabetic retinopathy (DR), albeit at lower doses than those given for systemic indications.
View Article and Find Full Text PDFScleroderma renal crisis is a serious complication that can develop in certain patients with systemic sclerosis. Some risks have been identified as potential triggers of scleroderma renal crisis, including the high-dose oral corticosteroids. Here, we present a patient who developed clinically severe systemic sclerosis and scleroderma renal crisis after exposure to oral corticosteroids and intravitreal vascular endothelial growth factor blockade with bevacizumab for cotton wool spots.
View Article and Find Full Text PDFBackground: It is unclear how high fructose consumption induces disparate metabolic responses in genetically diverse mouse strains.
Objective: We aimed to investigate whether the gut microbiota contributes to differential metabolic responses to fructose.
Methods: Eight-week-old male C57BL/6J (B6), DBA/2J (DBA), and FVB/NJ (FVB) mice were given 8% fructose solution or regular water (control) for 12 wk.
Rationale & Objective: Euvolemic hyponatremia often occurs due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Vasopressin 2 receptor antagonists may be used to treat SIADH. Several of the major trials used 15 mg of tolvaptan as the lowest effective dose in euvolemic and hypervolemic hyponatremia.
View Article and Find Full Text PDFPurpose: To elucidate the molecular events in solute carrier family 4 member 11 (SLC4A11)-deficient corneal endothelium that lead to the endothelial dysfunction that characterizes the dystrophies associated with SLC4A11 mutations, congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy 4.
Methods: Comparative transcriptomic analysis (CTA) was performed in primary human corneal endothelial cells (pHCEnC) and murine corneal endothelial cells (MCEnC) with normal and reduced levels of SLC4A11 (SLC4A11 KD pHCEnC) and Slc4a11 (Slc4a11-/- MCEnC), respectively. Validation of differentially expressed genes was performed using immunofluorescence staining of CHED corneal endothelium, as well as western blot and quantitative PCR analysis of SLC4A11 KD pHCEnC and Slc4a11-/- MCEnC.
C3 dominant immunofluorescence staining is present in a subset of patients with idiopathic immune complex membranoproliferative glomerulonephritis (iMPGN). It is increasingly recognized that iMPGN may be complement driven, as are cases of "typical" C3 glomerulopathy (C3G). In both iMPGN and C3G, a frequent membranoproliferative pattern of glomerular injury may indicate common pathogenic mechanisms via complement activation and endothelial cell damage.
View Article and Find Full Text PDFBromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural integrity of basement membranes. The formation of sulfilimine cross-links depends on the ability of peroxidasin to use bromide and hydrogen peroxide substrates to produce hypobromous acid (HOBr).
View Article and Find Full Text PDFThe advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion.
View Article and Find Full Text PDFDrug-induced lupus erythematosus has features distinct from primary systemic lupus erythematosus. It can occur with a wide variety of agents that result in the generation of anti-histone or other types of antibodies. Systemic manifestations of drug-induced systemic lupus erythematosus may include renal dysfunction due to circulating immune complexes or due to other immune reactions to the culprit medication(s).
View Article and Find Full Text PDFCertain diabetic and hypertensive patients started on intravitreal vascular endothelial growth factor inhibition for diabetic retinopathy may experience worsening of hypertension and proteinuria. The etiology of this is the newly recognized absorption of intravitreally injected vascular endothelial growth factor inhibitors, and the susceptibility of patients with pre-existing renal disease to exacerbations depends on the degree of systemic absorption. There are eighteen reported cases of worsening hypertension, woresening proteinuria, worsening renal function, thrombotic microangiopathy, and glomerular disease noted after initiation of intravitreal vascular endothelial growth factor blockade.
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