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European Journal of Heart Failure Oct 2018
Topics: Chlorides; Heart Failure; Homeostasis; Humans
PubMed: 30168648
DOI: 10.1002/ejhf.1302 -
Nature Medicine Feb 2016Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a...
Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.
Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Calcium-Binding Proteins; Capillaries; Endothelial Cells; Fibroblasts; Fibrosis; Fluorescent Antibody Technique; Humans; Hydrochloric Acid; Intercellular Signaling Peptides and Proteins; Jagged-1 Protein; Lung; Lung Injury; Macrophages; Membrane Proteins; Mice; Oligopeptides; Pulmonary Artery; Pulmonary Circulation; Pulmonary Fibrosis; RNA, Small Interfering; Receptors, CXCR; Receptors, Notch; Regeneration; Serrate-Jagged Proteins; Smad3 Protein; Vascular Endothelial Growth Factor Receptor-1; Wnt Signaling Pathway
PubMed: 26779814
DOI: 10.1038/nm.4035 -
American Journal of Respiratory and... May 2023In the EOLIA (ECMO to Rescue Lung Injury in Severe ARDS) trial, oxygenation was similar between intervention and conventional groups, whereas [Formula: see text]e was...
In the EOLIA (ECMO to Rescue Lung Injury in Severe ARDS) trial, oxygenation was similar between intervention and conventional groups, whereas [Formula: see text]e was reduced in the intervention group. Comparable reductions in ventilation intensity are theoretically possible with low-flow extracorporeal CO removal (ECCOR), provided oxygenation remains acceptable. To compare the effects of ECCOR and extracorporeal membrane oxygenation (ECMO) on gas exchange, respiratory mechanics, and hemodynamics in animal models of pulmonary (intratracheal hydrochloric acid) and extrapulmonary (intravenous oleic acid) lung injury. Twenty-four pigs with moderate to severe hypoxemia (Pa:Fi ⩽ 150 mm Hg) were randomized to ECMO (blood flow 50-60 ml/kg/min), ECCOR (0.4 L/min), or mechanical ventilation alone. [Formula: see text]o, [Formula: see text]co, gas exchange, hemodynamics, and respiratory mechanics were measured and are presented as 24-hour averages. Oleic acid versus hydrochloric acid showed higher extravascular lung water (1,424 ± 419 vs. 574 ± 195 ml; < 0.001), worse oxygenation (Pa:Fi = 125 ± 14 vs. 151 ± 11 mm Hg; < 0.001), but better respiratory mechanics (plateau pressure 27 ± 4 vs. 30 ± 3 cm HO; = 0.017). Both models led to acute severe pulmonary hypertension. In both models, ECMO (3.7 ± 0.5 L/min), compared with ECCOR (0.4 L/min), increased mixed venous oxygen saturation and oxygenation, and improved hemodynamics (cardiac output = 6.0 ± 1.4 vs. 5.2 ± 1.4 L/min; = 0.003). [Formula: see text]o and [Formula: see text]co, irrespective of lung injury model, were lower during ECMO, resulting in lower Pa and [Formula: see text]e but worse respiratory elastance compared with ECCOR (64 ± 27 vs. 40 ± 8 cm HO/L; < 0.001). ECMO was associated with better oxygenation, lower [Formula: see text]o, and better hemodynamics. ECCOR may offer a potential alternative to ECMO, but there are concerns regarding its effects on hemodynamics and pulmonary hypertension.
Topics: Animals; Acute Lung Injury; Carbon Dioxide; Hydrochloric Acid; Hypertension, Pulmonary; Oleic Acid; Respiration, Artificial; Swine
PubMed: 36848321
DOI: 10.1164/rccm.202212-2194OC -
Journal of Zhejiang University.... Mar 2016The purpose of this review is to objectively evaluate the biochemical and pathophysiological properties of 0.9% saline (henceforth: saline) and to discuss the impact of... (Review)
Review
The purpose of this review is to objectively evaluate the biochemical and pathophysiological properties of 0.9% saline (henceforth: saline) and to discuss the impact of saline infusion, specifically on systemic acid-base balance and renal hemodynamics. Studies have shown that electrolyte balance, including effects of saline infusion on serum electrolytes, is often poorly understood among practicing physicians and inappropriate saline prescribing can cause increased morbidity and mortality. Large-volume (>2 L) saline infusion in healthy adults induces hyperchloremia which is associated with metabolic acidosis, hyperkalemia, and negative protein balance. Saline overload (80 ml/kg) in rodents can cause intestinal edema and contractile dysfunction associated with activation of sodium-proton exchanger (NHE) and decrease in myosin light chain phosphorylation. Saline infusion can also adversely affect renal hemodynamics. Microperfusion experiments and real-time imaging studies have demonstrated a reduction in renal perfusion and an expansion in kidney volume, compromising O2 delivery to the renal parenchyma following saline infusion. Clinically, saline infusion for patients post abdominal and cardiovascular surgery is associated with a greater number of adverse effects including more frequent blood product transfusion and bicarbonate therapy, reduced gastric blood flow, delayed recovery of gut function, impaired cardiac contractility in response to inotropes, prolonged hospital stay, and possibly increased mortality. In critically ill patients, saline infusion, compared to balanced fluid infusions, increases the occurrence of acute kidney injury. In summary, saline is a highly acidic fluid. With the exception of saline infusion for patients with hypochloremic metabolic alkalosis and volume depletion due to vomiting or upper gastrointestinal suction, indiscriminate use, especially for acutely ill patients, may cause unnecessary complications and should be avoided. More education regarding saline-related effects and adequate electrolyte management is needed.
Topics: Acid-Base Equilibrium; Acidosis; Animals; Chlorides; Hemodynamics; Humans; Kidney; Sodium Chloride
PubMed: 26984838
DOI: 10.1631/jzus.B1500201 -
Journal of the American Chemical Society Jan 2023Selective functional group interconversions in complex molecular settings underpin many of the challenges facing modern organic synthesis. Currently, a privileged subset...
Selective functional group interconversions in complex molecular settings underpin many of the challenges facing modern organic synthesis. Currently, a privileged subset of functional groups dominates this landscape, while others, despite their abundance, are sorely underdeveloped. Amines epitomize this dichotomy; they are abundant but otherwise intransigent toward direct interconversion. Here, we report an approach that enables the direct conversion of amines to bromides, chlorides, iodides, phosphates, thioethers, and alcohols, the heart of which is a deaminative carbon-centered radical formation process using an anomeric amide reagent. Experimental and computational mechanistic studies demonstrate that successful deaminative functionalization relies not only on outcompeting the H-atom transfer to the incipient radical but also on the generation of polarity-matched, productive chain-carrying radicals that continue to react efficiently. The overall implications of this technology for interconverting amine libraries were evaluated via high-throughput parallel synthesis and applied in the development of one-pot diversification protocols.
Topics: Catalysis; Amines; Amides; Bromides; Chlorides
PubMed: 36548788
DOI: 10.1021/jacs.2c11453 -
Nutrients Mar 2024Potassium is a monovalent cation widely present in nature, where it is not in metallic form, but always in combination with other substances, especially chloride [...].
Potassium is a monovalent cation widely present in nature, where it is not in metallic form, but always in combination with other substances, especially chloride [...].
Topics: Humans; Potassium; Chlorides; Potassium Chloride
PubMed: 38542744
DOI: 10.3390/nu16060833 -
The Journal of Thoracic and... Feb 2019
Topics: Allografts; Heart; Heart Diseases; Humans; Sodium Chloride
PubMed: 30174127
DOI: 10.1016/j.jtcvs.2018.07.068 -
International Journal of Molecular... Oct 2022As an environmentally friendly separation medium, the ionic liquid (IL)-based aqueous two-phase system (ATPS) is attracting long-term attention from a growing number of... (Review)
Review
As an environmentally friendly separation medium, the ionic liquid (IL)-based aqueous two-phase system (ATPS) is attracting long-term attention from a growing number of scientists and engineers. Phase equilibrium data of IL-based ATPSs are an important basis for the design and optimization of chemical reactions and separation processes involving ILs. This article provides the recent significant progress that has been made in the field and highlights the possible directions of future developments. The effects of each component (such as salting-out agents and ILs) on the phase behavior of IL-based ATPSs are summarized and discussed in detail. We mainly focus on the phase behavior of ATPSs by using ILs, expecting to provide meaningful and valuable information that may promote further research and application.
Topics: Ionic Liquids; Water; Sodium Chloride
PubMed: 36293560
DOI: 10.3390/ijms232012706 -
Nutrients Oct 2021We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act,...
We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act, at least in part, via stimulation of estrogen receptors; furthermore, compared to residents of Western countries, residents of East Asian countries consume higher amounts of phytoestrogens and exhibit lower rates of pulmonary fibrosis. Therefore, we tested the hypothesis that dietary phytoestrogens ameliorate the severity of experimentally induced pulmonary fibrosis. Male mice placed on either regular soybean diet or phytoestrogen-free diet were instilled with 0.1 N HCl to provoke pulmonary fibrosis. Thirty days later, lung mechanics were measured as indices of lung function and bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed for biomarkers of fibrosis. Mice on phytoestrogen-free diet demonstrated increased mortality and stronger signs of chronic lung injury and pulmonary fibrosis, as reflected in the expression of collagen, extracellular matrix deposition, histology, and lung mechanics, compared to mice on regular diet. We conclude that dietary phytoestrogens play an important role in the pathogenesis of pulmonary fibrosis and suggest that phytoestrogens (e.g., genistein) may be useful as part of a therapeutic regimen against hydrochloric acid-induced lung fibrosis and chronic lung dysfunction.
Topics: Animals; Chronic Disease; Diet; Extracellular Matrix Proteins; Hydrochloric Acid; Inflammation; Leukocyte Count; Lung; Lung Injury; Male; Mice, Inbred C57BL; Models, Biological; Phytoestrogens; Pulmonary Fibrosis; RNA, Messenger; Signal Transduction; Transforming Growth Factor beta; Mice
PubMed: 34684599
DOI: 10.3390/nu13103599 -
Journal of the American Society of... May 2018
Topics: Animals; Biological Transport; Chlorides; Ion Transport; Malpighian Tubules; Signal Transduction
PubMed: 29650535
DOI: 10.1681/ASN.2018030318