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Clinical Journal of the American... Nov 2018Current therapies for hyponatremia have variable effectiveness and tolerability, and in certain instances, they are very expensive. We examined the effectiveness,...
BACKGROUND AND OBJECTIVES
Current therapies for hyponatremia have variable effectiveness and tolerability, and in certain instances, they are very expensive. We examined the effectiveness, safety, and tolerability of urea for the treatment of inpatient hyponatremia.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We identified all patients hospitalized at the University of Pittsburgh Medical Center between July 2016 and August 2017 with hyponatremia (plasma sodium <135 mEq/L) who received urea, including a subgroup of patients who received urea as the sole drug therapy for hyponatremia (urea-only treated). We matched urea only-treated patients to a group of patients with hyponatremia who did not receive urea (urea untreated) and compared changes in plasma sodium at 24 hours and the end of therapy as well as the proportion of patients who achieved plasma sodium ≥135 mEq/L. We abstracted data on adverse events and reported side effects of urea.
RESULTS
Fifty-eight patients received urea (7.5-90 g/d) over a median of 4.5 (interquartile range, 3-8) days and showed an increase in plasma sodium from 124 mEq/L (interquartile range, 122-126) to 131 mEq/L (interquartile range, 127-134; <0.001). Among 12 urea only-treated patients, plasma sodium increased from 125 mEq/L (interquartile range, 122-127) to 131 mEq/L (interquartile range, 129-136; =0.001) by the end of urea therapy. There was a larger increase in plasma sodium at 24 hours in urea only-treated patients compared with urea-untreated patients (2.5 mEq/L; interquartile range, 0-4.5 versus -0.5 mEq/L; interquartile range, -2.5 to 1.5; =0.04), with no difference in change in plasma sodium by the end of therapy (6 mEq/L; interquartile range, 3.5-10 versus 5.5 mEq/L; interquartile range, 3-7.5; =0.51). A greater proportion of urea only-treated patients achieved normonatremia, but this difference was not statistically significant (33% versus 8%; =0.08). No patients experienced overly rapid correction of plasma sodium, and no serious adverse events were reported.
CONCLUSIONS
Urea seems effective and safe for the treatment of inpatient hyponatremia, and it is well tolerated.
Topics: Aged; Female; Humans; Hyponatremia; Male; Middle Aged; Retrospective Studies; Sodium; Urea
PubMed: 30181129
DOI: 10.2215/CJN.04020318 -
Sub-cellular Biochemistry 2014Members of the urea transporter (UT) family mediate rapid, selective transport of urea down its concentration gradient. To date, crystal structures of two evolutionarily... (Review)
Review
Members of the urea transporter (UT) family mediate rapid, selective transport of urea down its concentration gradient. To date, crystal structures of two evolutionarily distant UTs have been solved. These structures reveal a common UT fold involving two structurally homologous domains that encircle a continuous membrane-spanning pore and indicate that UTs transport urea via a channel-like mechanism. Examination of the conserved architecture of the pore, combined with crystal structures of ligand-bound proteins, molecular dynamics simulations, and functional data on permeation and inhibition by a broad range of urea analogs and other small molecules, provides insight into the structural basis of urea permeation and selectivity.
Topics: Animals; Bacterial Proteins; Crystallography, X-Ray; Humans; Membrane Transport Proteins; Models, Molecular; Molecular Structure; Protein Binding; Protein Structure, Tertiary; Urea; Urea Transporters
PubMed: 25298339
DOI: 10.1007/978-94-017-9343-8_5 -
Physical Chemistry Chemical Physics :... Sep 2022Trimethylamine -oxide (TMAO) and urea are small organic biological molecules. While TMAO is known as a protective osmolyte that promotes the native form of biomolecules,...
Trimethylamine -oxide (TMAO) and urea are small organic biological molecules. While TMAO is known as a protective osmolyte that promotes the native form of biomolecules, urea is a denaturant. An understanding of the impact of TMAO and urea on water structure may aid in uncovering the molecular mechanisms that underlie this activity. Here we investigate binary solutions of TMAO-water, urea-water and ternary solutions of TMAO-urea-water using NMR spectroscopy at 300 K. An enhancement of the total hydrogen bonding in water was found upon the addition of TMAO and this effect was neutralised by a mole ratio of 1-part TMAO to 4-parts urea. Urea was found to have little effect on the strength of water's hydrogen bonding network and the dynamics of water molecules. Evidence was found for a weak interaction between TMAO and urea. Taken together, these results suggest that TMAO's function as a protective osmolyte, and its counteraction of urea, may be driven by the strength of its hydrogen bond interactions with water, and by a secondary reinforcement of water's own hydrogen bond network. They also suggest that the TMAO-urea complex forms through the donation of a hydrogen bond by urea.
Topics: Hydrogen Bonding; Magnetic Resonance Spectroscopy; Methylamines; Urea; Water
PubMed: 36040138
DOI: 10.1039/d2cp02475f -
CNS Spectrums Feb 2022Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in... (Review)
Review
Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2A receptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.
Topics: Dementia; Hallucinations; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Urea
PubMed: 32811586
DOI: 10.1017/S1092852920001765 -
Dermatology Online Journal Nov 2013Urea is an organic compound that has been used clinically for dermatological diseases for more than a century. Urea is a potent emollient and keratolytic agent, making... (Review)
Review
INTRODUCTION
Urea is an organic compound that has been used clinically for dermatological diseases for more than a century. Urea is a potent emollient and keratolytic agent, making urea an effective monotherapy for conditions associated with dry and scaly skin. A systematic review of the literature is needed to provide clinicians with evidence-based applications of urea in the treatment of dermatological diseases.
METHODS
A PubMed search was conducted using the term "urea" combined with "skin," "ichthyosis," "psoriasis," "xerosis," "emollient," "onychomycosis," "dermatitis," and "avulsion." A total of 81 publications met inclusion criteria and were evaluated. Treatment indication(s), test agents, number of subjects, treatment protocols, results, and side effects were recorded.
RESULTS
Effective treatment with urea has been reported for the following conditions: ichthyosis, xerosis, atopic dermatitis/eczema, contact dermatitis, radiation induced dermatitis, psoriasis/seborrheic dermatitis, onychomycosis, tinea pedis, keratosis, pruritus, and dystrophic nails. Furthermore, urea has been used with other medications as a penetration enhancing agent. Mild irritation is the most common adverse event, proving urea to be a safe and tolerable topical drug without systemic toxicity.
DISCUSSION/CONCLUSION
Urea is a safe, effective dermatologic therapy with wide-ranging clinical utility and minimal, non-systemic side effects. In order to optimize patient care, dermatologists should be well informed with regards to urea's indications and efficacy.
Topics: Dermatologic Agents; Humans; Skin Diseases; Urea
PubMed: 24314769
DOI: No ID Found -
Chemical Reviews Oct 2016Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds... (Review)
Review
Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C-N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.
Topics: Amidines; Aniline Compounds; Biological Products; Carbamates; Catalysis; Cyclization; Heterocyclic Compounds; Hydrazines; Hydrazones; Ligands; Palladium; Sulfonamides; Urea
PubMed: 27689804
DOI: 10.1021/acs.chemrev.6b00512 -
Angewandte Chemie (International Ed. in... Dec 2019The RNA world hypothesis assumes that life on Earth began with nucleotides that formed information-carrying RNA oligomers able to self-replicate. Prebiotic reactions... (Review)
Review
The RNA world hypothesis assumes that life on Earth began with nucleotides that formed information-carrying RNA oligomers able to self-replicate. Prebiotic reactions leading to the contemporary nucleosides are now known, but their execution often requires specific starting materials and lengthy reaction sequences. It was therefore proposed that the RNA world was likely proceeded by a proto-RNA world constructed from molecules that were likely present on the early Earth in greater abundance. Herein, we show that the prebiotic starting molecules bis-urea (biuret) and tris-urea (triuret) are able to directly react with ribose. The urea-ribosides are remarkably stable because they are held together by a network of intramolecular, bifurcated hydrogen bonds. This even allowed the synthesis of phosphoramidite building blocks and incorporation of the units into RNA. Investigations of the nucleotides' base-pairing potential showed that triuret:G RNA base pairs closely resemble U:G wobble base pairs. Based on the probable abundance of urea on the early Earth, we postulate that urea-containing RNA bases are good candidates for a proto-RNA world.
Topics: Humans; Nucleosides; RNA; Urea
PubMed: 31573740
DOI: 10.1002/anie.201911746 -
Organic & Biomolecular Chemistry Nov 2013It has been difficult to directly measure the spontaneous hydrolysis rate of urea and, thus, 1,1,3,3-tetramethylurea (Me4U) was used as a model to determine the...
It has been difficult to directly measure the spontaneous hydrolysis rate of urea and, thus, 1,1,3,3-tetramethylurea (Me4U) was used as a model to determine the "experimental" rate constant for urea hydrolysis. The use of Me4U was based on an assumption that the rate of urea hydrolysis should be 2.8 times that of Me4U hydrolysis because the rate of acetamide hydrolysis is 2.8 times that of N,N-dimethyl-acetamide hydrolysis. The present first-principles electronic-structure calculations on the competing non-enzymatic hydrolysis pathways have demonstrated that the dominant pathway is the neutral hydrolysis via the CN addition for both urea (when pH < ~11.6) and Me4U (regardless of pH), unlike the non-enzymatic hydrolysis of amides where alkaline hydrolysis is dominant. Based on the computational data, the substituent shift of the free energy barrier calculated for the neutral hydrolysis is remarkably different from that for the alkaline hydrolysis, and the rate constant for the urea hydrolysis should be ~1.3 × 10(9)-fold lower than that (4.2 × 10(-12) s(-1)) measured for the Me4U hydrolysis. As a result, the rate enhancement and catalytic proficiency of urease should be 1.2 × 10(25) and 3 × 10(27) M(-1), respectively, suggesting that urease surpasses proteases and all other enzymes in its power to enhance the rate of reaction. All of the computational results are consistent with available experimental data for Me4U, suggesting that the computational prediction for urea is reliable.
Topics: Biocatalysis; Hydrolysis; Quantum Theory; Urea; Urease
PubMed: 24097048
DOI: 10.1039/c3ob41055b -
Kidney International Feb 2015Once the standard of care for cerebral edema, urea can also be used to treat hyponatremia. The 2014 European Clinical Practice Guidelines recommend urea for the...
Once the standard of care for cerebral edema, urea can also be used to treat hyponatremia. The 2014 European Clinical Practice Guidelines recommend urea for the treatment of the syndrome of inappropriate antidiuretic hormone, while discouraging use of vasopressin antagonists. Although there is evidence that urea can diminish hypertonic injury to brain cells caused by rapid correction of hyponatremia, clinical trials are needed that include patients at high risk to develop complications from overcorrection.
Topics: Animals; Hyponatremia; Male; Urea
PubMed: 25635717
DOI: 10.1038/ki.2014.320 -
Magnetic Resonance in Medicine Mar 2020Renal function is characterized by concentration of urea for removal in urine. We tested urea as a CEST-MRI contrast agent for measurement of the concentrating capacity...
PURPOSE
Renal function is characterized by concentration of urea for removal in urine. We tested urea as a CEST-MRI contrast agent for measurement of the concentrating capacity of distinct renal anatomical regions.
METHODS
The CEST contrast of urea was examined using phantoms with different concentrations and pH levels. Ten C57BL/6J mice were scanned twice at 7 T, once following intraperitoneal injection of 2M 150 µL urea and separately following an identical volume of saline. Kidneys were segmented into regions encompassing the cortex, outer medulla, and inner medulla and papilla to monitor spatially varying urea concentration. Z-spectra were acquired before and 20 minutes after injection, with dynamic scanning of urea handling performed in between via serial acquisition of CEST images acquired following saturation at +1 ppm.
RESULTS
Phantom experiments revealed concentration and pH-dependent CEST contrast of urea that was both acid- and base-catalyzed. Z-spectra acquired before injection showed significantly higher CEST contrast in the inner medulla and papilla (2.3% ± 1.9%) compared with the cortex (0.15% ± 0.75%, P = .011) and outer medulla (0.12% ± 0.58%, P = .008). Urea infusion increased CEST contrast in the inner medulla and papilla by 2.1% ± 1.9% (absolute), whereas saline infusion decreased CEST contrast by -0.5% ± 2.0% (absolute, P = .028 versus urea). Dynamic scanning revealed that thermal drift and diuretic status are confounding factors.
CONCLUSION
Urea CEST has a potential of monitoring renal function by capturing the spatially varying urea concentrating ability of the kidneys.
Topics: Algorithms; Animals; Contrast Media; Female; Humans; Hydrogen-Ion Concentration; Image Interpretation, Computer-Assisted; Image Processing, Computer-Assisted; Kidney; Kidney Cortex; Kidney Function Tests; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Normal Distribution; Phantoms, Imaging; Reproducibility of Results; Urea
PubMed: 31483529
DOI: 10.1002/mrm.27968