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Advanced Emergency Nursing JournalAtrial fibrillation/flutter (AF) remains the most common rhythm disturbance in adult patients presenting to emergency departments (EDs). Although pharmacologic...
Atrial fibrillation/flutter (AF) remains the most common rhythm disturbance in adult patients presenting to emergency departments (EDs). Although pharmacologic cardioversion has been established as safe and effective in recent-onset AF, its use in U.S. EDs is uncommon. The purpose of this study was to assess the safety and efficacy of intravenous (IV) procainamide for pharmacologic cardioversion in patients presenting to the ED with AF of <48-hr duration. Patients presenting to the ED with recent-onset AF (<48 hr) undergoing a cardioversion strategy with IV procainamide from 2017 to 2019 were reviewed. Clinical outcomes assessed included rates of cardioversion, hospital admission, stroke, and return ED visits for arrhythmia or serious adverse events. A total of 64 patients received procainamide therapy-60.9% achieved cardioversion and 35.9% were admitted to the hospital. The mean dose was 1062.4 mg (12.1 mg/kg). No patients returned to the ED secondary to stroke and 9.4% experienced complications attributed to procainamide, the most common being hypotension. Within 30 days of therapy, 20.3% of patients returned to the ED secondary to arrhythmia recurrence. Patients experiencing cardioversion with procainamide were less likely to be admitted to the hospital (25.6% vs. 52.0%; p = 0.04) or receive a rate control agent (17.9% vs. 64.0%; p = 0.001). There was no significant difference in the rate of 30-day return between those who experienced pharmacologic cardioversion and those who did not (p = 0.220). The implementation of a procainamide-based acute cardioversion strategy for patients presenting to the ED with recent-onset AF resulted in a 60% cardioversion rate, which was associated with a significantly higher rate of discharge from the ED. Transient hypotension was the most common adverse event. Further investigation into ED-based protocols for management of recent-onset AF is necessary to better understand their safety and efficacy.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Emergency Service, Hospital; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Procainamide; Retrospective Studies
PubMed: 34397493
DOI: 10.1097/TME.0000000000000358 -
Journal of Pharmaceutical and... May 2017Malignant melanoma is the most aggressive form of skin cancer. The early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines... (Comparative Study)
Comparative Study
Malignant melanoma is the most aggressive form of skin cancer. The early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of this disease. Previous studies have shown that benzamide derivatives (e.g. procainamide) conjugated with PET radionuclides specifically bind to melanin pigment of melanoma tumors. Ga chelating agents can have high influence on physiological properties of Ga labeled bioactive molecules, as was experienced during the application of HBED-CC on PSMA ligand. The aim of this study was to assess this concept in the case of the melanin specific procaindamide (PCA) and to compare the melanin specificity of Ga-labeled PCA using HBED-CC and NODAGA chelators under in vitro and in vivo conditions. Procainamide (PCA) was conjugated with HBED-CC and NODAGA chelators and was labeled with Ga-68. The melanin specificity of Ga-HBED-CC-PCA and Ga-NODAGA-PCA was investigated in vitro and in vivo using amelanotic (MELUR and A375) and melanin containing (B16-F10) melanoma cell lines. Tumor-bearing mice were prepared by subcutaneous injection of B16-F10, MELUR and A375 melanoma cells into C57BL/6 and SCID mice. 21±2days after tumor cell inoculation and 90min after intravenous injection of the Ga-labelledlabeled radiopharmacons whole body PET/MRI scans were performed. Ga-NODAGA-PCA and Ga-HBED-CC-PCA were produced with excellent radiochemical purity (98%). In vitro experiments demonstrated that after 30 and 90min incubation time Ga-NODAGA-PCA uptake of B16-F10 cells was significantly (p≤0.01) higher than the Ga-HBED-CC-conjugated PCA accumulation in the same cell line. Furthermore, significant difference (p≤0.01 and 0.05) was found between the uptake of melanin negative and positive cell lines using Ga-NODAGA-PCA and Ga-HBED-CC-PCA. In vivo PET/MRI studies using tumor models revealed significantly (p≤0.01) higher Ga-NODAGA-PCA uptake (SUVmean: 0.46±0.05, SUVmax: 1.96±0.25,T/M ratio: 40.7±4.23) in B16-F10 tumors in contrast to Ga-HBED-CC-PCA where the SUVmean, SUVmax and T/M ratio were 0.13±0.01, 0.56±0.11 and 11.43±1.24, respectively. Melanin specific PCA conjugated with NODAGA chelator showed higher specific binding properties than conjugated with HBED-CC. The chemical properties of the bifunctional chelators used for Ga-labeling of PCA determine the biological behaviour of the probes. Due to the high specificity and sensitivity Ga-labeled PCA molecules are promising radiotracers in melanoma imaging.
Topics: Acetates; Animals; Drug Evaluation, Preclinical; Edetic Acid; Female; Gallium Radioisotopes; Heterocyclic Compounds, 1-Ring; Humans; Magnetic Resonance Imaging; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, SCID; Positron-Emission Tomography; Procainamide; Skin Neoplasms; Xenograft Model Antitumor Assays
PubMed: 28273651
DOI: 10.1016/j.jpba.2017.02.049 -
Frontiers in Chemistry 2018Rising awareness of the universal importance of protein N-glycosylation governs the development of further advances in N-glycan analysis. Nowadays it is well known that...
Rising awareness of the universal importance of protein N-glycosylation governs the development of further advances in N-glycan analysis. Nowadays it is well known that correct glycosylation is essential for proper protein function, which emanates from its important role in many physiological processes. Furthermore, glycosylation is involved in pathophysiology of multiple common complex diseases. In the vast majority of cases, N-glycosylation profiles are analyzed from enzymatically released glycans, which can be further derivatized in order to enhance the sensitivity of the analysis. Techniques wherein derivatized N-glycans are profiled using hydrophilic interaction chromatography (HILIC) with fluorescence (FLR) and mass spectrometry (MS) detection are now routinely performed in a high-throughput manner. Therefore, we aimed to examine the performance of frequently used labeling compounds -2-aminiobenzamide (2-AB) and procainamide (ProA), and the recently introduced Fluor-MS (RF-MS) fluorescent tag. In all experiments N-glycans were released by PNGase F, fluorescently derivatized, purified by HILIC solid phase extraction and profiled using HILIC-UPLC-FLR-MS. We assessed sensitivity, linear range, limit of quantification (LOQ), repeatability and labeling efficiency for all three labels. For this purpose, we employed in-house prepared IgG and a commercially available IgG as a model glycoprotein. All samples were analyzed in triplicates using different amounts of starting material. We also tested the performance of all three labels in a high-throughput setting on 68 different IgG samples, all in duplicates and 22 identical IgG standards. In general, ProA labeled glycans had the highest FLR sensitivity (15-fold and 4-fold higher signal intensities compared to 2-AB and RF-MS respectively) and RF-MS had the highest MS sensitivity (68-fold and 2-fold higher signal intensities compared to 2-AB and ProA, respectively). ProA and RF-MS showed comparable limits of quantification with both FLR and MS detection, whilst 2-AB exhibited the lowest sensitivity. All labeling procedures showed good and comparable repeatability. Furthermore, the results indicated that labeling efficiency was very similar for all three labels. In conclusion, all three labels are a good choice for N-glycan derivatization in high-throughput HILIC-UPLC-FLR-MS N-glycan analysis, although ProA and RF-MS are a better option when higher sensitivity is needed.
PubMed: 30094234
DOI: 10.3389/fchem.2018.00324 -
Clinical Rheumatology Jun 2024The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is... (Review)
Review
The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.
Topics: Humans; Sulfides; Quinolines; Cyclopropanes; Acetates; Leukotriene Antagonists; Female; Churg-Strauss Syndrome; Male; Granulomatosis with Polyangiitis; Middle Aged; Adult
PubMed: 38720163
DOI: 10.1007/s10067-024-07000-8 -
Small (Weinheim An Der Bergstrasse,... Apr 2024Green synthesis of stable metal-organic frameworks (MOFs) with permanent and highly ordered porosity at room temperature without needing toxic and harmful solvents and...
Green synthesis of stable metal-organic frameworks (MOFs) with permanent and highly ordered porosity at room temperature without needing toxic and harmful solvents and long-term high-temperature reactions is crucial for sustainable production. Herein, a rapid and environmentally friendly synthesis strategy is reported to synthesize the complex topological bismuth-based-MOFs (Bi-MOFs), [Bi(CHO)(HO)] (denoted CAU-17), in water under ambient conditions by surfactant-mediated sonochemical approach, which could also be applicable to other MOFs. This strategy explores using cetyltrimethylammonium bromide (CTAB) amphiphilic molecules as structure-inducing agents to control the removal of non-coordinated water (dehydration) and enhance the degree of deprotonation of the ligands, thereby regulating the coordination and crystallization in aqueous solutions. In addition, another two new strategies for synthesizing CAU-17 by crystal reconstruction and one-step synthesis in binary solvents are provided, and the solvent-induced synthesis mechanism of CAU-17 is studied. The as-prepared CAU-17 presents a competitive iodine capture capability and effective delivery of the antiarrhythmic drug procainamide (PA) for enteropatia due to the broad pH tolerance and the unique phosphate-responsive destruction in the intestine. The findings will provide valuable ideas for the follow-up study of surfactant-assisted aqueous synthesis of MOFs and their potential applications.
PubMed: 38050936
DOI: 10.1002/smll.202307484 -
Journal of Chromatography. B,... Dec 2018Affinity chromatography on procainamide-Sepharose has been an important step in the purification of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) since...
Affinity chromatography on procainamide-Sepharose has been an important step in the purification of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) since its introduction in 1978. The procainamide affinity gel has limitations. In the present report a new affinity gel called Hupresin® was evaluated for its ability to purify truncated, recombinant human butyrylcholinesterase (rHuBChE) expressed in a stably transfected Chinese Hamster Ovary cell line. We present a detailed example of the purification of rHuBChE secreted into 3940 mL of serum-free culture medium. The starting material contained 13,163 units of BChE activity (20.9 mg). rHuBChE was purified to homogeneity in a single step by passage over 82 mL of Hupresin® eluted with 0.1 M tetramethylammonium bromide in 20 mM TrisCl pH 7.5. The fraction with the highest specific activity of 630 units/mg contained 11 mg of BChE. Hupresin® is superior to procainamide-Sepharose for purification of BChE, but is not suitable for purifying native AChE because Hupresin® binds AChE so tightly that AChE is not released with buffers, but is desorbed with denaturing solvents such as 50% acetonitrile or 1% trifluoroacetic acid. Procainamide-Sepharose will continue to be useful for purification of AChE.
Topics: Animals; Butyrylcholinesterase; CHO Cells; Cholinesterase Inhibitors; Chromatography, Affinity; Cricetinae; Cricetulus; Gels; Humans; Recombinant Proteins; Sepharose; Tacrine
PubMed: 30384187
DOI: 10.1016/j.jchromb.2018.10.026 -
Journal of Chromatography. A May 2023Organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BChE) can be applied to confirm exposure in humans. A sensitive method for generic detection of G-...
Generic detection of organophosphorus nerve agent adducts to butyrylcholinesterase in plasma using liquid chromatography-tandem mass spectrometry combined with an improved procainamide-gel separation and pepsin digestion method.
Organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BChE) can be applied to confirm exposure in humans. A sensitive method for generic detection of G- and V-series OPNA adducts to BChE in plasma was developed by combining an improved procainamide-gel separation (PGS) and pepsin digestion protocol with ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Residual matrix interferences from prior PGS purification of OPNA-BChE adducts from plasma were found to be a critical cause of significantly reduced UHPLC-MS/MS detection sensitivity. In our developed on-column PGS approach, the matrix interference was successfully removed by adding an appropriate concentration of NaCl to the washing buffer, and it could capture ≥92.5% of the BChE in plasma. The lower pH value and the longer digestion time in all previous pepsin digestion methods were found to be a key accelerated aging factor of several adducts such as tabun (GA)-, cyclohexylsarin (GF)-, and soman (GD)-BChE nonapeptide adducts, making them difficult to detect. The aging event of several OPNA-BChE nonapeptide adducts was so successfully addressed that the formic acid level in enzymatic buffer and digestion time were lowered to 0.05% (pH 2.67) and 0.5 h, respectively, and the post-digestion reaction was immediately terminated. The improved condition parameters were optimal for pepsin digestion of all types of OPNA-BChE adducts into their individual unaged nonapeptide adducts with the highest yields, expanding the applicability of the method. The method had a nearly one-fold decrease in sample preparation time through the reduction of digestion time and removal of ultrafiltration procedure after digestion. The limit of identification (LOI) were determined respectively as 0.13 ng mL, 0.28 ng mL, 0.50 ng mL, 0.41 ng mL and 0.91 ng mL for VX-, sarin (GB)-, GA-, GF-, and GD-exposed human plasma, being low exposure value compared to previously documented approaches. The approach was utilized to fully characterize the adducted (aged and unaged) BChE levels of five OPNAs in a series of their individual exposed concentration (1.00-400 nM) of plasma sample, and successfully detect OPNA exposure from all unknown plasma samples from OPCW's second and third biomedical proficiency tests. The OPNA-BChE adducts, their aged adducts, and unadducted BChE from OPNA-exposed plasma can simultaneously be measured using the method. The study provides a recommended diagnostic tool for generic verification of any OPNA exposure with high confidence by detecting its corresponding BChE adduct.
Topics: Humans; Aged; Nerve Agents; Butyrylcholinesterase; Tandem Mass Spectrometry; Procainamide; Pepsin A; Organophosphorus Compounds; Chromatography, Liquid; Digestion
PubMed: 37075496
DOI: 10.1016/j.chroma.2023.463990 -
Brazilian Journal of Medical and... 2023Procainamide (PA) and its in vivo metabolite, N-acetylprocainamide (NAPA), display some pharmacological differences. Although it is agreed that PA is a class IA...
Molecular basis of the different effects of procainamide and N-acetylprocainamide on the maximum upstroke velocity and half-decay time of the cardiac action potential in guinea pig papillary muscle.
Procainamide (PA) and its in vivo metabolite, N-acetylprocainamide (NAPA), display some pharmacological differences. Although it is agreed that PA is a class IA antiarrhythmic, it has been reported that NAPA is a pure class III antiarrhythmic that affects only the repolarizing phase of the cardiac action potential. This last concept, observed exclusively in dogs, gained wide acceptance, appearing in classic pharmacology textbooks. However, evidence in species such as mice and rats indicates that NAPA can affect cardiac Na+ channels, which is unexpected for a pure class III antiarrhythmic drug. To further clarify this issue, the effects of PA (used as a reference drug) and NAPA on the maximum upstroke velocity (Vmax) and half-decay time (HDT) of the cardiac action potential were examined in the isolated right papillaris magnus of the guinea pig heart. Both PA and NAPA affected Vmax at lower concentrations than required to affect HDT, and NAPA had weaker effects on both variables. Thus, NAPA displayed typical class IA antiarrhythmic behavior. Therefore, the concept that NAPA is a pure class III antiarrhythmic drug is more species-dependent than previously envisioned. In addition, we demonstrated that the differential pharmacology of PA and NAPA is explainable, in molecular terms, by steric hindrance of the effects of NAPA and the greater number of potent aromatic-aromatic and cation π interactions with Na+ or K+ cardiac channels for PA.
Topics: Guinea Pigs; Animals; Dogs; Mice; Rats; Procainamide; Acecainide; Papillary Muscles; Anti-Arrhythmia Agents; Action Potentials
PubMed: 36722655
DOI: 10.1590/1414-431X2023e12073 -
RSC Advances Mar 2023First-principle calculations were systematically carried out to explore the structural and electronic properties of the non-covalent interaction of procainamide (PA)...
Non-covalent interaction, adsorption characteristics and solvent effect of procainamide anti-arrhythmias drug on silver and gold loaded silica surfaces: SERS spectroscopy, density functional theory and molecular docking investigations.
First-principle calculations were systematically carried out to explore the structural and electronic properties of the non-covalent interaction of procainamide (PA) anti-arrhythmias drug molecules on silver-loaded and gold-loaded silica nanostructures. Computed adsorption energies presented a higher affinity of PA towards the Ag-SiO as compared with Au-SiO surfaces. The non-covalent interaction analysis revealed a weak van der Waals type of forces and hydrogen bonding, associated with a noticeable repulsive steric interaction. It was conceived that silver and gold decorated silica can be used for drug administration in biological systems due to the fact that their frontier molecular orbital energy levels were considerably altered upon absorption, decreasing the pertinent energy gaps. Moreover, the electronic spectra of PA⋯Ag-SiO and PA⋯Au-SiO structures investigated in different solvents display a notable blue shift, suggesting that noble metal-loaded silica can be effective in the context of drug delivery systems. Therefore, silver- and gold-decorated silica of three possible drug adsorption scenarios was fully analyzed to realize the associated bioactivity and drug likeness. Theoretical findings suggest that Ag- and Au-SiO nanocomposites can be considered potential drug delivery platforms for procainamide in medication protocols.
PubMed: 36968042
DOI: 10.1039/d3ra00514c -
JACC. Clinical Electrophysiology Feb 2019
Topics: Bundle-Branch Block; Flecainide; Humans; Procainamide; Syncope
PubMed: 30784694
DOI: 10.1016/j.jacep.2018.10.012