-
Diagnostics (Basel, Switzerland) Jan 2021Acquiring high-quality cardiac magnetic resonance (CMR) images in patients with frequent ventricular arrhythmias remains a challenge. We examined the safety and efficacy...
Acquiring high-quality cardiac magnetic resonance (CMR) images in patients with frequent ventricular arrhythmias remains a challenge. We examined the safety and efficacy of procainamide when administered on the scanner table prior to CMR scanning to suppress ventricular ectopy and acquire high-quality images. Fifty consecutive patients (age 53.0 [42.0-58.0]; 52% female, left ventricular ejection fraction 55 ± 9%) were scanned in a 1.5 T scanner using a standard cardiac protocol. Procainamide was administered at intermittent intravenous bolus doses of 50 mg every minute until suppression of the ectopics or a maximum dose of 10 mg/kg. The average dose of procainamide was 567 ± 197 mg. Procainamide successfully suppressed premature ventricular contractions (PVCs) in 82% of patients, resulting in high-quality images. The baseline blood pressure (BP) was mildly reduced (mean change systolic BP -12 ± 9 mmHg; diastolic BP -4 ± 9 mmHg), while the baseline heart rate (HR) remained relatively unchanged (mean HR change -1 ± 6 bpm). None of the patients developed proarrhythmic changes. Bolus intravenous administration of procainamide prior to CMR scanning is a safe and effective alternative approach for suppressing PVCs and acquiring high-quality images in patients with frequent PVCs and normal or only mildly reduced systolic function.
PubMed: 33513676
DOI: 10.3390/diagnostics11020178 -
Analytical Biochemistry Dec 2021Glycosylation is critical for many biological processes and biotherapeutic development. One of the most powerful approaches for analyzing released glycans is hydrophilic...
Glycosylation is critical for many biological processes and biotherapeutic development. One of the most powerful approaches for analyzing released glycans is hydrophilic interaction chromatography coupled with electrospray ionization mass spectrometry (HILIC-ESI-MS). The high sensitivity of MS is crucial for detecting low-abundance glycans and elucidating their structures. In this study, we presented a simple solution to boost MS response of procainamide (ProcA) labeled glycans for 2- to over 60-fold by including 1 mM glycine in ammonium formate mobile phases for HILIC-ESI-MS. The glycine additive increased charge states, enhanced ion intensities and signal-to-noise ratios, and improved tandem MS spectral quality of various N- and O-glycans without affecting chromatographic performance. Furthermore, more homogeneous ionization among different ProcA labeled glycans was achieved by using the glycine additive, resulting in more comparable quantitative results relative to fluorescence-based quantification. We demonstrated that ammonium formate caused ion suppression to ProcA labeled glycans, which were likely mitigated by glycine with enhanced ESI ionization. Overall, simple addition of glycine to mobile phases during HILIC-ESI-MS analysis significantly improves MS detection sensitivity and will facilitate future profiling and quantitation of glycans released from N- and O-glycoproteins.
Topics: Chromatography, High Pressure Liquid; Formates; Glycine; Humans; Hydrophobic and Hydrophilic Interactions; Polysaccharides; Procainamide; Spectrometry, Mass, Electrospray Ionization
PubMed: 34742721
DOI: 10.1016/j.ab.2021.114447 -
Journal of Pharmaceutical Analysis Mar 2023Sialylated -glycan isomers with α2-3 or α2-6 linkage(s) have distinctive roles in glycoproteins, but are difficult to distinguish. Wild-type (WT) and glycoengineered...
Sialylated -glycan isomers with α2-3 or α2-6 linkage(s) have distinctive roles in glycoproteins, but are difficult to distinguish. Wild-type (WT) and glycoengineered (mutant) therapeutic glycoproteins, cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4-Ig), were produced in Chinese hamster ovary cell lines; however, their linkage isomers have not been reported. In this study, -glycans of CTLA4-Igs were released, labeled with procainamide, and analyzed by liquid chromatography-tandem mass spectrometry (MS/MS) to identify and quantify sialylated -glycan linkage isomers. The linkage isomers were distinguished by comparison of 1) intensity of the -acetylglucosamine ion to the sialic acid ion (Ln/Nn) using different fragmentation stability in MS/MS spectra and 2) retention time-shift for a selective value in the extracted ion chromatogram. Each isomer was distinctively identified, and each quantity (>0.1%) was obtained relative to the total -glycans (100%) for all observed ionization states. Twenty sialylated -glycan isomers with only α2-3 linkage(s) in WT were identified, and each isomer's sum of quantities was 50.4%. Furthermore, 39 sialylated -glycan isomers (58.8%) in mono- (3 -glycans; 0.9%), bi- (18; 48.3%), tri- (14; 8.9%), and tetra- (4; 0.7%) antennary structures of mutant were obtained, which comprised mono- (15 -glycans; 25.4%), di- (15; 28.4%), tri- (8; 4.8%), and tetra- (1; 0.2%) sialylation, respectively, with only α2-3 (10 -glycans; 4.8%), both α2-3 and α2-6 (14; 18.4%), and only α2-6 (15; 35.6%) linkage(s). These results are consistent with those for α2-3 neuraminidase-treated -glycans. This study generated a novel plot of Ln/Nn versus retention time to distinguish sialylated -glycan linkage isomers in glycoprotein.
PubMed: 37102108
DOI: 10.1016/j.jpha.2023.01.001 -
Journal of Alzheimer's Disease : JAD 2021Memantine, an NMDA receptor antagonist, is used for the treatment of Alzheimer's disease. There is a caution to refrain from administrating memantine in combination with...
Safety of Memantine in Combination with Potentially Interactive Drugs in the Real World: A Pharmacovigilance Study Using the Japanese Adverse Drug Event Report (JADER) Database.
BACKGROUND
Memantine, an NMDA receptor antagonist, is used for the treatment of Alzheimer's disease. There is a caution to refrain from administrating memantine in combination with some specific drugs such as amantadine or dextromethorphan due to potential interactions that might augment the adverse effects of memantine.
OBJECTIVE
This notification has not been validated in real-world data, which we aim to address using a large self-reporting database from Japan.
METHODS
We conducted a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database reported between April 2004 and March 2019 for detecting the neuropsychiatric adverse event (AE) signals associated with memantine and other potentially interactive drugs including amantadine, dextromethorphan, cimetidine, ranitidine, procainamide, quinidine, acetazolamide, citrate, and bicarbonate. Drug-drug interactions between memantine and these drugs were assessed using multiplicative and additive models.
RESULTS
There was no statistically robust evidence to support multiplicative or additive interactions between memantine and the aforementioned drugs to increase the reporting of any included neuropsychiatric AEs or AE categories.
CONCLUSION
The real-world JADER data did not raise the concern about the interactive increase in the neuropsychiatric AEs in patients with dementia taking memantine in combination with amantadine or dextromethorphan, suggesting there may be no urgent need to prohibit the co-administration of these drugs presently.
Topics: Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Alzheimer Disease; Databases, Factual; Drug Interactions; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Excitatory Amino Acid Antagonists; Female; Humans; Japan; Male; Memantine; Pharmacovigilance; Retrospective Studies
PubMed: 34151816
DOI: 10.3233/JAD-210524 -
International Journal of Biological... Jun 2024This work presents a magnetic purification method of human erythrocyte Acetylcholinesterase (EC 3.1.1.7; AChE) based on affinity binding to procainamide (Proca) as...
This work presents a magnetic purification method of human erythrocyte Acetylcholinesterase (EC 3.1.1.7; AChE) based on affinity binding to procainamide (Proca) as ligand. Acetylcholinesterase is an acetylcholine-regulating enzyme found in different areas of the body and associated with various neurological disorders, such as Parkinson, Alzheymer and Amyotrophic Lateral Sclerosis. AChE from human erythrocyte purification has been attempted in recent years with low degree of purity. Here, magnetic nanoparticles (MNP) were synthesized and coated with polyaniline (PANI) and procainamide (PROCA) was covalently linked to the PANI. The extracted human erythrocyte AChE formed a complex with the MNP@PANI-PROCA and an external magnet separated it from the undesired proteins. Finally, the enzyme was collected by increasing the ionic strength. Experimental Box-Behnken design was developed to optimize this process of human erythrocyte AChE purification protocol. The enzyme was purified in all fifteen experiments. However, the best AChE purification result was achieved, about 2000 times purified, when 100 mg of MNP@PANI-PROCA was incubated for one hour with 4 ml hemolysate extract. The SDS-PAGE of this preparation presented a molecular weight of approximately 70 kDa, corroborating with few previous studies of AChE from erythrocyte purification.
Topics: Humans; Acetylcholinesterase; Erythrocytes; Magnetite Nanoparticles; Procainamide; Aniline Compounds
PubMed: 38705318
DOI: 10.1016/j.ijbiomac.2024.132094 -
Life (Basel, Switzerland) Jan 2021The identification of patients with different brain tumors is solely built on imaging diagnostics, indicating the need for novel methods to facilitate disease...
The identification of patients with different brain tumors is solely built on imaging diagnostics, indicating the need for novel methods to facilitate disease recognition. Glycosylation is a chemical modification of proteins, reportedly altered in several inflammatory and malignant diseases, providing a potential alternative route for disease detection. In this paper, we report the quantitative analysis of serum N-glycosylation of patients diagnosed with primary and metastatic brain tumors. PNGase-F-digested and procainamide-labeled serum glycans were purified by magnetic nanoparticles, followed by quantitative liquid chromatographic analysis. The glycan structures were identified by the combination of single quad mass spectrometric detection and exoglycosidase digestions. Linear discriminant analysis provided a clear separation of different disease groups and healthy controls based on their N-glycome pattern. Altered distribution of biantennary neutral, sialylated but nonfucosylated, and sialylated-fucosylated structures were found to be the most significant changes. Our results demonstrate that serum glycosylation monitoring could improve the detection of malignancy.
PubMed: 33418875
DOI: 10.3390/life11010029 -
Annals of Medicine and Surgery (2012) Oct 2023Aluminum phosphide (ALP) is a commonly used suicidal agent in an agrarian country like Nepal. The unmasking of the Brugada pattern in the electrocardiogram (ECG)...
INTRODUCTION AND IMPORTANCE
Aluminum phosphide (ALP) is a commonly used suicidal agent in an agrarian country like Nepal. The unmasking of the Brugada pattern in the electrocardiogram (ECG) associated with ALP poisoning is a rare phenomenon, and studies pertaining to it are scarce in the medical literature.
CASE PRESENTATION
An 18-year-old female presented to the emergency department with multiple episodes of vomiting, headache, blurring of vision, and abdominal pain after 4 h of consumption of ALP with suicidal intent. A 12-lead ECG revealed a coved ST-segment elevation and T-wave inversion in leads V1-V3 with right bundle branch block suggestive of a type 1 Brugada pattern. Her past medical and family history was not significant. The patient made an uneventful recovery with the required supportive treatments.
CLINICAL DISCUSSION
Cardiac arrhythmias are the major cause of death in ALP poisoning. Unmasking of the Brugada ECG pattern is a rare but potentially fatal complication implicated in various pharmacological toxicities, including tricyclic antidepressants, cocaine, procainamide, disopyramide, flecainide, and rarely with ALP.
CONCLUSIONS
ALP poisoning can unmask the Brugada ECG pattern, which can lead to ventricular fibrillation and/or sudden cardiac death.
PubMed: 37811028
DOI: 10.1097/MS9.0000000000001129 -
Obesity Facts 2022Atrial natriuretic peptide plays a potential role in obesity with unclear molecular mechanisms. The objective of this study was to examine the association between its...
INTRODUCTION
Atrial natriuretic peptide plays a potential role in obesity with unclear molecular mechanisms. The objective of this study was to examine the association between its coding gene (natriuretic peptide A [NPPA]) methylation and obesity.
METHODS
Peripheral blood DNA methylation of NPPA promoter was quantified at baseline by targeted bisulfite sequencing for 2,497 community members (mean aged 53 years, 38% men) in the Gusu cohort. Obesity was repeatedly assessed by body mass index (BMI) and waist circumference (WC) at baseline and follow-up examinations. The cross-sectional, longitudinal, and prospective associations between NPPA promoter methylation and obesity were examined.
RESULTS
Of the 9 CpG loci assayed, DNA methylation levels at 6 CpGs were significantly lower in participants with central obesity than those without (all p < 0.05 for permutation test). These CpG methylation levels at baseline were also inversely associated with dynamic changes in BMI or WC during follow-up (all p < 0.05 for permutation test). After an average 4 years of follow-up, hypermethylation at the 6 CpGs (CpG2 located at Chr1:11908348, CpG3 located at Chr1:11908299, CpG4 located at Chr1:11908200, CpG5 located at Chr1:11908182, CpG6 located at Chr1:11908178, and CpG8 located at Chr1:11908165) was significantly associated with a lower risk of incident central obesity (all p < 0.05 for permutation test).
CONCLUSIONS
Hypomethylation at NPPA promoter was associated with increased future risk of central obesity in Chinese adults. Aberrant DNA methylation of the NPPA gene may participate in the mechanisms of central obesity.
Topics: Atrial Natriuretic Factor; Body Mass Index; China; Cross-Sectional Studies; DNA Methylation; Female; Humans; Longitudinal Studies; Male; Middle Aged; Obesity; Obesity, Abdominal; Procainamide
PubMed: 34875662
DOI: 10.1159/000521295 -
Turkish Journal of Chemistry 2022Glycosylation is an essential posttranslational modification observed in the living proteome. Glycosylation profiles in glycoproteins can change in commonly observed...
Glycosylation is an essential posttranslational modification observed in the living proteome. Glycosylation profiles in glycoproteins can change in commonly observed diseases such as cancer. Identifying these changes is crucial in discovering new biomarkers for the early diagnosis of cancer. One of the main steps of -glycan analysis is to release -glycans from glycoproteins by specific enzymes. The study compares common denaturing agent combinations used in -glycan release methods. In the study, human plasma was used to test the release methods of -glycans containing different detergent combinations. The released -glycans were labeled with the procainamide tag, purified using cellulose-containing solid-phase extraction cartridges, and analyzed by high-performance liquid chromatography-hydrophilic interaction liquid chromatography equipped with fluorescence detection (HPLC-HILIC-FLD). The results showed that the sodium dodecyl sulfate and sodium deoxycholate (SDS + SDC) detergent combination provided the highest average FLD signal areas and intensities in the -glycan analysis. The protocol with SDS resulted in more reproducible average FLD signal areas and intensities. It was also found that the average signal FLD signal areas and intensities of the detected -glycans were reduced when SDS and SDC were used with 1,4-dithiothreitol (DTT) reducing agents. In addition, deglycosylation of glycoproteins with various denaturing agents resulted in relatively minor variation in human plasma -glycosylation profiles.
PubMed: 37529735
DOI: 10.55730/1300-0527.3457 -
Cells Feb 2022Plasma concentrations of natriuretic peptides (NP) contribute to risk stratification and management of patients undergoing non-cardiac surgery. However, genetically...
Plasma concentrations of natriuretic peptides (NP) contribute to risk stratification and management of patients undergoing non-cardiac surgery. However, genetically determined variability in the levels of these biomarkers has been described previously. In the perioperative setting, genetic contribution to NP plasma level variability has not yet been determined. A cohort of 427 patients presenting for non-cardiac surgery was genotyped for single-nucleotide polymorphisms (SNPs) from the NPPA/NPPB locus. Haplotype population frequencies were estimated and adjusted haplotype trait associations for brain natriuretic peptide (BNP) and amino-terminal pro natriuretic peptide (NT-proBNP) were calculated. Five SNPs were included in the analysis. Compared to the reference haplotype TATAT (rs198358, rs5068, rs632793, rs198389, rs6676300), haplotype CACGC, with an estimated frequency of 4%, showed elevated BNP and NT-proBNP plasma concentrations by 44% and 94%, respectively. Haplotype CGCGC, with an estimated frequency of 9%, lowered NT-proBNP concentrations by 28%. ASA classification status III and IV, as well as coronary artery disease, were the strongest predictors of increased NP plasma levels. Inclusion of genetic information might improve perioperative risk stratification of patients based on adjusted thresholds of NP plasma levels.
Topics: Atrial Natriuretic Factor; Coronary Artery Disease; Haplotypes; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Nitrobenzoates; Peptide Fragments; Procainamide
PubMed: 35269388
DOI: 10.3390/cells11050766