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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 -
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 -
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 -
Academic Emergency Medicine : Official... Sep 2019
PubMed: 31002448
DOI: 10.1111/acem.13767 -
Experimental Physiology May 2020What is the central question of this study? Can antiarrhythmic drug effects on repolarization, conduction time and excitation wavelength in premature beats be determined...
NEW FINDINGS
What is the central question of this study? Can antiarrhythmic drug effects on repolarization, conduction time and excitation wavelength in premature beats be determined by prior cardiac activation frequency? What is the main finding and its importance? In premature beats induced after a series of cardiac activations at a slow rate, antiarrhythmics prolong repolarization but evoke little or no conduction delay, thus increasing the excitation wavelength, which indicates an antiarrhythmic effect. Fast prior activation rate attenuates prolongation of repolarization, while amplifying the conduction delay induced by drugs, which translates into the reduced excitation wavelength, indicating proarrhythmia. These findings suggest that a sudden increase in heart rate can shape adverse pharmacological profiles in patients with ventricular ectopy.
ABSTRACT
Antiarrhythmic drugs used to treat atrial fibrillation can occasionally induce ventricular tachyarrhythmia, which is typically precipitated by a premature ectopic beat through a mechanism related, in part, to the shortening of the excitation wavelength (EW). The arrhythmia is likely to occur when a drug induces a reduction, rather than an increase, in the EW of ectopic beats. In this study, I examined whether the arrhythmic drug profile is shaped by the increased cardiac activation rate before ectopic excitation. Ventricular monophasic action potential durations, conduction times and EW values were assessed during programmed stimulations applied at long (S -S [basic drive cycle length] = 550 ms) and short (S -S = 200 ms) cycle lengths in perfused guinea-pig hearts. The premature activations were induced with extrastimulus application immediately upon termination of the refractory period. With dofetilide, a class III antiarrhythmic agent, a prolongation in action potential duration and the resulting increase in the EW obtained at S -S = 550 ms were significantly attenuated at S -S = 200 ms, in both the regular (S ) and the premature (S ) beats. With class I antiarrhythmic agents (quinidine, procainamide and flecainide), fast S -S pacing was found to attenuate the drug-induced increase in action potential duration, while amplifying drug-induced conduction slowing, in both S and S beats. As a result, although the EW was increased (quinidine and procainamide) or not changed (flecainide) at the long S -S intervals, it was invariably reduced by these agents at the short S -S intervals. These findings indicate that the increased heart rate before ectopic activation shapes the arrhythmic profiles by facilitating drug-induced EW reduction.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Cardiac Complexes, Premature; Electrophysiological Phenomena; Female; Flecainide; Guinea Pigs; Heart; Heart Rate; In Vitro Techniques; Phenethylamines; Procainamide; Quinidine; Sulfonamides
PubMed: 32175633
DOI: 10.1113/EP088165 -
Global Heart 2022Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the...
BACKGROUND
Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the underlying mechanisms are not very clear. Here, we aimed to examine whether proANP and its coding gene methylation were associated with CVD in the Chinese population.
METHODS
Serum proANP and peripheral blood DNA methylation of natriuretic peptide A gene () promoter was quantified at baseline for 2,498 community members (mean aged 53 years, 38% men) in the Gusu cohort. CVD events were obtained during 10 years of follow-up. A competing-risks survival regression model was applied to examine the prospective associations of proANP and promoter methylation with incident CVD.
RESULTS
During follow-up, 210 participants developed CVD events, 50 participants died from non-cardiovascular causes, and 214 participants were lost. Per 1-nmol/L increment of serum proANP was associated with a 22% (HR = 1.22, 95%CI: 1.03-1.44, = 0.025) higher risk of CVD during follow-up. Of the 9 CpG sites assayed, per 2-fold increment of DNA methylation at CpG3 (located at Chr1:11908299) was significantly associated with a half lower risk of CVD (HR = 0.50, 95%CI: 0.30-0.82, = 0.006). The gene-based analysis found that DNA methylation of the 9 CpGs at promoter as a whole was significantly associated with incident CVD ( < 0.05).
CONCLUSIONS
Increased proANP and hypomethylation at promoter at baseline predicted an increased future risk of CVD in Chinese adults. Aberrant DNA methylation of the gene may participate in the mechanisms of CVD.
Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; China; DNA Methylation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptides; Procainamide; Promoter Regions, Genetic
PubMed: 35586748
DOI: 10.5334/gh.1116 -
Materials Today. Bio Jan 2022Controlling the crystal size and surface chemistry of MOF materials, and understanding their multifunctional effect are of great significance for the biomedical...
Controlling the crystal size and surface chemistry of MOF materials, and understanding their multifunctional effect are of great significance for the biomedical applications of MOF systems. Herein, we designed and synthesized a new anionic MOF, ZJU-64-NSN, which features 1D channels decorated with highly polarized thiadiazole groups, and its crystal size could be systematically tuned from 200 μm to 300 nm through a green and simple approach. As a result, the optimal nanosized ZJU-64-NSN is found to enable an ultrafast loading of cationic drug procainamide (PA) (21.2 wt% within 1 min). Moreover, the undesirable chemical stability of PA@ZJU-64-NSN is greatly improved by the surface coating of polyethylene glycol (PEG) biopolymer. The final drug delivery system PEG/PA@ZJU-64-NSN is found to effectively prevent PA from premature release under the harsh stomach environments due to the intense host-guest interaction, and mainly release PA to the targeted intestinal surroundings. Such controlled drug delivery is proved to be triggered by endogenic Na ions instead of H ions, well revealed by the study on the dynamics behavior of drug release and UV-Vis absorption spectrum. Good biocompatibility of ZJU-64-NSN and PEG-coated ZJU-64-NSN has been fully demonstrated by MTT assay as well as confocal microscopy imaging.
PubMed: 34927044
DOI: 10.1016/j.mtbio.2021.100180