scholarly journals Polymorphisms of Genes Related to Phase-II Metabolism and the Resistance of Clopidogrel

2021 ◽  
Author(s):  
Abdullah Alkattan ◽  
Ahmed alkhalifah ◽  
Eman Alsalameen ◽  
Fatimah Alghanim ◽  
Nashwa Radwan
Keyword(s):  
Phase Ii ◽  
Cardiovascular Events ◽  
Glutathione S Transferase ◽  
Sulfenic Acid ◽  
Glutathione Conjugate ◽  
Phase Ii Metabolism ◽  
Clopidogrel Resistance ◽  
Inactive Metabolite ◽  
Near Future ◽  
The Relationship

Clopidogrel is one of the thienopyridine antiplatelet drugs commonly used as a prophylactic medication to prevent coagulation in vessels and cardiovascular events. The molecule of clopidogrel is metabolized in the liver via phase-I and phase-II metabolism pathways. The sulfenic acid clopidogrel metabolite undergoes phase-II metabolism through conjugation with glutathione by the glutathione-s-transferase (GST) to form a glutathione conjugate of clopidogrel (inactive metabolite). A glutaredoxin enzyme removes the glutathione conjugated with clopidogrel to form cis-thiol-clopidogrel. This review focused on the polymorphisms of genes related to phase-II metabolism during the clopidogrel bioactivation process. Overall, no well-controlled studies were done about the relationship between the clopidogrel bioactivation process and genes related to phase-II metabolism’s enzymes. Nevertheless, some polymorphisms of G6PD, GCLC, GCLM, GSS, GST, GSR, HK, and GLRX genes could be responsible for clopidogrel resistance due to low glutathione conjugate or glutaredoxin plasma levels. Studies needed to be concerned with the relationship between clopidogrel resistance and phase-II metabolism issues in the near future.

scholarly journals A Comparative Assessment of the Chronic Effects of Micro- and Nano-Plastics on the Physiology of the Mediterranean Mussel Mytilus galloprovincialis

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 649
Author(s):  
Marco Capolupo ◽  
Paola Valbonesi ◽  
Elena Fabbri
Keyword(s):  
Mytilus Galloprovincialis ◽  
Acetylcholinesterase Activity ◽  
Particle Sizes ◽  
Glutathione S Transferase ◽  
Phase Ii Metabolism ◽  
Chronic Effects ◽  
Mediterranean Mussel ◽  
Metabolism Enzyme ◽  
The Mediterranean

The ocean contamination caused by micro- and nano-sized plastics is a matter of increasing concern regarding their potential effects on marine organisms. This study compared the effects of a 21-day exposure to 1.5, 15, and 150 ng/L of polystyrene microplastics (PS-MP, 3-µm) and nanoplastics (PS-NP, 50-nm) on a suite of biomarkers measured in the Mediterranean mussel Mytilus galloprovincialis. Endpoints encompassed immunological/lysosomal responses, oxidative stress/detoxification parameters, and neurotoxicological markers. Compared to PS-MP, PS-NP induced higher effects on lysosomal parameters of general stress. Exposures to both particle sizes increased lipid peroxidation and catalase activity in gills; PS-NP elicited greater effects on the phase-II metabolism enzyme glutathione S-transferase and on lysozyme activity, while only PS-MP inhibited the hemocyte phagocytosis, suggesting a major role of PS particle size in modulating immunological/detoxification pathways. A decreased acetylcholinesterase activity was induced by PS-NP, indicating their potential to impair neurological functions in mussels. Biomarker data integration in the Mussel Expert System identified an overall greater health status alteration in mussels exposed to PS-NP compared to PS-MP. This study shows that increasing concentrations of nanoplastics may induce higher effects than microplastics on the mussel’s lysosomal, metabolic, and neurological functions, eventually resulting in a greater impact on their overall fitness.

scholarly journals Metabolism of anabolic androgenic steroids

1996 ◽  
Vol 42 (7) ◽  
pp. 1001-1020 ◽  
Author(s):  
W Schänzer
Keyword(s):  
Phase I ◽  
Physical Performance ◽  
Phase Ii ◽  
Anabolic Androgenic Steroids ◽  
Phase Ii Metabolism ◽  
Steroid Molecule ◽  
High Extent ◽  
As Doping ◽  
General Metabolism ◽  
Androgenic Steroids

Abstract Anabolic androgenic steroids (AAS) are misused to a high extent in sports by athletes to improve their physical performance. Sports federations consider the use of these drugs in sports as doping. The misuse of AAS is controlled by detection of the parent AAS (when excreted into urine) and (or) their metabolites in urine of athletes. I present a review of the metabolism of AAS. Testosterone is the principal androgenic steroid and its metabolism is compared with that of AAS. The review is divided into two parts: the general metabolism of AAS, which is separated into phase I and phase II metabolism and includes a systematic discussion of metabolic changes in the steroid molecule according to the regions (A-D rings), and the specific metabolism of AAS, which presents the metabolism of 26 AAS in humans.

Abstract W P156: Arterial Stiffness in Older Adults With and Without Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Ada Tang ◽  
Daria Shkredova ◽  
Derek W Stouth ◽  
Maureen J MacDonald ◽  
Jennifer J Heisz
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Arterial Stiffness ◽  
Cardiovascular Events ◽  
Pulse Transit Time ◽  
Group Differences ◽  
Ongoing Work ◽  
Increased Risk ◽  
Stroke Group ◽  
The Relationship

Introduction: Silent cerebrovascular infarcts resulting from vascular disease can manifest as a decline in cognitive function. These silent events are also associated with increased risk of clinically overt stroke. Arterial stiffness is a marker that represents atherosclerotic progression and is a predictor of cardiovascular events and mortality. This study examined the relationship between arterial stiffness and cognitive impairment between adults aged 50-80 years old with and without stroke. Hypothesis: We hypothesized that elevated arterial stiffness would be observed in individuals with stroke, and also be associated with increased cognitive impairment across all participants. Methods: Cognition was assessed using the Montreal Cognitive Assessment (MoCA). Arterial stiffness was quantified using carotid-femoral pulse wave velocity (cfPWV, in m/s), calculated as cfPWV=D/Δt, where D was the distance measured between arterial sites and Δt was the pulse transit time. Higher values represent increased stiffness, and values >10 m/s are associated with increased risk for cardiovascular events. Results: Twenty-five participants were assessed: 11 participants 4.7±2.4 years post-stroke and 14 older adults without stroke. The non-stroke group was older (73.1±3.9 vs. 65.2±9.4 years, P=0.009), while the stroke group had lower MoCA scores (21.2±3.2 vs. 24.4±2.8, P=0.01). There were no between-group differences in cfPWV (stroke 9.4 m/s vs. older adults 9.9 m/s, P=0.49), when controlling for age and MoCA scores. In backward regression analysis, age explained 21% of the variance of cfPWV (P=0.03), while MoCA was not a contributor. Conclusions: In conclusion, these results suggest that age is a significant correlate of arterial stiffness, regardless of the presence of stroke or cognitive impairment. Ongoing work will examine whether stroke history also contributes to arterial stiffness when groups are matched for age.

The roles of immune cells in atherosclerotic calcification

Vascular ◽  
2021 ◽  
pp. 170853812110327
Author(s):  
Jingsong Cao ◽  
Xuyu Zu ◽  
Jianghua Liu
Keyword(s):  
B Cells ◽  
Immune Cells ◽  
Cardiovascular Events ◽  
Th2 Cells ◽  
Regulatory B Cells ◽  
T Helper ◽  
Relationship Of ◽  
The Relationship ◽  
Helper Type

Atherosclerosis is the leading cause of acute cardiovascular events, and vascular calcification is an important pathological phenomenon in atherosclerosis. Recently, many studies have shown that immune cells are closely associated with the development of atherosclerosis and calcification, but there are many conflicting viewpoints because of immune system complications, such as the pro-atherosclerotic and atheroprotective effects of regulatory B cells (Bregs), T helper type 2 (Th2) cells and T helper type 17 (Th17) cells. In this review, we summarize the studies on the roles of immune cells, especially lymphocytes and macrophages, in atherosclerotic calcification. Furthermore, we prepared graphs showing the relationship between T cells, B cells and macrophages and atherosclerotic calcification. Finally, we highlight some potential issues that are closely associated with the function of immune cells in atherosclerotic calcification. Based on current research results, this review summarizes the relationship between immune cells and atherosclerotic calcification, and it will be beneficial to understand the relationship of immune cells and atherosclerotic calcification.

Abstract 6277: Predictive Value of Estimated Glomerular Filtration Rate for Cardiovascular Events: The Treating to New Targets Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
James Shepherd ◽  
Chuan-Chuan Wun ◽  
Daniel J Wilson ◽  
Andrea L Zuckerman
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Cardiovascular Events ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Lipid Lowering ◽  
Final Visit ◽  
The Relationship ◽  
Dose Dependent

We previously demonstrated a dose-dependent improvement in renal function and reduction in cardiovascular risk in TNT with intensive lipid lowering with atorvastatin (ATV) 80 mg vs 10 mg. This post hoc analysis examines the relationship between the observed improvement in estimated glomerular filtration rate (eGFR) and reduction of major cardiovascular events (MCVE). After 8 weeks open-label therapy with ATV 10 mg, 10,001 patients with CHD were randomized to double-blind therapy with either ATV 10 or 80 mg. Patients were followed for a median of 4.9 years for the occurrence of MCVEs (CHD death, nonfatal MI, and stroke). The relationship between change from baseline eGFR (using the MDRD equation) at the final visit prior to a MCVE and the risk of MCVE was assessed using a Cox proportional hazards model adjusting for baseline eGFR and other baseline characteristics. Of 9656 patients with complete renal data, 156 had a MCVE before follow-up eGFR assessment and were excluded. In the remaining 9500 patients, mean baseline eGFR was 65.3 mL/min/1.73 m 2 and mean change from baseline was 4.3 mL/min/1.73 m 2 . This represented a reduction in the risk of MCVE of 2.7% per mL increase in eGFR (HR 0.973, 95% CI 0.967– 0.980, P <0.0001). This association remained significant in patients with eGFR <60 and those with eGFR ≥60 mL/min/1.73 m 2 at baseline, with no significant interaction between eGFR change and baseline renal status ( P =0.98). A 5 mL/min on-treatment improvement in eGFR was associated with a 12.6% reduction in MCVE, while a 5 mL/min reduction was associated with a 14.4% increase in MCVE. Mean change from baseline eGFR was 3.5 mL/min/1.73 m 2 with ATV 10 mg and 5.2 mL/min/1.73 m 2 with ATV 80 mg, representing significant 9.3% and 12.4% reductions in risk, respectively. Analysis of interaction between treatment and eGFR change for prediction of MCVE demonstrated a stronger association between eGFR change and MCVE in the ATV 80 mg treatment group ( P =0.011). Improvement in eGFR was highly associated with a reduction in MCVE, irrespective of baseline renal function. This relationship was dose dependent. Improvement in eGFR may be a biomarker for the response to atorvastatin, and for the stabilization of atherosclerotic cardiovascular disease.

scholarly journals Seasonal changes in oxidative stress biomarkers of the snail Viviparus acerosus from the Velika Morava River, Serbia

2012 ◽  
Vol 64 (3) ◽  
pp. 953-962 ◽  
Author(s):  
Svetlana Despotovic ◽  
Branka Perendija ◽  
Jelena Gavric ◽  
Slavica Borkovic-Mitic ◽  
M.M. Paunovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Phase Ii ◽  
Seasonal Changes ◽  
Important Variable ◽  
Whole Body ◽  
Glutathione S Transferase ◽  
Total Glutathione ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Morava River

The river snail (Viviparus acerosus) from the Velika Morava River, Serbia was chosen in our study in order to determine seasonal changes in oxidative stress biomarkers between July (summer) and September (autumn). The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and the phase II biotransformation enzyme glutathione-S-transferase (GST), as well as the concentration of total glutathione (GSH), were examined in the whole body of the river snails. The obtained results show significantly higher activities of CAT, GSH-Px, GR and biotransformation phase II enzyme GST in September compared to July, while the GSH concentration was lower. There was no general trend in the seasonal changes in the activity of SOD. The presented data show that animals in their natural environment are exposed to constant fluctuations of environmental conditions that could cause antioxidants to exhibit seasonal variations. This fact should be considered as an important variable in the interpretation of results in biomonitoring studies.

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