scholarly journals Monoamine Oxidase and Semicarbazide-Sensitive Amine Oxidase Kinetic Analysis in Mesenteric Arteries of Patients With Type 2 Diabetes

2011 ◽  
pp. 309-315 ◽  
Author(s):  
S. F. NUNES ◽  
I. V. FIGUEIREDO ◽  
J. S. PEREIRA ◽  
E. T. DE LEMOS ◽  
F. REIS ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Monoamine Oxidase ◽  
Kinetic Parameters ◽  
Amine Oxidase ◽  
Mesenteric Arteries ◽  
Patient Age ◽  
Mao B ◽  
Mao A ◽  
Type 2 Diabetic

Monoamine oxidase (MAO, type A and B) and semicarbazide-sensitive amine oxidase (SSAO) metabolize biogenic amines, however, the impact of these enzymes in arteries from patients with type 2 diabetes remains poorly understood. We investigated the kinetic parameters of the enzymes to establish putative correlations with noradrenaline (NA) content and patient age in human mesenteric arteries from type 2 diabetic patients. The kinetic parameters were evaluated by radiochemical assay and NA content by high-performance liquid chromatography (HPLC). The activity of MAO-A and SSAO in type 2 diabetic vascular tissues was significantly lower compared to the activity obtained in non-diabetic tissues. In the correlation between MAO-A (Km) and NA content, we found a positive correlation for both the diabetic and non-diabetic group, but no correlation was established for patient age. In both groups, MAO-B (Vmax) showed a negative correlation with age. The results show that MAO-A and SSAO activities and NA content of type 2 diabetic tissues are lower compared to the non-diabetic tissues, while MAO-B activity remained unchanged. These remarks suggest that MAO-A and SSAO may play an important role in vascular tissue as well as in the vascular pathophysiology of type 2 diabetes.

Blockade of Renin Angiotensin System Ameliorates the Cardiac Arrhythmias and Sympathetic Neural Remodeling in Hearts of Type 2 DM Rat Model

2020 ◽  
Vol 20 (3) ◽  
pp. 464-478 ◽  
Author(s):  
Yomna M. Yehya ◽  
Abdelaziz M. Hussein ◽  
Khaled Ezam ◽  
Elsayed A. Eid ◽  
Eman M. Ibrahim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiac Arrhythmias ◽  
Sympathetic Nerve ◽  
Renin Angiotensin System ◽  
Diabetic Rats ◽  
Angiotensin System ◽  
Type 2 Dm ◽  
Type 2 Diabetic ◽  
Diabetes Induction

Objectives:: The present study was designed to investigate the effects of renin angiotensin system (RAS) blockade on cardiac arrhythmias and sympathetic nerve remodelling in heart tissues of type 2 diabetic rats. Methods:: Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group: normal rats, b) DM group; after type 2 diabetes induction, rats received 2ml oral saline daily for 4 weeks, c) DM+ ACEi: after type 2 diabetes induction, rats were treated with enalapril (10 mg/kg, orally for 4 weeks) and d) DM+ ARBs: after type 2 diabetes induction, rats were treated with losartan (30 mg/kg, orally for 4 weeks). Results:: In type 2 diabetic rats, the results demonstrated significant prolongation in Q-T interval and elevation of blood sugar, HOMA-IR index, TC, TGs, LDL, serum CK-MB, myocardial damage, myocardial MDA, myocardial norepinephrine and tyrosine hydroxylase (TH) density with significant reduction in serum HDL, serum insulin and myocardial GSH and CAT. On the other hand, blockade of RAS at the level of either ACE by enalapril or angiotensin (Ag) receptors by losartan resulted in significant improvement in ECG parameters (Q-T), cardiac enzymes (CK-MB), cardiac morphology, myocardial oxidative stress (low MDA, high CAT and GSH) and myocardial TH density. Conclusions:: RAS plays a role in the cardiac sympathetic nerve sprouting and cardiac arrhythmias induced by type 2 DM and its blockade might have a cardioprotective effect via attenuation of sympathetic nerve fibres remodelling, myocardial norepinephrine contents and oxidative stress.

scholarly journals Inhibition of Butyrylcholinesterase and Human Monoamine Oxidase-B by the Coumarin Glycyrol and Liquiritigenin Isolated from Glycyrrhiza uralensis

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3896
Author(s):  
Geum Seok Jeong ◽  
Myung-Gyun Kang ◽  
Joon Yeop Lee ◽  
Sang Ryong Lee ◽  
Daeui Park ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Binding Affinity ◽  
Competitive Inhibitor ◽  
Glycyrrhiza Uralensis ◽  
Form Hydrogen Bond ◽  
Docking Simulations ◽  
Mao B ◽  
Mao A ◽  
Ic50 Values ◽  
Noncompetitive Inhibitor

Eight compounds were isolated from the roots of Glycyrrhiza uralensis and tested for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activities. The coumarin glycyrol (GC) effectively inhibited butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) with IC50 values of 7.22 and 14.77 µM, respectively, and also moderately inhibited MAO-B (29.48 µM). Six of the other seven compounds only weakly inhibited AChE and BChE, whereas liquiritin apioside moderately inhibited AChE (IC50 = 36.68 µM). Liquiritigenin (LG) potently inhibited MAO-B (IC50 = 0.098 µM) and MAO-A (IC50 = 0.27 µM), and liquiritin, a glycoside of LG, weakly inhibited MAO-B (>40 µM). GC was a reversible, noncompetitive inhibitor of BChE with a Ki value of 4.47 µM, and LG was a reversible competitive inhibitor of MAO-B with a Ki value of 0.024 µM. Docking simulations showed that the binding affinity of GC for BChE (−7.8 kcal/mol) was greater than its affinity for AChE (−7.1 kcal/mol), and suggested that GC interacted with BChE at Thr284 and Val288 by hydrogen bonds (distances: 2.42 and 1.92 Å, respectively) beyond the ligand binding site of BChE, but that GC did not form hydrogen bond with AChE. The binding affinity of LG for MAO-B (−8.8 kcal/mol) was greater than its affinity for MAO-A (−7.9 kcal/mol). These findings suggest GC and LG should be considered promising compounds for the treatment of Alzheimer’s disease with multi-targeting activities.

scholarly journals Risk stratification score for acute myocardial infarction and sudden cardiac death in type 2 diabetes mellitus

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
S Lee ◽  
J Zhou ◽  
CL Guo ◽  
WKK Wu ◽  
WT Wong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cardiac Death ◽  
Adverse Outcomes ◽  
Risk Scores ◽  
Diabetic Patients ◽  
Type 2 Diabetic

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Acute myocardial infarction (AMI) and sudden cardiac death (SCD) are major cardiovascular adverse outcomes in patients with type 2 diabetic mellitus. Although there are many risk scores on composite outcomes of major cardiovascular adverse outcomes or cardiovascular mortality for diabetic patients, these existing scores did not account for the difference in pathogenesis and prognosis between acute coronary syndrome and lethal ventricular arrhythmias. Furthermore, recent studies reported that HbA1c and lipid levels, which were often accounted for in these risk scores, have J/U-shaped relationships with adverse outcomes. Purpose The present study aims to evaluate the application of incorporating non-linear J/U-shaped relationships between mean HbA1c and cholesterol levels into risk scores for predicting for AMI and non-AMI related SCD respectively, amongst type 2 diabetes mellitus patients. Methods This was a territory-wide cohort study of patients with type 2 diabetes mellitus above the age 40 and free from prior AMI and SCD, with or without prescriptions of anti-diabetic agents between January 1st, 2009 to December 31st, 2009 at government-funded hospitals and clinics in Hong Kong. Risk scores were developed for predicting incident AMI and non-AMI related SCD. The performance of conditional inference survival forest (CISF) model compared to that of random survival forests (RSF) model and multivariate Cox model. Results This study included 261308 patients (age = 66.0 ± 11.8 years old, male = 47.6%, follow-up duration = 3552 ± 1201 days, diabetes duration = 4.77 ± 2.29 years). Mean HbA1c and high-density lipoprotein-cholesterol (HDL-C) were significant predictors of AMI under multivariate Cox regression and were linearly associated with AMI. Mean HbA1c and total cholesterol were significant multivariate predictors with a J-shaped relationship with non-AMI related SCD. The AMI and SCD risk scores had an area-under-the-curve (AUC) of 0.666 (95% confidence interval (CI)= [0.662, 0.669]) and 0.677 (95% CI= [0.673, 0.682]), respectively. CISF significantly improves prediction performance of both outcomes compared to RSF and multivariate Cox models. Conclusions A holistic combination of demographic, clinical, and laboratory indices can be used for the risk stratification of type 2 diabetic patients against AMI and SCD.

Development of Monoamine Oxidase and Aldehyde Dehydrogenase in Reaggregating Cultures of Fetal Rat Brain Cells

1989 ◽  
Vol 16 (3) ◽  
pp. 281-286
Author(s):  
Olof Tottmar ◽  
Maria Söderbäck ◽  
Anders Aspberg
Keyword(s):  
Monoamine Oxidase ◽  
Rat Brain ◽  
Aldehyde Dehydrogenase ◽  
Brain Cells ◽  
Mao B ◽  
Adult Rat ◽  
Fetal Rat ◽  
Adult Rat Brain ◽  
Mao A ◽  
Fetal Rat Brain

The development of monoamine oxidase (MAO) and aldehyde dehydrogenase (ALDH) in reaggregation cultures of fetal rat brain cells was compared with that of enzymatic markers for glial and neuronal cells. Only MAO-A was detected in the cultures during the first week, but, during the following three weeks, the activity of MAO-B increased more rapidly than that of MAO-A. The ratio MAO-A/MAO-B in four-week aggregates was close to that found in the adult rat brain. The activity of ALDH started to increase rapidly after 15 days, and the developmental pattern was intermediate to those of the glial and neuronal markers. The activity after four weeks was close to that found in the adult rat brain. Epidermal growth factor (EGF) caused a slight decrease in the activities of the low-Km ALDH (after four weeks) and the neuronal marker, choline acetyltransferase (after two weeks), whereas the other markers were not affected. By contrast, the activities of MAO-A and MAO-B were greatly increased during almost the entire culture period. It is suggested that this effect of EGF was the result of increased mitotic activity and/or biochemical differentiation of other cell types present in the cell aggregates, e.g. capillary endothelial cells.

scholarly journals In Vitro,In Vivo, and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

2013 ◽  
Vol 57 (7) ◽  
pp. 3060-3066 ◽  
Author(s):  
S. Flanagan ◽  
K. Bartizal ◽  
S. L. Minassian ◽  
E. Fang ◽  
P. Prokocimer
Keyword(s):  
Blood Pressure ◽  
Monoamine Oxidase ◽  
Clinical Research ◽  
Systolic Blood Pressure ◽  
Clinical Studies ◽  
Geometric Mean ◽  
Interaction Study ◽  
Mao B ◽  
Mao A

ABSTRACTTedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions.In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-Bin vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered atwww.clinicaltrials.govas NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).

scholarly journals Spontaneous Type 2 Diabetic Rodent Models

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang-wei Wang ◽  
Guang-dong Sun ◽  
Jing Sun ◽  
Shu-jun Liu ◽  
Ji Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Health Care ◽  
Animal Models ◽  
Rodent Models ◽  
Advantages And Disadvantages ◽  
Characteristic Features ◽  
Type 2 Diabetic

Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes.

scholarly journals Impact of a Booklet about Diabetes Genetic Susceptibility and Its Prevention on Attitudes towards Prevention and Perceived Behavioral Change in Patients with Type 2 Diabetes and Their Offspring

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Masakazu Nishigaki ◽  
Eiko Sato ◽  
Ryota Ochiai ◽  
Taiga Shibayama ◽  
Keiko Kazuma
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Susceptibility ◽  
Behavioral Change ◽  
Behavioral Changes ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
The Patient’S View ◽  
Self Administered Questionnaire ◽  
Type 2 Diabetic

Background. Offspring of type 2 diabetic patients are at a high risk of type 2 diabetes. Information on diabetes genetic susceptibility and prevention should be supplied to the offspring.Methods. A six-page booklet on diabetes genetic susceptibility and prevention was distributed to 173 patients who ere ordered to hand it to their offspring. The patients answered a self-administered questionnaire on booklet delivery and attitudinal and behavioral changes toward diabetes and its prevention in themselves and their offspring.Results. Valid responses were obtained from 130 patients. Forty-nine patients had actually handed the booklet. Booklet induces more relief than anxiety. From the patient's view, favorable attitudinal and/or behavioral changes occurred in more than half of the offspring who were delivered the booklet.Conclusion. The booklet worked effectively on attitudes and behaviors toward diabetes and its prevention both in patients and their offspring. However, the effectiveness of patients as information deliverers was limited.

Evaluation of Epicardial Adipose Tissue in Patients of Type 2 Diabetes Mellitus by Echocardiography and its Correlation with Intimal Medial Thickness of Carotid Artery

2017 ◽  
Vol 125 (09) ◽  
pp. 598-602 ◽  
Author(s):  
Zihang Wang ◽  
Yuhong Zhang ◽  
Weiwei Liu ◽  
Benli Su
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Carotid Artery ◽  
Epicardial Adipose Tissue ◽  
Control Group ◽  
Intimal Medial Thickness ◽  
Type 2 Diabetic

AbstractThe present study aimed to evaluate the diagnostic value of echocardiography in measuring the thickness of epicardial adipose tissue (EAT) of the patients of type 2 diabetes mellitus (T2DM) and its correlation with the intimal-medial thickness of the carotid artery (cIMT) to investigate the relationship between EAT and cIMT. 68 patients of T2DM were enrolled and were divided into 2 groups: group of T2DM with duration≤10 years (35 cases) and group of T2DM with duration>10 years (33 cases). And 30 healthy subjects were enrolled as the control group. The thickness of EAT and cIMT were measured by echocardiography and high-frequency ultrasonography. The thickness of EAT and IMT of the carotid artery of 2 type 2 diabetic groups (duration≤10 years and>10 years) were significantly higher than that of the control group (all p<0.05), and the thickness of EAT and cIMT of the group of T2DM with duration>10 years were significantly higher than that of the group of T2DM with duration≤10 years (p<0.05). In univariate analysis, the thickness of EAT was positively and significantly associated with age (r=0.412, p<0.05), BMI (r=0.566, p<0.05), waist circumference (r=0.475, p<0.05), LDL (r=0.425, p<0.05), TG (r=0.496, p<0.05), duration of diabetes (r=0.384, p<0.05) and cIMT (r=0.456, p<0.05). In multiple stepwise regression analyses, age, BMI and IMT of carotid artery were appeared to be significantly associated with EAT (p<0.05 for all). In conclusion, routine screening of EAT and cIMT by ultrasonography in type 2 diabetic patients helps us to predict cardiovascular risks and prevent further development of cardiovascular complications.

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