scholarly journals Apolipoprotein Mimetic Peptides: Potential New Therapies for Cardiovascular Diseases

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 597
Author(s):  
Anna Wolska ◽  
Mart Reimund ◽  
Denis O. Sviridov ◽  
Marcelo J. Amar ◽  
Alan T. Remaley
Keyword(s):  
Cardiovascular Diseases ◽  
Therapeutic Agents ◽  
Clinical Development ◽  
New Drugs ◽  
Peptide Mimetics ◽  
Diabetic Patients ◽  
Medical Disorders ◽  
Mimetic Peptides ◽  
Human Use ◽  
Potential Therapeutics

Since the seminal breakthrough of treating diabetic patients with insulin in the 1920s, there has been great interest in developing other proteins and their peptide mimetics as therapies for a wide variety of other medical disorders. Currently, there are at least 60 different peptides that have been approved for human use and over 150 peptides that are in various stages of clinical development. Peptides mimetic of the major proteins on lipoproteins, namely apolipoproteins, have also been developed first as tools for understanding apolipoprotein structure and more recently as potential therapeutics. In this review, we discuss the biochemistry, peptide mimetics design and clinical trials for peptides based on apoA-I, apoE and apoC-II. We primarily focus on applications of peptide mimetics related to cardiovascular diseases. We conclude with a discussion on the limitations of peptides as therapeutic agents and the challenges that need to be overcome before apolipoprotein mimetic peptides can be developed into new drugs.

A Clinical Decision Support System for Assessing the Risk of Cardiovascular Diseases in Diabetic Hemodialysis Patients

2020 ◽  
Vol 16 (3) ◽  
pp. 262-269
Author(s):  
Tahere Talebi Azad Boni ◽  
Haleh Ayatollahi ◽  
Mostafa Langarizadeh
Keyword(s):  
Decision Support ◽  
Cardiovascular Diseases ◽  
Decision Support System ◽  
Clinical Decision Support ◽  
Support System ◽  
Clinical Decision Support System ◽  
Clinical Decision ◽  
Diabetic Patients ◽  
K Value ◽  
Care Plans

Background: One of the greatest challenges in the field of medicine is the increasing burden of chronic diseases, such as diabetes. Diabetes may cause several complications, such as kidney failure which is followed by hemodialysis and an increasing risk of cardiovascular diseases. Objective: The purpose of this research was to develop a clinical decision support system for assessing the risk of cardiovascular diseases in diabetic patients undergoing hemodialysis by using a fuzzy logic approach. Methods: This study was conducted in 2018. Initially, the views of physicians on the importance of assessment parameters were determined by using a questionnaire. The face and content validity of the questionnaire was approved by the experts in the field of medicine. The reliability of the questionnaire was calculated by using the test-retest method (r = 0.89). This system was designed and implemented by using MATLAB software. Then, it was evaluated by using the medical records of diabetic patients undergoing hemodialysis (n=208). Results: According to the physicians' point of view, the most important parameters for assessing the risk of cardiovascular diseases were glomerular filtration, duration of diabetes, age, blood pressure, type of diabetes, body mass index, smoking, and C reactive protein. The system was designed and the evaluation results showed that the values of sensitivity, accuracy, and validity were 85%, 92% and 90%, respectively. The K-value was 0.62. Conclusion: The results of the system were largely similar to the patients’ records and showed that the designed system can be used to help physicians to assess the risk of cardiovascular diseases and to improve the quality of care services for diabetic patients undergoing hemodialysis. By predicting the risk of the disease and classifying patients in different risk groups, it is possible to provide them with better care plans.

scholarly journals Circulating Biomarkers of Diabetic Retinopathy: An Overview Based on Physiopathology

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Olga Simó-Servat ◽  
Rafael Simó ◽  
Cristina Hernández
Keyword(s):  
Diabetic Retinopathy ◽  
Therapeutic Strategy ◽  
New Drugs ◽  
Diagnostic Tools ◽  
Diabetic Patients ◽  
Circulating Biomarkers ◽  
Pharmacological Treatments ◽  
Early Stages ◽  
Working Age ◽  
Advanced Stages

Diabetic retinopathy (DR) is the main cause of working-age adult-onset blindness. The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. In early stages of DR the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR. Therefore, new pharmacological treatments for these early stages of the disease are required. In order to develop therapeutic strategies for early stages of DR new diagnostic tools are urgently needed. In this regard, circulating biomarkers could be useful to detect early disease, to identify those diabetic patients most prone to progressive worsening who ought to be followed up more often and who could obtain the most benefit from these therapies, and to monitor the effectiveness of new drugs for DR before more advanced DR stages have been reached. Research of biomarkers for DR has been mainly based on the pathogenic mechanism involved in the development of DR (i.e., AGEs, oxidative stress, endothelial dysfunction, inflammation, and proangiogenic factors). This review focuses on circulating biomarkers at both early and advanced stages that could be relevant for the prediction or detection of DR.

scholarly journals Aszimmetrikus dimetilarginin: a cardiovascularis betegségek prediktora?

2016 ◽  
Vol 157 (13) ◽  
pp. 483-487
Author(s):  
Balázs Németh ◽  
Péter Kustán ◽  
Ádám Németh ◽  
Zsófia Lenkey ◽  
Attila Cziráki ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
Asymmetric Dimethylarginine ◽  
Disease Onset ◽  
Cardiovascular Prevention ◽  
Competitive Inhibitor ◽  
Diabetic Patients ◽  
Artery Disease

Cardiovascular diseases are the most common diseases worldwide. They are responsible for one third of global deaths and they are the leading cause of disability, too. The usage of different levels of prevention in combination with effective risk assessment improved these statistical data. Risk assessment based on classic risk factors has recently been supported with several new markers, such as asymmetric dimethylarginine, which is an endogenous competitive inhibitor of nitric oxide synthase. Elevated levels of asymmetric dimethylarginine have been reported in obese, smoker, hypercholesterolemic, hypertensive and diabetic patients. According to previous studies, asymmetric dimethylarginine is a suitable indicator of endothelial dysfunction, which is held to be the previous state of atherosclerosis. Several researches found positive correlation between higher levels of asymmetric dimethylarginine and coronary artery disease onset, or progression of existing coronary disease. According to a study involving 3000 patients, asymmetric dimethylarginine is an independent risk factor of cardiovascular mortality in patients with coronary artery disease. This article summarizes the role of asymmetric dimethylarginine in prediction of cardiovascular diseases, and underlines its importance in cardiovascular prevention. Orv. Hetil., 2016, 157(13), 483–487.

scholarly journals Clinical Trial Regulations In India : Past, Present and Future

JMS SKIMS ◽  
2017 ◽  
Vol 20 (1) ◽  
pp. 5-17
Author(s):  
Haroon Rashid
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Disease Burden ◽  
International Standards ◽  
New Drugs ◽  
Safety And Efficacy ◽  
Long Time ◽  
Regulatory Bodies ◽  
Guidance Documents ◽  
Human Use

Clinical trials are the only way of establishing the safety and efficacy of any new drug before its introduction in the market for human use. Clinical trials (with safeguards) are necessary for introduction of new drugs for a country like India, considering its disease burden and emergence of new variants of disease.The regulatory bodies need to frame guidelines and regulatory approval processes on a par with international standards. Many of the new laws, guidance documents, notifications and initiatives for regulating pharmaceutical industry were in the charts for quite a long time. Indian regulatory authorities have started looking into speedy implementation and providing support in terms ofnecessary infrastructure and investment. JMS 2017; 20(1):5-17

Oxidative stress and diabetic cardiovascular disorders: roles of mitochondria and NADPH oxidaseThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Garry X. Shen
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Mitochondrial Dysfunction ◽  
Cardiovascular Complications ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
In Cells

Cardiovascular diseases are the predominant cause of death in patients with diabetes mellitus. Underlying mechanism for the susceptibility of diabetic patients to cardiovascular diseases remains unclear. Elevated oxidative stress was detected in diabetic patients and in animal models of diabetes. Hyperglycemia, oxidatively modified atherogenic lipoproteins, and advanced glycation end products are linked to oxidative stress in diabetes. Mitochondria are one of major sources of reactive oxygen species (ROS) in cells. Mitochondrial dysfunction increases electron leak and the generation of ROS from the mitochondrial respiratory chain (MRC). High levels of glucose and lipids impair the activities of MRC complex enzymes. NADPH oxidase (NOX) generates superoxide from NADPH in cells. Increased NOX activity was detected in diabetic patients. Hyperglycemia and hyperlipidemia increased the expression of NOX in vascular endothelial cells. Accumulated lines of evidence indicate that oxidative stress induced by excessive ROS production is linked to many processes associated with diabetic cardiovascular complications. Overproduction of ROS resulting from mitochondrial dysfunction or NOX activation is associated with uncoupling of endothelial nitric oxide synthase, which leads to reduced production of nitric oxide and endothelial-dependent vasodilation. Gene silence or inhibitor of NOX reduced oxidized or glycated LDL-induced expression of plasminogen activator inhibitor-1 in endothelial cells. Statins, hypoglycemic agents, and exercise may reduce oxidative stress in diabetic patients through the reduction of NOX activity or the improvement of mitochondrial function, which may prevent or postpone the development of cardiovascular complications.

scholarly journals Management of hypercholesterolemia, appropriateness of therapeutic approaches and new drugs in patients with high cardiovascular risk

2018 ◽  
Vol 12 (3) ◽  
pp. 203-212 ◽  
Author(s):  
Roberto Vettor ◽  
Roberto Serra
Keyword(s):  
Cardiovascular Risk ◽  
Clinical Trial Data ◽  
Statin Treatment ◽  
Clinical Development ◽  
New Drugs ◽  
Risk Category ◽  
Therapeutic Approaches ◽  
High Cardiovascular Risk ◽  
All Cause Mortality ◽  
Receive Treatment

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Lowering low-density lipoproteins-cholesterol (LDL-C) has been shown to decrease the risk of CVD and of all-cause mortality. For appropriate management, estimation of each individual’s total cardiovascular risk is critical, as patients should receive treatment according to their cardiovascular risk category as well as their LDL-C level. However, available data indicate that a large proportion of patients fail to achieve lipid goals despite treatment, and a significant percentage of patients are not able to tolerate statin treatment. Researchers have therefore focused considerable attention on the development of novel LDL-C-lowering agents that act via different mechanisms. Among the most recent advances in clinical development are the proprotein convertase subtilisin/kexin 9 antibody inhibitors, including alirocumab and evolocumab, which appear particularly promising, with clinical trial data indicating these agents to be both well tolerated and highly efficacious in lowering LDL-C.

Synthesis, in silico pharmacokinetics and biological evaluation of some new thiazolidinedione as PPAR-γ agonists and antibacterial agents

2021 ◽  
Vol 18 ◽  
Author(s):  
Zohor Mohammad Mahdi Alzhrani ◽  
Mohammad Mahboob Alam ◽  
Syed Nazreen
Keyword(s):  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Antibacterial Activities ◽  
Biological Evaluation ◽  
New Drugs ◽  
Diabetic Patients ◽  
Spectroscopic Techniques ◽  
Standard Drug ◽  
Ppar Γ

Background: The frequent uses of antimicrobial agents to treat infections in diabetic patients make them more drug resistance than non diabetic patients which accounts for higher mortality rate of diabetic patients. Therefore, it is a necessity today to synthesize new drugs with dual mode of action as antidiabetic and antibacterial agents. In the present work, new derivatives containing thiazolidinedione and 1,3,4-oxadiaozle have been synthesized and screened for PPAR-γ and antibacterial activities. Methods: Compound 5-12 have been synthesized from 2-methoxy benzaldehyde and thiazolidinedione and characterized using different spectroscopic techniques such as IR, NMR and mass spectrometry. These compounds were tested for in vitro PPAR-γ transactivation, PPAR-γ gene expression and antibacterial activities. Finally molecular docking was carried out to see the binding interactions of molecules with the target protein. Results: All the compounds follow Lipinski rule suggesting the synthesized derivatives have good drug likeness properties. Compound 11 and 12 exhibited promising PPAR-γ transactivation with 73.69% and 76.50%, respectively as well as showed significant antibacterial activity with comparable MIC of 3.12 μg/disc to standard drug amoxicillin. The docking result was found to be in consistent with the in vitro PPAR-γ transactivation results. Conclusion: Compounds 11 and 12 can be further investigated as lead molecules for the development of new and effective antidiabetic and antibacterial agents.

Ponatinib, Lestaurtinib and mTOR/PI3K inhibitors are promising repurposing candidates against Entamoeba histolytica

2021 ◽  
Author(s):  
Monica M. Kangussu-Marcolino ◽  
Upinder Singh
Keyword(s):  
Entamoeba Histolytica ◽  
Current Treatment ◽  
Clinical Development ◽  
New Drugs ◽  
Phase Iii ◽  
Significant Advance ◽  
Pi3k Inhibitors ◽  
Treatment Regimens ◽  
Clinical Resistance ◽  
Tk Inhibitors

Dysentery caused by Entamoeba histolytica affects millions of people annually. Current treatment regimens are based on metronidazole to treat invasive parasites combined with paromomycin for luminal parasites. Issues with treatment include significant side effects, inability to easily treat breastfeeding and pregnant women, the use of two sequential agents, and concern that all therapy is based on nitroimidazole agents with no alternatives if clinical resistance emerges. Thus, the need for new drugs against amebiasis is urgent. To identify new therapeutic candidates, we screened the ReFRAME library (11,948 compounds assembled for Repurposing, Focused Rescue, and Accelerated Medchem) against E. histolytica trophozoites. We identified 159 hits in the primary screen at 10 μM and 46 compounds were confirmed in secondary assays. Overall, 26 were selected as priority molecules for further investigation including 6 FDA approved, 5 orphan designation, and 15 which are currently in clinical trials (3 phase III, 7 phase II and 5 phase I). We found that all 26 compounds are active against metronidazole resistant E. histolytica and 24 are able to block parasite recrudescence after drug removal. Additionally, 14 are able to inhibit encystation and 2 (lestaurtinib and LY-2874455) are active against mature cysts. Two classes of compounds are most interesting for further investigations: the Bcr-Abl TK inhibitors, with the ponatinib (EC 50 0.39) as most potent and mTOR or PI3K inhibitors with 8 compounds in clinical development, of which 4 have nanomolar potency. Overall, these are promising candidates and represent a significant advance for drug development against E. histolytica .

Clinical Development of New Drugs

2011 ◽  
pp. 149-149 ◽  
Author(s):  
SK Gupta ◽  
Niranjan Gallpali
Keyword(s):  
Clinical Development ◽  
New Drugs
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