scholarly journals Bilirubin as a Metabolic Hormone: The Physiological Relevance of Low Levels

2020 ◽  
Author(s):  
Justin F. Creeden ◽  
Darren M Gordon ◽  
David E. Stec ◽  
Terry D Hinds
Keyword(s):  
Nuclear Receptors ◽  
Waste Product ◽  
Cardiovascular Complications ◽  
Metabolic Dysfunction ◽  
Research Directions ◽  
Hormonal Function ◽  
Physiological Relevance ◽  
Plasma Bilirubin ◽  
Low Levels ◽  
Metabolic Hormone

Recent research on bilirubin, a historically well-known waste product of heme catabolism, suggests an entirely new function as a metabolic hormone that drives gene transcription by nuclear receptors. Studies are now revealing that low plasma bilirubin levels, defined as 'hypobilirubinemia,' are a possible new pathology analogous to the other end of the spectrum of extreme hyperbilirubinemia seen in patients with jaundice and liver dysfunction. Hypobilirubinemia is most commonly presented in patients with metabolic dysfunction, which may lead to cardiovascular complications and possibly stroke. We address the clinical significance of low bilirubin levels. A better understanding of bilirubin's hormonal function may explain why hypobilirubinemia might be deleterious. We present mechanisms by which bilirubin may be protective at mildly elevated levels and research directions that could generate treatment possibilities for hypobilirubinemic patients, such as targeting of pathways that regulate its production or turnover or the newly designed bilirubin nanoparticles. Our review here calls for a shift in the perspective of an old molecule that could benefit millions of patients with hypobilirubinemia.

A narrative review of chronic alcohol-induced atrial fibrillation

2021 ◽  
Author(s):  
Rea Mittal ◽  
Lilly Su ◽  
Devyani Ramgobin ◽  
Ashwani Garg ◽  
Rahul Jain ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Alcohol Use ◽  
Alcohol Intake ◽  
Cardiovascular Complications ◽  
Chronic Alcohol ◽  
Higher Alcohol ◽  
Dependent Relationship ◽  
Increased Risk ◽  
Low Levels ◽  
Dose Dependent

Alcohol use disorder (AUD) is highly prevalent and can lead to many cardiovascular complications, including arrhythmias. Chronic alcohol use has a dose-dependent relationship with incidence of atrial fibrillation (AF), where higher alcohol intake (>3 drinks a day) is associated with higher risk of AF. Meanwhile, low levels of chronic alcohol intake (<1 drink a day) is not associated with increased risk of AF. Mechanistically, chronic alcohol intake alters the structural, functional and electrical integrity of the atria, predisposing to AF. Increased screening can help identify AUD patients early on and provide the opportunity to educate on chronic alcohol use related risks, such as AF. The ideal treatment to reduce risk of incident or recurrent AF in AUD populations is abstinence.

scholarly journals Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment

2021 ◽  
Vol 11 ◽  
Author(s):  
Drishti Tiwari ◽  
Pawan Gupta
Keyword(s):  
Nuclear Receptors ◽  
Dietary Habits ◽  
Allergic Diseases ◽  
Living Standards ◽  
Metabolic Dysfunction ◽  
Genomic Changes ◽  
Physiological Processes ◽  
Gene Regulatory ◽  
Critical Requirement ◽  
Allergy And Asthma

The escalation in living standards and adoption of ‘Western lifestyle’ has an allied effect on the increased allergy and asthma burden in both developed and developing countries. Current scientific reports bespeak an association between allergic diseases and metabolic dysfunction; hinting toward the critical requirement of organized lifestyle and dietary habits. The ubiquitous nuclear receptors (NRs) translate metabolic stimuli into gene regulatory signals, integrating diet inflences to overall developmental and physiological processes. As a consequence of such promising attributes, nuclear receptors have historically been at the cutting edge of pharmacy world. This review discusses the recent findings that feature the cardinal importance of nuclear receptors and how they can be instrumental in modulating current asthma pharmacology. Further, it highlights a possible future employment of therapy involving dietary supplements and synthetic ligands that would engage NRs and aid in eliminating both asthma and linked comorbidities. Therefore, uncovering new and evolving roles through analysis of genomic changes would represent a feasible approach in both prevention and alleviation of asthma.

scholarly journals Low human dystrophin levels prevent cardiac electrophysiological and structural remodelling in a Duchenne mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gerard A. Marchal ◽  
Maaike van Putten ◽  
Arie O. Verkerk ◽  
Simona Casini ◽  
Kayleigh Putker ◽  
...  
Keyword(s):  
Cardiac Involvement ◽  
Structural Characteristics ◽  
Sodium Current ◽  
Cardiovascular Complications ◽  
Neuromuscular Disorder ◽  
Dystrophin Expression ◽  
Low Levels ◽  
And Function ◽  
Human Dystrophin ◽  
Upstroke Velocity

AbstractDuchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder caused by loss of dystrophin. This lack also affects cardiac structure and function, and cardiovascular complications are a major cause of death in DMD. Newly developed therapies partially restore dystrophin expression. It is unclear whether this will be sufficient to prevent or ameliorate cardiac involvement in DMD. We here establish the cardiac electrophysiological and structural phenotype in young (2–3 months) and aged (6–13 months) dystrophin-deficient mdx mice expressing 100% human dystrophin (hDMD), 0% human dystrophin (hDMDdel52-null) or low levels (~ 5%) of human dystrophin (hDMDdel52-low). Compared to hDMD, young and aged hDMDdel52-null mice displayed conduction slowing and repolarisation abnormalities, while only aged hDMDdel52-null mice displayed increased myocardial fibrosis. Moreover, ventricular cardiomyocytes from young hDMDdel52-null animals displayed decreased sodium current and action potential (AP) upstroke velocity, and prolonged AP duration at 20% and 50% of repolarisation. Hence, cardiac electrical remodelling in hDMDdel52-null mice preceded development of structural alterations. In contrast to hDMDdel52-null, hDMDdel52-low mice showed similar electrophysiological and structural characteristics as hDMD, indicating prevention of the cardiac DMD phenotype by low levels of human dystrophin. Our findings are potentially relevant for the development of therapeutic strategies aimed at restoring dystrophin expression in DMD.

Prolonged influence of a neonatal cyproterone acetate treatment on renal androgen binding in mice

1988 ◽  
Vol 119 (2) ◽  
pp. 263-268
Author(s):  
G. Veyssiére ◽  
Ch. Gallon ◽  
M. Berger ◽  
Ch. Jean-Faucher ◽  
M. de Turckheim ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Cyproterone Acetate ◽  
Single Injection ◽  
Adult Males ◽  
Male Mice ◽  
Testosterone Levels ◽  
Low Levels ◽  
Androgen Binding

Abstract. To determine whether neonatal endogenous androgens influence adult renal androgen binding, newborn male mice were injected from 1 to 10 days of age with cyproterone acetate and newborn females with testosterone from 1 to 10 days and from 20 to 40 days of age. In controls, at adulthood, the total cellular androgen receptor content was significantly higher in males (1700 200 receptors per cell) than in females (1060 ± 50) and, as expected, the nuclear receptor content was 12-fold higher in males. While the total number of receptors (1650 ± 220 per cell) was unchanged in adult males neonatally treated with cyproterone acetate, their distribution between cytosol and nucleus was similar to that in control females despite normal circulating and renal testosterone levels. The nuclear receptors represented 50, 7 and 11% of the total receptors in control males, control females and cyproterone acetate-treated males, respectively. The very low levels of nuclear receptors present in the kidney of cyproterone acetate-treated males probably explain the decreased sensitivity of this organ to testosterone. The nuclear receptor accumulation measured in adult animals after a single injection of testosterone did not seem to be affected by neonatal hormonal manipulations.

scholarly journals Interventions related to cardiovascular complications in people hospitalized by covid-19: a scoping review

2021 ◽  
Vol 74 (suppl 1) ◽  
Author(s):  
José Hiago Feitosa de Matos ◽  
Emiliana Bezerra Gomes ◽  
Natália Pinheiro Fabricio Formiga ◽  
Maria Naiane Rolim Nascimento ◽  
Gabriela de Sousa Lima ◽  
...  
Keyword(s):  
Scoping Review ◽  
Myocardial Injury ◽  
Web Of Science ◽  
Scientific Evidence ◽  
Cardiovascular Complications ◽  
Nursing Interventions ◽  
Assessment Tests ◽  
Low Levels ◽  
Therapy Interventions ◽  
Cardiovascular Interventions

ABSTRACT Objective: To describe the scientific evidence of complications and the need for cardiovascular interventions in people hospitalized by Covid-19. Method: a scoping review carried out according to The Joanna Briggs Institute recommendations, in the MEDLINE, CINAHL, SCOPUS and Web of Science databases. Results: A total of 11 published studies from December of 2019 to April of 2020, presenting low levels of evidence were selected. The evidence described the myocardial injury as the most common cardiac complication reported in Covid-19, reported in approximately 8% to 12% of all severe individuals, with indications for oxygen therapy interventions, thrombotic disorders prevention and treatment, hemodynamic monitoring and assessment tests of cardiac function’s performance, along with biochemical markers of myocardial injury, yet not addressing nursing interventions. Conclusion: Cardiovascular complications and interventions have not shown consensus on the found evidence, requiring causal analysis by explanatory studies that support multi-professional clinical protocols in health.

scholarly journals Female AhR Knockout Mice Develop a Minor Renal Insufficiency in an Adenine-Diet Model of Chronic Kidney Disease

2020 ◽  
Vol 21 (7) ◽  
pp. 2483 ◽  
Author(s):  
Camélia Makhloufi ◽  
Fanny Nicolas ◽  
Nathalie McKay ◽  
Samantha Fernandez ◽  
Guillaume Hache ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Renal Insufficiency ◽  
Knockout Mice ◽  
Cardiovascular Complications ◽  
Crystal Deposition ◽  
Metabolism Enzymes ◽  
Low Levels

Cardiovascular complications observed in chronic kidney disease (CKD) are associated with aryl hydrocarbon receptor (AhR) activation by tryptophan-derived uremic toxins—mainly indoxyl sulfate (IS). AhR is a ligand-activated transcription factor originally characterized as a receptor of xenobiotics involved in detoxification. The aim of this study was to determine the role of AhR in a CKD mouse model based on an adenine diet. Wild-type (WT) and AhR−/− mice were fed by alternating an adenine-enriched diet and a regular diet for 6 weeks. Our results showed an increased mortality rate of AhR−/− males. AhR−/− females survived and developed a less severe renal insufficiency that WT mice, reflected by urea, creatinine, and IS measurement in serum. The protective effect was related to a decrease of pro-inflammatory and pro-fibrotic gene expression, an attenuation of tubular injury, and a decrease of 2,8-dihydroxyadenine crystal deposition in the kidneys of AhR−/− mice. These mice expressed low levels of xanthine dehydrogenase, which oxidizes adenine into 2,8-dihydroxyadenine, and low levels of the IS metabolism enzymes. In conclusion, the CKD model of adenine diet is not suitable for AhR knockout mice when studying the role of this transcription factor in cardiovascular complications, as observed in human CKD.

scholarly journals Serum levels of magnesium in sudden cardiac deaths among people with schizophrenia: hit or miss?

2012 ◽  
Vol 70 (10) ◽  
pp. 814-816 ◽  
Author(s):  
Fulvio A. Scorza ◽  
Marly de Albuquerque ◽  
Ricardo M. Arida ◽  
Roberta Monterazzo Cysneiros
Keyword(s):  
Heart Rate ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Potential Role ◽  
Serum Levels ◽  
Self Esteem ◽  
Metabolic Dysfunction ◽  
Qt Interval Prolongation ◽  
Increased Risk ◽  
Low Levels

Schizophrenia is a devastating mental disorder, affecting cognitive, emotional, and behavioral conditions, ability to work, social functioning, family stability and self-esteem of the patient. People with schizophrenia show a two to three-fold increased risk to die prematurely than those without schizophrenia. Understanding the mechanisms behind sudden cardiac death in individuals with schizophrenia is a key to prevention. Although different mechanisms may be related, there are clear indications that cardiac abnormalities play a potential role. Some antipsychotics may be associated with cardiovascular adverse events, e.g., QT interval prolongation, metabolic dysfunction, blood pressure and heart rate alterations. Magnesium (Mg) abnormalities may lead to various morphological and functional dysfunctions of the heart and low levels of serum Mg are considered to be at high risk for sudden cardiac death. As low serum Mg is associated with detrimental effects on the heart and that antipsychotic-treated schizophrenia patients frequently affect the heart rate, possibly, these factors together must change the normal functioning of the heart and consequently being able to culminate in a catastrophic event.

An inflammatory link in atherosclerosis and obesity

2015 ◽  
Vol 35 (03) ◽  
pp. 272-278 ◽  
Author(s):  
E. Lutgens ◽  
A. Zirlik
Keyword(s):  
Immune Cells ◽  
Major Part ◽  
Cell Activation ◽  
Immune Cell ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Types ◽  
Cardiovascular Complications ◽  
Metabolic Dysfunction ◽  
Immune Cell Activation ◽  
Necrosis Factor

SummaryAtherosclerosis and obesity-induced metabolic dysfunction are lipid-driven inflammatory pathologies responsible for a major part of cardiovascular complications. Immune cell activation as well as interactions between the different immune cells is dependent on and controlled by a variety of co-stimulatory signals. These co-stimulatory signals can either aggravate or ameliorate the disease depending on the stage of the disease, the cell-types involved and the signal transduction cascades initiated. This review focuses on the diverse roles of the most established co-stimulatory molecules of the B7 and Tumor Necrosis Factor Receptor (TNFR) families, ie the CD28/CTLA4-CD80/CD86 and CD40L/CD40 dyads in the pathogenesis of atherosclerosis and obesity. In addition, we will explore their potential as therapeutic targets in both atherosclerosis and obesity.

scholarly journals Thyronamines and Derivatives: Physiological Relevance, Pharmacological Actions, and Future Research Directions

Thyroid ◽  
2016 ◽  
Vol 26 (12) ◽  
pp. 1656-1673 ◽  
Author(s):  
Carolin Stephanie Hoefig ◽  
Riccardo Zucchi ◽  
Josef Köhrle
Keyword(s):  
Future Research ◽  
Research Directions ◽  
Physiological Relevance ◽  
Future Research Directions
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