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Trends in Molecular Medicine Apr 2023Bilirubin has several physiological functions, both beneficial and harmful. In addition to reactive oxygen species-scavenging activities, bilirubin has potent... (Review)
Review
Bilirubin has several physiological functions, both beneficial and harmful. In addition to reactive oxygen species-scavenging activities, bilirubin has potent immunosuppressive effects associated with long-term pathophysiological sequelae. It has been recently recognized as a hormone with endocrine actions and interconnected effects on various cellular signaling pathways. Current studies show that bilirubin also decreases adiposity and prevents metabolic and cardiovascular diseases. All in all, the physiological importance of bilirubin is only now coming to light, and strategies for increasing plasma bilirubin levels to combat chronic diseases are starting to be considered. This review discusses the beneficial effects of increasing plasma bilirubin, incorporates emerging areas of bilirubin biology, and provides key concepts to advance the field.
Topics: Humans; Bilirubin; Heme Oxygenase-1; Cardiovascular Diseases; Reactive Oxygen Species
PubMed: 36828710
DOI: 10.1016/j.molmed.2023.01.007 -
Trends in Endocrinology and Metabolism:... Mar 2018Bilirubin is a component of the heme catabolic pathway that is essential for liver function and has been shown to reduce hepatic fat accumulation. High plasma bilirubin... (Review)
Review
Bilirubin is a component of the heme catabolic pathway that is essential for liver function and has been shown to reduce hepatic fat accumulation. High plasma bilirubin levels are reflective of liver disease due to an injurious effect on hepatocytes. In healthy liver, bilirubin is conjugated and excreted to the intestine and converted by microbes to urobilinoids, which are reduced to the predominant pigment in feces, stercobilin, or reabsorbed. The function of urobilinoids in the gut or their physiological relevance of reabsorption is not well understood. In this review, we discuss the relationship of hepatic bilirubin signaling to the intestinal microbiota and its regulation of the liver-gut axis, as well as its capacity to mediate these processes.
Topics: Animals; Bilirubin; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Liver; Signal Transduction
PubMed: 29409713
DOI: 10.1016/j.tem.2018.01.002 -
Pediatric Research Mar 2016Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be... (Review)
Review
Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy.
Topics: Animals; Bile; Bilirubin; Crigler-Najjar Syndrome; Gilbert Disease; Glucuronic Acid; Glucuronosyltransferase; Humans; Hyperbilirubinemia, Hereditary; Hyperbilirubinemia, Neonatal; Jaundice, Chronic Idiopathic; Liver
PubMed: 26595536
DOI: 10.1038/pr.2015.247 -
Current Topics in Microbiology and... 2015Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding.... (Review)
Review
Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding. Infection results from direct or indirect exposure to infected reservoir host animals that carry the pathogen in their renal tubules and shed pathogenic leptospires in their urine. Although many wild and domestic animals can serve as reservoir hosts, the brown rat (Rattus norvegicus) is the most important source of human infections. Individuals living in urban slum environments characterized by inadequate sanitation and poor housing are at high risk of rat exposure and leptospirosis. The global burden of leptospirosis is expected to rise with demographic shifts that favor increases in the number of urban poor in tropical regions subject to worsening storms and urban flooding due to climate change. Data emerging from prospective surveillance studies suggest that most human leptospiral infections in endemic areas are mild or asymptomatic. Development of more severe outcomes likely depends on three factors: epidemiological conditions, host susceptibility, and pathogen virulence (Fig. 1). Mortality increases with age, particularly in patients older than 60 years of age. High levels of bacteremia are associated with poor clinical outcomes and, based on animal model and in vitro studies, are related in part to poor recognition of leptospiral LPS by human TLR4. Patients with severe leptospirosis experience a cytokine storm characterized by high levels of IL-6, TNF-alpha, and IL-10. Patients with the HLA DQ6 allele are at higher risk of disease, suggesting a role for lymphocyte stimulation by a leptospiral superantigen. Leptospirosis typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia, and headache and may be confused with other entities such as influenza and dengue fever. Newer diagnostic methods facilitate early diagnosis and antibiotic treatment. Patients progressing to multisystem organ failure have widespread hematogenous dissemination of pathogens. Nonoliguric (high output) renal dysfunction should be supported with fluids and electrolytes. When oliguric renal failure occurs, prompt initiation of dialysis can be life saving. Elevated bilirubin levels are due to hepatocellular damage and disruption of intercellular junctions between hepatocytes, resulting in leaking of bilirubin out of bile caniliculi. Hemorrhagic complications are common and are associated with coagulation abnormalities. Severe pulmonary hemorrhage syndrome due to extensive alveolar hemorrhage has a fatality rate of >50 %. Readers are referred to earlier, excellent summaries related to this subject (Adler and de la Peña-Moctezuma 2010; Bharti et al. 2003; Hartskeerl et al. 2011; Ko et al. 2009; Levett 2001; McBride et al. 2005).
Topics: Animals; Bilirubin; Cost of Illness; Humans; Leptospirosis; Rats
PubMed: 25388133
DOI: 10.1007/978-3-662-45059-8_5 -
Biomedicine & Pharmacotherapy =... Sep 2022As the host defense response to various injuries and pathogens in the body, inflammation can remove damaged cells and pathogens in the host organism and protect the... (Review)
Review
As the host defense response to various injuries and pathogens in the body, inflammation can remove damaged cells and pathogens in the host organism and protect the body. However, excessive inflammation may cause damage to normal tissue cells while removing pathogens, which in turn cause numerous inflammatory diseases and adversely affect the human health. Phycocyanin is an active substance extracted from algae; it has outstanding antioxidant and anti-inflammatory activities, and can effectively inhibit various diseases caused by inflammation. This review systematically summarizes recent applications of phycocyanin against various inflammatory diseases in lung, liver, cardiovascular, and cerebrovascular systems. In addition, possible anti-inflammatory action pathways of phycocyanin are reviewed to canvass the anti-inflammatory mechanism. At last, based on the existing research, phycocyanobilin in phycocyanin is proposed as a bilirubin analog by inducing heme oxygenase 1 in vivo to suppress inflammation.
Topics: Anti-Inflammatory Agents; Antioxidants; Bilirubin; Humans; Inflammation; Phycocyanin
PubMed: 36076518
DOI: 10.1016/j.biopha.2022.113362 -
American Journal of Physiology.... Feb 2021Recent research on bilirubin, a historically well-known waste product of heme catabolism, suggests an entirely new function as a metabolic hormone that drives gene... (Review)
Review
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 seen 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 patients with hypobilirubinemia, 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.
Topics: Animals; Bilirubin; Energy Metabolism; Gene Expression Regulation; Gilbert Disease; Heme; Hormones; Humans; Hyperbilirubinemia; Metabolic Networks and Pathways; PPAR alpha
PubMed: 33284088
DOI: 10.1152/ajpendo.00405.2020 -
Physiological Reviews Jul 2020Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated... (Review)
Review
Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated hyperbilirubinemia is common in newborn infants, but rare later in life. The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described. However, in the neonate, numerous variables related to nutrition, ethnicity, and genetic variants at several metabolic steps may be superimposed on the normal physiological hyperbilirubinemia that occurs in the first week of life and results in bilirubin levels that may be toxic to the brain. Bilirubin exists in several isomeric forms that differ in their polarities and is considered a physiologically important antioxidant. Here we review the chemistry of the bilirubin molecule and its metabolism in the body with a particular focus on the processes that impact the newborn infant, and how differences relative to older children and adults contribute to the risk of developing both acute and long-term neurological sequelae in the newborn infant. The final section deals with the interplay between the brain and bilirubin and its entry, clearance, and accumulation. We conclude with a discussion of the current state of knowledge regarding the mechanism(s) of bilirubin neurotoxicity.
Topics: Bilirubin; Brain; Humans; Infant, Newborn; Intestinal Mucosa; Liver
PubMed: 32401177
DOI: 10.1152/physrev.00004.2019 -
Hong Kong Medical Journal = Xianggang... Jun 2018Jaundice is caused by an accumulation of bilirubin in the blood. The presentation in infants and children can be indicative of a wide range of conditions, with some... (Review)
Review
Jaundice is caused by an accumulation of bilirubin in the blood. The presentation in infants and children can be indicative of a wide range of conditions, with some self-limiting and others potentially life-threatening. This article aims to provide a concise review of the common medical and surgical causes in children and discuss their diagnosis and management.
Topics: Bilirubin; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Jaundice; Laparoscopy
PubMed: 29807950
DOI: 10.12809/hkmj187245 -
The Cochrane Database of Systematic... Mar 2023Phototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been... (Review)
Review
BACKGROUND
Phototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been proposed as an equally effective alternative with practical advantages of improved maternal feeding and bonding. The effectiveness of intermittent phototherapy compared with continuous phototherapy is unknown.
OBJECTIVES
To assess the safety and effectiveness of intermittent phototherapy compared with continuous phototherapy.
SEARCH METHODS
Searches were conducted on 31 January 2022 in the following databases: CENTRAL via CRS Web, MEDLINE and Embase via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.
SELECTION CRITERIA
We included RCTs, cluster-RCTs and quasi-RCTs comparing intermittent phototherapy with continuous phototherapy in jaundiced infants (both term and preterm) up to the age of 30 days. We compared intermittent phototherapy with continuous phototherapy by any method and at any dose and duration as defined by the authors.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs). Our primary outcomes of interest were rate of decline of serum bilirubin, and kernicterus. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
We included 12 RCTs (1600 infants) in the review. There is one ongoing study and four awaiting classification. There was little or no difference between intermittent phototherapy and continuous phototherapy with respect to rate of decline of bilirubin in jaundiced newborn infants (MD -0.09 micromol/L/hr, 95% CI -0.21 to 0.03; I² = 61%; 10 studies; 1225 infants; low-certainty evidence). One study involving 60 infants reported no incidence of bilirubin induced brain dysfunction (BIND). It is uncertain whether either intermittent or continuous phototherapy reduces BIND because the certainty of this evidence is very low. There was little or no difference in treatment failure (RD 0.03, 95% CI 0.08 to 0.15; RR 1.63, 95% CI 0.29 to 9.17; 1 study; 75 infants; very low-certainty evidence) or infant mortality (RD -0.01, 95% CI -0.03 to 0.01; RR 0.69, 95% CI 0.37 to 1.31 I² = 0%; 10 studies, 1470 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: The available evidence detected little or no difference between intermittent and continuous phototherapy with respect to rate of decline of bilirubin. Continuous phototherapy appears to be more effective in preterm infants, however, the risks of continuous phototherapy and the potential benefits of a slightly lower bilirubin level are unknown. Intermittent phototherapy is associated with a decrease in the total number of hours of phototherapy exposure. There are theoretical benefits to intermittent regimens but there are important safety outcomes that were inadequately addressed. Large, well designed, prospective trials are needed in both preterm and term infants before it can be concluded that intermittent and continuous phototherapy regimens are equally effective.
Topics: Infant; Infant, Newborn; Humans; Jaundice, Neonatal; Phototherapy; Bilirubin; Family
PubMed: 36867730
DOI: 10.1002/14651858.CD008168.pub2 -
Anales de Pediatria Feb 2020Neonatal jaundice is common, especially in premature infants. Compliance with treatment protocols and standard serum bilirubin curves forces the clinician to separate... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
Neonatal jaundice is common, especially in premature infants. Compliance with treatment protocols and standard serum bilirubin curves forces the clinician to separate the child from the mother after birth for short phototherapy. The objective of this study is to evaluate the effectiveness and safety of two innovative devices for phototherapy including a LED light mesh: one sleeping bag and one blanket compared to conventional hospital or ambulatory phototherapy.
METHODS
Two randomised clinical trials were conducted: one with newborns >2,000g at birth in the Neonatal Care Unit and the other with premature infants followed-up in an outpatient clinic (PMC). The gold standard for bilirubin measurement was serum bilirubin, and ambulatory controls were performed with the Bilicheck®. Parents and health personnel completed a questionnaire on comfort and perceptions.
RESULTS
In the study using the bag, a linear regression was performed for the decrease in bilirubin in mg/dL/h, controlling by early jaundice (<36h) and the device type. The results were similar between the 2 devices. For the blanket trial in the PMC, the decrease in bilirubin levels with the new device was significantly greater with no differences in temperatures, duration of phototherapy, re-admission, mortality, or side effects for both trials. Parents and staff satisfaction with the two devices was identical for the 2 trials.
CONCLUSION
These 2 small studies add a 'grain of sand' to humanisation of newborn care, avoiding the mother-and-child separation for both the intra-hospital high-risk hyperbilirubinaemia, as well as for the lower-risk hyperbilirubinaemia in an outpatient clinic.
Topics: Bilirubin; Female; Humans; Infant, Newborn; Infant, Premature; Jaundice, Neonatal; Male; Phototherapy; Surveys and Questionnaires
PubMed: 30979682
DOI: 10.1016/j.anpedi.2019.02.008