Inhibition of autotaxin by bile salts and bile salt-like molecules increases its expression by feedback regulation.

Background: Autotaxin is an enzyme that converts lysophospholipid into lysophosphatidic acid (LPA), a highly potent signaling molecule through a range of LPA receptors. It is therefore important to investigate which factors play a role in regulating ATX expression. Since we have reported that ATX levels increase dramatically in patients with various forms of cholestasis, we embarked on a study to reveal factors that influence the enzyme activity ATX as well as its expression level in vitro and in vivo.

Reduced spontaneous itch in mouse models of cholestasis.

Pruritus is one of the most distressing symptoms in cholestatic patients. Plasma autotaxin (ATX) activity correlates with the severity of pruritus in cholestatic patients, but the pathophysiology is unclear. To study pruritus in mice, we measured scratch activity in cholestatic Atp8b1 mutant mice, a model for Progressive Familial Intrahepatic Cholestasis type 1, and wild type mice (WT) with alpha-naphthylisothiocyanate (ANIT)-induced cholestasis.

Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial.

Background And Aims: Pruritus may seriously impair quality of life in patients with cholestatic diseases such as primary or secondary sclerosing cholangitis (PSC, SSC) and primary biliary cholangitis (PBC). Pharmacologic strategies show limited efficacy and can provoke serious side effects. We hypothesized that bezafibrate, a broad peroxisome proliferator-activated receptor (PPAR) agonist, relieves cholestasis-associated itch by alleviating hepatobiliary injury.

Association Between Psychological Interventions and Chronic Pain Outcomes in Older Adults: A Systematic Review and Meta-analysis.

Importance: Chronic noncancer pain (hereafter referred to as chronic pain) is common among older adults and managed frequently with pharmacotherapies that produce suboptimal outcomes. Psychological treatments are recommended, but little information is available regarding their efficacy in older adults.

Objective: To determine the efficacy of psychological interventions in older adults with chronic pain and whether treatment effects vary by participant, intervention, and study characteristics.

Problem Adaptation Therapy for Pain (PATH-Pain): A Psychosocial Intervention for Older Adults with Chronic Pain and Negative Emotions in Primary Care.

Chronic pain is highly prevalent in older adults, contributes to activity restriction and social isolation, disrupts family and interpersonal relationships, and poses a significant economic burden to society. Negative emotions such as sadness, anxiety, helplessness, and hopelessness are associated with chronic pain and contribute to poor quality of life, impaired interpersonal and social functioning, and increased disability. Psychosocial interventions for older adults with chronic pain have been historically developed for, and are almost exclusively delivered to, cognitively intact patients.

A systematic approach to the management of cholestatic pruritus in primary biliary cirrhosis.

Pruritus (itch) is an important symptom of primary biliary cirrhosis (PBC), an archetypal cholestatic liver disease. Cholestatic pruritus can be a debilitating symptom causing significant deterioration in patients' quality of life. Effective management of pruritus in PBC involves awareness among clinicians to adequately assess its severity, and treatment with specific drug therapies in line with current practice guidelines.

Fibrates for the treatment of cholestatic itch (FITCH): study protocol for a randomized controlled trial.

Background: Pruritus (itch) is a frequent, burdensome and difficult-to-treat symptom in patients with cholestasis. Fibrates are currently under investigation for the treatment of primary biliary cholangitis in patients with a suboptimal response to ursodeoxycholic acid. Moreover, there is empirical evidence for a possible antipruritic effect.

Pharmacological Approaches for the Management of Persistent Pain in Older Adults: What Nurses Need to Know.

HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS 1.4 contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity.

Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.

Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function.

ATP11C targets basolateral bile salt transporter proteins in mouse central hepatocytes.

Unlabelled: ATP11C is a homolog of ATP8B1, both of which catalyze the transport of phospholipids in biological membranes. Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis type1 in humans, which is characterized by a canalicular cholestasis. Mice deficient in ATP11C are characterized by a conjugated hyperbilirubinemia and an unconjugated hypercholanemia.

Enteroendocrine cells are a potential source of serum autotaxin in men.

Objective: Serum autotaxin (ATX) activity is significantly increased in cholestatic patients. Our study aimed to unravel the source(s) of ATX in cholestasis.

Materials And Methods: ATX activity and protein were measured in sera of healthy (n=33) and cholestatic patients (n=152), including women with intrahepatic cholestasis of pregnancy.

Pathogenesis and Management of Pruritus in PBC and PSC.

Pruritus is a preeminent symptom in patients with chronic cholestatic liver disorders such as primary biliary cirrhosis and primary sclerosing cholangitis. More than two-thirds of these patients experience itching during the course of their disease. This symptom is also frequently observed in patients with other causes of cholestasis such as cholangiocarcinoma, inherited forms of cholestasis and intrahepatic cholestasis of pregnancy, but may accompany almost any other liver disease.

Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum.

Unlabelled: A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases.

Autotaxin activity has a high accuracy to diagnose intrahepatic cholestasis of pregnancy.

Background & Aims: Intrahepatic cholestasis of pregnancy (ICP) is defined by pruritus, elevated total fasting serum bile salts (TBS) and transaminases, and an increased risk of adverse fetal outcome. An accurate diagnostic marker is needed. Increased serum autotaxin correlates with cholestasis-associated pruritus.

Lysophosphatidic acid and signaling in sensory neurons.

Lysophosphatidic acid is a potent signaling lipid molecule that has initially been characterized as a growth factor. However, later studies have revealed many more functions such as modulation of cell shape, cell migration, prevention of apoptosis, platelet aggregation, wound healing, osteoclast differentiation, vasopressor activity, embryo implantation, angiogenesis, lung fibrosis, hair growth and more. The molecule mainly acts through the activation of a set of at least 6 G-protein-coupled receptors (LPA1-6), but intracellular LPA was also shown to signal through the activation of the nuclear receptor PPARγ.

[Risks of intrahepatic cholestasis of pregnancy].

Intrahepatic cholestasis of pregnancy (ICP) is defined as pruritus during pregnancy in the absence of primary skin lesions, combined with an increase in serum total bile salts and/or abnormal serum liver tests. This article provides an insight into the diagnostic and therapeutic considerations by presenting two cases. ICP usually presents around 34 weeks of gestation, but can be present early in pregnancy as described in a 32-year-old patient pregnant after in-vitro fertilization.

Advances in pathogenesis and management of pruritus in cholestasis.

Chronic pruritus is a burdensome feature of numerous hepatobiliary disorders such as primary biliary cirrhosis, primary sclerosing cholangitis, cholangiocarcinoma, inherited forms of cholestasis and intrahepatic cholestasis of pregnancy. Bile salts, μ-opioids, serotonin, histamine and steroids have been controversially discussed in the pathogenesis of cholestatic pruritus. However, for these substances neither a correlation with itch severity nor a causative link has ever been established.

Pruritus in cholestasis: facts and fiction.

Pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. Recent findings indicate that lysophosphatidic acid (LPA), a potent neuronal activator, and autotaxin (ATX; ectonucleotide pyrophosphatase/phosphodiesterase 2), the enzyme which forms LPA, may form a key element of the long-sought pruritogenic signaling cascade in cholestatic patients suffering from itch. Serum ATX, but no other pruritogen candidate studied so far, correlates with pruritus intensity and responds to therapeutic interventions.

Advances in pathogenesis and treatment of pruritus.

The pathogenesis of itch during cholestasis is largely unknown and treatment options are limited. Lysophosphatidate, female steroid hormones, and endogenous opioids are among the agents discussed as potential pruritogens in cholestasis. The itch-alleviating action of guideline-based therapeutic interventions with anion exchanger resins, rifampicin, opioid antagonists, and serotonin reuptake inhibitors are studied to unravel the molecular pathogenesis of itch.