Trends in the Detection of Erythropoietin Receptor Agonists (ERAs) in Anti-Doping: An Analysis of Recent Adverse Analytical Findings (AAFs).

Anti-doping efforts aim to reduce the prevalence of doping through a combination of education, deterrence, and detection. Detection of doping practices, for example through testing and/or investigations, aims both to catch committed dopers and deter potential dopers. To date, little empirical evidence is available examining the ability of detection strategies to deter athletes from doping.

Biological Variation Data in Triathletes for Metabolism and Growth-Related Biomarkers Included in the Athlete Biological Passport.

Background: When using biological variation (BV) data, BV estimates need to be robust and representative. High-endurance athletes represent a population under special physiological conditions, which could influence BV estimates. Our study aimed to estimate BV in athletes for metabolism and growth-related biomarkers involved in the Athlete Biological Passport (ABP), by 2 different statistical models.

Longitudinal Profiling of Endogenous Steroids in Blood Using the Athlete Biological Passport Approach.

Context: Detection of endogenous anabolic androgenic steroids (EAAS), like testosterone (T), as doping agents has been improved with the launch of the Steroidal Module of the Athlete Biological Passport (ABP) in urine samples.

Objective: To target doping practices with EAAS, particularly in individuals with low level of biomarkers excreted in urine, by including new target compounds measured in blood.

Design: T and T/androstenedione (T/A4) distributions were obtained from 4 years of anti-doping data and applied as priors to analyze individual profiles from 2 T administration studies in female and male subjects.

Long-Term Within- and Between-Subject Biological Variation Data of Hematological Parameters in Recreational Endurance Athletes.

Background: Hematological parameters have many applications in athletes, from monitoring health to uncovering blood doping. This study aimed to deliver biological variation (BV) estimates for 9 hematological parameters by a Biological Variation Data Critical Appraisal Checklist (BIVAC) design in a population of recreational endurance athletes and to assess the effect of self-reported exercise and health-related variables on BV.

Methods: Samples were drawn from 30 triathletes monthly for 11 months and measured in duplicate for hematological measurands on an Advia 2120 analyzer (Siemens Healthineers).

The Proteomic Signature of Recombinant Growth Hormone in Recreational Athletes.

Objective: Administration of human growth hormone (hGH) is prohibited in competitive sport and its detection in an athlete's sample triggers an adverse analytical finding. However, the biological processes that are modulated by recombinant hGH are not well characterized and associated blood serum proteins may constitute new biomarkers for hGH misuse.

Methods: Thirty-five recreational athletes were enrolled in a study to investigate the time- and dose-dependent response of serum protein levels to recombinant hGH administration.

Application of the Athlete Biological Passport Approach to the Detection of Growth Hormone Doping.

Context: Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population-derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay.

Objective: We tested the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse.

Standardization of reticulocyte counts in the athlete biological passport: A practical update.

Introduction: The athlete biological passport monitors blood variables over time to uncover blood doping. With the phasing in of a new series of blood analyzers, the Sysmex XN series, it was necessary to examine the comparability of results with the previously employed XT/XE series. A previous comparison between XN and XT/XE series suggested a small but significant bias between the two instruments in the measurements of RET%.

Biomarkers of doping: uses, discovery and validation.

A biomarker of doping indicates the biological response to the use of a prohibited substance or method. Uncovering novel biomarkers of doping is a key objective in order to improve antidoping outcomes such as the detection of doping and changing athlete behavior toward doping practices. While the antidoping field has been successful in validating novel metabolites of prohibited substances, there has been less success in developing new biomarkers of doping.

Standardization of reticulocyte counts in the athlete biological passport.

Introduction: The percentage of circulating reticulocytes (RET%) is a useful marker of blood doping in the context of the Athlete Biological Passport (ABP). The viability of the ABP depends on the comparability of sample data obtained across multiple laboratories for a given athlete. With the recent introduction of a different technology for the measurement of reticulocytes, the goal of this study was to compare currently employed Sysmex XT/XE analyzers to the recently introduced Sysmex XN analyzer.

Decreased PCSK9 expression in human hepatocellular carcinoma.

Background: The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration.

A genome-wide RNAi screen identifies regulators of cholesterol-modified hedgehog secretion in Drosophila.

Hedgehog (Hh) proteins are secreted molecules that function as organizers in animal development. In addition to being palmitoylated, Hh is the only metazoan protein known to possess a covalently-linked cholesterol moiety. The absence of either modification severely disrupts the organization of numerous tissues during development.

Analysis of beta-cell gene expression reveals inflammatory signaling and evidence of dedifferentiation following human islet isolation and culture.

The stresses encountered during islet isolation and culture may have deleterious effects on beta-cell physiology. However, the biological response of human islet cells to isolation remains poorly characterized. A better understanding of the network of signaling pathways induced by islet isolation and culturing may lead to strategies aimed at improving islet graft survival and function.

Evidence of endoplasmic reticulum stress mediating cell death in transplanted human islets.

A key limitation to the success of islet transplantation is islet cell exhaustion and cell death during islet isolation and following transplantation. Endoplasmic reticulum (ER) stress has been identified as an important mechanism in the development of β-cell dysfunction, cell death, and diabetes. This study investigated the role of ER stress in islet loss during human islet isolation and posttransplantation in a diabetic athymic mouse model.

Proinflammatory cytokines activate the intrinsic apoptotic pathway in beta-cells.

Objective: Proinflammatory cytokines are cytotoxic to beta-cells and have been implicated in the pathogenesis of type 1 diabetes and islet graft failure. The importance of the intrinsic mitochondrial apoptotic pathway in cytokine-induced beta-cell death is unclear. Here, cytokine activation of the intrinsic apoptotic pathway and the role of the two proapoptotic Bcl-2 proteins, Bad and Bax, were examined in beta-cells.

The role of kinases in the Hedgehog signalling pathway.

The Hedgehog (Hh) signalling pathway has a crucial role in several developmental processes and is aberrantly activated in a variety of cancers. In Drosophila, many of the canonical Hh pathway components are phosphorylated, yet the precise role of these phosphorylation events in the regulation of Hh signal transduction is unclear. Furthermore, the Hh pathway receives input from several kinases that have well-described roles in other cellular functions, some of which have both positive and negative effects on Hh signalling.

Islet neogenesis: a potential therapeutic tool in type 1 diabetes.

Current therapies for type 1 diabetes, including fastidious blood glucose monitoring and multiple daily insulin injections, are not sufficient to prevent complications of the disease. Though pancreas and possibly islet transplantation can prevent the progression of complications, the scarcity of donor organs limits widespread application of these approaches. Understanding the mechanisms of beta-cell mass expansion as well as the means to exploit these pathways has enabled researchers to develop new strategies to expand and maintain islet cell mass.

Islet neogenesis: a potential therapeutic tool in type 1 diabetes.

Current therapies for type 1 diabetes, including fastidious blood glucose monitoring and multiple daily insulin injections, are not sufficient to prevent complications of the disease. Though pancreas and possibly islet transplantation can prevent the progression of complications, the scarcity of donor organs limits widespread application of these approaches. Understanding the mechanisms of beta-cell mass expansion as well as the means to exploit these pathways has enabled researchers to develop new strategies to expand and maintain islet cell mass.

Cross-talk between phosphatidylinositol 3-kinase/AKT and c-jun NH2-terminal kinase mediates survival of isolated human islets.

Therapeutic strategies aimed at the inhibition of specific cell death mechanisms may increase islet yield and improve cell viability and function after routine isolation. The aim of the current study was to explore the possibility of AKT-JNK cross-talk in islets after isolation and the relevance of c-jun NH2-terminal kinases (JNK) suppression on islet survival. After routine isolation, increased AKT activity correlated with suppression of JNK activation, suggesting that they may be related events.

Inhibition of caspase-mediated PARP-1 cleavage results in increased necrosis in isolated islets of Langerhans.

The current procedure for isolation of islet cells from the pancreas for transplantation by enzymatic digestion is accompanied by significant islet cell loss. Therapeutic strategies aimed at the inhibition of islet cell damage could be expected to increase islet yield and improve cell viability, thereby making more efficient use of available donor tissue. The aim of the present work was to examine the effects of caspase and PARP-1 inhibition on islet survival.