NTx 428 regimen(Trillium Therapeutics, Inc.)

The full extent of doping in sport and exercise is unknown. Drugs are often used to increase muscle mass (anabolic drugs), decrease fat muscle (lipolytic drugs) or increase oxygen delivery to tissues. They have also been used to improve mood, steadiness, fatigue, confidence, euphoria, tolerance to pain, relaxation, alertness, concentration and reaction time. Diuresis to bring about a reduction in body weight is well recognised. The review by Bird, Greaves and Burke covers the history of doping in sport and, importantly, focuses on the manifold health risks: acne, virilisation, deepening of the voice, infertility, subdural haematomas, tendon injuries, altered liver and kidney function, peripheral oedema, cardiac hypertrophy, myocardial ischaemia and thrombosis. Some of these are irreversible and many drugs pose health risks including cardiovascular disease and death. Some drugs are taken to counteract the side-effects of the abused drugs. For example, aromatase inhibitors and selective oestrogens receptor modulators (SERMs) are sometimes taken to mask the gynaecomastia caused by anabolic steroid abuse. Doping control was introduced in 1968 by the International Olympic Committee (IOC). Initially amphetamines were the target of testing; anabolic steroids were added in 1974. Subsequently a wide range of drugs and drug groups have been added: beta-blockers, sympathomimetics, diuretics, narcotics, growth hormone, glucocorticosteroids and erythropoeitin. In recent years tests have been developed for dextrans, insulins, adiponectin receptor agonists, mechanogrowth factor (MGF), selective androgen receptor modulators (SARMs), peroxisome proliferator activated receptor (PPAR) gamma agonists, sirtuin activating compounds, erythropoiesis stimulating agents, gonadotrophins and releasing hormones. Initially, drug tests set out to detect pharmaceuticals which do not occur in the body. However, the detection of abuse of natural substances has been a challenge for the doping laboratories. ‘‘Natural’’ hormones can be produced commercially by chemical and in vitro techniques for recombinant proteins. Also, since drug testing has largely used urine samples, abuse of natural substances cannot be reliably detected from an increased concentration in the sample. Moreover, adulteration of samples with chemicals and enzymes is an additional problem. Tests therefore have been developed for metabolites and for disturbances of a hormonal axis. An additional approach has been to look for altered isotope ratios. For example, steroids for human use are produced from plant sterols. These have different carbon 12/carbon 13 isotope ratios from endogenous human steroids, allowing this difference to be exploited by testing. Drug testing in sport was originally based exclusively on collection of samples immediately after a race or competition, but awareness of this possibility meant that illicit use of performance-enhancing substances was timed so that the predictable timing of sampling coincided with a drug-free period (in contemporary parlance, the athlete had stopped ‘glowing’ by the time of sample collection). Unannounced (i.e. minimal warning) out-of-competition testing is therefore used in addition. Another comparatively recent development has been the introduction of long-term blood monitoring of various haematological parameters (providing the so-called athlete’s ‘biological passport’). Changes in the parameters may indicate drug abuse, warranting additional confirmatory testing. This approach was

The ability to cryopreserve and store for long term the structure and function of therapeutic cells and tissues plays a pivotal role in clinical medicine. In fact, it is an essential pre-requisite for the commercial and clinical application of stem cells since preserves cells at low temperature and creates a reserve for future uses. This requisite may also affect the encapsulated stem cells. Several parameters should be considered on encapsulated cell cryopreservation such as the time and temperature during the cryopreservation process, or the cryoprotectant solutions used. In this study, we have compared the influence of penetrating and nonpenetrating cryoprotectants on the viability and functionality of encapsulated mesenchymal stem cells genetically modified to secrete erythropoeitin. Several cryoprotectant solutions combining DMSO, glycerol and trehalose at different concentrations were studied. Although almost no differences among the studied cryoprotectant solutions were observed on the differentiation potential of encapsulated mesenchymal stem cells, the penetrating cryoprotectant DMSO at a concentration of 10% displayed the best viability and erythropoietin secretion profile compared to the other cryoprotectant solutions. These results were confirmed after subcutaneous implantation of thawed encapsulated mesenchymal stem cells secreting erythropoeitin on Balb/c mice. The hematocrit levels of these animals increased to similar levels of those detected on animals transplanted with noncryopreserved encapsulated cells. Therefore, DMSO 10% represents the most suitable cryoprotectant solution among the solutions here studied, for encapsulated mesenchymal stem cells cryopreservation and its translation into the clinic. Similar studies should be performed for the encapsulation of other cell types before they can be translated into the clinic.