Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum) levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate. METHODS: MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis. RESULTS: Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 ± 3.91 ng/ml; ± interquartile range; n = 115) compared with patients with no documented diagnosis of prostate cancer (2.19 ± 2.65 ng/ml; n = 158). ELISA diluent reagents that included bovine serum albumin (BSA) significantly reduced MIF serum detection (p < 0.01). MIF mRNA was localized to prostatic epithelium in all samples, but cancer showed statistically greater MIF expression. MIF and its receptor (CD74) were localized to prostatic epithelium. Increased secreted MIF was detected in culture medium from prostate cancer cell lines (LNCaP and PC-3). CONCLUSION: Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot) found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic adenocarcinoma compared to benign tissue from matched samples, supporting our earlier finding of increased MIF gene expression in prostate cancer

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health

Challenges in detecting substances for equine anti-doping

The artificial increase of the physical capability of horses using drugs is well known in racing and other equine sports. Both illicit and therapeutic substances are regarded as prohibited substances in competition in most countries. Some countries make distinctions for a few, specific drugs which are, however, allowed for use in other countries. The primary objective in the case of doping control is the detection of any trace of drug exposure, either parent drug or any of its metabolites, using the most powerful analytical methods which are generally based on chromatographic/mass spectrometric techniques. Of major concern in horseracing is the absence of a single organization regulating the anti-doping framework; instead of this, individual racing authorities provide rules and regulations often resulting in variations in the applied doping control programmes of different countries. The aim of this paper is to review the recent literature (approximately from 2012 to mid-2016) to highlight the numerous and diverse challenges faced in doping control of racing and equestrian sports, including the detection of designer drugs (anabolic steroids or stimulants) and of other emerging prohibited substances, such as peptides and noble gases in horse urine and plasma. Moreover, the application of ‘omics’ techniques (especially of metabolomics) deserves attention for establishing possible fingerprints of drug abuse as well as the evolution of instrumental analysis resulting a powerful ally in the fight against doping in equine sports. Copyright © 2017 John Wiley &amp; Sons, Ltd. Copyright © 2017 John Wiley &amp; Sons, Ltd

Effects of chronic mild stress (CMS) on thyroid hormone function in two rat strains

This work was carried out to assess the effects of chronic mild stress (CMS) on thyroid function. The CMS model produced an anhedonic effect (reduced preference to sucrose) in Sprague-Dawley and Wistar rats and this effect was reversed by imipramine (IMI) treatment. The effects of CMS on thyroid function were assessed by measuring tT4 (total Thyroxine), tT3 (total Triiodothyronine), TSH (Thyroid Stimulating Hormone) and fT4 (free Thyroxine) serum levels with appropriate immunoassays. CMS increased tT4 and tT3 serum levels in Sprague-Dawley and Wistar rats, but not TSH and fT4 serum levels. Imipramine (IMI) treatment normalized tT4 values. Albumin which binds a fraction of peripheral tT4 and tT3 was also significantly increased in response to CMS, possibly contributing to tT4 and tT3 elevations. The above findings suggest an impact of CMS on thyroid function, especially in tT4 values the changes being reversed with IMI treatment. (C) 2000 Elsevier Science Ltd

Use of nutritional supplements contaminated with banned doping substances by recreational adolescent athletes in Athens, Greece

Although the use of nutritional supplements by adult athletes has been extensively studied, information on supplements consumption by adolescent athletes is still limited. The present study reports on the use of nutritional supplements contaminated with banned doping substances among 170 recreational adolescent athletes from eleven, randomly selected, gym centres, in Athens, Greece. Nutritional supplements consumption was reported by almost 60% of the study population, with proteins/amino acids and vitamins being the most popular. Nine per cent of the users were found to consume nutritional supplements contaminated with anabolic steroids, prohormones, selective androgen receptor modulators (SARMs) and aromatase inhibitors, all pharmacological substances with endocrine modulating properties not stated on the label. None of these individuals had previously consulted a physician or a nutritionist. A representative sample (ca 15%) of the protein/aminoacids and creatine preparations used by the study population were also tested and found free from doping substances. The majority (63%) of adolescents purchased products from the internet. In conclusion, exercising adolescents can have easy access to contaminated nutritional supplements and “black market” products, which could constitute a risk for public health. Low level of awareness and low involvement of medical care professionals among recreational adolescent athletes is also observed. © 2018 Elsevier Lt

The effects of stress exposure on the hypothalamic-pituitary-adrenal axis, thymus, thyroid hormones and glucose levels

In the present study, an attempt was made to compare three stress models and their effects on the hypothalamic-pituitary-adrenal (HPA) axis, the thymus, the thyroid hormones and the glucose levels. The three different stress models were the chronic mild stress (CMS), the 14-day and the 1-day cold swim stress model. The CMS procedure caused a decrease in thymus weight and rendered no changes on glucose, the adrenocorticotropin hormone (ACTH) or the adrenals. Administration of imipramine (IMI) after the third week of CMS did not reverse the decrease in thymus weight. The 14-day cold swim stress doubled ACTH levels and the adrenal weight and reduced thymus weight, while total thyroxine (tT4), total triiodothyronine (tT3) and glucose levels were unaffected. IMI treatment restored the weights of the adrenal and thymus glands. One-day cold swim stress did not induce any statistically significant effect on the tested physiological parameters. The above findings indicate a distinct effect of the 14-day cold swim stress on HPA axis. Relative to CMS or the 14-day cold swim stress, no effect was induced by the 1-day cold swim stress. The IMI restoring effect, especially in the case of the 14-day cold swim stress, also suggests an association of antidepressant effect with the duration of drug treatment. © 2002 Elsevier Science Inc. All rights reserved

Human in vivo metabolism study of LGD-4033

Selective androgen receptor modulators (SARMs) are an emerging class of therapeutics targeted to cachexia, sarcopenia, and hypogonadism treatment. LGD-4033 is a SARM which has been included on the Prohibited List annually released by the World Anti-Doping Agency (WADA). The aim of the present work was the investigation of the metabolism of LGD-4033 in a human excretion study after administration of an LGD-4033 supplement, the determination of the metabolites&apos; excretion profiles with special interest in the determination of its long-term metabolites, and the comparison of the excretion time of the phase I and phase II metabolites. The results were also compared to those derived from previous LGD-4033 studies concerning both in vitro and in vivo experiments. Supplement containing LGD-4033 was administered to one human male volunteer and urine samples were collected up to almost 21 days. Analysis of the hydrolyzed (with β-glucuronidase) as well as of the non-hydrolyzed samples was performed using liquid chromatography–high resolution mass spectrometry (LC–HRMS) in negative ionization mode and revealed that, in both cases, the two isomers of the dihydroxylated metabolite (M5) were preferred target metabolites. The gluco-conjugated parent LGD-4033 and its gluco-conjugated metabolites M1 and M2 can be also considered as useful target analytes in non-hydrolyzed samples. The study also presents two trihydroxylated metabolites (M6) identified for the first time in human urine; one of them was recently reported in an LGD-4033 metabolism study in horse urine and plasma. © 2018 John Wiley &amp; Sons, Ltd