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Mario Thevis - One of the best experts on this subject based on the ideXlab platform.
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Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS
Analytical and Bioanalytical Chemistry, 2016Co-Authors: Andre Knoop, Eric Fichant, Andreas Thomas, Philippe Delahaut, Wilhelm Schanzer, Mario ThevisAbstract:The use of growth hormone-releasing hormones (GHRHs) is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA). The aim of the present study was to develop a method for the simultaneous detection of four different GHRHs and respective metabolites from human plasma by means of immunoaffinity purification and subsequent nano-ultrahigh performance liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry. The target analytes included Geref (Sermorelin), CJC-1293, CJC-1295, and Egrifta (Tesamorelin) as well as two metabolites of Geref and CJC-1293, which were captured from plasma samples using a polyclonal GHRH antibody in concert with protein A/G monolithic MSIA™ D.A.R.T.’S® (Disposable Automation Research Tips) prior to separation and detection. The method was fully validated and found to be fit for purpose considering the parameters specificity, linearity, recovery (19–37 %), lower limit of detection (
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Expanded test method for peptides >2 kDa employing immunoaffinity purification and LC-HRMS/MS.
Drug Testing and Analysis, 2015Co-Authors: Andreas Thomas, Eric Fichant, Philippe Delahaut, Wilhelm Schanzer, Katja Walpurgis, Laura Tretzel, Paul Thomas Brinkkötter, Mario ThevisAbstract:Bioactive peptides with an approximate molecular mass of 2-12 kDa are of considerable relevance in sports drug testing. Such peptides have been used to manipulate several potential performance-enhancing processes in the athlete's body and include for example growth hormone releasing hormones (Sermorelin, CJC-1293, CJC-1295, tesamorelin), synthetic/animal insulins (lispro, aspart, glulisine, glargine, detemir, degludec, bovine and porcine insulin), synthetic ACTH (synacthen), synthetic IGF-I (longR(3) -IGF-I) and mechano growth factors (human MGF, modified human MGF, 'full-length' MGF). A combined initial test method using one analytical procedure is a desirable tool in doping controls and related disciplines as requests for higher sample throughput with utmost comprehensiveness preferably at reduced costs are constantly issued. An approach modified from an earlier assay proved fit-for-purpose employing pre-concentration of all target analytes by means of ultrafiltration, immunoaffinity purification with coated paramagnetic beads, nano-ultra high performance liquid chromatography (UHPLC) separation, and subsequent detection by means of high resolution tandem mass spectrometry. The method was shown to be applicable to blood and urine samples, which represent the most common doping control specimens. The method was validated considering the parameters specificity, recovery (11-69%), linearity, imprecision (
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Mass Spectrometry in Sports Drug Testing: Characterization of Prohibited Substances and Doping Control Analytical Assays
2010Co-Authors: Mario ThevisAbstract:Preface. Acknowledgments. 1 History of Sports Drug Testing. 1.1 Historical Attempts of Artificial Performance Enhancement. 1.2 Background and Rationale of Doping Controls. 1.3 Early Detection Methods: Possibilities and Limitations of Assays Without Mass Spectrometry. 1.4 Introduction of Mass Spectrometry to Doping Control Analysis. References. 2. Mass Spectrometry and the List of Prohibited Substances and Methods of Doping. 2.1 Criteria for the Mass Spectrometric Identification of Prohibited Compounds. 2.2 Modern Mass Spectrometers in Doping Controls: Advantages and Disadvantages of Available Techniques. References. 3. Structure Characterization of Low Molecular Weight Target Analytes Electron Ionization. 3.1 Stimulants. 3.2 Narcotics. 3.3 Anabolic Androgenic Steroids. 3.4 Selective Androgen Receptor Modulators (SARMs). 3.5 Diuretics. 3.6 2-Agonists. 3.7 -Receptor Blocking Agents. 3.8 Calcium-Channel Modulators (RYCALS). 3.9 Carbohydrate-Based Agents. References. 4. Structure Characterization of Low Molecular Weight Target Analytes: Electrospray Ionization. 4.1 Stimulants. 4.2 Narcotics. 4.3 Anabolic Androgenic Steroids. 4.4 Selective Androgen Receptor Modulators (SARMs). 4.5 Diuretics. 4.6 2-Agonists. 4.7 Calcium-Channel Modulators (RYCALS). 4.8 Peroxisome-Proliferator Activated Receptor- (PPAR ) And Adenosine Monophosphate Activated Protein Kinase (AMPK) Agonists. 4.9 Hypoxia-Inducible Factor (HIF)-Stabilizers And Sirtuin Activators. 4.10 -Receptor Blocking Agents. 4.11 Glucuronic Acid and Sulfate Conjugates of Target Analytes. References. 5. Structure Characterization of High Molecular Weight Target Analytes: Electrospray Ionization. 5.1 Human Chorionic Gonadotrophin (hCG). 5.2 Erythropoietins (EPO). 5.3 Synacthen. 5.4 Insulins. 5.5 Hemoglobin-Based Oxygen Carriers (HBOCs). 5.6 Human Growth Hormone (hGH). 5.7 Sermorelin (Geref). 5.8 Insulin-Like Growth Factor-1 (IGF-1). 5.9 Gonadorelin (LHRH). References. 6. Modern Mass Spectrometry-Based Analytical Assays. 6.1 GC-MS and Isotope Ratio Mass Spectrometry. 6.2 LC-MS/MS. References. 7. Limitations and Perspectives of Mass Spectrometry-Based Procedures in Doping Control Analysis. 7.1 Recombinant Biomolecules. 7.2 Unknown Compounds. 7.3 Profiling of Urine and/or Blood. 7.4 Alternative Specimens. References. Index.
Frankenne Francis - One of the best experts on this subject based on the ideXlab platform.
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Perinatal growth hormone (GH) physiology : effect of GH-releasing factor on maternal and fetal secretion of pituitary and placental GH.
'The Endocrine Society', 1990Co-Authors: De Zegher F., Vanderschueren-lodeweyckx M., Spitz B., Faijerson Y., Blomberg F., Beckers Albert, Hennen Georges, Frankenne FrancisAbstract:peer reviewedaudience: researcher, professionalTo study regulation of the secretion of human pituitary GH (hGH) and placental GH (hPGH) in the pregnant woman and human fetus, the GH-releasing factor Sermorelin [GRF-(l–29)-NH2] was administered to pregnant women at term (n = 5), just before elective cesarean section; saline was administered in control studies (n = 5). The effects of GRF-(1–29)-NH2 administration on maternal and fetal serum concentrations of hGH and GRF-(l–29)-NH2 and maternal serum levels of hPGH were evaluated at birth. The mean time span between injection and birth was 20 min (range, 15–25 min). Cord serum hGH concentrations were similar in infants of GRF-(1–29)-NH2-injected mothers and control infants. GRF-(l–29)-NH2 elicited a consistent but small rise in maternal hGH serum concentrations (P = 0.08), whereas hPGH concentrations remained unaltered. Finally, GRF-(l–29)-NH2 concentrations were undetectable in cord serum, but readily detectable in concomitantly obtained maternal serum. In conclusion, these data suggest that hGH secretion in the pregnant woman at term is suppressed at the pituitary level, that GRF does not affect hPGH secretion, and that fetal hGH secretion is independent of circulating maternal GRF, probably because of lack of transplacental GRF passage
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Perinatal growth hormone (GH) physiology : effect of GH-releasing factor on maternal and fetal secretion of pituitary and placental GH.
1990Co-Authors: De Zegher F., Vanderschueren-lodeweyckx M., Spitz B., Faijerson Y., Blomberg F., Beckers Albert, Hennen Georges, Frankenne FrancisAbstract:To study regulation of the secretion of human pituitary GH (hGH) and placental GH (hPGH) in the pregnant woman and human fetus, the GH-releasing factor Sermorelin [GRF-(l–29)-NH2] was administered to pregnant women at term (n = 5), just before elective cesarean section; saline was administered in control studies (n = 5). The effects of GRF-(1–29)-NH2 administration on maternal and fetal serum concentrations of hGH and GRF-(l–29)-NH2 and maternal serum levels of hPGH were evaluated at birth. The mean time span between injection and birth was 20 min (range, 15–25 min). Cord serum hGH concentrations were similar in infants of GRF-(1–29)-NH2-injected mothers and control infants. GRF-(l–29)-NH2 elicited a consistent but small rise in maternal hGH serum concentrations (P = 0.08), whereas hPGH concentrations remained unaltered. Finally, GRF-(l–29)-NH2 concentrations were undetectable in cord serum, but readily detectable in concomitantly obtained maternal serum. In conclusion, these data suggest that hGH secretion in the pregnant woman at term is suppressed at the pituitary level, that GRF does not affect hPGH secretion, and that fetal hGH secretion is independent of circulating maternal GRF, probably because of lack of transplacental GRF passage.Peer reviewe
Karen L. Goa - One of the best experts on this subject based on the ideXlab platform.
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Sermorelin
BioDrugs, 1999Co-Authors: Amitabh Prakash, Karen L. GoaAbstract:Sermorelin, a 29 amino acid analogue of human growth hormone-releasing hormone (GHRH), is the shortest synthetic peptide with full biological activity of GHRH. Intravenous and subcutaneous Sermorelin specifically stimulate growth hormone secretion from the anterior pituitary. Hormone responses to intravenous Sermorelin 1μg/kg bodyweight appear to be a rapid and relatively specific test for the diagnosis of growth hormone deficiency. False positive growth hormone responses are observed in fewer children without growth hormone deficiency after Sermorelin than after other provocative tests. Adult data indicate that the combination of intravenous Sermorelin and arginine is a more specific test and this merits evaluation in children with growth hormone deficiency. However, normal growth hormone responses to intravenous Sermorelin cannot exclude growth hormone deficiency due to a hypothalamic deficit: subnormal growth hormone response to other provocative tests is needed to confirm the presence of disease in these patients. Limited data indicate that once daily subcutaneous Sermorelin 30 μg/kg bodyweight given at bedtime is effective in treating some prepubertal children with idiopathic growth hormone deficiency. Significant increases in height velocity were sustained during 12 months’ treatment with Sermorelin and data in a few children suggest the effect is maintained for 36 months of continued treatment. Sermorelin induced catch-up growth in the majority of growth hormone-deficient children. Slow growing, shorter children with delayed bone and height age appear to have a good response to treatment with Sermorelin. The effect of long term treatment with once daily subcutaneous Sermorelin 30 μg/kg bodyweight on final adult height is yet to be determined. The effects of the recommended dosage of Sermorelin have not been directly compared with those of somatropin. However, increases in height velocity from baseline values with subcutaneous Sermorelin 30 μg/kg bodyweight per day, given as continuous infusion or as 3 divided doses, were less than those in children receiving once daily subcutaneous somatropin 30 μg/kg bodyweight. Intravenous single dose and repeated once daily subcutaneous doses of Sermorelin are well tolerated. Transient facial flushing and pain at injection site were the most commonly reported adverse events. Conclusions : Sermorelin is a well tolerated analogue of GHRH which is suitable for use as a provocative test of growth hormone deficiency when given as a single intravenous 1 μg/kg bodyweight dose in conjunction with conventional tests. Limited data suggest that once daily subcutaneous Sermorelin 30 μg/kg bodyweight is effective in promoting growth in some prepubertal children with idiopathic growth hormone deficiency.
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Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency.
BioDrugs, 1999Co-Authors: Amitabh Prakash, Karen L. GoaAbstract:UNLABELLED Sermorelin, a 29 amino acid analogue of human growth hormone-releasing hormone (GHRH), is the shortest synthetic peptide with full biological activity of GHRH. Intravenous and subcutaneous Sermorelin specifically stimulate growth hormone secretion from the anterior pituitary. Hormone responses to intravenous Sermorelin 1 microg/kg bodyweight appear to be a rapid and relatively specific test for the diagnosis of growth hormone deficiency. False positive growth hormone responses are observed in fewer children without growth hormone deficiency after Sermorelin than after other provocative tests. Adult data indicate that the combination of intravenous Sermorelin and arginine is a more specific test and this merits evaluation in children with growth hormone deficiency. However, normal growth hormone responses to intravenous Sermorelin cannot exclude growth hormone deficiency due to a hypothalamic deficit: subnormal growth hormone response to other provocative tests is needed to confirm the presence of disease in these patients. Limited data indicate that once daily subcutaneous Sermorelin 30 microg/kg bodyweight given at bedtime is effective in treating some prepubertal children with idiopathic growth hormone deficiency. Significant increases in height velocity were sustained during 12 months' treatment with Sermorelin and data in a few children suggest the effect is maintained for 36 months of continued treatment. Sermorelin induced catch-up growth in the majority of growth hormone-deficient children. Slow growing, shorter children with delayed bone and height age appear to have a good response to treatment with Sermorelin. The effect of long term treatment with once daily subcutaneous Sermorelin 30 microg/kg bodyweight on final adult height is yet to be determined. The effects of the recommended dosage of Sermorelin have not been directly compared with those of somatropin. However, increases in height velocity from baseline values with subcutaneous Sermorelin 30 microg/kg bodyweight per day, given as continuous infusion or as 3 divided doses, were less than those in children receiving once daily subcutaneous somatropin 30 microg/kg bodyweight. Intravenous single dose and repeated once daily subcutaneous doses of Sermorelin are well tolerated. Transient facial flushing and pain at injection site were the most commonly reported adverse events. CONCLUSIONS Sermorelin is a well tolerated analogue of GHRH which is suitable for use as a provocative test of growth hormone deficiency when given as a single intravenous 1 microg/kg bodyweight dose in conjunction with conventional tests. Limited data suggest that once daily subcutaneous Sermorelin 30 microg/kg bodyweight is effective in promoting growth in some prepubertal children with idiopathic growth hormone deficiency.
Larry I. Lipshultz - One of the best experts on this subject based on the ideXlab platform.
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Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males
Translational Andrology and Urology, 2020Co-Authors: Deepankar K Sinha, Alexander W. Pastuszak, Adithya Balasubramanian, Alexander J. Tatem, Jorge Rivera-mirabal, Jason R. Kovac, Larry I. LipshultzAbstract:Male hypogonadism is an increasingly prevalent clinical condition that affects patients' quality of life and overall health. Obesity and metabolic syndrome can both cause and result from hypogonadism. Although testosterone remains the gold standard for hypogonadism management, its benefits are not always conserved across different populations, especially with regards to changes in body composition. Partially in response to this, growth hormone secretagogues (GHS) have emerged as a potential novel adjunctive therapy for some of the symptoms of hypogonadism, although current data on their clinical efficacy largely remain lacking. The present review examines the existing literature on the use of GHS and explores their potential complementary role in the management of hypogonadal and eugonadal males with metabolic syndrome or subclinical hypogonadism (SH). The GHS that will be discussed include Sermorelin, growth hormone-releasing peptides (GHRP)-2, GHRP-6, ibutamoren, and ipamorelin. All are potent GH and IGF-1 stimulators that can significantly improve body composition while ameliorating specific hypogonadal symptoms including fat gain and muscular atrophy. However, a paucity of data examining the clinical effects of these compounds currently limits our understanding of GHS' role in the treatment of men with hypogonadism, but does open opportunities for future investigation.
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Growth Hormone Secretagogue Treatment in Hypogonadal Men Raises Serum Insulin-Like Growth Factor-1 Levels.
American Journal of Men's Health, 2017Co-Authors: John T. Sigalos, Alexander W. Pastuszak, Andrew Allison, Samuel Ohlander, Amin S. Herati, Mark C. Lindgren, Larry I. LipshultzAbstract:Realizing the reported misuse of human growth hormone (GH), investigation of a safe alternative mechanism for increasing endogenous GH is needed. Several GH secretagogues are available, including GH-releasing peptides (GHRPs) GHRP-2 and GHRP-6, and the GH-releasing hormone analog, Sermorelin (SERM). Insulin-like growth factor 1 (IGF-1) serves as a surrogate marker for GH. Here, the effect of GHRP/SERM therapy on IGF-1 levels is evaluated. A retrospective review of medical records was performed for 105 men on testosterone (T) therapy seeking increases in lean body mass and fat loss who were prescribed 100 mcg of GHRP-6, GHRP-2, and SERM three times daily. Compliance with therapy was assessed, and 14 men met strict inclusion criteria. Serum hormone levels of IGF-1, T, free T (FT), estradiol (E), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were evaluated. Mean (SD) age of the cohort was 33.2 (2.9) years, and baseline IGF-1 level was 159.5 (26.7) ng/mL. Mean (SD) duration of continuous GH...
De Zegher F. - One of the best experts on this subject based on the ideXlab platform.
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Perinatal growth hormone (GH) physiology : effect of GH-releasing factor on maternal and fetal secretion of pituitary and placental GH.
'The Endocrine Society', 1990Co-Authors: De Zegher F., Vanderschueren-lodeweyckx M., Spitz B., Faijerson Y., Blomberg F., Beckers Albert, Hennen Georges, Frankenne FrancisAbstract:peer reviewedaudience: researcher, professionalTo study regulation of the secretion of human pituitary GH (hGH) and placental GH (hPGH) in the pregnant woman and human fetus, the GH-releasing factor Sermorelin [GRF-(l–29)-NH2] was administered to pregnant women at term (n = 5), just before elective cesarean section; saline was administered in control studies (n = 5). The effects of GRF-(1–29)-NH2 administration on maternal and fetal serum concentrations of hGH and GRF-(l–29)-NH2 and maternal serum levels of hPGH were evaluated at birth. The mean time span between injection and birth was 20 min (range, 15–25 min). Cord serum hGH concentrations were similar in infants of GRF-(1–29)-NH2-injected mothers and control infants. GRF-(l–29)-NH2 elicited a consistent but small rise in maternal hGH serum concentrations (P = 0.08), whereas hPGH concentrations remained unaltered. Finally, GRF-(l–29)-NH2 concentrations were undetectable in cord serum, but readily detectable in concomitantly obtained maternal serum. In conclusion, these data suggest that hGH secretion in the pregnant woman at term is suppressed at the pituitary level, that GRF does not affect hPGH secretion, and that fetal hGH secretion is independent of circulating maternal GRF, probably because of lack of transplacental GRF passage
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Perinatal growth hormone (GH) physiology : effect of GH-releasing factor on maternal and fetal secretion of pituitary and placental GH.
1990Co-Authors: De Zegher F., Vanderschueren-lodeweyckx M., Spitz B., Faijerson Y., Blomberg F., Beckers Albert, Hennen Georges, Frankenne FrancisAbstract:To study regulation of the secretion of human pituitary GH (hGH) and placental GH (hPGH) in the pregnant woman and human fetus, the GH-releasing factor Sermorelin [GRF-(l–29)-NH2] was administered to pregnant women at term (n = 5), just before elective cesarean section; saline was administered in control studies (n = 5). The effects of GRF-(1–29)-NH2 administration on maternal and fetal serum concentrations of hGH and GRF-(l–29)-NH2 and maternal serum levels of hPGH were evaluated at birth. The mean time span between injection and birth was 20 min (range, 15–25 min). Cord serum hGH concentrations were similar in infants of GRF-(1–29)-NH2-injected mothers and control infants. GRF-(l–29)-NH2 elicited a consistent but small rise in maternal hGH serum concentrations (P = 0.08), whereas hPGH concentrations remained unaltered. Finally, GRF-(l–29)-NH2 concentrations were undetectable in cord serum, but readily detectable in concomitantly obtained maternal serum. In conclusion, these data suggest that hGH secretion in the pregnant woman at term is suppressed at the pituitary level, that GRF does not affect hPGH secretion, and that fetal hGH secretion is independent of circulating maternal GRF, probably because of lack of transplacental GRF passage.Peer reviewe
