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Laurie R Braun, Meghan N Feldpausch, Natalia Czerwonka, Martin Torriani, Steven K Grinspoon, Takara L Stanley
OBJECTIVE: Fibroblast growth factor 21 (FGF21) ameliorates steatohepatitis but is increased in humans with fatty liver, potentially due to compensatory mechanisms and/or FGF21 resistance. Further, animal models suggest that GH increases serum FGF21. Tesamorelin, a growth hormone releasing hormone agonist, reduces liver fat in HIV-infected individuals. The objectives of this study were to investigate changes in FGF21 during tesamorelin treatment, to elucide the interplay between FGF21, GH augmentation, and liver fat reduction in humans...
December 2017: Growth Hormone & IGF Research
Lindsay T Fourman, Natalia Czerwonka, Meghan N Feldpausch, Julian Weiss, Jean-Claude Mamputu, Julian Falutz, Josée Morin, Christian Marsolais, Takara L Stanley, Steven K Grinspoon
OBJECTIVE: Tesamorelin reduces visceral adipose tissue (VAT) in HIV. We investigated whether reductions in VAT with tesamorelin are associated with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). DESIGN AND METHODS: We utilized data from two multicenter Phase III trials of tesamorelin among 806 HIV-infected patients with abdominal obesity. These studies showed that the majority of patients treated with tesamorelin are 'responders', defined a priori by the Food and Drug Administration as achieving at least 8% reduction in VAT...
October 23, 2017: AIDS
Paolo Maggi, Antonio Di Biagio, Stefano Rusconi, Stefania Cicalini, Maurizio D'Abbraccio, Gabriella d'Ettorre, Canio Martinelli, Giuseppe Nunnari, Laura Sighinolfi, Vincenzo Spagnuolo, Nicola Squillace
BACKGROUND: Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? DISCUSSION: Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments...
August 9, 2017: BMC Infectious Diseases
David R Clemmons, Sam Miller, Jean-Claude Mamputu
OBJECTIVE: Use of growth hormone is associated with side effects, including insulin resistance. The objective of this study was to determine whether tesamorelin, a stabilized growth hormone-releasing hormone analogue, would alter insulin sensitivity or control of diabetes. DESIGN: A 12-week randomized, placebo-controlled study of 53 patients with type 2 diabetes. Three treatment groups: placebo, 1 and 2 mg tesamorelin. MEASUREMENTS: Fasting glucose, glucose and insulin from oral glucose tolerance test, glycosylated hemoglobin (HbA1c), home blood glucose, insulin-like growth factor-1, and lipids...
2017: PloS One
Andre Knoop, Andreas Thomas, Eric Fichant, Philippe Delahaut, Wilhelm Schänzer, Mario Thevis
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...
May 2016: Analytical and Bioanalytical Chemistry
Alexandra Mangili, Julian Falutz, Jean-Claude Mamputu, Miganush Stepanians, Brooke Hayward
BACKGROUND: Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy. OBJECTIVES: 1) To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF) or the National Cholesterol Education Program (MetS-NCEP) and the Framingham Risk Score (FRS), as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2) To explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin...
2015: PloS One
Andreas Thomas, Katja Walpurgis, Laura Tretzel, Paul Brinkkötter, Eric Fichant, Philippe Delahaut, Wilhelm Schänzer, Mario Thevis
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)...
November 2015: Drug Testing and Analysis
Mario González-Sales, Olivier Barrière, Pierre Olivier Tremblay, Fahima Nekka, Jean-Claude Mamputu, Sylvie Boudreault, Mario Tanguay
BACKGROUND AND OBJECTIVES: Tesamorelin is a synthetic analogue of growth hormone-releasing factor (GRF), which increases basal and pulsatile growth hormone (GH) secretion and subsequently increases insulin-like growth factor (IGF)-1. Limited information is available about the pharmacokinetics of this compound. Consequently, the aim of this study was to characterize the population pharmacokinetics of tesamorelin in HIV-infected patients and healthy subjects. METHODS: A total of 38 HIV-infected patients and healthy subjects receiving subcutaneous tesamorelin doses of 1 or 2 mg administered daily during 14 consecutive days were included in the analysis...
March 2015: Clinical Pharmacokinetics
Takara L Stanley, Meghan N Feldpausch, Jinhee Oh, Karen L Branch, Hang Lee, Martin Torriani, Steven K Grinspoon
IMPORTANCE: Among patients infected with human immunodeficiency virus (HIV), visceral adiposity is associated with metabolic dysregulation and ectopic fat accumulation. Tesamorelin, a growth hormone-releasing hormone analog, specifically targets visceral fat reduction but its effects on liver fat are unknown. OBJECTIVE: To investigate the effect of tesamorelin on visceral and liver fat. DESIGN, SETTING, AND PATIENTS: Double-blind, randomized, placebo-controlled trial conducted among 50 antiretroviral-treated HIV-infected men and women with abdominal fat accumulation at Massachusetts General Hospital in Boston...
July 23, 2014: JAMA: the Journal of the American Medical Association
Hideo Makimura, Caitlin A Murphy, Meghan N Feldpausch, Steven K Grinspoon
CONTEXT: Few studies have assessed the relationship between GH and mitochondrial function. OBJECTIVE: The objective of this study was to determine the effects of improving IGF-I using a GHRH analog, tesamorelin, on mitochondrial function assessed by phosphocreatine (PCr) recovery using (31)P magnetic resonance spectroscopy in obese adults with reduced GH. DESIGN: A total of 39 obese men and women with reduced GH secretion as determined by GHRH-arginine stimulation tests underwent magnetic resonance spectroscopy as part of a 12-month, double-blind, randomized, placebo-controlled trial comparing tesamorelin vs placebo...
January 2014: Journal of Clinical Endocrinology and Metabolism
Fred R Sattler
Secretion of growth hormone (GH) and IGF-1 levels decline during advancing years-of-life. These changes (somatopause) are associated with loss of vitality, muscle mass, physical function, together with the occurrence of frailty, central adiposity, cardiovascular complications, and deterioration of mental function. For GH treatment to be considered for anti-aging, improved longevity, organ-specific function, or quality of life should be demonstrable. A limited number of controlled studies suggest that GH supplementation in older men increases lean mass by ∼2 kg with similar reductions in fat mass...
August 2013: Best Practice & Research. Clinical Endocrinology & Metabolism
Seth D Friedman, Laura D Baker, Soo Borson, J Eric Jensen, Suzanne M Barsness, Suzanne Craft, George R Merriam, Randolph K Otto, Edward J Novotny, Michael V Vitiello
IMPORTANCE: Growth hormone-releasing hormone (GHRH) has been previously shown to have cognition-enhancing effects. The role of neurotransmitter changes, measured by proton magnetic resonance spectroscopy, may inform the mechanisms for this response. OBJECTIVE: To examine the neurochemical effects of GHRH in a subset of participants from the parent trial. DESIGN: Randomized, double-blind, placebo-controlled substudy of a larger trial. SETTING: Clinical research unit at the University of Washington School of Medicine...
July 2013: JAMA Neurology
Shobhit Jain, Ninad Desai, Amrit Bhangoo
Aberrations in GHRH-GH -IGF-I axis are common in the complex of HIV, HAART and AIDS. There are 2 distinct mechanisms at play in HIV and AIDS. One is primarly associated with development of lipodystrophy and results in complications such as chronic inflammation, insulin resistance, lipid and metabolic abnormalities. HIV lipodystrophy is found especially in those on highly active anti-retroviral therapy (HAART). The various processes involved in lipodystrophy result in the suppression of pituitary GH production...
June 2013: Reviews in Endocrine & Metabolic Disorders
Hideo Makimura, Meghan N Feldpausch, Alison M Rope, Linda C Hemphill, Martin Torriani, Hang Lee, Steven K Grinspoon
CONTEXT: Obesity is associated with reduced GH secretion and increased cardiovascular disease risk. OBJECTIVE: We performed this study to determine the effects of augmenting endogenous GH secretion on body composition and cardiovascular disease risk indices in obese subjects with reduced GH secretion. DESIGN, PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled study was performed involving 60 abdominally obese subjects with reduced GH secretion...
December 2012: Journal of Clinical Endocrinology and Metabolism
Andy McLarnon
No abstract text is available yet for this article.
October 2012: Nature Reviews. Endocrinology
Laura D Baker, Suzanne M Barsness, Soo Borson, George R Merriam, Seth D Friedman, Suzanne Craft, Michael V Vitiello
BACKGROUND: Growth hormone–releasing hormone(GHRH), growth hormone, and insulin like growth factor 1 have potent effects on brain function, their levels decrease with advancing age, and they likely play a role in the pathogenesis of Alzheimer disease. Previously, we reported favorable cognitive effects of short-term GHRH administration in healthy older adults and provided preliminary evidence to suggest a similar benefit in adults with mild cognitive impairment (MCI). OBJECTIVE: To examine the effects of GHRH on cognitive function in healthy older adults and in adults with MCI...
November 2012: Archives of Neurology
Marie-Christine Vantyghem, Anne-Sophie Balavoine, Claire Douillard, Frédérique Defrance, Lucile Dieudonne, Fanny Mouton, Christine Lemaire, Nicole Bertrand-Escouflaire, Marie-Françoise Bourdelle-Hego, Fabrice Devemy, Anne Evrard, Dominique Gheerbrand, Caroline Girardot, Sophie Gumuche, Christine Hober, Hélène Topolinski, Blandine Lamblin, Bénédicte Mycinski, Amélie Ryndak, Wassila Karrouz, Etienne Duvivier, Emilie Merlen, Christine Cortet, Jacques Weill, Dominique Lacroix, Jean-Louis Wémeau
The spectrum of adipose tissue diseases ranges from obesity to lipodystrophy, and is accompanied by insulin resistance syndrome, which promotes the occurrence of type 2 diabetes, dyslipidemia and cardiovascular complications. Lipodystrophy refers to a group of rare diseases characterized by the generalized or partial absence of adipose tissue, and occurs with or without hypertrophy of adipose tissue in other sites. They are classified as being familial or acquired, and generalized or partial. The genetically determined partial forms usually occur as Dunnigan syndrome, which is a type of laminopathy that can also manifest as muscle, cardiac, neuropathic or progeroid involvement...
June 2012: Annales D'endocrinologie
Takara L Stanley, Julian Falutz, Christian Marsolais, Josée Morin, Graziella Soulban, Jean-Claude Mamputu, Hani Assaad, Ralph Turner, Steven K Grinspoon
BACKGROUND: Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%-20% over 6-12 months in individuals with human immunodeficiency virus (HIV)-associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes. METHODS: In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to receive tesamorelin or placebo for 26 weeks...
June 2012: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Linda M Spooner, Jacqueline L Olin
OBJECTIVE: To evaluate the efficacy and safety of tesamorelin, a growth hormone releasing factor analogue approved by the Food and Drug Administration in November 2010 for the treatment of lipodystrophy associated with HIV infection. DATA SOURCES: Literature was obtained through MEDLINE (1948-November 2011) and International Pharmaceutical Abstracts (1970-October 2011) using the search terms tesamorelin, TH9507, growth hormone releasing factor, and HIV-associated lipodystrophy syndrome...
February 2012: Annals of Pharmacotherapy
Roger Bedimo
HIV-infected patients on highly active antiretroviral therapy (HAART) develop a complex of body composition changes known, including peripheral fat loss (lipoatrophy) and central fat accumulation (lipohypertrophy). These changes may cause significant patient distress, which could in turn interfere with adherence to antiretroviral therapy. Treatment options - including antiretroviral switch, insulin sensitizers, and surgical approaches - have been associated with limited success and potential complications. The observation that low growth hormone levels are associated with central fat accumulation among HIV patients has led to the development of tesamorelin (a growth hormone releasing hormone analog) for the management of central fat accumulation...
2011: HIV/AIDS: Research and Palliative Care
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