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https://www.readbyqxmd.com/read/28551577/bioactive-growth-hormone-in-older-men-and-women-it-s-relationship-to-immune-markers-and-healthspan
#1
William J Kraemer, Mary J Kennett, Andrea M Mastro, Roger J McCarter, Connie J Rogers, William H DuPont, Shawn D Flanagan, William J Turbitt, Maren S Fragala, Emily M Post, Wesley C Hymer
OBJECTIVE: The consequences of age-related decline in the somatotropic axis of humans are complex and remain largely unresolved. We tested the hypothesis that hGH measurements of plasma by bioassay vs immunoassay from samples obtained from free-living, elderly individuals would reveal a dichotomy in GH activities that are correlated with the functional status of the donors, i.e. their healthspan. DESIGN: Forty-one men and women of advanced age (men: N=16, age, 80...
May 8, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28546545/extensive-phenotypic-characterization-of-a-new-transgenic-mouse-reveals-pleiotropic-perturbations-in-physiology-due-to-mesenchymal-hgh-minigene-expression
#2
Aimilios Kaklamanos, Jan Rozman, Manolis Roulis, Niki Karagianni, Maria Armaka, Moya Wu, Laura Brachthäuser, Julia Calzada-Wack, Marion Horsch, Johannes Beckers, Birgit Rathkolb, Thure Adler, Frauke Neff, Eckhard Wolf, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabe de Angelis, George Kollias
The human growth hormone (hGH) minigene used for transgene stabilization in mice has been recently identified to be locally expressed in the tissues where transgenes are active and associated with phenotypic alterations. Here we extend these findings by analyzing the effect of the hGH minigene in TgC6hp55 transgenic mice which express the human TNFR1 under the control of the mesenchymal cell-specific CollagenVI promoter. These mice displayed a fully penetrant phenotype characterized by growth enhancement accompanied by perturbations in metabolic, skeletal, histological and other physiological parameters...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28537648/an-anterior-inferior-iliac-spine-avulsion-fracture-in-a-14-year-old-boy-on-human-growth-hormone
#3
Anthony J Scillia, Todd P Pierce, Anthony Festa, Peter Goljan, Vincent K McInerney
We present the case of a young man with an anterior inferior iliac spine (AIIS) avulsion fracture who was taking human growth hormone (HGH) at the time his injury was diagnosed. He presented with chronic hip pain and no traumatic event. Physical exam revealed symptoms of hip impingement. Upon imaging, he was diagnosed with an AIIS avulsion fracture and underwent surgical repair. He returned to full activity six months post-operatively. At 18-months post-operatively, he was pain-free and performing all activities without difficulty...
May 24, 2017: Surgical Technology International
https://www.readbyqxmd.com/read/28525404/growth-hormone-treatment-for-growth-hormone-deficiency-and-idiopathic-short-stature-new-guidelines-shaped-by-the-presence-and-absence-of-evidence
#4
Adda Grimberg, David B Allen
PURPOSE OF REVIEW: The Pediatric Endocrine Society recently published new guidelines for the use of human growth hormone (hGH) and human insulin-like growth factor-I (hIGF-I) treatment for growth hormone deficiency, idiopathic short stature, and primary IGF-I deficiency in children and adolescents. This review places the new guidelines in historical contexts of the life cycle of hGH and the evolution of US health care, and highlights their future implications. RECENT FINDINGS: The new hGH guidelines, the first to be created by the Grading of Recommendations Assessment, Development and Evaluation approach, are more conservative than their predecessors...
May 18, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28515770/high-level-expression-of-recombinant-human-growth-hormone-in-escherichia-coli-crucial-role-of-translation-initiation-region
#5
Mahsa Ghavim, Khalil Abnous, Fatemeh Arasteh, Sahar Taghavi, Maryam Sadat Nabavinia, Mona Alibolandi, Mohammad Ramezani
For high-throughput production of recombinant protein in Escherichia coli (E. coli), besides important parameters such as efficient vector with strong promoter and compatible host, other important issues including codon usage, rare codons, and GC content specially at N-terminal region should be considered. In the current study, the effect of decreasing the percentage of GC nucleotides and optimizing codon usage at N-terminal region of human growth hormone (hGH) cDNA on the level of its expression in E. coli were investigated...
April 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28503764/interpretation-of-seemingly-contradictory-data-low-nmr-s2-order-parameters-observed-in-helices-and-high-nmr-s2-order-parameters-in-disordered-loops-of-the-protein-hgh-at-low-ph
#6
Lorna J Smith, Roya Athill, Wilfred F van Gunsteren, Niels Hansen
At low pH human growth hormone (hGH) adopts a partially folded state in which the native helices are maintained but the long loop regions and side-chain packing becomes disordered. Some of the S2 order parameters for backbone N-H vectors derived from NMR relaxation measurements for the hGH at low pH initially seem contradictory. Three isolated residues (15, 20 and 171) in helices A and D exhibit low order-parameter values (< 0.5) indicating flexibility while residue 143 in the centre of a long flexible loop region has a high order parameter (0...
May 15, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28427901/the-20kda-and-22kda-forms-of-human-growth-hormone-hgh-exhibit-different-intracellular-signalling-profiles-and-properties
#7
Liu Yao-Xia, Chen Jing-Yan, Tang Xia-Lian, Chen Ping, Zhang Min
Human Growth Hormone (hGH) includes two main variants. The first is 22kDa GH (22K-GH), which is predominant in the blood circulation. The second most abundant variant is 20K-GH, which makes up 5-10% of the blood circulation. Both bind and activate the same receptor, called the human growth hormone receptor (GHR). However, the reason why 22K-GH and 20K-GH exhibit similar, but not identical physiological activities remains poorly understood. In this article, the intracellular signalling profiles between these two hormones were examined...
April 17, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28421307/an-efficient-and-rapid-method-to-monitor-the-oxidative-degradation-of-protein-pharmaceuticals-probing-tyrosine-oxidation-with-fluorogenic-derivatization
#8
Rupesh Bommana, Olivier Mozziconacci, Y John Wang, Christian Schöneich
PURPOSE: The loss of potency of protein therapeutics can be linked to the oxidation of specific amino acid residues leading to a great variety of oxidative modifications. The comprehensive identification of these oxidative modifications requires high-resolution mass spectrometry analysis, which requires time and expensive resources. Here, we propose a fluorogenic derivatization method of oxidized Tyr and Phe yielding benzoxazole derivatives, as an orthogonal technique for the rapid screening of protein oxidation...
April 18, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28399519/pharmacokinetic-and-pharmacodynamic-modeling-of-mod-4023-a-long-acting-human-growth-hormone-in-growth-hormone-deficiency-children
#9
Dennis M Fisher, Ron G Rosenfeld, Michal Jaron-Mendelson, Leanne Amitzi, Ronit Koren, Gili Hart
BACKGROUND/AIMS: MOD-4023 is a long-acting human growth hormone (hGH) in clinical trials for the treatment of growth hormone deficiency (GHD). A key goal is maintenance of serum concentrations of insulin-like growth factor (IGF) 1 within normal range throughout GH dosing. The study aimed to develop a pharmacokinetic model for MOD-4023 and a pharmacodynamic model for the effect of MOD-4023 on IGF-1 to allow estimation of peak and mean IGF-1 and to identify the optimal IGF-1 sampling day...
April 11, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28349199/amyloid-%C3%AE-accumulation-in-the-cns-in-human-growth-hormone-recipients-in-the-uk
#10
Diane L Ritchie, Peter Adlard, Alexander H Peden, Suzanne Lowrie, Margaret Le Grice, Kimberley Burns, Rosemary J Jackson, Helen Yull, Michael J Keogh, Wei Wei, Patrick F Chinnery, Mark W Head, James W Ironside
Human-to-human transmission of Creutzfeldt-Jakob disease (CJD) has occurred through medical procedures resulting in iatrogenic CJD (iCJD). One of the commonest causes of iCJD was the use of human pituitary-derived growth hormone (hGH) to treat primary or secondary growth hormone deficiency. As part of a comprehensive tissue-based analysis of the largest cohort yet collected (35 cases) of UK hGH-iCJD cases, we describe the clinicopathological phenotype of hGH-iCJD in the UK. In the 33/35 hGH-iCJD cases with sufficient paraffin-embedded tissue for full pathological examination, we report the accumulation of the amyloid beta (Aβ) protein associated with Alzheimer's disease (AD) in the brains and cerebral blood vessels in 18/33 hGH-iCJD patients and for the first time in 5/12 hGH recipients who died from causes other than CJD...
March 27, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28323965/long-acting-c-terminal-peptide-modified-hgh-mod-4023-results-of-a-safety-and-dose-finding-study-in-ghd-children
#11
Nataliya Zelinska, Violeta Iotova, Julia Skorodok, Oleg Malievsky, Valentina Peterkova, Lubov Samsonova, Ron G Rosenfeld, Zvi Zadik, Michal Jaron-Mendelson, Ronit Koren, Leanne Amitzi, Dmitri Raduk, Oren Hershkovitz, Gili Hart
Context: Daily injections are required for growth hormone (GH) replacement therapy, which may cause low compliance as a result of inconvenience and distress in patients. Objective: C-terminal peptide-modified human GH (MOD-4023) is developed for once-a-week dosing regimen in GH-deficient (GHD) adults and children. The present trial was a safety and dose-finding study for weekly MOD-4023 in GHD children. Design: A multicenter, open-label, randomized, controlled phase 2 study in children with GHD, evaluating the safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy of three different weekly MOD-4023 doses, compared with daily recombinant human GH (r-hGH)...
May 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28321676/transdermal-delivery-of-human-growth-hormone-via-laser-generated-micropores
#12
Yang Song, Karishma Hemmady, Ashana Puri, Ajay K Banga
The epidermal skin barrier plays an important role in protecting underlying structures. It allows the passage of low molecular weight lipophilic molecules, but restricts the passage of hydrophilic molecules and macromolecules. The objective of this study was to investigate the feasibility of transdermal delivery of human growth hormone (hGH) through laser-microporated dermatomed porcine ear skin. The permeation of hGH was evaluated at different laser fluences and micropore densities. In vitro permeation studies were performed on vertical Franz diffusion cells using dermatomed porcine ear skin treated with ablative laser (2940 nm; P...
March 20, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28287223/bioresorbable-polypeptide-based-comb-polymers-efficiently-improves-the-stability-and-pharmacokinetics-of-proteins-in-vivo
#13
Md Hasan Turabee, Thavasyappan Thambi, Jae Seung Lym, Doo Sung Lee
Stimuli-responsive polypeptides are a promising class of biomaterials due to their tunable physicochemical and biological properties. Herein, a series of novel pH- and thermo-responsive block copolymers based on polypeptides were synthesized by ring-opening polymerization of γ-benzyl-l-glutamate-N-carboxyanhydride in the presence of poly(ethylene glycol)-diamine macroinitiator followed by aminolysis. The resulting polypeptide-based triblock copolymer, poly[(2-(dibutylamino)ethyl-l-glutamate)-co-(γ-benzyl-l-glutamate)]-poly(ethylene glycol)-b-poly[(2-(dibutylamino)ethyl-l-glutamate)-co-(γ-benzyl-l-glutamate)] (PNLG-co-PBLG-b-PEG-b-PBLG-co-PNLG), exists as a low viscous sol at low pH and temperature (≤pH 6...
March 13, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28253515/growth-promotion-ethics-and-the-challenge-to-resist-cosmetic-endocrinology%C3%A2
#14
David B Allen
The advancement of "human growth hormone (hGH)-for-height" - increasing height attainment in children short for reasons other than GH deficiency - arose from intuitive, deep-seated assumptions about the disability of short stature, its improvement with hGH-mediated height gain, and the safety of escalating dosages of hGH in healthy children. Evidence challenging these assumptions now strengthens criticism of hGH-for-height as cosmetic endocrinology. To counter this characterization, collective acceptance of guidelines is needed that advise nontreatment of the vast majority of short children, support strategies that minimize treatment duration and dosage, and restrain enhancement of normal adult stature...
2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28229576/hormonal-responses-during-two-different-concurrent-training-trials-in-youth-elite-soccer-players-does-changing-the-organisation-of-training-impact-the-hormonal-response-to-concurrent-exercise
#15
Kevin Enright, James Morton, John Iga, Barry Drust
BACKGROUND: There are no data describing the acute hormonal responses to concurrent- training programmes in youth elite soccer players. Therefore, the aim of this study was to describe the total testosterone (T), cortisol (C), and growth hormone (hGH) responses during two same-day concurrent-training (CT) trials in elite soccer players. METHODS: n=13 youth elite players (age: 17.0±0.2 yrs; height, 1.80±0.07 m; body mass, 73.1±5.7 kg; VO2 max, 64.4±4.8ml-1.kg-1...
February 22, 2017: Journal of Sports Medicine and Physical Fitness
https://www.readbyqxmd.com/read/28216260/optimal-expression-of-a-fab-effector-fusion-protein-in-escherichia-coli-by-removing-the-cysteine-residues-responsible-for-an-interchain-disulfide-bond-of-a-fab-molecule
#16
Hyeon-Ju Kang, Hye-Jin Kim, Mun-Sik Jung, Jae-Kyu Han, Sang-Hoon Cha
Development of novel bi-functional or even tri-functional Fab-effector fusion proteins would have a great potential in the biomedical sciences. However, the expression of Fab-effector fusion proteins in Escherichia coli is problematic especially when a eukaryotic effector moiety is genetically linked to a Fab due to the lack of proper chaperone proteins and an inappropriate physicochemical environment intrinsic to the microbial hosts. We previously reported that a human Fab molecule, referred to as SL335, reactive to human serum albumin has a prolonged in vivo serum half-life in rats...
February 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28131652/precise-and-combinatorial-pegylation-generates-a-low-immunogenic-and-stable-form-of-human-growth-hormone
#17
Ling Wu, Jingxian Chen, Yiming Wu, Bo Zhang, Xiaochun Cai, Ziwei Zhang, Yan Wang, LongLong Si, Huan Xu, YongXiang Zheng, ChuanLing Zhang, Chenggang Liang, Jing Li, Lihe Zhang, Qiang Zhang, Demin Zhou
In this study, we aimed to develop a safe and stable form of human growth hormone (hGH) and to refine PEGylation methods for therapeutic proteins via genetic code expansion. Through this precise approach, a series of polyethylene glycol (PEG) moieties and sites were combined in various ways. Additionally, the effects of combinatorial PEGylation on the biological, pharmacological, and immunogenic properties of hGH in vitro and vivo were analyzed. Our results showed that combinatorial PEGylation at Y35, G131, and K145 significantly reduced immunogenicity and improved pharmacokinetic (PK) profiles compared with mono-PEGylation, while retaining biological activity...
January 25, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28105973/selective-determination-of-human-growth-hormone-somatropin-in-the-presence-of-its-chemical-degradation-products
#18
Mamdouh R Rezk, Marwa F Mohamed, Faten Abdelaziz Fathalla, Mostafa A Shehata
A rapid and sensitive HPLC method was developedand validated for selective determination of thehuman growth hormone (hGH) somatropin in thepresence of its deamidated and oxidized degradationproducts. Reversed-phase chromatographywith an acetonitrile and ammonium bicarbonatemobile phase in gradient elution mode was used.A short run time of 15 min allowed rapid andcost-effective analysis, with an average retentiontime of 7.4 min for native hGH, 6.2 min for itsdeamidated form, and 4.3 and 6 min for its oxidizedvariants...
January 19, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28099130/epidermal-growth-factor-receptor-egfr-involvement-in-successful-growth-hormone-gh-signaling-in-gh-transduction-defect
#19
Eirini Kostopoulou, Andrea Paola Rojas-Gil, Alexia Karvela, Bessie E Spiliotis
BACKGROUND: Growth hormone (GH) transduction defect (GHTD) is a growth disorder with impaired signal transducer and activator of transcription 3 (STAT3) phosphorylation mediated by overexpression of cytokine-inducible SH2-containing protein (CIS), which causes increased growth hormone receptor (GHR) degradation. This study investigated the role of epidermal growth factor (EGF) in the restoration of normal GH signaling in GHTD. METHODS: Protein expression, cellular localization and physical contact of proteins of the GH and EGF signaling pathways were studied by Western immunoblotting, immunofluorescence and co-immunoprecipitation, respectively...
February 1, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28013084/expression-purification-and-characterization-of-the-authentic-form-of-human-growth-hormone-receptor-antagonist-g120r-hgh-obtained-in-escherichia-coli-periplasmic-space
#20
Ana C S C Menezes, Miriam F Suzuki, João E Oliveira, Maria T C P Ribela, Isadora C Furigo, José Donato, Paolo Bartolini, Carlos R J Soares
The human growth hormone receptor antagonist G120R-hGH precludes dimerization of GH and prolactin receptors and consequently JAK/STAT signaling. Some modifications in this antagonist resulted in a drug specific for the GH receptor, called Pegvisomant (Somavert(®)). However, the original G120R-hGH is usually synthesized in bacterial cytoplasm as inclusion bodies, not being a commercial product. The present work describes the synthesis and characterization of G120R-hGH secreted into bacterial periplasm and obtained with a vector based on a constitutive lambda-PL promoter...
December 22, 2016: Protein Expression and Purification
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