1,706 research outputs found
Growth hormone (GH) provocation tests and the response to GH treatment in GH deficiency
No full textObjective: To identify factors, particularly the growth hormone (GH) provocation test result, affecting growth response to GH treatment in children with GH deficiency (GHD).Subjects: A total of 337 prepubertal GHD patients aged,10 years from the UK Pharmacia KIGS database (GH response to provocation test >20 mU/l).Outcome measure: Annual change in height standard deviation score (SDS) (revised UK reference) in the first and second years of treatment.Results: Height increased by 0.74 SDS units (SD 0.39) in the first year of treatment and 0.37 units (SD 0.27) in the second. Adjusting for age, height, weight, midparent height, and injection frequency, the strongest predictor of first year growth response was the GH provocation test result; halving the result predicted an extra height increment of 0.09 units (p<0.0001). It predicted the second year response less well (p<0.0002) and after adjusting for the first year response was not predictive at all.Conclusions: Among patients referred for possible GHD, the GH provocation test, though not a gold standard for diagnosis, is a valuable predictor of growth response in the first year of treatment. A year's treatment is recommended for cases with a marginal provocation test result, with the option to continue treatment if the response is adequate. The value of unified protocols for single or repeated provocation tests needs to be assessed
GH responsiveness in a large multinational cohort of SGA children with short stature (NESTEGG) is related to the exon 3 GHR polymorphism
No full textObjective: The polymorphic deletion of exon 3 of the GH receptor (d3-GHR) has recently been linked to the magnitude of growth response to recombinant human GH (rhGH) therapy in short children with or without GH deficiency. We investigated this association in a large multinational cohort from the Network of European Studies of Genes in Growth (NESTEGG), comprising short children born small for gestational age (SGA). Design: The study included short prepubertal SGA children treated with rhGH for 1 or 2 years. Population: Two hundred and forty white Caucasian SGA children (138 male, 102 female) aged 6.6 ± 2.3 years with a height at -3.0 ± 0.7 SDS at start of rhGH treatment; 193 ethnically matched controls. Methods: The GHR polymorphism (fl/fl, fl/d3 or d3/d3) was genotyped by polymerase chain reaction (PCR) multiplex assay. Growth velocity (G/V) in cm/year and changes in GV during the first and second year of rhGH treatment were evaluated. Results: The change in GV was significantly greater in SGA children carrying one or two copies of the d3-GHR allele (P = 0.038 for the first year and P = 0.041 for the second year of GH treatment), but the change in height was not significantly different. Birthweight was significantly lower in SGA children with the d3/d3 genotype than in SGA children with the fl/fl genotype (P = 0.034) and in those with the fl/d3 genotype (P = 0.016). Conclusion: Our data, based on a large cohort, showed that the exon 3 GHR polymorphism is associated with responsiveness to rhGH treatment in SGA children with short stature
Short term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure
No full textInitiation of GH treatment in adults is frequently complicated by the development of symptomatic fluid retention. To investigate the mechanism and extent of fluid retention that occurs with dosages of GH used in the treatment of GH-deficient adults, we conducted a double blind study in which seven GH-deficient patients (aged 24-74 yr) each received in random order daily sc injections of placebo, a physiological dose of GH (0.04 U/kg, low dose), and a supraphysiological dose of GH (0.08 U/kg, high dose) for 7 days, separated by 21-day washout periods. On the seventh day, measurements were made of serum insulin-like growth factor I, body weight, exchangeable sodium, plasma volume, angiotensinogen, PRA, aldosterone, atrial natriuretic peptide (ANP), and mean 24-h ambulatory heart rate and blood pressure. GH significantly increased mean insulin-like growth factor I levels from 105 ± 11 to 304 ± 45 μg/L during low dose treatment (P = 0.006) and 400 ± 76 μg/L during high dose treatment (P = 0.004). High dose GH caused a 1.2 ± 0.3 kg increase in body weight (P = 0.01) and a 193 ± 65 mmol increase in exchangeable sodium (P = 0.008). Low dose GH had a lesser effect, with no significant increase in body weight, but an increase in exchangeable sodium of 113 ± 37 mmol (P = 0.02). Plasma volume was not significantly affected by GH treatment. Mean supine angiotensinogen levels were significantly higher during both GH treatments compared to placebo (low dose, P = 0.017; high dose, P = 0.028) as were mean supine pRA levels (low dose, P = 0.0002; high dose, P = 0.0025). Supine angiotensin II, aldosterone, and ANP levels were not significantly affected by GH treatment. There was no significant change from placebo in any of the sodium-regulating hormones in the erect posture. The mean 24-h heart rate was significantly higher during low dose (82 ± 2 beats/min; P = 0.0001) and high dose (88 ± 3 beats/min; P = 0.0001) GH treatment than during placebo (67 ± 3 beats/min). However, no significant change in mean 24-h systolic or diastolic blood pressure was observed. In summary, acute GH administration using doses currently employed in treating adults causes a dose-related increase in body weight and body sodium, but no associated increase in blood pressure. We conclude that 1) sodium retention is a physiological effect of GH, but does not cause an acute rise in blood pressure; and 2) the mechanism of sodium and fluid retention is not primarily due to enhanced aldosterone secretion or inhibition of ANP release, but more likely to a direct renal tubular effect
RNAseq analysis of fast skeletal muscle in restriction-fed transgenic coho salmon (Oncorhynchus kisutch) : an experimental model uncoupling the growth hormone and nutritional signals regulating growth
No full textBackground Coho salmon (Oncorhynchus kisutch) transgenic for growth hormone (Gh) express Gh in multiple tissues which results in increased appetite and continuous high growth with satiation feeding. Restricting Gh-transgenics to the same lower ration (TR) as wild-type fish (WT) results in similar growth, but with the recruitment of fewer, larger diameter, muscle skeletal fibres to reach a given body size. In order to better understand the genetic mechanisms behind these different patterns of muscle growth and to investigate how the decoupling of Gh and nutritional signals affects gene regulation we used RNA-seq to compare the fast skeletal muscle transcriptome in TR and WT coho salmon. Results Illumina sequencing of individually barcoded libraries from 6 WT and 6 TR coho salmon yielded 704,550,985 paired end reads which were used to construct 323,115 contigs containing 19,093 unique genes of which >10,000 contained >90 % of the coding sequence. Transcripts coding for 31 genes required for myoblast fusion were identified with 22 significantly downregulated in TR relative to WT fish, including 10 (vaspa, cdh15, graf1, crk, crkl, dock1, trio, plekho1a, cdc42a and dock5) associated with signaling through the cell surface protein cadherin. Nineteen out of 44 (43 %) translation initiation factors and 14 of 47 (30 %) protein chaperones were upregulated in TR relative to WT fish. Conclusions TR coho salmon showed increased growth hormone transcripts and gene expression associated with protein synthesis and folding than WT fish even though net rates of protein accretion were similar. The uncoupling of Gh and amino acid signals likely results in additional costs of transcription associated with protein turnover in TR fish. The predicted reduction in the ionic costs of homeostasis in TR fish associated with increased fibre size were shown to involve multiple pathways regulating myotube fusion, particularly cadherin signaling.Peer reviewe
GH and the cardiovascular system: an update on a topic at heart
No full textIn this review, the importance of growth hormone (GH) for the maintenance of normal cardiac function in adult life is discussed. Physiological effects of GH and underlying mechanisms for interactions between GH and insulin-like growth factor I (IGF-I) and the cardiovascular system are covered as well as the cardiac dysfunction caused both by GH excess (acromegaly) and by GH deficiency in adult hypopituitary patients. In both acromegaly and adult GH deficiency, there is also increased cardiovascular morbidity and mortality possibly linked to aberrations in GH status. Finally, the status of the GH/IGF-I system in relation to heart failure and the potential of GH as a therapeutic tool in the treatment of heart failure are reviewed in this article. © 2014 The Author(s)
Adjunctive treatment with oral AKL1, a botanical nutraceutical, in chronic obstructive pulmonary disease
No full textClaire Brockwell,1 Sundari Ampikaipakan,1,2 Darren W Sexton,1 David Price,3,4 Daryl Freeman,5 Mike Thomas,6 Muzammil Ali,4 Andrew M Wilson1,21Norwich Medical School, University of East Anglia, Norwich, UK; 2Norfolk and Norwich University Hospital Foundation Trust, Norwich, UK; 3Academic Primary Care, University of Aberdeen, Aberdeen, UK; 4Research in Real Life, Cambridge, UK; 5Mundesley Medical Centre, Mundesley, Norwich, UK; 6Primary Care Research, Aldermoor Health Centre, University of Southampton, Southampton, UKPurpose: The objective of this pilot trial was to evaluate the safety and efficacy of AKL1, a patented botanical formulation containing extracts of Picrorhiza kurroa, Ginkgo biloba, and Zingiber officinale, as add-on therapy for patients with chronic obstructive pulmonary disease (COPD) and chronic cough.Patients and methods: This randomized, double-blind, placebo-controlled trial enrolled male and female patients >18 years old with COPD and Leicester Cough Questionnaire (LCQ) score of <18. The 10-week study period comprised a 2-week single-blind placebo run-in period followed by add-on treatment with AKL1 or placebo twice daily for 8 weeks. The primary study endpoint was the change from week 0 to week 8 in cough-related health status, as assessed by the LCQ.Results: Of 33 patients enrolled, 20 were randomized to AKL1 and 13 to placebo. Patients included 19 (58%) men and 14 (42%) women of mean (standard deviation [SD]) age of 67 (9.4) years; 15 (45%) patients were smokers and 16 (49%) were ex-smokers. The mean (SD) change from baseline in LCQ score at 8 weeks was 2.3 (4.9) in the AKL1 group and 0.6 (3.7) in the placebo group, with mean difference in change of 1.8 (95% confidence interval: –1.5 to 5.1; P=0.28). The St George's Respiratory Questionnaire score improved substantially in the AKL1 treatment group by a mean (SD) of –7.7 (11.7) versus worsening in the placebo group (+1.5 [9.3]), with mean difference in change of –9.2 (95% confidence interval: –19.0 to 0.6; P=0.064). There were no significant differences between treatment groups in change from baseline to week 8 in other patient-reported measures, lung function, or the 6-minute walk distance.Conclusion: Further study is needed with a larger patient population and over a longer duration to better assess the effects of add-on therapy with AKL1 in COPD.Keywords: Leicester Cough Questionnaire, anti-inflammatory, Picrorhiza kurroa, Ginkgo biloba, Zingiber officinal
The GH-IGF-I axis and breast cancer
No full textMD (Res)Breast cancer remains one of the most common causes of death amongst women today.
Worldwide approximately 1.3 million women are diagnosed as having breast cancer
every year. Much research has been done in trying to unravel the cause and behaviour of
breast cancer and hormonal influences are known to play a role. In particular, two hormones known as growth hormone (GH) and insulin-like growth factor (IGF-1) have been found to play an important role in breast cancer growth and development. It has been found that women with breast cancer have higher levels of IGF-1 in their blood compared with women without breast cancer. Further studies have shown that if IGF-1 is added to breast cancer cells in laboratory conditions they grow rapidly. This evidence points to a strong link between IGF-1 and breast cancer. The majority of circulating IGF-1 is made by the liver in response to growth hormone, but as IGF-1 is also found in most cells in the human body, it is uncertain whether its possible effects on breast cancer may be due to local production of IGF-1 by breast cancer cells or to IGF-1 circulating in the blood. This research aims to study the link between IGF-1, GH and breast cancer. In order to do this, small specimens of breast tissue will be taken from women who are undergoing surgery for treatment of their breast cancer. Most cells removed will be cancer cells, but a rim of normal cells will surround them. I will then look at the different levels of IGF-1, growth hormone and other related hormones produced by the cancer or normal cells. During further research, I will aim to keep these cells alive for a few hours and see how they respond when various hormones are added to them. This research will give us more information about the hormonal control of breast cancer growth and may lead to novel treatments for breast cancer in the future
Book Review: Comrades Betrayed: Jewish World War I Veterans Under Hitler
No full textThis is a pre-copyedited, author-produced version of an article accepted for publication in [German History] following peer review. The version of record [Grady, T. (2021). [Review of the book Comrades Betrayed: Jewish World War I Veterans Under Hitler by M. Geheran]. German History, 39(3), 478–479] is available online at: https://academic.oup.com/gh/article/39/3/478/6308748Book review of Comrades Betrayed: Jewish World War I Veterans Under HitlerUnfundedAAM out of embargo 24/06/2023, output uploaded to CR 30/01/202
Espressione genica indotta dall'ormone somatotropo nei monociti di bambini sani e con deficit di GH
No full text2018 - 2019Somatotropic hormone (GH) has transcriptional effects on the cells of many organs, directly by activating its receptor (GHR) or indirectly through induction of IGF-1 or other mediators. The presence of GHR in almost all cellular tissues makes GH action systemic even if, to date, still not well characterized. The immune system is among the districts where the effect of the somatotropic hormone is documented by mechanisms that are still poorly understood.The primary objective of this study is to determine the transcriptional effect of GH on peripheral blood monocytes. These cells were chosen for the significant expression of GHR on their surface and because they are easily accessible. Although the transcriptional response to somatotropic hormone is specific tissue, the study of the effects of GH on monocytes can serve as a model for other cell types and highlight differences between healthy subjects and those with GH deficiency (GHD).The diagnosis of GHD, during the developmental age, is classically based on the clinical evaluation associated with radiological and laboratory investigations (GH-IGF-1 axis stimulus test). Although provocation tests represent diagnostic gold standard, they have poor reproducibility and accuracy and are characterized by a considerable number of false positives and sometimes negatives.The secondary objective of this study is to identify differential transcriptional profiles between healthy subjects and with GHD.For this purpose, the gene expression of monocytes from healthy children and with GHD was compared in culture, under basal conditions and after stimulation with recombinant GH (rh-GH).Two groups of 12 subjects were selected, group S: healthy male children with normal height and growth rate and group D: children of the same sex and age and suffering from GHD, not yet in replacement therapy. Peripheral blood monocytes were purified by subtraction with monoclonal antibodies and the purity level was determined by laminar flow cytofluorimetry with monoclonal antibodies. Monocytes were grown for 24 hours with and without rh-GH. Total RNA was extracted and frozen until the analysis was performed simultaneously for all the experimental points using the Next Generation Sequencing methodology on Illumina platform. Differential expression of mRNA was analyzed by comparing the monocytes of healthy children and with GHD, stimulated in culture with rh-GH or not stimulated: GHD not stimulated (D-CNTR) vs healthy not stimulated (S-CNTR); healthy non-stimulated (S-CNTR) vs healthy stimulated (S-GH); non-stimulated GHD (D-CNTR) vs stimulated GHD (D-GH); GHD stimulated (D-GH) vs healthy stimulated (S-GH).The analysis between D-CNTR vs S-CNTR groups identified 58 genes with differential expression. Furthermore, 23 genes were modulated by GH in healthy children and 4 genes in children with GHD. Differential analysis between D-GH vs S-GH groups, on the other hand, identified 150 genes with differential expression.Finally, analysis performed by Ingenuity Pathway Analysis software showed a significant increase in NFAT immune pathways and dendritic cell maturation and a consistent increase in the expression of dendritic markers (HLA-A, HLA-C, CCR7) in monocytes of children with GHD compared to healthy children, after stimulation in culture with recombinant GH.In conclusion, the results of this study have demonstrated a clear transcriptional effect of GH on monocytes, direct and indirect through intermediate mediators, suggesting to evaluate the pro-inflammatory status of children with growth hormone deficiency more in depth.Furthermore, this study identified a gene expression profile of monocytes in children with GHD which, once verified in a larger number of patients, could represent an alternative to stimulus tests and guide the diagnosis of GH deficiency.Finally, our study opens future perspectives in order to identify a transcriptional profile or specific genes specific to GHD condition. [edited by Author]XXXII cicl
Comparison of Two Methods for In Vivo Estimation of the Glenohumeral Joint Rotation Center (GH-JRC) of the Patients with Shoulder Hemiarthroplasty
No full textDetermination of an accurate glenohumeral-joint rotation center (GH-JRC) from marker data is essential for kinematic and dynamic analysis of shoulder motions. Previous studies have focused on the evaluation of the different functional methods for the estimation of the GH-JRC for healthy subjects. The goal of this paper is to compare two widely used functional methods, namely the instantaneous helical axis (IHA) and symmetrical center of rotation (SCoRE) methods, for estimating the GH-JRC in vivo for patients with implanted shoulder hemiarthroplasty. The motion data of five patients were recorded while performing three different dynamic motions (circumduction, abduction, and forward flexion). The GH-JRC was determined using the CT-images of the subjects (geometric GH-JRC) and was also estimated using the two IHA and SCoRE methods. The rotation centers determined using the IHA and SCoRE methods were on average 1.4760.62 cm and 2.0760.55 cm away from geometric GH-JRC, respectively. The two methods differed significantly (two-tailed p-value from paired t-Test ,0.02, post-hoc power ,0.30). The SCoRE method showed a significant lower (two-tailed p-value from paired t-Test ,0.03, post-hoc power ,0.68) repeatability error calculated between the different trials of each motion and each subject and averaged across all measured subjects (0.6260.10 cm for IHA vs. 0.4360.12 cm for SCoRE). It is concluded that the SCoRE appeared to be a more repeatable method whereas the IHA method resulted in a more accurate estimation of the GH-JRC for patients with endoprostheses.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin
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