1,338 research outputs found
Modulation of growth hormone (GH) secretion and GH mRNA level in cultured bovine adenohypophyseal cells : effects of neurohormones, steroids and insulin-like growth factor-I
No full textTypescript (photocopy).A series of experiments was conducted to investigate the regulation of GH synthesis/secretion in cultured bovine adenohypophyseal cells. The effects of: 1) bovine growth hormone-releasing factor (bGRF; 100 nM); 2) somatostatin-14 (SS; 100 nM); 3) forskolin (FSK; 10 ��M); 4) dibutyryl cAMP [(Bu)2cAMP; 1 mM]; 5)phorbol-12-myristate-13 acetate (PMA; 1 ��M); 6) dihydrotestosterone (DHT), progesterone (P) and zeranol (Z), each 1 ��M; 7) insulin-like growth factor-I (IFG-I; 1, 10, 20, or 100 ng/ml); or 8) medium alone (control) were studied in cow (F) or steer (M) cells. Medium content of GH was determined by radioimmunoassay and cellular content of GH m RNA was determined by Norther analysis. Bovine GRF increased (P.05) by cotreatment with SS..
Health-Related Quality of Life in sepsis survivors at six months to two years compared to the Welsh Population.
No full text<p>Radar chart of the health related quality of life in long term survivors of sepsis compared to Welsh population. Blue line with squares: all sepsis group results. Red line with diamonds: Welsh population results. PF: physical functioning, RP: role limitation physical, BP: bodily pain, GH: general health, VT: vitality, SF: social functioning, RE: role limitation emotional, MH: mental health.</p
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
Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation
No full textBackground: Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH) and insulin-like growth factor I (IGF-1). It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG) is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels.
Methods: Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG.
Results: One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was pound81,000/QALY and pound212,000/LYG. To reduce this to pound30K/QALY would require a reduction in drug cost by about one third.
Conclusion: PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK) for determining cost-effectiveness of therapies were to be applied to PEG it would be considered not to represent good value for money
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)
Narrative based medicine: narrative based medicine in an evidence based world
No full textSummary points: Even "evidence based" clinicians uphold the importance of clinical expertise and judgment. Clinical method is an interpretive act which draws on narrative skills to integrate the overlapping stories told by patients, clinicians, and test results. The art of selecting the most appropriate medical maxim for a particular clinical decision is acquired largely through the accumulation of "case expertise" (the stories or "illness scripts" of patients and clinical anecdotes).The dissonance we experience when trying to apply research findings to the clinical encounter often occurs when we abandon the narrative interpretive paradigm and try to get by on "evidence" alone
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
Effects of certain growth factors on in vitro maturation of rat fetal islet-like structures
No full textWe have previously studied the expression of protein tyrosine kinases in different preparations of insulin producing cells by polymerase chain reaction (PCR). Among the tyrosine kinases thus identified were the fibroblast growth factor receptor-4 (FGFR-4), c-Kit, the insulin-like growth factor (IGF-I) receptor, and the cytoplasmic tyrosine kinase Jak2, which associates with the activated receptor for growth hormone (GH). To elucidate the putative biological effects of the receptors identified, fetal islet-like structures were cultured in the absence or presence of the ligands to the receptors identified, namely, acidic FGF (aFGF), stem-cell factor (SCF), IGF-I, and GH, whereafter insulin and DNA contents as well as insulin secretion to the culture medium were determined. Nerve growth factor (NGF), the ligand to the tyrosine kinase receptor Trk-A, was also included. aFGF and GH were found to stimulate insulin release to the culture medium, whereas SCF augmented insulin contents/DNA as well as islet DNA contents. No effects of NGF or IGF-I were detected. Immunohistochemical studies of fetal rat pancreas showed localization of the c-Kit protein to the pancreatic ducts, whereas immuno-reactivity against FGFR-4 could be detected in both endocrine and exocrine parts of the pancreas as well as in the pancreatic ducts. It is concluded that tyrosine kinase receptors may be involved in the maturation of pancreatic beta cells.</p
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
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