Synthetic Growth Hormone Research Articles

Evaluating Synergistic Effects of Hyaluronic Acid, Human Umbilical Cord-Derived Mesenchymal Stem Cells, and Growth Hormones in Knee Osteoarthritis: A Multi-Arm Randomized Trial.

Knee osteoarthritis (OA) significantly affects quality of life and imposes economic burdens due to its prevalence and the disability it causes. The efficacy of current treatments is limited to alleviating the symptoms, and they cannot be used for regenerative purposes. This study aims to evaluate the efficacy and safety of combining hyaluronic acid (HA), human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), and synthetic human growth hormone (somatotropin) in the treatment of knee OA, assessing pain relief, functional improvement, and cartilage regeneration. A four-arm, double-blind randomized trial was conducted with 51 knees from 28 subjects aged ≥50 with primary knee OA. The treatments involved were HA alone, HA with hUC-MSCs, HA with somatotropin, and a combination of all three. Efficacy was measured through the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and visual analog score (VAS), and MRI T2 mapping of cartilage was conducted on pre-implantation at the 6th and 12th month. All treatment arms showed improvements in the VAS and WOMAC scores over 12 months, suggesting some pain relief and functional improvement. However, MRI T2 mapping showed no significant cartilage regeneration across the groups. While the combined use of HA, hUC-MSCs, and somatotropin improved symptoms of knee OA, it did not enhance cartilage regeneration significantly. This study highlights the potential of these combinations for symptom management but underscores the need for further research to optimize these therapies for regenerative outcomes.

Utilizing erythrosine B absorption spectrum shifts for quantitative determination of octreotide and bromocriptine in their pure forms and pharmaceutical formulations. Evaluation of the method greenness

In the present study, two drugs for treating acromegaly are investigated which are either synthetic growth hormone inhibiting hormone (GHIH) or dopamine receptor agonist. Octreotide (OCT) and bromocriptine (BCT) were quantified with a quick, simple, and sensitive spectrophotometric approach in their authentic forms and commercial dosage forms. This approach was based upon formation of ion pair complex between erythrosine B and investigated drugs in an aqueous buffered solution. For OCT determination the higher sensitivity was obtained using ΔA at 525 nm. On the other hand, BCT was estimated using the absorbance at 556 nm. Under optimal conditions for the reaction, construction of calibration curves were performed within concentration range of 0.4–4 µg ml−1 for OCT and 1–9 µg ml−1 for BCT with with low detection limits (0.094 and 0.235 µg ml−1) and low quantitation limits (0.29 and 0.71 µg ml−1) for OCT and BCT respectively. The developed approach was assessed for linearity, accuracy, precision, limits of detection, and limits of quantitation in compliance with ICH validation recommendations. The suggested approaches demonstrated good linearity, as evidenced by determination coefficients (r2) of 0.999 with a slope 0.14 for OCT and 0.9989 with a slope 0.06 for BCT. Additionally, the environmental friendliness of the investigated method was assessed with some of the recent green analytical chemistry metrics.

Effect of Aloe Vera, Wood Ash, and Indole-Butyric Acid on In-Vivo Macro Propagation of Robusta Coffee Stem Cuttings

Purpose: This study investigated the influence of Aloe Vera, Wood ash and a synthetic growth hormone Indole-butyric acid (IBA) on root and shoot in the proliferation of Coffee Wilt disease-resistant (CWD-R) Robusta coffee stem cuttings. Methodology: Stem cuttings of CWD-R Robusta coffee were treated with five levels of rooting natural substances and IBA independently and in combination. The treated cuttings were propagated in a uniform potting medium under humidity chamber conditions. Data was collected on the number of surviving cuttings, shoot and root number, and root and shoot lengths. At 90 days after planting, data on root proliferation, the number, and lengths of roots were collected and analyzed for variance (ANOVA) using GenStat 11th Edition. Findings: The survival, root, and shoot development were significantly (p<0.05) influenced by the rooting substances applied. A combination of Aloe Vera and IBA, 0.8% IBA, and Aloe Vera gel applied alone gave the highest percentages (90, 70 and 70%, respectively) of stem cuttings that survived to form roots and shoots. A mixture of aloe Vera and IBA, 0.8% IBA, and Aloe Vera gave the highest mean number of shoots and roots per cutting; that is (8.75, 8.5, and 8.5 cm) and (13.87, 12.85 and 12.39 cm) for shoots and roots respectively. Cuttings treated with wood ash and control gave the lowest mean number of shoots and roots that formed per cutting; that is (5.25 and 4.50 cm) and (11.75 and 11.38 cm) for shoots and roots respectively. Unique Contribution to Theory, Practice and Policy: Propagation of Coffea canephora, by stem cuttings can be adequately achieved by using Aloe Vera, IBA, or their mixture, but not with wood ash.

Dietary regimens appear to possess significant effects on the development of combined antiretroviral therapy (cART)-associated metabolic syndrome.

This study investigated the interactions between a low protein high calorie (LPHC) diet and an integrase inhibitor-containing antiretroviral drug regimen (INI-CR)in light of evidence suggesting that the initiation of cART in patients with poor nutritional status is a predictor of mortality independent of immune status. Freshly weaned Sprague Dawley rats (120) were randomized into the standard, LPHC and normal protein high calorie (NPHC) diet groups (n = 40/group) initially for 15 weeks. Thereafter, experimental animals in each diet group were further randomized into four treatment sub-groups (n = 10/group) Control (normal saline), group 1(TDF+3TC+DTG and Tesamorelin), group 2 (TDF+3TC+DTG), and Positive control (AZT+3TC+ATV/r) with treatment and diets combined for 9 weeks. Weekly body weights, fasting blood glucose (FBG), oral glucose tolerance test (OGTT); lipid profiles, liver weights, hepatic triglycerides and adiposity were assessed at week 24. At week 15, body weights increased between the diet group in phase 1(standard 146 ± 1.64 vs. 273.1 ± 1.56 g), (NPHC, 143.5 ± 2.40 vs. 390.2 ± 4.94 g) and (LPHC, 145.5 ± 2.28 g vs. 398.3 ± 4.89 g) (p< 0.0001). A similar increase was noted in the FBG and OGTT (p< 0.0001). In phase 2, there was an increase in FBG, OGTT, body weights, lipid profile, liver weights, hepatic triglycerides, adiposity and insulin levels in group 2 and positive control in both NPHC and LPHC diet groups (p<0.0001). Growth hormone levels were decreased in Tesamorelin-free group 2 and positive control in both NPHC and LPHC (p< 0.0001). The obesogenic activities of the LPHC diet exceeded that of the NPHC diet and interacted with both integrase-containing and classical cART drug regimens to reproduce cART associated metabolic dysregulation. The effects were however reversed by co-administration with tesamorelin, a synthetic growth hormone releasing hormone analogue.

Serum Ghrelin in a Sample of Egyptian Epileptic Patients

Ghrelin is a multifunctional hormone constituted of 28 amino acids, which is the endogenous ligand of the synthetic growth hormone secretagogue receptor 1a (GHS-R) ligands. Ghrelin is expressed in different tissues including the central nervous system (CNS). In addition, circulating ghrelin can access different structures of CNS such as hippocampus and ventral tegmental area. Ghrelin has various neuroprotective properties, and it appears to be related to memory retention and formation. In Rolandic epilepsy, although many changes in the physiology of hormones in the neuroendocrine system of patients can occur, the causes of these changes have not been fully elucidated. There are also relations between seizure activity and stages of sleep, which has been shown to affect both endocrine function and sleep. The purpose of this study was to evaluate serum levels of ghrelin in a sample of Egyptian epileptic patients and to evaluate its possible correlations with clinical findings. A total of 60 patients (age: 6.5±1.9) currently receiving antiepileptic drug therapy for Rolandicepilepsy were studied. The control group consisted of 60 healthy volunteers (age: 6.6±2.1) matched for age and gender. In all participants, serum levels of ghrelin were measured using ELISA technique. In the Rolandic epilepsy patients, the mean serum ghrelin level was 175.8±49.1pg/ml, and this was significantly lower than the control group’s level of 445.7±151.4pg/ml (p &lt; 0.001). In conclusion, the significant lower ghrelin serum level in patients with Rolandic epilepsy may support the hypothesis of ghrelin’s antiepilepticpotential and neuroprotective actions.

Growth hormone secretagogue peptide A233 upregulates Mx expression in teleost fish in vitro and in vivo.

Aquaculture constitutes an alternative source for food production and contributes to a reduction in the indiscriminate catching of aquatic organisms in their natural environment. However, high mortality during the larval state remains a challenge in this sector, mainly because of factors such as diet and diseases caused by pathogens. Therefore, growth and health management is a key strategy for sustainable aquaculture. Synthetic growth hormone secretagogues (GHSs) are a family of ligands that can stimulate pituitary growth hormone release as well as the function of ghrelin, contributing to the immune responses in a variety of vertebrates, including fish. The A233 decapeptide is a GHS with a demonstrated impact on growth, immune system function, and antioxidant defense in tilapia fish, but no antiviral activity has been described for this peptide. Here, using an in vitro model (TRG-2 cells) and two in vivo models (sea bream [Sparus aurata]) and zebrafish [Danio rerio]), we demonstrate for the first time the potential antiviral effect of A233 in teleost fish.

Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury.

Introduction: Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury characterized by (i) an intense inflammatory response, (ii) increased pulmonary vascular permeability, and (iii) the loss of respiratory pulmonary tissue. In this article we explore the therapeutic potential of hexarelin, a synthetic hexapeptide growth hormone secretagogue (GHS), in an experimental model of ARDS. Hexarelin has anti-inflammatory properties and demonstrates cardiovascular-protective activities including the inhibition of cardiomyocyte apoptosis and cardiac fibrosis, both of which may involve the angiotensin-converting enzyme (ACE) system. Methods: In our experimental model, ARDS was induced by the instillation of 100 mM HCl into the right bronchus; these mice were treated with hexarelin (320 μg/kg, ip) before (Pre) or after (Post) HCl challenge, or with vehicle. Respiratory system compliance, blood gas analysis, and differential cell counts in a selective bronchoalveolar lavage (BAL) were determined 6 or 24 hours after HCl instillation. In an extended study, mice were observed for a subsequent 14 days in order to assess lung fibrosis. Results: Hexarelin induced a significant improvement in lung compliance and a reduction of the number of total immune cells in BAL 24 hours after HCl instillation, accompanied with a lower recruitment of neutrophils compared with the vehicle group. At day 14, hexarelin-treated mice presented with less pulmonary collagen deposition compared with vehicle-treated controls. Conclusions: Our data suggest that hexarelin can inhibit the early phase of the inflammatory response in a murine model of HCl-induced ARDS, thereby blunting lung remodeling processes and fibrotic development.

Osteogenesis Imperfecta: Current and Prospective Therapies.

Osteogenesis Imperfecta (OI) is a group of connective tissue disorders with a broad range of phenotypes characterized primarily by bone fragility. The prevalence of OI ranges from about 1:15,000 to 1:20,000 births. Five types of the disease are commonly distinguished, ranging from a mild (type I) to a lethal one (type II). Types III and IV are severe forms allowing survival after the neonatal period, while type V is characterized by a mild to moderate phenotype with calcification of interosseous membranes. In most cases, there is a reduction in the production of normal type I collagen (col I) or the synthesis of abnormal collagen as a result of mutations in col I genes. Moreover, mutations in genes involved in col I synthesis and processing as well as in osteoblast differentiation have been reported. The currently available treatments try to prevent fractures, control symptoms and increase bone mass. Commonly used medications in OI treatment are bisphosphonates, Denosumab, synthetic parathyroid hormone and growth hormone for children therapy. The main disadvantages of these therapies are their relatively weak effectiveness, lack of effects in some patients or cytotoxic side effects. Experimental approaches, particularly those based on stem cell transplantation and genetic engineering, seem to be promising to improve the therapeutic effects of OI.

Stimulation of endogenous pulsatile growth hormone secretion by activation of growth hormone secretagogue receptor reduces the fat accumulation and improves the insulin sensitivity in obese mice.

Obese individuals often show low growth hormone (GH) secretion, which leads to reduced lipid mobilization and further fat accumulation. Pharmacological approaches to increase GH levels in obese individuals by GH injection or GH-releasing hormone receptor agonist showed promising effects on fat reduction. However, side effects on glucose metabolism and the heavy costs on making large peptides hindered their clinical application. Here, we tested whether stimulation of endogenous GH secretion by a synthetic GH secretagogue receptor (GHSR) agonist, hexarelin, improved the metabolism in a hyperphagic obese mouse model. Male melanocortin 4 receptor knockout mice (MC4RKO) were pair-fed and received continuous hexarelin (10.56μg/day) or vehicle infusion by an osmotic pump for 3-4weeks. Hexarelin treatment significantly increased the pulsatile GH secretion without detectable alteration on basal GH secretion in MC4RKO mice. The treated mice showed increased lipolysis and lipid oxidation in the adipose tissue, and reduced de novo lipogenesis in the liver, leading to reduced visceral fat mass, reduced triglyceride content in liver, and unchanged circulating free fatty acid levels. Importantly, hexarelin treatment improved the whole-body insulin sensitivity but did not alter glucose tolerance, insulin levels, or insulin-like growth factor 1 (IGF-1) levels. The metabolic effects of hexarelin were likely through the direct action of GH, as indicated by the increased expression level of genes involved in GH signaling pathways in visceral adipose tissues and liver. In conclusion, hexarelin treatment stimulated the pulsatile GH secretion and reduced the fat accumulation in visceral depots and liver in obese MC4RKO mice with improved insulin sensitivity without altered levels of insulin or IGF-1. It provides evidence for managing obesity by enhancing pulsatile GH secretion through activation of GHSR in the pituitary gland.

Elevated Intracranial Pressure Associated With Exogenous Hormonal Therapy Used for Gender Affirmation.

Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.

Peter Betts: saved many normal short children from unnecessary growth hormone treatment

Peter Betts undertook his paediatric training in Birmingham at a time when the many current subspecialties were beginning to develop. He was drawn to endocrinology and in 1978 was appointed consultant in Winchester and Southampton; he moved to Southampton full time in 1989. For children who were found to be short with growth hormone deficiency, human growth hormone was available to restore them to normal height, but very strict criteria had been developed to make sure this precious resource was properly used. The advent of synthetic growth hormone led to the possibility that constitutionally short (that is, short, normal) children might be made taller. At the time it was thought that short children were at a social and educational disadvantage, based on the presumption that being short was detrimental to a child’s development and, in particular, that personality and psychological functioning were adversely affected. If this were true, then almost 3% of a normal population would be under the third centile for height and potentially might be helped to achieve greater height by regular injections of growth hormone during their childhood and teenage years. Betts …

Production-related contaminants (pesticides, antibiotics and hormones) in organic and conventionally produced milk samples sold in the USA.

Consumption of cow's milk, which is associated with diet and health benefits, has decreased in the USA. The simultaneous increase in demand for more costly organic milk suggests consumer concern about exposure to production-related contaminants may be contributing to this decline. We sought to determine if contaminant levels differ by the production method used. Half-gallon containers of organic and conventional milk (four each) were collected by volunteers in each of nine US regions and shipped on ice for analysis. Pesticide, antibiotic and hormone (bovine growth hormone (bGH), bGH-associated insulin-like growth factor 1 (IGF-1)) residues were measured using liquid or gas chromatography coupled to mass or tandem mass spectrometry. Levels were compared against established federal limits and by production method. Laboratory analysis of retail milk samples. Current-use pesticides (5/15 tested) and antibiotics (5/13 tested) were detected in several conventional (26-60 %; n 35) but not in organic (n 34) samples. Among the conventional samples, residue levels exceeded federal limits for amoxicillin in one sample (3 %) and in multiple samples for sulfamethazine (37 %) and sulfathiazole (26 %). Median bGH and IGF-1 concentrations in conventional milk were 9·8 and 3·5 ng/ml, respectively, twenty and three times that in organic samples (P < 0·0001). Current-use antibiotics and pesticides were undetectable in organic but prevalent in conventionally produced milk samples, with multiple samples exceeding federal limits. Higher bGH and IGF-1 levels in conventional milk suggest the presence of synthetic growth hormone. Further research is needed to understand the impact of these differences, if any, on consumers.

Characterization of a third ghrelin receptor, GHS-R3a, in channel catfish reveals novel expression patterns and a high affinity for homologous ligand

A novel third channel catfish growth hormone secretagogue (ghrelin) receptor, GHS-R3a, gene was characterized. Identification and analysis of the genomic organization of channel catfish GHS-R3a revealed differences in exon/intron structure relative to the previously published GHS-R1a and GHS-R2a sequences. Amino acid sequence alignment of catfish GHS-R3a with -R1a and -R2a revealed 48 and 52% sequence identity, respectively. Phylogenetic analysis predicted a new clade of GHS-R3a receptors found only in fish, with representation in the teleost infradivisions Osteoglossomorpha, Clupeomorpha, and Euteleostei. In functional analyses, homologous catfish ghrelin increased intracellular Ca2+ concentration in human embryonic kidney (HEK) 293 cells stably expressing catfish GHS-R3a. On the contrary, intracellular Ca2+ concentration was unaffected by treatment with the synthetic growth hormone secretagogues GHRP-6 and hexarelin. Realtime PCR results indicated high expression of GHS-R3a in the brain and gonads, demonstrating tissue specificity among the catfish GHS-Rs. The effects of fasting and refeeding on all three ghrelin receptors were evaluated in catfish brain, pituitary, stomach, and Brockmann bodies. Most notably, GHS-R3a was the only receptor observed to significantly increase (2.9–6.3-fold) in brain, pituitary, and stomach within 4 days of fasting (P < .05). Stomach GHS-R1a also increased (P < .05) after 4 days; however, GHS-R2a was only elevated in brain and pituitary after refeeding for 1 week. Expression of all three ghrelin receptors were elevated (P < .05) in the Brockmann bodies after 2 weeks of fasting and returned to prefasting levels following refeeding. Together with the previously published characterization of GHS-R1a and -R2a, these results establish three ghrelin receptors, each altered by energy state, in channel catfish and add to the growing body of information on GHS-R evolution and function.

Enhanced Pulsatile Growth Hormone Secretion and Altered Metabolic Hormones by in Vivo Hexarelin Treatment in Streptozotocin-Induced Diabetic Rats.

Significant growth hormone (GH) reductions have been reported in diabetic animal models with disturbed metabolic balance coinciding with GH deficiency. Therefore, enhanced GH secretion may have beneficial effects in controlling diabetes. Thus, we aim to investigate the effect of hexarelin, a synthetic GH secretagogue (GHS), on GH secretion in streptozotocin (STZ, 65 mg/kg)-induced diabetic rats. Daily hexarelin (100 μg/kg) treatment was performed for two weeks in four-week-long STZ-diabetic and vehicle control rats. Pulsatile GH secretion in STZ-rats was significantly reduced in total, pulsatile, basal, and mass of GH secretion per burst. In addition, impaired GH secretion was followed by an increase in fasting-level free fatty acids (FFAs) and a decrease in insulin-like growth factor 1 (IGF-1) compared to control rats. After hexarelin treatment, pulsatile GH secretion in STZ-rats was significantly increased in total, pulsatile, and basal, but not in the mass GH secretion per burst, compared to STZ-rats without hexarelin treatment. However, there was no significant elevation in GH secretion in the hexarelin-treated control group. In addition, hexarelin-treated STZ-rats showed a significant decrease in fasting level FFAs, whereas suppression of fasting level for IGF-1 was maintained. These results suggest that STZ-induced diabetic rats have impaired pulsatile GH secretion, causing increased FFAs and decreased IGF-1 levels in circulation. Hexarelin injections for two weeks is able to normalize impaired pulsatile GH secretion with normal fasting levels of FFAs, but fails to recover IGF-1 levels.

Growth Hormone Secretagogue (A233) Improves Growth and Changes the Tissue Fatty Acid Profile in Juvenile Tilapia (Oreochromis niloticus).

Growth hormone (GH) release is a process that is well regulated by several factors, including GH secretagogues. GH can mediate the regulation of the fatty acid level and composition. The aim of this study was to determine the effect of a synthetic GH secretagogue peptide (A233) on the growth and fatty acid composition in tilapia (Oreochromis niloticus). To address this objective, we administrated a diet supplemented with A233 to juvenile tilapia for 60 days. The group fed with a diet supplemented with 600 μg of A233 per kg of feed increased in weight (4.81 ± 0.09 g) and specific growth rate (2.49 ± 0.03%/day) compared to the control diet group (3.63 ± 0.08 g, 2.07 ± 0.04%/day; respectively) (p < 0.001). In the muscle, the total lipids for the control diet group were higher than that in the group fed with 600 μg of A233 per kg feed; however, no differences were detected in the liver. In both tissues, the patterns of fatty acid composition and content were generally similar, with some exceptions. Tilapia fed with 600 μg of A233 per kg of feed showed, in liver and muscle, a significantly higher composition and content of n-3 polyunsaturated fatty acids (such as 20:5n-3, 22:5n-3, 22:6n-3) and n-3/n-6 PUFA than animals fed with the control diet. To our knowledge, this is the first report on the the effects of natural or synthetic GH secretagogues (GHS) on fatty acid composition, implying an increase in the nutritional quality of the tilapia.

Acromegaly: current therapies benefits and burdens

Acromegaly, caused by growth hormone overproduction, is associated with comorbidities causing significant clinical dysfunction and high mortality risk. Outcomes are hampered by late diagnosis and poor treatment tolerance and adherence. The goal of this paper is to present a scoping review of the benefits and characterize potential burdens of current treatments that may limit achieving disease control or treatment continuity. Current treatments include transsphenoidal surgery, often followed by the use of synthetic somatostatin analogues or growth hormone receptor antagonists. Radiotherapy is considered an adjunct to treatment for nonresponsive patients or recurrent tumors. Despite therapeutic benefits the burdens to the patient equate to an estimated one quarter of patients discontinuing treatment or that are lost to follow up with up to 88% of these cases having uncontrolled disease. Although disease outcomes are improved with early disease identification and prompt treatment, attention to long term treatment adherence is critical to outcomes. The most cost effective and efficacious strategies involve a significant understanding of the individual patient’s disease and treatment burdens, the patient’s knowledge regarding their disease and the full utilization of all health care team resources. Provider awareness of factors impacting follow-up, the application of precision medicine and implementation of a team approach that actively involves the patients, nurses, and physicians in treatment decisions, location convenient disease monitoring with coordination of treatment for co-morbidities and home drug administration are key factors in facilitating long term treatment adherence.

A surprising treatment response in a patient with rare isolated growth hormone deficiency, type IB.

Isolated Growth Hormone Deficiency (IGHD) is a rare cause of short stature, treated with the standard regimen of subcutaneous synthetic growth hormone (GH). Patients typically achieve a maximum height velocity in the first year of treatment, which then tapers shortly after treatment is stopped. We report a case of a 9-year-old male who presented with short stature (<3rd percentile for age and race). Basal hormone levels showed undetectable serum IGF1. Skeletal wrist age was consistent with chronologic age. Cranial MRI revealed no masses or lesions. Provocative arginine-GH stimulation testing demonstrated a peak GH level of 1.4 ng/mL. Confirmatory genetic testing revealed a rare autosomal recessive single-nucleotide polymorphism (SNP) with mutational frequency of 2%. GH supplementation was started and pursued for 2 years, producing dramatically increased height velocity. This velocity persisted linearly through adolescence, several years after treatment had been discontinued. Final adult height was >95th percentile for age and race. In conclusion, this is a case of primary hypopituitarism with differential diagnosis of IGHD vs Idiopathic Short Stature vs Constitutional Growth Delay. This case supports two objectives: Firstly, it highlights the importance of confirmatory genetic testing in patients with suspected, though diagnostically uncertain, IGHD. Secondly, it demonstrates a novel secondary growth pattern with implications for better understanding the tremendous variability of GH treatment response.Learning points:GHD is a common cause of growth retardation, and IGHD is a specific subtype of GHD in which patients present solely with short stature.The standard treatment for IGHD is subcutaneous synthetic GH until mid-parental height is reached, with peak height velocity attained in the 1st year of treatment in the vast majority of patients.Genetic testing should be strongly considered in cases of diagnostic uncertainty prior to initiating treatment.Future investigations of GH treatment response that stratify by gene and specific mutation will help guide treatment decisions.Response to treatment in patients with IGHD is variable, with some patients demonstrating little to no response, while others are ‘super-responders.’

Development of a confirmatory method for detecting recombinant bovine somatotropin in plasma by immunomagnetic precipitation followed by ultra-high performance liquid chromatography coupled to tandem mass spectrometry

ABSTRACTRecombinant bovine somatotropin (rbST), a synthetic growth hormone, is used to stimulate growth and enhance milk production in dairy cows. Both its use and the sale of dairy products from treated animals are prohibited in the European Union, as well as in Australia, Canada, Japan, and New Zealand, but authorised in several countries (e.g. Brazil, USA). Screening methods involve detecting anti-rbST antibodies (biomarkers) in treated cows. Confirmatory methods are required to prove rbST abuse. The major challenges in determining rbST are its potentially low levels, its high similarity to native bST, and matrix interferences. To overcome these obstacles, we have developed a method involving immunomagnetic precipitation followed by UHPLC-MS/MS for rbST detection. Briefly, protein G magnetic beads pre-coated with an in-house produced monoclonal antibody were added to plasma. Incubation at room temperature allowed rbST present in the sample to bind to the magnetic beads. After that, magnetic beads were isolated by centrifugation and thoroughly washed (PBS, PBS + 0.2% Tween 20). Finally, rbST was released by alkalinisation and the samples were trypsin digested prior to UHPLC-MS/MS analysis in the MRM mode. Validation was done in accordance with European Commission Decision 2002/657/CE. Matrix-matched calibration with internal standards was used. The decision limit (CCα) reached with this approach was 0.11 µg l−1.

Стимуляція продукції гормону росту у ягнят і поросят під дією Гамавіту

Among the most important issues of food safety, which conducted an extensive international discussion, is the use in livestock of drugs, such as recombinant bovine growth hormone, or somatotropin, and, in particular, ractopamine, stimulating the growth of cattle, pigs and poultry. Ractopamine is used in veterinary medicine to increase the meatiness of the carcass. Ractopamine improves feed conversion, reduces body fat through lipolysis and an intense muscle-building. In the United States, Australia, Argentina, Brazil, Canada and many other countries, ractopamine is allowed for usage as growth stimulator in livestock. However, in most countries of the European Union the use of ractopamine is forbidden. In this regard, it seems very important to develop effective and safe drugs that can stimulate the production of endogenous somatotropic hormone (STH). We propose to use for this purpose Gamavit – well-studied veterinary medicine stimulating metabolism and widely used by veterinary specialists in the Russian Federation, Ukraine, Belarus and some other countries. The aim of this work was to study the effect of Gamavit on STH production in suckling piglets and lambs. Previously it was shown elsewhere that Gamavit induced 2-fold increase in the STH blood level in calves. The experiment was done using 30 suckling piglets of Landrace breed at the age of 0 to 7 days and 10 newborn lambs of the Stavropol breed. All animals were kept in identical conditions, they were fed the same balanced diet. The study was conducted according to the following protocol: The piglets of the 1st group (control) received 0.9% NaCl solution at a dose of 0.5 ml/kg intramuscularly on the 1st, 2nd, 3rd and 5th days of the experiment. Piglets of group 2 (experimental) were inoculated with Gamavit at a dose of 0.5 ml/kg intramuscularly on the 1st, 2nd, 3rd and 5th days of the experiment. Lambs were inoculated with Gamavit at a dose of 0.5 ml/kg of body weight on 7th, 14th and 21st days after birth. Using method of enzyme immunoassay we shown that during the study level of STH in the experimental group of piglets inoculated with Gamavit gradually increased from 8.5 mIU/l before the experiment to 14.3 mIU/l on the 5th day. In the control group it ranged from 7.5 mIU/l to 10.2 mIU\l. At the end of the experiment greatest body weight gain was observed in the experimental group and amounted 45.450 g compared with 26,700 g in the control group piglets. In the experimental group of newborn lambs Gamavit induced raise in the STH serum level 2 from 6.5 mIU/l at day 0 to 13.1 mIU/l at day 21. Thus, Gamavit, unlike synthetic growth hormone, ractopamine and other beta-agonists used in livestock, induces the production of endogenous STH, which stimulates growth of the animal, while being safe and rapidly metabolizing on its own metabolic pathway.

Significant improvement of shrimp growth performance by growth hormone-releasing peptide-6 immersion treatments

Growth hormone-releasing peptide-6 (GHRP-6) is one of the earliest developed synthetic peptidyl growth hormone secretagogue receptor agonists. These compounds mimic the effect of the endogenous ligand ghrelin. In vertebrates, ghrelin is a potent circulating orexigenic hormone with functional roles in controlling food intake, energy expenditure, adiposity, growth hormone secretion and immunity. Ghrelin has been studied mainly in vertebrates; thus, little is known about its role in invertebrates, including crustaceans. We first evaluated the effect of GHRP-6 injection over feed intake in shrimp and its effects on shrimp growth when the peptide was administrated by successive immersion baths. GHRP-6 increased feed intake, body weight and size, the number of rostral spines and gill branches, protein concentration and haemocyte number in treated shrimps. We also evaluated the peptide uptake and clearance in a pharmacokinetics, using [H3]GHRP-6 administered to postlarvae. Given a limited exposure and efficient clearance of the peptide-associated radioactivity from larvae, our findings suggested that GHRP-6-treated Litopenaeus vannamei can be consumed safely by humans after aquaculture applications. These results propose that GHRP-6 could be an additional tool to study growth physiology in crustaceans and also a promising candidate for development into a new biotechnology product for improving shrimp growth and quality.