Journal of Pediatric Endocrinology and Metabolism, 2010
There is a huge market for ergogenic supplements for athletes. However, only a few products have ... more There is a huge market for ergogenic supplements for athletes. However, only a few products have been proven to have ergogenic effects and to be effective at improving muscle strength and body composition. One such supplement is beta-hydroxy beta-methylbutyrate (HMB). Derived from the amino acid leucine and its keto acid alpha-ketoisocaproate (KIC), HMB has been well documented as an oral ergogenic supplement commonly used by athletes. Several studies have shown that combining exercise training with HMB supplementation leads to increased muscle mass and strength, and there is some anecdotal evidence of aerobic improvement. However, HMB supplementation has been found to be effective mainly for untrained individuals. While previous reviews have emphasized three main pathways for HMB's mode of action: 1) enhancement of sarcolemmal integrity via cytosolic cholesterol, 2) inhibition of protein degradation via proteasomes, and 3) increased protein synthesis via the mTOR pathway, more recent studies have suggested additional possible mechanisms for its physiological effects. These include decreased cell apoptosis and enhanced cell survival, increased proliferation, differentiation and fusion via the MAPK/ERK and PI3K/Akt pathways, and enhanced IGF-I transcription. These are described here, and hormonal interactions are discussed, along with HMB dosage and safety issues.
The Journal of Clinical Endocrinology and Metabolism, Jul 1, 1986
Marginal salt loss occurs in patients with congenital adrenal hyperplasia due to 11 beta-hydroxyl... more Marginal salt loss occurs in patients with congenital adrenal hyperplasia due to 11 beta-hydroxylase (11-OHase) deficiency treated with dexamethasone and is accompanied by increased PRA. The present study was undertaken to evaluate the effect of the stimulated renin-angiotensin system on pituitary-adrenal suppression. Seven patients with 11-OHase deficiency were subjected to a series of treatments with dexamethasone, cortisol, and combined cortisol and 9 alpha-fluorohydrocortisone. The latter combination suppressed PRA and sodium excretion, and produced better control of the pituitary-adrenal axis, as measured by plasma ACTA and serum 11-deoxycortisol. We conclude that in children with 11-OHase deficiency, PRA needs to be monitored, and when it is elevated, mineralocorticoid replacement is indicated.
Vitamin A (VA) is required for normal growth and development retinoic acid may be the active meta... more Vitamin A (VA) is required for normal growth and development retinoic acid may be the active metabolite through binding to nuclear receptors. Recently a correlation between nocturnal growth hormone (GH) secretion and VA was was found in short slowly growing children. We determined the 24-hour integrated concentration of GH (IC-GH), GH response to provocative stimuli, IGF-I, IGF-binding protein-3 (IGF-BP3) and GH-binding protein (GH-BP) in 34 prepubertal children (25 m/9 f) 5-10 years of age, height -2.5 to 1.5 SDS and body mass index -1.5 to 1.5 SDS for age and sex. Since folic acid, vitamin B12, IGF-I, cholesterol, triglycerides and VA carrier proteins were normal we assumed that no major nutritional deficiency existed. The correlation matrix of the variates tested were p < 0.05 for VA and IC-GH and p < 0.006 for IGF-BP3. It is suggested that VA might have a direct affect on both ICGH and IGF-BP3.
Growth-promoting effect of human chorionic gonadotrophin (HCG) was studied in 40 boys of 2-8 year... more Growth-promoting effect of human chorionic gonadotrophin (HCG) was studied in 40 boys of 2-8 years with unilateral undescended testes. A transient acceleration of height and weight increase was noted that exceeded rates found in normal puberty. No significant advance in bone age was noted following treatment. On the basis of this study we conclude that short-term HCG treatment does not change the growth pattern or bone age of 2-8-year-old boys.
Purpose To assess the long-term efficacy of burosumab for paediatric patients with X-linked hypop... more Purpose To assess the long-term efficacy of burosumab for paediatric patients with X-linked hypophosphatemia, focusing on linear growth. Methods This multi-center retrospective study included 35 paediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results and rickets severity score (RSS), from two years prior to treatment initiation and up to four years after. Results Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6–15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1–4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after three months, and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8% to 90.1 ± 5.3% after 12 months of treatment...
Background Somatrogon is a long-acting recombinant human growth hormone (hGH) currently in develo... more Background Somatrogon is a long-acting recombinant human growth hormone (hGH) currently in development as a once-weekly injectable treatment for children with growth hormone deficiency (GHD). In a phase 2 (NCT01592500) and a phase 3 (NCT02968004) study, patients received either once-weekly somatrogon or once-daily Genotropin. Aims Compare the phase 2 and 3 study results with growth data from published literature and a database of children treated with once-daily Genotropin. Methods In the 12-month main portion of the phase 2 study (004), patients were randomized to 1 of 3 once-weekly somatrogon doses (0.25, 0.48, and 0.66 mg/kg/week) or once-daily Genotropin (0.24 mg/kg/week). After the main portion of 004, patients continued into the open-label extension (OLE), consisting of an additional 12 months at the original somatrogon dose (Genotropin recipients were randomized to 1 of the 3 somatrogon dose regimens), after which all patients received somatrogon at 0.66 mg/kg/week. In the 12...
Journal of Pediatric Endocrinology and Metabolism, 2010
There is a huge market for ergogenic supplements for athletes. However, only a few products have ... more There is a huge market for ergogenic supplements for athletes. However, only a few products have been proven to have ergogenic effects and to be effective at improving muscle strength and body composition. One such supplement is beta-hydroxy beta-methylbutyrate (HMB). Derived from the amino acid leucine and its keto acid alpha-ketoisocaproate (KIC), HMB has been well documented as an oral ergogenic supplement commonly used by athletes. Several studies have shown that combining exercise training with HMB supplementation leads to increased muscle mass and strength, and there is some anecdotal evidence of aerobic improvement. However, HMB supplementation has been found to be effective mainly for untrained individuals. While previous reviews have emphasized three main pathways for HMB&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s mode of action: 1) enhancement of sarcolemmal integrity via cytosolic cholesterol, 2) inhibition of protein degradation via proteasomes, and 3) increased protein synthesis via the mTOR pathway, more recent studies have suggested additional possible mechanisms for its physiological effects. These include decreased cell apoptosis and enhanced cell survival, increased proliferation, differentiation and fusion via the MAPK/ERK and PI3K/Akt pathways, and enhanced IGF-I transcription. These are described here, and hormonal interactions are discussed, along with HMB dosage and safety issues.
The Journal of Clinical Endocrinology and Metabolism, Jul 1, 1986
Marginal salt loss occurs in patients with congenital adrenal hyperplasia due to 11 beta-hydroxyl... more Marginal salt loss occurs in patients with congenital adrenal hyperplasia due to 11 beta-hydroxylase (11-OHase) deficiency treated with dexamethasone and is accompanied by increased PRA. The present study was undertaken to evaluate the effect of the stimulated renin-angiotensin system on pituitary-adrenal suppression. Seven patients with 11-OHase deficiency were subjected to a series of treatments with dexamethasone, cortisol, and combined cortisol and 9 alpha-fluorohydrocortisone. The latter combination suppressed PRA and sodium excretion, and produced better control of the pituitary-adrenal axis, as measured by plasma ACTA and serum 11-deoxycortisol. We conclude that in children with 11-OHase deficiency, PRA needs to be monitored, and when it is elevated, mineralocorticoid replacement is indicated.
Vitamin A (VA) is required for normal growth and development retinoic acid may be the active meta... more Vitamin A (VA) is required for normal growth and development retinoic acid may be the active metabolite through binding to nuclear receptors. Recently a correlation between nocturnal growth hormone (GH) secretion and VA was was found in short slowly growing children. We determined the 24-hour integrated concentration of GH (IC-GH), GH response to provocative stimuli, IGF-I, IGF-binding protein-3 (IGF-BP3) and GH-binding protein (GH-BP) in 34 prepubertal children (25 m/9 f) 5-10 years of age, height -2.5 to 1.5 SDS and body mass index -1.5 to 1.5 SDS for age and sex. Since folic acid, vitamin B12, IGF-I, cholesterol, triglycerides and VA carrier proteins were normal we assumed that no major nutritional deficiency existed. The correlation matrix of the variates tested were p &lt; 0.05 for VA and IC-GH and p &lt; 0.006 for IGF-BP3. It is suggested that VA might have a direct affect on both ICGH and IGF-BP3.
Growth-promoting effect of human chorionic gonadotrophin (HCG) was studied in 40 boys of 2-8 year... more Growth-promoting effect of human chorionic gonadotrophin (HCG) was studied in 40 boys of 2-8 years with unilateral undescended testes. A transient acceleration of height and weight increase was noted that exceeded rates found in normal puberty. No significant advance in bone age was noted following treatment. On the basis of this study we conclude that short-term HCG treatment does not change the growth pattern or bone age of 2-8-year-old boys.
Purpose To assess the long-term efficacy of burosumab for paediatric patients with X-linked hypop... more Purpose To assess the long-term efficacy of burosumab for paediatric patients with X-linked hypophosphatemia, focusing on linear growth. Methods This multi-center retrospective study included 35 paediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results and rickets severity score (RSS), from two years prior to treatment initiation and up to four years after. Results Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6–15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1–4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after three months, and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8% to 90.1 ± 5.3% after 12 months of treatment...
Background Somatrogon is a long-acting recombinant human growth hormone (hGH) currently in develo... more Background Somatrogon is a long-acting recombinant human growth hormone (hGH) currently in development as a once-weekly injectable treatment for children with growth hormone deficiency (GHD). In a phase 2 (NCT01592500) and a phase 3 (NCT02968004) study, patients received either once-weekly somatrogon or once-daily Genotropin. Aims Compare the phase 2 and 3 study results with growth data from published literature and a database of children treated with once-daily Genotropin. Methods In the 12-month main portion of the phase 2 study (004), patients were randomized to 1 of 3 once-weekly somatrogon doses (0.25, 0.48, and 0.66 mg/kg/week) or once-daily Genotropin (0.24 mg/kg/week). After the main portion of 004, patients continued into the open-label extension (OLE), consisting of an additional 12 months at the original somatrogon dose (Genotropin recipients were randomized to 1 of the 3 somatrogon dose regimens), after which all patients received somatrogon at 0.66 mg/kg/week. In the 12...
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