3.Comparative Study of the Effects of Different Growth Hormone Doses on Growth and Spatial Performance of Hypophysectomized Rats.
Min Jung KWAK ; Hee Ju PARK ; Mi Hyun NAM ; O Suk KWON ; So Young PARK ; So Yeon LEE ; Mi Jin KIM ; Su Jin KIM ; Kyung Hoon PAIK ; Dong Kyu JIN
Journal of Korean Medical Science 2009;24(4):729-736
This study was designed to examine the effects of recombinant human growth hormone replacement on somatic growth and cognitive function in hypophysectomized (HYPOX) female Sprague-Dawley rats. Rats (5 per group) were randomized by weight to 3 experimental groups: group 1, administered 200 microgram/kg of GH once daily for 9 days; group 2, administered 200 microgram/kg of GH twice daily; and group 3, administered saline daily. Somatic growth was evaluated by measurement of body weight daily and of the width of the proximal tibial growth plate of the HYPOX rats. Cognitive function was evaluated using the Morris water maze (MWM) test. The results indicated that GH replacement therapy in HYPOX rats promoted an increase in the body weight and the width of the tibial growth plate in a dose-dependent manner. On the third day of the MWM test, the escape latency in the GH-treated groups 1 and 2 was significantly shorter than that in the control rats (P<0.001 and P=0.032, respectively), suggesting that rhGH improved spatial memory acquisition in the MWM test. Therefore it is concluded that rhGH replacement therapy in HYPOX rats stimulates an increase in somatic growth in a dose-dependent manner and also has beneficial effects on cognitive functions.
Animals
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Body Weight
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Female
;
Growth/*drug effects
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Growth Plate/drug effects/pathology
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Human Growth Hormone/administration & dosage/*pharmacology
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Humans
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*Hypophysectomy
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Rats
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Rats, Sprague-Dawley
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Spatial Behavior/*drug effects
4.Efficacy and Safety of Sustained-Release Recombinant Human Growth Hormone in Korean Adults with Growth Hormone Deficiency.
Youngsook KIM ; Jae Won HONG ; Yoon Sok CHUNG ; Sung Woon KIM ; Yong Wook CHO ; Jin Hwa KIM ; Byung Joon KIM ; Eun Jig LEE
Yonsei Medical Journal 2014;55(4):1042-1048
PURPOSE: The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage(TM)) supplement in patients with growth hormone deficiency were evaluated. MATERIALS AND METHODS: This trial is 12-week prospective, single-arm, open-label trial. Men and women aged > or =20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. RESULTS: The IGF-1 level of 108.67+/-74.03 ng/mL was increased to 129.01+/-68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80+/-6.51 to 7.55+/-5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. CONCLUSION: Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events.
Adult
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Aged
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Delayed-Action Preparations
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Female
;
Growth Hormone/administration & dosage/*adverse effects/*therapeutic use
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Human Growth Hormone/*deficiency
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Humans
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Male
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Middle Aged
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Prospective Studies
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Recombinant Proteins/administration & dosage/*adverse effects/*therapeutic use
5.Attach great importance to the standardized clinical usage and safety monitoring of recombinant human growth hormone in children.
Chinese Journal of Pediatrics 2013;51(6):401-405
Body Height
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drug effects
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Child
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Drug Monitoring
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Growth Disorders
;
diagnosis
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drug therapy
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Human Growth Hormone
;
administration & dosage
;
adverse effects
;
therapeutic use
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Humans
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Practice Guidelines as Topic
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Recombinant Proteins
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administration & dosage
;
adverse effects
;
therapeutic use
;
Risk Factors
6.The influence of combined supplementation of glutamine and recombinant human growth hormone on the protein metabolism in severely burned patients.
Cai-jiao LU ; Cai LIN ; Jian-jun XU ; Peng ZHANG ; Guo-zhou CAO ; Bao-shun HONG
Chinese Journal of Burns 2004;20(4):220-222
OBJECTIVETo investigate the influence of combined supplementation of glutamine (Gln) and recombinant human growth hormone (rhGH) on the protein metabolism in severely burned patients.
METHODSSixty severely burned patients were enrolled in the study and were randomly divided into control (C, n = 20) and Gln with rhGH (Gln + rhGH, n = 20) groups. The patients in C group received glycine as the placebo, while those in Gln group took Gln orally in dose of 0.5 g kg(-1) d(-1) during 1-14 postburn days (PBDs). For the patients in Gln + rhGH group rhGH was administered subcutaneously in dose of 0.2 U kg(-1) d(-1) in addition to glutamine in same dosage beginning on the 7 PBD for 7 days. The plasma Gln concentration in the 3 groups of patients was determined on the 1st, 7th and 14th PBD and the plasma albumin level was determined on 14th and 21st PBD. The wound healing rate of the patients within 30 PBSs and the total hospital stay days were recorded.
RESULTSThe plasma Gln concentration in Gln + rhGH group of patients was evidently higher than that in C group after 7 PBD[(452.28 +/- 21.72) micromol/L vs(325.12 +/- 25.34) micromol/L, P < 0.05]. The plasma albumin level in Gln + rhGH group was obviously higher than that in C and Gln groups on the 21st PBD (P < 0.05). The wound healing rate in Gln + rhGH group was evidently higher than that in Gln and C groups on the 30th PBD (P < 0.05). The total hospital stay days in Gln + rhGH group were obviously less than that in C and Gln groups (P < 0.05 or 0.01).
CONCLUSIONCombined administration of Gln and rhGH could be beneficial to the elevation of plasma Gln level in severely burned patients and the systemic protein synthesis was therefore enhanced and the wound healing rate was improved.
Adult ; Aged ; Burns ; metabolism ; therapy ; Female ; Glutamine ; administration & dosage ; blood ; therapeutic use ; Human Growth Hormone ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Treatment Outcome ; Wound Healing ; drug effects ; Young Adult
7.Effect of gonadotropin-releasing hormone analog combined with stanazolol on final height in girls with idiopathic central precocious puberty and apparent decrease of linear growth.
Yan-hong LI ; Shun-ye ZHU ; Hua-mei MA ; Zhe SU ; Hong-shan CHEN ; Qiu-li CHEN ; Yu-fen GU ; Min-lian DU
Chinese Journal of Pediatrics 2013;51(11):807-812
OBJECTIVETo evaluate the effect of combined use of stanazolol (ST) on the final adult height (FAH) in girls with idiopathic central precocious puberty (ICPP) and apparently decreased linear growth during gonadotropin-releasing hormone analog (GnRHa) therapy.
METHODSixty-three girls with ICPP and decreased velocity of growth of height (HV<4 cm/yr) during GnRHa therapy were divided into 3 groups based on the following types of interventions:group 1 (n = 20), GnRHa+ST [25-30 µg/(kg·d) every 3-month followed by 3-month discontinuation], group 2 (n = 21), GnRHa+recombinant human growth hormone [rhGH, 1-1.1 U/(kg·w)], group 3 (n = 22), GnRHa alone.HV, the advancement of bone age (BA) for chronological age (CA) (ΔBA/ΔCA) and FAH were compared among groups.
RESULT(1)Total duration of ST combination therapy was (12.22 ± 3.62) months, while total duration of combination of rhGH was (13.22 ± 6.80) months. (2)HV increased significantly in both group 1 [ (2.79 ± 0.60) cm/yr vs. (6.27 ± 1.98) cm/yr, P < 0.01] and in group 2 [(2.80 ± 0.50) cm/yr vs. (6.25 ± 1.98) cm/yr, P < 0.01] during combined therapy, but maintained at low levels in group 3 [(3.95 ± 1.10) cm/yr vs. (3.34 ± 0.95) cm/yr, P > 0.05].No significant differences of ΔBA/ΔCA were found among the three groups [0.25(0.11∼0.28), 0.22(0.15∼0.31),0.19(0.10∼0.32), P > 0.05]. (3)FAH was significantly higher than predicted adult height (PAH) before combined therapy, as well as higher than target height (THt) in both group 1 [(156.25 ± 2.90) cm vs. (150.78 ± 3.70) cm, P < 0.01, (156.25 ± 2.90) cm vs. (153.94 ± 2.62) cm, P < 0.01], and in group2 [ (157.33 ± 4.69) cm vs. (152.61 ± 3.92) cm, P < 0.01, (157.33 ± 4.69) cm vs. (154.39 ± 4.72) cm, P = 0.01].In group 3, FAH was similar to PAH [(153.88 ± 2.6) cm vs. (152.54 ± 5.86) cm, P > 0.05], and was less than THt [(153.88 ± 2.6) cm vs. (155.60 ± 4.52) cm, P = 0.02]. (4)In girls treated with ST, no hirsutism, clitorism or hoarse voice was recorded.No polycystic ovary syndrome was found by B-mode ultrasound.
CONCLUSIONIntermittent combined use of low dose ST therapy can increase HV and thus improve FAH in girls with ICPP and apparently decreased linear growth during GnRHa therapy.
Body Height ; drug effects ; Bone Development ; Child ; Child Development ; drug effects ; Drug Therapy, Combination ; Female ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; therapeutic use ; Growth Disorders ; drug therapy ; Human Growth Hormone ; administration & dosage ; therapeutic use ; Humans ; Puberty, Precocious ; drug therapy ; physiopathology ; Stanozolol ; administration & dosage ; therapeutic use ; Treatment Outcome
8.Recombinant human growth hormone secreted from tissue-engineered bioartificial muscle improves left ventricular function in rat with acute myocardial infarction.
Shu-ling RONG ; Yong-jin WANG ; Xiao-lin WANG ; Yong-xin LU ; Chao CHANG ; Feng-zhi WANG ; Qi-yun LIU ; Xiang-yang LIU ; Yan-zhang GAO ; Shao-hua MI
Chinese Medical Journal 2009;122(19):2352-2359
BACKGROUNDExperimental studies and preliminary clinical studies have suggested that growth hormone (GH) treatment may improve cardiovascular parameters in chronic heart failure (CHF). Recombinant human GH (rhGH) has been delivered by a recombinant protein, by plasmid DNA, and by genetically engineered cells with different pharmacokinetic and physiological properties. The present study aimed to examine a new method for delivery of rhGH using genetically modified bioartificial muscles (BAMs), and investigate whether the rhGH delivered by this technique improves left ventricular (LV) function in rats with CHF.
METHODSPrimary skeletal myoblasts were isolated from several Sprague-Dawley (SD) rats, cultured, purified, and retrovirally transduced to synthesize and secrete human rhGH, and tissue-engineered into implantable BAMs. Ligation of the left coronary artery or sham operation was performed. The rats that underwent ligation were randomly assigned to 2 groups: CHF control group (n = 6) and CHF treatment group (n = 6). The CHF control group received non-rhGH-secreting BAM (GFP-BAMs) transplantation, and the CHF treatment group received rhGH-secreting BAM (GH-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: sham control group (n = 6) and sham treatment group (n = 6). The sham control group underwent GFP-BAM transplantation, and the sham treatment group underwent GH-BAM transplantation. GH-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats with ligation of the left coronary artery or sham operation was performed. Eight weeks after the treatment, echocardiography was performed. hGH, insulin-like growth factor-1 (IGF-1) and TNF-alpha levels in rat serum were measured by radioimmunoassay and ELISA, and then the rats were killed and ventricular samples were subjected to immunohistochemistry.
RESULTSPrimary rat myoblasts were retrovirally transduced to secrete rhGH and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted 1 to 2 microg of bioactive rhGH per day. When implanted into syngeneic rat, GH-BAMs secreted and delivered rhGH. Eight weeks after therapy, LV ejection fraction (EF) and fractional shortening (FS) were significantly higher in CHF rats treated with GH-BAMs than in those treated with GFP-BAMs ((65.0 +/- 6.5)% vs (48.1 +/- 6.8)%, P < 0.05), ((41.3 +/- 7.4)% vs (26.5 +/- 7.1)%, P < 0.05). LV end-diastolic dimension (LVEDD) was significantly lower in CHF rats treated with GH-BAM than in CHF rats treated with GFP-BAM (P < 0.05). The levels of serum GH and IGF-1 were increased significantly in both CHF and sham rats treated with GH-BAM. The level of serum TNF-alpha decreased more significantly in the CHF treatment group than in the CHF control group.
CONCLUSIONSrhGH significantly improves LV function and prevents cardiac remodeling in rats with CHF. Genetically modified tissue-engineered bioartificial muscle provides a method delivering recombinant protein for the treatment of heart failure.
Animals ; Bioartificial Organs ; Echocardiography ; Heart Failure ; therapy ; Human Growth Hormone ; administration & dosage ; Myoblasts, Skeletal ; metabolism ; Myocardial Infarction ; pathology ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; administration & dosage ; Tissue Engineering ; Tumor Necrosis Factor-alpha ; blood ; Ventricular Function, Left
9.Pharmacokinetics of rhGH decorated by polyethylene glycol in rat in vivo.
Ling JIANG ; Yong-ming CAI ; Yong ZENG ; Ji HUANG ; Zheng-min CHEN
Acta Pharmaceutica Sinica 2009;44(5):506-509
To study the pharmacokinetics of rhGH decorated by polyethylene glycol (PEG-rhGH) after sc administration in rat, serum PEG-rhGH concentrations were measured by 125I labeled method after sc in rat, the pharmacokinetic model and parameters were fitted and calculated by the 3P97 program. After sc injection at doses of 150, 300, and 600 microg x kg(-1) in rat, the serum PEG-rhGH concentration-time curves were fitted to a one-compartment model. The rhGH decorated by polyethylene glycol could prolong the action duration of rhGH in vivo, and reach the goal of long-action.
Animals
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Area Under Curve
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Delayed-Action Preparations
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Dose-Response Relationship, Drug
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Female
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Human Growth Hormone
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administration & dosage
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blood
;
pharmacokinetics
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Injections, Subcutaneous
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Male
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Polyethylene Glycols
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chemistry
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins
;
administration & dosage
;
blood
;
pharmacokinetics
10.Additive Effects of Intra-articular Injection of Growth Hormone and Hyaluronic Acid in Rabbit Model of Collagenase-induced Osteoarthritis.
Sang Beom KIM ; Dong Rak KWON ; Hyun KWAK ; Yong Beom SHIN ; Hyun jung HAN ; Jong Hwa LEE ; Seok Hwa CHOI
Journal of Korean Medical Science 2010;25(5):776-780
In a rabbit model of collagenase-induced osteoarthritis, the additive effects of intra-articular recombinant human growth hormone (GH) administration to hyaluronic acid (HA) were evaluated. After intra-articular collagenase injection, mature New Zealand white rabbits (n=30) were divided into 3 groups. Group 1 (control rabbits) received once weekly intra-articular saline injections for 4 weeks. Group 2 rabbits received 6 mg HA injections, and group 3 rabbits were injected with 6 mg HA and 3 mg recombinant human GH. These injections were initiated 4 weeks after collagenase injections. Lameness was observed for 9 weeks after collagenase injections. Macroscopic and histopathological knee joint findings were also evaluated at the end of 9 weeks after collagenase injections. Although all animals had lameness after collagenase injections, the duration and severity of lameness were significantly shorter and less severe in group 3 than group 1 and 2 (P<0.01). Macroscopic scores showed that femoral condyles of group 3 rabbits received significantly less cartilage damage than those of groups 1 and 2 rabbits (P<0.01). Histopathological score was also the lowest in group 3 (P<0.01). These results suggest that co-injection of intra-articular HA and recombinant human GH is more effective than HA injections alone in an osteoarthritis model.
Animals
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*Collagenases
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*Disease Models, Animal
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Drug Combinations
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Drug Synergism
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Human Growth Hormone/*administration & dosage
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Humans
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Hyaluronic Acid/*administration & dosage
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Injections, Intra-Articular
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Male
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Osteoarthritis/*chemically induced/diagnosis/*drug therapy
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Rabbits
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Treatment Outcome