Consensus ; Growth Disorders ; diagnosis ; drug therapy ; Hormone Replacement Therapy ; Human Growth Hormone ; administration & dosage ; deficiency ; therapeutic use ; Humans ; Practice Guidelines as Topic

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 ; Aged ; Delayed-Action Preparations ; Female ; Growth Hormone/administration & dosage/*adverse effects/*therapeutic use ; Human Growth Hormone/*deficiency ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recombinant Proteins/administration & dosage/*adverse effects/*therapeutic use

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

Body Height ; drug effects ; Child ; Drug Monitoring ; Growth Disorders ; diagnosis ; drug therapy ; Human Growth Hormone ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Practice Guidelines as Topic ; Recombinant Proteins ; administration & dosage ; adverse effects ; therapeutic use ; Risk Factors

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 ; *Collagenases ; *Disease Models, Animal ; Drug Combinations ; Drug Synergism ; Human Growth Hormone/*administration & dosage ; Humans ; Hyaluronic Acid/*administration & dosage ; Injections, Intra-Articular ; Male ; Osteoarthritis/*chemically induced/diagnosis/*drug therapy ; Rabbits ; Treatment Outcome

Human Growth Hormone ; administration & dosage ; pharmacology ; Recombinant Proteins ; administration & dosage ; pharmacology

OBJECTIVEProbe the effects of rhGH on severe degree burned patients' blood sugar in different age of years.

METHODSElected 210 patients hospitalized in the Third Affiliated Hospital of Wenzhou Medical College from January 2005 to December 2008, who were burned in 48 h, older than 18 years, ever had no diabetes and tumor history and placidly pull through shock stage. Among the patients there were 132 males and 78 females. The age was from 18 to 65 years old, average (40.7 +/- 7.2) years old. The extent of burn were form TBSA 25% to TBSA 86%, average TBSA (40.4 +/- 12.5)%. The depths of burn were from superficial second degree to third degree. All of the total divided into A (18 - 44 years old) and B (> 45 years old)groups. Each group had 105 patients. Two groups were randomly divided into A(1), A(2), A(0) and B(1), B(2), B(0) groups. Each group had 35 patients. The A(1) and B(1) groups were used 0.15 U/(kg.d) growth hormone (Somatropin, S19990021), A(2) and B(2) groups were used 0.2 U/(kg.d) growth hormone, A(0) and B(0) groups were used NS as control. Observed and analyzed the change of blood sugar and insulin amount used in 210 patients.

RESULTSOf all the patients in 6 groups, there were 190 patients finished the experimentation in four weeks. The insulin amount of A(1), A(2), A(0) groups used were (2123.3 +/- 152.3), (2885.6 +/- 148.5), (724.1 +/- 31.1) U, B(1), B(2), B(0) group were (2715.1 +/- 95.3), (3652.2 +/- 198.1), (801.8 +/- 22.2) U. The consequence showed that the number need insulin to control blood sugar in B group was more than A group, as well as using 0.2 U/(kg.d) does to 0.15 U/(kg.d) does, and using growth hormone to no using(P < 0.01). The time that blood sugar of A(1), A(2), B(1), B(2) group recovered to normal range without using insulin were (5.11 +/- 0.82), (4.93 +/- 0.89), (5.2 +/- 0.65), (5.13 +/- 1.02) d (P > 0.05).

CONCLUSIONSThe blood sugar's alteration has positive correlation with the age of years and the does of rhGH. As long as normative using rhGH it doesn't induce diabetes.

Adolescent ; Adult ; Age Factors ; Aged ; Blood Glucose ; drug effects ; metabolism ; Burns ; blood ; drug therapy ; Dose-Response Relationship, Drug ; Female ; Human Growth Hormone ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Young Adult

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

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 ; Area Under Curve ; Delayed-Action Preparations ; Dose-Response Relationship, Drug ; Female ; Human Growth Hormone ; administration & dosage ; blood ; pharmacokinetics ; Injections, Subcutaneous ; Male ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; administration & dosage ; blood ; pharmacokinetics

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 ; Body Weight ; Female ; Growth/*drug effects ; Growth Plate/drug effects/pathology ; Human Growth Hormone/administration & dosage/*pharmacology ; Humans ; *Hypophysectomy ; Rats ; Rats, Sprague-Dawley ; Spatial Behavior/*drug effects