Follicle-stimulating hormone (FSH) plays a central role in mammals reproduction, with the actions of FSH mediated by follicle-stimulating hormone receptors (FSHRs) on the surface of target cells. The purposes of this ...Follicle-stimulating hormone (FSH) plays a central role in mammals reproduction, with the actions of FSH mediated by follicle-stimulating hormone receptors (FSHRs) on the surface of target cells. The purposes of this study were to determine and evaluate the biological activities for the commercialization of recombinant follicle-stimulating hormone (rFSH) in vitro through the cellular internalization using cloned 293T-FSHR cell lines as target. Using imaging approaches we have found here that a little fluorescent signal from the surface of the cell transferred to the cytoplasm and accumulated around the nucleus by endocytosis. Compared with the control groups, the commercialization of rFSH have not the significant differences of internalization, but the rFSH have promoted the internalization of the fluorescent, suggested that this detection system might as a protocol for the bioactivity of recombinant therapeutic proteins in vitro.展开更多
Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was tre...Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34) 20 μg daily for 18 months,and the elcalonin group(CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months.Bone mineral density(BMD) of the lumbar spine 2-4(L_(2-4))and femoral neck,serum calcium and phosphorus,urinary calcium,serum hone specific alkaline phosphatase(BSAP).and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ /Cn were tested at baseline,and 6.12.and 18 months after treatment.Results:In PTH group.HMD of L_(2-4),at 6,12.and 18 months,BDM of Femoral neck at 18 month,BSAP at 6 and 12 months and uCTX- Ⅰ /Cr at 6.12 and 18 months were all significantly raised.In CT group.HMD of L_(2-4) at12 month and that of femoral neck at 12 and 18 months were significantly elevated,while HSAP was significantly decreased at 12 and 18 months,and no significant difference on CTX- Ⅰ /Cr was observed.When BMD growth and growth rate between two groups were compared.PTH group had better improvement in L_(2-4) BMD and growth rate than CT group at 6.12.and 18 months.BMD growth and growth rale of femoral neck al 12 month and its growth at 18 month in CT group were higher than in PTH group,hut there was no significant difference between two groups regarding the growth rates at 18 month.Besides,there were no significant differences regarding the rales ol adverse reactions between two groups.Conclusions:rhPTH(1—34),is safe and effective in the treatment of primary OP.It is superior to elcatonin in improving vertebral HMD at onset time,growth rate and growth range,but inferior to elcatonin at HMD of femoral neck.展开更多
In order to observe the nutrition state in the severe multiple trauma patients undergoing adjuvant recombinant human growth hormone (rhGH) nutritional support therapy, 45 patients with severe multiple traumas (ISS>...In order to observe the nutrition state in the severe multiple trauma patients undergoing adjuvant recombinant human growth hormone (rhGH) nutritional support therapy, 45 patients with severe multiple traumas (ISS>25) were randomly divided into 3 groups. All the 3 groups had been supplied with nitrogen and caloricity according to the need of patients for 16 days. The rhGH therapy started 48 h after surgery and lasted for 14 days in two rhGH-treated groups in which rhGH was 0.2 and 0.4 U/(kg·d) respectively, and the resting group served as control one. The levels of nitrogen balance, prealbumin and safety variables (blood sugar, Na+, TT3 and TT4) were observed and com- pared among the three groups. The levels of nitrogen balance on the postoperative day (POD) 3 and 5 in the rhGH-treated groups were -1.28±3.19, 5.45±2.00 and -0.18±2.55, 6.11±1.60, respectively, which were significantly higher than those in the control group (-5.17±1.68 and -1.08±3.31, P<0.01). The values of prealbumin on the POD 3 and 5 in the rhGH-treated groups were 180.19±27.15, 194.44±50.82 and 194.94±29.65, 194.11±16.17, respectively, which were significantly higher than those in the control group (117.42±19.10 and 135.63±28.31, P<0.01). There was no sig- nificant difference between the rhGH 0.2 U/(kg·d) group and rhGH 0.4 U/(kg·d) group in both of the levels of nitrogen balance and prealbumin. It is concluded that the nutritional support therapy with adjuvant rhGH which starts 48 h after surgery improves the nutrition state of the patients with severe multiple trauma. It is safe for severe multiple trauma patients who accept rhGH at the dose of 0.2 and 0.4 U/(kg·d).展开更多
Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to in...Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to investigate the effect and mechanism of recombinant human growth hormone (rhGH) and to alleviate intestinal translocation of bacteria and endotoxin in murine obstructive jaundice. METHODS:A group of 42 Wistar rats were divided into 3 groups:sham operation (SO), bile duct ligation (BDL), and BDL and rhGH treatment (rhGH). By the end of the experiment,on day 7, the animals were killed, and their liver function and serum endotoxin were measured, bacterial cultures of the liver, kidney and mesenchymal lymph were made. Terminal ileum mucosa was observed under an electron microscope. RESULTS:Liver function was improved more significantly in the rhGH group than in the BDL group. The value of endotoxin in the rhGH group was 0.38±0.03 EU/ml, significantly lower than that in the BDL group (0.65±0.04 EU/ml, P【0.01), and similar to that in the SO group (0.30±0.02 EU/ml, P】0.05). The rate of bacteria translocation in the liver, kidney and mesenteric lymph was much higher in the BDL group than in other two groups. The rate of bacteria translocation in mesenteric lymph was 64.29%,significantly higher than that in the SO group and the rhGH group (P【0.05). There was no significant difference in bacteria translocation rate between the SO group and the rhGH group (P】0.05). Under an electron microscope , ileum mucosa epithelial cells in the BDL group were necrotic, and organelle were markedly metamorphic. In the rhGH group, ultrastructural changes were less evident or similar to those in the SO group. CONCLUSION:rhGH has significant protective effects on intestinal mucosa barrier in obstructive jaundice, and reduces intestinal translocation of bacteria and endotoxin.展开更多
The current study was designed to determine the safety,tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone[rhPTH(1-84)]used for the treatment of osteoporosis.In the single-dose format ...The current study was designed to determine the safety,tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone[rhPTH(1-84)]used for the treatment of osteoporosis.In the single-dose format pharmacokinetic study,thirty-six healthy male volunteers received three dose levels of rhPTH(1-84)subcutaneously:1,2,and 4μg/kg.The blood was timing drawn and the serum concentration of rhPTH(1-84)was determined by enzyme linked immunosorbent assay(ELISA).Serum concentration-time curves of PTH(1-84)exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration.Serum terminal half-time of PTH(1-84)was approximately 2 h.The parameters indicated the serum levels were directly proportional to the administered dose,with the mean Cmax and AUC0-24 ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg·h·mL-1over the dose range.The drug was well tolerated,the clinical symptoms were generally mild and of short duration.展开更多
AIM:To explore the effects of recombinant human growth hormone (rhGH) on intestinal mucosal epithelial cell proliferation and nutritional status in patients with enterocutaneous fi stula. METHODS:Eight patients with e...AIM:To explore the effects of recombinant human growth hormone (rhGH) on intestinal mucosal epithelial cell proliferation and nutritional status in patients with enterocutaneous fi stula. METHODS:Eight patients with enterocutaneous fi stulas received recombinant human growth hormone (10 μg/d) for 7 d. Image analysis and immunohisto-chemical techniques were used to analyse the expression of proliferating cell nuclear antigen (PCNA) in intestinal mucosal epithelial cells in biopsy samples from the patients who had undergone an endoscopic biopsy through the fi stula at day 0,4 and 7. Body weights,nitrogen excretion,serum levels of total proteins,albumin,prealbumin,transferrin and fi bronectin were measured at day 0,4 and 7. RESULTS:Significant improvements occurred in the expression of PCNA in the intestinal mucosal epithelial cells at day 4 and 7 compared to day 0 (24.93 ± 3.41%,30.46 ± 5.24% vs 12.92 ± 4.20%,P < 0.01). These changes were accompanied by the significant improvement of villus height (500.54 ± 53.79 μm,459.03 ± 88.98 μm vs 210.94 ± 49.16 μm,P < 0.01),serum levels of total proteins (70.52 ± 5.13 g/L,74.89 ± 5.16 g/L vs 63.51 ± 2.47 g/L,P < 0.01),albumin (39.44 ± 1.18 g/L,42.39 ± 1.68 g/L vs 35.74 ± 1.75 g/L,P < 0.01) and f ibronectin (236.3 ± 16.5 mg/L,275.8 ± 16.9 mg/L vs 172.5 ± 21.4 mg/L,P < 0.01) at day 4 and 7,and prealbumin (286.38 ± 65.61 mg/L vs 180.88 ± 48.28 mg/L,P < 0.05),transferrin (2.61 ± 0.12 g/L vs 2.41 ± 0.14 g/L,P < 0.05) at day 7. Nitrogen excretion was signifi cantly decreased at day 7 (3.40 ± 1.65 g/d vs 7.25 ± 3.92 g/d,P < 0.05). No change was observed in the body weight. CONCLUSION:Recombinant human growth hormone could promote intestinal mucosal epithelial cell proliferation and protein synthesis in patients with enterocutaneous fi stula.展开更多
Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: ...Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.展开更多
Objective:To study the protective effect of perioperative recombinant human growth hormone (r-hGH) application on intestinal mucosal barrier function in patients with intestinal obstruction and the influence on the im...Objective:To study the protective effect of perioperative recombinant human growth hormone (r-hGH) application on intestinal mucosal barrier function in patients with intestinal obstruction and the influence on the immune inflammatory response.Methods:60 patients with intestinal obstruction who underwent surgical treatment in our hospital between February 2013 and July 2016 were selected as the research subjects and divided into the control group (n=34) who received conventional surgical treatment and the observation group (n=26) who received surgery combined with perioperative r-hGH treatment. The serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were not statistically significant between the two groups of patients. After treatment, serum intestinal mucosal barrier indexes Endotoxin, D-Lactate and DAO levels in observation group were lower than those in control group, immunoglobulin IgA, IgM and IgG levels were higher than those in control group, and inflammatory response indicators IL-1, IL-6, PCT and TNF-α levels were lower than those in control group patients. Conclusion:Perioperative r-hGH application in patients with intestinal obstruction can protect the intestinal mucosal barrier, also optimize the humoral immunity and suppress the systemic inflammatory response.展开更多
The enhanced cardiac contractility effect of human recombinant growth hormone (hr-GH) on the congestive heart failure (CHF) was studied on the pig. To build a pig model of congestive heart failure, a temporary artific...The enhanced cardiac contractility effect of human recombinant growth hormone (hr-GH) on the congestive heart failure (CHF) was studied on the pig. To build a pig model of congestive heart failure, a temporary artificial cardiac pacemaker was implanted in the pig’s body and paced at 220 beats to 240 beats per minute for 1 week. After the model of congestive heart failure was successfully set up, the frequency of the pacemaker was changed to 150 beats to 180 beats per minute to maintain the CHF model stable. Pigs were divided into three groups: The hr-GH group in which 0.5 mg/kg per day of hr-GH was administrated intramuscularly for 15 days, the injection control group in which an equal amount of physiological saline was injected intramuscularly, and a normal control group. The left ventricular diastolic end pressure was (10.60±2.41) mmHg in the hr-GH group, but (19.00±3.81) mmHg in the saline control group (P<0.01); Cardiac output was (1.86±0.13) L/min in the hr-GH group, but (1.56±0.18) L/min in the saline control group (P<0.05); Peripheral vascular resistance was (56.88±7.51) mmHg·(L/min) -1 in the hr-GH group, whereas (70.30±11.59) mmHg·(L/min) -1 in the saline control group (P<0.05); +dp/dt max was (2900±316.23) and (2280±286.36) in the hr-HG group and the saline control group respectively (P<0.05). The results show that hr-GH enhances myocardial contractility of CHF, and the CHF model built by a temporary artificial cardiac pacemaker at a high rate of stimulation is reasonable and applicable.展开更多
Objective:To investigate the effect of recombinant human brain natriuretic peptide (BNP) on inflammatory factors, neuroendocrine hormones and cardiac function indexes in patients with acute myocardial infarction compl...Objective:To investigate the effect of recombinant human brain natriuretic peptide (BNP) on inflammatory factors, neuroendocrine hormones and cardiac function indexes in patients with acute myocardial infarction complicated with heart failure.Methods:A total of91 cases of acute myocardial infarction with heart failure patients were divided into the control group (n=44) and observation group (n=47) according to the random data table, two groups of patients were given conventional treatment, based on this, the control group was given intravenous infusion of Nitroglycerin Injection treatment, the observation group received intravenous injection of recombinant human brain natriuretic peptide treatment, compared serum inflammatory factors, neuroendocrine hormone and cardiac function and other indexes of two groups before and after treatment.Results: there was no significant difference between the two groups before treatment. After treatment, the levels of TNF-α, hs-CRP, IL-6, MCP-1, LVESD and LVEDD in the two groups were significantly lower than those within the group before treatment, and the observation group was significantly lower than the control group;The two groups after treatment LVEF levels were significantly higher than those in the group before treatment, and the observation group was significantly higher than that of control group;the observation group after treatment PRA, Ang II and ALD and NE levels were significantly lower than those before treatment, and was significantly lower than the control group after treatment, the difference was significant, PRA, Ang, ALD and NE levels of control group before and after the treatment was no significant difference.Conclusion:recombinant human brain natriuretic peptide in the treatment of acute myocardial infarction with heart failure can effectively reduce the serum inflammatory factors and neuroendocrine hormone levels, improve heart function, and have a certain clinical value.展开更多
BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growt...BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growth hormone deficiency(GHD)is a significant factor.AIM To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone(PEG-rhGH)in the treatment of GHD in children.METHODS We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018.Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week,forming the high-dose group.Meanwhile,21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week,establishing the low-dose Group.The total treatment period was 2 years,during which we monitored the patients’height,annual growth velocity(GV),height standard deviation score(HtSDS),chronological age(CA),bone age(BA),and serum levels of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-binding protein-3(IGFBP-3)before treatment and at 6 mo,1 year,and 2 years after treatment initiation.We also monitored thyroid function,fasting plasma glucose,fasting insulin,and other side effects.Furthermore,we calculated the homeostatic model assessment for insulin resistance.RESULTS After 1 year of treatment,the GV,HtSDS,IGF-1,BA,and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels(P<0.05).Moreover,when comparing GV,HtSDS,IGF-1,BA,and IGFBP-3 between the two groups,there were no statistically significant differences either before or after the treatment(P>0.05).During the treatment intervals of 0-1.0 years and 1.0-2.0 years,both patient groups experienced a slowdown in GV and a decline in HtSDS improvement(P<0.05).CONCLUSION The use of PEG-rhGH in treating GHD patients was confirmed to be effective,with similar outcomes observed in both the high-dose group and low-dose groups,and no significant differences in the main side effects.展开更多
Objective:The goal of this study is to investigate the effects of recombinant human growth hormone(rh GH)on corneal healing,epithelial nerve regeneration and tear inflammatory factor levels in rabbits.Methods:After co...Objective:The goal of this study is to investigate the effects of recombinant human growth hormone(rh GH)on corneal healing,epithelial nerve regeneration and tear inflammatory factor levels in rabbits.Methods:After corneal epithelial injury models were established,fifty adult clean New Zealand white rabbits were randomly divided into two groups,normal saline was administered to the control group,while recombinant human growth hormone was administered to the observation group.The healing rate of corneal epithelial injury,the regeneration ability of corneal epithelial nerve and the level of inflammatory factors in tears were observed and compared between the two groups of rabbits before and 24,48,72 and 96 h after modeling.Results:There were significant differences in corneal epithelial healing rate,time and interaction between the two groups(P<0.05).The experimental group exhibited a superior healing rate of corneal epithelium at 24,48,72,and 96 h compared to the control group(P<0.05).There were significant differences in central cornea sensitivity between the two groups,along with variations in time and interaction(P<0.05).There was no significant difference in the central corneal sensitivity between the two groups before modeling and at 24,72 and 96 h after modeling(P>0.05),whereas the experimental group exhibited a higher central corneal sensitivity compared to the control group at 48 h after modeling(P<0.05).There were significant differences in IL-1α,TNF-α,IL-17a and IL-21 between the two groups(P<0.05).There were significant differences in IL-17a and IL-21 between the two groups(P<0.05).The experimental group exhibited a significant decrease in IL-1αlevels compared to the control group between 24 and 72 h after modeling(P<0.05),the experimental group exhibited a substantial increase in IL-17a levels compared to the control group at 72 h after modeling(P<0.05),and the level of TNF-αin the experimental group was significantly lower than that of the control group between 24 and 96 h after modeling.Conclusion:Recombinant human growth hormone aids in expediting the healing process of the healing of rabbit corneal epithelial injury,facilitating the restoration of epithelial nerve,and mitigating the inflammatory response.展开更多
To observe the effect of growth hormone on serum leptin levels, serum leptin concentrations were measured by enzyme immunoassay in 12 prebutal children with growth hormone deficiency 1, 3 and 6 months before and after...To observe the effect of growth hormone on serum leptin levels, serum leptin concentrations were measured by enzyme immunoassay in 12 prebutal children with growth hormone deficiency 1, 3 and 6 months before and after the treatment with recombinant human growth hormone (r hGH). For comparison, 34 normal prepubertal children were also investigated. Relationship between leptin levels and body mass index (BMI) was observed at the same time. Our results showed that serum leptin level in normal prepubertal children was 1.22±0.34 ng/ml; the pretreatment serun leptin levels in GHD children was 3.08±2.41 ng/ml, which was significantly different from those 1, 3 and 6 months after GH treatment (i.e. 1.64±1.37 ng/ml,1.57±1.40 ng/ml and 1.35±0.89 ng/ml respectively) (all P <0.001). Our results suggested that r hGH has a suppressive effect on leptin expression.展开更多
This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of childrenwith idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormonether...This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of childrenwith idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormonetherapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lowerFT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroupwas treated with L-T4 (0.5-3.0 g/(kg, d)) from the beginning of the study, and the non-L-T4-treated subgroupreceived placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as thehigher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulatinghormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lowerheight velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treatedsubgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV comparedwith children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormonedeficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.展开更多
Objective:: To observe the effect of recombinant human growth hormone (r-hGH) on osteoporotic fracture healing in rats, and to provide an effective therapy for osteoporotic fracture. Methods: Thirty-six female 8-month...Objective:: To observe the effect of recombinant human growth hormone (r-hGH) on osteoporotic fracture healing in rats, and to provide an effective therapy for osteoporotic fracture. Methods: Thirty-six female 8-month-old SD rats were randomized into two groups: therapy group and control group. After the experimental model of osteoporotic fracture was established, the therapy group was treated with r-hGH of 2.7 mg/kg body weigh/day (1 mg=3 IU) for 10 days continuously by daily subcutaneous injection; whereas the control group was treated with equivalent saline. Plasma insulin-like growth factor I concentration was detected and bone mineral density (BMD) as well as biomechanical strength of callus were measured at 2, 4, 8 weeks. Results: Plasma insulin-like growth factor I concentration in the therapy group was higher than that in the control group (P< 0.005 ) at 2nd week and began to decline at 4th week. At 8th week, there was no significant difference between the two groups. At 4th week, callus area and BMD in therapy group were higher than those in the control group, but at 8th week, they were lower and BMD had a significant difference between the two groups (P< 0.001 ). Biomechanical testing of callus showed that torsional strength of the therapy group was higher than that of the control group at 4th or 8th week, meanwhile maximum torsional angle had a significant difference between the two groups (P< 0.005 ).Conclusions: The results show that exogenous r-hGH can stimulate osteoporotic fracture healing in rats.展开更多
文摘Follicle-stimulating hormone (FSH) plays a central role in mammals reproduction, with the actions of FSH mediated by follicle-stimulating hormone receptors (FSHRs) on the surface of target cells. The purposes of this study were to determine and evaluate the biological activities for the commercialization of recombinant follicle-stimulating hormone (rFSH) in vitro through the cellular internalization using cloned 293T-FSHR cell lines as target. Using imaging approaches we have found here that a little fluorescent signal from the surface of the cell transferred to the cytoplasm and accumulated around the nucleus by endocytosis. Compared with the control groups, the commercialization of rFSH have not the significant differences of internalization, but the rFSH have promoted the internalization of the fluorescent, suggested that this detection system might as a protocol for the bioactivity of recombinant therapeutic proteins in vitro.
基金supported by Clinical Special Funds of China University Medical Journals(No:11321375)
文摘Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34) 20 μg daily for 18 months,and the elcalonin group(CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months.Bone mineral density(BMD) of the lumbar spine 2-4(L_(2-4))and femoral neck,serum calcium and phosphorus,urinary calcium,serum hone specific alkaline phosphatase(BSAP).and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ /Cn were tested at baseline,and 6.12.and 18 months after treatment.Results:In PTH group.HMD of L_(2-4),at 6,12.and 18 months,BDM of Femoral neck at 18 month,BSAP at 6 and 12 months and uCTX- Ⅰ /Cr at 6.12 and 18 months were all significantly raised.In CT group.HMD of L_(2-4) at12 month and that of femoral neck at 12 and 18 months were significantly elevated,while HSAP was significantly decreased at 12 and 18 months,and no significant difference on CTX- Ⅰ /Cr was observed.When BMD growth and growth rate between two groups were compared.PTH group had better improvement in L_(2-4) BMD and growth rate than CT group at 6.12.and 18 months.BMD growth and growth rale of femoral neck al 12 month and its growth at 18 month in CT group were higher than in PTH group,hut there was no significant difference between two groups regarding the growth rates at 18 month.Besides,there were no significant differences regarding the rales ol adverse reactions between two groups.Conclusions:rhPTH(1—34),is safe and effective in the treatment of primary OP.It is superior to elcatonin in improving vertebral HMD at onset time,growth rate and growth range,but inferior to elcatonin at HMD of femoral neck.
文摘In order to observe the nutrition state in the severe multiple trauma patients undergoing adjuvant recombinant human growth hormone (rhGH) nutritional support therapy, 45 patients with severe multiple traumas (ISS>25) were randomly divided into 3 groups. All the 3 groups had been supplied with nitrogen and caloricity according to the need of patients for 16 days. The rhGH therapy started 48 h after surgery and lasted for 14 days in two rhGH-treated groups in which rhGH was 0.2 and 0.4 U/(kg·d) respectively, and the resting group served as control one. The levels of nitrogen balance, prealbumin and safety variables (blood sugar, Na+, TT3 and TT4) were observed and com- pared among the three groups. The levels of nitrogen balance on the postoperative day (POD) 3 and 5 in the rhGH-treated groups were -1.28±3.19, 5.45±2.00 and -0.18±2.55, 6.11±1.60, respectively, which were significantly higher than those in the control group (-5.17±1.68 and -1.08±3.31, P<0.01). The values of prealbumin on the POD 3 and 5 in the rhGH-treated groups were 180.19±27.15, 194.44±50.82 and 194.94±29.65, 194.11±16.17, respectively, which were significantly higher than those in the control group (117.42±19.10 and 135.63±28.31, P<0.01). There was no sig- nificant difference between the rhGH 0.2 U/(kg·d) group and rhGH 0.4 U/(kg·d) group in both of the levels of nitrogen balance and prealbumin. It is concluded that the nutritional support therapy with adjuvant rhGH which starts 48 h after surgery improves the nutrition state of the patients with severe multiple trauma. It is safe for severe multiple trauma patients who accept rhGH at the dose of 0.2 and 0.4 U/(kg·d).
文摘Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to investigate the effect and mechanism of recombinant human growth hormone (rhGH) and to alleviate intestinal translocation of bacteria and endotoxin in murine obstructive jaundice. METHODS:A group of 42 Wistar rats were divided into 3 groups:sham operation (SO), bile duct ligation (BDL), and BDL and rhGH treatment (rhGH). By the end of the experiment,on day 7, the animals were killed, and their liver function and serum endotoxin were measured, bacterial cultures of the liver, kidney and mesenchymal lymph were made. Terminal ileum mucosa was observed under an electron microscope. RESULTS:Liver function was improved more significantly in the rhGH group than in the BDL group. The value of endotoxin in the rhGH group was 0.38±0.03 EU/ml, significantly lower than that in the BDL group (0.65±0.04 EU/ml, P【0.01), and similar to that in the SO group (0.30±0.02 EU/ml, P】0.05). The rate of bacteria translocation in the liver, kidney and mesenteric lymph was much higher in the BDL group than in other two groups. The rate of bacteria translocation in mesenteric lymph was 64.29%,significantly higher than that in the SO group and the rhGH group (P【0.05). There was no significant difference in bacteria translocation rate between the SO group and the rhGH group (P】0.05). Under an electron microscope , ileum mucosa epithelial cells in the BDL group were necrotic, and organelle were markedly metamorphic. In the rhGH group, ultrastructural changes were less evident or similar to those in the SO group. CONCLUSION:rhGH has significant protective effects on intestinal mucosa barrier in obstructive jaundice, and reduces intestinal translocation of bacteria and endotoxin.
文摘The current study was designed to determine the safety,tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone[rhPTH(1-84)]used for the treatment of osteoporosis.In the single-dose format pharmacokinetic study,thirty-six healthy male volunteers received three dose levels of rhPTH(1-84)subcutaneously:1,2,and 4μg/kg.The blood was timing drawn and the serum concentration of rhPTH(1-84)was determined by enzyme linked immunosorbent assay(ELISA).Serum concentration-time curves of PTH(1-84)exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration.Serum terminal half-time of PTH(1-84)was approximately 2 h.The parameters indicated the serum levels were directly proportional to the administered dose,with the mean Cmax and AUC0-24 ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg·h·mL-1over the dose range.The drug was well tolerated,the clinical symptoms were generally mild and of short duration.
基金Supported by National Natural Science Foundation of China, No. 30571797National Natural Science Foundation of Jiangsu Province, No. BK2006719
文摘AIM:To explore the effects of recombinant human growth hormone (rhGH) on intestinal mucosal epithelial cell proliferation and nutritional status in patients with enterocutaneous fi stula. METHODS:Eight patients with enterocutaneous fi stulas received recombinant human growth hormone (10 μg/d) for 7 d. Image analysis and immunohisto-chemical techniques were used to analyse the expression of proliferating cell nuclear antigen (PCNA) in intestinal mucosal epithelial cells in biopsy samples from the patients who had undergone an endoscopic biopsy through the fi stula at day 0,4 and 7. Body weights,nitrogen excretion,serum levels of total proteins,albumin,prealbumin,transferrin and fi bronectin were measured at day 0,4 and 7. RESULTS:Significant improvements occurred in the expression of PCNA in the intestinal mucosal epithelial cells at day 4 and 7 compared to day 0 (24.93 ± 3.41%,30.46 ± 5.24% vs 12.92 ± 4.20%,P < 0.01). These changes were accompanied by the significant improvement of villus height (500.54 ± 53.79 μm,459.03 ± 88.98 μm vs 210.94 ± 49.16 μm,P < 0.01),serum levels of total proteins (70.52 ± 5.13 g/L,74.89 ± 5.16 g/L vs 63.51 ± 2.47 g/L,P < 0.01),albumin (39.44 ± 1.18 g/L,42.39 ± 1.68 g/L vs 35.74 ± 1.75 g/L,P < 0.01) and f ibronectin (236.3 ± 16.5 mg/L,275.8 ± 16.9 mg/L vs 172.5 ± 21.4 mg/L,P < 0.01) at day 4 and 7,and prealbumin (286.38 ± 65.61 mg/L vs 180.88 ± 48.28 mg/L,P < 0.05),transferrin (2.61 ± 0.12 g/L vs 2.41 ± 0.14 g/L,P < 0.05) at day 7. Nitrogen excretion was signifi cantly decreased at day 7 (3.40 ± 1.65 g/d vs 7.25 ± 3.92 g/d,P < 0.05). No change was observed in the body weight. CONCLUSION:Recombinant human growth hormone could promote intestinal mucosal epithelial cell proliferation and protein synthesis in patients with enterocutaneous fi stula.
文摘Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.
文摘Objective:To study the protective effect of perioperative recombinant human growth hormone (r-hGH) application on intestinal mucosal barrier function in patients with intestinal obstruction and the influence on the immune inflammatory response.Methods:60 patients with intestinal obstruction who underwent surgical treatment in our hospital between February 2013 and July 2016 were selected as the research subjects and divided into the control group (n=34) who received conventional surgical treatment and the observation group (n=26) who received surgery combined with perioperative r-hGH treatment. The serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were not statistically significant between the two groups of patients. After treatment, serum intestinal mucosal barrier indexes Endotoxin, D-Lactate and DAO levels in observation group were lower than those in control group, immunoglobulin IgA, IgM and IgG levels were higher than those in control group, and inflammatory response indicators IL-1, IL-6, PCT and TNF-α levels were lower than those in control group patients. Conclusion:Perioperative r-hGH application in patients with intestinal obstruction can protect the intestinal mucosal barrier, also optimize the humoral immunity and suppress the systemic inflammatory response.
文摘The enhanced cardiac contractility effect of human recombinant growth hormone (hr-GH) on the congestive heart failure (CHF) was studied on the pig. To build a pig model of congestive heart failure, a temporary artificial cardiac pacemaker was implanted in the pig’s body and paced at 220 beats to 240 beats per minute for 1 week. After the model of congestive heart failure was successfully set up, the frequency of the pacemaker was changed to 150 beats to 180 beats per minute to maintain the CHF model stable. Pigs were divided into three groups: The hr-GH group in which 0.5 mg/kg per day of hr-GH was administrated intramuscularly for 15 days, the injection control group in which an equal amount of physiological saline was injected intramuscularly, and a normal control group. The left ventricular diastolic end pressure was (10.60±2.41) mmHg in the hr-GH group, but (19.00±3.81) mmHg in the saline control group (P<0.01); Cardiac output was (1.86±0.13) L/min in the hr-GH group, but (1.56±0.18) L/min in the saline control group (P<0.05); Peripheral vascular resistance was (56.88±7.51) mmHg·(L/min) -1 in the hr-GH group, whereas (70.30±11.59) mmHg·(L/min) -1 in the saline control group (P<0.05); +dp/dt max was (2900±316.23) and (2280±286.36) in the hr-HG group and the saline control group respectively (P<0.05). The results show that hr-GH enhances myocardial contractility of CHF, and the CHF model built by a temporary artificial cardiac pacemaker at a high rate of stimulation is reasonable and applicable.
基金Basic Research Program of Jiangsu Province(Natural Science Foundation of China)(BK2015125).
文摘Objective:To investigate the effect of recombinant human brain natriuretic peptide (BNP) on inflammatory factors, neuroendocrine hormones and cardiac function indexes in patients with acute myocardial infarction complicated with heart failure.Methods:A total of91 cases of acute myocardial infarction with heart failure patients were divided into the control group (n=44) and observation group (n=47) according to the random data table, two groups of patients were given conventional treatment, based on this, the control group was given intravenous infusion of Nitroglycerin Injection treatment, the observation group received intravenous injection of recombinant human brain natriuretic peptide treatment, compared serum inflammatory factors, neuroendocrine hormone and cardiac function and other indexes of two groups before and after treatment.Results: there was no significant difference between the two groups before treatment. After treatment, the levels of TNF-α, hs-CRP, IL-6, MCP-1, LVESD and LVEDD in the two groups were significantly lower than those within the group before treatment, and the observation group was significantly lower than the control group;The two groups after treatment LVEF levels were significantly higher than those in the group before treatment, and the observation group was significantly higher than that of control group;the observation group after treatment PRA, Ang II and ALD and NE levels were significantly lower than those before treatment, and was significantly lower than the control group after treatment, the difference was significant, PRA, Ang, ALD and NE levels of control group before and after the treatment was no significant difference.Conclusion:recombinant human brain natriuretic peptide in the treatment of acute myocardial infarction with heart failure can effectively reduce the serum inflammatory factors and neuroendocrine hormone levels, improve heart function, and have a certain clinical value.
文摘BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growth hormone deficiency(GHD)is a significant factor.AIM To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone(PEG-rhGH)in the treatment of GHD in children.METHODS We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018.Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week,forming the high-dose group.Meanwhile,21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week,establishing the low-dose Group.The total treatment period was 2 years,during which we monitored the patients’height,annual growth velocity(GV),height standard deviation score(HtSDS),chronological age(CA),bone age(BA),and serum levels of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-binding protein-3(IGFBP-3)before treatment and at 6 mo,1 year,and 2 years after treatment initiation.We also monitored thyroid function,fasting plasma glucose,fasting insulin,and other side effects.Furthermore,we calculated the homeostatic model assessment for insulin resistance.RESULTS After 1 year of treatment,the GV,HtSDS,IGF-1,BA,and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels(P<0.05).Moreover,when comparing GV,HtSDS,IGF-1,BA,and IGFBP-3 between the two groups,there were no statistically significant differences either before or after the treatment(P>0.05).During the treatment intervals of 0-1.0 years and 1.0-2.0 years,both patient groups experienced a slowdown in GV and a decline in HtSDS improvement(P<0.05).CONCLUSION The use of PEG-rhGH in treating GHD patients was confirmed to be effective,with similar outcomes observed in both the high-dose group and low-dose groups,and no significant differences in the main side effects.
文摘Objective:The goal of this study is to investigate the effects of recombinant human growth hormone(rh GH)on corneal healing,epithelial nerve regeneration and tear inflammatory factor levels in rabbits.Methods:After corneal epithelial injury models were established,fifty adult clean New Zealand white rabbits were randomly divided into two groups,normal saline was administered to the control group,while recombinant human growth hormone was administered to the observation group.The healing rate of corneal epithelial injury,the regeneration ability of corneal epithelial nerve and the level of inflammatory factors in tears were observed and compared between the two groups of rabbits before and 24,48,72 and 96 h after modeling.Results:There were significant differences in corneal epithelial healing rate,time and interaction between the two groups(P<0.05).The experimental group exhibited a superior healing rate of corneal epithelium at 24,48,72,and 96 h compared to the control group(P<0.05).There were significant differences in central cornea sensitivity between the two groups,along with variations in time and interaction(P<0.05).There was no significant difference in the central corneal sensitivity between the two groups before modeling and at 24,72 and 96 h after modeling(P>0.05),whereas the experimental group exhibited a higher central corneal sensitivity compared to the control group at 48 h after modeling(P<0.05).There were significant differences in IL-1α,TNF-α,IL-17a and IL-21 between the two groups(P<0.05).There were significant differences in IL-17a and IL-21 between the two groups(P<0.05).The experimental group exhibited a significant decrease in IL-1αlevels compared to the control group between 24 and 72 h after modeling(P<0.05),the experimental group exhibited a substantial increase in IL-17a levels compared to the control group at 72 h after modeling(P<0.05),and the level of TNF-αin the experimental group was significantly lower than that of the control group between 24 and 96 h after modeling.Conclusion:Recombinant human growth hormone aids in expediting the healing process of the healing of rabbit corneal epithelial injury,facilitating the restoration of epithelial nerve,and mitigating the inflammatory response.
文摘To observe the effect of growth hormone on serum leptin levels, serum leptin concentrations were measured by enzyme immunoassay in 12 prebutal children with growth hormone deficiency 1, 3 and 6 months before and after the treatment with recombinant human growth hormone (r hGH). For comparison, 34 normal prepubertal children were also investigated. Relationship between leptin levels and body mass index (BMI) was observed at the same time. Our results showed that serum leptin level in normal prepubertal children was 1.22±0.34 ng/ml; the pretreatment serun leptin levels in GHD children was 3.08±2.41 ng/ml, which was significantly different from those 1, 3 and 6 months after GH treatment (i.e. 1.64±1.37 ng/ml,1.57±1.40 ng/ml and 1.35±0.89 ng/ml respectively) (all P <0.001). Our results suggested that r hGH has a suppressive effect on leptin expression.
文摘This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of childrenwith idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormonetherapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lowerFT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroupwas treated with L-T4 (0.5-3.0 g/(kg, d)) from the beginning of the study, and the non-L-T4-treated subgroupreceived placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as thehigher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulatinghormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lowerheight velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treatedsubgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV comparedwith children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormonedeficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.
文摘Objective:: To observe the effect of recombinant human growth hormone (r-hGH) on osteoporotic fracture healing in rats, and to provide an effective therapy for osteoporotic fracture. Methods: Thirty-six female 8-month-old SD rats were randomized into two groups: therapy group and control group. After the experimental model of osteoporotic fracture was established, the therapy group was treated with r-hGH of 2.7 mg/kg body weigh/day (1 mg=3 IU) for 10 days continuously by daily subcutaneous injection; whereas the control group was treated with equivalent saline. Plasma insulin-like growth factor I concentration was detected and bone mineral density (BMD) as well as biomechanical strength of callus were measured at 2, 4, 8 weeks. Results: Plasma insulin-like growth factor I concentration in the therapy group was higher than that in the control group (P< 0.005 ) at 2nd week and began to decline at 4th week. At 8th week, there was no significant difference between the two groups. At 4th week, callus area and BMD in therapy group were higher than those in the control group, but at 8th week, they were lower and BMD had a significant difference between the two groups (P< 0.001 ). Biomechanical testing of callus showed that torsional strength of the therapy group was higher than that of the control group at 4th or 8th week, meanwhile maximum torsional angle had a significant difference between the two groups (P< 0.005 ).Conclusions: The results show that exogenous r-hGH can stimulate osteoporotic fracture healing in rats.