OBJECTIVETo study the effects of maternal folate deficiency on fetal growth and development and the methylation profiles of insulin-like growth factor system in the offspring rats.

METHODSTwenty-two Sprague-Dawley female rats were randomly assigned to two groups: a folate deficient group (n=12) and a control group (n=10). They were fed with folate deficient and normal diet respectively. Dams were mated after 2 weeks of feeding. Eight female rats from each group were pregnant. On the 20th day of gestation, the fetuses were delivered by caesarean section. Thirty-two fetal rats from each group were randomly selected and the body length and weight were measured. Eight fetal rats from each group were randomly selected and ELISA was used to measure the level of folate content, IGF-1 and IGFBP-3 in the fetal brain and liver. Three fetal rats from each group were randomly selected and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) was used to detect the methylation level of insulin-like growth factor system in the fetal brain and liver. ELISA was used to measure the level of IGF-1 and IGFBP-3 in the maternal serum from both groups.

RESULTSThe mean fetal length and weight were lower in the folate deficient group than in the control group (P<0.05). The levels of IGF-1 and IGFBP-3 in the maternal serum, as well as folate content and IGFBP-3 in the fetal brain and liver were significantly lower in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-2, IGFBP-5, IGFBP-6 and IGFBP-7 in the fetal brain were higher in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-3 and IGFBP-5 in the fetal liver were higher in the folate deficient group than in the control group. The methylation of IGF-2 gene showed a significant reduction in the folate deficient group (P<0.05).

CONCLUSIONSMaternal folate deficiency may cause retardation of growth and development of the offspring, which is possibly associated with the changes of methylation profiles of insulin-like growth factors.

Animals ; Brain ; metabolism ; DNA Methylation ; Female ; Fetal Development ; Fetus ; metabolism ; Folic Acid Deficiency ; metabolism ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Liver ; metabolism ; Rats ; Rats, Sprague-Dawley

PURPOSE: We investigated whether serum levels of insulin growth factor-1 (IGF-1) and insulin growth factor binding protein-3 (IGFBP-3) are valuable in predicting clinical outcomes or are correlated with other laboratory findings in children with Henoch-Schönlein purpura (HSP). METHODS: We examined 27 children who were consecutively admitted to our hospital with HSP between January 2011 and February 2012. Blood tests (C-reactive protein, white blood cell count, platelet count, erythrocyte sedimentation rate, albumin, immunoglobulin A, complement C3, antineutrophil cytoplasmic antibody, IGF-1, IGFBP-3) and urine tests were performed upon admission. IGF-1 and IGFBP-3 were resampled in the recovery phase. Controls included 473 children whose IGF-1 and IGFBP-3 were sampled for evaluating their growth, at the outpatient department of pediatric endocrinology in our hospital. IGF-1 and IGFBP-3 were compared between the HSP children and controls, and between the acute and recovery phases in HSP children. The ability of these values to predict clinical outcomes including renal involvement was analyzed using bivariate logistic regression analysis (BLRA). RESULTS: IGF-1 and IGFBP-3 were not different between the HSP children and controls (148.7±117.6 vs. 69.2±96.9, P=0.290: 3465.9±1290.9 vs. 3597.2±1,127.6, P=0.560, respectively). There was no significant difference in IGF-1 or IGFBP-3 between acute and recovery phases. Based on the BLRA, no variable, including IGF-1 and IGFBP-3, could predict clinical outcomes including the presence of nephritis. CONCLUSION: We concluded that IGF-1 and IGFBP-3 do not predict clinical outcomes of HSP, including renal involvement, in this study.
Antibodies, Antineutrophil Cytoplasmic ; Blood Sedimentation ; Child* ; Complement C3 ; Endocrinology ; Hematologic Tests ; Humans ; Immunoglobulin A ; Insulin* ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Leukocyte Count ; Logistic Models ; Nephritis ; Outpatients ; Platelet Count ; Purpura*

OBJECTIVETo investigate the efficacy and safety of different doses of recombinant human growth hormone (rhGH) in the treatment of short stature in children born small for gestational age (SGA).

METHODSA total of 37 children with short stature born SGA were enrolled, and based on the dose of rhGH treatment, they were divided into low-dose rhGH group (0.1-0.15 IU/kg daily) and high-dose rhGH group (0.16-0.2 IU/kg daily). The changes in height standard deviation score (ΔHtSDS), height velocity (HV), serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and fasting blood glucose at 3, 6, 9, 12, and 24 months after treatment were compared between the two groups.

RESULTSΔHtSDS and HV both increased after the treatment with high- and low-dose rhGH, but ΔHtSDS and HV in the high-dose rhGH group were significantly higher than in the low-dose rhGH group 9, 12 and 24 months after treatment (P<0.05). Both high- and low-dose rhGH treatment increased serum levels of IGF-1 and IGFBP-3. Serum levels of IGF-1 and IGFBP-3 were positively correlated with HtSDS in both groups. One child each in the high- and low-dose rhGH groups experienced transient slight increase in fasting blood glucose (6.1 mmol/L). There were no cases of abnormal thyroid function.

CONCLUSIONSrhGH has good efficacy in the treatment of short stature in children born SGA, with few adverse events, and high-dose rhGH has some advantages over low-dose rhGH.

Body Height ; Child ; Child, Preschool ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Infant, Small for Gestational Age ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Recombinant Proteins ; therapeutic use

Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I(high) or IGF-I(low)), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 +/- 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p < 0.0001). However, GH concentrations and GHR1A mRNA expression were comparable (p > 0.05). Thyroxine levels and ALS expression were higher in the IGF-I(high) cows compared to IGF-I(low) cows. Estradiol concentration tended to be greater in the IGF-I(low) group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.
Animals ; Cattle ; Estradiol/blood ; Female ; Growth Hormone/blood ; Insulin/blood ; Insulin-Like Growth Factor Binding Protein 2/analysis ; Insulin-Like Growth Factor Binding Protein 3/analysis ; Insulin-Like Growth Factor Binding Protein 4/analysis ; Insulin-Like Growth Factor I/*analysis/physiology ; Liver/chemistry ; Pregnancy/metabolism/physiology ; Pregnancy, Animal/*metabolism/physiology ; Progesterone/blood ; Suppressor of Cytokine Signaling Proteins/analysis ; Thyroid Hormones/blood

PURPOSE: It has been reported that daily recombinant human growth hormone (GH) treatment showed beneficial effects on growth in prepubertal children with idiopathic short stature (ISS). The present study aimed to validate the GH (Eutropin(R)) effect on growth promotion and safety after short-term GH treatment. MATERIALS AND METHODS: This study was an open-label, multicenter, interventional study conducted at nine university hospitals in Korea between 2008 and 2009. Thirty six prepubertal children with ISS were enrolled in this study to receive 6-month GH treatment. Yearly growth rate, height standard deviation score (SDS), and adverse events were investigated during treatment. RESULTS: After 26 weeks of GH treatment, the height velocity significantly increased by 6.36+/-3.36 cm/year (p<0.001). The lower end of one-sided 95% confidence interval was 5.22 cm/year, far greater than the predefined effect size. The gain in height SDS at week 26 was 0.57+/-0.27 (p<0.0001). Bone age significantly increased after GH treatment, however, bone maturation rate (bone age for chronological age) showed limited advancement. This 26-week GH treatment was effective in increasing serum levels of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 from baseline (p<0.0001). Eutropin was well tolerated and there were no withdrawals due to adverse events. No clinically significant changes in laboratory values were observed. CONCLUSION: This 6-month daily GH treatment in children with ISS demonstrated increased height velocity, improved height SDS, and increased IGF-I and IGFBP-3 levels with a favorable safety profile.
Child ; Female ; Growth Disorders/blood/*drug therapy ; Growth Hormone/*therapeutic use ; Humans ; Insulin-Like Growth Factor Binding Protein 3/blood ; Insulin-Like Growth Factor I/metabolism ; Male ; Treatment Outcome

BACKGROUND/AIMS: Many women with polycystic ovary syndrome (PCOS) exhibit insulin resistance. Adipose tissue plays an important role in insulin resistance, and adipokines including tumor necrosis factor (TNF)-alpha and adiponectin are altered in PCOS. Insulin-like growth factor binding protein-3 (IGFBP-3), alone or in conjunction with other adipokines, is also associated with insulin resistance. We evaluated the effects of TNF-alpha, adiponectin, and IGFBP-3 on insulin sensitivity and the relationships among these proteins in women with PCOS. METHODS: We recruited 40 women with PCOS and 40 age- and body mass index (BMI)-matched regular cycling women (controls). The women were divided into obese (BMI > or = 25 kg/m2) and nonobese (BMI < 25 kg/m2) groups. Anthropometric measurements were performed, and serum levels of TNF-alpha, adiponectin, and IGFBP-3 were determined. Insulin sensitivity was estimated using the metabolic clearance rate (MCR) of glucose calculated from the oral glucose tolerance test. RESULTS: Serum levels of TNF-alpha and IGFBP-3 did not differ between the PCOS and control groups, but adiponectin levels in the PCOS group were lower than those in control women in the nonobese group (p < 0.05). TNF-alpha, adiponectin, and IGFBP-3 levels were not correlated with each other in women with PCOS, but a significant positive correlation was observed between adiponectin levels and MCR (p < 0.05). Multiple regression analysis revealed that adiponectin levels were significantly associated with insulin sensitivity (p < 0.05) in women with PCOS. CONCLUSIONS: IGFBP-3 and TNF-alpha levels were not associated with insulin sensitivity, but adiponectin levels were related to insulin sensitivity in women with PCOS.
Adiponectin/*blood ; Adult ; Biological Markers/blood ; Case-Control Studies ; Female ; Humans ; *Insulin Resistance ; Insulin-Like Growth Factor Binding Protein 3/*blood ; Obesity/blood ; Polycystic Ovary Syndrome/*blood ; Tumor Necrosis Factor-alpha/*blood ; Young Adult

OBJECTIVETo investigate changes in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) and their significance in children with left-to-right shunt congenital heart disease (CHD) associated with heart failure (HF).

METHODSTwenty healthy children (control group), 20 children with HF, without basic heart disease (HF group), 20 children with left-to-right shunt CHD, without HF (CHD group), and 30 children with left-to-right shunt CHD associated with HF (CHD+HF group) were included in the study. These groups were compared in terms of serum IGF-1 and IGFBP-3 levels. According to the New York Heart Association (NYHA) Functional Classification, the CHD+HF group was further divided into NYHA-II, NYHA-III and NYHA-IV subgroups and the subgroups were compared in terms of serum IGF-1, IGFBP-3, and cardiac troponin I (cTnI) levels. The correlation of serum IGF-1 and IGFBP-3 levels with serum cTnI level in the CHD+HF group was analyzed.

RESULTSThe CHD group showed decreased serum IGF-1 and IGFBP-3 levels compared with the control group (P<0.01). The CHD+HF group showed a significantly decreased serum IGF-1 level compared with the control group (P<0.01) and CHD group (P<0.05). The HF group had significantly increased serum IGF-1 and IGFBP-3 levels compared with other groups (P<0.01). The NYHA-II subgroup had the highest serum IGF-1 level and the NYHA-IV subgroup had the lowest serum IGF-1 level (P<0.01). In the CHD+HF group, serum IGF-1 and IGFBP-3 levels were negatively correlated with serum cTnI level (r=-0.692, P<0.05; r=-0.530, P<0.05).

CONCLUSIONSSerum IGF-1 level can be used as an objective condition evaluation indicator for CHD, and low serum IGF-1 level is a risk factor for HF. This also provides a clinical basis for treatment of HF using exogenous IGF-1.

Child, Preschool ; Female ; Heart Defects, Congenital ; blood ; Heart Failure ; blood ; Humans ; Infant ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Troponin I ; blood

OBJECTIVETo analyze clinical manifestations and gene mutations in a child with severe short stature, explore its molecular mechanism and further clarify the diagnostic procedure for short stature.

METHODWe observed clinical characteristics of a patient with short stature and did diagnostic examinations, assessed the function of GH-IGF-1 axis, and surveyed its family members.Genomic DNA was extracted from peripheral blood, GHR, IGFALS, STAT5b and GH1 gene were amplified by PCR for sequencing, including exons and splicing areas.

RESULTThe patient presented symmetrical short stature (height -8.2 SDS) and facial features, and other congenital abnormalities.It displayed non-growth hormone deficiency. The baseline value of GH was 21 µg/L, and the peak was 57.9 µg/L. The value of IGF-1 was less than 25 µg/L, and the IGFBP-3 less than 50 µg/L. And IGF-1 generation test showed no response. There was no similar patients in the family members.Sequencing of GHR in the patient revealed a homozygous point mutation (c.Ivs6+1G>A), and her father and mother had the same heterozygous mutation. The same mutation was not identified for her sister.No other candidate gene was found.

CONCLUSIONAs the result of combined clinical characteristics and lab examinations, as well as gene detection, the case was diagnosed with Laron syndrome and GHR gene mutation is the molecular mechanism.We should explicit the etiological diagnosis for short stature, and avoid missed diagnosis and misdiagnosis.

Base Sequence ; Body Height ; Child ; DNA Mutational Analysis ; Exons ; Growth Disorders ; blood ; genetics ; pathology ; Human Growth Hormone ; blood ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Laron Syndrome ; blood ; genetics ; pathology ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Receptors, Somatotropin ; genetics ; STAT5 Transcription Factor ; genetics

OBJECTIVETo study the clinical significance of serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) in children with Henoch-Schonlein purpura (HSP) or Henoch-Schonlein purpura nephritis (HSPN).

METHODSThirty-one children with HSP were selected as the HSP group, and 28 children with HSPN were selected as the HSPN group. Another 31 healthy children were selected as the control group. ELISA was used to measure serum levels of IGF-1 and IGFBP-3 in each group. Measurement of 24-hour urinary protein excretion was performed using an automatic biochemical analyzer in the HSPN group. Serum immunoglobulin (Ig) levels, complement C3 level and complete blood counts in each group were determined, and urine analysis was also performed.

RESULTSSerum levels of IGF-1 and IGFBP-3 in the HSP group were significantly higher than in the control group (P<0.05), and serum levels of IGF-1 and IGFBP-3 in the HSPN group were significantly higher than in the HSP and control groups (P<0.05). Among 12 children who underwent renal puncture biopsy, patients with higher pathological grades had higher serum levels of IGF-1 and IGFBP-3. In children with HSPN, those with proteinuria had significantly higher serum levels of IGF-1 and IGFBP-3 than those without proteinuria (P<0.05). Levels of white cells, red cells, platelet count, complement C3, IgG, and IgA and IgA/C3 ratio were significantly higher in the HSP and HSPN groups than in the control group (P<0.05).

CONCLUSIONSIncreased serum levels of IGF-1 and IGFBP-3 are observed in the acute onset period of HSP, which may be related to the degree of proteinuria and renal damage. Serum levels of IGF-1 and IGFBP-3 may be indicators of renal involvement.

Child ; Child, Preschool ; Female ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Nephritis ; blood ; pathology ; Purpura, Schoenlein-Henoch ; blood ; pathology

PURPOSE: Laparoscopic colectomy has clinical benefits such as short hospital stay, less postoperative pain, and early return of bowel function. However, objective evidence of its immunologic and oncologic benefits is scarce. We compared functional recovery after open versus laparoscopic sigmoidectomy and investigated the effect of open versus laparoscopic surgery on acute inflammation as well as tumor stimulation. MATERIALS AND METHODS: A total of 57 patients who were diagnosed with sigmoid colon cancer were randomized for elective conventional or laparoscopically assisted sigmoidectomy. Serum samples were obtained preoperatively and on postoperative day 1. C-reactive protein (CRP) and interleukin-6 (IL-6) were measured as inflammation markers, and vascular endothelial growth factor (VEGF) and insulin-like growth factor binding protein-3 (IGFBP-3) were used as tumor stimulation factors. Clinical parameters and serum markers were compared. RESULTS: Postoperative hospital stay (p=0.031), the first day of gas out (p=0.016), and the first day of soft diet (p<0.001) were significantly shorter for the laparoscopic surgery group than the open surgery group. The levels of CRP, IL-6, and VEGF rose significantly, and the concentration of IGFBP-3 fell significantly after both open and laparoscopic surgery. However, there were no significant differences in the preoperative and postoperative levels of CRP, IL-6, VEGF, and IGFBP-3 between the two groups. CONCLUSION: Our data suggest that both open and laparoscopic surgeries are accompanied by significant changes in IL-6, CRP, IGFBP-3, and VEGF levels. Acute inflammation markers and tumor stimulating factors may not reflect clinical benefits of laparoscopic surgery.
Aged ; Biological Markers/blood ; C-Reactive Protein/metabolism ; Colectomy/*adverse effects/methods ; Female ; Humans ; Inflammation/etiology/metabolism ; Insulin-Like Growth Factor Binding Protein 3/blood ; Interleukin-6/blood ; Laparoscopy/adverse effects ; Male ; Middle Aged ; Postoperative Period ; Sigmoid Neoplasms/*surgery ; Treatment Outcome ; Vascular Endothelial Growth Factor A/blood