Insulin-like growth factor binding protein-1, non-alcoholic fatty liver disease, and its relationship with fructose consumption in children with obesity

Background Over consumption of added sugar is associated with obesity, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR). Objective The objective of the study was to study the insulin-like growth factor binding protein-1 (IGFBP-1) and NAFLD and their relationship with fructose consumption in children with obesity. Methods A cross-sectional study was carried out in children 6-11 years old with obesity. Anthropometric measurements, fructose consumption, glucose, lipid profile, insulin, and IGFBP-1 levels were evaluated; the homeostatic model assessment of IR (HOMA-IR) was used. NAFLD was evaluated by ultrasound. Results We studied 83 children with a mean age of 9.2 ± 1.3 years. About 93% of the girls presented IR and lower levels of IGFBP-1 (p = 0.0001). The group with the lower levels of IGFBP-1 had higher HOMA-IR (p = 0.000002); IGFBP-1 was associated with fructose consumption (r = −0.25; p = 0.03), body mass index (BMI) (r=−0.42; p = 0.02), and HOMA-IR (r=−0.61; p = 0.002). About 81% of the children were classified as having mild or moderate/severe NAFLD, and these groups had higher HOMA-IR (p = 0.036) and fructose consumption (p = 0.0014). Conclusions The girls had more metabolic alterations. The group with lower levels of IGFBP-1 (hepatic IR) was associated with higher BMI, HOMA-IR, and fructose consumption; the group with higher severity of NAFLD showed higher HOMA-IR and fructose consumption.

Human umbilical cord blood mesenchymal stem cells engineered to overexpress growth factors accelerate outcomes in hair growth

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and β-catenin; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.

Reduction of venous pressure during the resection of liver metastases compromises enteric blood flow: IGFBP-1 as a novel biomarker of intestinal barrier injury

OBJECTIVES: Disruption of the intestinal barrier and bacterial translocation commonly occur when intestinal blood flow is compromised. The aim of this study was to determine whether liver resection induces intestinal damage. METHODS: We investigated intestinal fatty-acid binding protein and insulin-like growth factor binding protein levels in the plasma of patients who underwent liver resection. RESULTS: We show that liver resection is associated with significant intestinal barrier injury, even if the Pringle maneuver is not performed. CONCLUSION: We propose the use of insulin-like growth factor binding protein-1 as a novel biomarker of intestinal damage in such situations.

Insulin-like growth factor (IGF)-I and IGF binding proteins axis in diabetes mellitus

Increasing evidence suggests an important role of the insulin-like growth factor (IGF)-IGF binding protein (IGFBP) axis in the maintenance of normal glucose and lipid metabolism. Significant changes occur in the local IGF-I-IGFBPs environment in response to the diabetic milieu. A significant reduction of serum IGF-I levels was observed in patients with type 1 diabetes mellitus (T1DM). Inversely, considerably increased serum levels of IGF-I and IGFBP-3 levels were detected in individuals with glucose intolerance including T2DM. Recently, several prospective studies indicated that baseline levels of IGF-I and IGFBPs are associated with the development of diabetes. These findings suggest that disturbances in insulin and IGF-I-IGFBP axis can affect the development of glucose intolerance including diabetes.

Predição do parto prematuro: avaliação sequencial do colo uterino e do teste para proteína-1 fosforilada ligada ao fator de crescimento insulina-símile / Preterm birth prediction: sequential evaluation of the cervix and the test for phosphorylated protein-1 linked to insulin-like growth factor

OBJETIVOS: Averiguar a utilidade da medida do comprimento do colo uterino e do teste para proteína-1 fosforilada ligada ao fator de crescimento insulina-símile (phIGFBP-1), realizados de maneira sequencial, na predição do parto prematuro e a existência de correlação entre os testes. MÉTODOS: Foram submetidos a análise secundária os dados de 101 gestantes assintomáticas com antecedente de prematuridade. A medida ultrassonográfica do comprimento do colo e o teste para phIGFBP-1 foram realizados em paralelo a cada três semanas, entre a 24ª e a 34ª semana. O melhor valor de corte do colo uterino para cada avaliação foi estabelecido por meio de curva ROC, e ambos os testes foram comparados entre si por meio de testes não paramétricos. Foram obtidas a sensibilidade, a especificidade e os valores preditivos de cada teste e da associação dos exames para a ocorrência de parto antes de 37 semanas. RESULTADOS: Houve 25 partos prematuros (24,8%). O comprimento do colo apresentou maior sensibilidade e foi capaz de predizer o parto prematuro em todas as avaliações, com acurácia semelhante em diferentes idades gestacionais. O teste para phIGFBP-1 não foi útil na 24ª semana, porém foi capaz de predizer independentemente a prematuridade na 27ª à 30ª e 33ª semana. A associação dos exames elevou a sensibilidade (81,8%) e o valor preditivo negativo (93,7%) quando comparada à utilização isolada dos testes. O comprimento cervical médio foi menor em gestantes com teste positivo. CONCLUSÕES: Tanto o comprimento cervical quanto o teste para phIGFBP-1 foram capazes de predizer independentemente o parto prematuro, e a associação sequencial de ambos os exames apresentou elevada sensibilidade e alto valor preditivo negativo.

PURPOSE: To investigate the usefulness of the measurement of cervical length and of the test for phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) performed sequentially in the prediction of preterm birth and the correlation between tests. METHODS: We analyzed data from 101 asymptomatic pregnant women with a history of premature delivery. The ultrasound measurement of cervical length and phIGFBP-1 test were performed in parallel every three weeks, between 24 and 34 week. The best cutoff value for each cervical evaluation was established by the ROC curve, and the two tests were compared using nonparametric tests. We determined the sensitivity, specificity and predictive values of each test and of the association of the exams for the occurrence of delivery before the 37th weeks. RESULTS: There were 25 preterm births (24.8%). The cervix length showed the highest sensitivity and was able to predict preterm birth in all evaluations, with similar accuracy at different gestational ages. The test for phIGFBP-1 was not helpful at 24 weeks, but was able to predict prematurity when performed at 27, 30 and 33 weeks. The combination of tests increased the sensitivity (81.8%) and negative predictive value (93.7%) when compared to the separate use of each test. The mean cervical length was lower in women with a positive test. CONCLUSIONS: Both cervical length and the test for phIGFBP-1 were able to predict premature delivery, and sequential combination of both tests showed a high sensitivity and high negative predictive value.

O Sistema do Hormônio de Crescimento: interações com a pele / Growth Hormone System: skin interactions

O artigo descreve o Sistema do Hormônio de Crescimento (GH), enfatizando suas possíveis ações nas células da epiderme, nas estruturas da derme e na cicatrização de feridas cutâneas. Para tanto, fez-se uma revisão dos conhecimentos sobre o hormônio do crescimento, seu receptor, a proteína carreadora deste hormônio e demais proteínas envolvidas no mecanismo que o GH utiliza para a sua manifestação nos tecidos cutâneos.

This paper describes the growth hormone system, emphasizing its possible effects on epidermal cells, dermal structures and wound healing. A review of the literature was conducted on studies concerning the growth hormone molecule, its receptor and carrier proteins and the other proteins involved in the mechanisms of its manifestation in dermal tissue.

Advances in insulin like growth factor binding protein 1 in the prognosis of acute myocardial infarction / 中国医学科学院学报

Insulin-like growth factor (IGF) is closely associated with cardiovascular diseases. Low IGF-I level and high insulin-like growth factor binding protein-1 (IGFBP-1) level in serum can be used as a marker in predicting the long term morbidity and mortality of acute myocardial infarction (AMI). The article reviews the recent advances in IGFBP-1 in the prognosis of AMI.

[Investigation on the levels of IGF-I receptor and IGF-I binding protein I in the brain of insulin resistant rats]

There is limited knowledge available on the metabolism of glucose in the brain, an insulin insensitive organ. Insulin receptors hybridize with insulin like growth factor receptor [IGF-I] to transducer the signals in different areas of the brain. In this article we aimed at investigating whether the expression of IGF-I receptor and IGF-I binding proteins [IGFBP1] is changed in the brain of the diabetic animal model. To induce insulin resistance, adult wistar rats were fed with fructose in their drinking water [10%]. The expression of IGF-I receptor and its binding protein were examined immunohistochemically. Our findings demonstrated that the expression of IGF-I receptor and IGF-I binding protein were not changed in different areas of the brain in insulin resistant rats, compared to those in the control rats. The unchanged expression levels of IGF-I and its binding protein I not imply the lack of involvement of the IGF-I signal transduction pathway in the insulin resistant brain, further investigations are to clarify the issue

Association of insulin, insulin-like growth factor and insulin-like growth factor binding proteins with the risk of colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the association of the changes of serum insulin, insulin-like growth factor (IGF-1), insulin-like growth factor binding proteins(IGFBPs), body mass index (BMI), waist and hip circumference ratio(WHR) with the genesis of colorectal cancer.</p><p><b>METHODS</b>Sera from 244 colorectal cancer patients before operation, 371 patients after operation and 150 healthy subjects were assayed for insulin, leptin, IGF-1, IGFBP-1 and IGFBP-3 by the enzyme-linked immunosorbent assay. SPSS 13.0 statistics software was applied to analyze the data.</p><p><b>RESULTS</b>The serum levels of insulin, IGF-1 and the ratio of IGF-1/ IGFBP-3 in colorectal cancer patients before and after surgical treatment were significantly higher than those in controls. The serum levels of IGFBP-3 in patients before and after operation were significantly lower than those in controls, and the differences were significant(P=0.015,P=0.001, respectively). The BMI in colorectal carcinoma patients was not significantly different to the healthy controls(P>0.05). The WHR in colorectal carcinoma patients was higher than that in healthy subjects, and the difference was significant(P=0.003, P=0.035 respectively). The WHR in colon cancer patients was different to that in rectal cancer patients(P=0.046). The WHR and BMI in colon carcinoma patients were positively correlated with the serum insulin level and the value of IGF/IGFBP3. The WHR and BMI were negatively correlated with IGFBP3. The WHR and BMI were not correlated with IGF-1 and IGFBP1.</p><p><b>CONCLUSIONS</b>The serum insulin, IGF-1 levels and the value of IGF-1/IGFBP-3 are significantly increased in colorectal cancer patients, and serum IGFBP-3 level is markedly decreased, which may be related to the genesis of colorectal cancer, but are not correlated with the progress and improvement of colorectal cancer. Central adipositas may be a risk factor for the genesis of colon cancer.</p>

Study of umbilical cord blood adiponectin, IGF-I, IGFBP-1, insulin and leptin levels in small for gestational age neonates at birth / 대한산부인과학회지

OBJECTIVE: Intrauterine growth is influenced by multiple factors like genetic, nutritional, environmental and hormonal factors. As birth weight is reported to be related to perinatal morbidity and mortality, we aimed to compare umbilical cord blood adiponectin, IGF-I, IGFBP-1, insulin and leptin levels between small for gestational age (SGA) and appropriate for gestational age (AGA) neonates at birth to investigate the influence of these factors on birth weight and ponderal index. METHODS: We investigated retrospectively 30 pregnant women with SGA and 30 pregnant women with AGA who delivered at Ewha Womans University Hospital and their babies from January 2007 to December 2007. Fetal umbilical cord venous blood adiponectin, IGF-I, IGFBP-1, insulin and leptin levels from SGA and AGA neonates were obtained at the time of delivery. The definition used to identify cases of SGA was individual birth weight ratio of less than 10th percentile and the definition of ponderal index (PI) was [BW (g)/ (height (cm))3]x100. RESULTS: Umbilical cord blood adiponectin, IGF-I and IGF/IGFBP ratio were significantly lower (P<0.05) in SGA than AGA. And umbilical cord blood IGFBP-1 were significantly higher (P<0.05) in SGA than AGA. But there was no significant difference in umbilical cord blood insulin and leptin levels between SGA and AGA neonates. Positive correlation was noted between adiponectin and IGF-I, IGF/IGFBP ratio, insulin and leptin. Negative correlation was noted between adiponectin and IGFBP-1, IGF-I and IGFBP-1. On multiple regression analysis, adiponectin and IGF-I were significant factors associated with body weight (BW), but only IGFBP-1 was significant factor associated with PI. CONCLUSION: These results suggest that fetal adiponectin, IGF-I, IGFBP-1 may have an important role in regulation of intrauterine growth and we will expect that evaluation of adiponectin and IGF-I in SGA may be helpful in prediction of neonatal outcome, and IGFBP-1 may be useful in diagnosis of asymmetric intrauterine growth retardation (IUGR).

Predicting preterm delivery in asymptomatic pregnant women with prior preterm delivery by measurement of cervical length, fetal fibronectin and phosphorylated insulin-like growth factor-binding protein-1

To evaluate the accuracy of cervical length measurement in combination with assessment of fetal fibronectin [FFN] and phosphorylated insulin-like growth factor-binding protein-1 [phIGFBP-1] in cervico-vaginal secretions as a predictor of preterm delivery in asymptomatic pregnant women with a history of preterm birth. 91 singleton pregnant mothers [between 22-24 weeks of gestation] with previous history of one or more unexplained preterm birth were included in the study. For all participants transvaginal sonographic measurement of cervical length was carried out together with qualitative assay of fetal fibronectin and quantitative measurement of phosphorylated insulin-like growth factor binding protein-1 in cervico-vaginal secretions. The primary outcome of the study was delivery before completed 37 weeks of gestation. There was a significant association between cervical length and the occurrence of preterm delivery [p=0.002], cervical length was 23.12 +/- 8.5mm in 33 cases who experienced preterm delivery compared to 29.34 +/- 9.4mm in 58 cases who delivered at term. Regarding fetal fibronectin assay in cervico-vaginal secretions, no statistically significant difference was found between those who delivered preterm and those who had term delivery [p=0.972]. Measurement of phosphorylated insulin-like growth factor-binding protein-1 [phIGFBP-1] in cervico-vaginal secretions showed statistically significant difference among patients who delivered preterm compared to those who did not [p=0.007]. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated for cervical length, phIGFBP-1, and for their combination, and our results demonstrated high sensitivity, specificity, positive and negative predictive values for the combined method compared with either method alone. Both cervical length and phIGFBP-1 measurement in cervico-vaginal secretions at 22-24 weeks are likely to be useful in predicting preterm delivery in asymptomatic women with a history of preterm birth and their combination increased their sensitivity, specificity, positive and negative predictive values as predictors

Maternal and cord blood levels of insulin-like growth factors--I and--II and insulin-like growth factor binding protein-1: correlation with birth weight and maternal anthropometric indices.

OBJECTIVES: To study the correlation of maternal and cord blood insulin like growth factor (IGF)-I and -II and IGF binding protein (IGFBP)-1 levels with birth weight and maternal anthropometric indices. DESIGN: Longitudinal prospective study. SETTING: Academic Institutions and a Tertiary Care Maternity Hospital. PARTICIPANTS: Women with uncomplicated singleton pregnancy (N = 35) and their newborns. MEASUREMENTS: Maternal weight, height, symphysiofundal height and serum levels of IGF-I, IGF-II, IGFBP-1 were measured thrice during the antenatal period, within 24 h of delivery and at 6 weeks and 6 months postpartum. Newborn anthropometric indices were recorded at birth, and at 6 weeks and 6 months of age. Cord blood levels of IGF-1, IGF-II, IGFBP-1, paternal height and weight, and placental weight measured. RESULTS: Maternal and cord blood IGF-I levels were lower than values reported for Caucasians. All newborns showed adequate growth at birth, and up to 6 months of age. Cord blood IGF-1 positively correlated with chest circumference (r = 0.4532, P = 0.0262), IGFBP-1, negatively with birth weight (r = -0.4024, P = 0.0461) and IGF-II had no effect. Cord blood IGF-I positively correlated with maternal levels at 28 +/- 2 (r = 0.4571, P = 0.0247) and 36 +/- 2 (r = 0.4291, P = 0.0364) weeks of amenorrhoea, whereas IGF-II and IGFBP-1 did not correlate with maternal values. Maternal IGF-I, IGF-II and IGFBP-1 did not correlate with newborn or maternal anthropometric indices. Placental weight correlated significantly with birth weight (r = 0.5299, P = 0.0348) and head circumference (r = 0.5031, P = 0.0470). CONCLUSIONS: Cord blood IGFBP-1 and placental weight appear to be determinants of birth weight variation even among appropriately grown for gestational age newborns.

Insulin-like growth factors-I and -II and insulin-like growth factor binding protein-1 during normal pregnancy: pattern of secretion and correlation with other placental hormones.

OBJECTIVES: To describe pattern of secretion of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (IGFBP)-1 and their correlation with each other and major placental hormones during normal pregnancy. DESIGN: Longitudinal study. SETTING: Academic Institutions and a Tertiary Care Maternity Hospital. PARTICIPANTS: Healthy women with singleton uncomplicated pregnancies (N = 35). MEASUREMENTS: Serum levels of IGF-I, IGF-II, IGFBP-1, chorionic gonadotrophin (HCG), placental lactogen (HPL), prolactin, oestradiol and progesterone were studied thrice during the antenatal period and within 24 h of delivery. RESULTS: IGF-I, IGFBP-1, HPL, prolactin, oestradiol and progesterone increased and HCG decreased significantly with advancing gestation (Repeated measures ANOVA: P < 0.01 to 0.0001). IGF-II levels were not significantly affected by period of gestation. Significant negative correlations (multiple regression analysis) were seen between IGFBP-1 and prolactin at 28 +/- 2 (P = 0.0226) and 36 +/- 2 (P = 0.0417) weeks of amenorrhoea (WOA) and between oestradiol and IGF-II at 36 +/- 2 WOA (P = 0.037). Prolactin and IGF-I at 14 +/- 2 WOA (P = 0.0225) and progesterone and IGFBP-1 at 28 +/- 2 WOA (P = 0.0216) correlated positively. CONCLUSIONS: Maternal IGF-I and IGFBP-1 but not IGF-II significantly increase as pregnancy advances. Components of the IGF system regulate or are affected by some of the placental hormones and the effects vary with the period of gestation.

Study of islet cell autoantibodies in serum of siblings of type 1 diabetics

Type 1 diabetes is an autoimmune disease that accounts for approximately 15% of the diabetic population. The pathogenesis of Type 1 diabetes could be divided into six stages. Stage I is genetic susceptibility which requires the presence of a triggering event [stage Il] that initiate the development of autoimmunity [stage Ill] which is characterized by lymphocytic infiltration of the islet cells and production of anti-islet autoantibodies e.g. islet cell cytoplasmic autoantibodies [ICCA], insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], and autoantibodies against irisulinoma-associated-2 autoantigen [IA-2A]. In stage IV, there is progressive loss of insulin secretion despite normal blood glucose level. Stage V develops when overt diabetes is first recognized. In stage VI, there is complete beta cell destruction. Since the clinical onset of Type 1 diabetes does not occur until 80-90% of the insulin-producing pancreatic beta cells have been destroyed, this prediabetic stage may last for a long time during which the immunologic disease markers are present and measurable. The present study aimed to determine the prevalence of the islet cell autoantibodies in siblings of type I diabetics for the presence of islet autoantibodies in an attempt to allow the opportunity for prediction and/or the prevention the clinical onset of the disease. 108 healthy siblings of Type 1 diabetic children [group I] and 100 healthy control subjects [group II] of matched age and sex were enrolled in the present study. IAA, GADA, and IA-2A autoantibodies were assayed in serum of all subjects by radioimmunoassay. Eight of the control subjects had autoantibodies in their sera which were of the IAA type only. In siblings of Type 1 diabetic children, the prevalence of GADA seropositivity showed the highest percentage [25%], followed by IAA [14.81%], then IA-2A [2.78%]. There was significant association between the brotherhood to Type 1 diabetic children and the presence of GADA alone [i.e. no concomitance with any other autoantibody], total GADA [GADA alone and in combination with other autoantibodies], and GADA+IAA [P=0.000, 0.000, and 0.018 respectively]. IAA+GADA+IA-2A or for IAA+lA-2A combinations were not detected in sera of siblings of Type 1 diabetic children. None of the siblings of Type 1 diabetics had lA-2A autoantibodies alone in the serum. From the present results it could be concluded that some degree of islet cell autoimmunity might develop in siblings of type 1 diabetic children as evidenced by the significant association between the presence of GADA or GADA+IAA and the brotherhood to type 1 diabetics. The present results also revealed that GADA is the most frequent autoantibody in serum of siblings of type 1 diabetics. They also showed that the presence of GADA per se conferred the highest significant association with the brotherhood to Type I diabetic children. However, a larger prospective study is recommended to ascertain the importance of the assay of these immunologic markers for the prediction and possible prevention of type 1 diabetes in individuals at risk e.g. sibling, parents, and offspring of Type 1 diabetics

Comparison of bedside test kits for prediction of preterm delivery: phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) test and fetal fibronectin test

<p><b>OBJECTIVE</b>The objective of the study was to compare the effectiveness of bedside test kits for pIGFBP-1 and fetal fibronectin test in predicting preterm delivery.</p><p><b>MATERIALS AND METHODS</b>Patients presenting with symptoms of preterm labour between 24 and 34 weeks of gestation were recruited. Both pIGFBP-1 and fetal fibronectin bedside tests were performed. Managing obstetricians and patients were blinded to the pIGFBP-1 and fetal fibronectin results. Tocolysis and steroid therapy were administered to all the recruited patients. Outcome data were collected after delivery.</p><p><b>RESULTS</b>One hundred and eight patients were recruited into the study. Fourteen patients had to be excluded from the final analysis due to incomplete data and failure to meet inclusion criteria. Ninety-four patients had complete data for analysis. Among those with negative pIGFBP-1 and fetal fibronectin results, the median [+/-standard deviation (SD)] gestational age at delivery was 37.4 weeks (+/-2.8 weeks) and 37.4 weeks (+/-2.1 weeks), respectively. Among those with positive pIGFBP-1 and fetal fibronectin results, the median (+/-SD) gestational age at delivery was 32.9 weeks (+/-4.0 weeks) and 34.2 weeks (+/-4.2 weeks), respectively (P <0.001 for both pIGFBP-1 and fetal fibronectin). A positive result with either test was associated with a significantly reduced admission-to-delivery interval. The median admission-to-delivery interval was 2.8 weeks shorter in the group with positive pIGFBP-1 results compared to those with a negative pIGFBP-1 result (2.3 weeks compared with 5.1 weeks) (P <0.001). This is 1.8 weeks shorter in the group with positive fibronectin results, compared to those with a negative result (3.3 weeks compared with 5.1 weeks) (P=0.002). Both pIGFBP-1 and fetal fibronectin tests have high negative predictive value (NPV) in predicting risk of delivery within 48 hours, 7, or 14 days (1.00; 0.92; 0.92 and 0.97; 0.89; 0.89, respectively).</p><p><b>CONCLUSIONS</b>Both pIGFBP-1 and fetal fibronectin tests are effective adjuvant bedside test kits for the prediction of preterm delivery in patients presenting with signs or symptoms of preterm labour. pIGFBP-1 has the higher NPV of 1.00 in predicting risk of delivery within 48 hours.</p>

Influence of Tumor Necrosis Factor-alpha on Expression of Insulin-like Growth Factor-II, Insulin-like Growth Factor Binding Protein-1, 2, 3, 5 in Cultured Human Luteinized Granulosa Cells / 대한산부인과학회지

OBJECTIVE: To investigate the influence of tumor necrosis factor (TNF)-alpha on the expression of insulin-like growth factor (IGF)-II, insulin-like growth factor binding protein (IGFBP)-1, 2, 3, and 5 mRNA in cultured human luteinized granulosa cells. METHODS: Human luteinized granulosa cells were obtained from the follicular fluid by transvaginal oocyte aspiration from infertile patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). The cells were cultured for 72 hours with TNF-alpha at concentrations of 1.0, 10.0, and 100.0 ng/mL, respectively. The cells not treated with TNF-alpha were served as control. Riverse transcription-polymerase chain reaction (RT-PCR) had been used to examine the expression of IGF-II, IGFBP-1, 2, 3, and 5 mRNA. Results were analyzed with Kolmogorov-Smirnov test and analysis of variance (ANOVA) and statical significance was defined as p<0.05. RESULTS: The expressions of IGF-II mRNA in 10.0 and 100.0 ng/mL of TNF-alpha groups were significantly lower than the control group (p<0.05, p<0.05, respectively). The expressions of IGFBP-2 mRNA were seemed to be decreased in 10.0 and 100.0 ng/mL of TNF-alpha groups than the control group (p=0.05, p=0.06, respectively). The expression of IGFBP-3 mRNA was seemed to be increased in 100.0 ng/mL of TNF-alpha group than the control group (p=0.08). There were no statistically significant differences in the expressions of IGFBP-1 and 5 in all groups. CONCLUSION: TNF-alpha might play a role as a regulator of human ovarian physiology by modulating the expression of IGF-II in luteinized granulosa cells.

Experimental study on effect of tiangui gengnian soft capsule on aged female rats with osteoporosis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Tiangui Gengnian soft capsule (TGC), which mainly consists of seabuckthorn fatty acid, on serum estrogen and estrogen receptor (ER) in multiple target tissues as uterus, liver and bone, in aged female rats, in order to explore its mechanism from the aspects of receptor and cytokines.</p><p><b>METHODS</b>Low (0.72 g/kg), middle (1.80 g/kg) and high (4.50 g/kg) dose of TGC were administered by gastrogavage to young and aged (22 months old) female rats with osteoporosis for 45 days, and diethylstilbestrol (0.02 mg/kg) was used as a positive control. The levels of serum estradiol (E2), transforming growth factor beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassay and ELISA method, the protein expression of their receptor in bone, uterus and liver was detected by SABC immunohistochemistry, and the mRNA expression of E2 in uterus and liver detected by in situ hybridization with digoxin probe.</p><p><b>RESULTS</b>Intervention of TGC could cause increase of serum E2, IGF-1 and TGF-beta1 levels, the TGF-beta1 reached 90.63 +/- 18.71 pg/L in the group administered with high dose, which was significantly different to that in the aged group (P < 0.01). There was no obvious effect of the mRNA expression of E2 in uterus and liver, and no effect of TGF-beta1 and IGF-1 in liver in rats.</p><p><b>CONCLUSION</b>TGC could improve the postmenopausal bone metabolism, alleviate and correct the bone loss, it is possibly realized by way of side-secreting/auto-secreting of E2 receptor and cytokines (TGF-beta1 and IGF-1) to improve the osteogenesis and inhibit the destruction of bone.</p>

Effect and risk analysis of misoprostol in stimulating cervical maturity for post-term pregnancy / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect and risk of misoprostol for stimulating cervical maturity in women with post-term pregnancy negative for insulin-like growth factor binding protein-1 (IGFBP-1) in cervical secretion with modified Bishop score less than 3.</p><p><b>METHODS</b>Seventy-one women with post-term pregnancy randomized into misoprostol group (n=37) and control group (n=34) received misoprostol placement at the posterior vaginal fornix and routine intravenous oxytocin infusion, respectively, to stimulate cervical maturity. Failure to respond to the treatment within the initial 24 h necessitated a repeated administration for no more than 3 times in all. Modified Bishop score was recorded and fetal heart monitored once every 24 h, and IGFBP-1 in the cervical secretion was detected at 24 and 48 h after drug administration.</p><p><b>RESULTS</b>The misoprostol group showed better effect of cervical maturity stimulation than the control group (P<0.001), and the positivity rates of IGFBP-1 24 and 48 h after drug administration were significantly higher than that of the control group (P<0.01 and 0.001). The number of cases with indication for cesarean section was significant higher in the control group (P<0.001). There were no significant differences in postpartum hemorrhage, excessive uterine contraction, incidence of fecal contamination of the amniotic fluid or Apgar score of the newborn between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>Misoprostol is safe and effective for stimulating cervical maturity in women with post-term pregnancy who have modified Bishop score lower than 3 and are negative for IGPBF-1 in cervical secretion. Oxytocin is not advised for use in such gravida for stimulating cervical maturity. IGFBP-1 in cervical secretion may serve as an important index for evaluating the cervical maturity.</p>

Serum insulin like growth factor 1 and insulin like growth factor binding protein 1 in primary antiphospholipid syndrome

To study maternal serum concentrations of insulin growth factor [IGF-I] and insulin growth factor binding protein [IGFBP-1] in women with primary antiphospholipid syndrome [PAPS]. A prospective study. Hospital of Obstetrics and Gynecology, Ain Shams University. Ten women with Primary Antiphospholipid Syndrome [PAPS] and Ten normal pregnant women were included in this prospective study. The mean age for both groups did not show significant difference. Patients with PAPS delivered earlier and with a lower birth weight. The difference between both groups were significant for both gestational age at labor and birth weight [p<0.0001]. Serum IGF-1 was lower in PAPS than the control group throughout pregnancy. The level of IGF-1 decreased significantly in the PAPS group [p<0.0001]. The level of IGF-1 increased significantly in the control group late in pregnancy [p=0.0317]. Serum IGFBP-1 was higher in the PAPS group than the control group in early and late pregnancy [p<0.0001]. The level of IGFBP-1 increased significantly in the PAPS group and in the control group [p<0.0001]. Primary Antiphospholipid Syndrome [PAPS] is associated with a progressive decrease in the levels of serum IGF-1 during pregnancy. The levels of IGFBP-1 increased in all pregnant women but were higher in patients with Primary Antiphospholipid Syndrome [PAPS]