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Abstract

Purpose

Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS.

Methods

This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment.

Results

Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin-II was well tolerated and safe over 1 year of treatment.

Conclusions

One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.

Angiopoietin-like protein 8 in early pregnancy improves the prediction of gestational diabetes

Posted by Y Huang, X Chen, XH Chen, et al. on 2017-12-18 00:00:21

 Abstract

Aims/hypothesis

 Screening high-risk individuals for gestational diabetes mellitus (GDM) in early pregnancy conventionally relies on established maternal risk factors; however, the sensitivity and specificity of these factors are not satisfactory. The present study aimed to determine whether the concentration of angiopoietin-like protein 8 (ANGPTL8), either alone or combined with other risk factors in early pregnancy, could be used to predict subsequent GDM.

 Methods

 From August 2015 to January 2016, 474 women receiving prenatal care at around 12—16 weeks of gestation were recruited into the study. ANGPTL8 levels were measured at the first prenatal visit. All the participants received a 75 g OGTT during weeks 24—28 of gestation.

 Results

 ANGPTL8 levels in early pregnancy were considerably higher in women who developed GDM than those who maintained normal glucose tolerance (2822 ± 938 vs 2120 ± 1118 pg/ml, respectively; p < 0.0001). Multivariable logistic regression revealed that ANGPTL8 levels were significantly associated with risk of GDM independent of conventional risk factors. In addition, women in the highest quartile of ANGPTL8 concentration had an 8.75-fold higher risk of developing GDM compared with women in the lowest quartile (OR8.75, 95%CI 2.43, 31.58). More importantly, incorporating ANGPTL8 into the conventional prediction model significantly increased the AUC for prediction of GDM (0.772vs 0.725; p = 0.019).

 Conclusions

 Our study suggests that ANGPTL8 levels in early pregnancy are significantly and independently associated with risk of GDM at 24–28 weeks of gestation. Combining ANGPTL8 levels with conventional risk factors could thus improve the prediction of GDM.

 

Abstract

Chronic kidney disease may lead to subsequent tissue fibrosis. However, many factors can combat injurious stimuli in these tissues aiming to repair, heal, and alleviate any disturbance. Chemokines release, migration of inflammatory cells to the affected site, and activation of fibroblasts for the production of extracellular matrix are commonly observed in this disease. In the last years, many studies have focused on spironolactone (SPL), a mineralocorticoid receptor antagonist, and its pharmacological effects. In the present study, SPL was selected as an anti-inflammatory agent to combat nephrotoxicity and renal fibrosis induced by cisplatin. Mesenchymal stem cells (MSCs) were also selected in addition as a referring agent. Renal fibrosis induced by cisplatin intake significantly increased creatinine, urea, nuclear factor kappa B, insulin-like growth factor-1, fibroblast growth factor-23, and kidney malondialdehyde (MDA) content. Hepatocyte growth factor and renal content of reduced glutathione demonstrated a significant decrease. Histopathological examination of kidney tissues demonstrated marked cellular changes which are correlated with the biochemical results. Oral SPL intake (20 mg/kg/body weight) daily for 4 weeks and MSCs administration (3 × 106 cell/rat) intravenous to the experimental rats resulted in a significant improvement of both the biomarkers studied and the histopathological profile of the renal tissue. Individual administration of spironolactone and MSCs exhibited a marked anti-inflammatory potential and alleviated to a great extent the nephrotoxicity and renal fibrotic pattern induced by cisplatin.

Serum IL-15 and IL-15Rα levels are decreased in lean and obese physically active humans

Posted by D. Valadés, J. Bujan, C.V Martínez, et al. on 2017-11-08 17:33:39

Abstract

Circulating IL-15 presence is required to stimulate anti-adipogenic effects of the IL-15/IL-15Ra axis in adipose tissue. Although exercise increases blood IL-15 expression post-exercise, it remains inconclusive whether physical activity can alter the baseline concentrations of this cytokine. The aim of this study was to determine whether physical activity regulates circulating IL-15 and IL-15Ra in lean and obese individuals. Two hundred and seventy-six participants were divided into five groups according to physical activity (PA), body mass and type 2 diabetes mellitus (T2DM) diagnosis: (a) lean PA (N = 25); (b) lean non-PA (N = 28); (c) obese PA (N = 64); (d) obese non-PA (N = 79); and (e) obese non-PA with T2DM (N = 80). Serum IL-15 and IL-15Ra, blood glucose/lipid profile and body composition were measured. Serum IL-15 and IL-15Ra decreased in PA participants compared to non-PA (P < .05), while IL-15 and IL-15Ra increased in obese with T2DM compared to obese without T2DM (P < .05). No differences were observed between lean non-PA and obese PA. Serum IL-15Ra was associated with fasting glucose (R2 = .063), insulin (R2 = .082), HbA1c (R2 = .108), and HOMA (R2 = .057) in obese participants. Circulating IL-15 and IL-15Ra are reduced in lean and obese participants who perform physical activity regularly (≥180 min/week), suggesting a regulative role of physical activity on the circulating concentrations of IL-15 and IL-15Ra at baseline. Moreover, the relationship observed between IL-15Ra and glucose profile may indicate a role of the alpha receptor in glucose metabolism.

ANGPTL8 (betatrophin) role in diabetes and metabolic diseases

Posted by M Abu-Farha, J Abubaker, J Tuomilehto. on 2017-11-01 19:38:03

Summary

Diabetes is a major disease worldwide that is reaching epidemic levels. Its increased prevalence as well as its association with a high number of complications such as cardiovascular diseases, nephropathy, and retinopathy makes it an important disease for investigation. ANGPTL8 is a recently identified hormone that has been associated with two functionally important processes in the development of type 2 diabetes, insulin resistance as well as lipid metabolism. Initial work has shown that ANGPTL8 was expressed in liver, white adipose, and brown adipose tissues. ANGPTL8 regulates the activity of lipoprotein lipase, which is a key enzyme in lipoprotein lipolysis pathway through its direct interaction with ANGPTL3. It has been also reported that it regulates the replication of beta-cells in response to insulin resistance. As a result, many recent studies have focused on the association of ANGPTL8 with diabetes and obesity as well as its association with various metabolic markers in order to better understand its physiological role in glucose homeostasis and lipid metabolism. In this review, we will highlight some of the key clinical findings, mainly from human studies, that investigated the role of ANGPTL8 in metabolic diseases such as diabetes, obesity, and the metabolic syndrome.

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