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Introduction: Total pancreatectomy (TP) markedly improves quality of life in children with chronic pancreatitis (CP), but results in brittle, insulinopenic diabetes. TP with IAT (TPIAT) may preserve insulin secretion. Minimal data are available regarding TPIAT in pediatric patients (Pts).

Methods: Between 2009-2016, TPIAT was performed in 13 Pts (7 boys) with median age 10.3 yrs (range 7-17 yrs). Six (46%) had a PRSS1 (protease, serine, 1) mutation, 2 (15.4%) had a CFTR (Cystic fibrosis transmembrane conductance regulator) mutation, 2 (15.4%) had combined CFTR/SPINK1 (serine protease inhibitor, Kazal-type, 1) mutations. All were euglycemic prior to TPIAT (normal fasting glucose and HbA1c; normal response to mixed meal tolerance test in a subset). Islet cells, isolated after TP, were infused in the portal vein. Pts were kept on an insulin infusion for (average) 6.8 days, then switched to MDI, with tight glycemic control.

Results: Six months after TPIAT, 5 Pts (38%) did not require insulin (HbA1c 5.5-6.1%), 3 Pts (23%) were on basal insulin only (0.03-0.35 U/Kg/day), with HbA1c of 5.5-6.7%, and 5 Pts (39%) required basal/bolus insulin therapy (0.5-1 U/Kg/day, median 0.6) with a HbA1c of 6.8-10.2%, median 7.6. Insulin requirements did not correlate with BMI-SDS (r=0.18) or number of islets/kg infused (r=-0.21). Pts with PRSS1 mutation had borderline lower (p=0.05, t-test) insulin requirements (0.1 U/kg/day) than Pts with CFTR mutation (0.46 U/kg/day). Ten Pts (77%) discontinued pain medication with complete pain resolution within 3 months. Complications including pyloric stenosis, intraabdominal adhesions, and gastroparesis occurred in 3 Pts; Spontaneous/exercise-induced hypoglycemia in 2 Pts.

Conclusions: TPIAT is an effective treatment for CP in children and adolescents. Within 6 months, it provided pain resolution in 77% and allowed good glycemic control with no insulin or low dose basal insulin in 61% of patients in this series.

Renalase in Children with Glomerular Kidney Diseases

Posted by Pitor S, Joanna P, Urszula D, et al. on 2017-08-16 20:09:20


Studies suggest that renalase, a renal catecholamine-inactivating enzyme, plays a major role in the pathogenesis of kidney and cardiovascular diseases in adults. This study seeks to determine the role of renalase in children with glomerular kidney diseases. We evaluated the serum renalase, arterial stiffness, intima-media thickness, blood pressure, and clinical and biochemical parameters in 78 children (11.9 ± 4.6 years of age) with glomerulopathies such as idiopathic nephrotic syndrome (40 cases), IgA nephropathy (12 cases), Henoch-Schönlein nephropathy (12 cases), and other glomerulopathies (14 cases). The control group consisted of 38 healthy children aged 11.8 ± 3.3 years. The mean renalase was 25.74 ± 8.94 μg/mL in the glomerulopathy group, which was not significantly different from the 27.22 ± 5.15 in the control group. The renalase level did not differ among various glomerulopathies either. However, proteinuric patients had a higher renalase level than those without proteinuria (28.43 ± 11.71 vs. 24.05 ± 6.23, respectively; p = 0.03). In proteinuric patients, renalase correlated with daily proteinuria. In the entire glomerulopathy group, renalase correlated with age, systolic central blood pressure (BP), diastolic peripheral and central BP, mean peripheral and central BP; peripheral diastolic BP Z-score, glomerular filtration rate, cholesterol, triglycerides, and pulse wave velocity. We conclude that in children with glomerulopathies renalase, although basically not enhanced, may underlie blood pressure elevation and arterial damage.

Urinary biomarkers in patients with detrusor underactivity with and without bladder function recovery

Posted by Sheng-Fu C, Yuan-Hong J, Hann-Chorng K. on 2017-08-16 19:31:02



Detrusor underactivity (DU) is frequently encountered in elderly patients. Part of patients with DU might have bladder function recovery after treatment. This study investigated urinary proteins in these DU patients with and without bladder function recovery.


A total of 37 patients with chronic urinary retention and urodynamically proven DU were enrolled. After treatment, 24 DU patients had bladder function recovery whereas 13 had not, after 1-year follow-up. Urine collection at baseline was performed, and the urinary protein including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2) were measured by ELISA. Twenty urodynamically normal, 34 detrusor overactivity (DO) and 15 detrusor hyperactivity and inadequate contractility (DHIC) patients served as comparative groups.


Urinary NGF levels were significantly higher than normal in patients with DU (9.2 ± 20.3 vs 1.85 ± 2.9 pg/ml, p = 0.037). Urinary BDNF level was only significantly higher in patients with DU than that of the control group (153 ± 199 vs 77.4 ± 47.7 pg/ml, p = 0.033) but not in patients with DHIC or DO. Compared with the control group, the urinary BDNF level was significantly higher in DU patients with bladder function recovery (190 ± 239 pg/ml, p = 0.033) but not in patients without recovery (85.8 ± 43.7 pg/ml, p = 0.612). The PGE2 level was significantly higher than the control group in DU patients with bladder function recovery (1290 ± 836 pg/ml, p < 0.0001) but not in patients without recovery (383 ± 237 pg/ml, p = 0.130).


Patients with DU and higher urinary PGE2 and BDNF levels might have a chance to recover bladder function than those with a lower protein level.



In the current study, we investigated the effect of low magnitude, low frequency (LMLF) mechanical vibrations on the osteogenic differentiation potential of human adipose derived mesenchymal stem cells (hASC), taken from elderly patients.


During 21 days in osteogenic culture medium, cells were periodically exposed to three different frequencies (25, 35 and 45 Hz) of continuous sinusoidal oscillation, using a vibration generator. We measured cell proliferation, cell morphology, calcium and phosphorus deposition using Almar Blue assay, fluorescence microscopy, scanning electron microscopy, and a EDX detector, respectively. Osteogenic differentiation was measured by assessing protein and mRNA levels. Osteogenesis was confirmed by detection of specific markers with alkaline phosphatase and enzyme-linked immunosorbent assays for: bone morphogenetic protein 2 (BMP-2), osteocalcin (OCL) and osteopontin (OPN).


We found that 25 Hz vibrations had the greatest impact on hASC morphology, ultrastructure, and proliferation. We observed the formation of osteocyte- and hydroxyapatite-like structures, an increased quantity of calcium and phosphorus deposits, and increased differentiation in the stimulated groups.


Our findings suggest that LMLF vibrations could be used to enhance cell-based therapies for treatment of bone deficits, particularly in elderly patients, where the need is greatest.

Oxidative stress contributes to hepatocyte growth factor-dependent pro-senescence activity of ovarian cancer cells

Posted by Justyna M, Martyna P, Konstantin M, et al. on 2017-08-15 23:14:21


The cancer-promoting activity of senescent peritoneal mesothelial cells (HPMCs) has already been well evidenced both in vitro and in vivo. Here we sought to determine if ovarian cancer cells may activate senescence in HPMCs. The study showed that conditioned medium (CM) from ovarian cancer cells (OVCAR-3, SKOV-3, A2780) inhibited growth and promoted the development of senescence phenotype (increased SA-β-Gal, γ-H2A.X, 53BP1, and decreased Cx43) in HPMCs. An analysis of tumors isolated from the peritoneum of patients with ovarian cancer revealed an abundance of senescent HPMCs in proximity to cancerous tissue. The presence of senescent HPMCs was incidental when fragments of peritoneum free from cancer were evaluated. An analysis of the cells secretome followed by intervention studies with exogenous proteins and neutralizing antibodies revealed hepatocyte growth factor (HGF) as the mediator of the pro-senescence impact of the cancer cells. The activity of cancerous CM and HGF was associated with an induction of mitochondrial oxidative stress. Signaling pathways involved in the senescence of HPMCs elicited by the cancer-derived CM and HGF included p38 MAPK, AKT and NF-κB. HPMCs that senesced prematurely in response to the cancer-derived CM promoted adhesion of ovarian cancer cells, however this effect was effectively prevented by the cell protection against oxidative stress. Collectively, our findings indicate that ovarian cancer cells can elicit HGF-dependent senescence in HPMCs, which may contribute to the formation of a metastatic niche for these cells within the peritoneal cavity.


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