A woman with raised alkaline phosphatase and forearm deformity

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Serum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes

Background The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing [endogenous secretory RAGE (esRAGE)] and/or by proteolytic cleavage of the membrane-bound receptor. We have investigated the role of A Disintegrin And Metalloproteinase 10 (ADAM10) in the ectodomain shedding of RAGE. Methods Constitutive and insulin-induced shedding of RAGE in THP-1 macrophages by ADAM10 was evaluated using an ADAM10-specific metalloproteinase inhibitor. Serum ADAM10 level was measured in type 1 diabetes and control subjects, and the association with serum soluble RAGE was determined. Serum total sRAGE and esRAGE were assayed by ELISA and the difference between total sRAGE and esRAGE gave an estimated measure of soluble RAGE formed by cleavage (cRAGE). Results RAGE shedding (constitutive and insulin-induced) was significantly reduced after inhibition of ADAM10 in macrophages, and insulin stimulated ADAM10 expression and activity. Diabetic subjects have higher serum total sRAGE and esRAGE (p<0.01) than controls, and serum ADAM10 was also increased (p<0.01). Serum ADAM10 correlated with serum cRAGE in type 1 diabetes (r = 0.40, p<0.01) and in controls (r = 0.31. p<0.01) but no correlations were seen with esRAGE. The association remained significant after adjusting for age, gender, BMI, smoking status and HbA1c. Conclusion Our data suggested that ADAM10 contributed to the shedding of RAGE. Serum ADAM10 level was increased in type 1 diabetes and was a significant determinant of circulating cRAGE.published_or_final_versio

Loss of Endometrial Plasticity in Recurrent Pregnancy Loss

© 2015 AlphaMed Press.Menstruation drives cyclic activation of endometrial progenitor cells, tissue regeneration, and maturation of stromal cells, which differentiate into specialized decidual cells prior to and during pregnancy. Aberrant responsiveness of human endometrial stromal cells (HESCs) to deciduogenic cues is strongly associated with recurrent pregnancy loss (RPL), suggesting a defect in cellular maturation. MeDIP-seq analysis of HESCs did not reveal gross perturbations in CpG methylation in RPL cultures, although quantitative differences were observed in or near genes that are frequently deregulated in vivo. However, RPL was associated with a marked reduction in methylation of defined CA-rich motifs located throughout the genome but enriched near telomeres. Non-CpG methylation is a hallmark of cellular multipotency. Congruently, we demonstrate that RPL is associated with a deficiency in endometrial clonogenic cell populations. Loss of epigenetic stemness features also correlated with intragenic CpG hypomethylation and reduced expression of HMGB2, coding high mobility group protein 2. We show that knockdown of this sequence-independent chromatin protein in HESCs promotes senescence and impairs decidualization, exemplified by blunted time-dependent secretome changes. Our findings indicate that stem cell deficiency and accelerated stromal senescence limit the differentiation capacity of the endometrium and predispose for pregnancy failure. Stem Cells 2016;34:346-356 Recurrent pregnancy loss is caused by endometrial stem cell deficiency, triggering heightened tissue senescence and impaired decidualization

Carbamylation of LDL in type 2 diabetes mellitus

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Gas in the renal shadow of a plain abdominal X-ray: emphysematous pyelonephritis

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Association between soluble receptor for advanced glycation end products and a disintegrin and metalloproteinase 10 in Type 1 diabetes

Session: MON 1011-1042-Immunology & Transplantation; Insulin Signaling; Islet Biology; Pathophysiology/Complications TranslationalThe Conference program's website is located at http://endowebcasting.com/endo/archives.htmThe receptor for advanced glycation end products (RAGE) plays an important role in the pathogenesis of diabetic complications and atherosclerosis. Soluble forms of the receptor (sRAGE) can act as decoy for RAGE ligands and counteract the detrimental action of the full-length receptor. Soluble RAGE is produced by alternative splicing [endogenous secretory RAGE (esRAGE)] and/or by proteolytic cleavage of the membrane-bound form of RAGE. It has been suggested that ectodomain shedding is one of the mechanisms for regulating the function of RAGE. A Disintegrin And Metalloproteinase (ADAM) is a major proteinase family that mediates ectodomain shedding of cell surface proteins. Our in vitro experiments showed that the RAGE shedding (both constitutive and insulin-induced) was significantly reduced after inhibition of the sheddase ADAM10 in macrophages. We further examined whether there was any relationship between ADAM10 and total sRAGE and esRAGE levels in type 1 diabetes. 102 type 1 diabetic patients and age- and sex-matched controls were recruited. Serum ADAM10 was measured by in-house competitive ELISA using a monoclonal anti-human ADAM10 antibody (Millipore, CA). Serum total sRAGE and esRAGE were assayed by commercial ELISA kits (Quantikine, R&D systems, MN, USA, and B-Bridge International Inc., CA, USA respectively). The difference between total sRAGE and esRAGE gave an estimated measure of soluble forms of RAGE formed by cleavage (cRAGE). Type 1 diabetic patients have higher serum total sRAGE [1038 (749-1217) pg/ml vs 802 (532-1129), median (interquartile range), p<0.01], esRAGE [367 (269-476) pg/ml vs 291 (214-389), p<0.01] and cRAGE [594 (447-812) pg/ml vs 484 (283-796), p<0.01] than controls. Serum ADAM10 was also increased in patients with type 1 diabetes [324 (179-433) ng/ml vs 156 (112-278), p<0.01]. Serum ADAM10 level correlated with serum cRAGE in type 1 diabetes (r=0.40, p<0.01) and in controls (r=0.31. p<0.01) but no correlations were seen with esRAGE. The association remained significant after adjusting for age, gender, body mass index and smoking status. In conclusion, our data suggested that ADAM10 contributed to the shedding of RAGE and ADAM10 level was significantly associated with serum cRAGE in type 1 diabetes and non-diabetic control.link_to_OA_fulltex

Protocol driven assessment programme effectively shortens new case waiting time

Service Priorities and Programmes Free Papers: SPP4.6 Quality and Safety in Healthcare 1Conference Theme: Consolidating Health Care - 固本培員, 健行不息Introduction: The waiting time for new cases in endocrine clinic has been rising due to increasing demand. The average waiting time has increased to 26.3 ± 5.5 weeks in February 2012. To improve the situation, a protocol driven assessment (PDA) programme has been established and incorporated into the triage pathway starting from April 2012. Objectives: (1) To shorten the waiting time of new case at the Endocrine Clinic; and (2) to enhance efficient work flow of triage system and improve patient care. Methodology: Protocols for endocrine diseases including obesity, hyperprolactinaemia, hypercalcaemia, hypopituitarism and hypogonadism were developed. Patients referred for such conditions were triaged to the PDA programme in which history taking, assessments, investigations and early interventions were carried out according to the protocols set by an endocrine nurse and subsequently followed by endocrinologists. Results: 225 referrals were screened from May 2012 to December 2012. 64 patients were triaged to the programme. The referralto-nurse and referral-to-endocrinologist times for the programme were 5.9 ± 4.9 and 9.8 ± 5.3 weeks respectively. This showed a significant improvement when compared with their original referral-to-endocrinologist time (26.6 ± 5.7 weeks, p<0.05). Referral-to-endocrinologist time for patients not recruited into the programme also showed significant improvement (10.3 ± 9.0 vs. 26.2 ± 5.4 weeks, p< 0.05) and the PDA programme was one of the measures that contributed to this success. Early intervention has been initiated during the initial nursing assessment of the programme. 18 obese patients received prompt referrals to relevant allied health disciplines before assessments by specialists. Four patients, referred for hyperprolactinaemia, had normal serum prolactin level after re-checked by endocrine nurse under a controlled non-stressed condition. They could be discharged from clinic at the first specialist assessment. More urgent conditions, such as visual field defects and high blood pressure, had also been detected early in the nursing assessment stage and resulted in prompt treatment action. The establishment of PDA programme, conducted by an experienced nurse, not only shortens waiting time but also provides patients with a more streamlined, timely and efficient model of care