E L Los


Publication Details
Article Title: Potential of nonpeptide (ant)agonists to rescue vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic diabetes insipidus.

First Author: E L Los

All Authors: Los EL, Deen PM, Robben JH

Journal Title: Journal of neuroendocrinology

Abstract: According to the body's need, water is reabsorbed from the pro-urine that is formed by ultrafiltration in the kidney. This process is regulated by the antidiuretic hormone arginine-vasopressin (AVP), which binds to its type 2 receptor (V2R) in the kidney. Mutations in the gene encoding the V2R often lead to the X-linked inheritable form of nephrogenic diabetes insipidus (NDI), a disorder in which patients are unable to concentrate their urine despite the presence of AVP. Many of these mutations are missense mutations that do not interfere with the intrinsic functionality of V2R, but cause its retention in the endoplasmic reticulum (ER), making it unavailable for AVP binding. Because the current treatments for NDI relieve its symptoms to some extent, but do not cure the disorder, cell-permeable antagonists (pharmacological chaperones) have been successfully used to stabilise the mutant receptors and restore their plasma membrane localisation. Recently, cell-permeable agonists also were shown to rescue ER-retained V2R mutants, leading to increased cAMP levels and translocation of aquaporin-2 to the apical membrane. This makes V2R-specific cell-permeable agonists very promising therapeutics for NDI as a result of misfolded V2R receptors.

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Reproductive health
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Authors: de Sousa Basso NA, Morceli G, Costa R, Dias A, Rudge MVC, Calderon IMP

Abstract: The present study validates a symphysis-fundal height chart (SFH-chart) for pregnant women with type 2 diabetes mellitus (DM2), gestational diabetes mellitus (GDM) and mild gestational hyperglycemia (MGH) attending at the Diabetes and Pregnancy Reference Service of the Botucatu Medical School, UNESP, Brazil.A cross-sectional study was carried out to evaluate the performance of the specific FHC in predicting small (SGA) and large (LGA) for gestational age newborns (NB). We evaluated 206 pregnant women with DM2, GDM or MGH and their NB. The last symphysis-fundal height measure, taken at birth, was used to determine the sensitivity index (Sens), specificity index (Spe), positive prediction value (PPV), negative prediction value (NPV) and accuracy in predicting SGA and LGA. The gold standard was the Lubchenco birth weight/gestational age ratio evaluated at birth.The mothers showed adequate glycemic control; 91.3 % of all pregnant women achieved HbA1c?

Social science & medicine (1982)
What do physicians gain (and lose) with experience? Qualitative results from a cross-national study of diabetes.

Authors: Elstad EA, Lutfey KE, Marceau LD, Campbell SM, von dem Knesebeck O, McKinlay JB

Abstract: An empirical puzzle has emerged over the last several decades of research on variation in clinical decision making involving mixed effects of physician experience. There is some evidence that physicians with greater experience may provide poorer quality care than their less experienced counterparts, as captured by various quality assurance measures. Physician experience is traditionally narrowly defined as years in practice or age, and there is a need for investigation into precisely what happens to physicians as they gain experience, including the reasoning and clinical skills acquired over time and the ways in which physicians consciously implement those skills into their work. In this study, we are concerned with 1) how physicians conceptualize and describe the meaning of their clinical experience, and 2) how they use their experience in clinical practice. To address these questions, we analyzed qualitative data drawn from in-depth interviews with physicians from the United States, United Kingdom, and Germany as a part of a larger factorial experiment of medical decision making for diabetes. Our results show that common measures of physician experience do not fully capture the skills physicians acquire over time or how they implement those skills in their clinical work. We found that what physicians actually gain over time is complex social, behavioral and intuitive wisdom as well as the ability to compare the present day patient against similar past patients. These active cognitive reasoning processes are essential components of a forward-looking research agenda in the area of physician experience and decision making. Guideline-based outcome measures, accompanied by underdeveloped age- and years-based definitions of experience, may prematurely conclude that more experienced physicians are providing deficient care while overlooking the ways in which they are providing more and better care than their less experienced counterparts.

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Authors: Sugunan D, Nair AK, Kumar H, Gopalakrishnapillai A

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Authors: Otgontuya D, Oum S, Palam E, Rani M, Buckley BS

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Herz
Noninvasive assessment of subclinical atherosclerosis in normotensive gravidae with gestational diabetes.

Authors: Atay AE, Simsek H, Demir B, Sakar MN, Kaya M, Pasa S, Demir S, Sit D

Abstract: Carotid artery intima-media thickness (CIMT), hyperhomocysteinemia, microalbuminuria, and nitric oxide reflect subclinical atherosclerosis and predict the risk of future cardiovascular events. We aimed to evaluate the presence of subclinical atherosclerosis and endothelial dysfunction in normotensive patients with gestational diabetes mellitus (GDM) noninvasively.We enrolled 41 normotensive patients with GDM and 44 healthy gravidae in the study. Serum homocysteine and nitric oxide levels, urinary albumin excretion (microalbuminuria), and CIMT were evaluated along with lipid parameters and anthropometric measurements.Patients with GDM had significantly higher levels of serum homocysteine, urinary albumin excretion, and increased CIMT (p?

Liver international : official journal of the International Association for the Study of the Liver
Diabetes pattern on the 75 g oral glucose tolerance test is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus.

Authors: Konishi I, Hiasa Y, Shigematsu S, Hirooka M, Furukawa S, Abe M, Matsuura B, Michitaka K, Horiike N, Onji M

Abstract: Patients with hepatitis C virus (HCV) frequently show glucose intolerance. Diabetes mellitus (DM) has been proposed to be a risk factor for hepatocellular carcinoma (HCC).The aim of this study is to clarify the influence of glucose intolerance as evaluated by the 75 g oral glucose tolerance test (OGTT) on hepatocarcinogenesis in patients with HCV.This study was carried out in a cohort of 197 patients with HCV who had not been previously diagnosed as having DM. All patients underwent the 75 g OGTT at entry. They were also screened for HCC and, thereafter, the rate of hepatocarcinogenesis was compared between the patients with and without glucose intolerance.Based on the results of the 75 g OGTT, 125 (63%) had normal glucose tolerance (NGT), 49 (25%) had impaired glucose tolerance (IGT) and 23 (12%) had the DM pattern. HCC occurred more frequently in patients with the DM pattern than in patients with either NGT or IGT. Even in patients without advanced liver fibrosis, HCC was more frequently observed in patients with DM than in patients with NGT. A multiple logistic regression analysis showed advanced liver fibrosis, the DM pattern on the 75 g OGTT, an older age and gamma-glutamyltransferase to all be independent risk factors related to hepatocarcinogenesis.A DM pattern on the 75 g OGTT was thus found to be associated with hepatocarcinogenesis and the 75 g OGTT is considered to be useful for identifying this risk factor for HCC in patients with HCV.

Organogenesis
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Authors: Gregory JM, Moore DJ

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Thrombosis and haemostasis
Inflammation and thrombosis in diabetes.

Authors: Hess K, Grant PJ

Abstract: Patients with diabetes mellitus are at increased risk of cardiovascular morbidity and mortality. Atherothrombosis, defined as atherosclerotic lesion disruption with superimposed thrombus formation, is the most common cause of death among these patients. Following plaque rupture, adherence of platelets is followed by local activation of coagulation, the formation of a cross-linked fibrin clot and the development of an occlusive platelet rich fibrin mesh. Patients with diabetes exhibit a thrombotic risk clustering which is composed of hyper-reactive platelets, up regulation of pro-thrombotic markers and suppression of fibrinolysis. These changes are mainly mediated by the presence of insulin resistance and dysglycaemia and an increased inflammatory state which directly affects platelet function, coagulation factors and clot structure. This prothrombotic state is related to increased cardiovascular risk and may account for the reduced response to antithrombotic therapeutic approaches, underpinning the need for adequate antithrombotic therapy in patients with diabetes to reduce their cardiovascular mortality.

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