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Reports Focused towards Combination in the Acridone Family of Natural Goods: Total Combination of Acronycines and Atalaphyllidines.
The mean age was 66.2; 51.5% were men; and the median follow-up was 6.0 years. The outcome with the highest incidence was nephropathy, with 24.4 cases per 1000 person-years in the reference category of 1.1≤ABI≤1.3. The incidences in this category for mortality and AMI were 15.4 and 4.1, respectively. In the Cox models, low ABI was associated with increased risk and was significant from ABI lower than 0.9; below this level, the risk kept increasing steeply. High ABI (over 1.3) was also associated with significant increased risk for most outcomes. CONCLUSIONS The studied categories of ABI were associated with different risks of type 2 diabetes complications in persons asymptomatic for PAD, who were in primary cardiovascular prevention. These findings could be useful to optimize preventive interventions according to the ABI category in this population. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Gestational diabetes mellitus (GDM), a common pregnancy disorder, increases the risk of fetal overgrowth and later metabolic morbidity in the offspring. The placenta likely mediates these sequelae, but the exact mechanisms remain elusive. Mitochondrial dynamics refers to the joining and division of these organelles, in attempts to maintain cellular homeostasis in stress conditions or alterations in oxygen and fuel availability. These remodeling processes are critical to optimize mitochondrial function, and their disturbances characterize diabetes and obesity. METHODS AND RESULTS Herein we show that placental mitochondrial dynamics are tilted toward fusion in GDM, as evidenced by transmission electron microscopy and changes in the expression of key mechanochemical enzymes such as OPA1 and active phosphorylated DRP1. In vitro experiments using choriocarcinoma JEG-3 cells demonstrated that increased exposure to insulin, which typifies GDM, promotes mitochondrial fusion. As placental ceramide induces mitochondrial fission in pre-eclampsia, we also examined ceramide content in GDM and control placentae and observed a reduction in placental ceramide enrichment in GDM, likely due to an insulin-dependent increase in ceramide-degrading ASAH1 expression. CONCLUSIONS Placental mitochondrial fusion is enhanced in GDM, possibly as a compensatory response to maternal and fetal metabolic derangements. Alterations in placental insulin exposure and sphingolipid metabolism are among potential contributing factors. Overall, our results suggest that GDM has profound impacts on placental mitochondrial dynamics and metabolism, with plausible implications for the short-term and long-term health of the offspring. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE Pancreatic beta cells proliferate in response to metabolic requirements during pregnancy, while failure of this response may cause gestational diabetes. A member of the vascular endothelial growth factor family, placental growth factor (PlGF), typically plays a role in metabolic disorder and pathological circumstance. The expression and function of PlGF in the endocrine pancreas have not been reported and are addressed in the current study. RESEARCH DESIGN AND METHODS PlGF levels in beta cells were determined by immunostaining or ELISA in purified beta cells in non-pregnant and pregnant adult mice. An adeno-associated virus (AAV) serotype 8 carrying a shRNA for PlGF under the control of a rat insulin promoter (AAV-rat insulin promoter (RIP)-short hairpin small interfering RNA for PlGF (shPlGF)) was prepared and infused into mouse pancreas through the pancreatic duct to specifically knock down PlGF in beta cells, and its effects on beta-cell growth were determined by beta-cell proliferation, beta-cell mass and insulin release. A macrophage-depleting reagent, clodronate, was coapplied into AAV-treated mice to study crosstalk between beta cells and macrophages. RESULTS PlGF is exclusively produced by beta cells in the adult mouse pancreas. Moreover, PlGF expression in beta cells was significantly increased during pregnancy. Intraductal infusion of AAV-RIP-shPlGF specifically knocked down PlGF in beta cells, resulting in compromised beta-cell proliferation, reduced growth in beta-cell mass and impaired glucose tolerance during pregnancy. Mechanistically, PlGF depletion in beta cells reduced islet infiltration of trophic macrophages, which appeared to be essential for gestational beta-cell growth. CONCLUSIONS Our study suggests that increased expression of PlGF in beta cells may trigger gestational beta-cell growth through recruited macrophages. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE Improvement in insulin alternatives is leading to a delayed presentation of microvascular and macrovascular complications of diabetes. The objective of this study was to evaluate the long-term outcomes of older (≥50 years) diabetic patients who receive a pancreas transplantation (PT). RESEARCH DESIGN AND METHODS We retrospectively evaluated all 338 PTs performed at our center between 2000 and 2016 (mean follow-up 9.4±4.9 years). Recipient and graft survivals were estimated for up to 10 years after PT. Major adverse cardiovascular events (MACEs) before and after PT were included in the analysis. RESULTS Thirty-nine patients (12%) were ≥50 years old (52.7±2.3 years) at the day of PT, of which 29 received a simultaneous pancreas-kidney transplantation (SPK) and 10 a pancreas after kidney transplantation (PAK). SPK recipients were first transplants, whereas in the PAK up to 50% were pancreas re-transplantations. Recipient and pancreas graft survivals at 10 years were similar between the group 0.05). The prevalence of MACE prior to PT was similar between both groups (31% vs 29%). Following PT, older recipients presented inferior post-transplant MACE-free survival. In a multivariate regression model, diabetes vintage (HR 1.054, p=0.03) and pre-transplantation MACE (HR 1.98, p=0.011), but not recipient age (HR 1.45, p=0.339), were associated with post-transplant MACE. NT157 CONCLUSIONS Long-term survival of older pancreas transplant recipients are similar to younger counterparts. Diabetes vintage, but not age, increased the risk of post-transplantation MACE. These results suggest pancreas transplantation is a valuable treatment alternative to older diabetic patients. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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