We present a microfluidic vascular device. Vascular cells in a 3D-ECM environment support hemodynamic flow and enable monocyte interaction.

Background and objectives: Sodium glucose transporter 2 (SGLT2)-inhibitor-induced uric acid lowering may contribute to kidney protective effects of the drug-class in people with type 2 diabetes. This study investigates mechanisms of plasma uric acid lowering by SGLT2-inhibitors in people with type 2 diabetes with a focus on urate transporter (URAT)1. Methods: We conducted an analysis of two randomized, clinical trials. First, in the Renoprotective Effects of Dapagliflozin in Type 2 Diabetes (RED) study, 44 people with type 2 diabetes were randomized to dapagliflozin or gliclazide for 12 weeks. Plasma uric acid, fractional uric acid excretion and hemodynamic kidney function were measured in the fasted state and during clamped eu- or hyperglycemia. Second, in the Uric Acid Excretion study (UREX) study, 10 people with type 2 diabetes received 1-week empagliflozin, benzbromarone and their combination in a cross-over design and effects on plasma uric acid, fractional uric acid excretion and 24-hr uric acid excretion were measured. Results: In the RED study, compared to the fasted state (5.3±1.1mg/dL), acute hyperinsulinemia and hyperglycemia significantly reduced plasma uric acid by 0.2±0.3 and 0.4±0.3 mg/dL (both p<0.001), while increasing fractional uric acid excretion (by 3.2±3.1% and 8.9±4.5% respectively (both p<0.001). Dapagliflozin reduced plasma uric acid by 0.8±0.8mg/dL, 1.0±1.0mg/dL and by 0.8±0.7mg/dL during fasting, hyperinsulinemic-euglycemic and hyperglycemic conditions (p<0.001), whereas fractional uric acid excretion in 24-hr urine increased by 3.0±2.1% (p<0.001) and 2.6±4.5% during hyperinsulinemic-euglycemic conditions (p=0.003). Fractional uric acid excretion strongly correlated to fractional glucose excretion (r= 0.35, p=0.02). In the UREX study, empagliflozin and benzbromarone both significantly reduced plasma uric acid and increased fractional uric acid excretion. Effects of combination therapy did not differ from benzbromarone monotherapy. Conclusion: In conclusion, SGLT2-inhibitors induce uric acid excretion, which is strongly linked to urinary glucose excretion and which is attenuated during concomitant pharmacological blockade of URAT1.

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The lymphatic system plays a crucial role in interstitial fluid drainage, lipid absorption, and immunological defense. Lymphatic dysfunction results in lymphedema, fluid accumulation, and swelling of soft tissues, as well as a potentially impaired immune response. Lymphedema significantly reduces quality of life of patients on a physical, mental, social, and economic basis. Current therapeutic approaches in treatment of lymphatic disease are limited. Over the last decades, great progress has been made in the development of therapeutic strategies to enhance vascular regeneration. These solutions to treat vascular disease may also be applicable in the treatment of lymphatic diseases. Comparison of the organogenic process and biological organization of the vascular and lymphatic systems and studies in the regulatory mechanisms involved in lymphangiogenesis and angiogenesis show many common features. In this study, we address the similarities between both transport systems, and focus in depth on the biology of lymphatic development. Based on the current advances in vascular regeneration, we propose different strategies for lymphatic tissue engineering that may be used for treatment of primary and secondary lymphedema.