Background Glucagon-like Peptide 1 (GLP-1) and glucagon shares the same precursor molecule proglucagon, but each arises from a distinct posttranslational process in a tissue-specific manner. Recently it has been shown that GLP-1 is co-expressed with glucagon in pancreatic islet cells. This study was aimed to investigate the progressive changes of GLP-1 vs glucagon production in pancreatic islets during the course of diabetes development. Methods Both type 1 (NOD mice) and type 2 (db/db mice) diabetes models were employed in this study. The mice were monitored closely for their diabetes progression, and were sacrificed at different stages according to their blood glucose levels. GLP-1 and glucagon expression in the pancreatic islets was examined using immunohistochemistry assays. Quantitative analysis was performed to evaluate the significance of the changes. Results The ratio of GLP-1-expressing cells to glucagon expressing cells in the islets showed significant, progressive increase with the development of diabetes in db/db mice. The increase of GLP-1 expression was in accordance with the upregulation of PC1/3 expression in these cells. Interestingly, intra-islet GLP-1 expression was not significantly changed during the development of type 1 diabetes in NOD mice. Conclusions The study demonstrated GLP-1 was progressively up-regulated in pancreatic islets during type 2 diabetes development. In addition, the data suggest clear differences in intra-islet GLP-1 production between type 1 and type 2 diabetes developments. These differences may have an impact on the clinical and pathophysiological processes of these diseases and may be a target for therapeutic approaches.
Based on Organ Procurement and Transplantation Network data as of December 2019, more than 113 000 patients require an organ transplantation, yet, over the course of this past year, only 36 000 patients received a transplant. This discrepancy between those that need a donor organ and those that receive one remains one of medicine’s biggest challenges. Multiple solutions, both biologic and artificial, have been proposed to mitigate this difference. One of the most promising approaches to generate bioartificial organs for transplantation involves re‐seeding decellularized scaffolds with appropriate cells. Decellularization involves physical, chemical, or biological methods that typically require intimate contact of various decellularization solutions with each cell. Consequently, conventional submersion decellularization has been limited to simple tissues such as heart valves. The invention of perfusion decellularization was a breakthrough that allowed the generation of tissue‐engineered scaffolds from tissues with higher structural organization and entire organs. Such scaffolds are composed of a myriad of extracellular matrix (ECM) components that include collagen, elastin, proteoglycans, and glycoproteins. Together, these components allow the scaffolds to fulfill specialized functions, such as structural functions as well as biological functions including the regulation of cellular processes and extracellular molecules. These specialized functions of decellularized scaffolds can increasingly be harnessed for applications in tissue engineering.
Background: While the standard of care for suspected tracheo-innominate artery fistula (TIF) necessitates sternotomy, perioperative mortality remains high. Endovascular interventions have been attempted, but reports have been anecdotal. The aim of this systematic review was to evaluate the outcomes of endovascular management of TIF by pooling the existing evidence. Methods: An electronic database search of Ovid MEDLINE, Scopus, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Controlled Trials Register was performed to identify all studies examining endovascular treatment of TIF. Patients greater than 14 years of age who underwent endovascular intervention for TIF were included. 25 studies consisting of 27 patients met the inclusion criteria. Results: 48.1% (13/27) of patients were male and median age was 39.0 [IQR 16.0, 47.5] years. Tracheostomy was present in 96.3% (26/27) of cases. Median duration from tracheostomy to TIF presentation was 2.2 months [0.5, 42.5]. On presentation, 84.6% (22/26) had tracheal hemorrhage, and 22.8% (6/27) were hemodynamically unstable. 96.3% (26/27) underwent covered stent graft placement while 1 patient (3.8%) had coil embolization. 18.5% (5/27) of patients required repeat endovascular intervention for recurrent bleeding, while 11.1% (3/27) required rescue sternotomy. Median hospital length of stay was 30 days [16.0, 46.5], and overall mortality was 29.6% (8/27) with a median follow-up time of 5 months [1.2, 11.5]. Conclusion: While uncommon, endovascular treatment of TIF may be a feasible alternative to sternotomy. The approach may be useful in those who are unable to undergo surgery or are likely to have adhesions from prior chest operations.
The ever‐widening gap between organ supply and demand has resulted in an organ shortage crisis that affects patients all over the world. For decades, static cold storage (SCS) was the gold standard preservation strategy because of its simplicity and cost‐effectiveness, but the rising unmet demand for donor organ transplants has prompted investigation into preservation strategies that can expand the available donor pool. Through ex vivo functional assessment of the organ prior to transplant, newer methods to preserve organs such as perfusion‐based therapy can potentially expand the available organ pool. This review will explain the physiologic rationale for SCS before exploring the advantages and disadvantages associated with the two broad classes of preservation strategies that have emerged to address the crisis: hypothermic and normothermic machine perfusion. A detailed analysis of how each preservation strategy works will be provided before investigating the current status of clinical data for each preservation strategy for the kidney, liver, pancreas, heart, and lung. For some organs there is robust data to support the use of machine perfusion technologies over SCS, and in others the data are less clear. Nonetheless, machine perfusion technologies represent an exciting frontier in organ preservation research and will remain a crucial component of closing the gap between organ supply and recipient demand.
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