Kagawa University

About: Kagawa University is a education organization based out in Takamatsu, Japan. It is known for research contribution in the topics: Cancer & Population. The organization has 6028 authors who have published 11918 publications receiving 224111 citations. The organization is also known as: Kagawa Daigaku.

Organ protection by SGLT2 inhibitors: role of metabolic energy and water conservation.

Abstract: Therapeutic inhibition of the sodium–glucose co-transporter 2 (SGLT2) leads to substantial loss of energy (in the form of glucose) and additional solutes (in the form of Na+ and its accompanying anions) in urine. However, despite the continuously elevated solute excretion, long-term osmotic diuresis does not occur in humans with SGLT2 inhibition. Rather, patients on SGLT2 inhibitor therapy adjust to the reduction in energy availability and conserve water. The metabolic adaptations that are induced by SGLT2 inhibition are similar to those observed in aestivation — an evolutionarily conserved survival strategy that enables physiological adaptation to energy and water shortage. Aestivators exploit amino acids from muscle to produce glucose and fatty acid fuels. This endogenous energy supply chain is coupled with nitrogen transfer for organic osmolyte production, which allows parallel water conservation. Moreover, this process is often accompanied by a reduction in metabolic rate. By comparing aestivation metabolism with the fuel switches that occur during therapeutic SGLT2 inhibition, we suggest that SGLT2 inhibitors induce aestivation-like metabolic patterns, which may contribute to the improvements in cardiac and renal function observed with this class of therapeutics. SGLT2 inhibitors induce a number of metabolic adaptations in response to increased glucose and Na+ excretion. This Perspective article describes how these adaptations suggest that SGLT2 inhibition triggers a body water-conserving mechanism, and discusses how these metabolic adjustments may contribute to the favourable cardiovascular and renal outcomes of this class of therapeutics.

A Collagen-Based Coil for Embolization of Saccular Aneurysms in a New Zealand White Rabbit Model

Abstract: BACKGROUND AND PURPOSE: In the treatment of cerebral aneurysms, platinum coils often fail to elicit a fibrotic response. We tested the hypothesis that a new, collagen-based endovascular coil would improve angiographic and histologic outcomes as compared with those achieved with platinum coils in a rabbit model of saccular aneurysms. METHODS: Elastase-induced aneurysms were created in 12 New Zealand White rabbits (body weight, 3–4 kg). Embolization was performed either by use of collagen-based coils (n = 6) or platinum coils (n = 6). In both coil groups, subjects were kept alive for either 2 weeks (n = 3 [collagen], n = 3 [platinum]) or 10 weeks (n = 3 [collagen], n = 3 [platinum]) after embolization and then were sacrificed. Digital subtraction angiography (DSA) was performed immediately after embolization and immediately before sacrifice. Postmortem histologic analysis of all coils was performed. RESULTS: Collagen-based coils were loosely packed in all cases because of limitations in size of coils available for embolization. In all six aneurysms packed with collagen-based coils, progressive thrombosis was noted at follow-up (DSA). Platinum coil samples were densely packed in all six cases. Progressive thrombosis was seen in one case, and interval regrowth was present in one case. Two weeks after embolization, collagen-based coil samples showed a marked peri-coil cellular response. Ten weeks after embolization, collagen-based samples had dense connective tissue matrix deposition in two of three cases. Platinum coils had unorganized thrombus at 2 weeks; loose-matrix deposition was only seen in the 10-week samples. Smooth muscle actin-positive cells were seen across the neck of the aneurysm in four of six collagen-based coil cases. CONCLUSION: Collagen-based coils show a marked cellular response in animal-model aneurysms, with resultant high rates of progressive occlusion after embolization. Dense matrix deposition is commonly seen with collagen-based coils. This contrasts with low rates of progressive thrombosis and high rates of loose matrix deposition seen with platinum coils.