Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter.

Sodium-glucose cotransporter 2 (SGLT2) is imporant in glucose reabsorption. SGLT2 inhibitors suppress renal glucose reabsorption, therefore reducing blood glucose levels in patients with type 2 diabetes. We and others have developed several SGLT2 inhibitors starting from phlorizin, a natural product.

A case of descending aortic dissection in a patient with unrepaired tetralogy of Fallot and pulmonary atresia.

Unlabelled: The prognosis of tetralogy of Fallot with pulmonary atresia (TOF/PA) is mainly determined by the development of major aorto-pulmonary collateral arteries (MAPCAs) that provide pulmonary blood perfusion. TOF/PA can be managed conservatively until adulthood in patients with adequate, but not excessive perfusion via MAPCAs. To the best of our knowledge, this is the first report of a patient with unrepaired TOF/PA who eventually developed descending aortic dissection (AD), and survived with medical treatment.

Pharmacokinetics of Single and Multiple Oral Administration of a Self-emulsifying Formulation of Highly Purified Eicosapentaenoic Acid Ethyl Ester (MND-2119) Compared With the Nonself-emulsifying Formulation in Healthy Male Subjects.

MND-2119 is a self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) designed to be administered once daily due to improved absorption compared with the nonself-emulsifying formulation. In these studies, MND-2119 was administered to healthy adult males in single or multiple doses. In the single administration study, MND-2119 (0.

Long-term safety and efficacy of MND-2119 (self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester) in patients with hypertriglyceridemia: Results from a multicenter, 52-week, open-label study.

Background: In Japan, eicosapentaenoic acid ethyl ester (EPA-E) is administered twice-daily or three-times-daily for dyslipidemia. We have developed MND-2119, a novel self-emulsifying formulation of highly purified EPA-E which can be administered once-daily.

Objective: The objective of this study was to investigate the safety and efficacy of long-term administration of MND-2119 in hypertriglyceridemia patients.

Efficacy and safety of self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (MND-2119) versus highly purified eicosapentaenoic acid ethyl ester in patients with hypertriglyceridemia: Results from a 12-week randomized, double-blind, active-controlled, phase 3 study.

Background: In Japan, eicosapentaenoic acid ethyl ester (EPA-E) is administered twice-daily or three-times-daily for dyslipidemia. We have developed MND-2119, a novel self-emulsifying formulation of highly purified EPA-E, which can be administered once-daily.

Objective: The objective of this study was to assess non-inferiority in the efficacy of MND-2119 in patients with hypertriglyceridemia compared with highly purified EPA-E.

Osteodiscus abyssicola, a new snailfish (Cottoidei: Liparidae) collected off the Pacific coast of northern Japan.

The snailfish Osteodiscus abyssicola sp. nov. is described from a single specimen collected off the Pacific coast of Hokkaido, northern Japan, at a depth of 4,6714,744 m.

Machine Learning-Based Screening of Healthy Meals From Image Analysis: System Development and Pilot Study.

Background: Recent research has led to the development of many information technology-supported systems for health care control, including systems estimating nutrition from images of meals. Systems that capture data about eating and exercise are useful for people with diabetes as well as for people who are simply on a diet. Continuous monitoring is key to effective dietary control, requiring systems that are simple to use and motivate users to pay attention to their meals.

A new species of snailfish of the genus (Liparidae) from the western North Pacific, with a redescription of the poorly known species .

A new snailfish, , is described on the basis of 18 specimens collected off the Pacific coast of Tohoku District, northern Japan at depths of 422-890 m. The new species is distinguished from 28 species of described from the North Pacific by the following combination of characters: mouth oblique; uppermost pectoral-fin base below horizontal through posterior margin of maxillary; 60-63 vertebrae, 54-58 dorsal-fin rays, 50 or 51 anal-fin rays, six principal caudal-fin rays, and 17-20 pectoral-fin rays. A maximum likelihood tree based on 106 COI gene sequences (492 bp) of recovered a monophyletic group comprising , , and .

Quantitative Volumetric Comparison of Direct Oral Anticoagulant and Vitamin K Antagonist Treatment for Pulmonary Thrombus Reduction During the Acute Phase in Symptomatic Patients.

Background: Recent clinical trials' findings have revealed the therapeutic noninferiority of direct oral anticoagulant (DOAC) to standard therapy with vitamin K antagonist (VKA) in patients with pulmonary thromboembolism (PTE). However, few studies have quantitatively analyzed thrombus reduction in the pulmonary artery.

Methods: This observational study included 38 symptomatic PTE patients with stable hemodynamics.

Effectiveness and safety of dabigatran warfarin in "real-world" Japanese patients with atrial fibrillation: A single-center observational study.

Background: In "real-world" practice, anticoagulant therapy is indicated for patients whose clinical profiles are not addressed in randomized clinical trials. We assessed the effectiveness and safety of dabigatran warfarin in "real-world" Japanese patients with non-valvular atrial fibrillation (NVAF).

Methods: Among 613 NVAF patients who initiated dabigatran or warfarin therapy during the period between 2011 and 2013, 362 patients were included in the study after propensity score adjustment.

Persistence of non-vitamin K antagonist oral anticoagulant use in Japanese patients with atrial fibrillation: A single-center observational study.

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) show a favorable balance between efficacy and safety compared with warfarin for patients with non-valvular atrial fibrillation (NVAF). In "real-world" practice, however, NOAC adherence and persistence among patients are not clear. The aim of this study is to evaluate NOAC and warfarin persistence in Japanese patients with NVAF who newly started these drugs.

P2X7 receptor and cytokines contribute to extra-territorial facial pain.

The whisker pad area (WP) is innervated by the second branch of the trigeminal nerve and experiences allodynia and hyperalgesia following transection of the mental nerve (MN; the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain remain unclear. The ionotropic P2X(7) ATP receptor (P2X(7)) in microglia is known to potentiate, via cytokines, the perception of noxious stimuli, raising the possibility that P2X(7) and cytokines are involved in this extra-territorial pain.

P2X7 receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury.

Background: The present study directly addresses the roles of the P2X(7) receptor (P2X(7)R), an ionotropic adenosine triphosphate (ATP) receptor, and cytokines in the induction of orofacial pain following chronic constriction injury (CCI) of the infraorbital nerve (IoN).

Methods: Rats were anesthetized, and ligatures of 4-0 chromic gut were tied around the IoN. A438079, a P2X(7)R antagonist or SB203580, a phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK) inhibitor, was infused intrathecally into CCI-treated rats.

A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure.

Infusion of bone marrow-derived mononuclear cells (BMMNC) has been reported to ameliorate cardiac dysfunction after acute myocardial infarction. In this study, we investigated whether infusion of BMMNC is also effective for non-ischemic heart failure model mice and the underlying mechanisms. Intravenous infusion of BMMNC showed transient cardioprotective effects on animal models with dilated cardiomyopathy (DCM) without their engraftment in heart, suggesting that BMMNC infusion improves cardiac function via humoral factors rather than their differentiation into cardiomyocytes.

Clinical outcome in Japanese elderly patients with non-valvular atrial fibrillation taking warfarin: a single-center observational study.

Background: Although a lower target prothrombin time-international normalized ratio (PT-INR) with warfarin therapy is recommended in Japan for atrial fibrillation (AF) patients ≥70 years of age, few studies have provided supporting data. The current study aimed to evaluate the clinical outcome in elderly Japanese patients with non-valvular AF who were taking warfarin.

Methods: We conducted a cohort study of 845 consecutive non-valvular AF patients ≥70 years of age who were taking warfarin (median age, 74 years; 30.

IL-1beta in the trigeminal subnucleus caudalis contributes to extra-territorial allodynia/hyperalgesia following a trigeminal nerve injury.

It has been reported that the whisker pad (WP) area, which is innervated by the second branch of the trigeminal nerve, shows allodynia/hyperalgesia following transection of the mental nerve (MN: the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain induction still remain unclear. Glia and cytokines are known to facilitate perception of noxious input, raising a possibility that these non-neuronal elements are involved in the induction and spread of allodynia/hyperalgesia at non-injured skin territory.

Total syntheses of (-)-fructigenine A and (-)-5-N-acetylardeemin.

The first total synthesis of (-)-fructigenine A and a novel approach to (-)-5-N-acetylardeemin through a common imine intermediate (+)-3 are described. The key steps include highly enantioselective preparation of (+)-3 via domino olefination/isomerization/Claisen rearrangement (OIC) of 5, reductive cyclization (RC), and regioselective oxidation of (-)-4 and a novel assembly of the pyrazino ring of these alkaloids via Ugi three-component reaction/cyclization of (+)-3 with the corresponding amino acid and isonitrile.

Increased P-selectin expression on platelets and decreased plasma thrombomodulin in Fontan patients.

Background: Thromboembolic events account for significant morbidity and mortality after the Fontan procedure, but the underlying mechanisms remain unclear. P-selectin on platelets indicates platelet activation. Thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium.

Circulating platelet and neutrophil activation correlates with the clinical course of unstable angina.

Recent studies have suggested important roles of inflammation in the pathophysiology of unstable angina (UA). We investigated whether activation of the circulating platelets and neutrophils were implicated in inflammatory reactions associated with unstable angina Expressions of platelet P-selectin and neutrophil CD11b, and neutrophil-platelet aggregates were evaluated by flow cytometry in anticoagulated peripheral venous blood from 71 patients with UA and 22 patients with stable angina (SA). Expressions of platelet P-selectin and neutrophil CD11b, and neutrophil-platelet aggregates on the admission day were all significantly higher in 71 patients with UA than 22 with SA (median, mean fluorescence intensity [MFI]: 7.

Increases in circulating T lymphocytes expressing HLA-DR and CD40 ligand in patients with dilated cardiomyopathy.

Inflammatory and immunological mechanisms are implicated in the development of idiopathic dilated cardiomyopathy (DCM). Since activated T lymphocytes express surface HLA-DR antigens, an increased level of these cells in the circulation could indicated an ongoing immune response. While the role of activated T lymphocytes in experimental myocarditis has been elucidated, the contribution of T lymphocyte activation in clinical DCM remains unclear.

High P-selectin expression and low CD36 occupancy on circulating platelets are strong predictors of restenosis after coronary stenting in patients with coronary artery disease.

Recent studies have shown that circulating platelets play an important role in the development of restenosis early after coronary stent implantation. We investigated P-selectin expression and CD36 blockade on platelets by flow cytometry in 48 consecutive patients who underwent coronary stenting. P-selectin expression was significantly higher 1 day after stenting in patients who had restenosis (n = 15) than in those who had no restenosis (n = 28), and the odds ratio for restenosis in patients with high P-selectin levels (MFI > 6.

Increased thrombogenesity in patients with cyanotic congenital heart disease.

Background: The basic mechanisms of thromboembolism in cyanotic congenital heart disease (CCHD) have not been well clarified. P-selectin on the platelets reflects platelet activation. Thrombomodulin is a critical cofactor for thrombin-mediated activation of protein C and reflects the anticoagulant activity of the endothelium.

Intracellular localization of glycoprotein VI in human platelets and its surface expression upon activation.

Glycoprotein (GP) VI is a major receptor for collagen and belongs to the immunoglobulin super family. Here, we examined the localization of GPVI in resting and activated human platelets by immunogold scanning and transmission electron microscopy and flow cytometry. Ultrastructural observation detected immunolabelling for GPVI that was distributed uniformly over the entire surface of resting platelets, and revealed that GPVI was also localized on both the membranes of the surface-connected open canalicular system (OCS) and alpha-granules.