Cardiac Malignant Lymphoma with Diffuse Extension to the Left Ventricle: A Case Report.

Malignant cardiac lymphoma is rare and commonly involves nodules on the right side of the heart. We herein report a case of malignant cardiac lymphoma with diffuse extension into the left ventricle. The patient was a woman in her 60s who complained of dyspnea and malaise.

Infectious Pulmonary Artery Pseudoaneurysm Secondary to a Lung Abscess Treated With Pulmonary Artery Coil Embolization: A Case Report.

Pulmonary artery pseudoaneurysms (PAPs) are uncommon, yet they frequently result in hemoptysis and are associated with a poor prognosis. We report a case of an 87-year-old male patient. Initially, he was admitted to a previous hospital, and diagnosed with a lung abscess in the left lower lobe.

Impact of pemafibrate on lipid profile and insulin resistance in hypertriglyceridemic patients with coronary artery disease and metabolic syndrome.

This study examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α agonist, on the serum biochemical parameters of male patients with coronary artery disease and metabolic syndrome (MetS). This was a post hoc analysis of a randomized, crossover study that treated hypertriglyceridemia with pemafibrate or bezafibrate for 24 weeks, followed by a crossover of another 24 weeks. Of the 60 patients enrolled in the study, 55 were male.

Discovery of a Novel Series of Potent, Selective, Orally Available, and Brain-Penetrable C1s Inhibitors for Modulation of the Complement Pathway.

A novel series of non-amidine-based C1s inhibitors have been explored. Starting from high-throughput screening hit , isoquinoline was replaced with 1-aminophthalazine to enhance C1s inhibitory activity while exhibiting good selectivity against other serine proteases. We first disclose a crystal structure of a complex of C1s and a small-molecule inhibitor (), which guided structure-based optimization around the S2 and S3 sites to further enhance C1s inhibitory activity by over 300-fold.

Effects of switching from sacubitril/valsartan to valsartan alone on plasma levels of natriuretic peptides and myocardial remodeling in heart failure with reduced ejection fraction.

Background: We examined the effect of switching from angiotensin receptor-neprilysin inhibitor (ARNI) to angiotensin-receptor blocker (ARB) on plasma levels of natriuretic peptides and myocardial remodeling.

Methods: This is a prospective study that included 11 patients with heart failure (HF) treated with ARNI. The patients were divided into two groups: 5 patients who continued treatment with sacubitril/valsartan 194/206 mg/day (ARNI-continue group) and 6 patients who were switched to valsartan 160 mg/day (ARB-switch group).

Structure-Activity Relationship Studies of Antimalarial Proteasome Inhibitors─Part II.

With increasing reports of resistance to artemisinins and artemisinin-combination therapies, targeting the proteasome is a promising strategy for antimalarial development. We recently reported a highly selective proteasome inhibitor with anti-malarial activity in the humanized mouse model. To balance the permeability of the series of macrocycles with other drug-like properties, we conducted further structure-activity relationship studies on a biphenyl ether-tethered macrocyclic scaffold.

Efficacy and Safety of Pemafibrate Versus Bezafibrate to Treat Patients with Hypertriglyceridemia: A Randomized Crossover Study.

Aim: Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor (PPAR)-α, a key regulator of lipid and glucose metabolism. We compared the efficacy and safety of pemafibrate with those of bezafibrate, a nonselective PPAR-α agonist.

Methods: In this randomized crossover study, 60 patients with hypertriglyceridemia (fasting triglyceride [TG] ≥ 150 mg/dL) were treated with pemafibrate of 0.

Design, Synthesis, and Optimization of Macrocyclic Peptides as Species-Selective Antimalaria Proteasome Inhibitors.

With over 200 million cases and close to half a million deaths each year, malaria is a threat to global health, particularly in developing countries. , the parasite that causes the most severe form of the disease, has developed resistance to all antimalarial drugs. Resistance to the first-line antimalarial artemisinin and to artemisinin combination therapies is widespread in Southeast Asia and is emerging in sub-Saharan Africa.

A case of hyperlipoprotein(a)emia undergoing catheter interventions for coronary artery disease, aortic valve stenosis, and peripheral artery disease.

A 79-year-old woman was admitted to our hospital for ischemic necrosis of the right first toe. During having normal lipid profiles, such as low-density lipoprotein cholesterol and triglyceride, plasma levels of lipoprotein(a) (Lp(a)] were abnormally high (141 mg/dL). She had a history of heart failure (HF) due to aortic valve stenosis (AS) and drug-eluting coronary stenting due to angina pectoris.

Transradial peripheral vascular intervention using Fowler's position and Terumo R2P system for patients with heart failure: two case reports.

Background: Positioning a patient on the catheterization table is important for proper cardiac or respiratory function during peripheral vascular interventions. Fowler's position, where the patient's head is a 45° angle, is more effective in reducing venous blood volume returning to the heart from the periphery compared with the supine position. The Terumo R2P system has been developed for transradial peripheral vascular interventions.

Macrocyclic Peptides that Selectively Inhibit the Proteasome.

Treatment of tuberculosis (TB) currently takes at least 6 months. Latent (Mtb) is phenotypically tolerant to most anti-TB drugs. A key hypothesis is that drugs that kill nonreplicating (NR) Mtb may shorten treatment when used in combination with conventional drugs.

Development of a Highly Selective Plasmodium falciparum Proteasome Inhibitor with Anti-malaria Activity in Humanized Mice.

Plasmodium falciparum proteasome (Pf20S) inhibitors are active against Plasmodium at multiple stages-erythrocytic, gametocyte, liver, and gamete activation stages-indicating that selective Pf20S inhibitors possess the potential to be therapeutic, prophylactic, and transmission-blocking antimalarials. Starting from a reported compound, we developed a noncovalent, macrocyclic peptide inhibitor of the malarial proteasome with high species selectivity and improved pharmacokinetic properties. The compound demonstrates specific, time-dependent inhibition of the β5 subunit of the Pf20S, kills artemisinin-sensitive and artemisinin-resistant P.

Plasma kinetics of mature PCSK9, furin-cleaved PCSK9, and Lp(a) with or without administration of PCSK9 inhibitors in acute myocardial infarction.

Background: There are two types of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9), mature and furin-cleaved. Most types of lipoprotein(a) [Lp(a)], an independent risk factor of cardiovascular events, bind to mature PCSK9.

Objective: This study examined the effects of monoclonal anti-PCSK9 antibody on plasma PCSK9 and Lp(a) levels in acute myocardial infarction (MI).

Clinical characteristics and prognostic factors in elderly patients with chronic heart failure -A report from the CHART-2 study.

Background: Since most of the randomized clinical trials for heart failure (HF) were designed to exclude elderly patients, limited data are available on their clinical characteristics, prognosis, and prognostic factors.

Methods: We compared clinical characteristics, prognosis, and prognostic factors among Stage C/D HF patients in our CHART-2 Study (N = 4876, mean 69 years, women 32%, 6.3-year follow-up) by age (G1, ≤64 years, N = 1521; G2, 65-74 years, N = 1510; and G3, ≥75 years, N = 1845).

Inhibition of MGAT2 modulates fat-induced gut peptide release and fat intake in normal mice and ameliorates obesity and diabetes in ob/ob mice fed on a high-fat diet.

Monoacylglycerol O-acyltransferase 2 (MGAT2) is one of the key enzymes responsible for triglyceride (TG) re-synthesis in the small intestine. We have previously demonstrated that pharmacological inhibition of MGAT2 has beneficial effects on obesity and metabolic disorders in mice. Here, we further investigate the effects of MGAT2 inhibition on (a) fat-induced gut peptide release and fat intake in normal mice and (b) metabolic disorders in high-fat diet (HFD)-fed ob/ob mice, a model of severe obesity and type 2 diabetes mellitus, using an orally bioavailable MGAT2 inhibitor Compound B (CpdB).

Decline of popliteal artery flow-mediated dilation with aging and possible involvement of asymmetric dimethylarginine in healthy men.

Purpose: We examined the influences of age and gender on flow-mediated endothelial function and the involvement of the competitive inhibition of L-arginine in endothelial function.

Methods: We measured brachial and popliteal flow-mediated vasodilation (FMD) responses, nitrate/nitrite (NOx) concentrations, and plasma levels of asymmetric dimethylarginine (ADMA) in four healthy, nonsmoking groups: young men (mean 26 ± 2 years, n = 17), middle-aged men (mean 50 ± 3 years, n = 19), young women (mean 27 ± 2 years, n = 16), and middle-aged women (mean 51 ± 2 years, n = 18).

Results: In young men, we found no significant differences between brachial and popliteal artery FMDs (10.

Impact of decreased insulin resistance by ezetimibe on postprandial lipid profiles and endothelial functions in obese, non-diabetic-metabolic syndrome patients with coronary artery disease.

The association between insulin resistance and lipid dysmetabolism after consuming a meal is unclear. We aimed at assessing the effects of ezetimibe on postprandial hyperlipidemia and hyperinsulinemia and to find out whether the medication improves endothelial function in obese metabolic syndrome (MetS) patients with coronary artery disease (CAD). We obtained oral fat loading test results (4 and 6 h after load) and brachial flow-mediated vasodilation (FMD) measurements before and 24 weeks after ezetimibe treatment initiation from 27 MetS patients with CAD and from 68 control patients with CAD alone.

Androgen induced cellular proliferation, neurogenesis, and generation of GnRH3 neurons in the brain of mature female Mozambique tilapia.

The neuroplastic mechanisms in the fish brain that underlie sex reversal remain unknown. Gonadotropin-releasing hormone 3 (GnRH3) neurons control male reproductive behaviours in Mozambique tilapia and show sexual dimorphism, with males having a greater number of GnRH3 neurons. Treatment with androgens such as 11-ketotestosterone (KT), but not 17β-estradiol, increases the number of GnRH3 neurons in mature females to a level similar to that observed in mature males.

Antimalarial proteasome inhibitor reveals collateral sensitivity from intersubunit interactions and fitness cost of resistance.

We describe noncovalent, reversible asparagine ethylenediamine (AsnEDA) inhibitors of the proteasome (Pf20S) β5 subunit that spare all active subunits of human constitutive and immuno-proteasomes. The compounds are active against erythrocytic, sexual, and liver-stage parasites, against parasites resistant to current antimalarials, and against strains from patients in Africa. The β5 inhibitors synergize with a β2 inhibitor in vitro and in mice and with artemisinin.