Structural analysis of interpenetrated methyl-modified MOF-5 and its gas-adsorption properties.

The first example of an interpenetrated methyl-modified MOF-5 with the formula ZnO(DMBDC)(DMF), where DMBDC is 2,5-dimethylbenzene-1,4-dicarboxylate and DMF is N,N-dimethylformamide (henceforth denoted as MeMOF-5-int), namely, poly[tris(μ-2,5-dimethylbenzene-1,4-dicarboxylato)bis(N,N-dimethylformamide)-μ-oxido-tetrazinc(II)], [Zn(CHO)O(CHNO)], has been obtained from a solvothermal synthesis of 2,5-dimethylbenzene-1,4-dicarboxylic acid and Zn(NO)·6HO in DMF. A systematic study revealed that the choice of solvent is of critical importance for the synthesis of phase-pure MeMOF-5-int, which was thoroughly characterized by single-crystal and powder X-ray diffraction (PXRD), as well as by gas-adsorption analyses. The Brunauer-Emmett-Teller surface area of MeMOF-5-int (660 m g), determined by N adsorption, is much lower than that of nonpenetrated MeMOF-5 (2420 m g).

Structural analysis of and selective CO adsorption in mixed-ligand hydroxamate-based metal-organic frameworks.

Two mixed-ligand metal-organic frameworks, [Zn(BDHA)(INA)] (MOF-1: HBDHA = benzene-1,4-dihydroxamic acid; HINA = isonicotinic acid) and [Co(BDHA)(INA)(DMF)] (MOF-2), were solvothermally synthesized and fully characterized by single-crystal X-ray crystallography as well as N, H, and CO gas-sorption measurements. The results constitute the first detailed analysis of the bonding environment around the hydroxamates in such MOFs, which are simultaneously decorated with Lewis-basic sites from the hydroxamate moieties and metal sites predisposed for coordinative unsaturation. MOF-2 shows a desirably selective adsorption of CO relative to N.

Efficacy of Complex Fractionated Atrial Electrogram-Guided Extensive Encircling Pulmonary Vein Isolation for Persistent Atrial Fibrillation.

In persistent AF, the effect of adjunctive ablation in addition to PV isolation (PVI) is controversial. We considered a new modified PVI including complex fractionated atrial electrogram (CFAE) area. In 57 patients with persistent AF undergoing first ablation, CFAE were mapped before ablation and CFAE-guided extensive encircling PVI (CFAE-guided EEPVI) was performed.

The ReACT Trial: Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial.

Objectives: The purpose of this study was to evaluate long-term clinical impact of routine follow-up coronary angiography (FUCAG) after percutaneous coronary intervention (PCI) in daily clinical practice in Japan.

Background: The long-term clinical impact of routine FUCAG after PCI in real-world clinical practice has not been evaluated adequately.

Methods: In this prospective, multicenter, open-label, randomized trial, patients who underwent successful PCI were randomly assigned to routine angiographic follow-up (AF) group, in which patients were to receive FUCAG at 8 to 12 months after PCI, or clinical follow-up alone (CF) group.

Impact of NAD(P)H oxidase-derived reactive oxygen species on coronary arterial remodeling: a comparative intravascular ultrasound and histochemical analysis of atherosclerotic lesions.

Background: Coronary arterial remodeling, which is a response to the growth of atherosclerotic plaques, is associated with plaque vulnerability. Oxidative stress induced by reactive oxygen species (ROS) via NAD(P)H oxidase in the vasculature also plays a crucial role in the pathogenesis of atherosclerosis-based cardiovascular disease. In this study, the relationship between coronary arterial remodeling and ROS generation was examined by comparing preinterventional intravascular ultrasound findings of atherosclerotic lesions to the histochemical findings of corresponding specimens obtained by directional coronary atherectomy.

Effect of culprit-lesion remodeling versus plaque rupture on three-year outcome in patients with acute coronary syndrome.

To investigate intravascular ultrasound predictors of long-term clinical outcome in patients with acute coronary syndrome, 94 patients with a first acute coronary syndrome with both preintervention intravascular ultrasound imaging and long-term follow-up were enrolled in this study. Remodeling index was defined as external elastic membrane cross-sectional area at the target lesion divided by that at the proximal reference. Arterial remodeling was defined as either positive (PR: remodeling index >1.

Phosphorylation of protein phosphatase 2Czeta by c-Jun NH2-terminal kinase at Ser92 attenuates its phosphatase activity.

The protein phosphatase 2C (PP2C) family represents one of the four major protein Ser/Thr phosphatase activities in mammalian cells and contains at least 13 distinct gene products. Although PP2C family members regulate a variety of cellular functions, mechanisms of regulation of their activities are largely unknown. Here, we show that PP2Czeta, a PP2C family member that is enriched in testicular germ cells, is phosphorylated by c-Jun NH 2-terminal kinase (JNK) but not by p38 in vitro.

Regulation of apoptosis signal-regulating kinase 1 by protein phosphatase 2Cepsilon.

ASK1 (apoptosis signal-regulating kinase 1), a MKKK (mitogen-activated protein kinase kinase kinase), is activated in response to cytotoxic stresses, such as H2O2 and TNFalpha (tumour necrosis factor alpha). ASK1 induction initiates a signalling cascade leading to apoptosis. After exposure of cells to H2O2, ASK1 is transiently activated by autophosphorylation at Thr845.

Impact of cutting balloon angioplasty (CBA) prior to bare metal stenting on restenosis.

Background: While stent restenosis and late thrombosis still occur even with drug-eluting-stents (DES), there remains a need to explore other strategies for preventing restenosis.

Methods And Results: Five hundred and twenty-one patients were randomized: 260 to cutting-balloon angioplasty (CBA) before bare-metal stent (CBA-BMS) and 261 to balloon-angioplasty (BA) before BMS (BA-BMS). Intravascular ultrasound (IVUS)-guided procedures were performed in 279 (54%) patients and angiographic guidance was used in the remainder.

PP2C family members play key roles in regulation of cell survival and apoptosis.

Although unlimited proliferation of cancer cells is supported by multiple signaling pathways involved in the regulation of proliferation, survival, and apoptosis, the molecular mechanisms coordinating these different pathways to promote the proliferation and survival of cancer cells have remained unclear. SAPK and integrin-ILK signaling pathways play key roles in the promotion of apoptosis and cell proliferation/survival, respectively. Studies of TNFalpha- and H2O2-induced apoptosis revealed that ASK1, a component of the SAPK system, mediates the TNFalpha and H2O2 signaling of apoptosis.

[Repeated percutaneous transluminal septal myocardial ablation leads to reduction of left ventricular outflow-tract pressure gradient in hypertrophic obstructive cardiomyopathy: a case report].

A 61-year-old man with hypertrophic obstructive cardiomyopathy was treated twice with percutaneous transluminal septal myocardial ablation (PTSMA). The first procedure improved the left ventricular outflow tract pressure gradient (LVOTG) from 148 to 48 mmHg and the New York Heart Association (NYHA) class from III to II in a week. However, the LVOTG increased to 197 mmHg and the NYHA class worsened to III within 3 months.

Procedural implications of intravascular ultrasound morphologic features of chronic total coronary occlusions.

Although the success rates of percutaneous coronary intervention of chronic total occlusions (CTOs) have improved, morphologic features are not well known. We analyzed experience at 4 centers where intravascular ultrasound (IVUS) was performed in 67 native artery CTO lesions (mean CTO duration 6.3 months) just after the lesion was crossed with a guidewire (n = 7) or after dilatation with a 1.

Soluble CD40 ligand and interleukin-6 in the coronary circulation after acute myocardial infarction.

Background: Inflammation, operated by blood, vascular and immune cells interaction, is implicated in plaque disruption and CD40 ligand (CD40L) was identified on activated T cells and platelets. We sought to investigate the roles of local inflammation in acute myocardial infarction (AMI).

Methods: Coronary sinus (CS) and arterial (A) levels of interleukin (IL)-6 and soluble CD40L (sCD40L) and matrix metalloproteinase (MMP)-9 activity in serial blood samples obtained until 48 h after percutaneous coronary intervention (PCI) were determined.

[Impact of metabolic syndrome and diabetes mellitus on cardiovascular events in coronary artery disease without ischemia on stress thallium-201 single photon emission computed tomography after percutaneous coronary intervention].

Objectives: The metabolic syndrome defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) is a predictor of cardiovascular events. However, the significance of metabolic syndrome for cardiovascular events has been not clarified in Japan. The impact of metabolic syndrome and diabetes mellitus on cardiovascular events was investigated, especially in the high risk group after percutaneous coronary intervention.

Possible role of brain-derived neurotrophic factor in the pathogenesis of coronary artery disease.

Background: The neurotrophin (NT) family, including nerve growth factor NT-3 and brain-derived neurotrophic factor (BDNF), has a critical role in the survival, growth, maintenance, and death of central and peripheral neurons. NTs and their receptors are expressed in atherosclerotic lesions; however, their significance in cardiovascular disease remains unclear.

Methods And Results: To clarify the role of NTs in the pathogenesis of coronary artery disease, NT plasma levels in the aorta, coronary sinus, and peripheral veins of patients with unstable angina (n=38), stable effort angina (n=45), and non-coronary artery disease (n=24) were examined.

Enantiomer ratio of MK-0767 in humans and nonclinical species.

MK-0767, (+/-)-5-[(2,4-dioxothiazolidin-5-yl)methyl]-2-methoxy-N-[[(4-trifluoromethyl)phenyl]methyl]benzamide, is a thiazolidinedione-containing dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist that has been studied as a potential treatment for patients with type 2 diabetes. MK-0767 contains a chiral center at the C-5 position of the thiazolidinedione ring and was being developed as the racemate, due to the rapid interconversion of its enantiomers in biological samples. In the present work the in vitro and in vivo concentration ratios of the (+)-(R) to (-)-(S) enantiomers of MK-0767 were determined in plasma from humans (in vitro only) and nonclinical species used in the toxicological evaluation of rac-MK-0767, namely CD-1 mice, Sprague-Dawley rats, beagle dogs, New Zealand white rabbits, and rhesus monkeys.

In vitro metabolism of MK-0767 [(+/-)-5-[(2,4-dioxothiazolidin-5-yl)methyl]-2-methoxy-N-[[(4-trifluoromethyl) phenyl]methyl]benzamide], a peroxisome proliferator-activated receptor alpha/gamma agonist. I. Role of cytochrome P450, methyltransferases, flavin monooxygenases, and esterases.

The metabolism of MK-0767, (+/-)-5-[(2,4-dioxothiazolidin-5-yl)methyl]-2-methoxy-N-[[(4-trifluoromethyl) phenyl]methyl]benzamide, a thiazolidinedione (TZD)-containing peroxisome proliferator-activated receptor alpha/gamma agonist, was studied in liver microsomes and hepatocytes from humans and rat, dog, and rhesus monkey, to characterize the enzyme(s) involved in its metabolism. The major site of metabolism is the TZD ring, which underwent opening catalyzed by CYP3A4 to give the mercapto derivative, M22. Other metabolites formed in NADPH-fortified liver microsomes included the TZD-5-OH derivative (M24), also catalyzed by CYP3A4, and the O-desmethyl derivative (M28), whose formation was catalyzed by CYP2C9 and CYP2C19.

Interaction of oxidative stress and inflammatory response in coronary plaque instability: important role of C-reactive protein.

Objective: C-reactive protein (CRP), a predictor of cardiovascular events, localizes in atherosclerotic arteries and exerts proinflammatory effects on vascular cells. Reactive oxygen species (ROS) have been implicated in atherogenesis and plaque instability.

Methods And Results: Expressional pattern of CRP in directional coronary atherectomy specimens from 39 patients was examined.

Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris: important role of NAD(P)H oxidase.

Objective: NADH/NADPH oxidase is an important source of reactive oxygen species (ROS) in the vasculature. Recently, we demonstrated that p22(phox), an essential component of this oxidase, was expressed in human coronary arteries and that its expression was enhanced with the progression of atherosclerosis. The present study was undertaken to investigate its functional importance in the pathogenesis of coronary artery disease.

Enantio-dependent binding and transactivation of optically active phenylpropanoic acid derivatives at human peroxisome proliferator-activated receptor alpha.

Optically active phenylpropanoic acid derivatives [(S)-5, and (R)-5] were prepared, and their affinities for peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma were evaluated. Binding assay and cell-based reporter assay indicated that the activity of these compounds is enantio-dependent, and resides exclusively on the (S)-isomer.

Design, synthesis and evaluation of substituted phenylpropanoic acid derivatives as peroxisome proliferator-activated receptor (PPAR) activators: novel human PPARalpha-selective activators.

A series of substituted phenylpropanoic acid derivatives was prepared as part of a search for subtype-selective human peroxisome proliferator-activated receptor (PPAR) activators. Structure-activity relationship studies indicated that the substituent at the alpha-position of the carboxyl group plays a key role in determining the potency and the selectivity for PPAR transactivation.