Plasminogen activator inhibitor 1 (PAI-1), an endogenous inhibitor of a major fibrinolytic factor, tissue-type plasminogen activator (tPA), can both promote and inhibit angiogenesis. The physiological role and the precise mechanisms underlying the angiogenic effects of PAI-1 remain unclear. Here we report that pharmacological inhibition of PAI-1 promoted angiogenesis and prevented tissue necrosis in a mouse model of hind limb ischemia. Improved tissue regeneration was due to an expansion of circulating and tissue-resident Gr-1(+) neutrophils, and to increased release of the angiogenic factor vascular endothelial growth factor-A (VEGF-A), the hematopoietic growth factor kit ligand, and the granulocyte colony stimulating growth factor (G-CSF). Immunohistochemical analysis indicated increased amounts of fibroblast growth factor-2 (FGF-2) in ischemic gastrocnemius muscle tissues of PAI-1 inhibitor-treated animals. Antibody neutralization and genetic knockout studies indicated that both the improved tissue regeneration, and the increase in both circulating and ischemic tissue resident Gr-1(+) neutrophils, depended on the activation of tPA and MMP-9, as well as on VEGF-A and FGF-2. These results suggest that pharmacologic PAI-1 inhibition activates the proangiogenic FGF-2 and VEGF-A pathways, which orchestrates neutrophil-driven angiogenesis and induces cell-driven revascularization, and is thus a potential therapy for ischemic diseases.

An efficient chemo-enzymatic process for construction of the α-linked disaccharide unit (GlcNAcα1-4Gal) found in gastric mucin has been developed. The process consists of a one-step preparation of a novel triazine type glycosyl donor in water and the subsequent transglycosylation to a galactose derivative catalysed by α-N-acetylglucosaminidase.

Increasing attention has been paid recently to the study of spontaneous brain activity; moreover, particular attention has been paid to the concept of a default-mode network of brain function. Although the functional significance of the default-mode network remains a matter of debate, it has been suggested to be a candidate for the network subserving basic functions related to consciousness. We report the case of a 29-year-old man with encephalopathy and a reversible lesion of the entire corpus callosum. Despite resolution of corpus callosum lesion on magnetic resonance imaging (MRI) within 1week, the patient persistently presented disturbance of consciousness. Resting-state functional MRI revealed that the posterior cingulate cortex/precuneus was functionally disconnected from other brain regions within the default-mode network. Our case report suggests that assessment of the functional connectivity in the resting-state default-mode network could be a useful marker of consciousness disturbance even in the presence of a reversible brain lesion.

PURPOSE To investigate whether interleukin 10 (IL10) gene polymorphisms are associated with the development of sarcoidosis in Japanese patients. METHODS Two hundred and eighty-eight Japanese sarcoidosis patients and 310 Japanese healthy controls were recruited. We genotyped 9 single-nucleotide polymorphisms in IL10 and assessed the allelic diversity between cases and controls. RESULTS No significant differences in the frequency of IL10 alleles, genotypes, and haplotypes in the sarcoidosis cases compared to the controls were detected. CONCLUSIONS Our results suggest that IL10 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.

(Circ J 2012; 76: 65-70).

BACKGROUND: Coronary thrombolytic therapy was first introduced for patients with acute myocardial infarction (AMI) during the early 1980s in Japan. Several modalities have been developed and primary percutaneous intervention with stent is the current preferred strategy for patients with AMI. METHODS AND RESULTS: From May 1981 to December 2010, 2782 patients with AMI underwent coronary angiography within 24h after the onset of symptoms at Hiroshima City Hospital. Patients were divided into 6 groups in chronological order. Thrombolysis was most frequently performed in the early 1980s. Balloon angioplasty became the most frequent choice in the late 1980s and angioplasty with stents in the late 1990s. Final thrombolysis in myocardial infarction-3 flow was obtained in only 39% in the early 1980s, which progressively increased to 93% in the late 2000s. In-hospital mortality was >10% in the 1980s, which decreased by half in the late 1990s. Post-infarction angina occurred in 30% in the early 1980s. It rapidly decreased, occurring in <1% in the 2000s. Reinfarction occurred in 8.8% in the late 1980s which decreased to <3% in the 2000s. The incidence of congestive heart failure remained unchanged ranging approximately from 5% to 10% until the early 2000s, which decreased to 2.8% in the late 2000s. CONCLUSION: Over the past 30 years, modality of reperfusion therapy has changed from thrombolysis to balloon angioplasty and further to angioplasty with stents. As the reperfusion rate increased, in-hospital outcomes after AMI have improved.

Here we demonstrate a facile approach to grow uniform and large area single layer graphene directly over polycrystalline metal foil from fullerene, where fullerene molecules formed rod-like polycrystals in the toluene solvent. The generated pressure on sandwich structures has enhanced the density (scalable) as well as quality of graphene at partially low temperatures.

Acute hyperglycemia is a common feature during the early phase after acute myocardial infarction (AMI), regardless of diabetes status. Numerous studies have demonstrated that patients with AMI and hyperglycemia on admission have high rates of mortality. It has been reported that there is a linear positive relation between admission blood glucose levels and mortality after AMI. However, recent studies showed that the relationship is U-shaped in patients with a history of diabetes. Diabetic patients with moderate hyperglycemia (glucose 9-11 mmol/L) had the lowest mortality and not only severe hyperglycemia (glucose ≥ 11 mmol/L) but also euglycemia (glucose < 7 mmol/L) was associated with higher mortality. Although it has been debated whether acute hyperglycemia is causally related to adverse outcomes after AMI or is simply an epiphenomenon of severely damaged myocardium, multiple physiological studies have demonstrated that hyperglycemia has a direct detrimental effect on ischemic myocardium through several mechanisms, including oxidative stress, inflammation, apoptosis, endothelial dysfunction, hypercoagulation, platelet aggregation and impairment of ischemic preconditioning. Current guidelines recommend the use of an insulin-based regimen to achieve and maintain glucose levels < 10.0 mmol/dl, and emphasize the avoidance of hypoglycemia. However, the optimal management goal of glucose levels for patients with acute hyperglycemia remains uncertain. Further studies are warranted into the appropriate management in patients with AMI and acute hyperglycemia.

Flow coefficients v_{n} for n=2, 3, 4, characterizing the anisotropic collective flow in Au+Au collisions at sqrt[s_{NN}]=200  GeV, are measured relative to event planes Ψ_{n}, determined at large rapidity. We report v_{n} as a function of transverse momentum and collision centrality, and study the correlations among the event planes of different order n. The v_{n} are well described by hydrodynamic models which employ a Glauber Monte Carlo initial state geometry with fluctuations, providing additional constraining power on the interplay between initial conditions and the effects of viscosity as the system evolves. This new constraint can serve to improve the precision of the extracted shear viscosity to entropy density ratio η/s.