Plasma B-type Natriuretic Peptide as a Predictor of Cardiovascular Events in Subjects with Atrial Fibrillation: A Community-Based Study

Objectives

Atrial fibrillation (AF) is a significant public health issue due to its high prevalence in the general population, and is associated with an increased risk of cardiovascular (CV) events including systemic thrombo-embolism, heart failure, and coronary artery disease. The relationship between plasma B-type natriuretic peptide (BNP) and CV risk in real world AF subjects remains unknown.

Methods

The subject of the study (n = 228; mean age = 69 years) was unselected individuals with AF in a community-based population (n = 15,394; AF prevalence rate = 1.5%). The CV event free rate within each BNP tertile was estimated, and Cox regression analysis was performed to examine the relative risk of the onset of CV events among the tertiles. The prognostic ability of BNP was compared to an established risk score for embolic events (CHADS2 score). In addition, to determine the usefulness of BNP as a predictor in addition to CHADS2 score, we calculated Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) indices.

Results

During the follow-up period 58 subjects experienced CV events (52 per 1,000 person-years). The event-free ratio was significantly lower in the highest tertile (p < 0.02). After adjustment for established CV risk factors, the hazard ratio (HR) of the highest tertile was significantly higher than that of the lowest tertile (HR = 2.38; p < 0.02). The predictive abilities of plasma BNP in terms of sensitivity and specificity for general CV events were comparable to those of CHADS2 score. Adding BNP to the CHADS2 score only model improved the NRI (0.319; p < 0.05) and the IDI (0.046; p < 0.05).

Conclusion

Plasma BNP is a valuable biomarker both singly or in combination with an established scoring system for assessing general CV risk including stroke, heart failure and acute coronary syndrome in real-world AF subjects.     

Distribution and development of P2Y1-purinoceptors in the mouse retina

There is increasing evidence that ATP acts on purinergic receptors and mediates synaptic transmission in the retina. In a previous study, we raised the possibility that P2X-purinoceptors, presumably P2X₂-purinoceptors in OFF-cholinergic amacrine cells, play a key role in the formation of OFF pathway-specific modulation. In this study, we examined whether the P2Y₁-purinoceptors can function in cholinergic amacrine cells in the mouse retina since cholinergic amacrine cells in the rat retina express P2Y₁-purinoceptors. P2Y₁-purinoceptors were shown to be expressed in dendrites of both ON- and OFF-cholinergic amacrine cells in adults. At postnatal day 7, there was immunoreactivity for P2Y₁-purinoceptors in the soma of cholinergic amacrine cells. At postnatal day 14, weak immunoreactivity for P2Y₁-purinoceptors was detected in the dendrites but not in the soma of cholinergic amacrine cells. At postnatal day 21, strong immunoreactivity for P2Y₁-purinoceptors was detected in dendrites of cholinergic amacrine cells. The expression pattern of P2Y₁-purinoceptors was not affected by visual experience. We concluded that P2Y₁-purinoceptors are not involved in the OFF-pathway-specific signal transmission in cholinergic amacrine cells of the mouse retina.     

Flavonoids isolated from the leaves of Melicope triphylla and their extracellular-superoxide dismutase-inducing activity

Two novel flavonoids, named meliflavones A (1) and B (2), were isolated from the leaves of Melicope triphylla (Lam.) Merr., along with thirteen known compounds (3–15). Four of the polymethoxyflavonoids bearing a prenyloxy (3-methylbut-2-enyloxy) function (1, 3–5) induced the expression of extracellular-superoxide dismutase (EC-SOD) in a human leukemic U937 cell-based assay.     

Novel isolation of resveratrol dimer O-glucosides with enantiomeric aglycones from the leaves of Shorea cordifolia

Two O-glucosides of resveratrol dimers, ampelopsin F-11b-O-β-glucopyranosides with enantiomeric aglycones [cordifoloside A (1) and cordifoloside B (2)] and an enantiomer of the aglycone [(?)-ampelopsin F] were isolated from the leaves of Shorea cordifolia (Dipterocarpaceae). These structures were identified on the basis of spectroscopic evidence and their absolute configurations were elucidated using circular dichroism data. This is the first report on oligostilbenoids that demonstrates the co-occurrence of diastereomeric O-glucosides with enantiomeric aglycones in this family.     

The Flavonoid Apigenin Downregulates CDK1 by Directly Targeting Ribosomal Protein S9

Flavonoids have been reported to inhibit tumor growth by causing cell cycle arrest. However, little is known about the direct targets of flavonoids in tumor growth inhibition. In the present study, we developed a novel method using magnetic FG beads to purify flavonoid-binding proteins, and identified ribosomal protein S9 (RPS9) as a binding partner of the flavonoid apigenin. Similar to treatment with apigenin, knockdown of RPS9 inhibited the growth of human colon cancer cells at the G2/M phase by downregulating cyclin-dependent kinase 1 (CDK1) expression at the promoter level. Furthermore, knockdown of RPS9 suppressed G2/M arrest caused by apigenin. These results suggest that apigenin induces G2/M arrest at least partially by directly binding and inhibiting RPS9 which enhances CDK1 expression. We therefore raise the possibility that identification of the direct targets of flavonoids may contribute to the discovery of novel molecular mechanisms governing tumor growth.     

Identification of the Argentine ant Linepithema humile (Hymenoptera: Formicidae) using an artificially synthesized trail pheromone and its effects on native Japanese ants

Applied Entomology and Zoology - Invasion by the Argentine ant Linepithema humile (Mayr) (Hymenoptera: Formicidae) causes the collapse of global ecosystems. Attempts to exterminate this invasive...     

The introduction to Japan of the Titan barnacle,Megabalanus coccopoma (Darwin, 1854) (Cirripedia: Balanomorpha) and the role of shipping in its translocation

The Titan Acorn barnacle, Megabalanus coccopoma, a native of the tropical eastern Pacific, has become established in the western Atlantic (Brazil and the northern Gulf of Mexico to the Carolinas), northwestern Europe and the western Indian Ocean (Mauritius), and therefore its dispersal capabilities are well known. This study reports its introduction to Japan and confirms its occurrence in Australia. In an attempt to determine the source of this introduction, phylogeographic techniques, involving cytochrome c oxidase I sequences of various widely separate populations of M. rosa and M. volcano, were utilized. No significant genetic differentiation or haplotype patterns between widely separated populations of each of the three species were found. Lack of such differentiation indicates recent geographical isolation and thus negates a null hypothesis predicting that the occurrence of one of more of these species in Australia was natural.     

Probability in biology: Overview of a comprehensive theory of probability in living systems

Probability is closely related to biological organization and adaptation to the environment. Living systems need to maintain their organizational order by producing specific internal events non-randomly, and must cope with the uncertain environments. These processes involve increases in the probability of favorable events for these systems by reducing the degree of uncertainty of events. Systems with this ability will survive and reproduce more than those that have less of this ability. Probabilistic phenomena have been deeply explored using the mathematical theory of probability since Kolmogorov's axiomatization provided mathematical consistency for the theory. However, the interpretation of the concept of probability remains both unresolved and controversial, which creates problems when the mathematical theory is applied to problems in real systems. In this article, recent advances in the study of the foundations of probability from a biological viewpoint are reviewed, and a new perspective is discussed toward a comprehensive theory of probability for understanding the organization and adaptation of living systems.     

Denitrification in soil amended with thermophile-fermented compost suppresses nitrate accumulation in plants

NO ₃ ^? is a major nitrogen source for plant nutrition, and plant cells store NO ₃ ^? in their vacuoles. Here, we report that a unique compost made from marine animal resources by thermophiles represses NO ₃ ^? accumulation in plants. A decrease in the leaf NO ₃ ^? content occurred in parallel with a decrease in the soil NO ₃ ^? level, and the degree of the soil NO ₃ ^? decrease was proportional to the compost concentration in the soil. The compost-induced reduction of the soil NO ₃ ^? level was blocked by incubation with chloramphenicol, indicating that the soil NO ₃ ^? was reduced by chloramphenicol-sensitive microbes. The compost-induced denitrification activity was assessed by the acetylene block method. To eliminate denitrification by the soil bacterial habitants, soil was sterilized with γ irradiation and then compost was amended. After the 24-h incubation, the N₂O level in the compost soil with presence of acetylene was approximately fourfold higher than that in the compost soil with absence of acetylene. These results indicate that the low NO ₃ ^? levels that are often found in the leaves of organic vegetables can be explained by compost-mediated denitrification in the soil.     

A novel,potent, and orally active VLA-4 antagonist with good aqueous solubility: trans-4-[1-[[2-(5-Fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl]acetyl]-(5S)-[methoxy(methyl)amino]methyl-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid

We have carried out the optimization of substituents at the C-3 or the C-5 position on the pyrrolidine ring of VLA-4 antagonist 3 with 2-(phenylamino)-7-fluorobenzoxazolyl moiety for the purpose of improving in vivo efficacy while maintaining good aqueous solubility. As a result, we successfully increased in vitro activity in the presence of 3% human serum albumin and achieved an exquisite lipophilic and hydrophilic balance of compounds suitable for oral administrative regimen. The modification resulted in the identification of zwitterionic compound 7n with (5S)-[methoxy(methyl)amino]methylpyrrolidine, which significantly alleviated bronchial hyper-responsiveness to acetylcholine chloride at 12.5 mg/kg, p.o. in a murine asthma model and showed favorable aqueous solubility (JP1, 89 μg/mL; JP2, 462 μg/mL). Furthermore, this compound showed good oral bioavailability (F = 54%) in monkeys.