Synthesis and Characterization of Carbon-Bridged (1(n))(2,6)pyridinophanes.

Pyridine-containing heterophanes, which possess a rigid non-flexible framework, similar to that of porphyrin backbones, are ideal structures to probe the electronic and/or steric effects within a highly electron-rich cavity. The syntheses of heteromacrocycles incorporating the 2,6-pyridino moiety are described. 2-Bromo-6-lithiopyridine, generated from 2,6-dibromopyridine and n-butyllithium, was used to synthesize 2,6-bis (2\sp\prime-(6\sp\prime-bromopicolinoyl)) pyridine and bis-2-(6-bromopyridyl)ketone in 36% and 63% yield, respectively. Ketalization of these ketones was accomplished by either standard acidic or basic conditions. To model a nucleophilic substitution route for cyclization of the resulting ketals, lithioacetonitriles were allowed to react with bromopyridines to produce symmetrical and unsymmetrical cyanomethine adducts in more than 47% yield. Reaction of 2,6-bis- (2\sp\prime-(6\sp\prime-bromopyridyl)-1,3-dioxolan-2-yl) pyridine or 2,2-bis-2\sp\prime-(6\sp\prime-bromopyridyl)-1,3-dioxolane with lithioacetonitrile afforded (1\sb{\rm n}) (2,6)pyridinophanes (n = 3,4), in which the pyridine rings were coupled with ketal and cyanomethine functionalities. At 80\sp\circC, cyclocondensation via nucleophilic substitution favors macrocycle formation because the intermediates are held in the desired syn-conformation by a metal ion template effect. The ketal and nitrile groups of the initially generated macrocycles were hydrolyzed under acidic conditions. Hydrolysis of the nitrile was accompanied by decarboxylation to produce methylenic intermediates (143 and 152), which were oxidized with SeO\sb2 to afford the desired triketone 115 and tetraketone 125, respectively. Alternatively, oxidation of the $\alpha$,$\beta$-unsaturated nitrile tautomers with m-chloroperbenzoic acid to a keto group; followed by deketalization under acidic conditions afforded the same ketones. Triketone 115 and tetraketone 125 contain only sp\sp2 carbon atoms and should be essentially planar; however, due predominantly to N,N-electron repulsions within the confines of the cavity, deformations from planarity were observed. The dihedral angles of pyridines in triketone 115 are 35.4, 41.4, and 46.5\sp\circ, respectively. Wittig reactions and the Knoevenagel condensations on the bridging carbonyl groups in triketone 115 were unsuccessful, but facile monohemiketalization of 115 was observed. X-ray analysis of a Cu(II) complex isolated from ethanol confirmed the presence of a hemiethyl ketal (178). Upon exposure to air, precursor 143 of triketone 115 underwent oxidization to afford dimeric (1\sb3) (2,6)-pyridinophane, which was subsequently dehydrogenated with either DDQ or air. X-ray data of these dimers confirm the juxtaposition of the two electron-rich cores

Study on Awareness of Preconception Care and Reproductive Health Behaviors in Pre-honeymooners

PURPOSE: The purpose of this study was 1) to examine levels of awareness on preconception care and pregnancy, and reproductive health promoting behavior among pre-honeymooners; and 2) to explore the relationship between awareness levels of preconception care and pregnancy, and reproductive health promoting behavior. METHODS: This study was a correlation design with a total of 134 participants (67 couples of pre-honeymooners). Data were collected with questionnaire. RESULTS: Mean score of self-perception of awareness of preconception care and pregnancy was 2.82 out of 4. Content awareness level was 6.83 out of 13, and reproductive health promoting behavior score was 3.02 out of 4, indicating low to mid-level. Women reported higher scores in all variables than those in men. Self-perception awareness and content awareness of care and pregnancy had a weak positive correlation (r=.18, p=.038). Reproductive health promoting behavior was positively related to self-perception awareness of care and pregnancy (r=.33, p<.001) and content awareness of care and pregnancy (r=.23, p=.008). CONCLUSION: Based on this results, a variety of nursing intervention strategies may need to promote reproductive health behavior such as raising awareness of the preconception care and pregnancy

Early versus Late Intravitreal Triamcinolone Acetonide for Macular Edema associated with Branch Retinal Vein Occlusion

PURPOSE: To compare the effect of early versus late intravitreal injection of triamcinolone in patients with macular edema due to branch retinal vein occlusion (BRVO). METHODS: Twenty eyes of 20 patients with macular edema from BRVO, including 10 with duration after onset of or 3 months, improvements in visual acuity and foveal thickness, though apparent at 1 month, were not maintained at 3 and 6 months post-triamcinolone. CONCLUSIONS: Intravitreal triamcinolone is more effective in patients with BRVO who are treated earlier

Ubiquitin-dependent proteasomal degradation of AMPK gamma subunit by Cereblon inhibits AMPK activity

Cereblon (CRBN), a substrate receptor for Cullin-ring E3 ubiquitin ligase (CRL), is a major target protein of immunomodulatory drugs. An earlier study demonstrated that CRBN directly interacts with the catalytic α subunit of AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis, down-regulating the enzymatic activity of AMPK. However, it is not clear how CRBN modulates AMPK activity. To investigate the mechanism of CRBN-dependent AMPK inhibition, we measured protein levels of each AMPK subunit in brains, livers, lungs, hearts, spleens, skeletal muscles, testes, kidneys, and embryonic fibroblasts from wild-type and Crbn^(−/−) mice. Protein levels and stability of the regulatory AMPKγ subunit were increased in Crbn^(−/−) mice. Increased stability of AMPKγ in Crbn^(−/−) MEFs was dramatically reduced by exogenous expression of Crbn. In wild-type MEFs, the proteasomal inhibitor MG132 blocked degradation of AMPKγ. We also found that CRL4^(CRBN) directly ubiquitinated AMPKγ. Taken together, these findings suggest that CRL4^(CRBN) regulates AMPK through ubiquitin-dependent proteasomal degradation of AMPKγ

A Structural Equation Modeling on Reproductive Health Promoting Behavior of Unmarried Women: Based on the Theory of Planned Behavior

PURPOSE: The purpose of this study was to construct and test a structural equation modeling on the reproductive health behavior of single women with sexual experiences. This study employed Ajzen's Theory of Planned Behavior (TPB). METHODS: The data were collected after receipt of consent from 250 single women with sexual experiences, and analyzed using SPSS 18.0 and AMOS 18.0. RESULTS: Model fit indices for the hypothetical model were suitable for the recommended level: x²=362.407, RMR=0.065, RMSEA=0.070, GFI=0.867. TLI=0.927, CFI=0.938, IFI=0.939, and x²/dF=2.237. Intention showed direct effect with the biggest effect being on reproductive health behavior. Attitude, subjective norm and perceived behavioral control were found to have a direct effect on intention. Among them, perceived behavioral control revealed the largest influence. CONCLUSION: This study suggests that the TPB is a suitable model in explaining the reproductive health behavior of single women with sexual experience. Strategic plans for educational and intervention programs should be aimed to encourage single women to engage in reproductive health behavior