Mechanochemical ring-opening metathesis polymerization: development, scope, and mechano-exclusive polymer synthesis.

Ruthenium-alkylidene initiated ring-opening metathesis polymerization has been realized under solid-state conditions by employing a mechanochemical ball milling method. This method promotes greenness and broadens the scope to include mechano-exclusive products. The carbene- and pyridine-based Grubbs 3rd-generation complex outperformed other catalysts and maintained similar mechanistic features of solution-phase reactions. High-speed ball milling provides sufficient mixing and energy to the solid reaction mixture, which is composed of an initiator and monomers, to minimize or eliminate the use of solvents. Therefore, the solubility and miscibility of monomers and Ru-initiators are not limiting factors in solid-state ball milling. A wide variety of solid monomers, including ionomers, fluorous monomers, and macromonomers, were successfully polymerized under ball milling conditions. Importantly, direct copolymerization of immiscible (ionic/hydrophobic) monomers exemplifies the synthesis of mechano-exclusive polymers that are difficult to make using traditional solution procedures. Finally, the addition of a small amount of a liquid additive (i.e., liquid-assisted grinding) minimized chain-degradation, enabling high-molecular-weight polymer synthesis.

Chemical Upcycling of Waste Poly(bisphenol A carbonate) to 1,4,2-Dioxazol-5-ones and One-Pot C-H Amidation.

Chemical upcycling of poly(bisphenol A carbonate) (PC) was achieved in this study with hydroxamic acid nucleophiles, giving rise to synthetically valuable 1,4,2-dioxazol-5-ones and bisphenol A. Using 1,5,7-triazabicyclo[4.4.0]-dec-5-ene (TBD), non-green carbodiimidazole or phosgene carbonylation agents used in conventional dioxazolone synthesis were successfully replaced with PC, and environmentally harmful bisphenol A was simultaneously recovered. Assorted hydroxamic acids exhibited good-to-excellent efficiencies and green chemical features, promising broad synthetic application scope. In addition, a green aryl amide synthesis process was developed, involving one-pot depolymerization from polycarbonate to dioxazolone followed by rhodium-catalyzed C-H amidation, including gram-scale examples with used compact discs.

Availability of preoperative systemic steroids on endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis.

PURPOSE: To analyze the outcome of endoscopic sinus surgery (ESS) after preoperative systemic steroid (PSS) treatment for chronic rhinosinusitis (CRS) with nasal polyposis (NP) and to investigate and compare clinicopathological factors associated with the outcome. MATERIALS AND METHODS: We performed a retrospective chart review of 468 patients with CRS with NP who underwent primary ESS between January 2005 and October 2011. 124 patients who met the inclusion criteria were included. Beginning from 2008, our clinic administered steroid preoperatively in patients of CRS with NP, thus there were 84 patients with preoperative systemic steroid (PSS group) and another 40 patients without such regimen (no PSS group). To evaluate the outcome after ESS, poor outcome and complication were analyzed according to the following parameters: age, sex, follow-up duration, eosinophilic infiltration, atopy, asthma, Lund-Mackay score, and polyp grade. RESULTS: There was no significant difference in poor outcome rates between the PSS and no PSS group (35.0% vs. 47.6%, p=0.185). There was no significant difference in complication rates between the PSS and no PSS group (10% vs. 6%, p=0.468). As with the multivariate analysis of the clinicopathological factors to the poor outcome rate, presence of asthma and eosinophilic infiltration were significantly related (odds ratio as 6.555 and 4.505, respectively), whereas PSS was confirmed as less likely related (odds ratio 0.611). CONCLUSION: Low dose PSS administration does not seem to have an effect on the outcome after ESS in patients who have CRS with NP. Eosinophilic infiltration and presence of asthma are important predictors of surgical outcome.

Morphological and histological changes of rabbit vocal fold after steroid injection.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate the morphological and histological change of vocal folds (VFs) after steroid injection in a rabbit model. STUDY DESIGN: Prospective animal study. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: Twenty-four New Zealand white rabbits were used in this study. We randomly classified rabbits into the 3 groups and triamcinolone acetonide suspension was injected to the right VF with different concentrations. Left VF was injected with the same volume of phosphate-buffered saline as control. Endoscopic evaluation was performed to measure morphological changes. The larynges were collected for histological analysis, and the VFs were stained with hematoxylin-eosin for assessing inflammatory response, glandular atrophy, and muscular atrophy and with Masson's trichrome for assessing collagen deposition. RESULTS: In morphological assessment, there were no differences in VF mass reduction, mucosal atrophy, and granulation formation between both VFs. Histological assessments showed no significant difference in inflammatory response, glandular atrophy, and collagen deposition between both VFs. However, there was a difference in muscular atrophy and epithelial layer thinning in steroid injected right VFs. Muscular atrophy had been completely recovered over time, but mild epithelial thinning was continued until 12 weeks. The longer exposure time and larger dose did not increase the intensity of muscular atrophy or epithelial thinning. CONCLUSION: We demonstrated that the VF steroid injection resulted in no significant changes in morphology and histology of rabbit VF. However, steroid injection may induce several VF histological changes and these results are needed to be considered when treating humans.

A noble function of BAY 11-7082: Inhibition of platelet aggregation mediated by an elevated cAMP-induced VASP, and decreased ERK2/JNK1 phosphorylations.

Platelets, though anucleated, possess several transcription factors, including NF-kappaB, that exert non-genomic functions regulating platelet activation. Since platelets have not only been recognized as central players of homeostasis, but also participated in pathological conditions such as thrombosis, atherosclerosis, and inflammation, we examined rat platelet NF-kappaB expression and evaluated the effects of anti-inflammatory drug BAY 11-7082, an inhibitor of NF-kappaB activation, in platelet physiology. Western blotting revealed that rat platelets express NF-kappaB. BAY 11-7082, dose dependently, inhibited collagen- or thrombin-induced-platelet aggregation. ATP release, TXB(2) formation, P-selectin expression, and intercellular Ca(2+) concentration activated by collagen were reduced in BAY 11-7082-treated platelets. BAY 11-7082 elevated intracellular levels of cAMP, but not cGMP, and its co-incubation with cAMP-activating agent (forskolin) or its hydrolyzing enzyme inhibitor (3-isobutyl-1-methylxanthine, IBMX), synergistically inhibited collagen-induced-platelet aggregation. In addition, vasodilator-stimulated-phosphoprotein (VASP) phosphorylation was enhanced in BAY 11-7082-treated platelets, which was partially inhibited by a protein kinase A (PKA) inhibitor, H-89. Moreover, while p38 mitogen-activated protein kinase (MAPK) was not affected, BAY 11-7082 attenuated c-Jun N-terminal kinase 1 (JNK1) and extracellular-signal-regulated protein kinase 2 (ERK2) phosphorylations. In conclusion, BAY 11-7082 inhibits platelet activation, granule secretion, and aggregation, and that this effect is mediated by inhibition of JNK1 and ERK2 phosphorylations, and partially by stimulation of cAMP-dependent PKA VASP phosphorylation. The ability of BAY 11-7082 to inhibit platelet function might be relevant in cases involving aberrant platelet activation where the drug is considered as anti-atherothrombosis, and anti-inflammatory therapy.

Inhibitory effects of cordycepin (3'-deoxyadenosine), a component of Cordyceps militaris, on human platelet aggregation induced by thapsigargin.

Cordycepin (3'-deoxyadenosine) is an adenosine analog, isolated from Cordyceps militaris, and it has been used as an anticancer and anti-inflammation ingredient in traditional Chinese medicine. We investigated the effects of cordycepin (3'-deoxyadenosine) on human platelet aggregation, which was induced by thapsigargin, a tumor promoter, and determined the cytosolic free Ca2+ levels ([Ca2+]i) (an aggregation-stimulating molecule) and cyclic-guanosine monophosphate (cGMP) (an aggregation-inhibiting molecule). Cordycepin inhibited thapsigargin-induced platelet aggregation in a dose-dependent manner, and it clearly reduced the levels of [Ca+]i, which was increased by thapsigargin (1 microM) or U46619 (3 microM). Cordycepin also increased the thapsigargin-reduced cGMP levels. Accordingly, our data demonstrated that cordycepin may have a beneficial effect on platelet aggregation-mediated thrombotic diseases through the [Ca2+]i-regulating system such as cGMP.

Augmentation of Ca2+-induced microsomal triglyceride transfer protein activity by glucose supply enhances hypertriglyceridemia in vivo.

We have investigated possible roles of intra-glucose supply on microsomal triglyceride (TG) transfer protein (MTP) in the secretion of TG-rich very low-density lipoprotein (VLDL) from the liver. Due to the activation of MTP, TG and apolipoprotein B (apoB) in the liver are assembled into VLDL and then the VLDL is transferred into the blood stream. High MTP activity can increase the release of VLDL into the blood stream, and this would lead high levels of TG and apoB in the blood. High MTP activity was found when the liver (or hepatocytes) contained a high level of total Ca2+ as a response of glucose administration. However, the MTP activity was reduced in response to the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7, Ki=25 microM), the intracellular Ca2+ chelator BAPTA-AM, and the extracellular Ca2+ chelator EDTA. These suggested that there might be a very close relationship between high MTP activity and high Ca2+ level in the liver by glucose administration. Glucose-derived hyperglycemic condition resulted from those elevations of TG and total cholesterol in the liver. This hyperglycemic phenomenon may be associated with the increase of TG and apoB levels in blood. The possibility for the regulation of VLDL formation in the liver and, further, those related circulatory diseases due to the excess of VLDL in the blood stream by controlling MTP activity in association with Ca2+ was investigated.

The possible role of Ca2+ on the activation of microsomal triglyceride transfer protein in rat hepatocytes.

Microsomal triglyceride (TG) transfer protein (MTP) is involved in the secretion of TG-rich very low-density lipoprotein (VLDL), a process which leads to the generation of hypertriglyceridemia and atherosclerosis. We investigated the possible role of Ca(2+) on MTP activity in hepatocytes. Exogenous CaCl(2) and calmodulin increased MTP activity dose-dependently, and calcium ionophore A23187 (A23187) also increased total Ca(2+) level and MTP activity in hepatocytes. Moreover, MTP activity increased by CaCl(2) or A23187 was abrogated in the presence of EDTA, a Ca(2+) chelator. MTP activity was increased by the simultaneous addition of CaCl(2) and calmodulin. However, this increase was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), a Ca(2+) antagonist. A23187 increased the release of TG and cholesterol from hepatocytes, and these were inhibited by EDTA. A23187 also increased the ratio of TG to HDL-cholesterol in hepatocytes culture medium, which indicates the release of TG is higher than that of HDL-cholesterol from hepatocytes. Thus, our findings demonstrate that hepatocellular Ca(2+) contributes directly or indirectly to MTP activation. In conclusion, the inhibition of MTP activity via the suppression of hepatocellular Ca(2+) may result in the inhibition of hypertriglyceridemia.