Azide function and polyaddition: reaction of 2-azido-2,4,4-trimethylpentane and monoazidopoly(2-methylpropene) with some dienophiles

The 1,3-dipolar addition of 2-azido-2,4,4-trimethylpentane ( 1 ) to acetylene and ethylene derivatives such as phenylacetylene (2), acrylonitrile, diphenyl fumarate ( 4 ) and N,N′-methylenebis(1,4-phenylene)dimaleimide ( 8 ) leads to the corresponding triazole and triazoline derivatives. This study demonstrates that tertiary azides are able to react with dienophiles, and the application of this reaction for the synthesis of block copolymers was investigated with monoazido-telechelic poly(2-methylpropene) (PMP). It was shown that the azido group is stable under the severe conditions of the polycondensation reaction without decomposition (170°C, 24 h), and the monoadduct PMP- 8 is produced with acceptable yield.     

Clinical characteristics of patients with exercise-induced ST-segment elevation without prior myocardial infarction.

BACKGROUND: Exercise-induced ST-segment elevation is a relatively uncommon problem and occurs more frequently in patients who have had a myocardial infarction. Data is limited on the characteristics of Taiwanese patients without prior myocardial infarction who develop exercise-induced ST-segment elevation. METHODS AND RESULTS: Exercise-induced ST-segment elevation developed in 9 of 6,147 consecutive patients without myocardial infarction who underwent treadmill exercise testing at out institution over a 4-year period. The clinical and angiographic characteristics of these patients were studied. Angiographically normal coronary arteries with coronary vasospasm were found in 5 patients, hemodynamically significant coronary stenosis was found in 3 patients, and coexisting spasm in angiographically normal coronary arteries combined with hemodynamically significant coronary stenosis in the different vessel was found in 1 patient. During a median follow-up of 71 months, 2 patients with coronary vasospasm developed recurrent angina after self-discontinuation of calcium antagonists and 2 patients (1 with coronary vasospasm and 1 with hemodynamically significant coronary stenosis) died of cardiac causes before arrival at the emergency department. CONCLUSION: Coronary vasospasm was a more common underlying pathology of exercise-induced ST-segment elevation in this Taiwanese cohort. Coronary angiography +/- intracoronary ergonovine provocation testing is necessary in these patients to identify the underlying pathology and appropriate treatment.     

Magnetic nanoparticle labeling of mesenchymal stem cells without transfection agent: cellular behavior and capability of detection with clinical 1.5 T magnetic resonance at the single cell level.

The purpose of this work was to evaluate the efficacy of labeling human mesenchymal stem cells (hMSCs) by ionic superparamagnetic iron oxide (SPIO) without a transfection agent and verifying its capability to be detected with clinical 1.5 T magnetic resonance (MR) at the single-cell level. Human hMSCs were incubated for 24 h with an ionic SPIO, Ferucarbotran. The labeling efficiency of hMSCs was determined by iron content measurement spectrophotometrically, and the influence of labeling on cell behavior was ascertained by examination of cell viability using the trypan blue exclusion method, cell proliferation analysis using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, mitochondrial membrane potential (MMP) change, differentiation capacity, and reactive oxygen species (ROS) production measured by dichlorofluorescein diacetate (DCFDA) fluorescent probe. Labeled hMSCs were scanned under 1.5 T MRI with three-dimensional (3D) and two-dimensional (2D) T(2)-weighted gradient echo (GRE) pulse sequences. Human hMSC labeling without transfection agent was efficient. The iron content in hMSCs was 23.4 pg Fe/cell. No significant change was found in viability, proliferation, MMP change, ROS production, or differentiation capacity. About 45.2% of the hMSCs could be detected using 1.5 T MRI at the single cell level with 3D GRE and four repetitions.     

石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

Effects of continuous distraction on cartilage in a moving joint: An investigation on adult rabbits

An animal model, using distraction force on adult rabbits, was developed to study the effects of nonweight-bearing on articular cartilage in a moving joint. Histologic evaluation was used to compare the morphology of chondrocytes, safranin O intensity, cartilage thickness, and structural changes between the test and contralateral joints. At 3 and 6 weeks, the chondrocytes in superficial and intermediate zones were round, with an increase in cellular volume density and mean cell volume and with less metachromasia; the safranin O intensity and cartilage thickness were the same as in the controls. In cartilage of the 9-week group, mean cell volume decreased with cell cloning in the superficial zone, while numerical density increased and mean matrix volume per cell decreased in the superficial and intermediate zones. The cartilage, with a 34% reduction in thickness and a 53–72% decrease in safranin O intensity from the superficial to the deep zone, had superficial fibrotic proliferation, suface erosion or depression, ard tidemark irregularity. Continuous distraction in a moving joint caused morphological changes in chondrocytes prior to degeneration of cartilage. These results support the hypothesis that the forces perceived by cells may dictate their shape and then stimulate alterations in cellular biochemistry and matrix metabolism.     

Development of sesquiterpenes from Alpinia oxyphylla as novel skin permeation enhancers.

To improve the drug permeation into and/or across the skin, essential oils extracted from Alpinia oxyphylla (AO) were evaluated using in vitro and in vivo permeation techniques with Wistar rats as the animal model. Hydrocarbons and oxygenated sesquiterpenes were the major components in the lower-polarity fraction (AO-1) and higher-polarity fraction (AO-2), respectively. Permeation of indomethacin was significantly enhanced after treatment with AO-1 and AO-2 in the in vitro and in vivo studies. AO-2 generally showed a higher ability to promote drug permeation compared to AO-1. The increment of skin/vehicle partitioning may be the predominant mechanism for this enhancing activity. Both transepidermal water loss (TEWL) and colorimetric evaluation showed limited irritation to skin by AO essential oils at the macroscopic level. Human skin fibroblasts were used to investigate the in vitro screening of skin toxicity. AO-1 slightly increased prostaglandin E(2) (PGE(2)) formation from skin fibroblasts. A striking result was observed with AO-2, which greatly inhibited the release of PGE(2). Moreover, both AO essential oils had no statistically significant effect on PGE(2) release by human lung epithelial cells. The results of this study indicate that skin disruption and inflammation do not necessary correspond to the enhancing efficiency of the enhancers tested.