Nitrate-induced coronary vasodilation by stress-magnetic resonance imaging: a novel noninvasive test of coronary vasomotion

PURPOSE: To evaluate the feasibility of assessing coronary vasodilation following exogenous nitrates, using magnetic resonance angiography (MRA). The assessment of coronary response to exogenous nitrovasodilators may have a diagnostic and prognostic impact in patients with coronary artery disease. To date, stress imaging of coronary artery vasomotion has been confined to the catheterization laboratory. MRA is emerging as a noninvasive tool for coronary artery imaging. MATERIALS AND METHODS: Coronary MRA was performed in 20 healthy volunteers (12 males, age = 33 +/- 8). We used spiral spoiled gradient echo (SSGE) sequences for imaging of coronary artery lumen. After the baseline short-axis view of the coronary artery was obtained, sublingual nitroglycerin (NTG) (0.3 mg) was administered. In all subjects, short-axis views of the coronary artery were acquired repetitively (8-10 times) from 1 up to 10 minutes after NTG administration. Measurements were obtained by two independent investigators. RESULTS: Interpretable short-axis view of left anterior descending artery (LAD) was obtained in 15 subjects (75%); in the remaining five subjects the right coronary artery (RCA) was examined. The interobserver variability was 15%, and the intraobserver variability 4%. The NTG-induced maximal vasodilation was 43 +/- 22%. The vasodilator response over time after NTG was maximal on average at 279 +/- 112 seconds, but with substantial heterogeneity. CONCLUSION: Entity and time course of nitrate-induced coronary vasodilation in the left anterior descending and/or RCA can be assessed using MRA with high feasibility and reproducibility. Coronary MRA has potential for dynamic imaging of coronary vasomotion.     

The contraceptive vaginal ring, NuvaRing, and antimycotic co-medication

We investigated the effect of antimycotic co-medication on the systemic exposure to etonogestrel (ENG) and ethinylestradiol (EE) released from the contraceptive vaginal ring, NuvaRing. Different formulations of miconazole nitrate and single as well as multiple dosing were investigated during two separate randomized, open-label, crossover studies. The first study recruited 12 women to compare the effects of co-use of NuvaRing and a single dose of antimycotic to NuvaRing alone. The second study recruited 14 women to compare the effects of multiple doses of an antimycotic vaginal suppository to an antimycotic vaginal cream equivalent. Co-administration of all three antimycotic formulations resulted in a slight increase in systemic exposure to ENG and EE over time, with suppositories having a more pronounced effect than a cream formulation in the multiple-dosing study. The increases in serum levels observed with the different antimycotic formulations are not expected to compromise NuvaRing's contraceptive efficacy or tolerability.     

Toxicity of indium arsenide, gallium arsenide, and aluminium gallium arsenide

Gallium arsenide (GaAs), indium arsenide (InAs), and aluminium gallium arsenide (AlGaAs) are semiconductor applications. Although the increased use of these materials has raised concerns about occupational exposure to them, there is little information regarding the adverse health effects to workers arising from exposure to these particles. However, available data indicate these semiconductor materials can be toxic in animals. Although acute and chronic toxicity of the lung, reproductive organs, and kidney are associated with exposure to these semiconductor materials, in particular, chronic toxicity should pay much attention owing to low solubility of these materials. Between InAs, GaAs, and AlGaAs, InAs was the most toxic material to the lung followed by GaAs and AlGaAs when given intratracheally. This was probably due to difference in the toxicity of the counter-element of arsenic in semiconductor materials, such as indium, gallium, or aluminium, and not arsenic itself. It appeared that indium, gallium, or aluminium was toxic when released from the particles, though the physical character of the particles also contributes to toxic effect. Although there is no evidence of the carcinogenicity of InAs or AlGaAs, GaAs and InP, which are semiconductor materials, showed the clear evidence of carcinogenic potential. It is necessary to pay much greater attention to the human exposure of semiconductor materials.     

Nitric oxide donor properties of hydroxyurea in patients with sickle cell disease

Hydroxyurea therapy reduces the rates of vaso-occlusive crisis in patients with sickle cell anaemia and recent data suggest that hydroxyurea treatment can generate nitric oxide (NO). Nitric oxide has been proposed as a novel therapy for sickle cell disease via a number of pathways. We therefore sought to determine whether hydroxyurea has NO donor properties in patients with sickle cell anaemia and explore potential mechanisms by which NO production could be therapeutic. Venous blood was collected from 19 fasting sickle cell anaemia patients, on chronic hydroxyurea therapy, at baseline and 2 and 4 h after a single morning dose of hydroxyurea, as well as 10 patients not taking hydroxyurea. The plasma and red cell NO reaction products nitrate, nitrite and nitrosylated- haemoglobin were measured using ozone-based chemiluminescent assays (using vanadium, KI and I3- reductants respectively). Consistent with NO release from hydroxyurea, baseline levels of total nitrosylated haemoglobin increased from 300 nmol/l to 500 nmol/l (P = 0.01). Plasma nitrate and nitrite levels also significantly increased with peak levels observed at 2 h. Glutathionyl-haemoglobin levels were unchanged, while plasma secretory vascular cellular adhesion molecule-1 levels were reduced in patients taking hydroxyurea (419 +/- 40 ng/ml) compared with control patients with sickle cell anaemia (653 +/- 55 ng/ml; P = 0.003), and were inversely correlated with fetal haemoglobin levels (r = -0.72; P = 0.002). These results demonstrate that hydroxyurea therapy is associated with the intravascular and intraerythrocytic generation of NO. The role of NO in the induction of fetal haemoglobin and possible synergy between NO donor therapy and classic cytostatic and differentiating medications should be explored.     

杜氏盐藻硝酸盐还原酶基因5'上游序列的克隆与序列分析

目的:克隆杜氏盐藻硝酸盐还原酶(NR)基因5'上游序列,并对其进行测序和序列分析.方法:提取杜氏盐藻基因组DNA,经过BamH I、EcoR I、Hind Ⅲ、Pst I、Sal Ⅰ及Xbal Ⅰ限制性内切酶分别酶切后,再与相应接头连接,分别构建盐藻步行基因组文库BL、EL、HL、PL、SL和XL.采用巢式(LA)-PCR方法,从上述步行基因组文库中扩增杜氏盐藻NR基因5'上游序列,克隆至pMD18-T,对酶切鉴定正确的克隆进行测序.结果:从HL里扩出约1 200 bp特异性片断,回收此片段并进行T载体克隆,对阳性克隆测序.该序列的3'端与已知NR基因cDNA 5'端序列完全一致.该序列含有多个与转录调控有关的保守序列(如CAAT-box和GAGA-box),含有与EBP、EFII、NF-E1、LV 等转录因子以及广谱激活剂Oct-1结合位点相似的核苷酸序列.结论:采用LA-PCR基因组步行方法,从已知cDNA 周围未知启动子或其他调控区域中克隆得到的NR基因的5'上游区序列,可能是一种新的杜氏盐藻启动子区序列.     

Low-dose bleomycin lung

A patient with retroperitoneal diffuse histiocytic lymphoma treated with combination chemotherapy developed breathlessness and fever after receiving 30 units of bleomycin. At this stage pulmonary function tests were impaired and gallium scanning showed diffuse uptake in both lungs although a chest X-ray film was normal. Bleomycin treatment was stopped but interstitial infiltrates appeared on subsequent chest X-ray films. Open lung biopsy showed histologic changes of bleomycin toxicity. After treatment with prednisone, the patient felt well and was shown to have a normal gallium scan and normal respiratory function studies.     

Nitrate-Melt Synthesized HT-LiCoO2 as a Superior Cathode-Material for Lithium-Ion Batteries

An electrochemically-active high-temperature form of LiCoO₂ (HT-LiCoO₂) is prepared by thermally decomposing its constituent metal-nitrates at 700 ºC. The synthetic conditions have been optimized to achieve improved performance with the HT-LiCoO₂ cathode in Li-ion batteries. For this purpose, the synthesized materials have been characterized by powder X-ray diffraction, scanning electron microscopy, and galvanostatic charge-discharge cycling. Cathodes comprising HT-LiCoO₂ exhibit a specific capacity of 140 mAhg^-1 with good capacity-retention over several charge-discharge cycles in the voltage range between 3.5 V and 4.2 V, and can sustain improved rate capability in contrast to a cathode constituting LiCoO₂ prepared by conventional ceramic method. The nitrate-melt-decomposition method is also found effective for synthesizing Mg-/Al- doped HT-LiCoO₂; these also are investigated as cathode materials for Li-ion batteries.     

Contact allergy to hydrocortisone and thixocortol pivalate: problems in the detection of corticosteroid sensitivity

Several of the difficulties involved in the detection of corticosteroid allergy are illustrated by the problems encountered in a patient sensitive to a preparation containing hydrocortisone and miconazole nitrate. The importance of appropriate concentrations and vehicles for patch testing, the possible role of impurities, and cross-sensitivity of corticosteroid molecules are discussed.     

抗霉菌药1-[β-(对硝基苯氧基)-2,4-二氯苯乙基]咪唑硝酸盐的合成

合成抗霉菌药1-[β-(对-硝基苯氧基)-2,4-二氯苯乙基]咪唑时,制备2',4'-二氯-2-(1-咪唑基)苯乙酮(Ⅲ),用过量咪唑作缩合剂效果较好(过量咪唑可以回收)。α-(2,4-二氯苯基)咪唑-1-乙醇和对-硝基氯苯缩合时,使用极性和非极性溶剂并使用适当触媒优于用四氢呋喃。