4-甲氧羰基-4-N-丙酰苯胺基哌啶1位衍生物的合成及其镇痛作用

本文报道了一系列N-[-1(2-苯乙基-4-甲氧羰基-4-哌啶基]-N-丙酰苯胺(4-甲氧羰基芬太尼)哌啶环1位取代衍生物的合成及其镇痛活性;讨论了结构与镇痛活性之间的关系。药理试验结果表明,大部分化合物具有典型的吗啡样镇痛活性,是一类作用极强的麻醉性镇痛剂。特别是哌啶环1位β-苯环被取代乙烯基替代的化合物具有相当或接近子母体化合物的镇痛活性。其代表物1321的镇痛活性(ED_(50)=0.005mg/kg ip,小鼠,热板法)略强于4-甲氧羰基芬太尼(ED_(50)=0.0063 mg/kg)。     

Delivery of a hammerhead ribozyme specifically down-regulates the production of fibrillin-1 by cultured dermal fibroblasts

The hammerhead ribozyme is a small catalytic RNA molecule. Potential hammerhead ribozymes that possess a catalytic domain and flanking sequence complementary to a target mRNA can cleave in trans at a putative cleavage site within the target molecule. We have investigated the potential of hammerhead ribozymes to down-regulate the product of the fibrillin-1 gene (FBN1). Fibrillin is a 347 kDa glycoprotein that is a major constituent of the elastin-associated microfibrils. Mutations in the FBN1 gene are responsible for Marfan syndrome (MFS), a common systemic disorder of the connective tissue. Many FBN1 mutations responsible for MFS appear to act in a dominant-negative fashion, raising the possibility that reduction of the amount of product from the mutant FBN1 allele might be a valid therapeutic approach for MFS. A trans-acting hammerhead ribozyme (FBN1-RZ1) targeted to the 5' end of the human FBN1 mRNA has been designed and synthesized, and shown to cleave its target efficiently in vitro. FBN1-RZ1 cleavage is magnesium dependent and efficient at both 37 and 50 degrees C. Delivery of the FBN1-RZ1 ribozyme into cultured dermal fibroblasts, by receptor- mediated endocytosis of a ribozyme-transferrin-polylysine complex, specifically reduces both cellular FBN1 mRNA and the deposition of fibrillin in the extracellular matrix. These results suggest that the use of hammerhead ribozymes is a valid approach to the study of fibrillin gene expression and possibly to the development of a therapeutic approach to MFS.      

Erythromycin treatment for gastrointestinal dysmotility in preterm infants

To report our clinical experience on the use of oral erythromycin for the treatment of severe gastrointestinal dysmotility in preterm infants.

Methodology:

A case series study of seven preterm infants (six were very low birthweight) with severe intestinal dysmotility in a tertiary neonatal centre.

Results:

All responded favourably without adverse effects and tolerated full enteral feeding within 1–2 weeks of the commencement of the drug.

Conclusions:

As prolonged total parenteral nutrition carries significant risk of complications, this therapy could be considered in selected preterm infants who fail to establish enteral feeding after an extended period, and in whom an anatomically obstructive lesion of the gastrointestinal tract has been excluded. Meanwhile, we would caution against the widespread implementation of this therapeutic approach until formal evaluation by randomized controlled trials have established the exact role of erythromycin, or its analogues, in the treatment of intestinal dysmotility in preterm infants.     

Bronchial artery embolization: monitoring with somatosensory evoked potentials. Work in progress

Surgery remains the treatment of choice for massive and recurrent hemoptysis. In some instances, however, immediate surgical intervention is contraindicated. In these situations, bronchial artery embolization (BAE) has proved to be a successful definitive treatment for non-surgical candidates and a palliative therapy in patients requiring hemodynamic stabilization prior to surgery. The most serious complication of BAE is spinal cord ischemia. This relates directly to the potential anastomotic connections between the bronchial circulation and the anterior spinal artery. Somatosensory evoked potentials (SSEPs) have been used in the past to monitor spinal cord ischemia during procedures that threaten the vascularity of the spinal cord. The authors report two cases in which SSEPs were employed to monitor spinal cord ischemia during bronchial artery embolization.     

大花紫玉盘中新多氧取代环己烯类的结构鉴定

从番荔枝科紫玉盘属植物大花紫玉盘( Uvaria grandiflora Roxb.)根茎中分得4种新的多氧取代环己烯及已知化合物zeylenol,应用波谱分析、X-射线衍射、园二色谱和 Mosher 酯制备等手段确定了全部新化合物的结构及其绝对构型,分别命名为大花紫玉盘醇A(1),B(2),E(3)和F(4)。     

Problems and advantages of continuous renal replacement therapy*

SUMMARY: The continuous replacement of renal function must facilitate fluid and solute homeostasis, nutrition and vital organ function, and, where possible, hasten the recovery of renal function. Difficulties with anticoagulation, biocompatibility, mobility and cost remain obstacles to be overcome. the use of continuous renal replacement therapy (CRRT) to remove systemic inflammatory mediators is yet to be confirmed. Although survival benefits of CRRT over intermittent dialysis remain controversial, the slow continuous removal of fluid, acid and solute has a number of advantages, especially where patients are haemodynamically unstable.     

Human burst-forming units-erythroid need direct interaction with stem cell factor for further development

To understand the factors that regulate the early growth and development of immature erythroid progenitor cells, the burst-forming units-erythroid (BFU-E), it is necessary to have both highly purified target cells and a medium free of serum. When highly purified human blood BFU-E were cultured in a serum-free medium adequate for the growth of later erythroid progenitors, BFU-E would not grow even with the addition of recombinant human interleukin-3 (rIL-3), known to be essential for these cells. However, the addition of recombinant human stem cell factor (rSCF), which supports germ cell and pluripotential stem cell growth, stimulated BFU-E to grow equally well in serum-free as in serum-containing medium. Limiting dilution studies showed that rSCF acts directly on the BFU-E that do not require accessory cells for growth. Furthermore, rSCF was necessary for BFU-E development during the initial 7 days of culture, until these cells reached the stage of the late progenitors, the colony-forming units-erythroid (CFU-E). These studies indicate that early erythropoiesis is dependent on the direct action of SCF that not only affects early stem cells but is continually necessary for the further development of committed erythroid progenitor cells until the CFU-E stage of maturation.     

丹酚酸A对大鼠半乳糖性白内障形成的抑制作用

业已证明,丹酚酸A有较强的抗氧化和清除自由基等多方面的作用。本实验用大鼠半乳糖性白内障模型,研究局部应用丹酚酸A对白内障形成的影响。结果表明,局部用0.05%的丹酚酸A(每日滴眼两次)对白内障的形成有一定的抑制作用,使白内障形成过程减缓。而且给药组动物晶体内过氧化氢和脂质过氧化产物(MDA)含量减少,蛋白巯基和总巯基增加。体外实验表明,丹酚酸A对醛糖还原酶有一定抑制作用。以上结果提示,丹酚酸A可通过不同途径抑制白内障的形成,对糖性白内障的防治有一定意义。