A comparative safety review of histone deacetylase inhibitors for the treatment of myeloma

Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.

Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.

Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.     

[Ca^2＋]i change in hippocampal neurons influenced by preconditioning of etomidate fat emulsion following cerebral ischemia in rats

BACKGROUND: It is known that intravenous anesthetic etomidate fat emulsion has cerebral protection. Now many scholars focus on the research of its cerebral protection from molecular biology, but the mechanism of cerebral protection is still fully unclear. OBJECTIVE: To observe the influence of etomidate fat emulsion on the [Ca2+]i in hippocampal neurons during the transient cerebral ischemia injury in rats. DESIGN: Randomized controlled observation. SETTING: Weifang Medical College. MATERIALS: This study was carried out in the functional laboratory of Weifang Medical College between October 2005 and March 2006. Twenty-four male healthy Wistar rats, aged 3 to 4 months, were involved. Etomidate fat emulsion was provided by the limited company of En-hua Medical Bloc in Jiangsu Province (code of H20020511) and the other agents and materials were provided by Laboratory Center of Weifang Medical College. METHODS: The 24 Wistar rats were randomized into 3 groups: sham-operation group, model group and etomidate preconditioning group, with 8 rats in each. Rat models of transient cerebral ischemia injury were made by the ligation of bilateral carotid arteries combined with descending blood pressure in the latter two groups. Before ischemia (ligation of bilateral common carotid artery), rats in the etomidate preconditioning group were intraperitoneally injected with 12 mg/kg etomidate fat emulsion and then persistently intraperitoneally injected with etomidate fat emulsion at 1.0 mg/kg per minute. Rats in the model group were not administrated. Rats in the sham-operation group were only performed bilateral common carotid artery isolation. When rats were modeled, their brain tissues were quickly taken out and detected. MAIN OUTCOME MEASURES: Change of the fluorescence pixel value of the [Ca2+]i in each group by the laser scanning confocal microscope. RESULTS: Twenty-four rats were involved in the final analysis. Fluorescence pixel value in the sham-operation group was in the low level. Fluorescence pixel value in the model group was significantly higher than that in the sham-operation group (P < 0.01). Fluorescence pixel value in the etomidate preconditioning group was significantly lower than that in the model group (P < 0.01). CONCLUSION: The protection of etomidate fat emulsion to the transient cerebral ischemic injury in rats is associated with the inhibition to the increase of [Ca2+]i to some extent.     

Adhesive fragment reattachment after orthodontic extrusion: a case report

Abstract –  In the treatment of crown fractures, adhesive fragment reattachment provides a good alternative to other restorative techniques, offering several advantages. The present paper reports a case in which the treatment of a cervical crown fracture was accomplished by reattaching the tooth fragment with a flowable resin composite. Orthodontic root extrusion was performed with a modified Hawley appliance prior to fragment reattachment. The clinical and radiographic results after 2.5 years were successful.     

The effect of topical parasympathomimetics on corneal epithelial healing in rabbits

Corneal wound healing is an important process that involves interaction between the different corneal cell layers, growth factors, and environmental conditions. More powerful therapies for the treatment of delayed epithelial wound healing are still being proposed. The objective of this study is to investigate the effects of the direct-acting parasympathomimetic agents on the healing process of corneal epithelium in rabbits. The corneal epithelial defects, 10 mm in diameter, were created in 32 eyes of 16 island rabbits by combination of chemical debridement using n-heptanol and mechanical scraping. Animals were randomly divided into four groups. Groups 1, 2 and 3 were treatment groups; each group consisted of four rabbits (8 eyes). The animals in these groups were treated with topical 1% acetylcholine (ACh), 2% pilocarpine, and 0.75% carbachol drops respectively. In group 4, four rabbits (8 eyes) were used as control group and left for spontaneous healing. The length and area of the defect were measured at days 3,6,9,12,15,18 and 22 after wounding. Areas of the photographically documented fluorescein-stained defects were measured by planimetry. All eyes in the treatment groups reepithelialized completely. The duration for reepithelialization in Groups 1 and 2 was 12 days, and 18 days for Group 3. In the control group reepithelialization occurred within 22 days. The healing rates of corneal epithelium were statistically significantly faster in all treatment groups as compared with the control group at all times (p=0.0001 to 0.0279). Although the rates of wound healing varied, all of the parasympathomimetics used in the present study were found to facilitate wound healing. Our results indicate that direct-acting cholinergic agents, especially ACh and pilocarpine, may have an important therapeutic role in the treatment of severe corneal epithelial injury.     

Midazolam in treatment of various types of seizures in children

Midazolam is a recently developed water-soluble benzodiazepine that shares anxiolytic, muscle relaxant, hypnotic and anticonvulsant actions with other members of this class. There are limited studies that midazolam can be used successfully to treat seizures in adults and children. In this study, 0.2 mg/kg intramuscular (IM) midazolam was administered to 11 children (eight boys and three girls), aged 3 days to 4 years (mean age 1.8±1.4 years), with seizures of various types. In all but one child, seizures stopped in 15 s–5 min after injection. No side effects were observed. These results suggest that IM administration of midazolam may be useful in a variety of seizures during childhood, especially in case of intravenous (IV) line problem.     

人工神经网络在避孕研究中的应用

人工神经网络作为一门新兴的边缘学科,已开始在许多领域应用.本文将神经网络的方法应用于避孕方法选择方面,并通过ROC曲线比较了神经网络方法与传统的多元LO-gistic回归分析方法对训练样本和检验样本的表现.结果提示,神经网络方法有望在统计学、医学领域得到进一步应用和发展.