The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1

Although the dominant approach to drug development is the design of compounds selective for a given target, compounds targeting more than one biological process may have superior efficacy, or alternatively a better safety profile than standard selective compounds. Here, this possibility has been explored with respect to the endocannabinoid system and pain. Compounds inhibiting the enzyme fatty acid amide hydrolase (FAAH), by increasing local endocannabinoid tone, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. Local increases in levels of the endocannabinoid anandamide potentiate the actions of cyclooxygenase inhibitors, raising the possibility that compounds inhibiting both FAAH and cyclooxygenase can be as effective as non-steroidal anti-inflammatory drugs but with a reduced cyclooxygenase inhibitory ‘load’. An ibuprofen analogue active in models of visceral pain and with FAAH and cyclooxygenase inhibitory properties has been identified. Another approach, built in to the experimental analgesic compound N-arachidonoylserotonin, is the combination of FAAH inhibitory and transient receptor potential vanilloid type 1 antagonist properties. Although finding the right balance of actions upon the two targets is a key to success, it is hoped that dual-action compounds of the types illustrated in this review will prove to be useful analgesic drugs.     

Monosegmental fixation for the treatment of fractures of the thoracolumbar spine

Background:

A short vertebral arthrodesis has been one of the objectives of the surgical treatment of fractures of the thoracolumbar spine. We present here clinical, functional and radiographic outcome obtained after monosegmental fixation (single posterior or combined anterior and posterior) of specific types of unstable thoracolumbar fractures.

Materials and Methods:

Twenty four patients with fractures of the thoracolumbar spine submitted to monosegmental surgical treatment (Group I - 18 single posterior monosegmental fixations and Group II - 6 combined anterior and posterior fixations) were retrospectively evaluated according to clinical, radiographic and functional parameters. The indication for surgery was instability or neurological deficit. All the procedures were indicated and performed by the senior surgeon (Helton LA Defino).

Results:

The patients from group I were followed-up from 2 to 12 years (mean: 6.65±2.96). The clinical, functional and radiographic results show that a single posterior monosegmental fixation is adequate and a satisfactory procedure to be used in specific types of thoracolumbar spine fractures, The patients from group II were followed-up from 9 to 15 years (mean: 13 ± 2,09 years). On group II the results of clinical evaluation showed moderate indices of residual pain and of satisfaction with the final result. The values obtained by functional evaluation showed that 66.6% of the patients were unable to return to their previous job and presented a moderate disability index (Oswestry = 16.6) and a significant reduction of quality of life based on the SF-36 questionnaire. Radiographic evaluation showed increased kyphosis of the fixed vertebral segment during the late postoperative period, accompanied by a reduction of the height of the intervertebral disk.

Conclusion:

It is possible to stabilize the fractures which have an anterior good load-bearing capacity by a standalone posterior monosegmental fixation. However this procedure, even with an anterior support is not suitable for fracture involving the vertebral body.     

Pterygium after hyperopic laser‐assisted sub‐epithelial keratomileusis (LASEK)

A 61‐year‐old Caucasian woman with hyperopia presented for laser refractive surgery. She had healthy eyes with the exception of a less than 0.5 mm Salzmann's nodule at 5 o'clock near the limbus of the right eye. She underwent bilateral hyperopic laser‐assisted sub‐epithelial keratomileusis (LASEK) combined with removal of the Salzmann's nodule. At six months, she was emmetropic with unaided vision of 6/6; however, at 10 months, she noticed a reduction of acuity in her right eye and was found to have a pterygium at 5 o'clock, encroaching 3.5 mm onto the corneal surface. She underwent excision biopsy, local application of mitomycin‐C (0.2 mg/ml for two minutes) and conjunctival auto‐grafting. Following surgery for the pterygium, vision returned to 6/6 unaided but six months later, there was limited recurrence (1.5 mm) of the pterygium reducing unaided vision to 6/9, due to the induction of astigmatism of ‐1.25 dioptres. This has remained stable for 14 months. Pterygium growth may be associated with surface excimer laser surgery and the presence of peripheral Salzmann's nodules might be a risk factor.     

冠心病患者巨细胞病毒检测结果及临床意义

为研究人巨细胞病毒感染与冠心病的关系，利用人巨细胞病毒磷酸化蛋白ＰＰ７１基因引物，采用聚合酶链反应检测了５６例冠心病患者和４２例健康对照者外周血人巨细胞病毒，同时应用全自动生物化学仪检测了血清总胆固醇、甘油三醇、载脂蛋白Ａ、载脂蛋白Ｂ含量。结果发现冠心病组血人巨细胞病毒阳性率为５８．９３％，显著高于对照组的２８．５７％（Ｐ〈０．０１），急性心肌梗死和不稳定型心绞痛患者血人巨细胞病毒的阳性率又高于其     

极低密度脂蛋白受体基因CGG串联重复序列多态性与冠心病的关系

极低密度脂蛋白受体基因５’非编码区起始密度子上游１９ｂｐ处存在ＣＧＧ三核苷酸串联重复序列，为探讨中国汉族人群极低密度脂蛋白受体基因ＣＧＧ串联重复序列多态性与冠心病的相关性，采用聚合酶链反应、变性聚丙烯酰胺凝胶电泳和银染等技术分析湖北地区７５例冠心病患者和１６０例正常汉族人ＣＧＧ串联重复序列。共检出ＣＧＧ串联重复次数为５、８、９、１１的四种等位基因及５／５、５／８、８／８、８／９、９／９、５／９、８