异位骨化

通过复习异位骨化的相关文献，详细介绍了异位骨化的发病机制、分类、发生率、分型、发病因素、临床表现、诊断、预防及治疗方法。异位骨化是指在正常情况下没有骨组织的软组织内形成的新生骨，在组织学上，成熟的异位骨化与骨痂一致。其形成一般需三个条件：①成骨诱导物；②成骨的前体细胞；③允许成骨的组织环境。早期表现包括关节周围疼痛、发热、红肿，逐渐出现关节活动受限。三相核素骨扫描是早期检测异位骨化的最敏感指标，并可以判断病变的活动性和成熟度。非甾体类消炎药(NSAIDs)是目前公认的预防人工髋关节置换和髋臼骨折术后异位骨化形成的最有效的药物。手术切除是异位骨化形成后导致严重关节功能障碍患者的唯一治疗手段。     

Do NSAIDs affect the progression of osteoarthritis?

NSAIDs are widely used to alleviate the symptoms of OA. It remains controversial as to what effects these agents have on the progression of OA. In vitro studies showed several types of NSAIDs (e.g., sodium salicylate, indomethacin) inhibited the synthesis of cartilage matrix component, but some types of NSAIDs (e.g., aceclofenac, meloxicam, nimesulide) increased the matrix component synthesis and protected the chondrocytes against apoptosis, while others (e.g., piroxicam) had no effects. Studies in animal models verified that NSAIDs had favourable or detrimental action on OA progression, even the same NSAID (e.g., naproxen, tiaprofenic acid) had reverse effects on articular cartilage in different studies. Preliminary clinical trials revealed some NSAIDs such as indomethacin had a negative influence on joint structure, other NSAIDs such as diclofenac and naproxen had no acceleration of radiographic damage to OA within 2-years of treatment. So far, there are no convincing data to show the widely used NSAIDs and recommended selective COX-2 inhibitor have favourable effects on cartilage. Therefore, it is necessary and valuable to clarify the effects of these NSAIDs on cartilage in patients with OA using validated non-invasive methods such as MRI.     

Treat the Whole Patient and Be Aware of Drug Interactions

The case of an elderly male with bilateral shoulder pain is presented. The pain had been successfully treated years earlier with surgery, but a repeat rotator cuff procedure when the pain recurred was not effective. The patient's physician asked about impact of systemic analgesics on the elderly patient and interactions with his blood pressure medications. Cardiovascular and renal risks of NSAOIDs are discussed as are potential toxicities of tramadol and too rapid withdrawal from it. Drug interactions of medications used are described.

This report is adapted from paineurope 2014; Issue 3, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http://www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.     

药(含中药)源性肝损伤的病因溯源

目的基于对药源性肝损伤(DILI)住院病例用药资料的详尽调查、核实及其肝生化检测数据的分析,探讨本地区DILI发生的原因与规律性特征,进而对DILI,特别是中药DILI的报告提出规范性建议。方法自2012年1月—2015年12月在复旦大学金山医院消化科住院的60例DILI病例,逐一详尽调查用药资料及其肝生化资料,进行分类、分析、总结,报告DILI的相关药物及影响因素,判断DILI的依据包括因果关系的明确、时间顺序关系的合理:即用药时出现临床症状、肝酶指标的异常升高或肝功能的恶化,停药后病情好转或正常。结果 DILI病例有肝酶指标的异常升高,平均年龄63.1岁。除DILI外,患1种以上疾病者60例,患2种以上疾病者56例,例均患病3.3种。例均用药5.7种,在致DILI的主药中,解热镇痛药27例,占45.0%;确定为纯中药相关者2例,占3.3%。DILI患者血白蛋白低于正常平均值者55例,占91.7%;前白蛋白低于正常平均值者58例,占96.7%;纤维蛋白原低于正常平均值者30例,占50.0%;血红蛋白低于正常平均值者53例,占88.3%;抗凝血酶活性共测45例,低于正常平均值者30例,占66.7%。结论 DILI病例以长期用多种药物的老年病例为主,大多数有以白蛋白水平降低为代表的慢性肝功能损害、有前白蛋白降低代表的新近肝功能损害,说明DILI的大多数是在有慢性肝损伤基础上产生的新近肝损伤。DILI的主要病因是解热镇痛药,而不是中药。报告DILI时,尤其是中药DILI,必需提供药物的生产厂家、批号,若是中药材必需提供足够的鉴定信息或来源证明。     

Groups I,II and III extracellular phospholipases A2: Selective inhibition of group II enzymes by indomethacin but not other NSAIDs

The three types (groups I, II and III) of stable extracellular 14 kDa phospholipase A₂ enzymes differ in their primary amino acid sequences and their properties. It may thus be possible to design low-molecular weight inhibitors targeted to the secretory form of mammalian PLA₂. this enzyme has been implicated in inflammatory disorders. We have studied the inhibition of four distinct PLA₂ enzymes by a range of NSAIDs, using³H-oleate release from prelabelled membranes ofE. coli for assay. The enzymes used were cobra venom PLA₂ (Naja naja, a group I enzyme), bee venom PLA₂ (Apis mellifera, group III), recombinant human synovial PLA₂ (group II) and rat peritoneal PLA₂ (group II). Under the conditions of the³H-oleateE. coli assay, 1 mM concentrations of aspirin, sodium salicylate, paracetamol (acetaminophen), oxphenbutazone, ibuprofen, flurbiprofen and nabumetone failed to inhibit significantly any of the four enzymes. However, indomethacin inhibited all four enzymes, although effects were greatest on the two group II enzymes (rat peritoneal and human synovial PLA₂). Approximate IC₅₀ values were 28 and 35 M, respectively. Inhibition by indomethacin was not time dependent and was greater at micromolar rather than millimolar levels of calcium. We conclude that indomethacin but not the other tested classes of NSAID inhibits the group II PLA₂ enzyme in a selective manner and suggest that this may be relevant both to its clinical spectrum and to the design of novel pharmaceutical leads.     

Effect of acute paracetamol overdose on changes in serum and urine electrolytes

What is already known about this subject

• Paracetamol causes renal failure in overdose. Experimental studies have shown that paracetamol can inhibit COX II systemically in a manner similar to selective COX-II inhibitors.
• In overdose nonsteroidal anti-inflammatory drugs such as ibuprofen, cause dose-dependent increase in urinary potassium excretion (FeK) and sodium retention, probably due to vasoconstriction.

What this study adds

• Paracetamol overdose is associated with dose-related hypokalaemia and kaliuresis of short duration (<24 h), suggesting a specific renal effect of paracetamol in overdose.
• This effect seems likely to be via cyclo-oxygenase inhibition and may be separate from the nephrotoxic effects of paracetamol.

Aims

To investigate the effects of acute paracetamol overdose on renal function, serum and urine electrolyte excretion in man.

Methods

Two studies were performed in patients admitted with paracetamol overdose: a retrospective study examining changes in serum electrolytes, and a prospective study evaluating changes in serum and urine electrolytes. A control group with SSRI overdose was included in the prospective study.

Results

There was a significant dose-dependent relationship between admission (4 h) paracetamol concentration and fall in serum potassium in the retrospective study (P < 0.01) and a significant positive relationship between serum paracetamol at 4 h and fractional excretion of potassium at 12 h postingestion (P < 0.01) in the prospective study. No changes were seen in the control group. No cases developed renal failure.

Conclusions

Paracetamol overdose is associated with dose-related hypokalaemia, and kaliuresis of short duration (<24 h), suggesting a specific renal effect of paracetamol in overdose perhaps via cyclo-oxygenase inhibition. This effect seems distinct from any nephrotoxic effect of paracetamol.     

Effect of oral administration of a continuous 18 day regimen of meloxicam on ovulation: experience of a randomized controlled trial

Background

Cyclooxygenase-2 (COX-2) is expressed in all female reproductive organs. Therefore, inhibitors of COX-2 may affect reproductive function. We evaluated the effect of extended administration of meloxicam on ovulation and the menstrual cycle. Our hypothesis was that meloxicam administered from menstrual cycle day 5- 22 could interfere with follicular rupture, without disrupting the menstrual cycle, and could be a potential non-hormonal contraceptive method.

Methods

The study was conducted in 56 healthy sterilized women. Before the onset of treatment and after the end of treatment, participants were observed during a control cycle to ensure that they had progesterone (P₄) serum levels (> 12 nmol/l) consistent with ovulation. Participants were treated for 18 days, during three consecutive cycles. They were randomized to 15 or 30 mg/day. The menstrual cycle was monitored with serial ultrasound and hormone assays in blood.

Results

Fifty-six volunteers completed the study. In 55% of cycles treated with 15 mg/day and in 78% of cycles treated with 30mg/day (p<0.001) we observed dysfunctional ovulation defined as follicular rupture not preceded 24–48 h earlier by an LH peak or preceded by a blunted LH peak (< 21 IU/l) or not followed by an elevated serum P₄ level > 12 nmol/l. Ovulation was observed in 44.6% and in 21.7% of women in the lower dose group and the higher dose group, respectively. There were no differences between the two doses in other parameters measured. There were no serious adverse events and adverse events were not different between doses or between control and treated cycles.

Conclusions

Although administration of meloxicam on menstrual cycle days 5- 22 resulted in a dose-dependent inhibition of ovulation, more than 20% of subjects had normal ovulation with the highest dose.

Implications

Previous studies have shown that oral meloxicam can delay follicle rupture. This study investigated daily oral meloxicam as a non-hormonal contraceptive. Since ovulation occurs in over 20% of cycles even with a high dose of 30 mg daily, it is not likely that the approach would be a highly effective contraceptive strategy.     

Phenolic anti-inflammatory antioxidant reversal of Aβ-induced cognitive deficits and neuropathology

Both oxidative damage and inflammation have been implicated in age-related neurodegenerative diseases including Alzheimer’s Disease (AD). The yellow curry spice, curcumin, has both antioxidant and anti-inflammatory activities which confer significant protection against neurotoxic and genotoxic agents. We used 22 month Sprague-Dawley (SD) rats to compare the effects of the conventional NSAID, ibuprofen, and curcumin for their ability to protect against amyloid β-protein (Aβ)-induced damage. Lipoprotein carrier-mediated, intracerebroventricular infusion of Aβ peptides induced oxidative damage, synaptophysin loss, a microglial response and widespread Aβ deposits. Dietary curcumin (2000 ppm), but not ibuprofen, suppressed oxidative damage (isoprostane levels) and synaptophysin loss. Both ibuprofen and curcumin reduced microgliosis in cortical layers, but curcumin increased microglial labeling within and adjacent to Aβ-ir deposits. In a second group of middle-aged female SD rats, 500 ppm dietary curcumin prevented Aβ-infusion induced spatial memory deficits in the Morris Water Maze and post-synaptic density (PSD)-95 loss and reduced Aβ deposits. Because of its low side-effect profile and long history of safe use, curcumin may find clinical application for AD prevention.