Quantitative determination of zidovudine diaryl phosphate triester pro-drugs in rat plasma by high-performance liquid chromatography–electrospray ionization tandem mass spectrometry

A rapid, simple, and sensitive high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI–MS/MS) method was developed and validated for quantitative analysis of 3′-azido-3′-deoxythymidine (zidovudine, AZT) diaryl phosphate triester pro-drugs, in rat plasma using 2′,3′-dideoxy-2′3′-didehydrothymidine (d4T) as internal standard (IS). The analytes were extracted from rat plasma with methanol after protein precipitation. The compounds were separated by HPLC with gradient elution (on a Shim-pack VP-ODS C₁₈ analytical column using a mobile phase of methanol/10 mM ammonium acetate). All the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation (LLOQ), precision, accuracy, recoveries and stability were determined. LLOQs were 10 ng mL⁻¹ for M1, M2, M3, M4, and M5, respectively. Correlation coefficient (r) values for the linear range of 10–10,000 ng mL⁻¹ were greater than 0.999 for all the analytes. The intra-day and inter-day precision and accuracy were higher than 7.13%. The relative and absolute recovery was above 72% and no matrix effects were observed for all the analytes. This validated method provides a modern, rapid, and robust procedure for the pharmacokinetic studies of the pro-drugs after intravenous administration to rats. Some important results of AZT diaryl phosphate triester pro-drugs concerning chemical effect on pharmacokinetic performance are also studied.     

血脂康胶囊治疗高尿酸血症疗效和安全性的随机双盲临床试验

目的评价血脂康胶囊治疗高尿酸血症的疗效和安全性。方法采用随机、双盲、安慰剂、对照的设计,将80例高尿酸血症患者随机分为两组,试验组和对照组各40例,进行治疗和比较,疗程为28d。结果共有75例完成了试验(试验组38例,对照组37例)。与用药前相比,试验组的尿酸、黄嘌呤氧化酶、空腹血浆胰岛素、胰岛素抵抗指数、三酰甘油、胆固醇、脂蛋白、超敏C反应蛋白、内皮素、尿β2微球蛋白下降和高密度脂蛋白升高均有统计学意义。试验过程中两组均未出现不良反应。结论血脂康胶囊治疗高尿酸血症具有很好的疗效和安全性。     

糖调节受损者之气虚证研究

目的：探讨气虚证糖调节受损（IGR）者的临床特点。方法：对所收集的辨证为气虚证的IGR者与同期收集的非气虚证的IGR者年龄、性别、体重指数、腰臀比、血脂、血糖、胰岛素等资料进行分析,以及对气虚证IGR患者的临床证候和出现频率以及证候与性别的关系进行分析。结果：IGR患者气虚证的总发病率为53.6%。与非气虚证者相比,糖调节受损之气虚证者的年龄和体重指数偏低,而空腹血糖和总胆固醇水平偏高,具有显著性差异（P〈0.05）。气虚证IGR者中CGI显著高于非气虚证IGR者,具有显著性差异（P〈0.05）。气虚证患者常见的证候分别是气虚兼血瘀、单纯气虚、气虚兼痰湿和气虚兼阴虚,且证候表现存在着一定的性别差异。结论：气虚证在IGR者中很常见,气虚证的临床特点常表现为年龄和体重指数偏低,而空腹血糖和总胆固醇水平偏高,并常兼血瘀、痰湿和阴虚等。     

中医诊治亚健康状态的优势

文章首先论述了亚健康状态的概念和表现形式，认为亚健康状态是处于疾病与健康之间的一种低体质状态。亚健康状态的表现形式有：有症状无阳性检查发现和无症状有轻度阳性检查发现两种。中医对亚健康状态的诊断沿袭传统的四诊，其中舌诊、脉诊和面色诊等体征诊断尤其有特别的意义，辨证方法上以病性辨证和脏腑辨证为主。中医对亚健康状态的治疗手段丰富多彩且疗效很好，除了方药以外，针灸、推拿、导引、食疗、气功都可选用，调摄情绪、注意生活起居、适度劳逸、合理的饮食对亚健康状态的辅助治疗意义重大。     

The interleukin-1 receptor-associated kinases: Critical regulators of innate immune signalling

The interleukin receptor-associated kinase (IRAK) family are involved in regulating Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways. TLRs are pattern recognition receptors of the innate immune response that are responsible for sensing pathogens and initiating immunity, while IL-1 is one of the key cytokines that mediates inflammation. As such, IL-1/TLR signalling pathways and the IRAK family are critical in anti-pathogen responses, inflammation and autoimmunity. The family comprises of four members, IRAK-1, IRAK-2, IRAK-M (IRAK-3) and IRAK-4, and has a role in both positive and negative regulation of signal transduction. While it was once thought that the family displayed some redundancy, each member of the family is emerging as a distinct and vital contributor to IL-1/TLR signalling mechanisms. Knockout mouse studies have explored the relative contribution of each of the IRAKs in IL-1/TLR signalling, while the recent generation of kinase-inactive knock-in IRAK-4 mice have revealed which of IRAK-4 functions require its kinase activity. IRAK-2, previously thought of as a pseudokinase, has recently been proposed to have kinase activity that is essential for TLR signalling. Not surprisingly given their critical role in IL-1/TLR signalling, the IRAK family members have been implicated in certain disease models including human immunodeficiencies. Thus the potential targeting of these essential protein kinases therapeutically is also discussed.     

Proton magnetic resonance imaging for assessment of lung function and respiratory dynamics

Since many pulmonary diseases present with a variable regional involvement, modalities for assessment of regional lung function gained increasing attention over the last years. Together with lung perfusion and gas exchange, ventilation, as a result of the interaction of the respiratory pump and the lungs, is an indispensable component of lung function. So far, this complex mechanism is still mainly assessed indirectly and globally. A differentiation between the individual determining factors of ventilation would be crucial for precise diagnostics and adequate treatment. By dynamic imaging of the respiratory pump, the mechanical components of ventilation can be assessed regionally. Amongst imaging modalities applicable to this topic, magnetic resonance imaging (MRI), as a tool not relying on ionising radiation, is the most attractive. Recent advances in MRI technology have made it possible to assess diaphragmatic and chest wall motion, static and dynamic lung volumes, as well as regional lung function.Even though existing studies show large heterogeneity in design and applied methods, it becomes evident that MRI is capable to visualise pulmonary function as well as diaphragmatic and thoracic wall movement, providing new insights into lung physiology. Partly contradictory results and conclusions are most likely caused by technical limitations, limited number of studies and small sample size. Existing studies mainly evaluate possible imaging techniques and concentrate on normal physiology. The few studies in patients with lung cancer and emphysema already give a promising outlook for these techniques from which an increasing impact on improved and quantitative disease characterization as well as better patient management can be expected.     

Effects of prostaglandin F2α analogues on endothelin-1-induced impairment of rabbit ocular blood flow: Comparison among tafluprost,travoprost, and latanoprost

We investigated the effects of prostaglandin F_2α (PGF_2α) analogues on the endothelin-1 (ET-1)-induced impairment of optic nerve head (ONH) blood flow and on ET-1-induced contraction in isolated ciliary artery segments. In male rabbits, one of four PGF_2α analogues [0.0015% tafluprost, 0.0015% 15-hydroxyl tafluprost (15-OH tafluprost), 0.005% latanoprost, or 0.004% travoprost] was topically administered at various pretreatment times before intravitreal ET-1 injection. ONH blood flow was estimated by the laser speckle method, which expresses blood velocity as a quantitative index, the squared blur rate (SBR). SBR was measured just before (baseline value) and at 30, 60, and 120 min after ET-1 injection. SBR was significantly decreased from 4.47 ± 0.20 to 3.50 ± 0.10 (78.6 ± 2.4% of baseline) at 120 min after intravitreal ET-1 injection (5 pmol/eye). The ET-1-induced decrease was almost completely prevented by tafluprost and significantly inhibited by the other three analogues. The inhibitory effect lasted longest with tafluprost, as indicated by the effective pretreatment times (tafluprost: 90, 120, or 240 min; 15-OH tafluprost: 90, but not 120 or 240 min; latanoprost and travoprost: 120, but not 240 min). In vitro, the effects of PGF_2α analogues on ET-1-induced contractions in male rabbit ciliary arteries were evaluated using an isometric tension recording system. Tafluprost, latanoprost, travoprost, and 15-OH tafluprost concentration-dependently relaxed the 10 nM ET-1-induced ciliary artery contraction. Improvement of the ocular circulation may be superior with tafluprost than with the other PGF_2α analogues. The underlying mechanism may involve relaxation of ocular resistance vessels.