Inhibitory effects of phenolic compounds from Artocarpus styracifolius on respiratory burst of rat neutrophils

Context: Searching for polymorphonuclear neutrophils (PMNs) respiratory burst inhibitors is an important topic in the treatment of human diseases associated with inflammation.

Objective: To investigate the inhibitory effects of phenolics isolated from Artocarpus styracifolius Pierre (Moraceae) on respiratory burst induced by phorbol myristate acetate (PMA).

Materials and methods: The anti-respiratory burst activities of eight phenolics (20?µM) were assessed by determining luminol-dependent chemiluminiscence in rat PMNs. Cytotoxicity of active compounds (1–1000?µM) was assayed by Trypan blue dye exclusion method. Cell-free models were employed to evaluate scavenging capacity of active compounds (20?µM) against reactive oxygen species.

Results: The PMA-induced respiratory burst was significantly inhibited (p?1–6) at the concentration of 20?µM (below the toxic concentration) with the inhibition rate ranging from 25.0 to 99.6%. The inhibitory potency estimated by IC₅₀ was in the order of AS1 (3.1?µM) >AS6 (5.9?µM) >AS2 (9.1?µM) >AS3 (10.0?µM) >AS5 (29.7?µM) >AS4 (57.7?µM). AS1–4, four isoprenylated flavones, potently quenched superoxide anion, hydroxyl radical, and hydrogen peroxide at the concentration of 20?µM with their scavenging rates in the range of 30.1–78.1%, 35.4–69.7%, and 65.5–86.3%, respectively. In contrast, AS5–6, two isoprenylated 2-arylbenzofurans, showed less effect than that exhibited by AS1–4.

Conclusion and discussion: The isoprenylated phenolics from A. styracifolius can potently inhibit PMA-induced respiratory burst in rat neutrophils without showing cytotoxicity. The inhibitory effects of these isoprenylated phenolics on the respiratory burst might depend on their different types of structure.     

高效液相色谱法测定脑栓康复浓缩丸三七中人参皂苷Rg1的含量

目的：建立脑栓康复浓缩丸中人参皂苷Rg1的含量测定方法。方法：采用反相高效液相色谱（RP-HPLC）法,色谱柱Di-amosil C18柱（4.6mm×250mm,5μm）,流动相为乙腈-0.1%磷酸溶液（20∶80）;检测波长为203nm,流速为1ml/min,进样量为20μl。结果：人参皂苷Rg1的线性范围1.77～17.70μg（r=0.9998）,平均加样回收率（N=6）100.30%,RSD 1.35%。结论：本法准确、简便,重复性好,可作为脑栓康复浓缩丸的质量控制方法。     

Is there an anti-androgen withdrawal syndrome for enzalutamide?

Background

The anti-androgen withdrawal syndrome (AAWS) can be seen in one-third of patients after discontinuation of first-generation non-steroidal anti-androgen therapy. With the introduction of new agents for anti-androgen therapy as well as alternate mechanisms of action, new therapeutic options before and after docetaxel chemotherapy have arisen (Ohlmann et al. in World J Urol 30(4):495–503, 2012). The question regarding the occurrence of an enzalutamide withdrawal syndrome (EWS) has not been evaluated yet. In this study, we assess prostate-specific antigen (PSA) response after discontinuation of enzalutamide.

Methods

In total 31 patients with metastatic castration-resistant prostate cancer (mCRPC) underwent an enzalutamide withdrawal and were evaluated. Data were gathered from 6 centres in Germany. Patients with continuous oral administration of enzalutamide with rising serum PSA levels were evaluated, starting from enzalutamide withdrawal until subsequent therapy was initiated, follow-up ended or death of the patient occurred. Statistical evaluation was performed applying one-sided binomial testing using R-statistical software, version 3.0.1.

Results

Mean withdrawal follow-up was 6.5 weeks (range 1–26.1 weeks). None of the 31 patients showed a PSA decline. Mean relative PSA rise over all patients was 73.9 % (range 0.5–440.7 %) with a median of 44.9 %.

Conclusions

If existent, an AAWS is at least very rare for enzalutamide in patients with mCRPC after taxane-based chemotherapy and does not play a clinical role in this setting. This may be attributed to the different pharmacodynamics of enzalutamide. Longer duration of therapy or a longer withdrawal interval may reveal a rare EWS in the future.     

成人髋关节发育不良不同Crowe分型的三维CT影像学特征

 目的 通过三维CT重建分析成人髋关节发育不良不同Crowe分型之间髋臼形态的演变规律。方法 2010年6月至2013年1月收治成人髋关节发育不良患者62例68髋,男6例8髋,女56例60髋;年龄47~59岁,平均（53.7±5.8）岁。CroweⅠ型14例17髋,Ⅱ型17例17髋,Ⅲ型15例17髋,Ⅳ型16例17髋。行标准髋关节CT扫描及三维重建。在侧位三维图像上标记Harris窝,确定髋臼旋转中心,利用十字坐标轴确定髋臼旋转中心的冠状面和横断面位置;在正位三维图像上利用Ranwant三角确定髋臼旋转中心的矢状面位置;在髋臼水平重建图像上确定髋臼旋转中心。观察髋臼前后缘增生及髋臼前后柱发育不良程度,测量并比较不同Crowe分型患者的髋臼前倾角、前覆盖角、后覆盖角和内壁宽度。结果 随Crowe分型增加,髋臼前倾角逐渐加大,两者呈正相关,除CroweⅠ型和Ⅱ型组间外,其余组间差异有统计学意义;髋臼前覆盖角逐渐减小,两者呈负相关,各组间差异均有统计学意义,CroweⅢ、Ⅳ型组平均值小于50°;髋臼后覆盖角逐渐减小,两者呈负相关,各组间差异均有统计学意义, CroweⅢ、Ⅳ型组平均值小于90° ;髋臼内壁宽度逐渐增加,两者呈正相关,各组间差异均有统计学意义。结论 不同Crowe分型成人髋关节发育不良的髋臼形态变化存在一定的演变规律。对CroweⅠ型和Ⅱ型髋臼的重建可充分利用髋臼前后柱骨量,对CroweⅢ、Ⅳ型髋臼的重建可适度上移和（或）内移髋臼中心。     

Efficacy of Anti-inflammatory Agents to Improve Symptoms in Patients With Schizophrenia: An Update

Background: The inflammatory hypothesis of schizophrenia is not new, but recently it has regained interest because more data suggest a role of the immune system in the pathogenesis of schizophrenia. If increased inflammation of the brain contributes to the symptoms of schizophrenia, reduction of the inflammatory status could improve the clinical picture. Lately, several trials have been conducted investigating the potential of anti-inflammatory agents to improve symptoms of schizophrenia. This study provides an update regarding the efficacy of anti-inflammatory agents on schizophrenic symptoms in clinical studies performed so far. Methods: An electronic search was performed using PubMed, Embase, the National Institutes of Health web site http://www.clinicaltrials.gov, Cochrane Schizophrenia Group entries in PsiTri, and the Cochrane Database of Systematic Reviews. Only randomized, double-blind, placebo-controlled studies that investigated clinical outcome were included. Results: Our search yielded 26 double-blind randomized controlled trials that provided information on the efficacy on symptom severity of the following components: aspirin, celecoxib, davunetide, fatty acids such as eicosapentaenoic acids and docosahexaenoic acids, estrogens, minocycline, and N-acetylcysteine (NAC). Of these components, aspirin (mean weighted effect size [ES]: 0.3, n = 270, 95% CI: 0.06–0.537, I² = 0), estrogens (ES: 0.51, n = 262, 95% CI: 0.043–0.972, I² = 69%), and NAC (ES: 0.45, n = 140, 95% CI: 0.112–0.779) showed significant effects. Celecoxib, minocycline, davunetide, and fatty acids showed no significant effect. Conclusion: The results of aspirin addition to antipsychotic treatment seem promising, as does the addition of NAC and estrogens. These 3 agents are all very broadly active substances, and it has to be investigated if the beneficial effects on symptom severity are indeed mediated by their anti-inflammatory aspects.Key words: add-on antipsychotic therapy, aspirin, N-acetylcysteine, estrogens     

2型糖尿病患者高同型半胱氨酸血症与早期肾脏疾病的相关性

目的探讨2型糖尿病(type 2 diabetes mellitus,T2DM)住院患者高同型半胱氨酸血症对早期肾脏疾病患病风险的影响。方法本研究为回顾性研究。选取南京江北医院2020年10月至2022年6月收住的T2DM患者306例。根据糖尿病肾脏疾病(diabetic kidney disease,DKD)诊断标准分为单纯T2DM组(n=252)和早期DKD组(n=54),比较两组临床资料。结果T2DM患者早期肾脏疾病患病率为17.6%。与单纯T2DM组相比,早期DKD组年龄较大、糖尿病病程较长、同型半胱氨酸水平较高、高同型半胱氨酸血症和高血压占比较大,差异有统计学意义(均P<0.05)。多因素Logistic回归分析显示,高同型半胱氨酸血症使T2DM患者早期肾脏疾病患病风险显著增加5.361倍(OR:6.361,95%CI:3.043-13.296,P<0.05),且同型半胱氨酸水平与T2DM早期肾脏疾病患病风险呈剂量-反应关系,同型半胱氨酸水平每增加1μmol/L,T2DM早期肾脏疾病患病风险增加14.1%(OR:1.141,95%CI:1.061-1.227,P<0.05)。结论T2DM患者高同型半胱氨酸血症显著增加早期肾脏疾病的患病风险,且同型半胱氨酸水平与早期肾脏疾病患病风险增加呈剂量-反应关系。     

Activation of extrasynaptic GABA. receptors inhibits cyclothiazide- induced epileptiform activity in hippocampal CA1 neurons

Extrasynaptic GABAA receptors （GABAARs）-mediated tonic inhibition is reported to involve in the patho- genesis of epilepsy. In this study, we used cyclo- thiazide （CTZ）-induced in vitro brain slice seizure model to explore the effect of selective activation of extrasynaptic GABAARS by 4,5,6,7-tetra- hydroisoxazolo[5,4-c] pyridine-3-ol （THIP） on the CTZ-induced epileptiform activity in hippocampal neurons. Perfusion with CTZ dose-dependently induced multiple epileptiform peaks of evoked population spikes （PSs）in CA1 pyramidal neurons, and treatment with THIP （5 μmol/L） significantly reduced the multiple PS peaks induced by CTZ stimulation. Western blot showed that the 6-subunit of the GABAAR, an extrasynaptic specific GABAAR subunit, was also significantly down-regulated in the cell membrane 2 h after CTZ treatment. Our results suggest that the CTZ-induced epileptiform activity in hippocampal CA1 neurons is suppressed by the activation of extrasynaptic GABAARs, and further support the hypothesis that tonic inhibition mediated by extrasynaptic GABAARs plays a prominent role in seizure generation.