银杏萜内酯类注射液治疗缺血性脑卒中疗效及安全性的系统评价

目的 系统性评价银杏萜内酯类注射液治疗缺血性脑卒中的疗效及安全性。方法 检索中国期刊全文数据库（CNKI）、维普中文科技期刊全文数据库（VIP）、中国生物医学文献数据库（CBM）、万方数据库、EMBASE、Pubmed和The Cochrane Library,检索截止日期为2017年12月。纳入银杏萜内酯类注射液治疗缺血性脑卒中的随机对照试验研究,采用RevMan5.2软件对临床疗效及神经功能缺损评分进行Meta-分析。结果 最终纳入临床研究13项,涉及患者1 330例。Meta-分析结果显示,银杏内酯注射液治疗缺血性脑卒中患者的临床疗效优于对照组[RR=1.14,95%CI（1.03,1.25）,Z=2.59,P=0.009];银杏内酯B注射液治疗缺血性脑卒中患者的临床疗效与对照组相当[RR=1.13,95%CI（0.95,1.33）,Z=1.36,P=0.17];银杏二萜内酯葡胺注射液治疗缺血性脑卒中患者的临床疗效优于对照组[RR=1.17,95%CI（1.08,1.27）,Z=3.69,P=0.0002];银杏内酯注射液改善缺血性脑卒中患者的神经功能缺损评分与对照组相当[MD=-0.43,95%CI（-4.32,3.46）,Z=0.22,P=0.83];银杏内酯B注射液改善缺血性脑卒中患者的神经功能缺损评分与对照组相当[[MD=-0.87,95%CI（-2.64,0.91）,Z=0.96,P=0.34];银杏二萜内酯葡胺注射液改善缺血性脑卒中患者的神经功能缺损评分优于对照组[MD=-1.62,95%CI（-2.63,-0.60）,Z=3.13,P=0.002];纳入研究均未报道银杏萜内酯类注射液引起严重不良反应。结论 银杏萜内酯类注射液治疗缺血性脑卒中患者可提高临床疗效、减少神经功能缺损,但缺乏临床意义证据。尚需更多高质量研究以增加证据的强度。     

头孢拉定不良反应的meta分析

目的 系统评价拉氧头孢及其对照药物在治疗感染时不良反应的发生率。方法 由2位研究者分别独立检索中国知网、万方数据库、维普期刊数据库、中国生物医学文献数据库、PubMed、Embase、Cochrane Library等数据库自建库至2018年3月有关头孢拉定及其不良反应的临床随机对照试验文献,严格按照纳入与排除标准筛选文献,评价文献质量并提取相关数据,采用RevMan 5.3软件进行meta分析,试验序贯分析（trial sequential analysis,TSA）软件进行TSA。结果 共纳入符合条件文献50篇,总计7 477例患者。Meta分析以及TSA结果显示：①头孢拉定组与对照组在不良反应发生率上差异具有统计学意义[RR=0.62,95%CI（0.54,0.72）,P<0.000 01]。②适应证亚组分析中呼吸道感染亚组中,头孢拉定组与对照组在不良反应发生率上差异具有统计学意义[RR=0.66,95%CI（0.53,0.80）,P<0.000 1],其他适应证因样本量过少未予分析。③对照药物亚组分析结果显示,头孢拉定组不良反应发生率高于阿奇霉素、头孢克肟、头孢克洛3组,而低于阿莫西林/克拉维酸组,仅阿奇霉素组差异具有统计学意义[RR=0.44,95%CI（0.28,0.70）,P=0.000 5],同时,TSA结果表明证据确切。④剂量亚组分析结果显示超剂量组[RR=0.70,95%CI（0.54,0.91）,P=0.008]与常规剂量组[RR=0.61,95%CI（0.52,0.71）,P≤0.000 01]不良反应发生率差异均具有统计学意义。结论 头孢拉定不良反应的发生率明显高于对照药物组,故临床用药时应严格按照说明规定用量进行用药,警惕其不良反应的发生。     

丹珍头痛胶囊治疗偏头痛疗效的Meta分析

目的 评价丹珍头痛胶囊治疗偏头痛的疗效及安全性。方法 检索中国生物医学文献数据库（CBM）、中国学术期刊全文数据库（CNKI）、维普中文科技期刊数据库（VIP）、万方数据库和Pubmed数据库有关丹珍头痛胶囊治疗偏头痛的随机对照试验（RCTs）,采用Modified Jadad评分量表对纳入文献进行质量评价,应用RevMan 5.3软件进行统计分析。结果 最终纳入9篇RCTs,共891例患者。Meta分析结果显示,丹珍头痛胶囊治疗偏头痛的总有效率高于西药组[RR=1.26,95%CI（1.19,1.35）],差异有统计学意义（P < 0.001）。亚组分析显示,单纯应用丹珍头痛胶囊比单纯使用常规西药总有效率更高[RR=1.28,95%CI（1.19,1.39）,P < 0.001],在常规西药基础上加用丹珍头痛胶囊可提高治疗的总有效率[RR=1.22,95%CI（1.10,1.36）,P=0.000 3],丹珍头痛胶囊治疗偏头痛总有效率高于盐酸氟桂利嗪[RR=1.26,95%CI（1.17,1.34）,P < 0.001]和加巴喷丁[RR=1.32,95%CI（1.10,1.57）,P=0.002],差异均有统计学意义（P < 0.05）。丹珍头痛胶囊组未见严重不良反应。结论 丹珍头痛胶囊治疗偏头痛的疗效可能优于常规西药,在常规西药基础上联合丹珍头痛胶囊可提高疗效。为提高结论的可靠性,尚需更多高质量、多中心、大样本的RCTs。     

壳聚糖对临床手术创面修复的Meta分析

目的评价壳聚糖对临床手术创面修复的有效性及安全性。方法检索Cochrane图书馆临床对照试验资料库（CCTR）,Medline、Embase、PubMed数据库,中国期刊全文数据库（CNKI）、万方数字化期刊全文库、中文科技期刊全文数据库（VIP）和中文生物医学期刊文献库（CMCC）,收集壳聚糖修复手术创面的随机对照临床试验,使用RevMan 5.0软件进行Meta分析。结果共纳入16项研究,3 414例患者。Meta分析结果显示：壳聚糖对手术创面修复的愈合时间明显短于对照组[WMD=-0.64,95%CI（-0.69~-0.59）,P<0.000 01],且能更好地促进切口愈合[RR=1.03,95%CI（1.01~1.04）,P=0.0002];明显减轻术后疼痛[WMD=-3.49,95%CI（-5.07~-1.91）,P<0.000 1];减少术后感染[RR=0.49,95% CI：0.33~0.71,P=0.000 2]。结论壳聚糖能缩短术后伤口愈合时间,更好地促进伤口愈合,减轻疼痛,减少感染;但纳入的研究质量均不高,仍亟需更多高质量的临床试验进一步验证壳聚糖对临床手术后创面修复的有效性和安全性。     

中国人群予以不同剂量阿替普酶治疗急性缺血性脑卒中的Meta-分析

目的 系统评价中国人群分别予以标准剂量（0.9 mg/kg）和低剂量（0.6 mg/kg）阿替普酶治疗急性缺血性脑卒中的临床疗效和安全性,为临床提供循证医学证据。方法 计算机检索EMbase、PubMed、中国生物医学文献数据库（CBM）、中国学术期刊全文数据库（CNKI）、维普中文科技期刊数据库（VIP）和万方数据库,收集急性缺血性脑卒中患者分别采用标准剂量和低剂量阿替普酶静脉溶栓的随机对照研究（RCT）,检索时限均为建库—2018年3月,提取数据后采用RevMan 5.2软件进行Meta-分析。结果 共纳入16个RCTs,1 745例患者。Meta-分析结果显示：标准剂量组在总有效率（RR=0.95,95%CI=0.92~0.99,P=0.01）、降低NIHSS评分（SMD=0.27,95%CI=0.14~0.40,P<0.001）、提高预后良好率（RR=0.85,95%CI=0.78~0.92,P=0.000 2）和降低脑出血率（RR=0.59,95%CI=0.38~0.92,P=0.02）方面均优于低剂量组,差异均有统计学意义（P<0.05）,但是病死率（RR=1.23,95%CI=0.84~1.80,P=0.28）差异无统计学意义。结论 现有证据表明,标准剂量阿替普酶静脉溶栓具有更好的临床疗效,但可能增加溶栓后脑出血的风险,临床医务人员应予以重点关注。     

万古霉素静脉滴注联用鞘内注射治疗颅内感染的Meta分析

目的 评价万古霉素静脉滴注联用鞘内注射治疗颅内感染的有效性和安全性。方法 检索2000年1月-2017年5月PubMed、中国知网（CNKI）、万方数据库、维普全文数据库（VIP）中的数据,收集万古霉素静脉滴注联用鞘内注射治疗颅内感染的临床随机对照研究（RCT）,采用RevMan 5.2软件进行Meta分析。结果 共纳入9项RCTs,469例患者。Meta分析结果显示：相对于万古霉素静脉滴注,联用鞘内注射能显著提高临床治愈率[RR=0.70,95%CI（0.61,0.81）,P < 0.001]和耐甲氧西林金黄色葡萄球菌清除率[RR=0.90,95%CI（0.81,1.00）,P=0.04],缩短治愈时间[SMD=3.26,95%CI（2.84,3.68）,P < 0.001];两组不良反应发生率无统计学差异[RR=0.73,95%CI（0.35,1.49）,P=0.38],但中枢神经根刺激症发生率较大[RR=0.05,95%CI（0.00,0.92）,P=0.04]。结论 万古霉素静脉滴注联用鞘内注射治疗颅内感染疗效确切,安全性好。     

丁苯酞软胶囊治疗进展性卒中的系统评价

目的 系统评价丁苯酞软胶囊治疗进展性卒中的疗效和安全性。方法 检索Cochrane图书馆、万方、CNKI等数据库收集关于丁苯酞治疗进展性卒中的随机对照试验（randomized controlled trials，RCTs），时间截至2018年12月，根据明确的纳入与排除标准筛选相关研究，采用RevMan 5.3软件进行统计分析。结果 共纳入26个RCTs（2 519例患者），meta分析结果示，与对照组比较，丁苯酞治疗进展性卒中疗效更好（RR=1.23，95%CI 1.17~1.29，P<0.000 01）；丁苯酞治疗进展性卒中在神经功能缺损评分（The National Institutes of Health Stroke Scale，NIHSS）（MD=-3.01，95%CI -3.49~-2.52，P<0.000 01）、卒中评分量表（Chinese Stroke Scale，CSS）评分（MD=-3.39，95%CI -4.70~-2.08，P<0.000 01）及日常生活活动能力评分量表（Barthel Index，BI）评分（MD=9.84，95%CI 6.06~13.62，P<0.000 01）改善方面均优于对照组，差异有统计学意义。2组在不良反应方面差异无统计学意义（RR=1.27，95%CI 0.50~3.18，P=0.61）。结论 丁苯酞软胶囊能有效改善进展性卒中患者的神经功能，且不增加不良反应。     

前列腺癌去势疗法与糖尿病相关性的Meta分析

目的 探讨去势疗法是否会增加前列腺癌（PCa）患者罹患糖尿病的风险。方法 系统检索Medline、Embase、Cochrane Library Central关于去势疗法（ADT）应用于PCa并报道该治疗与糖尿病相关性的临床试验研究,对文献进行数据提取及Meta分析。结果 共8项临床研究,涉及65 695名应用ADT及91 893名未应用去势疗法（non-ADT）的PCa患者纳入分析。应用ADT的患者其糖尿病的发病率较non-ADT者高出39%[RR=1.39,95%CI（1.27~1.53）,P<0.01];亚组分析发现,不同的ADT对糖尿病发病率亦有不同的相关性,促雄性激素释放激素抑制剂能明显增加PCa患者罹患糖尿病的风险[RR=1.45,95%CI（1.36~1.54）,P<0.01];促雄性激素释放激素抑制剂联合口服抗雄性激素药物[RR=1.40,95%CI（1.01~1.93）,P<0.01],以及睾丸切除术也可明显增加糖尿病患病的风险[RR=1.34,95%CI（1.20~1.50）,P<0.01],而单纯服用抗雄性激素的药物则与糖尿病无明显相关性[RR=1.33,95%CI（0.75~2.36）,P=0.33]。结论 ADT可明显增加PCa罹患糖尿病的风险,提示临床应用该疗法需考虑采取相应的预防措施。     

质子泵抑制剂治疗功能性消化不良的Meta-分析

目的 系统评价质子泵抑制剂（PPI）治疗功能性消化不良的临床疗效和安全性。方法 计算机检索Pubmed、Embase、Central、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）和万方数据库,收集PPI治疗功能性消化不良的随机对照试验（RCT）,检索时限均从建库至2017年9月30日,并同时追溯纳入研究的参考文献。由两名研究者根据纳入和排除标准独立进行文献筛选、资料提取、质量评价并交叉核对后,采用RevMan 5.3和R软件进行Meta-分析。结果 最终纳入15个RCTs,共6 350例患者（试验组4 266例,对照组2 084例）。Meta-分析结果显示：PPI与安慰剂组相比,在综合疗效[RR=1.27,95%CI（1.12,1.44）,P=0.000 2]和整体症状完全缓解[RR=1.42,95%CI（1.13,1.80）,P=0.003]方面,两组差异有统计学意义,而在不良反应发生率[RR=1.18,95%CI（0.97,1.43）,P=0.09]方面,差异无统计学意义。而PPI对亚洲国家功能性消化不良患者未显示出优势[RR=1.26,95%CI（0.80,1.97）,P=0.32]。结论 PPI能提高功能性消化不良的综合疗效和整体症状完全缓解率,与安慰剂比较安全性相当。受纳入研究样本量和质量的限制,PPI对亚洲国家功能性消化不良患者的疗效有待大样本、高质量的RCT进一步验证。     

鼠神经生长因子联合神经节苷脂治疗新生儿缺氧缺血性脑病的Meta-分析

目的 系统评价鼠神经生长因子联合神经节苷脂治疗新生儿缺氧缺血性脑病（HIE）的疗效和安全性。方法 计算机检索中国期刊全文数据库（CNKI）、维普中文科技期刊全文数据库（VIP）、中国生物医学文献数据库（CBM）、万方数据库、PubMed、EMbase等数据库,收集鼠神经生长因子联合神经节苷脂治疗新生儿HIE的随机对照研究,提取资料并评价质量后,采用RevMan 5.1软件进行Meta-分析。结果 共纳入8篇文献,716例患儿;Meta-分析结果显示,与单用神经节苷脂比较,鼠神经生长因子联合神经节苷脂：显著提高临床有效率[RR=1.32,95%CI（1.22,1.43）,P<0.01]和NBNA评分[MD=4.00,95%CI（3.54,4.46）,P<0.01];显著缩短意识恢复时间[MD=-1.74,95%CI（-2.44,-1.04）,P<0.01]、惊厥消失时间[MD=-1.47,95%CI（-1.88,-1.06）,P<0.01]、肌张力恢复时间[MD=-2.73,95%CI（-3.19,-2.28）,P<0.01]和反射恢复时间[MD=-2.57,95%CI（-3.32,-1.82）,P<0.01];显著降低血清神经元特异性烯醇化酶（NSE）[MD=-5.04,95%CI（-6.26,-3.82）,P<0.01]和血管内皮生长因子（VEGF）[MD=-29.63,95%CI（-33.11,-26.16）,P<0.01];显著提高智力发育指数（MDI）[MD=8.87,95%CI（7.92,9.82）,P<0.01]和心理运动发育指数（PDI）[MD=9.89,95%CI（8.52,11.27）,P<0.01]。结论 鼠神经生长因子联合神经节苷脂对新生儿HIE受损脑神经元及神经胶质细胞神经元功能具有协同修复作用,与协同降低血清NSE和VEGF水平有关。     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

Effects of Nitro-L-Arginine on Blood Pressure and Cardiac Index in Anesthetized Rats: A Pharmacokinetic-Pharmacodynamic Analysis

Purpose. Nitric oxide synthase (NOS) inhibitors such as Nitro-L-arginine (L-NA) are being considered for the management of hypotension observed in septic shock. However, little information is available regarding the pharmacokinetic and pharmacodynamic properties of these agents. Our objective was to examine the relationships between L-NA plasma concentration and various hemodynamic effects such as cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) elicited by L-NA administration in rats. Methods. L-NA was infused at doses between 2.5 – 20 mg/kg/hr in anesthetized rats over one hour. Hemodynamic effects and plasma L-NA levels were determined. Results. Infusion of L-NA resulted in dose-dependent increases in MAP and systemic vascular resistance (SVR), decreases in CI, and minimal change in HR. The relationships between the hemodynamic effects and plasma L-NA levels were not monotonic, and hysteresis was observed. Using nonparametric analysis, the equilibration half-time (t_1/2,keo) between plasma L-NA and the hypothetical effect site was determined to be 51.5 ± 6.6 min, 42.4 ± 10.1 min, 43.4 ± 9.0 min for MAP, CI, and SVR, respectively (n = 14). The E_max and EC₅₀ values obtained were + 32.5 ± 8.4 and 2.6 ± 1.3 g/ml for MAP and –52.9 ± 15.6 and 3.7 ± 1.8 g/ml for CI, respectively. Conclusions. Although L-NA can bring about beneficial elevation of MAP, such effect is always accompanied by a stronger effect on CI depression. Dose escalation of L-NA may bring about detrimental negative inotropic effect and loss of therapeutic efficacy.     

The pathogenesis of,and pharmacological treatment for,Canavan disease

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HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

洛美沙星体内外抗菌活性研究

洛美沙星对革兰氏阴性菌具有强的抑菌活力。对克氏肺炎杆菌的抗菌活性最强,MIC_(50)为0.12mg/L;对痢疾杆菌、产气杆菌、粘质沙雷氏菌、不动杆菌和枸椽酸杆菌的MIC_(50)分别为1和4mg/L。洛美沙星对肠细菌科细菌的活力比诺氟沙星和依诺沙星强2～16倍,明显地比丁胺卡那霉素、庆大霉素强。对金葡球菌MIC_(50)为1mg/L, MRSA对洛美沙星同样敏感。洛美沙星对表葡球菌、链球菌、粪链球菌及肺炎双球菌等的抗菌活性与地氟沙星相似,比诺氟沙星、依诺沙星、丁胺卡那霉素、庆大霉素和头孢三嗪分别强2～4倍。 洛美沙星对小鼠全身感染的疗效优于诺氟沙星。对大肠杆菌、克氏肺炎杆菌和绿脓杆菌感染小鼠iv的ED_(50)分别是0.74、0.13和3.45mg/kg, po的ED_(50)分别是0.94、1.46和6.20mg/kg。     

乙酰吉他霉素临床前药理学研究

乙酰吉他霉素对临床分离的革兰氏阳性球菌有较好的抑菌活力，其对金葡球菌、β－溶血性链球菌、表葡球菌的ＭＩＣ_（５０）分别为１、０．２２和４ｍｇ／Ｌ，对耐红霉素、青霉素的金葡球菌、表葡球菌半数以上较敏感，与吉他霉素相似，但其对革兰氏阴性菌无明显作用。乙酰吉他霉素对小鼠实验性细菌感染有明显保护作用。对金葡球菌、肺炎双球菌感染小鼠口服用药的ＥＤ_（５０）分别为７９．６和２５．１ｍｇ／ｋｇ。其疗效与吉他霉素、麦白霉素、乙酰螺旋霉素相似。乙酰吉他霉素小鼠１次口服的ＬＤ_（５０）＞１５ｇ／ｋｇ，与吉他霉素相比毒性无差异。     

大鼠溃疡性结肠炎模型的实验研究

目的对不同剂量的三硝基苯磺酸（ＴＮＢＳ）引起的大鼠溃疡性结肠炎（ＵＣ）模型进行观察和评价。方法采用一次性直肠注入大鼠ＴＮＢＳ（２５～１５０ｍｇ·ｋｇ－１）的３０％乙醇溶液，引起慢性炎症性肠疾病（ＩＢＤ），３ｗｋ后外死动物对各剂量下动物结肠的重量、髓过氧化物酶（ＭＰＯ）活性及组织形态学变化进行观察和评价。结果ＴＮＢＳ在１００～１５０ｍｇ·ｋｇ－１剂量下引起的ＵＣ肠壁明显增厚，炎症和溃疡至少维持７ｗｋ时间，ＭＰＯ活性值显著性升高，组织学检查发现粘膜及粘膜下层有大量中性粒细胞及淋巴细胞、巨噬细胞、纤维细胞浸润，肉芽组织及隐窝脓肿形成，５０ｍｇ·ｋｇ－１剂量时有一较轻度的损伤。２５ｍｇ·ｋｇ－１时对结肠的重量、ＭＰＯ活性及损伤指数都没有显著性改变（Ｐ＞０．０５）。结论用ＴＮＢＳ引起大鼠实验性ＵＣ，其溃疡和炎症维持一较长时间，这一病理特征为炎症性疾病防治药物的研究提供了条件；本模型的最佳剂量为１００ｍｇ·ｋｇ－１左右     

Protective role of exogenous α-lipoic acid (ALA) on hippocampal antioxidant status and memory function in rat pups exposed to sodium arsenite during the early post-natal period

The present work focussed on the effect of exogenous α-lipoic acid (ALA) administration on retention memory and oxidative stress markers in the hippocampus subsequent to early post-natal exposure of rat pups to sodium arsenite (NaAsO₂). Wistar rat pups were divided into the control groups receiving either no treatment (Ia) or distilled water by intraperitoneal route (i.p.) (Ib) and the experimental groups receiving either NaAsO₂ alone (1.5 and 2.0?mg/kg body wt.) (IIa, IIb) or NaAsO₂ (1.5 and 2.0?mg/kg body wt.) followed by ALA (70?mg/kg body wt.) (IIIa, IIIb) (i.p.) from post-natal day (PND) 4–15. The initial and retention transfer latency (ITL and RTL) was determined on PND 14 and 15 using elevated plus maze. The animals were sacrificed by cervical decapitation (PND 16) and the brains were obtained. The dissected out hippocampus was processed for estimation of oxidative stress markers, glutathione (GSH), and superoxide dismutase (SOD). NaAsO₂ exposure resulted in longer RTL in animal groups IIa and IIb, thereby suggestive of arsenic-induced impairment in retention memory. RTL was significantly shorter in animal groups (IIIa, IIIb) receiving ALA following NaAsO₂, thereby suggestive of improvement in retention memory. GSH and SOD levels were significantly decreased in animals receiving NaAsO₂ alone as against group Ib and administration of ALA following NaAsO₂ increased the levels of hippocampal GSH and SOD. These observations are suggestive of the role of exogenous ALA in ameliorating the adverse effects induced by NaAsO₂ exposure of rat pups on retention memory and oxidative stress markers.     

Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications

Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.     

Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications

Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aβ_1-42 and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aβ accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aβ accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aβ clearance.