前列腺素E1对梗阻性黄疸大鼠肝脏缺血再灌注损伤时白介素-1β表达的影响

目的:探讨前列腺素(PG)E1对梗阻性黄疸肝脏缺血再灌注损伤的保护作用以及对IL-1β表达的影响.方法:将♂Wistar大鼠随机分为PGE1处理组(PG组,n=18)和生理盐水对照组(NS组,n=18).参照Yoshidome法结扎并切断胆总管建立梗阻性黄疸模型,1 wk后Pringle法阻断肝门15 min,再灌注后建立胆道再通.于缺血前15 min至再灌注60 min,PG组经门静脉持续泵入PGE1 0.5 μg/(kg·min),NS组给予等量生理盐水.于再灌注1、6和24 h 3个时点取材,检测血清ALT,AST,总胆红素(total bilirubin,TBIL),直接胆红素(direct bilirubin,DBIL)水平,测定肝组织GSH,MDA含量.ELISA法测定肝组织IL-1β表达,并观察肝脏病理组织学改变.结果:再灌注各时点PG组血清ALT水平(1 h:1939±1427 nkat/L vs 5596±2975 nkat/L;6 h:3409±1708 nkat/L vs 9279±4404 nkat/L;24 h:1434±274 nkat/L vs 2264±630 nkat/L)和AST(1 h:21746±12083 nkat/L vs 37552±12382 nkat/L;6 h:55039±35471 nkat/L vs 98811±11126 nkat/L;24 h:9394±1662nkat/L vs 27664±15856 nkat/L)、肝组织MDA含量(1 h:0.89±0.18 μmol/g vs 1.21±0.24 μmol/g;6 h:1.08±0.23 μmol/g vs 1.45±0.13 μmol/g;24 h:1.03±0.08 μmol/g vs 1.45±0.26 μmol/g)以及肝组织IL-1β表达水平(1 h:304.1±67.9 ng/L vs 362.8±137.1 ng/L;6 h:376.8±74.6 ng/L vs 618.8±217.8 ng/L;24 h:273.0±69.0 ng/L vs 373.0±71.7 ng/L)均显著低于NS组(P＜0.05),而肝组织GSH含量显著高于NS组(1 h:945.1±121.2 mg/g vs 720.0±80.1 mg/g;6 h:753.5±118.6 mg/g vs 553.6±140.0 mg/g;24 h:768.0±135.9 mg/g vs 596.3±36.4 mg/g,P＜0.05),但两者胆红素水平无明显差异(P＞0.05).PG组肝脏病理组织学损伤程度也较NS组明显减轻.结论:PGE1下调肝组织IL-1β表达,对梗阻性黄疸肝脏缺血再灌注损伤具有保护作用.     

实验性肝损伤大鼠肝脏HO-1的表达及CO水平变化

目的研究急性肝损伤时大鼠肝脏HO-1的表达情况和CO水平,探讨HO-1和内源性CO在大鼠急性肝损伤中的作用.方法制备急性四氯化碳肝损伤模型,采用RT-PCR和免疫组化法测定不同时间点大鼠肝脏HO-1 mRNA和蛋白的表达情况;测定各时间点肝组织SOD、MDA含量变化,同时测定股静脉血中HbCO水平和ALT、AST肝功能指标.结果HO-1mRNA在正常大鼠有弱表达,染毒3 h后表达显著增强,于24 h时间点表达最强,与对照组相比差异非常显著(P＜0.01);免疫组化结果显示;HO-1蛋白在正常大鼠表达较低或无,染毒3h后即有明显表达,16至48h的时间点内表达均显著增强,主要定位于肝实质细胞、库普细胞的胞浆内.对照组HbCO水平极低,给予四氯化碳3 h后HbCO水平开始升高,此后各时间点均明显高于对照组,差异有显著性,这与HO-1表达情况相一致.此外,染毒后大鼠血清ALT、AST和MDA明显升高,SOD活性则显著降低,和对照组相比差异均十分显著.结论大鼠急性肝损伤后出现HO-1表达持续上调和血中CO水平迅速增高,提示HO/CO系统参与急性肝损伤的病理生理过程,其表达增加可能对机体有重要调节作用.     

番石榴叶提取物对三硝基苯磺酸诱导大鼠结肠炎结肠组织的保护作用

目的:研究番石榴叶提取物对大鼠结肠炎组织损伤的保护作用及其机制.方法:用健康Wistar大鼠建立大鼠结肠炎模型,灌胃用药2 wk后,评价大鼠结肠黏膜损伤指数(CMDI),检测结肠组织髓过氧化物酶(MPO)及超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和细胞肿瘤因子(TNF)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)水平.结果:不同剂量番石榴叶提取物(200,500,800 mg/kg)灌胃均能不同程度降低模型大鼠CMDI(2.62±0.47,2.06±0.54,1.83±0.43 vs 3.15±0.39,P＜0.05,P＜0.01,P＜0.01),MPO活性(2240.78±479.26,2078.42±377.91,1748.85±236.71 nkat/g vs 2695.37±624.79 nkat/g P＜0.05,P＜0.01,P＜0.01),减少MDA含量(2.16±0.41,1.97±0.35,1.96±0.30,P＜0.05,P＜0.01,P＜0.01),提高SOD活性(3618.06±538.44,3756.92±577.45,4197.51±375.74 nkat/g vs 2663.37±603.79,P＜0.05,P＜0.01,P＜0.01),降低TNF(2.65±0.40,2.51±0.47,2.21±0.41 μg/L vs 3.30±0.63 μg/L,P＜0.05,P＜0.01,P＜0.01)、IL-8(1.20±0.33,1.05±0.24,0.92±0.13 μg/L vs 1.53±0.38 μg/L,P＜0.05,P＜0.01,P＜0.01)、IL-10(39.36±9.65,50.26±11.32.59.68±13.65 ng/L vs 30.74±12.91 ng/L,P＜0.05,P＜0.01,P＜0.01)水平,且与用药剂量呈一定量效关系.结论:番石榴叶提取物通过拮抗氧化、免疫调节、损伤修复作用缓解结肠炎大鼠炎症反应,减轻结肠损伤.     

乌司他丁对急性肝功能衰竭大鼠肝组织中血红素加氧酶-1 mRNA和蛋白表达的影响

目的 探讨乌司他丁对急性肝功能衰竭的保护作用及对血红素加氧酶-1(hemeoxygenase-1,HO-1)的影响.方法 66只S-D大鼠分为对照组、模型组和乌司他丁干预组,通过腹腔注射D-氨基半乳糖(D-Gal)及脂多糖(LPS)建立大鼠急性肝功能衰竭模型,动态观察(6、12、24、36和48 h)大鼠血清ALT、AST和丙二醛(MDA)含量变化,RT-PCR检测肝脏HO- mRNA变化,免疫组织化学方法检测HO-1蛋白表达.多组间差异比较采用单因素方差分析,两两比较采用LSD法.结果 D-Gal/LPS联合注射成功诱导大鼠急性肝功能衰竭模型,表现为造模6 h后血清ALT、AST水平以及肝组织MDA浓度均显著升高(F值分别为23.864、38.446、18.051,均P＜0.01),以12至24 h之间最为显著.造模24 h后,模型组与干预组ALT、AST、MDA分别达到(8 346.7±1 363.1)U/L、(9 766.7±1 274.1)U/L、(8.34±1.13)μmol/g与(4 151.3±970.0)U/L、(4 696.7±1 476.9)U/L、(4.66±0.91)μmol/g,均较对照组的(24.0±2.0)U/L、(82.3±16.9)U/L、(2.55±0.22)μmol/g高(F值分别为55.684、55.501、47.843,均P＜0.01),但干预组显著低于模型组(P＜0.01);与对照组相比,模型组HO-1 mRNA及其蛋白表达增加(P＜0.01),干预组的上升更加显著(P＜0.01).结论 乌司他丁能上调HO-1 mRNA和蛋白表达,提示乌司他丁可能通过HO-1通路发挥其在急性肝功能衰竭中抗炎抗氧化的保护作用.     

HO-1诱导对大鼠急性肝损伤的保护作用及其机制

目的研究诱导HO-1高表达对大鼠急性肝损伤的保护作用及其机制探讨。方法随机将大鼠分成4组,即正常对照组、四氯化碳染毒组（CCl4）、血晶素（hemin）组、hemin＋CCl4组。采用western blot法测定HO-1蛋白的诱导表达情况：测定各组大鼠血清ALT、AST水平,肝组织MDA浓度和SOD活性以及Caspase-3活性和TNF-α水平变化;HE染色观察肝组织病理形态学改变。结果CCl4成功诱导了大鼠急性肝损伤,表现为染毒24 h后血清ALT、AST水平以及肝组织MDA浓度、Caspase-3活性和TNF-α水平均显著升高,SOD活性下降,和正常对照组相比差异有统计学意义（P〈0.01）;病理学检测结果显示肝脏有严重损伤,大量肝细胞发生凋亡。给予hemin预处理能显著诱导大鼠肝脏HO-1的表达,并对肝脏产生明显的保护作用,表现为大鼠血清ALT、AST水平和MDA浓度明显降低,SOD活性升高,组织TNF-α水平和Caspase-3活性明显低于CCl4组;此外,hemin预处理亦使染毒大鼠的病理学指标得到明显改善。结论HO-1诱导表达对急性肝损伤大鼠产生明显的保护作用,提示HO-1在防治急性肝损伤的病理生理过程中占有重要地位;HO-1的保护机制可能与其减轻脂质过氧化反应,抑制Caspase-3活性和降低TNF-α水平有关。     

小檗碱对胰岛素抵抗大鼠肝脏葡萄糖激酶及其调节蛋白的影响

目的:研究小檗碱对胰岛素抵抗大鼠肝脏葡萄糖激酶(GK)活性及肝脏GK与葡萄糖激酶调节蛋白(GKRP)表达的影响.方法:选用♂Wistar大鼠,以高脂高热量饲料喂养8 wk,复制胰岛素抵抗大鼠模型,成模后随机分成模型组、小檗碱组、二甲双胍组,各药干预4 wk后,比较各组大鼠胰岛素敏感性、肝糖原、肝脏GK活性、肝脏GK与GKRP蛋白(Western blot法)表达的差异.结果:比模型组比较,小檗碱组胰岛索敏感性提高(-4.93±0.30 vs-5.35±0.40,P＜0.05),肝糖原含量明显升高(136.58±52.57 μg/g vs 65.88±27.80 μg/g,P＜0.05),肝脏GK活性升高(226.55±10.62 μkat/g vs 92.69±6.43 μkat/g,P＜0.05),肝脏GK蛋白表达增强(1.71±0.49 vs 1.24±0.22,P＜0.05),而GKRP表达减弱(1.19±0.20 vs 1.94±0.56,P＜0.01);与二甲双胍组比较,小檗碱组肝糖原含量高(136.584±52.574 μg/g vs 89.427±31.97l μg/g,P＜0.05),余指标无显著性差异(P＞0.05).结论:小檗碱改善胰岛素抵抗的作用机制可能与提高肝脏GK活性有关.     

无机砷对Chang liver细胞血红素单加氧酶-1表达的活化作用

目的 观察无机砷(NaAsO2)对正常人肝细胞株Changliver细胞血红素单加氧酶-1(heme oxygenase-1,HO-1)表达的活化作用.方法 采用细胞培养的方法,将Chang liver细胞分别暴露于10 μmol/L NaAsO2后0(对照)、2、6、12、24 h和0(对照)、5、10、25、50 μmol/L后12 h,收集细胞,Western blot技术检测细胞内HO-1蛋白的表达.结果 Chang liver细胞染砷10 μmol/L.体外培养6、12、24 h,细胞内HO-1蛋白表达(3.97±0.72、12.92±2.98、23.29±3.82)明显高于对照组(1.00±0.00).组问比较和各组分别与对照组比较.差异有统计学意义(F=85.83,P＜0.01;t值分别为-9.42、-8.95、-13.83,P＜0.05或＜0.01).染砷5、10、25、50 μmo]/L.体外培养12 h,细胞内HO-1蛋白表达(6.34±0.25、7.75±0.39、7.93±0.14、12.48±-0.35)明显高于对照组(1.00±0.00),组间比较和各组分别与对照组比较,差异有统计学意义(F=709.66,P＜0.01;t值分别为-36.25、-30.19、-86.40、-56.40,P＜0.01).结论 无机砷能够诱导Chang Liver细胞内HO-1的活化,促进蛋白表达,并且具有时间和剂量效应.     

肿瘤坏死因子-α、细胞间黏附分子-1与扑热息痛肝损害

目的:探讨肿瘤坏死因子-α(TNF-α)、细胞间黏附分子-1(ICAM-1)在扑热息痛肝损害中的作用.方法:应用扑热息痛(AAP)建立Sprague Dawley(SD)大鼠肝损害模型;分别于给药后3、6、12、24 h处死大鼠,AAP组和对照组分别测定ALT水平,HE染色光镜下观察肝脏病理的改变,放射免疫分析法测定血清TNF-α水平、RT-PCR方法检测肝组织ICAM-1mRNA的表达.结果:AAP组给药后24 h血清TNF-α(μg/L)水平显著高于对照组(5.69±0.46vs2.64±0.27,P＜0.01),且与血清ALT水平呈显著的正相关(r=0.773,P＜0.01),肝组织ICAM-1 mRNA表达在各时间点均显著高于对照组(3、6、12、24 h的值分别为:1.58±0.21vs0.62±0.05,1.24±0.09 vs0.63±0.04,0.88±0.08vs 0.32±0.06,0.55±0.14 vs 0.28±0.03,P＜0.01),于3 h达高峰,24 h时仍高于正常水平,同时血清ALT(nkat/L)进行性升高(3、6、12、24 h的值分别为:1166.90±151.03vs586.78±89.35.2153.84±254.55vs573.45±75.18,4220.84±928.52vs750.15±81.68,13202.64±1392.78 vs 780.16±161.37,P＜0.01)和肝脏病理损伤进行性加剧,于24h达高峰.结论:TNF-α、ICAM-1在扑热息痛肝损害的发生、发展过程中发挥着关键作用.     

缺血预处理对高原大鼠肝脏缺血/再灌注损伤早期的影响

目的:了解在高原缺血预处理(IPC)对肝脏缺血/再灌注损伤(I/R)早期保护作用及其机制.方法:SD大鼠45只随机分为3组:假手术组、缺血再灌注组、缺血预处理组.各组恢复血流后分别于1,3,6 h取血液标本,检测血清ALT(nkat/L)、丙二醛(MDA,mmol/L)、NO(μmol/L)的含量.结果:缺血预处理组NO的水平明显高于缺血再灌注组(1 h:95.8±10.1 vs 64.2±6.8,P＜0.01;3 h:91.2±9.7 vs 69.5±7.2,P＜0.01;6 h:77.4±8.6 vs 63.7±6.1,P＜0.01),低于假手术组;而ALT(1 h:2257.1±201.7 vs 2912.2±398.4,P＜0.01;3 h:2465.5±243.4 vs 3637.4±441.8,P＜0.01;2545.5±223.4 vs 4027.5±496.8,P＜0.01)、MDA(1 h:25.1±4.3 vs 38.7±7.6,P＜0.01;3 h:27.5±5.4 vs 45.3±8.8,P＜0.01;34.2±6.7 vs 53.2±10.5,P＜0.01)明显低于缺血再灌注组,高于假手术组.结论:在高原缺氧环境下,缺血预处理对大鼠肝脏缺血再灌注损伤有明显保护作用,其机制可能与缺血与预处理抑制肝脏脂质过氧化物的产生,提高内源性NO的产生,改善肝脏的微循环有关.     

前列腺素E1对梗阻性黄疸大鼠肝脏缺血再灌注损伤时白介素-1β表达的影响

目的: 探讨前列腺素(PG)E1对梗阻性黄疸肝脏缺血再灌注损伤的保护作用以及对IL-1beta表达的影响. 方法: 将♂Wistar大鼠随机分为PGE1处理组(PG组, n = 18)和生理盐水对照组(NS组, n = 18). 参照Yoshidome法结扎并切断胆总管建立梗阻性黄疸模型, 1 wk后Pringle法阻断肝门15 min, 再灌注后建立胆道再通. 于缺血前15 min至再灌注60 min, PG组经门静脉持续泵入PGE1 0.5 mug/(kg·min), NS组给予等量生理盐水. 于再灌注1、6和24 h 3个时点取材, 检测血清ALT, AST, 总胆红素(total bilirubin, TBIL), 直接胆红素(direct bilirubin, DBIL)水平, 测定肝组织GSH, MDA含量. ELISA法测定肝组织IL-1beta表达, 并观察肝脏病理组织学改变. 结果: 再灌注各时点PG组血清ALT水平(1 h: 1939±1427 nkat/L vs 5596±2975 nkat/L; 6 h: 3409±1708 nkat/L vs 9279±4404 nkat/L; 24 h: 1434±274 nkat/L vs 2264±630 nkat/L)和AST(1 h: 21746±12083 nkat/L vs 37552±12382 nkat/L; 6 h: 55039±35471 nkat/L vs 98811±11126 nkat/L; 24 h: 9394±1662 nkat/L vs 27664±15856 nkat/L)、肝组织MDA含量(1 h: 0.89±0.18 mumol/g vs 1.21±0.24 mumol/g; 6 h: 1.08±0.23 mumol/g vs 1.45±0.13 mumol/g; 24 h: 1.03±0.08 mumol/g vs 1.45±0.26 mumol/g)以及肝组织IL-1beta表达水平(1 h: 304.1±67.9 ng/L vs 362.8±137.1 ng/L; 6 h: 376.8±74.6 ng/L vs 618.8±217.8 ng/L; 24 h: 273.0±69.0 ng/L vs 373.0±71.7 ng/L)均显著低于NS组(P<0.05), 而肝组织GSH含量显著高于NS组(1 h: 945.1±121.2 mg/g vs 720.0±80.1 mg/g; 6 h: 753.5±118.6 mg/g vs 553.6±140.0 mg/g; 24 h: 768.0±135.9 mg/g vs 596.3±36.4 mg/g, P<0.05), 但两者胆红素水平无明显差异(P>0.05). PG组肝脏病理组织学损伤程度也较NS组明显减轻. 结论: PGE1下调肝组织IL-1beta表达, 对梗阻性黄疸肝脏缺血再灌注损伤具有保护作用.     

Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo

Pyronaridine is a Mannich base anti-malarial with demonstrated efficacy against drug resistant Plasmodium falciparum, P. vivax, P. ovale and P. malariae. However, resistance to pyronaridine can develop quickly when it is used alone but can be considerably delayed when it is administered with artesunate in rodent malaria models. The aim of this study was to evaluate the efficacy of pyronaridine in combination with artesunate against P. falciparum in vitro and in rodent malaria models in vivo to support its clinical application. Pyronaridine showed consistently high levels of in vitro activity against a panel of six P. falciparum drug-sensitive and resistant strains (Geometric Mean IC50=2.24 nM, 95% CI=1.20-3.27). In vitro interactions between pyronaridine and artesunate showed a slight antagonistic trend, but in vivo compared to pyronaridine and artesunate administered alone, the 3:1 ratio of the combination, reduced the ED90 of artesunate by approximately 15.6-fold in a pyronaridine-resistant P. berghei line and by approximately 200-fold in an artesunate-resistant line of P. berghei. Complete cure rates were achieved with doses of the combination above or equal to 8 mg/kg per day against P. chabaudi AS. These results indicate that the combination had an enhanced effect over monotherapy and lower daily doses of artesunate could be used to obtain a curative effect. The data suggest that the combination of pyronaridine and artesunate should have potential in areas of multi-drug resistant malaria.     

Parameters of anorectal and colonic motility in health and in severe constipation

Anorectal function and colonic transit was assessed in 17 severely constipated patients and 15 age-matched controls. The constipated patients were divided into those who had immobile perineum (perineal descent 1.0 cm during attempted defecation) and those who had a normal descent (>1.0 cm) of the perineum. When constipation was accompanied by an immobile perineum, patients had impaired balloon expulsion, impaired and delayed artificial stool expulsion, decreased straightening of the anorectal angle, decreased descent of the pelvic floor with defecation, and prolonged rectosigmoid colon transit compared with the patients with constipation who had a mobile perineum and with normal controls. The mobile-perineum group differed from controls only in colon transit times, having prolonged total colon transit. Anal sphincter resting pressures, immediate artificial stool expulsion, resting anorectal angles, and electromyography of the external anal sphincter and puborectalis did not differentiate the constipated patients from the controls. We concluded that descent of the perineum of <1 cm was associated with impaired expulsion, an adynamic anorectal angle, and slowed distal colon transit. This simple sign of pelvic floor function distinguished constipated patients with disordered expulsion from constipated patients with normal pelvic floor function. These patients may respond poorly to surgery and conventional management and would therefore be candidates instead for pelvic floor retraining. Accurate characterization and appreciation of pelvic floor dysfunction in patients with severe chronic constipation may improve the selection for and results of surgical and nonsurgical intervention.Supported in part by Research Grants DK37990, RR585, and DK34988 from the National Institutes of Health and by the Mayo Foundation, Rochester, Minnesota.     

Effects of dietary phytoestrogens in vivo and in vitro in rainbow trout and Siberian sturgeon: interests and limits of the in vitro studies of interspecies differences

A study of the effects of dietary genistein on trout and sturgeon in vivo showed that sturgeon was sensitive to 20 ppm of genistein, whereas trout was not. To analyze the origin of this interspecies difference in sensitivity, a cell culture technique was developed with hepatocytes from sturgeon and compared to results obtained with hepatocytes from trout in the same system. The hepatocyte culture proved to be useful as bioassay for estrogenicity. Vitellogenin (VTG), assayed by a specific enzyme-linked immunosorbent assay, was used as a biomarker of the estrogenic activity. 17 beta-Estradiol, its glucuronide and sulfate derivatives, and estradiol analogues (ethynylestradiol and diethylstilbestrol) were tested. Nonestrogenic compounds such as androgens, progesterone, and cortisol were tested as negative controls. VTG production was monitored at doses ranging from 1 nM to 10 microM estradiol. Phytoestrogens, from the isoflavone family, were tested individually at increasing doses exhibiting dose response curves for concentrations from 500 nM to 10 microM. With tamoxifen, an antagonist of estrogen receptors, the estrogenic effect was partially reduced. The effect was the same with ICI182,780 in sturgeon, whereas the effect was the opposite in trout. The estrogenic potency of the isoflavones ranged differently between the two species in the following order: biochanin A < daidzein = formononetin < genistein < equol in trout and biochanin A < genistein < daidzein < formononetin < equol in sturgeon. Further, in sturgeon, formononetin was the most potent phytoestrogen in vitro, whereas its activity was weakest in vivo. These data suggest that one must reconsider the relevance of heterologous estrogenic tests and of homologous in vitro tests for estrogenic potency of chemicals.     

The role of alcohol and drugs in homicides in England and Wales

BACKGROUND: The annual number of homicide convictions in England and Wales is increasing. Previous studies have highlighted the aetiological role of alcohol and drugs in homicide. AIMS: To examine rates of alcohol and drug misuse and dependence in people convicted of homicide; the role of alcohol and drugs in the offence; the social and clinical characteristics of alcohol- and drug-related homicides; and the social and clinical characteristics of patients with dual diagnosis who commit homicide. METHODS: A national clinical survey based on a 3-year (1996-9) consecutive sample of people convicted of homicide in England and Wales. Information on rates of alcohol and drug misuse/dependence, the role of alcohol and drugs in the offence and social and clinical characteristics of perpetrators were collected from psychiatric reports prepared for the court in homicide convictions. Detailed clinical information was gathered from questionnaires completed by mental health teams for those in contact with mental health services. RESULTS: Of the 1594 homicide perpetrators, more than one-third (42%) occurred in people with a history of alcohol misuse or dependence and 40% in people with a history of drug misuse or dependence. Alcohol or drug misuse played a contributory role in two-fifths of homicides. Alcohol played a major role in 52 (6%) and a minor role in 364 (39%) homicides. Drugs played a major role in six (1%) and a minor role in 138 (14%) homicides. Forty-two homicides (17%) were committed by patients with severe mental illness and substance misuse. Alcohol- and drug-related homicides were generally associated with male perpetrators who had a history of violence, personality disorders, mental health service contact and with stranger victims. CONCLUSIONS: Substance misuse contributes to the majority of homicides in England and Wales. A public health approach to homicide would highlight alcohol and drugs before severe mental illness.     

Trends in COPD mortality and hospitalizations in countries and regions of Asia-Pacific

Background and objective: The growing burden of COPD in the Asia‐Pacific region supports the need for more intensive research and analysis of the epidemiology of COPD to raise awareness of the disease and its causes, to ensure the development of effective national health policies and to facilitate equitable deployment of finite health‐care resources in the prevention and management of COPD. This study estimated and compared COPD mortality and hospital morbidity rates and trends in these rates over time across countries and regions of Asia‐Pacific. Methods: Data consistent with standard definitions of COPD (ICD‐9/ICD‐10) for the period 1991–2004 were obtained from national health statistics agencies. For countries/regions with complete national mortality and hospitalization data (Australia, Pacific Canada (British Columbia, Hong Kong, South Korea and Taiwan), annual age‐standardized mortality and hospitalization rates were calculated for men and women aged ≥ 40 years. Negative binomial regression modelling was used to estimate rate ratios for country/region, gender and age differences and general trends over time. Results: Mortality rates per 10 000 population ranged 6.4–9.2 in men, 2.1–3.5 in women and 3.7–5.3 overall in 2003. Corresponding ranges for morbidity were 32.6–334.7, 21.2–129 and 28.1–207.3 per 10 000. Trend analysis of data since 1997 produced annual percentage changes in mortality versus hospitalization of ?4.4% versus ?0.7% in Australia, ?3.6% versus 7.5% in Pacific Canada (British Columbia), ?7.15% versus ?5.6% in Hong Kong and ?2.9% versus ?4.2% in Taiwan. Conclusions: In Asia‐Pacific, overall mortality and morbidity rates are high and trends in mortality and morbidity vary between countries/regions. Differences in rates and trends for men and women most likely reflect the different trends in historical and prevalent smoking profiles for COPD in the different countries and regions.     

Morbidity and maternal and infant outcomes of hypertensive disorder in pregnancy in China in 2018

Hypertensive disorder in pregnancy is a disease that occurs during pregnancy. We aimed to analyze the morbidity and maternal and infant outcomes with respect to the hypertensive disorder in pregnancy in China in 2018. Clinical data of 38 590 cases from 161 hospitals were retrospectively collected. The differences in morbidity and maternal and infant mortality among the major regions and provinces were compared. The overall national average morbidity was 4.74%, and the ratios of gestational hypertension, preeclampsia, eclampsia, chronic hypertension, and chronic hypertension with superimposed preeclampsia were 29.17%, 55.02%, 0.66%, 6.53%, and 8.62%, respectively. The overall maternal mortality was 0.61/100 000, and the case fatality was 0.13%. Morbidity associated with hypertensive disorder in pregnancy was 7.74% in North China, 6.62% in Northwest China, 6.40% in Central China, 5.83% in Northeast China, 4.28% in East China, 3.85% in South China, and 2.88% in Southwest China. The morbidity in each province was 1.62‐11.28%. The overall perinatal mortality was 3.59% (81.09% for stillbirths; 18.91% for neonatal deaths). Perinatal mortality decreased with increasing gestational weeks from 24 to 37 + 6 weeks. Perinatal mortality for delivery at 32 weeks of gestation in all regions of the country was <10%. Morbidity varied across regions in China, with the lowest in Southwest and the highest in North China. The low maternal mortality is related to the large‐scale development of standardized maternal health care in China. For severe hypertensive disorder patients, gestation should be prolonged to 32 weeks as often as possible for better neonatal survival rates.     

Qualitative and quantitative changes of melatonin levels in physiological and pathological aging and in centenarians

Melatonin secretion is an endogenous synchronizer, and it may possess some anti-aging properties. Thus we examined melatonin levels in physiological aging, in extreme senescence and in senile dementia. In healthy old (age 66-94 yr) and young subjects (age 23-39 yr) and in demented patients (age 68-91 yr) plasma melatonin was measured by radioimmunoassay in eight serial blood samples. In centenarians (age 100-107 yr) melatonin levels were estimated by assaying urinary 6-hydroxymelatonin sulfate (aMT6s) in two different urine samples collected from 08:00 to 20:00 hours and from 20:00 to 08:00 hours. These data were compared with the aMT6s excretion of old and young controls. Elderly subjects, demented or not, exhibited a flattened circadian profile of plasma melatonin, because of the suppression of the nocturnal peak. An age-related decline of the circadian amplitude of the melatonin rhythm occurred in old subjects, especially in demented individuals. Furthermore, the melatonin nocturnal peak was significantly correlated with the severity of the cognitive impairment. aMT6s urinary excretion also declined with age. However, as in young controls, in centenarians the aMT6s excretion was significantly higher at night than during the day. In conclusion, pineal melatonin secretion is affected by age and by the degree of cognitive impairment. In centenarians the maintenance of the circadian organization of melatonin secretion may suggest that the amplitude of the nocturnal peak and/or the persistence of a prevalent nocturnal secretion may be an important marker of biological age and of health status.