急性冠状动脉综合征患者血浆氧化型低密度脂蛋白、高敏C反应蛋白与血管内皮损伤的关系

目的观察急性冠状动脉综合征患者外周血浆氧化型低密度脂蛋白、高敏C反应蛋白、循环内皮细胞计数和一氧化氮的变化,探讨氧化型低密度脂蛋白与高敏C反应蛋白的相关性,以及两者与血管内皮损伤的关系,研究其在急性冠状动脉综合征发生和发展中的意义。方法急性冠状动脉综合征患者51例,临床及选择性冠状动脉造影排除冠心病20例为对照组。测定外周血浆中的氧化型低密度脂蛋白、高敏C反应蛋白、循环内皮细胞计数和一氧化氮水平。结果急性冠状动脉综合征组氧化型低密度脂蛋白、高敏C反应蛋白、循环内皮细胞计数较对照组明显升高,分别为氧化型低密度脂蛋白(686±168μg/L比349±172μg/L,P<0.01)、高敏C反应蛋白(6.15±1.75mg/L比1.53±1.64mg/L,P<0.01)、循环内皮细胞计数[(8.9±1.6)×106个/L比(2.4±0.4)×106个/L,P<0.01]。急性冠状动脉综合征组一氧化氮水平较对照组明显降低(52.2±16.5μmol/L比77.3±21.0μmol/L,P<0.05)。血浆氧化型低密度脂蛋白与循环内皮细胞计数(r=0.781,P<0.001)和一氧化氮(r=0.792,P<0.001)均呈正相关,血浆高敏C反应蛋白与循环内皮细胞计数(r=0.776,P<0.001)和一氧化氮(r=0.897,P<0.001)也均呈正相关,血浆氧化型低密度脂蛋白与高敏C反应蛋白呈正相关(r=0.768,P<0.001),血浆循环内皮细胞计数与一氧化氮呈正相关(r=0.951,P<0.001)。结论血浆氧化型低密度脂蛋白、高敏C反应蛋白可能与血管内皮损伤有关,相互协同作用参与了急性冠状动脉综合征的发病过程。     

C反应蛋白直接刺激人单核细胞肿瘤坏死因子α与白细胞介素6的表达

目的　比较急性冠状动脉综合征患者与健康人外周血单核细胞对一定浓度的C反应蛋白或细菌脂多糖刺激的炎症反应,并观察普伐他汀的干预效应。方法　采集并培养急性冠状动脉综合征患者(急性冠状动脉综合征组,n =15 )和健康志愿者(健康组,n =15 )的外周血单核细胞,分别用C反应蛋白(终浓度为2 0mg/L)或细菌脂多糖(终浓度10 μg/L)直接刺激2 4h。或用不同浓度(1、5和10 μmol/L)的普伐他汀预先孵育细胞2h ,再用C反应蛋白刺激。采用酶联免疫吸附试验法检测培养上清液中的肿瘤坏死因子α和白细胞介素6水平。结果　健康组受C反应蛋白刺激后肿瘤坏死因子α和白细胞介素6表达增加,分别为5 5 8±15 2ng/L和987±10 2ng/L ;受细菌脂多糖刺激后肿瘤坏死因子α和白细胞介素6增加显著,分别为10 5 4±371ng/L和185 4±4 6 7ng/L。急性冠状动脉综合征组受C反应蛋白刺激后肿瘤坏死因子α和白细胞介素6表达水平分别为15 5 4±784ng/L和312 9±333ng/L ;受细菌脂多糖刺激后分别为186 5±75 3ng/L和32 16±70 3ng/L。急性冠状动脉综合征组在1、5和10 μmol/L普伐他汀干预后,肿瘤坏死因子α表达分别下降14 %、36 %和4 9% ;白细胞介素6表达分别下降18%、2 6 %和36 % ,各亚组与C反应蛋白单独刺激组比较均有显著差异。健康组在普伐     

卡维地洛对冠状动脉成形术后患者外周血内皮素及一氧化氮的影响

为探讨卡维地洛对冠心病患者经皮腔内冠状动脉成形术后血中内皮素及一氧化氮的影响 ,本文选择经冠状动脉造影证实有一支或二支以上≥ 70 %狭窄需行经皮腔内冠状动脉成形术的患者 5 1例 ,随机分成卡维地洛组2 8例和常规治疗组 2 3例 ,测定经皮腔内冠状动脉成形术前后及用药前后外周血内皮素及一氧化氮含量。结果发现 ,经皮腔内冠状动脉成形术后血中内皮素 (卡维地洛组为 84 .9± 14 .7μg/L、常规治疗组为 85 .6± 15 .4 μg/L)较术前 (卡维地洛组为 70 .6± 12 .8μg/L、常规治疗组为 71.5± 13.3μg/L)增高 ;一氧化氮 (卡维地洛组为 5 0 .3± 13.4μmol/L、常规治疗组为 5 0 .9± 12 .6 μmol/L)较术前 (卡维地洛组为 6 2 .9± 14 .2 μmol/L、常规治疗组为 6 3.5± 13.1μmol/L)降低 (P <0 .0 5 ) ;卡维地洛组内皮素为 74 .6± 15 .6 μg/L ,较用药前 (84 .4± 14 .9μg/L)降低 ;一氧化氮为 6 2 .7± 12 .8μmol/L ,较用药前 (5 1.6± 12 .5 μmol/L)增高 (P <0 .0 5 ) ,常规治疗组内皮素和一氧化氮观察两周均无显著变化 (P >0 .0 5 )。提示卡维地洛具有改善冠状动脉成形术后血管内皮功能的作用     

阿托伐他汀对急性冠状动脉综合征患者血清C反应蛋白的影响

目的探讨阿托伐他汀对急性冠状动脉综合征患者血清C反应蛋白的影响。方法选择急性冠状动脉综合征患者46人,随机分为阿伐他汀组和常规治疗组,阿伐他汀组在常规治疗的基础上加用阿托伐他汀每天40mg,常规治疗组采用常规治疗。分别于治疗前和治疗后两周测定血清C反应蛋白和血脂水平,比较其差异。结果46例急性冠状动脉综合征患者中,不稳定心绞痛17例,急性心肌梗死29例。血清C反应蛋白水平,心绞痛者为1.37±0.52 g/L,心肌梗死者为2.23±0.45 g/L,均高于正常对照组的0.30±0.22 g/L(P<0.05),心肌梗死患者较心绞痛者C反应蛋白升高显著(P<0.05)。阿托伐他汀治疗两周,血清C反应蛋白水平由1.88±0.45 g/L降至0.52±0.22 g/L,治疗前后相比有显著性差异(P<0.05)。常规治疗组血清C反应蛋白水平由1.85±0.50 g/L降至1.77±0.60 g/L,治疗前后相比无显著性差异(P>0.05)。结论C反应蛋白可能参与动脉粥样硬化的形成,短期使用阿托伐他汀即能明显降低急性冠状动脉综合征患者的血浆C反应蛋白水平,提示阿托伐他汀调脂作用之外还有抗炎作用。     

心绞痛患者血管内皮功能与冠状动脉病变的关系及临床意义

目的探讨血管内皮功能损伤在冠状动脉(冠脉)粥样硬化发生发展中的作用及相关的临床意义.方法不稳定型心绞痛组患者68例,稳定型心绞痛组58例.冠状动脉造影前检测一氧化氮、内皮素含量和高敏C反应蛋白,并检测肱动脉内皮舒张功能.根据造影结果将冠状动脉病变分为复杂狭窄和光滑狭窄.结果不稳定型心绞痛患者一氧化氮浓度低于稳定型心绞痛组(49.92μmol/L±10.46μmol/L比75.19μmol/L±5.21μmol/L,P=0.036),高敏C反应蛋白则高于稳定型心绞痛患者(4.21 mg/L±0.003 mg/L比0.50 mg/L±0.015 mg/L,P=0.004),两组内皮素浓度无明显差别;两组中有复杂狭窄者同无复杂狭窄者相比内皮素、一氧化氮浓度有明显差异,不稳定心绞痛组中有复杂狭窄者的内皮素明显高于稳定型心绞痛组中无复杂狭窄者(216.52pg/ml±33.63pg/ml比173.35 pg/ml±36.12 pg/ml,P＜0.001);两组肱动脉内皮功能检测无明显差异,但不稳定心绞痛组中有复杂病变者的肱动脉血流介导的血管扩张反应显著降低.结论不稳定心绞痛患者血管内皮功能损伤较稳定型心绞痛患者为重.冠脉造影所见的冠脉病变结合相关血管内皮功能检测,有助于更确切地评估冠脉病变进而评估斑块的稳定性.     

急性冠状动脉综合征患者降胆固醇治疗对内皮依赖性血管舒张功能、血小板及纤溶活性的影响

目的探讨急性冠状动脉综合征降低胆固醇水平后对内皮依赖性血管舒张功能、血小板表面活性颗粒膜蛋白(CD63)、溶酶体膜蛋白(CD62P)及血浆纤溶酶原激活物抑制物-1(PAI-1)的影响.方法70例急性冠状动脉综合征患者随机分成普伐他汀治疗组(普伐他汀组)38例及常规治疗组(常规组)32例,比较观察治疗6周前后应用超声检测肱动脉流量介导性扩张(FMD)的血管内皮舒张功能,血小板CD63、CD62P含量及血浆PAI-1、内皮素-1(ET1)水平的变化.结果(1)治疗前两组比较,内皮依赖性血管舒张功能差异无显著性[(4.91±0.81)%与(4.93±0.86)%,P＞0.05];治疗6周后,常规组内皮依赖性血管舒张功能较治疗前差异无显著性[(5.25±0.77)%与(4.93±0.86)%,P＞0.05],而普伐他汀组治疗后差异有十分显著性[(6.92±0.94)%与(4.91±0.81)%,P＜0.01].(2)普伐他汀组治疗6周后血小板CD63、CD62P及血浆PAI-1、ET-1各项指标较治疗前[(15.48±3.94)%、(14.97±3.24)%、(11.73±3.18)Au/ml、(5.97±2.84)ng/L]均有不同程度降低[(10.12±2.92)%、(10.46±3.45)%、(8.12±2.72)Au/ml、(3.28±1.85)ng/L,P＜0.01].结论急性冠状动脉综合征患者在降胆固醇治疗6周后可改善内皮依赖性血管舒张功能,同时抑制血小板活性,改善纤溶活性.     

同型半胱氨酸与急性冠状动脉综合征相关性研究

目的:探讨血浆同型半胱氨酸与急性冠状动脉综合征(ACS)发作期和自身缓解期的相关性。方法:对64例ACS患者的发作期和自身缓解期及64例对照组分别测定血浆同型半胱氨酸浓度并进行比较,同时测定C-反应蛋白对照观察。结果:ACS发作期血浆同型半胱氨酸水平[(26.72±3.2)μmol/L]显著高于对照组[(8.94±2.1)μmol/L]和自身缓解期[(17.88±2.8)μmol/L],均P<0.01。血浆C-反应蛋白在ACS发作期[(14.54±3.1)mg/L]与对照组[(4.36±1.8)mg/L]比较差异有统计学意义(P<0.01)。与自身缓解期[(13.72±5.3)mg/L]比较,则(P>0.05)。结论:ACS患者发作期血浆同型半胱氨酸水平与ACS的发生有关,是动脉粥样硬化斑块不稳定的标志;C-反应蛋白对动脉粥样硬化斑块不稳定性的预测比同型半胱氨酸差。     

冠状动脉慢血流患者一氧化氮和内皮素1浓度的变化

目的探讨冠状动脉慢血流(coronary slow flow,CSF)患者的血管内皮功能。方法选择因胸痛行冠状动脉造影的患者40例,根据造影结果分为CSF组20例和对照组20例。2组分别于静息和多巴酚丁胺负荷试验结束时立即抽取血标本,检测血浆内皮素1、血清NO浓度,并进行比较。结果 CSF组静息时血浆内皮素1浓度较对照组升高,但差异无统计学意义(P>0.05),而药物负荷试验后血浆内皮素1浓度较对照组明显升高,差异有统计学意义[(37.60±6.93)ng/L vs(14.16±5.73)ng/L,P<0.01]。CSF组静息时和药物负荷试验后血清NO浓度均明显低于对照组,差异有统计学意义[(42.36±9.72)μmol/L vs(50.39±9.77)μmol/L,(24.88±9.28)μmol/L vs(61.06±8.20)μmol/L,P<0.01)]。结论 CSF患者无论静息或者药物负荷状态下均存在内皮素1及NO平衡失调,负荷状态下这种平衡失调现象更加明显。     

早期反应生长因子1特异的脱氧核酶对大鼠动脉损伤后血管内皮功能的保护及超微结构的影响

目的探讨早期反应生长因子1特异的脱氧核酶对大鼠实验性颈总动脉损伤后内皮功能及超微结构的影响。方法Wistar大鼠96只,随机分为假手术组、对照组1(MgCl2)、对照组2(FuGENE6)和ED5治疗组,每组24只。行左颈总动脉内膜剥脱术后,ED5治疗组经球囊导管将ED5 500μg、注入损伤的血管节段内,作用20 min。对照组1注入200μL的1 mmol/L MgCl2液,对照组2注入含FuGENE6 30μL的1 mmol/L MgCl2液200μL。分别于第3、7、14和第21天各处死动物6只,处死前心脏取血检测一氧化氮、一氧化氮合酶、内皮素,同时光镜及透射电镜观察血管形态学变化。结果ED5治疗组一氧化氮和一氧化氮合酶含量均较两对照组增高,第14天最明显,此时一氧化氮与两对照组相比分别为57.1±1.9μmol/L比38.7±1.9μmol/L和57.1±1.9μmol/L比38.3±1.9μmol/L,差异有显著性统计学意义(P<0.05);一氧化氮合酶分别为11.1±0.4μmol/L比8.1±0.4μmol/L和11.1±0.4μmol/L比8.0±0.4μmol/L,差异有显著性统计学意义(P<0.05)。而内皮素浓度较两对照组有所降低,以第14天最显著,分别为111.2±7.2 pg/L比136.6±7.2 pg/L和111.2±7.2 pg/L比135.5±7.2 pg/L,差异有显著性统计学意义(P<0.05)。光镜观察发现ED5治疗组新生内膜厚度较两对照组明显减轻,以第21天最明显(64.0±4.2μm比81.1±4.9μm和64.0±4.2μm比80.0±3.9μm,P<0.01)。透射电镜观察发现对照组血管新生内膜的平滑肌细胞呈“合成型”改变,而治疗组新生内膜的血管平滑肌细胞呈“收缩型”改变。结论早期反应生长因1特异的脱氧核酶可改善动脉球囊损伤后的血管内皮功能,抑制血管平滑肌细胞的表型改变,从而减轻内膜增生程度。     

阿托伐他汀对急性冠脉综合征患者血清高敏C反应蛋白和妊娠相关血浆蛋白-A水平的影响

目的探讨阿托伐他汀干预对急性冠脉综合征(ACS)患者血清高敏C反应蛋白(hs-CRP)和妊娠相关血浆蛋白-A(PAPP-A)水平的影响。方法采用酶联免疫吸附法测定不稳定型心绞痛患者(UAP,n=37)、急性心肌梗死患者(AMI,n=24)、稳定型心绞痛患者(SAP,n=29)和健康体检者(n=32)的hs-CRP和PAPP-A水平。同时将ACS患者(包括UAP和AMI组,n=61)随机分为常规治疗组(n=30)和阿托伐他汀干预组(阿托伐他汀10mg/d,n=31),并于治疗前后分别测定血清hs-CRP和PAPP-A水平。结果(1)hs-CRP和PAPP-A水平在UAP组[(16.7±1.24)mg/L,(63.88±1.82)μg/L]、AMI组[(18.52±1.96)mg/L,(66.41±1.24)μg/L]比SAP组[(4.6±1.16)mg/L,(47.56±0.72)μg/L]、正常对照组[(3.2±0.88)mg/L,(45.17±1.28)μg/L]显著升高(P<0.05)。(2)2周后,阿托伐他汀干预组血清hs-CRP和PAPP-A水平较治疗前明显降低[hs-CRP(18.52±2.37)mg/Lvs.(3.58±1.33)mg/L;PAPP-A(67.83±2.15)μg/Lvs.(45.62±1.58)μg/L,P<0.05],且较常规治疗组治疗2周后亦有显著降低[hs-CRP(3.58±1.33)mg/Lvs.(5.23±1.98)mg/L;PAPP-A(45.62±1.58)μg/Lvs.(51.35±2.15)μg/L,P<0.05]。结论阿托伐他汀干预可以减少急性冠脉综合征患者动脉粥样硬化斑块的炎症反应,具有稳定斑块的作用。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.