Effect of taurine on intracellular free calcium concentration in cultured neonatal rat heart cells

在培养的单个ＳＤ乳鼠心肌细胞，观察了牛磺酸对ＫＣｌ，去甲肾上腺素（ＮＥ）和毒毛花苷Ｇ引起的胞浆游离Ｃａ２＋浓度（［Ｃａ２＋］ｉ）变化的影响．当细胞外ＣａＣｌ２浓度为１．３ｍｍｏｌ·Ｌ－１时，牛磺酸１０，２０ｍｍｏｌ·Ｌ－１不影响心肌细胞静息［Ｃａ２＋］ｉ；但能浓度依赖性地抑制３５ｍｍｏｌ·Ｌ－１ＫＣｌ和１μｍｏｌ·Ｌ－１毒毛花苷Ｇ升高［Ｃａ２＋］ｉ的作用．１０μｍｏｌ·Ｌ－１ＮＥ在含Ｃａ２＋的缓冲液中能引起双相的［Ｃａ２＋］ｉ变化，即快速升高相和持续升高相．牛磺酸２０ｍｍｏｌ·Ｌ－１能抑制ＮＥ引起的［Ｃａ２＋］ｉ持续升高，而对快速升高相无显著影响．在无Ｃａ２＋的缓冲液中，牛磺酸不影响ＮＥ升高［Ｃａ２＋］ｉ的作用．结果提示牛磺酸可能通过减少心肌细胞电压依赖性Ｃａ２＋内流和Ｎａ＋／Ｃａ２＋交换而抑制ＫＣｌ，ＮＥ和毒毛花苷Ｇ引起的［Ｃａ２＋］ｉ升高．     

钾通道开放剂降低血管平滑肌细胞内游离钙浓度

研究ＰＣＯ－Ｐｉｎ，Ｎｉｃ，Ｌｅｍ及ＲＰ对ＶＭＳＣ内［Ｃａ＾２＋］ｉ的改变及其可能机制。ＶＳＭＣ加入Ｆｕｒａ－２ＡＭ２．５μｍｏｌ．Ｌ＾－１３７℃下孵育５０ｍｉｎ，［Ｃａ＾２＋］ｉ用荧光分光光度计检测。４种ＰＣＯ能较弱地抑制Ｋ＾＋３０ｍｍｏｌ．Ｌ＾－１诱导的［Ｃａ＾２＋］ｉ增加，但明显抑制ＡＴＰ０．１ｍｍｏｌ．Ｌ＾－１诱导的［Ｃａ＾２＋］ｉ峰相及持续相增加，且呈剂量依赖性。格列苯脲完全阻断Ｐｉｎ，     

前列腺素中间体－顺－6－氯－7－羧基二环［2．2．1］庚－3－酮的拆分

前列腺素中间体－顺－６－氯－７－羧基二环［２．２．１］庚－３－酮的拆分陈敏华，游开铭（上海五洲药厂，上海２０００５２）ＲＥＳＯＬＵＴＩＯＮＯＦｃｉｓ－６－ＣＨＬＯＲＯ－７－ＣＡＲＢＯＸＹＢＩＣＹＣＬＯ［２．２．１］ＨＥＰＴＡＮ－３－ＯＮＥＦＯＲＰＲＯ...     

Mobilization of intracellular Ca~(2 ) modulates activation of Na~ /H~ exchange in thrombin-stimulated platelets

目的：研究凝血酶诱导的血小板活化中细胞内钙动员和Ｎａ＋／Ｈ＋交换的关系．方法：Ｆｕｒａ２负载测［Ｃａ２＋］ｉ和ＢＣＥＣＦ负载测ｐＨｉ．结果：凝血酶０１ＩＵ·Ｌ－１引起［Ｃａ２＋］ｉ和ｐＨｉ增加，［Ｃａ２＋］ｉ增加先于ｐＨｉ增加．在无钠溶液中，Ｎａ＋／Ｈ＋交换被抑制而［Ｃａ２＋］ｉ增加不受影响；用尼日利亚菌素（１ｍｇ·Ｌ－１）使胞内酸化可抑制［Ｃａ２＋］ｉ增加．用依他酸（ＥＧＴＡ）阻断外钙内流，胞浆碱化不受影响．伊屋诺霉素加ＥＧＴＡ耗竭胞内钙池时，胞浆硷化效应被取消，且静息ｐＨｉ更低，加入１ｍｍｏｌ·Ｌ－１外钙重新充填钙池，胞浆碱化效应又被恢复．结论：细胞内钙动员调控Ｎａ＋／Ｈ＋交换，后者需［Ｃａ２＋］ｉ增加达一定有效浓度．     

Vilsmeier－Haack反应制备2，4－二羟基苯甲醛

Ｖｉｌｓｍｅｉｅｒ－Ｈａａｃｋ反应制备２，４－二羟基苯甲醛ＭｅｎｄｅｌｓｏｎＷＬ等［ＳｙｎＣｏｍｍｕｎ，１９９６；２６：６０３］间苯二酚和ＰＯＣｌ３／ＤＭＦ／ＣＨ３ＣＮ或（ＣＯＣｌ）２／ＤＭＦＣＨ３ＣＮ在０℃下反应得中间产物，续在５０℃水中水解得纯产...     

有机锡化合物抗肿瘤生物活性研究

有机锡（ＩＶ）化合物能明显地抑制大鼠脑组织中ＰＫＣ活性和肿瘤细胞增殖，且两者之间存在着相关性。抗肿瘤活性的构效关系是：（１）有机基团Ｒ决定整个化合物的生物活性，Ｐｈ＞Ｅｔ＞ｎ－Ｂｕ；（２）卤素的电负性影响化合物活性的大小。抗肿瘤活性可能通过［ＳｎＲ２］２＋实现。并能部分地阻断ＨＬ－６０细胞周期中的Ｇ１期向ｓ期的移行。［ＳｎＰｈ２Ｆ２］，［ＳｎＰｈ２（ＣｙｓＯＳ）］ＨＯ２和［ＳｎＰｈ２Ｃｌ２·ｐｈｅｎ（ＣＨ３）２］对ＰＫＣ的ＩＣ５０值分别为２５，１５和２０μｍｏｌ·Ｌ－１，对ＨＬ－６０细胞的ＩＣ５０值分别为０．５，４．０和０．３μｍｏｌ·Ｌ－１。但它们无诱导分化ＨＬ－６０和Ｋ５６２细胞的作用。     

α－氟羧酸的简便合成法

α－氟羧酸的简便合成法ＯｌｉｖｅｒＪＥ等［Ｓｙｎｔｈｅｓｉｓ，１９９４：２７３］１，１，１－三氯－２－醇［ＲＣＨ［ＯＨ］ＣＣｌ３］在氟化四丁铵及氟化铯存在下，于ＴＨＦ和Ｅｔ３Ｎ中加热反应可制得α－氟羧酸ＲＣＨＦＣＯＯＨ．４例收率７６～１００％。［胡琦...     

粉防己碱对大鼠心肌细胞电压依赖性钙通道的作用

运用钙离子荧光指示剂Ｆｕｒａ－２／ＡＭ，检测了粉防己碱（Ｔｅｔ）对成年大鼠心室肌细胞电压依赖性钙通道的影响。结果显示：基础状态下心肌细胞内钙离子（［Ｃａ２＋］ｉ）为１６２．６±７．３ｎｍｏｌ·Ｌ－１，５０ｍｍｏｌ·Ｌ－１氯化钾能使［Ｃａ２＋］ｉ增加至４８０．８±９．３ｎｍｏｌ·Ｌ－１（Ｐ＜０．０１），在无细胞外钙条件下，这种增加作用消失，而预先给予Ｔｅｔ和维拉帕米（Ｖｅｒ）则能阻断高钾升高［Ｃａ２＋］ｉ的作用。结果提示：Ｔｅｔ是通过阻断电压依赖性钙通道而发挥作用的。     

内钙动员调控凝血酶诱导的血小板Na^＋／H^＋交换

目的：研究凝血酶诱导的血小板活化中细胞内钙动员和Ｎａ＾＋／Ｈ＾＋交换的关系。方法Ｆｕｒａ－２负载测［Ｃａ＾２］ｉ和ＢＣＥＣＦ负载测ｐＨｉ。结果：凝血酶０．１ＩＵ·Ｌ＾－１引起［Ｃａ＾２＋］ｉ和ｐＨｉ，［Ｃａ＾２］ｉ增加先于ｐＨｉ增加。在无钠溶液中，Ｎａ＾＋／Ｈ＾＋交换被抑制而［Ｃａ＾２］ｉ增加不受影响；用尼日利亚菌素（１ｍｇ·Ｌ＾－１）使胞内酸化可抑制［Ｃａ＾２＋］ｉ增加，用依他酸（ＢＧＴＡ）阻断     

Effects of hyperin on free intracellular calcium in dissociated neonatal rat brain cells

目的：研究金丝桃苷（Ｈｙｐ）对新生大鼠的脑细胞内游离钙浓度的作用．方法：分离新生大鼠的脑细胞;用钙离子荧光指示剂Ｆｕｒａ２测定静息和激动剂存在时新生鼠脑细胞内游离钙浓度．结果：在ＣａＣｌ２１３ｍｍｏｌ·Ｌ－１的Ｈａｎｋｓ液中,静息［Ｃａ２＋］ｉ为（２０８±１２）ｎｍｏｌ·Ｌ－１（ｎ＝１７）,Ｈｙｐ对静息［Ｃａ２＋］ｉ无明显影响;Ｈｙｐ１０,４０,１６０μｍｏｌ·Ｌ－１呈浓度依赖性显著抑制ＫＣｌ５０ｍｍｏｌ·Ｌ－１致［Ｃａ２＋］ｉ增高;Ｈｙｐ１６０μｍｏｌ·Ｌ－１显著抑制去甲肾上腺素１,２,４和８μｍｏｌ·Ｌ－１诱发的［Ｃａ２＋］ｉ的增高;Ｈｙｐ１６０μｍｏｌ·Ｌ－１还可显著抑制谷氨酸和５羟色胺致［Ｃａ２＋］ｉ增高．结论：Ｈｙｐ对新生大鼠脑细胞钙内流有阻滞作用．     

五聚素3对高脂血症小鼠血脂水平的影响及作用机制研究

目的 探讨五聚素3(PTX3)对高脂血症小鼠血脂的影响及其作用机制.方法 10只小鼠分为高脂组6只和正常组4只,高脂组给予高脂饮食,正常组给予正常饮食,检测2组小鼠血清中血脂水平及肾组织中PTX3和核因子-κB(NF-κB)通路蛋白的表达水平.将高脂组小鼠分为实验组和对照组各3只,实验组经尾静脉注射PTX3抗体,对照组注射生理盐水,检测2组高脂血症小鼠血脂水平及肾组织中PTX3和NF-κB通路蛋白的表达情况.结果 高脂组血脂水平和肾组织PTX3和NF-κB通路蛋白表达水平高于正常组(P＜0.05).实验组血脂、PTX3和NF-κB通路蛋白表达水平低于对照组(P＜0.05).结论 PTX3抗体可通过抑制NF-κB通路下调血脂水平,而减缓动脉粥样硬化进程.     

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro

Aim:

To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro.

Methods:

Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer.

Results:

Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca²⁺ concentration, while Na⁺ and K⁺ concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca²⁺ and Na⁺ concentrations. Si⁴⁺ (0.2434 g/L) and Al³⁺ (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl₂ that contained Ca²⁺ concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl₂.

Conclusion:

Zeolite releases Ca²⁺ into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.     

肾移植病人西罗莫司血药浓度/剂量比与CYP3A5基因多态性的关系

目的:研究肾移植术后病人CYP3A5基因多态性与免疫抑制剂西罗莫司临床个体化给药剂量的关系。方法:采用聚合酶链反应(PCR)和限制性内切片段多态性(RFLP)的方法对105例健康受试者和50例肾移植术后病人进行CYP3A5基因分型。使用高效液相色谱(HPLC)测定病人的西罗莫司血药浓度。比较不同基因型之间的西罗莫司的血药浓度与每千克体重的剂量(C/D)比值的差异。结果:健康受试者和肾移植病人的CYP3A5 A6986G SNPs,CYP3A5*3的发生频率分别为72.9％和71％,差异无显著意义(P>0.05)。肾移植*1/*3型病人的C/D比值(362±s108)μg·L~(-1)per mg·kg~(-1)和*3/*3型病人的C/D比值(375±123)μg·L~(-1)per mg·kg~(-1)差异无显著意义(P>0.05),但两者C/D值均明显高于*1/*1型病人(199±65)μxg·L~(-1)per mg·kg~(-1),差异具有显著意义(P<0.05)。结论:肾移植病人的CYP3A5基因多态性与西罗莫司血药浓度具有相关性,*1/*3型和*3/*3型病人拟取得相似的血药浓度要比*1/*1型病人服用更低剂量的西罗莫司。研究肾移植病人的CYP3A5基因型,有利于肾移植病人术后西罗莫司个体化用药方案的制定。     

The possible role of metabolic acidosis in acetazolamide-induced gastric lesion formation in rats

The effects of acetazolamide on blood acid/base balance and the relationship of the latter to gastric lesion formation were studied in rats. Acetazolamide (200 mg/kg, s.c.) produced haemorrhagic gastric lesions which were accompanied by lowered arterial blood pH and HCO3- levels. High dose (6.2%) of NaHCO3 infusion normalised the arterial blood pH and decreased lesion formation. It also markedly raised the blood HCO3- level. However, a lower dose (3.1%) of the drug only raised the HCO3- to a normal level and slightly reduced the severity of ulceration. These results suggest that metabolic acidosis is the main causative factor while depletion of blood HCO3- may play a minor role in acetazolamide-evoked lesion formation in rat stomachs.     

Arsenic speciation of arsine-exposed blood samples by high-performance liquid chromatography-inductively coupled plasma mass spectrometry and as-adduct, a possible indicator of AsH3 exposure

Arsine (AsH(3))-exposed human blood samples were analyzed by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for arsenic speciation. After exposure of human blood samples to AsH(3) vapor for 90 min at room temperature, partial hemolysis was observed. Plasma samples from these whole blood samples were prepared by centrifugation at 1600 x g for 10 min and analyzed by HPLC-ICP-MS. In addition to arsenite [As(III); degraded from AsH(3)], an unidentified arsenic species (As-adduct) was detected at a retention time of 1.1 min. Following ultrafiltration of the plasma samples using a molecular weight cut-off of 10 kDa, As-adduct was not detected in the filtrate. To clarify the origin of As-adduct, AsH(3) was added to blank plasma and As(III) was added to both whole blood and hemolyzed blood. Although As(III) was detected in all samples, As-adduct was not detected. These results indicate that As-adduct was derived from erythrocytes during the process of hemolysis by AsH(3) and further suggest that As(III) and plasma ingredients do not contribute to As-adduct production. Therefore, the presence of As-adduct in blood could represent an indicator of acute arsine poisoning.     

急性胰腺炎患者早期C-反应蛋白、血乳酸与APACHEⅡ和Ranson评分的关系

目的探讨C-反应蛋白(CRP)、血乳酸(LA)水平对急性胰腺炎(AP)患者早期病情危重度的评估价值。方法测定97例AP患者发病早期的CRP、血LA水平、APACHEⅡ评分和Ranson评分;按不同的评分方法分为重症胰腺炎(A)组(APACHEⅡ评分≥8分,Ranson评分≥3分)和轻型胰腺炎(B)组(APACHEⅡ评分<8分,Ranson评分<3分)。50例健康人为对照(C)组,同时测定相同指标。分析AP患者的CRP、血乳酸测定值与APACHEⅡ评分和Ranson评分值相关性。结果 A组CRP和血LA水平高于B组,A、B两组CRP和血LA水平均高于C组(P<0.05);CRP、血LA水平和APACHEⅡ评分呈正相关(P<0.05)。结论 AP患者早期血CRP、血LA水平可以用来评估病情的危重程度。     

可调钠透析对维持性血液透析患者血压变化的影响

目的探讨可调钠透析对维持性血液透析患者血压变化的影响。方法对在我院行维持性血液透析的患者按血压情况分组。A组为高血压组,B组为理想血压组,两组患者均在原有治疗基础上,先给予标准钠透析(SSD)3个月,再给予可调钠透析(VSD)3个月,观察不同治疗方案分别对两组患者血压及血清钠浓度的影响。结果血压在不同透析方案治疗后,变化不同,其中原有高血压组患者在行可调钠透析3个月后血压明显改善,原理想血压组患者在接受标准钠透析3个月后血压明显上升,两组数据均有统计学意义。(P<0.05),而原有高血压组患者在接受标准钠透析3个月后,血压变化无明显统计学意义。两种治疗方案对患者血清钠离子浓度无明显改变。结论可调钠透析对维持性血液透析患者血压存在明显有利影响,对患者血清钠离子浓度无明显影响。但对不同亚组患者血压影响存在差异。     

The distribution of 3H-labelled cardenolides between isolated guinea-pig atrial tissue and circulating, oxygenated whole blood

1. An experimental method was developed that allowed the incubation of isolated organs in circulating whole blood. The circulating blood was oxygenated with a specially designed disc-oxygenator and drawn through the system by means of a roller pump.2. The method proved suitable for guinea-pig isolated atria, rabbit duodenum and to a lesser extent for chronically denervated rat diaphragm. Isolated atria could be kept for several hours. Various parameters of the circulating blood (haemolysis, pH, O(2) saturation, concentration of electrolytes) remained satisfactory for at least 5 hr. The method proved convenient for pharmacological and kinetic studies on isolated organs, suspended in whole blood of the corresponding species. The organs showed normal spontaneous mechanical activity and also responded to electrical stimuli and various drugs.3. The uptake of (3)H-labelled ouabain, digoxin, digitoxin and digitoxigenin was studied in guinea-pig isolated atria, suspended in circulating blood. The uptake reached equilibrium after 60-90 min. With respect to the total serum radio-activity the "apparent" tissue/medium (T/M) ratios obtained for the four drugs were within the range 0.4-1.1. If, however, the amount of free, non protein bound drug was taken as a base for the calculations, the following "true" T/M ratios were obtained: (3)H-ouabain 0.45; (3)H-digoxin 1.6; digitoxin 8.8; digitoxigenin 8.4. These values are virtually the same as those obtained with atria, suspended in an aqueous medium. Obviously, the uptake of (3)H-cardenolides from whole blood is determined by the amount of free non-protein-bound drug.4. (3)H-digitoxin and (3)H-digitoxigenin were taken up by guinea-pig erythrocytes to a small extent. No measurable amounts of (3)H-ouabain and (3)H-digoxin were taken up by erythrocytes.     

The role of the cytochrome P450 3A5 enzyme for blood pressure regulation in the general Caucasian population

Cytochrome P450 3A (CYP3A) enzymes are important for drug metabolism in gut and liver. The CYP3A5 isoenzyme is also expressed in the kidney and has been implicated in renal sodium reabsorption and blood pressure regulation. Its expression and activity is strongly linked to a polymorphism (i.e. 6986G > A). Thus, appreciable expression is found in carriers of the CYP3A5*1 (6986A) but not in homozygous carriers of the CYP3A5*3 (6986G) allele. We tested whether the presence of CYP3A5*1 affects blood pressure in Caucasian individuals who were enrolled in the Prevention of REnal and Vascular ENd stage Disease (PREVEND) study. In addition, we evaluated whether the genetic effect of CYP3A5*1 on blood pressure is modulated by sodium intake. CYP3A5*1 was found in 13.3% (901 individuals) of the cohort (6777 individuals). Diastolic blood pressure was not affected by CYP3A5*1. Overall, systolic and pulse pressure were significantly lower in carriers of CYP3A5*1, both after univariate analysis adjusted for age (P = 0.012 and P = 0.008) and in logistic regression analysis (P = 0.015 and P = 0.012). The effect on systolic blood pressure was significantly modulated by sodium intake (P = 0.038). In separate analysis according to gender, CYP3A5*1 accounted for a significant age adjusted decrease in systolic blood pressure (-1.6 mmHg, P = 0.04) and pulse pressure (-1.2 mmHg, P = 0.04) in females but not in men. The present study demonstrates that the CYP3A5*1 allele affects systolic blood pressure and pulse pressure in the general population. Its role in hypertensive disease and potential gender differences should be investigated in further studies.     

Biomarkers of oxidative stress after controlled human exposure to ozone

This study was aimed at evaluating whether controlled short-term exposure to ozone (O(3)) induces changes in biomarkers of lung inflammation and oxidative stress in exhaled breath condensate (EBC) and blood of healthy subjects. Twenty-two volunteers were exposed to 0.1 ppm of O(3) for 2 h while performing moderate intermittent exercise. EBC and blood were collected before, immediately after and 18 h after exposure. Changes in biomarkers were measured both in EBC and blood, without significant alterations of lung function tests. Changes in EBC, but not in blood, were mainly accounted for by a subgroup of 'susceptible' individuals bearing the wild genotype for NAD(P)H:quinone oxidoreductase (NQO1) and the null genotype for glutathione-S-transferase M1 (GSTM1). Thus, a single 2-h exposure to 0.1 ppm of O(3) induces changes in biomarkers of inflammation and oxidative stress. Polymorphic NQO1 and GSTM1 act as modifier of the lung response to O(3).