Growth,regression and cell death in rat liver as related to tissue levels of the hepatomitogen cyproterone acetate

Previous studies have shown that xenobiotic compounds such as the environmental pollutant -hexa-chlorocyclohexane (-HCH) and the synthetic sex steroid cyproterone acetate (CPA) induce growth of rat liver by hypertrophy and hyperplasia. After withdrawal of the growth stimuli, liver hypertrophy was usually found to be readily reversible. Conflicting observations were made concerning the fate of liver hyperplasia: hepatic hyperplasia persisted when induced by -HCH but was found to be partially reversible when induced by CPA. The present study confirms the reversibility of hepatic hyperplasia induced by CPA in rats: about 30% of liver DNA present at maximal liver enlargement disappeared within 6 days after cessation of CPA treatment. Simultaneously, a dramatic increase in the rate of cell elimination by apoptosis was found. Glutamate-pyruvate transaminase and alkaline phosphatase in serum did not show major increases, suggesting that cell death was not due to lytic membrane damage. Furthermore, if treatment with CPA was continued or resumed, the enhanced DNA content persisted and the number of apoptotic bodies was greatly reduced. These observations suggest that the occurrence of cell death is due to withdrawal of the growth stimulus CPA. It may reflect a regulatory phenomenon serving to maintain homeostasis of cell number.Further studies showed that CPA is rapidly eliminated from rat liver and serum: t 1/2 in the liver is about 11 h. In contrast, -HCH was previously found to be eliminated more slowly: t 1/2 approximately 144 h. The present study revealed that -HCH, CPA and nafenopin lower the number of apoptotic bodies. This suggests that inducers of liver growth can inhibit hepatocellular death by apoptosis. It is concluded that the regression of hyperplasia after CPA withdrawal may be due to its rapid elimination. On the other hand the relatively long persistence of -HCH may result in inhibition of cell death and thereby stabilize hepatic hyperplasia.Abbreviations CPA cyproterone acetate - -HCH -hexachlorocyclohexane - PB phenobarbital - NAF nafenopin - AB apoptotic body - b.w. body weight - p. admin. post-administration - GPT glutamate-pyruvate transaminase - ALP alkaline phosphatase Dedicated to Professor W. Koransky on the occasion of his 65th birthday     

Determination of free fractions of tricyclic antidepressants

Summary The plasma protein binding of amitriptyline, imipramine, clomipramine, and their primary demethylated metabolites were studied by means of a method combining dialysis and gas chromatography. Equilibrium in dialysis of serum containing amitriptyline and its metabolite nortriptyline was attained in about 0.5 h with the drug dissolved in the serum compartment, and in about 2 h with the drug passing from the buffer to the serum compartment.The calculation of free fractions was influenced by variations with dialysis time in the volumes of serum and buffer. Increase of pH in serum increased the protein binding of the weakly basic drugs studied, and made the Donnan distribution effects more pronounced. At pH 7.4, the Donnan effect was negligible.Binding parameters for the 6 tricyclic antidepressant substances studied were estimated for the binding to ₁-acid glycoprotein and for total binding in serum. For ₁-acid glycoprotein, the k-values ranged from 1·10⁵ to 8·10⁵ M^–1, and for pooled serum from 0.4·10⁵ to 8·10⁵ M^–1. The determined number of binding sites on the ₁-acid glycoprotein was, on average 0.87 for the 6 substances. In serum, the binding capacity was 2–14 times the concentration of ₁-acid glycoprotein.     

Perioperative Cefamandolprophylaxe bei aortocoronaren Bypass-Operationen Serumkonzentrationsverlauf während der extrakorporalen Zirkulation

Zusammenfassung Eine perioperative antibiotische Kurzprophylaxe mit 2 g Cefamandol intravenös bei Narkoseeinleitung wurde bei 12 Patienten während coronarchirurgischer Eingriffe unter Verwendung der Herz-Lungen-Maschine durchgeführt. Bei Beginn der extrakorporalen Zirkulation (= EKZ) kam es infolge Hämodilution zu einem Absinken der Serumkonzentrationen von 110,96 ± 40,29 mcg/ml auf 70,89 ± 34,65 g/ml innerhalb von 10 min. Im weiteren Verlauf der EKZ war der Abfall der Serumspiegel gleich schnell wie davor und danach. Nach 240 min fanden sich noch Serumspiegel von 16,80 ± 9,32 g/ml. Als Ursache für das Versagen einer antibiotischen Prophylaxe kommt bei einer Operationsdauer von mehr als 4 h das Absinken der Serumspiegel unter die minimale Hemmkonzentration der entsprechenden Keime in Frage.

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Perioperative cefamandole prophylaxis in aortocoronary bypass operations: Course of serum concentration during extracorporeal circulation

Summary Antibiotic prophylaxis with 2 g Cefamandole at induction of anaesthesia was performed in 12 male patients undergoing aortocoronary bypass surgery. Caused by hemodilution, there was a marked decrease of serum concentration at the beginning of extracorporeal circulation, from 110.96 ± 40.29 mcg/ml to 70.89 ± 34.65 mcg/ml within 10 min. During extracorporeal circulation, elimination was as fast as before and after perfusion. 240 min after application, mean serum concentrations of 16.80 ± 9.32 mcg/ml were measured. Failure of antibiotic prophylaxis in operations exceeding 4 h might be due to unadaequate antibiotic concentrations, beyond the minimal inhibitory concentration for the pathogens, reported to cause infections after cardiac operations.

     

气相色谱-串联质谱法测定血清中的16种多环芳烃

目的 建立血清中16种多环芳烃的气相色谱-串联质谱测定方法。方法 血清样经甲醇沉淀蛋白,加入正己烷与二氯甲烷混合溶剂萃取,萃取物氮吹至近干后,正己烷和二氯甲烷混合溶剂复溶,取1 μl上清液进样分析。16种待测多环芳烃经DB-5色谱柱(30 m×0.25 mm,0.25 μm)分离,多反应监测模式监测,内标法定量。结果 本法在1.0 μg/L～2.0×10² μg/L范围内线性良好,方法检出限为4.20×10^-2 μg/L～0.27 μg/L,加标回收率为79.7%～108.0%,精密度为2.57%～6.76%。结论 本方法具有灵敏、快速、回收率和重复性好等优点,满足人血清中多种多环芳烃测定的要求。     

腺样体肥大患儿血清炎症介质和淋巴细胞亚群表达特征及与患儿预后的相关性

目的研究腺样体肥大患儿血清炎症介质、淋巴细胞亚群表达特征及其与患儿预后的相关性。方法选取浙江中医药大学附属第三医院收治的86例腺样体肥大患儿(观察组)和86例健康儿童(对照组)作为研究对象,采集血液标本测定血清炎症介质及淋巴细胞亚群相关指标,对比两组儿童的测定结果。分析腺样体肥大患儿的肥大程度、腺样体再增生情况,对比不同肥大程度患儿的血清指标,并分析各指标与患儿病情程度及预后(腺样体再增生)的关系。结果观察组患儿肿瘤坏死因子-α(TNF-α)、可溶性白细胞介素-2受体(sIL-2R)及白细胞介素-6(IL-6)水平分别为(492.44±50.56)mg/L、(420.48±61.79)U/ml及(33.65±4.51)pg/ml,对照组儿童分别为(301.22±41.65)mg/L、(236.55±57.90)U/ml及(16.25±3.27)pg/ml,差异均有统计学意义(t=16.004,P<0.05;t=20.311,P<0.05;t=8.995,P<0.05)。观察组CD4⁺、CD8⁺及CD4⁺/CD8⁺水平分别为(35.75±7.05)、(16.22±2.69)及(1.46±0.67),对照组分别为(34.25±4.53)、(17.62±2.35)及(1.40±0.62),差异均无统计学意义(t=1.036,P>0.05;t=0.905,P>0.05;t=0.823,P>0.05)。相比腺样体中度肥大患儿,重度肥大患儿的TNF-α、sIL-2R、IL-6、CD4⁺及CD4⁺/CD8⁺水平明显更高(P<0.05)。相比未增生患儿,腺样体再增生患儿的TNF-α、sIL-2R、IL-6、CD4⁺及CD4⁺/CD8⁺水平明显更高(P<0.05)。相关分析显示,患儿腺样体肥大程度与TNF-α、sIL-2R、IL-6、CD4⁺及CD4⁺/CD8⁺水平均呈正相关(P<0.05)。患儿腺体再增生与TNF-α、sIL-2R、IL-6、CD4⁺及CD4⁺/CD8⁺水平也呈正相关(P<0.05)。结论腺样体肥大患儿的血清炎症介质及部分T淋巴细胞亚群表达显著升高,其与腺样体肥大程度、患儿预后密切相关。     

超高效液相色谱-串联质谱法同时快速检测微量血清中6种脂溶性维生素

目的 建立超高效液相色谱-串联质谱法（UPLC-MS/MS）同时快速检测微量血清中维生素A、维生素D（25-OH-VD2 、25-OH-VD3 ）、维生素E（α-、β-和γ-生育酚）的方法。方法 血清中脂溶性维生素经甲醇-乙腈（50:50, v/v)沉淀蛋白、正己烷萃取,以Phenomenex Kinetex F5色谱柱为分离柱,2.5 mmol/L甲酸铵-0.1%甲酸水溶液和甲醇为流动相,梯度洗脱,电喷雾电离（ESI+ ）、多反应监测（MRM）模式下检测,同位素内标法定量。结果 血清中6种脂溶性维生素线性范围内线性关系良好,相关系数 r >0.995;6种脂溶性维生素的检测限为0.20~1.25 ng/ml,定量限为0.39~3.88 ng/ml;加标回收率为86.6%~107.7%,日内精密度<9.6%,日间精密度<9.3%。NIST标准参照品SRM 968f验证方法准确度,结果偏差均在5%以内。结论 本方法准确度高、重现性好、用血量少,适于婴幼儿等采血困难者微量血样中多种脂溶性维生素的同时快速检测。     

血清硝酸盐的快速测定

目的建立一种血清硝酸盐的快速测定方法.方法血清经去蛋白后,直接在酸性条件下用麝香草酚显色分光光度法测定.结果方法的检测下限为0.05μg,相对标准差为4.6%～9.6%,回收率为90.0%～95.9%(平均为93.6%).血清硝酸盐氮含量为0.13±0.011μg时,批间变异系数为8.6%.结论本法快速、简便、灵敏、特效性好,适用于血清中NO3-测定.     

血清胆红素与冠脉病变程度及血脂的相关性分析

目的分析血清胆红素与冠脉病变程度及血脂的关系。方法对冠状动脉造影术确诊的冠心病者和非冠心病者进行病例-对照研究。结果冠心病组血清胆红素水平低于非冠心病组,差异有显著性(P＜0.05)。多元逐步回归分析血清直接胆红素进入回归方程,提示血清直接胆红素与冠脉病变程度呈独立负相关,其相关强度与甘油三脂(TG)和空腹血糖(FBS)相似。血清胆红素与血脂直线相关分析提示血清胆红素与甘油三脂、总胆固醇(TCHO)和低密度脂蛋白胆固醇(LDL-C)呈显著负相关。结论血清直接胆红素水平与冠脉病变程度呈独立负相关,低血清胆红素是冠状动脉粥样硬化的危险因素,血清胆红素与甘油三脂、总胆固醇和低密度脂蛋白胆固醇呈负相关。     

冠心病心力衰竭患者血清尿酸浓度变化及临床意义

目的 探讨冠心病心力衰竭患者血清尿酸浓度变化及其临床意义。方法 采用尿酸酶法测定３０例冠心不合并心力衰竭患者。２８例冠心合并心力衰竭患者入院时血清尿酸浓度,同步测血脂。结果 冠心力衰竭组血清尿酸均值明显高于冠心病无心力衰竭组,有极显著性差异（Ｐ＜0.０１）;血清胆固醇、甘油三脂、高密度脂蛋白和低密度脂蛋白在两组间无明显差异。结论 冠心病心力衰竭患者血清尿酸增高可能为心血管系统严重受损的标志。     

正常孕产妇的血脂分析

目的探讨正常孕产妇在不同时期的血脂变化.方法测定201例正常孕妇、189例正常产妇及69例正常非孕妇女的甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-L)、载脂蛋白A(apo-A)、载脂蛋白B(apo-B).结果妊娠过程中,血脂各项指标随孕周的增加而明显增高,至晚孕期显著高于正常非孕妇女.产后逐渐下降,产褥晚期基本恢复到正常水平.结论妊娠期、产褥期妇女常伴有血脂的变化.孕末期妇女有高脂血症倾向,监测其血脂极有必要.