Malignant hypertension in young women is related to previous hypertension in pregnancy, not oral contraception

Previous studies have suggested that one-third of women of childbearing age who develop malignant phase hypertension (MHT) are likely to be taking oral contraceptives (OC). We surveyed 104 women with a history of MHT. None of the 65 aged > 45 years were taking OC or other sex hormones. Thirty-nine (mean age 34.9 years, SD 8.0) were aged 15-44 years at presentation: 22 Caucasian, 10 Black/Afro-Caribbean and seven Indo-Asian. Of these 39, 22 had a history of hypertension in pregnancy (group 1), and 17 did not (group 2). Three of group 1 also had a history of OC-induced hypertension. None were pregnant, but one was taking an OC at presentation with MHT. Blood pressures at presentation and follow-up, and mean serum urea and creatinine at presentation were similar between groups, as was median survival (96 vs. 47 months, Lee- Desu statistic 0.75, p = 0.38). There was a trend towards poorer renal function at follow-up in group 1 patients, with higher mean serum urea and creatinine levels. The causes of death were renal failure (5), stroke (4) and heart disease (2). The OC was not a common cause of MHT- amongst our sample of women of childbearing age, but a past history of hypertension in pregnancy was important. Such patients also had a longer duration of hypertension and poorer renal function at follow-up.      

增生性瘢痕增生期与成熟期相关基因谱表达的差异

目的:从基因水平探索增生性瘢痕退行性变的机制,筛选调控增生性瘢痕从过度增殖向成熟稳定期转化的退行性变相关基因。方法:实验于2003-05/2005-03在解放军第二军医大学整形外科实验室和上海联合基因集团博星基因芯片公司进行。收集8例烧伤后增生性瘢痕患者的病理标本,每张芯片以同一患者同一部位退变成熟期的瘢痕组织为实验组,增生活跃期的瘢痕组织为对照组。按一步法抽提出瘢痕组织总RNA,纯化mRNA,分别制成Cy3和Cy5荧光标记cDNA探针,与含有14112个cDNA的高密度基因微矩阵芯片杂交,通过计算机扫描生物信息学分析筛选差异表达基因。结果:在14112个基因中,8例患者退变后稳定期的增生性瘢痕组织与增殖活跃的增生性瘢痕组织之间比较存在差异表达基因共有840条,其中上调基因438条,下调基因362条,新基因102条;包括细胞凋亡基因、原癌基因和抑癌基因、细胞骨架和运动基因、细胞受体、免疫相关、细胞信号和传递蛋白、代谢蛋白、发育相关等多种基因。结论:增生性瘢痕的退行性变与多种基因的差异表达有关。     

Use and validation of HT/HC assays to support 21st century toxicity evaluations

Advances in high throughput and high content (HT/HC) methods such as those used in the fields of toxicogenomics, bioinformatics, and computational toxicology have the potential to improve both the efficiency and effectiveness of toxicity evaluations and risk assessments. However, prior to use, scientific confidence in these methods should be formally established. Traditional validation approaches that define relevance, reliability, sensitivity and specificity may not be readily applicable. HT/HC methods are not exact replacements for in vivo testing, and although run individually, these assays are likely to be used as a group or battery for decision making and use robotics, which may be unique in each laboratory setting. Building on the frameworks developed in the 2010 Institute of Medicine Report on Biomarkers and the OECD 2007 Report on (Q)SAR Validation, we present constructs that can be adapted to address the validation challenges of HT/HC methods. These are flexible, transparent, and require explicit specification of context and purpose of use such that scientific confidence (validation) can be defined to meet different regulatory applications. Using these constructs, we discuss how anchoring the assays and their prediction models to Adverse Outcome Pathways (AOPs) could facilitate the interpretation of results and support scientifically defensible fit-for-purpose applications.     

Investigating the relationship between in vitro-in vivo genotoxicity: derivation of mechanistic QSAR models for in vivo liver genotoxicity and in vivo bone marrow micronucleus formation which encompass metabolism

Strategic testing as part of an integrated testing strategy (ITS) to maximize information and avoid the use of animals where possible is fast becoming the norm with the advent of new legislation such as REACH. Genotoxicity is an area where regulatory testing is clearly defined as part of ITS schemes. Under REACH, the specific information requirements depend on the tonnage manufactured or imported. Two types of test systems exist to meet these information requirements, in vivo genotoxicity assays, which take into account the whole animal, and in vitro assays, which are conducted outside the living mammalian organism using microbial or mammalian cells under appropriate culturing conditions. Clearly, with these different broad experimental categories, results for a given chemical can often differ, which presents challenges in the interpretation as well as in attempting to model the results in silico. This study attempted to compare the differences between in vitro and in vivo genotoxicity results, to rationalize these differences with plausible hypothesis in concert with available data. Two proof of concept (Q)SAR models were developed, one for in vivo genotoxicity effects in liver and a second for in vivo micronucleus formation in bone marrow. These "mechanistic models" will be of practical value in testing strategies, and both have been implemented into the TIMES software platform ( http://oasis-lmc.org ) to help predict the genotoxicity outcome of new untested chemicals.     

Effect of Selective Inhibition of Potassium Channels on Vasorelaxing Response to Cromakalim,Nitroglycerin and Nitric Oxide of Canine Coronary Arteries

A comparative study was performed on the sensitivity of in-vitro vasorelaxation by nitroglycerin and cromakalim to block glibenclamide, a blocker of ATP-sensitive potassium channels, and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channels. In isolated canine coronary arteries preconstricted with 25 μM prostaglandin F_2α, nitroglycerin (0.005–1.8 μM) and cromakalim (0.15–9.6 μM) produced dose-dependent vasodilations. Glibenclamide (30 μM) had no significant effect on relaxation of the dose-response curve to nitroglycerin and almost completely abolished the relaxation by cromakalim, a known opener of ATP-sensitive potassium channels. Iberiotoxin (90 nM) decreased the maximal response to nitroglycerin and had no effect on the vasodilation induced by cromakalim. The effect of iberiotoxin on the vasorelaxing action of nitric oxide, the active metabolite of nitroglycerin, was also examined. In a low potassium chloride (14.4–20.4 mM) medium, as a contractile stimulus, iberiotoxin inhibited relaxations by exogenous nitric oxide (100–200 nM). Enhancement of potassium concentrations to 35.4–40.4 mM significantly decreased relaxation by nitric oxide and under these conditions the inhibitory action of iberiotoxin disappeared. The present study demonstrated that in canine coronary arteries, the functional role of two potassium channels can be separated by pharmacological means. Nitroglycerin-induced vasorelaxation may be mediated, at least in part, by its enzymatic breakdown product, nitric oxide that activates large-conductance calcium-activated potassium channels.     

西陵知母中新芒果甙的分离与结构鉴定

西陵知母中新芒果甙的分离与结构鉴定洪永福韩公羽郭学敏（第二军医大学药学院中西药研究室，上海２００４３３）知母（ＡｎｅｍａｒｈｅｎａａｓｐｈｏｄｅｌｏｉｄｅｓＢｇｅ．）为常用中药，以根茎入药。文献［１］记载，我国河北易县西陵出产的为最佳品，以“西陵知母...     

血管紧张素转化酶抑制剂——卡托普利酯类衍生物的合成和药理作用

卡托普利(巯甲丙脯酸)为一新型的血管紧张素转化酶抑制剂,临床用于治疗高血压和充血性心力衰竭,但半衰期短。为延长药物作用时间和提高药效,本文合成了它的酯类衍生物。初步药理试验结果表明,某些酯类化合物呈现明显降压恬性和延长作用时间。     

Acid-Base and Electrolyte Changes during Exchange Transfusion

In connection with blood exchange transfusions carried out on forty newborn infants it has been found that the majority of the newborns requiring exchange transfusion have metabolic acidosis increasing to possibly critical severity by the end the exchange transfusion. The acidosis, however, is soon normalized spontaneously. Pretreatment with sodium bicarbonate infusion normalizes the pretrans fusion shift in acid-base balance and vents the development of a severe acidosis following the exchange transfusion without risking a subsequent alkalosis. Before exchange transfusion a slight hypernatraemia has often been observed and this increases transiently after blood exchange. Pretreatment with infusion did not modify this phenomenon. In our material no hyperpotassaemia has been encountered by the end of ex- change transfusion. I n response to pre-treatment with sodium bicarbonate infusion the plasma K⁺ level decreased slightly. By promoting the conjugation of bilirubin to proteins, pretreatment with sodium bicarbonate may presumably improve also the efficiency of the exchange transfusion; this, however, requires further proof.     

复方蚁酒的薄层鉴别研究

目的：制订复方蚁酒中蚂蚁、枸杞子的薄层鉴别方法。方法：用薄层色谱法,经溶剂提取制备样品,分别以正丁醇－冰醋酸－水（３：２：１）、甲苯－乙酸乙酯－甲醇－甲酸（４：３：０．８：０．２）为展开剂。结果：供试品色谱中,在与对照品色谱相应位置上,显相同颜色的斑点。结论：斑点清晰、重现性好,可作为该制剂的质量控制方法之一。     

Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis by dietary olive oil and squalene

Epidemiological studies have suggested that frequent olive oil consumption may be a protective factor against lung cancer formation. Squalene, a characteristic compound in olive oil, is an inhibitor of 3- hydroxy-3-methylglutaryl coenzyme A reductase activity and has been proposed to inhibit the farnesylation of ras oncoproteins. The present study investigated the effect of dietary olive oil and squalene in a mouse lung tumorigenesis model. Female A/J mice were fed AIN-76A diets containing 5% corn oil (control), 19.6% olive oil, or 2% squalene starting at 3 weeks before a single dose of 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK) (103 mg/kg, i.p.). Animals were maintained on their respective diets throughout the study. At 16 weeks after NNK administration, 100% of the mice in the control group had lung tumors with a tumor multiplicity of 16 tumors per mouse. The olive oil and squalene diets significantly (P < 0.05) decreased the lung tumor multiplicity by 46 and 58%, respectively. The squalene diet significantly (P < 0.05) decreased lung hyperplasia by 70%. In mice fed a diet containing 2% squalene for 3 weeks, the activation of NNK was increased by 1.4- and 2.0-fold in lung and liver microsomes, respectively, but its relationship to the inhibition of carcinogenesis is not clear. These results demonstrate that dietary olive oil and squalene can effectively inhibit NNK-induced lung tumorigenesis.