肾血管性高血压和肾上腺腺瘤患者肾素-血管紧张素-醛固酮含量分析

目的 探讨肾素-血管紧张素-醛固酮系统、内皮素、一氧化氮在肾血管性高血压患者、肾上腺腺瘤患者中的作用和意义.方法 采用放射免疫分析的方法测量肾血管性高血压组(40例)、肾上腺腺瘤组(35例)和健康对照组(35例)血清肾素、血管紧张素Ⅱ、醛固酮、内皮素含量,用酶免疫法测定上述人群一氧化氮合酶(NOS)的含量来表示NO的量.结果 肾血管性高血压患者肾素、血管紧张素、醛固酮、内皮素含量高于健康对照组(P＜0.01),NOS含量低于健康对照组(P＜0.05);肾上腺腺瘤组醛固酮和内皮素含量高于健康对照组(P＜0.01),肾素、血管紧张素低于健康对照组(P＜0.05).结论 肾索、血管紧张素、醛固酮、内皮素和NO的检测可为临床早期诊断肾上腺腺瘤、肾血管性高血压提供依据.     

高血压引起的主动脉夹层患者60例用药分析

目的 了解主动脉夹层(AD)患者降压药物使用情况.方法 选择由高血压引起的AD患者60例,对其降压药物使用情况及血压、心率达标情况进行统计分析.结果 入院时为尽快达到目标血压,首选硝普钠静脉用药联合多种口服降压药物;口服降压药物使用率排列:β受体阻滞剂>钙离子拮抗剂(CCB)>血管紧张素受体拮抗剂(ARB)>血管紧张素转换酶抑制剂(ACEI)≥α受体阻滞剂>利尿剂;出院用药仍为多种降压药物联合使用;患者出院时血压、心率达标率显著高于入院时,差异有统计学意义(P<0.01).结论 高血压引起的AD患者降压药物使用特点为强效、多药联合,有效缓解了病情,但临床药师仍应加强药物不良反应监测、出院教育及随访工作.     

高血压合并急性心肌梗死临床分析

目的 探讨高血压合并急性心肌梗死(AMI)患者的病变特点及临床特征.方法 选择87例AMI患者为研究对象,根据有无高血压病史分为高血压组56例和对照组31例,比较2组患者的病变特点及临床特征.结果 2组临床症状、收缩压下降值、舒张压下降值、血压下降率、心功能分级构成、主要并发症的发生率差异有统计学意义(P＜0.05),2组冠状动脉造影情况比较,差异有统计学意义(P＜0.05),高血压组多支血管病变所占比重大,弥漫性病变及小血管病变多见.结论 高血压是AMI的危险因素,早期积极控制血压对AMI的发生、发展及预后有重要临床意义.     

高血压药物临床分析与应用

目的 分析临床高血压药物的使用情况,为合理选择高血压药物提供依据.方法 分析我院治疗的高血压患者220例的临床资料,分析患者抗高血压药物的使用情况.结果 220例患者,有167例患者为单一使用抗高血压药物,53例患者为高血压药物联合使用,单一用药患者与联合用药患者相比,均为钙离子拮抗剂为最常用抗高血压药物,其次为利尿剂、血管紧张素转化酶抑制剂、β受体阻断剂、血管紧张素受体拮抗剂和复方制剂,两组患者相比,药物的选择情况相比,无明显差异(P>0.05).结论 目前临床上最常用的抗高血压药物为钙离子拮抗剂,根据患者的高血压情况选择适合的抗高血压药物单一或联合用药,可以有效的控制患者血压.     

血液透析病人并发高血压应用降压药物处方分析

目的 调查血液透析病人并发高血压降压药物使用情况,探讨药物使用的合理性,为临床合理用药提供参考.方法 收集某医院2015年1-3月血液透析病人高血压用药的电子处方,对各类药物的用药频率及联合用药情况进行分析.结果 在含有高血压药物的处方中,最为常用的抗高血压药物依次为钙通道阻滞剂(CCB)、血管紧张素Ⅱ受体阻滞剂(ARB)、β-受体阻滞剂(β-RB)和血管紧张素转化酶抑制剂(ACEI).抗高血压药应用频率最高为硝苯地平控释片,处方中采用单一用药进行降压的占44.00%,二联占30.00%,三联及其以上占26.00%.结论 某医院血液透析病人并发高血压降压用药基本符合当前高血压治疗原则及个体化治疗方案,无滥用药物情况,但仍需提高用药的合理性.     

螺内酯对难治性高血压患者RAAS指标的影响研究

目的 探究螺内酯对难治性高血压患者肾素-血管紧张素-醛固酮系统(RAAS)指标的影响.方法 选择2013年1月-2014年12月仙桃市第-人民医院收治的116例难治性高血压作为研究对象,随机分为观察组和对照组各58例.对照组接受常规治疗,观察组在常规治疗基础上服用螺内酯.治疗后,分析两组RAAS指标(肾素活性、血管紧张素Ⅱ以及醛固酮水平)变化情况及临床效果.结果 两组治疗10周后较治疗前肾素活性、血管紧张素Ⅱ以及醛固酮水平比较均显著降低(P＜0.05);观察组较对照组水平均显著降低(P＜0.05);治疗5周及10周后观察组显效率及总有效率均高于对照组(P＜0.05).结论 螺内酯可以有效地将交感神经活性阻断,降低RAAS指标,其机制可能是通过阻断肾素、血管紧张素Ⅱ以及醛固酮三者的产生,起到协同降压的效果.     

中西医结合治疗原发性高血压临床观察

目的 探讨中西医结合治疗原发性高血压的临床疗效.方法 100例患者随机分为观察组和对照组各50例.对照组选用血管紧张素受体阻断剂(ARB)、钙离子通道拮抗剂(CCB)、血管紧张素转换酶抑制剂(ACEI)、α受体阻滞剂、β受体阻滞剂等降压治疗.观察组在对照组治疗的基础上加服自拟降压方.20d为1个疗程.观察2组降压疗效、症状积分疗效及不良反应发生情况.结果 观察组降压疗效总有效率为96%高于对照组的92%,差异有统计学意义(P<0.05).观察组症状积分疗效总有效率为96%高于对照组的84%,差异有统计学意义(P<0.05).对照组出现头晕、头痛、大便干燥4例,观察组出现2例,但仍坚持治疗.结论 中西医联合用药较单纯西药治疗原发性高血压疗效更佳.     

降压药在老年高血压病患者中的临床药学分析

目的 分析老年高血压病患者使用降压药物的情况.方法 选择2008年1月至2011年6月我院门诊治疗的原发性老年高血压患者900例,分析其降压药物的应用情况.结果 ①老年高血压患者收缩压控制理想(＜140 mm Hg)的占51%,舒张压控制率优于收缩压控制率.②降压药物使用由高到低依次是:钙离子阻滞剂、血管紧张素转化酶抑制剂、β-受体拮抗剂、血管紧张素Ⅱ受体阻滞剂(ARB)、利尿剂、直接舒张血管平滑肌药.③踝部水肿、低血钾、干咳、心动过缓、体位性低血压等为其主要副作用.结论 老年高血压病降压药物使用基本符合规范,部分患者存在药物不良反应.     

社区高血压综合防治措施应用探讨

目的 探讨实施社区内高血压防治综合措施应用的效果.方法 随机选择2006年6月到2011年3月我院确诊高血压患者、高危人群和健康人群各50例,对入选对象进行问卷调查和健康教育.结果 高血压患者治疗率从47%上升到90.2%;血压控制率从40.6%上升至85.1%,差异有统计学意义(P＜0.05).高危人群组以及健康人群组的高血压防治知识掌握程度从29.06%上升至95.46%,差异有统计学意义(P＜0.05).结论 社区高血压综合防治措施能够有效提高人们的高血压防治知识掌握程度,纠正不良行为习惯和生活方式.     

高血压病患者血清瘦素水平与血管紧张素Ⅱ及一氧化氮的相关性研究

目的 探讨原发性高血压患者血清瘦素(Leptin)与血管紧张素II(Angiotensin-II,AngⅡ)及一氧化氮(Nitric Oxide,NO)的相关性.方法 原发性高血压患者86例,对照组87例,测定其空腹血清Leptin、NO、胆固醇(TC)、甘油三酯(TG)、体重指数(BMI)、AngⅡ,分析原发性高血压患者血清Leptin与AngⅡ及NO的关系.结果 高血压组的Leptin、AngⅡ、BMI、TC、TG显著高于对照组,差异有统计学意义(P＜0.05),NO显著低于对照组(P＜0.05).多元逐步回归分析显示瘦素与AngⅡ正相关,与NO负相关.结论 原发性高血压患者血清瘦素水平与AngⅡ及NO有相关性.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture

Arsenic at a nonlethal level in drinking water consumed over a period of time has been reported to produce chronic toxicity and various types of health problems ranging from skin cancer to disturbance in memory. Neurotoxic effects have been reported in clinical cases with chronic exposure to arsenic. Physiological detoxication of arsenic occurs partially through methylation. Arsenic and its methylated derivatives are distributed in different organs and systems. The present study examined the possible interference in the neuronal development and differentiation due to the exposure to arsenic during gestation. The experiments were carried out to examine short and long term effects of arsenic on brain explants and cells grown and maintained in tissue culture system. The effects of arsenic exposure showed changes in brain cell membrane function indicated by generation and release of reactive oxygen-nitrogen intermediates. On the morphological aspect the explants' growth was reduced, ground matrix was lost and neural networking was inhibited. Cells showed signs of apoptotic changes. Arsenic toxicity may induce damage to brain cells prior to more visible clinical conditions. The deleterious effects also pass from the maternal to fetal tissue across the transplacental barrier.     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85–100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Circulating nucleic acids in plasma and serum: roles in diagnosis and prognosis in diabetes and cancer

The presence of DNA and RNA circulating in human plasma and serum is described. The possible sources of the DNA/RNA in blood, their ability to enter other cells and to express in the recipient cells are discussed and the relationship with metastases considered. The possible role(s) of the DNA/RNA in clinical diagnosis, in monitoring treatment and in prognosis are considered for diabetes and oncology.     

SalB stimulates neurogenesis and angiogenesis in vitro and in vivo

Aims： Previous studies suggested that Salvianolic acid B （SalB） has strong protective effect against cerebral ischemia. Recently, Sal B has been reported to enhance angiogenesis in vitro. Based on the information above, in this study we are interested in the effect of SalB on neurogenesis and angiogenesis. Methods：In vitro study, we used embryonic mouse （El6） primary cortical neural cultures. Neuron was recognized by anti-MAP2 with immunocytochemistry. Neurogenesis was tested with BrdU incorporation by ELSA method. SalB（ 10 -6 -10 -8M） or vehicle was added to the culture medium 24 hrs before BrdU addition. In vivo, middle cerebral artery occlusion （MCAO） rats were used as focal cerebral ischemia model.     

Metabolic interaction between imipramine and carbamazepine in vivo and in vitro in rats

Summary The pharmacokinetic consequences of the combination of carbamazepine with imipramine in male Wistar rats have been investigated. It was found that a 2-week treatment with the combination resulted in the increase of the concentrations of the parent compounds and a simultaneous decrease in their metabolites in blood plasma i.e. carbamazepine inhibited imipramine demethylation in the side chain while imipramine inhibited carbamazepine 10,11-epoxidation. The velocity of imipramine 2-hydroxylation and 10,11-epoxy-carbamazepine hydration did not seem to be changed by the combination. On the basis of studies in vitro it is concluded that the observed metabolic interaction between carbamazepine and imipramine is due to the competition of the drugs for the active centre of cytochrome P 450 and to a certain qualitative alteration of the enzyme by imipramine as can be deducted from the decrease of carbamazepine binding to the cytochrome. Send offprint requests to K. J. Netter     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85-100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants

INTRODUCTION: There is a lack of high-quality data regarding optimal chemotherapy dosage regimens among infants. Dosing regimens for chemotherapy during the first year of life are commonly based on empiric recommendations extrapolated from older children; however, balancing efficacy and toxicity is critical as severe adverse drug reactions may lead to treatment failure or reduced adherence to needed medications. AREAS COVERED: This review describes pharmacokinetic and pharmacogenetic considerations when administering chemotherapeutic agents to infants. Examples of commonly used agents are provided with practical recommendations for dosing adjustments. EXPERT OPINION: Optimal chemotherapy for children and infants in particular has lagged behind the remarkable progress in cancer treatment and it is clear that far more basic and clinical research are needed with respect to the mechanistic basis of age-dependent differences in pharmacokinetic parameters. More recent studies which have combined pharmacokinetic data with clinical toxicity and outcome data have resulted in a number of more evidence-based guidelines at least for the initial chemotherapy dosing; however, at present, the dosing of chemotherapy drugs in neonates and infants remains largely empiric.     

Consistency in catecholamine and cortisol excretion in males and females

Data from a series of experiments performed on 24 female and 24 male subjects were used to evaluate the consistency in urinary catecholamine and cortisol excretion. Data were available from 8 laboratory situations of varying activity level and content, spaced at intervals of maximum 3 months. Correlational analyses showed that for cortisol, interindividual consistency was higher for measures obtained on the same day than for measures obtained on different days. Interindividual consistency was generally high in catecholamine and cortisol excretion during non-stressful situations in both sexes. During experimental stress, however, consistency was as high as during nonstress for males, while it was lower for females. Analysis of variance components confirmed these results and showed that in males variation due to interindividual differences was high during both baseline and experimental-stress situations, while in females it was high during baseline situations only. During experimental stress, variation for females was due primarily to interaction. It is suggested that the males showed a more generalized stress response over situations than the females.     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.