抗癫痫药物对患者外周血叶酸及维生素B12的影响

目的：探讨抗癫痫药物（AEDs）对患者外周血叶酸及维生素B12的影响。方法：选择2014年5月～2016年5月我院收治的癫痫患者120例,根据用药情况将120例患者分为如下几组,即丙戊酸钠组23例,德巴金组20例,卡马西平组20例,奥卡西平组19例,托吡酯组18例,未应用AEDs组20例。观察比较各组患者外周血维生素B12、叶酸与Hcy的水平。结果：丙戊酸钠组、德巴金组叶酸水平与未应用AEDs组、对照组比较差异无统计学意义（P>0.05）。卡巴西平组、奥卡西平组及托吡酯组叶酸、维生素B12水平低于未应用AEDs组、对照组（P<0.05）。卡马西平组、奥卡西平组与托吡酯组Hcy水平高于未应用AEDs组、对照组（P<0.05）。结论：采取AEDs治疗癫痫应常规监测外周血叶酸、维生素B12与Hcy水平,以便积极预防血栓事件,保证治疗质量。     

奥卡西平与丙戊酸钠对小儿部分性癫痫发作的疗效及其安全性比较

目的:比较奥卡西平与丙戊酸钠对小儿部分性癫痫发作的疗效及其安全性。方法:选取2014年6月—2016年5月间住院治疗的3岁以下小儿部分性癫痫发作患儿78例,采用平行、随机、双盲方法将其分成奥卡西平组(40例)和丙戊酸钠组(38例),分别采用奥卡西平和丙戊酸钠治疗,评价两组患儿治疗后癫痫发作的控制情况、总有效率及不良反应的发生率。结果:两组患儿治疗后脑电图的好转率和总有效率经组间比较其异无统计学意义(P>0.05),不过奥卡西平组患儿治疗后癫痫发作完全控制率和不良反应的发生率优于丙戊酸钠组(P<0.05)。结论:奥卡西平和丙戊酸钠二药抗癫痫发作的总体疗效相近,均可作为备选药品治疗;对于3岁以下婴幼儿部分性癫痫发作均有较好的控制性和安全性,这有助于长期用药,确保治疗的连续性。     

奥卡西平联合丙戊酸钠对脑梗死后继发癫痫患者疗效及血液流变学的影响

目的 分析奥卡西平联合丙戊酸钠对脑梗死后继发癫痫患者疗效及血液流变学的影响。方法 选取2019年1月至2021年12月湖北省丹江口市第一医院收治的脑梗死继发癫痫的患者100例作为研究对象,按照随机数字表法分为观察组（50例）和对照组（50例）。对照组采用常规抗癫痫药物丙戊酸钠进行治疗,观察组采用奥卡西平联合丙戊酸钠进行治疗,比较分析两组患者治疗后的效果、治疗前后脑电图指标、血液流变学指标和不良反应。结果 观察组治疗6个月后,治疗效果高于对照组,不良反应总发生率低于对照组,差异有统计学意义（P<0.05）。观察组治疗6个月后,α波低于对照组,δ波、θ波均高于对照组,差异有统计学意义（P<0.05）。治疗6个月后观察组全血高切黏度、低切黏度和纤维蛋白原水平低于对照组,差异有统计学意义（P<0.05）。结论 奥卡西平联合丙戊酸钠对脑梗死继发癫痫患者疗效确切,而且可以有效地改变血液流变学水平,降低不良反应发生率,值得临床推广。     

丙戊酸钠联合生酮饮食治疗癫痫致血氨升高

1例3岁女性癫痫患儿服用丙戊酸钠180 mg、1次/12 h,因效果欠佳,加用生酮饮食疗法。生酮饮食治疗前血氨为64μmol/L。生酮饮食第1～3天患儿饮食中脂肪与碳水化合物及蛋白质的比例由1∶1逐渐增加至3∶1,第4天调整为4∶1,血氨为63μmol/L。生酮饮食第7天患儿血氨升至95μmol/L,丙戊酸钠调整为120 mg、1次/12 h口服。生酮饮食第10天,丙戊酸钠减至60 mg、1次/12 h口服。第11天血氨为68μmol/L。生酮饮食第13天,继续减量服用丙戊酸钠。生酮饮食治疗期间,患儿癫痫发作控制良好。     

丙戊酸诱发癫痫患儿高血氨的影响因素研究

目的：研究影响丙戊酸诱发高血氨的遗传及非遗传因素。方法：将260例服用丙戊酸的癫痫患儿（年龄<16岁）按血氨水平分为高血氨组130例、对照组130例。记录各组患儿人口学信息（包括性别、身高、体质量、年龄）、肝功能指标和用药信息（日剂量、合并用药等）,同时测定相关代谢酶CYP2C9,UGT1A6,UGT2B7,UGT1A4,转录因子AhR及尿素循环酶CPS1基因多态性,通过多因素Logistic回归分析遗传及非遗传因素对丙戊酸诱发高血氨的影响。结果：高血氨组肝功能指标GGT、丙戊酸的剂量、合并托吡酯的比例及合并服用其他抗癫痫药的数量均明显高于对照组。2组间CPS1,AhR和UGT2B7的基因型分布存在差异。CPS1 rs1047891 CA和AA型（P<0.001）以及AhR rs2066853 AG和AA型（P<0.001）是丙戊酸导致血氨升高的危险因素。结论：丙戊酸诱发的高血氨与多种遗传和非遗传风险因素相关,在癫痫儿童应用丙戊酸进行治疗时,建议定期监测体内血氨浓度,避免高血氨的发生。     

丙戊酸钠和奥卡西平对癫痫儿童生长速度和骨代谢的潜在影响

目的探讨丙戊酸钠和奥卡西平治疗癫痫患儿的临床疗效及对生长速度和骨代谢的影响。方法66例癫痫患儿按随机双盲法分为对照组和研究组,各33例。对照组给予丙戊酸钠治疗,研究组给予奥卡西平治疗。对比两组临床疗效、生长发育情况、治疗前后骨代谢相关指标及不良反应发生情况。结果研究组治疗总有效率为93.94%高于对照组的69.70%,差异具有统计学意义(P<0.05)。治疗后1、3、6个月,研究组的体质量指数(BMI)分别为(16.0±0.2)、(16.2±0.5)和(16.3±0.3)kg/m2,均高于对照组的(15.3±0.3)、(15.5±0.4)和(15.4±0.2)kg/m2,差异具有统计学意义(P<0.05)。观察组治疗前后血钙离子、血磷离子及甲状旁腺激素水平对比,差异无统计学意义(P>0.05)。治疗后,对照组血钙离子、血磷离子及甲状旁腺激素水平低于治疗前,差异均具有统计学意义(P<0.05)。研究组不良反应发生率为6.06%低于对照组的30.30%,差异具有统计学意义(P<0.05)。结论奥卡西平与丙戊酸钠相比,奥卡西平在治疗效果、安全性、生长发育等方面均具有明显优势,可以推广应用。     

癫痫儿童服用丙戊酸钠或卡马西平后血同型半胱氨酸的变化

目的:探讨癫痫儿童服用抗癫痫药物丙戊酸钠或卡马西平后血同型半胱氨酸( homocysteine,hcy)水平的变化,以便减少其潜在风险及不利影响.方法:选取67例癫痫患儿,按使用药物分为卡马西平组与丙戊酸钠组.卡马西平和丙戊酸钠的剂量分别为10 ～20 mg/(kg·d)和10～40 mg/(kg·d),并依据血药浓度适度调整剂量,疗程2～5年.在用药前、用药后6个月、用药后1年监测hcy水平,比较各组hcy水平变化.结果:共有67例患儿完成本研究,丙戊酸钠组36例,卡马西平组31例.丙戊酸钠组和卡马西平组hcy在用药前分别为(6.94±2.47)μmoL/L、(8.11±3.04) μmol/L,两组比较差异无统计学意义(P＞0.05);6个月时分别为(7.42±2.51) μmol/L、( 8.39±2.75) μmol/L,两组比较差异无统计学意义(P＞0.05);1年后分别为(8.92±2.81) μmol/L、(10.45±3.98) μmol/L,两组hcy水平均较前明显升高(P＜0.01).相关分析未发现癫痫发作及抗癫痫药物浓度与hcy呈明显相关性(P＞0.05).结论:丙戊酸钠或卡马西平引起hcy水平升高,6月以后更明显,临床需注意定期监测癫痫患儿的hcy水平并适当予以干预.     

不同药物联合治疗老年脑卒中后癫痫发作效果观察

目的:探究奥卡西平与左乙拉西坦联合丙戊酸钠治疗老年脑卒中后癫痫发作患者的效果.方法:选取2018-10～2020-02安阳市人民医院120例老年脑卒中后癫痫发作患者,根据治疗方案不同分为两组,单药组57例给予丙戊酸钠,联合组63例给予丙戊酸钠、奥卡西平与左乙拉西坦,比较两组治疗效果、脑电控制情况、治疗前后认知功能(SP...     

卡马西平联合丙戊酸钠治疗继发性癫痫的疗效研究

目的:探讨分析卡马西平联合丙戊酸钠治疗继发性癫痫的临床疗效。方法:在我院所收治的继发性癫痫患者中选取95例作为研究对象,分为3组,分别进行单纯卡马西平、单纯丙戊酸钠以及卡马西平联合丙戊酸钠治疗,比较三者治疗效果差异。结果:卡马西平联合丙戊酸钠治疗的总有效率(93.0%)明显比另2组(76.0%和86.0%)高,具有统计学意义。结论:卡马西平联合丙戊酸钠治疗继发性癫痫的疗效更高,不良反应的发生率较低。     

过量奥卡西平致定向力障碍及共济失调

1例6岁男性癫痫患儿,曾先后口服苯妥英钠、拉莫三嗪、丙戊酸钠、苯巴比妥治疗,因不能规律服药致使癫痫反复发作且进行性加重,家属自行给予其口服奥卡西平300 mg、3次/d,上述症状未再发作。但40 d后出现行走不稳、反应迟钝,且癫痫症状也加重。入院诊断为癫痫,全身强直-阵挛发作,奥卡西平致定向力障碍及共济失调。停用奥卡西平,给予丙戊酸钠、还原性谷胱甘肽、维生素C,次日癫痫得到控制。第8天定向力障碍及共济失调消失,癫痫未再发作,遂出院。出院后规律服用丙戊酸钠和氯硝西泮。随访1个月,未再出现癫痫发作、定向力障碍和共济失调。     

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     

Mechanisms of antiplatelet and antithrombotic activity of midazolam in in vitro and in vivo studies

Dopamine regulates various physiological functions in the central nervous system and the periphery. Dysfunction of the dopamine system is implicated in a wide variety of disorders and behaviors including schizophrenia, addiction, and attention-deficit hyperactivity disorder. Medications that modulate dopamine signaling have therapeutic efficacy on the treatment of these disorders. However, the causes of these disorders and the role of dopamine are still unclear. Studying the dopamine system in a model organism, such as Caenorhabditis elegans, allows the genetic analysis in a simple and well-described nervous system, which may provide new insight into the molecular mechanisms of dopamine signaling. In this review, we summarize recent findings on pharmacological and biochemical properties of the C. elegans dopamine receptors and their physiological role in the control of behavior.     

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.     

Extraction and determination of prednisolone in drugs and excipients in ointments and creams and the uniformity of distribution in prednisolone ointment

For the purpose of measuring the contents of prednisolone in low concentrated ointments and creams an instruction was elaborated that includes several steps of extraction, in the resulting solution of which the assay of the steroid by Blue Tetrazolium reaction will be done. The procedure permits the determination of prednisolone in presence of most of usual ingredients of ointment bases except wool alcohols. Also no influence is given by some remedies combined with prednisolone for topical application except coal tar solution. The results confirm a correct reflection of the steroid contents declared respectively the recovery of the steroid added to various ointment bases. Introducing discussion to content uniformity concerning low concentrated ointments is made, and some deviations are shown.     

Strain-dependency in motor activity and in concentration and turnover of catecholamines in synchronized rats

Circadian rhythm in motor activity was studied with an Animex motimeter in six strains of rats (ACI, BH, BS, DA, LEW, TNO) synchronized by a 12 hr light: 12 hr dark cycle. ANOVA revealed significant interstrain differences in motor activity as well as in the concentration and turnover of central noradrenaline and dopamine. Strain-dependent differences were also found with regard to tyrosine hydroxylase inhibition on motor activity. However, no significant interstrain correlations were found between endogenous concentration and/or turnover rates of the catecholamines and motor activity in normal and drug-treated rats.     

Pharmacokinetics and tolerability of artesunate and amodiaquine alone and in combination in healthy volunteers

Objectives  The WHO recommends artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria. At least 15 African countries have adopted artesunate plus amodiaquine as treatment policy. As no pharmacokinetic data on this combination have been published to date, we investigated its pharmacokinetic interactions and tolerability in healthy volunteers in Africa. Methods  In a randomized, three-phase, cross-over study, amodiaquine (10 mg/kg) and artesunate (4 mg/kg) were given as single oral doses to 15 healthy volunteers. Artesunate was given to all volunteers on day 0. On day 7 they received either amodiaquine or amodiaquine plus artesunate and the alternative regimen on day 28. The pharmacokinetics of artesunate and amodiaquine and their main active metabolites dihydroartemisinin and desethylamodiaquine were compared following monotherapy and combination therapy using analysis of variance. Results  Thirteen volunteers completed the study, and pharmacokinetic parameters could be determined for twelve volunteers. When given in combination, the mean AUC was lower for dihydroartemisinin [ratio 67% (95% CI 51–88%); P = 0.008] and desethylamodiaquine [ratio 65% (95% CI 46–90%); P = 0.015] when compared with monotherapy. Adverse events of concern occurred in four volunteers (27%): grade 3 transaminitis (n = 1), neutropaenia (n = 2), and hypersensitivity (n = 1). Conclusion  The total drug exposure to both drugs was reduced significantly when they were given in combination. The clinical significance of these interactions is unclear and must be studied in malaria patients. The frequency and nature of adverse events among the healthy volunteers were of concern, and suggest laboratory monitoring would be needed in malaria patients treated with artesunate plus amodiaquine.     

Simultaneous Determination of Sulfation and Glucuronidation of Flavones in FVB Mouse Intestine in Vitro and in Vivo

Glucuronidation and sulfation are the two major phase II metabolic pathways for flavones, natural compounds that hold great potential for improving human health. We investigated the positional preference for sulfation and glucuronidation of seven structurally similar flavones in vitro and in situ. An FVB mouse intestinal perfusion model was used in addition to three small intestine S9 fractions catalyzing sulfation only (Sult enzymes), glucuronidation only (Ugt enzymes) or both (Sult and Ugt enzymes). In both the single and co‐reaction S9 systems, flavones containing 7‐OH groups were conjugated only at 7‐OH despite the presence of other hydroxyl groups, and 7‐OH glucuronidation was faster than sulfation (P < 0.05). The sulfation rate was enhanced in the Sult‐Ugt co‐reaction system, while glucuronidation was usually unchanged by the presence of Sult. In the intestinal perfusate, sulfation patterns were the same in the small intestine and colon, and the excretion rate of 7‐O‐sulfate was the fastest or second fastest. The excretion of 7‐O‐glucuronidates was faster in small intestine (P < 0.05) than in colon. The S9‐mediated sulfation rates of the different flavones were significantly correlated with the excretion rates of the same flavones from perfused intestine. In conclusion, flavone glucuronidation and sulfation rates were sensitive to minor changes in molecular structure. In intestinal S9 fractions, both Ugts and Sults preferentially catalyzed reactions at 7‐OH. The sulfation rate was significantly enhanced by simultaneous glucuronidation, but glucuronidation was unaltered by sulfation. Sulfation rates in mouse S9 fractions correlated with sulfation rates in perfused intestine. Copyright © 2011 John Wiley & Sons, Ltd.     

Comparative in vivo and in vitro studies of phenytoin protein binding and in vitro lipolysis in plasma of pregnant and nonpregnant rats

This investigation was designed to determine the cause of the changes in drug protein binding that occur in rat plasma, particularly in plasma from pregnant animals, during in vitro drug-protein binding measurements. In vivo estimates of phenytoin binding in plasma were obtained from steady-state CSF-plasma concentration ratios in pregnant and nonpregnant rats. Immediate ultrafiltration of heparin- or EDTA-anticoagulated plasma yielded phenytoin free fraction values that were in good agreement with in vivo estimates for nonpregnant rats but that were about one-third higher than in vivo estimates for pregnant animals. In vitro free fraction values tended to increase during incubation of plasma and/or during equilibrium dialysis. The concentrations of the four major endogenous free fatty acids were similar in plasma of pregnant and nonpregnant rats if determined immediately after blood collection. Six hours of incubation at 37 degrees C caused fatty acid concentrations to increase about fivefold and twofold in heparin-anticoagulated plasma from pregnant and nonpregnant animals, respectively. The corresponding increases in EDTA-anticoagulated plasma were only about twofold and 1.14-fold, respectively. These changes were associated with decreased plasma protein binding of phenytoin. The in vivo differences between pregnant and nonpregnant rats with respect to phenytoin binding in plasma are not due to differences in fatty acid concentrations, but the in vitro differences are due primarily to corresponding differences in free fatty acid concentrations if extensive in vitro lipolysis occurs.     

A review of in vitro and in vivo models of oesophageal and gastric cancer

Importance of the field: Oesophageal and gastric cancers are leading causes of cancer-related mortality. In the era of targeted therapy and individualized treatment strategies, novel treatments for upper-gastrointestinal cancers are only just emerging compared to significant advances in other solid tumour types such as colorectal, breast and lung cancers. Clinical trials are investigating the value of established targeted agents for the treatment of oesophageal and gastric malignancies; however none are used in routine clinical practice.

Areas covered in this review: In this review we have looked at current in vitro and in vivo models of oesophageal and gastric cancers which may improve our understanding of the biology of these tumours and lead to the development of new preventative, diagnostic and therapeutic approaches.

What the reader will gain: We discuss the limitations of our current models and the challenges associated with research into these cancers.

Take home message: The lack of appropriate models for drug development in oesophageal and gastric cancers has hindered the progress of targeted therapy in this field.     

葛根芩连煎剂中小檗碱在犬体内药动学研究

目的:测定葛根芩连煎剂与黄连单煎剂犬血中小檗碱的含量,分析配伍后(全方)对小檗碱体内过程的影响。方法:采用高效液相色谱法,测定不同时间点犬血浆中小檗碱的含量,WinNonlin软件计算药动学参数。结果:葛根芩连煎剂及黄连单煎剂中小檗碱在犬体内药-时曲线均符合一室模型,主要药动学参数AUC(0-∞)(1·25±0·06)、(14·71±0·54)(μg·h)/ml,tmax(1·92±0·31)、(3·03±0·07)h,Cmax(0·17±0·01)、(1·79±0·03)μg/ml。结论:葛根芩连煎剂配伍后与单方比较小檗碱入血浓度及生物利用度都降低。