Removal of pharmaceuticals in microcosm constructed wetlands using Typha spp. and LECA

Microcosm constructed wetlands systems established with a matrix of light expanded clay aggregates (LECA) and planted with Typha spp. were used to evaluate their ability to remove pharmaceuticals ibuprofen, carbamazepine and clofibric acid from wastewaters. Seasonal variability of these systems’ performances was also evaluated. Overall, removal efficiencies of 96%, 97% and 75% for ibuprofen, carbamazepine and clofibric acid, respectively, were achieved under summer conditions after a retention time of 7 days. In winter, a maximum loss of 26% in removal efficiency was observed for clofibric acid. Removal kinetics was characterized by a fast initial step (>50% removal within 6 h) mainly due to adsorption on LECA but, on a larger timescale, plants also contributed significantly to the system’s performance. Despite the fact that further tests using larger-scale systems are required, this study points to the possible application of these low-cost wastewater treatment systems for dealing with pharmaceuticals contaminated wastewater.     

Extrashot-ODS, a syringe-type minicolumn sample injector for a reversed-phase high-performance liquid chromatographic column: Application to antiepileptics in human sera

Extrashot-ODS (EXS-ODS) is a syringe-type minicolumn developed for sample injection into reversed-phase high-performance liquid chromatographic columns. EXS-ODS consists of (a) a stainless-steel needle fitted to an ordinary syringe-loading sample injector for HPLC, (b) a 45-μl minicolumn tube made of polytetrafluoroethylene (PTFE) and packed with ODS-silica and (c) a minicolumn holder made of polystyrene, which is connected to the needle on one side and the other side is shaped so as to be fitted with a solvent syringe. Using the device, we simultaneously analyzed three antiepileptics in 20 μl of human sera. First, we introduced a 20-μl serum specimen diluted with 100 μl of buffer solution into the device and, second, 100 μl of distilled water. Then the device was attached to the HPLC injector and 130 μl of methanol were introduced into the HPLC column through the device. Then, reversed-phase HPLC was conducted in the usual manner, with the chromatogram reading at a wavelength of 210 nm for the assays of 5,5-diphenylhydantoin, phenobarbital and carbamazepine. The results obtained by direct peak-height calibration were comparable to those given by the immunological method.     

CYP3A5*3 基因多态性对癫痫患者卡马西平及其主要代谢物浓度的影响

背景:卡马西平(carbamazepine,CMZP)主要由CYP3A酶家族代谢,其代谢酶主要包括CYP3A5。本研究探讨了CYP3A5基因多态性与卡马西平血清浓度(CMZP)之间的关系,对个体化药物治疗的开展具有十分积极的意义。目的:CYP3A5*3的基因型可以影响CYP3A药物的药代动力学。本研究旨在评估CYP3A基因多态性对癫痫患者血清卡马西平稳态浓度及其代谢物水平的影响。方法:研究共纳入278例患者,检测个体卡马西平的血清浓度及CYP3A5基因型,并探讨CYP3A5基因型对卡马西平稳态血药浓度的影响。结果:根据基因型分为成CYP3A5表达组(CYP3A5*1/*1和CYP3A5*1/*3)和非表达组(CYP3A5*3/*3)两组。278例患者中120例为CYP3A5表达组,158例患者为CYP3A5非表达组。CYP3A5非表达组的总卡马西平剂量和剂量标准化后的卡马西平血清浓度均高于CYP3A5表达组(P=0.608和P=0.000)。CYP3A5表达组中卡马西平环氧化物浓度更高(P=0.000),但这两组间的血清药物浓度无显著差异(P=0.090)。结论:CYP3A5*3基因多态性与卡马西平的血清浓度之间有密切的关系。CYP3A5基因影响了卡马西平血药浓度水平和代谢过程,其可能是导致卡马西平在癫痫患者中个体变异的一个重要因素。     

拉莫三嗪治疗部分性发作癫痫患者的疗效及对认知功能及生活质量的影响

目的:探讨拉莫三嗪对部分性发作癫痫患者的疗效及对认知功能及生活质量的影响。方法:选择2012年6月到2013年12月在我院接收治疗的部分性发作癫痫患者60例,按随机数字表法随机分为对照组(n=30)和治疗组(n=30);对照组患者给予卡马西平进行治疗,治疗组患者给予拉莫三嗪进行治疗。治疗20周后,对比两组患者的治疗效果、认知功能及生活质量。结果:治疗组患者的无发作率和总有效率分别为20.00%和80.00%,均显著高于对照组的6.67%和53.33%(P0.05);治疗后治疗组患者认知功能总评分明显高于对照组,(P0.05);治疗后治疗组患者各项生活质量评分均明显高于对照组(均P0.05)。结论:拉莫三嗪对部分性发作癫痫患者有显著疗效,能够有效控制癫痫发作,对改善患者认知功能及生活质量有重要作用。     

卡马西平与丙戊酸钠对儿童癫痫部分性发作脑电图的临床对照研究

目的:探究卡马西平与丙戊酸钠对儿童癫痫部分发作患儿发作脑电图影响,并实施组间对照研究。方法:选择2017年1月至2020年1月于我院接受治疗的81例癫痫部分性发作患儿为研究对象,按照其接受治疗的差异将其分为卡马西平组(40例)和丙戊酸钠组(41例),对比两组患儿接受药物治疗后脑电图以及脑电地形图变化情况。结果:(1)卡马西平组患儿接受治疗后脑电图检测显示间歇期痫样活动减少≥50%者占比高达67.50%(27/40),而丙戊酸钠组占比仅为43.90%(18/41),两组比较差异明显(P<0.05);(2)脑电背景活动变化比较显示,治疗后卡马西平组患儿α波无影响者占比65.00%,明显高于丙戊酸钠组36.59%,同时丙戊酸钠组患儿δ波数(20 s内)药物治疗后变化较卡马西平组更为明显;(3)脑电功率比较显示,卡马西平组患儿治疗后仅θ频段相对功率出现明显变化(P<0.05),但丙戊酸钠组患儿α频段相对功率、θ频段相对功率和θ频段绝对功率均出现明显变化(P<0.05)。结论:丙戊酸钠应用于儿童癫痫部分性发作时患儿脑电背景活动会明显变慢,甚至有出现间歇期痫样放电的风险,而卡马西平相对更为稳定,对患儿脑电图的影响更小,安全性更高。     

Chronotherapeutic Dose Schedule of Phenytoin and Carbamazepine in Epileptic Patients

The objective of this study was to compare the efficacy and safety of a chronotherapeutic dosing schedule of phenytoin and carbamazepine versus a conventional dosing schedule for the treatment of tonic‐clonic epileptic patients. Of 148 epileptic subjects found to have subtherapeutic trough drug levels (subtherapeutic group, STG), 103 subjects who completed the study were randomized to either STG I (n=51) for treatment by the conventional dosing schedule (tablet phenytoin 100–400 mg/day OD or BD, tablet carbamazepine 200–800 mg BD, or both, equally divided doses with no fixed time of drug intake), with a dose increment but no change in usual time of drug administration allowed; or to STG II (n=52), with no dose increment permitted but a shift in all or most (two‐thirds or three‐fourths) of the daily dose of one or both medications to 20:00 h. The 62 patients who experienced drug toxicity reactions (toxicity group, TG) and who had serum drug levels in the toxic range were assigned to TG I for dose reduction or TG II for dose reduction and drug administration at 20:00 h. Those 16 subjects in STG I and 47 subjects in STG II who initially evidenced subtherapeutic trough drug concentrations exhibited therapeutic drug levels by the end of four weeks of treatment (p<0.01). A significantly greater number of TG II, as compared to TG I, subjects who experienced toxic reactions showed improved drug tolerance. There were no poor responders and more good responders (control of epilepsy for one year) in STG II compared to STG I subjects. The findings of this study indicate that a chronotherapeutic dosing schedule of phenytoin and carbamazepine involving the administration of most or all the daily dose of medication(s) at 20:00 h can improve the response of diurnally active epileptic patients not responding to standard doses, achieve therapeutic drug levels, and reduce toxic manifestations in subjects having drug concentrations beyond the therapeutic range.     

Nefopam is more potent than carbamazepine for neuroprotection against veratridine <Emphasis Type="Italic">in vitro</Emphasis> and has anticonvulsant properties against both electrical and chemical stimulation

Summary. Nefopam (NEF) is a known analgesic that has recently been shown to be effective in controlling both neuropathic pain and convulsions in rodents. In this study we compared nefopam to carbamazepine (CBZ), a reference antiepileptic drug (AED), for their ability to protect cerebellar neuronal cultures from neurodegeneration induced by veratridine (VTD). Furthermore, we tested nefopam for protection against both, maximal electroshock-induced seizures (MES), and isoniazid-induced seizures in mice. Both NEF and CBZ were effective in preventing both signs of excitotoxicity and neurodegeneration following exposure of cultures to 5 μM veratridine for 30 min and 24 h, respectively. Concentrations providing full neuroprotection were 500 μM CBZ and 50 μM NEF, while the concentration providing 50% neuroprotection was 200 μM for CBZ and 20 μM for NEF. Neither NEF nor CBZ reduced excitotoxicity following direct exposure of cultures to glutamate, but CBZ failed to reduce increases in intracellular calcium following stimulation of L-type voltage sensitive calcium channels. In vivo, NEF (20 mg/kg i.p.) significantly reduced MES and fully prevented MES-induced terminal clonus (TC). In comparison, NEF was significantly more effective than CBZ in preventing MES, although both drugs were equally effective against MES-induced TC. Furthermore, nefopam provided protection against isoniazid-induced seizures at doses similar to those protecting against MES.     

Modulation of antioxidant defence system in brain of rainbow trout (Oncorhynchus mykiss) after chronic carbamazepine treatment

We investigated the effect of long-term exposure to CBZ on the antioxidant system in brain tissue of rainbow trout. Fish were exposed to sublethal concentrations of CBZ (1.0 μg/L, 0.2 mg/L or 2.0 mg/L) for 7, 21, and 42 days. Oxidative stress indices (LPO and CP) and activities of antioxidant enzymes (SOD, CAT, GPx and GR) in fish brain were measured. In addition, non-enzymatic antioxidant (GSH) was determined after 42 days exposure. Carbamazepine exposure at 0.2 mg/L led to significant increases (p < 0.05) of LPO and CP after 42 days and, at 2.0 mg/L, after 21 days. Activities of the antioxidant enzymes SOD, CAT, and GPx in CBZ-treated groups slightly increased during the first period (7 days). However, activities of all measured antioxidant enzymes were significantly inhibited (p < 0.05) at 0.2 mg/L exposure after 42 days and after 21 days at 2.0 mg/L. After 42 days, the content of GSH in fish brain was significantly lower (p < 0.05) in groups exposed to CBZ at 0.2 mg/L and 2.0 mg/L than in other groups. Prolonged exposure to CBZ resulted in excess reactive oxygen species formation, finally resulting in oxidative damage to lipids and proteins and inhibited antioxidant capacities in fish brain. In short, a low level of oxidative stress could induce the adaptive responses of antioxidant enzymes, but long-term exposure to CBZ could lead to serious oxidative damage in fish brain.     

卡马西平联合左甲状腺素对甲状腺功能减退症患者血清IGFBP-3、25(OH)D3的影响

目的:探讨卡马西平联合左甲状腺素对甲状腺功能减退症患者血清胰岛素样生长因子结合蛋白-3(IGFBP-3)、25羟维生素D3(25(OH)D_3)的影响。方法:选择2017年5月～2018年6月本院接诊的103例甲状腺功能减退症患者进行研究,通过随机数表法分为观察组52例和对照组51例,对照组给予左甲状腺素口服治疗,观察组在对照组基础上联合卡马西平口服治疗,两组患者均连续治疗8周。比较两组临床疗效、治疗前后甲状功能、血清IGFBP-3和25(OH)D_3的变化情况及不良反应。结果:治疗后,观察组患者的临床疗效为94.23%,明显高于对照组患者的84.31%(P0.05);观察组血清FT3、TSH均明显比对照组低,FT4明显高于对照组(P0.05);两组患者治疗后IGFBP-3和25(OH)D_3的指标水平均高于治疗前,且观察组结果高于对照组(P0.05);观察组不良反应总发生率为5.76%,低于对照组的13.73%,两组不良反应总发生率差异无统计学意义(P0.05)。结论:卡马西平联合左甲状腺素对甲状腺功能减退症患者临床效果显著,可有效改善患者甲状腺功能,调节患者血清IGFBP-3和25(OH)D_3的表达水平,且不良反应少、安全性高,值得推广。     

Chronic Carbamazepine Administration Attenuates Dopamine D<Subscript>2</Subscript>-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

Observations that dopaminergic antagonists are beneficial in bipolar disorder and that dopaminergic agonists can produce mania suggest that bipolar disorder involves excessive dopaminergic transmission. Thus, mood stabilizers used to treat the disease might act in part by downregulating dopaminergic transmission. In agreement, we reported that dopamine D2-like receptor mediated signaling involving arachidonic acid (AA, 20:4n-6) was downregulated in rats chronically treated with lithium. To see whether chronic carbamazepine, another mood stabilizer, did this as well, we injected i.p. saline or the D2-like receptor agonist, quinpirole (1 mg/kg), into unanesthetized rats that had been pretreated for 30 days with i.p. carbamazepine (25 mg/kg/day) or vehicle, and used quantitative autoradiography to measure regional brain incorporation coefficients (k*) for AA, markers of signaling. We also measured brain prostaglandin E2 (PGE2), an AA metabolite. In vehicle-treated rats, quinpirole compared with saline significantly increased k* for AA in 35 of 82 brain regions examined, as well as brain PGE2 concentration. Affected regions belong to dopaminergic circuits and have high D2-like receptor densities. Chronic carbamazepine pretreatment prevented the quinpirole-induced increments in k* and in PGE2. These findings are consistent with the hypothesis that effective mood stabilizers generally downregulate brain AA signaling via D2-like receptors, and that this signaling is upregulated in bipolar disorder.