山楂籽黄酮提取物抗实验性心律失常作用的研究

目的观察山楂籽黄酮提取物对三氯甲烷及乌头碱诱发的心律失常作用。方法采用三氯甲烷诱导小鼠心律失常,静注乌头碱诱发大鼠心率失常,术前5 d给予山楂籽黄酮提取物,心电图连续示波观察并记录心室颤动、室性早搏、室性心动过速的发生次数、室性早搏出现时间以及乌头碱累积消耗量。结果与模型组相比山楂籽黄酮提取物能明显降低三氯甲烷诱导的小鼠室颤发生率,且可明显增加诱发大鼠发生心律失常的乌头碱消耗量,推迟心率失常出现时间,但对降低室性早搏和室性心动过速的发生次数无明显作用。结论山楂籽黄酮提取物能明显减轻由三氯甲烷及乌头碱引起的实验性心律失常。     

克班宁灌胃给药抗心律失常作用的研究

目的研究克班宁灌胃给药抗心律失常的作用。方法分别采用氯仿致小鼠心律失常和氯化钡、乌头碱致大鼠心律失常2种动物模型,以BL-420生物机能实验系统地观察心电图的相关指标,记录并分析心电图曲线。观察不同剂量的克班宁对小鼠、大鼠心律失常的保护作用。结果与空白组比较,克班宁各剂量组能明显拮抗氯仿所致的室颤发生率(P<0.05),能推迟氯化钡诱发的心律失常发生时间并缩短心律失常持续时间(P<0.01,P<0.05),延长乌头碱诱发的各种室性心律失常出现时间(P<0.05)。结论克班宁灌胃给药可对抗氯仿、氯化钡和乌头碱诱发的实验性心律失常。     

茉莉根提取物抗实验性心律失常的研究

目的研究茉莉根提取物的抗实验性心律失常作用。方法取茉莉根提取物分别注入由氯仿诱发心室颤动的小鼠、乌头碱诱发心律失常的大鼠、氯化钙诱发心室颤动的大鼠和肾上腺素诱发心律失常的家兔体内,观察其对实验动物心律失常的影响。结果①茉莉根提取物(腹腔注射2.0mg/kg、3.0mg/kg)对氯仿诱发的小鼠心室颤动有明显的预防作用;②茉莉根提取物(静脉注射1.0mg/kg、1.5mg/kg)对乌头碱诱发的大鼠心律失常有明显的治疗效果;③茉莉根提取物(静脉注射2.0mg/kg、3.0mg/kg)对氯化钙诱发的大鼠心室颤动具有预防作用,且能明显地降低大鼠的死亡率;④茉莉根提取物(静脉注射2.0mg/kg、3.0mg/kg)还能对抗肾上腺素诱发的家兔心律失常。以上作用具有明显的剂量依赖性。结论茉莉根提取物有明显的抗心律失常作用,可能与其抑制Na+内流、Ca2+内流及与阻断β-肾上腺素受体有关。     

改良技术虫草头孢菌粉提取物对缺血性心律失常和心肌细胞动作电位的影响

目的 观察采用改良技术获得的虫草头孢菌粉（Cordyceps Cephalosporium Mycelia,CCM）提取物对豚鼠乳头肌动作电位的影响,探讨CCM提取物实验性抗室性心律失常的机制。方法 利用垂体后叶素（Pit）诱发的大鼠缺血性心律失常模型,观察用药前后心电图的改变。采用标准玻璃微电极技术,记录豚鼠乳头肌跨膜动作电位（TAP）。在频率为1.0 Hz刺激下,观察不同浓度的CCM提取物（10,30,100 mg·L^-1）对标准Tyrode液灌流心肌TAP的影响。结果 大鼠在尾静脉注射Pit后,其心电图T波波幅发生双向性改变,CCM提取物可明显减弱Pit对T波的影响,并降低Pit诱导的心律失常发生率。不同浓度的CCM提取物可浓度依赖性地降低动作电位幅度（APA）以及0相最大上升速率（Vmax）;可延长动作电位复极50%和90%的时间（APD50、APD90）;但对静息电位（RP）无明显影响。结论 改良技术获得的CCM对APA和Vmax的抑制及对心室肌APD的延长可能是其抗心律失常作用的电生理基础。     

硫酸镁抗实验性心律失常作用

硫酸镁250mg/kg静脉注射能降低小鼠吸入氯仿诱发室颤的发生率,也能缩短BaCl_2诱发的家兔心律失常持续时间,并对抗氯仿一肾上腺素所致的家兔心律失常,明显延长乌头碱引起的大鼠室早和室速发生时间,并阻止其引起的室颤发生。     

槐胺碱的心血管作用

槐胺碱(Sa)对麻醉猫、兔和大鼠均有明显的降压作用,降压机理与交感神经节阻断作用和直接扩张外周血管有关。离体心脏实验表明,Sa有负性频率,增加冠脉流量和一定的正性肌力作用。Sa能推迟乌头碱诱发的大鼠心律失常发生时间,缩短心律失常的持续时间,并能降低氯仿诱发的小鼠室颤发生率。其对实验性血栓形成和ADP诱导的血小板聚集作用无影响。     

葛根黄酮抗心律失常作用

本实验比较了黄豆甙元、葛根素和葛根乙醇提取物对实验性心律失常的对抗作用。结果表明:静脉注射或灌服葛根素能明显对抗乌头碱和氯化钡引起的大鼠心律失常。灌服相应克分子的黄豆甙元或葛根乙醇提取物也能明显对抗以上两种心律失常,并能预防氯化钙所致的大鼠室颤和氯仿所致的小鼠室颤。连续灌服黄豆甙元能减少结扎大鼠冠脉后所致的心室纤颤发作时间。静注葛根素还能明显延长在体猫心的动作电位时程和有效不应期,反映有降低心肌兴奋性的作用。     

峨嵋唐松草碱抗实验性心律失常作用

峨嵋唐松草碱10mg/kg,可以显著提高乌头碱诱发大鼠及哇巴因诱发豚鼠致心律失常用量;能明显地预防氯仿所致小鼠心室纤颤的发生;能显著对抗大鼠心肌缺血复灌引起的心律失常。峨嵋唐松草碱对大鼠心电图的影响,表现为显著的减慢大鼠心率,延长P—R及Q—Tc间期。     

安心颗粒抗心律失常及心肌缺血的作用研究

目的研究安心颗粒对心律失常和心肌缺血的改善作用。方法制备氯化钙、氯仿和乌头碱所致的小鼠心律失常模型及异丙肾上腺素（ISO）引起的小鼠心肌缺血模型,经安心颗粒治疗后,通过观察室颤发生率和心动过速的发生时间等指标评价其抗心律失常作用;通过检测血清超氧化物歧化酶（SOD）、脂质过氧化产物丙二醛（MDA）、乳酸脱氢酶（LDH）和磷酸肌酸激酶（CK）等指标评价其改善心肌缺血的作用。结果安心颗粒可降低氯仿诱发小鼠的室颤发生率;延迟氯化钙引起大鼠室性心动过速的发生时间;提高大鼠对乌头碱的耐受剂量。在ISO所致心肌缺血模型中,安心颗粒可增加SOD的活性,减少MDA的含量,降低血清LDH、CK的水平。结论安心对氯仿、氯化钙和乌头碱引起的心率失常及ISO引起的心肌缺血均有较好的改善作用。     

氧化苦参碱抗大鼠实验性心律失常的作用探讨

目的观察氧化苦参碱的抗心律失常作用。方法将SD大鼠随机分为两组,制作乌头碱诱发大鼠室性心律失常模型和结扎左冠状动脉前降支诱发的大鼠室性心律失常,以及对氯仿所致大鼠的室颤,一组静脉注射生理盐水,另一组静注氧化苦参碱,观察两组心律失常的变化。结果氧化苦参(OM)20 mg/kg能明显对抗乌头碱和结扎左冠状动脉前降支诱发的大鼠室性心律失常,也能预防对氯仿所致小鼠的室颤的发生。结论氧化苦参碱对大鼠有明显的抗心律失常作用,此实验为氧化苦参碱的临床应用提供了实验依据。     

High-performance liquid chromatographic determination of 12 antiarrhythmic drugs in plasma using solid-phase column extraction

Monitoring of plasma concentrations of antiarrhythmic drugs may assist in individualizing dosage regimens and in assessing patient compliance. A rapid high-performance liquid chromatographic assay using solid-phase column extraction was developed for the following antiarrhythmic drugs: amiodarone, aprindine, disopyramide, flecainide, lidocaine, lorcainide, mexiletine, procainamide, propafenone, sotalol, tocainide, and verapamil. As most of the antiarrhythmic drugs are basic compounds, good adsorption on the extraction columns was obtained by alkalinization; aprindine, however, was applied at neutral pH and amiodarone at pH 3.5. After washing with water, the compounds were eluted with methanol, but amiodarone was eluted with a mixture of acetonitrile and acetate buffer at pH 5 (8/2, vol/vol). Most of the eluates were evaporated to dryness and reconstituted in the mobile phase; for amiodarone, disopyramide, and tocainide, direct injection onto the column was performed. Separation was done on a Spherisorb hexyl 5 mu column (150 x 4.6 mm I.D.) and the mobile phases consisted of mixtures of acetonitrile or methanol with phosphate or acetate buffers at different pH values. Detection was performed by UV or fluorescence detector. Coefficients of variation were lower than 10% with good recovery and linearity in the expected therapeutic ranges.     

The effects of methyl beta-carboline-3-carboxylate on social interaction and locomotor activity when microinjected into the nucleus raphé dorsalis of the rat.

Intraperitoneal and intracerebral injections of methyl beta-carboline-3-carboxylate (beta CCM) and intracerebral injections of RO 15-1788 were given to rats. The performance of the rats in the social interaction test was measured to determine if changes in social interaction induced by beta CCM were mediated in part by the nucleus raphé dorsalis (NRD). Intraperitoneal injections of beta CCM, 2 and 4 mg kg-1, reduced social interaction. Intracerebral microinjections of beta CCM (10-0.1 ng in 0.5 microliter) into the NRD reduced social interaction. Injections outside the NRD did not have this effect. Intracerebral microinjections of RO 15-1788 (1 ng in 0.5 microliters) into the NRD had no effect when given alone, but blocked the reduction in social interaction caused by intracerebral or intraperitoneal injections of beta CCM. No effect was observed when R 15-1788 was microinjected into sites outside the NRD. Changes in social interaction may reflect changes in anxiety. The NRD may be one of the important sites for the expression of the anxiogenic actions of beta CCM.     

Financial reimbursement and productivity metrics for pharmacist-led chronic care management services in rural practice settings

BackgroundThe implementation of chronic care management (CCM) services has often been hindered by issues with reimbursement, raising concerns about sustainability. To date, little if any literature has examined the financial feasibility and sustainability of CCM services in rural practice settings.ObjectiveAssess financial reimbursement and productivity metrics for pharmacist-led CCM services at a rural, medically underserved family medicine clinic.MethodsThis study retrospectively examined data from the clinic's CCM program from October 2020 through May 2021 and included total clinical encounters, minutes of pharmacist time spent on calls, CCM claims, work relative value units (wRVU), financial reimbursement, and overall personnel costs.ResultsOver an 8-month period, 46 patients were enrolled in CCM services. Of the 49 CCM calls placed during this time, 31 (63.3%) were billable, though only 20 (64.5% of billable calls) were ultimately reimbursed. Approximately 37% of pharmacist “time-on-task” was not billable. Compared to the $643 required to cover pharmacist time on CCM calls, $822 of reimbursement was collected. This $179 profit, or 27.8% return-on-investment, is similar to results from more urbanized practices. Furthermore, services were “net productive” in wRVU generation, which may appeal to physician stakeholders interested in such targets.ConclusionsConcerns about profitability and sustainability have prevented more widespread CCM implementation. In the present study, pharmacist-led CCM services achieved a 27.8% return-on-investment. Though rural-based CCM services may never attain significant profit margins, this data suggests they can still be financially self-sustaining and “net productive,” all while providing high-quality patient care.     

Measurement of tocainide in serum by capillary gas chromatography

A rapid and simple analytical method is described for the determination of tocainide in serum using flame ionization capillary gas chromatography. Following a single extraction with chloroform, tocainide is quantitated on an OV-17 bonded fused silica column, utilizing orphenadrine as internal standard. No interference was detected from endogenous substrates, tocainide metabolites, or other commonly used antiarrhythmic drugs. The lowest detectable tocainide concentration by this method is approximately 0.2 mg/L of serum, which is sufficiently sensitive for therapeutic monitoring. Utilizing temperature programming, this method for tocainide is applicable for several antiarrhythmic drugs.     

姜黄素对HL-60细胞的增殖抑制与凋亡诱导的影响

目的研究姜黄素对人原髓细胞白血病HL-60细胞的增殖抑制及凋亡诱导作用,探讨其诱导细胞凋亡的机理。方法应用MTT比色法、细胞荧光染色法和Western blotting检测姜黄素对HL-60细胞的增殖抑制、凋亡诱导以及对HL-60细胞表达Bcl-2、Caspase9和c-myc的影响。结果姜黄素对HL-60细胞的增殖抑制与剂量相关(P<0.05);经姜黄素作用后HL-60细胞的形态差异明显,表现凋亡的特征性变化,而且姜黄素作用后HL-60细胞的Bcl-2和原癌基因c-myc的表达量低于对照组(P<0.05),而Caspase9的表达量则明显高于对照组(P<0.05)。结论姜黄素可有效抑制体外培养的HL-60细胞增殖,其诱导HL-60细胞凋亡的途径可能通过线粒体介导。     

Identification of antiarrhythmic drugs and their metabolites in urine

Identification of the antiarrhythmic drugs ajmaline, aprindine, diltiazem, disopyramide, flecainide, gallopamil, lidocaine, lorcainide, mexiletine, phenytoin, prajmaline, propafenone, quinidine, sparteine, tocainide and verapamil and their metabolites in urine is described. After acid hydrolysis of the conjugates, extraction and acetylation, the urine samples were analysed by computerized gas chromatography-mass spectrometry. Using ion chromatography with the selective ions m/z 58, 72, 84, 86, 136, 224, 266, and 426, the possible presence of antiarrhythmic drugs and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The method presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.     

The interaction of lead exposure and CCM3 defect plays an important role in regulating angiogenesis through eNOS/NO pathway

In this study, we aimed to explore the role of nitric oxide (NO) in regulating angiogenesis in cerebral cavernous malformations 3 gene (CCM3)-deficient mice exposed to lead during vascular development; further, we aimed to identify and study the potential mechanism involved as well. Angiogenesis was detected by whole mount immunofluorescent staining of retinal vessels in WT and CCM3^+/− mice. Brain microvascular endothelial cells (BMECs) isolated from WT and CCM3^+/− mice, primary HUVECs, and immortalized HUVECs (imHUVECs) (CCM3^+/+ and CCM3^-/-) were used and treated with lead acetate (PbAc). RT-PCR and Western blotting were used to detect the mRNA and protein expression of iNOS, eNOS, and VEGF genes. The results showed that both lead exposure and CCM3 gene deficiency adversely affected endothelial cell function, causing abnormal angiogenesis and vascular remodeling. The mRNA expression of eNOS and iNOS was significantly different in WT and CCM3^+/− BMECs (0.04 ± 0.001 vs. 0.016 ± 0.002; 0.26 ± 0.002 vs. 0.306 ± 0.002, respectively), and the expression of eNOS and iNOS in imHUVECs (CCM3^+/+ and CCM3^-/-) also increased after PbAc exposure. In conclusion, CCM3 gene-deficient mice were more susceptible to abnormal vascular development after low-level lead exposure, probably due to the release of NO.     

Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity

Curcumin (CCM), a yellow natural polyphenol extracted from turmeric (Curcuma longa), has potent anti-cancer properties as has been demonstrated in various human cancer cells. However, the widespread clinical application of this efficient agent in cancer and other diseases has been limited by its poor aqueous solubility and bioavailability. In this study, we prepared novel CCM-loaded human serum albumin (HSA) nanoparticles (CCM-HSA-NPs) for intravenous administration using albumin bound technology. Field emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS) investigation confirmed a narrow size distribution in the 130-150nm range. Furthermore, CCM-HSA-NPs showed much greater water solubility (300-fold) than free CCM, and on storage, the biological activity of CCM-HSA-NPs was preserved with negligible activity loss. In vivo distributions and vascular endothelial cells transport studies demonstrated the superiority of CCM-HSA-NPs over CCM. Amounts of CCM in tumors after treatment with CCM-HSA-NPs were about 14 times higher at 1h after injection than that achieved by CCM. Furthermore, vascular endothelial cell binding of CCM increased 5.5-fold, and transport of CCM across a vascular endothelial cell monolayer by Transwell testing was 7.7-fold greater for CCM-HSA-NPs than CCM. Finally, in vivo antitumor tests revealed that CCM-HSA-NPs (10 or 20mg/kg) had a greater therapeutic effect (50% or 66% tumor growth inhibition vs. PBS-treated controls) than CCM (18% inhibition vs. controls) in tumor xenograft HCT116 models without inducing toxicity. We attribute this potent antitumor activity of CCM-HSA-NPs to enhanced water solubility, increased accumulation in tumors, and an ability to traverse vascular endothelial cell.     

CCM111 prevents hepatic fibrosis via cooperative inhibition of TGF-β, Wnt and STAT3 signaling pathways

CCM111 is an aqueous extract of Antrodia cinnamomea (AC) that has exhibited anti-liver fibrosis functions. However, the detailed mechanisms of AC action against liver fibrosis have not been elucidated yet. The present research showed that CCM111 significantly lowered the levels of the hepatic enzyme markers glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT), prevented liver damage and collagen deposition, and downregulated TGF-β/Smad signaling in a dose-dependent manner compared with CCl₄ treatment alone. CCM111 markedly inhibited TGF-β, Wnt and STAT3 signaling pathway-regulated downstream genes in the liver by next-generation sequencing. The antifibrotic mechanisms of CCM111 were further demonstrated in HSC-T6 cells. Our data demonstrated for the first time that CCM111 can protect against CCl₄-induced liver fibrosis by the cooperative inhibition of TGF-β-, Wnt- and STAT3-dependent proinflammatory and profibrotic mediators, suggesting that CCM111 might be a candidate for preventing and treating chronic fibrotic liver diseases.