Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs

This paper describes the development and validation of a liquid chromatography–mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test), as an instant-release tablet (IR-reference) and as the market leader sustained-release capsule (Rythmol, SR-reference) in male beagle dogs (n=8). In Study A comparing SR-test with IR-reference in a crossover design T_max and t_1/2 of propafenone for SR-test were significantly higher than those for IR-reference while C_max and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed C_max and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively) were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively) although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.KEY WORDS: Propafenone, Pharmacokinetics, Sustained-release, Beagle dog, Plasma     

Calycosin-7-O-β-d-glucopyranoside stimulates osteoblast differentiation through regulating the BMP/WNT signaling pathways

The isoflavone calycosin-7-O-β-d-glucopyranoside (CG) is a principal constituent of Astragalus membranaceus (AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this study was to investigate the osteogenic effects of CG and its underlying mechanism in ST2 cells. The results show that exposure of cells to CG in osteogenic differentiation medium increases ALP activity, osteocalcin (Ocal) mRNA expression and the osteoblastic mineralization process. Mechanistically, CG treatment increased the expression of bone morphogenetic protein 2 (BMP-2), p-Smad 1/5/8, β-catenin and Runx2, all of which are regulators of the BMP- or wingless-type MMTV integration site family (WNT)/β-catenin-signaling pathways. Moreover, the osteogenic effects of CG were inhibited by Noggin and DKK-1 which are classical inhibitors of the BMP and WNT/β-catenin-signaling pathways, respectively. Taken together, the results indicate that CG promotes the osteoblastic differentiation of ST2 cells through regulating the BMP/WNT signaling pathways. On this basis, CG may be a useful lead compound for improving the treatment of bone-decreasing diseases and enhancing bone regeneration.Abbreviations: ALP, alkaline phosphatase; AR, Astragalus membranaceus; BMP, bone morphogenetic protein; CG, calycosin-7-O-β-d-glucopyranoside; DKK-1, dickkopf-1; ECL, enhanced chemiluminescence; FGF, fibroblast growth factor; HAase, hyaluronidase; IGF1, insulin-like growth factor 1; MAPK, mitogen-activated protein kinase; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; OBM, osteogenic differentiation medium; Ocal, osteocalcin; OPN, osteopontin; OVX, ovariectomized; PVDF, polyvinylidine fluoride; TGF-β, transforming growth factor β; WNT, wingless-type MMTV integration site familyKEY WORDS: BMP signaling pathway, WNT/β-catenin signaling pathway, Osteoblastic differentiation, Calycosin-7-O-β-d-glucopyranoside, ST2 cells     

Phytochemical and Pharmacological Profile of Vitex negundo

The article aims to review all the chemical constituents and pharmacological properties of Vitex negundo L. (Verbenaceae) (VN). VN is an important medicinal plant used as reputed herbal medicine with versatile pharmacological activities in China, India and Japan. A total of 104 referred articles about VN were compiled from major databases and academic publishers, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. As a result, a total of 120 compounds isolated from VN can be divided mainly into four classes: flavonoids, lignans, terpenoids and steroids. The crude extracts and purified compounds of VN exhibited promising bioactivities, including anti‐nociceptive, antiinflammatory, anti‐tumor, anti‐oxidant, insecticidal, antimicrobial, anti‐androgenic, anti‐osteoporotic, anti‐cataract, hepatoprotective and anti‐hyperglycemic activity. All the reported data lead us to conclude that VN has convincing medicinal potential. However, further researches are needed to explore its bioactive constituents, the structure–activity relationship and their molecular mechanisms of action. Copyright © 2015 John Wiley & Sons, Ltd.     

Anti‐Arthritic and Antiinflammatory Effects of the Traditional Uighur Formula Kursi Caper In Vivo

Kursi Caper (KC) is a Uighur medicine based on caper which is widely used to treat arthritis and rheumatism, and preliminary studies in our laboratory showed that this traditional formula may possess potent antiinflammatory effects. This study confirms the antiinflammatory effect of KC in the adjuvant induced arthritis (AIA) model, the carrageenan and cotton‐pellet induced granuloma rat models, and further investigates in vivo the mechanism of action by measuring relevant indicators of anti‐arthritic activity. KC showed significant and dose‐dependent anti‐arthritic and antiinflammatory effects, demonstrated by reduced paw edema and arthritic scores in all animal models. Histopathological examination showed that KC reduced levels of synovial inflammatory factors in AIA rats. The overproduction of TNF‐α and IL‐1β was attenuated, and CAT, MDA and SOD levels were restored to normal in KC‐treated rats. KC also significantly reduced LPS‐induced proliferation of B lymphocytes and ConA induced proliferation of T lymphocytes in a dose‐dependent manner. Flow cytometry showed that the high dose KC‐treated group had a significantly decreased frequency of Th17 cells. This study indicates that KC can significantly attenuate arthritis and inflammation in rats by decreasing the levels of inflammatory cytokines, regulating oxidative stress, reducing lymphocyte proliferation and decreasing Th17. This supports the traditional use of KC as a potential modern therapeutic agent for the treatment of arthritis and related conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Hindfoot arthrodesis for neuropathic deformity

Acquired neurologic disorders of the foot lead to arthrosis, deformities, instabilities, and functional disabilities. Hindfoot arthrodesis is the current option available for irreducible or nonbraceable deformities of neuropathic feet. However, the role of ankle arthrodesis in these patients has been questioned because of high nonunion and complication rates. From 1990 to 2001, 17 cases of acquired neuropathic foot deformities were treated by four tibiotalocalcaneal (TTC) arthrodeses and 13 ankle arthrodeses. TTC arthrodesis was performed on cases with combined ankle and subtalar arthritis or cases whose deformities or instabilities could not be corrected by ankle fusion alone. There was no nonunion of TTC arthrodesis and seven ununited ankle arthrodeses were salvaged by two TTC-attempted arthrodeses and five revision ankle-attempted arthrodeses. Eventually in these cases, there was one nonunion in TTC arthrodesis and one nonunion in revision ankle arthrodesis. The final fusion rate was 88% (15 of 17 cases) with average union time of 6.9 months (range, 2.5-18 months). The American Orthopaedic Foot and Ankle Society ankle hindfoot functional scores were evaluated: one was excellent (5.8%), seven were good (41%), eight were fair (53.3%), and one was poor (5.8%) in terms of total functional outcome. We conclude that TTC arthrodesis is indicated for cases with ankle and subtalar involvement and ankle arthrodesis is an alternative for cases with intact subtalar joint. We recommend revision ankle arthrodesis if the ankle fails to fuse and the bone stock of the talus is adequate. TTC arthrodesis is reserved for ankles with poor bone stock of the talus with fragmentation.     

Assessment of hepatocellular carcinoma vascularity before and after transcatheter arterial chemoembolization by using first pass perfusion weighted MR imaging

AIM: To assess the vascularity of hepatocellular carcinoma (HCC) before and after transcatheter arterial chemoembolization (TACE) with the quantitative parameters obtained by first pass perfusion weighted MR imaging (FP-MRI). METHODS: Seventeen consecutive patients with one to three lesions in liver underwent FP-MRI before treatment. FP-MRI was also performed one, three, six, nine months, and one year after TACE. The baseline signal intensity (S0) of pre-TACE and one month after TACE was analyzed, the vascularity of HCC assessed by steepest slope of the signal intensity versus time curves (SS) was blindly correlated with their DSA feature and clinical outcome. RESULT: No significant difference was found on baseline signal intensity (S0) between pre-TACE and one month after TACE (F=0.309, P=0.583), The SS (mean, 32% per second) of lesion one month after TACE was lower than that of pre-TACE (mean, 69% per second), but with no statistical significance (F=3.067, P=0.092). When local recurrence occurred, the time intensity curves became steeper. The vascularity of HCC before and after TACE graded by SS closely correlated with that by DSA (K=0.453, P<0.05). CONCLUSION: FP-MRI is a useful criterion for selecting effective interventional treatment for patients with HCC in their initial treatment and during follow up.     

支气管哮喘患者血清IL-33、IL-35水平及相关性分析

目的 研究支气管哮喘患者血清IL-33、IL-35的表达水平,分析IL-33、IL-35间相关性.方法 采用酶联免疫法(ELISA)检测81例非细菌性感染所致中-重度支气管哮喘急性发作期患者治疗前及80名正常对照者血清IL-35、IL-33水平,采用血细胞分析仪检测白细胞数(WBC)、中性粒细胞绝对值(N)、嗜酸性粒细胞绝对值(EOS).细胞培养实验分为空白对照组、细胞刺激素组和IL-35刺激组,ELISA法检测其培养上清IL-33浓度.统计分析支气管哮喘患者急性发作期与正常对照组血清中IL-35、IL-33、WBC、N、EOS,并分析IL-35、IL-33间的相关性.结果 ①哮喘组血WBC、N及EOS计数均高于正常对照组[(7.82±2.93)×109/L vs.(6.38±2.14)×109/L;(5.63±1.47)×109/L vs.(4.57±1.22)×109/L;(0.43±0.27)×109/L vs.(0.22±0.15)×109/L;P＜0.001].②哮喘组血清IL-33水平较正常对照组明显升高[(217.26±52.31)ng/L vs.(105.43±31.64)ng/L],IL-35水平较对照组明显降低[(156.71±24.29)ng/L vs.(311.62±35.28)ng/L],差异有统计学意义(P＜0.001);总体IL-35与IL-33水平呈负相关(r=-0.803,P＜0.05).③哮喘组经过IL-35刺激IL-33水平与仅细胞刺激素相比更低[(15.08±1.92)ng/L vs.(57.33±15.62)ng/L],差异有统计学意义(P＜0.01).结论 IL-35、IL-33均参与了支气管哮喘的发病,支气管哮喘发作期存在各细胞因子间调节失衡.     

抗菌药物使用的多变量监控

目的 建立基于多变量数据分析(multivariate data analysis,MVA)的抗菌药物监控模型,为规范临床抗菌药物的合理使用提供依据。方法 提取浙江省立同德医院住院患者2011—2013年共12个季度81种抗菌药物的用药频度(defined daily doses,DDDs)数据,建立主成分分析(principal component analysis,PCA)模型。通过构建得分图和X区块模型距离(distance to model X block,DModX)控制图,结合变量贡献图,对不同季度的抗菌药物进行监控,评价季度一致性,分析导致异常的原因。结果 2011年第4季度和2012年、2013年4个季度抗菌药物DDDs的一致性较好。2011年第1~3季度的DModX统计值超出了控制限,主要原因为3种特殊使用级抗菌药物(头孢噻利、夫西地酸、去甲万古霉素)、8种限制使用级抗菌药物(头孢米诺、哌拉西林/舒巴坦、阿莫西林/舒巴坦、呋苄西林、头孢丙烯、头孢唑肟、异帕米星、奥硝唑)和4种非限制使用级抗菌药物(氯唑西林、头孢氨苄、头孢羟氨苄、头孢噻肟)的DDDs偏高。结论 本研究证明了MVA在抗菌药物监控中的有效性,为临床抗菌药物监控提供新的方法。     

传统经支气管针吸活检术对肺癌的诊断价值

评价传统的经支气管针吸活检术（C-TBNA）在肺癌中的诊断价值及安全性。于2013年3月至2014年6月,对29例临床诊断肺癌或胸部CT检查显示纵隔/肺门淋巴结肿大或胸内气管或支气管旁肿物患者进行C-TBNA,取标本涂片送病理。29例患者中,25例为临床诊断肺癌者结果判定为阳性23例,阴性2例。25例中,1例经随访诊断为结节病(TBNA结果为涂片见淋巴细胞,结果判定为阴性);1例经随访诊断为结核(TBNA结果为涂片见核异质细胞,结果判定为阴性);1例肠癌术后患者肺部及纵隔占位,不能确定是原发或转移（TBNA结果为涂片见淋巴细胞,右B1刷片为癌疑,结果判定为阴性）;1例食管鳞癌术后右肺及纵隔占位（TBNA结果为涂片疑鳞癌,结果判定为阳性）。本次研究结果,敏感性为82.76%（24/29）,特异性为100.00%(2/2),准确性89.66%（26/29)。29例TBNA均穿刺成功。操作过程安全,无并发症发生。C-TBNA是诊断肺癌安全、有效的方法。     

经导管封堵主动脉窦瘤破口的初步临床应用

目的探讨经导管封堵主动脉窦瘤破口的可行性及有效性。方法4例患者,年龄7～57岁,均为主动脉右窦窦瘤破裂人右心室,破口直径2～10mm,其中3例为先天性,1例患者为获得性（医源性）。通过建立股动脉．主动脉窦瘤破口．右心室．右心房-股静脉的轨道,在透视和超声的引导下经股静脉顺行性置人合适的动脉导管未闭封堵器（Amplatzer duct occluder,ADO）,所选择的ADO直径较破口大1～2mm。结果主动脉窦瘤破口全部封堵成功,仅1例患者术后存在微量残余分流,次日超声证实分流消失。无并发症发生。随访3个月,4例患者症状和体征均消失,超声证实封堵器形态位置良好,无残余分流、栓塞、细菌性心内膜炎、主动脉瓣反流等发生。结论经导管主动脉窦瘤破口封堵术为一种微创、安全和有效的治疗方法,适合于不合并其他需外科处理心血管病变的主动脉窦瘤破裂。其近期疗效良好,中远期疗效有待于进一步观察。