复方丹参滴丸对过氧化氢损伤PC12细胞的保护作用

目的 研究复方丹参滴丸对过氧化氢（H₂O₂）损伤PC12细胞的保护作用,探讨复方丹参滴丸治疗缺血性脑血管病的作用机制.方法 采用细胞培养和H₂O₂诱导细胞损伤的方法,观察复方丹参滴丸对PC12细胞的保护作用.结果 复方丹参滴丸 6.25,12.50,25.00 μg•mL^-1均可明显对抗100和500 μmol•L^-1 H2O2引起的PC12细胞凋亡（P＜0.01）.结论 复方丹参滴丸可以促进PC12细胞的营养和增殖作用,并有抗H2O2诱导细胞凋亡作用.     

高效液相色谱法测定养血祛风丸中士的宁的含量

目的 建立高效液相色谱法测定养血祛风丸中士的宁的含量. 方法 采用HyperClone BDS C₁₈柱（250 mm×4.6 mm,5 μm）; 流动相：乙腈 0.01 mol•L^-1庚烷磺酸钠与0.02 mol•L^-1磷酸二氢钾等量混合溶液（用10%磷酸调节pH值为2.8）（21：79）; 流速1.0 mL•min^-1; 检测波长：260 nm; 柱温35 ℃. 结果 士的宁浓度的线性范围为4.8～191.8 μg•mL^-1,r＝0.999 8,回收率为101.30%,RSD＝1.3%. 结论 该方法方便、快速、准确,可用于养血祛风丸的质量控制.     

右旋布洛芬分散片含量测定及其有关物质研究

目的 采用高效液相色谱法测定右旋布洛芬分散片中右旋布洛芬及其有关物质的含量.方法 色谱柱ODS-C₁₈柱（250 mm×4.6 mm,5 μm）;以乙腈-0.02 mol•L^-1磷酸二氢钾溶液（pH值=3.50）（63：37）为流动相;检测波长为263 nm.结果回归方程A=1 728.90 C－971.03,线性范围为4×10-3～100×10-3 g•L^-1（r＝1）,含量测定的平均回收率为99.69%,RSD为0.92%（n＝9）.结论 该方法重现性好,准确度高,适于右旋布洛芬分散片的质量控制.     

甲巯咪唑致粒细胞减少和肝损害及皮疹1例

患者,女,30岁.因心悸,怕热多汗,消瘦2个月,于2010年9月3日来我院就诊.入院体检：体温37.2 ℃,心率93次•min^-1,呼吸20次•min^-1,血压110/70 mmHg(1 mmHg=0.133 kPa),实验室检查血白细胞 5.9×109•L^-1,中性粒细胞计数3.4×109•L^-1;血生化丙氨酸氨基转移酶(alanine aminotransferase,ALT)22 U•L^-1、天冬氨酸氨基转移酶(aspartate aminotransferase,AST) 28 U•L^-1等均正常;尿常规正常.甲状腺功能检测：总三碘甲状腺原氨酸3.19 nmol•L^-1,甲状腺素总量16.81 nmol•L^-1,促甲状腺激素0.01 U•L^-1,游离三碘甲状腺原氨酸11.24 pmol•L^-1,游离甲状腺素2.49 pmol•L^-1.甲状腺超声显示：甲状腺回声不均并血流丰富改变.诊断：甲状腺机能亢进(甲亢).给予甲巯咪唑片10 mg,bid,普萘洛尔片10 mg,tid,po.用药15 d后患者躯干、四肢及面部出现红色皮疹,高出皮面,伴有刺痒,以双髋部及膝盖等处为著,并有食欲下降、恶心等症状.体检：体温37.1 ℃,心率95次•min^-1.复查血常规及生化：白细胞3.2×109•L^-1,中性粒细胞1.8×109•L^-1,ALT 175 U•L^-1,AST 67 U•L^-1.考虑为甲巯咪唑引起的白细胞减少、肝功能异常及皮疹,遂停用甲巯咪唑,其他治疗不变,并给予还原型谷胱甘肽1.2 g + 0.9%氯化钠注射液250 mL,qd,静脉滴注;氯雷他定10 mg,qd,po;利可君40 mg,tid,po,盐酸小檗胺4片,tid,po.6 d后复查血白细胞 4.37×109•L^-1,中性粒细胞3.0×109•L^-1,皮疹逐渐消失.继续给予保肝治疗,1周后复查肝功能：ALT 24 U•L^-1,AST 18 U•L^-1.逐步恢复至正常值     

药源性血小板减少和血尿1例

患者,女, 53岁. 因卵巢癌术后2 a出现纳差、咳嗽、头晕加重1周住院,近2 a先后进行2次卵巢癌根治术,术后行10次化学药物治疗(化疗),2个月前出现咳嗽,纳差、消瘦住院,诊断：卵巢癌术后纵隔、锁骨、腹膜后、肾门等多处转移,行γ-刀治疗及中药治疗,疗效差. 体检：体温36.7 ℃,脉搏84次•min-1、血压130/90 mmHg(1 mmHg＝0.133 kPa),神志清楚,消瘦,皮肤巩膜无黄染,颈软,左侧颈中部可扪及2 cm×2 cm大小淋巴结,活动好,无压痛,皮肤多处见瘀斑,腹部隆起,下腹中见手术瘢痕,四肢活动无受限. 实验室检查：白细胞(WBC) 1.6×109•L^-1、血红蛋白(Hb) 84 g•L^-1、血小板(PLT)计数 65×109•L^-1,总胆红素(T-BiL)12.9 μmol•L^-1, 丙氨酸氨基转移酶(ALT) 30 U•L^-1 ,天冬氨酸氨基转移酶(AST)28 U•L^-1,血糖(Glu) 7.84 mmol•L-1,血尿素氮(BUN) 6.34 mmol•L^-1,血肌酐(Cr) 72.2 μmol•L^-1, HBsAg(-),PT9.6 s,胸部X 线片：右下肺纹理稍增多,余心肺膈未见异常;CT：考虑卵巢癌向纵隔、肝脏、胃底及腹膜后多处转移可能. 诊断：卵巢癌术后复发转移. 治疗：参麦注射液20 mL•d^-1、苦参素注射液20 mL•d^-1、艾迪注射液100 mL•d^-1、胰岛素8 U.d^-1、rh-CSF125 μg,每周2次,输全血、复合氨基酸等支持治疗. 患者PLT进行性下降,皮肤瘀斑无好转. 10 d后加服斑蝥胶囊,入院后的3周出现肉眼血尿,这时考虑可能与斑蝥有关,停用艾迪注射液和斑蝥胶囊,同时加用止血药物治疗,2 d血尿消失. 又过2周患者死亡,死于多器官功能衰竭.     

柱切换高效液相色谱法测定血浆左氧氟沙星浓度

目的 应用柱切换高效液相色谱(HPLC)技术直接测定血浆中左氧氟沙星的浓度.方法 采用手动柱切换装置,分析柱采用大连依利特公司的Hypersil ODS C18柱（200 mm×4.6 mm,5 μm）,预柱采用μBondapak C18（50 mm×4.6 mm,37～50 μm,干法自填）.分析流动相（AMP）为甲醇 磷酸二氢钾缓冲液（0.01 mol•L-1,pH值＝2.5） 四丁基溴化铵（0.05 mol•L-1） 三乙胺＝40：60：4：0.2（V/V）;预处理流动相（PMP）为磷酸二氢钾缓冲液（0.01 mol•L^-1,pH值＝2.5） 四丁基溴化铵（0.05 mol•L^-1）＝100：1（V/V）.分析流动相流速1 mL•min^-1,预处理流动相流速2 mL•min^-1.检测波长为294 nm.结果左氧氟沙星在100～8 000 ng•mL^-1内有良好的线性关系.相关系数r＝0.999 8,方法平均相对回收率98.8%,日内及日间差小于10%,最低检测限0.05 μg•mL^-1（S/N≥3）.结论 样品无须预处理,直接进样分析测定,简便易行.     

丁二磺酸腺苷蛋氨酸致过敏性荨麻疹1例

患者, 女, 36岁. 因反复乏力、纳差2 a余, 巩膜及皮肤黄染3 d, 于2008年入住我院感染科治疗. 否认既往药物变态反应史. 实验室检查肝功能：丙氨酸氨基转移酶(ALT)537 U•L^-1, 天冬氨酸氨基转移酶(AST) 436 U•L^-1, 碱性磷酸酶(ALP) 107 U•L^-1, r-谷氡酰转肽酶(r-GT) 113 U•L^-1, 总胆汁酸(TBA) 79.4 μmol•L^-1, 总胆红素(T-BiL) 134.8 μmol•L-1, 直接胆红素(D-BiL) 80 μmol•L^-1, TP 67g•L^-1, A/G 36/31 g•L^-1. 乙肝全套定性：HBsAg(+), HBsAb(+), HBeAg(+), HBeAb(-), HBcAb(+). 腹部B超显示胆囊壁增厚、胆汁淤积, 脾稍大. 诊断：慢性乙型肝炎急性发作期. 入院后首先单用5%葡萄糖注射液250 mL+注射用丁二磺酸腺苷蛋氨酸1 000 mg, 静脉滴注. 当丁二磺酸腺苷蛋氨酸输入后约10 min, 患者从脸部开始出现红色斑块, 逐渐扩散至颈部, 上胸部, 腹部两侧及大腿上部, 红色斑块密集, 感觉不适, 但无瘙痒, 拟诊为过敏性荨麻疹. 生命体征平稳, 体检：体温 37.0 ℃, 呼吸率 20次•min^-1, 心率 80次•min^-1, 血压126/80 mmHg(1 mmHg＝0.133 kPa). 立即停药, 换用输液器, 静脉注射10 mg地塞米松, 10%葡萄糖酸钙注射液10 mL, 约30 min后皮疹部分消退, 直至完全消退. 以后未再使用该药, 其他治疗继续, 也未再发生类似反应.     

液相色谱-串联质谱法测定肾移植患者的麦考酚酸血浆浓度及其药动学研究

目的 建立液相色谱-串联质谱（LC-MS/MS）法评价免疫抑制剂麦考酚酸酯（MMF）在术后2～3周肾移植患者中连续口服的药动学特点. 方法 受试者口服MMF（0.75 g,bid）,2～3周后用LC-MS/MS法测定血浆中活性代谢物麦考酚酸（MPA）的浓度,并用非房室模型计算药动学参数. 结果 MPA在0.1～51.2 μg•mL^-1 范围内线性关系良好,批内、批间RSD＜10%,准确度在90%～110%,方法学验证符合生物样品分析方法的要求. MMF的体内代谢呈明显的个体差异,药动学参数：AUC0 t为（36.65±11.42） mg•h•L^-1; AUC0 ∞为（43.34±18.02） mg•h•L^-1; Cmax为（15.89±5.77） mg•L-1; t _max为（1.08±0.47） h; t_1/2为（3.34±1.63） h; MRT0 t为（3.42±1.12） h; Vd为（194.88±156.45） L; CL为（41.02±18.19） L• h^-1. 结论 LC MS/MS法用于MPA血浆浓度测定,操作简便,结果灵敏、特异性好.     

头孢他啶对奈替米星体内药动学的影响

目的 考察头孢他啶对奈替米星在受试者体内药动学的影响,为临床合理用药提供依据. 方法 12例受试者在单剂量静脉滴注奈替米星（单用组）或奈替米星加头孢他啶（联用组）后,采用高效液相色谱 间接光度法测定不同时间点血清及尿液中奈替米星浓度,计算其药动学参数及尿药回收率. 结果 单用、合用头孢他啶后奈替米星的体内过程均符合二房室开放模型,其药动学参数单用组AUC_0-t,t_1/2β,CL与0～24 h尿药回收率分别为（52.93±5.58） mg•L^-1•h、（3.68±0.33） h、（4.49±0.53） L•h^-1与72.22%,联用组分别为（71.81±8.03 ）mg•L^-1•h、（5.06±0.57） h、（2.95±0.37） L•h^-1与59.20%. 两组比较差异有显著性. 结论 奈替米星与头孢他啶联用后,其消除过程减慢,连续应用可能导致药物体内蓄积,二者合用时应适当减少奈替米星的剂量.     

高效凝胶色谱法测定注射用盐酸头孢甲肟中的高分子杂质

目的 建立高效凝胶色谱法测定注射用盐酸头孢甲肟中的高分子杂质. 方法采用高效凝胶色谱法,色谱柱为高效凝胶Tsk gel G2000 SWxl(300 mm×7.8 mm,5 μm),流动相为pH7.0的0.005 mol•L^-1磷酸盐缓冲液[0.005 mol•L^-1磷酸氢二钠溶液 0.005 mol•L^-1磷酸二氢钠溶液(61:39)]-乙腈(95:5);流速:0.8 mL•min^-1;检测波长为234 nm,进样量为20 μL. 结果 供试品溶液在0.067～2.700 mg•mL^-1浓度范围内,溶液的浓度与高分子杂质的峰面积总和呈良好的线性关系(r＝0.998 8);盐酸头孢甲肟在0.001～0.010 mg•mL^-1浓度范围内,与峰面积呈良好的线性关系(r＝0.999 9). 结论 该测定方法简便,重复性好,可靠性高,可用于注射用盐酸头孢甲肟中高分子杂质的质量控制.     

基质金属蛋白酶-2及基质金属蛋白酶抑制剂-2在子宫内膜异位症中的表达及分析

目的通过检测组织中基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶抑制剂-2(TI MP-2)的表达,探讨它们在子宫内膜异位症发生、发展中的作用。方法用原位杂交染色技术对MMP-2和TI MP-2mRNA进行测定。结果①MMP-2在异位内膜的表达高于在位内膜(P<0·05);在位内膜MMP-2的表达显著强于正常子宫内膜(P<0·05),而且异位组中Ⅲ、Ⅳ期组与Ⅰ、Ⅱ期组间差异有统计学意义(P<0·05)。TI MP-2在位内膜的表达低于正常子宫内膜(P<0·05),异位内膜中TI MP-2的表达显著低于在位内膜(P<0·05),而且异位组中Ⅲ、Ⅳ期组与Ⅰ、Ⅱ期组间差异有统计学意义(P<0·05)。②在正常内膜中,MMP-2与TI MP-2之间呈负相关,r=-0·710。结论患者组织中MMP-2和TI MP-2的异常表达在子宫内膜异位症的发生、发展中起重要的作用。     

2-Hydroxylaminoimidazoles--unstable intermediates in the reduction of 2-nitroimidazoles

An unstable 2-hydroxylaminoimidazole (2-hydroxylamino-1-methylimidazole) was prepared by the reaction of 2-fluoro-1-methylimidazole with hydroxylamine. This substance was sufficiently stable (half-life of 1-2 days) in acid solutions to be observed and characterized by NMR spectroscopy; decomposition at neutrality was, however, rapid (half-life of 1-10 min). Radiochemical and electrochemical reduction experiments were carried out at pH 4 and pH 7 with 2-nitro-1-methylimidazole and misonidazole [1-(3'-methoxy-2'-hydroxypropyl)-2-nitroimidazole]. A four electron stoichiometry was found in every case. The pH 4 reduced product was identified as the 2-hydroxylamino derivative (greater than 80% yield). The pH 7 reduced solutions, on the other hand, showed no aromatic 1H NMR signals, suggesting that a simple imidazole ring was no longer present. A shift to pH 7 of the hydroxylamine produced at pH 4, however, resulted in very similar NMR spectra. The conclusion, therefore, is that the hydroxylamine was produced initially on reduction of the nitroimidazole, but it was not stable.     

Clinical implication of SGLT2 inhibitors in type 2 diabetes

Treatment of type 2 diabetes mellitus (T2DM) continues to present challenges, with many patients failing to achieve glycemic targets. Despite the availability of many oral and injectable anti-diabetic agents, therapeutic efficacy is often offset by undesirable side effects such as hypoglycemia, weight gain and cardiovascular complications. Therefore, the search for new therapeutic agents with an improved benefit–risk profile continues. Recent research has focused on the kidney as a potential therapeutic target, especially because maximal renal glucose reabsorption is increased in T2DM. Under normal physiological conditions, nearly all filtered glucose is reabsorbed in the proximal tubule of the nephron via the sodium/glucose co-transporter 2 (SGLT2). SGLT2-inhibitors are a new class of oral anti-diabetes, which reduce hyperglycemia by increasing urinary glucose excretion independently of insulin secretion or action. Canagliflozin and dapagliflozin in US market, and ipragliflozin and luseogliflozin in Japan market are now available for glycemic control in type 2 diabetics. There are several phase III clinical ongoing trials involving this new class of medications. This review examines some of the key efficacy and safety data from clinical trials of the SGLT2 inhibitors approved, and their future perspectives in the treatment of T2DM.     

内源性H2S参与了肝癌细胞HepG-2的耐热

目的探讨内源性硫化氢（hydrogen sulfide,H2S）是否参与了耐热肝癌细胞HepG-2/thermotolerance（HepG-2/tt）的耐热。方法通过PI染色流式细胞仪检测和比较HepG-2细胞与HepG-2/tt细胞耐热后的细胞凋亡率,用亚甲基蓝显色分光光度计法检测和比较HepG-2细胞与HepG-2/tt细胞耐热后H2S生成量和H2S合酶活性的差异。结果 43℃环境培养24 h后,耐热肝癌细胞HepG-2/tt的细胞凋亡率较普通肝癌细胞HepG-2明显下降（P〈0.01）;且HepG-2/tt细胞中H2S含量和H2S合酶活性均较普通HepG-2细胞明显增加（P〈0.01）。结论 HepG-2/tt较HepG-2细胞具有热耐受性,并且其内源性硫化氢合酶活性和硫化氢生成量均有提高。     

Pharmacokinetics of 2-methoxyphenylmetyrapone and 2-bromophenylmetyrapone in rats.

The pharmacokinetics of two 2-substituted phenylmetyrapone analogues, 2-methoxyphenylmetyrapone (2-MPMP) and 2-bromophenylmetyrapone (2-BrPMP), developed as potential adrenal imaging agents, were investigated in conscious male rats following an intravenous dose of 25 mg/kg. Arterial blood samples (0.25 ml) were collected at various intervals for up to 7 h after dose and subjected to reversed-phase HPLC analysis. Blood concentrations versus time profile for each compound was determined and the pharmacokinetic parameters calculated using the model-independent approach. Blood concentrations of 2-MPMP declined biexponentially with mean initial (t1/2alpha) and terminal (t1/2beta) half-lives of 3.6 and 23.1 min, respectively. The corresponding area under the curve (AUC(0-infinity)) was 159.3 microg x min/ml, the total blood clearance (CI) was 158.3 ml/min and the volume of distribution (Vd) was 5.2 l. Two metabolites of 2-MPMP, namely 2-hydroxyphenylmetyrapone (2-OHPMP) and 2-methoxyphenylmetyrapone N-oxide (2-MPMP-NO), were detected in the blood and their elimination from blood was almost parallel to that of the parent compound. The maximum blood concentrations (Cmax) of 2-OHPMP and 2-MPMP-NO were approximately 0.9 and 1.7 microg/ml, respectively. Blood concentrations of 2-BrPMP declined monoexponentially with a mean t1/2beta of 12.0 min. The pharmacokinetic parameters for 2-BrPMP were: AUC(0-infinity), 193.7 microg x min/ml; Cl, 131.7 ml/min and Vd, 2.3 l. 2-Bromophenylmetyrapone N-oxide was the only one metabolite detected in the blood, its Cmax and AUC0-infinity were 10.1 microg/ml and 1690.0 microg x min/ml, respectively.     

Formation of 1,4-dioxo-2-butene-derived adducts of 2'-deoxyadenosine and 2'-deoxycytidine in oxidized DNA

Oxidation of deoxyribose in DNA produces a variety of electrophilic residues that are capable of reacting with nucleobases to form adducts such as M(1)dG, the pyrimidopurinone adduct of dG. We now report that deoxyribose oxidation in DNA leads to the formation of oxadiazabicyclo(3.3.0)octaimine adducts of dC and dA. We previously demonstrated that these adducts arise in reactions of nucleosides and DNA with trans-1,4-dioxo-2-butene, the beta-elimination product of the 2-phosphoryl-1,4-dioxobutane residue arising from 5'-oxidation of deoxyribose in DNA, and with cis-1,4-dioxo-2-butene, a metabolite of furan. Treatment of DNA with enediyne antibiotics capable of oxidizing the 5'-position of deoxyribose (calicheamicin and neocarzinostatin) led to a concentration-dependent formation of oxadiazabicyclo(3.3.0)octaimine adducts of dC and dA, while the antibiotic bleomycin, which is capable of performing only 4-oxidation of deoxyribose, did not give rise to the adducts. The nonspecific DNA oxidant, gamma-radiation, also produced the adducts that represented approximately 0.1% of the 2-phosphoryl-1,4-dioxobutane residues formed during the irradiation. These results suggest that the oxadiazabicyclo(3.3.0)octaimine adducts of dC and dA could represent endogenous DNA lesions arising from oxidative stresses that also give rise to other DNA adducts.     

Stability of T-2, HT-2, and T-2 tetraol in biological fluids

The stabilities of tritium-labeled T-2, HT-2, and T-2 tetraol were studied in blood and urine at -70 degrees, 4 degrees, and 23 degrees C for 6 months in the presence of EDTA or NaF. Samples were counted with a radiochromatographic scanner and results indicated the stability of T-2 tetraol greater than T-2 greater than HT-2. Toxins were most stable when stored at -70 degrees C, in the presence of NaF, and in urine (pH 6). They were less stable in saline (control, pH 7) and least stable in blood (pH 8). These results suggest that urine and T-2 tetraol are the biological fluid and metabolite of choice for diagnostic purposes.     

The effect of Mn2+, Zn2+, Ba2+ and Ca2+ on spontaneous motility in sheep duodenum in vitro

• 1.1. The effects of several ions, Mn²⁺, Zn²⁺, Ba²⁺ and Ca²⁺, on spontaneous motility were investigated in longitudinal smooth muscle strips from sheep duodenum, in vitro
• 2.2. Mn²⁺ (0.5–1.5 mM) and Zn²⁺ (0.5–5 mM) inhibited both the amplitude and frequency of motility in Krebs solution and in Ca²⁺-free medium.
• 3.3. Ba²⁺(0.5–5 mM) evoked three types of contractile responses: (i) an increase in the frequency and a reduction of the amplitude of spontaneous contractions; (ii) a slight increase in muscle tone of the phasic contractions; and (iii) a rapid initial phasic contraction followed by slowly fading contraction. Ca²⁺ induced two kinds of responses in spontaneous motility: (i) a fast phasic contraction, followed by an increase in the amplitude and frequency of phasic contractions with no changes in its tone; and (ii) an increase in the amplitude of contractions.
• 4.4. The Ba²⁺-induced contractions were inhibited by EDTA, verapamil and diltiazem, but were not modified by sodium nitroprusside. The Ca²⁺-induced contractions were reduced by verapamil and diltiazem.
• 5.5. Our results show that Mn²⁺ and Zn²⁺ behave as inhibitors of sheep duodenum motility. In contrast, Ba²⁺ and Ca²⁺ stimulate motility. It is suggested that Ba²⁺ can penetrate the cells through voltage-dependent Ca²⁺ channels and behave as a partial substitute for Ca²⁺.