头孢噻肟钠致低钾周期性麻痹1例

患者, 男, 35岁. 因发热、咳嗽、咳黄色黏痰7 d入院, 体检：右下肺可闻及少许湿啰音, 呼吸音稍低 ;神经系统未见异常. 诊断为“肺炎”. 查血常规提示：白细胞（WBC） 15.6×109•L^-1, 中性白细胞 0.84, 淋巴细胞 0.16;电解质：钾离子（K+ ）4.1 mmol•L 1, 钠离子（Na+）141.1 mmol•L^-1, 氯离子（Cl^-）121.9 mmol•L^-1, 钙离子（Ca²⁺）2.77 mmol•L^-1. 给予0.9%氯化钠注射液100 mL+头孢噻肟钠2.0 g静脉滴注, 在输注头孢噻肟钠约30 min后, 出现双侧下肢麻木、无力, 双下肢肌力约为3级, 病理症阴性. 辅助检查：K⁺ 2.9 mmol•L^-1, Na⁺ 141.1 mmol•L^-1, Cl^-121.9 mmol•L^-1, Ca²⁺ 2.77 mmol•L^-1. 予以补钾等治疗后, 患者症状明显减轻, 复查血K⁺ 3.8 mmol•L^-1. 但再次静脉滴注头孢噻肟钠时, 患者又出现双侧下肢麻木、无力, 复查血K⁺ 3.0 mmol•L^-1. 考虑由于头孢噻肟钠导致低钾性周期性麻痹, 立即停用头孢噻肟钠, 并予以补钾等对症治疗, 患者症状消失, 复查电解质恢复到入院时的水平. 追问病史, 该患者既往静脉滴注头孢类抗生素均有似现象发生.     

两种药用植物总黄酮体外抗氧化活性比较

目的研究藤茶总黄酮和铁包金总黄酮的体外抗氧化活性。方法建立体外二苯代苦味酰基自由基（DPPH•）、氧自由基（O－2•）和羟自由基（•OH）发生体系，检测藤茶总黄酮和铁包金总黄酮对DPPH•、O－2•和•OH的清除作用。结果藤茶总黄酮对DPPH•、O－2•、•OH的清除作用比铁包金总黄酮和维生素C强，其三种体系的半数抑制浓度（IC50）分别为（3.32±0.18），（227.41±184.45），（5.22±3.75） mg•L－1。铁包金总黄酮对DPPH•、O－2•、•OH的清除作用弱于维生素C，其DPPH•体系的IC50为（36.41±9.68） mg•L－1。结论藤茶总黄酮具有抗氧化活性，但铁包金总黄酮不能单独作抗氧化剂。     

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     

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.     

万古霉素致多系统损害1例

患者,男,54岁. 因头痛9 h,门诊拟诊断为蛛网膜下腔出血、颅内感染. 于2007年6月26日收住入院. 入院后患者体温增高至38.8 ℃,脑脊液常规检查：Pandy test（ + + +）,葡萄糖（Glu）1.5 mmol•L^-1,白细胞（WBC）13 000×10⁶•L^-1,镜检WBC（+ + + +）,红细胞（RBC）（+ + +）,N 0.82,CL 128 mmol•L^-1,蛋白定量9.8 g•L^-1. 根据患者病史特点及脑脊液检查结果,诊断为化脓性脑膜炎. 给予美罗培南抗感染治疗,2 g,q 8 h,静脉滴注;2007年6月29日复查血常规示：WBC 21.3×10⁹•L^-1,N 0.95,脑脊液涂片检查存在革兰阳性（G+）球菌. 当日加用万古霉素0.5 g ,q 8 h,静脉滴注. 2007年6月30日起患者意识逐渐好转,体温下降,血常规呈持续性降低,2007年7月2日血常规WBC 6.7×10⁹•L^-1,N 0.86,抗感染治疗有效. 7月3日查肝、肾功能,丙氨酸氨基转移酶（ALT）111 U•L^-1,天冬氨酸氨基转移酶（AST）214 U•L-1,BUN 9.9 mmol•L-1,加用护肝药物. 2007年7月5日复查肝、肾功能:ALT 54 U•L^-1,谷氨酰转肽酶（GGT）237 U•L^-1,BUN 8.6 mmol•L^-1,肌酐正常,尿素氮指标有所好转,考虑应激性增高可能,未予特殊处理. 2007年7月7日复查腰穿脑脊液示：Pandy test（+ +）,Glu 4.4 mmol•L^-1,WBC 466×10⁶•L^-1,镜检WBC（+ +）,N 0.88,CL 115 mmol•L^-1,蛋白定量1.2 g•L^-1. 患者病情趋于平稳,急性脑膜炎症状明显改善,继续原治疗方案. 7月11日起患者反复出现发热,最高38.9 ℃;2007年7月15日患者全身出现散在深红色斑疹,以面部及肢体明显,因患者2007年7月11日起规律性发热,最高体温基本相似,且全身出现皮疹,考虑药疹可能,但患者颈抵抗（±）,故停用除万古霉素外的其他药物进行观察,同时给予抗组胺受体治疗. 2007年7月16日患者诉耳鸣、听力下降（以右耳明显）,仍有发热（最高38.5 ℃）,全身皮疹明显加重,全身密集红色皮疹,胸、背及双上肢融合成片状,压之褪色,双下肢皮疹呈紫红色,按之不褪色,因其他药物已撤,遂考虑万古霉素导致药物热、变态反应. 2007年7月17日停用万古霉素,加用琥珀氢化可的松抗变态反应,予前列地尔（凯时）增加肾血流量护肾. 2007年7月18日患者体温、心率下降,全身皮疹有所消退（以面部及肢体明显）,复查肾功能示：肌酐166.8 μmol•L^-1、BUN正常. 但患者右耳听力明显下降,至出院时患者右耳听力仍未恢复.     

针毛蕨乙醇提取物体外抗氧化活性研究

目的研究针毛蕨乙醇提取物总黄酮含量及体外抗氧化活性。方法体外抗氧化活性采用 ABTS 自由基、超氧阴离子（O 2•）自由基、H2O2自由基和羟基自由基（•OH）清除实验;总黄酮含量测定采用芦丁显色法。结果针毛蕨乙醇提取物表现出较强的自由基清除能力,且在一定范围内呈剂量依赖性。每克针毛蕨乙醇提取物中总黄酮含量（28.23 ± 0.18） mg。结论针毛蕨乙醇提取物具有一定的体外抗氧化活性。     

甲巯咪唑致粒细胞缺乏死亡1例

患者,女, 51岁. 既往无肝炎、血液病病史, 无食物、药物变态反应史. 此次患者因消瘦乏力4 a, 加重伴高热、双下肢水肿4月, 于2007年12月14日17：00入院. 患者4 a前因无明显诱因出现乏力、进行性消瘦, 诊断为甲状腺功能亢进症(甲亢), 坚持服用2 a甲巯咪唑20 mg, tid, 甲状腺片120 mg, qd, 后觉症状好转, 自行停药. 4个月前无明显诱因再次感乏力, 消瘦明显, 同时有视物模糊, 颈部明显增粗, 自行服用甲巯咪唑10 mg, tid, 甲状腺片120 mg, qd, 症状无明显缓解. 半个月前, 患者有咽痛、腹泻、咳嗽, 自诉咳粉红色泡沫痰, 活动后气喘明显. 入院后急查血常规：WBC 0.97×109&#8226;L^-1, N 0.186, Hb 93 g&#8226;L^-1 , PLT 50×109&#8226;L^-1. 体检：体温40.2 ℃, 脉搏84次&#8226;min^-1, 呼吸率22次&#8226;min^-1, 血压114/67 mmHg(1 mmHg＝0.133 kPa), 神清, 精神萎, 面色潮红, 平卧位, 查体合作, 指颤明显, 皮肤巩膜轻微黄染, 无出血. 扁桃体Ⅱ度肿大, 颈软, 气管居中, 双侧甲状腺Ⅱ度肿大, 质中, 甲状腺区未闻及血管杂音, 未扪及震颤. 呼吸稍促, 双肺呼吸音粗, 未闻及干湿音, 心脏向两侧扩大, 心率84次&#8226;min^-1, 律不齐, 心尖区可闻及Ⅲ级收缩期杂音. 腹软, 无压痛、反跳痛, 肝、脾未触及. 双下肢轻度凹陷性水肿, 足背动脉搏动有力, 四肢肌力正常, 生理反射存在, 病理征未引出. 实验室检查：天冬氨酸氨基转移酶(AST) 81 U&#8226;L^-1,丙氨酸氨基转移酶(ALT)80 U&#8226;L^-1, γ-谷氨酰转移酶(γ-GT) 379 U&#8226;L^-1,清蛋白32.6 g&#8226;L^-1. 尿素氮(BUN)2.8 mmol&#8226;L^-1, 血肌酐(SCr) 35.5 μmol&#8226;L^-1. 血钾离子(K+)3.0 mmol&#8226;L-1,钠离子(Na+)133 mmol&#8226;L^-1,钙离子(Ca²⁺)1.48 mmol&#8226;L^-1,磷离子(P3+)0.72 mmol&#8226;L^-1, 余正常. 尿蛋白(+ +)、隐血(+ + + +). 甲状腺功能检查：游离三碘甲腺原氨酸 (FT3)38.66 pmol&#8226;L^-1, 游离甲状腺素(FT4)95.42 pmol&#8226;L^-1, 促甲状腺素(TSH) <0.005 μU&#8226;mL^-1. 心电图：窦性心律, 频发室性期前收缩、部分二联律、室性心动过速、T波高尖、QT间期延长. 诊断：甲状腺功能亢进,粒细胞缺乏症,肺部感染, 甲亢性心脏病,药物性肝损伤.     

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&#8226;L^-1, 天冬氨酸氨基转移酶(AST) 436 U&#8226;L^-1, 碱性磷酸酶(ALP) 107 U&#8226;L^-1, r-谷氡酰转肽酶(r-GT) 113 U&#8226;L^-1, 总胆汁酸(TBA) 79.4 μmol&#8226;L^-1, 总胆红素(T-BiL) 134.8 μmol&#8226;L-1, 直接胆红素(D-BiL) 80 μmol&#8226;L^-1, TP 67g&#8226;L^-1, A/G 36/31 g&#8226;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&#8226;min^-1, 心率 80次&#8226;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.     

大鼠烯丙基半胱氨酸浓度的测定及组织分布

目的 建立高效液相色谱法测定血清和组织烯丙基半胱氨酸（SAC）浓度的 方法 , 并进行组织分布研究. 方法 采用Hypersil ODS2 色谱柱, 以50 mmol&#8226;L^-1 醋酸盐缓冲液 （pH 5.8 ）：甲醇：乙腈（50：22：28）为流动相; 柱温为35 ℃ , 荧光检测激发波长为350 nm , 发射波长为455 nm.样品的预处理后邻苯二甲醛（OPA）-2-巯基乙醇柱前衍生; 进样10 μL. 结果 血清样品在2～120 mg&#8226;L^-1浓度范围内, 线性关系良好; 组织样品在2～120 mg&#8226;g^-1浓度范围内, 线性关系良好.低、中、高3种浓度的萃取回收率为70.9%～83.5%; 相对回收率为90.2%～110.0%; 日内、日间RSD为4.1%～7.7%.肾脏达峰浓度Cmax为65.7 mg&#8226;kg^-1, 肝脏为58.1 mg&#8226;kg^-1, 脾脏为51.3 mg&#8226;kg^-1, 心脏为43.3 mg&#8226;kg^-1, 肺为35.1 mg&#8226;kg^-1, 脑组织为26.7 mg&#8226;kg^-1 ; 各组织AUC _0~8肾脏为171.9 mg&#8226;h&#8226;kg^-1, 心脏为113.9 mg&#8226;h&#8226;kg^-1, 肝脏为107.2 mg&#8226;h&#8226;kg^-1, 脾脏为90.4 mg&#8226;h&#8226;kg^-1, 肺为93.6 mg&#8226;h&#8226;kg^-1,脑组织为79.8 mg&#8226;h&#8226;kg^-1. 结论 该法简便、快速、准确、灵敏、选择性强, SAC在大鼠体内分布广泛, 其中肾脏分布较多, 而在脑组织中分布较少.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.