A multifaceted approach to calcium channel blocker overdose: a case report and literature review

Calcium channel blocker toxicity can be devastating. Initial therapy with fluid, calcium, and adrenoreceptor agonists should be prompt and novel therapies can be added if no response. Determining cardiogenic shock versus vasoplegia with echocardiogram or other hemodynamic monitoring may guide treatment options.     

多西紫杉醇-海豹油纳米结构脂质载体的抗肿瘤活性评价

目的探讨多西紫杉醇(docetaxel,DTX)海豹油脂质体的抗肿瘤活性以及与脂肪乳的比较。方法采用正交试验设计法筛选处方,通过高压乳匀法制备多西紫杉醇海豹油脂质体。测定其粒径、电位、包封率、体外释药、血浆中稳定性等。并采用四甲基偶氮唑盐〔3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT〕进行体外抗肿瘤活性研究,以及采用荷肉瘤S180小鼠进行体内抗肿瘤活性研究,考察各组抑瘤率和存活率。结果多西紫杉醇海豹油脂质体的粒径在200 nm左右,Zeta电位为-30~-50 m V,包封率达95%以上。体外释放研究证明多西紫杉醇脂肪乳与多西紫杉醇海豹油脂质体具有一定的p H敏感性,且推测多西紫杉醇海豹油脂质体具有更强的缓释作用。血浆中稳定性研究证明多西紫杉醇脂肪乳与多西紫杉醇海豹油脂质体在血浆中较稳定,释放行为缓慢。结论由MTT法结果得多西紫杉醇海豹油脂质体、多西紫杉醇脂肪乳与DTX均表现出较强的细胞毒性作用,且多西紫杉醇海豹油脂质体具有一定的缓释作用。以荷肉瘤S180小鼠为模型的体内抗肿瘤活性研究表明多西紫杉醇脂肪乳与多西紫杉醇海豹油脂质体在血浆中12 h内累积释放量分别为(13.82±0.59)%与(12.91±0.60)%。说明剂型在血浆中较稳定,释放行为缓慢。另外,DTX组小鼠9 d存活率为0,多西紫杉醇脂肪乳组于9 d存活率为93.3%,而多西紫杉醇海豹油脂质体组小鼠9 d存活率为100%,说明多西紫杉醇海豹油脂质体使得耐受剂量提高,降低了药物的不良反应,提高用药安全性与用药的顺应性。     

鸦胆子油乳注射液联合卡培他滨治疗晚期结肠癌的疗效分析

目的研究鸦胆子油乳注射液联合卡培他滨治疗晚期结肠癌的临床疗效及毒副作用,为延长晚期结肠癌患者的生存时间提供指导。方法将36例晚期结肠癌患者随机分为治疗组和对照组,对照组患者采用卡培他滨(1250mg/m2,bid,口服,共14 d)进行化疗,治疗组在对照组基础上再加用鸦胆子油乳注射液(30mL静脉注射,qd,共7 d)进行联合治疗,3周为一个疗程,共8个疗程。对两组患者进行24个月的随访观察,比较两组的疗效及毒副作用和生存时间。结果治疗组的受益率显著高于对照组(P0.05),但两组总有效率比较差异不显著(P0.05);对两组患者的治疗效果进行24个月随访观察,观察组的DFS(%)为16(66.67%),OFS(%)为11(45.83)均高于对照组的7(58.33%)、5(41.67%),但是差异不具有统计学意义(P0.05);中性粒细胞减少、血小板减少在两组间差异具有统计学意义(P0.05),对照组的发生率明显高于治疗组。其他不良反应在两组间比较差异不具有统计学意义(P0.05);采用寿命表法计算两组中位生存期(治疗组为12个月、对照组9个月),两组比较差异不具有统计学意义(Z=2.688,P=0.1010.05)。结论鸦胆子油联合卡培他滨治疗晚期结肠癌虽然对患者生存时间和疗效上差别不大,但是可以提高总体受益率,并且可以降低患者化疗的不良反应。     

Discovery of Surfactant-Like Peptides from a Phage-Displayed Peptide Library

Peptides with specific affinities for various materials have been identified in the past three decades and utilized in materials science and engineering. A peptide’s capability to specifically interact with materials is not naturally derived but screened from a biologically constructed peptide library displayed on phages or cells. To date, due to limitations in the screening procedure, the function of screened peptides has been primarily limited to the affinity for target materials. Herein, we demonstrated the screening of surfactant-like peptides from a phage-displayed peptide library. A screened phage clone displaying a peptide showed high activity for accumulating at emulsion surfaces with certain assembled structures, resulting in stable emulsions. The surface tension for the solution of the chemically synthesized peptide decreased with increasing peptide concentration, demonstrating certain surface activity, which corresponded to the ability to decrease the surface tension of liquids (e.g., water), owing to the accumulation of molecules at the air–liquid or liquid–liquid interface. Peptides with a randomized sequence did not lower the surface tension, indicating the essential role of amino acid sequences in surface activity. Our strategy for identifying novel functional peptides from a phage-displayed peptide library can be used to expand the applicability of peptidyl materials and biosurfactants.     

长链脂肪乳剂预处理对大鼠心肌缺血再灌注损伤的保护作用

目的：探讨长链脂肪乳剂预处理对大鼠心肌缺血再灌注（I/R）损伤的保护作用。方法：成年SD大鼠21只,随机分为3组,每组7只;假手术组（Sham组）：不进行任何药物处理;模型组（Model组）：0.9%氯化钠溶液2 mg·kg-1·d-1静脉注射5 d;长链脂肪乳剂组（LE组）：Intralipid 2 mg·kg-1·d-1静脉注射5 d。末次给药后24 h建立大鼠左前降支结扎I/R模型,其中Sham组只穿线不结扎。持续监测大鼠血流动力学,取心脏进行梗死面积分析,取血检测乳酸脱氢酶（LDH）。结果：与Model组比较,LE组心肌梗死面积占危险区心肌百分比（IR/AAR）和梗死面积占左室面积百分比（IR/LV）显著降低（均P＜0.05）,LDH释放量显著降低（P＜0.05）。与Sham组比较,Model组缺血期及再灌注期平均动脉压（MAP）及心率与收缩压的乘积（RPP）均显著降低（均P＜0.05）;而LE组和Sham组缺血期及再灌注期MAP及RPP比较差异均无统计学意义（P＞0.05）。结论：长链脂肪乳剂预处理能够缩小大鼠心肌I/R损伤后梗死面积、减少LDH释放,同时减缓因I/R损伤所致的血流动力学改变。     

Development,characterisation and efficacy evaluation of biochemical fungicidal formulations for postharvest control of anthracnose (Colletotrichum gloeosporioides Penz) disease in mango

The objectives of the study are to develop and characterise formulations with volatile molecules in an emulsifiable concentrate form, for their antimicrobial properties and to evaluate their efficacies against Colletotrichum gloeosporioides Penz., to control anthracnose in mangoes after harvest. Results showed EC39 and EC40 among formulations were characterised for their excellent emulsification properties, the droplet size of 192.34?±?0.48?nm and 227.4?±?0.71?nm and Zeta potential of ?52.5?±?2.76?mv and ?48.84?±?2.62?mv, respectively, with better storage stability at 10?±?20?°C and RH 80?±?5%. In vitro assay, 100% inhibition of visual spore germination by 0.15% and 0.2% MIC value for EC39 and EC40, respectively Studies on the efficacy of their fungicide properties also indicated the IC50 value of 0.161% and 0.162% for EC39 and EC40 respectively for mycelial growth inhibition. In vivo testing too, EC39 and EC40 effectively controlled anthracnose incidence in mango in a dosage-dependent manner.     

Dodecafluoropentane Emulsion in Acute Ischemic Stroke: A Phase Ib/II Randomized and Controlled Dose-Escalation Trial

PurposeThis randomized, placebo-controlled, double-blind, dose-escalation acute ischemic stroke trial was designed to demonstrate maximum tolerated dose, characterize adverse events (AEs), and explore clinical outcomes when intravenous dodecafluoropentane emulsion (DDFPe) was used as neuroprotection.MethodsAcute ischemic stroke patients (n = 24) with National Institutes of Health Stroke Scale (NIHSS) score of 2–20 were randomized to either 3 doses of intravenous DDFPe or placebo, 1 every 90 minutes, starting within 12 hours of symptom onset. Doses were given without affecting standard stroke care. Each of the 3 dose cohorts included 8 patients, with 2 receiving placebo and 6 receiving DDFPe. Primary outcomes were serious adverse events (SAEs), AEs, NIHSS score, and modified Rankin Score (mRS).ResultsNo dose-limiting toxicities were encountered, and no maximum tolerated dose was defined. One unrelated delayed death occurred in a DDFPe patient, and another occurred in the placebo group. Group SAEs and AEs were similar in incidence and severity. Early initiation of DDFPe treatment resulted in better NIHSS score response than late initiation (P = .03). Thirty- and 90-day mRS after high-dose therapy suggested clinical improvement (P = .01 and P = .03, respectively). However, the significance of differences in clinical outcomes was limited by small patient numbers and differences in stroke severity between cohorts.ConclusionsIntravenous DDFPe appears to be safe at all doses tested. Clinical improvements in NIHSS score and mRS were significant but compromised by small sample size.     

Systemic toxic effects of local anaesthetics

Local anaesthetics are widely used in the provision of local/regional anaesthesia and the management of acute and chronic pain. Their mechanism of action temporarily inhibits voltage gated sodium channels in neuronal plasma membranes. Local anaesthetic systemic toxicity (LAST) is a serious yet largely preventable complication that can occur by any of the multiple routes of administration. LAST predominantly affects the central nervous and cardiovascular systems. Awareness of LAST and vigilance during administration of local anaesthetics may help in early recognition and successful management of the toxicity. Intralipid emulsion (ILE) infusions have been successfully used in reversing local anaesthetic-induced cardiotoxicity. Since 2007 in the UK, ILE infusion has been incorporated into the safety guidelines for management of LAST.     

两种脂肪乳剂不同肠外营养时间对早产儿临床结局影响的比较:一项随机对照多中心研究北大核心CSCD

目的比较两种脂肪乳剂不同肠外营养时间对早产儿临床结局的影响。方法将符合纳入标准的早产儿随机分为两组:中/长链脂肪乳(medium/long-chain triglyceride fat emulsion,简称MCT/LCT)组和多种油脂肪乳[含大豆油、中链甘油三酯、橄榄油、鱼油(soybean oil,medium-chain triglycerides,olive oil,and fish oil),简称SMOF]组。根据肠外营养持续时间(15~21 d、22~28 d、≥29 d)分层分析,比较两组早产儿的临床特征、营养状况、生化指标和临床结局。结果与MCT/LCT组相比,SMOF组肠外营养持续时间分别为15~21 d、22~28 d、≥29 d的早产儿住院期间甘油三酯的峰值水平均较低(P<0.05)。logistic回归趋势性分析显示,随着肠外营养时间延长,MCT/LCT组早产儿肠外营养相关性胆汁淤积症(parenteral nutrition-associated cholestasis,PNAC)及支气管肺发育不良(bronchopulmonary dysplasia,BPD)的发生风险均明显增高(P<0.05),脑损伤的发生风险无明显变化(P>0.05);SMOF组早产儿随着肠外营养时间延长,PNAC及BPD的发生风险均无明显变化(P>0.05),而脑损伤的发生风险明显降低(P=0.006)。结论与MCT/LCT相比,SMOF具有较好的脂质耐受性;随着肠外营养持续时间延长,SMOF不增加PNAC、BPD的发生风险,且对脑损伤具有保护作用,表明在需要长期肠外营养的早产儿中使用SMOF优于MCT/LCT。