Solubilization and Thermodynamic Analysis of Isotretinoin in Eleven Different Green Solvents at Different Temperatures

The solubilization and thermodynamic analysis of isotretinoin (ITN) in eleven distinct green solvents, such as water, methyl alcohol (MeOH), ethyl alcohol (EtOH), 1-butyl alcohol (1-BuOH), 2-butyl alcohol (2-BuOH), ethane-1,2-diol (EG), propane-1,2-diol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO) was studied at several temperatures and a fixed atmospheric pressure. The equilibrium approach was used to measure the solubility of ITN, and the Apelblat, van’t Hoff, and Buchowski–Ksiazczak λh models were used to correlate the results. The overall uncertainties were less than 5.0% for all the models examined. The highest ITN mole fraction solubility was achieved as 1.01 × 10⁻¹ in DMSO at 318.2 K; however, the least was achieved as 3.16 × 10⁻⁷ in water at 298.2 K. ITN solubility was found to be enhanced with an increase in temperature and the order in which it was soluble in several green solvents at 318.2 K was as follows: DMSO (1.01 × 10⁻¹) > EA (1.73 × 10⁻²) > PEG-400 (1.66 × 10⁻²) > THP (1.59 × 10⁻²) > 2-BuOH (6.32 × 10⁻³) > 1-BuOH (5.88 × 10⁻³) > PG (4.83 × 10⁻³) > EtOH (3.51 × 10⁻³) > EG (3.49 × 10⁻³) > MeOH (2.10 × 10⁻³) > water (1.38 × 10⁻⁶). ITN–DMSO showed the strongest solute–solvent interactions when compared to the other ITN and green solvent combinations. According to thermodynamic studies, ITN dissolution was endothermic and entropy-driven in all of the green solvents tested. The obtained outcomes suggested that DMSO appears to be the best green solvent for ITN solubilization.     

钛夹联合内镜下黏膜切除术治疗重度胃黏膜脱垂症的临床观察

目的：观察钛夹联合内镜下黏膜切除术对重度胃黏膜脱垂症的治疗效果及安全性。方法：对53例经胃镜确诊的重度胃黏膜脱垂症患者采用钛夹联合内镜下黏膜切除术治疗,并分别于术后4周、8周行临床症状随访和胃镜复查。结果：53例患者治疗成功率100％,4周有效率98．1％,8周有效率100％,无出血、穿孔等并发症发生。结论：钛夹联合内镜下黏膜切除术治疗重度胃黏膜脱垂症疗效确切,安全性高,是目前比较先进的微创治疗方法之一。     

经皮腔内顺行球囊扩张结合内切开术治疗肾盂输尿管连接部梗阻

目的观察经皮腔内顺行球囊扩张结合内切开术治疗肾盂输尿管连接部梗阻(UPJO)的疗效。方法回顾分析2010年3月至2012年9月我院采用经皮腔内顺行球囊扩张结合内切开术治疗肾盂输尿管连接部梗阻23例患者的病例资料并行随访。结果患者23例,男性14例,女性9例;年龄21~71岁,平均(39±10.5)岁;左侧10例,右侧13例;原发性UPJO 18例(合并肾结石12例),经皮肾镜碎石术后2例,肾盂输尿管连接部结石开放取石术后1例,开放肾盂成形术后1例,腹腔镜肾盂成形术后1例,狭窄段长度均不超过2cm。所有患者均手术成功,围手术期无严重并发症发生。17例患者纳入随访,其中原发性UPJO患者12例,经皮肾穿刺取石术(PCN)术后患者2例,开放输尿管切开取石术后1例,腹腔镜下肾盂成形术后1例,开放肾盂成形术后1例,术后随访7~31月,未见复发。结论经皮腔内顺行球囊扩张结合内切开术是治疗UPJO安全、有效的手术方式,具有微创、患者耐受度好、术后恢复快的特点,可有选择性地作为治疗UPJO的初始治疗手段。     

综合ICU呼吸机相关性肺炎病原菌分布及耐药性研究

目的：分析综合重症监护病房（IC U ）呼吸机相关性肺炎病原菌的分布及耐药特性,为临床抗菌药物的合理应用提供依据。方法对解放军306医院综合IC U病房2012年1～12月进行机械通气大于48 h的122例患者进行回顾性分析,统计并分析呼吸机相关性肺炎病原菌分布特点及其耐药性。结果122例机械通气患者确诊为呼吸机相关性肺炎55例,发病率为45．08％。共检出病原菌122株,其中革兰阴性菌78株（63．93％）,前3位依次为鲍曼不动杆菌、肺炎克雷伯菌、铜绿假单胞菌,其中4株肺炎克雷伯菌为产超广谱β内酰胺酶（产ESBL ）。革兰阳性菌19株（15．57％）,主要为金黄色葡萄球菌,检出1株耐万古霉素菌株;真菌25株（20．49％）,主要为白色念珠菌。革兰阴性菌对氨苄西林、环丙沙星、亚胺培南、头孢曲松、优立新耐药明显。与不产ESBL菌株相比,产ESBL肺炎克雷伯菌对绝大多数常用抗菌药物耐药,而对亚胺培南和哌拉西林/他巴唑相对敏感。结论该院综合IC U呼吸机相关性肺炎的主要病原菌为革兰阴性菌,分析其耐药特性可为临床经验性治疗呼吸机相关性肺炎及合理使用抗菌药物提供依据。     

Monitoring transfusionist practices: a strategy for improving transfusion safety

BACKGROUND: Data from New York State indicate that about 1 of every 33,000 red cell units transfused is ABO-incompatible with the recipient. National application of these data suggests that as many as 360 ABO-incompatible whole blood and red cell transfusions might occur annually in the United States. Phlebotomy and blood bank laboratory errors cause some of these ABO-incompatible transfusions, but the greatest number result either partially or solely from the failure of transfusionists to identify properly either a patient or the blood component a patient receives. STUDY DESIGN AND METHODS: A quality assessment/quality improvement (QA/QI), process is described that allowed for the direct oversight (monitoring) of transfusionists' practices and for the assessment of institutional policies for blood administration. RESULTS: At the beginning of the QA/QI process, monitoring of blood administration practices revealed that a variance from institutional blood administration policy occurred during 50 percent of blood and component transfusions. As a result of the QA/QI process, the percentage of transfusions with an associated variance from institutional policy dropped to nearly zero. CONCLUSION: The QA/QI process described in this report, or one similar to it, could improve transfusion safety and serve as a model for increased involvement by transfusion service medical directors in the oversight of transfusionists' practices.     

Safety and efficacy of liraglutide in patients with type 2 diabetes with elevated liver enzymes: individual patient data meta-analysis of the LEAD programme

BackgroundFatty liver disease has reached epidemic proportions in type 2 diabetes. Glucagon-like peptide-1 (GLP-1) analogues are licensed for treatment of type 2 diabetes, yet little data exist on efficacy and safety in liver injury. We aimed to assess the safety and efficacy of 26 weeks' liraglutide on liver function compared with an active placebo.MethodsIndividual patient data meta-analysis was done with patient level data combined from six 26-week, phase 3, double-blind randomised controlled trials on type 2 diabetes, which comprise the Liraglutide Effect and Action in Diabetes (LEAD) programme. In addition, the LEAD-2 sub-study was analysed to assess the effect on CT-measured hepatic steatosis.FindingsOf 4442 patients analysed, 2241 (50·8%) had an abnormal alanine aminotransferase (ALT) at baseline (mean 33·8 IU/L [SD 14·9] in female participants; 47·3 [18·3] in male participants). Liraglutide 1·8 mg reduced ALT in these patients compared with placebo (?8·20 vs ?5·01 IU/L, p=0·003), and was dose dependent (no significant differences vs placebo with liraglutide 0·6 or 1·2 mg). This effect was lost after adjustment for liraglutide's effect on reduction of weight (corrected mean ALT difference vs placebo ?1·41 IU/L, p=0·21) and HbA1c (corrected mean ALT difference vs placebo 0·57 IU/L, p=0·63). Adverse effects with 1·8 mg liraglutide were similar between patients with and without baseline abnormal ALT. In the LEAD-2 sub-study, liraglutide 1·8 mg (26 weeks) improved hepatic steatosis (CT-measured liver:spleen attenuation ratio) from baseline (0·10, p=0·001) and showed a trend towards improvement compared with placebo (0.10 vs 0·00, p=0·07).Interpretation26 weeks of liraglutide (1·8 mg) is safe, well tolerated, and improves liver enzymes compared with placebo in patients with type 2 diabetes.FundingWellcome Trust.     

Evaluation of proniosomes as an alternative strategy to optimize piroxicam transdermal delivery

The current investigation aims to evaluate the transdermal potential of niosomes bearing a potent non-steroidal anti-inflammatory, piroxicam. Piroxicam-loaded niosomes were prepared and characterized for surface morphology, entrapment efficiency and in vitro permeation across excised rat skin from various proniosome gel formulations using Franz diffusion cells. Various non-ionic surfactants were used to achieve optimum encapsulation efficiency. The prepared proniosomes significantly improved drug permeation and reduced the lag time (p < 0.05). Proniosomes prepared with Span 60 provided a higher piroxicam flux across the skin than did those prepared with Tween 80. Niosomes prepared using Span 60 showed a higher release rate than those prepared using non-ionic surfactants, Span 20 and Span 80, while those prepared from Tween showed higher release rate than formula prepared with Span. This indicates that lipophilicity and hydrophilicity of surfactant has a main role in release rates of piroxicam. Particle size of piroxicam niosomal vesicles formed by proniosome was determined by scanning electron microscopy. The encapsulation efficiency was evaluated by a specific high performance liquid chromatography method. Niosomes formed from using Spans and Tweens exhibited very high encapsulation efficiency. The results are very encouraging and suggest that niosomes can act as promising carriers offering an alternative approach for transdermal delivery of piroxicam.     

Early and late components of error monitoring in violent offenders with psychopathy

BACKGROUND: One of the most recognizable features of psychopathy is the reduced ability to successfully learn and adapt overt behavior. This might be due to deficient processing of error information indicating the need to adapt controlled behavior. METHODS: Event-related potentials (ERPs) and behavioral components of error-monitoring processes were investigated in 16 individuals with psychopathy and in 18 healthy subjects. A letter version of the Eriksen flanker task was used in two conditions. The first condition (normal condition) required participants to press one of two buttons depending on the identity of the target stimulus. The second condition (signaling condition) required them to signal each time they had committed an error by making a second press on a signaling button. Early stages of error monitoring were investigated by using the error-related negativity (ERN/Ne) and post-error slowing as indexes. Later stages were explored by examining the error positivity (Pe) and signaling rates. RESULTS: Both groups showed similar ERN amplitudes and amounts of post-error slowing. The psychopathic group exhibited both reduced Pe amplitudes and diminished error-signaling rates compared with the control group. CONCLUSIONS: Individuals with psychopathy show intact early error processing and automatic behavioral adaptation but have deficits in later stages of error processing and controlled behavioral adaptation. This is an indication that individuals with psychopathy are unable to effectively use error information to change their behavior adequately.     

Optimization of 5-flurouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer

Solid lipid nanoparticle (SLNs) formulae were utilized for the release of 5-flurouracil (5-FU) inside the colonic medium for local treatment of colon cancer. SLNs were prepared by double emulsion-solvent evaporation technique (w/o/w) using triglyceride esters, Dynasan™ 114 or Dynasan™ 118 along with soyalecithin as the lipid parts. Different formulation parameters; including type of Dynasan, soyalicithin:Dynasan ratio, drug:total lipid ratio, and polyvinyl alcohol (PVA) concentration were studied with respect to particle size and drug entrapment efficiency. Results showed that formula 8 (F8) with composition of 20% 5-FU, 27% Dynasan™ 114, and 53% soyalithicin and F14 (20% 5-FU, 27% Dynasan™ 118, and 53% soyalithicin), which were stabilized by 0.5% PVA, as well as F10 with similar composition as F8 but stabilized by 2% PVA were considered the optimum formulae as they combined small particle sizes and relatively high encapsulation efficiencies. F8 had a particle size of 402.5 nm ± 34.5 with a polydispersity value of 0.005 and an encapsulation efficiency of 51%, F10 had a 617.3 nm ± 54.3 particle size with 0.005 polydispersity value and 49.1% encapsulation efficiency, whereas formula F14 showed a particle size of 343 nm ± 29 with 0.005 polydispersity, and an encapsulation efficiency of 59.09%. DSC and FTIR results suggested the existence of the lipids in the solid crystalline state. Incomplete biphasic prolonged release profile of the drug from The three formulae was observed in phosphate buffer pH 6.8 as well as simulated colonic medium containing rat caecal contents. A burst release with magnitudes of 26%, 32% and 28.8% cumulative drug released were noticed in the first hour samples incubated in phosphate buffer pH 6.8 for both F8, F10 and F14, respectively, followed by a slow release profile reaching 50%, 46.3% and 52% after 48 hours.