顺铂聚乳酸微球的药物释放特性及肝动脉栓塞研究

对顺铂聚乳酸微球进行了体外药物释放和家犬肝动脉栓塞研究。该微球粒径范围为50～200μm,平均粒径为115.76±35.94μm,顺铂含量为37.16%(W/W);体外药物释放机制符合Higuchi方程;肝动脉栓塞后8h,肝组织顺铂浓度高达21.55±12.18μg/g,明显高于肝动脉灌注顺铂组:3.16±0.09μg/g(P<0.05);肝动脉栓塞组的顺铂血浓峰值、各取血点浓度及曲线下面积AUC皆低于肝动脉灌注顺铂组。可望达到提高栓塞部位的药物疗效,降低全身毒副反应的作用。     

2-甲酰(乙酰)取代喹啉缩氨基硫脲的合成

缩氨基硫脲类化合物有抗肿瘤、抗病毒和抗菌等多种药理活性。Barret等首次报道了乙二醛二缩氨基硫脲(Ⅰ)的抗疟活性。Klayman等研究了缩     

Pharmaceutical care services: a systematic review of published studies, 1990 to 2003, examining effectiveness in improving patient outcomes

Objective To systematically review the evidence for the effect of pharmaceutical care practice on patient outcomes. Setting Community and outpatient setting. Method Randomised controlled trials (RCTs) published in English between 1990 and 2003 were identified through a systematic literature search. To be included, studies had to assess the effect of a pharmaceutical care intervention, defined as a one‐to‐one consultation between each patient and a pharmacist with a focus on managing health or resolving drug‐related problems, development of a care plan and follow‐up. Key findings Twenty‐two RCTs met the review criteria. Studies targeted general patient populations at risk of drug‐related problems, disease‐specific target groups or patients with risk factors including hypertension and raised cholesterol. While a number of trials have been undertaken, the variability in the application of endpoints utilised means the evidence for effectiveness of single endpoints apart from quality of life is generally limited to one or two controlled trial results. Collectively, the studies provide evidence that the service improves signs and symptoms for people with asthma, surrogate endpoints such as blood pressure, cholesterol levels and glycosylated haemoglobin and medication use, but do not provide evidence supporting improved health‐related quality of life. One study showed an improvement in combined all‐cause mortality and non‐fatal heart failure‐related events in patients with heart failure. Conclusion Pharmaceutical care services are effective in improving medication use and surrogate endpoints, but improvement in other outcomes is less conclusive. Given that the focus of the service is to resolve medication‐related problems, consideration should be given to the use of adverse drug events and resolution of medication‐related problems as an outcome measure in future studies.     

Qualitative and quantitative assessment of flavins in cow's milk

Although milk is one of the primary sources of riboflavin in the North American diet, the amounts of riboflavin and other flavin derivatives in milk have not been accurately quantified. In this study, a comprehensive assessment of milk was performed to identify and quantify greater than 95% of the flavins in this food. Riboflavin and flavin adenine dinucleotide (FAD) were the predominant flavins in all milk samples; 10-(2'-hydroxyethyl)flavin was next most common. The latter is potentially an antivitamin that may exert its effect at either the absorption or utilization level. Therefore, the presence of this analog should be considered when evaluating the riboflavin efficiency of milk. The large quantity of FAD indicates that precautions against underestimating FAD are warranted when determining total flavin content by fluorescence. This is particularly important because the fluorescence of FAD at pH 7.0 is only 10-20% of that for riboflavin. The presence of 7 alpha-hydroxyriboflavin (7-hydroxymethylriboflavin) in milk was ascertained by extensive testing. Traces of 8 alpha-hydroxyriboflavin (8-hydroxymethylriboflavin) were also detected. These metabolites may serve as indicators of cellular biochemical activity.     

Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD)

A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha- synuclein gene were amplified by PCR from index cases of 30 European and American Caucasian kindreds affected with autosomal dominant PD. Each product was sequenced directly and examined for mutations in the open reading frame. No mutations were found in any of the samples examined. We conclude that the A53T change described in the alpha- synuclein gene is a rare cause of PD or may even be a rare variant. Mutations in the regulatory or intronic regions of the gene were not excluded by this study.      

Adaptation in iron absorption: iron supplementation reduces nonheme-iron but not heme-iron absorption from food

BACKGROUND: Results of cross-sectional studies suggest that in healthy people, iron absorption adapts to meet physiologic needs and stabilize iron stores, but this has not been adequately tested in longitudinal studies. OBJECTIVE: We tested whether heme- and nonheme-iron absorption decrease in response to increased iron intake and whether iron stores reach a steady state. DESIGN: In a randomized, placebo-controlled trial, heme- and nonheme-iron absorption by healthy men and women (n = 57) were measured before and after 12 wk of supplementation with 50 mg Fe/d as ferrous sulfate. Serum and fecal ferritin were measured during supplementation and for 6 mo thereafter. RESULTS: Initially, both heme- and nonheme-iron absorption were inversely associated with serum ferritin concentration. Volunteers who took iron supplements, even those with serum ferritin <21 microg/L (n = 5), adapted to absorb less nonheme iron (3.2% at week 12 compared with 5.0% at week 0, P: < 0.001) but not less heme iron from a beef-based meal. Serum ferritin concentration was slightly but significantly higher after iron supplementation than after placebo (difference = 13 microg/L). This higher ferritin concentration persisted for >/=6 mo after supplementation, except in subjects with low iron stores, whose serum ferritin returned to baseline within 3 mo. Fecal ferritin excretion increased 2.5-fold (P: < 0.05) during supplementation. CONCLUSIONS: Healthy individuals, even those with low iron stores, had reduced nonheme-iron absorption from food in response to iron supplementation. Despite this partial adaptation, iron stores were greater after iron supplementation than after placebo and this difference was sustained, except in individuals with the lowest iron stores.     

Effects of perioperative immunostimulating nutritional therapy on the phagocytic activity of blood platelets in patients with various clinical stages of gastric cancer

PurposeThe aim of this study was to evaluate the total blood platelets count, fraction of phagocytizing thrombocytes (PhT%), and phagocytic index of thrombocytes (PhIT) in gastric cancer considering the stage of the disease, and perioperative immunonutrition support.MethodsOur study included 44 patients operated for gastric cancer divided into 2 groups depending on the clinical stage, and 40 healthy volunteers –a control group. Group I included 18 patients with stage I-III locoregional malignancies and Group II included 26 patients with stage IV peritoneal dissemination. All patients received immunonutrition during the perioperative period. The phagocytic activity of blood platelets was assessed by measuring PhT% and PhIT prior to and after nutritional therapy.ResultsIn Group I, the pre-treatment PhT% and PhIT amounted to 1.08 and 0.99, respectively, and 1.26, and 1.1 after the therapy (p<0.01). In Group II, pre-treatment PhT% and PhIT were 1.12 and 0.97, after 1.18 and 1.06, respectively (p<0.05). In the controls, PhT% and PhIT were 2.26 and 1.83, respectively, significantly higher comparing to gastric cancer patients (p<0.01).ConclusionSevere impairment of the thrombocyte phagocytic activity in gastric cancer patients has been found. Phagocytic activity of blood platelets was partially improved as a result of perioperative immunonutrition both in locoregional disease and in peritoneal dissemination.     

Heart failure after conventional metal-on-metal hip replacements

Background and purpose — It is unclear whether metal particles and ions produced by mechanical wear and corrosion of hip prostheses with metal-on-metal (MoM) bearings have systemic adverse effects on health. We compared the risk of heart failure in patients with conventional MoM total hip arthroplasty (THA) and in those with metal-on-polyethylene (MoP) THA.

Patients and methods — We conducted a retrospective cohort study using data from the Australian Government Department of Veterans’ Affairs health claims database on patients who received conventional THA for osteoarthritis between 2004 and 2012. The MoM THAs were classified into groups: Articular Surface Replacement (ASR) XL Acetabular System, other large-head (LH) (> 32?mm) MoM, and small-head (SH) (≤ 32?mm) MoM. The primary outcome was hospitalization for heart failure after THA.

Results — 4,019 patients with no history of heart failure were included (56% women). Men with an ASR XL THA had a higher rate of hospitalization for heart failure than men with MoP THA (hazard ratio (HR)?=?3.2, 95% CI: 1.6–6.5). No statistically significant difference in the rate of heart failure was found with the other LH MoM or SH MoM compared to MoP in men. There was no statistically significant difference in heart failure rate between exposure groups in women.

Interpretation — An association between ASR XL and hospitalization for heart failure was found in men. While causality between ASR XL and heart failure could not be established in this study, it highlights an urgent need for further studies to investigate the possibility of systemic effects associated with MoM THA.