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     

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.      

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.     

Multisite evaluation of a new dipstick for albumin, protein, and creatinine

The goal of our study was to perform a multisite evaluation of a new urine dipstick called Multistix PROtrade mark (Bayer, Elkhart, IN), which has reagent pads for the simultaneous assay of urinary albumin, protein, and creatinine. Patients' urine specimens were assayed at four sites with these dipsticks and with the familiar Bayer Multistix 10SG dipsticks for protein. The new dipstick pads for albumin are impregnated with bis (3',3"-diiodo-4',4"-dihydroxy-5',5"-dinitrophenyl)-3,4,5,6-tetrabromo-sulfonephthalein (DIDNTB) dye. These dipsticks also have a novel pad that estimates urinary creatinine using the peroxidase activity of the copper-creatinine complex. We determined the interlaboratory agreement of these dipsticks by comparing dipstick results to values obtained by quantitative analytical methods. We found that dividing the dipsticks' albumin or protein results by the creatinine concentration reduced the number of false-positive albumin or protein values observed in concentrated urines, and reduced the number of false negatives in dilute urines. The ratio of albumin to creatinine, or protein to creatinine gives a better measure of albumin or protein excretion. Compared to reading by eye, the dipstick results agreed better with the quantitative assays when they were read by a reflectometer (Bayer Clinitek).     

A Chronic Iron-Deficient/High-Manganese Diet in Rodents Results in Increased Brain Oxidative Stress and Behavioral Deficits in the Morris Water Maze

Iron deficiency (ID) is especially common in pregnant women and may even persist following childbirth. This is of concern in light of reports demonstrating that ID may be sufficient to produce homeostatic dysregulation of other metals, including manganese (Mn). These results are particularly important considering the potential introduction of the Mn-containing gas additive, methyl cyclopentadienyl manganese tricarbonyl (MMT), in various countries around the world. In order to model this potentially vulnerable population, we fed female rats fed either control (35 mg Fe/kg chow; 10 mg Mn/kg chow) or low iron/high-manganese (IDMn; 3.5 mg Fe/kg chow; 100 mg Mn/kg chow) diet, and examined whether these changes had any long-term behavioral effects on the animals’ spatial abilities, as tested by the Morris water maze (MWM). We also analyzed behavioral performance on auditory sensorimotor gating utilizing prepulse inhibition (PPI), which may be related to overall cognitive performance. Furthermore, brain and blood metal levels were assessed, as well as regional brain isoprostane production. We found that treated animals were slightly ID, with statistically significant increases in both iron (Fe) and Mn in the hippocampus, but statistically significantly less Fe in the cerebellum. Additionally, isoprostane levels, markers of oxidative stress, were increased in the brain stem of IDMn animals. Although treated animals were indistinguishable from controls in the PPI experiments, they performed less well than controls in the MWM. Taken together, our data suggest that vulnerable ID populations exposed to high levels of Mn may indeed be at risk of potentially dangerous alterations in brain metal levels which could also lead to behavioral deficits.     

Population sub-structuring among <Emphasis Type="Italic">Trypanosoma evansi</Emphasis> stocks

To investigate the population genetic structure of Trypanosoma evansi from domesticated animals, we have analysed 112 stocks from camels, buffaloes, cattle and horses using the tandemly repeated coding sequence (MORF2) and minisatellite markers 292 and cysteine-rich acidic integral membrane protein (CRAM). We recorded a total of six alleles at the MORF2 locus, seven at 292 and 12 at the CRAM loci. Nei’s genetic distance showed reduced allelic diversity between buffaloes and cattle stocks (1.2) as compared to the diversity between camels and buffaloes (3.75) and camels and cattle stock (1.69). The mean index of association (I _A = 0.92) significantly deviated from zero, and the average number of multilocus genotypes (G/N ratio) was 0.21. Twenty-four multilocus genotypes were defined from the combination of alleles at the three loci. The Kenyan sub-populations showed F _st = 0.28 and analysis of molecular variance showed significant divergence (22.7%) between the Laikipia, Kulal and Galana regions. The regional and host distribution of multi-locus genotypes significant population differentiation and high Nei’s genetic distances suggest existence of genetic sub-structuring within T. evansi stocks while the few multi-locus genotypes and deviation of association index from zero indicate the lack of recombination. In conclusion, this study reveals that some genetic sub-structuring does occur within T. evansi, which has a clonal population structure.     

Iohexol in serum determined by capillary electrophoresis.

Iohexol, a nonionic compound used as a contrast medium for angiography and as a measure of the glomerular filtration rate, was quantified in serum by capillary electrophoresis. Comparable results were obtained for serum samples deproteinized with acetonitrile or analyzed directly after 50-fold dilution with borate buffer. Serum samples were electrophoresed for 2.6 min at 12 kV in a borate buffer with detection at 254 nm and with 3-isobutyl-1-methylxanthine as internal standard. Acetonitrile deproteinization gave a greater sensitivity than did sample dilution. Between-run CVs were between 4.7% and 6.7%, and within-run CVs were between 2.5 and 3.2%. Analytical recoveries were 95-105%. Results of the method compared well with those by high-performance liquid chromatography (slope 0.96, intercept 0.005 g/L). This method demonstrates the potential of capillary electrophoresis for rapid and simple quantification of small molecules.