Inhibition by albumin of merocyanine 540-mediated photosensitization of platelets and viruses

The effect of the photosensitizer merocyanine 540 (MC 540) on platelets and on three marker viruses was examined to assess its potential in reducing virus transmission by blood products. The results demonstrated several deleterious effects of MC 540 (4-24 micrograms/mL) on platelet morphology and function in both the absence and presence of light (450-600 nm). Treatment of washed platelets with MC 540 in the dark resulted in a significant release of serotonin in the absence of added agonist, as well as a diminished response to thrombin as measured in vitro. In addition, photosensitization caused spontaneous platelet aggregation and release of 92 percent of the releasable serotonin without the addition of an agonist. Because photo-treatment of blood products is likely to be performed in a protein-rich medium, the influence of albumin on the phototoxic effects on platelets was assessed. Albumin added to the suspension medium at concentrations greater than or equal to 1.0 percent protected the platelets against the effects of MC 540 in the dark, whereas 5-percent albumin was required for protection against the phototoxic effects of MC 540 on the platelet response to thrombin. The antiviral activity of MC 540 and light was examined by using the lipid-containing viruses herpes simplex virus (HSV) and bacteriophages phi 6 and PM2. Of the lipid-enveloped viruses, HSV was 25 times more photosensitive to MC 540 than was phi 6 (15 micrograms/mL). PM2, which has an internal lipid layer, was almost 300 times less sensitive to MC 540 and light than was HSV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Three patterns of cytochrome P450 gene expression during liver maturation in mice

The neonatal period of liver development is an often overlooked phase of development. For instance, ontogeny of xenobiotic-metabolizing enzymes can markedly affect biotransformation as the liver matures. To systematically examine the ontogenic gene expression patterns of cytochrome P450 genes (P450) in mice, the gene expression profiles of 19 xenobiotic-metabolizing P450 in Cyp1 to 4 families were determined. The mRNA levels in C57BL/6 mouse livers were quantified using branched DNA technology at the following ages: gestational day 17 (2 days before birth) and postnatal days 0, 1, 3, 5, 10, 15, 20, 30, and 45. Among the 13 P450 genes expressed in mouse livers, three distinct ontogenic expression patterns were identified by cluster analysis. Genes in group 1 (Cyp3a16 as well as 3a41b in male) were expressed in the perinatal period, but they were essentially nondetectable by 30 days of age. Genes in group 2 (Cyp2e1, 3a11, and 4a10 as well as 3a41b in female) quickly increased after birth and reached maximal expression levels by day 5. Genes in group 3 (Cyp1a2, 2a4, 2b10, 2c29, 2d22, 2f2, 3a13, and 3a25) were expressed at low levels until days 10 to 15, but they markedly increased at day 20 to a high and stable level. In conclusion, the developmental expression of P450 in mouse liver can be divided into three patterns, suggesting that different mechanisms are responsible for the expression of P450 during liver maturation.     

尼莫地平胃内滞留漂浮型缓释片的研究

将尼莫地平先制成速释型固体分散体,再压制成胃内滞留漂浮型缓释片(NM-FSRT)。均匀设计法优选处方,并考察处方因素对尼莫地平释放的影响,在人体内对NM-FSRT进行了初步评价。结果表明优选处方于体外漂浮达10h,0.15～6h释放符合零级动力学。HPMC量越大,药物释放越慢,PEG 6000量越大,释放越快。饮食后NM-FSRT于胃内滞留时间约5h,空腹时约3h;对照非漂浮片饭后服滞留时间为3h,空腹2h排空。体内相对生物利用度为391.46%,MRT较普通片延长一倍多。     

羊红膻根中羊红膻素A及羊红膻素B的分离和鉴定

从草药羊红膻(Pimpinela thelungiana Wolf)根中分得2个化合物,经光谱解析(UV,IR,MS,¹HNMR,¹H ¹HCOSY,¹³CNMR,¹³C-¹HCOSY和DEPT),鉴定为2-(1-ethoxy-2-hydroxy)propyl-4-methoxyphenol(I)和2-(1-ethoxy-2-hydroxy)propyl-4-methoxyphenyl-2-methyl-butyrate(II),分别命名为羊红膻素A及羊红膻素B,为2个新的天然产物,药理实验表明这2个新化合物均有较明显的降压活性。     

口服用硝苯地平缓释微球的研究

用丙酮/液状石蜡乳剂一溶剂挥发法制备硝苯地平一EudragitRL缓释微球。微球中药物以非晶态分散于EudragitRL载体中。微球体外释药过程符合Higuchi方程。在不同条件下存贮6个月内微球的药物含量、药物分散状态和释药速率均无明显变化。经8名健康志愿者单剂量口服实验,缓释微球相对于进口缓释片的生物利用度为102.5%,两者具有生物等价性。缓释微球的体内外相关性显著(P<0.01)。     

Marrow transplantation for patients with acute lymphoblastic leukemia: a long-term follow-up

Twenty-two patients with acute lymphoblastic leukemia in second or subsequent remission and 26 with acute lymphoblastic leukemia in relapse were given cyclophosphamide (60 mg/kg on each of 2 days), total body irradiation (920 rad), and marrow transplants from HLA-identical siblings. With a minimum follow-up of more than 5 yr, an actuarial analysis shows a survival and apparent cure of 27% of the patients transplanted in remission and 15% of the patients transplanted in relapse.     

A three-allele restriction-fragment-length polymorphism at the hypoxanthine phosphoribosyltransferase locus in man.

Using cloned cDNA sequences of murine and human hypoxanthine phosphoribosyltransferase (HPRT: IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8), we have identified and characterized a three-allele restriction-fragment-length polymorphism for the restriction endonuclease BamHI at the human HPRT locus. The alleles are expressed phenotypically on Southern blots as three distinct pairs of fragments that hybridize to HPRT cDNA: (i) a 22-kilobase (kb)/25-kb pair, (ii) a 12-kb/25-kb pair, and (iii) a 22-kb/18-kb pair. In addition to fragments from the HPRT locus, sequences recognized by both HPRT cDNA probes are also present on at least two autosomes in the human genome. Allele frequencies in an unselected Caucasian population are 0.77 for the 22-kb/25-kb allele. 0.16 for the 12-kb/25-kb allele, and 0.07 for the 22-kb/18-kb allele, resulting in an average heterozygosity of 38% in females in this population. This polymorphism should facilitate gene mapping by linkage in this region of the human X chromosome.     

头颈部鳞癌的条件生存率

头颈部鳞癌（HNSCC）患者生存率的统计通常是从疾病被诊断时开始．但对疾病确诊后生存一段时间的患者很少应用条件生存率（conditional survival，CS）进行分析，CS分析能够提供判断患者预后的重要信息。该文旨在应用大规模的癌症数据库寻求CS参数。对1973～1998年间美国国立癌症研究院（the National Cancer Institute。NCI）的监测、流行病学和最终结果（the surveillance，epidemiology and end-results，SEER）计划（Surveillance．Epidemiology，and End Results，