Antioxidant properties of β-seleno amines against lipid peroxidation in rat brain and liver

β-Seleno amines were screened for in vitro antioxidant activity. The compounds (C1-C4) were tested against lipid peroxidation induced by iron and sodium nitroprusside in rat brain and liver homogenates. The compounds showed inhibition against thiobarbituric acid reactive species (TBARS) induced by different pro-oxidants (10μM FeSO(4) and 5μM sodium nitroprusside (SNP) in rat brain and liver homogenates. The compounds exhibited strong antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and phosphomolybdenum assays. The IC(50) values revealed that the β-seleno amines in which the amino group was protected with protecting groups tert-butyloxycarbonyl (Boc) and Tosyl (Ts) groups showed better antioxidant profiles compared to the free monoselenides. The total antioxidant activity of C1, C2, C3 and C4 were found to be 85.2±11.5, 114±7.9, 138±8.5, 125.81±5.2μM/ml of ascorbic acid respectively. Therefore, these compounds may be used as synthetic antioxidants.     

High incidence of instability and loss of heterozygosity in three loci in breast cancer patients receiving chemotherapy: a prospective study

ABSTRACT: BACKGROUND: The aim of the study was to evaluate potential chemotherapy-induced microsatellite instability, loss of heterozygosity, loss of expression in mismatch repair proteins and associations with clinical findings in breast cancer patients, especially resistance to chemotherapy and/or development of other tumors in the four years following chemotherapy treatment. METHODS: A comprehensive study of chemotherapy-related effects with a follow-up period of 48 months post treatment was conducted. A total of 369 peripheral blood samples were collected from 123 de novo breast cancer patients. Microsatellite instability and loss of heterozygosity in five commonly used marker loci (including Tp53-Alu of the tumor suppressor gene TP53) were analyzed in blood samples. Sampling was conducted on three occasions; 4--5 weeks prior to the first chemotherapy session (pre-treatment), to serve as a baseline, followed by two consecutive draws at 12 weeks intervals from the first collection. Mismatch repair protein expression was evaluated in cancer tissues using immunohistochemistry for three mismatch-repair related proteins. RESULTS: A total of 70.7% of the patients showed microsatellite instability for at least one locus, including 18.6% marked as high-positive and 52.1% as low-positive; 35.8% showed loss of heterozygosity in addition to microsatellite instability, while 29.3% exhibited microsatellite stability. The following incidence rates for microsatellite instability and loss of heterozygosity were detected: 39.08% positive for Tp53-Alu, 31.1% for locus Mfd41, and 25.3% for locus Mfd28. A higher occurrence of loss of heterozygosity was noted with alleles 399 and 404 of Tp53-Alu. The mismatch repair protein expression analysis showed that the chemotherapy caused a loss of 29.3% in hMLH1 expression, and 18.7% and 25.2% loss in hMSH2 and P53 expression, respectively. A strong correlation between low or deficient hMSH2 protein expression and occurrence of mismatch repair/loss of heterozygosity events in Mfd41, Tp53-Alu, and Mfd28 was evident. A significant association between mismatch repair/loss of heterozygosity and incidence of secondary tumors was also established CONCLUSION: Our results suggest that microsatellite instability, loss of heterozygosity, and deficiency in mismatch repair may serve as early prognostic factors for potential chemotherapy-related side effects in breast cancer patients.     

Comparison of effects of adrenocorticotropin and Lys-gamma 3-melanocyte-stimulating hormone on steroidogenesis, adenosine 3',5'-monophosphate production, and phospholipid metabolism in rat adrenal fasciculata-reticularis cells in vitro

Synthetic bovine Lys-gamma 3MSH was found to potentiate the steroidogenic action of ACTH during incubation of rat adrenal fasciculata-reticularis cells in vitro. On the other hand, Lys-gamma 3MSH did not increase basal levels of or ACTH-induced (submaximal) increases in cellular concentrations of cAMP or phosphatidylinositol. Thus, Lys-gamma 3MSH does not appear to simply increase the overall action of ACTH, and moreover, it appears to potentiate steroidogenesis by a mechanism that is considerably different from that employed by ACTH. Observance of an effect of ACTH and failure to observe an effect of gamma 3MSH on adrenal phosphatidylinositol are in keeping with our previous postulation that phospholipids in the phosphatidate-inositide cycle play an important role in promoting cholesterol side-chain cleavage, since ACTH, but not gamma 3MSH, reportedly increases cholesterol side-chain cleavage. In addition, we also presently observed that Lys-gamma 3MSH can markedly increase corticosterone production in the face of a fixed, relatively small, submaximal, ACTH-induced increase in phosphatidylinositol. Thus, if gamma 3MSH enhances steroidogenesis by increasing free cholesterol availability, the latter may require another factor to initiate steroidogenesis, but is, nevertheless, an important determinant of the rate of steroidogenesis.     

Angiotensin II rapidly increases phosphatidate-phosphoinositide synthesis and phosphoinositide hydrolysis and mobilizes intracellular calcium in cultured arterial muscle cells.

Smooth muscle cells were cultured from rat thoracic aorta and labeled to a stable specific activity with 45Ca2+, myo-[2-3H]inositol, or 32Pi. The efflux of 45Ca2+ was monitored over 10-sec intervals. Angiotensin II (AII) increased the amount of 45Ca2+ lost by 5-fold in the first 10-sec interval after the addition of AII and by 10-fold in the second 10-sec interval. AII-stimulated 45Ca2+ release was blocked by the angiotensin antagonist [1-sarcosine, 8-leucine]AII and by La3+. The removal of external Ca2+ had no effect on AII-stimulated 45Ca2+ release. Depolarization with high external K+ only slightly increased 45Ca2+ efflux and had no effect on AII-induced 45Ca2+ release. AII had no effect on the initial rate of 45Ca2+ influx. These results indicate that the rapid 45Ca2+ efflux evoked by AII is probably due to the release of 45Ca2+ sequestered intracellularly rather than to an increase in the Ca2+ permeability of the plasma membrane. AII provoked rapid increases in the levels of phosphatidic acid and phosphoinositides in the cells. These increases in phospholipids were associated with increases in phospholipase C-generated inositol phosphates (tri-, di-, and mono-). It appears that AII simultaneously increases phosphoinositide hydrolysis and synthesis in vascular smooth muscle, and both phospholipid effects may contribute to inositol triphosphate generation, which was sufficiently rapid to have a role in intracellular Ca2+ mobilization.     

Effect of Side Chains on Charge Transport of Anthracene‐Based PPE–PPV Copolymers

The variation of the drift mobility of positive and negative charge carriers in films of anthracene‐containing poly(p‐phenylene‐ethynylene)‐alt‐poly(p‐phenylene‐vinylene)s ( AnE‐PVs ), differently substituted, is investigated as a function of the applied electric field. Branched 2‐ethylhexyl and linear alkoxy side chains of different lengths are considered, as well as well‐defined and random distributions of lateral substituents. The same conditions are used both for the deposition of the polymer films and for their characterization, which allows for the establishment of a clear relationship between the chemical structure and the charge carrier mobility.

     

天山假狼毒化学成分预实验

目的采用系统预试法对天山假狼毒可能的化学成分进行预实验,初步探索天山假狼毒的化学成分。方法采用试管反应法,对提取天山假狼毒中的石油醚、水、95%乙醇提取物进行预示,通过多种指示剂和显色剂的沉淀反应或颜色反应,对天山假狼毒可能含有的化学成分进行初步判断。结果天山假狼毒中可能含有氨基酸、蛋白质、糖、有机酸、皂苷、黄酮类、酚类、鞣质、香豆素、内酯类、甾体、三萜和挥发油等化学成分。结论初步确定天山假狼毒含有多种有效成分,为天山假狼毒的进一步开发利用提供了实验基础。