Preparation, Characterization, and In Vitro pH-sensitivity Evaluation of Superparamagnetic Iron Oxide Nanoparticle- Misonidazole pH-sensitive Liposomes.

BACKGROUND: The use of Misonidazole (MISO), the first and a potential hypoxic tumor cell radiosensitizer, has been limited by peripheral neurotoxicity, thus discouraging phase III clinical trials. OBJECTIVE: To develop a targeted drug delivery and tracing System with pH-sensitive liposomes (SpHLs) and Superparamagnetic Iron Oxide Nanoparticles (SPIONs) to counter MISO-related adverse effects and to enable tracing under magnetic resonance. METHODS: SPION-MISO-SpHLs were prepared by a reverse evaporation and freeze-thawing method. HPLC and phenanthroline spectrophotometry were established for MISO and Fe determination. The characterization and in vitro pH-sensitivity of SPION-MISO-SpHLs were evaluated. RESULTS: The maximal entrapment efficiencies of MISO and SPIONs in SPION-MISO-SpHLs were 30.2% and 23.7%, respectively. The cumulative release rates of MISO and SPIONs were respectively 2.49 and 2.47 times higher in pH 5.5 than in pH 7.4 buffer. The mean particle size of SPION-MISOSpHLs was 950 nm. The zeta potential was -58.9 mV in pH 7.4 buffer and 36.3 mV in pH 5.5 buffer. SEM imaging showed that SPION-MISO-SpHLs had similar spherical morphologies. SPIONs were packed in the center of liposomes and were well dispersed in a TEM graph. Magnetization curve showed that SPION-MISO-SpHLs retained superparamagnetic properties. SPION-MISO-SpHLs were compared with MISO+SPION+blank liposome in hypoxia and control groups of A549 cells. MISO and SPION concentrations in culture medium showed significant differences between the same concentration groups (P < 0.0001) and at different times (P < 0.0001). CONCLUSION: SPION-MISO-SpHLs possess pH-dependent release ability and superparamagnetism, and thus provides a system for targeted delivery and tracing under magnetic resonance.

[Effects of Four Renin-Angiotensin System' s Regulators on the Human Leukemia HEL Cell Growth].

OBJECTIVE: To investigate the effects of 4 renin-angiotensin system's(RAS) regulators (losartan, telmisartan, aliskiren and angiotenisin) on the human leukemia HEL cell growth. METHODS: The HEL cells were treated with losartan, telmisartan, aliskiren and Angiotensin-(1-7) (Ang-(1-7)) for 12 days, respectively. The cell proliferation was measured by CCK-8 kit, the cell cycle and apoptosis were measured by flow cytometry. RESULTS: The 10-7 mol/L Ang-(1-7) markedly inhibited the growth of HEL cells, blocked cells at G0/G1 phase and markedly increased the late apoptotic cells (P< 0.001). The 10-5 mol/L losartan and telmisartan, 10-4 mol/L aliskiren had no effects on the proliferation, cell cycle and apoptosis of HEL cells (P>0.05). CONCLUSION: Ang-(1-7), one of renin-angiotensin system's regulators, can inhibit the growth of HEL cells and promote the cell apoptosis. Ang-(1-7) may be one potential therapeutic drug for polycythemia vera with JAK2 mutation.

[Prognostic significance of morbidly hematopoietic characteristics in 69 patients with myelodysplastic syndrome].

OBJECTIVE: This study was to investigate the influence of morbidly hematopoietic characteristics on the prognosis of patients with myelodysplastic syndrome (MDS). METHODS: A total of 69 cases of MDS were analyzed retrospectively on ralatienship between sex, age, MDS types, WBC count, hemoglobin (Hb) level, platelet (Plt) count at diagnosis, morbidly cytologic features of bone marrow and survival time of MDS patients. RESULTS: The median survival time of 69 cases of MDS was 29.90 months. The patients of different sexes and Plt level at diagnosis did not display statistically significant difference in median survival time (P > 0.05); the patients with different ages, WBC count and Hb level showed statistically significant difference in median survival time (P < 0.05); the median survival time of patients with different MDS types was significant different (P < 0.01); the MDS patients with myeloid lineage containing nuclear plasma development imbalance, micronuclei, abnormal mitotic figures, with erythroid lineage containing megaloblastic degeneration, cell size disparity, nuclcar budding and muclear fragmentation, and with megakaryocyte lineage containing micromegaryocytes, excessive muclear leaves, displayed significant difference in median survival time (P < 0.05). The MDS patients with ALIP positive, fibrosis in bone marrow blopsy showed significant difference in median survival time. CONCLUSION: The age, MDS types, Hb level and WBC count at diagnosis are indicators influencing the prognosis. The unbalanced development of muclear plasma, micronuclei, abnormal mitotic figures in myeloid morbid hematopoiesis, the megaloblastic degeneration, cell size disperity, muclear budding, nuclear fragmentation in erythroid morbid hematopoiesis, the micro-megakaryocytes, excessive nuclear leaves in megakaryocytic morbid hematopoiesis, and existance of ALIP posstive and fibrosis in bone marrow biopsy indicate important values for evaluation of MDS prognosis.