DNA interaction,anti-proliferative effect of copper oxide nanocolloids prepared from metallosurfactant based microemulsions acting as precursor,template and reducing agent

In the present study, we have synthesized mixed cuprous/copper oxide nanosuspensions by metallosurfactant based microemulsion technique. Three metallosurfactants were synthesized which includes two non-ionic double chained metallosurfactants with C₁₂, C₁₆ chains with coordinated copper i.e. Cudda and Cuhexa, respectively. Another cationic double chained metallosurfactant with loosely bound metal (Cuctac) was also prepared. The prepared metallocomplexes were characterized using FTIR, elemental analysis, and NMR. The effect of the position of metallosurfactant in microemulsion on the fabrication and properties of nanosuspensions was elucidated. In this method, no external reducing agent and capping agent were added and tween 80 acted both as reducing and stabilizing agent for the nanoparticles. The synthesized nanoparticles were characterized and it was observed that mixed copper and cuprous oxide particles are present in colloidal suspension for all the three studied metallosurfactants. The kinetics of formation of mixed copper/cuprous oxide nanosuspensions (Ns) and their stability was estimated using Uv-visible spectroscopy. Further, the binding and interactions of copper nanosuspensions with calf Thymus DNA (CT-DNA) were assessed using Uv–vis spectroscopy, circular dichroism and gel electrophoresis. Additionally, the antioxidant activity of the Cu Ns was checked using DPPH assay. The role of positive charge on nanoparticles as evaluated from Zeta potential was responsible for DNA affinity. The DNA conformational changes in the presence of nanosuspensions and relevant scavengers were investigated. Further, the anti-proliferative activity of copper Ns was assessed using HeLa cells and Cuhexa derived Ns were proved to be active with highest activity at a low concentration and were nontoxic towards normal cell lines. In summary, this work demonstrates a softer approach for the synthesis of copper nanosuspensions with a size range of 2–5?nm and evaluated the role of type and structure of metallosurfactant on size, stability of particles and anti-proliferative activity.     

Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia

In a phase 2 study, 62 patients with relapsed and refractory acute myeloid leukemia (AML; n = 31), myelodysplastic syndrome (MDS; n = 8), chronic myeloid leukemia in blastic phase (CMLBP; n = 11), and acute lymphocytic leukemia (ALL; n = 12) received 40 mg/m2 clofarabine intravenously over 1 hour daily for 5 days, every 3 to 6 weeks. Twenty patients (32%) achieved complete response (CR), 1 had a partial response (PR), and 9 (15%) achieved CR but without platelet recovery (CRp), for an overall response rate of 48%. In AML, responses were noted in 2 (18%) of 11 patients in first salvage with short first CR (相似文献   

Efficacy of granulocyte-macrophage colony-stimulating factor or lamivudine combination with recombinant interferon in non-responders to interferon in hepatitis B virus-related chronic liver disease patients

BACKGROUND AND AIMS: Non-response to interferon (IFN) monotherapy is a major therapeutic problem in the management of chronic hepatitis B infection. The efficacy of combination therapy to enhance the immunomodulatory effect of IFN by combining granulocyte-macrophage colony-stimulating factor (GMCSF) or decreasing viral load by adding an antiviral agent such as lamivudine was evaluated prospectively. METHODS: Twenty-four patients with chronic hepatitis B who were non-responders to previous IFN therapy were randomized to receive an IFN and GMCSF (group A, n = 10) or IFN and lamivudine (group B, n = 14) combination for 6 months. The end-of-treatment response was assessed by hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg) determination. RESULTS: All patients successfully completed both the treatment schedules. The mean age, alanine aminotransferase (ALT) levels, liver histology, HBV-DNA levels and distribution of HBV genotypes were comparable between the two groups. At the end of treatment there was a significant decrease in mean ALT levels. The HBV-DNA and HBeAg loss was seen in six of 10 (60%) patients in group A and in seven of 14 (50%) patients in group B. During a mean follow-up of 15 +/- 3 months, two of six (33%) patients in group A and three of seven (43%) patients in group B relapsed with HBV-DNA and HBeAg positivity, which meant an overall sustained response of 40% and 28%, respectively. None of the factors such as HBV viral load, ALT levels or liver histology could predict the non-response to combination therapy or occurrence of relapse. There was a trend in patients with genotype A compared with genotype D towards non-response to therapy, although the difference was not significant. CONCLUSIONS: The combination of IFN plus GMCSF or lamivudine was effective in non-responders to IFN monotherapy. Larger studies using such combination therapies would be helpful in improving treatment strategies for chronic hepatitis B.     

Synergistic effect between nisin and polymyxin B against pandrug-resistant and extensively drug-resistant Acinetobacter baumannii

Acinetobacter baumannii is an opportunistic pathogen predominantly associated with nosocomial infections. The World Health Organization's data on antibiotic-resistant ‘priority pathogens’ reports carbapenem-resistant A. baumannii as a pathogen which is in critical need of research and development of new antimicrobials. Emerging resistance against polymyxins, last-resort drugs for carbapenem-resistant A. baumannii, increases the need for new therapeutic approaches such as synergistic combinations. Nisin, an antibacterial peptide produced by the Gram-positive bacteria L. lactis, is a US Food and Drug Administration approved food preservative with bactericidal action predominantly against other Gram-positive bacteria. A 2008 study reported that topical nisin was effective against staphylococcal mastitis in humans. Additionally, nisin has shown activity against Gram-negative bacteria in combination with antimicrobials such as polymyxin B. A recent in vitro study reported that nisin and polymyxin B exhibited synergistic activity against one isolate each of A. baumannii, Acinetobacter lwoffii and Acinetobacter calcoaceticus using time-kill assay and checkerboard technique. We evaluated the synergistic potential of nisin and polymyxin B against 15 unique clinical A. baumannii isolates using time-kill assay. Three of eight (38%) extensively drug-resistant and six of seven (86%) pandrug-resistant A. baumannii isolates showed synergy with one or more combinations of nisin and polymyxin B. The synergy seen with the use of lower concentrations of polymyxin B may help in reducing the dose-dependent side effects. Additional studies involving pharmacokinetics and pharmacodynamics of nisin are required to explore clinical possibilities.     

Conversion to the buffy coat method and quality of frozen plasma derived from whole blood donations in Canada

BACKGROUND: Canada converted from the platelet‐rich plasma (PRP) method to the buffy coat (BC) method of processing whole blood donations between 2006 and 2008. We measured coagulation variables in plasma units during this transition, in 2006 (PRP only), 2007 (BC and PRP), and 2008 (BC only) to test the hypothesis that this conversion would not affect frozen plasma (FP) quality. STUDY DESIGN AND METHODS: Fresh‐frozen plasma (FFP; frozen within 8 hr of collection) or FP (frozen within 24 hr of collection) units were shipped on dry ice from 12 plasma manufacturing sites, thawed, and characterized using an automated coagulation analyzer, at a single testing site. RESULTS: FP made by the BC method (FP‐BC) exhibited fibrinogen, Factor (F)V, ABO‐matched FVIII, and antithrombin levels at least as high as FP made by the PRP method (FP‐PRP) and supported global clotting, as measured by prothrombin time or activated partial thromboplastin time, to an indistinguishable extent as FP‐PRP. FP‐BC and FP‐PRP did not differ in ABO‐matched FVIII levels, but both contained 30% to 35% less FVIII than FFP. There was no discernible effect of the site of manufacturing on plasma quality. FP‐BC units leukoreduced by centrifugation contained more FV activity than those leukoreduced by filtration, but the difference was unlikely to be of clinical significance. CONCLUSION: Our data suggest that no reduction in FP quality, at least in the characteristics we tested, accompanied the switch from the PRP to the BC method processing of whole blood donations in Canada.