Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines.

Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a potential candidate for treatment of GB. To facilitate efficient delivery of therapeutic doses of curcumin into cells, we encapsulated the drug in surface-modified polyamidoamine (PAMAM) dendrimers. We studied the in vitro effectiveness of a traditional PAMAM dendrimer (100% amine surface, G4 NH2), surface-modified dendrimer (10% amine and 90% hydroxyl-G4 90/10-Cys), and curcumin (Cur)-encapsulated dendrimer (G4 90/10-Cys-Cur) on three species of glioblastoma cell lines: mouse-GL261, rat-F98, and human-U87. Using an MTT assay for cell viability, we found that G4 90/10-Cys-Cur reduced viability of all three glioblastoma cell lines compared to non-cancerous control cells. Under similar conditions, unencapsulated curcumin was not effective, while the non-modified dendrimer (G4 NH2) caused significant death of both cancerous and normal cells. By harnessing and optimizing the components of PAMAM dendrimers, we are providing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.

Multicentre study of appendicitis management comparing a large South Island metropolitan hospital, to its referring regional and rural centres.

BACKGROUND: Globally, patients presenting with acute surgical disease in rural areas have poorer outcomes when compared to urban areas; little data are available regarding outcomes for New Zealand (NZ) rural patients. This study aimed to compare the surgical management of appendicitis in a large metropolitan centre with its regional referral centres. METHODS: In this retrospective cohort study, patient data were collated from the studied centres between November 2014 and October 2019. In addition to patient demographics, patterns of referral and presentation, the primary outcome was time to the theatre; secondary outcomes were perforation rates, length of stay and complications. Data are presented as medians (interquartile range). RESULTS: A total of 3533 patients underwent appendicectomy over the period studied. For those presenting directly to the metropolitan centre, the median wait-time to the theatre was 16 h (9.2-23.2); if patients were transferred, they waited for 20.8 h (13.6-27). Patients presenting to regional centres waited for 7.6 h (4.5-15.4, P < 0.001). Perforation rates for transferred patients were 31% which was greater than for those presenting to the metropolitan (20%) or regional centres (17%, P = 0.014). Complications were also highest in transferred patients (20%) when compared to the metropolitan (17%) or regional centres (10%, P < 0.001). CONCLUSION: Patients who were transferred to Christchurch Hospital from rural centres without surgical services had a longer wait-time than those who presented to Christchurch Hospital directly or were treated in regional centres. This was associated with higher rates of perforated appendicitis.

Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine.

Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response to HIV-derived peptide delivered to DCs using two different polycationic nanoparticles: a G4 PAMAM dendrimer modified to a 70/30 ratio of hydroxyl groups/amines and a cyclodextrin derivative. We have studied peptide delivery using a fluorescence peptide and have studied the immune response generation by cytokine determination and flow cytometry. We have found a robust delivery of the antigenic peptide to DCs and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction. However, no expression of markers indicating activation of either B or T lymphocytes was observed. Moreover, the release of the pro-inflammatory cytokine TNF-α or IL-2 was only observed when DCs treated with either the dendrimer or the dendriplex containing the peptide. Antigenic peptide delivery to DCs is a promising approach to generate a vaccine against HIV-1 infection. However, more studies, including the simultaneous delivery of several antigenic peptides from different viral proteins, can markedly improve the immune response.