In this first report on biocompatibility of intravenously administered pSi structures, we examined the tolerability of negatively (-32.5 +/- 3.1 mV) and positively (8.7 +/- 2.5 mV) charged S1MP PLK inhibitor in acute single dose (10(7), 10(8), 5x 10(8) S1MP/animal) and subchronic multiple dose (10(8) 51MP/animal/week for 4 weeks) administration
schedules. Our data demonstrate that S1MP did not change plasma levels of renal (BUN and creatinine) and hepatic (LDH) biomarkers as well as 23 plasma cytokines. LDH plasma levels of 145.2 +/- 23.6, 115.4 +/- 29.1 vs. 127.0 +/- 10.4; and 155.8 +/- 38.4, 135.5 +/- 52.3 vs. 178.4 +/- 74.6 were detected in mice treated with 108 negatively charged S1MP, 10(8) positively charged 51 MP vs. saline control in single and multiple
dose schedules, respectively. PR-171 supplier The S1MPs did not alter LDH levels in liver and spleen, nor lead to infiltration of leukocytes into the liver, spleen, kidney, lung, brain, heart, and thyroid. Collectively, these data provide evidence of a safe intravenous administration of S1MPs as a drug delivery carrier. (c) 2010 Elsevier BM. All rights reserved.”
“Transmission of excreted vaccine-derived infectious virus from vaccinated to unvaccinated individuals is possible within close contacts. This randomized (1:1), double-blind study evaluated the potential for transmission of human rotavirus vaccine strain, HRV (Rotarix (TM)) from vaccine recipients to unvaccinated close contacts (twins). 100 pairs of healthy twins aged 6-14 weeks at the time of Dose 1 of HRV vaccine/placebo were enrolled and one randomly selected twin from each pair received two vaccine doses and the other received placebo doses (at 2 and 4 months of age). Presence of vaccine strain in the stool samples of placebo recipients was an indicator of transmission. Serial stool samples were tested for rotavirus using ELISA at pre-determined time points; rotavirus positive stool samples were tested with RT-PCR and reverse hybridization assay to identify
G1P vaccine strain. If G1P vaccine strain was detected, the complete genome was sequenced to assess the YM155 solubility dmso similarity between viral isolates. Immunogenicity and safety of HRV vaccine in transmission cases was assessed. 15 transmission cases were reported in 80 evaluable twins who received placebo and the transmission rate was 18.8% (95% Cl: 10.9-29.0%). None of the transmission cases was associated with gastroenteritis symptoms. Anti-rotavirus IgA seroconversion was 62.5% (95% CI: 51.0-73.1%) (HRV) and 21.3% (95% CI: 12.9-31.8%) (placebo) 7-weeks post-Dose 2; seroconversion in transmission cases was 26.7% (95% CI: 7.8-55.1%). Genetic variations or amino acid substitutions in transmission cases were similar to that seen in corresponding vaccine recipients.