Effects of Two Weeks of High-intensity Interval Training (HIIT) on Monocyte TLR2 and TLR4 Expression in High BMI Sedentary Men

International Journal of Exercise Science 6(1) : 81-90, 2013. Monocyte TLR expression has been shown to be reduced after a combination of aerobic and resistance exercise, but more studies considering the influences of different exercise intensities, type and duration on TLR expression are needed. Although there is an agreement about the importance of physical exercise, the minimal amount needed to improve health status is uncertain. Therefore, the aim of this study was to analyse the influence of 2 weeks of high-intensity intermittent exercise training on CD14+ monocyte TLR4 expression in a sedentary, high BMI population. As a secondary purpose, this study covers the influence of exercise on classical and pro-inflammatory monocytes and the TLR4 expression before and after a training period in these monocyte subsets. Six high-intensity interval training (HIIT) sessions over a 2 week period (three sessions per week) were completed by 11 sedentary participants (24 ± 5 years old). Blood samples were taken at the beginning and end of the training period for analysis of haematocrit, haemoglobin, total white blood cell (leukocyte), monocyte counts, monocyte CD14+ TLR4 expression and monocyte subsets. Two weeks of high-intensity intermittent exercise training increased VO2peak and total CD14+ monocyte TLR4 expression in a sedentary, high BMI population. There was no influence of training on the proportions of classical and pro-inflammatory monocyte subsets, but TLR4 expression in the majority of these monocyte subsets (apart from CD14++CD16+) was higher after the six training sessions

Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

<p>Abstract</p> <p>Background</p> <p>Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting.</p> <p>Objective</p> <p>To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method.</p> <p>Methods</p> <p>We cultured myeloma-positive CD34⁺PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34⁺cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, ΔNGFR). We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture.</p> <p>Results</p> <p>Overall recovery of CD34⁺cells after culture was 128.5%; ΔNGFR transduction rate was 28.8% for CD34⁺cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34⁺cells after ΔNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7–1.4 logs in tumor load after the CD34⁺cell selection, and up to 2.3 logs after culture and ΔNGFR selection.</p> <p>Conclusion</p> <p>We conclude that <it>ex-vivo </it>culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging.</p

Effects of the H2-Receptor Antagonist Famotidine on the Pharmacokinetics of Atazanavir-Ritonavir With or Without Tenofovir in HIV-Infected Patients

Significant pharmacokinetic interactions can result between acid-suppressing agents and some protease inhibitors (PIs) in the management of HIV infection. In healthy subjects, famotidine, an H2-receptor antagonist, reduces exposures of atazanavir by 4–28% at doses of 20–40 mg twice daily. This study evaluated the effect of famotidine 20–40 mg twice daily on the pharmacokinetics of atazanavir/ritonavir 300/100 mg once daily with and without tenofovir disoproxil fumarate (TDF) 300 mg in HIV-infected patients (n=40; 87.5% male; mean age 42, range 26–63 years; 55% white). Coadministration of famotidine 40 mg and atazanavir/ritonavir to HIV-infected patients reduced exposures of atazanavir by approximately 20%. This is comparable to reductions seen in HIV-uninfected subjects. Coadministration of famotidine 20 mg had less impact on atazanavir exposures, with no reduction of atazanavir geometric mean plasma concentration at 24 h postdose (Cmin). In the presence of TDF, administration of famotidine 20–40 mg twice daily 2 h after and 10 h before atazanavir/ritonavir reduced exposures of atazanavir by 19–25%. However, all individual atazanavir Cmin values remained at least five-fold above the population mean protein-binding adjusted 90% maximum effect (EC90) against wild-type HIV (14 ng/mL). No viral load rebound was observed at end of study. The results confirmed that coadministration of an H2-receptor antagonist with atazanavir/ritonavir in HIV-infected patients resulted in similar magnitude of reductions in atazanavir exposures as in healthy subjects. This supports the current dose recommendations for coadministration of an H2-receptor antagonist with atazanavir/ritonavir