Effect of P-glycoprotein on flavopiridol sensitivity

Flavopiridol is the first potent inhibitor of cyclin-dependent kinases (CDKs) to enter clinical trials. Little is known about mechanisms of resistance to this agent. In order to determine whether P-glycoprotein (Pgp) might play a role in flavopiridol resistance, we examined flavopiridol sensitivity in a pair of Chinese hamster ovary cell lines differing with respect to level of Pgp expression. The IC 50 s of flavopiridol in parental AuxB1 (lower Pgp) and colchicine-selected CHRC5 (higher Pgp) cells were 90.2 ± 6.6 nM and 117 ± 2.3 nM, respectively (P< 0.01), suggesting that Pgp might have a modest effect on flavopiridol action. Consistent with this hypothesis, pretreatment with either quinidine or verapamil (inhibitors of Pgp-mediated transport) sensitized CHRC5 cells to the antiproliferative effects of flavopiridol. Because of concern that colony forming assays might not accurately reflect cytotoxicity, we also examined flavopiridol-treated cells by trypan blue staining and flow cytometry. These assays confirmed that flavopiridol was less toxic to cells expressing higher levels of Pgp. Further experiments revealed that flavopiridol inhibited the binding of [3H]-azidopine to Pgp in isolated membrane vesicles, but only at high concentrations. Collectively, these results identify flavopiridol as a weak substrate for Pgp. © 2001 Cancer Research Campaign www.bjcancer.co

Combined rotation scarf and Akin osteotomies for hallux valgus: a patient focussed 9 year follow up of 50 patients

<p>Abstract</p> <p>Background</p> <p>The Cochrane review of hallux valgus surgery has disputed the scientific validity of hallux valgus research. Scoring systems and surrogate measures such as x-ray angles are commonly reported at just one year post operatively but these are of dubious relevance to the patient. In this study we extended the follow up to a minimum of 8 years and sought to address patient specific concerns with hallux valgus surgery. The long term follow up also allowed a comprehensive review of the complications associated with the combined rotation scarf and Akin osteotomies.</p> <p>Methods</p> <p>Between 1996 and 1999, 101 patients underwent rotation scarf and Akin osteotomies for the treatment of hallux valgus. All patients were contacted and asked to participate in this study. 50 female participants were available allowing review of 73 procedures. The average follow up was over 9 years and the average age at the time of surgery was 57. The participants were physically examined and interviewed.</p> <p>Results</p> <p>Post-operatively, in 86% of the participants there were no footwear restrictions. Stiffness of the first metatarsophalangeal joint was reported in 8% (6 feet); 10% were unhappy with the cosmetic appearance of their feet, 3 feet had hallux varus, and 2 feet had recurrent hallux valgus. There were no foot-related activity restrictions in 92% of the group. Metatarsalgia occurred in 4% (3 feet). 96% were better than before surgery and 88% were completely satisfied with their post-operative result. Hallux varus was the greatest single cause of dissatisfaction. The most common adverse event in the study was internal fixation irritation. Hallux valgus surgery is not without risk and these findings could be useful in the informed consent process.</p> <p>Conclusions</p> <p>When combined the rotation scarf and Akin osteotomies are an effective treatment for hallux valgus that achieves good long-term correction with a low incidence of recurrence, footwear restriction or metatarsalgia. The nature of the osteotomies allows early return to normal shoes and activity without the need for postoperative immobilisation in a plaster cast.</p

Condições topoclimáticas e serviços ecossistêmicos prestados pelas castanheiras no Bioma Amazônia.

Visando garantir o protagonismo do Brasil no mercado nacional e internacional e a conservação da espécie, o objetivo neste capítulo foi analisar áreas impactadas pelo processo antrópico com potencial topoclimático para a castanheira como estratégia de inclusão da espécie em ações de restauração florestal que possam receber apoio de políticas de pagamentos por serviços ambientais (PSA) na Amazônia brasileira.ODS 2, ODS 3, ODS 8, ODS 11, ODS 12, ODS 13, ODS 17

Barcoding T Cell Calcium Response Diversity with Methods for Automated and Accurate Analysis of Cell Signals (MAAACS)

International audienceWe introduce a series of experimental procedures enabling sensitive calcium monitoring in T cell populations by confocal video-microscopy. Tracking and post-acquisition analysis was performed using Methods for Automated and Accurate Analysis of Cell Signals (MAAACS), a fully customized program that associates a high throughput tracking algorithm, an intuitive reconnection routine and a statistical platform to provide, at a glance, the calcium barcode of a population of individual T-cells. Combined with a sensitive calcium probe, this method allowed us to unravel the heterogeneity in shape and intensity of the calcium response in T cell populations and especially in naive T cells, which display intracellular calcium oscillations upon stimulation by antigen presenting cells

Ecosystem services provided by Bertholletia excelsa in the Brazilian Amazon.

Abstracts of the XXV IUFRO World Congress, 2019

Agriculture and forest: A sustainable strategy in the Brazilian Amazon.

Large-scale agriculture is increasing in anthropogenically modified areas in the Amazon Basin. Crops such as soybean, maize, oil palm, and others are being introduced to supply the world demand for food and energy. However, the current challenge is to enhance the sustainability of these areas by increasing efficiency of production chains and to improve environmental services. The Amazon Basin has experienced a paradigm shift away from the traditional slash-and-burn agricultural practices, which offers decision makers the opportunity to make innovative interventions to enhance the productivity in previously degraded areas by using trees to ecological advantage. This study describes a successful experiment integrating the production of soybean and paricá (Glycine max L. and Schizolobium amazonicum) based on previous research that indicated potential topoclimatic zones for planting paricá in the Brazilian state of Pará. This paper shows that a no-tillage system reduces the effects of drought compared to conventional tillage still used by many farmers in the region. The integrated system was implemented during the 2014/2015 season in 234.6 ha in the high-potential zone in the municipality of Ulianópolis, Pará. Both soybean and paricá were planted simultaneously. Paricá was planted in 5 m x 2 m inter-tree spacing totaling 228x103 trees per hectare and soybean, in 4 m x 100 m spacing, distributed in nine rows with a 0.45 m inter-row distance, occupying 80% of the area. The harvested soybean production was 3.4 t ha-1, higher than other soybean monocultures in eastern Pará. Paricá benefited from soybean fertilization in the first year: It exhibited rapid development in height (3.26 m) and average diameter (3.85 cm). Trees and crop rotation over the following years is six years for forest species and one year for each crop. Our results confirm there are alternatives to the current production systems able to diminish negative impacts resulting from monoculture. In addition, the system provided environmental services such as reduced soil erosion and increased carbon stock by soil cover with no-tillage soybean cultivation. The soybean cover contributes to increased paricá thermal regulation and lower forestry costs. We concluded that innovative interventions are important to show local farmers that it is possible to adapt an agroforest system to large-scale production, thus changing the Amazon.201

Cutting edge : a naturally occurring mutation in CD1e impairs lipid antigen presentation

The human CD1a-d proteins are plasma membrane molecules involved in the presentation of lipid Ags to T cells. In contrast, CD1e is an intracellular protein present in a soluble form in late endosomes or lysosomes and is essential for the processing of complex glycolipid Ags such as hexamannosylated phosphatidyl-myo-inositol, PIM(6). CD1e is formed by the association of beta(2)-microglobulin with an alpha-chain encoded by a polymorphic gene. We report here that one variant of CD1e with a proline at position 194, encoded by allele 4, does not assist PIM(6) presentation to CD1b-restricted specific T cells. The immunological incompetence of this CD1e variant is mainly due to inefficient assembly and poor transport of this molecule to late endosomal compartments. Although the allele 4 of CD1E is not frequent in the population, our findings suggest that homozygous individuals might display an altered immune response to complex glycolipid Ags