In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells

Much effort has been made to try to understand the relationship between chemotherapeutic treatment of cancer and the immune system. Whereas much of that focus has been on the direct effect of chemotherapy drugs on immune cells and the release of antigens and danger signals by malignant cells killed by chemotherapy, the effect of chemotherapy on cells surviving treatment has often been overlooked. In the present study, tumour cell lines: A549 (lung), HCT116 (colon) and MCF-7 (breast), were treated with various concentrations of the chemotherapeutic drugs cyclophosphamide, gemcitabine (GEM) and oxaliplatin (OXP) for 24 hours in vitro. In line with other reports, GEM and OXP upregulated expression of the death receptor CD95 (fas) on live cells even at sub-cytotoxic concentrations. Further investigation revealed that the increase in CD95 in response to GEM sensitised the cells to fas ligand treatment, was associated with increased phosphorylation of stress activated protein kinase/c-Jun N-terminal kinase and that other death receptors and activatory immune receptors were co-ordinately upregulated with CD95 in certain cell lines. The upregulation of death receptors and NKG2D ligands together on cells after chemotherapy suggest that although the cells have survived preliminary treatment with chemotherapy they may now be more susceptible to immune cell-mediated challenge. This re-enforces the idea that chemotherapy-immunotherapy combinations may be useful clinically and has implications for the make-up and scheduling of such treatments

Emissions generated by sugarcane burning promote genotoxicity in rural workers: a case study in Barretos, Brazil

Background: To determine the possible genotoxic effect of exposure to the smoke generated by biomass burning on workers involved in manual sugar cane harvesting. Methods: The frequency of micronuclei in exfoliated buccal cells and peripheral blood lymphocytes was determined in sugarcane workers in the Barretos region of Brazil, during the harvest season and compared to a control population, comprised of administrative employees of Barretos Cancer Hospital. Results: The frequency of micronuclei was higher in the sugar cane workers. The mean frequency in blood lymphocytes (micronuclei/1000 cells) in the test group was 8.22 versus 1.27 in the control group. The same effect was observed when exfoliated buccal cells were considered (22.75 and 9.70 micronuclei/1000 cells for sugar cane workers and controls, respectively). Conclusion: Exposure to emissions produced by the burning of sugar cane during harvesting induces genomic instability in workers, indicating the necessity of adopting more advanced techniques of harvesting sugar cane to preserve human health.We thank the Researcher Support Center of Barretos Cancer Hospital, especially the statistician Zanardo C. for assisting in the statistical analysis. We thank Oliveira R. for technical support, and we acknowledge financial support from FAPESP Proc. 2010/10192-6

New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum

Background: The emergence and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy in Southeast Asia prompted the need to develop new endoperoxide-type drugs. Methods: A chemically diverse library of endoperoxides was designed and synthesized. The compounds were screened for in vitro and in vivo anti-malarial activity using, respectively, the SYBR Green I assay and a mouse model. Ring survival and mature stage survival assays were performed against artemisinin-resistant and artemisinin-sensitive P. falciparum strains. Cytotoxicity was evaluated against mammalian cell lines V79 and HepG2, using the MTT assay. Results: The synthesis and anti-malarial activity of 21 new endoperoxide-derived compounds is reported, where the peroxide pharmacophore is part of a trioxolane (ozonide) or a tetraoxane moiety, flanked by adamantane and a substituted cyclohexyl ring. Eight compounds exhibited sub-micromolar anti-malarial activity (IC50 0.3–71.1 nM), no cross-resistance with artemisinin or quinolone derivatives and negligible cytotoxicity towards mammalian cells. From these, six produced ring stage survival < 1% against the resistant strain IPC5202 and three of them totally suppressed Plasmodium berghei parasitaemia in mice after oral administration. Conclusion: The investigated, trioxolane–tetrazole conjugates LC131 and LC136 emerged as potential anti-malarial candidates; they show negligible toxicity towards mammalian cells, ability to kill intra-erythrocytic asexual stages of artemisinin-resistant P. falciparum and capacity to totally suppress P. berghei parasitaemia in mice.info:eu-repo/semantics/publishedVersio

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Qualidade nutricional de cenoura e alface cultivadas em Mossoró-RN em função da densidade populacional Nutritional quality of carrot and lettuce grown in Mossoró-RN, Brazil, as affected by plant densities

O experimento foi realizado durante o período de junho a setembro de 2003, na área experimental do departamento de Ciências Vegetais da Universidade Federal Rural do Semi-Árido (UFERSA), em Mossoró-RN, com o objetivo de avaliar o efeito de densidades populacionais de cenoura e de alface, em segundo, cultivo na qualidade nutricional desses cultivos em sistema de consorciação em faixa. O delineamento experimental utilizado foi o de blocos casualizados, com os tratamentos arranjados em esquema fatorial 4 x 4, com três repetições. As populações de referência para o cultivo solteiro (PRCS) foram de 500.000 plantas.ha-1 para a cenoura e de 250.000 plantas.ha-1 para a alface, que corresponderam à densidade populacional de 100%. Os tratamentos foram resultantes da combinação de quatro populações de cenoura (40%, 60%, 80% e 100% da PRCS) com quatro populações de alface (40%, 60%, 80% e 100% da PRCS). As características avaliadas nas raízes da cenoura foram firmeza, conteúdo de vitamina C, carotenóides totais e beta-caroteno, e nas folhas da alface firmeza, conteúdo de vitamina C, carotenóides totais e clorofila total. Foram utilizadas a cv Brasília (cenoura) e a cv. Tainá (alface). As associações de densidades populacionais de cenoura e alface não afetaram qualquer característica de ambas as culturas. Porém, as densidades populacionais da cenoura influenciaram as características da cenoura, e as densidades de alface afetaram as características da folha de alface. A firmeza, conteúdo de vitamina C e de beta-caroteno nas raízes da cenoura diminuíram com o aumento da densidade deste cultivo, enquanto que o conteúdo de carotenóides totais aumentou com o incremento na densidade populacional desta cultura. Mesmo comportamento decrescente também foi observado no conteúdo de vitamina C, carotenóides totais e de clorofila total nas folhas de alface com o aumento da densidade populacional de alface.<br>The experiment was carried out from June to September of 2003, in the experimental area of "Universidade Federal Rural do Semi-Árido" (UFERSA), in Mossoró, Rio Grande do Norte state, Brazil, in order to evaluate the effect of carrot and lettuce populational densities in a second growing period on their nutritional quality in a strip-intercropping system. A randomized complete block design was used with the treatments arranged in a 4 x 4 factorial scheme with three replications. The treatments consisted of the combination of four carrot-plant densities (40%, 60%, 80% and 100% of the recommended sole crop density - RSCD) with four lettuce-plant densities (40%, 60%, 80% and 100% of the RSCD). The reference populations for carrot and lettuce in sole crop, corresponding to 100%, were of 500,000 plants.ha-1 and 250,000 plants.ha-1, respectively. Carrot cv. Brasília and lettuce cv. Tainá were planted. Quality characteristics evaluated were firmness and content of vitamin C, total carotenoids and beta-carotene for carrot roots and firmness, contents of vitamin C, total carotenoids and total chlorophyll for lettuce leaves. The associations of plant densities of carrot and lettuce did not affect any of the assessed characteristics in both crops. However, both carrot and lettuce plant densities affected the traits evaluated in both crops. The firmness, contents of vitamin C and beta-carotene in carrot roots decreased as the plant densities of carrot increased, while the content of total carotenoids increased as carrot population increased. The same decreasing behavior was observed in contents of vitamin C, total carotenoids and chlorophyll in the lettuce leaves with an increase in the plant densities of lettuce