Cytokine profile of Ehrlich ascites tumor treated with Bothrops jararaca venom.

We previously demonstrated that Bothrops jararaca venom (BjV) has an antitumor effect on Ehrlich ascites tumor (EAT) cells and induces an increase of polymorphonuclear leukocytes in early stages of tumor growth. It has been reported that this venom presents an important inflammatory effect when inoculated in animal models and in human snakebites, and that cytokine levels have been detected in these cases. To evaluate whether the cytokines can be involved with the suppression of the tumoral growth, we evaluate the cytokine profile in the peritoneal cavity of mice inoculated with EAT cells and treated with BjV. Swiss mice were inoculated with EAT cells by the intraperitoneal route and treated with BjV venom (0.4 mg/kg, intraperitoneally), on the 1st, 4th, 7th, 10th, and 13th day. Mice were evaluated for cytokine levels on the 2nd, 5th, 8th, 11th and 14th day. Analysis was performed using an enzyme-linked immunosorbent assay for interleukin (IL)-1alpha, IL-2, IL4, IL-6, IL-10, IL-13, and tumor necrosis factor-alpha (TNF-alpha) levels in the peritoneal washing supernatant. Results were analyzed statistically by the Kruskal-Wallis and Dunn's tests at the 5% level of significance. We observed that EAT implantation induces IL-6 production on the 11th and 14th days of tumor growth, IL-10 on the 11th day and TNF-alpha on the 14th day. The treatment with BjV suppresses production of these cytokines. In addition, IL-13 was produced by animals that were inoculated only with venom on the 11th and 14th days, and by the group inoculated with EAT cells and treated with venom on the 2nd and 14th days. Furthermore, we suggest that the IL-6 detected in the present study is produced by the EAT cells and the suppression of its production could be associated with the antitumor effect of BjV

Antitumor effect of Bothrops jararaca venom.

Many experimental studies have been carried out using snake venoms for the treatment of animal tumors, with controversial results. While some authors have reported an antitumor effect of treatment with specific snake venom fractions, others have reported no effects after this treatment. The aim of this study was to evaluate the effect of Bothrops jararaca venom (BjV) on Ehrlich ascites tumor (EAT) cells in vivo and in vitro. In the in vivo study, Swiss mice were inoculated with EAT cells by the intraperitoneal (i.p.) route and treated with BjV venom (0.4 mg/kg, i.p.), on the 1st, 4th, 7th, 10th, and 13th days. Mice were evaluated for total and differential cells number on the 2nd, 5th, 8th, 11th and 14th days. The survival time was also evaluated after 60 days of tumor growth. In the in vitro study, EAT and normal peritoneal cells were cultivated in the presence of different BjV concentrations (2.5, 5.0, 10.0, 20.0, 40.0, and 80 microg) and viability was verified after 3, 6, 12 and 24 h of cultivation. Results were analyzed statistically by the Kruskal-Wallis and Tukey tests at the 5% level of significance. It was observed that in vivo treatment with BjV induced tumor growth inhibition, increased animal survival time, decreased mortality, increased the influx of polymorphonuclear leukocytes on the early stages of tumor growth, and did not affect the mononuclear cells number. In vitro treatment with BjV produced a dose-dependent toxic effect on EAT and peritoneal cells, with higher effects against peritoneal cells. Taken together, our results demonstrate that BjV has an important antitumor effect. This is the first report showing this in vivo effect for this venom

Ship Routing with Pickup and Delivery for a Maritime Oil Transportation System: MIP Modeland Heuristics

This paper examines a ship routing problem with pickup and delivery and time windows for maritime oil transportation, motivated by the production and logistics activities of an oil company operating in the Brazilian coast. The transportation costs from offshore platforms to coastal terminals are an important issue in the search for operational excellence in the oil industry, involving operations that demand agile and effective decision support systems. This paper presents an optimization approach to address this problem, based on a mixed integer programming (MIP) model and a novel and exploratory application of two tailor-made MIP heuristics, based on relax-and-fix and time decomposition procedures. The model minimizes fuel costs of a heterogeneous fleet of oil tankers and costs related to freighting contracts. The model also considers company-specific constraints for offshore oil transportation. Computational experiments based on the mathematical models and the related MIP heuristics are presented for a set of real data provided by the company, which confirm the potential of optimization-based methods to find good solutions for problems of moderate sizes

PHYTOPLANKTON BIOMASS INCREASES IN A SILT-IMPACTED AREA IN AN AMAZONIAN FLOOD-PLAIN LAKE OVER 15 YEARS

Funding Information: We thank Mineração Rio do Norte S.A. and Limnologia/UFRJ for fieldwork support, Dr. Janet W. Reid (JWR Associates) for language revision, and Leonardo Preza Rodrigues for map charting. VLMH, JCN, FAE, RLB, and FR are partially supported by the National Council for Scientific and Technological Development (CNPq), Brazil, RLB, and FAE by FAPERJ, Brazil, and CGR financially supported by Sakari Alhopuro Foundation, Finland. Publisher Copyright: © 2022, Universidade Federal do Rio de Janeiro. All rights reserved.Tailings from bauxite mining in Porto Trombetas (Pará state, Central Amazonia, Brazil) was discharged (1979–1989) into Batata Lake affecting about 30% of its area. The lake belongs to a clear-water flood-plain system along the Trombetas River, a tributary of the Amazon River. Siltation is the main perceived factor impacting aquatic and flooded communities. Besides natural regeneration, a program to restore a section of igapó forest in the impacted area (IA) has been conducted since 1991. Decreased light is the main factor reducing total phytoplankton biomass (PhyBM) in IA. We hypothesized that PhyBM in IA increases over time because of the improvement of the underwater light conditions due to the natural regeneration and restoration. We sampled quarterly PhyBM and limnological variables (depth, transparency, temperature, pH, conductivity, dissolved oxygen, turbidity, suspended solids, total Kjeldahl nitrogen, and total phosphorus), over 15 years (2005–2019) at eight sampling sites in the two areas (N = 349). We also obtained daily climatic and hydrologic data. PhyBM was higher in NIA than in IA. The temporal trend in the annual mean of PhyBM increased significantly over time only in the IA, approximating the NIA values, confirming our general hypothesis. The increase of PhyBM in the IA was negatively related to the residual light attenuation caused by non-phytoplankton turbidity and to total phosphorus, and positively to air temperature and site depth (p < 0.05; Marginal r2 = 0.18; Conditional r2 = 0.29). Instead, in NIA, PhyBM was explained only by the increase in air temperature (p < 0.05; Marginal r2 = 0.15; Conditional r2 = 0.34). We concluded that the PhyBM in the IA positively responds to the synergy between increasing light availability, air temperature, and site depth, and decreasing total phosphorus concentrations, regardless of hydrologic phase.Peer reviewe