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

Candida albicans in patients with oronasal communication and obturator prostheses

Patients using obturator prostheses often present denture-induced stomatitis. In order to detect the presence of oral Candida albicans in patients with oronasal communications and to evaluate the effectiveness of a topical antifungal treatment, cytological smears obtained from the buccal and palatal mucosa of 10 adult patients, and from the nasal acrylic surface of their obturator prostheses were examined. A therapeutic protocol comprising the use of oral nystatin (Mycostatin®) and prosthesis disinfection with sodium hypochlorite was prescribed for all patients. Seven patients were positive for C. albicans in the mucosa, with 1 negative result for the prosthetic surface in this group of patients. Post-treatment evaluation revealed the absence of C. albicans on prosthesis surface and on the oral mucosa of all patients. The severity of the candidal infection was significantly higher in the palatal mucosa than in the buccal mucosa, but similar in the palatal mucosa and prosthesis surface, indicating that the mucosa underlying the prosthesis is more susceptible to infection. The therapeutic protocol was effective in all cases, which emphasizes the need for denture disinfection in order to avoid reinfection of the mucosa.Os pacientes portadores de prótese obturadora freqüentemente apresentam estomatite protética. Com o objetivo de detectar a presença de Candida albicans oral em pacientes com comunicação oronasal e avaliar a eficácia de um tratamento tópico antifúngico foi realizada citologia esfoliativa da mucosa palatina e jugal e da superfície acrílica nasal da prótese obturadora. O protocolo terapêutico consistiu de nistatina (Mycostatin®) para tratamento da mucosa oral e uma solução de hipoclorito de sódio para desinfecção da prótese. Sete pacientes (70%) apresentaram resultado positivo para C. albicans na mucosa, com um resultado negativo para a superfície protética neste grupo. A avaliação após o tratamento revelou ausência de C. albicans na mucosa oral de todos os pacientes, bem como na superfície protética. A infecção por C. albicans das mucosas jugal e palatina diferiram significantemente, enquanto que a mucosa palatina e a superfície protética apresentaram valores semelhantes. O grau de infecção da mucosa palatina foi significantemente maior quando comparado àquele da mucosa jugal e semelhante ao apresentado pela prótese, sugerindo que a mucosa subjacente à prótese é mais susceptível à infecção. O protocolo terapêutico foi efetivo em todos os casos, o que enfatiza a necessidade da desinfecção protética para se evitar a reinfecção da mucosa oral

Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

Background/Aims: We investigated the effects of leptin in the development of lipopolysaccharide (LPS)-induced acute lung inflammation (ALI) in lean mice. Methods: Mice were administered leptin (1.0 mu g/g) or leptin (1.0 mu g/g) followed by LPS (1.5 mu g/g) intranasally. Additionally, some animals were given LPS (1.5 mu g/g) or saline intranasally alone, as a control. Tissue samples and fluids were collected six hours after instillation. Results: We demonstrated that leptin alone did not induce any injury. Local LPS exposure resulted in significant acute lung inflammation, characterized by a substantial increase in total cells, mainly neutrophils, in bronchoalveolar lavages (BAL). We also observed a significant lymphocyte influx into the lungs associated with enhanced lung expression of chemokines and cytokines (KC, RANTES, TNF-alpha, IFN-beta, GM-CSF and VEGF). LPS-induced ALI was characterized by the enhanced expression of ICAM-1 and iNOS in the lungs. Mice that received LPS showed an increase in insulin levels. Leptin, when administered prior to LPS instillation, abolished all of these effects. LPS induced an increase in corticosterone levels, and leptin potentiated this event. Conclusion: These data suggest that exogenous leptin may promote protection during sepsis, and downregulation of the insulin levels and upregulation of corticosterone may be important mechanisms in the amelioration of LPS-induced ALI.Copyright (c) 2014 S. Karger AG, BaselConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Complex Fluids INCTFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Inst Biomed Sci 1, Dept Pharmacol, Lab Hypertens, BR-1524 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Immunol, Lab Transplantat Immunobiol, BR-1524 São Paulo, BrazilUniv São Paulo, Lab Inflammat & Vasc Pharmacol, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Lab Clin & Expt Immunobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Lab Clin & Expt Immunobiol, São Paulo, BrazilFAPESP: 12/51104-8FAPESP: 10/01404-0FAPESP: 12/02270-2FAPESP: 12/10512-6Web of Scienc

Avaliação biomecânica dos trabalhadores em marcenarias no Distrito Federal.

The aim of this study was the biomechanical assessment of carpentry woodworkers, located in Brasília, DF. It was filmed the profile of each worker during the performance of his activities in the carpentry and the forces involved in the work were assessed. The image of each woodworker was congealed to accomplish the measurement of articulation angles. The data were submitted to the software of posture analysis “Winowas” (OWAS Method) and to the biomechanic model of posture prognosis and static forces, developed by Michigan University. The OWAS method showed that, for all machines and carpentries assessed, the worst posture occurred when the worker lifted and placed the pieces of wood on the floor and during the feeding in the smoother. The tridimensional biomechanic model registered the worst posture in different phases of the work cycle. In the first one, there were problems in all articulations, except the hips, when placing the pieces on the floor from the smoother. In the second one, there were problems in all articulations, except the elbows and the L5-S1 column disc, by feeding the surface planer. The third one, the ankles were the most injured when feeding the smoother, the surface planer, the circular saw and the band saw. According to the results, the woodworkers should try to eliminate the constant work standing upright, use auxiliary machinery to handle pieces of wood, reduce the load during feeding the machines and improve postures.A pesquisa foi desenvolvida com base em dados coletados com funcionários de marcenarias no Distrito Federal com o objetivo de fazer uma avaliação biomecânica do trabalhador nas mais diversas máquinas. A avaliação foi feita com a filmagem dos trabalhadores em perfil, avaliação das forças envolvidas e posterior congelamento das imagens e medição dos ângulos das articulações para análise no software "Winowas" de análise de posturas e no modelo biomecânico tridimensional de predição de posturas e forças estáticas desenvolvido pela Universidade de Michigan. Os resultados mostraram que, pelo método OWAS, as piores posturas foram obtidas durante o levantamento e deposição das peças no piso em todas as máquinas e postos de trabalho avaliados e durante a alimentação na desengrossadeira, necessitando de reorganização ergonômica em breve. Pela análise com o modelo desenvolvido pela Universidade de Michigan, as fases do ciclo de trabalho mais problemáticas foram a deposição das peças no piso na desengrossadeira quando houve o comprometimento de todas as articulações com exceção dos quadris. Durante a alimentação na desempenadeira, houve grande comprometimento das articulações com exceção dos cotovelos e do disco L5-S1 da coluna. Na fase de alimentação na desengrossadeira, desempenadeira, serra circular e serra de fita, as articulações mais prejudicadas foram os tornozelos. Para melhoria das posturas adotadas, deve-se buscar eliminar o constante trabalho em pé, utilizar mecanização auxiliar para manuseio das peças, diminuir o peso manuseado durante a alimentação das máquinas (menor número e tamanho de peças) e realizar treinamentos específicos constantes para adoção de melhores posturas

Finding Multiple Equilibria for Raiffa–Kalai–Smorodinsky and Nash Bargaining Equilibria in Electricity Markets: A Bilateral Contract Model

In a deregulated market, energy can be exchanged like a commodity and the market agents including generators, distributors, and the end consumers can trade energy independently settling the price, volume, and the supply terms. Bilateral contracts (BCs) have been applied to hedge against price volatility in the electricity spot market. This work introduces a model to find all solutions for the equilibria implementing the Raiffa–Kalai–Smorodinski (RKS) and the Nash Bargaining Solution (NBS) approaches in an electricity market based on BCs. It is based on creating “holes” around an existing equilibrium within the feasibility set, yielding a new (smaller) feasibility set at each iteration. This research has two players: a generation company (GC) and an electricity supplier company (ESC), aiming to achieve the highest profit for each of them. The results present all possible RKS and NBS, in addition to showing all assigned energies for a case study at different time frames. The multiple equilibria solutions allow the ESC and the GC to apply different strategies knowing that they can still achieve an optimal solution

UNA NUEVA ESPECIE DE TRINIBACULUM (MONOGENEA: DACTYLOGYRIDAE) PARÁSITO DE LAS BRANQUIAS DE ASTYANAX FASCIATUS (CUVIER, 1819) (CHARACIFORMES: CHARACIDAE) EN UN RÍO NEOTROPICAL, ESTADO DE SÃO PAULO, BRASIL

A new species of Monogenea - Trinibaculum pinctiarum n. sp. is described from the gills of Astyanax fasciatus known as "lambari do rabo vermelho", sampled in the Paranapanema River, Jurumirim reservoir, São Paulo State, Brazil. The new species is allocated to the genus Trinibaculum because it has a double ventral bar and dextro-lateral vagina. It is the second species (first species is Trinibaculum altiparanae) belonging to this genus that parasitizes the gills of the fish genus Astyanax. This monogenean is similar to T. altiparanae regarding the haptor structures and the bulbous distal vagina. However, Trinibaculum pinctiarum n. sp. differs in having: (1) coiled male copulatory organ, (2) accessory structure shaped as tweezers, (3) absence of postmedian process in the ventral bar, and (4) hooks with depressed thumb. The phylogenetic hypothesis of the genus Trinibaculum (Consistency index = 87%, Retention index = 80%, length = 16) based on 13 transformation series is (Trinibaculum rotundus, T. brazilensis, T. altiparanae, T. pinctiarum n. sp.). Such hypothesis corroborates current phylogenies of characiformes fishes. Moreover, this study includes a new identification key for the species of the genus Trinibaculum based in morphological characters.Una nueva especie de Monogenea Trinibaculum pinctiarum n. sp. fue reportada parasitando las branquias de Astyanax fasciatus, conocido popularmente como "lambarí de rabo rojo", capturado en el río Paranapanema, reservatorio Jurumirim, São Paulo, Brasil. La nueva especie se asigna al género Trinibaculum por la presentación de una barra ventral doble y la apertura vaginal dextrolateral. Esta es la segunda especie, junto con T. altiparanae, perteneciente a este género que parasita las branquias de los peces del género Astyanax. Esta especie se parece con T. altiparanae en las partes del haptor y la presencia de la vagina distal con el bulbo, pero difiere por tener: (1) un órgano copulador masculino enrollado, (2) pieza accesoria en forma de pinza, (3) proceso posteroventral ausente en la barra dorsal, (4) ganchos con el pulgar deprimido. La filogenia hipotética de especies de Trinibaculum (Índice de Consistencia = 87%, Índice de Retención = 80%, longitud = 16) sobre la base de 13 series de transformación es (Trinibaculum rotundus (T. brazilensis (T. altiparanae, Trinibaculum pinctiarum n. sp.))). Esta hipótesis se corrobora con la actual filogenia de los peces characiformes. Además en este estudio se presenta una nueva clave de identificación para las especies del género Trinibaculum basada en caracteres morfológicos

Well-posedness of minimal time problems with constant dynamics in Banach spaces

This paper concerns the study of a general minimal time problem with a convex constant dynamics and a closed target set in Banach spaces. We pay the main attention to deriving sufficient conditions for the major well-posedness properties that include the existence and uniqueness of optimal solutions as well as certain regularity of the optimal value function with respect to state variables. Most of the results obtained are new even in finite-dimensional spaces. Our approach is based on advanced tools of variational analysis and generalized differentiation