619 research outputs found

    Desafios para a avaliação toxicológica de agrotóxicos no Brasil: desregulação endócrina e imunotoxicidade

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    Intense usage of pesticides in Brazil poses a risk concerning arising of various and hazardously toxic effects such as towards to immunological and endocrine systems. Assays recommended by national and international guidelines possess limitations to perform a complete predictive evaluation of the broad spectrum of molecules and target-organs by pesticides with those properties.On the other hand interactions among immunological, endocrine and nervous systems difficult investigation of those hazards that may impact reproduction, metabolic processes, host resistance to pathogens and tumoral cells. Similar to drugs, a periodic licensing review of pesticides in Brazil must be adopted in urgent character in order to identify and ban de usage of health extremely hazardous pesticides. Although prescribed in law, licensing review demanded by health and environmental agencies is oftenly judicialized, preventing or delaying conclusion in several years. It is also upon demand a governmental policy regarding a transition from the current production model tied to agrobusiness to a production of agroecological basis.O uso intensivo de agrotóxicos no Brasil impõe o risco do aparecimento de efeitos tóxicos diversos e altamente deletérios, como os efeitos sobre o sistema imunológico e endócrino. Os testes preconizados pelas diretrizes nacionais e internacionais possuem limitações para uma avaliação preditiva completa do amplo espectro de moléculas, receptores, células e órgãos-alvo dos agrotóxicos com essas propriedades. Além disso, a interação entre os sistemas nervoso, endócrino e imunológico acaba por dificultar o estudo desses efeitos que podem impactar a reprodução, processos metabólicos e a resistência a patógenos e o combate a tumores. A exemplo do que ocorre com medicamentos, a revisão periódica do registro de agrotóxicos no Brasil deve ser adotada em caráter urgente para identificar e proibir o uso de agrotóxicos que sejam extremamente danosos à saúde. Apesar de prevista na lei, a revisão do registro demandada pelos órgãos da saúde e do meio ambiente passa por processo de judicialização, impedindo ou atrasando em vários anos a sua conclusão. Também se mostra urgente uma política governamental para a transição do atual modelo de produção vinculado ao agronegócio para um de produção de base agroecológica

    Engaging Student Learning with Interactive Videos

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    The experiences of passively watching a video online and actively engaging in a lecture in person are markedly different. During an on-campus lecture, an instructor has the ability to pose questions to students and give individualized feedback based on responses. In an online environment, however, these questions are at best rhetorical, and students\u27 ability to receive feedback on their responses is limited. As a result, students are unable to check their understanding of a topic while watching a video. Similarly, non-classroom environments may prove to be more distracting for students, and the resulting potential decrease in engagement may be detrimental to learning outcomes. We will share some video tools that allow you to add questions and other interactive elements to your videos. We will also show some examples of completed videos and share useful tips and resources. Multiple Audiences

    A comprehensive review: The evolution of animal models in pulmonary hypertension research; are we there yet?

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    Pulmonary hypertension (PH) is a disorder that develops as a result of remodeling of the pulmonary vasculature and is characterized by narrowing/obliteration of small pulmonary arteries, leading to increased mean pulmonary artery pressure and pulmonary vascular resistance. Subsequently, PH increases the right ventricular afterload, which leads to right ventricular hypertrophy and eventually right ventricular failure. The pathophysiology of PH is not fully elucidated, and current treatments have only a modest impact on patient survival and quality of life. Thus, there is an urgent need for improved treatments or a cure. The use of animal models has contributed extensively to the current understanding of PH pathophysiology and the investigation of experimental treatments. However, PH in current animal models may not fully represent current clinical observations. For example, PH in animal models appears to be curable with many therapeutic interventions, and the severity of PH in animal models is also believed to correlate poorly with that observed in humans. In this review, we discuss a variety of animal models in PH research, some of their contributions to the field, their shortcomings, and how these have been addressed. We highlight the fact that the constant development and evolution of animal models will help us to more closely model the severity and heterogeneity of PH observed in humans

    Entwicklung eines Konzeptes zur Erzeugung von Öko-Ziegenlammfleisch aus melkenden Beständen (Vortrag)

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    In contrast to the increasing demand for dairy goat products in Germany, a market for goat kid meat as a related product is more or less non-existing. Thus, the objective of our study was to develop a concept for organic goat kid meat production for dairy goat farms. In collaboration with a wholesaler, organic dairy goat farmers and marketing research the experimental part of our study was to find out if cross-breeding of meat-goats could improve meat quality and performance of fattening goat kids together with other factors like concentrate ratio of the diet, housing system as well as raising strategy. First results indicate that a low input level of concentrates of 10 % of total dry matter intake per goat kid and year is not sufficient to meet the requested carcass weight of 12 kg at slaughter

    Potential of electrospun cationic BSA fibers to guide osteogenic MSC differentiation via surface charge and fibrous topography

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    Large or complex bone fractures often need clinical treatments for sufficient bone repair. New treatment strategies have pursued the idea of using mesenchymal stromal cells (MSCs) in combination with osteoinductive materials to guide differentiation of MSCs into bone cells ensuring complete bone regeneration. To overcome the challenge of developing such materials, fundamental studies are needed to analyze and understand the MSC behavior on modified surfaces of applicable materials for bone healing. For this purpose, we developed a fibrous scaffold resembling the bone/bone marrow extracellular matrix (ECM) based on protein without addition of synthetic polymers. With this biomimetic in vitro model we identified the fibrous structure as well as the charge of the material to be responsible for its effects on MSC differentiation. Positive charge was introduced via cationization that additionally supported the stability of the scaffold in cell culture, and acted as nucleation point for mineralization during osteogenesis. Furthermore, we revealed enhanced focal adhesion formation and osteogenic differentiation of MSCs cultured on positively charged protein fibers. This pure protein-based and chemically modifiable, fibrous ECM model allows the investigation of MSC behavior on biomimetic materials to unfold new vistas how to direct cells’ differentiation for the development of new bone regenerating strategies

    A practice-related risk score (PRS): a DOPPS-derived aggregate quality index for haemodialysis facilities

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    Background. The Dialysis Outcomes and Practice Patterns Study (DOPPS) database was used to develop and validate a practice-related risk score (PRS) based on modifiable practices to help facilities assess potential areas for improving patient care. Methods. Relative risks (RRs) from a multivariable Cox mortality model, based on observational haemodialysis (HD) patient data from DOPPS I (1996-2001, seven countries), were used. The four practices were the percent of patients with Kt/V >= 1.2, haemoglobin >= 11 g/dl (110 g/l), albumin >= 4.0 g/dl (40g/l) and catheter use, and were significantly related to mortality when modelled together. DOPPS II data (2002-2004, 12 countries) were used to evaluate the relationship between PRS and mortality risk using Cox regression. Results. For facilities in DOPPS I and II, changes in PRS over time were significantly correlated with changes in the standardized mortality ratio (SMR). The PRS ranged from 1.0 to 2.1. Overall, the adjusted RR of death was 1.05 per 0.1 points higher PRS (P < 0.0001). For facilities in both DOPPS I and II (N = 119), a 0.2 decrease in PRS was associated with a 0.19 decrease in SMR (P = 0.005). On average, facilities that improved PRS practices showed significantly reduced mortality over the same time frame. Conclusions. The PRS assesses modifiable HD practices that are linked to improved patient survival. Further refinements might lead to improvements in the PRS and will address regional variations in the PRS/mortality relationship

    Cloning and characterization of an adenoviral vector for highly efficient and doxycycline – suppressible expression of bioactive human single – chain interleukin 12 in colon cancer

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    BACKGROUND: Interleukin-12 (IL-12) is well characterized to induce cellular antitumoral immunity by activation of NK-cells and T-lymphocytes. However, systemic administration of recombinant human IL-12 resulted in severe toxicity without perceptible therapeutic benefit. Even though intratumoral expression of IL-12 leads to tumor regression and long-term survival in a variety of animal models, clinical trials have not yet shown a significant therapeutic benefit. One major obstacle in the treatment with IL-12 is to overcome the relatively low expression of the therapeutic gene without compromising the safety of such an approach. Our objective was to generate an adenoviral vector system enabling the regulated expression of very high levels of bioactive, human IL-12. RESULTS: High gene expression was obtained utilizing the VP16 herpes simplex transactivator. Strong regulation of gene expression was realized by fusion of the VP16 to a tetracycline repressor with binding of the fusion protein to a flanking tetracycline operator and further enhanced by auto-regulated expression of its fusion gene within a bicistronic promoter construct. Infection of human colon cancer cells (HT29) at a multiplicity of infection (m.o.i.) of 10 resulted in the production of up to 8000 ng/10(6 )cells in 48 h, thus exceeding any published vector system so far. Doxycycline concentrations as low as 30 ng/ml resulted in up to 5000-fold suppression, enabling significant reduction of gene expression in a possible clinical setting. Bioactivity of the human single-chain IL-12 was similar to purified human heterodimeric IL-12. Frozen sections of human colon cancer showed high expression of the coxsackie adenovirus receptor with significant production of human single chain IL-12 in colon cancer biopsies after infection with 3*10(7 )p.f.u. Ad.3r-scIL12. Doxycycline mediated suppression of gene expression was up to 9000-fold in the infected colon cancer tissue. CONCLUSION: VP16 transactivator-mediated and doxycycline-regulated expression of the human interleukin-12 gene enables highly efficient and tightly controlled cytokine expression in human cancer. These data illustrate the potential of the described adenoviral vector system for the safe and superior expression of therapeutic genes in the treatment of colorectal cancer and other malignancies
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