A experimentação animal na Universidade Federal de Goiás: elementos para uma abordagem crítica

Animal experimentation is any practice that uses non-human animals for didactic and/or scientific purposes, including dissection and vivisection. The practice comes from the instrumental value - deeply rooted in our history - that humans give to other living creatures. This work explores the moral attitudes towards this methodology among 38 researchers/teachers of the Federal University of Goiás, Campuses I and II, who practice animal experimentation. The results indicate that the majority are open to alternative methods, although they believe that animal experimentation is indispensable for science. This scientific method directly affects the concepts and behavior of students and those practicing in the biological sciences in general.A experimentação animal diz respeito a qualquer prática que faz uso de animais não-humanos para fins didáticos e/ou científicos, abrangendo a dissecação e a vivissecção. A prática advém da valoração instrumental que os animais humanos conferem aos demais, o que tem raízes muito antigas em nossa história. Este trabalho explora o posicionamento moral frente a tal metodologia entre 38 pesquisadores/professores da Universidade Federal de Goiás (Goiânia), campi I e II, que a praticam. Os resultados indicam que a maioria apresenta abertura quanto aos métodos substitutivos, embora considere que a experimentação animal seja indispensável para a ciência. Este modo de fazer ciência afeta diretamente concepções e comportamentos dos/as estudantes e atuantes das áreas biológicas em geral

HLA-DR and HLA-DQ alleles in patients from the south of Brazil: markers for leprosy susceptibility and resistance

<p>Abstract</p> <p>Background</p> <p>Many epidemiological studies have shown that the genetic factors of the host play a role in the variability of clinical response to infection caused by <it>M. leprae</it>. With the purpose of identifying genes of susceptibility, the present study investigated the possible role of HLA-DRB1 and DQA1/DQB1 alleles in susceptibility to leprosy, and whether they account for the heterogeneity in immune responses observed following infection in a Southern Brazilian population.</p> <p>Methods</p> <p>One hundred and sixty-nine leprosy patients and 217 healthy controls were analyzed by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers(One Lambda^®, CA, USA).</p> <p>Results</p> <p>There was a positive association of HLA-DRB1*16 (*1601 and *1602) with leprosy <it>per se </it>(7.3% <it>vs</it>. 3.2%, <it>P </it>= 0.01, OR = 2.52, CI = 1.26–5.01), in accord with previous serological studies, which showed DR2 as a marker of leprosy. Although, HLA-DQA1*05 frequency (29.8% <it>vs</it>. 20.9%, <it>P </it>= 0.0424, OR = 1.61, CI = 1.09–2.39) was higher in patients, and HLA-DQA1*02 (3.0% <it>vs</it>. 7.5%, <it>P </it>= 0.0392, OR = 0.39, CI = 0.16 – 0.95) and HLA-DQA1*04 (4.0% <it>vs</it>. 9.1%, <it>P </it>= 0.0314, OR = 0.42, CI = 0.19 – 0.93) frequencies lower, <it>P</it>-values were not significant after the Bonferroni's correction. Furthermore, HLA-DRB1*1601 (9.0% <it>vs</it>. 1.8%; <it>P </it>= 0.0016; OR = 5.81; CI = 2.05–16.46) was associated with susceptibility to borderline leprosy compared to control group, and while HLA-DRB1*08 (11.2% <it>vs</it>. 1.2%; <it>P </it>= 0.0037; OR = 12.00; CI = 1.51 – 95.12) was associated with susceptibility to lepromatous leprosy, when compared to tuberculoid leprosy, DRB1*04 was associated to protection.</p> <p>Conclusion</p> <p>These data confirm the positive association of HLA-DR2 (DRB1*16) with leprosy <it>per se</it>, and the protector effect of DRB1*04 against lepromatous leprosy in Brazilian patients.</p

Proposal of measures of performance evaluation for the clinical engineering centre and bio equipment - HCFMRP-USP

O objetivo deste estudo foi propor uma lista de indicadores como forma de avaliação de desempenho para o Centro de Engenharia Clínica e Bioequipamentos do HCFMRP-USP. Indicadores são importantes ferramentas de controle e de qualidade e fornecem bases para melhorar o desempenho do estabelecimento de saúde. Para a coleta de dados, foi utilizada a literatura, referente aos indicadores para a área de Engenharia Clínica. Equipe multidisciplinar composta pelos autores do artigo foi formada para discutir e escolher os indicadores que seriam propostos como medidas de avaliação de desempenho. Foi desenvolvido um estudo na bibliografia disponível sobre o tema e também entrevistas com os gestores-chaves que estão responsáveis pela área. Adotou-se o BSC - Balanced Scorecard, em suas perspectivas financeira, de clientes, de processos internos e de aprendizado e crescimento como mapa estruturante dos indicadores. Foram propostos dezesseis indicadores nas quatro perspectivas do BSC.The aim of this study was to propose a list of indicators as a mean of performance evaluation for the Clinical Engineering Center of the Hospital of Pharmaceutical Sciences and Medicine of Ribeirão Preto (HCFMRP – USP). Indicators are important tools of quality control and supply bases to enhance the performance of the health facility. In order to collect data, it was used the literature regarding the indicators for the area of Clinical Engineering. Multidisciplinary team was formed to discuss and choose the indicators that were proposed as measures of performance evaluation. A study in the literature available about the topic and also interviews with the key managers who are responsible for the area were developed. It was adopted the BSC - Balanced Scorecard as a structural map of the indicators. Sixteen indicators were proposed in the four BSC perspectives

Chamomile gel versus urea cream to prevent acute radiation dermatitis in head and neck cancer patients : results from a preliminary clinical trial

We assessed safety and potential efficacy of a chamomile gel compared with urea cream to prevent acute radiation dermatitis in head and neck cancer patients. We assessed safety and potential efficacy of the chamomile gel in escalating concentrations of 2.50%, 5.00% and 8.35% of chamomile. Concentration of 8.35% was chosen for a randomized trial comparing chamomile gel (8.35%) with urea cream (n=24per group), for potential efficacy to delay or prevent radiation dermatitis in these patients. Preliminary results demonstrate a delayed onset of dermatitis, with onset of Grade 2 dermatitis at 5.1 (1.3) weeks in the chamomile group and 4.5 (1.3) weeks in the urea group (effect size of 0.46). Itching, burning and hyperpigmentation were more frequently reported in the urea group. Results indicates a potential efficacy of the chamomile gel. Further studies are needed to confirm the effect of the chamomile gel in reducing or delaying the occurrence of radiation dermatitis

The Barretos Cancer Hospital Animal Facility: implementation and results of a dedicated platform for preclinical oncology models

The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and ApcMin mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the progress and challenges in establishing these models and the need for having an appropriate representation of our cancer population to better understand tumor biology and to identify cancer biomarkers, which could be putatively targeted, allowing for personalized therapy.This study was funded by the Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer) and by Pio XII Foundation, Barretos Cancer Hospital internal funds, Grant Number: 13/2021

Transcription activity contributes to the firing of non-constitutive origins in African trypanosomes helping to maintain robustness in S-phase duration

The co-synthesis of DNA and RNA potentially generates conflicts between replication and transcription, which can lead to genomic instability. In trypanosomatids, eukaryotic parasites that perform polycistronic transcription, this phenomenon and its consequences are still little studied. Here, we showed that the number of constitutive origins mapped in the Trypanosoma brucei genome is less than the minimum required to complete replication within S-phase duration. By the development of a mechanistic model of DNA replication considering replication-transcription conflicts and using immunofluorescence assays and DNA combing approaches, we demonstrated that the activation of non-constitutive (backup) origins are indispensable for replication to be completed within S-phase period. Together, our findings suggest that transcription activity during S phase generates R-loops, which contributes to the emergence of DNA lesions, leading to the firing of backup origins that help maintain robustness in S-phase duration. The usage of this increased pool of origins, contributing to the maintenance of DNA replication, seems to be of paramount importance for the survival of this parasite that affects million people around the world

Biomedical potential of fucoidan, a seaweed sulfated polysaccharide: from a anticancer agent to a building block of cell encapsulating systems for regenerative medicine

Marine macroalgae or seaweeds synthesize a wide variety of polymers and smaller compounds with several bioactivities, among which the sulfated polysaccharides acquire greater relevance not only due to the reported antioxidant, antiviral and anticancer[1] activities, but also to the resemblance of extracellular matrix glycosaminoglycans found in the human body[2]. In this study, the potential of fucoidan (Fu) isolated from brown seaweed Fucus vesiculosus for therapeutical use has been evaluated, focusing in its performance as antitumoral agent (bioactive role) or as building block of cell encapsulating systems (structural role). Materials and Methods: The anticancer activity of Fu extracts was assessed by evaluating the cytotoxic behavior over two human breast cancer cell lines (MCF-7 and MDA-MB-231) in in-vitro culture, using human fibroblasts and endothelial cells (HPMEC-ST1 and MRC-5, respectively) as reference. Regarding the structural role, Fu was modified by methacrylation reaction (MFu) using methacrylic acid and further crosslinked using visible radiation and triethanolamine and eosin-y as photoinitiators. The photocrosslinking was performed on MFu solution droplets placed in a silica-based superhydrophobic surface[3], allowing the formation of particles[4] (since natural Fu is highly soluble in water and ion gelation is not effective). Biological performance of the developed particles was assessed by in vitro culture of fibroblasts and pancreatic cells (L929 and 1.1B4, respectively) in contact with MFu particles, up to 7 days. The ability of the developed materials to support adhesion and proliferation of cells was evaluated for both types of cells. Results and Discussion: The tested anticancer activity is not ubiquitous on Fu extracts, being dependent on its chemical features, with molecular weight (Mw) representing a particular role. Specifically, Mw values around 60 kDa exhibited cytotoxic effects to human breast cancer cell lines, while not affecting normal fibroblasts or endothelial cells (which represent the cells of the healthy tissue that would be closer to the tumor in a real situation). A concentration range of 0.2 to 0.3 mg mL-1 from the selected Fu extract could be considered as the therapeutic window for further studies. Regarding fucoidanâ s role on innovative biomaterials, the developed MFu particles could support the proliferation of fibroblasts (L929), but also of human pancreatic beta cells (1.1B4), which tend to form pseudo-islets after 7 days in culture (Fig. 1). This pancreatic cells could be also successfully encapsulated, opening a new route for a diabetes mellitus type 1 therapeutic approach. Fig. 1: Confocal microscopy images of 1.1B4 cells cultured in the presence of fucoidan-based particles and organized in pseudo-islets (red â actin; blue â nuclei). Conclusion: The present work establishes fucoidan as a high performance building block for the development of advanced therapies for cancer (targeted therapy) or tissue and organ regeneration. It shed light on the relation between chemical structure and biological activity towards anti-cancer effect and proposes novel beta cell laden particles as injectable insulin producing systems to tackle diabetes.Funding from projects 0687_NOVOMAR_1_P (co-funded by INTERREG 2007-2013 / POCTEP), CarbPol_u_Algae (EXPL/MAR-BIO/0165/2013, funded by the Portuguese Foundation for Science and Technology, FCT), POLARIS (FP7-REGPOT-CT2012-316331) and ComplexiTE (ERC-2012-ADG 20120216-321266), funded by the European Union’s Seventh Framework Programme for Research and Development is acknowledged. ASF, SSS, NMO and DSC are also thankful to FCT for their individual fellowships

Activation of cannabinoid type 1 receptor (CB1) modulates oligodendroglial process branching complexity in rat hippocampal cultures stimulated by olfactory ensheathing glia-conditioned medium

The endocannabinoid system (ECS) refers to a complex cell-signaling system highly conserved among species formed by numerous receptors, lipid mediators (endocannabinoids) and synthetic and degradative enzymes. It is widely distributed throughout the body including the CNS, where it participates in synaptic signaling, plasticity and neurodevelopment. Besides, the olfactory ensheathing glia (OEG) present in the olfactory system is also known to play an important role in the promotion of axonal growth and/or myelination. Therefore, both OEG and the ECS promote neurogenesis and oligodendrogenesis in the CNS. Here, we investigated if the ECS is expressed in cultured OEG, by assessing the main markers of the ECS through immunofluorescence, western blotting and qRT-PCR and quantifying the content of endocannabinoids in the conditioned medium of these cells. After that, we investigated whether the production and release of endocannabinoids regulate the differentiation of oligodendrocytes co-cultured with hippocampal neurons, through Sholl analysis in oligodendrocytes expressing O4 and MBP markers. Additionally, we evaluated through western blotting the modulation of downstream pathways such as PI3K/Akt/mTOR and ERK/MAPK, being known to be involved in the proliferation and differentiation of oligodendrocytes and activated by CB1, which is the major endocannabinoid responsive receptor in the brain. Our data show that OEG expresses key genes of the ECS, including the CB1 receptor, FAAH and MAGL. Besides, we were able to identify AEA, 2-AG and AEA related mediators palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in the conditioned medium of OEG cultures. These cultures were also treated with URB597 10-9 M, a FAAH selective inhibitor, or JZL184 10-9 M, a MAGL selective inhibitor, which led to the increase in the concentrations of OEA and 2-AG in the conditioned medium. Moreover, we found that the addition of OEG conditioned medium (OEGCM) enhanced the complexity of oligodendrocyte process branching in hippocampal mixed cell cultures and that this effect was inhibited by AM251 10-6 M, a CB1 receptor antagonist. However, treatment with the conditioned medium enriched with OEA or 2-AG did not alter the process branching complexity of premyelinating oligodendrocytes, while decreased the branching complexity in mature oligodendrocytes. We also observed no change in the phosphorylation of Akt and ERK 44/42 in any of the conditions used. In conclusion, our data show that the ECS modulates the number and maturation of oligodendrocytes in hippocampal mixed cell cultures