Publications by authors named "Cristiano Pereira"

20 Publications

  • Page 1 of 1

Effects of Intravitreal Bevacizumab Therapy in Patients with Proliferative Diabetic Retinopathy.

Diabetes Metab Syndr Obes 2020 10;13:3149-3155. Epub 2020 Sep 10.

Clinical Analysis Laboratory, Centro Universitário Saúde ABC/Faculdade De Medicina Do ABC, Santo André, Brazil.

Introduction: Diabetes mellitus (DM) stands out as one of the chronic diseases with the highest morbidity and mortality rates worldwide. Among the many complications of DM, diabetic retinopathy (DR) is one of the causes of blindness in patients aged between 20 and 64 years. At least 90% of the new cases showed to have the retinal structure and function restored when proper treatment was provided.

Aim: To evaluate the efficacy of the antiangiogenic bevacizumab in the treatment of DR according not only to the clinical laboratory parameters for glycated hemoglobin (HbA1C) and capillary glycemia but also to the ophthalmological parameters for optical coherence tomography (OCT) and best-corrected visual acuity (BCVA).

Patients And Methods: A total of 11 individuals were included and followed up for 12 months after 3 administrations of bevacizumab.

Results: Upon associating the ophthalmological and laboratory variables throughout the treatment, no significant alterations could be seen regarding the analyzed variables. However, it was observed that HbA1c values and the total leukocyte count negatively interfered with the treatment response.

Conclusion: The current study showed that HbA1c values and the amount of leukocytes negatively interfere with the therapeutic response. Therefore, laboratory analyses of these parameters are recommended for diabetic patients undergoing the above-mentioned treatment.
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http://dx.doi.org/10.2147/DMSO.S243873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495346PMC
September 2020

Larvae of the South Atlantic coral Favia gravida are tolerant to salinity and nutrient concentrations associated with river discharges.

Mar Environ Res 2020 Oct 17;161:105118. Epub 2020 Aug 17.

Instituto Coral Vivo, R. dos Coqueiros 87, Parque Yaya, Santa Cruz Cabrália, BA, Brazil; Departamento de Invertebrados, Museu Nacional, Universidade Federal do Rio de Janeiro, Quinta da Boa Vista, São Cristóvão, Rio de Janeiro, RJ, Brazil.

Rivers release freshwater, nutrients and pollutants into reefs. This type of environmental stress reduces coral larvae settlement and alter its energy metabolism. We investigated the tolerance of Favia gravida (Scleractinia) larvae to river discharges. We exposed larvae to (i) different salinities (25, 30, 35 and 40 PSU); and (ii) dilutions of river water containing nutrients and metals (0, 20, 40, 60, 80 and 100% river water) under control salinity of 35 PSU. We then examined settlement and larval enzymatic activity. No differences in settlement were detected among salinities. Settlement was also similar to control for larvae under 100% river water. Enzymatic activity for citrate synthase remained unaltered for all treatments. Lactate dehydrogenase activity was slightly altered under different salinities, suggesting a mild stress response. Findings suggest that F. gravida larvae are tolerant to a wide range of salinity and nutrient conditions and that this is a stress-tolerant species.
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http://dx.doi.org/10.1016/j.marenvres.2020.105118DOI Listing
October 2020

Emerging patent landscape for non-viral vectors used for gene therapy.

Nat Biotechnol 2020 02;38(2):151-157

Department of Basic Medical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA.

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http://dx.doi.org/10.1038/s41587-019-0402-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308177PMC
February 2020

Vallissiana universitaria (Lepidoptera: Gracillariidae): a new genus and species of leaf-mining moth associated with Erythroxylum (Erythroxylaceae) in the Atlantic Forest of Brazil.

Zootaxa 2019 May 13;4604(1):zootaxa.4604.1.5. Epub 2019 May 13.

PPG Biologia Animal, Departamento de Zoologia, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre RS, 91501-970, Brazil.

Vallissiana universitaria Pereira Arévalo, a new genus and species of leaf-miner moth (Gracillariidae: Gracillariinae) is described and illustrated with the aid of optical and scanning electron microscopy, including adults, larva, pupa and the mine. Its monophyletic status is confirmed within the subfamily based on a DNA barcode CoI tree. The immature stages are associated with Erythroxylum argentinum O. E. Schulz (Erythroxylaceae) and four larval instars are found, all forming a round blotch mine from the beginning of ontogeny. The first two instars are sap-feeders, using only the epidermal cells, whereas the last two are tissue-feeders, mining the parenchyma cells. Pupation occurs inside the leaf mine within a flimsy, silk-made cocoon. This is the third endemic genus of gracillariid moths described from the Atlantic Forest of Brazil and the first associated with Erythroxylum P. Browne. Characteristics found on the forewing and in the last abdominal segments of the adult were determinant for the proposition of the new genus. The CoI tree indicated that it is closely related to Aspilapteryx, while this genus was recovered as polyphyletic in the analyses. Morphological evidence supports this polyphyly. Consequently, Sabulopteryx Triberti, 1985, stat. nov. is considered a valid genus.
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http://dx.doi.org/10.11646/zootaxa.4604.1.5DOI Listing
May 2019

Environmental health in southwestern Atlantic coral reefs: Geochemical, water quality and ecological indicators.

Sci Total Environ 2019 Feb 13;651(Pt 1):261-270. Epub 2018 Sep 13.

Instituto Coral Vivo, Rua dos Coqueiros, 87, Santa Cruz Cabralia, BA 45807000, Brazil; Instituto de Ciências Biológicas, Universidade Federal do Rio Grande (ICB/FURG), Av Itália, km 8, Rio Grande, RS 96203900, Brazil.

Climate change, pollution and increased runoff are some of the main drivers of coral reefs degradation worldwide. However, the occurrence of runoff and marine pollution, as well as its ecological effects in South Atlantic coral reefs are still poorly understood. The aim of the present work is to characterize the terrigenous influence and contamination impact on the environmental health of five reefs located along a gradient of distance from a river source, using geochemical, water quality, and ecological indicators. Stable isotopes and sterols were used as geochemical indicators of sewage and terrigenous organic matter. Dissolved metal concentrations (Cu, Zn, Cd, and Pb) were used as indicators of water quality. Population density, bleaching and chlorophyll α content of the symbiont-bearing foraminifer Amphistegina gibbosa, were used as indicators of ecological effects. Sampling was performed four times during the year to assess temporal variability. Sediment and water quality indicators showed that reefs close to the river discharge experience nutrient enrichment and sewage contamination, and metals concentrations above international environmental quality guidelines. Higher levels of contamination were strongly related to the higher frequency of bleaching and lower density in A. gibbosa populations. The integrated evaluation of stable isotopes, sterols and metals provided a consistent diagnostic about sewage influence on the studied reefs. Additionally, the observed bioindicator responses evidenced relevant ecological effects. The water quality, geochemical and ecological indicators employed in the present study were effective as biomonitoring tools to be applied in reefs worldwide.
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http://dx.doi.org/10.1016/j.scitotenv.2018.09.154DOI Listing
February 2019

Patent mining and landscaping of emerging recombinant factor VIII through network analysis.

Nat Biotechnol 2018 07;36(7):585-590

School of Economics, Business Administration and Accounting, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

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http://dx.doi.org/10.1038/nbt.4178DOI Listing
July 2018

Uncovering Innovation Features and Emerging Technologies in Molecular Biology through Patent Analysis.

Methods Mol Biol 2018 ;1674:15-34

School of Economics, Business Administration and Accounting at Ribeirão Preto - FEA-RP, University of São Paulo, Av. Bandeirantes 3900, 14040-900, Ribeirão Preto, São Paulo, Brazil.

Scientific research at universities has a crucial role in leveraging a country's innovative potential. Sectors that require greater investments in technology for the development of their research, such as biotechnology, need to be aware of the frontier state-of-the-art technology and the knowledge incrusted within it. Although the information available in scientific articles is well explored in academic environment, the patent literature, where much of the technological information is present, is still poorly accessed. This chapter is intended to instruct students and researchers at universities to look at patent document analysis as a source of scientific and technological information and explore its applications. Within this chapter, we use the technological area regarding immunoglobulins inventions (monoclonal and polyclonal antibodies) as example to provide directions on how to develop a patent landscape to get an overview of the inventions in a certain field; how to map a collaborative network of inventors/assignees to help the pursuit and identification of future partnerships; and lastly we describe the steps of how to set up a network of patent citations with the aim of forecasting emerging technologies. We strongly believe that incorporate data from patents in planning phase of research projects at academia, as well as to establish partnerships and join R&D efforts to invest on promising technologies, is of great relevance to leverage the growth of the biotechnology sector.
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http://dx.doi.org/10.1007/978-1-4939-7312-5_2DOI Listing
May 2018

Copper effects on biomarkers associated with photosynthesis, oxidative status and calcification in the Brazilian coral Mussismilia harttii (Scleractinia, Mussidae).

Mar Environ Res 2017 Sep 10;130:248-257. Epub 2017 Aug 10.

Programa de Pós-Graduação em Oceanografia Biológica, Instituto de Oceanografia, Universidade Federal do Rio Grande, Av. Itália, km 8, Rio Grande, RS 96203-900, Brazil; Instituto Coral Vivo, Rua dos Coqueiros, Parque Yaya, Santa Cruz Cabrália, BA 45.807-000, Brazil; Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Av. Itália, km 8, Rio Grande, RS 96203-900, Brazil. Electronic address:

Seawater contamination with metals, such as copper (Cu), is a notable local impact threatening coral reefs. Cu effects on biomarkers associated with photosynthesis, oxidative status and calcification were evaluated in the Brazilian coral Mussismilia harttii using a marine mesocosm facility. Polyps were kept under control conditions (1.9 μg L Cu) or exposed to dissolved Cu (3.0, 4.8, and 6.7 μg L) for 12 days. Photochemical efficiency of the photosystem II of symbiotic algae (zooxanthellae) was measured and polyps were analyzed for antioxidant capacity, lipid peroxidation, DNA damage, and carbonic anhydrase Ca-ATPase, Mg-ATPase and (Ca,Mg)-ATPase activities after 12 days. Results highlighted the effects of Cu exposure, leading corals to an oxidative stress condition [increased total antioxidant capacity (TAC) and DNA damage] and a possible reduced calcification ability [decreased (Ca,Mg)-ATPase activity]. Therefore, biomarkers associated with oxidative status (TAC and DNA damage) and calcification [(Ca, Mg)-ATPase] are indicated as good predictors of corals health.
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http://dx.doi.org/10.1016/j.marenvres.2017.08.002DOI Listing
September 2017

Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation.

Cell Biol Toxicol 2017 06 30;33(3):233-250. Epub 2016 Dec 30.

Regional Blood Center of Ribeirão Preto, Rua Tenente Catão Roxo, 2501, Ribeirão Preto, São Paulo, 14051-140, Brazil.

Ten years have passed since the first publication announcing the generation of induced pluripotent stem cells (iPSCs). Issues related to ethics, immune rejection, and cell availability seemed to be solved following this breakthrough. The development of iPSC technology allows advances in in vitro cell differentiation for cell therapy purpose and other clinical applications. This review provides a perspective on the iPSC potential for cell therapies, particularly for hematological applications. We discuss the advances in in vitro hematopoietic differentiation, the possibilities to employ iPSC in hematology studies, and their potential clinical application in hematologic diseases. The generation of red blood cells and functional T cells and the genome editing technology applied to mutation correction are also covered. We highlight some of the requirements and obstacles to be overcome before translating these cells from research to the clinic, for instance, iPSC variability, genotoxicity, the differentiation process, and engraftment. Also, we evaluate the patent landscape and compile the clinical trials in the field of pluripotent stem cells. Currently, we know much more about iPSC than in 2006, but there are still challenges that must be solved. A greater understanding of molecular mechanisms underlying the generation of hematopoietic stem cells is necessary to produce suitable and transplantable hematopoietic stem progenitor cells from iPSC.
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http://dx.doi.org/10.1007/s10565-016-9377-2DOI Listing
June 2017

Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis.

Nutrients 2016 Jun 28;8(7). Epub 2016 Jun 28.

Departamento de ClínicaMédica, Faculdade de Medicina, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil.

Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries; it can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocarcinoma. The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients. In a randomized, controlled clinical trial, involving 50 biopsy-proven NASH patients, we investigated the effects of synbiotic supplementation on metabolic parameters, hepatic steatosis, intestinal permeability, small intestinal bacterial overgrowth (SIBO) and lipopolysaccharide (LPS) serum levels. Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone. Before and after the intervention we assessed steatosis by magnetic resonance imaging, intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing. NASH patients presented high gut permeability, but low prevalence of SIBO. After the intervention, only the synbiotic group presented a reduction in steatosis, lost weight, diminished BMI and waist circumference measurement. Synbiotic did not improve intestinal permeability or LPS levels. We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss.
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http://dx.doi.org/10.3390/nu8070397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963873PMC
June 2016

RMEL3, a novel BRAFV600E-associated long noncoding RNA, is required for MAPK and PI3K signaling in melanoma.

Oncotarget 2016 Jun;7(24):36711-36718

Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Previous work identified RMEL3 as a lncRNA with enriched expression in melanoma. Analysis of The Cancer Genome Atlas (TCGA) data confirmed RMEL3 enriched expression in melanoma and demonstrated its association with the presence of BRAFV600E. RMEL3 siRNA-mediated silencing markedly reduced (95%) colony formation in different BRAFV600E melanoma cell lines. Multiple genes of the MAPK and PI3K pathways found to be correlated with RMEL3 in TCGA samples were experimentally confirmed. RMEL3 knockdown led to downregulation of activators or effectors of these pathways, including FGF2, FGF3, DUSP6, ITGB3 and GNG2. RMEL3 knockdown induces gain of protein levels of tumor suppressor PTEN and the G1/S cyclin-Cdk inhibitors p21 and p27, as well as a decrease of pAKT (T308), BRAF, pRB (S807, S811) and cyclin B1. Consistently, knockdown resulted in an accumulation of cells in G1 phase and subG0/G1 in an asynchronously growing population. Thus, TCGA data and functional experiments demonstrate that RMEL3 is required for MAPK and PI3K signaling, and its knockdown decrease BRAFV600E melanoma cell survival and proliferation.
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http://dx.doi.org/10.18632/oncotarget.9164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095033PMC
June 2016

Effects of Ocean Acidification and Temperature Increases on the Photosynthesis of Tropical Reef Calcified Macroalgae.

PLoS One 2016 9;11(5):e0154844. Epub 2016 May 9.

Universidade Federal Rural de Pernambuco, Departamento de Biologia, R. Dom Manoel de Medeiros, s/n, Dois Irmãos, 52171-900, Recife, PE, Brazil.

Climate change is a global phenomenon that is considered an important threat to marine ecosystems. Ocean acidification and increased seawater temperatures are among the consequences of this phenomenon. The comprehension of the effects of these alterations on marine organisms, in particular on calcified macroalgae, is still modest despite its great importance. There are evidences that macroalgae inhabiting highly variable environments are relatively resilient to such changes. Thus, the aim of this study was to evaluate experimentally the effects of CO2-driven ocean acidification and temperature rises on the photosynthesis of calcified macroalgae inhabiting the intertidal region, a highly variable environment. The experiments were performed in a reef mesocosm in a tropical region on the Brazilian coast, using three species of frondose calcifying macroalgae (Halimeda cuneata, Padina gymnospora, and Tricleocarpa cylindrica) and crustose coralline algae. The acidification experiment consisted of three treatments with pH levels below those occurring in the region (-0.3, -0.6, -0.9). For the temperature experiment, three temperature levels above those occurring naturally in the region (+1, +2, +4°C) were determined. The results of the acidification experiment indicate an increase on the optimum quantum yield by T. cylindrica and a decline of this parameter by coralline algae, although both only occurred at the extreme acidification treatment (-0.9). The energy dissipation mechanisms of these algae were also altered at this extreme condition. Significant effects of the temperature experiment were limited to an enhancement of the photosynthetic performance by H. cuneata although only at a modest temperature increase (+1°C). In general, the results indicate a possible photosynthetic adaptation and/or acclimation of the studied macroalgae to the expected future ocean acidification and temperature rises, as separate factors. Such relative resilience may be a result of the highly variable environment they inhabit.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154844PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861303PMC
July 2017

A novel marine mesocosm facility to study global warming, water quality, and ocean acidification.

Ecol Evol 2015 Oct 30;5(20):4555-66. Epub 2015 Sep 30.

Instituto Coral Vivo Rio de Janeiro Brazil ; Museu Nacional Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil.

We describe a completely randomizable flow-through outdoor mesocosm for climate change and ecotoxicology studies that was built with inexpensive materials. The 16 raceway tanks allow up to 6× water renewal per hour, avoiding changes in natural abiotic seawater conditions. We use an open-source hardware board (Arduino) that was adapted to control heaters and an innovative CO 2 injection system. This system reduced seawater pH up to -0.9 units and increased temperature up to +6°C in three treatments and a control. Treatments can be continuously compared with the control and vary according to diel fluctuations, thus following the diel range observed in the sea. The mesocosm facility also includes an integrated secondary system of 48 aquaria for ecotoxicology studies. We validated the reproducibility and relevance of our experimental system by analyzing the variation of the total DNA of the microbial community extracted from corals in three elevated temperature scenarios during a 40-day experiment. We also present data from temperature, acidification, and copper contamination trials, which allowed continuous, reliable, and consistent treatment manipulations.
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http://dx.doi.org/10.1002/ece3.1670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670062PMC
October 2015

Inhibition of mTORC1/2 overcomes resistance to MAPK pathway inhibitors mediated by PGC1α and oxidative phosphorylation in melanoma.

Cancer Res 2014 Dec 8;74(23):7037-47. Epub 2014 Oct 8.

Departments of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Department of Systems Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.

Metabolic heterogeneity is a key factor in cancer pathogenesis. We found that a subset of BRAF- and NRAS-mutant human melanomas resistant to the MEK inhibitor selumetinib displayed increased oxidative phosphorylation (OxPhos) mediated by the transcriptional coactivator PGC1α. Notably, all selumetinib-resistant cells with elevated OxPhos could be resensitized by cotreatment with the mTORC1/2 inhibitor AZD8055, whereas this combination was ineffective in resistant cell lines with low OxPhos. In both BRAF- and NRAS-mutant melanoma cells, MEK inhibition increased MITF expression, which in turn elevated levels of PGC1α. In contrast, mTORC1/2 inhibition triggered cytoplasmic localization of MITF, decreasing PGC1α expression and inhibiting OxPhos. Analysis of tumor biopsies from patients with BRAF-mutant melanoma progressing on BRAF inhibitor ± MEK inhibitor revealed that PGC1α levels were elevated in approximately half of the resistant tumors. Overall, our findings highlight the significance of OxPhos in melanoma and suggest that combined targeting of the MAPK and mTORC pathways may offer an effective therapeutic strategy to treat melanomas with this metabolic phenotype.
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http://dx.doi.org/10.1158/0008-5472.CAN-14-1392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347853PMC
December 2014

Molecular profiling of patient-matched brain and extracranial melanoma metastases implicates the PI3K pathway as a therapeutic target.

Clin Cancer Res 2014 Nov 6;20(21):5537-46. Epub 2014 May 6.

Departments of Melanoma Medical Oncology, Systems Biology and.

Purpose: An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches.

Experimental Design: Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and quantitative analysis of protein expression and activation by reverse-phase protein array (RPPA) analysis were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors.

Results: The status of 154 previously reported hotspot mutations, including driver mutations in BRAF and NRAS, were concordant in all evaluable patient-matched pairs of tumors. Overall patterns of CNV, mRNA expression, and protein expression were largely similar between the paired samples for individual patients. However, brain metastases demonstrated increased expression of several activation-specific protein markers in the PI3K/AKT pathway compared with the extracranial metastases.

Conclusions: These results add to the understanding of the molecular characteristics of melanoma brain metastases and support the rationale for additional testing of the PI3K/AKT pathway as a therapeutic target in these highly aggressive tumors.
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http://dx.doi.org/10.1158/1078-0432.CCR-13-3003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216765PMC
November 2014

The involvement of heparin in retinal infection by Toxoplasma gondii in a chick model revealed an ontogenetic-dependent pattern.

Parasitol Int 2014 Apr 12;63(2):337-40. Epub 2013 Dec 12.

Laboratório de Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Brazil. Electronic address:

This work aimed to test the influence of heparin on the susceptibility of retinal cells to Toxoplasma gondii infection. Primary cultures of retinas from chick embryos of 8 (E8) or 11 (E11) days and fibroblasts (control) were used. To determine the influence of heparin in T. gondii infection, tachyzoites of the RH strain were treated with heparin before addition in the culture. A monoclonal anti-heparin antibody was used to analyze the heparin distribution on fibroblast and retinal cell surfaces. Our results showed that retinal cells (E8 and E11) had a higher infection rate than fibroblasts (91% and 24% versus 13%, respectively). Pre-treatment of T. gondii with heparin decreased infection of E8 retinal cells when compared with non-treated parasites (45% versus 91%, respectively), but not of E11 cells (35% versus 48%). In accordance, retinal cells presented an intense heparin staining by immunofluorescence assay. In conclusion, retinal cells from chick embryos were more susceptible to infection by T. gondii compared to fibroblasts and, pre-treatment of tachyzoites with heparin decreased the number of infected cells and parasite burden particularly for E8 retinal cells.
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http://dx.doi.org/10.1016/j.parint.2013.11.013DOI Listing
April 2014

Novel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.

PLoS One 2010 Oct 20;5(10):e13510. Epub 2010 Oct 20.

Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0013510PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958148PMC
October 2010

Pyogenic granuloma after retinal detachment surgery with scleral buckle: case report.

Arq Bras Oftalmol 2009 Jul-Aug;72(4):543-4

Departamento de Oftalmologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

The authors relate an uncommon case of pyogenic granuloma restricted to tarsal conjunctiva post retinopexy with scleral buckle.
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http://dx.doi.org/10.1590/s0004-27492009000400021DOI Listing
March 2010

Different isolates from Leishmania braziliensis complex induce distinct histopathological features in a murine model of infection.

Vet Parasitol 2009 Nov 19;165(3-4):231-40. Epub 2009 Jul 19.

Laboratório de Biologia Molecular, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Brazil.

The aim of this study was to evaluate the histopathological features in tissues of mice infected by human isolates (I, II, and III) or the reference M2903 strain of Leishmania braziliensis complex. BALB/c and C57Bl/6 mice were infected in the hind footpad with 10(6) stationary-phase promastigotes of L. braziliensis complex. The evolution of lesions was observed for 10 weeks and the animals were then euthanized and liver, spleen and popliteal lymph nodes were collected. Tissues were stained with hematoxylin and eosin and analyzed by immunohistochemistry assay. Increased thickness of infected footpads was observed in all animals, lesions were nodular and non-ulcerated. Mice infected with isolate I presented inflammatory infiltrates consisting predominantly of mononuclear cells in all tissues examined, and also a great number of megakaryocytes, compared with other isolates. Infection with isolate II led to an infected footpad enlargement not seen in other isolates. In addition, mononuclear infiltrates in the liver and hemosiderin in spleen were noted. Conversely, mice infected with either isolate III or M2903 strain only showed an increased number of megakaryocytes in spleen. All tissues examined had detectable amastigote forms of Leishmania by immunohistochemistry in all groups. Taking together, our results showed an unforeseen behavior of different isolates of L. braziliensis complex that led to diverse pathological findings.
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http://dx.doi.org/10.1016/j.vetpar.2009.07.019DOI Listing
November 2009