Effect of trivalent arsenicals on cell proliferation in mouse and human microvascular endothelial cells

AbstractChronic exposure to high levels of inorganic arsenic (iAs) has been associated with cancerous and non-cancerous health effects, including cardiovascular effects. However, the mechanism for a presumed toxic effect of arsenic on vascular tissue is not clear. Our working hypothesis is that inorganic trivalent arsenic and its methylated metabolites react with cysteine-containing cellular proteins and alter their function leading to adverse events such as cytotoxicity or proliferation. In this study, human microvascular endothelial cells (HMEC1) and mouse microvascular endothelial cells (MFP-MVEC) were exposed to arsenite (iAsIII), monomethylarsonous acid (MMAIII), or dimethylarsinous acid (DMAIII) for 72h to evaluate cytotoxicity, and for 24, 48 or 72h to evaluate cell proliferation. Both cell lines showed similar LC50 values, from 0.1 to 2.4μM, for all three trivalent arsenicals. The endothelial cells treated with1nM to 1μM concentrations of the three trivalent arsenicals did not show increased cell proliferation at 24, 48 or 72h or increased rate of proliferation at 72h of exposure. Overall, cytotoxicity of trivalent arsenicals to microvascular endothelial cells is similar to their cytotoxicity to epithelial cells, and that these compounds are not mitogenic

A 30-Year Clinical and Magnetic Resonance Imaging Observational Study of Multiple Sclerosis and Clinically Isolated Syndromes

OBJECTIVE: Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long-term clinical outcomes in MS, and to identify early prognostic features of these outcomes. METHODS: One hundred thirty-two people presenting with a clinically isolated syndrome were prospectively recruited between 1984 and 1987, and followed up clinically and radiologically 1, 5, 10, 14, 20, and now 30 years later. All available notes and magnetic resonance imaging scans were reviewed, and MS was defined according to the 2010 McDonald criteria. RESULTS: Clinical outcome data were obtained in 120 participants at 30 years. Eighty were known to have developed MS by 30 years. Expanded Disability Status Scale (EDSS) scores were available in 107 participants, of whom 77 had MS; 32 (42%) remained fully ambulatory (EDSS scores ≤3.5), all of whom had relapsing-remitting MS (RRMS), 3 (4%) had RRMS and EDSS scores >3.5, 26 (34%) had secondary progressive MS (all had EDSS scores >3.5), and MS contributed to death in 16 (20%). Of those with MS, 11 received disease-modifying therapy. The strongest early predictors (within 5 years of presentation) of secondary progressive MS at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at 1 year. INTERPRETATION: Thirty years after onset, in a largely untreated cohort, there was a divergence of MS outcomes; some people accrued substantial disability early on, whereas others ran a more favorable long-term course. These outcomes could, in part, be predicted by radiological findings from within 1 year of first presentation. ANN NEUROL 2020;87:63-74

Wheezing in infants: frequency, clinical characteristics and treatment

OBJECTIVE: To estimate the frequency and describe the clinical characteristics and respective treatments of previous history of wheezing. METHODS: Infants aged 6-23 months with upper respiratory tract complaints and reporting previous wheezing were followed-up retrospectively. Data were registered on a validated standardized form. RESULTS: Out of 451 infants, 164 (36.4%; 95%CI: 31.9-41.0) had a report of prior history of wheezing, 148 (32.8%; 95%CI: 28.5-37.4) during the first year of life. The mean age at the first episode of wheezing was 5.3±3.9 months. Among those who had had their first episode before 12 months of age, 38.5% reported 3 to 6 episodes and 14.2% > 6 episodes. Mean age at first episode was lower for those with > 3 episodes in comparison with those with seis episódios. A média da idade no primeiro episódio foi menor para os que apresentaram > três episódios em comparação aos que apresentaram até dois episódios (3,2±2,7 versus 5,7±2,5 meses, p < 0,001). CONCLUSÃO: Um terço dos lactentes apresentou chiado no primeiro ano de vida. Quanto mais cedo ocorre o primeiro episódio, mais frequente é a recorrência do chiado.Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal da Bahia Faculdade de Medicina da Bahia Programa de Pós-Graduação em Ciências da SaúdeUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUniversidade de São Paulo Faculdade de Saúde Pública Departamento de EpidemiologiaEscola Bahiana de Medicina e Saúde PúblicaUFBAUFBA Faculdade de Medicina da Bahia Departamento de Anatomia Patológica e Medicina LegalUFBA Faculdade de Medicina da Bahia Departamento de PediatriaUNIFESP, EPM, Depto. de PediatriaSciEL

PRODH Polymorphisms, Cortical Volumes and Thickness in Schizophrenia

Schizophrenia is a neurodevelopmental disorder with high heritability. Several lines of evidence indicate that the PRODH gene may be related to the disorder. Therefore, our study investigates the effects of 12 polymorphisms of PRODH on schizophrenia and its phenotypes. To further evaluate the roles of the associated variants in the disorder, we have conducted magnetic resonance imaging (MRI) scans to assess cortical volumes and thicknesses. A total of 192 patients were evaluated using the Structured Clinical Interview for DSM-IV (SCID), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) instruments. the study included 179 controls paired by age and gender. the samples were genotyped using the real-time polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-PCR and Sanger sequencing methods. A sample of 138 patients and 34 healthy controls underwent MRI scans. One polymorphism was associated with schizophrenia (rs2904552), with the G-allele more frequent in patients than in controls. This polymorphism is likely functional, as predicted by PolyPhen and SIFT, but it was not associated with brain morphology in our study. in summary, we report a functional PRODH variant associated with schizophrenia that may have a neurochemical impact, altering brain function, but is not responsible for the cortical reductions found in the disorder.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo UNIFESP, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psiquiatria, São Paulo, BrazilFac Med ABC FMABC, Dept Ginecol & Obstet, Disciplina Genet & Reprod Humana, São Paulo, BrazilFed Univ Para, Lab Genet Humana & Med, BR-66059 Belem, Para, BrazilUniv Fed ABC, Ctr Math Computat & Cognit, Santo Andre, BrazilUniversidade Federal de São Paulo UNIFESP, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psiquiatria, São Paulo, BrazilFAPESP: 2011/50740-5FAPESP: 2007/58736-1Web of Scienc

The term basal plate of the human placenta as a source of functional extravillous trophoblast cells

Background\ud Extravillous trophoblast (EVT) cells are of pivotal importance in human embryo implantation and homeostasis of the maternal fetal interface. Invasion of the endometrium by EVT contributes to placental anchorage, spiral artery remodeling, immunological defense, tolerogenic responses, and several collaborative cross talks involved in establishing and maintaining a successful pregnancy. We report here an improved protocol for the isolation of fully differentiated EVT cells from the basal plate of the human term placenta.\ud \ud \ud Methods\ud The basal plate was carefully dissected from the villous tissue and the amniochorion membrane prior to enzymatic digestion. Term basal EVT cells were isolated using a 30 and 60% Percoll gradient. A panel of markers and characteristics of the isolated cells were used to confirm the specificity and efficiency of the method so that their potential as an investigative tool for placental research could be ascertained.\ud \ud \ud Results\ud Isolated cells were immunoreactive for cytokeratin-7 (CK-7), placental growth factor, placental alkaline phosphatase, human leukocyte antigen G1 (HLA-G1), and α1 and α5 integrins, similarly to the EVT markers from first trimester placental villi. Around 95% of the isolated cells labeled positively for CK-7 and 82% for HLA-G1. No significant change in viability was observed during 48 h of EVT culture as indicated by propidium iodide incorporation and trypan blue test exclusion. Genes for metalloproteinases MMP-2 and MMP9 (positive regulators of trophoblast invasiveness) were expressed up to 48 h of culturing, as also the gelatinolytic activity of the isolated cells. Transforming growth factor (TGF)-beta, which inhibits proliferation, migration, and invasiveness of first-trimester EVT cells, also reduced invasion of isolated term EVT cells in transwell assays, whereas epidermal growth factor was a positive modulator.\ud \ud \ud Conclusions\ud Term basal plate may be a viable source of functional EVT cells that is an alternative to villous explant-derived EVT cells and cell lines. Isolated term EVT cells may be particularly useful in investigation of the role of trophoblast cells in pathological gestations, in which the precise regulation and interactive ability of extravillous trophoblast has been impaired.Fundação de Amparo à Pesquisa do Estado de São Paulo [2009/05354-0; 2013/12243-5]Conselho Nacional de Desenvolvimento Científico e Tecnológico [40088/2010-5]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [4178-11-4]Austrian Science Funds [P-22687-B13

FAM5C Contributes to Aggressive Periodontitis

Aggressive periodontitis is characterized by a rapid and severe periodontal destruction in young systemically healthy subjects. A greater prevalence is reported in Africans and African descendent groups than in Caucasians and Hispanics. We first fine mapped the interval 1q24.2 to 1q31.3 suggested as containing an aggressive periodontitis locus. Three hundred and eighty-nine subjects from 55 pedigrees were studied. Saliva samples were collected from all subjects, and DNA was extracted. Twenty-one single nucleotide polymorphisms were selected and analyzed by standard polymerase chain reaction using TaqMan chemistry. Non-parametric linkage and transmission distortion analyses were performed. Although linkage results were negative, statistically significant association between two markers, rs1935881 and rs1342913, in the FAM5C gene and aggressive periodontitis (p = 0.03) was found. Haplotype analysis showed an association between aggressive periodontitis and the haplotype A-G (rs1935881-rs1342913; p = 0.009). Sequence analysis of FAM5C coding regions did not disclose any mutations, but two variants in conserved intronic regions of FAM5C, rs57694932 and rs10494634, were found. However, these two variants are not associated with aggressive periodontitis. Secondly, we investigated the pattern of FAM5C expression in aggressive periodontitis lesions and its possible correlations with inflammatory/immunological factors and pathogens commonly associated with periodontal diseases. FAM5C mRNA expression was significantly higher in diseased versus healthy sites, and was found to be correlated to the IL-1β, IL-17A, IL-4 and RANKL mRNA levels. No correlations were found between FAM5C levels and the presence and load of red complex periodontopathogens or Aggregatibacter actinomycetemcomitans. This study provides evidence that FAM5C contributes to aggressive periodontitis

Biodiversity, threats and conservation challenges in the Cerrado of Amapá, an Amazonian savanna

An Amazonian savanna in northern Brazil known as the Cerrado of Amapá is under imminent threat from poor land-use planning, the expansion of large-scale agriculture and other anthropogenic pressures. These savannas house a rich and unique flora and fauna, including endemic plants and animals. However, the area remains under-sampled for most taxa, and better sampling may uncover new species. We estimate that only ∼9.16% of these habitats have any kind of protection, and legislative changes threaten to further weaken or remove this protection. Here we present the status of knowledge concerning the biodiversity of the Cerrado of Amapá, its conservation status, and the main threats to the conservation of this Amazonian savanna. To secure the future of these unique and imperilled habitats, we suggest urgent expansion of protected areas, as well as measures that would promote less-damaging land uses to support the local population. Copyright © 2017 Karen Mustin et al

Frequency of Equine Monocytic Ehrlichiosis (EME) in Brazil

From a cross-sectional observational study with convenience samples, 347 blood samples from horses were collected from different physiographic regions, as follows: Santa Catarina Plateau (Santa Catarina State - SC), Médio Paraíba do Sul (São Paulo State - SP and Rio de Janeiro State RJ), Mountainous and Metropolitan regions (Rio de Janeiro State - RJ). Samples were tested for the presence of antibodies (IgG) anti Neorickettsia risticii by indirect immunofluorescence assay (IFA). The frequency obtained in this study corroborates with the ones obtained in the U.S.A., which refers to endemic regions. Fisher's exact test showed significant differences in the number of positive animals between regions, indicating that the probability of an animal becoming infected varies depending on the area. The CI 95% revealed no association between infection and geopolitical space. Moreover, Odds ratio test showed differences of an animal getting infected in different regions. This event could be influenced by the type of treatment used in each area, as the seasonal frequency of injury or even potential vectors. Therefore, there are seropositive animals for N. risticii in the studied areas, suggesting that this agent may be circulating in those regions. Future studies mainly based on molecular analyzes are needed to confirm these serological findings

Factors influencing terrestriality in primates of the Americas and Madagascar

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (bodymass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use