Mast cell repopulation of the peritoneal cavity: contribution of mast cell progenitors versus bone marrow derived committed mast cell precursors

<p>Abstract</p> <p>Background</p> <p>Mast cells have recently gained new importance as immunoregulatory cells that are involved in numerous pathological processes. One result of these processes is an increase in mast cell numbers at peripheral sites. This study was undertaken to determine the mast cell response in the peritoneal cavity and bone marrow during repopulation of the peritoneal cavity in rats.</p> <p>Results</p> <p>Two mast cell specific antibodies, mAb AA4 and mAb BGD6, were used to distinguish the committed mast cell precursor from more mature mast cells. The peritoneal cavity was depleted of mast cells using distilled water. Twelve hours after distilled water injection, very immature mast cells could be isolated from the blood and by 48 hours were present in the peritoneal cavity. At this same time the percentage of mast cells in mitosis increased fourfold. Mast cell depletion of the peritoneal cavity also reduced the total number of mast cells in the bone marrow, but increased the number of mast cell committed precursors.</p> <p>Conclusions</p> <p>In response to mast cell depletion of the peritoneal cavity, a mast cell progenitor is released into the circulation and participates in repopulation of the peritoneal cavity, while the committed mast cell precursor is retained in the bone marrow.</p

Role of 5-HT1A and 5-HT2C receptors of the dorsal periaqueductal gray in the anxiety- and panic-modulating effects of antidepressants in rats

Antidepressant drugs are first-line treatment for panic disorder. Facilitation of 5-HT1A receptor-mediated neurotransmission in the dorsal periaqueductal gray (dPAG), a key panic-associated area, has been implicated in the panicolytic effect of the selective serotonin reuptake inhibitor fluoxetine. However, it is still unknown whether this mechanism accounts for the antipanic effect of other classes of antidepressants drugs (ADs) and whether the 5-HT interaction with 5-HT2C receptors in this midbrain area (which increases anxiety) is implicated in the anxiogenic effect caused by short-term treatment with ADs. The results showed that previous injection of the 5-HT1A receptor antagonist WAY-100635 in the dPAG blocked the panicolytic-like effect caused by chronic systemic administration of the tricyclic AD imipramine in male Wistar rats tested in the elevated T-maze. Neither chronic treatment with imipramine nor fluoxetine changed the expression of 5-HT1A receptors in the dPAG. Treatment with these ADs also failed to significantly change ERK1/2 (extracellular-signal regulated kinase) phosphorylation level in this midbrain area. Blockade of 5-HT2C receptors in the dPAG with the 5-HT2C receptor antagonist SB-242084 did not change the anxiogenic effect caused by a single acute injection of fluoxetine or imipramine in the Vogel conflict test. These results reinforce the view that the facilitation of 5-HT1A receptor mediated neurotransmission in the dPAG is a common mechanism involved in the panicolytic effect caused by chronic administration of ADs. On the other hand, the anxiogenic effect observed after short-term treatment with these drugs does not depend on 5-HT2C receptors located in the dPAG.Peer reviewe

Seroprevalence of Chikungunya Virus after Its Emergence in Brazil.

Chikungunya has had a substantial impact on public health because of the magnitude of its epidemics and its highly debilitating symptoms. We estimated the seroprevalence, proportion of symptomatic cases, and proportion of chronic form of disease after introduction of chikungunya virus (CHIKV) in 2 cities in Brazil. We conducted the population-based study through household interviews and serologic surveys during October-December 2015. In Feira de Santana, we conducted a serologic survey of 385 persons; 57.1% were CHIKV-positive. Among them, 32.7% reported symptoms, and 68.1% contracted chronic chikungunya disease. A similar survey in Riachão do Jacuípe included 446 persons; 45.7% were CHIKV-positive, 41.2% reported symptoms, and 75.0% contracted the chronic form. Our data confirm intense CHIKV transmission during the continuing epidemic. Chronic pain developed in a high proportion of patients. We recommend training health professionals in management of chronic pain, which will improve the quality of life of chikungunya-affected persons

Alunos hiperativos x professor: construindo um elo harmonioso

Atualmente, ouve-se falar muito na questão da inclusão. Percebe-se que os professores sentem-se despreparados diante do problema. Apesar dos cursos oferecidos na área do Ensino Especial, os professores ainda se sentem incapazes de lidar com alunos hiperativos. Este trabalho objetivou colher informações pertinentes sobre hiperatividade no intuito de colaborar com pais e professores que vivenciam e compartilham com essas crianças suas inseguranças, a exclusão social e sua agitação diária e permanente. A pesquisa foi em uma abordagem qualitativa onde teve como participantes especialistas em educação e professores do Ensino Fundamental das séries iniciais. Todos da rede pública do Distrito Federal que trabalham com crianças acometidas pelo TDAH. O instrumento de coleta de dados utilizado neste trabalho, foi o questionário. As categorias selecionadas para professores foram: características de aluno hiperativo; dificuldades pedagógicas com aluno hiperativo; fatores positivos e negativos que influenciam na aprendizagem de aluno hiperativo; possíveis suportes oferecidos pelo sistema de ensino para o aperfeiçoamento do professor; a afetividade e auto-estima de aluno hiperativo; procedimentos utilizados no trabalho com aluno hiperativo. Para os especialistas, as categorias foram: diferença entre hiperatividade e falta de limites; conseqüências da falta do tratamento em uma criança hiperativa; faixa etária para um diagnóstico seguro; administração e / ou auto-superação de uma criança hiperativa sem o tratamento apropriado; identificação da hiperatividade pelos professores na escola; postura de professores e familiares diante de uma criança hiperativa; profissionais que podem diagnosticar e tratar o TDAH. Após a coleta, análise e discussão dos dados concluiu-se que as características da hiperatividade envolvem principalmente a inquietação e desatenção, e, conseqüentemente, a dificuldade de aprendizagem. Os professores despreparados sentem-se angustiados por não saberem lidar com o aluno acometido de tal distúrbio, e sugerem que se deve manter sempre um diálogo como também uma valorização para com o aluno. A hiperatividade pode decorrer de situações traumáticas, distúrbios psicológicos etc. O diagnóstico e o tratamento devem sempre ser feitos o mais cedo possível, mas, caso estes forem realizados aos sete anos de idade e mediante relatórios de professores e psicopedadgogos, terão maiores sucessos. Um ambiente com poucas atrações visuais e trabalhos com atividades dinâmicas, favorecem uma maior concentração do aluno hiperativo. O diagnóstico do TDAH deve ser feito por neuropediatras e psicólogos complementados pelos relatórios dos psicopedagogos, professores e pais. Ao final deste trabalho, pode-se concluir que, apesar deste ser um assunto recente, os profissionais de educação estão buscando informações sobre o mesmo. Este distúrbio precisa ser orientado por órgãos competentes no intuito de se levar o conhecimento aos professores e, assim, melhorar o relacionamento com essas crianças

EMG, functional and postural responses to a physical therapy treatment for patellofemoral syndrome

A síndrome femoropatelar (SFP), patologia de difícil tratamento, decorrede um desequilíbrio das forças que incidem sobre a patela durante seu movimento normal; freqüentemente não se obtém alívio total da dor. Este estudo visou avaliar o efeito de tratamento fisioterapêutico em seis sujeitos com SFP, tendo entre 18 e 35 anos, diagnosticados clinicamente pelo Ambulatório de Ortopedia do Hospital Universitário (grupo GFP); cinco sujeitos saudáveis, de mesma idade e nível de atividade física do GFP formaram o grupo controle. Nos dois grupos realizaram-se, antes e após o tratamento, avaliação funcional – usando escalas de Lysholm e visual analógica de dor, da articulação segundo Karlsson, do alinhamento postural de membros inferiores e teste de compressão patelar – e avaliação biomecânica por eletromiografia dos músculos vasto medial e vasto lateral O GFP submeteu-se durante cinco semanas a exercícios de alongamento e fortalecimento muscular, tendo resultado em redução de 50% no sinal positivo da compressão patelar, melhora nos escores das escalas funcionais e diminuição dos arcos longitudinais rebaixados e tornozelos valgos; não houve, porém, melhora da dor. Os dados eletromiográficos mostraram maior eficiência do vasto medial na realização de exercícios excêntricos e aumento da ativação do vasto lateral durante a marcha e na fase de subida do agachamento. O tratamento permitiu pois melhora na funcionalidade, no alinhamento dos joelhos e pés e na ativação dos músculos avaliados.Patellofemoral Syndrome (PFS), a challenging pathology to treat – wherein full pain relief is rarely obtained – results from force imbalance exerted on the patella during its normal movement. This study assessed the effect of a physical therapy treatment on six 18-to-35 year-old subjects with PFS, diagnosed by the University Hospital Orthopedic Outpatient Clinic; five healthy subjects having the same age and level of physical activity as the patients made up the control group. Both groups were submitted to assessment before and after PFS group treatment: of pain through the visual analogical scale; of the patellofemoral joint according to Karlsson; Lysholm scale) lower limb postural alignment; patellar compression test; and electromyography of the vastus medialis and vastus lateralis muscles. PFS group treatment consisted in muscle stretching and strengthening exercises during 5 weeks, after which we observed a 50% reduction in positive signs of patellar compression, better Lysholm and Karlsson scores, lower plantar arches and reduction of valgus ankle; however, no pain relief was reported. Electromyographic data showed higher efficiency of the vastus medialis muscle in carrying out eccentric exercises and increased activity of the vastus lateralis while walking and during upward movement after squatting

Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer

Background: Breast cancer comprises clinically and molecularly distinct tumor subgroups that differ in cell histology and biology and show divergent clinical phenotypes that impede phase III trials, such as those utilizing cathepsin K inhibitors. Here we correlate the epithelial-mesenchymal-like transition breast cancer cells and cathepsin K secretion with activation and aggregation of platelets. Cathepsin K is up-regulated in cancer cells that proteolyze extracellular matrix and contributes to invasiveness. Although proteolytically activated receptors (PARs) are activated by proteases, the direct interaction of cysteine cathepsins with PARs is poorly understood. In human platelets, PAR-1 and -4 are highly expressed, but PAR-3 shows low expression and unclear functions. Methods: Platelet aggregation was monitored by measuring changes in turbidity. Platelets were immunoblotted with anti-phospho and total p38, Src-Tyr-416, FAK-Tyr-397, and TGF beta monoclonal antibody. Activation was measured in a flow cytometer and calcium mobilization in a confocal microscope. Mammary epithelial cells were prepared from the primary breast cancer samples of 15 women with Luminal-B subtype to produce primary cells. Results: We demonstrate that platelets are aggregated by cathepsin K in a dose-dependent manner, but not by other cysteine cathepsins. PARs-3 and -4 were confirmed as the cathepsin K target by immunodetection and specific antagonists using a fibroblast cell line derived from PARs deficient mice. Moreover, through co-culture experiments, we show that platelets activated by cathepsin K mediated the up-regulation of SHH, PTHrP, OPN, and TGF beta in epithelial-mesenchymal-like cells from patients with Luminal B breast cancer. Conclusions: Cathepsin K induces platelet dysfunction and affects signaling in breast cancer cells.Associacao Beneficente de Coleta de Sangue (Colsan)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Univ Fed Sao Paulo, Dept Gynecol, BR-04024002 Sao Paulo, SP, BrazilCOLSAN, Charitable Assoc Blood Collect, BR-04080006 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biophys, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biochem, BR-04024002 Sao Paulo, SP, BrazilAntonio Prudente Fdn, AC Camargo Canc Ctr, AC Camargo Hosp Biobank, Dept Pathol, BR-01509010 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Cellular Gynecol Lab, Dept Gynecol, Rua Napoleao Barros 608, BR-04024002 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Gynecol, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biophys, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biochem, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Cellular Gynecol Lab, Dept Gynecol, Rua Napoleao Barros 608, BR-04024002 Sao Paulo, BrazilFAPESP: 2012/19780-3FAPESP: 2012/19851-8FAPESP: 2009/53766-5Web of Scienc

Brazilian Propolis: Correlation Between Chemical Composition and Antimicrobial Activity

The chemical composition of ethanol extracts from samples of Brazilian propolis (EEPs) determined by HPLC and their activity against Trypanosoma cruzi, Staphylococcus aureus, Streptococcus pneumoniae, Klebisiella pneumoniae, Candida albicans, Sporothrix schenckii and Paracoccidioides brasiliensis were determined. Based on the predominant botanical origin in the region of samples' collection, the 10 extracts were separated into three groups: A (B. dracunculifolia + Auraucaria spp), B (B. dracunculifolia) and C (Araucaria spp). Analysis by the multiple regression of all the extracts together showed a positive correlation, higher concentrations leading to higher biological effect, of S. aureus with p-coumaric acid (PCUM) and 3-(4-hydroxy-3-(oxo-butenyl)-phenylacrylic acid (DHCA1) and of trypomastigotes of T. cruzi with 3,5-diprenyl-4-hydroxycinnamic acid derivative 4 (DHCA4) and 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran (DCBEN). When the same approach was employed for each group, due to the small number of observations, the statistical test gave unreliable results. However, an overall analysis revealed for group A an association of S. aureus with caffeic acid (CAF) and dicaffeoylquinic acid 3 (CAFQ3), of S. pneumoniae with CAFQ3 and monocaffeoylquinic acid 2 (CAFQ2) and of T. cruzi also with CAFQ3. For group B, a higher activity against S. pneumoniae was associated DCBEN and for T. cruzi with CAF. For group C no association was observed between the anitmicrobial effect and any component of the extracts. The present study reinforces the relevance of PCUM and derivatives, especially prenylated ones and also of caffeolyquinic acids, on the biological activity of Brazilian propolis

Mental impact of Covid-19 among Spanish healthcare workers. A large longitudinal survey

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Ministerio de Ciencia e Innovación; Gerencia Regional de Salud de Castilla y León (SACYL, GRS COVID 32/A/20).Aims Longitudinal data on the mental health impact of the coronavirus disease 2019 (Covid-19) pandemic in healthcare workers is limited. We estimated prevalence, incidence and persistence of probable mental disorders in a cohort of Spanish healthcare workers (Covid-19 waves 1 and 2) -and identified associated risk factors. Methods 8996 healthcare workers evaluated on 5 May-7 September 2020 (baseline) were invited to a second web-based survey (October-December 2020). Major depressive disorder (PHQ-8 ≥ 10), generalised anxiety disorder (GAD-7 ≥ 10), panic attacks, post-traumatic stress disorder (PCL-5 ≥ 7), and alcohol use disorder (CAGE-AID ≥ 2) were assessed. Distal (pre-pandemic) and proximal (pandemic) risk factors were included. We estimated the incidence of probable mental disorders (among those without disorders at baseline) and persistence (among those with disorders at baseline). Logistic regression of individual-level [odds ratios (OR)] and population-level (population attributable risk proportions) associations were estimated, adjusting by all distal risk factors, health care centre and time of baseline interview. Results 4809 healthcare workers participated at four months follow-up (cooperation rate = 65.7%; mean = 120 days s.d. = 22 days from baseline assessment). Follow-up prevalence of any disorder was 41.5%, (v. 45.4% at baseline, p < 0.001); incidence, 19.7% (s.e. = 1.6) and persistence, 67.7% (s.e. = 2.3). Proximal factors showing significant bivariate-adjusted associations with incidence included: work-related factors [prioritising Covid-19 patients (OR = 1.62)], stress factors [personal health-related stress (OR = 1.61)], interpersonal stress (OR = 1.53) and financial factors [significant income loss (OR = 1.37)]. Risk factors associated with persistence were largely similar. Conclusions Our study indicates that the prevalence of probable mental disorders among Spanish healthcare workers during the second wave of the Covid-19 pandemic was similarly high to that after the first wave. This was in good part due to the persistence of mental disorders detected at the baseline, but with a relevant incidence of about 1 in 5 of HCWs without mental disorders during the first wave of the Covid-19 pandemic. Health-related factors, work-related factors and interpersonal stress are important risks of persistence of mental disorders and of incidence of mental disorders. Adequately addressing these factors might have prevented a considerable amount of mental health impact of the pandemic among this vulnerable population. Addressing health-related stress, work-related factors and interpersonal stress might reduce the prevalence of these disorders substantially. Study registration number: NCT0455656

Os Audience Response Systems como instrumento de inovação no ensino e na aprendizagem ativa: aplicações no âmbito de uma comunidade de prática e inovação em ensino e aprendizagem e perceções dos alunos

[Extrato] Introdução A atual geração de alunos universitários, nascida em finais da década de noventa e inícios do novo milénio, cresceu com a internet e as tecnologias digitais, sendo apelidados de "nativos digitais" (Anshari et al., 2017). O smartphone tornou-se indispensável no seu quotidiano, permitindo-lhes estar constantemente ligados à internet e desenvolver diversas atividades ao longo do dia, como verificar o email, navegar na web ou interagir nas redes sociais (Grinols & Rajesh, 2014).[...