In Vitro Transdifferentiation Potential of Equine Mesenchymal Stem Cells into Schwann-Like Cells.

Schwann cells (SCs) are essential for the regenerative processes of peripheral nerve injuries. However, their use in cell therapy is limited. In this context, several studies have demonstrated the ability of mesenchymal stem cells (MSCs) to transdifferentiate into Schwann-like cells (SLCs) using chemical protocols or co-culture with SCs. Here, we describe for the first time the in vitro transdifferentiation potential of MSCs derived from equine adipose tissue (AT) and equine bone marrow (BM) into SLCs using a practical method. In this study, the facial nerve of a horse was collected, cut into fragments, and incubated in cell culture medium for 48 h. This medium was used to transdifferentiate the MSCs into SLCs. Equine AT-MSCs and BM-MSCs were incubated with the induction medium for 5 days. After this period, the morphology, cell viability, metabolic activity, gene expression of glial markers glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), p75 and S100ß, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), and the protein expression of S100 and GFAP were evaluated in undifferentiated and differentiated cells. The MSCs from the two sources incubated with the induction medium exhibited similar morphology to the SCs and maintained cell viability and metabolic activity. There was a significant increase in the gene expression of BDNF, GDNF, GFAP, MBP, p75, and S100ß in equine AT-MSCs and GDNF, GFAP, MBP, p75, and S100ß in equine BM-MSCs post-differentiation. Immunofluorescence analysis revealed GFAP expression in undifferentiated and differentiated cells, with a significant increase in the integrated pixel density in differentiated cells and S100 was only expressed in differentiated cells from both sources. These findings indicate that equine AT-MSCs and BM-MSCs have great transdifferentiation potential into SLCs using this method, and they represent a promising strategy for cell-based therapy for peripheral nerve regeneration in horses.

Modifying effects of menthol against benzo(a)pyrene-induced forestomach carcinogenesis in female Swiss mice.

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon widespread in the environment and closely associated to tobacco use, which is an important risk factor for highly incident stomach cancer. Menthol, a monoterpene extracted from Mentha genus species, has multiple biological properties, including anti-inflammatory and gastroprotective properties, but its effects on carcinogenesis are still to be fully understood. Thus, we evaluated the modifying effects of Ment against BaP-induced forestomach carcinogenesis. Female Swiss mice received BaP by intragastrical (i.g.) administration (50 mg/kg of body weight [b wt], 2×/week), from weeks 1-5 weeks. Concomitantly, mice received Menthol at 25 (Ment25) or 50 (Ment50) mg/kg b wt (i.g, 3×/week). Animals were euthanized at weeks 5 (n = 5 mice/group) or 30 (n = 10 mice/group). At week 5, both Ment doses reduced peripheral leukocyte blood genotoxicity 4 h after the last BaP administration, but only Ment50 attenuated this biomarker 8 h after the last BaP administration. In accordance to these findings, both Ment interventions attenuated BaP-induced increase in the percentage of H2A.X-positive forestomach epithelial cells. Moreover, Ment50 reduced cell proliferation and apoptosis (i.e., Ki-67 and caspase-3, respectively) in forestomach epithelium but exerted no significant effects on NFκB, and Nrf2 protein levels. At week 30, Ment50 reduced by ~55% the incidence of BaP-induced forestomach diffuse hyperplasia and multiplicity of forestomach tumors (squamous cell papillomas and carcinomas). Our findings indicate that Ment50, administered during initiation phase, attenuates forestomach carcinogenesis by reducing early genotoxicity, cell proliferation, and apoptosis induced by BaP.

Paracoccidioides brasiliensis Releases a DNase-Like Protein That Degrades NETs and Allows for Fungal Escape.

Paracoccidioidomycosis is a systemic fungal disease, considered endemic in Latin America. Its etiological agents, fungi of the Paracoccidioides complex, have restricted geographic habitat, conidia as infecting form, and thermo-dimorphic characteristics. Polymorphonuclear neutrophils (PMNs) are responsible for an important defense response against fungus, releasing Neutrophil Extracellular Traps (NETs), which can wrap and destroy the yeasts. However, it has been described that some pathogens are able to evade from these DNA structures by releasing DNase as an escape mechanism. As different NETs patterns have been identified in PMNs cultures challenged with different isolates of Paracoccidioides brasiliensis, the general objective of this study was to identify if different patterns of NETs released by human PMNs challenged with Pb18 (virulent) and Pb265 (avirulent) isolates would be correlated with fungal ability to produce a DNase-like protein. To this end, PMNs from healthy subjects were isolated and challenged in vitro with both fungal isolates. The production, release, and conformation of NETs in response to the fungi were evaluated by Confocal Microscopy, Scanning Microscopy, and NETs Quantification. The identification of fungal DNase production was assessed by DNase TEST Agar, and the relative gene expression for hypothetical proteins was investigated by RT-qPCR, whose genes had been identified in the fungal genome in the GenBank (PADG_11161 and PADG_08285). It was possible to verify the NETs release by PMNs, showing different NETs formation when in contact with different isolates of the fungus. The Pb18 isolate induced the release of looser, larger, and more looking like degraded NETs compared to the Pb265 isolate, which induced the release of denser and more compact NETs. DNase TEST Agar identified the production of a DNase-like protein, showing that only Pb18 showed the capacity to degrade DNA in these plates. Besides that, we were able to identify that both PADG_08528 and PADG_11161 genes were more expressed during interaction with neutrophil by the virulent isolate, being PADG_08528 highly expressed in these cultures, demonstrating that this gene could have a greater contribution to the production of the protein. Thus, we identified that the virulent isolate is inducing more scattered and loose NETs, probably by releasing a DNase-like protein. This factor could be an important escape mechanism used by the fungus to escape the NETs action.

Differential effects of natural Curcumin and chemically modified curcumin on inflammation and bone resorption in model of experimental periodontitis.

OBJECTIVE: The purpose of this study was to compare the effects of the oral administration of natural curcumin and a chemically modified curcumin (CMC2.24) on osteoclast-mediated bone resorption, apoptosis, and inflammation in a murine model of experimental periodontal disease. DESIGN: Fifty male rats were distributed among the following treatment groups: (i) 2% carboxymethylcellulose, (ii) CMC2.24 30 mg/kg body weight, (iii) Curcumin 100 mg/kg body weight and (iv) no treatment. Compounds were administered daily by oral intubation over a 15-day period of time. Periodontal disease was induced by injections of LPS (lipopolysaccharide) into the gingival tissues three times per week. Contralateral sides were injected with the same volume of PBS (phosphate buffered saline) vehicle. After 15 days, hemimaxillae and gingival tissues were harvested. Bone resorption was assessed by µCT (microcomputer tomography). Formalin-fixed, paraffin embedded histological sections were stained with haematoxylin/eosin (H/E) for the assessment of cellular infiltrate or subjected to immunohistochemistry for detecting TRAP (tartrate-resistant acid phosphatase)-positive cells and caspase-3. Apoptosis was assessed in the gingival tissues by DNA fragmentation. RESULTS: CMC2.24 and curcumin caused a significant reduction of the inflammatory cell infiltrate, however µCT analysis showed that only CMC2.24 reduced bone resorption and the number of TRAP-positive multinucleated cells (osteoclasts). Curcumin, but not CMC2.24, significantly reduced the number of apoptotic cells in the gingival tissues and of osteocytes in the alveolar bone crest. CONCLUSIONS: The results suggest that CMC2.24 and curcumin inhibit inflammation by different mechanisms, but only CMC2.24 was capable of reducing alveolar bone resorption in the LPS-induced model of periodontitis.

Evaluation of antimalarial activity and toxicity of a new primaquine prodrug.

Plasmodium vivax is the most prevalent of the five species causing malaria in humans. The current available treatment for P. vivax malaria is limited and unsatisfactory due to at least two drawbacks: the undesirable side effects of primaquine (PQ) and drug resistance to chloroquine. Phenylalanine-alanine-PQ (Phe-Ala-PQ) is a PQ prodrug with a more favorable pharmacokinetic profile compared to PQ. The toxicity of this prodrug was evaluated in in vitro assays using a human hepatoma cell line (HepG2), a monkey kidney cell line (BGM), and human red blood cells deficient in the enzyme glucose-6-phosphate-dehydrogenase (G6PD). In addition, in vivo toxicity assays were performed with rats that received multiple doses of Phe-Ala-PQ to evaluate biochemical, hematological, and histopathological parameters. The activity was assessed by the inhibition of the sporogonic cycle using a chicken malaria parasite. Phe-Ala-PQ blocked malaria transmission in Aedes mosquitoes. When compared with PQ, it was less cytotoxic to BGM and HepG2 cells and caused less hemolysis of G6PD-deficient red blood cells at similar concentrations. The prodrug caused less alteration in the biochemical parameters than did PQ. Histopathological analysis of the liver and kidney did show differences between the control and Phe-Ala-PQ-treated groups, but they were not statistically significant. Taken together, the results highlight the prodrug as a novel lead compound candidate for the treatment of P. vivax malaria and as a blocker of malaria transmission.

O que pode o psicanalista frente às dificuldades da profissão impossível? / How can the psychoanalyst face the impossible profession's difficulties?

Este estudo aborda o trabalho do psicanalista tomando como vértice de investigação as dificuldades que esses profissionais atravessam na sua prática clínica cotidiana. Nesse contexto, mudanças no perfil dos pacientes, crises de demanda frente ao incremento da concorrência com psicofármacose psicoterapias diversas, significativas exigências da formação, estabelecimento de laços com outros analistas e vicissitudes na relação com a família podem ser considerados índices do mal-estar do psicanalista frente ao ato de psicanalisar nos dias atuais. Tendo por objetivo, então, aprofundar o olhar sobre as dificuldades da profissão impossível sublinhada por Freud, toma como guia para seu percurso metodológico um conceito central intitulado narcisismo profissional, forjado a partir da concepção de narcisismo proposta por Freud e desenvolvida por Lacan. O estudo problematiza as formas de enfrentamento das dificuldades apontadas: o tratamento possível pela análise pessoal dos psicanalistas a, construção de novos laços entre os participantes do campo, o envolvimento com a leitura e o estudo diligente de autores de dentro e de fora da Psicanálise, e com a escrita, tomada como uma forma de elaboração do psicanalista em relação aos impasses da clínica. Conclui-se que cada psicanalista necessita ressignificar sua atividade, o que inclui o constante exercício de desidealização de diversos aspectos inerentes à profissão, e o cuidado com sua oferta na Cultura, com a difusão da Psicanálise, além de uma nova tomada de posição frente à formação geral e específica. (AU)

This study broaches lhe psychoanalyst 's work taking as investigation 'svertex lhe difficulties of those professionals on their clinical quotidiano ln this context, modification in patients' profile, crisis of demand caused bygrowing of competition with drugs and various psychoterapies, expressiveformation 's exigencies, involvement with others psychoanalysts and vicissitudes in relationships whith family, can be considered index of psychoanalyst's discomfort face lhe psychoanalytic act nowadayso 50, having as his purpose to look over lhe impossible profession 's difficulties enhanced by Freud lhe author takes as guide in his methodological course a central concept entitled professional narcissism, forged from lhe concept of narcissism proposed by Freud and developped by lacan. The study rendersproblematic lhe forms of facing lhe difficulties designed: lhe possibletreatment of psychoanalysts in their own analysis, lhe construction of newfies among those who takes parI in lhe field, lhe involvement with lectureand lhe laborious study of authors inside and outside lhe Psychoanalysis,and also lhe writing, taken as psychoanalyst 's elaboration regarding lhe clinical dilemmaso The study ends concluding that each psychoanalystneeds signify his activity once more, which includes lhe constant practiceto reduce lhe idealization in several intrinsics aspects of lhe pro.fession, aswell as its aferI in culture, lhe dijilsion of Pychoanalysis besides a new positionface lhe general and specific formation. (AU)

O trabalho do psicanalista: das dificuldades da prática aos riscos do narcisismo profissional / The labour of the psychoanalyst: from the difficulties of practice to the risks of professional narcissism

Este estudo aborda o trabalho do psicanalista, tomando como vértice de investigação as dificuldades que esses profissionais atravessam na sua prática clínica cotidiana. Nesse contexto, mudanças no perfil dos pacientes, crises de demanda frente ao incremento da concorrência com psicofármacos e psicoterapias diversas, significativas exigências da formação, estabelecimento de laços com outros analistas e vicissitudes na relação com a família podem ser considerados índices do mal-estar do psicanalista frente ao ato de psicanalisar nos dias atuais. Tendo por objetivo, então, aprofundar o olhar sobre as dificuldades da profissão impossível sublinhada por Freud, toma como guia para seu percurso metodológico um conceito central intitulado narcisismo profissional, forjado a partir da concepção de narcisismo proposta por Freud e desenvolvida por Lacan. Investiga por meio de recortes específicos três autores, Freud, Ferenczi e Lacan. Em Freud, prioriza as dificuldades ligadas ao manejo da transferência e às exigências do próprio analista frente ao seu fazer. Quanto a Ferenczi, evidencia os percalços desse psicanalista nas questões do tempo e do dinheiro, especialmente no que relata por meio da correspondência trocada com Freud. No que diz respeito a Lacan, prioriza o depoimento e os testemunhos de quem com ele conviveu, apontando as múltiplas formas de identificação geradas e o advento do lacanismo, que faz surgir um novo tipo de psicanalista, que toma como missão defender a verdadeira psicanálise no mundo, a partir do retorno a Freud empreendido por Lacan. O estudo problematiza as formas de enfrentamento das dificuldades apontadas: o tratamento (...)

... possível pela análise pessoal dos psicanalistas, a construção de novos laços entre os participantes do campo, o envolvimento com a leitura e o estudo diligente de autores de dentro e de fora da Psicanálise, e com a escrita, tomada como uma forma de elaboração do psicanalista em relação aos impasses da clínica. Conclui-se que cada psicanalista necessita ressignificar sua atividade, o que inclui o constante exercício de des-idealização de diversos aspectos inerentes à profissão, e o cuidado com sua oferta na Cultura, com a difusão da Psicanálise, além de uma nova tomada de posição frente à formação geral e específica

This study approaches the psychoanalysts labour, taking as its apex of investigation the difficulties these professionals are faced with in their daily practice. In this context, changes in the patients profile, the crises of demand due to the varied and expanding competition of psychofarmacotherapy and psychotherapy, relevant requirements in his/her professional formation, the establishment of bonds with other analysts, and the vicissitudes related to quality time can be considered as indicators of the uneasiness the psychoanalyst feels when he/she is involved in the process of psychoanalyzing nowadays. Thus, keeping the goal of delving into the tribulations of the impossible profession so stressed by Freud, this research takes as its methodological guideline a central concept called professional narcissism, conceived from the notion of narcissism suggested by Freud and developed by Lacan. By means of specific pieces, it investigates three authors Freud, Ferenczi and Lacan. In Freud it prioritises the problems related to handling transference and the demands of the analyst himself/herself in his professional practice. As to Ferenczi, it reveals the troubles the psychoanalyst goes through concerning issues such as time and money, especially as to what he reports by means of the correspondence exchanged with Freud. As far as Lacan is concerned, it prioritises testimonies and reports of those he lived close to, pointing at the multiple forms of identification generated and the advent of Lacanism, which has led to the emergence of a new sort of psychoanalyst, one who takes over the mission of defending the true psychoanalysis in the world, by returning to Freud via Lacan. This study problematizes the forms of confrontation of the difficulties mentioned: a possible treatment through personal analysis of the psychoanalysts themselves, the building of new bonds among the field participants, their involvement with reading and careful study of authors

... inside and outside Psychoanalysis, and with writing here taken as a means of elaboration by the psychoanalyst with regard to the predicaments in his/her practice. The conclusion, thus, is that each psychoanalyst needs to resignify his/her activity, which includes the constant exercise of deidealization of various aspects inherent in the profession, and caution in providing and diffusing psychoanalysis to Culture, besides taking a new stand concerning his/her general and specific formation

O que é uma criança feliz? Uma contribuição adicional ao debate sobre a questão do gozo e o infantil

Este artigo discute a questão do gozo no tratamento psicanalítico com as crianças, com um foco especial na direção do tratamento, considerando-se que a análise não é uma promessa de felicidade (AU)

Adolescência, psicanálise e educação: o mestre "possível" de adolescentes

Resenha do livro Adolescência, psicanálise e educação: o mestre 'possível' de adolescentes, 2003, editora Avercamp escrito por Beatriz Cauduro Cruz, psicanalista e doutoranda no campo da psicanálise e educação, onde difere de certa literatura que se propõe a dizer algo definitivo sobre esse personagem tão atual: o adolescente (AU)

O dia em que Lacan me adotou: minha análise com Lacan

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A criança, o trauma e a escola: repensando seus efeitos na clínica cotidiana / The child, the trauma and the school: rethinking their affects in daily clinic

Este artigo aborda o conceito de trauma no imaginário escolar e como ele afeta a abordagem clínica. Com base em Freud e Lacan, o autor problematiza alguns pontos que concernem a esse sintoma social contemporâneo e a seus efeitos na prática do psicanalista(AU)

Psicanálise: uma inspira-ação para a psicologia escolar? / Psychoanalysis: an inspire-action to the school psychology?

Investiga a possibilidade de uma inspiração pelo referencial psicanalítico na prática do psicólogo escolar. Parte da narrativa e problematização de uma intervenção realizada entre os anos de 1996 e 1997, junto a um grupo de 10 professores de primeiro grau em uma escola pública. Em 2002, retorna a essa unidade escolar e efetua pesquisa com os professores que participaram da experiência, fazendo uso de entrevistas abertas. Por meio desses testemunhos, analisa as conseqüências desse modelo de intervenção, a viabilidade dessa inspiração pelo referencial psicanalítico e a amplitude da possibilidade da extensão dos conceitos psicanalíticos na Cultura. Conclui, com base nos dados obtidos, articulando-os com a sustentação teórica dos pesquisadores do campo da intersecção entre psicanálise e educação, que a experiência possibilitou desvelar variáveis que devem ser tomadas como objeto de reflexão: a formação do psicólogo para além da repetição de técnicas; a possível relação do psicólogo com a psicanálise, as implicações da transmissão dessa teoria na graduação de psicologia e as questões subjetivas de cada psicólogo que podem estar ligadas às suas escolhas. Por fim, sugere alterações na forma de transmissão de saber que ocorre nos cursos de psicologia (AU)

A criança, seu lugar na contemporaneidade e as implicações na clínica psicanalítica

Porque uma criança é levada ao psicanalista hoje? algo mudou desde os primórdios, quando Melanie Klein e Anna Freud iniciaram suas práticas clínicas nas questões da infância? Este artigo tenta interrogar sobre a posição ética do psicanalista quando é defrontado com as demandas atuais, especialmente aquelas geradas na escola, bem como aquelas relacionadas com o narcisismo parental (AU)

O psicólogo e sua prática na escola pública. Apontamentos para uma reflexão sobre a criticidade, a ousadia e a angústia

Este texto discute e questiona a ação do psicólogo num campo específico: a escola pública. Atualmente, um grande número de pesquisas aponta para um aspecto: o fracasso escolar é criado dentro das escolas, fato que deveria ser cuidadosamente focado nas intervenções dos psicólogos. Desafor-tunadamente, tal atitude não tem sido encontrada nas práticas regulares dos profissionais, devido a uma falta de criticidade, derivada prioritariamente de uma formação lacunar, facilmente encontrada na maioria dos cursos de Psicologia (AU)

Psicanálise: mais uma receita para a salvação das escolas?

Este trabalho se refere a uma problematização sobre a utilização do referencial psicanalítico no campo educativo. Trata da busca por saberes que caracterizam a contemporaneidade e suas instituições, em particular a escola e seus fenômenos característicos. Propõe também alguns caminhos para o deslizamento nesta questão, apontando outros ângulos desse fenômeno (AU)

Psicanálise e educação: um olhar sobre a criança-consumidora e a escola nos dias atuais / Psychoanalysis and education: a look at child-consumers and schools today

O que é uma criança, hoje? Essa questão é a base para este artigo, e tenta interrogar sobre a posição ética do psicanalista frente às variadas demandas, especialmente aquelas derivadas da escola e também aquelas conjugadas com o narcisismo dos pais(AU)

A escola pública, as crianças que não aprendem e os psicólogos clínicos. Repensando essa relação complicada

O artigo aponta os limites da visão predominante clínica para as questões do trabalho do educador e propõe um modo alternativo de reflexão sobre a realidade escolar(AU)