Coordenação gestual na produção de encontros consonantais em crianças com desenvolvimento de linguagem típico e atípico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Minimal change disease associated with type 1 and type 2 diabetes mellitus

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents. Arq Bras Endocrinol Metab. 2012;56(5):331-5

Signal transduction in Plasmodium-Red Blood Cells interactions and in cytoadherence

Malaria is responsible for more than 1.5 million deaths each year, especially among children (Snow et al. 2005). Despite of the severity of malaria situation and great effort to the development of new drug targets (Yuan et al. 2011) there is still a relative low investment toward antimalarial drugs. Briefly there are targets classes of antimalarial drugs currently being tested including: kinases, proteases, ion channel of GPCR, nuclear receptor, among others (Gamo et al. 2010). Here we review malaria signal transduction pathways in Red Blood Cells (RBC) as well as infected RBCs and endothelial cells interactions, namely cytoadherence. The last process is thought to play an important role in the pathogenesis of severe malaria. The molecules displayed on the surface of both infected erythrocytes (IE) and vascular endothelial cells (EC) exert themselves as important mediators in cytoadherence, in that they not only induce structural and metabolic changes on both sides, but also trigger multiple signal transduction processes, leading to alteration of gene expression, with the balance between positive and negative regulation determining endothelial pathology during a malaria infection.

Abscesso hepático de origem hematogênica em paciente com febre de origem indeterminada

OBJETIVO: Descrever uma apresentação atípica de abscesso hepático em paciente pediátrico e realizar uma revisão da literatura no que diz respeito às diferenças observadas na etiopatogenia do quadro, quando considerados os países desenvolvidos e aqueles em desenvolvimento. DESCRIÇÃO DO CASO: Paciente de 13 anos, do sexo masculino, foi trazido ao pronto-socorro pediátrico devido à febre diária e à perda de peso, sem alterações ao exame físico. Na investigação realizada, o ultrassom abdominal evidenciou área heterogênea nodulariforme relativamente definida, compatível com abscesso hepático. Foi realizada drenagem cirúrgica e antibioticoterapia. No material da drenagem houve crescimento de Staphylococcus aureus sensível à oxacilina. COMENTÁRIOS: O caso demonstra a importância de o pediatra conhecer as principais causas da febre de origem indeterminada, saber desenvolver a abordagem investigativa e, frente ao diagnóstico de abscesso hepático, aferir a possibilidade de o agente etiológico ser o Staphylococcus aureus, principalmente quando houver relato de rotura da pele.

Base racional e plano de estudo prospectivo para avaliar o efeito de terapêutica antiplaquetária e vasodilatadora microcirculatória em pacientes com cardiopatia chagásica crônica e distúrbios microvasculares coronários

INTRODUÇÃO: Há evidência, embasada por estudos em modelos experimentais de infecção pelo Trypanosoma cruzi, e também por investigações histopatológicas em humanos com a doença de Chagas, de que distúrbios de natureza isquêmica participem da patogênese de lesões miocárdicas na fase crônica da moléstia. Esses distúrbios isquêmicos derivam de desregulação microcirculatória. Dor precordial atípica é sintoma comum em pacientes na fase crônica da doença de Chagas. Em substancial proporção desses pacientes, apesar da inexistência de obstruções coronárias angiograficamente detectáveis, documenta-se com cintilografia miocárdica a ocorrência de distúrbios perfusionais durante o estresse, que são reversíveis após repouso. MÉTODOS: Estudo unicêntrico, prospectivo, de coorte única, com intervenção terapêutica seguida de reavaliação quantitativa, após 90 dias, da área ventricular apresentando alterações perfusionais isquêmicas inicialmente detectadas em pacientes cardiopatas chagásicos com coronárias angiograficamente normais. A cintilografia miocárdica de perfusão será executada com o método SPECT, antes e após 90 dias da intervenção terapêutica, tendo o sestamibi-Tc99m como radiotraçador e o esforço físico ou o estímulo vasodilatador com dipiridamol como estressores. A intervenção terapêutica consistirá de ácido acetilsalicílico (dose de 100 mg diária) associado a verapamil (dose diária de 160 mg, em duas tomadas de 80 mg). O desfecho primário do estudo será redução > 50% da área ventricular de isquemia miocárdica reversível calculada pelo mapa polar da cintilografia miocárdica de perfusão. CONCLUSÕES: Este é o primeiro estudo de intervenção terapêutica para atenuar ou reverter alterações miocárdicas isquêmicas de origem microvascular em pacientes com cardiopatia chagásica crônica.

IFN-γ-induced priming maintains long-term strain-transcending immunity against blood-stage Plasmodium chabaudi malaria

The mechanism by which protective immunity to Plasmodium is lost in the absence of continued exposure to this parasite has yet to be fully elucidated. It has been recently shown that IFN-γ produced during human and murine acute malaria primes the immune response to TLR agonists. In this study, we investigated whether IFN-γ-induced priming is important to maintain long-term protective immunity against Plasmodium chabaudi AS malaria. On day 60 postinfection, C57BL/6 mice still had chronic parasitemia and efficiently controlled homologous and heterologous (AJ strain) challenge. The spleens of chronic mice showed augmented numbers of effector/effector memory (TEM) CD4(+) cells, which is associated with increased levels of IFN-γ-induced priming (i.e., high expression of IFN-inducible genes and TLR hyperresponsiveness). After parasite elimination, IFN-γ-induced priming was no longer detected and protective immunity to heterologous challenge was mostly lost with >70% mortality. Spontaneously cured mice had high serum levels of parasite-specific IgG, but effector T/TEM cell numbers, parasite-driven CD4(+) T cell proliferation, and IFN-γ production were similar to noninfected controls. Remarkably, the priming of cured mice with low doses of IFN-γ rescued TLR hyperresponsiveness and the capacity to control heterologous challenge, increasing the TEM cell population and restoring the CD4(+) T cell responses to parasites. Contribution of TLR signaling to the CD4(+) T cell responses in chronic mice was supported by data obtained in mice lacking the MyD88 adaptor. These results indicate that IFN-γ-induced priming is required to maintain protective immunity against P. chabaudi and aid in establishing the molecular basis of strain-transcending immunity in human malaria.

Liver accumulation of Plasmodium chabaudi-infected red blood cells and modulation of regulatory T Cell and dendritic cell responses

It is postulated that accumulation of malaria-infected Red Blood Cells (iRBCs) in the liver could be a parasitic escape mechanism against full destruction by the host immune system. Therefore, we evaluated the in vivo mechanism of this accumulation and its potential immunological consequences. A massive liver accumulation of P. c. chabaudi AS-iRBCs (PciRBCs) was observed by intravital microscopy along with an over expression of ICAM-1 on day 7 of the infection, as measured by qRT-PCR. Phenotypic changes were also observed in regulatory T cells (Tregs) and dendritic cells (DCs) that were isolated from infected livers, which indicate a functional role for Tregs in the regulation of the liver inflammatory immune response. In fact, the suppressive function of liver-Tregs was in vitro tested, which demonstrated the capacity of these cells to suppress naive T cell activation to the same extent as that observed for spleen-Tregs. On the other hand, it is already known that CD4+ T cells isolated from spleens of protozoan parasite-infected mice are refractory to proliferate in vivo. In our experiments, we observed a similar lack of in vitro proliferative capacity in liver CD4+ T cells that were isolated on day 7 of infection. It is also known that nitric oxide and IL-10 are partially involved in acute phase immunosuppression; we found high expression levels of IL-10 and iNOS mRNA in day 7-infected livers, which indicates a possible role for these molecules in the observed immune suppression. Taken together, these results indicate that malaria parasite accumulation within the liver could be an escape mechanism to avoid sterile immunity sponsored by a tolerogenic environment.

MyD88 signaling is directly involved in the development of murine placental Malaria

Malaria is a widespread infectious disease caused by the parasite Plasmodium. During pregnancy, malaria infection leads to a range of complications that can affect both the mother and fetus, including stillbirth, infant mortality, and low birth weight. In this study, we utilized a mouse model of placental malaria (PM) infection to determine the importance of the protein MyD88 in the host immune response to Plasmodium during pregnancy. Initially, we demonstrated that Plasmodium berghei NK65GFP adhered to placental tissue via chondroitin sulfate A and induced PM in mice with a C57BL/6 genetic background. To evaluate the involvement of MyD88 in the pathology of PM, we performed a histopathological analysis of placentas obtained from MyD88(-/-) and wild-type (WT) mice following infection on the 19th gestational day. Our data demonstrated that the detrimental placental alterations observed in the infected mice were correlated with the expression of MyD88. Moreover, in the absence of this protein, production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) was significantly reduced in the infected mice. More importantly, in contrast to fetuses from infected WT mice, which exhibited a reduction in body weight, the fetuses from infected MyD88(-/-) mice did not display significant weight loss compared to their noninfected littermates. In addition, we observed a decrement of maternal care associated with malaria infection, which was attenuated in the MyD88-deficient mice. Collectively, the results of this study illustrate the pivotal importance of the MyD88 signaling pathway in the pathogenesis of placental malaria, thus presenting new possibilities for targeting MyD88 in therapeutic interventions.

Viagem sem volta. [Depoimento a Rodrigo de Oliveira Andrade]

Fêmeas de pinguins-de-magalhães morrem mais que machos durante migração anual.

A study of the anti-plasmodium activity of angiotensin II analogs

Controlling the dissemination of malaria requires the development of new drugs against its etiological agent, a protozoan of the Plasmodium genus. Angiotensin II and its analog peptides exhibit activity against the development of immature and mature sporozoites of Plasmodium gallinaceum. In this study, we report the synthesis and characterization of angiotensin II linear and cyclic analogs with anti-plasmodium activity. The peptides were synthesized by a conventional solid-phase method on Merrifield's resin using the t-Boc strategy, purified by RP-HPLC and characterized by liquid chromatography/ESI (+) MS (LC-ESI(+)/MS), amino acid analysis, and capillary electrophoresis. Anti-plasmodium activity was measured in vitro by fluorescence microscopy using propidium iodine uptake as an indicator of cellular damage. The activities of the linear and cyclic peptides are not significantly different (p < 0.05). Kinetics studies indicate that the effects of these peptides on plasmodium viability overtime exhibit a sigmoidal profile and that the system stabilizes after a period of 1 h for all peptides examined. The results were rationalized by partial least-square analysis, assessing the position-wise contribution of each amino acid. The highest contribution of polar amino acids and a Lys residue proximal to the C-terminus, as well as that of hydrophobic amino acids in the N-terminus, suggests that the mechanism underlying the anti-malarial activity of these peptides is attributed to its amphiphilic character.

Dinámicas cognitivas de la complejidad poética y lingüística del concepto "TIEMPO". Modelización conceptual en el texto de T.S. Eliot."The Waste Land" (1992)

Programa de doctorado: Nuevas perspectivas cognitivas en los estudios de lengua, literatura, y traducción. Tesis doctoral europea

Reacciones titulares liquenoides

Fil: Rivarola, Emilce. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas

¿Una vanguardia sin vanguardismo? : José Lezama Lima y la revista orígenes

En una evaluación retrospectiva de las actitudes que guiaron al grupo de Orígenes, Cintio Vitier propone una fórmula que procura describir el gesto a la vez disruptivo y conciliador del movimiento liderado por José Lezama Lima: se trataría de una "atípica vanguardia sin vanguardismo". Suprimiendo el "ismo" final, Vitier desea subrayar lo que define como la "catolicidad incorporativa (...) llevada por Lezama hasta sus últimas consecuencias posibles en el mundo contemporáneo" ("La aventura de Orígenes", 1991). Se trataría de constituir una propuesta estética y cultural superadora de parricidios generacionales, exclusiones y negaciones. Sin embargo, si Orígenes no abre su primer número con un manifiesto, sí lo hace manifestándose contra todo ademán beligerante y efímero, a favor de lo "esencial" y perdurable en el arte: "Como no cambiamos de piel con las estaciones, no tenemos que justificar en extensos alegatos una piel de camaleón". Sin embargo Lezama lleva adelante su propuesta integradora contra ciertas actitudes propias de la generación anterior -la relacionada con la revista de avance.¿Habría que coincidir entonces con la fórmula de Vitier respecto de una "vanguardia sin vanguardismo" en el grupo de Orígenes, y más específicamente, en la poética de Lezama? ¿Cuáles son las posibles contradicciones en los planteos lezamianos? Estas son algunas preguntas que guiarán las reflexiones de esta comunicación.

¿Una vanguardia sin vanguardismo? : José Lezama Lima y la revista orígenes

En una evaluación retrospectiva de las actitudes que guiaron al grupo de Orígenes, Cintio Vitier propone una fórmula que procura describir el gesto a la vez disruptivo y conciliador del movimiento liderado por José Lezama Lima: se trataría de una "atípica vanguardia sin vanguardismo". Suprimiendo el "ismo" final, Vitier desea subrayar lo que define como la "catolicidad incorporativa (...) llevada por Lezama hasta sus últimas consecuencias posibles en el mundo contemporáneo" ("La aventura de Orígenes", 1991). Se trataría de constituir una propuesta estética y cultural superadora de parricidios generacionales, exclusiones y negaciones. Sin embargo, si Orígenes no abre su primer número con un manifiesto, sí lo hace manifestándose contra todo ademán beligerante y efímero, a favor de lo "esencial" y perdurable en el arte: "Como no cambiamos de piel con las estaciones, no tenemos que justificar en extensos alegatos una piel de camaleón". Sin embargo Lezama lleva adelante su propuesta integradora contra ciertas actitudes propias de la generación anterior -la relacionada con la revista de avance.¿Habría que coincidir entonces con la fórmula de Vitier respecto de una "vanguardia sin vanguardismo" en el grupo de Orígenes, y más específicamente, en la poética de Lezama? ¿Cuáles son las posibles contradicciones en los planteos lezamianos? Estas son algunas preguntas que guiarán las reflexiones de esta comunicación.

¿Una vanguardia sin vanguardismo? : José Lezama Lima y la revista orígenes

En una evaluación retrospectiva de las actitudes que guiaron al grupo de Orígenes, Cintio Vitier propone una fórmula que procura describir el gesto a la vez disruptivo y conciliador del movimiento liderado por José Lezama Lima: se trataría de una "atípica vanguardia sin vanguardismo". Suprimiendo el "ismo" final, Vitier desea subrayar lo que define como la "catolicidad incorporativa (...) llevada por Lezama hasta sus últimas consecuencias posibles en el mundo contemporáneo" ("La aventura de Orígenes", 1991). Se trataría de constituir una propuesta estética y cultural superadora de parricidios generacionales, exclusiones y negaciones. Sin embargo, si Orígenes no abre su primer número con un manifiesto, sí lo hace manifestándose contra todo ademán beligerante y efímero, a favor de lo "esencial" y perdurable en el arte: "Como no cambiamos de piel con las estaciones, no tenemos que justificar en extensos alegatos una piel de camaleón". Sin embargo Lezama lleva adelante su propuesta integradora contra ciertas actitudes propias de la generación anterior -la relacionada con la revista de avance.¿Habría que coincidir entonces con la fórmula de Vitier respecto de una "vanguardia sin vanguardismo" en el grupo de Orígenes, y más específicamente, en la poética de Lezama? ¿Cuáles son las posibles contradicciones en los planteos lezamianos? Estas son algunas preguntas que guiarán las reflexiones de esta comunicación.