Working memory impairment in multiple sclerosis relapsing-remitting patients with episodic memory deficits

Episodic memory is impaired in multiple sclerosis (MS) patients, possibly because of deficits in working memory (WM) functioning. If so, WM alterations should necessarily be found in patients with episodic memory deficits, but this has not yet been demonstrated. In this study we aimed at determining whether episodic memory deficits in relapsing-remitting MS are found in conjunction with impaired WM. We evaluated 32 MS patients and 32 matched healthy controls. Nineteen of the 32 patients had episodic memory impairment, and as a group only these individuals showed deficits in WM capacity, which may lead to difficulty in encoding, and/or retrieving information from episodic memory.

New insights into Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada disease (VKH), a well-established multiorgan disorder affecting pigmented structures, is an autoimmune disorder of melanocyte proteins in genetically susceptible individuals. Several clinical and experimental data point to the importance of the effector role of CD4+ T cells and Th1 cytokines, the relevance of searching a target protein in the melanocyte, and the relevance of the HLA-DRB1*0405 in the pathogenesis of the disease. Vogt-Koyanagi-Harada disease has a benign course when early diagnosed and adequatey treated. Full-blown recurrences are rare after the acute stage of Vogt-Koyanagi-Harada disease is over. On the other hand, clinical findings, such as progressive tissue depigmentation (including sunset glow fundus) and uveitis recurrence, indicate that ocular inflammation may persist after the acute phase. Additionally, indocyanine green angiography findings suggest the presence of choroidal inflammation in eyes without clinically detectable inflammation. The aim of this paper is to review the latest research results on Vogt-Koyanagi-Harada disease pathogenesis and chronic/convalescent stages, which may help to better understand this potentially blinding disease and to improve its treatment.

Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease

Therapeutic failure of benznidazole (BZ) is widely documented in Chagas disease and has been primarily associated with variations in the drug susceptibility of Trypanosoma cruzi strains. In humans, therapeutic success has been assessed by the negativation of anti-T. cruzi antibodies, a process that may take up to 10 years. A protocol for early screening of the drug resistance of infective strains would be valuable for orienting physicians towards alternative therapies, with a combination of existing drugs or new anti-T. cruzi agents. We developed a procedure that couples the isolation of parasites by haemoculture with quantification of BZ susceptibility in the resultant epimastigote forms. BZ activity was standardized with reference strains, which showed IC50 to BZ between 7.6-32 µM. The assay was then applied to isolates from seven chronic patients prior to administration of BZ therapy. The IC50 of the strains varied from 15.6 ± 3-51.4 ± 1 µM. Comparison of BZ susceptibility of the pre-treatment isolates of patients considered cured by several criteria and of non-cured patients indicates that the assay does not predict therapeutic outcome. A two-fold increase in BZ resistance in the post-treatment isolates of two patients was verified. Based on the profile of nine microsatellite loci, sub-population selection in non-cured patients was ruled out.

A century of research: what have we learned about the interaction of Trypanosoma cruzi with host cells?

Since the discovery of Trypanosoma cruzi and the brilliant description of the then-referred to "new tripanosomiasis" by Carlos Chagas 100 years ago, a great deal of scientific effort and curiosity has been devoted to understanding how this parasite invades and colonises mammalian host cells. This is a key step in the survival of the parasite within the vertebrate host, and although much has been learned over this century, differences in strains or isolates used by different laboratories may have led to conclusions that are not as universal as originally interpreted. Molecular genotyping of the CL-Brener clone confirmed a genetic heterogeneity in the parasite that had been detected previously by other techniques, including zymodeme or schizodeme (kDNA) analysis. T. cruzi can be grouped into at least two major phylogenetic lineages: T. cruzi I, mostly associated with the sylvatic cycle and T. cruzi II, linked to human disease; however, a third lineage, T. cruziIII, has also been proposed. Hybrid isolates, such as the CL-Brener clone, which was chosen for sequencing the genome of the parasite (Elias et al. 2005, El Sayed et al. 2005a), have also been identified. The parasite must be able to invade cells in the mammalian host, and many studies have implicated the flagellated trypomastigotes as the main actor in this process. Several surface components of parasites and some of the host cell receptors with which they interact have been described. Herein, we have attempted to identify milestones in the history of understanding T. cruzi- host cell interactions. Different infective forms of T. cruzi have displayed unexpected requirements for the parasite to attach to the host cell, enter it, and translocate between the parasitophorous vacuole to its final cytoplasmic destination. It is noteworthy that some of the mechanisms originally proposed to be broad in function turned out not to be universal, and multiple interactions involving different repertoires of molecules seem to act in concert to give rise to a rather complex interplay of signalling cascades involving both parasite and cellular components.

Search for cytotoxic agents in multiple Laurencia complex seaweed species (Ceramiales, Rhodophyta) harvested from the Atlantic Ocean with emphasis on the Brazilian State of Espírito Santo

The development of new anti-cancer drugs of algal origin represents one of the least explored frontiers in medicinal chemistry. In this regard, the diversity of micro- and macroalgae found in Brazilian coastal waters can be viewed as a largely untapped natural resource. In this report, we describe a comparative study on the cytotoxic properties of extracts obtained from the Laurencia complex: Laurencia aldingensis, L. catarinensis, L. dendroidea, L. intricata, L. translucida, L. sp, and Palisada flagellifera. All of these species were collected in the coastal waters of the State of Espírito Santo, Brazil. Four out of the twelve samples initially investigated were found to show significant levels of toxicity towards a model tumor cell line (human uterine sarcoma, MES-SA). The highest levels of cytotoxicity were typically associated with non-polar (hexane) algal extracts, while the lowest levels of cytotoxicity were found with the corresponding polar (methanol) extracts. In this report, we also describe a biological model currently in development that will not only facilitate the search for new anti-cancer drug candidates of algal origin, but also permit the identification of compounds capable of inducing the destruction of multi-drug resistant tumors with greater efficiency than the pharmaceuticals currently in clinical use.

Fatores relacionados à ocorrência de leishmaniose tegumentar no Vale do Ribeira

INTRODUÇÃO: este estudo teve como objetivo identificar fatores ambientais e sociais determinantes na incidência da leishmaniose tegumentar americana no Vale do Ribeira no período de 1998 a 2006. MÉTODOS: foram utilizados dados secundários de domínio público dos 23 municípios que integram a região. O intervalo de tempo foi dividido em três períodos, pelas características gráficas dos coeficientes de incidência, os quais foram submetidos à análise por regressão linear múltipla. RESULTADOS: para o período de 1998 a 2000, as variáveis correlacionadas com a LTA foram índice de desenvolvimento humano médio (p = 0,007), renda per capita (p =0,390) e grau de urbanização (p = 0,079). No período de 2001 a 2003 e 2004 a 2006 as variáveis correlacionadas com LTA foram: a existência de flebotomíneos (p = 0,000 e p = 0,001) e a população urbana média (p = 0,007 e p = 0,001). CONCLUSÕES: esses dados demonstram a tendência de pauperização e urbanização da doença.

Mortes por doenças infecciosas em mulheres: ocorrências no ciclo gravídico-puerperal

OBJETIVO: Descrever os óbitos por doenças infecciosas como causa básica ou múltipla, caracterizando os casos de doença infecciosa preexistente ou desenvolvida na gravidez, aqueles que são mortes maternas por causas obstétricas indiretas e os óbitos por Aids ou outras doenças infecciosas, ocorridos no ciclo gravídico puerperal, havendo dúvidas na classificação. MÉTODOS: Adotou-se a metodologia RAMOS (partindo-se da declaração de óbito -DO- original, dados reais são resgatados por entrevista domiciliar, consultas a prontuários hospitalares e laudos de autopsia; elaborando-se uma nova DO, com as reais causas de morte). População foi constituída pelos óbitos femininos de 10 a 49 anos, de residentes nas capitais brasileiras, do 1º semestre de 2002. As causas foram analisadas em básicas e múltiplas. RESULTADOS: Dos 7.332 óbitos, 917 apresentaram uma doença infecciosa como causa básica (Aids e tuberculose, principalmente). Em 37 casos, a falecida estava no ciclo gravídico puerperal ampliado (englobando, inclusive, mortes ocorridas de 43 dias até um ano pós-parto); 10 não foram classificadas como obstétricas indiretas permanecendo como infecciosas e 14 eram obstétricas indiretas. Quanto às causas múltiplas, para 791 mortes, cujas causas básicas não eram maternas nem infecciosas, houve 1.016 menções de doenças infecciosas (média de 1,28 menção/óbito). CONCLUSÃO: Como o número de mortes maternas é pequeno, recomenda-se, que investigações dos casos graves de complicações da gravidez, parto e puerpério que não faleceram (near-miss) sejam feitas, pois, sendo mais numerosos, representam importante subsídio para estudos da mortalidade materna.

Simplified flow cytometric assay to detect minimal residual disease in childhood with acute lymphoblastic leukemia

The detection of minimal residual disease (MRD) is an important prognostic factor in childhood acute lymphoblastic leukemia (ALL) providing crucial information on the response to treatment and risk of relapse. However, the high cost of these techniques restricts their use in countries with limited resources. Thus, we prospectively studied the use of flow cytometry (FC) with a simplified 3-color assay and a limited antibody panel to detect MRD in the bone marrow (BM) and peripheral blood (PB) of children with ALL. BM and PB samples from 40 children with ALL were analyzed on days (d) 14 and 28 during induction and in weeks 24-30 of maintenance therapy. Detectable MRD was defined as > 0.01% cells expressing the aberrant immunophenotype as characterized at diagnosis among total events in the sample. A total of 87% of the patients had an aberrant immunophenotype at diagnosis. On d14, 56% of the BM and 43% of the PB samples had detectable MRD. On d28, this decreased to 45% and 31%, respectively. The percentage of cells with the aberrant phenotype was similar in both BM and PB in T-ALL but about 10 times higher in the BM of patients with B-cell-precursor ALL. Moreover, MRD was detected in the BM of patients in complete morphological remission (44% on d14 and 39% on d28). MRD was not significantly associated to gender, age, initial white blood cell count or cell lineage. This FC assay is feasible, affordable and readily applicable to detect MRD in centers with limited resources.

Causas múltiplas de morte relacionadas às doenças cerebrovasculares no Estado do Paraná

OBJETIVO: Identificar as causas associadas de morte e o número de causas informadas nas declarações de óbito por doenças cerebrovasculares entre residentes no Estado do Paraná. MATERIAL E MÉTODOS: O banco de dados de mortalidade do ano de 2004 foi obtido do Sistema de Informação de Mortalidade disponível no endereço eletrônico do Datasus. A população escolhida foi separada pelo programa TabWin e as causas múltiplas foram processadas pelo programa Tabulador de Causas Múltiplas de Morte. RESULTADOS: O número médio de causas informadas foi de 2,92 para as mulheres e 2,97 para os homens. A maioria dos óbitos (74,8%) foi de pessoas com 65 anos ou mais de idade. Entre as causas associadas aos óbitos por doenças cerebrovasculares se destacaram as doenças do aparelho respiratório (37,9%), as doenças hipertensivas (37,5%) e os sintomas, sinais e achados anormais de exames clínicos e de laboratório (32,3%). CONSIDERAÇÕES FINAIS: Foi observada relativa melhora na qualidade dos dados de mortalidade em relação ao número de causas citadas. A hipertensão arterial como uma das principais causas associadas sugere a necessidade do seu controle no combate à mortalidade por doenças cerebrovasculares. Incentivos devem ser promovidos para estudos com causas múltiplas, para que se utilizem melhor informações tão importantes, que são desprezadas em estudos de mortalidade feitos somente com a causa básica de morte.

Doença pulmonar obstrutiva crônica e fatores associados em São Paulo, SP, 2008-2009

OBJETIVO: Estimar a prevalência e fatores associados à doença pulmonar obstrutiva crônica. MÉTODOS: Estudo transversal, de base populacional com 1.441 indivíduos de ambos os sexos e com 40 anos de idade ou mais no município de São Paulo, SP, entre 2008 e 2009. As informações foram coletadas por meio de entrevistas domiciliares e os participantes foram selecionados a partir de amostragem probabilística, estratificada por sexo e idade, e por conglomerados em dois estágios (setores censitários e domicílios). Foi realizada regressão múltipla de Poisson na análise ajustada. RESULTADOS: Dos entrevistados, 4,2% (IC95% 3,1;5,4) referiram doença pulmonar obstrutiva crônica. Após análise ajustada, identificaram-se os seguintes fatores independentemente associados ao agravo: número de cigarros fumados na vida (> 1.500/nenhum) RP = 3,85 (IC95%: 1,87;7,94), cansar-se com facilidade (sim/não) RP = 2,61 (IC95% 1,39;4,90), idade (60 a 69 anos/50 a 59 anos) RP = 3,27 (IC95% 1,01;11,24), idade (70 anos e mais/50 a 59 anos) RP = 4,29 (IC95% 1,30;14,29), problemas de saúde nos últimos 15 dias (sim/não) RP = 1,31 (IC95% 1,02;1,77), e atividade física no tempo livre (sim/não) RP = 0,57 (IC95% 0,26;0,97). CONCLUSÕES: A prevalência da doença pulmonar obstrutiva crônica é elevada e está associada ao uso do tabaco e idade acima de 60 anos. Os problemas de saúde freqüentes e redução da atividade física no tempo livre podem ser considerados conseqüências dessa doença.

Síndrome metabólica e baixa estatura em adultos da região metropolitana de São Paulo (SP, Brasil)

A desnutrição pregressa, expressa pela baixa estatura, pode ser fator de risco para síndrome metabólica (SM). O objetivo deste estudo foi verificar a prevalência de SM e sua relação com a baixa estatura, possível resultante de desnutrição crônica na infância, em população adulta. Foi feito um estudo transversal em população adulta, com idades entre 20 e 64 anos, residente em município da região metropolitana da cidade de São Paulo (SP). A amostra foi composta por 287 indivíduos, sendo 214 (74,6%) do sexo feminino e 75 (25,4%) do sexo masculino. Foram obtidos dados antropométricos, por meio de exame físico, dados bioquímicos (glicemia, colesterol total e frações, triglicérides) pela coleta de sangue em jejum e dados clínicos. A prevalência padronizada por sexo e idade para a síndrome metabólica foi de 34,0% e para a baixa estatura, 29,0%. A análise por regressão logística múltipla demonstrou associação entre a baixa estatura e a SM, ajustada por sexo, idade, escolaridade, renda, tabagismo, etilismo, atividade física, antecedentes familiares de doenças coronarianas, hipertensão arterial, diabetes e índice de massa corporal. Neste estudo, encontrou-se associação entre SM e baixa estatura, sugerindo que a desnutrição pregressa seja fator de risco para essa morbidade.

Inpatient dermatological consultations in a university hospital

INTRODUCTION: Dermatology is primarily an outpatient specialty, but it also plays an important role in the care of inpatients. METHODS: We conducted a prospective study that recorded data from inpatient dermatology consultation request forms over a period of four months. The study evaluated 313 requests that led to 566 visits, 86 biopsies, 35 laboratory exams, 41 direct microscopic studies, 18 direct immunofluorescence analyses, 14 skin cultures and a few other exams. RESULTS: The most frequent requesting service was internal medicine (24%), followed by neurology (12%), cardiology (11%), infectious diseases and pediatrics (8% each) and psychiatry and general surgery (6% each). The most frequent diagnostic groups were infectious diseases (25%, divided into fungal infections (13%), bacterial infections (7%) and viral infections (5%)), eczemas (15%) and drug reactions (14%). To our knowledge, this is the first study to attempt to evaluate the impact of the consultations by asking multiple-choice questions that were analyzed by the authors. In 31% of the cases, the consultation was considered extremely relevant because it aided in managing the disease that led to admission or treated a potentially severe dermatological disease. In 58% of the cases, the consultation was considered important because it facilitated diagnosis and/or treatment of a dermatological disease that was unrelated to the reason for admission.

Heartworm (Dirofilaria immitis) disease in a Brazilian oncilla (Leopardus tigrinus)

Heartworm disease is caused by the intravascular nematode Dirofilaria immitis, a pathogen of public health importance usually associated to domestic dogs and cats, and to a lesser extend to other mammal species. The oncilla (Leopardus tigrinus) is a threatened neotropic felid species that naturally occurs in Brazil. Here, we report the encounter of adult and larval stages of heartworms in a female specimen of L. tigrinus, probable of free-ranging origin, from Ubatuba, São Paulo, Brazil, which died showing clinical signals compatible with heartworm disease. This was the first reported case of D. immitis infection and associated disease in L. tigrinus, also suggesting that the oncilla acted as a definitive host for this parasite. The present findings confirmed D. immitis as a pathogenic agent for this felid species, thus supporting the recommendation for the inclusion of diagnostic testing for this pathogen in routine health screening procedures for captive and free-ranging oncillas in Brazil, especially in those localities where climate conditions support the occurrence of the parasite. Potential reservoirs as oncillas are established beyond the reach of veterinary care, thus representing a continuing risk for domestic animals and humans acquiring heartworm infection. We encourage further serologic and molecular studies aiming to establish D. immitis prevalences in L. tigrinus and other wild carnivores in the region of Ubatuba, as well as ecological and veterinary studies to access the role of this pathogen for the survival of this threatened felid species.

Spatial clustering analysis of the foot-and-mouth disease outbreaks in Mato Grosso do Sul state, Brazil - 2005

In the southern region of Mato Grosso do Sul state, Brazil, a foot-and-mouth disease (FMD) epidemic started in September 2005. A total of 33 outbreaks were detected and 33,741 FMD-susceptible animals were slaughtered and destroyed. There were no reports of FMD cases in other species than bovines. Based on the data of this epidemic, it was carried out an analysis using the K-function and it was observed spatial clustering of outbreaks within a range of 25km. This observation may be related to the dynamics of foot-and-mouth disease spread and to the measures undertaken to control the disease dissemination. The control measures were effective once the disease did not spread to farms more than 47 km apart from the initial outbreaks.