Multifunctional CD4⁺ T cells in patients with American cutaneous leishmaniasis

Leishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)-γ-producing CD4(+) T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of multifunctional CD4(+) T cells (28% of the total Th1 response evaluated), whereas LaAg induced predominantly single-positive cells (68%), and 57% of those were IFN-γ single-positives. Multifunctional CD4(+) T cells showed the highest mean fluorescence intensity (MFI) for the three Th1 cytokines assessed and MFIs for IFN-γ and interleukin-2 from those cells stimulated with LbAg were significantly higher than those obtained after LaAg stimulation. These major differences observed in the generation of multifunctional CD4(+) T cells suggest that the quality of the Th1 response induced by L. amazonensis antigens can be involved in the mechanisms responsible for the high susceptibility observed in L. amazonensis-infected individuals. Ultimately, our results call attention to the importance of studying a Th1 response regarding its quality, not just its magnitude, and indicate that this kind of evaluation might help understanding of the complex and diverse immunopathogenesis of American tegumentary leishmaniasis.     

Wild, synanthropic and domestic hosts of Leishmania in an endemic area of cutaneous leishmaniasis in Minas Gerais State, Brazil

Domestic, synanthropic and wild hosts of Leishmania spp. parasites were studied in an area endemic for American tegumentary leishmaniasis (ATL), specifically in northern Minas Gerais State, Brazil. Domestic dogs and small forest mammals are reservoir hosts for L. (Leishmania) infantum. However, the role that these animals play in the transmission cycle of the Leishmania spp. that cause cutaneous leishmaniasis is not well known. This study evaluated 72 rodents, 25 marsupials and 98 domestic dogs found in two villages of the Xakriabá Indigenous Territory, an area of intense ATL transmission. A total of 23 dogs (23.47%) were shown to be positive according to at least one test; 8 dogs (8.16%) tested positive in a single serological test and 15 dogs (15.31%) tested positive by IFAT and ELISA. Eleven dogs were euthanised to allow for molecular diagnosis, of which nine (81.8%) tested positive by PCR for Leishmania in at least one tissue. Seven animals were infected only with L. (L.) infantum, whilst two displayed a mixed infection of L. (L.) infantum and L. (V.) braziliensis. Isoenzymatic characterisation identified L. (L.) infantum parasites isolated from the bone marrow of two dogs. Of the 97 small mammals captured, 24 tested positive for Leishmania by PCR. The results showed that L. (V.) braziliensis, L. (L.) infantum and L. (V.) guyanensis are circulating among wild and synanthropic mammals present in the Xakriabá Reserve, highlighting the epidemiological diversity of ATL in this region.     

Prenatal care and management of hypertension in pregnant women in the public healthcare system in Rio de Janeiro, Brazil

The aim of this study was to assess the adequacy of prenatal care for pregnant women with hypertension as compared to those at low risk. Adequate management of hypertension and associated factors were also investigated. A cross-sectional study was conducted with 1,947 women, 187 of whom with hypertension, in public prenatal care units in Rio de Janeiro, Brazil, in 2007-2008. Demographic and socioeconomic data, obstetric history, and information on adequacy of prenatal care were collected using interviews and prenatal care cards. Adequacy of management of hypertension was evaluated according to performance of health professionals and health services and women's individual characteristics. Chi-square and multivariate logistic regression were used to compare groups and identify factors associated with management of hypertension. Adequacy of prenatal care was 79% and did not differ between groups. Only 27% of pregnant women with hypertension received appropriate management, with poor professional performance. Hypertensive pregnant women with better prenatal care were those with previous neonatal deaths and/or stillbirths and those with 35 years of age and older. Despite adequate use of prenatal care, management of hypertension in pregnant women was inadequate.     

Corticosterone replacement restores normal morphological features to the hippocampal dendrites, axons and synapses of adrenalectomized rats

A thorough evaluation of hippocampal dendrites, axons and synaptic contacts has not been undertaken following prolonged periods of absence of corticosteroids despite the marked granule cell loss which occurs in the dentate gyrus of adrenalectomized rats. Thus, we have applied morphometric techniques to analyse the dendrites of granule and pyramidal cells, the mossy fiber system, and the number and morphology of synapses between the mossy fibers and the excrescences of CA3 pyramidal cells in rats submitted to different periods of adrenalectomy. In addition, to search for the presence of neuritic reorganisation in the hippocampal formation once normal corticosteroid levels were re-established, we incorporated in this study a group of rats replaced with corticosterone one month after adrenalectomy. The results obtained in adrenalectomized rats showed a striking impoverishment of the dendrites of surviving granule cells, subtle alterations in the apical dendritic arborization of CA3 pyramidal cells and no changes in the apical dendrites of CA1 pyramidal cells. In addition, in adrenalectomized rats there was a progressive reduction in the total number of synapses established between mossy fibers and CA3 pyramids, as a consequence of a reduction in the volume of the suprapyramidal part of the mossy fiber system, and profound changes in the morphology of mossy fiber terminals and CA3 dendritic excrescences. A remarkable reorganisation of neurites was found to occur following the administration of low doses of corticosterone, completely reversing the adrenalectomy-induced synaptic loss and partially restoring the morphology of hippocampal axons and dendrites. These plastic mechanisms provide a sound structural basis for the reversibility of cognitive deficits observed after corticosterone administration to adrenalectomized rats.     

Direction of the mental canal in human mandibles

The direction of the mental canal was calculated in the horizontal and vertical planes with a view to aiding anaesthetic techniques. Based on our data, it is advisable to give the following approximate inclinations to the needle when penetrating the mental canal in anaesthetic procedures: 55 degrees postero-anteriorly in relation to a horizontal plane and 40 degrees latero-medially in relation to a horizontal line tangent to the body of the mandible at the level of the mental foramen.     

Síndrome coronária aguda em doente oncológico: um problema evitável?

5-Fluorouracil is a first‐line agent in several cancer‐therapy regimens. Cardiotoxicity is common, with coronary artery disease being an important risk factor. We report the case of an acute coronary syndrome presumably induced by 5‐FU, in a patient with previously unknown and asymptomatic coronary artery disease, with an estimated intermediate risk for cardiovascular events. Pre‐chemotherapy risk evaluation and optimal patient care are still not standardized in this clinical scenario.     

Molecular Pharming: future targets and aspirations

Molecular Pharming represents an unprecedented opportunity to manufacture affordable modern medicines and make these available at a global scale. The area of greatest potential is in the prevention of infectious diseases, particular in underdeveloped countries where access to medicines and vaccines has historically been limited. This is why, at St. George's, we focus on diseases such as HIV, TB and rabies, and aim to develop production strategies that are simple and potentially easy to transfer to developing countries.