Early Effects on T lymphocyte Response to Iron Deficiency in Mice. Short Communication

Iron deficiency is a common nutritional disorder, affecting about 30% of the world population. Deficits in iron functional compartments have suppressive effects on the immune system. Environmental problems, age, and other nutrient deficiencies are some of the situations which make human studies difficult and warrant the use of animal models. This study aimed to investigate alterations in the immune system by inducing iron deficiency and promoting recuperation in a mouse model. Hemoglobin concentration, hematocrit, liver iron store, and flow cytometry analyses of cell-surface transferrin receptor (CD71) on peripheral blood and spleen CD4+ and CD8+ T lymphocyte were performed in the control (C) and the iron-deficient (ID) groups of animals at the beginning and end of the experiment. Hematological indices of C and ID mice were not different but the iron stores of ID mice were significantly reduced. Although T cell subsets were not altered, the percentage of T cells expressing CD71 was significantly increased by ID. The results suggest that iron deficiency induced by our experimental model would mimic the early events in the onset of anemia, where thymus atrophy is not enough to influence subset composition of T cells, which can still respond to iron deficiency by upregulating the expression of transferrin receptor.

DNAhsp65 vaccination induces protection in mice against Paracoccidioides brasiliensis infection

Heat-shock proteins are Molecules with extensive data showing their potential as immunomodulators of different types of diseases, The gene of HSP65 from Mycobacterium leprae has shown prophylactic and immunotherapeutic effects against a broad arrays of experimental models including tuberculosis, leishmaniasis, arthritis and diabetes. With this in mind, we tested the DNAhsp65 vaccine using an experimental model of Paraccocidiodomycosis, an important endemic mycosis in Latin America. The intramuscular immunization with DNAhsp65 induced, in BALB/c mice, an increase of Th1-levels cytokines and a reduction of fungal burdens resulted in a marked reduction of collagen and lung remodeling. DNAhsp65 may be an attractive candidate for prevention, therapy and as an adjuvant for mycosis treatment. (C) 2008 Elsevier Ltd. All rights reserved.

Amphotericin B in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles against paracoccidioidomycosis

The present study reports on the preparation and testing of a desoxycholate amphotericin B (D-AMB) sustained delivery system based on poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) polymeric blends (Nano-D-AMB) aimed at reducing the number of AMB administrations required to treat mycosis. BALB/c mice were infected with the yeast Paracoccidioides brasiliensis intravenously to mimic the chronic form of paracoccidioidomycosis. At 30 days post-infection, the animals were treated with Nano-D-AMB [6 mg/kg of encapsulated D-AMB, intraperitoneally (ip), interval of 72 h] or D-AMB (2 mg/kg, ip, interval of 24 h). Drug efficacy was investigated by the fungal burden recovery from tissues. Toxicity was assessed by renal and hepatic biochemical parameters, physical appearance of the animals and haematological investigation. The control groups used were non-infected and the infected mice mock treated with PBS. Nano-D-AMB presented results comparable to free D-AMB, with a marked antifungal efficacy. The Nano-D-AMB-treated group presented lower loss of body weight and absence of stress sign (piloerection and hypotrichosis) observed after D-AMB treatment. No renal [blood urea nitrogen (BUN), creatinine] or hepatic (pyruvic and oxalacetic glutamic transaminases) biochemical abnormalities were found. The micronucleus assay showed no significant differences in both the micronucleus frequency and percentage of polychromatic erythrocytes for Nano-D-AMB, indicating the absence of genotoxicity and cytotoxic effects. The D-AMB-coated PLGA-DMSA nanoparticle showed antifungal efficacy, fewer undesirable effects and a favourable extended dosing interval. Nano-D-AMB comprises an AMB formulation able to lessen the number of drug administrations. Further studies would elucidate whether Nano-D-AMB would be useful to treat systemic fungal infections such as paracoccidioidomycosis, candidiasis, aspergillosis and cryptococcosis.

Heroin-assisted treatment as a response to the public health problem of opiate dependence

Injection drug use (involving the injection of illicit opiates) poses serious public health problems in many countries. Research has indicated that injection drug users are at higher risk for morbidity in the form of HIV/AIDS and Hepatitis B and C, and drug-related mortality, as well as increased criminal activity. Methadone maintenance treatment is the most prominent form of pharmacotherapy treatment for illicit opiate dependence in several countries, and its application varies internationally with respect to treatment regulations and delivery modes. In order to effectively treat those patients who have previously been resistant to methadone maintenance treatment, several countries have been studying and/or considering heroin-assisted treatment as a complementary form of opiate pharmacotherapy treatment. This paper provides an overview of the prevalence of injection drug use and the opiate dependence problem internationally, the current opiate dependence treatment landscape in several countries, and the status of ongoing or planned heroin-assisted treatment trials in Australia, Canada and certain European countries.

The Internationalization Process as Generator Element of Dynamic Capacities: the case of WEG in Argentina and China

The objective of he article is to research the dynamic capacities developed and used by WEG in its internationalization process and to explain how these capacities help the company defends and supports competitive advantage. The article presents an exploratory study of the internationalization process of WEG in Argentina and China. This article has as analysis approach the dynamic capacities, contributes to the literature of international management in two aspects. First, it adds the analytical look of the internationalization based on dynamic capacities that are still well restricted. Second, when working the dynamic capacities as central element of the analysis of the internationalization process, it Proposes one framework of integrative analysis of the economic and behavioral theories that are used to explain the process of companies`-internationalization, although they are dealt independently and sometimes antagonistic way. The result shows as the dynamic capacities are articulated in the base of WEG in its process of internationalization for Argentina and the subsequent movement for China. The developed dynamic capacities in Argentina were acquired for the Brazilian headquarter and could have been applied in the process of internationalization for China. However, a more complex organizational structure cannot be identified where the inter-subsidiary relationships could share dynamic capacities as proposed in framework.

Cranial anatomy of a new genus of hyperodapedontine rhynchosaur (Diapsida, Archosauromorpha) from the Upper Triassic of southern Brazil

Detailed description of the cranial anatomy of the rhynchosaur previously known as Scaphonyx sulcognathus allows its assignment to a new genus Teyumbaita. Two nearly complete skulls and a partial skull have been referred to the taxon, all of which come from the lower part of the Caturrita Formation, Upper Triassic of Rio Grande do Sul, southern Brazil. Cranial autapomorphies of Teyumbaita sulcognathus include anterior margin of nasal concave at midline, prefrontal separated from the ascending process of the maxilla, palatal ramus of pterygoid expanded laterally within palatines, dorsal surface of exoccipital markedly depressed, a single tooth lingually displaced from the main medial tooth-bearing area of the maxilla, and a number of other characters (such as skull broader than long; a protruding orbital anterior margin; anguli oils extending to anterior ramus of the jugal; bar between the orbit and the lower temporal fenestra wider than 0.4 of the total orbital opening; mandibular depth reaching more than 25% of the total length) support its inclusion in Hyperodapedontinae. T. sulcognathus is the only potential Norian rhynchosaur, suggesting that the group survived the end-Carnian extinction event.

Multicusped crocodyliform teeth from the Upper Cretaceous (Sao Jose do Rio Preto Formation, Bauru Group) of Sao Paulo, Brazil

The six peculiar multicusped teeth described here were collected from sediments of the Upper Cretaceous of Sao Jose do Rio Preto Formation, near Ibira (northeastern Sao Paulo, Brazil). Their bulbous crowns are slightly labio-lingual compressed, and bear a main plus two accessory cusps, which conceal a well developed cingulum. Wear facets are seen on the main and distal accessory cusps. Comparison to the known Crocodyliformes with multicusped teeth show that the new material is not referable to ""protosuchians"" or eusuchians, nor related to two unnamed forms from Morocco and ""notosuchians"" such as Uruguaysuchus, Chiamaerasuchus, and Simosuchus. On the other hand, possible affinities with Candidodon and Malawisuchus were maintained based on shared traits. This includes teeth with the main cusp and some accessory cusps arranged in more than one axis, a previously defined unambiguous apomorphy of the putative clade composed of Candidodon plus Malawisuchus. The term Candidodontidae can be applied to this group, and defined as all taxa closer to Candidodon itapecuruensis than to Notosuchus terrestris, Uruguaysuchus aznarezi, Comahuesuchus brachybuccalis, Sphagesaurus huenei, Baurusuchus pachecoi, and Crocodylus niloticus. (C) 2009 Elsevier Ltd. All rights reserved.

In Vitro Antifungal Activity and Toxicity of Itraconazole in DMSA-PLGA Nanoparticles

Itraconazole (ITZ) is a drug used to treat various fungal infections and may cause side effects. The aim of this study was to develop and evaluate the in vitro activity of DMSA-PLGA nanoparticles loaded with ITZ against Paracoccidioides brasiliensis, as well as their cytotoxicity. Nanoparticles were prepared using the emulsification-evaporation technique and characterized by their encapsulation efficiency, morphology (TEM), size (Nanosight) and charge (zeta potential). Antifungal efficacy in P brasiliensis was determined by minimal inhibition concentration (MIC), and cytotoxicity using MU assay. ITZ was effectively incorporated in the PLGA-DMSA nanoparticles with a loading efficiency of 72.8 +/- 3.50%. The shape was round with a solid polymeric structure, and a size distribution of 174 +/- 86 nm (Average +/- SD). The particles were negatively charged. ITZ-NANO presented antifungal inhibition (MIC = 6.25 ug/mL) against P brasiliensis and showed lower in vitro cytotoxicity than free drug (ITZ).

Bioreduction of beta-carboline imines to amines employing Saccharomyces bayanus

beta-Carboline imine reductions mediated by Saccharomyces bayanus have been described achieving moderate to good enantiomeric excesses of the amine products. The enantiomeric excesses of the bioreduction showed a dependence on the imine substituents. Compounds presenting C(1)-C(11) aliphatic substituent groups afforded amines with an (S)-configuration, whereas C(15) and higher aliphatic, and aromatic substituted B-carboline imines achieved inversion of the configuration in the final (R)-2 amine products. Based on this data, a model for the Saccharomyces reduction is proposed. (C) 2010 Elsevier Ltd. All rights reserved.

A New Family of Distance Functions for Perceptual Similarity Retrieval of Medical Images

A long-standing challenge of content-based image retrieval (CBIR) systems is the definition of a suitable distance function to measure the similarity between images in an application context which complies with the human perception of similarity. In this paper, we present a new family of distance functions, called attribute concurrence influence distances (AID), which serve to retrieve images by similarity. These distances address an important aspect of the psychophysical notion of similarity in comparisons of images: the effect of concurrent variations in the values of different image attributes. The AID functions allow for comparisons of feature vectors by choosing one of two parameterized expressions: one targeting weak attribute concurrence influence and the other for strong concurrence influence. This paper presents the mathematical definition and implementation of the AID family for a two-dimensional feature space and its extension to any dimension. The composition of the AID family with L (p) distance family is considered to propose a procedure to determine the best distance for a specific application. Experimental results involving several sets of medical images demonstrate that, taking as reference the perception of the specialist in the field (radiologist), the AID functions perform better than the general distance functions commonly used in CBIR.

Sweeping democracy: considerations on the political relations between Janio Quadros and the National Congress

This article examines the relation between President Janio Quadros and the National Congress during the early 1960`s. Based on the analysis of the discourse of these figures, it proposes that Quadros maneuvered to diminish the legitimacy of the Congress in the public opinion, thus disrespecting its constitutional competencies. Consequently, it shows that not only did the Congress structure political mechanisms in an attempt to recover its credibility with society, but also that this dispute and its results had important effects on President Joao Goulart`s administration and even on the 1964 military coup.

Persistence of ventilatory defect after resolution of pulmonary interstitial emphysema in a preterm baby

Pulmonary interstitial emphysema is a common complication of mechanical ventilation in preterm babies. We report a case of severe unilateral pulmonary interstitial emphysema in a premature newborn, treated with high-frequency oscillatory ventilation, lateral decubitus positioning and selective intubation. After complete radiological resolution of the pulmonary emphysema in the left lung, the patient was studied by electrical impedance tomography and a marked reduction of ventilation was identified in the left lung despite radiological resolution of the cysts. This finding indicates that functional abnormalities may persist for longer periods after radiologic resolution of such lesions.

Bladder irrigation with amphotericin B and fungal urinary tract infection-systematic review with meta-analysis

Background: Candiduria is a hospital-associated infection and a daily problem in the intensive care unit. The treatment of asymptomatic candiduria is not well established and the use of amphotericin B bladder irrigation (ABBI) is controversial. The aim of this systematic review was to determine the best place for this therapy in practice. Methods: The databases searched in this study included MEDLINE, EMBASE, Web of Science, and LILACS (January 1960-June 2007). We included manuscripts with data on the treatment of candiduria using ABBI. The studies were classified as comparative, dose-finding, or non-comparative. Results: From 213 studies, nine articles (377 patients) met our inclusion criteria. ABBI showed a higher clearance of the candiduria 24 hours after the end of therapy than fluconazole (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.32-1.00). Fungal culture 5 days after the end of both therapies showed a similar response (OR 1.51, 95% CI 0.81-2.80). The evaluation of ABBI using an intermittent or continuous system of delivery showed an early candiduria clearance (24 hours after therapy) of 80% and 82%, respectively (OR 0.87, 95% CI 0.52-1.36). Candiduria clearance at >5 days after the therapy showed a superior response using continuous bladder irrigation with amphotericin B (OR 0.52, 95% CI 0.29-0.94). The use of continuous ABBI for more than 5 days showed a better result (88% vs. 78%) than ABBI for less than 5 days, but without significance (OR 0.55, 95% CI 0.34-1.04). Conclusion: Although the strength of the results in the underlying literature is not sufficient to allow the drawing of definitive conclusions, ABBI appears to be as effective as fluconazole, but it does not offer systemic antifungal therapy and should only be used for asymptomatic candiduria. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Local immunological factors associated with recurrence of mucosal leishmaniasis

Recurrence of mucosal leishmaniasis (ML) is frequent, but the causative mechanisms are unknown. Our aim was to compare cellular and cytokine patterns of lesions from ML that evolved to recurrence or cure in order to determine the risk factor associated with recurrence. Lesions were evaluated by immunohistochemistry before and after therapy, and patients were followed-up for five years. Higher levels of CD4(+) T and IFN-gamma-producing cells were detected in active lesions and decreased after therapy. Macrophages and IL-10 were markedly increased in cured patients. Conversely, CD8(+) T and NK cells were higher in relapsed than in cured cases. Notably, a decrease in these cells in addition to decreased IL-10 and IFN-gamma was also observed after therapy. These data suggest that exacerbated CD8(+) activity, in addition to a poor regulatory response, could underlie an unfavorable fate with regard to ML. These markers may be useful for predicting the prognosis of ML in lesion studies. (C) 2008 Elsevier Inc. All rights reserved.