Critical analysis of the allocation policy for liver transplantation in Brazil

Liver transplantation is now the standard treatment for end-stage liver disease. Given the shortage of liver donors and the progressively higher number of patients waiting for transplantation, improvements in patient selection and optimization of timing for transplantation are needed. Several solutions have been suggested, including increasing the donor pool; a fair policy for allocation, not permitting variables such as age, gender, and race, or third-party payer status to play any role; and knowledge of the natural history of each liver disease for which transplantation is offered. To observe ethical rules and distributive justice (guarantee to every citizen the same opportunity to get an organ), the "sickest first" policy must be used. Studies have demonstrated that death has no relationship with waiting time, but rather with the severity of liver disease at the time of inclusion. Thus, waiting time is no longer part of the United Network for Organ Sharing distribution criteria. Waiting time only differentiates between equally severely diseased patients. The authors have analyzed the waiting list mortality and 1-year survival for patients of the State of São Paulo, from July 1997 through January 2001. Only the chronological criterion was used. According to "Secretaria de Estado da Saúde de São Paulo" data, among all waiting list deaths, 82.2% occurred within the first year, and 37.6% within the first 3 months following inclusion. The allocation of livers based on waiting time is neither fair nor ethical, impairs distributive justice and human rights, and does not occur in any other part of the world.

Efeitos do arsênico sôbre a cultura do algodoeiro em terra arenosa

The authors studied the action of arsenic, in the form of lead arsenate and sodium arsenite, on cotton in white sandy soil of Piracicaba, State of S. Paulo, Brazil. The experiment was carried out in Mitscherlich pots, applying increasing quantities of the above mentioned compounds. The following conclusions were reached: sodium arsenite is more toxic than lead arsenate. 48 pounds per acre of lead arsenate and 16 pounds per acre of sodium arsenite reduced the vegetative development and the production of cotton. The roots were more seriously affected than the aerial parts. Sandy soils were sensitive to arsenic toxicity. The arsenic mobilization in the soil seems to depend upon factors such as, the a- cidity, the concentration of Fe2O3, CaO, P2O5 and soil colloids, both clay and humus components. The authors suggest, based on their own experiment and after a detailed study of the literature, the use of organic insecticids which may not leave toxic residues, rotation of crops, application of lime and reduction of arsenical sprays to a mini mum. Arsenic compounds should not be used in soils destined to the cultivation of food plants. Rice should not be planted in soils contaminated by arsenic compounds during several years of cotton cultivation. Future experiments are planed, using other soils such as "terra roxa", in Mitscherlich pots and in field plots.

Gonadal hybrid dysgenesis in Drosophila sturtevanti (Diptera, Drosophilidae)

The occurrence of hybrid dysgenesis was investigated in Drosophila sturtevanti Duda, 1927 using diagnostic crosses similar to those used for induction of dysgenics traits in D. melanogaster. Reciprocal test crosses were made, at 27° C, between an old laboratory strain of D. sturtevanti (COL, from Colombia), assumed to be an M'-like strain, and eight freshly collected strains from several natural populations. The gonadal dysgenesis indices were under 10% in most of crosses, except in hybrids of COL with I27, a strain from Minas Gerais (Brazil), in which the index values were moderate in both directions of crosses (25.71 and 12.87). The smallest productivity was also observed in hybrids of females COL mated to I27 males. No causal relationship between the observed gonadal dysgenesis and mobilization of P element or another transposable element could be effectively established.

Analysis of phenotypes altered by temperature stress and hipermutability in Drosophila willistoni

Drosophila willistoni (Sturtevant, 1916) is a species of the willistoni group of Drosophila having wide distribution from the South of USA (Florida) and Mexico to the North of Argentina. It has been subject of many evolutionary studies within the group, due to its considerable ability to successfully occupy a wide range of environments and also because of its great genetic variability expressed by different markers. The D. willistoni 17A2 strain was collected in 1991 in the state of Rio Grande do Sul, Brazil (30°05'S, 51°39'W), and has been maintained since then at the Drosophila laboratory of UFRGS. Different to the other D. willistoni strains maintained in the laboratory, the 17A2 strain spontaneously produced mutant males white-like (white eyes) and sepia-like (brown eyes) in stocks held at 17°C. In order to discover if this strain is potentially hypermutable, we submitted it to temperature stress tests. Eighteen isofemale strains were used in our tests and, after the first generation, all the individuals produced in each strain were maintained at 29°C. Different phenotype alterations were observed in subsequent generations, similar to mutations already well characterized in D. melanogaster (white, sepia, blistered and curly). In addition, an uncommon phenotype alteration with an apparent fusion of the antennae was observed, but only in the isofemale line nº 31. This last alteration has not been previously described as a mutation in the D. melanogaster species. Our results indicate that the D. willistoni 17A2 strain is a candidate for hypermutability, which presents considerable cryptic genetic variability. Different factors may be operating for the formation of this effect, such as the mobilization of transposable elements, effect of inbreeding and alteration of the heat-shock proteins functions.

Lesões microscopicas do baço na purpura trombocitopenica idiopatica

Histopathological changes strikingly similar were found in the spleen of four cases (young female subjects) of idiopathic thrombocytopenic purpura hemorrhagica in which splenectomy was performed. The chief changes reported are enlargement of the marginal zone of the malpighian corpuscles, proliferation and mobilization of the reticulo-endothelial cells, myeloid metaplasia, local (tissue) eosinophilia, and stoppage of the circulation or stasis of platelets from which results a filling of the spelenic sinuses by such elements. The latter phenomenon will possibly present some bearing with thrombocytopenia which is such a characteristic feature in this disease and will perhaps account for the rapid increase in blood platelets which usually follows splenectomy and or the finding of increased megakaryocytes in the bone marrow.

In vivo kinetics of eosinophils and mast cells in experimental murine Schistosomiasis

During the schistosomiasis infection there is a [quot ]dance of the cells[quot ], varying from site to site and related to the time of infection. 1 - Eosinophil levels exhibit a bimodal pattern, with the first peak related to the egg deposition and maturation and increased Kupfferian hyperplasia; the second peak precedes the death of some adult worms; 2 - The peritoneal eosinophilic levels are inversely proportional to the blood eosinophilic levels; 3 - Eosinopoiesis in the bone marrow begins at day 40, reaching the highest levels at day 50 and coincides with hepatic eosinophilic and neutrophilic metaplasia; 4 - Peritoneal mast cell levels present a bimodal pattern similar to the blood eosinophils, and inverse to the peritoneal eosinophils. They also show a cyclic behaviour within the hepatic and intestinal granulomas. Integral analysis of the events related to the eosinophils in the blood, bone marrow, peritoneal cavity and hepatic and intestinal granulomas allows the detection of two important eosinophilic phases: the first is due to mobilization and redistribution of the marginal pool and the second originates from eosinophilic production in the bone marrow and liver. The productive phase is characterized by an increase in the number of eosinophils and monocyte/macrophages, and a decrease in neutrophils and stabilization of megakariocytes and erithroid lineages.

Experimental murine schistosomiasis mansoni: estabilishment of the chronic phase of the disease

After the acute hyperergic phase of schistosomal infection, the chronic phase of the disease corresponds to the estabilishment of a relative equilibrium between the host and the parasite. This involves: (1) A shift from the predominance of the TH2 response observed in the acute phase, to the predominance of the TH1 response in the chronic phase of the disease, with modification of lymphokine and immunoglobulin secretions patterns. (2) Redistribution of hosts responses to parasite, with predominance of systemic controls in the acute phase, and a shift towards local tissue responses in the chronic phase. This redistribution relieves the hyperergic responses involving the whole body of the host, and delimits cellular and molecular reactions to parasites to only those tissues that are directly involved by the adult parasites and their eggs. Mobilization of eosinophil granulocytes in schistosomal periovular granulomas is one of examples of this redistribution.

Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

Penetration Sites and Migratory Routes of Angiostrongylus costaricensis in the Experimental Intermediate Host (Sarasinula marginata)

The intermediate hosts of Angiostrongylus costaricensis are terrestrian molluscs, mostly of the family Veronicellidae. The present work aimed at clarifying more accurately the sites of penetration and the migratory routes of A. costaricensis in the tissue slugs and at verifying the pattern of the perilarval reaction at different times of infection. Slugs were individually infected with 5,000 L1, and killed from 30 min to 30 days after infection. From 30 min up to 2 hr after infection, L1 were found within the lumen of different segments of the digestive tube having their number diminished in more advanced times after exposition until complete disappearance. After 30 min of exposition, percutaneous infection occurred, simultaneously to oral infection. Perilarval reaction was observed from 2 hr of infection around larvae in fibromuscular layer, appearing later (after 6 hr) around larvae located in the viscera. A pre-granulomatous reaction was characterized by gradative concentration of amebocytes around larvae, evolving two well-organized granulomas. In this work we confirmed the simultaneous occurrence of oral and percutaneous infections. Perilarval reaction, when very well developed, defined typical granulomatous structure, including epithelioid cell transformation. The infection also caused a systemic mobilization of amebocytes and provoked amebocyte-endothelium interactions.

Parameters affecting cellular invasion and escape from the parasitophorous vacuole by different infective forms of Trypanosoma cruzi

In this study we have examined certain aspects of the process of cell invasion and parasitophorous vacuole escape by metacyclic trypomastigotes and extracellular amastigote forms of Trypanosoma cruzi (G strain). Using Vero (and HeLa) cells as targets, we detected differences in the kinetics of vacuole escape by the two forms. Alcalinization of intercellular pH influenced both invasion as well as the escape from the parasitophorous vacuole by metacyclic trypomastigotes, but not the escape kinetics of extracellular amastigotes. We used sialic acid mutants as target cells and observed that the deficiency of this molecule facilitated the escape of both infective forms. Hemolysin activity was only detected in extracellular amastigotes and neither form presented detectable transialidase activity. Invasion of extracellular amastigotes and trypomastigotes in Vero cells was affected in different ways by drugs that interfere with host cell Ca2+ mobilization. These results are in line with previous results that indicate that metacyclic trypomastigotes and extracellular amastigote forms utilize mechanisms with particular features to invade host cells and to escape from their parasitophorous vacuoles.

Primary culture of the region of the amebocyte-producing organ of the snail Biomphalaria glabrata, the intermediate host of Schistosoma mansoni

Biomphalaria glabrata snails are major hosts for the digenetic trematoda Schistosoma mansoni, the causative agent of human schistosomiasis. The success or failure of the infection will be dependent on the mobilization of the molluskan internal defense system, where a major role will be played by circulating hemocytes produced by the APO (amebocyte-producing organ) of the snail. In this report, the primary culture of the APO region of B. glabrata was obtained for the first time, as well as a control culture of the ovotestis. Three different cell populations migrated easily from the explants in culture, with no need of any dispersion agent. The cells grew in suspension at an incubation temperature of 15ºC and the cultures were maintained viable for up to two weeks. Two of these cell populations obtained resembled cell types known to be present in the hemolymph of Biomphalaria. The availability of APO cells in culture may contribute to a better understanding of the internal defense in mollusks, in general, as well as the specific response of B. glabrata to S. mansoni infection.

Hitchhiking Trypanosoma cruzi minicircle DNA affects gene expression in human host cells via LINE-1 retrotransposon

The horizontal transfer of Trypanosoma cruzi mitochondrial minicircle DNA to the genomes of naturally infected humans may play an important role in the pathogenesis of Chagas disease. Minicircle integrations within LINE-1 elements create the potential for foreign DNA mobility within the host genome via the machinery associated with this retrotransposon. Here we document integration of minicircle DNA fragments in clonal human macrophage cell lines and their mobilization over time. The movement of an integration event in a clonal transfected cell line was tracked at three months and three years post-infection. The minicircle sequence integrated into a LINE-1 retrotransposon; one such foreign fragment subsequently relocated to another genomic location in association with associated LINE-1 elements. The p15 locus was altered at three years as a direct effect of minicircle/LINE-1 acquisition, resulting in elimination of p15 mRNA. Here we show for the first time a molecular pathology stemming from mobilization of a kDNA/LINE-1 mutation. These genomic changes and detected transcript variations are consistent with our hypothesis that minicircle integration is a causal component of parasite-independent, autoimmune-driven lesions seen in the heart and other target tissues associated with Chagas disease.

The girl from the Church of the Sacrament: a case of congenital syphilis in XVIII century Lisbon

Syphilis is a sexually or congenitally transmitted infectious disease with an impact on the health of human populations that has undergone important cycles in different countries and periods of history. Its presence was first diagnosed in Europe in the late XIV century. In Portugal, although there are various written records of the infection in the last centuries, there are rare references to it in archeological findings (mummified bodies are also rare in Portugal). The current study describes a probable case of congenital syphilis in an 18-month-old girl buried in the Church of the Sacrament in Lisbon. Her body, dating to the XVIII century, was found mummified together with dozens of others, still not studied. Symmetrical periostitis of the long bones, osteitis, metaphyseal lesions, left knee articular, and epiphyseal destruction, and a rarefied lesion with a radiological appearance compatible with Wimberger's sign all point to a diagnosis of congenital syphilis. The diagnosis of this severe form of the infection, possibly related to the cause of death in this upper-class girl, calls attention to the disease's presence in XVIII century Lisbon and is consistent with the intense mobilization at the time in relation to the risks posed by so-called heredosyphilis. It is the first case of congenital syphilis in a child reported in archeological findings in Portugal, and can be correlated with other cases in skeletons of adults buried in cemeteries in Lisbon (in the XVI to XVIII centuries) and Coimbra (XIX century). Finally, this finding highlights the need to study the entire series of mummified bodies in the Church of the Sacrament in order to compare the paleopathological findings and existing historical documents on syphilis, so as to expand the paleoepidemiological knowledge of this infection in XVIII century Lisbon.

Antimalarial drugs disrupt ion homeostasis in malarial parasites

Plasmodium chabaudi malaria parasite organelles are major elements for ion homeostasis and cellular signaling and also target for antimalarial drugs. By using confocal imaging of intraerythrocytic parasites we demonstrated that the dye acridine orange (AO) is accumulated into P. chabaudi subcellular compartments. The AO could be released from the parasite organelles by collapsing the pH gradient with the K+/H+ ionophore nigericin (20 µM), or by inhibiting the H+-pump with bafilomycin (4 µM). Similarly, in isolated parasites loaded with calcium indicator Fluo 3-AM, bafilomycin caused calcium mobilization of the acidic calcium pool that could also be release with nigericin. Interestingly after complete release of the acidic compartments, addition of thapsigargin at 10 µM was still effective in releasing parasite intracellular calcium stores in parasites at trophozoite stage. The addition of antimalarial drugs chloroquine and artemisinin resulted in AO release from acidic compartments and also affected maintenance of calcium in ER store by using different drug concentrations.

Portraying innovation in the public service of Brazil: Frameworks, systematization and characterization

ABSTRACT Innovation is essential for improving organizational performance in both the private and public sectors. This article describes and analyzes the 323 innovation experiences of the Brazilian federal public service that received prizes during the 16 annual competitions (from 1995 to 2012) of the Award for Innovation in Federal Public Management held by the Brazilian National School of Public Administration (ENAP). It is a qualitative and quantitative study in which were employed as categories for analysis the four types of innovation defined in the Copenhagen Manual: product, process, organizational and communication. The survey results allow us to affirm that there is innovation in the public sector, in spite of the skepticism of some researchers and the incipient state of theoretical research on the subject. It was possible to observe that organizational innovation was the one with the highest number of award- -winning experience, followed respectively by process, communication and product innovation, with citizen services and improvement of work processes being the main highlights. The results showed that, although the high incidence of innovation occurs at the national level, a significant number of innovations also occur at the local level, probably because many organizations of the federal government have their actions spread only at this level of government. Concerning the innovative area, health and education predominate, with almost 33% of initiatives, which can be explained by capillarity of these areas and the fact that both maintain a strong interaction with the user. The contributions of this work include the use of theoretical model of innovation analysis in the public sector in Brazil still upcoming, and the systematization of knowledge in empirical basis for this innovation. In this sense, it also contributes to the development of the theory with the presentation of evidence that the characteristics, determinants and consequences of innovation in the public sector differ not only from innovation in the industry, but also from innovation in services in the private sector.