Coevolutionary networks: a novel approach to understanding the relationships of humans with the infectious agents

Human organism is interpenetrated by the world of microorganisms, from the conception until the death. This interpenetration involves different levels of interactions between the partners including trophic exchanges, bi-directional cell signaling and gene activation, besides genetic and epigenetic phenomena, and tends towards mutual adaptation and coevolution. Since these processes are critical for the survival of individuals and species, they rely on the existence of a complex organization of adaptive systems aiming at two apparently conflicting purposes: the maintenance of the internal coherence of each partner, and a mutually advantageous coexistence and progressive adaptation between them. Humans possess three adaptive systems: the nervous, the endocrine and the immune system, each internally organized into subsystems functionally connected by intraconnections, to maintain the internal coherence of the system. The three adaptive systems aim at the maintenance of the internal coherence of the organism and are functionally linked by interconnections, in such way that what happens to one is immediately sensed by the others. The different communities of infectious agents that live within the organism are also organized into functional networks. The members of each community are linked by intraconnections, represented by the mutual trophic, metabolic and other influences, while the different infectious communities affect each other through interconnections. Furthermore, by means of its adaptive systems, the organism influences and is influenced by the microbial communities through the existence of transconnections. It is proposed that these highly complex and dynamic networks, involving gene exchange and epigenetic phenomena, represent major coevolutionary forces for humans and microorganisms.

Understanding the mechanisms of lung mechanical stress

Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area) or strain (any forced change in length in relation to the initial length) and shear stress (the stress component parallel to a given surface). The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.

The study of public administration in India, the Philippines, Canada and Australia: the universal struggle against epistemic colonization, and toward critical assimilation

The study of public administration has been characterized as a strong international focus, as both governments and scholars have sought to learn from the experience of other societies. While in a perfect world, one would expect a sort of pragmatic universalism, instead, many scholars tend to bring lessons from one country, or from a single cultural reality. This modest contribution lies in showing a series of national experiences rarely brought to the discourse about public administration in Brazil: Canada, Australia, India and the Philippines. Special emphasis will be given to the following: the origins and the development of public administration; the influence of ideology; and the complex tension between global theory and local practices.

Chagas' disease and ageing: the coexistence of other chronic diseases with Chagas' disease in elderly patients

This study aimed to identify the main comorbidities in elderly chagasic patients treated in a reference service and identify possible associations between the clinical form of Chagas' disease and chronic diseases. Ninety patients aged 60 years-old or over were interviewed and their clinical diagnoses recorded. The study population profile was: women (55.6%); median age (67 years); married (51.1%); retired (73.3%); up to four years' education (64.4%); and earning less than two minimum wages (67.8%). The predominant forms of Chagas' disease were the cardiac (46.7%) and mixed forms (30%). There was a greater proportion of mild cardiac dysfunction (84.1%), frequently in association with megaesophagus. The mean number of concurrent diseases was 2.856 ± 1.845, and 33% of the patients had four or more comorbidities. The most frequent were systemic arterial hypertension (56.7%), osteoporosis (23.3%), osteoarthritis (21.2%) and dyslipidemia (20%). Positive correlations were verified between sex and comorbidities and between age group and comorbidities.

Understanding the experiences of caregivers of children with tuberculosis in directly observed therapy

Objective To understand the situations and communications experienced by caregivers of children with tuberculosis (TB) with regard to directly observed therapy (DOT). Method A descriptive exploratory study with a qualitative approach was applied and developed in the ambulatory of Programa Einstein na Comunidade de Paraisópolis (PECP). The data were collected using semi-structured interviews of 13 caregivers of children with TB in DOT. The Collective Subject Discourse (CSD) method was used to analyze the data. Results Seven CSDs were identified and grouped into four categories: "Living in a difficult situation", "Changing the family routine", "Responsibility almost always fall son the mother", and "Adapting to the DOT". Conclusions The difficulties faced by the caregiver of the child at the beginning of DOT significantly changed the familiar routine. The responsibility for its continuity was assigned to the mother, who must adapt to the demands of the treatment and face the situation.

The influence of the human genome on chronic viral hepatitis outcome

The mechanisms that determine viral clearance or viral persistence in chronic viral hepatitis have yet to be identified. Recent advances in molecular genetics have permitted the detection of variations in immune response, often associated with polymorphism in the human genome. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virulence of microbial agents. Several recent advances concerning the influence of human genes in chronic viral hepatitis B and C are discussed in this article: a) the associations between human leukocyte antigen polymorphism and viral hepatic disease susceptibility or resistance; b) protective alleles influencing hepatitis B virus (HBV) and hepatitis C virus (HCV) evolution; c) prejudicial alleles influencing HBV and HCV; d) candidate genes associated with HBV and HCV evolution; d) other genetic factors that may contribute to chronic hepatitis C evolution (genes influencing hepatic stellate cells, TGF-beta1 and TNF-alpha production, hepatic iron deposits and angiotensin II production, among others). Recent discoveries regarding genetic associations with chronic viral hepatitis may provide clues to understanding the development of end-stage complications such as cirrhosis or hepatocellular carcinoma. In the near future, analysis of the human genome will allow the elucidation of both the natural course of viral hepatitis and its response to therapy.

The role of IL-12 in experimental Trypanosoma cruzi infection

Host resistance to Trypanosoma cruzi infection is dependent on both natural and acquired immune responses. During the early acute phase of infection in mice, natural killer (NK) cell-derived IFN-g is involved in controlling intracellular parasite replication, mainly through the induction of nitric oxide biosynthesis by activated macrophages. We have shown that IL-12, a powerful inducer of IFN-g production by NK cells, is synthesized soon after trypomastigote-macrophage interaction. The role of IL-12 in the control of T. cruzi infection in vivo was determined by treating infected mice with anti-IL-12 monoclonal antibody (mAb) and analyzing both parasitemia and mortality during the acute phase of infection. The anti-IL-12 mAb-treated mice had higher levels of parasitemia and mortality compared to control mice. Also, treatment of infected mice with mAb specific for IFN-g or TNF-a inhibited the protective effect of exogenous IL-12. On the other hand, TGF-ß and IL-10 produced by infected macrophages inhibited the induction and effects of IL-12. Therefore, while IL-12, TNF-a and IFN-g correlate with resistance to T. cruzi infection, TGF-ß and IL-10 promote susceptibility. These results provide support for a role of innate immunity in the control of T. cruzi infection. In addition to its protective role, IL-12 may also be involved in the modulation of T. cruzi-induced myocarditis, since treatment of infected mice with IL-12 or anti-IL-12 mAb leads to an enhanced or decreased inflammatory infiltrate in the heart, respectively. Understanding the role of the cytokines produced during the acute phase of T. cruzi infection and their involvement in protection and pathogenesis would be essential to devise new vaccines or therapies.

The role of chemokines and chemokine receptors in eosinophil activation during inflammatory allergic reactions

Chemokines are important chemotactic cytokines that play a fundamental role in the trafficking of leukocytes to sites of inflammation. They are also potent cell-activating factors, inducing cytokine and histamine release and free radical production, a fact that makes them particularly important in the pathogenesis of allergic inflammation. The action of chemokines is regulated at the level of agonist production and processing as well as at the level of receptor expression and coupling. Therefore, an analysis of the ligands must necessarily consider receptors. Eosinophils are target cells involved in the allergic inflammatory response since they are able to release a wide variety of mediators including CC and CXC chemokines and express their receptors. These mediators could damage the airway epithelial cells and might be important to stimulate other cells inducing an amplification of the allergic response. This review focuses on recently emerging data pertaining to the importance of chemokines and chemokine receptors in promoting eosinophil activation and migration during the allergic inflammatory process. The analysis of the function of eosinophils and their chemokine receptors during allergic inflammation might be a good approach to understanding the determinants of asthma severity and to developing novel therapies.

Studies on mosquitoes (Diptera: Culicidae) and anthropic environment: 3- Survey of adult stages at the rice irrigation system and the emergence of Anopheles albitarsis in South-Eastern, Brazil

A study of adult Culicidae ecology was carried out from January 1992 through January 1993 at the rice irrigation system of the Ribeira Valley Experimental Station. The adaptation of Anopheles albitarsis to the anthropic environment became evident through the adult collections made at its various habitats represented by the irrigation system and the edge of the residual pond, as well as at those made within the local patchy residual woods. Other potential disease vectors were prevalent in the irrigated system too. There were Aedes scapularis, Culex nigripalpus and Cx. ribeirensis that were collected at various habitats. Remarkable differences among their prevalences were obtained such as between the natural forest and anthropic environments. In the former An. albitarsis was practically non-existent, thus suggesting that it might be considered as eusynathropic. As the populations of other species seemed to increase in the anthropic environment, they may be regarded as hemisynanthropes. Observations suggest the hypothesis that the development of irrigated land may be a factor in the emergence of An. albitarsis, and some other species, as well as the possibility of an increase in the transmission of mosquito-borne diseases such as malaria.

Recommendations for the detection of Leptospira in urine by PCR

In the present study PCR was applied to detect leptospires in human urine. Several approaches for sample processing were evaluated to optimize the detection of leptospires in urine mixed with this bacterium. Furthermore, some changes in the composition of the reaction mix were studied. No amplification was observed in acidic urine, therefore neutralization of the sample immediately after collection is strongly recommended. PBS gave better results than Tris or NaOH as neutralizing reagents. Freezing and thawing of samples before processing yielded negative results. Elimination of epithelial cells, leukocytes and crystals by centrifugation at 3,000 rpm at room temperature increased sensitivity. In addition, both the washing step after collecting leptospires by centrifugation and the inclusion of 0.1% bovine serum albumin in the reaction mix minimized the interference of other inhibitory compounds. These modifications were useful to improve the detection of Leptospira in urine by PCR.

First report of Eratyrus mucronatus, Stal, 1859, (Hemiptera, Reduviidae, Triatominae), in the State of Rondônia, Brazil

INTRODUCTION: This paper reports, for the first time, the presence of the Eratyrus mucronatus species in the State of Rondonia, Brazil. METHODS: These specimens were caught by chance in the forest and later they were collected using luminous traps. RESULTS: After finding these specimens, the number of the Triatominae genera in Rondonia rose to four, while its species rose to seven. CONCLUSIONS: Complimentary studies will be conducted in order to allow for clearer understanding the ecology of this arthropod, its possible role in transmitting Chagas' disease and its current geographical distribution.

Genetic diversity of dengue virus serotypes 1 and 2 in the State of Paraná, Brazil, based on a fragment of the capsid/premembrane junction region

INTRODUCTION: The precise identification of the genetic variants of the dengue virus is important to understand its dispersion and virulence patterns and to identify the strains responsible for epidemic outbreaks. This study investigated the genetic variants of the capsid-premembrane junction region fragment in the dengue virus serotypes 1 and 2 (DENV1-2). METHODS: Samples from 11 municipalities in the State of Paraná, Brazil, were provided by the Central Laboratory of Paraná. They were isolated from the cell culture line C6/36 (Aedes albopictus) and were positive for indirect immunofluorescence. Ribonucleic acid (RNA) extracted from these samples was submitted to the reverse transcription polymerase chain reaction (RT-PCR) and nested PCR. RESULTS: RT-PCR revealed that 4 of the samples were co-infected with both serotypes. The isolated DENV-1 sequences were 95-100% similar to the sequences of other serotype 1 strains deposited in GenBank. Similarly, the isolated DENV-2 sequences were 98-100% similar to other serotype 2 sequences in GenBank. According to our neighbor-joining tree, all strains obtained in this study belonged to genotype V of DENV-1. The DENV-2 strains, by contrast, belonged to the American/Asian genotypes. CONCLUSIONS: The monitoring of circulating strains is an important tool to detect the migration of virus subtypes involved in dengue epidemics.

Perceptions of the usefulness of external support to immunization coverage in Guinea-Bissau: a Delphi analysis of the GAVI-Alliance cash-based support

INTRODUCTION: Although many countries have improved vaccination coverage in recent years, some, including Guinea-Bissau, failed to meet expected targets. This paper tries to understand the main barriers to better vaccination coverage in the context of the GAVI-Alliance (The Global Alliance for Vaccines and Immunisation) cash-based support provided to Guinea-Bissau. METHODS: The analysis is based on a document analysis and a three round Delphi study with a final consensus meeting. RESULTS: Consensus attributed about 25% of the failure to perform better to implementation problems; and about 10% to governance and also 10% to scarce resources. The qualitative analysis validates the importance of implementation issues and upgraded the relevance of the human resources crisis as an important drawback. The recommendations were balanced in their upstream-downstream focus but were blind to health information issues and logistical difficulties. CONCLUSIONS: It is commendable that such a fragile state, with all sorts of barriers, manages to sustain a slow steady growth of its vaccination coverage. Not reaching the targets set reflects the inappropriateness of those targets rather than a lack of commitment of the health workforce. In the unstable context of countries such as Guinea-Bissau, the predictability of the funds from global health initiatives like the GAVI-Alliance seem to make all the difference in achieving small consistent health gains even in the presence of other major bottlenecks.

Demographic determinants of survival of people living with HIV attending an outpatient reference unit in the city of Três Lagoas, state of Mato Grosso do Sul, Brazil, in the period 1984-2009

INTRODUCTION: While the incidence of HIV infection and AIDS is increasing in small Brazilian cities, epidemiological studies are often conducted in large urban centers. METHODS: Our group conducted a retrospective analysis of survival determinants among 358 patients who attended a reference unit in a small city. RESULTS: Death risk was lower among men that had sex with men, patients with an HIV-seropositive partner, and those admitted after highly active antiretroviral therapy (HAART) was available. CONCLUSIONS: The study documents the striking beneficial effect of HAART. The finding of other groups with improved survival may aid in the development of programmatic strategies.