Dynamics of Capillaria-hepatica-induced hepatic septal fibrosis in rats

INTRODUCTION: The pathogenesis of septal hepatic fibrosis, induced in rats by Capillaria hepatica infection, was studied with the aid of a large collection of stored paraffin blocks, representative of the different evolutive phases of fibrosis which appeared in 100% of infected rats. METHODS: Studies were conducted involving histology, immunohistochemistry, immunofluorescence and morphometric methods, in order to observe the dynamic behavior of the cellular and matrix components of fibrosis, over a one year period of evolution. RESULTS: Observation verified that septal fibrosis originates from several portal spaces simultaneously. Its origin and progression involve blood vessel proliferation (angiogenesis), multiplication of actin-positive cells (pericytes and myofibroblasts) and progressive collagen deposition. By the end of 4-5 months, a progressive decrease in all these components was observed, when signs of regression of septal fibrosis became more evident over time. CONCLUSIONS: Besides indicating the fundamental role played by angiogenesis in the pathogenesis of fibrosis, these morphological data concerning the dynamics of this C. hepatica experimental model proved to be adequate for future investigations regarding the functional aspects of fibrosis induction, progression and regression.

Dimensions and dynamics in integrin function

Integrins play crucial roles in cell adhesion, migration, and signaling by providing transmembrane links between the extracellular matrix and the cytoskeleton. Integrins cluster in macromolecular complexes to generate cell-matrix adhesions such as focal adhesions. In this mini-review, we compare certain integrin-based biological responses and signaling during cell interactions with standard 2D cell culture versus 3D matrices. Besides responding to the composition of the matrix, cells sense and react to physical properties that include three-dimensionality and rigidity. In routine cell culture, fibroblasts and mesenchymal cells appear to use focal adhesions as anchors. They then use intracellular actomyosin contractility and dynamic, directional integrin movements to stretch cell-surface fibronectin and to generate characteristic long fibrils of fibronectin in "fibrillar adhesions". Some cells in culture proceed to produce dense, three-dimensional matrices similar to in vivo matrix, as opposed to the flat, rigid, two-dimensional surfaces habitually used for cell culture. Cells within such more natural 3D matrices form a distinctive class of adhesion termed "3D-matrix adhesions". These 3D adhesions show distinctive morphology and molecular composition. Their formation is heavily dependent on interactions between integrin alpha5ß1 and fibronectin. Cells adhere much more rapidly to 3D matrices. They also show more rapid morphological changes, migration, and proliferation compared to most 2D matrices or 3D collagen gels. Particularly notable are low levels of tyrosine phosphorylation of focal adhesion kinase and moderate increases in activated mitogen-activated protein kinase. These findings underscore the importance of the dimensionality and dynamics of matrix substrates in cellular responses to the extracellular matrix.

Thymocyte migration: an affair of multiple cellular interactions?

Cell migration is a crucial event in the general process of thymocyte differentiation. The cellular interactions involved in the control of this migration are beginning to be defined. At least chemokines and extracellular matrix proteins appear to be part of the game. Cells of the thymic microenvironment produce these two groups of molecules, whereas developing thymocytes express the corresponding receptors. Moreover, although chemokines and extracellular matrix can drive thymocyte migration per se, a combined role for these molecules appears to contribute to the resulting migration patterns of thymocytes in their various stages of differentiation. The dynamics of chemokine and extracellular matrix production and degradation is not yet well understood. However, matrix metalloproteinases are likely to play a role in the breakdown of intrathymic extracellular matrix contents. Thus, the physiological migration of thymocytes should be envisioned as a resulting vector of multiple, simultaneous and/or sequential stimuli involving chemokines, adhesive and de-adhesive extracellular matrix proteins, as well as matrix metalloproteinases. Accordingly, it is conceivable that any pathological change in any of these loops may result in the alteration of normal thymocyte migration. This seems to be the case in murine infection by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas' disease. A better knowledge of the physiological mechanisms governing thymocyte migration will provide new clues for designing therapeutic strategies targeting developing T cells.

An outline of military technological dynamics as restraints for acquisition, international cooperation and domestic technological development

The expectation that technological returns from defense expenditure through acquisition, international cooperation and domestic research would further national development underappreciates the different technological dynamic of the armed services. This paper outlines the technological dynamic the stems from fighting in the air, at sea and on land, exemplifying consequences for the case of acquisition.

Network dynamics in scientific knowledge acquisition: an analysis in three public universities in the state of Bahia

This paper aims to cast some light on the dynamics of knowledge networks in developing countries by analyzing the scientific production of the largest university in the Northeast of Brazil and its influence on some of the remaining regional research institutions in the state of Bahia. Using a methodology test to be employed in a larger project, the Universidade Federal da Bahia (UFBA) (Federal University of Bahia), the Universidade do Estado da Bahia (Uneb) (State of Bahia University) and the Universidade Estadual de Santa Cruz (Uesc)'s (Santa Cruz State University) scientific productions are discussed in one of their most traditionally expressive sectors in academic production - namely, the field of chemistry, using social network analysis of co-authorship networks to investigate the existence of small world phenomena and the importance of these phenomena in research performance in these three universities. The results already obtained through this research bring to light data of considerable interest concerning the scientific production in unconsolidated research universities. It shows the important participation of the UFBA network in the composition of the other two public universities research networks, indicating a possible occurrence of small world phenomena in the UFBA and Uesc networks, as well as the importance of individual researchers in consolidating research networks in peripheral universities. The article also hints that the methodology employed appears to be adequate insofar as scientific production may be used as a proxy for scientific knowledge.

Imported and autochthonous cases in the dynamics of dengue epidemics in Brazil

OBJECTIVE: To estimate the basic reproduction number (R0) of dengue fever including both imported and autochthonous cases. METHODS: The study was conducted based on epidemiological data of the 2003 dengue epidemic in Brasília, Brazil. The basic reproduction number is estimated from the epidemic curve, fitting linearly the increase of initial cases. Aiming at simulating an epidemic with both autochthonous and imported cases, a "susceptible-infectious-resistant" compartmental model was designed, in which the imported cases were considered as an external forcing. The ratio between R0 of imported versus autochthonous cases was used as an estimator of real R0. RESULTS: The comparison of both reproduction numbers (only autochthonous versus all cases) showed that considering all cases as autochthonous yielded a R0 above one, although the real R0 was below one. The same results were seen when the method was applied on simulated epidemics with fixed R0. This method was also compared to some previous proposed methods by other authors and showed that the latter underestimated R0 values. CONCLUSIONS: It was shown that the inclusion of both imported and autochthonous cases is crucial for the modeling of the epidemic dynamics, and thus provides critical information for decision makers in charge of prevention and control of this disease.

Dynamics of transmission of Trypanosoma cruzi in a rural area of Argentina: III. Persistence of T. cruzi parasitemia among canine reservoirs in a two-year follow-up

A new cross-sectional survey of household- associated mongrel dogs as well as follow-up of previously parasitemic individuals was carried out in 1984 toy means of xenodiagnosis and serologic techniques to get a deeper insight into the relationship of T. cruzi parasitemia and age among canine hosts in a rural area of Argentina. Persistence of detectable parasitemia was age-independent, or at most, loosely related to age, confirming the pattern observed in 1982. Similarly no significant age-decreasing effect was recorded among seropositive dogs in: a) the probability of detecting parasites in a 2-year follow-up; b) their intensity of infectiousness (=infective force) for T. infestans 3rd-4th instar nymphs, as measured by the percentage of infected bugs observed in each dog xenodiagnosis. Moreover, not only was the infective force of seropositive dogs for bugs approximately constant through lifetime, but it was significantly higher than the one recorded for children in the present survey, and for human people by other researchers. Therefore, and since T. infestans field populations show high feeding frequencies on dogs, the latter are expected to make the greatest contribution to the pool of infected vectors in the rural household of Argentina. This characteristic should be sufficient to involve canine reservoirs definitely as a risk factor for human people residing in the same house. The increased severity of parasitemia observed among dogs in this survey may be related to the acute undernutrition characteristic of canine populations of poor rural areas in our country, which is expected to affect the ability of the host to manage the infection.

Population dynamics and biting rhythm of the anthropophilic sandfly Lutzomyia cruciata (Diptera: Psychdidae) in Southeast, Mexico

Sandflies attracted by human bait were caught in an endemic focus of localized cutaneous leishmaniasis in the state of Campeche, Mexico. Catches were carried out monthly from February 1994 to January 1995 between 18:00 and 22:00 h. Lutzomyia cruciata was the only species caught. The highest population peak of Lu. cruciata was found in March with lesser peaks in February, December 1994, and January 1995. Maximum biting rate of Lu. cruciata was found between 18:00 and 19:00 h. The host-seeking females of Lu. cruciata were directly related to levels of humidity between 88 and 100%. Low and high temperature had a negative effect upon Lu. cruciata activity. The possible role of Lu. cruciata as vector of leishmaniasis in the state of Campeche, Mexico is discussed.

DETECTION OF IgM ANTIBODIES TO Schistosoma mansoni GUT-ASSOCIATED ANTIGENS FOR THE STUDY OF THE DYNAMICS OF SCHISTOSOMIASIS TRANSMISSION IN AN ENDEMIC AREA WITH LOW WORM BURDEN

For a period of 2 years, five follow-up measures of prevalence and incidence rates were estimated in a prospective study of S. mansoni infection in a group of schoolchildren who were living in a rural area of the Municipality of Itariri (São Paulo, Brazil), where schistosomiasis is transmitted by Biomphalaria tenagophila. Infection was determined by the examination of three Kato-Katz stool slides, and the parasitological findings were analyzed in comparison to serological data. In the five surveys, carried out at 6-month intervals (March-April and September-October), the prevalences were, respectively, 8.6, 6.8, 9.9, 5.8 and 17.2% by the Kato-Katz, and 56.5, 52.6, 60.8, 53.5 and 70.1% by the immunofluorescence test (IFT). Geometric mean egg counts were low: 57.8, 33.0, 35.6, 47.3 and 40.9 eggs per gram of feces, respectively. Of the total of 299 schoolchildren, who submitted five blood samples at 6-month intervals, one for each survey, 40% were IFT-positive throughout the study, and 22% were IFT-negative in all five surveys. Seroconversion from IFT negative to positive, indicating newly acquired S. mansoni infection, was observed more frequently in surveys carried out during March-April (after Summer holidays), than during September-October. Seasonal trends were not statistically significant for detection of S. mansoni eggs in stool. The results indicate that the use of IgM-IFT is superior to parasitological methods for detection of incidence of S. mansoni infection in areas with low worm burden.

Typhoid fever as cellular microbiological model

The knowledge about typhoid fever pathogenesis is growing in the last years, mainly about the cellular and molecular phenomena that are responsible by clinical manifestations of this disease. In this article are discussed several recent discoveries, as follows: a) Bacterial type III protein secretion system; b) The five virulence genes of Salmonella spp. that encoding Sips (Salmonella invasion protein) A, B, C, D and E, which are capable of induce apoptosis in macrophages; c) The function of Toll R2 and Toll R4 receptors present in the macrophage surface (discovered in the Drosophila). The Toll family receptors are critical in the signalizing mediated by LPS in macrophages in association with LBP and CD14; d) The lines of immune defense between intestinal lumen and internal organs; e) The fundamental role of the endothelial cells in the inflammatory deviation from bloodstream into infected tissues by bacteria. In addition to above subjects, the authors comment the correlation between the clinical features of typhoid fever and the cellular and molecular phenomena of this disease, as well as the therapeutic consequences of this knowledge.