Masayuki Okumura

Megabladder in experimental Chagas disease: pathological features of the bladder wall

Mega-organs, primarily in the digestive tract, are well known to occur in chronic Chagas disease. Acute experimental infection with Trypanosoma cruzi results in parasitism of a wide range of cells, tissues, and organs, including the urinary bladder. Infection of BALB/c mice with 100,000 bloodstream forms of the Y strain of T. cruzi induced acute infection with intense parasitism of all layers of the urinary bladder. Parasites were found in the mucosa, lamina propria, muscular, adventitial connective, and fat tissue. Desquamate epithelial cells with amastigotes in the bladder lumen were also found. After 60 days of infection, mice inoculated with 50 bloodstream forms developed dilated, thin-walled bladders that had inflammatory infiltrates and foci of fibrosis replacing areas of damaged muscular layer. These lesions result from direct damage to the muscle fibers by the T. cruzi, leading to myosites, muscle damage, and scarring. Direct damage of paraganglia cells secondary to parasitism, leading to dilatation, damage of muscle fibers, and scarring with replacement of muscular tissue with connective tissue, should also be considered as a cause of functional disturbance of the urinary bladder.

Cytokine-like substance: origin and fate in Chagas' disease a new hypothesis about the local inflammatory reaction etiopathogenesis (experimental study in white mice)

The authors began the study of cytokines or the so-called plasma activators of the acute inflammatory reaction in infections in September 1997. As far back as with the origina report describing the Chagas’ Disease (CD), Carlos Chagas (1911)3,4 , Gaspar Vianna (1911)15 and Okumura (1967)11 interpreted the etiopathogenesis of the Chagas’ Disease as follows. The first event is the invasion of the host cell by the trypomastigote form of the Trypanosoma cruzi (Chagas 1909)2. The flagellum becomes disconnected from the parasite and the trypomastigotes change into the amastigote form. The amastigotes multiply by successive binary fission clustering together to form a compact nest of parasites inside the host cell. The parasites subsequently evolve to the epiand trypomastigote flagellate forms releasing their cellular content into the nest fluid. These flagellate forms move actively in the nest fluid, provoking the rupture of the amastigote nest and consequently host cell injury. Lastly, the epi and trypomastigote forms gain access the interstitial space. These authors3,11,15 stressed the fact that absolutely no inflammatory changes surrounding the unruptured nest were recorded as long as the amastigote nests remained intact or at the time of the nest rupture. Amastigote cell nest rupture releases several chemical factors produced by the distinct evolutionary stages of the parasite, that is, the trypo, epi, and amastigote forms. These chemical factors are metabolic and degradation products, namely, proteins, lipids, carbohydrates, RNA and DNA fractions, cytoplasmic, and cell membrane particles11,12,13. The authors’ objectives in this experiment were to study the formation and the action of these factors in experimental Chagas’ Disease. The description of several factors in the 70’s , namely, lymphocyte activating factor by Gery & Waksman7, the leucocytic endogenous mediator by Merriman et al.9, and the cytokines by Dinarello in 19846 who described “ the activators of immunity in defense of the host”, led us to believe that a familiar substance participates actively in the etiopathogenesis of the experimental Chagas ́Disease. (Figs. 1, 2, 3, 4). Using cytokine markers, we observed that while the mastigote nest remains intact or at the moment of nest rupture, no cytokine markers are detected. However, the interstitial cell space becomes stained brown or chestnut brown immediately after the acute inflammatory reaction is in proRHCFAP/2965

Megaesophagus in Experimental Chagas’ Disease

Chagas’ disease is a parasitosis and its etiological agent is the flagellate protozoa Trypanosoma cruzi [1]. The parasite is a hemoflagellate, Phylum Protozoa, subphylum Mastigophora, order Kinetoplastida, suborder Trypanosomatidae, and section Stercoraria. Described for the first time by the Brazilian scientist Carlos Chagas when, during the construction of the Brazilian Central Railway and a malaria prevention program in the town of Lassance in northern Minas Gerais state, his attention was drawn to an hematophagous insect found in the region and known in Brazil by the common name “barbeiro” (barber bug), Conorhinus megistus, Triatoma megistus and presently Panstrongylus megistus. He examined the content of the caudal portion of the insect’s intestine and succeeded in isolating a Trypanosoma flagellate with “critidia” characteristics.