Pathology of complete atrioventricular block in chronic Chagas' myocarditis.
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Adult↗
Biomedical subjects
S G Andrade
Publications and source records attributed to S G Andrade.
Trypanosoma cruzi antigens detected by immunoelectron microscopy in the spleen of mice serologically positive but parasitologically cured by chemotherapy. (Preliminary report).
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Animals↗
[Therapy of the chronic phase of the experimental infection by Trypanosoma cruzi with benzonidazole and nifurtimox].
Fifty-eight mice, chronically infected with different T. cruzi strains (Types II and III) were submitted to chemotherapy either with Nifurtimox (Bay 2502) or Benznidazole (Ro 7-1051). Twenty one mice were not treated and were used as infected controls. The duration of infection was from 90 to 400 days. Inocula varied from 1 x 10(4) to 5 x 10(4) blood forms. Treatment lasted for 90 days, doses being 200mg/kg/day during 4 days, followed by 50mg/kg/day for Nifurtimox and 100mg/kg/day for Benznidazole. Parasitological tests (xenodiagnosis, inoculations into baby mice and hemoculture) showed 85.3% negativation for Type II strains and 43% for Type III in animals treated with Benznidazole. As for Nifurtimox, there were 71.4% of parasitological negativation for the animals infected with Type II strains and 66% for those infected with Type III. IFA tests remained positive in 90% of treated and cured animals. Disappearance or marked regression of myocardial and skeletal muscle lesions was seen in the treated and parasitologically negative animals. The conclusion is that the treatment in the chronic phase of T. cruzi infection can result in parasitological cure in a high percentage of cases with regression of histopathological lesions, although with persistence of positivity of the IFA tests.
Animals↗
[Behavior of Trypanosoma cruzi strains after passage in different triatominae species].
To study the influence of the intermediate host stage on the course of mouse infection, Trypanosoma cruzi belonging to the Peruvian (Type I), 12 SF (Type II) and Colombian (Type III) strains were passaged through either Rhodnius prolixus, Panstrongylus megistus or Triatoma infestans. T. cruzi metacyclic forms (dose 10(4)) from the different strains were obtained from each bug and inoculated into 8-10 gm mice. Comparison was made in mice inoculated with blood forms. Parasitaemia curves were plotted in the peripheral blood for each strain, reaching more elevated peaks with Peruvian strain parasites from P. megistus and R. prolixus, 12 SF strain from P. megistus and Colombian strain from R. prolixus. Tissue tropism and histopathological patterns were those usually seen in mice infected with each respective strain type. Peruvian virulence was the same for all groups. Slender forms predominate among mice inoculated with metacyclic forms of Colombian and 12 SF strains, probably an adaptative parasite change related to the intermediate host.
Animals↗
Biochemical behavior of Trypanosoma cruzi strains isolated from mice submitted to specific chemotherapy.
To investigate the influence of chemotherapy on the biochemical behavior of Trypanosoma cruzi strains, three groups of mice were infected with one of three strains of T. cruzi of different biological and isoenzymic patterns (Peruvian, 21SF and Colombian strains). Each group was subdivided into subgroups: 1-treated with nifurtimox; 2-treated with benznidazole and 3-untreated infected controls. At the end of treatment, that lasted for 90 days, xenodiagnosis, subinocculation of blood into new born mice and hemoculture were performed as tests of cure. From the positive tests, 22 samples of T. cruzi were isolated from all subgroups. Electrophoretic analysis of the isoenzymes PGM, GP1, ALAT and ASAT failed to show any difference between parasite strains isolated from treated and untreated mice, which indicates that no detectable clonal selection or parasite genetic markers alterations concerning the isoenzymes analysed have been determined by treatment with drugs of recognized antiparasitic effect, suggesting stability of the phenotypic characteristics of the three biological types of T. cruzi strains.
Animals↗
Biodemes and zymodemes of Trypanosoma cruzi strains: correlations with clinical data and experimental pathology.
With the objective of establishing biological and biochemical characteristics of a significant number of Trypanosoma cruzi strains from different geographical areas, 138 strains isolated from naturally infected humans, triatomine or vertebrate hosts were studied; 120 were isolated from different areas of Brazil and 18 from other South and Central American countries. Inocula from triatomine or culture forms were injected into suckling Swiss mice, followed by passages into mice 10 to 12 g. Biological characters and histopathological study permitted the inclusion of the strains into three Types or biodemes: I, II, III. Isoenzymic analysis confirmed a correspondence between the biodemes and zymodemes: Type I and Z2b, Type II and Z2, Type III and Z1. Results showed the ubiquitary distribution of the several types of strains. The predominance of the same Type and zymodeme in one geographical area was confirmed: Type II strains among the human cases from eastern Bahia and east of Goiás; Type III strains from humans of north Brazil and Central America and from silvatic vectors or vertebrates from other geographical areas. The biological types of strains correlate with different histopathological lesions considering cardiac involvement and neuronal lesions. These findings suggest that the biological behavior together with isoenzymes patterns and pathological pictures in the vertebrate host can be an important tool for establishing correlations between strains behavior and clinico-pathological manifestations of Chagas' disease in different geographical areas.
Acute Disease↗
Clonal structure of Trypanosoma cruzi Colombian strain (biodeme Type III): biological, isoenzymic and histopathological analysis of seven isolated clones.
The clonal structure of the Colombian strain of Trypanosoma cruzi, biodeme Type III and zymodeme 1, was analyzed in order to characterize its populations and to establish its homogeneity or heterogeneity. Seven isolated clones presented the basic characteristics of Biodeme Type III, with the same patterns of parasitemic curves, tissue tropism to skeletal muscle and myocardium, high pathogenicity with extensive necrotic-inflammatory lesions from the 20th to 30th day of infection. The parental strain and its clones C1, C3, C4 and C6, determined the higher levels of parasitemia, 20 to 30 days of infection, with high mortality rate up to 30 days (79 to 100%); clones C2, C5 and C7 presented lower levels of parasitemia, with low mortality rates (7.6 to 23%). Isoenzymic patterns, characteristic of zymodeme 1, (Z1) were similar for the parental strain and its seven clones. Results point to a phenotypic homogeneity of the clones isolated from the Colombian strain and suggest the predominance of a principal clone, responsible for the biological behavior of the parental strain and clones.
Animals↗
[Pathology of experimental Chagas disease in dogs].
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Animals↗
Malignant transformation of a rat fibroma by the treatment with an anti-fibrosing drug: CY-168F (Plastenan).
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Aminocaproates↗
[Behavior of the Y and Peruvian strains of Trypanosoma cruzi in mice, after passage through various media].
The behavior of two strains of Trypanosoma cruzi (Y and Peruvian strains) in experimental mouse infection, after being passed through different conditions of maintainance and cultivation was studied. The conditions were: Warren's acellular culture medium, cryopreservation in liquid Nitrogen, passage through the insect vector and direct blood passage from mice to mice. The parameters considered for comparative study were as follows: parasitemia, mortality rate, maximum survival time, morphology of parasites in peripheral blood, tissue tropism and histopathological lesions. Each experimental group consisted of two sub-groups according to the inocula: 10.000 or 50.000 trypomastigotes. The basic characteristics of the strains remained unchanged. These were macrophagotropism, predominance of slender forms of the parasite in early infection and 100 per cent mortality rate in the acute phase of the infection. However, decrease in the virulence was observed when the culture forms were used or when the infection with low inoculum was used (10.00 forms). Therefore the main biological characteristics of the strains tended to remain the same, regardless of the conditions used for maintainance and cultivation.
Animals↗
[Immunological aspects of infection of 6 inbred strains of mice by 3 different strains of Trypanosoma cruzi].
We evaluated humoral and cellular immune responses in 6 inbred mouse strains (BALB/c, B-10, C3H, A/J, AKR and DBA) infected with 3 Trypanosoma cruzi strains (Peruvian, 21 SF and Colombian), which are the standards for the 3 strains Types of Andrade's classification. Negative delayed-type hipersensitivity reactions to parasite antigens were evidence of suppressed cell-mediated immunity. An early drop of IgG1 and rise of IgM levels were observed in almost all mouse strains infected by any T. cruzi strain. Elevation of IgG2a and/or IgG2b levels was higher in resistant mouse strains. Anti-T. cruzi antibody levels (Indirect immunofluorescence and ELISA) did not correlate with survival. Despite some differences among mouse strains there was a definition of an overall pattern of host response and the maintenance of biological standards which characterize the basic types of T. cruzi strains.
Animals↗
Chronic murine myocarditis due to Trypanosoma cruzi--an ultrastructural study and immunochemical characterization of cardiac interstitial matrix.
In an attempt to define the mouse-model for chronic Chagas' disease, a serological, histopathological and ultrastructural study as well as immunotyping of myocardium collagenic matrix were performed on Swiss mice, chronically infected with Trypanosoma cruzi strains: 21 SF and Mambaí (Type II); PMN and Bolivia (Type III), spontaneously surviving after 154 to 468 days of infection. Haemagglutination and indirect immunofluorescence tests showed high titres of specific antibodies. The ultrastructural study disclosed the cellular constitution of the inflammatory infiltrate showing the predominance of monocytes, macrophages with intense phagocytic activity, fibroblasts, myofibroblasts and abundant collagen matrix suggesting the association of the inflammatory process with fibrogenesis in chronic chagasic cardiomyopathy. Arteriolar and blood capillary alterations together with dissociation of cardiac cells from the capillary wall by edema and inflammation were related to ultrastructural lesions of myocardial cells. Rupture of parasitized cardiac myocells contribute to intensify the inflammatory process in focal areas. Collagen immunotyping showed the predominance of Types III and IV collagen. Collagen degradation and phagocytosis were present suggesting a reversibility of the fibrous process. The mouse model seems to be valuable in the study of the pathogenetic mechanisms in Chagas cardiomyopathy, providing that T. cruzi strains of low virulence and high pathogenicity are used.
Animals↗
The conduction system of the heart in mice chronically infected with Trypanosoma cruzi: histopathological lesions and electrocardiographic correlations.
Chronic focal and diffuse myocarditis with interstitial fibrosis developed in Swiss outbred mice and in the inbred AKR and A/J strains of mice which were chronically infected with several Trypanosoma cruzi strains belonging to three biological types (Type I, II and III). High incidence of electrocardiographic changes with predominance of intraventricular conduction disturbances, 1st. and 2nd. degree AV block, arrhythmias, comparable with those found in human Chagas' disease, were also present. Morphological study of the conduction tissue of the heart revealed inflammatory and fibrotic changes. The presence of inflammation in the inter-atrial septum almost always coincided with the inflammatory involvement of the ventricular conduction system. Focal inflammation was associated with vacuolization and focal necrosis of the specific fibers. Most of the lesions were seen affecting the His bundle (76.3% of the cases), the right bundle branch (73.3%), AV node (43.9%) and left bundle branch (37.5%). Correlation between morphological changes in the conduction tissue and electrocardiographic alteration occurred in 53.0 to 62.5% of the cases, according to the experimental groups.
Animals↗
[Isoenzymatic pattern of Trypanosoma cruzi Y strain after specific chemotherapy].
The isoenzyme pattern of the Trypanosoma cruzi Y strain recovered from mice inoculated with 15 x 10(4) blood trypomastigotes and previously treated with either Bay 2502 (Nifurtimox) or Ro 7-1051 (Benzonidazol) was analyzed in the following situations: a) strain resistant to Bay 2502 and again treated with the same drug; b) strain resistant to Bay 2502 and treated with Ro 7-1051; c) strain resistant to Ro 7-1051 and treated with that same drug. Although marked drug resistance was noted in all cases, the isoenzyme pattern of the Y strain for GPI, PGM, ALAT and ASAT remained throughout the same. The pattern was similar to that of the Peruvian strain, which also belongs to the same strain Type of the Y strain, but differed from those of the 21 SF (Type II) and Colombian (Type III) strains. Thus, the appearance of drug resistance in T. cruzi strain was not associated with a change in its isoenzymatic pattern.
Animals↗
Influence of Trypanosoma cruzi strain on the pathogenesis of chronic myocardiopathy in mice.
The murine model of chronic Chaga's myocardiopathy was developed in 201 inbred and outbred mice. The experimental groups consisted of 1st: 73 inbred AKR and A/J mice inoculated with one of the following Trypanosoma cruzi strains: Peruvian (Type I), 12 SF (Type II) or Colombian (Type III); 2nd: 128 outbred Swiss mice, chronically infected either with Type II or Type III strains isolated from human patients from different geographical areas. All T. cruzi strains were previously characterized by their morphobiological behaviour in mice and by isoenzymatic patterns. For the 1st group the inoculum was 5 x 10(4) for the Peruvian strain and 1 x 10(5) for the 12 SF and Colombian strains. In the 2nd group-Swiss mice the inoculum size varied from 2 x 10(4) to 2 x 10(5). The inbred animals were killed at a 3 time-point scale (90, 180 and 240 days) post-infection. The Swiss mice were killed from 180 to 660 days after infection. The evaluation of parasitemia and serology (xenodiagnosis and indirect immunofluorescent test) was performed. The incidence of macroscopic alterations of the heart and cardiac index were evaluated. Histopathological lesions of the myocardium were graded. The influence of T. cruzi strain on the intensity of cardiac lesions was evaluated by the Chi-square test; the incidence of inflammatory lesions and its relationship to the parasite strain was evaluated by the Fisher test. The influence of the duration of infection was evaluated by using the Gamma Coefficient of Kruskal and Goodman and its measure of significance. Slight to severe microscopic alterations occurred in 85% of the chronically infected mice. There were a clear predominance on the incidence and intensity of inflammatory and fibrotic alterations for the mice infected with Type III strains. Statistical analysis has shown significant differences among the infected groups, in the inflammatory and fibrotic lesions. Macroscopic alterations (right cavities dilatation and apex aneurism of left ventricle), differed in incidence according to mice strains; in Swiss and AKR mice, significant differences were seen in mice infected with different T. cruzi strains, but the A/J mice failed to show significant differences correlated with different parasite strains. The duration of infection, from 90 to 240 days, could not be correlated with the degree of lesions in the several groups.
Animals↗
Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi, under specific chemotherapy.
UNLABELLED: This investigation was performed to verify the effect of specific chemotherapy (Benznidazole or MK-436) on the inflammatory and fibrotic cardiac alterations in mice chronically infected with the strains 21 SF (Type II) and Colombian (Type III) of Trypanosoma cruzi. To obtain chronically infected mice, two groups of 100 Swiss mice each, were infected with either the 21 SF or the Colombian strain (2 x 10(4) and 5 x 10(4) blood forms respectively). The rate of mortality in the acute phase was of 80% for both groups. Twenty surviving mice chronically infected with the 21 SF strain and 20 with the Colombian strain were then divided in treated and untreated groups. Excluding those that died during the course of treatment, 14 mice chronically infected with the 21 SF strain and 15 with the Colombian strain were finally evaluated in the present study. Chemotherapy was performed with Benznidazole (N-benzil-2-nitro-1-imidazolacetamide) in the dose of 100 mg/k.b.w/day, for 60 days, or with the MK-436 (3(1-methyl-5 nitroimidazol-2-yl) in two daily doses of 250 mg/k.b.w, for 20 days. Parasitological cure tests were performed (xenodiagnosis, haemoculture, subinoculation of the blood into newborn mice), and serological indirect immunofluorescence test. The treated and untreated mice as well as intact controls were killed at different periods after treatment and the heart were submitted to histopathological study with hematoxilineosin and picrosirius staining; ultrastructural study; collagen immunotyping, fibronectin and laminin identification by immunofluorescence tests. RESULTS: the untreated controls either infected with 21 SF or Colombian strain, showed inflammatory and fibrotic alterations that were mild to moderate with the 21 SF strain and intense with the Colombian strain. Redpicrosirius staining showed bundles of collagen in the interstitial space and around cardiac fibers. Increased deposits of matritial components and collagen fibers, macrophages and fibroblasts appeared at the ultrastructural examination. Deposits of fibronectin, laminin, pro-III and IV collagens were seen, most intense in those infected with the Colombian strain. Treated mice, parasitologically cured, presented clear-cut regression of the inflammatory lesions and of the interstitial matrix thickening. Mice infected with the Colombian strain and treated with MK-436, was parasitologically cured in 5/6 cases and showed mild inflammatory infiltration and fibrosis. The mice treated with Benznidazole (Colombian strain) did not cure and showed moderate fibrosis and inflammation. Treatment of the mice infected with the 21 SF with Benznidazole determined parasitological cure of all animals, that showed mild inflammation and fibrosis of the myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Morphological aspects of the myocarditis and myositis in Calomys callosus experimentally infected with Trypanosoma cruzi: fibrogenesis and spontaneous regression of fibrosis.
Calomys callosus a wild rodent, is a natural host of Trypanosoma cruzi. Twelve C. callosus were infected with 10(5) trypomastigotes of the F strain (a myotropic strain) of T. cruzi. Parasitemia decreased on the 21st day becoming negative around the 40th day of infection. All animals survived but had positive parasitological tests, until the end of the experiment. The infected animals developed severe inflammation in the myocardium and skeletal muscle. This process was pronounced from the 26th to the 30th day and gradually subsided from the 50th day becoming absent or residual on the 64th day after infection. Collagen was identified by the picro Sirius red method. Fibrogenesis developed early, but regression of fibrosis occurred between the 50th and 64th day. Ultrastructural study disclosed a predominance of macrophages and fibroblasts in the inflammatory infiltrates, with small numbers of lymphocytes. Macrophages had active phagocytosis and showed points of contact with altered muscle cells. Different degrees of matrix expansion were present, with granular and fibrillar deposits and collagen bundles. These alterations subsided by the 64th days. Macrophages seem to be the main immune effector cell in the C. callosus model of infection with T. cruzi. The mechanisms involved in the rapid fibrogenesis and its regression deserve further investigation.
Animals↗
Trypanosoma cruzi strains and autonomic nervous system pathology in experimental Chagas disease.
Lesions involving the sympathetic (para-vertebral ganglia) and para-sympathetic ganglia of intestines (Auerbach plexus) and heart (right atrial ganglia) were comparatively analyzed in mice infected with either of three different strain types of Trypanosoma cruzi, during acute and chronic infection, in an attempt to understand the influence of parasite strain in causing autonomic nervous system pathology. Ganglionar involvement with neuronal destruction appeared related to inflammation, which most of the times extended from neighboring adipose and cardiac, smooth and striated muscular tissues. Intraganglionic parasitism was exceptional. Inflammation involving peripheral nervous tissue exhibited a focal character and its variability in the several groups examined appeared unpredictable. Although lesions were generally more severe with the Y strain, comparative qualitative study did not allow the conclusion, under the present experimental conditions, that one strain was more pathogenic to the autonomic nervous system than others. No special tropism of the parasites from any strain toward autonomic ganglia was disclosed.
Animals↗