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S G Andrade

Publications and source records attributed to S G Andrade.

At least 19 recordsLinked to original sources
PubMed2001

TNF-alpha is expressed at sites of parasite and tissue destruction in the spleen of mice acutely infected with Trypanosoma cruzi.

Mice infected with a macrophagotropic strain of Trypanosoma cruzi develop progressive splenomegaly due to reactive hyperplasia with increased number of lymphocytes and macrophages, culminating in parasite disintegration and necrosis of parasitized cells. Necrotic changes have been attributed to the liberation of toxic cytokines, including TNF-alpha, from parasitized macrophages. In the present study, the presence of TNF-alpha was investigated in situ. In addition the participation of destroyed parasites in inducing the liberation of TNF-alpha was examined in two highly susceptible mice strains (C3H and Swiss) and a more resistant strain (DBA). Swiss (90) C3H/He (83) and DBA (30) mice were infected with the Peruvian strain of T. cruzi. Nineteen infected Swiss mice, and 22 infected C3H/He were treated with Benznidazole (one or two doses, 100 mg/kg bw/day), on the 8th and 9th days after infection. Necrotic splenic lesions occurred in both susceptible and resistant strains of mice. Although differing in degree, lesions were more intense in C3H and Swiss than in DBA mice. Comparing untreated and treated susceptible mice, necrotic lesions were significantly less intense in the latter. By specific monoclonal antibody immunolabelling, TNF-alpha was demonstrated in the cytoplasm of macrophages and within necrotic areas, from Swiss, C3H/He and DBA mouse spleens. In conclusion, TNF-alpha, probably synthesized by macrophages, was strongly expressed at the sites of parasite and cell destruction, thus appearing to play a pivotal role in splenic necrotic changes associated with severe experimental T. cruzi infection.

Acute Disease↗
PubMed1999

Apoptosis in a canine model of acute Chagasic myocarditis.

Histologic, ultrastructural and nick end labeling studies were made to evaluate the occurrence of apoptosis in the hearts of dogs with acute myocarditis due to experimental infection with T. cruzi. The best results for the detection of apoptosis by nick end labeling were obtained by a method combining the use of terminal deoxynucleotidyl transferase, CoCl2 and fluorescein-conjugated deoxyuridine triphosphate, followed by counterstaining of DNA with 4'6-diamidino-2-phenylindole (DAPI) and examination by laser scanning confocal fluorescence microscopy. Apoptosis was found in: (1) cardiac myocytes; (2) endothelial cells of capillaries and venules: (3) immune effector cells, including macrophages, interstitial dendritic cells (antigen-presenting cells) and granular and agranular lymphocytes, and (4) intra- and extracellular forms of T. cruzi. The apoptosis in myocytes and endothelial cells affected cells that were not infected by T. cruzi and was probably caused by the release of toxic mediators of inflammation. The apoptosis of immune effector cells could be related either to the subsidence of inflammation or to modulation (and even failure) of the immune response. The finding of apoptosis in T. cruzi confirms the results of other studies showing that this phenomenon occurs during the differentiation of trypomastigotes in vitro. Thus, apoptosis constitutes an important and multifactorial event in the pathogenesis of acute Chagasic myocarditis.

Animals↗
PubMed1997

Influence of treatment with immunosuppressive drugs in mice chronically infected with Trypanosoma cruzi.

Latent Trypanosoma cruzi infection may be reactivated in immunosuppressed individuals, with unusual clinical patterns, such as meningoencephalitis, pseudo neoplastic lesions in the central nervous system, and myocarditis with numerous parasites in the heart muscle. To investigate this problem 68 Swiss mice chronically infected with different strains of T. cruzi were treated with different combinations of immunosuppressive drugs (azathioprine, cyclosporine and betamethasone), in such a way as to imitate the situation during post transplantation treatment. Mortality varied from 6 to 25% in treated mice. There were no deaths in untreated controls. Normal mice have been submitted to the same schedules of immunosuppression as controls of treatment and no deaths were registered during treatment. Chronically infected mice showed significant elevation of total number of leukocytes and lymphocytes in comparison with intact controls; a significant decrease in blood leukocytes and lymphocytes occurred post-treatment in two of the treated experimental groups. Exacerbation of myocarditis and myositis and a high incidence of brain lesions, with focal necrosis, granulomatous lesions and glial proliferation even in the absence of parasites were present in immunosuppressed mice but not in infected controls. Although differing in some aspects from Chagas' disease in immunosuppressed humans, the murine model did show some features that resembled it, especially the peculiar pattern of central nervous system involvement.

Animals↗
PubMed1997

The indeterminate phase of Chagas' disease: ultrastructural characterization of cardiac changes in the canine model.

The indeterminate phase of Chagas' disease is defined as the prolonged period of clinically silent infection that follows the phase of acute primary infection with Trypanosoma cruzi. The dog is the only experimental animal model in which the indeterminate phase progresses to the late phase of severe, chronic myocarditis. This report describes the cardiac histologic and ultrastructural findings in dogs that survived the acute phase of infection with T. cruzi, becoming clinically and electrocardiographically normal for up to 3.5 years, while maintaining positive serologic test results during this period of time. Most of the myocardium appeared morphologically normal; however, small foci of mild, chronic myocarditis were present, with interstitial edema, mild fibrosis, and infiltration by lymphocytes, macrophages, and plasma cells. No microvascular lesions and no areas of close contact between immune effector cells and endothelial cells or cardiac myocytes were present. These findings were in sharp contrast to those observed in the canine model during the acute infection with T. cruzi. In this model, acute myocyte damage and lesions in the microcirculation, including fibrin microthrombi, were associated with close contacts between immune effector cells and myocytes or endothelial cells. Focally inflamed interstitial tissue showed increased deposition of amorphous and collagenous extracellular matrix as well as evidence of breakdown of collagen. The features of the inflammatory cells in the indeterminate phase of Chagas' disease were interpreted as indicating a self-limited cycle of focal inflammatory changes, with modulation and suppression of cell-mediated immune responses. Thus, we consider the indeterminate phase of Chagas' disease to be a stage of host-parasite equilibrium rather than a process of progressive damage.

Animals↗
PubMed1996

[Clinico-pathological correlation in the indeterminate form of experimental Chagas' disease in dogs].

PURPOSE: To study the functional cardiac component of the indeterminate form of experimental Chagas' disease in dogs. METHODS: Four dogs chronically infected with Trypanosoma cruzi and eight normal controls were used. They were submitted to several invasive procedures, either in the presence of complete autonomic block or not, to test for disturbances in the origin and conduction of electric stimuli and the function of cardiac muscle. Histological examination of the heart and its conduction systems was performed in all animals. RESULTS: Mild to moderate focal myocarditis was found in infected dogs, often involving the conduction system of the heart. Sections of the heart from control dogs were histologically normal. Functional data on excitability, intra and interatrial conduction time and sinus node recovering time were essentially similar for both infected and control animals. CONCLUSION: Focal myocarditis, the hallmark of the indeterminate form of Chagas' disease, did not alter the normal parameters of cardiac function, as seen after investigation with sensitive invasive techniques. It is probable that subjects considered as belonging to the indeterminate form of Chagas' disease, but presenting mild alterations at sensitive exploratory tests, may have more severe lesions than that usually described or may be already in the early progressive cardiac form of the disease.

Animals↗
PubMed1995

Interferon-gamma levels during the course of Trypanosoma cruzi infection of Calomys callosus (Rodentia-Cricetidae) and Swiss mice.

Serum levels of interferon-gamma (IFN-gamma) were evaluated in Calomys callosus and Swiss mice during the course of infection by four strains of Trypanosoma cruzi. All strains stimulated the production of this interleukine; however, the timing of its onset and permanence varied among strains and between the two animal models. When chronically infected animals with no detectable serum IFN-gamma were challenged with the homologous strain, they produced quantities comparable with those obtained during the acute phase of infection. In C. callosus there was a correlation between H2O2 liberation by peritoneal macrophages and serum IFN-gamma levels, whereas no such correlation was found in mice. C. callosus had a higher capacity to heal histopathological lesions, whereas lesions in mice were progressive. The results obtained suggest that C. callosus develops well-adapted immune mechanisms that may be important for its role as a reservoir of T. cruzi.

Animals↗
PubMed1994

Myocardial changes in acute Trypanosoma cruzi infection. Ultrastructural evidence of immune damage and the role of microangiopathy.

Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease.

Animals↗
PubMed1991

Experimental chemotherapy of Trypanosoma cruzi infection: persistence of parasite antigens and positive serology in parasitologically cured mice.

Mice infected with Trypanosoma cruzi, but parasitologically cured after specific chemotherapy, continued to exhibit positive indirect immunofluorescence serological tests 3-6 months after the therapy. Treatment of trypanosome antigens with monospecific antisera produced in rabbits, and examination by immunoelectron-microscopy following peroxidase labelling disclosed the presence of membrane deposits in cell processes in the spleens of the mice. Similar deposits were observed in the external membranes of T. cruzi amastigotes in the spleens of acutely infected mice, but not in normal control mice. No reaction occurred in tissues not previously treated with the monospecific anti-T. cruzi serum. Positive cells in treated and cured mice, as well as in the not cured or untreated control mice, were located in germinal centres of the splenic white pulp and presented long and branching cytoplasmic processes, which are indicative of dendritic cells of the lymphoid follicles of the spleen.

Animals↗
PubMed1989

Sequential changes of the connective matrix components of the myocardium (fibronectin and laminin) and evolution of cardiac fibrosis in mice infected with Trypanosoma cruzi.

Interstitial matrix alterations due to chronic Trypanosoma cruzi myocarditis were studied in mice by immunofluorescent microscopy with specific purified antibodies against the main different collagen isotypes, laminin and fibronectin. During the early subacute stage (26-30 days postinfection), sarcolemmal and perivascular deposits of laminin and fibronectin were prominent. The presence of fibronectin appeared to correlate with the presence of inflammatory cells. By the late subacute phase and early chronic phase (50-90 and 80-90 days postinfection, respectively), laminin and Type IV collagen were present. These were the principal features, although fibronectin continued to be found among inflammatory cells, and pro-III and III collagens formed irregular bands and periarteriolar deposits. During the late chronic phase (150-200 days postinoculation) the interstitium was enlarged and irregular, with positive staining for laminin, Types III, pro-III, and IV collagens; fibronectin appeared as focal, subendocardial, interstitial, and perivascular deposits. The relative absence of Type I collagen and the apparent positive correlation between interstitial matrix amplification and the presence of mononuclear inflammatory cells suggest that fibrotic changes in chronic T. cruzi myocarditis can be reversed if the inflammatory changes subside.

Animals↗
PubMed1989

Treatment of chronic experimental Trypanosoma cruzi infections in mice with MK-436, a 2-substituted 5-nitroimidazole.

The antiprotozoal drug 3-(1-methyl-5-nitroimidazol-2-yl)-3a, 4,5,6,7,7a-hexahydro-1,2-benzisoxazole (MK-436) is highly efficacious for treating mice chronically infected with different strains of Trypanosoma cruzi. The compound was administered by gavage in two daily doses of 250 mg per kg body weight to 130 mice that had been infected for 90 to 400 days with either type II or III strains of T. cruzi. The following parasitological cure tests were carried out: xenodiagnosis, haemoculture, and inoculation of blood into newborn mice. Indirect immunofluorescence tests and histopathological studies were also performed. The results indicate that the drug is highly efficacious against chronic infection caused by both type II (cure rate, 90%) and type III strains (cure rate, 95.7%). Histopathological examinations showed complete clearance of the cardiac and muscular lesions in 36% of the mice infected with type II strains and a decrease in the intensity and extension of the lesions in mice infected with type III strains. Indirect immunofluorescence tests were persistently positive for all the mice 3-6 months after the treatment.

Animals↗
PubMed1987

Trypanosoma cruzi strain-specific monoclonal antibodies: identification of Colombian strain flagellates in the insect vector.

Spleen cells from mice immunized with insect-derived Trypanosoma cruzi metacyclic trypomastigotes were used to obtain Colombian strain-specific monoclonal antibodies. At least 4 different strain-specific antigens were recognized by the monoclonal antibodies on epimastigotes or metacyclic trypomastigotes. There was no reactivity with other stages of Colombian strain T. cruzi, nor with any stage of 15 other T. cruzi strains or isolates, nor with 22 other Trypanosomatidae. One of the monoclonal antibodies was used to identify, by indirect immunofluorescence, Colombian strain flagellates in cryostat sections or glass-slide smears of the insect vector's intestine.

Animals↗
PubMed1987

Therapeutic action of MK-436 (2,5-nitroimidazole) on Trypanosoma cruzi infections in mice: a parasitological, serological, histopathological, and ultrastructural study.

The anti-protozoal drug MK-436 (3-(1-methyl-5-nitroimidazol-2-yl)-3a,4,5,6,7,7a-hexahydro-1,2-benzisoxazole) was found to be effective against Trypanosoma cruzi infections in mice (2 daily doses of 250 mg per kg body weight). Parasitaemia disappeared within 24 hours of treatment which was commenced during the early or late stages of acute infection. Intracellular T. cruzi parasites were also affected by the drug, ultrastructural findings showing severe cytoplasmic vacuolization and membrane alterations. Positive serological responses persisted in the majority of treated and parasitologically cured mice in the study. Cure rates varied from 72% to 100% and were similar regardless of the T. cruzi strain used (Y strain, type I; 12 SF strain, type II; or Colombian strain, type III). However, the proportion of positive serological tests and the frequency of inflammatory lesions were greatest for mice that were infected with the Colombian strain of the parasite.

Animals↗
PubMed1987

Enhancement of chronic Trypanosoma cruzi myocarditis in dogs treated with low doses of cyclophosphamide.

An enhancement of chronic myocarditis was obtained in dogs chronically infected with Trypanosoma cruzi protozoa soon after they were submitted to treatment with low doses of cyclophosphamide (50 mg/sq m bs three times a week for 3 weeks). Such treatment did not cause immunodepression. Myocarditis varied in intensity, but was quite severe and diffuse in some animals, with focal fibrinoid, coagulative, and lytic necrosis and invasion of disintegrating myocardial fibers by the mononuclear inflammatory cells. Untreated infected controls exhibited mild focal myocarditis, usually represented by accumulation of lymphocytes in the interstitial connective tissue. It is suggested that the administration of low doses of cyclophosphamide interfered with the immunologic suppressor network that is thought to maintain the chronic indeterminate (or latent) phase of T cruzi infection.

Animals↗
PubMed1986

Electrocardiographic changes in experimental chronic murine Chagas' disease.

An electrocardiographic study was performed on 26 AKR and 32 A/J inbred mice and on 100 Swiss outbred mice, chronically infected with different strains of T. cruzi, characterized as Types I, II and III. The incidence of electrocardiographic alterations in AKR mice was of 87.0%, 80.0% and 83.3% respectively for infection with the Type I, Type II and Type III strains of T. cruzi. In A/J mice the incidence of electrocardiographic alterations was 100% in the infection with the Type I and Type III strains and 26.1% with the Type II strain of T. cruzi. In Swiss mice the electrocardiographic alterations occurred in 53.5% of the mice infected with the Type II strain and in 71.4% of those infected with the Type III strain of T. cruzi. The most frequent electrocardiographic alterations in chronically infected mice, independently of mouse or T. cruzi strain, were first degree AV block, intraventricular conduction abnormalities, sinus tachycardia and bradycardia. The predominant alterations caused by each of the T. cruzi strains varied according to mouse strain. In A/J mice, the electrocardiographic alterations were more frequent in those animals infected with Type I and III strains of T. cruzi and in Swiss mice the alterations were more frequent in those infected with the Type III strain. The results presented in this study demonstrate that the murine model is suitable for electrocardiographic studies related to the heart lesions that occur in Chagas' disease.

Animals↗
PubMed1985

Immunological response of Swiss mice to infection with three different strains of Trypanosoma cruzi.

The immunological response of Swiss mice to infection with three strains of Trypanosoma cruzi which differ in their morphobiological, antigenic and isoenzymic characters [Peruvian, 12 SF (São Felipe) and Colombian strains] was investigated. The three strains stimulated an elevation of the immunoglobulin fractions IgG2a, IgG2b and IgM during acute infection, as measured by radial immunodiffusion, and an early drop of IgG1 levels. There were low levels of specific antibodies and a negative cutaneous delayed hypersensitivity test to T. cruzi antigens. Cellular reaction of the spleen was evident, with proliferation of lymphocytes and the presence of blastic lymphoid cells in the red and white pulp, and hyperplasia of germinal centres of the lymphoid follicles. Those aspects were consistent with a depletion of the T-cell zone (periarteriolar lymphocyte sheath). Despite these common features, there were clear differences in the onset, intensity and evolution of the splenic cellular reaction and IgG serum levels and in the relationship between these levels and parasitaemia in the mice infected with the three strains of T. cruzi. A positive correlation was seen between high IgG levels and mortality, corresponding to intense exudative tissue lesions, showing that a raised immunoglobulin level was not associated with protection. It is worth observing that the 12 SF strain, which showed the lowest parasitaemic profile and mortality rate, stimulated the greatest elevation of IgG2b during acute infection; and also that IgG2a and IgG2b were the immunoglobulins which showed the greatest increases following infection by all three strains of T. cruzi.

Animals↗