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Biomedical subjects

A Riarte

Publications and source records attributed to A Riarte.

At least 19 recordsLinked to original sources

Soluble platelet selectin (sP-selectin) and soluble vascular cell adhesion molecule-1 (sVCAM-1) decrease during therapy with benznidazole in children with indeterminate form of Chagas' disease.

The immune response against Trypanosoma cruzi infection has been associated with both protection and pathogenesis. Central events in host defence system- and immune-mediated damage are tightly regulated by cell adhesion molecules (CAM). Levels of sP-selectin and sVCAM-1 were measured in sera from 41 children with the indeterminate phase of Chagas' disease. Simultaneously, levels of soluble adhesion molecule were also quantified in Chagas' disease children undergoing specific chemotherapy with benznidazole. Levels of sP-selectin and sVCAM-1 were found to be elevated in children with indeterminate Chagas' disease before aetiologic therapy was started. However, a small group of patients showed sP-selectin and sVCAM-1 levels comparable to those of non-infected children. A positive correlation between levels of sVCAM-1 and sP-selectin in sera from Chagas' disease patients was found. There was a significantly greater decrease in the titres of sP-selectin and sVCAM-1 in those children receiving benznidazole therapy compared with those children receiving placebo. Measurement of soluble adhesion molecules revealed differences in the activation of the immune system in children with the indeterminate form of Chagas' disease. The early decrease of sP-selectin and sVCAM-1 levels after anti-parasitic treatment suggests that these molecules might be valuable indicators of effective parasitologic clearance.

Chagas Disease↗

Chagas' disease in patients with kidney transplants: 7 years of experience 1989-1996.

Chagas' disease was present in 17.22% of persons undergoing kidney transplantation in an Argentine Hospital. The criterion for attributing reactivation of chronic Chagas' disease and transmission of Trypanosoma cruzi to grafts was detection of parasites in blood (patent parasitemia) or tissues. Reactivation was diagnosed in 5 (21.7%) of 23 recipients. Ten (43.4%) of 23 chagasic recipients without reactivation of chronic Chagas' disease had abrogation of serological reactivity. T. cruzi infection was transmitted to 3 (18.7%) of 16 non-chagasic recipients. Reactivation and infection were diagnosed by patent parasitemia or cutaneous panniculitis. For diagnosis, detection of parasites in blood and tissues had more relevance than serology. Sequential monitoring detected early reactivation and infection, permitting application of preemptive or therapeutic therapy with benznidazole, thus inhibiting, in all patients, severe clinical disease produced by a progressive and systemic replication of the parasite.

Adolescent↗

Recipients and donors of bone marrow transplants suffering from Chagas' disease: management and preemptive therapy of parasitemia.

We report the clinical course of five adult patients with chronic Chagas' disease (Cd) who underwent BMT. Two patients with non-Hodgkin's lymphoma and one with ALL received an ABMT. Allogeneic BMT was performed in two patients with AML and CML respectively. One donor had chronic Cd. Samples of peripheral blood for parasite investigation by the Strout method, blood culture, and immunological studies by indirect immunofluorescent assay, ELISA and indirect hemagglutination tests were performed weekly from the start of chemotherapy until day +60 for ABMT and during the period of immunosuppression for allogeneic BMT. No prophylaxis was given to any of these patients. In only one ABMT patient were trypomastigotes detected early by blood culture without symptoms of reactivation. Benznidazole as preemptive treatment was administered at 5-8 mg/kg/daily for 30 days. Parasitemia was rapidly cleared and at the end of therapy xenodiagnosis was negative. The other Cd patients showed no evidence of relapse of parasitemia or signs and symptoms of reactivation. In brief, evidence of Cd should be sought in all BMT patients coming from endemic areas because parasitemia and reactivation are potential complications during the period of neutropenia and immunosuppression. The strategy used for early detection and treatment of parasitemia and reactivation was safe and effective.

Adult↗

[Clinical features and diagnosis of mucocutaneous leishmaniasis in patients of an endemic area in Salta].

A total of 39 patients with a clinical diagnosis of mucocutaneous leishmaniasis, in an endemic area for leishmaniasis in Salta, Argentina, were examined between June 1990 and December 1992. Of these cases, 87% (34/39) presented the cutaneous simple form, 10.3% the cutaneous multiple form and 2.6% the mucosal form. Lesions were more frequently located in legs and arms (71.8%), followed by trunk and multiple location (10.3%). Of the patients, 43% were housewives, students or children, suggesting that the infection could be contracted in the domestic or peridomestic environment. Of 39 patients diagnosed, in 22 (56.4%) the parasite was found. Direct microscopy (smear) permitted a diagnosis in 13 (59.4%) of these 22 patients. Among these, 5 (22.7%) had positive diagnosis by culture, and 9 (40.9%) by inoculation in hamsters. Ten parasite isolates (45.4%) were obtained. The smear is recommended as a diagnostic method for epidemiological surveillance due to the sensibility demonstrated herein and its easy application in the endemic area. The time of clinical evolution, from the appearance of the lesion up to the detection of the patient by Sanitary Agents, was approximately 90 days. This would be related to the frequency of the visits, usually every 3 months. Only one of 30 treated patients had a relapse at 6 months, due to non fulfillment of the treatment.

Adolescent↗

Leishmania (Viannia) braziliensis: biological behavior in golden hamsters of isolates from Argentine patients.

This study reports intraspecific variations of native isolates of Leishmania (Viannia) braziliensis from patients with leishmaniasis from Salta, Argentina. These isolates induced skin lesions in golden hamsters, initially showing rapid development, reaching their largest size between 28 and 35 days postinfection (PI). Thereafter, the infections were self-limiting and total regression was observed at 80-150 days PI. The majority of the native isolates were characterized by low infectivity in the experimental animals, and a classic pattern of dissemination to systemic organs was established. However, unusual features for L. braziliensis were displayed by two isolates; one showed evidence of high infectivity in hamsters characterized by a short prepatent period and larger, severe and persistent lesions at the inoculation site. The other isolate, of low infectivity, showed cutaneous metastasis and recurrent systemic dissemination in the same animals, suggesting dissociation between infectivity and pathogenicity. Metastasis has been frequently described in hamsters infected with L. (V) guyanensis and L. (V) panamensis, but not in infections induced by L. (V) braziliensis, as was observed in this study. Active and/or regressive histopathologic lesions were observed, depending on the stage of the infection. An exudative and mixed inflammatory pattern with microabscesses and necrotic areas was observed during early infection, while well-defined granulomas and collagen formation were the predominant features detected at a later time. Amastigotes were easily detected in the tissues, although in low numbers. Schaumann bodies were always detected. The characterization of the unique features of these native isolates, and the verification of their reproducibility in vitro and in vivo will be useful tools in tests related to immunoprophylaxis and chemotherapy.

Animals↗

Increased expression and secretion of ICAM-1 during experimental infection with Trypanosoma cruzi.

In the present study we demonstrate that spleens and hearts from BALB/c mice infected with the virulent Tulahuén or the low virulent CA-I strains of Trypanosoma cruzi, contain substantially higher ICAM-1 transcripts than uninfected controls. ICAM-1 expression in heart cells was also increased in the protein level, as measured by flow cytometry, ELISA and immunohistochemistry. The adhesive receptor was observed not only on inflammatory cells but also on sarcolemma of cardiac myocytes from T. cruzi infected mice. ICAM-1 expression was higher during the acute phase than in the chronic phase of infection, and paralleled the density of inflammatory leukocytes. Elevated titres of soluble ICAM-1 (s-ICAM-1) were detected in sera from mice during the acute phase of infection with CA-I or Tulahuén parasites. Cytokines, including IFN-gamma, IL-1 alpha, IL-6 and TNF-alpha have been shown to modulate expression of ICAM-1. Spleens and hearts from mice infected with CA-I or Tulahuen strains showed increased accumulation of mRNAs specific for these cytokines, which peaked during the acute phase of infection. However, IFN-gamma activity was not necessary for ICAM-1 induction, as its levels were also increased during infection in IFN-gamma receptor knock-out (IFN-gamma R- ) mice. Upregulation of ICAM-1 expression might be a direct consequence of parasite infection, since its density on cell lines of different lineages was enhanced after 24 or 48 h of infection with T. cruzi.

Animals↗

Outcome of infection with different strains of Trypanosoma cruzi in mice lacking CD4 and/or CD8.

Mice lacking CD4 and/or CD8 gene expression, generated by embryonic stem-cell technology, were used to study the role of CD4+ and CD8+ cells in the resistance to the acute infection with virulent (Tulahuén and RA) or mild (CA-I) strains of Trypanosoma cruzi. The presence of both CD4+ and CD8+ cells contributed to the survival of mice infected with T. cruzi, and each T-cell subtype was able to sustain protective functions in the absence of the other one. However, in certain host-parasite combinations, CD8+ cell-independent mechanisms were able to control the parasite load. Moreover, CD8- mice chronically infected with a low virulent strain of T. cruzi were protected from an otherwise lethal challenge with the parasite. A different organ distribution of parasite nests was observed when mutant (but not wild type) animals infected with different parasite strains were compared. CD4- mice produced high levels of IgG antibodies against peptide antigens or a whole homogenate from the parasite after infection with CA-I strain. A dramatic enhancement of IgG1- and IgG2a-specific antibodies was observed.

Amino Acid Sequence↗

Cognitive impairment in human chronic Chagas' disease.

UNLABELLED: We proposed to investigate subclinical cognitive impairment secondary to chronic Chagas' disease (CCD). No similar study was previously done. The neuropsychological performance of 45 chronic Chagasic patients and 26 matched controls (age, education place and years of residency in endemic area) was compared using the Mini Mental State Exam (MMSE), Weschler Memory Scale (WMS) and the Weschler Adult Intelligent Scale (WAIS). Non-parametric tests and Chi2 were used to compare group means and multivariate statistics in two way frequency tables for measures of independence and association of categorical variables with the disease. RESULTS: Chagasic patients showed lower MMSE scores (p < .004), poor orientation (p < .004), and attention (p < .007). Lower WMS MQ were associated with CCD (Chi2 5.9; p < .01; Fisher test p < .02). Lower WAIS IQ were associated with CCD (Chi2 6.3, p < .01; Fisher test p < .01) being the digit symbol (p < .03), picture completion (p < .03), picture arrangement (p < .01) and object assembly (p < .03) subtests the most affected. The impairment in non-verbal reasoning, speed of information processing, problem solving, learning and sequencing observed in chronic Chagas disease patients resembles the cognitive dysfunction associated with white matter disease.

Adult↗

Trypanosoma cruzi: T-cell-dependent mechanisms of resistance during chronic infection.

Effector mechanisms of resistance exerted by T cells from BALB/c mice chronically infected with Trypanosoma cruzi, Tulahuén strain, were studied. Spleen cells from chronically infected mice (Chro-SC) prestimulated with heat-killed trypomastigotes (HKT) and/or IL-2 destroyed PHA-labeled p-815 mastocytoma cells, HKT-pulsed macrophages, and normal peritoneal macrophages. However, HKT-stimulated Chro-SC did not affect the infectivity of free bloodstream forms of the parasite. Upon HKT stimulation, Chro-SC or their culture supernatant activated peritoneal macrophages for the destruction of intracellular amastigotes. The effect was abolished after Thy 1.2+ cell depletion. The addition of Cyclosporin A (CyA), which blocks T-cell activation, during HKT-stimulation of Chro-SC, diminished their ability to activate the trypanocidal activity of macrophages. CyA also inhibited the production of both macrophage-activating factors and interferon-gamma by HKT-stimulated Chro-SC. CyA administration to recipients of nylon-wool nonadherent spleen cells from chronically infected mice inhibited their adoptively acquired resistance against T. cruzi, suggesting that the conferred resistance depended on the effect of specifically activated cells. When administered during the chronic stage of the infection, CyA abrogated the antigen-specific delayed type hypersensitivity response but increased the levels of anti-T. cruzi IgG antibodies. Neither parasitemia, tissular parasitism in myocardium or skeletal muscle, nor mortality were detected after CyA treatment, suggesting the presence of a CyA nonsensitive mechanism(s) in the control of T. cruzi during the chronic phase of the infection.

Animals↗

The skunk Conepatus chinga as new host of Trypanosoma cruzi in Argentina.

We report the first systematic epidemiological research carried out in Argentina on the skunk Conepatus chinga. Forty-nine animals were captured in the settlements of Amamá, Trinidad, and nearby forested areas located in the Department of Moreno, Province of Santiago del Estero, between April 1985 and May 1989. Isolation of parasites was done through xenodiagnosis, and their identification as Trypanosoma cruzi was achieved by biological and biochemical criteria. The isolate was highly virulent and pathogenic in inoculated C3H mice. Prevalence was 4.1% (2 of 49). Two facts account for a possible domestic source of infection: both infected skunks were captured near Trinidad, in an area that had never been treated with insecticides, and electrophoretic isoenzyme patterns of the parasites isolated from the skunks were identical to those found in humans. Because extensive deforestation probably would increase the distribution area of C. chinga, further investigation should be performed to evaluate the epidemiological role of this wild mammal.

Animals↗

Immunoprotection of mice against Trypanosoma cruzi with a lyophilized flagellar fraction of the parasite plus adjuvant.

The immunization with the flagellar (F) fraction from epimastigotes of Trypanosoma cruzi has been shown to protect mice against a challenge of bloodstream trypomastigotes of the parasite, both in terms of mortality and decrease in parasitemia. We have compared the immunoprotective properties of the fresh F fraction with those of a lyophilized F (LF) fraction, alone or together with Bordetella pertussis (Bp) as adjuvant. The best results were obtained with LF + Bp: after challenge with 1 X 10(3) metacyclic trypomastigotes, 100% of the mice immunized with LF + Bp survived, and 60% of them showed no signs of parasitemia. Only the animals in which patent parasitemia was demonstrated presented heart and muscle infiltrates.

Adjuvants, Immunologic↗