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Biomedical subjects

O A Bottasso

Publications and source records attributed to O A Bottasso.

At least 19 recordsLinked to original sources
PubMed2003

Age-related increase in resistance to acute Trypanosoma cruzi infection in rats is associated with an appropriate antibody response.

Inoculation at weaning with Trypanosoma cruzi in inbred "l" rats resulted in a self-resolving acute infection characterized by marked parasitaemias, whereas challenge to adult rats revealed a mild disease with extremely low parasitaemias. To explore the mechanisms underlying such age-associated differences in disease outcome, we analysed the in vitro replication of T. cruzi, nitric oxide and tumour necrosis factor-alpha (TNF-alpha) production in peritoneal macrophages (PMs), the serum concentrations of the specific immunoglobulins (Igs) IgM and IgG, antibodies exhibiting lytic activity against bloodstream forms of T. cruzi and circulating levels of nitrate, TNF-alpha and interferon-gamma (IFN-gamma). Macrophages from young rats were as effective as their adult counterparts for restraining intracellular parasite replication. When stimulated with IFN-gamma, culture supernatants from young PMs contained higher amounts of nitrite and TNF-alpha. Serum samples from 4 and 7 days post infection revealed easily detectable amounts of nitrate, with values being further augmented by day 7 post infection and significantly higher in the young group. TNF-alpha levels were only detected in the young group by day 7 post infection. Both groups had increased amounts of IFN-gamma in their sera, although in adult rats, this trend was followed by a significant drop at day 7, with young rats showing values still higher by the same time point evaluation. In contrast, young rats presented significantly lower levels of IgM and IgG antibodies during the first week of infection. Increased resistance in adult rats seems to be the result of a more appropriate antibody production.

Age Factors↗
PubMed2001

Treatment with benznidazole and its immunomodulating effects on Trypanosoma cruzi-infected rats.

Because benznidazole (BZL) was found to downregulate nitric oxide (NO) and cytokine synthesis by murine macrophages, we analyzed the potential immunological repercussions of BZL treatment in Trypanosoma cruzi-infected rats. To evaluate whether the effects of BZL were also observed in the presence of an immunostimulating cytokine, four groups of acutely infected rats were subjected to one of the following 20-day therapeutic schedules: (1) a curative BZL oral regimen, (2) recombinant interferon (IFN-gamma) injections, (3) a suboptimal BZL regimen (25% of curative dose), (4) the latter plus IFN-gamma. All BZL doses markedly reduced NO-derived metabolites either in the circulation or in cultured macrophage supernatants. This was observed in rats simultaneously treated with IFN-gamma, which contrasted with the augmented NO production seen in animals given this cytokine alone. The untreated rats, and groups receiving monotherapy with IFN-gamma or 25% BZL, had increased circulating interleukin (IL)-1beta and IL-2 levels, which were reduced in those given BZL plus IFN-gamma. Although combined treatment failed to cause the virtually undetectable blood parasite levels induced by optimal BZL doses, chronic myocardial lesions were reduced to the same extent as in those receiving the curative schedule. The beneficial effects of BZL in this trypanosomiasis may also depend on some immunomodulating influences.

Adjuvants, Immunologic↗
PubMed2001

Association between high serum prolactin levels and concomitant infections in HIV-infected patients.

Although prolactin (PRL) is now recognized as a cytokine and persistent immune activation is a common immunopathogenic feature of the human immunodeficiency virus infection (HIV), the circumstances associated with the onset of hyperprolactinemia during the course of this infection remain controversial. Given that PRL is able to exert not only endocrinologic effects but also immunologic influences, a study was conducted to investigate whether raised serum levels of PRL were more likely to prevail when HIV-infected patients developed concomitant infections. Serum PRL concentrations, as well as immunoglobulin isotypes, plasmatic viral burden, CD3+, CD4+, CD8+, CD19+, and natural killer (NK) cell counts were measured in 46 nonselected HIV-infected patients stratified on the basis of the presence or absence of clinically active concomitant infections. Serum PRL levels were significantly higher in patients presenting secondary infections as compared with the asymptomatic ones, with hyperprolactinemia being detected in 10/18 (55%) and 2/28 (7%) of these patient groups, respectively. Hyperprolactinemia was not related with viral burden, antiretroviral treatment, gender differences, or CD4+ cell counts. CD3+, CD4+, CD8+, and CD19+ cells were significantly lower in the group presenting active infections, whereas comparisons in NK cell counts, immunoglobulin levels and HIV viral burden revealed no differences between groups. These results provide evidence that hyperprolactinemia is more prevalent during the onset of secondary infections, which might have diagnostic and therapeutic consequences.

AIDS-Related Opportunistic Infections↗
PubMed2000

Protected Trypanosoma cruzi infection in rats born to mothers receiving interferon-gamma during gestation is associated with a decreased intramacrophage parasite growth and preferential synthesis of specific IgG2b antibodies.

We demonstrated that administration of interferon gamma (IFN-gamma) to pregnant rats conferred partial resistance in their offspring to further challenge with Trypanosoma cruzi. Because of the effects of IFN-gamma on macrophage activation and immunoglobulin isotype selection, offspring were now studied to ascertain whether this intervention modifies the in vitro replication of T. cruzi and nitric oxide (NO) production by peritoneal macrophages (PE), together with the anti-T. cruzi IgG isotypes. To evaluate the possibility of a detrimental effect of IFN-gamma, serum levels of anti-sulphatide autoantibodies were also investigated. Offspring were born to mothers undergoing one of the following procedures during gestation: treatment with recombinant rat IFN-gamma, 50,000 IU/rat, five times/week for 3 weeks, which was started on the day of mating; infection with 10(6) trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-gamma treatment as given to the former group; the same protocol except that physiological saline was injected instead of IFN-gamma; injection of physiological saline only. Offspring were challenged at weaning with a similar dose of T. cruzi, to constitute four groups of infected young, plus an additional group of age-matched uninfected rats born to control mothers. PE were harvested at day 7 postinfection (pi), exposed to parasites and further investigated for the replication of T. cruzi and NO production, whereas ELISA studies for measuring serum anti-T. cruzi IgG subclasses and anti-sulphatide autoantibodies were performed at day 30 pi. The number of intracellular parasites in PE was markedly decreased in young born to IFN-gamma-treated mothers, this not being accompanied by higher nitrite levels in culture supernatants. Offspring delivered by IFN-gamma-treated mothers showed no higher serum concentrations of anti-sulphatide autoantibodies, but exhibited a preferential synthesis of anti-T. cruzi IgG2b antibodies. This rat isotype is known to fix complement and constitutes the rat counterpart of IgG2a mouse immunoglobulins whose synthesis is favoured by IFN-gamma.

Animals↗
PubMed2000

Influence of disease severity on nitrite and cytokine production by peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis (TB).

Earlier studies in patients with pulmonary TB have revealed a higher production of Th1 cell type cytokines in moderate TB, with predominant Th2-like responses in advanced disease. Given the influence of IL-12 in T cell differentiation, as well as the roles of transforming growth factor-beta (TGF-beta), nitric oxide and tumour necrosis factor-alpha (TNF-alpha) in the immune response against intracellular pathogens, we decided to analyse the interferon-gamma (IFN-gamma), IL-4, IL-12, TGF-beta, TNF-alpha and nitrite concentrations in culture supernatants of PBMC from TB patients showing different degrees of lung involvement. The sample population comprised 18 untreated TB patients with either moderate (n = 9) or advanced (n = 9) disease and 12 age- and sex-matched healthy controls (total population (patients and controls) 12 women, 18 men, aged 37 +/- 13 years (mean +/- s.d.)). PBMC were stimulated with whole sonicate from Mycobacterium tuberculosis and the supernatants were collected on day 4 for measurement of cytokine and nitrite levels. Antigen-stimulated IFN-gamma, TGF-beta and TNF-alpha production was found to be significantly increased in TB patients, both moderate and advanced, compared with the controls. Levels of IFN-gamma were significantly higher in moderate disease than advanced cases, whereas advanced cases showed significantly higher IL-12, TGF-beta and TNF-alpha concentrations when compared with cases of moderate TB. Nitrite levels were also increased in TB patients and the increase was statistically significant when advanced cases were compared with controls. These findings may contribute to a clearer picture of the net effect of cytokine interactions in TB, essential for a better understanding of the immunopathological mechanisms underlying the distinct clinical forms of the disease.

Adolescent↗
PubMed1999

Evidence that antisulfatide autoantibodies from rats experimentally infected with Trypanosoma cruzi bind to homologous neural tissue.

Earlier studies in Trypanosoma cruzi-infected rats revealed an increased antibody activity against sulfatide, a specific constituent of both myelin sheaths of peripheral nerves and T. cruzi epimastigotes. To investigate further the characteristics of such anti-sulfatide antibodies, we analyzed their IgG isotypes as well as their ability to bind to homologous neural host structures. Antisulfatide IgG-enriched fractions were obtained from rats acutely infected with T. cruzi. Immunoglobulin isotypes were determined by an enzyme-linked immunosorbent assay (ELISA) method to show that IgG2a and, more significantly, IgG2b were the predominant isotypes of antisulfatide autoantibodies. Further immunofluorescence studies carried out in coronal sections of the rat forebrain revealed, in turn, that antisulfatide antibodies were capable of reacting with homologous neural tissues. Specific binding of these rat autoantibodies to sulfocerebroside on cell surfaces in vivo may in theory play some detrimental role, given the reported ability of rat IgG2b to fix complement or to mediate antibody-dependent cell-mediated cytotoxicity reactions.

Acute Disease↗
PubMed1999

In vitro synthesis of interferon-gamma, interleukin-4, transforming growth factor-beta and interleukin-1 beta by peripheral blood mononuclear cells from tuberculosis patients: relationship with the severity of pulmonary involvement.

Given the role of cell-mediated immune responses in resistance to mycobacteria, we sought to analyse whether there was a relationship between the severity of pulmonary tuberculosis (TB) and lymphocyte proliferation as well as in vitro cytokine production. To achieve this, 25 untreated TB patients showing mild (n = 5), moderate (n = 9) or advanced (n = 11) pulmonary disease, and 12 age-matched healthy controls (mean+/-SD, 37+/-14.5 years) were studied. Peripheral blood mononuclear cells were cultured for 5 days with 10 microg/ml whole, sonicated Mycobacterium tuberculosis (WSA) or 2.5 microg/ml Concanavalin A (Con A). Supernatants were collected on day 4, from cultures grown with or without WSA, for measurement of interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-1beta and transforming growth factor-beta (TGF-beta). Antigen-specific proliferation was found to be reduced among patients and more profound in those with advanced disease who also displayed a depressed response to Con A. Patients with mild TB showed a preferential production of IFN-gamma over IL-4, gave the highest level of IFN-gamma synthesis upon specific antigen stimulation and showed increased levels of IL-1beta production. Findings in patients with moderate TB appeared compatible with a mixed production of IFN-gamma and IL-4 coexisting with a higher synthesis of TGF-beta, by comparison to patients with mild TB. Advanced disease showed the highest IL-4 and TGF-beta production, with IFN-gamma synthesis readily noticeable, yet decreased in comparison with the other patient groups. Differences in cytokine response according to the amount of lung involvement suggest a role for such mediators in the immunopathogenesis underlying the distinct clinical forms of pulmonary TB, that is a predominant T helper Th)1-like or Th2-like activity in mild or in progressive TB, respectively.

Adolescent↗
PubMed1997

Depressed autoantibody synthesis in Trypanosoma cruzi-infected rats born to mothers undergoing this infection during pregnancy.

Earlier work indicated that Trypanosoma cruzi infection in pregnant rats decreased the amount of myocardial damage that developed in their chronically infected offspring. Given the suspected role of autoimmune mechanisms in the generation of chronic myocarditis, we evaluated whether this maternal intervention was likely to affect the synthesis of autoantibodies in infected young. Autoantibodies were investigated against molecules exhibiting cross-reactivity with T. cruzi antigens or not, that is cerebroside sulphate (sulphatide) and actin, respectively. Female '1' rats (75 days old) that had been mated with syngeneic sires were separated into two groups, one challenged with living trypomastigotes at 7, 14 and 21 days following mating, and the other one given physiologic saline at the same intervals. At the time of weaning, offspring were injected with 10(6)/T. cruzi to constitute two infected groups: young born to infected mothers (InMoTc) and young delivered by uninfected mothers (CoMoTc). Serum antibodies were investigated by ELISA at 30 and 60 days post-infection, which represents acute and chronic infection, respectively. T. cruzi infection was associated with the production of anti-sulphatide antibodies, but the phenomenon was significantly less evident in InMoTc young and virtually unnoticeable during their chronic infection. Unlike the anti-sulphatide results, levels of anti-actin antibodies showed no differences between CoMoTc and InMoTc rats when compared during acute or chronic infection. The decreased production of anti-sulphatide autoantibodies of InMoTc offspring may be due to a modification of the immune repertoire of offspring because of the contact with parasite antigens during ontogeny.

Actins↗
PubMed1996

Protection of young rats from acute Trypanosoma cruzi infection by interferon-gamma given to their mothers during pregnancy.

We investigated whether administration of interferon-gamma (IFN-gamma) to pregnant rats, infected or not with Trypanosoma cruzi, was likely to protect their offspring from trypanosomal infection. Upon mating with syngeneic sires, four groups of 70-day-old female 1 rats were subjected to one of the following procedures: treatment with recombinant rat (Rr)IFN-gamma 50,000 IU/rat five times/week for three weeks; infection with 1 x 10(6) trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-gamma treatment as given to the former group; the same protocol but IFN-gamma injections being replaced by injection with physiologic saline. Offspring were nursed by their mothers until weaning and then infected with a similar dose of T. cruzi. Pregnant rats showed no exacerbated infection but a self-resolving mild disease, regardless of whether or not they had received IFN-gamma. Maternal infection with T. cruzi and/or IFN-gamma treatment did not affect gestational outcome. Offspring born to both groups of IFN-gamma-treated mothers were almost fully protected from acute infection, and showed higher levels of anti-T. cruzi IgG antibodies when compared with young born to their respective IFN-gamma-untreated mothers. Measurements of IFN-gamma serum activities indicated that ameliorated acute disease in offspring whose mothers were given IFN-gamma during gestation, was not associated with increased levels of endogenously produced IFN-gamma.

Animals↗
PubMed1994

Cellular immune response to common mycobacterial antigens in subjects seropositive for Trypanosoma cruzi.

The immune response is impaired in the silent stage of Chagas' disease. We used quadruple skin-testing with new tuberculins in 37 adults who were symptom-free but seropositive for Trypanosoma cruzi and in 37 matched seronegative controls. Whereas 19% of controls responded to common mycobacterial antigens, none of the Chagas' seropositive group responded to them (p < 0.006), demonstrating specificity in their unresponsiveness. The enhanced tuberculin reactivity after BCG vaccination in the control group was suppressed in seropositive subjects (p < 0.002). Selective loss of response to common mycobacterial antigens may have implications for the autoimmune pathology of Chagas' disease, and for susceptibility to tuberculosis, leprosy, and HIV disease.

Adult↗
PubMed1994

Infection with Trypanosoma cruzi during pregnancy in rats and a decrease in chronic myocardial lesions in their infected offspring.

To ascertain whether maternal infection with Trypanosoma cruzi may influence the course of the parasitic infection in offspring, two groups of female 1 rats were mated with syngeneic sires. One group of females was infected with 10(6) trypomastigotes of T. cruzi three times at weekly intervals. All offspring were nursed by their mothers until weaning and then separated into two groups of young, one to be infected with the same dose of T. cruzi, and the other to remain uninfected. Infection of pregnant rats caused no aggravated disease but resulted in a self-controlled infection that did not cause any deaths or affect their reproductive capacity. The number of young delivered, litter size, fertility coefficient, and offspring weights at weaning were also unaffected by maternal infection; however, the survival coefficient decreased in comparison with values recorded in the offspring of uninfected mothers. The latter finding is likely due to neonatal transmission, since bloodstream forms of T. cruzi were observed in a few offspring of infected mothers. While infected offspring whose mothers had been inoculated with T. cruzi during pregnancy were not protected from acute infection, the occurrence of chronic focal myocarditis was less prevalent when compared with that recorded in chronically infected offspring born to uninfected mothers.

Acute Disease↗
PubMed1993

Enhanced myocardial lesions in chronically Trypanosoma cruzi-infected rats subjected to adult thymectomy.

Control animals and rats infected 90 days earlier, by inoculation of 1 x 10(6) trypomastigotes of Trypanosoma cruzi at weaning, were subjected to adult thymectomy (ATx) or sham operation (S-ATx) and assessed 3 months later for the presence of myocardial lesions and levels of lymph node and spleen T-cell populations. Chronic focal myocarditis (CFM) developed in 78% and 84% of S-ATx or ATx infected rats, respectively. While the two groups of infected rats did not differ as to the occurrence of myocardial lesions, large foci of CFM were more prevalent in ATx infected rats. Chronic T. cruzi (Tc) infection resulted in decreased CD4+ and increased CD8+ lymph node and spleen cell, with CD8+ lymphocytes being lowered to normal values in the spleen of the ATx infected group. It is suggested that ATx might act by interfering with a down-regulating immunoregulatory mechanism, leading to an exacerbation of autoimmune reactions believed to be involved in the generation of myocardial damage.

Animals↗
PubMed1993

Altered calcium-binding ability of plasma proteins as the cause of hypocalcemia in lepromatous leprosy.

This paper reports a study performed on 10 lepromatous leprosy outpatients and on the same number of age- and sex-matched contacts. All of the lepromatous patients were hypocalcemic, but plasma levels of ionized calcium and the acid-base status were normal. The average daily food intake assessed through a questionnaire revealed adequate nutrition of patients and controls. Plasma proteins and 1,25-dihydroxyvitamin D3 and intestinal absorption of calcium were discarded as the causes of the hypocalcemia. In vitro experiments designed to investigate the effect of hydrogen ion concentration on the equilibrium between calcium ion and proteins revealed that, at normal pH values, plasma proteins from lepromatous leprosy patients bind a smaller fraction of total plasma calcium than those from controls. This phenomenon produces a normal concentration of ionized calcium that determines a normal parathyroid status as indicated by the normal urinary excretion of hydroxyproline and plasma concentrations of alkaline phosphatase (total and bone isoenzyme) and tartrate-resistant acid phosphatase.

Absorption↗
PubMed1991

Biological false positive test for syphilis in lepromatous leprosy patients with concomitant hepatitis B virus infection.

Within the wide range of immunological abnormalities occurring in lepromatous leprosy (LL), antiphospholipid antibodies unrelated to treponemal infection, the so-called biological false positive test for syphilis (BFP), have long been recognized. Considering that BFP may also be encountered in different clinical situations, the fact that whether BFP in LL occurs solely or is associated with other concomitant infections or serological abnormalities was investigated. For this purpose, two groups of LL patients with similar clinical features and no evidence of treponemal infection were studied, one group with BFP (n = 21) and the other without BFP (n = 13). At the time of study, patients underwent the following tests: hepatitis B surface antigen (HBsAg), anti-Trypanosoma cruzi specific antibodies, infectious mononucleosis-associated heterophil antibodies, rheumatoid factors, antinuclear antibodies, anti-dsDNA antibodies and gamma-globulin serum levels. Except for HBsAg, which was more frequently detected in patients with BFP (p < 0.02), the other variables showed no significant differences between groups. This finding suggests the possibility that simultaneous infection with hepatitis B virus could contribute, to some extent as an additional factor, to the generation of an altered humoral immune response. The possible physiopathologic significance of anti-phospholipid antibodies, in the light of current knowledge, is also discussed.

False Positive Reactions↗
PubMed1990

Depressed adjuvant arthritis in rats transferred with spleen cells from Trypanosoma cruzi-infected syngeneic donors.

In the present study we investigated whether the attenuating effect of chronic Trypanosoma cruzi (Tc) infection on adjuvant arthritis (AA) in the rat could be transferred to naive recipients. Transfer of whole spleen cells, but not of serum, from Tc-infected rats reduced AA (means +/- SEM: 11 +/- 0.5) in recipient animals (control values, means +/- SEM: 19 +/- 0.7). Transfer of a T-cell-enriched subpopulation from spleen cells of Tc-infected rats (obtained by filtration through a nylon wool column) resulted in a similar attenuation of AA (means +/- SEM: 7.5 +/- 2.2). The arthritic response of rats intraperitoneally inoculated with 2 x 10(5) Tc 48 h before induction did not differ from that observed in controls. Neither parasites nor specific antibodies were observed in suckling mice inoculated with serum or cell suspensions employed in transfer experiments. Consequently, the depressive effect on AA could not be directly attributed to Tc per se. We hypothesize that a homeostatic immunosuppressor mechanism may be responsible for this phenomenon.

Animals↗