Modulation of parasitemia and antibody responce to Trypanosoma cruzy by cyclophosphamide in Calomys callosus (Rodentia, Cricetidae)

Calomys callosus a wild rodent, previously described as harboring Trypanosoma cruzi, has a low susceptibility to infection by this protozoan. Experiments were designed to evaluate the contribution of the immune response to the resistance to T. cruzi infection exhibited by C. calossus. Animals were submitted to injections of high (200 mg/kg body weight) and low (20 mg/kg body weight) doses of cyclophosphamide on days -1 or -1 and +5, and inoculated with 4 x 10³ T. cruzi on day O. Parasitemia, mortality and antibody response as measured by direct agglutination of trypomastigotes were observed. Two hundred mg doses of cyclophosphamide resulted in higher parasitemia and mortality as well as in suppression of the antibody response. A single dose of 20 mg enhanced antibody levels on the 20th day after infection, while an additional dose did not further increase antibody production. Parasitemia levels were not depressed, but rather increased in both these groups as compared to untreated controls. Passive transfer of hyperimmune C. callosus anti-T. cruzi serum to cyclophosphamide immunosuppressed animals resulted in lower parasitemia and mortality rates. These results indicate that the immune response plays an important role in the resistance of C. callossus to T. cruzi.

The effect of chronic ingestion of ethanol on modulation of granulomatous inflammation in experimental schistosomiasis in mice

We studied the role of ethanol on the modulation of liver granulomata around Schistosoma mansoni eggs in mice. Albino mice, receiving 7% ethanol as the sole drinking liquid, at 60 and 90 days post-infection, presented smaller granulomata than controls did, when sacrificed at 120 days post-infection. No differences in diameters could be observed, when ethanol was given 4 months before up to 120 days after infection. The results suggested that modulation of schistosome granulomata by ethanol ingestion varies with time and duration of drug consumption.

Schistosoma mansoni in mice: modulation of granulomatous response after reinfection and chemotherapeutic treatment

Mice previously infected with Schistosoma mansoni, and cured by specific treatment (400mg/kg oxamniquine, p. o.) in the chronic phase of the disease, were reinfected 20 days after treatment to assess their capacityfor modulation ofthe granulomatous response. Histopathologic examination of the animals ' liver, at 60 days after reinfection, evidenced the presence of typical granulomas of the chronic phase in most animals. This infer that the capacity for modulation of the granulomatous response had been maintained, thus preventing a new acute phase of the disease. Conversely, a group of previously infected mice, untreated and submitted to reinfection, showed reactivation of the granulomatous response in 50% of the animals. The possible implications of these findings in human schistosomiasis mansoni are discussed.

Autonomic Modulation of the Heart in Systemic Arterial Hypertension

OBJECTIVE: To analyze the heart rate variability in patients with mild to moderate systemic arterial hypertension. METHODS: Thirty-two healthy (group I) and 70 systemic arterial hypertensive (group II) individuals, divided according to age (40 to 59 and 60 to 80 years old, respectively) and with a similar distribution by sex were studied. Thirty-one had left ventricular hypertrophy (LVH), 22 were overweight, and 16 had Type II diabetes mellitus. Smoking, alcohol ingestion, and sedentary habits were the same between groups. Variability in heart rate was analyzed in the time domain, using standard deviations of normal RR intervals (SDNN) and the differences between maximal brady- and tachycardia (D-BTmax) during sustained inspiration. Analysis of the frequency band of the power spectrum between 0.05 and 0.40 Hz at rest and during controlled respiration was chosen for analysis of the frequency domain. RESULTS: In both time and frequency domains, variables were lower in group II than in group I. Within groups, statistically significant variables were only found for individuals in the 40 to 59 year old group. The presence of LVH, overweight, or diabetes mellitus did not influence the variability in heart rate to a significant extent. CONCLUSION: Variability in heart rate was a valuable instrument for analyzing autonomic modulation of the heart in arterial hypertension. The autonomic system undergoes significant losses in cardio-modulatory capacity, more evident in subjects between 40 and 59 years old. In those over 60 years old, reduced variability in heart rate imposed by aging was not significantly influenced by the presence of systemic arterial hypertension.

Immunopathology of american cutaneous leishmaniasis. Modulation of MHC class II gene products by Keratinocytes before and after glucantime therapy

Epidermal changes from 32 cutaneous and 3 mucosal American leishmaniasis (ACL) active lesions were studied for HLA-DR, -DP expression, Lanerhans cells and lymphocyte infiltration. In addition to a DR and DQ positivity at the surface of the cells of the inflammatory infiltrate, a strong reaction for DR antigens was detected on keratinocytes. Hyperplasia of Langerhans cells was present in al cutaneous lesions and epidermis was infiltrated by T lymphocytes. When healed lesions of 14 of these subjects were re-biopsied 1 to 12 months after the end of pentavalent antimonial therapy, MHC class antigens could no longer be seen on keratinocytes. Our data represrn evidence for hhe reversibility of the abnormal HLA-DR expression by keratinocytes in ACL after Glucantime therapy or spontaneous scar formation, demonstrating that this expresion is restricted to the period of active lesions. The present findings can be regarded as an indirect evidence that keratinocytes may be involved in the immunopathology of ACL.

Role of Immune Complexes from Pacients with Different Clinical Forms of Schistosomiasis in the Modulation of In Vitro Granuloma Reaction

Schistosomiasis is a disease whose pathology is strongly related to the granulomatous reaction formed around parasite eggs trapped in host tissues. Studies have shown that the chronic intestinal form (INT) of this infection is associated with a variety of immunoregulatory mechanisms which lead to a diminished granulomatous reaction. Using an in vitro model of granuloma reaction, we show that immune complexes (IC) isolated from sera of INT patients are able to reduce granulomatous reaction developed by peripheral blood mononuclear cells (PBMC) from acute (AC), INT and hepatosplenic (HE) patients to soluble egg antigen (SEA)-conjugated polyacrylamide beads (PB-SEA). This inhibitory activity is also observed in cell proliferation assay of PBMC from INT and HE patients stimulated with SEA and adult worm antigen (SWAP). Furthermore, IC isolated from sera of patients with different clinical forms of the disease are also able to suppress INT patients PBMC reactivity. Therefore, our results show that circulating IC present in sera of patients with different clinical forms of schistosomiasis may down-regulate PBMC reactivity to parasite antigens resulting in a diminished granuloma reaction to parasite eggs

Cytokines in the modulation of eosinophilia

In this review we discuss our recently results showing interleukin 5 (IL-5) involvement in eosinophil migration and in the maintenance of eosinophilia in blood, bone marrow, lung and peritoneal cavity, in a visceral larva migrans syndrome model using guinea-pigs infected with Toxocara canis. We also describe the sequential release of TNF-alpha and IL-8 during the course of infection, and the interaction between these cytokines and IL-5 during infection. Finally we propose a new biological role for IL-5, at least in our model, as a modulator of IL-8 release and secretion.

Systemic modulation of peripheral eosinophilia (air pouch model) in Schistosoma mansoni infection

Schistosoma mansoni infection induces in their hosts a marked and sustained eosinophilia, which is influenced or modulated by complex mechanisms, that vary according to the phase of infection. To address this phenomenon, we used the air pouch (AP) model in control and infected Swiss webster mice, analyzing the cellular, tissue response and local expression of adhesion molecules [CD18 (beta 2-chain), CD44, ICAM-1 (CD54), L-selectin (CD62L), CD49d (alpha 4-chain), LFA1 (CD11a)]. Infected animals were studied at 3 (pre-oviposition phase), 7 (acute phase), and 14 (chronic phase) weeks after infection (5-6 mice/period of infection). Normal mice were age-matched. Results showed that after egg stimulation, compared with matched controls, the infected mice, at each point of infection, showed a lower eosinophil response in the acute (7 weeks) and chronic phase (14 weeks) of infection. However, when the infected mice were in pre-oviposition phase (3 weeks) their eosinophil response surpassed the control ones. In the AP wall of infected mice, a significant decrease in the expression of ICAM-1 and CD44 in fibroblastic-like cells and a reduction in the number of CD18 and CD11a in migratory cells were observed. The other adhesion molecules were negative or weakly expressed. The results indicated that in the air pouch model, in S. mansoni-infected mice: (1) eosinophil response is strikingly down-regulated, during the acute ovular phase; (2) in the pre-oviposition phase, in contrast, it occurs an up-regulatory modulation of eosinophil response, in which the mechanisms are completely unknown; (3) in the chronic phase of the infection, the down modulation of eosinophil response is less pronounced; 4) Down-regulation of adhesion molecules, specially of ICAM-1 appear to be associated with the lower eosinophil response.

Down-modulation of lymphoproliferation and interferon-gamma production by beta-glucan derived from Saccharomyces cerevisiae

beta-glucan, one of the major cell wall components of Saccharomyces cerevisiae, has been found to enhance immune functions. This study investigated in vivo and in vitro effects of beta-glucan on lymphoproliferation and interferon-gamma (IFN-gamma) production by splenic cells from C57BL/6 female mice. All experiments were performed with particulate beta-glucan derived from S. cerevisiae. Data demonstrated that both, i.p administration of particulate beta-glucan (20 or 100 µg/animal) and in vitro stimulation of splenic cells (20 or 100 µg/ml of culture) decreased lymphoproliferation and IFN-gamma production induced by concanavalin A. These results suggest that beta-glucan can trigger a down-modulatory effect regulating a deleterious immune system hyperactivity in the presence of a strong stimulus.

Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis

In this study, we investigated the expression and activity of liver cytochrome P450s (CYPs) and praziquantel (PZQ) kinetics in mice infected with Schistosoma mansoni. Swiss Webster (SW) mice of both genders were infected (100 cercariae) on postnatal day 10 and killed on post-infection days (PIDs) 30 or 55. Non-infected mice of the same age and sex served as controls. Regardless of mouse sex, infection depressed the activities of CYP1A [ethoxy/methoxy-resorufin-O-dealkylases (EROD/MROD)], 2B9/10 [pentoxy/benzyloxy-resorufin-O-dealkylases (PROD, BROD)], 2E1 [p-nitrophenol-hydroxylase (PNPH)] and 3A11 [erythromycin N-demethylase (END)] on PID 55 but not on PID 30. On PID 55, infection decreased liver CYP mRNA levels (real-time reverse transcription-polymerase chain reaction). On PID 30, whereas mRNA levels remained unaltered in males, they were depressed in females. Plasma PZQ (200 and 400 mg/kg body weight intraperitoneally) levels were measured (high-performance liquid chromatography) at different post-treatment intervals. In males and females, infection delayed the PZQ clearance on PID 55, but not on PID 30. Therefore, it can be concluded that schistosomiasis down-modulated CYP expression and activity and delayed PZQ clearance on PID 55, when a great number of parasite eggs were lodged in the liver. On PID 30, when egg-laying was initiated by the worms, no change of CYP expression and activity was found, except for a depression of CYP1A2 and 3A11 mRNAs in female mice.

Water-induced modulation of Helicobacter pylori virulence properties

While the influence of water in Helicobacter pylori culturability and membrane integrity has been extensively studied, there are little data concerning the effect of this environment on virulence properties. Therefore, we studied the culturability of water-exposed H. pylori and determined whether there was any relation with the bacterium’s ability to adhere, produce functional components of pathogenicity and induce inflammation and alterations in apoptosis in an experimental model of human gastric epithelial cells. H. pylori partially retained the ability to adhere to epithelial cells even after complete loss of culturability. However, the microorganism is no longer effective in eliciting in vitro host cell inflammation and apoptosis, possibly due to the non-functionality of the cag type IV secretion system. These H. pylori-induced host cell responses, which are lost along with culturability, are known to increase epithelial cell turnover and, consequently, could have a deleterious effect on the initial H. pylori colonisation process. The fact that adhesion is maintained by H. pylori to the detriment of other factors involved in later infection stages appears to point to a modulation of the physiology of the pathogen after water exposure and might provide the microorganism with the necessary means to, at least transiently, colonise the human stomach.

Modulation of Trypanosoma cruzi-specific T-cell responses after chemotherapy for chronic Chagas disease

The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease.T-helper (Th)1 and interleukin (IL)-10Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively orvice versa, depending on the T. cruziantigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ) treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruziresults from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.

Fast and slow voltage modulation of apical Cl- permeability in toad skin at high [K+]

The influence of voltage on the conductance of toad skin was studied to identify the time course of the activation/deactivation dynamics of voltage-dependent Cl- channels located in the apical membrane of mitochondrion-rich cells in this tissue. Positive apical voltage induced an important conductance inhibition which took a few seconds to fully develop and was instantaneously released by pulse inversion to negative voltage, indicating a short-duration memory of the inhibiting factors. Sinusoidal stimulation at 23.4 mM [Cl-] showed hysteresis in the current versus voltage curves, even at very low frequency, suggesting that the rate of voltage application was also relevant for the inhibition/releasing effect to develop. We conclude that the voltage modulation of apical Cl- permeability is essentially a fast process and the apparent slow components of activation/deactivation obtained in the whole skin are a consequence of a gradual voltage build-up across the apical membrane due to voltage sharing between apical and basolateral membranes

Modulation of staphylokinase-dependent plasminogen activation by mono- and divalent ions

The effect of several ions (Cl-, Na+, K+, Ca2+) on the rate of plasminogen (Pg) activation by recombinant staphylokinase (rSTA) is reported. Both monovalent and divalent ions affect the rate at which Pg is activated by rSTA, in a concentration-dependent manner (range 0-100 mM). In almost all cases, a decrease of the initial velocity of activation was observed. Cl- showed the most striking inhibitory effect at low concentrations (64% at 10 mM). However, in the presence of a fibrin surface, this inhibition was attenuated to 38%. Surprisingly, 10 mM Ca2+ enhanced the Pg activation rate 21% when a polymerized fibrin matrix was present. These data support the idea that ions can modulate the rate of Pg activation through a mechanism that may be associated with changes in the molecular conformation of the zymogen. This effect is strongly dependent on the presence of a fibrin clot.