Behavior of Schistosoma mansoni-induced histopathological lesions in Biomphalaria glabrata submitted to ionizing radiation

Present report demonstrates that repeated radiation of Schistosoma mansoni-infected Biomphalaria glabrata, totaling 15,000 rads, caused a sudden, albeit transient, suppression of cercarial shedding. Initially, sporocysts practically disappeared from the snail tissues. The more resistant developing cercariae presented nuclear clumping and vacuolation, before undergoing lysis. No host tissue reaction was evident at any time. Thirty-four days after the last irradiation, the snails resumed cercarial elimination. By that time numerous sporocysts and developing cercariae were detected, disseminated throughout snail tissues in a pattern similar to that of a highly malignant neoplasm, with no signs of host cellular reactions, which on the other hand were present in non-irradiated infected controls. The region of the ovo-testis was apparently destroyed after radiation, but returned to its normal appearance around 40 days after the last radiation. Ionizing radiation affected both host and parasite in S. mansoni-infected Biomphalaria glabrata, but the resulting impressive changes were soon reversed.

Activity of natural killer cells during HIV-1 infection in Brazilian patients

Natural killer cells are increasingly being considered an important component of innate resistance to viruses, but their role in HIV infection is controversial. Some investigators have found that natural killer cells do not confer a protective effect during the progression of HIV disease, whereas others have shown that natural killer cells may be protective and retard the progression of the disease, either through their lytic activity or by a chemokine-related suppression of HIV replication. In this study, we analyzed functional alterations in the activity of natural killer cells during HIV-1 infection using a natural killer cells activity assay with K562 cells as targets. RESULTS: Our results show that the activity of natural killer cells decreases only in the advanced phase of HIV infection and when high (40:1) effector cell-target cell ratios were used. The depression at this stage of the disease may be related to increased levels of some viral factors, such as gp120 or gag, that interfere with the binding capacity of natural killer cells, or to the decreased production of natural killer cells -activity-stimulating cytokines, such as IFN-a and IL-12, by monocytes, a subset of cells that are also affected in the late stage of HIV infection. The data suggest that decreased natural killer cells cell activity may contribute to the severe impairment of the immune system of patients in the late stages of HIV infection.

The effect of intravenous zoledronic acid on glucocorticoid-induced multiple vertebral fractures in juvenile systemic lupus erythematosus

Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement.

Treatment of atrial fibrillation with radiofrequency ablation and simultaneous multipolar mapping of the pulmonary veins

OBJECTIVE: To demonstrate the feasibility and safety of simultaneous catheterization and mapping of the 4 pulmonary veins for ablation of atrial fibrillation. METHODS: Ten patients, 8 with paroxysmal atrial fibrillation and 2 with persistent atrial fibrillation, refractory to at least 2 antiarrhythmic drugs and without structural cardiopathy, were consecutively studied. Through the transseptal insertion of 2 long sheaths, 4 pulmonary veins were simultaneously catheterized with octapolar microcatheters. After identification of arrhythmogenic foci radiofrequency was applied under angiographic or ultrasonographic control. RESULTS: During 17 procedures, 40 pulmonary veins were mapped, 16 of which had local ectopic activity, related or not with the triggering of atrial fibrillation paroxysms. At the end of each procedure, suppression of arrhythmias was obtained in 8 patients, and elimination of pulmonary vein potentials was accomplished in 4. During the clinical follow-up of 9.6±3 months, 7 patients remained in sinus rhythm, 5 of whom were using antiarrhythmic drugs that had previously been ineffective. None of the patients had pulmonary hypertension or evidence of stenosis in the pulmonary veins. CONCLUSION: Selective and simultaneous catheterization of the 4 pulmonary veins with microcatheters for simultaneous recording of their electrical activity is a feasible and safe procedure that may help ablation of atrial fibrillation.

Endogenous and exogenously-induced immunomodulation of tumour-host responsiveness

In spite of the availability of multiple effector mechanisms of the immune system to combat tumour growth and metastases, their impairment frequently accompanies the appearance of cancer. Factors contributing to this impairment may be related to properties of the host and/or the tumour itself and may be with respect to their origin -endogenous or exogenour. Based on the unique biological behavior of prostate cancer (PCa), and its apparent escape from immune surveillance in the presence of tumour immuno genicity, continuing investigation of endogenous and exogenous factors thought to be relevant to its pathogenesis have been made. For this purpose further studies of the suggested role of human seminal plasma (SePl) and the synthetic oestrogen, diethylstiboestrol (DES), as representative endogenous and exogenous immunomodulatory factors (IMF) of tumour-host responsiveness, together with evaluation of human prostatic tissue extracts and leuprolide (the luteinizing-hormone-releasing-hormone proposed as an alternate to DES therapy) have been made by evaluating their effect on the lytic activity of natural killer (NK) cells. SePl and prostate extracts significantly suppressed NK cell lysis. Physicochemical studies suggest SePl and prostate IMF to be associated with high and low molecular weight macromolecules; and implicate the participation of transglutaminase and prostaglandins. Comparative study of therapeutic levels of DES vs. leuprolide on NK cell lysis demonstrated significant suppression by DES vs. a negligible effect of leuprolide. Metastases are highly prevalent in PCa, and contribute significantly to its morbidity and mortality. Further knowledge of the range of effects of endogenous and exogenous IMF on effector mechanisms of tumour-host responsiveness, to include suppression of NK cells, and elucidation of their nature, may contribute toward our understanding of the unique biological behavior of tumours of the prostate, in addition to improvement in their clinical management.

Thalidomide failed to inhibit angiogenesis and fibrosis in hepatic schistosomiasis of the mouse

The relationship between angiogenesis and fibrosis has been demonstrated in several pathological conditions, one of them being schistosomiasis. To observe whether suppression of angiogenesis would interfere with fibrosis, Thalidomide, an anti-angiogenesis drug, was administered during 30 consecutive days to mice with experimental schistosomiasis. Computerized morphometric measurements of fibrosis, and the counting of blood vessels from hepatic schistosomal lesions did not significantly differ when treated animals and their controls were compared at the end of the experiments. These rather unexpected results are presented under the understanding that they may be of interest during further studies on the anti-angiogenesis properties of thalidomide, and the relationship between angiogenesis and fibrosis.

Sustainability of vector control strategies in the Gran Chaco Region: current challenges and possible approaches

Sustainability has become a focal point of the international agenda. At the heart of its range of distribution in the Gran Chaco Region, the elimination of Triatoma infestans has failed, even in areas subject to intensive professional vector control efforts. Chagas disease control programs traditionally have been composed of two divorced entities: a vector control program in charge of routine field operations (bug detection and insecticide spraying) and a disease control program in charge of screening blood donors, diagnosis, etiologic treatment and providing medical care to chronic patients. The challenge of sustainable suppression of bug infestation and Trypanosoma cruzi transmission can be met through integrated disease management, in which vector control is combined with active case detection and treatment to increase impact, cost-effectiveness and public acceptance in resource-limited settings. Multi-stakeholder involvement may add sustainability and resilience to the surveillance system. Chagas vector control and disease management must remain a regional effort within the frame of sustainable development rather than being viewed exclusively as a matter of health pertinent to the health sector. Sustained and continuous coordination between governments, agencies, control programs, academia and the affected communities is critical.

Antigenic extracts of Leishmania braziliensis and Leishmania amazonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production

This study evaluated two vaccine candidates for their effectiveness in protecting BALB/c mice against Leishmania chagasiinfection. These immunogenic preparations were composed of Leishmania amazonensisor Leishmania braziliensisantigenic extracts in association with saponin adjuvant. Mice were given three subcutaneous doses of one of these vaccine candidates weekly for three weeks and four weeks later challenged with promastigotes of L. chagasiby intravenous injection. We observed that both vaccine candidates induced a significant reduction in the parasite load of the liver, while the L. amazonensisantigenic extract also stimulated a reduction in spleen parasite load. This protection was associated with a suppression of both interleukin (IL)-10 and IL-4 cytokines by spleen cells in response to L. chagasiantigen. No change was detected in the production of IFN-γ. Our data show that these immunogenic preparations reduce the type 2 immune response leading to the control of parasite replication.

Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells

Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH) has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs) in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

Experimental benznidazole treatment of Trypanosoma cruzi II strains isolated from children of the Jequitinhonha Valley, Minas Gerais, Brazil, with Chagas disease

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.

Essential oil of mustard to control Rhizoctonia solani causing seedling damping off and seedling blight in nursery

The essential oil extracted from mustard (Brassica rapa) seeds was evaluated for its effect on suppression of Rhizoctonia solani growth in vitro, and in field soils, for reducing saprophytic substrate colonization and seedling damping off and blight using snap beans as indicator plant, the in vitro growth was completely inhibited at a concentration of 50 mul/l. The saprophytic substrate colonization in soils 24 h after treatment was drastically reduced to 45% at 150 mul/kg soil concentration, in contrast to 100% colonization at concentrations of 0, 50, or 75 mul/kg. This recovery rate gradually declined to 6% and 60%, respectively, in nine days. A control of pre and post-emergence seedling damping off and blight in common beans (Phaseolus vulgaris), without any apparent phytotoxic effect was achieved by irrigating R. solani infested soils with water containing the emulsified essential oil to provide 150 mul/l soil volume ten days prior to planting, gave over 95%. The effect of the mustard essential oil was not influenced by the physical soil texture, and it appears to be a good substitute for methyl bromide fumigation in nurseries for seedling production.

Grass straw mulching to suppress emergence and early growth of weeds

Sorghum, pearl millet, and Brachiaria ruziziensis have similar characteristics which have led to their use for mulch formation in no-till systems. This study was carried out to evaluate the potential of these three species as straw suppliers to suppress weed emergence. Initial findings led to the conclusion that both pearl millet and Brachiaria ruziziensis have similar or superior potential as weed suppressors, compared to sorghum straw, a species with recognized allelopathic potential. Subsequently, new trials were conducted under greenhouse conditions by sowing weed species in pots, followed by covering of the soil with the straw under evaluation. Independent experiments were conducted for Euphorbia heterophylla and Bidens pilosa. In each experiment, the factors analyzed were type of straw (pearl millet and B. ruziziensis), amount of straw (equivalent to 4 and 8 t ha-1 dry mass) and irrigation method (surface and subsurface). Both pearl millet and B. ruziziensis have shown to be species that can be cultivated to produce straw with allelopathic potential. These effects were effective in suppressing the emergence or early growth of E. heterophylla and B. pilosa. There was no difference in the suppression of emergence of these species when the soil cover level was alternated between 4 and 8 t ha-1 dry mass.

Regulation of T cell response to leishmania antigens by determinants of histocompatibility leukocyte class I and II molecules

It has been shown that HLA class I molecules play a significant role in the regulation of the proliferation of T cells activated by mitogens and antigens. We evaluated the ability of mAb to a framework determinant of HLA class I molecules to regulate T cell proliferation and interferon gamma (IFN-g) production against leishmania, PPD, C. albicans and tetanus toxoid antigens in patients with tegumentary leishmaniasis and healthy subjects. The anti-major histocompatibility complex (MHC) mAb (W6/32) suppressed lymphocyte proliferation by 90% in cultures stimulated with aCD3, but the suppression was variable in cultures stimulated with leishmania antigen. This suppression ranged from 30-67% and was observed only in 5 of 11 patients. IFN-g production against leishmania antigen was also suppressed by anti-HLA class I mAb. In 3 patients IFN-g levels were suppressed by more than 60%, while in the other 2 cultures IFN-g levels were 36 and 10% lower than controls. The suppression by HLA class I mAb to the proliferative response in leishmaniasis patients and in healthy controls varied with the antigens and the patients or donors tested. To determine whether the suppression is directed at antigen presenting cells (APCs) or at the responding T cells, experiments with antigen-primed non-adherent cells, separately incubated with W6/32, were performed. Suppression of proliferation was only observed when the W6/32 mAb was added in the presence of T cells. These data provide evidence that a mAb directed at HLA class I framework determinants can suppress proliferation and cytokine secretion in response to several antigens.

Oncogene-mediated downregulation of RECK, a novel transformation suppressor gene

The RECK gene was initially isolated as a transformation suppressor gene encoding a novel membrane-anchored glycoprotein and later found to suppress tumor invasion and metastasis by regulating matrix metalloproteinase-9. Its expression is ubiquitous in normal tissues, but undetectable in many tumor cell lines and in fibroblastic lines transformed by various oncogenes. The RECK gene promoter has been cloned and characterized. One of the elements responsible for the oncogene-mediated downregulation of mouse RECK gene is the Sp1 site, where the Sp1 and Sp3 factors bind. Sp1 transcription factor family is involved in the basal level of promoter activity of many genes, as well as in dynamic regulation of gene expression; in a majority of cases as a positive regulator, or, as exemplified by the oncogene-mediated suppression of RECK gene expression, as a negative transcription regulator. The molecular mechanisms of the downregulation of mouse RECK gene and other tumor suppressor genes are just beginning to be uncovered. Understanding the regulation of these genes may help to develop strategies to restore their expression in tumor cells and, hence, suppress the cells' malignant behavior.

Extracts of Ascaris suum egg and adult worm share similar immunosuppressive properties

Adult Ascaris suum body extract (Asc) prepared from male and female worms (with stored eggs) down-regulates the specific immune response of DBA/2 mice to ovalbumin (OA) and preferentially stimulates a Th2 response to its own components, which is responsible for the suppression of the OA-specific Th1 response. Here, we investigated the participation of soluble extracts prepared from male or female worms or from eggs (E-Asc) in these immunological events. Extracts from either sex (1 mg/animal) or E-Asc (0.35 or 1 mg protein/animal) suppressed the delayed-type hypersensitivity (DTH) reaction (60-85%), proliferative response (50-70%), IL-2 and IFN-gamma secretion (below detection threshold) and IgG1 antibody production (70-90%) of DBA/2 mice to OA. A dose of 0.1 mg E-Asc/animal did not change DTH or proliferation, but was as effective as 0.35 mg in suppressing IL-2 and IFN-gamma, and OA-specific IgG1 antibodies. Lymph node cells from DBA/2 mice injected with Asc (1 mg/animal) or a high dose of E-Asc (1 mg protein/animal) secreted IL-4 upon in vitro stimulation with concanavalin A. As previously demonstrated for Asc, the cytokine profile obtained with the E-Asc was dose dependent and changed towards Th1 when a low dose (0.1 mg protein/animal) was used. Taken together, these results suggest that adult worms of either sex and eggs induce the same type of T cell response and share similar immunosuppressive properties.