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Lechiguana is a disease of cattle caused by an interaction between Dermatobia hominis warble and the bacteria Manheimia granulomatis. It is characterized by subcutaneous swellings that grow rapidly and result in death after 3 to 8 months. The objective of this paper was to investigate some vascular and fibrogenic changes of the disease at different lesion stages by histochemical and immunohistochemical techniques. A peculiar histopathological aspect observed during a proliferative phase (before treatment) was the intense vasculitis, described as degenerative and fibro-proliferative, expressed by the oncogene p53, possibly caused by the presence of bacteria in close contact with enthotelial cells, along with dense accumulations of lymphoid cells around venules. The synthesis of collagen fibers during the development of Lechiguana lesions assume a structural aspect of star arrangement with fiber radiation centers that gradually interconnect to design the Extracellular Matrix (ECM) framework, seen by Confocal Laser Scanning Microscopy (CSLM). Angiogenesis was the most characteristic finding in both proliferative and regressive stages as seen by the immunohistochemical expression of cytoskeleton proteins and von Willebrand (Factor VIII-Related Antigen). Additionally, in all tissues samples, active ECM elements like Metalloproteinases (MMPs), Tissue Inhibitors Metalloproteinases (TIMP) and Fibronectin (FN) were mainly associated to vessels structures. The extraordinary regression of exuberant granulation tissue after treatment is undoubtedly associated to the maintenance of the vascular components observed during the regressive phase.

Angiostrongylus costaricensis is a parasitic nematode that can cause severe gastrointestinal disease, known as abdominal angiostrongiliasis, in humans. This paper presents the characterization of first- and third-stage larvae and male and female adult worms of A. costaricensis by scanning electron and light microscopy. Several novel anatomical structures were identified by scanning electron microscopy, including details of the cuticular striations of the spicules in male worms and a protective flap of the cuticle covering the vulvar aperture in female worms. Other taxonomic features revealed by light microscopy include the gubernaculum and the esophageal-intestinal valve. The use of two microscopy techniques allowed a detailed characterization of the morphology of this nematode. A number of previously identified taxonomic features, such as the striated nature of the spicules and the lateral alae were confirmed; however, the use of scanning electron microscopy resulted in a reassessment of the correct number of papillae distributed around the oral opening and behind the cloacal opening. These observations, in combination with light microscopy-based characterization of the gubernaculum and esophageal valves, have allowed a more detailed description of this nematode taxonomy.

Angiostrongylus costaricensis is a nematode that causes abdominal angiostrongyliasis, a widespread human parasitism in Latin America. This study aimed to characterize the protease profiles of different developmental stages of this helminth. First-stage larvae (L1) were obtained from the faeces of infected Sigmodon hispidus rodents and third-stage larvae (L3) were collected from mollusks Biomphalaria glabrata previously infected with L1. Adult worms were recovered from rodent mesenteric arteries. Protein extraction was performed after repeated freeze-thaw cycles followed by maceration of the nematodes in 40 mM Tris base. Proteolysis of gelatin was observed by zymography and found only in the larval stages. In L3, the gelatinolytic activity was effectively inhibited by orthophenanthroline, indicating the involvement of metalloproteases. The mechanistic class of the gelatinases from L1 could not be precisely determined using traditional class-specific inhibitors. Adult worm extracts were able to hydrolyze haemoglobin in solution, although no activity was observed by zymography. This haemoglobinolytic activity was ascribed to aspartic proteases following its effective inhibition by pepstatin, which also inhibited the haemoglobinolytic activity of L1 and L3 extracts. The characterization of protease expression throughout the A. costaricensis life cycle may reveal key factors influencing the process of parasitic infection and thus foster our understanding of the disease pathogenesis.

A peptide (SmB2LJ; r175-194) that belongs to a conserved domain from Schistosoma mansoni SmATPDase 2 and is shared with potato apyrase, as predicted by in silico analysis as antigenic, was synthesised and its immunostimulatory property was analysed. When inoculated in BALB/c mice, this peptide induced high levels of SmB2LJ-specific IgG1 and IgG2a subtypes, as detected by enzyme linked immunosorbent assay. In addition, dot blots were found to be positive for immune sera against potato apyrase and SmB2LJ. These results suggest that the conserved domain r175-194 from the S. mansoni SmATPDase 2 is antigenic. Western blots were performed and the anti-SmB2LJ antibody recognised in adult worm (soluble worm antigen preparation) or soluble egg antigen antigenic preparations two bands of approximately 63 and 55 kDa, molecular masses similar to those predicted for adult worm SmATPDase 2. This finding strongly suggests the expression of this same isoform in S. mansoni eggs. To assess localisation of SmATPDase 2, confocal fluorescence microscopy was performed using cryostat sections of infected mouse liver and polyclonal antiserum against SmB2LJ. Positive reactions were identified on the external surface from the miracidium in von Lichtenberg's envelope and, in the outer side of the egg-shell, showing that this soluble isoform is secreted from the S. mansoni eggs.

This paper presents many types of interplays between parasites and the host, showing the history of parasites, the effects of parasites on the outcome of wars, invasions, migrations, and on the development of numerous regions of the globe, and the impact of parasitic diseases on the society and on the course of human evolution. It also emphasizes the pressing need to change the look at the parasitism phenomenon, proposing that the term “cohabitant” is more accurate than parasite, because every living being, from bacteria to mammals, is a consortium of living beings in the pangenome. Even the term parasitology should be replaced by cohabitology because there is no parasite alone and host alone: both together compose a new adaptive system: the parasitized-host or the cohabitant-cohabited being. It also suggests switching the old paradigm based on attrition and destruction, to a new one founded on adaptation and living together.

Parasite‐derived lipids may play important roles in host‐pathogen interactions and escape mechanisms. Herein, we evaluated the role of schistosomal‐derived lipids in Toll‐like receptor (TLR)-2 and eosinophil activation in Schistosoma mansoni infection. Mice lacking TLR2 exhibited reduced liver eosinophilic granuloma, compared with that of wild‐type animals, following S. mansoni infection. Decreased eosinophil accumulation and eosinophil lipid body (lipid droplet) formation, at least partially due to reduced production of eotaxin, interleukin (IL)‐5, and IL‐13 in S. mansoni-infected TLR2-/- mice, compared with the corresponding production in wild‐type mice, was noted. Although no differences were observed in survival rates during the acute schistosomal infection (up to 50 days), increased survival of TLR2-/- mice, compared with survival of wild‐type mice, was observed during the chronic phase of infection. Schistosomal lipid extract– and schistosomal‐derived lysophosphatidylcholine (lyso‐PC)-stimulated macrophages in vitro induced TLR2‐dependent NF‐kB activation and cytokine production. Furthermore, in vivo schistosomal lyso‐PC administration induced eosinophil recruitment and cytokine production, in a mechanism largely dependent on TLR2. Taken together, our results suggest that schistosomal‐derived lyso‐PC may participate in cytokine production and eosinophil activation through a TLR2‐dependent pathway in S. mansoni infection. Moreover, our results suggest that TLR2‐dependent inflammatory reaction, cytokine production, and eosinophil recruitment and activation may contribute to the pathogenesis and lethality in the chronic phase of infection.

In vertebrate animals, pleural and peritoneal cavities are repositories of milky spots (MS), which constitute an organised coelom-associated lymphomyeloid tissue that is intensively activated by Schistosoma mansoni infection. This study compared the reactive patterns of peritoneal MS to pleural MS and concluded from histological analysis that they represent independent responsive compartments. Whole omentum, lungs and the entire mediastinum of 54 S. mansoni-infected mice were studied morphologically. The omental MS of infected animals were highly activated, modulating from myeloid-lymphocytic (60 days of infection) to lymphomyeloid (90 days of infection) and lymphocytic or lymphoplasmacytic (160 days of infection) types. The non-lymphoid component predominated in the acute phase of infection and was expressed by monocytopoietic, eosinopoietic and neutropoietic foci, with isolated megakaryocytes and small foci of late normoblasts and mast cells. Nevertheless, pleural or thoracic MS of infected mice were monotonous, consisting of small and medium lymphocytes with few mast and plasma cells and no myeloid component. Our data indicate that compartmentalisation of the MS response is dependent on the lymphatic vascularisation of each coelomic cavity, limiting the effects or consequences of any stimulating or aggressive agents, as is the case with S. mansoni infection.

Objectives To describe clinical presentation and results of diagnostic and therapeutic procedures in seven children from an epidemic of panuveitis in the Brazilian Amazonia, as well as environmental analysis and etiological aspects involved. Methods Patients underwent full pediatric and ophthalmic examinations, B-scan, ultrasound biomicroscopy, and serological tests. Ocular samples were thoroughly analyzed, including two enucleation specimens. Environmental investigation encompassed water, soil, and river fauna. Results All patients had bathed in the waters of a regional river, the Araguaia. Six of them presented with intermediate uveitis, with snowbanking. Five had cataract and four showed inferior endothelial opacity, with localized anterior synechiae. One showed total leukoma, with flat anterior chamber. Only two had active uveitis, one of them with anterior chamber nodule. Serology revealed high prevalence of anti-Toxocara canis immunoglobulin G (IgG) antibodies. In three cases, vitreous and lens samples disclosed spicules of freshwater sponges Drulia uruguayensis and D. ctenosclera, also detected in the waters of the river. Conclusion Freshwater sponge spicules could be potential new etiological agents of ocular pathology, but further studies are needed, considering the heterogeneity of the ocular lesions and results of serological and environmental studies.

Schistosomiasis haematobia or urinary schistosomiasis is one of the main public health problems in Africa and the Middle East. A single dose of 40 mg praziquantel per kg body weight continues to be the treatment of choice for this infection. The aims of this follow-up were to study the post-treatment course of a patient infected with S. haematobium and not submitted to re-exposure, and to identify complications of the disease and/or therapeutic failure after praziquantel treatment by histopathological analysis. Treatments were repeated under medical supervision to ensure the correct use of the drug. In view of the suspicion of lesions in cystoscopy, the patient was submitted to bladder biopsy. The histopathological characteristics observed in biopsies obtained, after each treatment, indicated viability of parasite eggs and activity of granulomas.

Twenty Schistosoma mansoni strains were isolated from three groups of patients (intestinal, hepatointestinal and hepatosplenic clinical forms) born and living in the town of Capitão Andrade, Minas Gerais, Brazil. Schistosomal isolate from each group was inoculated into three sets of mice with 25, 50 and 100 cercariae. The animals were killed 90 and 180 days after infection and submitted to extensive histopathological study of the liver, lung, intestine and spleen to determine qualitative and quantitative morphological characteristics, mainly of the granulomas. The histopathological changes caused the same patterns of infection in mice and were proportional to the inoculum and the time of infection, confirming the relevance of quantitative aspects in the determination of the disease. These data indicate three possibilities: (1) mouse model is not adequate to predict possible differences in the S. mansoni isolates obtained from patients; (2) field isolates are probably genetic polymorphic and undifferentiated; (3) schistosomiasis in human does not depend on parasite intrinsic factors, but on multivariable factors, such as intensity and duration of infection, time of infection, age and gender and other characteristics such as host response.

The extracellular matrix in skeletal tissue besides being responsible for its structure and function also provides key regulatory signals for cell proliferation and differentiation by interacting directly with cell receptors, controlling the diffusion of soluble growth factors. Immature bone marrow cells can migrate through capillaries to systemic circulation as well as return to bone marrow. This phenomenon is the biological basis for bone marrow transplant. The mechanisms that control the migration and the return of these immature bone marrow cells are still to be described in a generally accepted model. Thirty days-old Wistar rats were employed as recipients for the implantation of ceramic blocks or demineralized femur diaphysis. The material was implanted subcutaneously at the dorsum. The rats were euthanized with CO2 at 15, 40 and 68 days after implantation. The whole area of implantation was harvested from skin deep up to the muscle. Liver, spleen, lungs, femurs and the vertebral spine, ribs and sternum were also harvested. The harvested material was fixed in Millonig formalin and decalcified with EDTA, if applicable. The material was then progressively dehydrated in alcohol, immersed in xylol, impregnated and embedded in paraffin. The paraffin blocks were then sliced in 5µm sections with a microtome, stained in Haematoxilin – Eosin, Lennert's Giemsa and Gomori's reticulin for histological analysis under brightfield optical microscopy. All implants produced an intense fibroblastic reaction, angiogenesis and subsequent modulation into a loose stroma. However, hematopoesis was not observed. Implantation of endogenous haematopoetic cells in an inductive stroma, which might propitiate hematopoesis is a model scarcely studied. Experiments such as the one described here might be good models for understanding the sequence of events leading to formation of the stroma and implantation and differentiation of haematopoetic precursors.

Extracellular matrix (ECM) proteins are important modulators of migration, differentiation and proliferation for the various cell types present in the lungs; they influence the immune response as well as participate in the adherence of several fungi including Paracoccidioides brasiliensis. The expression, deposition and arrangement of ECM proteins such as laminin, fibronectin, fibrinogen, collagen and proteoglycans in the lungs of mice infected with P. brasiliensis conidia has been evaluated in this study, together with the elastic fibre system. Lungs of BALB/c mice infected with P. brasiliensis conidia were analysed for the different ECM proteins by histological and immunohistochemical procedures at different times of infection. In addition, laser scanning confocal microscopy and scanning electron microscopy were used. During the early periods, the lungs of infected animals showed an inflammatory infiltrate composed mainly of polymorphonuclear neutrophils (PMNs) and macrophages, while during the later periods, mice presented a chronic inflammatory response with granuloma formation. Re-arrangement and increased expression of all ECM proteins tested were observed throughout all studied periods, especially during the occurrence of inflammatory infiltration and formation of the granuloma. The elastic fibre system showed an elastolysis process in all experiments. In conclusion, this study provides new details of pulmonary ECM distribution during the course of paracoccidioidomycosis.

In life cycle of Angiostrongylus costaricensis, veronicellidae mollusks participate as the invertebrate host while rodents as the main vertebrate host. The current work shows a sequential larval development of A. costaricensis in Sarasinula marginata, individually killed and digested from day 1 to 43, post infection. Some larvae, recovered from sedimentation, were submitted to selective staining after paraffin embedded or inclusion in JB-4 to study inner structures. As control, four slugs were used, two killed at the beginning of infection and the others at the end of the experiment. At day 2 post infection, larvae were motionless and thick, presenting initial retention of granules. At day 4, L2 were detected, persisting until 43 days post infection. Larvae L2 displayed a large amount of granules rich in lipids and carbohydrates through its overall body, with more accumulation at the medial third corresponding to the esophagus–intestine transition site. Lipid granules, the main energetic source, were located at the basal and apical regions of intestinal cells. Both L1 and L3 presented bilateral alae, which is also common in other nematodes. Transition forms between L2 to L3 molts were also observed.

Matrix-assisted laser desorption ionization (MALDI), Peptide Mass Fingerprinting (PMF) and MALDI-MS/MS ion search (using MASCOT) have become the preferred methods for high-throughput identification of proteins. Unfortunately, PMF can be ambiguous, mainly when the genome of the organism under investigation is unknown and the quality of spectra generated is poor and does not allow confident identification. The post-source decay (PSD) fragmentation of singly charged tryptic peptide ions generated by MALDI-TOF/TOF typically results in low fragmentation efficiency and/or complex spectra, including backbone fragmentation ions (series b and y), internal fragmentation etc. Interpreting these data either manually and/or using de novo sequencing software can frequently be a challenge. To overcome this limitation when studying the proteome of adult Angiostrongylus costaricensis, a nematode with unknown genome, we have used chemical N-terminal derivatization of the tryptic peptides with 4-sulfophenyl isothiocyanate (SPITC) prior to MALDI-TOF/TOF MS. This methodology has recently been reported to enhance the quality of MALDI-TOF/TOF-PSD data, allowing the obtainment of complete sequence of most of the peptides and thus facilitating de novo peptide sequencing. Our approach, consisting of SPITC derivatization along with manual spectra interpretation and Blast analysis, was able to positively identify 76% of analyzed samples, whereas MASCOT analysis of derivatized samples, MASCOT analysis of nonderivatized samples and PMF of nonderivatized samples yielded only 35, 41 and 12% positive identifications, respectively. Moreover, de novo sequencing of SPITC modified peptides resulted in protein sequences not available in NCBInr database paving the way to the discovery of new protein molecules.

In a recent outbreak of human ocular injuries that occurred in the town of Araguatins, at the right bank of Araguaia river, state of Tocantins, Brazil, along the low water period of 2005, two patients (8 and 12-year-old boys) presented inferior adherent leukoma in the left eye (OS), and peripherical uveites, with snowbanking in the inferior pars plana. The third one (13-year-old girl) showed posterior uveites in OS, also with snowbanking. Histopathological analysis of lensectomy material from the three patients and vitrectomy from the last one revealed several silicious spicules (gemmoscleres) of the freshwater sponges Drulia uruguayensis and D. ctenosclera. This work brings material evidences, for the first time in the literature, that freshwater sponge spicules may be a surprising new etiological agent of ocular pathology.

We have previously showed that Schistosoma mansoni ATP-diphosphohydrolase and Solanum tuberosum potato apyrase share epitopes and the vegetable protein has immunostimulatory properties. Here, it was verified the in situ cross-immunoreactivity between mice NTPDases and anti-potato apyrase antibodies produced in rabbits, using confocal microscopy. Liver samples were taken from Swiss Webster mouse 8 weeks after infection with S. mansoni cercariae, and anti-potato apyrase and TRITC-conjugated anti-rabbit IgG antibody were tested on cryostat sections. The results showed that S. mansoni egg ATP diphosphohydrolase isoforms, developed by anti-potato apyrase, are expressed in miracidial and egg structures, and not in granulomatous cells and hepatic structures (hepatocytes, bile ducts, and blood vessels). Therefore, purified potato apyrase when inoculated in rabbit generates polyclonal sera containing anti-apyrase antibodies that are capable of recognizing specifically S. mansoni ATP diphosphohydrolase epitopes, but not proteins from mammalian tissues, suggesting that autoantibodies are not induced during potato apyrase immunization. A phylogenetic tree obtained for the NTPDase family showed that potato apyrase had lower homology with mammalian NTPDases 1-4, 7, and 8. Further analysis of potato apyrase epitopes could implement their potential use in schistosomiasis experimental models.

Experimental infection of marmoset monkeys (Callithrix jacchus) with Leptospira interrogans serovar Copenhageni showed microscopic patterns of tissue reactions comparable to those seen in the severe forms of human leptospirosis, including intra-alveolar hemorrhage. The most impressive microscopic changes were seen in the lung and kidney of animals killed at days 6 and 12 after inoculation. There were extensive and irregular areas of hemorrhage predominating around main bronchial branches or diffusely spread to the pulmonary parenchyma, as well as severe tubulointerstitial nephritis. Antibody response detected by the microscopic agglutination test was quantitatively similar to those seen in humans and paralleled severity of tissue lesions. The distribution of leptospires or antigenic debris in infected tissues was observed by immunofluorescence and confocal laser scanning microscopy. Large numbers of typical leptospires were seen in the lumen of proximal renal tubules. Positive reactions showing antigenic debris were closely associated with sites of tissue damage.

The association between worm infections and bacterial diseases has only recently been emphasized. This study examined the effect of experimental Angiostrongylus costaricensis infection on endogenous intestinal flora of Swiss Webster mice. Eight mice aging six weeks were selected for this experiment. Four were infected with A. costaricensis and the other four were used as controls. Twenty eight days after the worm infection, all mice in both groups were sacrificed and samples of the contents of the ileum and colon were obtained and cultured for aerobic and anaerobic bacteria. In the mice infected with A. costaricensis there was a significant increase in the number of bacteria of the endogenous intestinal flora, accompanied by a decrease in the number of Peptostreptococcus spp. This alteration in the intestinal flora of mice infected by the nematode may help to understand some bacterial infections described in humans.

The fact that theSchistosoma mansoniegg has two ATP diphosphohydrolase (EC 3.6.1.5) isoforms with different net charges and an identical molecular weight of 63000, identified by non-denaturing polyacrylamide gel electrophoresis and immunological cross-reactivity with potato apyrase antibodies, is shown. In soluble egg antigen (SEA), only the isoform with the lower net negative charge was detected and seemed to be the predominant species in this preparation. By confocal fluorescence microscopy, using anti-potato apyrase antibodies, theS. mansoniegg ATP diphosphohydrolase was detected on the external surface of miracidium and in von Lichtenberg's envelope. Intense fluorescence was also seen in the outer side of the egg-shell, entrapped by the surface microspines, suggesting that a soluble isoform is secreted. ATP diphosphohydrolase antigenicity was tested using the vegetable protein as antigen. The purified potato apyrase was recognized in Western blots by antibodies present in sera from experimentallyS. mansoni-infected mice. In addition, high levels of IgG anti-ATP diphosphohydrolase antibodies were detected by ELISA in the same sera. This work represents the first demonstration of antigenic properties ofS. mansoniATP diphosphohydrolase and immunological cross-reactivity between potato apyrase and sera from infected individuals.

Schistosomiasis, a chronic disease with considerable social impact, is an important health problem in many countries. To investigate the possible use of immunomodulators as coadjuvants in the treatment of chronic Schistosoma mansoni infection, we evaluated the effect of dexamethasone on histological, hematological, and biochemical parameters that reflect disease severity and morbidity. Animals treated from the first day or after 35 days of infection, were analyzed. In both groups, dexamethasone: (1) induced a decrease in the number of granulomas in hepatic tissue without affecting the alanine aminotransferase profile, (2) reduced splenomegaly and hepatomegaly associated with disease, and (3) improved hemoglobin concentration, hematocrit values and reduced the percentage of reticulocytes, preventing the development of anemia that occurs in the chronic phase of infection. These data suggest that treatment with dexamethasone results in a mild course of murine schistosomiasis and point to this drug as a promising agent to complement S. mansoni specific treatment.

We characterized herein the microarchitecture of the equine thymus along with post-natal development (6 months→18 years). Thymuses showed an involutional process, beginning before the puberty and defined by five histological grades, which consider the progressive cortical thymocyte depletion, shrinkage and rearrangement of the epithelial network and increase in extracellular matrix (ECM). A second feature of the equine thymus was the presence of eosinopoiesis, erythropoiesis, mastocytopoiesis and plasmacytogenesis. Additionally, lymphatic vessels, full of lymphocytes, were particularly prominent. Distribution of ECM proteins was heterogeneous, being denser in the medulla, as well as basement membranes of capsule, septa and perivascular spaces, thus similar to the patterns seen in other mammals. In vitro, horse thymic nurse cells produce ECM proteins, which are relevant in thymocyte/epithelial cell interactions. In conclusion, the equine thymus presents morphological and involutional characteristics similar to other mammals, exhibiting particular features, as prominent non-lymphoid hematopoiesis and lymphatic vessels.

A comparative morphometric study was performed to identify host-induced morphological alterations in Schistosoma mansoni adult worms. A wild parasite population was obtained from a naturally infected rodent (Nectomys squamipes) and then recovered from laboratory infected C3H/He mice. Furthermore, allopatric worm populations maintained for long-term under laboratory conditions in Swiss Webster mice were passed on to N. squamipes. Suckers and genital system (testicular lobes, uterine egg, and egg spine) were analyzed by a digital system for image analysis. Confocal laser scanning microscopy (CLSM) showed details of the genital system (testicular lobes, vitelline glands, and ovary) and the tegument just below the ventral sucker. Significant morphological changes (p < 0.05) were detected in male worms in all experimental conditions, with no significant variability as assessed by CLSM. Significant changes (p < 0.05) were evident in females from the wild population related to their ovaries and vitelline glands, whereas allopatric females presented differences only in this last character. We conclude that S. mansoni worms present the phenotypic plasticity induced by modifications in the parasite's microenvironment, mainly during the first passage under laboratory conditions.

Angiostrongylus cantonensis, A. costaricensis, and A. vasorum are etiologic agents of human parasitic diseases. Their identification, at present, is only possible by examining the adult worm after a 40-day period following infection of vertebrate hosts with the third-stage larvae. In order to obtain a diagnostic tool to differentiate larvae and adult worm from the three referred species, polymerase chain reaction-restriction fragment length polymorphism was carried out. The rDNA second internal transcribed spacer (ITS2) and mtDNA cytochrome oxidase I regions were amplified, followed by digestion of fragments with the restriction enzymes RsaI, HapII, AluI, HaeIII, DdeI and ClaI. The enzymes RsaI and ClaI exhibited the most discriminating profiles for the differentiation of the regions COI of mtDNA and ITS2 of rDNA respectively. The methodology using such regions proved to be efficient for the specific differentiation of the three species of Angiostrongylus under study.

Human abdominal angiostrongyliasis is a severe eosinophilic disease caused by Angiostrongylus costaricensis. Previous studies have demonstrated that wild rodents are critically involved as definitive hosts to this nematode in nature. In this study, we have evaluated the susceptibility of Wistar rats (Rattus norvegicus) to A. costaricensis infection. Kinetics of parasitological and pathological changes, including the number of adult worms recovered from mesenteric arteries, and of IgE, mast cell and eosinophil levels in several compartments have been assessed. The oral inoculation of third-stage larvae (L3) into adult Wistar rats led to a marked accumulation of worms in the branches of the mesenteric arteries 25 and 50 days post-inoculation. Intense bone marrow eosinophilia ranging from 7 to 50 days was accompanied by marked accumulation of eosinophils in the blood, peritoneal and bronchoalveolar spaces. Eosinophilic periarteritis, oedema and granuloma in the intestinal and lung tissues were also histologically evident. Total serum IgE and specific anti-parasite IgE peaked at 25 days post-infection, as measured by ELISA and by the passive cutaneous anaphylaxis test, respectively. At that time point, there was a drastic reduction in the number of intact mast cells in the peritoneal effluent. These findings indicate that Wistar rats are permissive to A. costaricensis infection. IgE-mast cell activation and massive tissue eosinophil infiltration are marked features in the process and are likely to play a crucial role in the immune-response evoked by this parasite.

Background: Pentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The simultaneous use of PTX and antifungal therapy (itraconazole) has previously been evaluated in anexperimental model of pulmonary paracoccidioidomycosis (PCM), a systemic fungal disease caused by the fungus Paracoccidioides brasiliensis (Pb) and characterized by chronic inflammation and lung fibrosis that appears even after a successful course of antifungal therapy. The results revealed prompt and statistically significant reductions in inflammation and fibrosis when compared to itraconazole alone. However, the effect of monotherapy with PTX on the host response to PCM has not been well-documented. Our aim was to determine the effect of PTX on the course of pulmonary lesions and on the local immune response. Results: At the middle and end of treatment, the Pb-infected-PTX-treated mice exhibited significant reductions in lung density compared to the Pb-infected-non-treated mice as assessed by the quantification of Hounsfield units on high-resolution computed tomography (HRCT) (p

We previously reported that portal veins from mice infected with male Schistosoma mansoni exhibited an increased reactivity to 5-hydroxytryptamine (5-HT). Here, we extended our observations to mice infected by both male and female worms and we further investigated another constrictor agent and the mechanism(s) responsible for the enhanced maximal contraction ( E(max)). Bisexual infection increased the E(max) of 5-HT (from 0.66+/-0.06 mN.s to 1.56+/-0.38 mN.s), in a similar way to the unisexual (male) infection. Infection with male worms increased portal vein reactivity to acetylcholine, as revealed by a higher E(max) (1.03+/-0.2 mN.s) in relation to non-infected control animals ( E(max)= 0.54+/-0.08 mN.s). Sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibition with 100 nM thapsigargin reduced the E(max) of 5-HT by 35% in both tissues, discharging a deficiency of SERCA pump in infected animals. In contrast, the number of voltage-dependent Ca(2+) channels (L-type) was higher in portal veins from infected than non-infected control mice. Inhibition of Ca(2+)-activated chloride channels (Cl(Ca)) with 10 micro M niflumic acid reduced the E(max) of 5-HT in portal veins more from infected than non-infected animals (remaining tension = 60.9+/-2.2% and 70.4+/-2.3%, respectively). Histopathological analysis revealed an increased content of collagen and elastin in portal veins from male S. mansoni-infected mice, compatible with an increased intraluminal pressure. In conclusion, male S. mansoni altered portal vein physiology, increasing the E(max) of two vasoconstrictors, possibly by increasing membrane depolarisation through a more effective opening of Cl(Ca) channels, with calcium entering through L-type Ca(2+) channels.

To investigate the possible use of immunomodulators as coadjuvants in the treatment of chronic schistosomiasis, the study described in the present report evaluated the effects of dexamethasone on several parameters which reflect disease severity and morbidity. Parasitological, immunological, and histological parameters were analyzed in animals treated from the first day of infection or after 35 days of infection. In both situations, dexamethasone had no effect on the parasite burden but altered the egg distribution in tissue, indicating that under the schedule used it did not interfere with the development of adult worms or oviposition. Treated mice showed a decrease in the number of eggs in hepatic tissue, reduced granuloma sizes, reduced levels of granuloma maturation, and reduced collagen contents. Dexamethasone-treated mice also had decreased gamma interferon, interleukin-12 (IL-12), and IL-4 levels in serum and increased IL-10 levels in serum. Taken together, these data suggested a decrease in the severity of murine schistosomiasis and point to dexamethasone as a convenient and promising coadjuvant agent in the therapy of this infection.