Schistosomiasis Mansoni Infection Research Articles

Evaluation of Silybin Nanoparticles against Liver Damage in Murine Schistosomiasis mansoni Infection.

Silybin (SIB) is a hepatoprotective drug known for its poor oral bioavailability, attributed to its classification as a class IV drug with significant metabolism during the first-pass effect. This study explored the potential of solid lipid nanoparticles with (SLN-SIB-U) or without (SLN-SIB) ursodeoxycholic acid and polymeric nanoparticles (PN-SIB) as delivery systems for SIB. The efficacy of these nanosystems was assessed through in vitro studies using the GRX and Caco-2 cell lines for permeability and proliferation assays, respectively, as well as in vivo experiments employing a murine model of Schistosomiasis mansoni infection in BALB/c mice. The mean diameter and encapsulation efficiency of the nanosystems were as follows: SLN-SIB (252.8 ± 4.4 nm, 90.28 ± 2.2%), SLN-SIB-U (252.9 ± 14.4 nm, 77.05 ± 2.8%), and PN-SIB (241.8 ± 4.1 nm, 98.0 ± 0.2%). In the proliferation assay with the GRX cell line, SLN-SIB and SLN-SIB-U exhibited inhibitory effects of 43.09 ± 5.74% and 38.78 ± 3.78%, respectively, compared to PN-SIB, which showed no inhibitory effect. Moreover, SLN-SIB-U demonstrated a greater apparent permeability coefficient (25.82 ± 2.2) than PN-SIB (20.76 ± 0.1), which was twice as high as that of SLN-SIB (11.32 ± 4.6) and pure SIB (11.28 ± 0.2). These findings suggest that solid lipid nanosystems hold promise for further in vivo investigations. In the murine model of acute-phase Schistosomiasis mansoni infection, both SLN-SIB and SLN-SIB-U displayed hepatoprotective effects, as evidenced by lower alanine amino transferase values (22.89 ± 1.6 and 23.93 ± 2.4 U/L, respectively) than those in control groups I (29.55 ± 0.7 U/L) and I+SIB (34.29 ± 0.3 U/L). Among the prepared nanosystems, SLN-SIB-U emerges as a promising candidate for enhancing the pharmacokinetic properties of SIB.

Effect of environmental factors in reducing the prevalence of schistosomiasis in schoolchildren: An analysis of three extensive national prevalence surveys in Brazil (1950-2018).

Over seven decades, Brazil has made admirable progress in controlling schistosomiasis, and a frequent question about the explanation for this reduction refers to the effect of improving environmental factors in the country. This article seeks to identify factors related to the change in the epidemiological situation of schistosomiasis mansoni infection by analyzing three national prevalence surveys conducted since 1950. This is an ecological study analyzing an unbalanced panel of data based on national surveys and considering the municipality as the unit of analysis. The sample consisted of 1,721 Brazilian municipalities, in which a total of 1,182,339 schoolchildren aged 7-14 were examined during the three periods corresponding to each survey (1947-1953, 1975-1979, and 2010-2015). The percentage of municipalities with zero cases of schistosomiasis was: 45.4%, 54.2% and 73.7%, respectively for those periods. A zero-inflated Poisson regression model, with fixed and random effects, was fitted to assess the association between candidate factors and disease prevalence using a significance level of 5%. There was a significant decrease in disease prevalence between the first and last periods analyzed (RR 0.214, CI 0.184-0.249), with a protective association with access to sanitation (RR 0.996, CI 0.994-0.998), urbanization (RR 0.991, CI 0.989-0.993), and living in own households (RR 0.986, CI 0.983-0.989); and an inverse association with piped water supply (RR 1.010, CI 1.008-1.011). The findings of this study indicate a decrease in the prevalence of schistosomiasis over seven decades in schoolchildren from the analyzed Brazilian municipalities, associated with environmental factors and social conditions. The increased access to piped water in the municipalities apparently triggers other ways of contact with unsafe water bodies, generating new transmission routes and suggesting the need for a systemic approach concerning contact with water.

Accuracy of the urine point-of-care circulating cathodic antigen assay for diagnosing Schistosomiasis mansoni infection in Brazil: A multicenter study.

The World Health Organization recommends a market-ready, urine-based point-of-care diagnostic test for circulating cathodic antigens (CCA) to determine the prevalence of S. mansoni. This study evaluated the performance of the URINE CCA (SCHISTO) ECO TESTE® (POC-ECO), which is currently available in Brazil. Residents from eight sites with different prevalence estimates provided one urine sample for POC-ECO and one stool sample for Kato-Katz (KK) and Helmintex® (HTX) testing as an egg-detecting reference for infection status. None of the study sites had significantly higher POC-ECO accuracy than KK. POC-ECO is not currently recommended in Brazilian schistosomiasis elimination programs.

Role of IL-17A in enhancing liver fibrosis induced by TGF-β1 and IL-13 in Schistosoma mansoni infected mice

Schistosoma mansoni liver fibrosis is a complicated multicellular process involving numerous cytokines, chemokines, and growth factors. Transforming growth factor beta 1 (TGF-1) and interleukin (IL)-13 have been identified as critical pro-fibrotic mediators in many studies. IL-17A was linked to enhanced TGF- and IL-13-induced pathologies. This case-control study aimed to explore the effect of IL-17A on TGF- and IL-13-induced liver fibrosis during experimentally schistosomiasis mansoni infection. A total of 40 laboratory-bred female C57BL/6 mice were divided into four equal groups (G), G1 non-infected, G2 infected wild type (WT), G3 infected/anti-IL-17 monoclonal antibodies (mAb) and G4 treated mice. Mice were infected percutaneously with 40±5 cercariae per mouse. Neutralizing IL-17 mAb was administered to G3 intraperitoneally 3 weeks after infection and then every third day until 2 days before sacrification; mice of G4 were treated with a single dose of praziquantel. Serum levels of TGF-, IL-13, IL-17A, and proinflammatory cytokines were measured by ELISA. Liver granulomas were identified by hematoxylin-eosin stain and measured by an ocular micrometer. There was a significantly increased serum concentration of TGF-, IL-13, and IL-17A in infected WT mice (P<0.01), but praziquantel treatment reduced cytokine levels (P<0.03). Neutralization of IL-17A activity remarkably reduced serum concentrations of TGF- and IL-13 (P <0.03) resulting in improved liver functions and reduced granuloma size. Secretion of IL-IL-6 and TNF-were markedly enhanced by infection, however, mice that received anti-mouse IL-17 mAb displayed fewer inflammatory mediators (P<0.03). In conclusion, IL-17A might contribute to the progress of liver fibrosis by enhancing the profibrotic effect of TGF- and IL-13 in mice infected with S. mansoni.

Role of IL-17A in enhancing liver fibrosis induced by TGF-β1 and IL-13 in Schistosoma mansoni infected mice

Background: Schistosoma mansoni liver fibrosis is a complicated multicellular process involving numerous cytokines, chemokines, and growth factors. TGF-b1 and IL-13 have been identified as critical pro-fibrotic mediators in many studies. IL-17A was linked to enhanced TGF-b1 and IL-13-induced pathologies. Objective: This case-control study aimed to explore the effect of IL-17A on TGF-b1 and IL-13-induced liver fibrosis during experimentally schistosomiasis mansoni infection. Material and Methods: A total of forty laboratory-bred female C57BL/6 mice were divided into four equal groups, G1 non-infected, G2 infected wild type (WT), G3 infected/anti-IL-17 mAb and G4 treated mice. Mice were infected percutaneously with 40±5 cercariae per mouse. Neutralizing IL-17 mAb was administered to G3 intraperitoneally 3 weeks after infection and then every third day until 2 days before sacrification; mice of G4 were treated with a single dose of praziquantel. Serum levels of TGF-b1, IL-13, IL-17A and proinflammatory cytokines were measured by ELISA. Liver granulomas were identified by hematoxylin-eosin stain and measured by an ocular micrometer. Results: There was a significantly increased serum concentration of TGF-b1, IL-13, and IL-17A in infected WT mice, but praziquantel treatment reduced cytokine levels.

Noninvasive diagnosis of periportal fibrosis in schistosomiasis mansoni: A comprehensive review.

Schistosomiasis mansoni is a neglected disease and key public health problem, mainly due to its high prevalence, the scarcity of public policies, and the severity of some clinical forms. Periportal fibrosis (PPF) is the commonest complication of chronic schistosomiasis mansoni and its diagnosis requires different techniques. Even though wedge biopsy of the liver is considered the gold standard, it is not justified in non-surgical patients, and percutaneous liver biopsy may be informative but does not have sufficient sensitivity. Noninvasive PPF tests mostly include biological (serum biomarkers or combined scores) or physical assessments (imaging assessment of fibrosis pattern or tissue stiffness). Moreover, imaging techniques, such as ultrasound, computed tomography, magnetic resonance imaging, and elastography are applied not only to support the diagnosis of schistosomiasis, but also to assess and detect signs of portal hypertension and organ damage due to chronic schistosomiasis. A combination between a comprehensive history and physical examination with biomarkers for liver fibrosis and imaging methods seems to offer the best approach for evaluating these patients. In addition, understanding their strengths and limitations will allow a more accurate interpretation in the clinical context and can lead to greater accuracy in estimating the degree of fibrosis in patients with Schistosomiasis mansoni (S. mansoni) infection. This review will discuss the different noninvasive methods that are currently available for the evaluation of PPF in S. mansoni infection, and their application, advantages, and limitations in clinical practice.

ASSESSMENT OF PATHOLOGICAL CHANGE OF SCHISTOSOMA MANSONI INFECTIONIN THE LIVER USING ULTRASOUNOGRAPHY

Background: Schistosomiasis is a tropical parasitic disease caused by blood flukes of the genus Schistosoma, causes periportal fibrosis and portal hypertension in approximately 13%-18% of those afflicted with the disease in the Gezira irrigated areas of Sudan. This a prospective study compromise of 360 consecutive patients at North Gezira State between 2016 to 2019 aimed to assessment of pathological change in schistosomiasismansoni infection using B-mode grayscale ultrasound, The images done by portable Sono Scape- A6 machine using convex probe with frequency range from 3.5 to 5 MHz and the data analyzed by SPSS version 15. The result showed that the majority of patients were male and periportal fibrosis had high incidence associated with schistosomiasismansoni, Out of 360 patients with schistosomal PPF under study there were no PPF noted in 56 (15.6%) , while the remaining had mild in106 (29.4%), moderate in166 (46.1%), and severe PPF in 32 (8,9%) The study concluded that the B- mode Gray scale portable ultrasound machine is the most frequently used imaging modality to assess patients for the presence of periportalfibrosis especially in the endemic area.

Sensitivity and specificity of the circulating cathodic antigen rapid urine test in the diagnosis of Schistosomiasis mansoni infection and evaluation of morbidity in a low- endemic area in Brazil.

The Kato-Katz technique is the standard diagnostic test for Schistosoma mansoni infection in rural areas. However, the utility of this method is severely limited by the day-to-day variability in host egg excretion in the stool. In high-transmission areas, the point-of-care circulating cathodic antigen (POC-CCA) urine assay has proven to be a reliable test. However, investigations of the reliability of the POC-CCA assay in low-transmission regions are under way. This study aimed to evaluate the sensitivity and specificity of the POC-CCA assay and the morbidity of schistosomiasis in a low-endemic area in Brazil. Pains City is a low-transmission zone for schistosomiasis. A total of 300 subjects aged 7-76 years were randomly selected for the POC-CCA cassette test. For S. mansoni diagnosis, three stool samples on six slides were compared with one urine sample for each subject. The sensitivity and specificity in the absence of a gold standard were calculated using latent class analysis. Clinical examinations and abdominal ultrasounds were performed in 181 volunteers to evaluate morbidity associated with schistosomiasis. The sensitivity and specificity of the Kato-Katz technique were 25.6% and 94.6%, respectively. By contrast, the sensitivity and specificity of the POC-CCA assay were 68.1% and 72.8%, respectively. Hepatosplenic schistosomiasis was diagnosed in two patients (1.1%). Overall, the POC-CCA urine assay proved to be a useful test for diagnosing S. mansoni in a low-endemic area in Brazil. Severe clinical forms of schistosomiasis can be present even in such low-endemic areas.

Schistosomiasis mansoni infection is associated with reduced liver function and increased liver fibrosis

Schistosomiasis mansoni infection is associated with reduced liver function and increased liver fibrosis

Cytokine profile, proliferation and phosphorylation of ERK1/2 and Akt in circulating mononuclear cells from individuals during the chronic intestinal phase of Schistosomiasis mansoni infection

BackgroundThe immune response to Schistosoma mansoni is characterized by a granulomatous reaction around the parasite eggs that are trapped in the host liver, and this reaction modulates the immune response during the chronic phase of the disease. The typical peripheral blood mononuclear cell (PBMC) response of patients during the chronic intestinal phase of infection is characterized by a decreased response to an S. mansoni soluble egg antigen. To obtain a greater understanding of Schistosoma infections, this study investigated the effects of the soluble egg antigen (SEA) and soluble adult worm antigen (SWAP) of S. mansoni on cellular proliferation, cytokine production, and ERK1/2 and Akt phosphorylation in PBMCs from infected (XTO) and egg-negative (NI) individuals living in the same endemic area.MethodsThe activation status was evaluated by cell immunophenotypic staining (cytometry). The cell proliferation assay was by CFSE method. Cytokine detection assay (Th1 and Th2) was by Cytometric Bead and Array phosphorylation status was by ELISA.ResultsThe XTO, NI and BD (blood donor) individuals from an area not endemic for schistosomiasis were compared. The CD4+ T lymphocyte proliferation rate was lower in the XTO group, but not the NI group, after SEA stimulation compared to the BD group. The CD8+ T cell proliferation rate was lower in the XTO group in the unstimulated cultures and after both SEA and SWAP stimulation compared to the BD group. Cytokine analysis after either SEA or SWAP stimulation showed a balanced cytokine pattern in the XTO and NI groups. ERK1/2 and Akt phosphorylation were only marginally detected in all groups; however, a decrease in ERK 1/2 phosphorylation was observed in the SWAP-stimulated XTO group compared to both the NI and BD groups.ConclusionsThe data indicate that SEA-stimulated CD4+ T cells from infected patients have a lower proliferation rate than the same cells from the NI group. Furthermore, we observed that SWAP stimulation influences ERK1/2 phosphorylation in the XTO group.

Schistosomiasis transmission and environmental change: a spatio-temporal analysis in Porto de Galinhas, Pernambuco--Brazil.

BackgroundIn Brazil, schistosomiasis mansoni infection is an endemic disease that mainly affects the country’s rural populations who carry out domestic and social activities in rivers and water accumulations that provide shelter for the snails of the disease. The process of rural migration to urban centers and the disorderly occupation of natural environments by these populations from endemic areas have favored expansion of schistosomiasis to locations that had been considered to be disease-free. Based on environmental changes that have occurred in consequent to an occupation and urbanization process in the locality of Porto de Galinhas, the present study sought to identify the relationship between those chances, measure by remote-sensing techniques, and establish a new endemic area for schistosomiasis on the coast of Pernambuco State - Brazil.MethodsTo gather prevalence data, two parasitological census surveys were conducted (2000 and 2010) using the Kato-Katz technique. Two malacological surveys were also conducted in the same years in order to define the density and infection rate of the intermediate host. Based on these data, spatial analyses were done, resulting in maps of the risk of disease transmission. To ascertain the environmental changes that have occurred at the locality, images from the QuickBird satellite were analyzed, thus resulting in land use maps.ResultsOver this 10-year period, the foci of schistosomiasis became more concentrated in the Salinas district. This area was considered to be at the greatest risk of schistosomiasis transmission and had the highest prevalence rates over this period. The study illustrated that this was the area most affected by the environmental changes resulting from the disorderly urbanization process, which gave rise to unsanitary environments that favored the establishment and maintenance of foci of schistosomiasis transmission, thereby consolidating the process of expansion and endemization of this parasitosis.

Potential effects of Cramoll 1,4 lectin on murine Schistosomiasis mansoni

Cratylia mollis is a natural forage plant from the Northeast of Brazil. C. mollis seed lectin (Cramoll) containing molecular forms 1 and 4 (Cramoll 1,4) has shown anti-inflammatory and wound-healing activities. This work analyzed the effect of Cramoll 1,4 on experimental schistosomiasis in mice. Experimental groups (n=15/group) were composed of female albino Swiss mice, which were subcutaneously and caudally infected with Schistosoma mansoni (BH strain, 100 cercariae/mouse) and were treated with an intraperitoneal dose after infection as follows: (1) Cramoll 1,4 (50mgkg−1 single dose – after 40 days of infection), (2) Cramoll 1,4 (7mgkg−1 daily dose – for 7 days after infection) and control (untreated mice). Mice were sacrificed 8 weeks after infection and adult worms were recovered from the portal-hepatic system. Livers were fixed in 10% (v/v) formaldehyde/0.15M NaCl and tissue sections were processed for haematoxilin and Masson's trichrome stainings. Mice infected subcutaneously harboured no or very few worms and hence the effect of Cramoll 1,4 could not be assessed. Results (P≤0.05) were obtained with Cramoll 1,4 using the two treatments, with reduction of: egg excretion (79 and 80%), adult worm recovery (71 and 79%) and liver granulomas (40 and 73.5%) in relation to control. This study showed the potential anti-helminthic activity of Cramoll 1,4 when tested against Schistosomiasis mansoni infection in mice.

Experimental Infection withSchistosoma mansoniin CCR5-Deficient Mice Is Associated with Increased Disease Severity, as CCR5 Plays a Role in Controlling Granulomatous Inflammation

The plasma level of the chemokine CCL3 is elevated in patients with chronic severe schistosomiasis mansoni. We have previously shown that CCL3(-/-) mice with experimental infection showed diminished pathology and worm burden compared to those of wild-type (WT) mice. To elucidate further the role of CC chemokines during schistosomiasis mansoni infection, we evaluated the course of infection in C57BL/6J mice deficient in CCR5, one of the receptors for CCL3. The CCR5 deficiency proved to be remarkably deleterious to the host, since mortality rates reached 70% at 14 weeks postinfection in CCR5(-/-) mice and 19% in WT mice. The increased lethality was not associated with an increased parasite burden, since similar numbers of eggs and adult worms were found in mice from both groups. Liver granulomas of chronically infected CCR5(-/-) mice were larger and showed greater numbers of cells and collagen deposition than liver granulomas from WT mice. This was associated with higher levels of production of intereleukin-5 (IL-5), IL-13, CCL3, and CCL5 in infected CCR5(-/-) mice than in infected WT mice. Moreover, at 8 weeks after infection, just before changes in pathology and mortality, the numbers of FoxP3-positive cells were lower in liver granulomas of CCR5(-/-) mice than in WT mice. In conclusion, the CCR5 deletion is deleterious to mice infected with Schistosoma mansoni, and this is associated with enhanced fibrosis and granulomatous inflammation.

Esterologia hepática da infecção esquistossomótica aguda em camundongos das linhagens C57BL/10 e CBA

Previous studies have shown that the outcome of the experimental schistosomiasis mansoni infection depends on the genetic background of the host. To test whether Schistosoma mansoni infected mice strains present different hepatic pathological pattern during acute infection, we examined liver alterations (hepatocytes, sinusoids, and fibrosis), using stereological approach. Changes in liver organization in adult inbreed females C57BL/10 and CBA mice were examined 8 weeks postinfection. Volume density of hepatocytes Vv[h], sinusoids Vv[s] and hepatic fibrosis Vv[fh] were determined by point counting (M42 system-test) and video-microscopy, using light microscopy. In both mouse strains, Vv[h] and Vv[s] were significantly (p&lt;0.05) reduced in comparison to control group. The largest values of Vv[fh] were found in the C57BL/10 strain. We demonstrate that schistosome infection markedly reduced hepatocytes (CBA mice), sinusoids (C57Bl/10), whereas fibrosis was higher in C57BL/10 strain in comparison to that in CBA/ strain.

Immunohistochemical expression of oestrogen and progesterone receptors during experimental acute and chronic murine Schistosomiasis mansoni

The responsibility of Schistosoma mansoni in female infertility is still controversial. This study was conducted to evaluate the effect of acute and chronic schistosomiasis mansoni infection on the endometrium using immunohistochemical analysis of uterine hormone receptor expression. Twenty-four nonpregnant swiss albino mice were divided into three groups: control, noninfected; acute; and chronic Schistosoma mansoni infection. Histological sections of uterine specimens were examined by light microscope with an image analyzing system to detect structural histological, estrogen receptor (ER) and progesterone receptor (PR) expression in the endometrium. No secretory phase was detected in the endometrium in acute and chronic Schistosoma infection. Hormone receptor expression (ER and PR) showed statistically significant differences among the groups (p< 0.05), with significant low ER hormone expression in chronic infection, compared to control proliferative, control secretory and acute infection cases, and statistically significant high PR expression in both acute and chronic infection cases compared to the control secretory cases (p< 0.05). Schistosomiasis mansoni seems to have an important impact on the hormone expression of affected women. Further studies to explore the mechanism of such changes are recommended.

Effect of experimental Schistosomiasis mansoni infection on serum levels of iron, zinc and copper in the olive baboon (Papio anubis)

Schistosoma mansoniasis is a disease of grave concern due to its high morbidity and mortality in parts of the world. This study aimed at providing insight into the pathogenesis of S. mansoniasis as an aid in the development of effective control methods. Iron, zinc and copper concentrations were spectrophotometrically measured in sequential serum specimens obtained from baboons throughout the course of acute S. mansoni infection, following curative treatment with praziquantel and following post-treatment challenge with a second cercarial infection. The initial infection resulted in a two-fold increase in copper concentrations by Day 102 post-infection. Iron concentrations fell to almost half of pre-infection concentrations by Day 123 post-infection, while those of zinc fell to a third of pre-infection concentrations by Day 81 post-infection. These changes were seen to recover several weeks following treatment, though pre-infection concentrations were never achieved. Haptoglobin, a sensitive biomarker in the acute phase response of S. mansoni, was also measured at all sampling points. Haptoglobin changes were in concordance with those of the cations. The findings demonstrate that iron, zinc and copper are reactants in the acute phase response of S. mansoni in the nonhuman primate model, Papio anubis. Furthermore, these reactants are modulated in challenge infections and may be important in the immunopathology of the disease. Key words: Acute phase response, Schistosomiasis mansoni, serum iron, serum zinc, serum copper.

REDUCED SERUM CONCENTRATIONS OF RETINOL AND α-TOCOPHEROL AND HIGH CONCENTRATIONS OF HYDROPEROXIDES ARE ASSOCIATED WITH COMMUNITY LEVELS OF S. MANSONI INFECTION AND SCHISTOSOMAL PERIPORTAL FIBROSIS IN ETHIOPIAN SCHOOL CHILDREN

To study the relationship between micronutrient malnutrition and schistosomiasis mansoni, a cross-sectional study was undertaken involving 421 schoolchildren (mean age 12.6 years; 333 from schistosomiasis mansoni-endemic villages (Workemado and Sille) and 88 non-endemic controls from Sheno). Prevalence of schistosomiasis mansoni infection in Workemado and Sille was comparable (90.6% versus 95%, respectively), and prevalence of PPF in Workemado was significantly higher than in Sille (7.0% versus 0.6%, P < 0.001). Compared with non-endemic controls, serum retinol concentrations were significantly lower and hydroperoxides were significantly higher in subjects from schistosomiasis mansoni-endemic areas. Furthermore, serum alpha-tocopherol concentrations in subjects from an area with high prevalence of PPF were significantly reduced while the concentrations in subjects from an area with low prevalence of PPF were comparable to the levels found in non-endemic healthy controls. In conclusion, micronutrient malnutrition and oxidative stress are associated with Schistosoma mansoni infection and levels of schistosomal PPF.

Cytokine secretion profile associated with periportal fibrosis in S. mansoni-infected Egyptian patients

Periportal fibrosis (PPF) is a major pathological consequence of S. mansoni infection. Ultrasonography is a well-established tool for diagnosis and grading of schistosomiasis-related pathology. This work is performed to study the effect of schistosomiasis mansoni infection on the cytokine secretion profile in S. mansoni-infected patients at various grades of fibrosis, as determined by ultrasonography using Cairo Working Group classification. The levels of IL-2, IL-4, IL5, IL-10, IFN-gamma, and TNF-alpha were measured in the absence of in vitro antigen stimulation and after stimulation with worm and egg antigens. Simple intestinal (INT) patients are characterized by strong proliferation to worm antigen and high levels of IL-10 and TNF-alpha compared to patients at various grades of infection. GradeII (GdII)-infected patients are characterized by higher IL-5 production than are patients with other clinical forms of the disease. Sharp reduction of almost all cytokines in response to both worm and egg antigens was detected in GdIII-infected patients. These results stressed the role of both IL-10 and TNF-alpha in the early stages of hepatic fibrosis, while IL-5 could be employed as a potential predictive marker for advanced stages. In conclusion, PPF is associated with cytokine production profiles that vary with the magnitude of the fibrosis.

Hepatic stereology of schistosomiasis mansoni infected-mice fed a high-fat diet

High-fat diets induce weight gain and fatty liver in wild-type mice. Schistosomiasis mansoni infection also promotes hepatic injury. This study was designed to quantify hepatic alterations in schistosomiasis mansoni-infected mice fed a high fat-rich chow compared to mice fed a standard rodent chow, using stereology. Female SW mice fed each either high-fat diet (29% lipids) or standard chow (12% lipids) over 8 months, and then were infected with Schistosoma mansoni cercariae. Four experimental groups were studied: infected mice fed a high-fat diet (IHFC) or standard chow (ISC), uninfected mice fed a high-fat diet (HFC) or standard chow (SC). Mice were sacrificed during early infection (9 weeks from exposure). The following hepatic biometry and the stereology parameters were determined: volume density (hepatocytes [h], sinusoids [s], steatosis [st] and hepatic fibrosis [hf]); numerical density (hepatocyte nuclei - Nv[h]); absolute number of total hepatocyte N[h], normal hepatocyte N[nh], and binucleated hepatocyte N[bh], percentage of normal hepatocyte P[nh] and binucleated hepatocyte P[bh]. IHFC and HFC groups exhibited TC, HDL-C, LDL-C, and body mass significantly greater (p < 0.05) than control group. No significant differences were found regards liver volume (p = 0.07). Significant differences were observed regards P[nh] (p = 0.0045), P[bh] (p = 0.0045), Nv[h] (p = 0.0006), N[h] (p = 0.0125), N[bh] (p = 0.0164) and N[nh] (p = 0.0078). IHFC mice group presented 29% of binucleated hepatocytes compared to HFC group (19%), ISC group (17%) and SC (6%). Volume density was significantly different between groups: Vv[h] (p = 0.0052), Vv[s] (p = 0.0025), Vv[st] (p = 0.0004), and Vv[hf] (p = 0.0007). In conclusion, schistosomiasis mansoni infection with concurrent high-fat diet promotes intensive quantitative changes in hepatic structure, contributing to an increasing on hepatic regeneration.

Preliminary results on interleukin-4 and interleukin-10 cytokine production in malnourished, inducible nitric oxide synthase-deficient mice with schistosomiasis mansoni infection

Schistosoma mansoni infected C57Bl/6 inducible nitric oxide synthase (iNOS)-deficient and non-deficient malnourished mice, both fed a balanced controlled diet were studied. Interleukins, IL-4 and IL-10 responses to soluble egg antigens (SEA) 90 days after infection, were determined. Our results suggest that in iNOS deficient, malnourished mice, 90 days after of infection, nitric oxide has a downregulating effect on IL-4 and IL-10 production. We are currently investigating the biological significance of these findings.